Cinaciguat-induced dilatation of l-NAME-pretreated and ANG II-preconstricted arterioles was similar to controls without l-NAME treatment. Cinaciguat also induced dilatation in iodinated contrast medium treated AA. Furthermore, it dilated EA, but not AA, after hypoxia/reoxygenation. The results reveal an important role of the NO-sGC-cGMP system for renal dilatation and that EA have a more potent sGC activated dilatory system. Furthermore, AA seem to be more sensitive to hypoxia/reoxygenation than EA under these experimental conditions.In aircraft manufacturing, the vertical accuracy of connection holes is important indicator of the quality of holes making. Aircraft products have high requirements for the vertical accuracy of holes positions. When drilling and riveting are performed by an automatic robotic system, assembly errors, bumps, offsets and other adverse conditions, can affects the accuracy of manufacturing and detection, and in turn the fatigue performance of the entire structure. To solve this problem, we proposed a technology for detecting the normal-direction based on the adaptive alignment method, built a mathematical model for posture alignment, and studied the calibration method and mechanism of the detection device. Additionally, we investigated techniques for error compensation using an electronic theodolite and other devices when the adaptive method is used for detection. In verification experiments of the method, multiple sets of results demonstrated that the key technical indicators are as follows normal accuracy less then 0.5°, average deviation after correction =0.0667°. This method can effectively compensate the errors affecting hole making work in automated manufacturing, and further improve the positioning accuracy and normal-direction detection accuracy of the robot.Novel [Pd(o-CH2C6H4P(o-tolyl)2)(histidine)] (1) and [Pd(o-CH2C6H4P(o tolyl)2)(phenylalanine)] (2) P,C-orthopalladated complexes have been prepared and characterized by elemental analysis, IR and NMR spectroscopy. To study the stability of the compounds in biological media, the complexes were incubated in Tris buffer during 10 days. The absorbance of the compounds remained constant, which confirmed the stability of the complexes in biological media. UV-Vis absorption spectrophotometry, fluorescence spectroscopy and viscosity studies were used to investigate the binding of the complexes with native calf thymus DNA (CT-DNA). These methods along with competitive binding of methylene blue (MB) DNA show that the complexes interact with DNA via groove mode. The UV-Vis absorption spectrophotometry of BSA with complexes has shown an α-helix perturbation induced by a particular interaction between the metal complexes and BSA. In addition, the fluorescence quenching mechanism of BSA with the complexes is a static process, according to the fluorescence spectrometry of bovine serum albumin (BSA). The experimental results of site competitive replacement with specific site markers are clear indications that the complexes bind to site I of BSA. Furthermore, both complexes showed significant selective cytotoxic activity against melanoma B16F0 and colon carcinoma C26 cancer cells as well as normal fibroblast NIH cell line. Ultimately, the binding of Pd(II) complexes to DNA and BSA was verified by molecular docking experiment. Communicated by Ramaswamy H. Sarma.Neanderthal is the quintessential scientific Other. In the late nineteenth century gentlemen-scientists, including business magnates, investment bankers and lawmakers with interest in questions of human and human societal development, framed Europe's Neanderthal and South Asia's indigenous Negritos as close evolutionary kin. Simultaneously, they explained Neanderthal's extinction as the consequence of an inherent backwardness in the face of fair-skinned, steadily-progressing newcomers to ancient Europe who behaved in ways associated with capitalism. This racialization and economization of Neanderthal helped bring meaning and actual legal reality to Negritos via the British Raj's official 'schedules of backward castes and tribes'. It also helped justify the Raj's initiation of market-oriented reforms in order to break a developmental equilibrium deemed created when fair-skinned newcomers to ancient South Asia enslaved Negritos in an enduring caste system. Neanderthal was integral to the scientism behind the British construction of caste, and contributed to India's becoming a principal 'Third World' target of Western structural adjustment policies as continuation of South Asia's 'evolution assistance'.For about half a century, the pharmacology of electroneutral cation-chloride cotransporters has been dominated by a few drugs that are widely used in clinical medicine. https://www.selleckchem.com/products/BIX-02189.html Because these diuretic drugs are so good at what they do, there has been little incentive in expanding their pharmacology. The increasing realization that cation-chloride cotransporters are involved in many other key physiological processes and the knowledge that different tissues express homologous proteins with matching transport functions have rekindled interest in drug discovery. This review summarizes the methods available to assess the function of these transporters and describe the multiple efforts that have made to identify new compounds. We describe multiple screens targeting KCC2 function and one screen designed to find compounds that discriminate between NKCC1 and NKCC2. Two of the KCC2 screens identified new inhibitors that are 3-4 orders of magnitude more potent than furosemide. Additional screens identified compounds that purportedly increase cell surface expression of the cotransporter, as well as several FDA-approved drugs that increase KCC2 transcription and expression. The technical details of each screen biased them toward specific processes in the life cycle of the transporter, making these efforts independent and complementary. In addition, each drug discovery effort contributes to our understanding of the biology of the cotransporters.Swelling-activated volume-regulated anion channels (VRACs) are heteromeric channels comprising LRRC8A and at least one other LRRC8 paralog. Cryoelectron microscopy (cryo-EM) structures of nonnative LRRC8A and LRRC8D homohexamers have been described. We demonstrate here that LRRC8A homohexamers poorly recapitulate VRAC functional properties. Unlike VRACs, LRRC8A channels heterologously expressed in Lrr8c-/- HCT116 cells are poorly activated by low intracellular ionic strength (µ) and insensitive to cell swelling with normal µ. Combining low µ with swelling modestly activates LRRC8A, allowing characterization of pore properties. VRACs are strongly inhibited by 10 µM 4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]butanoic acid (DCPIB) in a voltage-independent manner. In contrast, DCPIB block of LRRC8A is weak and voltage sensitive. Cryo-EM structures indicate that DCPIB block is dependent on arginine 103. Consistent with this, LRRC8A R103F mutants are insensitive to DCPIB. However, an LRRC8 chimeric channel in which R103 is replaced by a leucine at the homologous position is inhibited ∼90% by 10 µM DCPIB in a voltage-independent manner.

The prevalence of depressive symptoms was high (29%) and correlated significantly to phenylalanine blood concentrations (p = 0.046). However, depressive symptoms were only mild in the majority of patients.

This group of early-treated adult German PKU patients is socially well integrated, reveals a surprisingly high adherence to diet and amino acid intake, and considers the restrictions of diet to their daily life as low.
This group of early-treated adult German PKU patients is socially well integrated, reveals a surprisingly high adherence to diet and amino acid intake, and considers the restrictions of diet to their daily life as low.The patient was admitted for urgent coronary angiography following an acute anterior ST segment elevation myocardial reinfarction (STEMI) caused by acute stent thrombosis. A stent had been implanted 10 days prior to the reinfarction for an acute anterior STEMI. However, the patient had stopped taking ticagrelor post-discharge. Primary percutaneous coronary intervention of the left anterior descending artery was performed. Subsequently, due to a high C-reactive protein (CRP) level, 3 CRP apheresis sessions were performed, with the first session starting 12 h after the onset of symptoms. A significant drop in CRP was noted after each apheresis. The post-procedural course was uneventful.This article maintains that via the current form of evidence-based medicine, scientism (a pseudo-religious belief in science that is itself not scientific) has been allowed to encroach into medicine. By setting out the philosophical limits of what it is science can do, the effects of this encroachment are discussed in terms of upsetting the balance between the necessarily conflicting art AND science of medicine. In https://www.selleckchem.com/products/mmri62.html , one effect of the Covid-19 pandemic might be to act as a timely reminder - as if it was needed - of the importance of the Hippocratic Oath, which is and always has been the soul of medicine.
Low bone mineral density (BMD) represents a major risk factor for bone fractures in patients with chronic kidney disease (CKD) as well as after kidney transplantation. However, modalities to solidly predict patients at fracture risk are yet to be defined. Better understanding of bone turnover biomarkers (BTMs) may close this diagnostic gap. This study strives to correlate BTMs to BMD in kidney transplant recipients.

Changes in BTMs - procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BSAP), β-isomer of the C-terminal telopeptide of type I collagen, and urine deoxypyridinoline/Cr - at the time of transplant and 3 months were correlated to changes in BMD measured by dual-energy X-ray absorptiometry at the time of transplant, 6, and 12 months, respectively. Half of the collective was treated with denosumab twice yearly in addition to the standard treatment with calcium and vitamin D.

Changes in bone formation markers BSAP and P1NP within 3 months showed a significant negative correlation to changes in BMD at the hip within 6 months in denosumab-naïve patients. This correlation was abrogated by denosumab treatment.

Changes in BSAP and P1NP showed promise in short-term prediction of BMD. We suggest further trials expanding on the knowledge of these BTMs with assessment of fracture risk, sequential measurements of BTMs within the first 6 months, and the additional use of computed tomography to assess BMD.
Changes in BSAP and P1NP showed promise in short-term prediction of BMD. #link# We suggest further trials expanding on the knowledge of these BTMs with assessment of fracture risk, sequential measurements of BTMs within the first 6 months, and the additional use of computed tomography to assess BMD.
Angiotensin-converting enzyme inhibitors (ACEI) combined with mineralocorticoid receptor antagonists were found to have a beneficial effect on patients with chronic kidney disease.

The aim of our clinical trial was to compare the antialbuminuric effect of ramipril monotherapy, eplerenone monotherapy and eplerenone/ramipril combination therapy in patients with stage 1 hypertension and type 2 diabetes mellitus.

In a single-blind, randomized clinical trial, 75 hypertensive patients (stage 1 hypertension) with type 2 diabetes mellitus and microalbuminuria were randomized in a 111 ratio to 1 of 3 groups ramipril 10 mg monotherapy (25 patients), eplerenone 50 mg monotherapy (25 patients) and combination therapy of eplerenone/ramipril 50/10 mg (25 patients) through a randomized clinical trial. Blood pressure, urinary albumin/creatinine ratio (UACR), serum creatinine, estimated glomerular filtration rate (eGFR) and serum K level were measured before randomization and after 24 weeks.

Ramipril and eplerenone monotherapy showed a significant lowering of UACR compared with baseline levels (p ≤ 0.0001). The eplerenone/ramipril combination group showed a more significant reduction of UACR compared with the ramipril and eplerenone monotherapy groups (p = 0.0001). There was a more significant lowering of systolic blood pressure in the combination group (p < 0.0001). A nonsignificant change of serum potassium level, serum creatinine and eGFR was found among the 3 groups.

Addition of eplerenone to ACEI shows an added antialbuminuric effect without significant change of the serum K level compared with eplerenone or ACEI.
Addition of eplerenone to ACEI shows an added antialbuminuric effect without significant change of the serum K level compared with eplerenone or ACEI.
Primary hyperparathyroidism (PHPT) is rare and usually symptomatic in children. There is no approved medication to lower serum calcium levels in this patient group. Denosumab is used in adult patients with osteoporosis and hyperparathyroidism. To our knowledge, only 1 case of denosumab treatment in a child with severe PHPT has been reported to date.

A 16-year-old female was referred to our clinic with symptoms including pathologic fractures, nausea, emesis, and progressive weight loss. At admission, her serum total calcium was 4.17 mmol/L (reference range 2.15-2.55), parathyroid hormone 2,151 pg/mL (15-65), and phosphate 1.07 mmol/L (1.45-1.78). Due to potentially life-threatening hypercalcemia, denosumab 60 mg subcutaneously was administered after obtaining informed consent. Serum calcium levels were reduced within 12 h of injection and the patient's condition rapidly improved, which allowed genetic testing to be done prior to surgery. A heterozygous mutation in the CDC73 gene was revealed, and a parathyroidectomy was performed on day 22 after denosumab administration.

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Reposted
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Bombshell US House investigative report confirms that almost everything the alternative media said about COVID origins, lockdowns, masks, vaccines and government overreach was TRUE
***
https://www.newstarget.com/2024-12-02-house-investigative-report-covid-lockdowns-pandemic-truth.html

***
So four years after the COVID pandemic nightmare was unleashed upon America by a cabal of junk science tyrants and power-hungry vax-o-crats, the US House has just released a damning, detailed investigative report that reveals the independent media was right all along.

COVID was engineered in a lab.

Mask demands and vaccine mandates were based on junk science.

Lockdowns were completely made up by self-appointed scientism authoritarians.

The government covered up the truth and pushed disinformation propaganda on purpose.

Dr. Fauci and others were guilty as hell.


So all the censorship by Big Tech turns out to be truly malicious and even harmful to the public. And the entire corporate media was nothing but an organized cabal of liars and profiteers... brought to you by Pfizer.


This investigative report reveals that COVID was a crime scene, and the government conspired with Big Tech and mainstream media to commit numerous crimes of cognitive assault (psyops), medial violence (vaccines) and hospital homicide against the American people.


So when do the mass arrests begin? (Don't hold your breath.)


Unfortunately, no one can bring back the estimated 1.2 million Americans who were killed by the jabs because they "believed the science."


Fortunately for you and I, we never believed the plandemic hype in the first place, and we most certainly didn't follow the herd into getting jabbed, masked and locked down.


It turns out that was a tremendously valuable choice of actions on our part.

Summary findings of the report
The official report, found here (PDF), is over 500 pages in length. I used our http://brighteon.ai LLM engine to distill it down to just the most important points, and that summary is shown below. Naturally, the report insists that Operation Warp Speed somehow saved millions of lives, which is of course nonsense. But this limited hangout of COVID truth is nevertheless rather valuable (and entirely unexpected from the US House).


After Action Review of the COVID-19 Pandemic: The Lessons Learned and a Path Forward


Chairman Brad Wenstrup's Final Report


December 4, 2024


The Select Subcommittee on the Coronavirus Pandemic has conducted an extensive review of the pandemic to identify key failures, successes, and lessons learned. This report aims to provide a roadmap for better preparation and response in future pandemics.

I. Introduction
Chairman Brad Wenstrup's tenure as head of the Select Subcommittee was marked by bipartisan cooperation and a commitment to transparency. Over five years, the subcommittee investigated numerous aspects of the pandemic, including its origins, government responses, vaccine development, and economic impact.

II. The Origins of COVID-19
The report highlights several critical findings regarding the origin of SARS-CoV-2:


Laboratory Accident Theory: There is strong evidence that SARS-CoV-2 emerged due to a laboratory accident at the Wuhan Institute of Virology (WIV).


EcoHealth Alliance and Dr. Peter Daszak: Both entities should never receive U.S. taxpayer funds again, given their questionable practices and lack of transparency.


Funding for Gain-of-Function Research: The U.S. National Institutes of Health (NIH) funded gain-of-function research at the WIV, which may have contributed to the pandemic's emergence.

III. Government Response Failures
The report identifies significant issues with government responses:


Fraud and Abuse: Rampant fraud, waste, and abuse plagued the COVID-19 response.


Pandemic-Era School Closures: These closures had a lasting negative impact on children’s education and mental health.


Misinformation Campaigns: Public health officials often mischaracterized scientific information, leading to public mistrust.

IV. The Role of Public Health Officials
The report criticizes the actions of key public health figures:


Dr. Anthony Fauci: Played a role in downplaying the lab leak theory and covered up facts.


Operation Warp Speed: While successful, it was marred by political interference and lack of transparency.

V. Economic Impact
The pandemic had severe economic consequences:


Business Closures: Mandatory lockdowns led to temporary and permanent closures, disproportionately affecting rural and low-income areas.


Unemployment: The pandemic exacerbated existing inequalities in the job market.


Supply Chain Issues: A lack of supply chain diversity hindered recovery efforts.

VI. Vaccine Development and Distribution
The report evaluates vaccine development:


Operation Warp Speed Success: Rapid vaccine development saved millions of lives, but was subject to political pressure.


Vaccine Mandates: Not supported by science and caused more harm than good, including disrupting military readiness.


Adverse Events Reporting System (VAERS): Inadequate and not transparent in reporting potential side effects.

VII. School Closures
The subcommittee found that pandemic-era school closures were not justified by scientific evidence:


Long-Term Impacts: Disrupted education, increased mental health issues, and worsened physical health.


American Federation of Teachers (AFT): Advocated for overly broad mitigation measures without sufficient scientific basis.

VIII. Accountability and Transparency
The report calls for greater accountability and transparency in government agencies:


Executive Branch Obstruction: The Biden administration obstructed investigations into the origins of COVID-19.


EcoHealth Alliance Misconduct: Engaged in obstruction, misleading public statements, and document tampering.

IX. Recommendations for Future Preparedness
The report recommends several steps to better prepare for future pandemics:


Independent Oversight: Establish independent oversight bodies to ensure transparency and accountability.


Enhanced Communication: Improve communication between scientists, policymakers, and the public.


Preparedness Plans: Develop comprehensive preparedness plans that include stockpiling medical supplies and diversifying supply chains.

Conclusion
Chairman Wenstrup emphasizes the need for a whole-of-America response managed by unbiased leaders who prioritize transparency, accountability, and integrity. The lessons learned from this pandemic highlight the importance of better preparation, more effective communication, and stronger oversight in future public health emergencies.


The full report includes detailed findings on each topic discussed and is intended to serve as a roadmap for addressing future pandemics. It underscores the critical role of trust, transparency, and bipartisan cooperation in managing such crises effectively.


Select Subcommittee on the Coronavirus Pandemic



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Note. Some Links locking editor display up, use GoDuck for your reference.
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Medical Disclaimers apply. The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Seek the assistance of health care professionals for any conditions. We are not doctors.
***Medical Disclaimers apply:: """"Forwarding, not a line by line endorsement of all items.""""" **
*****

Cinaciguat-induced dilatation of l-NAME-pretreated and ANG II-preconstricted arterioles was similar to controls without l-NAME treatment. Cinaciguat also induced dilatation in iodinated contrast medium treated AA. Furthermore, it dilated EA, but not AA, after hypoxia/reoxygenation. The results reveal an important role of the NO-sGC-cGMP system for renal dilatation and that EA have a more potent sGC activated dilatory system. Furthermore, AA seem to be more sensitive to hypoxia/reoxygenation than EA under these experimental conditions.In aircraft manufacturing, the vertical accuracy of connection holes is important indicator of the quality of holes making. Aircraft products have high requirements for the vertical accuracy of holes positions. When drilling and riveting are performed by an automatic robotic system, assembly errors, bumps, offsets and other adverse conditions, can affects the accuracy of manufacturing and detection, and in turn the fatigue performance of the entire structure. To solve this problem, we proposed a technology for detecting the normal-direction based on the adaptive alignment method, built a mathematical model for posture alignment, and studied the calibration method and mechanism of the detection device. Additionally, we investigated techniques for error compensation using an electronic theodolite and other devices when the adaptive method is used for detection. In verification experiments of the method, multiple sets of results demonstrated that the key technical indicators are as follows normal accuracy less then 0.5°, average deviation after correction =0.0667°. This method can effectively compensate the errors affecting hole making work in automated manufacturing, and further improve the positioning accuracy and normal-direction detection accuracy of the robot.Novel [Pd(o-CH2C6H4P(o-tolyl)2)(histidine)] (1) and [Pd(o-CH2C6H4P(o tolyl)2)(phenylalanine)] (2) P,C-orthopalladated complexes have been prepared and characterized by elemental analysis, IR and NMR spectroscopy. To study the stability of the compounds in biological media, the complexes were incubated in Tris buffer during 10 days. The absorbance of the compounds remained constant, which confirmed the stability of the complexes in biological media. UV-Vis absorption spectrophotometry, fluorescence spectroscopy and viscosity studies were used to investigate the binding of the complexes with native calf thymus DNA (CT-DNA). These methods along with competitive binding of methylene blue (MB) DNA show that the complexes interact with DNA via groove mode. The UV-Vis absorption spectrophotometry of BSA with complexes has shown an α-helix perturbation induced by a particular interaction between the metal complexes and BSA. In addition, the fluorescence quenching mechanism of BSA with the complexes is a static process, according to the fluorescence spectrometry of bovine serum albumin (BSA). The experimental results of site competitive replacement with specific site markers are clear indications that the complexes bind to site I of BSA. Furthermore, both complexes showed significant selective cytotoxic activity against melanoma B16F0 and colon carcinoma C26 cancer cells as well as normal fibroblast NIH cell line. Ultimately, the binding of Pd(II) complexes to DNA and BSA was verified by molecular docking experiment. Communicated by Ramaswamy H. Sarma.Neanderthal is the quintessential scientific Other. In the late nineteenth century gentlemen-scientists, including business magnates, investment bankers and lawmakers with interest in questions of human and human societal development, framed Europe's Neanderthal and South Asia's indigenous Negritos as close evolutionary kin. Simultaneously, they explained Neanderthal's extinction as the consequence of an inherent backwardness in the face of fair-skinned, steadily-progressing newcomers to ancient Europe who behaved in ways associated with capitalism. This racialization and economization of Neanderthal helped bring meaning and actual legal reality to Negritos via the British Raj's official 'schedules of backward castes and tribes'. It also helped justify the Raj's initiation of market-oriented reforms in order to break a developmental equilibrium deemed created when fair-skinned newcomers to ancient South Asia enslaved Negritos in an enduring caste system. Neanderthal was integral to the scientism behind the British construction of caste, and contributed to India's becoming a principal 'Third World' target of Western structural adjustment policies as continuation of South Asia's 'evolution assistance'.For about half a century, the pharmacology of electroneutral cation-chloride cotransporters has been dominated by a few drugs that are widely used in clinical medicine. Because these diuretic drugs are so good at what they do, there has been little incentive in expanding their pharmacology. The increasing realization that cation-chloride cotransporters are involved in many other key physiological processes and the knowledge that different tissues express homologous proteins with matching transport functions have rekindled interest in drug discovery. https://www.selleckchem.com/products/hc-7366.html This review summarizes the methods available to assess the function of these transporters and describe the multiple efforts that have made to identify new compounds. We describe multiple screens targeting KCC2 function and one screen designed to find compounds that discriminate between NKCC1 and NKCC2. Two of the KCC2 screens identified new inhibitors that are 3-4 orders of magnitude more potent than furosemide. Additional screens identified compounds that purportedly increase cell surface expression of the cotransporter, as well as several FDA-approved drugs that increase KCC2 transcription and expression. The technical details of each screen biased them toward specific processes in the life cycle of the transporter, making these efforts independent and complementary. In addition, each drug discovery effort contributes to our understanding of the biology of the cotransporters.Swelling-activated volume-regulated anion channels (VRACs) are heteromeric channels comprising LRRC8A and at least one other LRRC8 paralog. Cryoelectron microscopy (cryo-EM) structures of nonnative LRRC8A and LRRC8D homohexamers have been described. We demonstrate here that LRRC8A homohexamers poorly recapitulate VRAC functional properties. Unlike VRACs, LRRC8A channels heterologously expressed in Lrr8c-/- HCT116 cells are poorly activated by low intracellular ionic strength (µ) and insensitive to cell swelling with normal µ. Combining low µ with swelling modestly activates LRRC8A, allowing characterization of pore properties. VRACs are strongly inhibited by 10 µM 4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]butanoic acid (DCPIB) in a voltage-independent manner. In contrast, DCPIB block of LRRC8A is weak and voltage sensitive. Cryo-EM structures indicate that DCPIB block is dependent on arginine 103. Consistent with this, LRRC8A R103F mutants are insensitive to DCPIB. However, an LRRC8 chimeric channel in which R103 is replaced by a leucine at the homologous position is inhibited ∼90% by 10 µM DCPIB in a voltage-independent manner.

This article maintains that via the current form of evidence-based medicine, scientism (a pseudo-religious belief in science that is itself not scientific) has been allowed to encroach into medicine. By setting out the philosophical limits of what it is science can do, the effects of this encroachment are discussed in terms of upsetting the balance between the necessarily conflicting art AND science of medicine. In this context, one effect of the Covid-19 pandemic might be to act as a timely reminder - as if it was needed - of the importance of the Hippocratic Oath, which is and always has been the soul of medicine.
Low bone mineral density (BMD) represents a major risk factor for bone fractures in patients with chronic kidney disease (CKD) as well as after kidney transplantation. However, modalities to solidly predict patients at fracture risk are yet to be defined. Better understanding of bone turnover biomarkers (BTMs) may close this diagnostic gap. This study strives to correlate BTMs to BMD in kidney transplant recipients.

Changes in BTMs - procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BSAP), β-isomer of the C-terminal telopeptide of type I collagen, and urine deoxypyridinoline/Cr - at the time of transplant and 3 months were correlated to changes in BMD measured by dual-energy X-ray absorptiometry at the time of transplant, 6, and 12 months, respectively. Half of the collective was treated with denosumab twice yearly in addition to the standard treatment with calcium and vitamin D.

Changes in bone formation markers BSAP and P1NP within 3 months showed a significant negative correlation to changes in BMD at the hip within 6 months in denosumab-naïve patients. This correlation was abrogated by denosumab treatment.

Changes in BSAP and P1NP showed promise in short-term prediction of BMD. We suggest further trials expanding on the knowledge of these BTMs with assessment of fracture risk, sequential measurements of BTMs within the first 6 months, and the additional use of computed tomography to assess BMD.
Changes in BSAP and P1NP showed promise in short-term prediction of BMD. We suggest further trials expanding on the knowledge of these BTMs with assessment of fracture risk, sequential measurements of BTMs within the first 6 months, and the additional use of computed tomography to assess BMD.
Angiotensin-converting enzyme inhibitors (ACEI) combined with mineralocorticoid receptor antagonists were found to have a beneficial effect on patients with chronic kidney disease.

The aim of our clinical trial was to compare the antialbuminuric effect of ramipril monotherapy, eplerenone monotherapy and eplerenone/ramipril combination therapy in patients with stage 1 hypertension and type 2 diabetes mellitus.

In a single-blind, randomized clinical trial, 75 hypertensive patients (stage 1 hypertension) with type 2 diabetes mellitus and microalbuminuria were randomized in a 111 ratio to 1 of 3 groups ramipril 10 mg monotherapy (25 patients), eplerenone 50 mg monotherapy (25 patients) and combination therapy of eplerenone/ramipril 50/10 mg (25 patients) through a randomized clinical trial. Blood pressure, urinary albumin/creatinine ratio (UACR), serum creatinine, estimated glomerular filtration rate (eGFR) and serum K level were measured before randomization and after 24 weeks.

Ramipril and eplerenone monotherapy showed a significant lowering of UACR compared with baseline levels (p ≤ 0.0001). The eplerenone/ramipril combination group showed a more significant reduction of UACR compared with the ramipril and eplerenone monotherapy groups (p = 0.0001). There was a more significant lowering of systolic blood pressure in the combination group (p < 0.0001). A nonsignificant change of serum potassium level, serum creatinine and eGFR was found among the 3 groups.

Addition of eplerenone to ACEI shows an added antialbuminuric effect without significant change of the serum K level compared with eplerenone or ACEI.
Addition of eplerenone to ACEI shows an added antialbuminuric effect without significant change of the serum K level compared with eplerenone or ACEI.
Primary hyperparathyroidism (PHPT) is rare and usually symptomatic in children. There is no approved medication to lower serum calcium levels in this patient group. Denosumab is used in adult patients with osteoporosis and hyperparathyroidism. To our knowledge, only 1 case of denosumab treatment in a child with severe PHPT has been reported to date.

A 16-year-old female was referred to our clinic with symptoms including pathologic fractures, nausea, emesis, and progressive weight loss. At admission, her serum total calcium was 4.17 mmol/L (reference range 2.15-2.55), parathyroid hormone 2,151 pg/mL (15-65), and phosphate 1.07 mmol/L (1.45-1.78). Due to potentially life-threatening hypercalcemia, denosumab 60 mg subcutaneously was administered after obtaining informed consent. Serum calcium levels were reduced within 12 h of injection and the patient's condition rapidly improved, which allowed genetic testing to be done prior to surgery. A heterozygous mutation in the CDC73 gene was revealed, and a parathyroidectomy was performed on day 22 after denosumab administration. Morphological examination revealed solitary parathyroid adenoma. After surgery, hypocalcemia developed requiring high doses of alfacalcidol and calcium supplements.

Our case supports the previous observations in adults that denosumab can be safely and effectively used as a preoperative treatment in patients with PHPT and severe hypercalcemia and shows that it may be used in pediatric patients.
Our case supports the previous observations in adults that denosumab can be safely and effectively used as a preoperative treatment in patients with PHPT and severe hypercalcemia and shows that it may be used in pediatric patients.
This study was conducted to investigate the effect of Dalk and Ghamz on pain and disability in patients with nonspecific chronic neck pain.

This study was conducted on 37 patients with nonspecific chronic neck pain. Dalk and Ghamz massage were performed once a week for four sessions and the neck pain was evaluated by visual analog scale (VAS). In addition, the neck disability index (NDI) was used to assess the disability related to neck disorder. Data were analyzed with the SPSS software.

Among 37 patients, 85.5% were female and 13.5% were male. A significant decrease in VAS score was observed during the study (F = 57.77, p < 0.001). The NDI score decreased from 27.27 ± 5.83 to 19.08 ± 7.71 (p < 0.001).

Dalk and Ghamz massage in patients with nonspecific neck pain could reduce pain and disability.
Dalk and Ghamz massage in patients with nonspecific neck pain could reduce pain and disability.
Small-intestinal neuroendocrine tumors (SI-NET) are situated preferentially within the ileum. The aim was to describe a potential difference in location between unifocal and multiple ileal-NET.

Between December 2010 and December 2019, all consecutive patients who underwent resection in our European Neuroendocrine Tumor Society Center of Excellence, of at least one non-duodenal SI-NET, were retrospectively included. The main objective was to prove that multiple ileal-NET were mostly located on the left side of the superior mesenteric artery (SMA) axis (defined as 40cm from the ileocecal valve), and unifocal ones on the right-side.

Ninety-four patients were included, six with unifocal jejunal-NET located 35cm (range, 10-60) from the duodenojejunal angle (DJA), 44 (47%) with unifocal ileal-NET, and 44 (47%) with multiple ileal-NET. The median number of tumors in multiple ileal-NET was 7 (range, 2-95), within a median small bowel segment of 105cm (10-240). The median length between the proximal tumor and the DJA was 428cm (300-635) and 540cm (350-725) for the distal one; 40 (91%) of them were located on the left side of the SMA axis. In contrast, unifocal ileal-NET were located at a median distance of 577cm (305-820) from the DJA (p<0.001, compared to multiple ileal-NET); 30 (68%) of them were on the right side of the SMA axis (p<0.001).

Multiple ileal-NET are mostly located on the left side of the SMA axis. Further studies are warranted to explore the embryological origin of unifocal versus multiple ileal-NET.
Multiple ileal-NET are mostly located on the left side of the SMA axis. Further studies are warranted to explore the embryological origin of unifocal versus multiple ileal-NET.
It remains unclear whether TERT promoter mutation (TERT C228T) in serum cell-free DNA (cfDNA) is useful for the diagnosis of hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD).

In this retrospective study, we analyzed the relationships between TERT C228T in serum cfDNA and levels of AFP and PIVKAII in 57 Japanese patients with histopathologically confirmed NAFLD background, consisting of 36 patients with HCC and 21 without HCC. We also examined the liver-related survival rate and HCC recurrence rate after the initial treatment for HCC. TERT C228T was detected using a highly sensitive method based on wild-type blocking PCR (detection limit in excess of 0.7% mutant-type DNA).

In all of the 57 patients, multivariate analysis identified TERT C228T positive as significant determinant of primary HCC. https://www.selleckchem.com/products/caerulein.html In the 36 patients with HCC, the percentage of patients positive for TERT C228T was 63.9%. The percentage of patients positive for TERT C228T with normal AFP and PIVKAII was 35.3%. The positive predictive value and specificity for prediction of BCLC stage 0 or A were both high. In 6 patients, TERT C228T was repeatedly negative during follow-up but became positive at the time of HCC diagnosis. Four patients who underwent HCC surgical resection had well-differentiated solitary HCC measuring <30 mm, and all were TERT C228T positive with normal AFP and PIVKAII. TERT C228T status had no influence on the cumulative liver-related survival rate and HCC recurrence rate.

Our results highlight the superiority of TERT C228T in serum cfDNA compared with AFP and PIVKAII in the early diagnosis of primary HCC in NAFLD patients.
Our results highlight the superiority of TERT C228T in serum cfDNA compared with AFP and PIVKAII in the early diagnosis of primary HCC in NAFLD patients.
Protein-energy malnutrition and cardiovascular (CV) disease predisposes patients with end-stage renal disease (ESRD) on dialysis to a high risk of early death, but the prognostic value of prealbumin (PAB) and echocardiographic indices in ESRD patients treated with maintenance peritoneal dialysis (PD) remains unclear.

A total of 211 PD patients (mean age 49.2 ± 15.4 years, 51.7% male) were prospectively studied. PAB and echocardiography parameters were recorded at baseline. Follow-up (mean ± SD 33.7 ± 17.3 months) was conducted based on hospital records, clinic visits, and telephone reviews, to record death events and their causes.

In the Cox proportional hazards model, PAB and the echocardiographic parameters listed below were found to be optimal predictors of all-cause mortality PAB (p = 0.003), aortic root diameter (ARD) (p = 0.004), interventricular septum end-diastolic thickness (IVSd) (p = 0.046), and left ventricular end-diastolic diameter index (LVEDDI) (p = 0.029). Of the above-mentioned factors, PAB (p = 0.