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02/09/2025


5 vs. 42.3%; p = 0.028). The 5-year OS was lower among patients with a lower lymphocyte value (≤1.82 × 103) (29.0 vs. 75.6%; p = 0.010). There was a tendency towards worse OS among patients with a higher platelet count (>281 × 103) (4.5-year OS 16.7 vs. 65.8%; p = 0.056). The 5-year OS was insignificantly lower in the group with NLRs >2.74 than in the group with NLRs ≤2.74 (37.5 vs. 62.8%; p = 0.078). A worse OS rate was associated with an elevated PLR (>169.1) (22.2 vs. 70.1%; p = 0.008). https://www.selleckchem.com/products/xl177a.html Similarly, there was worse OS in the group with higher MLR (>0.30) (41.8 vs. 78.3%; p = 0.025). CONCLUSIONS The present results reveal that elevated MLRs (>0.30) and PLRs (>169.1) are associated with poor OS among male BC patients. Similarly, but insignificantly, an elevated NLR (>2.74) affected OS. © 2020 S. Karger AG, Basel.BACKGROUND Sporadic Creutzfeldt-Jakob disease (sCJD) is an extremely rare fatal and infectious neurodegenerative brain disorder characterized by rapidly progressive dementia, cerebellar ataxia, and visual disturbances. This article summarizes the retrospective analysis of 104 sCJD patients in the First Medical Center of Chinese PLA General Hospital from 2003 to 2019. METHODS A retrospective analysis of the medical records of the 104 patients diagnosed with sCJD was performed from the aspects of demographic data, clinical manifestations, laboratory examinations, cerebrospinal fluid analysis, electroencephalograms (EEGs), diffusion-weighted imaging (DWI) scans, positron emission tomography (PET) scans, and prion protein gene mutations. RESULTS In the 104 sCJD patients, pathological evidence of a spongiform change was found in 11 patients, while the remaining 93 patients were probable sCJD. The 104 patients included 57 males and 47 females, with the age of onset ranging from 29 to 82 (mean 58, median 60) years. The time from disease onset to death ranged from 1 to 36 months. Most of the patients died 7-12 months after the onset of sCJD. In most patients, rapidly progressive dementia appeared as the initial symptom, followed by cerebellar ataxia, visual disturbances, and neurobehavioral disorders. Most patients' DWI images showed symmetric or asymmetric hyperintensity in the cortex. In terms of EEGs, 38.2% of the patients had periodic sharp wave complexes. The sensitivity of 14-3-3 protein detection was 34.1%. The brain PET scans of 50 patients with sCJD presented 96% sensitivity for the diagnosis of sCJD. CONCLUSIONS This study indicated that sCJD occurred at an early age in patients in China. The sensitivity of 14-3-3 protein detection was significantly low, but brain PET was highly sensitive in the diagnosis of sCJD. © 2020 S. Karger AG, Basel.Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3, was originally described in members of the families of Machado, Thomas, and Joseph from São Miguel Island, Azores, Portugal, in 1972. The purpose of this article is to present previous descriptions of hereditary ataxia resembling the heterogeneous phenotypic intra-familiar presentation of MJD. We suggest that the condition would best be called dominant spino-pontine atrophy. © 2020 S. Karger AG, Basel.INTRODUCTION Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a rare cause of adrenal insufficiency and T-box pituitary restricted transcription factor (TBX19) mutations are responsible for two-thirds of the neonatal onset form of the disease. IAD presents with hypoglycemia and prolonged jaundice in the neonatal period. TBX19 is important for both pro-opiomelanocortin (POMC) gene transcription and differentiation of POMC-expressing cells. We describe 2 patients, 1 with a reported and 1 with a novel TBX19 mutation, and present information about the long-term follow-up of these patients. CASE PRESENTATION Both patients had critical illnesses, recurrent hypoglycemia, convulsions, and neonatal hyperbilirubinemia. They also had low cortisol and ACTH levels, while other pituitary hormones were within the normal range. Pituitary imaging was normal. After hydrocortisone treatment, there was resolution of the hypoglycemia and the convulsions were controlled. Genetic studies of the patients revealed both had inherited a homozygous mutation of the TBX19 gene. The first patient had an alteration of NM_005149.3c.856C>T (p.R286*) and the second patient had a novel NM_005149.3c.584C>T (p.T195I) mutation, analyzed by next-generation sequencing. The noteworthy findings of the patients at follow-up were short stature, microcephaly, and decreased pubic hair in the first, and dysmorphic features, Chiari type 1 malformation, tall stature, and low bone mineral density (BMD) in the second. CONCLUSION Congenital IAD can be life-threatening if it is not recognized and treated early. TBX19 mutations should be considered in the differential diagnosis of IAD. Further cases or functional analyses are needed for genotype-phenotype correlations. Low BMD, dysmorphic features, Chiari type 1 malformation, and sparse pubic hair are some of the important features in these patients. © 2020 S. Karger AG, Basel.INTRODUCTION Short stature homeobox-containing gene (SHOX) haploinsufficiency is associated with short stature, Madelung deformity and mesomelia. Current clinical screening tools are based on patients with intragenic variants or deletions. However, recent discoveries showed that deletions of the enhancer elements are quite common. The majority of these patients show less body disproportion and respond better to recombinant human growth hormone treatment. We redefined clinical criteria for genetic analysis to facilitate detection of the full spectrum of SHOX haploinsufficiency. METHODS We analyzed 51 children with SHOX variants or deletions and 25 children with a deletion in its enhancer region. Data were compared to 277 children referred for suspicion of growth failure without endocrine or genetic pathology. RESULTS Only half of the patients with an enhancer region deletion fulfilled any of the current screening criteria. We propose new clinical criteria based on sitting height to height ratio >1 SDS or arm span ≥3 cm below height, with a sensitivity of 99%. When these criteria are combined with obligatory short stature, the sensitivity to detect SHOX haploinsufficiency is 68.1%, the specificity 80.6%, and the number needed to screen 21 patients. CONCLUSION Novel clinical criteria for screening for SHOX haploinsufficiency allow the detection of patients within the full genetic spectrum, that is, intragenic variants and enhancer region deletions. © 2020 The Author(s) Published by S. Karger AG, Basel.

02/07/2025


Using normalization of CD4 counts as the main evaluation parameter of complete immune restoration for HIV-1 patients under antiretroviral therapy (ART) might be not enough. A comprehensive evaluation system more accurately reflecting immune restoration are urgently needed. Totally, 91,805 HIV-1 patients from 17 tertiary hospitals in China during 2005-2018 were included in this study. Immune restoration and mortality were assessed. Patients initiated ART with baseline CD4 counts less then 50, 50-199, 200-349, 350-499, and ≥500 cells/μL, and results showed an increase in the median CD4 counts to 445 (12-year), 467 (12-year), 581 (11-year), 644 (7-year), and 768 cells/µL (5-year), as well as the CD4/CD8 ratio to 0.59 (12-year), 0.65 (12-year), 0.79 (11-year), 0.82 (7-year), 0.9 (5-year), respectively. The median CD8 count was relatively high (median range 732-845 cells/μL), regardless of the baseline CD4 counts. Furthermore, the probabilities of death in patients achieving CD4 counts ≥500 cells/μL and CD4/CD8 ratio ≥0.8 simultaneously were significantly lower than those in patients achieving either CD4 counts ≥500 cells/μL (2.77% vs 3.50%, p=0.02) or CD4/CD8 ≥ 0.8 (2.77% vs 4.28%, p less then 0.001) after 12-year of ART. In this study, a new binary-indicator would accurately assess immune restoration in the era of "treat all."Introduction Ankle injuries are common in daily orthopaedic trauma practice, with a high incidence of lateral ligament complex (lat-lig-com) injuries of the ankle joint (AJ). Primarily, these lat-lig-com injuries heal sufficiently, although there is a risk of developing chronic ankle instability. https://www.selleckchem.com/products/scutellarin.html However, there is a lack of knowledge about the clinical application and routine for rehabilitation strategies so as to prevent chronic instability. This study investigates the current rehabilitation concepts in clinical routine after ligament injuries of the AJ. Methods Rehabilitation protocols, provided by orthopaedic and trauma surgery institutions in German speaking countries, were analysed in terms of weight-bearing, range of motion (ROM), physiotherapy and choice of orthosis. All protocols for operatively and non-operatively (nop) treated ligament ruptures of the AJ were included. Results 120 of 213 institutions provided protocols of lat-lig-com injuries of the AJ. Regarding the orthosis, the nop-treatment group mainly used ankle braces; in contrast, the operative group preferred the use of an ankle boot. The operative group recommends 6-12 weeks for duration of orthosis in contrast to only 6 weeks in the nop group. Significant differences prevail in ROM, with free ROM in non-operative treatment from the first day after trauma (p less then 0.001) in contrast to a careful increase in ROM in the first 6 weeks post-operatively. Conclusion Early functional treatment is clinical standard in rehabilitation after lat-lig-com injuries of the ankle. Regarding current literature the differences of restrictions in ROM and orthosis treatment after lat-lig-com injuries suggest a trivialization of conservative treatment in the first period after trauma compared to post-operative aftercare.Genomic surveillance of SARS-CoV-2 was rapidly implemented in Portugal by the National Institute of Health in collaboration with a nationwide consortium of >50 hospitals/laboratories. Here, we track the geotemporal spread of a SARS-CoV-2 variant with a mutation (D839Y) in a potential host-interacting region involving the Spike fusion peptide, which is a target motif of anti-viral drugs that plays a key role in SARS-CoV-2 infectivity. The Spike Y839 variant was most likely imported from Italy in mid-late February and massively disseminated in Portugal during the early epidemic, becoming prevalent in the Northern and Central regions of Portugal where it represented 22% and 59% of the sampled genomes, respectively, by 30 April. Based on our high sequencing sampling during the early epidemics [15.5% (1275/8251) and 6.0% (1500/24987) of all confirmed cases until the end of March and April, respectively], we estimate that, between 14 March and 9 April (covering the epidemic exponential phase) the relative frequency of the Spike Y839 variant increased at a rate of 12.1% (6.1%-18.2%, CI 95%) every three days, being potentially associated with 24.8% (20.8-29.7%, CI 95%; 3177-4542 cases, CI 95%) of all COVID-19 cases in Portugal during this period. Our data supports population/epidemiological (founder) effects contributing to the Y839 variant superspread. The potential existence of selective advantage is also discussed, although experimental validation is required. Despite huge differences in genome sampling worldwide, SARS-CoV-2 Spike D839Y has been detected in 13 countries in four continents, supporting the need for close surveillance and functional assays of Spike variants.Despite progress in increasing the use of modern contraceptives in most Latin American countries over the last few decades, important challenges remain, including the heavy reliance on out-of-pocket spending to access contraceptives, which may expose consumption to macroeconomic fluctuations. Out-of-pocket spending on contraceptives and/or the proportion of women aged 15-49 who received free contraceptives at a public health facility or as part of statutory health insurance were estimated for 13 Latin American countries using the most recently available household budget surveys and demographic and health or similar household surveys. Data on contraceptive retail sales in 12 countries over the 2006-2010 period and publicly available macroeconomic indicators were used to examine the relationship between changes in sales and macroeconomic indicators using multiple regression models. On average, women aged 15-49 spent close to US$1 per month out-of-pocket on contraceptives. However, almost three out of five women received them free of charge. A 1% increase in the percentage of the population living on less than US$ 3.2/day (2011 PPP values), or the percentage unemployed in the labour force, predicted about a 2% decrease in the growth of contraceptive retail sales (measured in couple-years of protection, CYP, per capita) the subsequent year. The analysis revealed the sensitivity of contraceptive retail sales to changes in macroeconomic variables, particularly changes in poverty levels. Achieving universal access to family planning by 2030 will require improving contraceptive financing schemes.

02/07/2025


Genitourinary tuberculosis is the fourth most common cause of extrapulmonary tuberculosis, although often underestimated by clinicians due to its rare and non-specific symptoms. One of the disease's complications is infertility. Although Portugal is one of the European countries with the highest prevalence of tuberculosis, its impact on Portuguese female fertility is unknown. With this study, we intend to evaluate the prevalence of genital tuberculosis, its presenting symptoms, and pregnancy outcomes in infertile women followed in a Portuguese tertiary hospital.

Retrospective and descriptive study, performed using an electronic database and consultation of clinical files. https://www.selleckchem.com/products/lb-100.html Studied population infertile women followed from 2000 until 2019 at the reproductive unit of a Portuguese tertiary hospital, who underwent endometrial biopsy/curettage in the context of their etiological investigation. The diagnosis of genital tuberculosis was based on histological criteria.

Over the 19years, 2653 endometrial specimens were analyzed. Pathological evaluation was positive for tuberculosis in 19 cases (0.72%). There was a decrease in new diagnoses throughout the observation period.

Despite being one of the European countries with the highest prevalence of tuberculosis, genital TB does not appear to have a significant impact on the etiology of female infertility in Portugal. Nevertheless, it is a diagnosis to be considered in selected patients.
Despite being one of the European countries with the highest prevalence of tuberculosis, genital TB does not appear to have a significant impact on the etiology of female infertility in Portugal. Nevertheless, it is a diagnosis to be considered in selected patients.Congenital or acquired cerebellum alterations are associated with a complex pattern of motor, cognitive and social disorders. These disturbances may reflect the involvement of the cerebellum in generating and updating the internal models that sub-serve-the prediction of sensory events. Here, we tested whether the cerebellar involvement in using contextual expectations to interpret ambiguous sensory sceneries is specific for social actions or also extends to physical events. We applied anodic, cathodic and sham cerebellar transcranial Direct Current Stimulation (ctDCS) to modulate the performance of an adult sample in two tasks requiring the prediction of social actions or moving shapes. For both tasks, in an earlier implicit-learning phase (familiarization), we manipulated the probability of co-occurrence between a particular action/shape and contextual elements, which could provide either strongly or moderately informative expectations. The use of these expectations was then tested when participants had to predict the unfolding of temporally occluded videos, in situations of perceptual uncertainty (testing). Results showed that in the testing, but not in the familiarization phase, cathodic as compared to anodic and sham ctDCS hindered participants' sensitivity in predicting actions embedded in strongly, but not moderately, informative contexts. Conversely, anodic as compared to sham ctDCS boosted the prediction of actions embedded in moderately, but not strongly, informative contexts. We observed no ctDCS effects for the shape prediction task, thus pointing to a specific involvement of the cerebellum in forming expectations related to social events. Our results encourage the exploration of rehabilitative effects of ctDCS in patients with social perception deficits.Bullous pemphigoid constitutes a rare dermatological immune-related adverse event of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors. Herein, we review all published cases of anti-PD-1/PD-L1 related bullous pemphigoid and discuss current knowledge on this condition. Clinical and diagnostic findings were found to resemble those of classic bullous pemphigoid. A delayed onset of bullous pemphigoid after commencement of immunotherapy as well as a frequent precendence of a refractory pruritic eruption prior to blister development was oberved, both posing diagnostic challenges. In addition to topical and systemic treatment, most patients required either discontinuation or permanent interruption of immunotherapy. Assessment of tumour outcome did not reveal improved survival in patients developing bullous pemphigoid during immunotherapy, as suggested for other types of skin toxicity, including vitiligo. Better understanding of the pathogenetic mechanism and prognostic implications of this increasingly-reported adverse event is essential in order to establish optimal diagnostic and therapeutic management of these patients.Sensitive skin is commonly assessed on the basis of self-reports from patients, and sometimes questionnaires, such as the Sensitive Scale-10, are used. The severity of sensitive skin follows a continuum, from the absence of sensitive skin to very sensitive skin. The aims of this cross-sectional study were to compare subjects with and without symptomatic sensitive skin and to propose diagnostic criteria for sensitive skin. A total of 160 women, between 18 and 65 years of age, with and without sensitive skin, and without any associated skin diseases, were recruited. Mean age was 41 years old. Fifty-five percent of participants reported having "very sensitive" or "sensitive" skin. In the sensitive skin group, the participants mainly experienced skin irritability (100%), tautness (97.5%), discomfort (90%) and redness (90%). According to the receiver operating characteristic curve, a Sensitive Scale-10 (SS-10) cut-off value of 12.7 can be used to detect sensitive skin (with a sensitivity of 72.4% and specificity of 90.3%).Granular deposits of IgA represent the specific cutaneous marker of dermatitis herpetiformis. The prevalence of IgA deposits in the skin of patients with coeliac disease without dermatitis herpetiformis remains unknown. In this prospective case-control study, skin biopsies from newly diagnosed coeliac patients without dermatitis herpetiformis were analysed by direct immunofluorescence. Controls included healthy volunteers and patients with both bowel symptoms and skin eruptions unrelated to coeliac disease. Clinical data and serum level of anti-tissue transglutaminase and anti-epidermal transglutaminase IgA antibodies were collected from patients and controls. Granular deposits of IgA or IgA1 in the skin were found in 29 out of 45 patients with coeliac disease (64.4%), and in none of the included controls (specificity 100%; sensitivity 64.4%). Positive direct immunofluorescence correlated significantly with an increased serum level of anti-epidermal transglutaminase IgA antibodies (p  less then  0.005). This study shows that granular deposits of IgA represent a low sensitive, but highly specific, cutaneous marker of coeliac disease independent of dermatitis herpetiformis.

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02/09/2025


5 vs. 42.3%; p = 0.028). The 5-year OS was lower among patients with a lower lymphocyte value (≤1.82 × 103) (29.0 vs. 75.6%; p = 0.010). There was a tendency towards worse OS among patients with a higher platelet count (>281 × 103) (4.5-year OS 16.7 vs. 65.8%; p = 0.056). The 5-year OS was insignificantly lower in the group with NLRs >2.74 than in the group with NLRs ≤2.74 (37.5 vs. 62.8%; p = 0.078). A worse OS rate was associated with an elevated PLR (>169.1) (22.2 vs. 70.1%; p = 0.008). https://www.selleckchem.com/products/xl177a.html Similarly, there was worse OS in the group with higher MLR (>0.30) (41.8 vs. 78.3%; p = 0.025). CONCLUSIONS The present results reveal that elevated MLRs (>0.30) and PLRs (>169.1) are associated with poor OS among male BC patients. Similarly, but insignificantly, an elevated NLR (>2.74) affected OS. © 2020 S. Karger AG, Basel.BACKGROUND Sporadic Creutzfeldt-Jakob disease (sCJD) is an extremely rare fatal and infectious neurodegenerative brain disorder characterized by rapidly progressive dementia, cerebellar ataxia, and visual disturbances. This article summarizes the retrospective analysis of 104 sCJD patients in the First Medical Center of Chinese PLA General Hospital from 2003 to 2019. METHODS A retrospective analysis of the medical records of the 104 patients diagnosed with sCJD was performed from the aspects of demographic data, clinical manifestations, laboratory examinations, cerebrospinal fluid analysis, electroencephalograms (EEGs), diffusion-weighted imaging (DWI) scans, positron emission tomography (PET) scans, and prion protein gene mutations. RESULTS In the 104 sCJD patients, pathological evidence of a spongiform change was found in 11 patients, while the remaining 93 patients were probable sCJD. The 104 patients included 57 males and 47 females, with the age of onset ranging from 29 to 82 (mean 58, median 60) years. The time from disease onset to death ranged from 1 to 36 months. Most of the patients died 7-12 months after the onset of sCJD. In most patients, rapidly progressive dementia appeared as the initial symptom, followed by cerebellar ataxia, visual disturbances, and neurobehavioral disorders. Most patients' DWI images showed symmetric or asymmetric hyperintensity in the cortex. In terms of EEGs, 38.2% of the patients had periodic sharp wave complexes. The sensitivity of 14-3-3 protein detection was 34.1%. The brain PET scans of 50 patients with sCJD presented 96% sensitivity for the diagnosis of sCJD. CONCLUSIONS This study indicated that sCJD occurred at an early age in patients in China. The sensitivity of 14-3-3 protein detection was significantly low, but brain PET was highly sensitive in the diagnosis of sCJD. © 2020 S. Karger AG, Basel.Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3, was originally described in members of the families of Machado, Thomas, and Joseph from São Miguel Island, Azores, Portugal, in 1972. The purpose of this article is to present previous descriptions of hereditary ataxia resembling the heterogeneous phenotypic intra-familiar presentation of MJD. We suggest that the condition would best be called dominant spino-pontine atrophy. © 2020 S. Karger AG, Basel.INTRODUCTION Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a rare cause of adrenal insufficiency and T-box pituitary restricted transcription factor (TBX19) mutations are responsible for two-thirds of the neonatal onset form of the disease. IAD presents with hypoglycemia and prolonged jaundice in the neonatal period. TBX19 is important for both pro-opiomelanocortin (POMC) gene transcription and differentiation of POMC-expressing cells. We describe 2 patients, 1 with a reported and 1 with a novel TBX19 mutation, and present information about the long-term follow-up of these patients. CASE PRESENTATION Both patients had critical illnesses, recurrent hypoglycemia, convulsions, and neonatal hyperbilirubinemia. They also had low cortisol and ACTH levels, while other pituitary hormones were within the normal range. Pituitary imaging was normal. After hydrocortisone treatment, there was resolution of the hypoglycemia and the convulsions were controlled. Genetic studies of the patients revealed both had inherited a homozygous mutation of the TBX19 gene. The first patient had an alteration of NM_005149.3c.856C>T (p.R286*) and the second patient had a novel NM_005149.3c.584C>T (p.T195I) mutation, analyzed by next-generation sequencing. The noteworthy findings of the patients at follow-up were short stature, microcephaly, and decreased pubic hair in the first, and dysmorphic features, Chiari type 1 malformation, tall stature, and low bone mineral density (BMD) in the second. CONCLUSION Congenital IAD can be life-threatening if it is not recognized and treated early. TBX19 mutations should be considered in the differential diagnosis of IAD. Further cases or functional analyses are needed for genotype-phenotype correlations. Low BMD, dysmorphic features, Chiari type 1 malformation, and sparse pubic hair are some of the important features in these patients. © 2020 S. Karger AG, Basel.INTRODUCTION Short stature homeobox-containing gene (SHOX) haploinsufficiency is associated with short stature, Madelung deformity and mesomelia. Current clinical screening tools are based on patients with intragenic variants or deletions. However, recent discoveries showed that deletions of the enhancer elements are quite common. The majority of these patients show less body disproportion and respond better to recombinant human growth hormone treatment. We redefined clinical criteria for genetic analysis to facilitate detection of the full spectrum of SHOX haploinsufficiency. METHODS We analyzed 51 children with SHOX variants or deletions and 25 children with a deletion in its enhancer region. Data were compared to 277 children referred for suspicion of growth failure without endocrine or genetic pathology. RESULTS Only half of the patients with an enhancer region deletion fulfilled any of the current screening criteria. We propose new clinical criteria based on sitting height to height ratio >1 SDS or arm span ≥3 cm below height, with a sensitivity of 99%. When these criteria are combined with obligatory short stature, the sensitivity to detect SHOX haploinsufficiency is 68.1%, the specificity 80.6%, and the number needed to screen 21 patients. CONCLUSION Novel clinical criteria for screening for SHOX haploinsufficiency allow the detection of patients within the full genetic spectrum, that is, intragenic variants and enhancer region deletions. © 2020 The Author(s) Published by S. Karger AG, Basel.

02/07/2025


Using normalization of CD4 counts as the main evaluation parameter of complete immune restoration for HIV-1 patients under antiretroviral therapy (ART) might be not enough. A comprehensive evaluation system more accurately reflecting immune restoration are urgently needed. Totally, 91,805 HIV-1 patients from 17 tertiary hospitals in China during 2005-2018 were included in this study. Immune restoration and mortality were assessed. Patients initiated ART with baseline CD4 counts less then 50, 50-199, 200-349, 350-499, and ≥500 cells/μL, and results showed an increase in the median CD4 counts to 445 (12-year), 467 (12-year), 581 (11-year), 644 (7-year), and 768 cells/µL (5-year), as well as the CD4/CD8 ratio to 0.59 (12-year), 0.65 (12-year), 0.79 (11-year), 0.82 (7-year), 0.9 (5-year), respectively. The median CD8 count was relatively high (median range 732-845 cells/μL), regardless of the baseline CD4 counts. Furthermore, the probabilities of death in patients achieving CD4 counts ≥500 cells/μL and CD4/CD8 ratio ≥0.8 simultaneously were significantly lower than those in patients achieving either CD4 counts ≥500 cells/μL (2.77% vs 3.50%, p=0.02) or CD4/CD8 ≥ 0.8 (2.77% vs 4.28%, p less then 0.001) after 12-year of ART. In this study, a new binary-indicator would accurately assess immune restoration in the era of "treat all."Introduction Ankle injuries are common in daily orthopaedic trauma practice, with a high incidence of lateral ligament complex (lat-lig-com) injuries of the ankle joint (AJ). Primarily, these lat-lig-com injuries heal sufficiently, although there is a risk of developing chronic ankle instability. https://www.selleckchem.com/products/scutellarin.html However, there is a lack of knowledge about the clinical application and routine for rehabilitation strategies so as to prevent chronic instability. This study investigates the current rehabilitation concepts in clinical routine after ligament injuries of the AJ. Methods Rehabilitation protocols, provided by orthopaedic and trauma surgery institutions in German speaking countries, were analysed in terms of weight-bearing, range of motion (ROM), physiotherapy and choice of orthosis. All protocols for operatively and non-operatively (nop) treated ligament ruptures of the AJ were included. Results 120 of 213 institutions provided protocols of lat-lig-com injuries of the AJ. Regarding the orthosis, the nop-treatment group mainly used ankle braces; in contrast, the operative group preferred the use of an ankle boot. The operative group recommends 6-12 weeks for duration of orthosis in contrast to only 6 weeks in the nop group. Significant differences prevail in ROM, with free ROM in non-operative treatment from the first day after trauma (p less then 0.001) in contrast to a careful increase in ROM in the first 6 weeks post-operatively. Conclusion Early functional treatment is clinical standard in rehabilitation after lat-lig-com injuries of the ankle. Regarding current literature the differences of restrictions in ROM and orthosis treatment after lat-lig-com injuries suggest a trivialization of conservative treatment in the first period after trauma compared to post-operative aftercare.Genomic surveillance of SARS-CoV-2 was rapidly implemented in Portugal by the National Institute of Health in collaboration with a nationwide consortium of >50 hospitals/laboratories. Here, we track the geotemporal spread of a SARS-CoV-2 variant with a mutation (D839Y) in a potential host-interacting region involving the Spike fusion peptide, which is a target motif of anti-viral drugs that plays a key role in SARS-CoV-2 infectivity. The Spike Y839 variant was most likely imported from Italy in mid-late February and massively disseminated in Portugal during the early epidemic, becoming prevalent in the Northern and Central regions of Portugal where it represented 22% and 59% of the sampled genomes, respectively, by 30 April. Based on our high sequencing sampling during the early epidemics [15.5% (1275/8251) and 6.0% (1500/24987) of all confirmed cases until the end of March and April, respectively], we estimate that, between 14 March and 9 April (covering the epidemic exponential phase) the relative frequency of the Spike Y839 variant increased at a rate of 12.1% (6.1%-18.2%, CI 95%) every three days, being potentially associated with 24.8% (20.8-29.7%, CI 95%; 3177-4542 cases, CI 95%) of all COVID-19 cases in Portugal during this period. Our data supports population/epidemiological (founder) effects contributing to the Y839 variant superspread. The potential existence of selective advantage is also discussed, although experimental validation is required. Despite huge differences in genome sampling worldwide, SARS-CoV-2 Spike D839Y has been detected in 13 countries in four continents, supporting the need for close surveillance and functional assays of Spike variants.Despite progress in increasing the use of modern contraceptives in most Latin American countries over the last few decades, important challenges remain, including the heavy reliance on out-of-pocket spending to access contraceptives, which may expose consumption to macroeconomic fluctuations. Out-of-pocket spending on contraceptives and/or the proportion of women aged 15-49 who received free contraceptives at a public health facility or as part of statutory health insurance were estimated for 13 Latin American countries using the most recently available household budget surveys and demographic and health or similar household surveys. Data on contraceptive retail sales in 12 countries over the 2006-2010 period and publicly available macroeconomic indicators were used to examine the relationship between changes in sales and macroeconomic indicators using multiple regression models. On average, women aged 15-49 spent close to US$1 per month out-of-pocket on contraceptives. However, almost three out of five women received them free of charge. A 1% increase in the percentage of the population living on less than US$ 3.2/day (2011 PPP values), or the percentage unemployed in the labour force, predicted about a 2% decrease in the growth of contraceptive retail sales (measured in couple-years of protection, CYP, per capita) the subsequent year. The analysis revealed the sensitivity of contraceptive retail sales to changes in macroeconomic variables, particularly changes in poverty levels. Achieving universal access to family planning by 2030 will require improving contraceptive financing schemes.

02/07/2025


Genitourinary tuberculosis is the fourth most common cause of extrapulmonary tuberculosis, although often underestimated by clinicians due to its rare and non-specific symptoms. One of the disease's complications is infertility. Although Portugal is one of the European countries with the highest prevalence of tuberculosis, its impact on Portuguese female fertility is unknown. With this study, we intend to evaluate the prevalence of genital tuberculosis, its presenting symptoms, and pregnancy outcomes in infertile women followed in a Portuguese tertiary hospital.

Retrospective and descriptive study, performed using an electronic database and consultation of clinical files. https://www.selleckchem.com/products/lb-100.html Studied population infertile women followed from 2000 until 2019 at the reproductive unit of a Portuguese tertiary hospital, who underwent endometrial biopsy/curettage in the context of their etiological investigation. The diagnosis of genital tuberculosis was based on histological criteria.

Over the 19years, 2653 endometrial specimens were analyzed. Pathological evaluation was positive for tuberculosis in 19 cases (0.72%). There was a decrease in new diagnoses throughout the observation period.

Despite being one of the European countries with the highest prevalence of tuberculosis, genital TB does not appear to have a significant impact on the etiology of female infertility in Portugal. Nevertheless, it is a diagnosis to be considered in selected patients.
Despite being one of the European countries with the highest prevalence of tuberculosis, genital TB does not appear to have a significant impact on the etiology of female infertility in Portugal. Nevertheless, it is a diagnosis to be considered in selected patients.Congenital or acquired cerebellum alterations are associated with a complex pattern of motor, cognitive and social disorders. These disturbances may reflect the involvement of the cerebellum in generating and updating the internal models that sub-serve-the prediction of sensory events. Here, we tested whether the cerebellar involvement in using contextual expectations to interpret ambiguous sensory sceneries is specific for social actions or also extends to physical events. We applied anodic, cathodic and sham cerebellar transcranial Direct Current Stimulation (ctDCS) to modulate the performance of an adult sample in two tasks requiring the prediction of social actions or moving shapes. For both tasks, in an earlier implicit-learning phase (familiarization), we manipulated the probability of co-occurrence between a particular action/shape and contextual elements, which could provide either strongly or moderately informative expectations. The use of these expectations was then tested when participants had to predict the unfolding of temporally occluded videos, in situations of perceptual uncertainty (testing). Results showed that in the testing, but not in the familiarization phase, cathodic as compared to anodic and sham ctDCS hindered participants' sensitivity in predicting actions embedded in strongly, but not moderately, informative contexts. Conversely, anodic as compared to sham ctDCS boosted the prediction of actions embedded in moderately, but not strongly, informative contexts. We observed no ctDCS effects for the shape prediction task, thus pointing to a specific involvement of the cerebellum in forming expectations related to social events. Our results encourage the exploration of rehabilitative effects of ctDCS in patients with social perception deficits.Bullous pemphigoid constitutes a rare dermatological immune-related adverse event of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors. Herein, we review all published cases of anti-PD-1/PD-L1 related bullous pemphigoid and discuss current knowledge on this condition. Clinical and diagnostic findings were found to resemble those of classic bullous pemphigoid. A delayed onset of bullous pemphigoid after commencement of immunotherapy as well as a frequent precendence of a refractory pruritic eruption prior to blister development was oberved, both posing diagnostic challenges. In addition to topical and systemic treatment, most patients required either discontinuation or permanent interruption of immunotherapy. Assessment of tumour outcome did not reveal improved survival in patients developing bullous pemphigoid during immunotherapy, as suggested for other types of skin toxicity, including vitiligo. Better understanding of the pathogenetic mechanism and prognostic implications of this increasingly-reported adverse event is essential in order to establish optimal diagnostic and therapeutic management of these patients.Sensitive skin is commonly assessed on the basis of self-reports from patients, and sometimes questionnaires, such as the Sensitive Scale-10, are used. The severity of sensitive skin follows a continuum, from the absence of sensitive skin to very sensitive skin. The aims of this cross-sectional study were to compare subjects with and without symptomatic sensitive skin and to propose diagnostic criteria for sensitive skin. A total of 160 women, between 18 and 65 years of age, with and without sensitive skin, and without any associated skin diseases, were recruited. Mean age was 41 years old. Fifty-five percent of participants reported having "very sensitive" or "sensitive" skin. In the sensitive skin group, the participants mainly experienced skin irritability (100%), tautness (97.5%), discomfort (90%) and redness (90%). According to the receiver operating characteristic curve, a Sensitive Scale-10 (SS-10) cut-off value of 12.7 can be used to detect sensitive skin (with a sensitivity of 72.4% and specificity of 90.3%).Granular deposits of IgA represent the specific cutaneous marker of dermatitis herpetiformis. The prevalence of IgA deposits in the skin of patients with coeliac disease without dermatitis herpetiformis remains unknown. In this prospective case-control study, skin biopsies from newly diagnosed coeliac patients without dermatitis herpetiformis were analysed by direct immunofluorescence. Controls included healthy volunteers and patients with both bowel symptoms and skin eruptions unrelated to coeliac disease. Clinical data and serum level of anti-tissue transglutaminase and anti-epidermal transglutaminase IgA antibodies were collected from patients and controls. Granular deposits of IgA or IgA1 in the skin were found in 29 out of 45 patients with coeliac disease (64.4%), and in none of the included controls (specificity 100%; sensitivity 64.4%). Positive direct immunofluorescence correlated significantly with an increased serum level of anti-epidermal transglutaminase IgA antibodies (p  less then  0.005). This study shows that granular deposits of IgA represent a low sensitive, but highly specific, cutaneous marker of coeliac disease independent of dermatitis herpetiformis.

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Moreover, the antioxidant activity might be related to the total phenolic content and the types of polyphenolics, especially phlorotannins. The findings presented in this study indicate that A. nodosum could be used as an important substitute for functional ingredients in foods and pharmaceutical preparations, as well as a raw material for phlorotannins research.The P2X7 receptor for extracellular ATP is a well-established mediator of tumoral development and progression both in solid cancers and hematological malignancies. The human P2X7 gene is highly polymorphic, and several splice variants of the receptor have been identified in time. P2X7 single-nucleotide polymorphisms (SNPs) have been broadly analyzed by studies relating them to pathologies as different as infectious, inflammatory, nervous, and bone diseases, among which cancer is included. Moreover, in the last years, an increasing number of reports concentrated on P2X7 splice variants' different roles and their implications in pathological conditions, including oncogenesis. Here, we give an overview of established and recent literature demonstrating a role for human P2X7 gene products in oncological conditions, mainly focusing on current data emerging on P2X7 isoform B and nfP2X7. We explored the role of these and other genetic variants of P2X7 in cancer insurgence, dissemination, and progression, as well as the effect of chemotherapy on isoforms expression. The described literature strongly suggests that P2X7 variants are potential new biomarkers and therapeutical targets in oncological conditions and that their study in carcinogenesis deserves to be further pursued.The public perception of renewable energy sources is generally positive, due to their role in air pollution and CO2 emission mitigation policies. However, there are local environmental detrimental effects, and empirical evidence is not consistent as to the support of local communities. In the present paper, we analyse the antecedents of public generic perceptions of renewables grounded on objective location-related factors. Personal location-related factors can originate in the involvement of individuals with renewable energy sources. Regional location-related factors concern the importance of the renewable energy source in the district of residence and in relation to other renewables. We implement a questionnaire on public perceptions of renewable energy sources by the general population in mainland Portugal and complement respondent-level responses with renewable energy district information. Regression analysis shows that these objective location-related factors, both personal and regional, help explain public perceptions of renewables and thus we find empirical support for the proposed approach. These results can inform and guide policymakers in tackling future social acceptance issues of renewable energy policies towards lower carbon emissions and less polluting energy production.Phospholipid-coated microbubbles are ultrasound contrast agents that can be employed for ultrasound molecular imaging and drug delivery. For safe and effective implementation, microbubbles must respond uniformly and predictably to ultrasound. Therefore, we investigated how lipid handling and phase distribution affected the variability in the acoustic behavior of microbubbles. Cholesterol was used to modify the lateral molecular packing of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)-based microbubbles. To assess the effect of lipid handling, microbubbles were produced by a direct method, i.e., lipids directly dispersed in an aqueous medium or indirect method, i.e., lipids first dissolved in an organic solvent. The lipid phase and ligand distribution in the microbubble coating were investigated using confocal microscopy, and the acoustic response was recorded with the Brandaris 128 ultra-high-speed camera. In microbubbles with 12 mol% cholesterol, the lipids were miscible and all in the same phase, which resulted in more buckle formation, lower shell elasticity and higher shell viscosity. Indirect DSPC microbubbles had a more uniform response to ultrasound than direct DSPC and indirect DSPC-cholesterol microbubbles. The difference in lipid handling between direct and indirect DSPC microbubbles significantly affected the acoustic behavior. https://www.selleckchem.com/products/pf-06952229.html Indirect DSPC microbubbles are the most promising candidate for ultrasound molecular imaging and drug delivery applications.Pseudomonas mendocina is an environmental bacterium, rarely isolated in clinical specimens, although it has been described as producing endocarditis and sepsis. Little is known about its genome. Whole genome sequencing can be used to learn about the phylogeny, evolution, or pathogenicity of these isolates. Thus, the aim of this study was to analyze the resistome, virulome, and phylogenetic relationship of two P. mendocina strains, Ps542 and Ps799, isolated from a healthy Anas platyrhynchos fecal sample and a lettuce, respectively. Among all of the small number of P.mendocina genomes available in the National Center for Biotechnology Information (NCBI) repository, both strains were placed within one of two well-defined phylogenetic clusters. Both P. mendocina strains lacked antimicrobial resistance genes, but the Ps799 genome showed a MOBP3 family relaxase. Nevertheless, this study revealed that P. mendocina possesses an important number of virulence factors, including a leukotoxin, flagella, pili, and the Type 2 and Type 6 Secretion Systems, that could be responsible for their pathogenesis. More phenotypical and in vivo studies are needed to deepen the association with human infections and the potential P. mendocina pathogenicity.Melilotus officinalis is known to contain several types of secondary metabolites. In contrast, the carotenoid composition of this medicinal plant has not been investigated, although it may also contribute to the biological activities of the drug, such as anti-inflammatory effects. Therefore, this study focuses on the isolation and identification of carotenoids from Meliloti herba and on the effect of isolated (all-E)-lutein 5,6-epoxide on primary sensory neurons and macrophages involved in nociception, as well as neurogenic and non-neurogenic inflammatory processes. The composition of the plant extracts was analyzed by high performance liquid chromatography (HPLC). The main carotenoid was isolated by column liquid chromatography (CLC) and identified by MS and NMR. The effect of water-soluble lutein 5,6-epoxide-RAMEB (randomly methylated-β-cyclodextrin) was investigated on Ca2+-influx in rat primary sensory neurons induced by the activation of the transient receptor potential ankyrin 1 receptor agonist to mustard-oil and on endotoxin-induced IL-1β release from isolated mouse peritoneal macrophages.

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No significant correlation was found between noise and any other patient demographic including age, sex, height, body weight, or body mass index. Kaplan-Meier survivorship analysis with revision for any reason and an aseptic loosening of either component as the end point, revealed a cumulative survival rate at 10 years of 98.4% and 99.1% respectively.

The long-term clinical and radiographic outcome of cementless COC THA is excellent, but we should be vigilant for noise from COC bearings.
The long-term clinical and radiographic outcome of cementless COC THA is excellent, but we should be vigilant for noise from COC bearings.
Arthroscopic resection of tarsal coalitions is a relatively new technique. This systematic review aimed to investigate the post-operative complications and functional outcomes in arthroscopic resection of tarsal coalitions.

PubMed, Medline, Embase and Cochrane library were searched for studies that reported outcomes in arthroscopic resection of tarsal coalitions.

8 studies met the inclusion criteria. Post-operative outcomes were reported in 103 cases. The overall complication rate was 13.6%. Tibial nerve injury was reported in 1 patient. All included studies demonstrated post-operative improvement in functional outcomes.

Arthroscopic resection is a feasible and effective treatment method for symptomatic tarsal coalitions.
Arthroscopic resection is a feasible and effective treatment method for symptomatic tarsal coalitions.Instabilities of electron plasma waves in high-mobility semiconductor devices have recently attracted a lot of attention as a possible candidate for closing the THz gap. Conventional moments-based transport models usually neglect time derivatives in the constitutive equations for vectorial quantities, resulting in parabolic systems of partial differential equations (PDE). To describe plasma waves however, such time derivatives need to be included, resulting in hyperbolic rather than parabolic systems of PDEs; thus the fundamental nature of these equation systems is changed completely. Additional nonlinear terms render the existing numerical stabilization methods for semiconductor simulation practically useless. On the other hand there are plenty of numerical methods for hyperbolic systems of PDEs in the form of conservation laws. Standard numerical schemes for conservation laws, however, are often either incapable of correctly handling the large source terms present in semiconductor devices due to built-in electric fields, or rely heavily on variable transformations which are specific to the equation system at hand (e.g. https://www.selleckchem.com/products/4u8c.html the shallow water equations), and can not be generalized easily to different equations. In this paper we develop a novel well-balanced numerical scheme for hyperbolic systems of PDEs with source terms and apply it to a simple yet non-linear electron transport model.Despite the growing popularity of multidimensional poverty measurement and analysis, its use to measure the impact of social protection programs remains scarce. Using primary data collected for the evaluation of HIV Prevention Trials Network (HPTN) 068, a randomized, conditional cash transfer intervention for young girls in South Africa that ran from 2011 to 2015, we construct an individual-level measure of multidimensional poverty, a major departure from standard indices that use the household as the unit of analysis. We construct our measure by aggregating multiple deprivation indicators across six dimensions and using a system of nested weights where each domain is weighted equally. Our findings show that the cash transfer consistently reduces deprivations among girls, in particular through the domains of economic agency, violence, and relationships. These results show how social protection interventions can improve the lives of young women beyond single domains and demonstrate the potential for social protection to simultaneously address multiple targets of the SDGs.Working from home has become engraved in modern working life. Although advocated as a solution to combine work with family life, surprisingly little empirical evidence supports that it decreases work-family conflict. In this paper we examine the role of a supportive organizational context in making working from home facilitate the combination of work and family. Specifically, we address to what extent perceptions of managerial support, ideal worker culture, as well as the number of colleagues working from home influence how working from home relates to work-family conflict. By providing insight in the role of the organizational context, we move beyond existing research in its individualistic focus on the experience of the work-family interface. We explicitly address gender differences since women experience more work-family conflict than men. We use a unique, multilevel organizational survey, the European Sustainable Workforce Survey conducted in 259 organizations, 869 teams and 11,011 employees in nine countries (Bulgaria, Finland, Germany, Hungary, Netherlands, Portugal, Spain, Sweden, United Kingdom). Results show that an ideal worker culture amplifies the increase in work family conflict due to working from home, but equally for men and women. On the other hand, women are more sensitive to the proportion of colleagues working from home, and the more colleagues are working from home the less conflict they experience.This special brings together innovative and multidisciplinary research (sociology, economics, and social work) using data from across Europe and the US to examine the potential flexible working has on the gender division of labour and workers' work-life balance. Despite numerous studies on the gendered outcomes of flexible working, it is limited in that the majority is based on qualitative studies based in the US. The papers of this special issue overcome some of the limitations by examining the importance of context, namely, family, organisational and country context, examining the intersection between gender and class, and finally examining the outcomes for different types of flexible working arrangements. The introduction to this special issue provides a review of the existing literature on the gendered outcomes of flexible working on work life balance and other work and family outcomes, before presenting the key findings of the articles of this special issue. The results of the studies show that gender matters in understanding the outcomes of flexible working, but also it matters differently in different contexts.