Late-Onset Autosomal Dominant Macular Degeneration Caused by Deletion of the CRX Gene.

PURPOSE: To characterize the phenotype observed in a case series with macular disease and determine the cause. DESIGN: Multicenter case series. PARTICIPANTS: Six families (7 patients) with sporadic or multiplex macular disease with onset at 20 to 78 years, and 1 patient with age-related macular degeneration. METHODS: Patients underwent ophthalmic examination; exome, genome, or targeted sequencing; and/or polymerase chain reaction (PCR) amplification of the breakpoint, followed by cloning and Sanger sequencing or direct Sanger sequencing. MAIN OUTCOME MEASURES: Clinical phenotypes, genomic findings, and a hypothesis explaining the mechanism underlying disease in these patients. RESULTS: All 8 cases carried the same deletion encompassing the genes TPRX1, CRX, and SULT2A1, which was absent from 382 control individuals screened by breakpoint PCR and 13 096 Clinical Genetics patients with a range of other inherited conditions screened by array comparative genomic hybridization. Microsatellite genotypes showed that these 7 families are not closely related, but genotypes immediately adjacent to the deletion breakpoints suggest they may share a distant common ancestor. CONCLUSIONS: Previous studies had found that carriers for a single defective CRX allele that was predicted to produce no functional CRX protein had a normal ocular phenotype. Here, we show that CRX whole-gene deletion in fact does cause a dominant late-onset macular disease.

Effect of eCG dose on ovarian haemodynamics, hormonal profiles and prolificacy rate when oestrus was induced during low-breeding season in Beetal goats.

The objectives of the experiment were to determine the effect of two doses of equine chorionic gonadotropin (eCG) in a standard synchronization protocol based on a short-term progesterone (P4 ) priming on ovarian structures and haemodynamics, concentrations of steroid hormones and prolificacy rate when oestrus was induced during low-breeding season (LBS) in Beetal dairy goats. We hypothesized that inclusion of eCG in a short-term P4 priming-based synchronization protocol would increase the blood perfusion to ovarian structures leading to enhance oestrous and ovulatory responses and prolificacy rate in goats. Forty-two multiparous acyclic goats were blocked by body condition and, within block, assigned randomly to receive saline as control (CON), low eCG (L-eCG; 300 IU) or high eCG (H-eCG; 600 IU) dose. Initially, a controlled internal drug release (CIDR) device was placed in the anterior vagina on d -8, followed by removal of CIDR on d -3, concurrent with the administration of PGF2α and eCG according to their respective treatments. Goats were monitored for oestrous response. B-mode and Doppler ultrasonography was performed with 12-h interval, starting from day -3 until natural breeding (day 0), and then on days 5, 10, 15 and 20 post-breeding to monitor follicular and luteal dynamics and blood flow, respectively. Blood was sampled at 0, 12, 24, 36 and 60 h after CIDR removal to quantify plasma concentrations of estradiol-17ß (E2 ), whereas plasma concentrations of P4 were assayed at days 5, 10, 15 and 20 after breeding. Pregnancy and prolificacy rates were determined at day 30 and 150 after breeding, respectively. Data were analysed with mixed-effects models, and orthogonal contrasts were used to evaluate the effect of treatment [Con vs. (½ L-eCG + ½ H-eCG)] and dose of eCG (L-eCG vs. H-eCG). Data are presented in sequence as CON, L-eCG, H-eCG (LSM ± SEM). The oestrous intensity score (152.9 vs. 182.7 vs. 186.5 ± 15.1; p = .02) was greater in eCG-treated goats as compared to CON. Administration of eCG reduced the intervals to standing oestrus (66.2 vs. 41.8 vs. 48.9 h ± 5.5; p = .05), breeding (70.2 vs. 44.4 vs. 45.4 h ± 4.5; p = .03) and ovulation (84.5 vs. 61.2 vs. 63.4 h ± 6.2; p = .05) compared with CON goats. The mean growth rate of pre-ovulatory follicle was greater (1.11 vs. 1.49 vs. 1.45 mm ± 0.08; p = .01) in eCG-treated goats resulting in an increased diameter of pre-ovulatory follicle (6.27 vs. 7.20 vs. 7.31 mm ± 0.07; p < .01) and corpora lutea (6.75 vs. 8.26 vs. 8.07 mm ± 0.42; p = .04) than CON. The mean follicular blood flow did not differ among treatments; however, the mean luteal blood flow was greater in L-eCG-treated goats (0.81 vs. 1.61 vs. 1.07 cm2 ± 0.12; p = .001). The mean concentrations of E2 (4.03 vs. 5.21 vs. 4.78 pg/ml ± 0.42; p = .04) and P4 (4.85 vs. 6.39 vs. 6.22 ng/ml ± 0.34; p = .04) were greater in eCG-treated goats. The twinning rate did not differ between treatments; nevertheless, prolificacy rate was greater (p = .04) in L-eCG-treated goats. Collectively, our data suggest that the administration of eCG improves the induction of oestrous and ovarian dynamics. Administration of L-eCG enhances prolificacy rate, therefore, a low dose of eCG might be practically beneficial to improve reproduction during LBS in acyclic Beetal dairy goats.

Diversity and distribution of thermophilic microorganisms and their applications in biotechnology.

Hot springs ecosystem is the most ancient continuously inhabited ecosystem on earth which harbors diverse thermophilic bacteria and archaea distributed worldwide. Life in extreme environments is very challenging so there is a great potential biological dark matter and their adaptation to harsh environments eventually producing thermostable enzymes which are very vital for the welfare of mankind. There is an enormous need for a new generation of stable enzymes that can endure harsh conditions in industrial processes and can either substitute or complement conventional chemical processes. Here, we review at the variety and distribution of thermophilic microbes, as well as the different thermostable enzymes that help them survive at high temperatures, such as proteases, amylases, lipases, cellulases, pullulanase, xylanases, and DNA polymerases, as well as their special properties, such as high-temperature stability. We have documented the novel isolated thermophilic and hyperthermophilic microorganisms, as well as the discovery of their enzymes, demonstrating their immense potential in the scientific community and in industry.

A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC).

Inherited retinal diseases (IRDs) cause visual loss due to dysfunction or progressive degeneration of photoreceptors. These diseases show marked phenotypic and genetic heterogeneity. The Israeli IRD consortium (IIRDC) was established in 2013 with the goal of performing clinical and genetic mapping of the majority of Israeli IRD patients. To date, we recruited 2,420 families including 3,413 individuals with IRDs. On the basis of our estimation, these patients represent approximately 40% of Israeli IRD patients. To the best of our knowledge, this is, by far, the largest reported IRD cohort, and one of the first studies addressing the genetic analysis of IRD patients on a nationwide scale. The most common inheritance pattern in our cohort is autosomal recessive (60% of families). The most common retinal phenotype is retinitis pigmentosa (43%), followed by Stargardt disease and cone/cone-rod dystrophy. We identified the cause of disease in 56% of the families. Overall, 605 distinct mutations were identified, of which 12% represent prevalent founder mutations. The most frequently mutated genes were ABCA4, USH2A, FAM161A, CNGA3, and EYS. The results of this study have important implications for molecular diagnosis, genetic screening, and counseling, as well as for the development of new therapeutic strategies for retinal diseases.

LONGITUDINAL STUDY OF RPE65-ASSOCIATED INHERITED RETINAL DEGENERATIONS.

PURPOSE: To study the disease course of RPE65-associated inherited retinal degenerations (IRDs) as a function of the genotype, define a critical age for blindness, and identify potential modifiers. METHODS: Forty-five patients with IRD from 33 families with biallelic RPE65 mutations, 28 stemming from a genetic isolate. We collected retrospective data from medical charts. Coexisting variants in 108 IRD-associated genes were identified with Molecular Inversion Probe analysis. RESULTS: Most patients were diagnosed within the first years of life. Daytime visual function ranged from near-normal to blindness in the first four decades and met WHO criteria for blindness for visual acuity and visual field in the fifth decade. p.(Thr368His) was the most common variant (54%). Intrafamilial variability and interfamilial variability in disease severity and progression were observed. Molecular Inversion Probe analysis confirmed all RPE65 variants and identified one additional variant in LRAT and one in EYS in two separate patients. CONCLUSION: All patients with RPE65-associated IRDs developed symptoms within the first year of life. Visual function in childhood and adolescence varied but deteriorated inevitably toward blindness after age 40. In this study, genotype was not predictive of clinical course. The variance in severity of disease could not be explained by double hits in other IRD genes.

EYS mutation update: In silico assessment of 271 reported and 26 novel variants in patients with retinitis pigmentosa.

Mutations in Eyes shut homolog (EYS) are one of the most common causes of autosomal recessive (ar) retinitis pigmentosa (RP), a progressive blinding disorder. The exact function of the EYS protein and the pathogenic mechanisms underlying EYS-associated RP are still poorly understood, which hampers the interpretation of the causality of many EYS variants discovered to date. We collected all reported EYS variants present in 377 arRP index cases published before June 2017, and uploaded them in the Leiden Open Variation Database (www.LOVD.nl/EYS). We also describe 36 additional index cases, carrying 26 novel variants. Of the 297 unique EYS variants identified, almost half (n = 130) are predicted to result in premature truncation of the EYS protein. Classification of all variants using the American College of Medical Genetics and Genomics guidelines revealed that the predicted pathogenicity of these variants cover the complete spectrum ranging from likely benign to pathogenic, although especially missense variants largely fall in the category of uncertain significance. Besides the identification of likely benign alleles previously reported as being probably pathogenic, our comprehensive analysis underscores the need of functional assays to assess the causality of EYS variants, in order to improve molecular diagnostics and counseling of patients with EYS-associated RP.

Cooking, storage, and reheating effect on the formation of cholesterol oxidation products in processed meat products.

BACKGROUND: Cholesterol is an important biological compound; however, its oxidation products have been proven to be harmful to human health. Cooking, storage, and reheating methods significantly affect the safety of meat products, as they contribute to the production of cholesterol oxidation products (COPs). METHODS: Three cooking methods were used to cook sausages, loin ham, bacon, luncheon meat, and pressed ham, in order to investigate the effect of cooking, storage, and reheating on total cholesterol and on the formation of COPs. Cooked samples were stored at 4 °C and reheated after 3 and 6 storage days by the same cooking method or by microwaving. The samples were assessed for total lipids, cholesterol, and cholesterol oxides. RESULTS: The average cholesterol content in the processed meat varied from 76.0 mg/100 g to 201.70 mg/100 g. Microwaved ham showed the lowest cholesterol content compared to that of other processed meat products. Significant differences were found in cholesterol content and cholesterol oxidation products depending on cooking, storage, and reheating methods. Six cholesterol oxides were found in processed meat, of which 7ß-hydroxycholesterol and α-epoxides were detected as the major oxidation products. CONCLUSIONS: Microwaving and oven grilling resulted in higher production of COPs in processed meat as compared with other cooking methods. Refrigerated storage tended to significantly increase the COPs content.

Identification of novel CYP1B1 gene mutations in patients with primary congenital and primary open-angle glaucoma.

BACKGROUND: CYP1B1 is the most commonly mutated gene in primary congenital glaucoma (PCG), and mutations have also been identified in primary open-angle glaucoma (POAG). This study was undertaken to describe mutations in CYP1B1 in patients and families with PCG and POAG from Pakistan. DESIGN: Case-control series. PARTICIPANTS: Forty families, 190 sporadic POAG cases and 140 controls from Pakistan. METHODS: Patients and healthy individuals of one consanguineous Pakistani family were genotyped with high-resolution single nucleotide polymorphism microarrays. Homozygosity mapping was performed using HomozygosityMapper. Direct sequencing of CYP1B1 gene was performed in probands of the families, sporadic POAG cases and control individuals. MAIN OUTCOME MEASURES: Mutations in the CYP1B1 gene in PCG and POAG patients. RESULTS: Homozygosity mapping in a consanguineous Pakistani family revealed one 11-Mb homozygous region encompassing the CYP1B1 gene. A homozygous CYP1B1 missense mutation (p.Arg390His) was identified in this family. Sequence analysis of CYP1B1 in 39 additional families revealed one known and three novel homozygous mutations in PCG (p.Ala288Pro, p.Asp242Ala, p.Arg355* and p.Arg290Profs*37). In POAG, one novel heterozygous missense mutation (p.Asp316Val) was identified in one family and a previously reported mutation (p.Glu229Lys) was identified in three families. Analysis of CYP1B1 in a panel of 190 sporadic POAG patients revealed three novel heterozygous variants (p.Thr234Lys, p.Ala287Pro and p.Gln362*) and three previously reported heterozygous variants (p.Gly61Glu, p.Glu229Lys and p.Arg368His). The p.Glu229Lys variant was significantly associated with POAG (P = 0.03; odds ratio 2.49). CONCLUSIONS: This study confirms that CYP1B1 mutations are associated with POAG and PCG in the Pakistani population.

Mutations in IMPG2, encoding interphotoreceptor matrix proteoglycan 2, cause autosomal-recessive retinitis pigmentosa.

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases caused by progressive degeneration of the photoreceptor cells. Using autozygosity mapping, we identified two families, each with three affected siblings sharing large overlapping homozygous regions that harbored the IMPG2 gene on chromosome 3. Sequence analysis of IMPG2 in the two index cases revealed homozygous mutations cosegregating with the disease in the respective families: three affected siblings of Iraqi Jewish ancestry displayed a nonsense mutation, and a Dutch family displayed a 1.8 kb genomic deletion that removes exon 9 and results in the absence of seven amino acids in a conserved SEA domain of the IMPG2 protein. Transient transfection of COS-1 cells showed that a construct expressing the wild-type SEA domain is properly targeted to the plasma membrane, whereas the mutant lacking the seven amino acids appears to be retained in the endoplasmic reticulum. Mutation analysis in ten additional index cases that were of Dutch, Israeli, Italian, and Pakistani origin and had homozygous regions encompassing IMPG2 revealed five additional mutations; four nonsense mutations and one missense mutation affecting a highly conserved phenylalanine residue. Most patients with IMPG2 mutations showed an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. The patient with the missense mutation, however, was diagnosed with maculopathy. The IMPG2 gene encodes the interphotoreceptor matrix proteoglycan IMPG2, which is a constituent of the interphotoreceptor matrix. Our data therefore show that mutations in a structural component of the interphotoreceptor matrix can cause arRP.

Selective deposition of dietary α-lipoic acid in mitochondrial fraction and its synergistic effect with α-tocoperhol acetate on broiler meat oxidative stability.

The use of bioactive antioxidants in feed of broiler to mitigate reactive oxygen species (ROS) in biological systems is one of promising nutritional strategies. The aim of present study was to alleviate ROS production in mitochondrial fraction (MF) of meat by supplemented dietary antioxidant in feed of broiler. For this purpose, mitochondria specific antioxidant: α-lipoic acid (25 mg, 75 mg and 150 mg) with or without combination of α-tocopherol acetate (200 mg) used in normal and palm olein oxidized oil (4%) supplemented feed. One hundred and eighty one day old broiler birds were randomly divided into six treatments and provided the mentioned feed from third week. Feed intake, feed conversion ratio (FCR) remained statistically same in all groups while body weight decreased in supplemented groups accordingly at the end of study. The broiler meat MF antioxidant potential was significantly improved by feeding supplemented feed estimated as 1,1-di phenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, 2,2-azinobis-(3- ethylbenzothiazoline-6-sulphonic acid) (ABTS+) and thiobarbituric acid reactive substances (TBARS). The maximum antioxidant activity was depicted in group fed on 150 mg/kg α-lipoic acid (ALA) and 200 mg/kg α-tocopherol acetate (ATA) (T4) in both breast and leg MF. Moreover, TBARS were higher in leg as compared to breast MF. Although, oxidized oil containing feed reduced the growth, lipid stability and antioxidant potential of MF whilst these traits were improved by receiving feed containing ALA and ATA. ALA and ATA showed higher deposition in T4 group while least in group received oxidized oil containing feed (T5). Positive correlation exists between DPPH free radical scavenging activity and the ABTS + reducing activity. In conclusion, ALA and ATA supplementation in feed had positive effect on antioxidant status of MF that consequently diminished the oxidative stress in polyunsaturated fatty acid enriched meat.

Doctors' Perception Regarding Bariatric Surgery and Major Barriers in Referral of Morbidly Obese Patients for Surgery in Khyber Pakhtunkhwa.

INTRODUCTION: Obesity is on the rise worldwide and has emerged as a global health concern. It has presented itself as the leading cause of morbidity, disability, and healthcare utilization. Bariatric surgery is a viable treatment option that offers sustained weight loss and improvement in comorbidities. The aim of this study is to determine the perception of doctors regarding bariatric surgery and the major barriers to the referral of morbidly obese for surgery. METHOD: This study is a cross-sectional descriptive study conducted from November 1, 2022, to December 31, 2022. It involved prospective data collection through online questionnaires filled by doctors practicing in Peshawar. The sampling technique was non-probability convenience-based sampling. The sample size was 152. Doctors from all age groups and both genders were included in our study. Non-consenting doctors and those who were practicing bariatric surgery were excluded. Data were analyzed using a statistical package for social sciences (SPSS) version 25.0 (IBM Inc., Armonk, NY). Categorical variables have been presented as frequencies and percentages. Numerical variables have been presented as mean ± SD. RESULTS: A total of 152 doctors participated in our research study; 92 were physicians and 60 were surgeons. The majority of our study participants' patient load per week was >75. Around 47% believed bariatric surgery was a valuable tool in the treatment of morbid obesity. The most commonly reported barrier to referral was surgical complications or side effects (28.9%). CONCLUSION: The study concluded that the awareness regarding bariatric and metabolic surgery remains flimsy among the doctor community. Most of the physicians were unaware of the benefits of the surgical management of obesity. They also had doubts regarding the safety of the procedure. We need proper utilization of awareness strategies to overcome these barriers.

Can Milking-Like Effect Be the First Clue of a Ventricular Free Wall Rupture?

Ventricular free wall rupture (VFWR) is a catastrophic complication of myocardial infarction that poses an imminent surgical emergency. Early recognition is essential as it can expedite the process for a life-saving surgical intervention. We present a case of an acute left VFWR resulting from an underlying myocardial infarction which showed a "milking-like effect" during diagnostic angiography. "Milking-like effect" is an angiographic phenomenon typically seen in myocardial bridging, which occurs due to the compression of the intramyocardial coronary segments during systole. The presence of this phenomenon is believed to occur due to the extrinsic compression of the coronary by the evolving hemopericardium.

Study on Various Luteal Characteristics Using Doppler Ultrasonography for Early Pregnancy Diagnosis in Nili-Ravi Buffaloes.

The objective of current study was to assess the trend in various luteal characteristics viz luteal size (LS), plasma progesterone (P4) concentration, and luteal blood flow (LBF) using color Doppler imaging (CDI) and power Doppler imaging (PDI) modes in pregnant and nonpregnant Nili-Ravi buffaloes. Lactating, cyclic, and healthy Nili-Ravi buffaloes (n = 09) without any reproductive abnormality were selected in present study. Buffaloes were synchronized using Ov-Synch, and fixed-time artificially insemination was performed (day = 0). Pregnancy was diagnosed on 30-day post-AI using B-mode ultrasonography based on presence or absence of embryonic heartbeat. Ovaries of all animals were scanned from day 5 till 21 post-AI using both B-mode and Doppler ultrasonography to measure LS and LBF. After each ovarian ultrasound examination, blood samples were collected via jugular venipuncture to determine plasma P4 concentration. According to results, LBF using CDI and PDI was significantly higher (P ≤ 0.05) in pregnant buffaloes on days 13 and 15 post-AI, respectively. The mean LS and plasma P4 concentration did not differ (P ≥ 0.05) between pregnant and nonpregnant animals until day 15 post-AI. However, a significant difference (P ≤ 0.05) was noticed for both on day 17 and onwards. It is concluded that LBF is a more sensitive luteal character as compared to LS and P4 for earlier pregnancy diagnosis in Nili-Ravi buffaloes when ascertained through CDI.

Bi and Sn Doping Improved the Structural, Optical and Photovoltaic Properties of MAPbI3-Based Perovskite Solar Cells.

One of the most amazing photovoltaic technologies for the future is the organic-inorganic lead halide perovskite solar cell, which exhibits excellent power conversion efficiency (PCE) and can be produced using a straightforward solution technique. Toxic lead in perovskite can be replaced by non-toxic alkaline earth metal cations because they keep the charge balance in the material and some of them match the Goldschmidt rule's tolerance factor. Therefore, thin films of MAPbI3, 1% Bi and 0%, 0.5%, 1% and 1.5% Sn co-doped MAPbI3 were deposited on FTO-glass substrates by sol-gel spin-coating technique. XRD confirmed the co-doping of Bi-Sn in MAPbI3. The 1% Bi and 1% Sn co-doped film had a large grain size. The optical properties were calculated by UV-Vis spectroscopy. The 1% Bi and 1% Sn co-doped film had small Eg, which make it a good material for perovskite solar cells. These films were made into perovskite solar cells. The pure MAPbI3 film-based solar cell had a current density (Jsc) of 9.71 MA-cm-2, its open-circuit voltage (Voc) was 1.18 V, its fill factor (FF) was 0.609 and its efficiency (η) was 6.98%. All of these parameters were improved by the co-doping of Bi-Sn. The cell made from a co-doped MAPbI3 film with 1% Bi and 1% Sn had a high efficiency (10.03%).

The Effect of 600 keV Ag Ion Irradiation on the Structural, Optical, and Photovoltaic Properties of MAPbBr3 Films for Perovksite Solar Cell Applications.

A competitive new technology, organic metallic halide perovskite solar cells feature a wide working area, low manufacturing costs, a long lifespan, and a significant amount of large efficacy of power conversion (PCE). The spin-coating technique was utilized for the fabrication of pure CH3NH3PbBr3 (MAPbBr3) thin films, and these films are implanted with 600 keV silver (Ag) ions at fluency rate of 6 × 1014 and 4 × 1014 ions/cm2. XRD analysis confirmed the cubic structure of MAPbBr3. A high grain size was observed at the fluency rate of 4 × 1014 ions/cm2. The UV-Vis spectroscopic technique was used to calculate the optical properties such as the bandgap energy (Eg), refractive index (n), extinction coefficients (k), and dielectric constant. A direct Eg of 2.44 eV was measured for the pristine film sample, whereas 2.32 and 2.36 eV were measured for Ag ion-implanted films with a 4 × 1014 and 6 × 1014 ions/cm2 fluence rate, respectively. The solar cells of these films were fabricated. The Jsc was 6.69 mA/cm2, FF was 0.80, Voc was 1.1 V, and the efficiency was 5.87% for the pristine MAPbBr3-based cell. All of these parameters were improved by Ag ion implantation. The maximum values were observed at a fluency rate of 4 × 1014 ions/cm2, where the Voc was 1.13 V, FF was 0.75, Jsc was 8.18 mA/cm2, and the efficiency was 7.01%.

Effect of COVID-19 on presentations of decompensated liver disease in Scotland.

BACKGROUND AND AIMS: SARS-CoV-2 and consequent pandemic has presented unique challenges. Beyond the direct COVID-related mortality in those with liver disease, we sought to determine the effect of lockdown on people with liver disease in Scotland. The effect of lockdown on those with alcohol-related disease is of interest; and whether there were associated implications for a change in alcohol intake and consequent presentations with decompensated disease. METHODS: We performed a retrospective analysis of patients admitted to seven Scottish hospitals with a history of liver disease between 1 April and 30 April 2020 and compared across the same time in 2017, 2018 and 2019. We also repeated an intermediate assessment based on a single centre to examine for delayed effects between 1 April and 31 July 2020. RESULTS: We found that results and outcomes for patients admitted in 2020 were similar to those in previous years in terms of morbidity, mortality, and length of stay. In the Scotland-wide cohort: admission MELD (Model for End-stage Liver Disease) (16 (12-22) vs 15 (12-19); p=0.141), inpatient mortality ((10.9% vs 8.6%); p=0.499) and length of stay (8 days (4-15) vs 7 days (4-13); p=0.140). In the Edinburgh cohort: admission MELD (17 (12-23) vs 17 (13-21); p=0.805), inpatient mortality ((13.7% vs 10.1%; p=0.373) and length of stay (7 days (4-14) vs 7 days (3.5-14); p=0.525)). CONCLUSION: This assessment of immediate and medium-term lockdown impacts on those with chronic liver disease suggested a minimal effect on the presentation of decompensated liver disease to secondary care.

HnRNP F and hnRNP H1 regulate mRNA stability of amyloid precursor protein.

Amyloid precursor protein (APP) is a transmembrane protein that plays a crucial role in the production of amyloid-ß peptides. Any disruption in APP protein production, its mRNA decay rate or processing may result in abnormal production of amyloid-ß peptides and subsequent development of protein aggregation diseases. Therefore, the equilibrium is crucial for neuronal function. An association study of heterogeneous nuclear ribonucleoprotein (hnRNP)-F and hnRNP H1 with APP was carried out in Neuro-2a (N2a) cells. In the present study, we found that hnRNP F and hnRNP H1 were significantly upregulated in the hippocampus of APP/PS1 mice. The changes in APP expression were positively associated with hnRNP F and hnRNP H1 when hnRNP F and hnRNP H1 were depleted or increased in N2a cells. Importantly, cross-linked RNA immunoprecipitation demonstrated binding affinities of hnRNP F and hnRNP H1 for App mRNA. Mechanistically, mRNA stability assay revealed that overexpression of hnRNP F or hnRNP H1 increases the APP level by stabilizing App mRNA half-life, implying that levels of hnRNP F and hnRNP H1 can change the production of APP. Further understanding of the regulatory mechanism of APP expression in association with hnRNP F and hnRNP H1 would provide insights into the mechanism underlying the maintenance of brain health and cognition. This study provides a theoretical basis for the development of hnRNP-stabilizing compounds to regulate APP.

Anomalous Origin of the Right Coronary Artery From the Ascending Aorta Above the Left Sinus of Valsalva.

Congenital anomalous origin of the coronary arteries is a rare but well-described cause of myocardial ischemia and sudden cardiac death. Anomalous origin of the right coronary artery from the ascending aorta is an extraordinarily rare occurrence. We report a case of anomalous origin of the right coronary artery from the ascending aorta posteriorly above the left sinus of Valsalva found during coronary angiography for evaluation of newly diagnosed cardiomyopathy.

Feasibility and Acceptability of Instructions of Daily Care in Overweight and Obese Knee Osteoarthritis Participants.

INTRODUCTION: Knee Osteoarthritis (OA) is a weight-bearing joint disease and is more common in overweight and obese persons. The objective of the study was to assess the feasibility and acceptability of Instructions of Daily Care (IDC) on pain, mobility, and Body Mass Index (BMI) among knee OA participants who are overweight or obese. MATERIALS AND METHODS: The study was an open-label randomized controlled trial of six weeks. Forty overweight and obese participants with knee OA were randomly divided into two groups by a computer-generated number. The participants in the Instruction Group (IG) were provided with leaflets explaining IDC for the duration of six weeks. Both groups were instructed to take low doses of the non-steroid anti-inflammatory drug (NSAIDs) on alternate days. The outcome measures were pain, mobility and BMI. The feasibility and acceptability of knee pain and mobility were assessed using a questionnaire designed by experts in rehabilitation. RESULTS: Participants in the IG reported more statistically significant pain relief as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index score (p=0.001) and improvement in mobility (p=0.000) assessed by the Timed Up and Go test score after six weeks compared to the Control Group (CG). Both groups did not demonstrate any significant change in BMI (p-value > 0.05). The results of descriptive statistics showed a significantly higher satisfaction score for participants who received a combination of IDC and NSAIDs, indicating an acceptable intervention. CONCLUSION: The IDC is effective and acceptable in terms of improving pain and mobility and should be recommended as the usual care of treatment.

Early prediction keys for COVID-19 cases progression: A meta-analysis.

BACKGROUNDː: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), within few months of being declared as a global pandemic by WHO, the number of confirmed cases has been over 75 million and over 1.6 million deaths since the start of the Pandemic and still counting, there is no consensus on factors that predict COVID-19 case progression despite the diversity of studies that reported sporadic laboratory predictive values predicting severe progression. We review different biomarkers to systematically analyzed these values to evaluate whether are they are correlated with the severity of COVID-19 disease and so their ability to be a predictor for progression. METHODS: The current meta-analysis was carried out to identify relevant articles using eight different databases regarding the values of biomarkers and risk factors of significance that predict progression of mild or moderate cases into severe and critical cases. We defined the eligibility criteria using a PICO model. RESULTS: Twenty-two relevant articles were selected for meta-analysis the following biomarkers C-reactive protein, interleukin-6, LDH, neutrophil, %PD-1 expression, D-dimer, creatinine, AST and Cortisol all recorded high cut-off values linked to severe and critical cases while low lymphocyte count, and low Albumin level were recorded. Also, we meta- analyzed age and comorbidities as a risk factors of progression as hypertension, Diabetes and chronic obstructive lung diseases which significantly correlated with cases progression (p < 0.05). CONCLUSIONS: ː The current meta-analysis is the first step for analysing and getting cut-off references values of significance for prediction COVID-19 case progression. More studies are needed on patients infected with SARS-CoV-2 and on a larger scale to establish clearer threshold values that predict progression from mild to severe cases. In addition, more biomarkers testing also help in building a scoring system for the prediction and guiding for proper timely treatment.