Pontocerebellar Hypoplasia Type 9: A New Case with a Novel Mutation and Review of Literature.

Pontocerebellar hypoplasia type 9 (PCH-9) is a very rare autosomal recessive neurodegenerative disorder. Affected infants present early with severe developmental delay, spasticity, with the unique magnetic resonance imaging picture of thin corpus callosum, atrophied pons, and cerebellum. It is caused by loss of function mutations in the AMPD2 gene, encoding for the adenosine monophosphate deaminase enzyme-paralog 2. This gene is expressed in different somatic tissues with high level of expression in cerebellum and its encoded enzyme catalyzes a critical step in de novo biosynthesis of purines and its deficiency in the developing neurons severely affects neuronal differentiation and cell viability. We clinically evaluated an Emirati patient presented with severe developmental and growth delay, as well as corpus callosum agenesis and atrophy of brainstem and cerebellum. We performed exome sequencing, Sanger sequencing, and segregation analysis to identify the genetic cause of the phenotype, followed by in silico and in vitro analysis. We identified the novel variant (NM_004037.9:c.1471G > A) in AMPD2 gene leading to a single amino acid substitution (p.Gly491Arg) in adenosine monophosphate deaminase-2 enzyme. This variant is predicted to be pathogenic using several in silico tools, and resulted in a decrease in the enzyme function in the patient's polymorphonuclear cells by 82% (95% confidence interval: 73.3-91.7%, p = 0.029) compared with the control. This data establishes that the affected child is affected by PCH-9. Furthermore, we review all reported cases in literature to summarize the main clinical features of this rare disease.

A novel MALT1 variant in an Egyptian patient presenting with exfoliative dermatitis: a case-based review.

Inborn errors of the CARD11-BCL10-MALT1 (CBM) signalosome have recently been shown to underlie severe combined immunodeficiency (SCID) and combined immunodeficiency (CID) with variable immunological and clinical phenotypes, and patients usually present with recurrent bacterial, viral, and fungal infections, periodontal disease, enteropathy, dermatitis, and failure to thrive. In the present study, we describe the clinical and immunological characteristics of an Egyptian patient with a mutation in the MALT1 gene. The patient suffered from an itchy exfoliative skin rash and eczematous lesions over his face and flexural surface of the limbs. He also had dental enamel erosion, repeated attacks of diarrhea, and pneumonia. He had elevated serum IgE and normal B- and T-lymphocyte subset counts, but there was an arrest in the B-cell maturation. DOCK8 expression on the lymphocytes by flow cytometry was normal. Next-generation sequencing revealed a novel homozygous variant in the MALT1 gene (c.762dup in exon 5 of 17; p.Ile255TyrfsTer10); this variant is likely pathogenic, thus supporting the genetic diagnosis of immunodeficiency-12 (IMD12). Although the presence of eczema, recurrent sinopulmonary, and staphylococcal infections are suggestive of DOCK8 deficiency, they are also a finding in CARD11 and MALT1 deficiency. Thus, whenever DOCK 8 has been excluded, the molecular diagnosis is mandatory as this could lead to discovering more patients hence better understanding and reporting of the phenotype and natural history of the disease especially since there are very few documented cases. Early diagnosis will also enable the proper patient management by hematopoietic stem cell transplantation (HSCT) prior to the establishment of infections and pulmonary damage leading to a better outcome.

Knowledge and Perception of Artificial Intelligence among Faculty Members and Students at Batterjee Medical College.

Background: Mounting research suggests that artificial intelligence (AI) is one of the innovations that aid in the patient's diagnosis and treatment, but unfortunately limited research has been conducted in this regard in the Kingdom of Saudi Arabia (KSA). Hence, this study aimed to assess the level of knowledge and awareness of AI among faculty members and medicine students in one of the premier medical colleges in KSA. Methods: A cross-sectional descriptive study was conducted at Batterjee Medical College (BMC), Jeddah (KSA), from November 2022 to April 2023. Result: A total of 131 participants contributed to our study, of which three were excluded due to incomplete responses, thereby giving a response rate of 98%. Conclusion: 85.4% of the respondents believe that AI has a positive impact on the healthcare system and physicians in general. Hence, there should be a mandatory course in medical schools that can prepare future doctors to diagnose patients more accurately, make predictions about patients' future health, and recommend better treatments.

Establishing Reference Intervals for Serum and Salivary Cortisol in a Selected Population in Kano, Nigeria.

OBJECTIVE: Serum cortisol has long been used in the assessment of disorders of the hypothalamic-pituitary-adrenal axis. The reference interval for cortisol in both serum and saliva depends on the analytical methodology and the population studied; hence, a locally derived population-based reference interval is recommended. To our knowledge, there are no studies on reference interval determination in the study area, raising concerns about the use of reference intervals established in European and North American populations. This work aimed to establish reference intervals for baseline serum and salivary cortisol levels among healthy adults in Kano, Nigeria, using methods available in our laboratory. METHODS: A cross-section of 148 apparently healthy reference individuals aged 16 to 67 years were recruited from a local community in Kano, Nigeria, using a systematic sampling technique. Baseline serum cortisol was analyzed using highly sensitive and specific electrochemiluminescence quantitative measurements on an automated immunology analyzer. Salivary cortisol levels were measured using Salimetrics' competitive enzyme-linked immunosorbent assay test kits. Parametric methods with a 95% confidence interval were used to calculate reference intervals. RESULTS: The reference intervals for cortisol in serum and saliva were 72.0 nmo/L to 554.0 nmol/L and 0.40 nmol/L to 18.0 nmol/L, respectively. There was a weak positive correlation between serum and salivary cortisol values, but this association was not statistically significant. CONCLUSION: The development of locally derived adult reference intervals can improve the diagnostic utility of serum and salivary cortisol assessment and strengthen the reliability of adrenal insufficiency diagnoses in our population.

Discovery and Optimization of Potent, Efficacious and Selective Inhibitors Targeting EGFR Exon20 Insertion Mutations.

Herein, we report the identification and optimization of a series of potent inhibitors of EGFR Exon20 insertions with significant selectivity over wild-type EGFR. A strategically designed HTS campaign, multiple iterations of structure-based drug design (SBDD), and tactical linker replacement led to a potent and wild-type selective series of molecules and ultimately the discovery of 36. Compound 36 is a potent and selective inhibitor of EGFR Exon20 insertions and has demonstrated encouraging efficacy in NSCLC EGFR CRISPR-engineered H2073 xenografts that carry an SVD Exon20 insertion and reduced efficacy in a H2073 wild-type EGFR xenograft model compared to CLN-081 (5), indicating that 36 may have lower EGFR wild-type associated toxicity.

Analysis of Clinical, Immunological and Molecular Features of Leukocyte Adhesion Deficiency Type I in Egyptian Children.

PURPOSE: Leukocyte adhesion deficiency (LAD) represents a rare group of inherited inborn errors of immunity (IEI) characterized by bacterial infections, delayed umbilical stump separation, and autoimmunity. This single-center study aimed at describing the clinical, immunological, and molecular characterizations of 34 LAD-I Egyptian pediatric patients. METHODS: Details of 34 patients' personal medical history, clinical and laboratory findings were recorded; Genetic material from 28 patients was studied. Mutational analysis was done by Sanger sequencing. RESULTS: Omphalitis, skin and soft tissue infections with poorly healing ulcers, delayed falling of the umbilical stump, and recurrent or un-resolving pneumonia were the most common presentations, followed by chronic otitis media, enteropathy, periodontitis; and recurrent oral thrush. Persistent leukocytosis and neutrophilia were reported in all patients, as well as CD18 and CD11b deficiency. CD18 expression was < 2% in around 90% of patients. Sixteen different pathological gene variants were detected in 28 patients who underwent ITGß2 gene sequencing, of those, ten were novel and six were previously reported. Three families received a prenatal diagnosis. Patients were on antimicrobials according to culture's results whenever available, and on prophylactic Trimethoprim-Sulfamethoxazole 5 mg/kg once daily, with regular clinical follow up. Hematopoietic stem cell transplantation (HSCT) was offered for 4 patients. However due to severity of the disease and delay in diagnosis, 58% of the patients passed away in the first 2 years of life. CONCLUSION: This study highlights the importance of early diagnosis and distribution of ITGß2 gene mutation in Egyptian children. Further molecular studies, however, remain a challenging necessity for better disease characterization in the region.

Comparison of pain and healing period after frenectomy using diode laser and Er:YAG laser: randomized controlled trial.

OBJECTIVES: The frenum is a mucous membrane fold that attaches the lip and the cheek to the alveolar mucosa, the gingiva, and the underlying periosteum. Frenectomy is the surgical removal of the whole frenum, including the area connected to the bones. This study's purpose was to compare the healing period and postsurgical pain experienced by patients operated with diode and erbium:yttrium-aluminium-garnet (Er:YAG) lasers. METHODS: Twenty referred patients need to excision of the abnormal upper labial frenum were included in this study. Patients were randomly assigned into two groups; Diode group (810 nm, 2W, continuous emission, initiated tip) and Er:YAG group (2940 nm, 2W, 200 mJ, 10 Hz). Both lasers were applied in contact mode. Post-operative pain was assessed with Numerical Rating Scale (NRS) at post-operative 3rd hour and every day during the first week. Epithelialization process of the wound surface was evaluated by hydrogen peroxide solution applied to the wound on days 7, 14, 30, 60 and 90 following operations. RESULTS: The result shows mean values in Pain index after 3 hours (Diode Group 2.1±2.0, Er:YAG Group 2.6±1.4), 1st day (Diode Group 1.1±1.1, Er:YAG Group 1.9±1.4), and 2nd day (Diode Group 0, Er:YAG Group 0.9±1.1) and shows no significant difference after (3-7 days); p =1.00). In Healing index the results shows a significant difference between the Diode Group and the Er:YAG Group (after 7 days; p = 0.029 and 14 days; p = 0.001) and show no significant difference after (30-60-90 days; p = 1.00). CONCLUSIONS: The Er:YAG laser has better clinical results in healing wounds, whereas the diode laser is better in decreasing pain after frenectomy during follow-up periods.

Tapping the biosynthetic potential of marine Bacillus licheniformis LHG166, a prolific sulphated exopolysaccharide producer: structural insights, bio-prospecting its antioxidant, antifungal, antibacterial and anti-biofilm potency as a novel anti-infective lead.

The escalating global threat of antimicrobial resistance necessitates prospecting uncharted microbial biodiversity for novel therapeutic leads. This study mines the promising chemical richness of Bacillus licheniformis LHG166, a prolific exopolysaccharide (EPSR2-7.22 g/L). It comprised 5 different monosaccharides with 48.11% uronic acid, 17.40% sulfate groups, and 6.09% N-acetyl glucosamine residues. EPSR2 displayed potent antioxidant activity in DPPH and ABTS+, TAC and FRAP assays. Of all the fungi tested, the yeast Candida albicans displayed the highest susceptibility and antibiofilm inhibition. The fungi Aspergillus niger and Penicillium glabrum showed moderate EPSR2 susceptibility. In contrast, the fungi Mucor circinelloides and Trichoderma harzianum were resistant. Among G+ve tested bacteria, Enterococcus faecalis was the most susceptible, while Salmonella typhi was the most sensitive to G-ve pathogens. Encouragingly, EPSR2 predominantly demonstrated bactericidal effects against both bacterial classes based on MBC/MIC of either 1 or 2 superior Gentamicin. At 75% of MBC, EPSR2 displayed the highest anti-biofilm activity of 88.30% against B. subtilis, while for G-ve antibiofilm inhibition, At 75% of MBC, EPSR2 displayed the highest anti-biofilm activity of 96.63% against Escherichia coli, Even at the lowest dose of 25% MBC, EPSR2 reduced biofilm formation by 84.13% in E. coli, 61.46% in B. subtilis. The microbial metabolite EPSR2 from Bacillus licheniformis LHG166 shows promise as an eco-friendly natural antibiotic alternative for treating infections and oxidative stress.

Investigating foliar application of bulk and nanoparticles titanium dioxide on fennel productivity to mitigate the negative effects of saline irrigation water.

BACKGROUND: Fennel essential oils are fragrance compounds used in food and pharmaceutical sectors. One of the major impediments to expansion of fennel farming in Egypt's reclamation areas is saline water. Titanium dioxide (TiO2) or TiO2 nano particles (TiO2NP) can be utilized to boost the yield of aromatic plants cultivated under saline irrigation water. Saline water, particularly which contains sodium chloride can harm fennel plant; consequently, it was predicted that fennel production would fail in Egypt's reclaimed area, where the primary source of irrigation is groundwater consisting sodium chloride. This study sought to help fennel respond to sodium chloride by applying Ti forms to their leaves in order to reduce the detrimental effects of sodium chloride on them for expanding their production in the newly reclamation areas as a natural source of essential oil. Ti forms were applied as foliar application at 0, 0.1, 0.2 TiO2, 0.1 TiO2NP, and 0.2 TiO2NP, mM under irrigation with fresh water (0.4 dS m-1), or saline water (51.3 mM or 4.7 dS m-1). RESULTS: Plants exposed to 0.1 mM TiO2NP under fresh water resulted in the maximum values of morphological characters, estragole, oxygenated monoterpenes and photosynthetic pigments; while those subjected to 0.1 mM TiO2NP under saline water gave the greatest values of essential oil, proline, antioxidant enzymes and phenols. The greatest amounts of soluble sugars were recorded with 0.2 mM TiO2NP irrigated with saline water. Plants subjected to 0 mM TiO2 under saline water produced the greatest values of flavonoids, hydrogen peroxide and malondialdehyde. CONCLUSION: To mitigate the negative effects of salty irrigation water on fennel plant production, TiO2NP application is suggested as a potential strategy.

Capacity for the management of kidney failure in the International Society of Nephrology Africa region: report from the 2023 ISN Global Kidney Atlas (ISN-GKHA).

The burden of chronic kidney disease and associated risk of kidney failure are increasing in Africa. The management of people with chronic kidney disease is fraught with numerous challenges because of limitations in health systems and infrastructures for care delivery. From the third iteration of the International Society of Nephrology Global Kidney Health Atlas, we describe the status of kidney care in the ISN Africa region using the World Health Organization building blocks for health systems. We identified limited government health spending, which in turn led to increased out-of-pocket costs for people with kidney disease at the point of service delivery. The health care workforce across Africa was suboptimal and further challenged by the exodus of trained health care workers out of the continent. Medical products, technologies, and services for the management of people with nondialysis chronic kidney disease and for kidney replacement therapy were scarce due to limitations in health infrastructure, which was inequitably distributed. There were few kidney registries and advocacy groups championing kidney disease management in Africa compared with the rest of the world. Strategies for ensuring improved kidney care in Africa include focusing on chronic kidney disease prevention and early detection, improving the effectiveness of the available health care workforce (e.g., multidisciplinary teams, task substitution, and telemedicine), augmenting kidney care financing, providing quality, up-to-date health information data, and improving the accessibility, affordability, and delivery of quality treatment (kidney replacement therapy or conservative kidney management) for all people living with kidney failure.

Enhanced Regularized Ensemble Encoderdecoder Network for Accurate Brain Tumor Segmentation.

BACKGROUND: Segmenting tumors in MRI scans is a difficult and time-consuming task for radiologists. This is because tumors come in different shapes, sizes, and textures, making them hard to identify visually. OBJECTIVE: This study proposes a new method called the enhanced regularized ensemble encoder-decoder network (EREEDN) for more accurate brain tumor segmentation. METHODS: The EREEDN model first preprocesses the MRI data by normalizing the intensity levels. It then uses a series of autoencoder networks to segment the tumor. These autoencoder networks are trained using back-propagation and gradient descent. To prevent overfitting, the EREEDN model also uses L2 regularization and dropout mechanisms. RESULTS: The EREEDN model was evaluated on the BraTS 2020 dataset. It achieved high performance on various metrics, including accuracy, sensitivity, specificity, and dice coefficient score. The EREEDN model outperformed other methods on the BraTS 2020 dataset. CONCLUSION: The EREEDN model is a promising new method for brain tumor segmentation. It is more accurate and efficient than previous methods. Future studies will focus on improving the performance of the EREEDN model on complex tumors.

Rare case in Somalia: Fahr's syndrome.

Introduction and importance: Fahr's syndrome is primarily familial, autosomal dominant, and genetically diverse. Basal ganglia calcification that is bilaterally symmetrical is a hallmark of this illness. Although the specific origins of this illness are unknown, it may be brought on by problems with calcium metabolism, infections, toxins, hereditary factors, hypoparathyroidism, and pseudohypoparathyroidism. The prevalence of this syndrome is less than 0.5%. Case presentation: An 11-year-old female comes to the Emergency Department with her parents complaining of high-grade fever and convulsions for 1 week. Convulsion, which is a generalized tonic-clonic seizure, duration was ~5 min and associated with urinary incontinence and biting tongue. On examination, the patient was confused and irritable. Vital signs were normal; there is weakness in the right arm and right leg, associated with irregular movement. There was alternation in her level of consciousness, slurring of speech, and psychiatric symptoms. Another aspect of the neurological examination and systems was normal, and there was no meningeal irritation. Clinical discussion: The pathogenesis of Fahr's syndrome is not completely known. The calcification is caused by flaws in the transport of radioactive particles and tissue damage caused by free radicals. Bilateral calcification found on a computed tomography (CT) scan of the brain, autosomal dominant inheritance, the absence of any infection, drugs, or toxins, the absence of mitochondrial dysfunction, and the presence of progressive neurological dysfunction is the clinical criteria for diagnosing Fahr's syndrome. Conclusion: Basal ganglia calcification that is bilaterally symmetrical is a hallmark of Fahr's syndrome. CT scans are the gold standard for conclusively diagnosing Fahr's syndrome.

A large-scale study on the prevalence of math anxiety in Qatar.

BACKGROUND: Math anxiety (MA) is a worldwide appearing academic anxiety that can affect student mental health and deter students from math and science-related career choices. METHOD: Using the Arabic version of the Modified-Abbreviated Math Anxiety Scale (m-AMAS), the prevalence of MA was investigated in a very large sample of students (N = 10093) from grades 7 to 12 in Qatar. RESULTS: The results showed a better fit to the original two-factor model of the m-AMAS (learning MA and Evaluation MA) than to a single-factor solution. This two-factor model was also confirmed in each grade. Notably, the distribution of MA scores was right-skewed, especially for learning MA. Using the inter-quartiles ranges, norms for MA were provided: A score of ≤16 indicates low MA whereas a score of ≥30 identifies high MA. Previous studies conducted in Western countries defined high math-anxious students as those who score above the 90th percentile corresponding to a score of 30 on the m-AMAS. Using this cut-off criterion, the current study found that one-fifth of students in Qatar were highly math-anxious, with a higher proportion of females than males. We also calculated the percentage of participants selecting each response category for each questionnaire item. Results showed that attending a long math class was the context that elicited the highest levels of learning MA. In contrast, having an unexpected math test was the situation that triggered the highest levels of evaluation MA. CONCLUSION: The prevalence of MA might vary across different cultures.

Retraction: Amyand Hernia With Acute Appendicitis: A Rare Type of Hernia.

[This retracts the article DOI: 10.7759/cureus.18720.].

High-Density Lipoprotein Is Located Alongside Insulin in the Islets of Langerhans of Normal and Rodent Models of Diabetes.

Recent studies have implicated pre-beta and beta lipoproteins (VLDL and LDL) in the etiopathogenesis of complications of diabetes mellitus (DM). In contrast, alpha lipoprotein (HDL) is protective of the beta cells of the pancreas. This study examined the distribution of HDL in the islets of Langerhans of murine models of type 1 diabetic rats (streptozotocin (STZ)-induced DM in Wistar rats) and type 2 models of DM rats (Goto-Kakizaki (GK), non-diabetic Zucker lean (ZL), and Zucker diabetic and fatty (ZDF)). The extent by which HDL co-localizes with insulin or glucagon in the islets of the pancreas was also investigated. Pancreatic tissues of Wistar non-diabetic, diabetic Wistar, GK, ZL, and ZDF rats were processed for immunohistochemistry. Pancreatic samples of GK rats fed with either a low-fat or a high-fat diet were prepared for transmission immune-electron microscopy (TIEM) to establish the cytoplasmic localization of HDL in islet cells. HDL was detected in the core and periphery of pancreatic islets of Wistar non-diabetic and diabetic, GK, ZL, and ZDF rats. The average total of islet cells immune positive for HDL was markedly (<0.05) reduced in GK and ZDF rats in comparison to Wistar controls. The number of islet cells containing HDL was also remarkably (p < 0.05) reduced in Wistar diabetic rats and GK models fed on high-fat food. The co-localization study using immunofluorescence and TIEM techniques showed that HDL is detected alongside insulin within the secretory granules of ß-cells. HDL did not co-localize with glucagon. This observation implies that HDL may contribute to the metabolism of insulin.

Male reproductive hormone disorders among copper smelter workers.

Male workers in copper smelting are exposed to copper, lead, and arsenic. This study aimed to assess the effects of combined exposure to these metals on male reproductive hormone levels and assesses malondialdehyde (MDA) as an oxidative stress parameter. The study was conducted on 40 copper smelter workers compared with 40 non-exposed workers. Laboratory investigations included levels of serum copper, blood lead, serum arsenic, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and MDA. Levels of copper, arsenic, lead, FSH, and LH were significantly increased compared to controls. However, a statistically significant decrease in the mean value of testosterone was found among exposed workers. Positive correlations between serum copper and both serum FSH and MDA levels were statistically significant as were correlations between serum arsenic and MDA levels. Testosterone levels showed significant negative correlations with both copper and arsenic among exposed workers. A linear regression model of copper, arsenic, and lead levels as independent variables with FSH, LH, and testosterone as dependent variables revealed a significant negative association between serum copper and testosterone levels. The current study concluded that combined exposure to copper, arsenic, and lead in secondary copper smelters had a negative impact on male reproductive hormone levels that may be mediated by oxidative stress.

Phosphorylation bar-coding of free fatty acid receptor 2 is generated in a tissue-specific manner.

Free fatty acid receptor 2 (FFAR2) is activated by short-chain fatty acids and expressed widely, including in white adipocytes and various immune and enteroendocrine cells. Using both wild-type human FFAR2 and a designer receptor exclusively activated by designer drug (DREADD) variant we explored the activation and phosphorylation profile of the receptor, both in heterologous cell lines and in tissues from transgenic knock-in mouse lines expressing either human FFAR2 or the FFAR2-DREADD. FFAR2 phospho-site-specific antisera targeting either pSer296/pSer297 or pThr306/pThr310 provided sensitive biomarkers of both constitutive and agonist-mediated phosphorylation as well as an effective means to visualise agonist-activated receptors in situ. In white adipose tissue, phosphorylation of residues Ser296/Ser297 was enhanced upon agonist activation whilst Thr306/Thr310 did not become phosphorylated. By contrast, in immune cells from Peyer's patches Thr306/Thr310 become phosphorylated in a strictly agonist-dependent fashion whilst in enteroendocrine cells of the colon both Ser296/Ser297 and Thr306/Thr310 were poorly phosphorylated. The concept of phosphorylation bar-coding has centred to date on the potential for different agonists to promote distinct receptor phosphorylation patterns. Here, we demonstrate that this occurs for the same agonist-receptor pairing in different patho-physiologically relevant target tissues. This may underpin why a single G protein-coupled receptor can generate different functional outcomes in a tissue-specific manner.

Risk factors and outcomes associated with pregnancy-related acute kidney injury in a high-risk cohort of women in Nigeria.

INTRODUCTION: Despite a decline in developed countries, pregnancy-related acute kidney injury (PRAKI) remains a significant contributor to maternal mortality and adverse fetal outcomes in resource-constrained settings. Little is known about the impact of pregnancy-related acute kidney injury in Nigeria. Therefore, this study aimed to assess the incidence and maternal-fetal outcomes associated with pregnancy-related acute kidney injury among a cohort of high-risk women in Nigeria. METHODS: This prospective multicenter study included women at high risk of acute kidney injury, who were more than 20 weeks pregnant or within 6 weeks postpartum and admitted to the Obstetrics and Gynecology units of two large public hospitals between September 1, 2019, and July 31, 2022. Acute kidney injury was defined and classified using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: A total of 433 women, with mean age (± standard deviation) of 28 ± 6 years, were included in the evaluation. Pregnancy-related acute kidney injury occurred in 113 women (26.1%; 95% confidence interval [CI]: 21.1%-30.2%). The leading cause was preeclampsia (n = 57; 50.1%); 19 women died (4.4%), with 17 deaths (15%) occurring in the PRAKI group. Increasing severity of pregnancy-related acute kidney injury was independently associated with maternal mortality: adjusted odds ratio (aOR) for KDIGO stage 2 = 4.40; 95% CI 0.66-29.34, p = 0.13, and KDIGO stage 3 aOR = 6.12; 95% CI 1.09-34.34, p = 0.04. The overall perinatal mortality was 15% (n = 65), with 28 deaths (24.8%) occurring in the PRAKI group. Pregnancy-related acute kidney injury was also associated with an increased risk of perinatal mortality, aOR = 2.23; 95 CI 1.17-4.23, p = 0.02. CONCLUSIONS: The incidence of pregnancy-related acute kidney injury was high, and significantly associated with maternal and perinatal mortality. The leading causes were hypertensive disorders of pregnancy.

Resistomycin Suppresses Prostate Cancer Cell Growth by Instigating Oxidative Stress, Mitochondrial Apoptosis, and Cell Cycle Arrest.

Globally, prostate cancer is among the most threatening and leading causes of death in men. This study, therefore, aimed to search for an ideal antitumor strategy with high efficacy, low drug resistance, and no or few adverse effects. Resistomycin is a natural antibiotic derived from marine actinomycetes, and it possesses various biological activities. Prostate cancer cells (PC3) were treated with resistomycin (IC12.5: 0.65 or IC25: 1.3 µg/mL) or 5-fluorouracil (5-FU; IC25: 7 µg/mL) for 24 h. MTT assay and flow cytometry were utilized to assess cell viability and apoptosis. Oxidative stress, apoptotic-related markers, and cell cycle were also assessed. The results revealed that the IC50 of resistomycin and 5-FU on PC3 cells were 2.63 µg/mL and 14.44 µg/mL, respectively. Furthermore, treated cells with the high dose of resistomycin showed an increased number of apoptotic cells compared to those treated with the lower dose. Remarkable induction of reactive oxygen species generation and lactate dehydrogenase (LDH) leakage with high malondialdehyde (MDA), carbonyl protein (CP), and 8-hydroxyguanosine (8-OHdG) contents were observed in resistomycin-treated cells. In addition, marked declines in glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in PC3 cells subjected to resistomycin therapy were observed. Resistomycin triggered observable cell apoptosis by increasing Bax, caspase-3, and cytosolic cytochrome c levels and decreasing Bcl-2 levels. In addition, notable downregulation of proliferating cell nuclear antigen (PCNA) and cyclin D1 was observed in resistomycin-treated cancerous cells. According to this evaluation, the antitumor potential of resistomycin, in a concentration-dependent manner, in prostate cancer cells was achieved by triggering oxidative stress, mitochondrial apoptosis, and cell cycle arrest in cancer cells. In conclusion, our investigation suggests that resistomycin can be considered a starting point for developing new chemotherapeutic agents for human prostate cancer.