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10/14/2024


Bridelia tomentosa (B. tomentosa) is a traditional medicinal plant for treating diverse ailments. Hence, we designed our study to scrutinize the protective effect of the methanol extract of B. tomentosa leaf (BTL) against carbofuran-induced oxidative stress-mediated hepato-toxicity in Sprague-Dawley rats for the first time, along with the identification and quantification of phenolic acids and flavonoids by high-performance liquid chromatography (HPLC) and evaluation of antioxidant and antiradical activities of this extract. HPLC analysis confirmed the existence of tannic acid, gallic acid, salicylic acid, and naringin in B. tomentosa leaf extract which showed in-vitro antioxidant potentialities with DPPH, nitric oxide, hydrogen peroxide, and hydroxyl radical scavenging properties. Co-administration of B. tomentosa leaf extract with carbofuran showed dose-dependent significant protective effects of hepatic toxicity on serum markers such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl-transferase, lactate dehydrogenase, total bilirubin, total protein, albumin, globulin, lipid profile, urea, uric acid, and creatinine. Carbofuran intoxication also revealed an upsurge in malondialdehyde (MDA) and a decline in cellular endogenous antioxidant enzyme levels in rats compared with the control group. However, B. tomentosa leaf extract co-treatment increased the levels of hepatic antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, and amended the MDA level. Similarly, histopathological evaluation further assured that BTL could keep the hepatocyte from carbofuran-induced damage. https://www.selleckchem.com/Proteasome.html Therefore, all of our findings may conclude that the phenolic acids and flavonoids of B. tomentosa leaf extract are responsible to neutralize the toxic free radical-mediated oxidative hepatic damages.Prostatic PIRADS 4 and 5 lesions on multiparametric MRI typically represent adenocarcinoma with small lymphocytic lymphoma being a rare pathological finding. We report a case of small lymphocytic lymphoma masquerading as PIRADS 4 and 5 lesions with associated lymphadenopathy in a 69-year-old male on active surveillance for low-risk prostate cancer that was subsequently confirmed on targeted and systematic prostate biopsy. Following treatment of lymphoma with ibrutinib, there was complete resolution of the PIRADS lesions on follow-up mpMRI.Penile necrosis is an uncommon condition associated, in most cases, with calciphylaxis, also known as calcific uremic arteriolopathy. It is a progressive disease found in approximately 1%-4% of patients with end stage renal disease. Patients with penile calciphylaxis present a mortality rate of up to 70%, with life expectancy of two-and a half months following the diagnosis. We report a severe calciphylaxis case that had to be submitted to a penectomy but survived the penile event.The Exstrophy - Epispadias Complex (EEC) is a spectrum of rare congenital malformations involving the urinary, genital and musculoskeletal systems. We present an atypical or variant case of EEC in which a bladder plate is found involving a small omphalocele, separated pubic bones and bladder and urethral duplication. The treatment had a favorable outcome, with bladder control and the child voiding normally. Perhaps the best accepted embryonic theory to explain exstrophy and its variants should be reviewed as it fails to satisfactorily explain the alterations we found.Congenital diverticulum is a very rare disease of the urethra in which there is a sacculus enlargement on its ventral surface. We present a Case of a 2-year-old boy with symptoms of urinary hesitancy and swelling in the penoscrotal angle that appears during micturition. The diagnosis of urethral diverticulum is confirmed by retrograde urethrography and voiding cystogram. An open operation was performed - diverticulectomy and primary repair of the urethra.Pembrolizumab, an anti-programmed death-1 specific monoclonal antibody is a second-line treatment for metastatic urothelial carcinoma. Physicians should be aware of adverse immune-related events associated with the use of immune checkpoint inhibitors, particularly adrenocortical insufficiency, which poses a risk of death. We report a case of secondary adrenocortical insufficiency due to isolated adrenocorticotropic hormone deficiency with empty sella syndrome after pembrolizumab treatment in a patient with metastatic renal pelvic cancer. Fortunately, a therapeutic effect was observed 4 months after discontinuation of pembrolizumab, and a durable antitumor response has persisted for 5 months.Placement of foreign bodies within the urethra has intrigued urologists for years. We present the case of a 30-year-old man who had self-inserted 6 kidney beans into his urethra for sexual pleasure. Conservative attempts at removal with bedside interventions were unsuccessful. The patient required operative intervention with cystoscopy and urethral foreign body retrieval. No additional trauma was appreciated and all beans were extracted. Management of patients with a urethral foreign body can be attempted with bedside extraction, however proximal or challenging objects may require surgical extraction via either endoscopic or open approaches.
Mitochondrial alanyl-tRNA synthetase 2 gene (
) related disease is a rare genetic disorder affecting mitochondrial metabolism, leading to severe cardiac disease in infants or progressive leukodystrophy in young adults. The disease is considered ultra-rare with only 39 cases of AARS2-leukodystrophy previously reported.

We present the case of a young man of consanguineous heritage suffering from cognitive decline and progressive spasticity as well as weakness of the proximal musculature. Utilizing MRI and whole genome sequencing, the patient was diagnosed with a homozygous
missense variant (NM_020745.3c.650C>T; p.(Pro217Leu)) and a homozygous
variant (NM_000070.2 c.1469G>A; p.(Arg490Gln)), both variants have previously been identified in patients suffering from
related leukodystrophy and limb-girdle muscular dystrophy, respectively.

This case report presents a case of homozygous AARS2 leukodystrophy and serves to highlight the importance of whole genome sequencing in diagnosing rare neurological diseases as well as to add to the awareness of adult onset leukodystrophies.
This case report presents a case of homozygous AARS2 leukodystrophy and serves to highlight the importance of whole genome sequencing in diagnosing rare neurological diseases as well as to add to the awareness of adult onset leukodystrophies.
A reliable biomarker is urgently needed in the diagnosis and management of acid sphingomyelinase deficiency (ASMD, also known as Niemann Pick A, A/B, and B). Lyso-sphingomyelin (LSM) has previously been proposed as a biomarker for this disease. However, existing studies have not investigated the relationship between LSM levels and clinical subtype or severity. The purpose of this study is to address this gap in knowledge.

We present a cross-sectional study of 28 patients with ASMD, enrolled in an ongoing natural history study at the Icahn School of Medicine at Mount Sinai and The Children's Hospital at Montefiore. Plasma LSM levels from 28 patients were analyzed, including 7 patients with the infantile neurovisceral phenotype (ASMD type A), 3 patients with chronic neurovisceral disease (ASMD type A/B) and 18 patients with chronic visceral ASMD (ASMD type B). The association between LSM levels and clinical subtype, dichotomized as infantile (type A) or chronic (type A/B and B), was analyzed using the Wilcoidentified greater LSM elevations in patients with infantile ASMD compared to those with chronic ASMD. Among patients with chronic ASMD, LSM levels were positively associated with clinical severity. These data support investigation of LSM as a biomarker for ASMD. Future studies are required to determine if LSM levels are predictive of phenotype in pre-symptomatic patients and how such levels correlate in response to treatment.Candida albicans is found to be part of the normal flora in human skin, oral, and respiratory tract, and is known to be an opportunistic infection in immunocompromised populations; rarely is it a cause of meningitis. This case of a patient with Acquired Immune Deficiency Syndrome (AIDS) and Candida albicans meningitis illustrates the subtle symptoms and insidious onset of fungal meningitis. This case and review of literature identify the importance of early identification and therapy.This case highlights the diagnostic dilemma and emphasis the role of Optical Coherence Tomography (OCT) to differentiate between spontaneous coronary artery dissection and recanalized thrombus with multiple channels in a patient with dextrocardia.
New onset atrial fibrillation leads to worse outcomes in patients with sepsis. The association between new onset atrial fibrillation (AF) in COVID19 patients with COVID19 outcomes are lacking. This study aims to determine whether new onset atrial fibrillation in COVID19 patients admitted in the ICU is a risk factor for death or requirement of mechanical ventilation (MV).

This is a retrospective study conducted in a cohort of COVID-19 patients admitted to Bahrain Defence Force COVID19 Field ICU between April 2020 to November 2020. Data were extracted from the electronic medical records. The patients who developed new onset AF during admission were compared to patients who remained in sinus rhythm. Multivariate logistic regression models were used to control for confounders and estimate the effect of AF on the outcomes of these patients.

Our study included a total of 492 patients out of which 30 were diagnosed with new onset AF. In the AF group, the primary outcome occurred in 66.7% of patients (n = 20). In the control group, 17.1% (n = 79) developed the primary outcome. Upon adjusting for the confounders in the multivariate regression model, AF had an odds ratio of 3.96 (95% CI 1.05-14.98; p = 0.042) for the primary outcome.

Our results indicate that new onset AF is a risk factor for worse outcomes in patients admitted with COVID19 in the ICU.
Our results indicate that new onset AF is a risk factor for worse outcomes in patients admitted with COVID19 in the ICU.Recently, the benefits of cognitive behavioral therapy (CBT)-based interventions for patients with hypertension have been recognized, but there has been no systematic review that has comprehensively analyzed the efficacy of CBT on health outcomes in this population. We aimed to explore the therapeutic effect of CBT-based interventions on hypertension patients through a meta-analysis. Relevant randomized controlled trials (RCTs) were obtained by searching electronic databases. The primary outcomes were physiological indicators (blood pressure, blood lipid profile). Secondary outcomes were psychological indicators (anxiety, depression), and the quality of sleep. Stata version 15.0 software was used to analyze the results. A total of 15 RCTs were included. The main analysis revealed that CBT-based interventions reduced systolic pressure -8.67 (95% CI -10.67 to -6.67, P = 0.000); diastolic pressure -5.82 (95% CI -7.82 to -3.81, P = 0.000); total cholesterol levels -0.43 (95% CI -0.76 to -0.10, P = 0.010); depressive symptoms -3.

10/14/2024


In the present review article, the possible role of integrative medicine across the breast cancer care continuum has been discussed along with the concept of integrating complementary practices into mainstream health delivery. We have focused on breast cancer as a model cancer that is well amenable to prevention, early detection and stage appropriate treatment. However, our observations are pertinent for other common cancers, for which there are several opportunities for improving the continuum of care, especially in developing countries like India.Due to their potent immune stimulation, tumor necrosis factor alpha (TNFα) variants with tumor-homing activity are attractive as novel antitumor drugs. The promising antitumor effect of NGR-TNFα in clinical trials triggered extensive interest in developing novel tumor-homing TNFα variants in recent years. Owing to its promising antitumor effect, NGR-TNFα is usually used as a control for newly developed tumor-homing TNFα variants. In our previous works, we produced a pericyte-targeting Z-TNFα at high levels using the Escherichia coli (E. coli) M15-pQE30 system. To further compare Z-TNFα and NGR-TNFα, we attempted to express NGR-TNFα using the same system. Surprisingly, native NGR-TNFα was expressed at a low (~ 0.2 mg/L) level in E. coli M15 containing the pQE30 plasmid. However, a single nucleotide mutation of C to G, resulting in a substitution of leucine (L) with valine (V) at the start of TNFα, increased the expression of NGR-TNFα by ~ 100 times through improving transcription. In addition, the amino acid substitution showed a little impact on the receptor binding, in vitro cytotoxicity, and in vivo antitumor effect of NGR-TNFα. As fusing NGR to the N-terminus of TNFα with a valine substitution did not reduce the protein yield, the TNFα gene with a C > G mutation might be used to prepare novel tumor-homing TNFα when the native TNFα-based variant is expressed at an extremely low level in E. coli. Notably, in addition to the mutated valine, the impact of N-terminal additional amino acids provided by pQE30 vector on the function of TNFα variant must be carefully evaluated. KEY POINTS • A single nucleotide mutation increased the expression of NGR-TNFα by two orders. • Nucleotide mutation-induced amino acid substitution did not reduce NGR-TNFα activity.Since the discovery of human leukocyte antigens (HLAs), the function of major histocompatibility complex (MHC) gene families in a wide range of diseases have been the subject of research for decades. In particular, the associations of autoimmune disorders to allelic variants and candidate genes encoding the MHC are well documented. However, despite decades of research, the knowledge of MHC associations with human disease susceptibility have been predominantly studied in European origin, with limited understanding in different populations and ethnic groups. This is particularly evident in countries and ethnic populations of the Arabian Peninsula. Human MHC haplotypes, and its association with diseases, of the variable ethnic groups of this region are poorly studied. This review compiled published manuscripts that have reported a list of autoimmune diseases (insulin-dependent diabetes mellitus, systemic lupus erythematosus, myasthenia gravis, rheumatoid arthritis, psoriasis vulgaris, and multiple sclerosis) associated with MHC class I and class II in the populations of the Arabian Peninsula, specifically Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, the United Arab Emirates, and Yemen. Data available was compared with other three ethnic groups, namely Caucasians, Asians, and Africans. The limited data available in the public domain on the association between MHC gene and autoimmune diseases highlight the challenges in the Middle Eastern region.Lead (Pb) is a highly toxic metal for humans, animals and plants even at low concentrations in the soil. The ingestion of chocolate produced from contaminated beans can contribute to consumer exposure to Pb. While, Mn is an element essential for plants and participates as enzymatic cofactors in several metabolic pathways. The objective of this study was to evaluate the influence of Mn on mitigation of Pb toxicity in seedling of the cacao clonal CCN 51 genotype grown in soils with different doses of Pb, Mn and Mn+Pb, through physiological, biochemical, molecular and nutritional responses. It was found that the seedling of the cacao clonal CCN 51 genotype grown in soils with high Pb, Mn and Mn+Pb contents accumulated these heavy metals in the roots and leaves. Mn doses reduced the Pb uptake by root system and prevented that the Pb accumulated at toxic levels in the roots and leaves of the plants. High doses of Pb applied in soil were highly toxic to the plants, leading, in some cases, them to death. However, no51 genotype grown in contaminated soils.
Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. TGFβ1 has been the mostly accepted factor to fuel normal fibroblasts transformation into CAFs. Ca
/calmodulin-dependent protein kinase II (CaMKII) is thought to play an important role in fibroblasts activation induced by TGFβ1. The aim of this study is to investigate the potential role of CaMKII in TGFβ1-induced fibroblasts activation and CAF-like differentiation. Cross talk between CaMKII-dependent fibroblasts and colon cancer in colon cancer progression also was addressed RESULTS Immunostaining demonstrated that in colon cancer stroma, CaMKII overexpressed in stromal CAFs. In vitro, TGFβ1 increased CAF markers expression in human colon fibroblasts CCD-18Co, but not in CaMKII depletion fibroblasts. CaMKII knockdown by CaMKII shRNA significantly inhibited TGFβ1-induced fibroblasts activation and CAF-like differentiation. https://www.selleckchem.com/products/smoothened-agonist-sag-hcl.html Smad3, AKT, and MAPK were targeted in TGFβ1-CaMKII-mediated pathway. Human colon cancer cell line HCT-116 activated fibroblasts directly, whereas CaMKII depletion dragged CCD-18Co fibroblasts undergoing CAF-associated trans-differentiation. Furthermore, increased proliferation, migration, and invasion of colon cancer cells were stimulated when co-cultured with normal fibroblasts, but not with CaMKII depletion fibroblasts.

These findings provide evidence that CaMKII is a critical mediator in TGFβ1-induced fibroblasts activation and is involved in the cross talk with colon cancer cells. CaMKII is a potentially effective target for future treatment of colon cancer.
These findings provide evidence that CaMKII is a critical mediator in TGFβ1-induced fibroblasts activation and is involved in the cross talk with colon cancer cells. CaMKII is a potentially effective target for future treatment of colon cancer.

10/14/2024


Many autoimmune diseases can affect the central nervous system, and their varying clinical presentations often confound a straightforward diagnosis. In this report, we describe a unique presentation of CLIPPERS syndrome. To our knowledge, this is the first case to demonstrate significant supratentorial involvement with symmetric and non-confluent lesions in the medial orbitofrontal cortex; additionally, this is the second case to describe an association between diagnoses of hypothyroidism and CLIPPERS.Retinopathy of prematurity is defined as retinal abnormalities that occur during development as a consequence of disturbed oxygen conditions and nutrient supply after preterm birth. Both neuronal maturation and retinal vascularization are impaired, leading to the compensatory but uncontrolled retinal neovessel growth. Current therapeutic interventions target the hypoxia-induced neovessels but negatively impact retinal neurons and normal vessels. Emerging evidence suggests that metabolic disturbance is a significant and underexplored risk factor in the disease pathogenesis. Hyperglycemia and dyslipidemia correlate with the retinal neurovascular dysfunction in infants born prematurely. Nutritional and hormonal supplementation relieve metabolic stress and improve retinal maturation. Here we focus on the mechanisms through which metabolism is involved in preterm-birth-related retinal disorder from clinical and experimental investigations. We will review and discuss potential therapeutic targets through the restoration of metabolic responses to prevent disease development and progression.Accurate prediction models have become the first goal for aiding pandemic-related decisions. Modeling and predicting the number of new active cases and deaths are important steps for anticipating and controlling COVID-19 outbreaks. The aim of this research was to develop an accurate prediction system for the COVID-19 pandemic that can predict the numbers of active cases and deaths in the Gulf countries of Saudi Arabia, Oman, the United Arab Emirates (UAE), Kuwait, Bahrain, and Qatar. The novelty of the proposed approach is that it uses an advanced prediction model-the bidirectional long short-term memory (Bi-LSTM) network deep learning model. The datasets were collected from an available repository containing updated registered cases of COVID-19 and showing the global numbers of active COVID-19 cases and deaths. Statistical analyses (e.g., mean square error, root mean square error, mean absolute error, and Spearman's correlation coefficient) were employed to evaluate the results of the adopted Bi-LSTM model. The Bi-LSTM results based on the correlation metric gave predicted confirmed COVID-19 cases of 99.67%, 99.34%, 99.94%, 99.64%, 98.95%, and 99.91% for Saudi Arabia, Oman, the UAE, Kuwait, Bahrain, and Qatar, respectively, while testing the Bi-LSTM model for predicting COVID-19 mortality gave accuracies of 99.87%, 97.09%, 99.53%, 98.71%, 95.62%, and 99%, respectively. The Bi-LSTM model showed significant results using the correlation metric. Overall, the Bi-LSTM model demonstrated significant success in predicting COVID-19. The Bi-LSTM-based deep learning network achieves optimal prediction results and is effective and robust for predicting the numbers of active cases and deaths from COVID-19 in the studied Gulf countries.Depression is one of the most common mental disorders in the world that negatively affects the daily functioning of patients. Numerous studies are currently being conducted to examine the antidepressant potential of innovative synthetic compounds and herbal substances. Yacon, Smallantchus sonchifolius, belongs to plants with numerous health-beneficial properties. Yacon-based products are regarded as a functional food. In our study, we attempted to check whether administration of Yacon tuber extract would have an antidepressant effect in the forced swim test (FST) in mice and whether its intake could influence the activity of conventional antidepressant drugs with different mechanisms of action, i.e., imipramine hydrochloride, fluoxetine hydrochloride, and reboxetine mesylate. The spontaneous locomotor activity of the tested mice was also investigated to eliminate any false-positive results. We demonstrated that an intragastric administration of the Yacon tuber extract at a dose of 100 mg/kg induced the antidepressant-like behavior in the FST in mice and that a combined administration of the sub-effective doses of the Yacon extract (50 mg/kg) with imipramine hydrochloride (7.5 mg/kg), fluoxetine hydrochloride (20 mg/kg), or reboxetine mesylate (5 mg/kg) significantly reduced the immobility time of animals in this behavioral test. The obtained results were not affected by the increased locomotor activity of the tested subjects. In conclusion, our findings suggest that Yacon tuber extract is promising as an alternative mood-improving product since it possesses an antidepressant potential and it can acts synergistically with conventional antidepressant drugs.The appearance of cervical adenopathies can occur in many pathologies in a non-specific manner; Erdheim-Chester disease (ECD) is characterized by xanthogranulomatous and xanthomatous infiltration of different tissues with numerous foamy histiocytes. Bone lesions are frequent and radiological features are pathognomonic for diagnosis, but lymph node involvement is exceptional and is not a form of presentation reported in the literature. https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html Recurrent BRAFV600E mutation and others have been discovered in recent years. Since then, several treatments targeting the BRAF and MEK pathways have been developed with high success rates; even so, interferon-α continues to be one of the most widely used treatments. The best imaging test for the study and monitoring of the disease is PET-CT. The prognosis of ECD is relatively poor, with a survival of 43% of patients after 32 months follow-up. Higher survival rates have been reported in patients treated with interferon. The authors present an exceptional case of ECD with cervical adenopathies as a debut, highlighting the need for the knowledge of the disease for differential diagnosis, early treatment, and the importance of communication between the clinician and the pathologist. The main features of the disease and a brief discussion of current diagnosis and treatment are reviewed.The discovery of new drugs is required in the time of global aging and increasing populations. Traditional drug development strategies are expensive, time-consuming, and have high risks. Thus, drug repurposing, which treats new/other diseases using existing drugs, has become a very admired tactic. It can also be referred to as the re-investigation of the existing drugs that failed to indicate the usefulness for the new diseases. Previously published literature used maximum flow approaches to identify new drug targets for drug-resistant infectious diseases but not for drug repurposing. Therefore, we are proposing a maximum flow-based protein-protein interactions (PPIs) network analysis approach to identify new drug targets (proteins) from the targets of the FDA (Food and Drug Administration) drugs and their associated drugs for chronic diseases (such as breast cancer, inflammatory bowel disease (IBD), and chronic obstructive pulmonary disease (COPD)) treatment. Experimental results showed that we have successfully turned the drug repurposing into a maximum flow problem. link2 Our top candidates of drug repurposing, Guanidine, Dasatinib, and Phenethyl Isothiocyanate for breast cancer, IBD, and COPD were experimentally validated by other independent research as the potential candidate drugs for these diseases, respectively. This shows the usefulness of the proposed maximum flow approach for drug repurposing.Argan oil is rich in long-chain unsaturated fatty acids (FA), mostly oleic and linoleic, and natural antioxidants. This study addresses the production of low-calorie structured lipids by acidolysis reaction, in a solvent-free system, between caprylic (C80; system I) or capric (C100; system II) acids and argan oil, used as triacylglycerol (TAG) source. Three commercial immobilized lipases were tested Novozym® 435, Lipozyme® TL IM, and Lipozyme® RM IM. Higher incorporation degree (ID) was achieved when C100 was used as acyl donor, for all the lipases tested. link3 Lipozyme® RM IM yielded the highest ID for both systems (28.9 ± 0.05 mol.% C100, and 11.4 ± 2.2 mol.% C80), being the only catalyst able to incorporate C80 under the reaction conditions for biocatalyst screening (molar ratio 21 FA/TAG and 55 °C). The optimal conditions for Lipozyme® RM IM in system II were found by response surface methodology (66 °C; molar ratio FA/TAG of 41), enabling to reach an ID of 40.9 mol.% of C100. Operational stability of Lipozyme® RM IM in system II was also evaluated under optimal conditions, after eight consecutive 24 h-batches, with biocatalyst rehydration between cycles. The biocatalyst presented a half-life time of 103 h.Background Advances in management have improved mortality of individuals with chronic respiratory failure (CRF), leading to an increase in need for long-term oxygen therapy and/or ventilatory support. These individuals require frequent visits and monitoring of their physiological parameters as well as of the functioning of their devices, such as ventilators or oxygen concentrators. Telemedicine is a clinical application of Information Communication Technology connecting patients to specialised care consultants. This narrative review aims to explore the current available telemonitoring options for individuals with CRF and reported or potential results. Methods The research focused on EMBASE, CINALH, PubMed, and Scopus databases. Papers published between 2003 and 2021 in English were considered. Results Different sensors, transmission devices and systems, and interventions are used with promising but not conclusive clinical results. However, legal problems are still unsolved, and economic advantages for health care systems, although potentially high, are still under debate. Conclusions Telemonitoring systems for individuals with CRF are increasingly used; with promising results still to be clarified, legal, economical and organisational issues must be defined.To understand the biological effects of radiation, it is important to determine how ionizing radiation deposits energy in micrometric targets. The energy deposited in a target located in an irradiated tissue is a function of several factors such as the radiation type and the irradiated volume size. We simulated the energy deposited by energetic ions in spherical targets of 1, 2, 4, and 8 µm radii encompassed in irradiated parallelepiped volumes of various sizes using the stochastic radiation track structure code Relativistic Ion Tracks (RITRACKS). Because cells are usually part of a tissue when they are irradiated, electrons originating from radiation tracks in neighboring volumes also contribute to energy deposition in the target. To account for this contribution, we used periodic boundary conditions in the simulations. We found that the single-ion spectra of energy deposition in targets comprises two components the direct ion hits to the targets, which is identical in all irradiation conditions, and the contribution of hits from electrons from neighboring volumes, which depends on the irradiated volume.

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10/14/2024


Bridelia tomentosa (B. tomentosa) is a traditional medicinal plant for treating diverse ailments. Hence, we designed our study to scrutinize the protective effect of the methanol extract of B. tomentosa leaf (BTL) against carbofuran-induced oxidative stress-mediated hepato-toxicity in Sprague-Dawley rats for the first time, along with the identification and quantification of phenolic acids and flavonoids by high-performance liquid chromatography (HPLC) and evaluation of antioxidant and antiradical activities of this extract. HPLC analysis confirmed the existence of tannic acid, gallic acid, salicylic acid, and naringin in B. tomentosa leaf extract which showed in-vitro antioxidant potentialities with DPPH, nitric oxide, hydrogen peroxide, and hydroxyl radical scavenging properties. Co-administration of B. tomentosa leaf extract with carbofuran showed dose-dependent significant protective effects of hepatic toxicity on serum markers such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl-transferase, lactate dehydrogenase, total bilirubin, total protein, albumin, globulin, lipid profile, urea, uric acid, and creatinine. Carbofuran intoxication also revealed an upsurge in malondialdehyde (MDA) and a decline in cellular endogenous antioxidant enzyme levels in rats compared with the control group. However, B. tomentosa leaf extract co-treatment increased the levels of hepatic antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, and amended the MDA level. Similarly, histopathological evaluation further assured that BTL could keep the hepatocyte from carbofuran-induced damage. https://www.selleckchem.com/Proteasome.html Therefore, all of our findings may conclude that the phenolic acids and flavonoids of B. tomentosa leaf extract are responsible to neutralize the toxic free radical-mediated oxidative hepatic damages.Prostatic PIRADS 4 and 5 lesions on multiparametric MRI typically represent adenocarcinoma with small lymphocytic lymphoma being a rare pathological finding. We report a case of small lymphocytic lymphoma masquerading as PIRADS 4 and 5 lesions with associated lymphadenopathy in a 69-year-old male on active surveillance for low-risk prostate cancer that was subsequently confirmed on targeted and systematic prostate biopsy. Following treatment of lymphoma with ibrutinib, there was complete resolution of the PIRADS lesions on follow-up mpMRI.Penile necrosis is an uncommon condition associated, in most cases, with calciphylaxis, also known as calcific uremic arteriolopathy. It is a progressive disease found in approximately 1%-4% of patients with end stage renal disease. Patients with penile calciphylaxis present a mortality rate of up to 70%, with life expectancy of two-and a half months following the diagnosis. We report a severe calciphylaxis case that had to be submitted to a penectomy but survived the penile event.The Exstrophy - Epispadias Complex (EEC) is a spectrum of rare congenital malformations involving the urinary, genital and musculoskeletal systems. We present an atypical or variant case of EEC in which a bladder plate is found involving a small omphalocele, separated pubic bones and bladder and urethral duplication. The treatment had a favorable outcome, with bladder control and the child voiding normally. Perhaps the best accepted embryonic theory to explain exstrophy and its variants should be reviewed as it fails to satisfactorily explain the alterations we found.Congenital diverticulum is a very rare disease of the urethra in which there is a sacculus enlargement on its ventral surface. We present a Case of a 2-year-old boy with symptoms of urinary hesitancy and swelling in the penoscrotal angle that appears during micturition. The diagnosis of urethral diverticulum is confirmed by retrograde urethrography and voiding cystogram. An open operation was performed - diverticulectomy and primary repair of the urethra.Pembrolizumab, an anti-programmed death-1 specific monoclonal antibody is a second-line treatment for metastatic urothelial carcinoma. Physicians should be aware of adverse immune-related events associated with the use of immune checkpoint inhibitors, particularly adrenocortical insufficiency, which poses a risk of death. We report a case of secondary adrenocortical insufficiency due to isolated adrenocorticotropic hormone deficiency with empty sella syndrome after pembrolizumab treatment in a patient with metastatic renal pelvic cancer. Fortunately, a therapeutic effect was observed 4 months after discontinuation of pembrolizumab, and a durable antitumor response has persisted for 5 months.Placement of foreign bodies within the urethra has intrigued urologists for years. We present the case of a 30-year-old man who had self-inserted 6 kidney beans into his urethra for sexual pleasure. Conservative attempts at removal with bedside interventions were unsuccessful. The patient required operative intervention with cystoscopy and urethral foreign body retrieval. No additional trauma was appreciated and all beans were extracted. Management of patients with a urethral foreign body can be attempted with bedside extraction, however proximal or challenging objects may require surgical extraction via either endoscopic or open approaches.
Mitochondrial alanyl-tRNA synthetase 2 gene (
) related disease is a rare genetic disorder affecting mitochondrial metabolism, leading to severe cardiac disease in infants or progressive leukodystrophy in young adults. The disease is considered ultra-rare with only 39 cases of AARS2-leukodystrophy previously reported.

We present the case of a young man of consanguineous heritage suffering from cognitive decline and progressive spasticity as well as weakness of the proximal musculature. Utilizing MRI and whole genome sequencing, the patient was diagnosed with a homozygous
missense variant (NM_020745.3c.650C>T; p.(Pro217Leu)) and a homozygous
variant (NM_000070.2 c.1469G>A; p.(Arg490Gln)), both variants have previously been identified in patients suffering from
related leukodystrophy and limb-girdle muscular dystrophy, respectively.

This case report presents a case of homozygous AARS2 leukodystrophy and serves to highlight the importance of whole genome sequencing in diagnosing rare neurological diseases as well as to add to the awareness of adult onset leukodystrophies.
This case report presents a case of homozygous AARS2 leukodystrophy and serves to highlight the importance of whole genome sequencing in diagnosing rare neurological diseases as well as to add to the awareness of adult onset leukodystrophies.
A reliable biomarker is urgently needed in the diagnosis and management of acid sphingomyelinase deficiency (ASMD, also known as Niemann Pick A, A/B, and B). Lyso-sphingomyelin (LSM) has previously been proposed as a biomarker for this disease. However, existing studies have not investigated the relationship between LSM levels and clinical subtype or severity. The purpose of this study is to address this gap in knowledge.

We present a cross-sectional study of 28 patients with ASMD, enrolled in an ongoing natural history study at the Icahn School of Medicine at Mount Sinai and The Children's Hospital at Montefiore. Plasma LSM levels from 28 patients were analyzed, including 7 patients with the infantile neurovisceral phenotype (ASMD type A), 3 patients with chronic neurovisceral disease (ASMD type A/B) and 18 patients with chronic visceral ASMD (ASMD type B). The association between LSM levels and clinical subtype, dichotomized as infantile (type A) or chronic (type A/B and B), was analyzed using the Wilcoidentified greater LSM elevations in patients with infantile ASMD compared to those with chronic ASMD. Among patients with chronic ASMD, LSM levels were positively associated with clinical severity. These data support investigation of LSM as a biomarker for ASMD. Future studies are required to determine if LSM levels are predictive of phenotype in pre-symptomatic patients and how such levels correlate in response to treatment.Candida albicans is found to be part of the normal flora in human skin, oral, and respiratory tract, and is known to be an opportunistic infection in immunocompromised populations; rarely is it a cause of meningitis. This case of a patient with Acquired Immune Deficiency Syndrome (AIDS) and Candida albicans meningitis illustrates the subtle symptoms and insidious onset of fungal meningitis. This case and review of literature identify the importance of early identification and therapy.This case highlights the diagnostic dilemma and emphasis the role of Optical Coherence Tomography (OCT) to differentiate between spontaneous coronary artery dissection and recanalized thrombus with multiple channels in a patient with dextrocardia.
New onset atrial fibrillation leads to worse outcomes in patients with sepsis. The association between new onset atrial fibrillation (AF) in COVID19 patients with COVID19 outcomes are lacking. This study aims to determine whether new onset atrial fibrillation in COVID19 patients admitted in the ICU is a risk factor for death or requirement of mechanical ventilation (MV).

This is a retrospective study conducted in a cohort of COVID-19 patients admitted to Bahrain Defence Force COVID19 Field ICU between April 2020 to November 2020. Data were extracted from the electronic medical records. The patients who developed new onset AF during admission were compared to patients who remained in sinus rhythm. Multivariate logistic regression models were used to control for confounders and estimate the effect of AF on the outcomes of these patients.

Our study included a total of 492 patients out of which 30 were diagnosed with new onset AF. In the AF group, the primary outcome occurred in 66.7% of patients (n = 20). In the control group, 17.1% (n = 79) developed the primary outcome. Upon adjusting for the confounders in the multivariate regression model, AF had an odds ratio of 3.96 (95% CI 1.05-14.98; p = 0.042) for the primary outcome.

Our results indicate that new onset AF is a risk factor for worse outcomes in patients admitted with COVID19 in the ICU.
Our results indicate that new onset AF is a risk factor for worse outcomes in patients admitted with COVID19 in the ICU.Recently, the benefits of cognitive behavioral therapy (CBT)-based interventions for patients with hypertension have been recognized, but there has been no systematic review that has comprehensively analyzed the efficacy of CBT on health outcomes in this population. We aimed to explore the therapeutic effect of CBT-based interventions on hypertension patients through a meta-analysis. Relevant randomized controlled trials (RCTs) were obtained by searching electronic databases. The primary outcomes were physiological indicators (blood pressure, blood lipid profile). Secondary outcomes were psychological indicators (anxiety, depression), and the quality of sleep. Stata version 15.0 software was used to analyze the results. A total of 15 RCTs were included. The main analysis revealed that CBT-based interventions reduced systolic pressure -8.67 (95% CI -10.67 to -6.67, P = 0.000); diastolic pressure -5.82 (95% CI -7.82 to -3.81, P = 0.000); total cholesterol levels -0.43 (95% CI -0.76 to -0.10, P = 0.010); depressive symptoms -3.

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In the present review article, the possible role of integrative medicine across the breast cancer care continuum has been discussed along with the concept of integrating complementary practices into mainstream health delivery. We have focused on breast cancer as a model cancer that is well amenable to prevention, early detection and stage appropriate treatment. However, our observations are pertinent for other common cancers, for which there are several opportunities for improving the continuum of care, especially in developing countries like India.Due to their potent immune stimulation, tumor necrosis factor alpha (TNFα) variants with tumor-homing activity are attractive as novel antitumor drugs. The promising antitumor effect of NGR-TNFα in clinical trials triggered extensive interest in developing novel tumor-homing TNFα variants in recent years. Owing to its promising antitumor effect, NGR-TNFα is usually used as a control for newly developed tumor-homing TNFα variants. In our previous works, we produced a pericyte-targeting Z-TNFα at high levels using the Escherichia coli (E. coli) M15-pQE30 system. To further compare Z-TNFα and NGR-TNFα, we attempted to express NGR-TNFα using the same system. Surprisingly, native NGR-TNFα was expressed at a low (~ 0.2 mg/L) level in E. coli M15 containing the pQE30 plasmid. However, a single nucleotide mutation of C to G, resulting in a substitution of leucine (L) with valine (V) at the start of TNFα, increased the expression of NGR-TNFα by ~ 100 times through improving transcription. In addition, the amino acid substitution showed a little impact on the receptor binding, in vitro cytotoxicity, and in vivo antitumor effect of NGR-TNFα. As fusing NGR to the N-terminus of TNFα with a valine substitution did not reduce the protein yield, the TNFα gene with a C > G mutation might be used to prepare novel tumor-homing TNFα when the native TNFα-based variant is expressed at an extremely low level in E. coli. Notably, in addition to the mutated valine, the impact of N-terminal additional amino acids provided by pQE30 vector on the function of TNFα variant must be carefully evaluated. KEY POINTS • A single nucleotide mutation increased the expression of NGR-TNFα by two orders. • Nucleotide mutation-induced amino acid substitution did not reduce NGR-TNFα activity.Since the discovery of human leukocyte antigens (HLAs), the function of major histocompatibility complex (MHC) gene families in a wide range of diseases have been the subject of research for decades. In particular, the associations of autoimmune disorders to allelic variants and candidate genes encoding the MHC are well documented. However, despite decades of research, the knowledge of MHC associations with human disease susceptibility have been predominantly studied in European origin, with limited understanding in different populations and ethnic groups. This is particularly evident in countries and ethnic populations of the Arabian Peninsula. Human MHC haplotypes, and its association with diseases, of the variable ethnic groups of this region are poorly studied. This review compiled published manuscripts that have reported a list of autoimmune diseases (insulin-dependent diabetes mellitus, systemic lupus erythematosus, myasthenia gravis, rheumatoid arthritis, psoriasis vulgaris, and multiple sclerosis) associated with MHC class I and class II in the populations of the Arabian Peninsula, specifically Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, the United Arab Emirates, and Yemen. Data available was compared with other three ethnic groups, namely Caucasians, Asians, and Africans. The limited data available in the public domain on the association between MHC gene and autoimmune diseases highlight the challenges in the Middle Eastern region.Lead (Pb) is a highly toxic metal for humans, animals and plants even at low concentrations in the soil. The ingestion of chocolate produced from contaminated beans can contribute to consumer exposure to Pb. While, Mn is an element essential for plants and participates as enzymatic cofactors in several metabolic pathways. The objective of this study was to evaluate the influence of Mn on mitigation of Pb toxicity in seedling of the cacao clonal CCN 51 genotype grown in soils with different doses of Pb, Mn and Mn+Pb, through physiological, biochemical, molecular and nutritional responses. It was found that the seedling of the cacao clonal CCN 51 genotype grown in soils with high Pb, Mn and Mn+Pb contents accumulated these heavy metals in the roots and leaves. Mn doses reduced the Pb uptake by root system and prevented that the Pb accumulated at toxic levels in the roots and leaves of the plants. High doses of Pb applied in soil were highly toxic to the plants, leading, in some cases, them to death. However, no51 genotype grown in contaminated soils.
Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. TGFβ1 has been the mostly accepted factor to fuel normal fibroblasts transformation into CAFs. Ca
/calmodulin-dependent protein kinase II (CaMKII) is thought to play an important role in fibroblasts activation induced by TGFβ1. The aim of this study is to investigate the potential role of CaMKII in TGFβ1-induced fibroblasts activation and CAF-like differentiation. Cross talk between CaMKII-dependent fibroblasts and colon cancer in colon cancer progression also was addressed RESULTS Immunostaining demonstrated that in colon cancer stroma, CaMKII overexpressed in stromal CAFs. In vitro, TGFβ1 increased CAF markers expression in human colon fibroblasts CCD-18Co, but not in CaMKII depletion fibroblasts. CaMKII knockdown by CaMKII shRNA significantly inhibited TGFβ1-induced fibroblasts activation and CAF-like differentiation. https://www.selleckchem.com/products/smoothened-agonist-sag-hcl.html Smad3, AKT, and MAPK were targeted in TGFβ1-CaMKII-mediated pathway. Human colon cancer cell line HCT-116 activated fibroblasts directly, whereas CaMKII depletion dragged CCD-18Co fibroblasts undergoing CAF-associated trans-differentiation. Furthermore, increased proliferation, migration, and invasion of colon cancer cells were stimulated when co-cultured with normal fibroblasts, but not with CaMKII depletion fibroblasts.

These findings provide evidence that CaMKII is a critical mediator in TGFβ1-induced fibroblasts activation and is involved in the cross talk with colon cancer cells. CaMKII is a potentially effective target for future treatment of colon cancer.
These findings provide evidence that CaMKII is a critical mediator in TGFβ1-induced fibroblasts activation and is involved in the cross talk with colon cancer cells. CaMKII is a potentially effective target for future treatment of colon cancer.

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Many autoimmune diseases can affect the central nervous system, and their varying clinical presentations often confound a straightforward diagnosis. In this report, we describe a unique presentation of CLIPPERS syndrome. To our knowledge, this is the first case to demonstrate significant supratentorial involvement with symmetric and non-confluent lesions in the medial orbitofrontal cortex; additionally, this is the second case to describe an association between diagnoses of hypothyroidism and CLIPPERS.Retinopathy of prematurity is defined as retinal abnormalities that occur during development as a consequence of disturbed oxygen conditions and nutrient supply after preterm birth. Both neuronal maturation and retinal vascularization are impaired, leading to the compensatory but uncontrolled retinal neovessel growth. Current therapeutic interventions target the hypoxia-induced neovessels but negatively impact retinal neurons and normal vessels. Emerging evidence suggests that metabolic disturbance is a significant and underexplored risk factor in the disease pathogenesis. Hyperglycemia and dyslipidemia correlate with the retinal neurovascular dysfunction in infants born prematurely. Nutritional and hormonal supplementation relieve metabolic stress and improve retinal maturation. Here we focus on the mechanisms through which metabolism is involved in preterm-birth-related retinal disorder from clinical and experimental investigations. We will review and discuss potential therapeutic targets through the restoration of metabolic responses to prevent disease development and progression.Accurate prediction models have become the first goal for aiding pandemic-related decisions. Modeling and predicting the number of new active cases and deaths are important steps for anticipating and controlling COVID-19 outbreaks. The aim of this research was to develop an accurate prediction system for the COVID-19 pandemic that can predict the numbers of active cases and deaths in the Gulf countries of Saudi Arabia, Oman, the United Arab Emirates (UAE), Kuwait, Bahrain, and Qatar. The novelty of the proposed approach is that it uses an advanced prediction model-the bidirectional long short-term memory (Bi-LSTM) network deep learning model. The datasets were collected from an available repository containing updated registered cases of COVID-19 and showing the global numbers of active COVID-19 cases and deaths. Statistical analyses (e.g., mean square error, root mean square error, mean absolute error, and Spearman's correlation coefficient) were employed to evaluate the results of the adopted Bi-LSTM model. The Bi-LSTM results based on the correlation metric gave predicted confirmed COVID-19 cases of 99.67%, 99.34%, 99.94%, 99.64%, 98.95%, and 99.91% for Saudi Arabia, Oman, the UAE, Kuwait, Bahrain, and Qatar, respectively, while testing the Bi-LSTM model for predicting COVID-19 mortality gave accuracies of 99.87%, 97.09%, 99.53%, 98.71%, 95.62%, and 99%, respectively. The Bi-LSTM model showed significant results using the correlation metric. Overall, the Bi-LSTM model demonstrated significant success in predicting COVID-19. The Bi-LSTM-based deep learning network achieves optimal prediction results and is effective and robust for predicting the numbers of active cases and deaths from COVID-19 in the studied Gulf countries.Depression is one of the most common mental disorders in the world that negatively affects the daily functioning of patients. Numerous studies are currently being conducted to examine the antidepressant potential of innovative synthetic compounds and herbal substances. Yacon, Smallantchus sonchifolius, belongs to plants with numerous health-beneficial properties. Yacon-based products are regarded as a functional food. In our study, we attempted to check whether administration of Yacon tuber extract would have an antidepressant effect in the forced swim test (FST) in mice and whether its intake could influence the activity of conventional antidepressant drugs with different mechanisms of action, i.e., imipramine hydrochloride, fluoxetine hydrochloride, and reboxetine mesylate. The spontaneous locomotor activity of the tested mice was also investigated to eliminate any false-positive results. We demonstrated that an intragastric administration of the Yacon tuber extract at a dose of 100 mg/kg induced the antidepressant-like behavior in the FST in mice and that a combined administration of the sub-effective doses of the Yacon extract (50 mg/kg) with imipramine hydrochloride (7.5 mg/kg), fluoxetine hydrochloride (20 mg/kg), or reboxetine mesylate (5 mg/kg) significantly reduced the immobility time of animals in this behavioral test. The obtained results were not affected by the increased locomotor activity of the tested subjects. In conclusion, our findings suggest that Yacon tuber extract is promising as an alternative mood-improving product since it possesses an antidepressant potential and it can acts synergistically with conventional antidepressant drugs.The appearance of cervical adenopathies can occur in many pathologies in a non-specific manner; Erdheim-Chester disease (ECD) is characterized by xanthogranulomatous and xanthomatous infiltration of different tissues with numerous foamy histiocytes. Bone lesions are frequent and radiological features are pathognomonic for diagnosis, but lymph node involvement is exceptional and is not a form of presentation reported in the literature. https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html Recurrent BRAFV600E mutation and others have been discovered in recent years. Since then, several treatments targeting the BRAF and MEK pathways have been developed with high success rates; even so, interferon-α continues to be one of the most widely used treatments. The best imaging test for the study and monitoring of the disease is PET-CT. The prognosis of ECD is relatively poor, with a survival of 43% of patients after 32 months follow-up. Higher survival rates have been reported in patients treated with interferon. The authors present an exceptional case of ECD with cervical adenopathies as a debut, highlighting the need for the knowledge of the disease for differential diagnosis, early treatment, and the importance of communication between the clinician and the pathologist. The main features of the disease and a brief discussion of current diagnosis and treatment are reviewed.The discovery of new drugs is required in the time of global aging and increasing populations. Traditional drug development strategies are expensive, time-consuming, and have high risks. Thus, drug repurposing, which treats new/other diseases using existing drugs, has become a very admired tactic. It can also be referred to as the re-investigation of the existing drugs that failed to indicate the usefulness for the new diseases. Previously published literature used maximum flow approaches to identify new drug targets for drug-resistant infectious diseases but not for drug repurposing. Therefore, we are proposing a maximum flow-based protein-protein interactions (PPIs) network analysis approach to identify new drug targets (proteins) from the targets of the FDA (Food and Drug Administration) drugs and their associated drugs for chronic diseases (such as breast cancer, inflammatory bowel disease (IBD), and chronic obstructive pulmonary disease (COPD)) treatment. Experimental results showed that we have successfully turned the drug repurposing into a maximum flow problem. link2 Our top candidates of drug repurposing, Guanidine, Dasatinib, and Phenethyl Isothiocyanate for breast cancer, IBD, and COPD were experimentally validated by other independent research as the potential candidate drugs for these diseases, respectively. This shows the usefulness of the proposed maximum flow approach for drug repurposing.Argan oil is rich in long-chain unsaturated fatty acids (FA), mostly oleic and linoleic, and natural antioxidants. This study addresses the production of low-calorie structured lipids by acidolysis reaction, in a solvent-free system, between caprylic (C80; system I) or capric (C100; system II) acids and argan oil, used as triacylglycerol (TAG) source. Three commercial immobilized lipases were tested Novozym® 435, Lipozyme® TL IM, and Lipozyme® RM IM. Higher incorporation degree (ID) was achieved when C100 was used as acyl donor, for all the lipases tested. link3 Lipozyme® RM IM yielded the highest ID for both systems (28.9 ± 0.05 mol.% C100, and 11.4 ± 2.2 mol.% C80), being the only catalyst able to incorporate C80 under the reaction conditions for biocatalyst screening (molar ratio 21 FA/TAG and 55 °C). The optimal conditions for Lipozyme® RM IM in system II were found by response surface methodology (66 °C; molar ratio FA/TAG of 41), enabling to reach an ID of 40.9 mol.% of C100. Operational stability of Lipozyme® RM IM in system II was also evaluated under optimal conditions, after eight consecutive 24 h-batches, with biocatalyst rehydration between cycles. The biocatalyst presented a half-life time of 103 h.Background Advances in management have improved mortality of individuals with chronic respiratory failure (CRF), leading to an increase in need for long-term oxygen therapy and/or ventilatory support. These individuals require frequent visits and monitoring of their physiological parameters as well as of the functioning of their devices, such as ventilators or oxygen concentrators. Telemedicine is a clinical application of Information Communication Technology connecting patients to specialised care consultants. This narrative review aims to explore the current available telemonitoring options for individuals with CRF and reported or potential results. Methods The research focused on EMBASE, CINALH, PubMed, and Scopus databases. Papers published between 2003 and 2021 in English were considered. Results Different sensors, transmission devices and systems, and interventions are used with promising but not conclusive clinical results. However, legal problems are still unsolved, and economic advantages for health care systems, although potentially high, are still under debate. Conclusions Telemonitoring systems for individuals with CRF are increasingly used; with promising results still to be clarified, legal, economical and organisational issues must be defined.To understand the biological effects of radiation, it is important to determine how ionizing radiation deposits energy in micrometric targets. The energy deposited in a target located in an irradiated tissue is a function of several factors such as the radiation type and the irradiated volume size. We simulated the energy deposited by energetic ions in spherical targets of 1, 2, 4, and 8 µm radii encompassed in irradiated parallelepiped volumes of various sizes using the stochastic radiation track structure code Relativistic Ion Tracks (RITRACKS). Because cells are usually part of a tissue when they are irradiated, electrons originating from radiation tracks in neighboring volumes also contribute to energy deposition in the target. To account for this contribution, we used periodic boundary conditions in the simulations. We found that the single-ion spectra of energy deposition in targets comprises two components the direct ion hits to the targets, which is identical in all irradiation conditions, and the contribution of hits from electrons from neighboring volumes, which depends on the irradiated volume.

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24; 95% CI 1.004-1.53). In a chart review sample of 200 patients, less than half (n = 85) had a documented reason for not receiving CCRT. Among these, 29% declined treatment, and 71% did not receive CCRT due to "not being a candidate" for reasons related to frailty or lung nodules being too far apart for radiation therapy.

CCRT rates among VHA patients with unresectable, stage III NSCLC slightly increased from 2013 to 2017; however in 2017, only half were receiving CCRT. Older patients and those with multiple comorbidities were less likely to receive CCRT and even when controlling for these factors, non-white patients were less likely to receive CCRT.
CCRT rates among VHA patients with unresectable, stage III NSCLC slightly increased from 2013 to 2017; however in 2017, only half were receiving CCRT. Older patients and those with multiple comorbidities were less likely to receive CCRT and even when controlling for these factors, non-white patients were less likely to receive CCRT.
Being able to use COVID-19 RT-PCR Ct values as simple clinicalmarkers of disease outcome or prognosis would allow for the easy and proactive identification and triaging of high-risk cases. This study's objective was thus to explore whether a correlation exists between COVID-19 viral loads, as indicated by RT-PCR Ct values, and disease severity, as indicated by respiratory indices.

A multi-centre cross-sectional retrospective study was conducted, using data obtained from Bahrain's National COVID-19 Task force's centralised database. The study period ranged from May 2, 2020 to July 31, 2020. A multivariable logistic regression was used to assess for a correlation using data from a total of 1057 admitted COVID-19 cases. The covariates adjusted for included sex, age, presentation, and comorbidities. In our cohort, Ct value showed no statistical significance for an association with requirement for oxygenation on admission (Odds ratio 1.046; 95%CI 0.999 to 1.096, p = 0.054).

Viral load, as indicated by Ct values, did not seem to be associated with requirement for oxygenation on admission in our cohort. We postulate however that time since onset of symptom may have acted as an unaccounted-for confounder.As such,RT-PCR Ct values may not be a useful prognostic clinicaltool in isolation.
Viral load, as indicated by Ct values, did not seem to be associated with requirement for oxygenation on admission in our cohort. We postulate however that time since onset of symptom may have acted as an unaccounted-for confounder. As such, RT-PCR Ct values may not be a useful prognostic clinical tool in isolation.
Older patients with multiple morbidities are a particularly vulnerable population that is likely to face complex medical decisions at some time in their lives. A patient-centered medical care fosters the inclusion of the patients' perspectives, priorities, and complaints into clinical decision making.

This article presents a short and non-normative assessment tool to capture the priorities and problems of older patients. The so-called LAVA ("Life and Vitality Assessment") tool was developed for practical use in seniors in the general population and for residents in nursing homes in order to gain more knowledge about the patients themselves as well as to facilitate access to the patients. The LAVA tool conceptualizes well-being from the perspectives of older individuals themselves rather than from the perspectives of outside individuals.

The LAVA tool is graphically presented and the assessment is explained in detail. Exemplarily, the outcomes of the assessments with the LAVA of three multimorbid older patients are presented and discussed. In each case, the assessment pointed out resources as well as at least one problem area, rated as very important by the patients themselves.

The LAVA tool is a short, non-normative, and useful approach that encapsulates the perspectives of well-being of multimorbid patients and gives insights into their resources and problem areas.
The LAVA tool is a short, non-normative, and useful approach that encapsulates the perspectives of well-being of multimorbid patients and gives insights into their resources and problem areas.
The prognosis of lung cancer with synchronous brain metastasis (LCBM) is very poor, and patients often die within a short time. https://www.selleckchem.com/products/disodium-r-2-hydroxyglutarate.html However, little is known about the early mortality and related factors in patients with LCBM.

Patients diagnosed with LCBM between 2010 and 2016 were enrolled from the Surveillance, Epidemiology, and End Result (SEER) database. Univariate and multivariate logistic regression analysis were used to identify significant independent prognostic factors, which were used to construct nomograms of overall and cancer-specific early death. Then, the prediction ability of the model was verified by receiver operating characteristic (ROC) curve. At last, the clinical application value of the model was tested through decision curve analysis (DCA).

A total of 29,902 patients with LCBM were enrolled in this study. Among them, 13,275 (44.4%) patients had early death, and 11,425 (38.2%) cases died of lung cancer. The significant independent risk factors for overall and cancer-specific early deato predict early death in lung cancer patients with synchronous brain metastases. Nomograms may help oncologists develop better treatment strategies, such as clinical trials and hospice care.
Circulating tumour cell (CTC) and CTC-white blood cell (CTC-WBC) clusters are related to the prognosis of tumour patients. However, the relationship between CTC-WBC clusters and prognosis in renal cell carcinoma (RCC) patients is not clear. We evaluated the prognostic value of CTC-WBC clusters using metastasis-free survival (MFS) and overall survival (OS) in patients with RCC.

The baseline, survival, and CTC data of patients with RCC were statistically analysed by R.

The Cox risk proportional regression model suggests that the total CTCs, pathology type, and CTC-WBC clusters can be used as prognostic indicators for the MFS of RCC patients. Total CTCs and solid tumour diameter can be used as prognostic indicators for the OS of RCC patients. Using Kaplan-Meier survival analysis, we found that patients with total CTCs, pathology, and CTC-WBC clusters greater than the cut-off value had a worse MFS, and patients with total CTCs greater than the cut-off value had a worse OS.

The analysis of the clinical sample data in patients with RCC shows that CTC-WBC clusters play an important role in monitoring the prognosis of RCC.

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In conclusion, this study shows that Eurasian griffon vultures in north-eastern Spain are carriers of widespread AMR zoonotic Salmonella and Campylobacter. More comprehensive analyses are still needed to understand the potential risk of spill-over from those wild birds to humans.The comprehensive consideration of climate warming and by-product management in the iron and steel industry, has a significant impact on the realization of environmental protection and green production. Blast furnace slag (BFS) and steel slag (SS), collectively called iron and steel slags, are the main by-products of steelmaking. The economical and efficient use of iron and steel slags to reduce greenhouse gas (GHG) emissions is an urgent problem to be solved. This paper reviewed the carbonization and waste heat recovery of iron and steel slags, and the utilization of iron and steel slags as soil amendments, discussed their application status and limitations in GHG reduction. Iron and steel slags are rich in CaO, which can be used as CO2 adsorbents to achieve a maximum concentration of 0.4-0.5 kg CO2/kg SS. Blast furnace molten slag contains a considerable amount of waste heat, and thermal methods can recover more than 60 % of the heat energy. Chemical methods can use waste heat in the reaction to generate gas fuel, and iron in slags can be used as a catalytic component to promote chemical reaction. Waste heat recovery saves fuel and reduces the CO2 emissions caused by combustion. When iron and steel slags are used as soil amendments, the iron oxides, alkaline substances, and SiO2 in iron and steel slags can affect the emission of CH4, N2O, and CO2 from soil, microorganisms, and crops, and achieve a maximum reduction of more than 60 % of the overall GHG of paddy fields. Finally, This paper provided valuable suggestions for future GHG reduction studies of iron and steel slags in energy, industry, and agriculture.In contrast to research on heat waves, there are no studies in recent years that analyze the temporal evolution of threshold temperatures (Tthreshold) for extremely cold days (ECD). It is unknown whether threshold temperatures have increased more quickly than the minimum daily temperature (Tmin) in recent years. The objective of this study was to analyze the temporal evolution of the minimum daily temperature (Tmin) in a group of Spanish provinces and compare it with the evolution of threshold temperatures. An ecological, retrospective time series study was carried out using daily observations between January 1, 1983 and December 31, 2018 (36 years) in 10 provinces that are representative of the different climate territories in Spain. For each representative observatory in each province, the values of Tmin were obtained for the winter months (November-March). The value of Tthreshold was determined for each province and each year, using dispersion diagrams for the pre-whitened series, with daily mortality due to natural causes displayed on the Y axis (CIEX A00-R99) and Tmin grouped by 10 degree intervals on the X axis. To determine the temporal evolution of Tmin and Tthreshold for each province, linear models were fitted, with time as the independent variable. During the winter months, Tmin increased at an average rate of 0.2 °C/decade (IC95 0.1-0.3), while Tthreshold remained practically constant during the period, at 0.1 °C/decade (IC95% -0.1 0.3). These values are much lower than those obtained in the case of heat, both in terms of the evolution of maximum daily temperature and that of Tthreshold. In conclusion, the fact that this trend has been maintained across time in a scenario of climate change, with a slow increase in minimum daily temperatures and constant values of Threshold, suggests a decrease in the number of ECD.Accurately investigating long-term information about open-surface water bodies can contribute to water resource protection and management. However, due to the limits of big-data calculations for remote sensing, there has been no specific study on the long-term changes in the water bodies in the Yellow River Basin. Thus, in this study, we developed a new combined extraction rule to build an entire annual-scale open-surface water body dataset for 1986-2020 with excellent effectiveness in eliminating the interference of shadows in the Yellow River Basin using all of the available Landsat images. For the first time, the spatial distribution, change trends, conversion processes, and the heterogeneity of the surface water bodies in the Yellow River Basin were analyzed comprehensively to the best of our knowledge. The extraction results had an overall accuracy of 99.70 % and a kappa coefficient of 0.90, which were validated using 34,073 verification points selected on high-resolution Google Earth images and random Landsat images. The total area of water bodies initially decreased (1986-2000) and then increased (2001-2020); however, only the size of the permanent water bodies increased in most areas, while the size of most of the seasonal water bodies decreased. In regions with human-made water bodies, the non-water areas were substantially converted to seasonal and permanent water bodies; however, in areas with natural water bodies, many permanent and seasonal water bodies were gradually converted to non-water areas. Thus, most of the increases in the water bodies occurred in the form of artificial lakes and reservoirs, while most of the decreases in the water body area occurred in natural wetlands and lakes. The areas of both the permanent and seasonal water bodies were positively correlated with precipitation, but only the area of the seasonal water bodies was negatively correlated with temperature.Nonylphenol (NP) is one of the most toxic and ubiquitously present endocrine disrupting compounds. Numerous studies have shown that NP exposure induces liver injury, but the interactions between epigenetic factors and necroptosis in this context have not been examined. In this study, rats received daily NP administration (15, 45, and 135 mg/kg/day) via oral gavage over a 28-day period. The upregulation of lncRNA PVT1 was associated with the elevated expression of necroptosis-related proteins (ZBP1, RIPK3, MLKL, and p-MLKL). Moreover, similar effects were also observed after NP exposure in BRL-3A cells. LncRNA PVT1 was predominantly expressed in the nucleus, and ASO was chosen to knock down lncRNA PVT1 in BRL-3A cells. Experimental techniques such as RNA immunoprecipitation, chromatin immunoprecipitation, and co-immunoprecipitation were used to verify direct binding interactions among lncRNA PVT1, EZH2, DNMT1, and ZBP1. The evidence obtained indicated that lncRNA PVT1 could bind to DNMT1 via EZH2 and increase methylation at the ZBP1 promoter, thereby promoting necroptosis. Meanwhile, the demethylation of the highly expressed gene TET1 also promoted ZBP1 upregulation, inducing necroptosis. Taken together, these findings provide valuable insights into the potential molecular mechanisms underlying liver injury in response to NP exposure. Hence, they lay a mechanistic foundation for the evaluation of NP biosafety.Despite their acute climatic susceptibility, the hot, arid Middle Eastern countries are among the world's largest energy consumers and emitters of greenhouse gases, particularly carbon dioxide (CO2). Nonetheless, no study has been conducted to decompose regionally the influential primary factors of the Middle East's carbon emissions. This study utilized the logarithmic mean Divisia index (LMDI) method to fill this knowledge gap and investigate the driving forces of CO2 emissions in 12 Middle Eastern countries, namely, Bahrain, Iran, Iraq, Jordan, Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, Syria, the United Arab Emirates, and Yemen (1990-2020). https://www.selleckchem.com/products/dasa-58.html The research confirmed that, with a contribution rate of 53.89 %, population growth is the primary driver of CO2 emissions in the Middle East, followed by energy intensity (31.97 %) and economic growth (18.42 %); and the most straightforward approach to reduce emissions, are boosting energy efficiency and reforming energy subsidies. It also concluded that the West Asian economy is gradually decoupling from CO2 due to the effective decarbonization of countries, such as Saudi Arabia and Kuwait, based on the Tapio decoupling model results. Furthermore, each country's future emissions (2020-2026) were projected using a novel group method of data handling (GMDH) approach based on the main identified factors. The countries' decoupling status confirms the accuracy of the projected data on CO2 emissions growth. The region's CO2 emissions are expected to rise 13.28 % by 2026, with Syria and Yemen experiencing the most significant increases (129.45 % and 112.14 %, respectively) due to post-civil war economic growth. Other aspects of regional conflicts and migration impacts on the CO2 emission influencing factors were also explored. Indeed, besides providing a comprehensive analysis of the current and future status of CO2 emissions in the Middle East, the effects of military conflicts on CO2 emissions have been investigated using this regional case study for global application.To recycle fertilizing contents in wastewater activated sludge (WAS) is attracting increasing interest. Dissolved organic matters (DOMs) in WAS with high content are biologically active. In this work, the molecular composition of DOMs derived from two typical bio-stabilized WAS (DOMBWS), aerobic composting (DOMACS) and anaerobic digestion (DOMADS), were analyzed. The mitigative effect and molecular mechanisms of DOMBWS on rice seedlings (Oryza sativa L.) under Cd-stress were investigated. Our study indicated that DOMBWS significantly alleviated Cd-stress and facilitated growth recovery of rice seedlings with distinct absorption mechanisms. DOMACS, primarily composed of CHO class with low molecular weight rich in carboxyl groups, forming labile Cd-DOM complexes, which promoted Cd-absorption of rice seedlings. While DOMADS comprised large molecular weight of CHON class interacted with Cd to produce stable macromolecular complexes in the form of microaggregates, consequently reducing Cd-absorption. At transcriptional level, DOMBWS restored auxin signal transduction and phenylpropanoid biosynthesis pathways in root cells, and got the expression of glutathione S-transferase well. Besides, DOMACS significantly promoted the metabolism of amino acids to alleviate phytotoxicity, while DOMADS improved the DNA repair function of rice seedlings. These findings provided novel insights into land-use of bio-stabilized WAS for remediation of heavy metals contaminated soils and food security.Rangeland ecosystems are changing worldwide with the abandonment of extensive pastoralism practices and greater interest for species coexistence. However, the lack of compiled data on current changes in the abundance and distribution of herbivores challenges rangeland management decisions. Here we gathered and made available for the first time the most extensive set of occurrence data for rangeland herbivores in Iceland in an Open Access framework for transparent and repeatable science-based decisions. We mapped fine scale species distribution overlap to identify areas at risk for wildlife-livestock conflict and overgrazing. Nationwide and long term (1861-2021) occurrence data from 8 independent datasets were used alongside 11 predictor raster layers ("Big Data") to data mine and map the distribution of the domestic sheep (Ovis aries), feral reindeer (Rangifer tarandus tarandus), pink-footed geese (Anser brachyrhynchus), and rock ptarmigan (Lagopus muta islandorum) over the country during the summer. Using algorithms of Maxent in R, RandomForest, TreeNet (stochastic gradient boosting) and MARS (Splines) in Minitab-SPM 8.