Skeletal growth is enhanced by a shared role for SOX8 and SOX9 in promoting reserve chondrocyte commitment to columnar proliferation.

SOX8 was linked in a genome-wide association study to human height heritability, but roles in chondrocytes for this close relative of the master chondrogenic transcription factor SOX9 remain unknown. We undertook here to fill this knowledge gap. High-throughput assays demonstrate expression of human SOX8 and mouse Sox8 in growth plate cartilage. In situ assays show that Sox8 is expressed at a similar level as Sox9 in reserve and early columnar chondrocytes and turned off when Sox9 expression peaks in late columnar and prehypertrophic chondrocytes. Sox8-/- mice and Sox8fl/flPrx1Cre and Sox9fl/+Prx1Cre mice (inactivation in limb skeletal cells) have a normal or near normal skeletal size. In contrast, juvenile and adult Sox8fl/flSox9fl/+Prx1Cre compound mutants exhibit a 15 to 20% shortening of long bones. Their growth plate reserve chondrocytes progress slowly toward the columnar stage, as witnessed by a delay in down-regulating Pthlh expression, in packing in columns and in elevating their proliferation rate. SOX8 or SOX9 overexpression in chondrocytes reveals not only that SOX8 can promote growth plate cell proliferation and differentiation, even upon inactivation of endogenous Sox9, but also that it is more efficient than SOX9, possibly due to greater protein stability. Altogether, these findings uncover a major role for SOX8 and SOX9 in promoting skeletal growth by stimulating commitment of growth plate reserve chondrocytes to actively proliferating columnar cells. Further, by showing that SOX8 is more chondrogenic than SOX9, they suggest that SOX8 could be preferred over SOX9 in therapies to promote cartilage formation or regeneration in developmental and degenerative cartilage diseases.

Impact of Cachexia on Chemotherapy Efficacy and Survival in Pancreatic Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Pancreatic cancer (PC) is a significant cause of cancer-related mortality, with limited curative options and high rates of cachexia, a debilitating syndrome associated with poor prognosis. While previous research has linked sarcopenia to poor outcomes in PC, the correlation between cachexia and treatment outcomes remains underexplored. This meta-analysis aims to investigate the association between cachexia and overall survival and time to treatment failure in advanced PC patients undergoing first-line chemotherapy. METHOD: A systematic search of electronic databases was conducted following PRISMA guidelines. Eligible studies compared cachexic and non-cachexic PC patients, reporting outcomes of observed survival or time to treatment failure. Data extraction and analysis were performed using Comprehensive Meta-Analysis Version 3.3, employing random-effects models and sensitivity analyses to assess heterogeneity and bias. RESULTS: Seven observational studies involving 2834 PC patients were included. The incidence of cachexia was 45% (95% CI: 0.27-0.65), with a higher prevalence in East Asian populations. Cachexic patients experienced significantly earlier treatment failure (SDM: -2.22, 95% CI: -2.6 to -1.7, P = 0.0001) and higher mortality risk (HR: 2.02, 95% CI: 1.17-3.48, P = 0.011) compared to non-cachexic patients. Overall survival was lower in cachexic patients (SDM: -2.34, 95% CI: -3.7 to -0.90, P = 0.001), with considerable heterogeneity across studies. Meta-regression analysis revealed significant differences between countries but insignificant correlations with age. CONCLUSION: Cachexia is associated with reduced overall survival, early chemotherapy failure, and elevated mortality in advanced PC patients undergoing first-line chemotherapy. Recognition and management of cachexia are crucial for optimizing treatment outcomes and improving patient survival. Future research should focus on prospective studies to better understand the impact of cachexia on treatment response and develop tailored interventions to mitigate its adverse effects.

Pancreatic cancer (PC) presents a formidable challenge due to its limited treatment options and association with cachexia, a debilitating condition linked to poor prognosis. This meta-analysis investigates the relationship between cachexia and treatment outcomes in advanced PC patients undergoing first-line chemotherapy. Seven observational studies encompassing 2834 patients were analyzed, revealing a 45% incidence of cachexia, notably higher in East Asian populations. Cachexic patients exhibited earlier treatment failure and higher mortality risk compared to non-cachexic counterparts. Their overall survival was significantly reduced, although with notable heterogeneity across studies. Meta-regression analysis highlighted variations between countries but found no significant correlation with age. The findings underscore the importance of recognizing and addressing cachexia to optimize treatment outcomes and enhance patient survival. Future research should emphasize prospective studies to further elucidate cachexia's impact on treatment response and develop tailored interventions to alleviate its adverse effects.

Assessing the effectiveness of greater occipital nerve block in chronic migraine: a systematic review and meta-analysis.

BACKGROUND & AIMS: Chronic migraine poses a global health burden, particularly affecting young women, and has substantial societal implications. This study aimed to assess the efficacy of Greater Occipital Nerve Block (GONB) in individuals with chronic migraine, focusing on the impact of local anesthetics compared with placebo. METHODS: A meta-analysis and systematic review were conducted following the PRISMA principles and Cochrane Collaboration methods. Eligible studies included case-control, cohort, and randomized control trials in adults with chronic migraine, adhering to the International Classification of Headache Disorders, third edition (ICHD3). Primary efficacy outcomes included headache frequency, duration, and intensity along with safety assessments. RESULTS: Literature searches across multiple databases yielded eight studies for qualitative analysis, with five included in the final quantitative analysis. A remarkable reduction in headache intensity and frequency during the first and second months of treatment with GONB using local anesthetics compared to placebo has been reported. The incidence of adverse events did not differ significantly between the intervention and placebo groups. CONCLUSION: The analysis emphasized the safety and efficacy of GONB, albeit with a cautious interpretation due to the limited number of studies and relatively small sample size. This study advocates for further research exploring various drugs, frequencies, and treatment plans to enhance the robustness and applicability of GONB for chronic migraine management.

Sodium bicarbonate Ringer's solution for hemorrhagic shock: A meta-analysis comparing crystalloid solutions.

BACKGROUND: The choice of fluid resuscitation in Traumatic Hemorrhagic shock (THS) remains a critical aspect of patient management. Bicarbonated Ringers solution (BRS) has shown promise due to its composition resembling human Extracellular Fluid and its potential benefits on hemodynamics. OBJECTIVE: To evaluate the efficacy, mortality rates, hemodynamic effects, and adverse outcomes of Sodium Bicarbonate Ringer's Solution in the treatment of hemorrhagic shock, as compared to other relevant interventions. METHOD: A comprehensive examination of the available literature was performed by conducting systematic searches in prominent databases such as Cochrane, EMBASE, MEDLINE, and PubMed. The process employed predefined criteria to extract relevant data and evaluate the quality of the studies. The outcome measures considered encompassed survival rates, mortality, mean arterial pressure (MAP), heart rate (HR), and adverse events. RESULT: The meta-analysis of three studies showed that compared to the other crystalloids, the use of BRS had an odds ratio for survival of 1.86 (95% CI: 0.94, 3.71; p = 0.08; I2 = 0%), an odds ratio for total adverse events of 0.14 (95% CI: 0.06, 0.35; p < 0.0001; I2 = 22%), a mean difference in heart rate of -4.49 (95% CI: -7.55, -1.44; p = 0.004; I2 = 13%), and a mean difference in mean arterial pressure of 2.31 (95% CI: -0.85, 5.47; p = 0.15; I2 = 66%). CONCLUSION: BRS demonstrated a significant reduction in complications, including adult respiratory distress syndrome (ARDS), Multiple Organ Dysfunction (MODS), and Total Adverse Effects, when compared to other solutions in the treatment of THS. Additionally, THS patients resuscitated with BRS experienced a notable decrease in heart rate. The findings suggest BRS may contribute to organ stability and potential survival improvement due to its similarity to human Extracellular Fluid and minimal impact on the liver.

Assessing the impact of pre-hospital airway management on severe traumatic Brain injury: A systematic review and Meta-analysis.

OBJECTIVE: This study aimed to assess the impact of establishing a pre-hospital definitive airway on mortality and morbidity compared with no prehospital airway in cases of severe traumatic brain injury (TBI). BACKGROUND: Traumatic brain injury (TBI) is a global health concern that is associated with substantial morbidity and mortality. Prehospital intubation (PHI) has been proposed as a potential life-saving intervention for patients with severe TBI to mitigate secondary insults, such as hypoxemia and hypercapnia. However, their impact on patient outcomes remains controversial. METHODS: A systematic review and meta-analysis were conducted to assess the effects of prehospital intubation versus no prehospital intubation on morbidity and mortality in patients with severe TBI, adhering to the PRISMA guidelines. RESULTS: 24 studies, comprising 56,543 patients, indicated no significant difference in mortality between pre-hospital and In-hospital Intubation (OR 0.89, 95% CI 0.65-1.23, p = 0.48), although substantial heterogeneity was noted. Morbidity analysis also showed no significant difference (OR 0.83, 95% CI 0.43-1.63, p = 0.59). These findings underscore the need for cautious interpretation due to heterogeneity and the influence of specific studies on the results. CONCLUSION: In summary, an initial assessment did not reveal any apparent disparity in mortality rates between individuals who received prehospital intubation and those who did not. However, subsequent analyses and randomized controlled trials (RCTs) demonstrated that patients who underwent prehospital intubation had a reduced risk of death and morbidity. The dependence on biased observational studies and the need for further replicated RCTs to validate these findings are evident. Despite the intricacy of the matter, it is crucial to intervene during severe airway impairment.

Letter to editor: C­reactive protein levels, the prognostic nutritional index, and the lactate dehydrogenase­to­lymphocyte ratio are important prognostic factors in primary central nervous system lymphoma: a single­center study of 223 patients.

This critique evaluates a letter to the editor discussing prognostic factors in primary central nervous system lymphoma (PCNSL), focusing on C-reactive protein (CRP) levels, prognostic nutritional index (PNI), and lactate dehydrogenase (LDH)-to-lymphocyte ratio. While the letter provides valuable insights, limitations including reliance on a single-center dataset, lack of consideration for potential confounders, insufficient contextualization within existing literature, and limited discussion of clinical implications are identified. Addressing these limitations is crucial for enhancing the relevance and applicability of the findings in PCNSL management.

SOX9 keeps growth plates and articular cartilage healthy by inhibiting chondrocyte dedifferentiation/osteoblastic redifferentiation.

Cartilage is essential throughout vertebrate life. It starts developing in embryos when osteochondroprogenitor cells commit to chondrogenesis, activate a pancartilaginous program to form cartilaginous skeletal primordia, and also embrace a growth-plate program to drive skeletal growth or an articular program to build permanent joint cartilage. Various forms of cartilage malformation and degeneration diseases afflict humans, but underlying mechanisms are still incompletely understood and treatment options suboptimal. The transcription factor SOX9 is required for embryonic chondrogenesis, but its postnatal roles remain unclear, despite evidence that it is down-regulated in osteoarthritis and heterozygously inactivated in campomelic dysplasia, a severe skeletal dysplasia characterized postnatally by small stature and kyphoscoliosis. Using conditional knockout mice and high-throughput sequencing assays, we show here that SOX9 is required postnatally to prevent growth-plate closure and preosteoarthritic deterioration of articular cartilage. Its deficiency prompts growth-plate chondrocytes at all stages to swiftly reach a terminal/dedifferentiated stage marked by expression of chondrocyte-specific (Mgp) and progenitor-specific (Nt5e and Sox4) genes. Up-regulation of osteogenic genes (Runx2, Sp7, and Postn) and overt osteoblastogenesis quickly ensue. SOX9 deficiency does not perturb the articular program, except in load-bearing regions, where it also provokes chondrocyte-to-osteoblast conversion via a progenitor stage. Pathway analyses support roles for SOX9 in controlling TGFß and BMP signaling activities during this cell lineage transition. Altogether, these findings deepen our current understanding of the cellular and molecular mechanisms that specifically ensure lifelong growth-plate and articular cartilage vigor by identifying osteogenic plasticity of growth-plate and articular chondrocytes and a SOX9-countered chondrocyte dedifferentiation/osteoblast redifferentiation process.

Surgical strategies in acute subdural hematoma: a meta-analysis of decompressive craniectomy vs. craniotomy.

OBJECTIVE: Acute subdural hematoma (ASDH) stands as a significant contributor to morbidity after severe traumatic brain injuries (TBI). The primary treatment approach for patients experiencing progressive neurological deficits or notable mass effects is the surgical removal of the hematoma, which can be achieved through craniotomy (CO) or decompressive craniectomy (DC). Nevertheless, the choice between these two procedures remains a subject of ongoing debate and controversy. MATERIALS AND METHODS: We conducted a comprehensive literature review, utilizing prominent online databases and manually searching references related to craniotomy and craniectomy for subdural hematoma evacuation up to November 2023. Our analysis focused on outcome variables such as the presence of residual subdural hematoma, the need for revision procedures, and overall clinical outcomes. RESULTS: We included a total of 11 comparative studies in our analysis, encompassing 4269 patients, with 2979 undergoing craniotomy and 1290 undergoing craniectomy, meeting the inclusion criteria. Patients who underwent craniectomy displayed significantly lower scores on the Glasgow Coma Scale (GCS) during their initial presentation. Following surgery, the DC group exhibited a significantly reduced rate of residual subdural (P = 0.009). Additionally, the likelihood of a poor outcome during follow-up was lower in the CO group. Likewise, the mortality rate was lower in the CO group compared to the craniectomy group (OR 0.63, 95% CI 0.41-0.98, I2 = 84%, P = 0.04). CONCLUSION: Our study found that CO was associated with more favorable outcomes in terms of mortality, reoperation rate, and functional outcome while DC was associated with less likelihood of residual subdural hematoma. Upon further investigation of patient characteristics who underwent into either of these interventions, it was very clear that patients in DC cohort have more serious and low pre-op characteristics than the CO group. Nonetheless, brain herniation and advanced age act as independent factor for predicting the outcome irrespective of the intervention.

Predictors of Seeking Mental Health Treatment in Black Men: Therapy Fears and Expectations About Counseling.

The current study examined predictors of mental health treatment among Black men while incarcerated. Participants were 76 individuals who identified as Black Americans and were recruited from a correctional setting. Using secondary data analysis (Shaw, L. B., & Morgan, R. D. (2011). Inmate attitudes toward treatment: Mental health service utilization and treatment effects. Law and Human Behavior, 35(4), 249-261. https://doi.org/10.1007/s10979-010-9233-5 .), results indicated that Black men with a mental health diagnosis were more likely than those without a diagnosis to report receiving mental health treatment while incarcerated. Additionally, linear regression analyses indicated that only expectations about treatment (i.e., personal commitment; not therapy fears or history of mental health diagnosis) significantly predicted the current use of mental health treatment. Implications for research and practice are discussed.

De Novo SOX6 Variants Cause a Neurodevelopmental Syndrome Associated with ADHD, Craniosynostosis, and Osteochondromas.

SOX6 belongs to a family of 20 SRY-related HMG-box-containing (SOX) genes that encode transcription factors controlling cell fate and differentiation in many developmental and adult processes. For SOX6, these processes include, but are not limited to, neurogenesis and skeletogenesis. Variants in half of the SOX genes have been shown to cause severe developmental and adult syndromes, referred to as SOXopathies. We here provide evidence that SOX6 variants also cause a SOXopathy. Using clinical and genetic data, we identify 19 individuals harboring various types of SOX6 alterations and exhibiting developmental delay and/or intellectual disability; the individuals are from 17 unrelated families. Additional, inconstant features include attention-deficit/hyperactivity disorder (ADHD), autism, mild facial dysmorphism, craniosynostosis, and multiple osteochondromas. All variants are heterozygous. Fourteen are de novo, one is inherited from a mosaic father, and four offspring from two families have a paternally inherited variant. Intragenic microdeletions, balanced structural rearrangements, frameshifts, and nonsense variants are predicted to inactivate the SOX6 variant allele. Four missense variants occur in residues and protein regions highly conserved evolutionarily. These variants are not detected in the gnomAD control cohort, and the amino acid substitutions are predicted to be damaging. Two of these variants are located in the HMG domain and abolish SOX6 transcriptional activity in vitro. No clear genotype-phenotype correlations are found. Taken together, these findings concur that SOX6 haploinsufficiency leads to a neurodevelopmental SOXopathy that often includes ADHD and abnormal skeletal and other features.

The Imposter Syndrome In Surgical Residents.

Imposter syndrome (IS) is an internal sensation of intellectual phoniness in persons who feel fraudulence and worthlessness. The purpose of this study was to assess the prevalence of imposter syndrome among surgical residents. A web-based survey was conducted among all surgical residents of PGMI, Khyber Pakhtunkhwa, Pakistan, from May 1, 2022 to May 30, 2022. Of the 156 respondents, 104 (66.7%) were males and 52 (33.3%) were females. Moderate imposterism was seen in 81(51.9%) of the respondents and 57 (36.5%) respondents reported severe or intense imposterism. Among postgraduate residents, no significant differences in Clance Imposter Phenomenon Scale score by year was noted (p = 0.291). Imposter syndrome was highly prevalent among surgical residents, i.e. 138(88.5%) falling in the range of either moderate, severe, or intense imposterism. Prevalence was more among female residents as compared to male residents. Year of training didn't have any impact on the grades of imposterism.

Using Culture Sensitivity Reports to Optimize Antimicrobial Therapy: Findings and Implications of Antimicrobial Stewardship Activity in a Hospital in Pakistan.

Background: There are concerns with inappropriate prescribing of antibiotics in hospitals especially broad spectrum in Pakistan and the subsequent impact on antimicrobial resistance rates. One recognized way to reduce inappropriate prescribing is for empiric therapy to be adjusted according to the result of culture sensitivity reports. Objective: Using culture sensitivity reports to optimize antibiotic prescribing in a teaching hospital in Pakistan. Methods: A retrospective observational study was undertaken in Ghurki Trust Teaching Hospital. A total of 465 positive cultures were taken from patients during the study period (May 2018 and December 2018). The results of pathogen identification and susceptibility testing from patient-infected sites were assessed. Additional data was collected from the patient's medical file. This included demographic data, sample type, causative microbe, antimicrobial treatment, and whether empiric or definitive treatment as well as medicine costs. Antimicrobial data was assessed using World Health Organization's Defined Daily Dose methodology. Results: A total of 497 isolates were detected from the 465 patient samples as 32 patients had polymicrobes, which included 309 g-negative rods and 188 g-positive cocci. Out of 497 isolates, the most common Gram-positive pathogen isolated was Staphylococcus aureus (Methicillin-sensitive Staphylococcus aureus) (125) (25.1%) and the most common Gram-negative pathogen was Escherichia coli (140) (28.1%). Most of the gram-negative isolates were found to be resistant to ampicillin and co-amoxiclav. Most of the Acinetobacter baumannii isolates were resistant to carbapenems. Gram-positive bacteria showed the maximum sensitivity to linezolid and vancomycin. The most widely used antibiotics for empiric therapy were cefoperazone plus sulbactam, ceftriaxone, amikacin, vancomycin, and metronidazole whereas high use of linezolid, clindamycin, meropenem, and piperacillin + tazobactam was seen in definitive treatment. Empiric therapy was adjusted in 220 (71.1%) cases of Gram-negative infections and 134 (71.2%) cases of Gram-positive infections. Compared with empiric therapy, there was a 13.8% reduction in the number of antibiotics in definitive treatment. The average cost of antibiotics in definitive treatment was less than seen with empiric treatment (8.2%) and the length of hospitalization also decreased. Conclusions: Culture sensitivity reports helped reduced antibiotic utilization and costs as well as helped select the most appropriate treatment. We also found an urgent need for implementing antimicrobial stewardship programs in hospitals and the development of hospital antibiotic guidelines to reduce unnecessary prescribing of broad-spectrum antibiotics.

Antibiotic Susceptibility Surveillance in the Punjab Province of Pakistan: Findings and Implications.

Background and Objectives: The increase in antimicrobial resistance (AMR) across countries has seriously impacted the effective management of infectious diseases, with subsequent impact on morbidity, mortality and costs. This includes Pakistan. Antimicrobial surveillance activities should be mandatory to continually assess the extent of multidrug-resistant bacteria and the implications for future empiric prescribing. The objective of this retrospective observational study was to monitor the susceptibility pattern of microbes in Pakistan. Materials and Methods: Clinical samples from seven laboratories in Punjab, Pakistan were collected between January 2018 and April 2019, with Punjab being the most populous province in Pakistan. The isolates were identified and their antimicrobial susceptibility was tested using the Kirby-Bauer disc diffusion assay and micro broth dilution methods. The antibiotics assessed were those typically prescribed in Pakistan. Results: In total, 2523 bacterial cultural reports were studied. The most frequently isolated pathogens were Staphylococcus aureus (866, 34.3%), followed by Escherichia coli (814, 32.2%), Pseudomonas aeruginosa (454, 18.0%) and Klebsiella pneumoniae (269, 10.7%). Most pathogens were isolated from pus (1464, 58.0%), followed by urine (718, 28.5%), blood (164, 6.5%) and sputum (81, 3.2%). Conclusions: The findings suggest that current antimicrobial options are severally restricted in Pakistan due to the emergence of multidrug-resistant pathogens. This calls for urgent actions including initiating antimicrobial stewardship programs to enhance prudent prescribing of antibiotics. This includes agreeing on appropriate empiric therapy as part of agreed guidelines, in line with the WHO EML and AWaRe book, whilst awaiting culture reports. This is alongside other measures to reduce inappropriate antimicrobial prescribing and reverse the threat of rising AMR.

Antibiotics for preventing infection at the surgical site: Single dose vs. multiple doses.

Background: Surgical site infections are common and expensive infections that can cause fatalities or poor patient outcomes. To prevent these infections, antibiotic prophylaxis is used. However, excessive antibiotic use is related to higher costs and the emergence of antimicrobial resistance. Objectives: The present meta-analysis aimed to compare the effectiveness of a single dosage versus several doses of antibiotics in preventing the development of surgical site infections. Methods: PubMed was used to find clinical trials evaluating the effectiveness of a single dosage versus several doses of antibiotics in avoiding the development of surgical site infections. The study included trials that were published between 1984 and 2022. Seventy-four clinical trials were included in the analysis. Odds ratios were used to compare groups with 95% confidence intervals. The data were displayed using OR to generate a forest plot. Review Manager (RevMan version 5.4) was used to do the meta-analysis. Results: Regarding clean operations, there were 389 surgical site infections out of 5,634 patients in a single dose group (6.90%) and 349 surgical site infections out of 5,621 patients in multiple doses group (6.21%) (OR = 1.11, lower CI = 0.95, upper CI = 1.30). Regarding clean-contaminated operations, there were 137 surgical site infections out of 2,715 patients in a single dose group (5.05%) and 137 surgical site infections out of 2,355 patients in multiple doses group (5.82%) (OR = 0.87, lower CI = 0.68, upper CI = 1.11). Regarding contaminated operations, there were 302 surgical site infections out of 3,262 patients in a single dose group (9.26%) and 276 surgical site infections out of 3,212 patients in multiple doses group (8.59%) (OR = 1.11, lower CI = 0.84, upper CI = 1.47). In general, there were 828 surgical site infections out of 11,611 patients in a single dose group (7.13%) and 762 surgical site infections out of 11,188 patients in multiple doses group (6.81%) (OR = 1.05, lower CI = 0.93, upper CI = 1.20). The difference between groups was not significant. Conclusion: The present study showed that using a single-dose antimicrobial prophylaxis was equally effective as using multiple doses of antibiotics in decreasing surgical site infections.

De Novo SOX4 Variants Cause a Neurodevelopmental Disease Associated with Mild Dysmorphism.

SOX4, together with SOX11 and SOX12, forms group C of SRY-related (SOX) transcription factors. They play key roles, often in redundancy, in multiple developmental pathways, including neurogenesis and skeletogenesis. De novo SOX11 heterozygous mutations have been shown to cause intellectual disability, growth deficiency, and dysmorphic features compatible with mild Coffin-Siris syndrome. Using trio-based exome sequencing, we here identify de novo SOX4 heterozygous missense variants in four children who share developmental delay, intellectual disability, and mild facial and digital morphological abnormalities. SOX4 is highly expressed in areas of active neurogenesis in human fetuses, and sox4 knockdown in Xenopus embryos diminishes brain and whole-body size. The SOX4 variants cluster in the highly conserved, SOX family-specific HMG domain, but each alters a different residue. In silico tools predict that each variant affects a distinct structural feature of this DNA-binding domain, and functional assays demonstrate that these SOX4 proteins carrying these variants are unable to bind DNA in vitro and transactivate SOX reporter genes in cultured cells. These variants are not found in the gnomAD database of individuals with presumably normal development, but 12 other SOX4 HMG-domain missense variants are recorded and all demonstrate partial to full activity in the reporter assay. Taken together, these findings point to specific SOX4 HMG-domain missense variants as the cause of a characteristic human neurodevelopmental disorder associated with mild facial and digital dysmorphism.

Mitigation of greenhouse gas emissions from a red acidic soil by using magnesium-modified wheat straw biochar.

To mitigate greenhouse gas (GHG) emissions, different strategies have been proposed, including application of dolomite, crop straw and biochar, thus contributing to cope with the increasing global warming affecting the planet. In the current study, pristine wheat straw biochar (WBC) and magnesium (MgCl2.6H2O) modified wheat straw biochar (MWBC) were used. Treatments included control (CK), two WBC dosages (1% and 2.5%), and two MWBC doses (1% and 2.5%). After 90 days of incubation, WBC and MWBC improved the soil physiochemical properties, being more pronounced with increasing rates of biochar. MWBC2.5 significantly decreased microbial biomass carbon (MBC), while microbial biomass nitrogen (MBN) increased when both biochar materials (WBC1 and MWBC1) were applied at low rate. Compared to control soil, Urease and Alkaline phosphatase activities increased with the increasing rate of WBC and MWBC. The activities of dehydrogenase and ß-glucosidase decreased with the WBC and MWBC application, compared to CK. The fluxes of all the three GHGs evaluated (CO2, CH4 and N2O) decreased with time for both biochar amendments, while cumulative emission of CO2 increased by 58% and 45% for WBC, and by 54% and 41% for MWBC, as compared to CK. The N2O cumulative emissions decreased by 18 and 34% for WBC, and by 25 and 41% for MWBC, compared to CK, whereas cumulative methane emission showed non-significant differences among all treatments. These findings indicate that Mg-modified wheat straw biochar would be an appropriate management strategy aiding to reduce GHG emissions and improving the physiochemical properties of affected soils, and specifically of the red dry land soil investigated in the current work.

Knowledge, attitude, and perception of community pharmacists towards antimicrobial stewardship in Saudi Arabia: A descriptive cross-sectional study.

Background: Antimicrobial resistance is of paramount concern globally. Community pharmacists (CPs) play a vital role in supporting judicious antimicrobial use in the community as they are the key healthcare providers at a public level. This study aimed to assess the knowledge, attitude, and perception of CPs towards antimicrobial stewardship at the community level in Saudi Arabia. Methods: A self-administered questionnaire was distributed to all community pharmacies in four major cities of Saudi Arabia. A simple random sampling approach was used to select pharmacies in each chain. Results: A total of 520 CPs responded to the survey with a response rate of 98.6 %. Most of the pharmacists (n = 479, 92.1 %) accepted that antimicrobial stewardship programs are essential tools to limit injudicious usage of antimicrobials at the community level. Interestingly, very few (n = 105, 21 %) agreed to recommend antibiotics for common illnesses, including upper respiratory tract infections, cold, and flu without a valid prescription. Further, we found a significant role of Saudi health authorities, e.g., Saudi food & drug authorities and the Ministry of Health, in restricting antimicrobials sale in community pharmacies without a valid prescription. Conclusion: Our study findings revealed that CPs had good knowledge about antimicrobial stewardship in Saudi Arabia. The CPs play an active role in the optimization of antimicrobial therapy and infections caused by different microbes. Strict policies by the Saudi health care authority regarding the restricted dispensing of antimicrobials are welcomed by the CPs and thus may contribute toward lowering of antimicrobial resistance burden on the patients and Saudi health care authorities.

Longevity of Middle East Respiratory Syndrome Coronavirus Antibody Responses in Humans, Saudi Arabia.

Understanding the immune response to Middle East respiratory syndrome coronavirus (MERS-CoV) is crucial for disease prevention and vaccine development. We studied the antibody responses in 48 human MERS-CoV infection survivors who had variable disease severity in Saudi Arabia. MERS-CoV-specific neutralizing antibodies were detected for 6 years postinfection.

Digestive Manifestations in Patients Hospitalized With Coronavirus Disease 2019.

BACKGROUND & AIMS: The prevalence and significance of digestive manifestations in coronavirus disease 2019 (COVID-19) remain uncertain. We aimed to assess the prevalence, spectrum, severity, and significance of digestive manifestations in patients hospitalized with COVID-19. METHODS: Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were abstracted manually from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. RESULTS: A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least 1 gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were increased to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio, 0.93; 95% CI, 0.76-1.15) or liver test abnormalities on admission (odds ratio, 1.31; 95% CI, 0.80-2.12) were not associated independently with mechanical ventilation or death. CONCLUSIONS: Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common, but the majority were mild and their presence was not associated with a more severe clinical course.

SOX9 is dispensable for the initiation of epigenetic remodeling and the activation of marker genes at the onset of chondrogenesis.

SOX9 controls cell lineage fate and differentiation in major biological processes. It is known as a potent transcriptional activator of differentiation-specific genes, but its earliest targets and its contribution to priming chromatin for gene activation remain unknown. Here, we address this knowledge gap using chondrogenesis as a model system. By profiling the whole transcriptome and the whole epigenome of wild-type and Sox9-deficient mouse embryo limb buds, we uncover multiple structural and regulatory genes, including Fam101a, Myh14, Sema3c and Sema3d, as specific markers of precartilaginous condensation, and we provide evidence of their direct transactivation by SOX9. Intriguingly, we find that SOX9 helps remove epigenetic signatures of transcriptional repression and establish active-promoter and active-enhancer marks at precartilage- and cartilage-specific loci, but is not absolutely required to initiate these changes and activate transcription. Altogether, these findings widen our current knowledge of SOX9 targets in early chondrogenesis and call for new studies to identify the pioneer and transactivating factors that act upstream of or along with SOX9 to prompt chromatin remodeling and specific gene activation at the onset of chondrogenesis and other processes.