The effect of supplemental arginine on the gut microbial homeostasis of broilers during sub-clinical necrotic enteritis challenge.

Necrotic enteritis (NE) is an enteric disease of poultry that alters the structure of the gut microbial community causing dysbiosis. This 28 day experiment investigated the effects of 125% and 135% arginine diets on the gut microbial diversity and composition of broilers during a subclinical NE challenge. One hundred and twenty one-day-old chicks were randomly allocated to 4 treatments with six replicates each- Uninfected + Basal, NE + Basal, NE + Arg 125%, and NE + Arg 135% diet groups. NE was induced by inoculating 1 × 104 E. maxima sporulated oocysts on day 14 and 1 × 108 CFU C. perfringens on days 19, 20, and 21 of age. The NE challenge significantly decreased the number of observed amplicon sequence variants (p = 0.03), the abundance of the phylum Firmicutes (p < 0.01), and the species Mediterraneibacter cottocaccae (p = 0.01) in the ceca of birds on day 21. The NE challenge significantly increased the Bray-Curtis index (p < 0.01), and the abundance of the phylum Bacteroidota (p < 0.01), family Odoribacteraceae (p < 0.01), genus Odoribacter (p < 0.01), and species O. splanchnicus (p = 0.01) on day 21. During NE, the 125% arginine diet restored the abundance of the phylum Bacteroidota (p = 0.03), family Odoribacteraceae (p = 0.03) and Oscillospiraceae (p = 0.03), genus Odoribacter (p = 0.03), and species O. splanchnicus (p = 0.03) and M. cottocaccae (p < 0.01) on day 21. The 135% arginine diet effectively restored the loss in alpha diversity (p = 0.01) caused by NE, the abundance of the phylum Firmicutes (p = 0.01) and Bacteroidota (p < 0.01), family Oscillospiraceae (p = 0.03) and Odoribacteraceae (p < 0.01), genus Odoribacter (p < 0.01), and species O. splanchnicus (p < 0.01) and M. cottocaccae (p < 0.01) on day 21. On day 28, the treatments had a significant effect on the cecal propionate (p = 0.01), butyrate (p = 0.04), and total SCFA (p = 0.04) concentrations. In conclusion, the 125% and 135% arginine diets restored gut microbial composition during a subclinical NE challenge, but not the cecal SCFA profile. Hence, arginine in combination with other feed additives could be used in restoring gut microbial homeostasis during NE in poultry.

Takayasu arteritis and interstitial lung disease: a case report and literature review.

Introduction and importance: Although pulmonary artery involvement is well recognized, the incidence of interstitial lung disease (ILD) with Takayasu arteritis is very rare. The pathophysiology of ILD in Takayasu is still incompletely understood, in contrast to several studies establishing the relationship between ANCA-associated vasculitis and ILD. The management of this patient involved a multidisciplinary approach with long-term follow-up. Case presentation: The authors present a case of HRCT-proven interstitial lung disease in a patient with Takayasu arteritis and heart failure. The patient was on long-term corticosteroids on and off for several years and recently developed progressive dyspnea with a dry cough. After reviewing her history and physical examination, pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) were performed, and interstitial lung disease was diagnosed. The patient was managed by a team of pulmonologists, rheumatologists, and cardiologists and gradually improved after adjustment of medications, including corticosteroids and mycofenolate, and via long-term oxygen therapy. Clinical discussion: Takayasu arteritis is a rare form of systemic vasculitis that can involve the pulmonary vasculature, such vasculitis with associated parenchymal involvement is rare. ILDs have been demonstrated with ANCA-associated vasculitis; however, whether the pathophysiology applies to Takayasu is unknown. Since Takayasu can be debilitating to the patient, the association of ILDs can have further prognostic implications. Given that no established guidelines exist to address this association, management is based on clinical expertise. Conclusion: The authors report a case of Takayasu arteritis and associated ILD and its pharmacological management. Takayasu arteritis is a very uncommon type of vasculitis, and pulmonary parenchymal involvement further contributes to this case's rarity. As the management of Takayasu arteritis alone is cumbersome, the addition of another significant comorbidity, such as ILD, can pose several threats to the patient. Given the rarity of this association, no established guidelines exist, making clinical expertise crucial for managing such patients. Further research is needed to explore the underlying mechanisms and develop evidence-based treatment strategies for this rare combination.

Multi-organ transcriptome atlas of a mouse model of relative energy deficiency in sport.

Insufficient energy intake to meet energy expenditure demands of physical activity can result in systemic neuroendocrine and metabolic abnormalities in activity-dependent anorexia and relative energy deficiency in sport (REDs). REDs affects >40% of athletes, yet the lack of underlying molecular changes has been a hurdle to have a better understanding of REDs and its treatment. To assess the molecular changes in response to energy deficiency, we implemented the "exercise-for-food" paradigm, in which food reward size is determined by wheel-running activity. By using this paradigm, we replicated several aspects of REDs in female and male mice with high physical activity and gradually reduced food intake, which results in weight loss, compromised bone health, organ-specific mass changes, and altered rest-activity patterns. By integrating transcriptomics of 19 different organs, we provide a comprehensive dataset that will guide future understanding of REDs and may provide important implications for metabolic health and (athletic) performance.

Challenges, Barriers, and Facilitators in Telemedicine Implementation in India: A Scoping Review.

Telemedicine has revolutionized healthcare access by breaking geographical barriers and facilitating remote consultations. The eSanjeevani platform has been pivotal in India, especially during the COVID-19 pandemic. Despite its benefits, implementing telemedicine faces various challenges and barriers. This scoping review aims to identify these challenges, barriers, and facilitators in the Indian context. This review follows the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) guidelines. A comprehensive literature search was conducted using PubMed and Google Scholar to identify studies published between January 2019 and January 2024. Studies on telemedicine adoption, barriers, and facilitators in India were included. Data were extracted and synthesized from 26 quantitative, qualitative, and mixed-methods research studies. Individual-level challenges include limited digital literacy, particularly among older adults and those in rural areas, and health literacy issues. Barriers such as limited smartphone access, unreliable internet connectivity, and socio-cultural preferences for in-person consultations were identified. Facilitators at this level include family involvement, training programs, and community outreach. Provider-level challenges involve a lack of training and concerns about care quality, while barriers include insufficient infrastructure and medico-legal concerns. Facilitators include ongoing training, clear guidelines, and user-friendly telehealth systems. System-level challenges include integrating telemedicine into existing infrastructure and ensuring data security. Barriers include inadequate funding and resistance to change, while facilitators include policy support, investment in infrastructure, and collaborative efforts. Telemedicine holds great potential to enhance remote healthcare access in India, but its successful implementation requires addressing significant challenges and barriers. Strengthening digital infrastructure, enhancing digital literacy, standardizing protocols, and developing clear regulatory frameworks are essential. Collaborative efforts and tailored approaches that respect local cultures can further facilitate telemedicine adoption. Continuous research and public awareness campaigns are necessary to ensure telemedicine's sustainable and effective use in India.

A solution-processable benzothiazole-substituted formazanate zinc(II) complex designed for a robust resistive memory device.

A novel mononuclear bis(formazanate)zinc complex (1) based on a redox-active 1-(benzothiazol-2-yl)-5-(2-benzoyl-4-chlorophenyl)-3-phenyl formazan ligand has been synthesized and characterized. Complex 1 was prepared by reacting one equivalent of Zn(OCOCH3)·2H2O with two equivalents of the corresponding formazan derivative. X-ray crystallography was employed to ascertain the solid-state structure of compound 1, and the analysis revealed a distorted octahedral geometry for the complex where the symmetrical ligands exhibit a preference for coordinating with the zinc center in the 'open' form, generating five-membered chelate rings. Moreover, cyclic voltammetry analysis reveals that complex 1 exhibits the capacity for electrochemical reduction as well as oxidation, resulting in the formation of radical anionic (L2Zn-) and dianionic (L2Zn2-) states as well as the oxidation state of 1. Additionally, the developed solution-processable complex 1 was employed as the fundamental building material for resistive switching memory applications. The [FTO/ZnIIL2(1)]/Ag RRAM device demonstrates exceptional resistive memory switching properties, with a substantial ION/IOFF ratio (103), low operational VSET and VRESET (0.9 V and -0.75 V) voltages, excellent endurance stability (100 cycles), and decent retention time (more than 2000 seconds). The findings presented in this study underscore the importance of redox-active formazanate metal complexes for creating promising memory storage devices.

Time Lens Photon Doppler Velocimetry (TL-PDV) for extreme measurements.

Capturing extreme surface velocities with  >50 km/s dynamic range, which arise in shock physics such as inertial confinement fusion (ICF), is beyond the reach of conventional photon Doppler velocimetry (PDV) systems due to the need for extremely large electrical bandwidth under such conditions. The recent ignition in ICF calls for new velocimetry that can measure velocities exceeding 100 km/s. Time lens PDV (TL-PDV) is a solution where the high frequency beat signal from a conventional PDV system is periodically temporally magnified in the optical domain using a time lens. Here we experimentally demonstrate TL-PDV for the first time, validate the performance over a 74 km/s velocity range with high accuracy using a temporal magnification factor of 7.6, and verify excellent agreement with conventional PDV for laser driven micro-flyer experiments. TL-PDV currently provides the largest velocity dynamic range among PDV systems and is scalable to even higher velocities, which makes it an ideal candidate for material characterization under the most extreme conditions such as optimizing fuel efficiency in ICF experiments.

Correction: Raha et al. Lipid-Lowering Drug Gemfibrozil Protects Mice from Tay-Sachs Disease via Peroxisome Proliferator-Activated Receptor α. Cells 2023, 12, 2791.

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Evaluation and comparison of autologous particulate dentin with demineralized freeze dried bone allograft in ridge preservation procedures - a prospective clinical study.

OBJECTIVES: To compare effectiveness of Autologous Particulate Dentin (APD) with Demineralized Freeze-Dried Bone Allograft (DFDBA) in ridge preservation, using radiographic and clinical parameters. MATERIALS AND METHODS: Thirty subjects with indication of mandibular posterior teeth extraction were randomly assigned to either test or control group. After atraumatic extraction, ridge preservation was performed using APD or DFDBA mixed with i-PRF in test and control groups respectively. Both groups had sockets sealed with A-PRF membrane. Clinical parameters (plaque, gingival and healing indices) and radiographic parameters (vertical ridge height, horizontal ridge width) were assessed at baseline and 6 months using CBCT. Statistical analysis was performed using an independent t-test to compare clinical and radiographic parameters between the groups. RESULTS: Both groups had significant decreases in ridge dimensions over 6 months (p < 0.001). The test group showed less reduction in ridge dimensions than control group at 6 months (p < 0.001). Mean change in vertical height was not significant (1.37 ± 1.32, 1.7311 ± 0.563), but in horizontal ridge width (1.3120 ± 1.13, 1.8093 ± 1.16) was significantly different between test and control groups respectively. There was no statistical difference in clinical parameters between the groups at 6 months (p > 0.001). CONCLUSIONS: APD grafts resulted in significant improvements in radiographic parameters, specifically in vertical ridge height and horizontal ridge width, compared to DFDBA group. CLINICAL RELEVANCE: Autologous particulate dentin is a promising, versatile substitute for regenerative procedures. While more research on its long-term efficacy and application is needed, current evidence suggests it could significantly improve patient care and outcomes.

Herbal Insights: Exploring the Therapeutic Potential of Indian Dietary Herbs in Diabetic Cardiomyopathy Management.

BACKGROUND: Diabetic Cardiomyopathy (DCM) poses a substantial healthcare challenge, necessitating innovative therapeutic strategies. This review delves into the evolving role of traditional Indian dietary herbs in managing DCM, aiming to shed light on their potential contributions. METHODS: A comprehensive examination of the existing body of literature was conducted, synthesizing data from studies exploring the effects of various Indian dietary herbs on DCM. Molecular mechanisms, clinical outcomes, and safety profiles were scrutinized to establish a holistic perspective on their therapeutic potential. RESULTS: The review illuminates the multifaceted benefits of Indian dietary herbs in DCM management. These herbs have demonstrated efficacy in mitigating cardiac dysfunction, reducing oxidative stress, and modulating inflammatory responses. Molecular insights highlight their role in the intricate signaling pathways underlying DCM. Furthermore, their safety profiles render them promising candidates for adjunct therapy. CONCLUSION: Indian dietary herbs emerge as promising allies in the battle against DCM, offering a holistic approach to the management of this intricate condition. Their cardioprotective effects, coupled with their ability to address the underlying molecular mechanisms, herald a new era in DCM therapy. This review underscores the need for further research to harness the potential of these herbs fully and provides a beacon of hope for individuals affected by DCM.

Event-Triggered Reduced-Order Filtering for Continuous Semi-Markov Jump Systems With Imperfect Measurements.

This article conducts the issue of event-triggered reduced-order filtering for continuous-time semi-Markov jump systems with imperfect measurements as well as randomly occurring uncertainties (ROUs). Specifically, the sojourn-time-dependent transition probability matrix (TPM) is presumed to be polytopic and a quantizer is introduced to quantize output signals aiming to reflect the reality. Both ROUs and sensor failures are generated by individual random variables belonging to be mutually independent Bernoulli-distributed white sequences. First, sufficient conditions for the existence of the event-triggered reduced-order filter are obtained by utilizing the dissipativity-based technique to ensure the asymptotical stability with a strictly dissipative performance of the filtering error system. The time-varying TPM is then fractionalized, which enhances the results as stated. Furthermore, the required reduced-order filter parameters are obtained by introducing slack symmetric matrix as well as cone complementarity linearization algorithm. The effectiveness of the suggested event-triggered reduced-order filter design method is shown through simulation results.

Effects of Local Wound Infiltration Post-Mastectomy Using Bupivacaine Alone, Bupivacaine With Ketamine, and Bupivacaine With Dexmedetomidine: A Randomized Double-Blind Study.

Background and aim While the infiltration of surgical incisions with local anesthetics is not a new practice, it remains a crucial component of contemporary multimodal analgesia protocols. This study aimed to evaluate the efficacy and safety of using adjuvants in combination with local anesthetic wound infiltration for pain management in patients undergoing mastectomy surgery. Methods Eighty-one patients aged 18-60 years, classified as American Society of Anesthesiologists (ASA) grade I or II, were scheduled for unilateral mastectomy and randomly assigned to three groups of 27 each. The groups were designated as Group C (bupivacaine alone), Group D (bupivacaine with dexmedetomidine), and Group K (bupivacaine with ketamine). Group C received 0.25% bupivacaine alone, Group D received 0.25% bupivacaine with 1 mcg/kg dexmedetomidine, and Group K received 0.25% bupivacaine with 1 mg/kg ketamine. The time to achieve a Visual Analogue Scale (VAS) score of 3 following local wound infiltration was recorded for each group. Additionally, total postoperative fentanyl intake during the first 24 hours, as measured by the patient-controlled analgesia (PCA) pump, was compared among the groups. Sedation levels were assessed using the Ramsay Sedation Scale (RSS). Data were analyzed using the Chi-Square test and one-way ANOVA in IBM SPSS Statistics for Windows, Version 28.0 (Released 2021; IBM Corp., Armonk, NY, USA). Results Demographic factors were similar across the three groups. Analysis of the VAS scores revealed that the ketamine group provided better postoperative pain control than the dexmedetomidine group (p < 0.001). Groups D (71.72 ± 71.73) and K (3.53 ± 13.42) had significantly lower 24-hour fentanyl intake (in mcg) compared to Group C (the control group), as measured by PCA. Additionally, Group C had a significantly lower RSS at the sixth hour (p = 0.003) compared to both Groups D and K. Conclusion Ketamine, when used as an adjuvant to bupivacaine for local infiltration, enhances the effectiveness and prolongs postoperative analgesia more effectively than dexmedetomidine in patients undergoing mastectomy.

High-throughput quantification of quasistatic, dynamic and spall strength of materials across 10 orders of strain rates.

The response of metals and their microstructures under extreme dynamic conditions can be markedly different from that under quasistatic conditions. Traditionally, high strain rates and shock stresses are achieved using cumbersome and expensive methods such as the Kolsky bar or large spall experiments. These methods are low throughput and do not facilitate high-fidelity microstructure-property linkages. In this work, we combine two powerful small-scale testing methods, custom nanoindentation, and laser-driven microflyer (LDMF) shock, to measure the dynamic and spall strength of metals. The nanoindentation system is configured to test samples from quasistatic to dynamic strain-rate regimes. The LDMF shock system can test samples through impact loading, triggering spall failure. The model material used for testing is magnesium alloys, which are lightweight, possess high-specific strengths, and have historically been challenging to design and strengthen due to their mechanical anisotropy. We adopt two distinct microstructures, solutionized (no precipitates) and peak-aged (with precipitates) to demonstrate interesting upticks in strain-rate sensitivity and evolution of dynamic strength. At high shock-loading rates, we unravel an interesting paradigm where the spall strength vs. strain rate of these materials converges, but the failure mechanisms are markedly different. Peak aging, considered to be a standard method to strengthen metallic alloys, causes catastrophic failure, faring much worse than solutionized alloys. Our high-throughput testing framework not only quantifies strength but also teases out unexplored failure mechanisms at extreme strain rates, providing valuable insights for the rapid design and improvement of materials for extreme environments.

Scanning electron microscopic analysis of 5% glycolic acid as a novel alternative to 17% ethylenediaminetetraacetic acid in root biomodification: An in vitro study.

Background: Nonsurgical periodontal therapy results in the formation of a smear layer which inhibits tissue regeneration. Root biomodification (RB) using various agents has been tried for the enhancement of new attachment formation. However, no substantial therapeutic advantages of currently available root conditioning agents have been reported emphasizing the need for additional biologically acceptable agents. Glycolic acid (GA) due to its antimicrobial nature and ability of initiation and proliferation of fibroblasts may potentially modify root surface enabling regeneration. Materials and Methods: Eighty specimens from 40 single-rooted teeth were treated with 17% ethylenediaminetetraacetic acid (EDTA) and 5% GA and scanning electron microscopy analysis was done. The micrographs were examined for the evaluation of smear layer removal, total number of dentinal tubules, total number of patent dentinal tubules, mean diameter and surface area of dentinal tubules, and dentin erosion. Statistical analysis was done using unpaired t-test for intergroup comparison. Results: The efficacy of smear layer removal (P = 0.01) and dentin erosion (P = 0.042) was significantly better in the GA group. Both the groups showed no difference in dentinal tubule-related parameters. Conclusion: GA showed improved RB with greater smear layer removal and lesser dentin erosion, indicating its use as a potent alternative to the conventional EDTA root conditioning.

Bioflavonoid combination attenuates diabetes-induced nephropathy in rats via modulation of MMP-9/TIMP-1, TGF-ß, and GLUT-4-associated pathways.

Background: Diabetic nephropathy represents a significant microvascular complication of diabetes, characterized by extracellular matrix accumulation, loss of cell-cell junctions, microalbuminuria, and diminished creatinine clearance. Despite its prevalence, therapeutic options dedicated to this condition are currently lacking. Natural products like bioflavonoids have garnered attention for their potential therapeutic benefits. The present study aimed to evaluate the efficacy of a bioflavonoid combination, including ginger extract, soy extract, and hesperetin, in a diabetic rat model. Methods: Diabetes was initiated in the rat pups via intraperitoneal injection of streptozotocin on the fifth postnatal day. After six weeks, rats exhibiting blood sugar levels exceeding 160 mg/dL were allocated into diabetic control and treatment groups, with eight animals each. A subset of rats received citrate buffer as a control. The treatment group received the bioflavonoid combination orally for twenty-four weeks. Various parameters, including glycemic levels, urinary parameters, antioxidant status, mRNA expression via Western blot, gel zymography, and immunohistochemistry, were assessed at the study's conclusion. Results: The bioflavonoid combination demonstrated significant reductions in hyperglycemia and various urinary parameters compared to controls. Notably, it modulated MMP-9/TIMP-1 expression, upregulated GLUT-4, and downregulated TGF-ß. Additionally, the combination enhanced total antioxidant capacity, indicating potential antioxidative benefits. Conclusions: This study highlights the therapeutic potential of a bioflavonoid combination (ginger extract, soy extract, and hesperetin) in improving renal function in diabetic nephropathy. By modulating key factors such as MMP-9/TIMP-1, TGF-ß, and GLUT-4, this combination presents a promising avenue for further exploration in managing diabetic nephropathy. These findings underscore the importance of natural products as potential therapeutic agents in addressing diabetic complications.

Neoadjuvant T-DM1 for HER2-positive breast cancer used as a bridging strategy during COVID-19 pandemic: lessons learned-a case series.

Background: Coronavirus disease 19 (COVID-19) has played a pivotal role in changing medical care around the world. During the pandemic, the operating rooms (ORs) were closed to elective surgery. Since breast cancer surgery is not regarded as an emergent procedure, there was an adoption of treatment regimen modification due to delays in treatment. Therefore, a decision was made to bridge early-stage HER2-positive breast cancer patients with neoadjuvant treatment to postpone surgery. Consequently, to reduce the frequency of dosing and the number of visits, as well as avoid steroid premedication, these patients were treated with ado-trastuzumab emtansine (T-DM1) every three weeks as opposed to weekly taxol and herceptin (TH). Case Description: Five patients with early-stage HER2-positive cancer were treated with neoadjuvant T-DM1 3.6 mg/kg IV every three weeks. Three of the five patients developed cancer progression identified by their physical exam and/or imaging. T-DM1 was discontinued, and all three patients underwent immediate surgery. The remaining two patients, 4 and 5, had a complete and partial pathological response, respectively. All five patients received adjuvant therapy after surgery, and currently, none of these patients show evidence of disease on follow-up. Conclusions: Our findings underscore the obstacles and treatment challenges encountered during the COVID-19 pandemic while preventing the spread of the virus and cancer progression. Furthermore, the use of T-DM1 for neoadjuvant treatment remains controversial, particularly when T-DM1 is used as a bridge to surgery during critical times. Perhaps better patient selection or a different drug regimen could have resulted in a better outcome in our study.

Improvement of Cardiac Function and Subcellular Defects Due to Chronic Diabetes upon Treatment with Sarpogrelate.

In order to investigate the subcellular mechanisms underlying the beneficial effects of sarpogrelate-a 5-HT2A receptor antagonist-on diabetic cardiomyopathy, diabetes was induced in rats by injecting streptozotocin (65 mg/kg). Diabetic animals were treated with or without sarpogrelate (5 mg/kg daily) for 6 weeks; diabetic animals were also treated with insulin (10 units/kg daily) for comparison. Elevated plasma levels of glucose and lipids, depressed insulin levels, hemodynamic alterations and cardiac dysfunction in diabetic animals were partially or fully attenuated by sarpogrelate or insulin treatment. Diabetes-induced changes in myocardial high-energy phosphate stores, as well as depressed mitochondrial oxidative phosphorylation and Ca2+-uptake activities, were significantly prevented by these treatments. Reductions in sarcolemma Na+-K+ ATPase, Na+-Ca2+ exchange, Ca2+-channel density and Ca2+-uptake activities were also attenuated by treatments with sarpogrelate and insulin. In addition, decreases in diabetes-induced sarcoplasmic reticulum Ca2+-uptake, Ca2+-release and Ca2+-stimulated ATPase activities, myofibrillar Mg2+-ATPase and Ca2+-stimulated ATPase activities, and myosin Mg2+-ATPase and Ca2+-ATPase activities were fully or partially prevented by sarpogrelate and insulin treatments. Marked alterations in different biomarkers of oxidative stress, such as malondialdehyde, superoxide dismutase and glutathione peroxidase, in diabetic hearts were also attenuated by treating the animals with sarpogrelate or insulin. These observations suggest that therapy with sarpogrelate, like that with insulin, may improve cardiac function by preventing subcellular and metabolic defects as a consequence of a reduction in oxidative stress.

Retrospective analysis of neoplasms in patients using angiotensin receptor blockers.

In recent years, regulatory agencies have raised concerns about the presence of potentially carcinogenic substances in certain formulations of Angiotensin Receptor Blockers (ARBs). Specifically, nitrosamines and azido compounds have been identified in some ARB products. Nitrosamines are known to have carcinogenic properties and are associated with an increased risk of neoplasms. Spontaneous safety reports from the EudraVigilance Data Analysis System (EVDAS) database were analyzed to investigate cases of neoplasms associated with ARBs. A disproportionality analysis was conducted, calculating the reporting odds ratio (ROR) and 95% confidence intervals (CIs) using a case/non-case approach for each ARB drug. The EVDAS database contained 68,522 safety reports related to ARBs (including Azilsartan, Candesartan, Irbesartan, Olmesartan, Losartan, Valsartan, and Telmisartan), among which 3,396 (5%) cases were associated with neoplasms. The majority of these cases were reported in Germany (11.9%), followed by France (9.7%). Approximately 70% of the reports were submitted by healthcare professionals such as physicians and nurses. Among the ARBs, valsartan had the highest ROR for neoplasm (ROR 1.949, 95% CI 1.857-2.046). This association remained significant when comparing ARBs with other classes of antihypertensive drugs, including ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics. Our study identifies a possible signal of an association between ARBs, particularly valsartan, and the risk of neoplasms. However, further observational and analytical studies are necessary to confirm these findings and elucidate the underlying mechanisms.

Fast boulder fracturing by thermal fatigue detected on stony asteroids.

Spacecraft observations revealed that rocks on carbonaceous asteroids, which constitute the most numerous class by composition, can develop millimeter-to-meter-scale fractures due to thermal stresses. However, signatures of this process on the second-most populous group of asteroids, the S-complex, have been poorly constrained. Here, we report observations of boulders' fractures on Dimorphos, which is the moonlet of the S-complex asteroid (65803) Didymos, the target of NASA's Double Asteroid Redirection Test (DART) planetary defense mission. We show that the size-frequency distribution and orientation of the mapped fractures are consistent with formation through thermal fatigue. The fractures' preferential orientation supports that these have originated in situ on Dimorphos boulders and not on Didymos boulders later transferred to Dimorphos. Based on our model of the fracture propagation, we propose that thermal fatigue on rocks exposed on the surface of S-type asteroids can form shallow, horizontally propagating fractures in much shorter timescales (100 kyr) than in the direction normal to the boulder surface (order of Myrs). The presence of boulder fields affected by thermal fracturing on near-Earth asteroid surfaces may contribute to an enhancement in the ejected mass and momentum from kinetic impactors when deflecting asteroids.

Early childhood height is a determinant of young adult stature in rural Nepal.

BACKGROUND: Does preschool height predict adult stature in undernourished settings? The extent to which preschool length or height forecasts young adult stature is unclear in chronically undernourished populations. METHODS: In 2006-8, we assessed height in a cohort of 2074 young adults, aged 16-23 years, in rural Nepal who, as preschoolers (≤ 4 year), were measured at baseline and again 16 months later during a vitamin A supplementation trial in 1989-91. We assessed by linear regression the ability of preschool length (L, measured < 24 mo) or height (Ht, 24-59 mo), at each year of age to predict 16-23 year old height, adjusted for month of young adult age, interval duration (in months), caste, preschool weight-for-height z-score and, in young women, time since menarche, marriage status and pregnancy history. RESULTS: Young women were a mean of 0.81, 1.11, 0.82, 0.24, 0.44 cm taller (all p < 0.01) and young men, 0.84, 1.18, 0.74, 0.64 and 0.48 cm taller (all p < 0.001) per cm of attained L/Ht at each successive preschool year of age and, overall, were 2.04 and 2.40 cm taller for each unit increase in preschool L/Ht z-score (L/HAZ) (both p < 0.001). Coefficients were generally larger for 16-month follow-up measurements. The percent of young adult height attained by children with normal L/HAZ (>-1) increased from 38-40% mid-infancy to ∼ 69-74% by 6 years of age. By 3-6 years of age heights of stunted children (L/HAZ<-2) were consistently ∼ 4-7% lower in their young adult height versus normal statured children. There was no effect of preschool vitamin A receipt. CONCLUSIONS: Shorter young children become shorter adults but predictive effects can vary by sex, age assessed, and may be influenced by year or season of measurement.

Consensus-Based Guidelines for Acute Myeloid Leukemia Management in Gulf Cooperation Council Countries: Addressing Unmet Regional Needs and the Changing AML Landscape.

PURPOSE: AML is a heterogeneous hematologic malignancy. Region-specific recommendations for AML management can enhance patient outcomes. This article aimed to develop recommendations for the Gulf Cooperation Council (GCC) countries. METHODS: Ten AML panel members from Kuwait, Oman, Qatar, and the United Arab Emirates (KOQU) participated in a modified two-round Delphi process. The panel first identified the unmet regional needs and finalized a list of core variables. Next, they voted on iterative statements drawn from international recommendations and provided feedback via a questionnaire. Consensus voting ≤70% was discussed, and additional clinical decision making statements were suggested. At round closure, a consensus vote took place on revised statements. RESULTS: The panel reached ≥97.8% consensus on AML management. The panel agreed to use international risk stratification categories for personalized treatment of AML. The presence of ≥10% blasts for recurrent genetic abnormalities was required for a diagnosis of AML. Key consensus was reached for different treatment stages. The panel noted that older patients pose a challenge because of poor cytogenetics and genetic anomalies and require different treatment approaches. The panel recommended venetoclax-hypomethylating agents; fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor; and targeted therapy for AML relapsed/refractory disease. Supportive care is considered on the basis of prevailing organisms and drug resistance. CONCLUSION: The GCC KOQU's consensus-based recommendations for managing AML include an evidence-based and region-specific framework.