A novel combination therapy targets sonic hedgehog signaling by the dual inhibition of HMG-CoA reductase and HSP90 in rats with non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is characterized by liver inflammation, fat accumulation, and collagen deposition. Due to the limited availability of effective treatments, there is a pressing need to develop innovative strategies. Given the complex nature of the disease, employing combination approaches is essential. Hedgehog signaling has been recognized as potentially promoting NASH, and cholesterol can influence this signaling by modifying the conformation of PTCH1 and SMO activity. HSP90 plays a role in the stability of SMO and GLI proteins. We revealed significant positive correlations between Hedgehog signaling proteins (Shh, SMO, GLI1, and GLI2) and both cholesterol and HSP90 levels. Herein, we investigated the novel combination of the cholesterol-lowering agent lovastatin and the HSP90 inhibitor PU-H71 in vitro and in vivo. The combination demonstrated a synergy score of 15.09 and an MSA score of 22.85, as estimated by the ZIP synergy model based on growth inhibition rates in HepG2 cells. In a NASH rat model induced by thioacetamide and a high-fat diet, this combination therapy extended survival, improved liver function and histology, and enhanced antioxidant defense. Additionally, the combination exhibited anti-inflammatory and anti-fibrotic potential by influencing the levels of TNF-α, TGF-ß, TIMP-1, and PDGF-BB. This effect was evident in the suppression of the Col1a1 gene expression and the levels of hydroxyproline and α-SMA. These favorable outcomes may be attributed to the combination's potential to inhibit key Hedgehog signaling molecules. In conclusion, exploring the applicability of this combination contributes to a more comprehensive understanding and improved management of NASH and other fibrotic disorders.

Unusual massive venous hemorrhage after pancreatoduodenectomy treated by endovascular approach.

Most post-pancreaticoduodenectomy hemorrhages (PPH) are of arterial origin, and some studies have suggested that an interventional radiology approach is most effective in reducing mortality. Venous PPH is rare, and identifying its source can be challenging. We report a case of late venous PPH in the context of a pancreatic fistula following pancreaticoduodenectomy. During surgical exploration, the area of ​​potential bleeding was inaccessible due to major inflammatory adhesions aggravated by the presence of pancreatic fistula and the delay of relaparotomy. No intra-abdominal bleeding was detected on imaging studies or during abdominal exploration; only a massive bleeding through the drain orifice, which required packing, was observed. Percutaneous transhepatic portography was performed to localize and treat the origin of the bleeding. The hemorrhage was successfully treated by endovascular approach. We found no reports in the literature on the use of interventional radiology with venous stenting to treat venous PPH, except in cases of gastrointestinal variceal hemorrhage due to portal occlusion.

The prevalence and associated factors for primary headache disorders in adolescents in eastern Sudan: a community-based cross-sectional study.

Background: Headache disorder is the second-highest cause of disability worldwide; however, data are scarce on headache among adolescents, especially in Africa. There has yet to be published data on headache among adolescents in Sudan, the third-largest country in Africa. This study aimed to assess the prevalence of primary headache disorders and associated factors among adolescents (10-19 years) in eastern Sudan. Methods: A community-based cross-sectional study was conducted in the city of Gadarif in eastern Sudan. Questionnaires were used to gather the adolescents' sociodemographic characteristics. Headache diagnostic questions were based on the beta version of the International Classification of Headache Disorders-III (ICHD-3). Multivariate analysis was conducted to assess the associated factors for primary headache disorders, and the results were expressed as risk ratios (RRs) and 95.0% confidence interval (CI). Results: Of the 401 enrolled adolescents, 186 (46.4%) and 215 (53.6%) were male and female, respectively. The median (IQR) age was 14.0 (12.1-16.2) years. Eighty-one (20.2%) of the 401 adolescents reported experiencing primary headache disorders, including migraine with aura in 16 (4.0%), migraine without aura in 33 (8.2%), tension-type in 14 (3.5%), and undifferentiated headache in 18 (4.5%) adolescents. The prevalence of primary headache disorders was significantly higher in females than in males [55/215 (67.9%) vs. 26/186 (32.1%), p = 0.004]. In the multivariate analysis, increased age (RR = 1.09, 95.0 CI = 1.02-1.16) and being female (RR = 1.75, 95.0 CI = 1.14-2.67) were associated with increased RR of primary headache disorders. Parents' education level and occupation, smoking/snuff use, and body mass index were not associated with primary headache disorders. Conclusion: One-fifth of the adolescents in eastern Sudan reported experiencing primary headache disorders, which was more common in females and with increased age.

Tracking the therapeutic efficacy of a ketone mono ester and ß-hydroxybutyrate for ulcerative colitis in rats: New perspectives.

Ulcerative colitis (UC) is an inflammatory condition that affects the colon's lining and increases the risk of colon cancer. Despite ongoing research, there is no identified cure for UC. The recognition of NLRP3 inflammasome activation in the pathogenesis of UC has gained widespread acceptance. Notably, the ketone body ß-hydroxybutyrate inhibits NLRP3 demonstrating its anti-inflammatory properties. Additionally, BD-AcAc 2 is ketone mono ester that increases ß-hydroxybutyrate blood levels. It has the potential to address the constraints associated with exogenous ß-hydroxybutyrate as a therapeutic agent, including issues related to stability and short duration of action. However, the effects of ß-hydroxybutyrate and BD-AcAc 2 on colitis have not been fully investigated. This study found that while both exogenous ß-hydroxybutyrate and BD-AcAc 2 produced the same levels of plasma ß-hydroxybutyrate, BD-AcAc 2 demonstrated superior effectiveness in mitigating dextran sodium sulfate-induced UC in rats. The mechanism of action involves modulating the NF-κB signaling, inhibiting the NLRP3 inflammasome, regulating antioxidant capacity, controlling tight junction protein expression and a potential to inhibit apoptosis and pyroptosis. Certainly, BD-AcAc 2's anti-inflammatory effects require more than just increasing plasma ß-hydroxybutyrate levels and other factors contribute to its efficacy. Local ketone concentrations in the gastrointestinal tract, as well as the combined effect of specific ketone bodies, are likely to have contributed to the stronger protective effect observed with ketone mono ester ingestion in our experiment. As a result, further investigations are necessary to fully understand the mechanisms of BD-AcAc 2 and optimize its use.

Item analysis: the impact of distractor efficiency on the difficulty index and discrimination power of multiple-choice items.

BACKGROUND: Distractor efficiency (DE) of multiple-choice questions (MCQs) responses is a component of the psychometric analysis used by the examiners to evaluate the distractors' credibility and functionality. This study was conducted to evaluate the impact of the DE on the difficulty and discrimination indices. METHODS: This cross-sectional study was conducted from April to June 2023. It utilizes the final exam of the Principles of Diseases Course with 45 s-year students. The exam consisted of 60 type A MCQs. Item analysis (IA) was generated to evaluate KR20, difficulty index (DIF), discrimination index (DIS), and distractor efficiency (DE). DIF was calculated as the percentage of examinees who scored the item correctly. DIS is an item's ability to discriminate between higher and lower 27% of examinees. For DE, any distractor selected by less than 5% is considered nonfunctional, and items were classified according to the non-functional distractors. The correlation and significance of variance between DIF, DI, and DE were evaluated. RESULTS: The total number of examinees was 45. The KR-20 of the exam was 0.91. The mean (M), and standard deviation (SD) of the DIF of the exam was 37.5(19.1), and the majority (69.5%) were of acceptable difficulty. The M (SD) of the DIS was 0.46 (0.22), which is excellent. Most items were excellent in discrimination (69.5%), only two were not discriminating (13.6%), and the rest were of acceptable power (16.9%). Items with excellent and good efficiency represent 37.3% each, while only 3.4% were of poor efficiency. The correlation between DE and DIF (p = 0.000, r= -0.548) indicates that items with efficient distractors (low number of NFD) are associated with those having a low difficulty index (difficult items) and vice versa. The correlation between DE and DIS is significantly negative (P = 0.0476, r=-0.259). In such a correlation, items with efficient distractors are associated with low-discriminating items. CONCLUSIONS: There is a significant moderate negative correlation between DE and DIF (P = 0.00, r = -0.548) and a significant weak negative correlation between DE and DIS (P = 0.0476, r = -0.259). DIF has a non-significant negative correlation with DIS (P = 0.7124, r = -0.0492). DE impacts both DIF and DIS. Items with efficient distractors (low number of NFD) are associated with those having a low difficulty index (difficult items) and discriminating items. Improving the quality of DE will decrease the number of NFDs and result in items with acceptable levels of difficulty index and discrimination power.

Maternal Diabetes Mellitus and Neonatal Outcomes in Bisha: A Retrospective Cohort Study.

BACKGROUND: Maternal diabetes mellitus (MDM) is associated with increased risks for adverse neonatal outcomes. However, the impact of MDM on neonatal outcomes in Bisha, a city in Saudi Arabia, is not well documented. This study aims to investigate the impact of MDM on neonatal outcomes in the Maternity and Children's Hospital (MCH), Bisha, Saudi Arabia. METHODS: A retrospective cohort study was conducted on 181 pregnant women with diabetes and their neonates who were diagnosed at the Maternity and Children's Hospital (MCH), Bisha, Saudi Arabia, between 5 October 2020 and 5 November 2022. The primary outcome was a composite of adverse neonatal outcomes, including stillbirth, neonatal death, macrosomia, preterm birth, respiratory distress syndrome, hypoglycemia, and congenital anomalies. Logistic regression analyses were used to adjust for potential confounders. RESULTS: The total sample size was 181. The average age of patients was 34 years (SD = 6.45). The majority of the patients were diagnosed with GDM, 147 (81.2%), and pre-GDM, 34 (18.8%). Neonates born to mothers with MDM had a higher risk of adverse neonatal outcomes compared to those born to mothers without MDM (adjusted odds ratio [aOR] = 1.46, 95% confidence interval [CI]: 1.25-1.70). The risks of macrosomia (aOR = 1.74, 95% CI: 1.38-2.19), LBW (aOR = 1.32, 95% CI: 1.06-1.66), and RDS (aOR = 1.57, 95% CI: 1.28-1.93) were significantly higher among neonates born to mothers with MDM. The types of DM were statistically significant in terms of their correlation with the following neonatal outcomes: hypoglycemia (p-value = 0.017), macrosomia (p-value = 0.050), and neonatal death (p-value = 0.017). CONCLUSIONS: MDM is associated with an increased risk of adverse neonatal outcomes in Bisha. The early identification and management of MDM may improve neonatal outcomes and reduce the burden of neonatal morbidity and mortality in this population.

miRNAs dysregulation in ankylosing spondylitis: A review of implications for disease mechanisms, and diagnostic markers.

Epigenetic processes, including non-coding RNA, histone modifications, and DNA methylation, play a vital role in connecting the environment to the development of a disorder, especially when there is a favorable genetic background. Ankylosing Spondylitis (AS) is a chronic type of spinal arthritis that highlights the significance of epigenetics in diseases related to autoimmunity and inflammation. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in both normal and aberrant pathological and physiological gene expression. This study focuses on the pathophysiological pathways to clarify the role of miRNAs in AS. We have conducted a thorough investigation of the involvement of miRNAs in several processes, including inflammation, the production of new bone, T-cell activity, and the regulation of pathways such as BMP, Wnt, and TGFß signaling. Undoubtedly, miRNAs play a crucial role in enhancing our comprehension of the pathophysiology of AS, and their promise as a therapeutic strategy is quickly expanding.

Corrigendum: Unveiling the therapeutic potential of exogenous ß-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis.

[This corrects the article DOI: 10.3389/fphar.2023.1239025.].

miRNAs Role in Wilms tumor pathogenesis: Signaling pathways interplay.

Wilms' tumors (WTs) are the most common type of kidney tumor in children, and a negative outlook is generally associated with widespread anaplastic. MicroRNAs (miRNAs) are crucial in the development of WT by regulating the expression of specific genes. There is an increasing amount of research that connects the dysregulation of miRNAs to the development of various renal illnesses. The conditions encompassed are renal fibrosis, renal cancers, and chronic and polycystic kidney disease. Dysregulation of several important miRNAs, either oncogenic or tumor-suppressing, has been found in WT. The present state of knowledge on the involvement of dysregulated miRNAs in the progression of WT is summarized in this review.

Late onset neonatal sepsis: Can plasma gelsolin be a promising diagnostic marker?

Plasma gelsolin (pGSN) correlates with clinical improvement in septic patients. We aimed to investigate pGSN levels as a diagnostic and prognostic marker of neonatal late-onset-sepsis (LOS). A case-control study was done on 184 neonates (92 with LOS and 92 controls). All participants were subjected to detailed history taking, full clinical evaluation, sepsis workup, and pGSN enzyme-linked immunosorbent-assay measurement. We detected significantly lower pGSN level among cases compared to controls (90.63 ±â€…20.64 vs 451.83 ±â€…209.59). It was significantly related to the severity of sepsis and mortality, with significantly lower values among cases with septic shock and multiorgan failure and non-survivors. Follow-up pGSN significantly increased after sepsis improvement in survivors compared to admission values. pGSN might be a reliable diagnostic and prognostic marker for LOS.

Adenocarcinoma-Induced Sigmoid Colon Intussusception and Postoperative Parastomal Evisceration in an Elderly Patient: A Case Report and Literature Review.

Intussusception in adults is less frequent than in children, and it is less commonly seen in the colon than in the intestines. This may be explained by the fixation of the colon to the retroperitoneum. We herein describe a case of sigmoid colon intussusception caused by a sigmoid colon adenocarcinoma. An 81-year-old man presented with abdominal pain and signs and symptoms of gastrointestinal obstruction. CT revealed a "target sign" with a mass in the sigmoid colon. We diagnosed the patient with colonic obstruction secondary to intussusception of the sigmoid colon and performed an emergency transverse colostomy. On the first postoperative day, the patient had a parastomal evisceration. Oncologic resection of the sigmoid colon without reduction of the intussusception was performed. The tumor was pathologically diagnosed as well-differentiated adenocarcinoma and classified as pT3N0. The patient was discharged on the ninth postoperative day with an uneventful postoperative course. The surveillance was validated for this patient.

The role of matrix metalloproteinase-2 and miR-196a2 in bronchial asthma pathogenesis and diagnosis.

Background: Bronchial asthma is a persistent inflammatory respiratory condition that restricts the passage of air and causes hyperresponsiveness. Chronic asthma can be classified into three categories: mild, moderate, and severe. Remodeling took place as the extracellular matrix accumulated in the walls of the airways. Inflammation occurs as a result of the damage caused by matrix metalloproteinase-2 (MMP-2) to basement membrane type IV collagen. The severity of asthma may be associated with miR-196a2. The objective of our study was to investigate the underlying mechanisms and clinical relevance of miR-196a2 and MMP-2 serum levels in relation to the severity of asthma. Methods: This study recruited 85 controls and 95 asthmatics classified as mild, moderate, or severe. Expression of miR-196a2 was measured by quantitative reverse transcriptase PCR. Using the enzyme-linked immunosorbent assay (ELISA), MMP-2, IL-6, and total immunoglobulin E (IgE) levels in the serum of asthmatics of various grades were compared to a control group. MMP-2's diagnostic and prognostic potential was determined using ROC curve analysis. This study also measured blood Eosinophils and PFTs. We examined MMP-2's connections with IgE, blood Eosinophils, and PFTs. Results: The current investigation found that miR-196a2 expression was significantly higher in the control group than in asthmatic patients as a whole. The study found that severe asthmatics had higher MMP-2, IL-6, and IgE serum levels than healthy controls. We identified the MMP-2 serum concentration cutoff with great sensitivity and specificity. Significant relationships between MMP-2 serum level and miR-196a2 expression in the patient group with severe asthmatics were found. The MMP-2, IL-6, and IgE serum levels were considerably higher in mild, moderate, and severe asthmatics than controls. The miR-196a2 expression and MMP-2 serum concentration correlated positively with IgE and blood eosinophils % and negatively with all lung function tests in the asthmatic patient group.Conclusion: the study revealed that the elevated miR-196a2 expression and serum concentration of MMP-2, IL-6, and IgE associated with elevated blood eosinophils % is associated with pathophysiology and degree of asthma severity. The miR-196a2 expression and MMP-2 serum concentration have a promising diagnostic and prognostic ability in bronchial asthma.

Linagliptin, a DPP-4 inhibitor, activates AMPK/FOXO3a and suppresses NFκB to mitigate the debilitating effects of diethylnitrosamine exposure in rat liver: Novel mechanistic insights.

Accumulating evidence suggests that dysregulation of FOXO3a plays a significant role in the progression of various malignancies, including hepatocellular carcinoma (HCC). FOXO3a inactivation, driven by oncogenic stimuli, can lead to abnormal cell growth, suppression of apoptosis, and resistance to anticancer drugs. Therefore, FOXO3a emerges as a potential molecular target for the development of innovative treatments in the era of oncology. Linagliptin (LNGTN), a DPP-4 inhibitor known for its safe profile, has exhibited noteworthy anti-inflammatory and anti-oxidative properties in previous in vivo studies. Several potential molecular mechanisms have been proposed to explain these effects. However, the capacity of LNGTN to activate FOXO3a through AMPK activation has not been investigated. In our investigation, we examined the potential repurposing of LNGTN as a hepatoprotective agent against diethylnitrosamine (DENA) intoxication. Additionally, we assessed LNGTN's impact on apoptosis and autophagy. Following a 10-week administration of DENA, the liver underwent damage marked by inflammation and early neoplastic alterations. Our study presents the first experimental evidence demonstrating that LNGTN can reinstate the aberrantly regulated FOXO3a activity by elevating the nuclear fraction of FOXO3a in comparison to the cytosolic fraction, subsequent to AMPK activation. Moreover, noteworthy inactivation of NFκB induced by LNGTN was observed. These effects culminated in the initiation of apoptosis, the activation of autophagy, and the manifestation of anti-inflammatory, antiproliferative, and antiangiogenic outcomes. These effects were concomitant with improved liver function and microstructure. In conclusion, our findings open new avenues for the development of novel therapeutic strategies targeting the AMPK/FOXO3a signaling pathway in the management of chronic liver damage.

Parental Knowledge, Attitude, and Practice Toward Children's Developmental Milestones in the Western Region of Saudi Arabia.

INTRODUCTION: Parents' ability to engage and raise their children in a safe and appropriate manner is largely influenced by their knowledge of child development and childrearing. This study aimed to evaluate the parenting and developmental milestone (MS) knowledge of Western region Saudi parents and identify the related elements that influence their knowledge. METHODS: This cross­sectional study was conducted for a period of six months. Ethical approval was duly sanctioned by the Institutional Review Board (IRB), and prior to participation, written informed consent was diligently procured from all the individuals involved in the study. In adherence to the paramount principles of privacy, rigorous measures were employed to de­identify the personal data of the participants, thereby safeguarding their confidentiality and anonymity. All research procedures were meticulously executed in strict compliance with the pertinent guidelines and regulatory standards governing research ethics. The study cohort consisted of Saudi parents from the Western Province of Saudi Arabia who had children aged up to six years and expressed a genuine willingness to participate in the research. This commitment was reaffirmed through their informed consent. Notably, the inclusion criteria for parental involvement did not impose any restrictions based on age or ethnic origin, ensuring a diverse and inclusive representation of this crucial demographic group. RESULTS: For assessing parental awareness and knowledge about children's developmental MSs, we examined a diverse sample of 873 participants, predominantly comprising females (77.00%). The age distribution revealed that a substantial portion of the respondents were below 30 (37.00%). Most respondents (62.40%) sought information from medical physicians and pediatricians. Gender had a significant effect, with males showing a lower awareness level compared to females (Beta = -0.582, 95% confidence interval (CI) [-0.890, -0.274], p-value < 0.001). Marital status demonstrated significance, where divorced individuals showed a lower awareness level than widowed participants (Beta = -1.641, 95% CI [-2.993, -0.288], p-value = 0.017). At the same time, no significant differences were found for singles or married individuals. CONCLUSION: Saudi parents lacked understanding of other parenting skills, such as a baby's personality and temperament, but they were well educated about some areas of childrearing, primarily physical safety precautions. It is advised that nurses and doctors give parenting advice to families at every step of their children's growth to educate and support them.

Retinoid Therapy in a Case of Harlequin Ichthyosis with a Short Literature Review.

Harlequin ichthyosis (HI) is a genetically inherited epidermal disorder due to the mutation of the ABCA12 gene, which is responsible for lipid transportation, and presents with large keratinised scales characterised by deep erythematous fissures, with ectropion and eclabium. A moderate number of cases and a high mortality rate have been recorded. In this case report, a pregnant lady gave birth to a 33-week-old premature foetus with characteristic symptoms of HI. After admitting him to the NICU, a multidisciplinary treatment approach was conducted with paediatric dermatologists, ophthalmologists, urologists, and dieticians. The prognosis is positive, with desquamation of the hyperkeratotic plate revealing an erythematous and shiny skin. A short literature review on HI characteristics, diagnostic aids, and management has also been added.

Itraconazole halts hepatocellular carcinoma progression by modulating sonic hedgehog signaling in rats: A novel therapeutic approach.

Liver cancer stands as the fourth leading global cause of death, and its prognosis remains grim due to the limited effectiveness of current medical interventions. Among the various pathways implicated in the development of hepatocellular carcinoma (HCC), the hedgehog signaling pathway has emerged as a crucial player. Itraconazole, a relatively safe and cost-effective antifungal medication, has gained attention for its potential as an anticancer agent. Its primary mode of action involves inhibiting the hedgehog pathway, yet its impact on HCC has not been elucidated. The main objective of this study was to investigate the effect of itraconazole on diethylnitrosamine-induced early-stage HCC in rats. Our findings revealed that itraconazole exhibited a multifaceted arsenal against HCC by downregulating the expression of key components of the hedgehog pathway, shh, smoothened (SMO), and GLI family zinc finger 1 (GLI1), and GLI2. Additionally, itraconazole extended survival and improved liver tissue structure, attributed mainly to its inhibitory effects on hedgehog signaling. Besides, itraconazole demonstrated a regulatory effect on Notch1, and Wnt/ß-catenin signaling molecules. Consequently, itraconazole displayed diverse anticancer properties, including anti-inflammatory, antiangiogenic, antiproliferative, and apoptotic effects, as well as the potential to induce autophagy. Moreover, itraconazole exhibited a promise to impede the transformation of epithelial cells into a more mesenchymal-like phenotype. Overall, this study emphasizes the significance of targeting the hedgehog pathway with itraconazole as a promising avenue for further exploration in clinical studies related to HCC treatment.

The emerging role of miRNAs in myocardial infarction: From molecular signatures to therapeutic targets.

Globally, myocardial infarction (MI) and other cardiovascular illnesses have long been considered the top killers. Heart failure and mortality are the results of myocardial apoptosis, cardiomyocyte fibrosis, and cardiomyocyte hypertrophy, all of which are caused by MI. MicroRNAs (miRNAs) play a crucial regulatory function in the progression and advancement of heart disease following an MI. By consolidating the existing data on miRNAs, our aim is to gain a more comprehensive understanding of their role in the pathological progression of myocardial injury after MI and to identify potential crucial target pathways. Also included are the primary treatment modalities and their most recent developments. miRNAs have the ability to regulate both normal and pathological activity, including the key signaling pathways. As a result, they may exert medicinal benefits. This review presents a comprehensive analysis of the role of miRNAs in MI with a specific emphasis on their impact on the regeneration of cardiomyocytes and other forms of cell death, such as apoptosis, necrosis, and autophagy. Furthermore, the targets of pro- and anti-MI miRNAs are comparatively elucidated.

"Progressive myoclonic ataxia and developmental/epileptic encephalopathy associated with a novel homozygous mutation in TCN2 gene".

BACKGROUND: Transcobalamin II (TCN2) defect is a rare metabolic disorder associated with a range of neurological manifestations, including mild developmental delay, severe intellectual disability, ataxia, and, in some cases, seizures. Cobalamin, an essential nutrient, plays a crucial role in central nervous system myelination. CLINICAL PRESENTATION: We present a family with an index patient who exhibited progressive neurodevelopmental regression starting at 9 months of age, accompanied by myoclonic seizures, ataxia, and tremor. No significant hematological abnormalities were observed. Exome sequencing analysis identified a novel homozygous mutation, c.3G>A - P(Met1I), affecting the acceptor site of intron 4 of the TCN2 gene (chromosome 22: 31003321, NM_000355.4), leading to likely pathogenic variant potentially affecting translation. Following treatment with hydroxocobalamin, the patient demonstrated partial clinical improvement. He has a sibling with overt hematological abnormalities and subtle neurological abnormalities who is homozygous to the same mutation. Both parents are heterozygous for the same mutation. CONCLUSIONS: In infants presenting with unexplained non-specific neurological symptoms, irrespective of classical signs of vitamin B12 deficiency, evaluation for TCN2 defect should be considered. Early diagnosis and appropriate management can lead to favorable outcomes.

Unraveling Alström syndrome: Homozygous mutation c.2729C>G in ALMS1 gene across an extended family.

BACKGROUND: Alström syndrome (AS) represents an exceptionally rare genetic disorder characterized by a constellation of features including cardiomyopathy, progressive hearing and vision impairment, as well as obesity. This study seeks to elucidate the genetic underpinnings of this syndrome within the Saudi Arabian population. METHODS: Employing an extended family cohort, we conducted an exhaustive molecular genetic assessment to delineate the presence of Alström syndrome. Additionally, we conducted an extensive review of existing literature from Saudi population to contextualize our findings within the broader understanding of the disorder in our country. RESULTS: Within our studied extended family, we identified two individuals harboring the homozygous pathogenic mutation (c.2729C>G) in the ALMS1 gene [NM_015120.4:c.2729C>G (p.Ser910*)]. Notably, carrier status was observed in the parents, whereas some siblings exhibited typical alleles while others were carriers of the mutation. Intriguingly, a review of the literature unveiled six distinct reports documenting a total of 20 Alström syndrome patients within the Saudi Arabian population, each presenting with distinct novel mutations. CONCLUSIONS: In cases featuring cardiomyopathy, obesity, and progressive hearing and vision loss, Alström syndrome merits inclusion within the differential diagnosis. To confirm the diagnosis, molecular genetic assessment of the ALMS1 gene is imperative, offering definitive clarity amidst the complex clinical presentation. This investigation reinforces the importance of genetic scrutiny for precise diagnosis and highlights the unique genetic landscape of Alström syndrome within the Saudi Arabian population.

Renal angina index in critically ill children as an applicable and reliable tool in the prediction of severe acute kidney injury: Two tertiary centers' prospective observational study from the Middle East.

Acute kidney damage (AKI) is a common cause of pediatric intensive care unit (PICU) admissions. Implementing a reno-protective strategy for AKI prediction can significantly enhance outcomes. The renal angina index (RAI) is a risk stratification tool used to predict severe AKI. We aim to assess the reliability and accuracy of the RAI scoring system in predicting AKI as compared to other conventional AKI markers. A prospective, observational study was conducted in the PICU of 2 tertiary medical centers in the Middle East. A total of 446 patients, aged 1-month to 14-years, without chronic kidney disease were enrolled. The RAI was calculated using the renal risk and renal injury score within the first 8 to 12 hours of admission. The accuracy of RAI was compared to changes in serum creatinine from baseline. The outcome was assessed on Day 3 for presence of AKI according to the kidney disease improving global outcome (KDIGO) criteria and associated sequelae. A positive RAI (RA+) was defined as RAI readings ≥ 8. Among the patients, 89 (19.9%) had a positive RAI within the first 8 to 12 hours of admission. The RA + group had a significantly higher occurrence of Day 3 severe AKI (KDIGO stages 2&3) compared to the RA- group (60.6% vs 4.2%, P < .001). The RA + group also had a significantly higher utilization of renal replacement therapy (RRT) (21.3% vs 1.1%, P < .001), longer mean PICU length of stay in days (11.1 ±â€…3.5 vs 5.5 ±â€…2.1, P < .001), and increased mortality (31.4% vs 2.8%, P < .001) compared to the RA- group. The RAI score demonstrated superior predictive ability for Day 3 AKI, with a sensitivity of 72%, specificity of 95%, and area under the curve (AUC) of 0.837, compared to changes in serum creatinine from baseline (sensitivity: 65%, specificity: 89%, AUC: 0.773), fluid overload (sensitivity: 43.7%, specificity: 79%, AUC: 0.613), and illness severity scores (sensitivity: 52.4%, specificity: 80.5%, AUC: 0.657). RAI proved to be a reliable and rapid bedside test for identifying critically ill children at risk of developing severe AKI. This enables physicians to implement reno-protective measures and intervene early, thereby improving prognosis.