Exome sequencing revealed variants in SGCA and SIL1 genes underlying limb girdle muscular dystrophy and Marinesco-Sjögren syndrome patients.

BACKGROUND: Inherited neuromuscular (NMD) and neurodegenerative diseases (NDD) belong to two distinct categories that disturb different components of the nervous system, leading to a variety of different symptoms and clinical manifestations. Both NMD and NDD are a heterogeneous group of genetic conditions. Genetic variations in the SGCA and SIL1 genes have been implicated in causing Limb Girdle Muscular Dystrophy (LGMD), a type of neuromuscular disorder, and Marinesco-Sjögren Syndrome (MSS) which is a neurodegenerative disorder. METHODS: In the present study, we have investigated four patients presenting LGMD and five patients with MSS features. After collecting detailed clinical and family history, necessary laboratory investigations, including estimation of a skeletal muscle marker enzyme serum creatine kinase (CK), nerve conduction study (NCS), electromyography (EMG), echocardiography (Echo), Magnetic resonance imaging (MRI -brain), CT-brain and X-rays were performed. Whole exome followed by Sanger sequencing was employed to search for the disease-causing variants. RESULTS: Physical examination in LGMD patients revealed poor muscle tone and facing difficulty in straightening up from the floor. Clinical history revealed frequent falls and strenuousness in climbing stairs. They started toe-walking in early childhood. Laboratory investigations confirmed elevated CK levels and abnormal NCS and EMG. The MSS patients showed abnormalities in gate and jerking movement, abnormal speech, and strabismus with cataract. MRI-brain showed cerebral atrophy in some MSS patients with elevated CK levels. Whole exome sequencing revealed a nonsense variant [c.C574T, p.(Arg192*)] in the SGCA gene and a frameshift [c.936dupG, p.(Leu313AlaFs*39)] in the SIL1 gene in LGMD and MSS patients, respectively. CONCLUSION: Our study emphasizes the significance of integrating clinical and genetic analyses for precise diagnosis and tailored management strategies in inherited NMD and NDD disorders. To the best of our knowledge, this is the first study documenting SGCA and SIL1 recurrent variants in subcontinent populations with few rare clinical features. The recurrent mutations expanding the global understanding of the mutation's geographic and ethnic distribution and contributing valuable epidemiological data. The study will facilitate genetic counseling for families experiencing similar clinical features, both within Pakistani populations and in other regions.

Effect of medication adherence on quality of life, activation measures, and health imagine in the elderly people: a cross-sectional study.

BACKGROUND: Usually, old age brings a poor quality of life due to illness and frailty. To prolong their lives and ensure their survival, all elderly patients with chronic diseases must adhere to their medications. In our study, we investigate medication adherence for elderly patients and its impact on the general health of the patient. METHODS: We implemented a cross-sectional survey-based study with four sections in April 2022 in Saudi Arabia. Data about the participants' demographic characteristics, the Morisky Medication Adherence Scale, Patient Activation Measure (PAM) 13, and EQ-5D-5 L. RESULTS: A total of 421 patients participated in this study, their mean age was 60.4 years, and most of them were males. Most of our population is living independently 87.9%. The vast majority of people have a low adherence record in the Morisky Medication Adherence Scale (8-MMAS) classes (score = < 6). Moreover, the average PAM13 score is 51.93 (Level2) indicating a low level of confidence and sufficient knowledge to take action. Our analysis showed a significant correlation between socioeconomic status and medication adherence. Also, there was an association between housing status and medication adherence. On the other hand, we found no correlation between medication adherence and quality of life (QOL) by EQ-5D-5 L. CONCLUSION: Medication adherence is directly affected by living arrangements, as patients who live with a caretaker who can remind them to take their medications at the appropriate times have better medication adherence than those who live alone. Medication adherence was also significantly influenced by socioeconomic status, perhaps as a result of psychological effects and the belief of the lower-salaried population that they would be unable to afford the additional money required to cure any comorbidities that arose as a result of the disease. On the other hand, we did not find any correlation between medication adherence and quality of life. Finally, awareness of the necessity of adherence to medication for the elderly is essential.

Quantum Efficiency Measurement and Modeling of Silicon Sensors Optimized for Soft X-ray Detection.

Hybrid pixel detectors have become indispensable at synchrotron and X-ray free-electron laser facilities thanks to their large dynamic range, high frame rate, low noise, and large area. However, at energies below 3 keV, the detector performance is often limited because of the poor quantum efficiency of the sensor and the difficulty in achieving single-photon resolution due to the low signal-to-noise ratio. In this paper, we address the quantum efficiency of silicon sensors by refining the design of the entrance window, mainly by passivating the silicon surface and optimizing the dopant profile of the n+ region. We present the measurement of the quantum efficiency in the soft X-ray energy range for silicon sensors with several process variations in the fabrication of planar sensors with thin entrance windows. The quantum efficiency for 250 eV photons is increased from almost 0.5% for a standard sensor to up to 62% as a consequence of these developments, comparable to the quantum efficiency of backside-illuminated scientific CMOS sensors. Finally, we discuss the influence of the various process parameters on quantum efficiency and present a strategy for further improvement.

Development of Novel Class of Phenylpyrazolo[3,4-d]pyrimidine-Based Analogs with Potent Anticancer Activity and Multitarget Enzyme Inhibition Supported by Docking Studies.

Phenylpyrazolo[3,4-d]pyrimidine is considered a milestone scaffold known to possess various biological activities such as antiparasitic, antifungal, antimicrobial, and antiproliferative activities. In addition, the urgent need for selective and potent novel anticancer agents represents a major route in the drug discovery process. Herein, new aryl analogs were synthesized and evaluated for their anticancer effects on a panel of cancer cell lines: MCF-7, HCT116, and HePG-2. Some of these compounds showed potent cytotoxicity, with variable degrees of potency and cell line selectivity in antiproliferative assays with low resistance. As the analogs carry the pyrazolopyrimidine scaffold, which looks structurally very similar to tyrosine and receptor kinase inhibitors, the potent compounds were evaluated for their inhibitory effects on three essential cancer targets: EGFRWT, EGFRT790M, VGFR2, and Top-II. The data obtained revealed that most of these compounds were potent, with variable degrees of target selectivity and dual EGFR/VGFR2 inhibitors at the IC50 value range, i.e., 0.3-24 µM. Among these, compound 5i was the most potent non-selective dual EGFR/VGFR2 inhibitor, with inhibitory concentrations of 0.3 and 7.60 µM, respectively. When 5i was tested in an MCF-7 model, it effectively inhibited tumor growth, strongly induced cancer cell apoptosis, inhibited cell migration, and suppressed cell cycle progression leading to DNA fragmentation. Molecular docking studies were performed to explore the binding mode and mechanism of such compounds on protein targets and mapped with reference ligands. The results of our studies indicate that the newly discovered phenylpyrazolo[3,4-d]pyrimidine-based multitarget inhibitors have significant potential for anticancer treatment.

Vaginal preparation with different antiseptic solutions before cesarean section for preventing postoperative infections: A systematic review and network meta-analysis.

AIMS: We aimed to investigate the effect of various vaginal wash solutions on reducing risks of post-cesarean endometritis, wound infections, fever, and hospital stay duration. METHODS: Scopus, Web of Science, PubMed, and Cochrane Library were searched for randomized clinical trials that compared different vaginal wash solutions to each other or to "no vaginal cleaning"; without restriction on the age of parturients or site where trials were conducted. We analyzed this frequentist network meta-analysis using the netmeta package in R software version 4.1.2; synthesized data as mean difference or risk ratio with their 95% confidence intervals. RESULTS: Our network meta-analysis included 29 RCTs with a total sample size of 9311 women undergoing CS. Regarding post-cesarean endometritis, we found that povidone-iodine had the highest significant risk reduction compared to "no vaginal cleaning" (RR = 0.08, 95% CI [0.01, 0.69]). While regarding post-cesarean reduction of wound infection, fever, and hospital stay duration, we found that chlorhexidine 4% (RR = 0.17, 95% CI [0.05, 0.65]), saline 0.9% (RR = 0.12, 95% CI [0.03; 0.48]), and saline 0.9% (MD = -1.29, 95% CI [-2.18; -0.39]), respectively, had the highest significant risk reduction compared to "no vaginal cleaning." CONCLUSION: Vaginal wash solutions were associated with a significant reduction of post-cesarean endometritis, wound infection, fever, and hospital stay duration. Since povidone-iodine had the highest significant reduction of post-cesarean endometritis, we recommend setting povidone-iodine as the standard practice as pre cesarean vaginal wash solution; consistent practice guidelines of Enhanced Recovery After Surgery (ERAS).

Solar radiation-induced synthesis of bacterial cellulose/silver nanoparticles (BC/AgNPs) composite using BC as reducing and capping agent.

In the present work, a simple, novel, and ecofriendly method for synthesis of silver nanoparticles (AgNPs) and BC/AgNP composite using bacterial cellulose (BC) nanofibers soaked in AgNO3 solution under induction action of solar radiation. The photochemical reduction of silver Ag + ions into silver nanoparticles (Ago) was confirmed using UV visible spectra; the surface plasmon resonance of synthesized AgNPs was localized around 425 nm. The mean diameter of AgNPs obtained by DLS analysis was 52.0 nm with a zeta potential value of - 9.98 mV. TEM images showed a spherical shape of AgNPs. The formation of BC/AgNP composite was confirmed by FESEM, EDX, FTIR, and XRD analysis. FESEM images for BC showed the 3D structures of BC nanofibers and the deposited AgNPs in the BC crystalline nanofibers. XRD measurements revealed the high crystallinity of BC and BC/AgNP composite with crystal sizes of 5.13 and 5.6 nm, respectively. BC/AgNP composite and AgNPs exhibited strong antibacterial activity against both Gram-positive and Gram-negative bacteria. The present work introduces a facile green approach for BC/AgNP composite synthesis and its utility as potential food packaging and wound dressings, as well as sunlight indicator application.

Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome Patients: An Updated Systematic Review and Meta-Analysis.

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disease characterized by abdominal discomfort and bloating, diarrhea, and/or constipation. Fecal microbiota transplantation (FMT) is transferring the fecal bacteria and other microorganisms from a healthy person to another. We performed this systematic review and meta-analysis to assess the efficacy of FMT in treating IBS patients. We searched Scopus, PubMed, Cochrane, and Web of Science databases through June 2021 using relevant key words. We included 19 studies. Fecal microbiota transplantation was significantly superior to placebo in IBS quality of life after 4 weeks (mean difference [MD] = 7.47, 95% confidence interval [CI]: 2.05-12.89, p = .04), 12 weeks (MD = 9.99, 95% CI: 5.78-14.19, p < .00001), and 24 weeks (MD = 8.49, 95% CI: 0.47-16.52, p = .04), with no difference regarding IBS improvement symptoms and the IBS Severity Scoring System (SSS). Single-arm analysis revealed that the incidence of improvement of IBS symptoms was 57.8% (45.6%-69.9%) with reduction in IBS-SSS (MD = -74, 95% CI: -101.7 to -46.3). Fecal microbiota transplantation was superior to placebo in improving quality of life after 4, 12, and 24 weeks. Also, FMT improved IBS symptoms and reduced the IBS-SSS score. However, no deference was detected between FMT and placebo in IBS-SSS score and IBS symptoms improvement.

Plagiarism among nursing students: A systematic review and meta-analysis.

AIM: To summarize the findings from literature regarding the prevalence of plagiarism and its various types, knowledge, and attitudes of students toward plagiarism, factors associated with plagiarism, and the applied interventions to decrease the incidence of plagiarism. BACKGROUND: Plagiarism is a major form of academic dishonesty practiced by students at all educational levels. INTRODUCTION: Academic dishonesty was defined as any unauthorized help that adds to students' formal academic performance. These dishonest behaviors can be categorized as falsifying information, hiding errors, collaborating with colleagues when not allowed, and plagiarism. METHODS: Systematic search of databases was conducted in September 2021 to identify studies that discussed plagiarism in nursing studies. We included 31 studies in this systematic review and meta-analysis, with a total of 9,175 nursing students. The analysis was conducted using RevMan software. RESULTS: Plagiarism was the most frequent academic misconduct among nursing students (practiced by 55.3%). Paraphrasing without referencing was the most practiced form (39.53%), while submitting others' work without acknowledgment was the least one (9.61%). Most students were aware of the concept of plagiarism (80.8%) and had positive ethical attitudes toward it (88.26%). Plagiarism was negatively associated with age, parenting, and completing semester credits. However, it was positively correlated with average grades and liberal educators. Plagiarism was a significant predictor of clinical misconduct. DISCUSSION: A gap in the students' knowledge and skills were noticed. These gaps may be contributing to the high occurrence of plagiaristic acts, besides the unethical attitudes. CONCLUSION: Plagiarism is a serious academic misconduct practice that can be associated with subsequent clinical misconduct. There is a need to fill the knowledge and skills gap, and to set effective policies. IMPLICATION FOR NURSING AND HEALTH POLICY: In their attempts to eliminate plagiarism, nurse educators are encouraged to provide effective educational training and practical tasks, in order to fill the gaps in knowledge and skills. Additionally, implementing clear and effective punishment policies would prevent intentional plagiaristic acts. This would aid in introducing qualified nurses accountable for the health of patients.

New functionalized 6-thienylpyrimidine-5-carbonitriles as antiproliferative agents against human breast cancer cells.

6-Thienylpyrimidine-5-carbonitrile derivatives were synthesized and screened for their in vitro antiproliferative activities against two human breast cancer cell lines in comparison to 5-fluorouracil as a reference. Compounds 2, 3a-c, and 6b evolved as the most active congeners against both cell lines, while others showed selectivity for only one cell line. Compound 2 exerted its effect through inhibition of the epidermal growth factor receptor (EGFR), while 6b showed less aromatase inhibitory activity than letrozole. The rest of the tested compounds did not show significant inhibition, and it can be assumed that they exert their antiproliferative activity through different target mechanisms. In addition, caspase-9 protein activation assays, cell cycle analysis using flow cytometry, and annexin V-fluorescein isothiocyanate-propidium iodide (FITC/PI) dual staining assays were performed for the most active compounds. All the tested compounds were found to be potent pyrimidine derivatives able to initiate apoptosis in MCF-7 and MDA-MB-231 cells.

Unexplained anemia: A case report of metachronous adenocarcinoma arising in the transverse colon following right hemicolectomy for a primary cecal carcinoma.

Metachronous colonic carcinomas arise from months to years after the resection of the first or index primary colorectal cancer. They are not a result of tumor recurrence or metastasis and likely arise as a result of the field cancerization effect. This report presents the case of a 63-year-old male patient without family history of a colorectal cancer but had an index primary adenocarcinoma of the cecum (stage IIIC) five years ago that was treated with surgical resection and adjuvant radiotherapy and chemotherapy. He presented with fatigue and anemia of 6-month duration secondary to recurrent melena, and the specific cause of which remained obscure despite intensive diagnostic workup. Recurrence of a malignancy at the previous anastomosis site was ruled out. The patient continued to have recurrent and intermittent gastrointestinal bleeding until a nuclear red blood cell scan detected a bleeding spot in the epigastric region, which actually turned out to be a second primary carcinoma (stage I) arising from an adenoma in the transverse colon. The patient underwent a left colectomy with ileosigmoid anastomosis formation. During a two-month postoperative follow-up, the patient did not experience any episode of melena or anemia. Even though metachronous colon cancers rarely present with a recurrent and intermittent gastrointestinal bleeding with melena, an aggressive workup must be aimed at ruling out a second independent malignancy in patients who are in remission after an index primary colorectal cancer resection through hemicolectomy. Any neoteric lesion found on colonoscopy in such cases should be dealt with a higher degree of suspicion. Therefore, the need for surveillance colonoscopy as recommended by the National Comprehensive Cancer Network guidelines is imperative and should be practiced in resource-limited countries.

Detection of tetracycline and streptomycin in beef tissues using Charm II, isolation of relevant resistant bacteria and control their resistance by gamma radiation.

BACKGROUND: Misuse of antibiotics in veterinary medicine has the potential to generate residues in animal derived products, which could contributing to the development of an important health risk either through the exposure to antibiotic residues or the transfer of antibiotic resistance among foodborne pathogens as well. Tetracycline (TE) and eptomycin (ST) are commonly used as antibiotics in the Egyptian animal husbandry. The objective of this study, quick detection of TE and ST in fresh local beef tissue samples using radioimmunoassay Charm II technique, isolation and identification of relevant highly resistant bacterial strains. In addition to investigating the effect of gamma radiation on the susceptibility of such resistant strains to TE and ST. RESULTS: Tetracycline (TE) was detected in all collected samples, while ST was detected in 38.46% (5/13) and 87.5% (7/8) of meat and liver samples, respectively. Fifty-one bacterial isolates were isolated from the tested samples, among them, the highest resistant isolates to TE or ST were identified as Streptococcus thoraltensis, Proteus mirabilis (2 isolates) and E. coli (3 isolates). Among them, the highest D10-values in phosphate buffer; 0.807 and 0.480; kGy were recorded with S. thoraltensis and E. coli no.3, respectively. Such values increased to record 0.840 and 0.549 kGy, respectively after artificial inoculation into meat, indicating increased resistance to gamma radiation. Gamma radiation at dose 3 kGy increased the susceptibility of S. thoraltensis up to 50% to TE and ST, while the sensitivity of E. coli no.3 reached up 56% to both antibiotics at the same dose. CONCLUSIONS: High prevalence of TE in all fresh collected tissue samples suggests an extensively use of TE as antimicrobial in conventional beef production as compared to ST in the Egyptian cows' husbandry. Moreover, irradiation of food from animal origin by gamma radiation could potentially provide protection against resistant strains. In spite of limited samples used in this study, our data could raise the concerns of public health professionals about a withdrawal period before animals slaughtering, and address the importance of gamma radiation to minimize the hazards of foodborne resistant bacteria.

Design and synthesis of pyrazolo[3,4-d]pyrimidinone derivatives: Discovery of selective phosphodiesterase-5 inhibitors.

A novel series of 1,6-disubstituted pyrazolo[3,4-d]pyrimidin-7-one derivatives, 2a-h, 4a-d, 5 and 6, were successfully synthesized, which showed promising, and potent inhibition of phosphodiesterase 5 (PDE5). The inhibitory activities of 5, 4b, 2a, 2d, 2f, 4d and 4a against PDE5 were similar to that of sildenafil (100%). These compounds exhibited potent relaxant effects on isolated rat cavernosum tissue with pEC50 values ranging from 8.31 to 5.16 µM. Pyrazolo[3,4-d]pyrimidin-7-one scaffolds have been rationally designed via consecutive molecular modelling studies prior to their synthesis and biological evaluation. In addition, the results of the pharmacophore-based virtual screening revealed that 1v0p_PVB might have promising activity as a PDE-5 inhibitor.

Efficacy and Safety of Intravenous Tramadol versus Intravenous Paracetamol for Relief of Acute Pain of Primary Dysmenorrhea: A Randomized Controlled Trial.

INTRODUCTION: Many pharmaceutical, surgical, and complementary medical interventions are used for primary dysmenorrhea treatment. However, no consensus has been reached about the most effective intervention. OBJECTIVE: To compare the efficacy and safety of IV tramadol versus IV paracetamol in relieving acute pain of primary dysmenorrhea. METHODS: This randomized controlled trial was conducted in a tertiary referral hospital and included 100 patients between 18 and 35 years old diagnosed with primary dysmenorrhea. Patients received either 1-g paracetamol or 100-mg tramadol in 100-mL normal saline as an IV infusion over 10 min. Pain intensity was measured by using a visual analog scale at 15, 30, 60 min, and 2 h. We recorded drug side effects and requirements for rescue analgesics. RESULTS: Pain scores were significantly lower in the tramadol group compared with the paracetamol group at 15, 30, 60 min, and 2 h (p < 0.001). Fewer patients in the tramadol group needed rescue analgesics compared with the paracetamol group (p = 0.04). No significant differences were reported in side effects between both groups. CONCLUSIONS: IV tramadol is superior to IV paracetamol in relieving acute pain of primary dysmenorrhea with a comparable side effect profile.

Facile synthesis and potential application of Ni0.6Zn0.4Fe2O4 and Ni0.6Zn0.2Ce0.2Fe2O4 magnetic nanocubes as a new strategy in sewage treatment.

Disinfection using chlorine has paramount importance in the treatment of either drinking water or sewage since it can kill and inhibit all waterborne pathogens, but it may result in carcinogenic substances when interacting with organic matter. An eco-friendly sol-gel process with citrate was used to prepare the nano-cubic activated nickel-zinc ferrite magnetic nanostructures (Ni0.6Zn0.4Fe2O4 and Ni0.6Zn0.2Ce0.2Fe2O4). The activated nanomagnetic samples were characterized using XRD, HR-TEM, HR-SEM, FTIR, and VSM techniques. The structural and magnetic results showed that the nano-cubes magnetic-structures exhibited higher crystalline degrees and an increase in the total magnetization, enabling spinel nano-ferrite to possess potentials for excellent industry various applications. Likewise, the VSM results reveal that Ce2O3 had a significant influence on the magnetic behavior such as the coercivity (Hc; 69.226-133.15) saturation and magnetization (Ms; 24.562-52.174). The results revealed that all Magnetic nanoparticles (MNPs) had an outstanding inhibitory effect on microbes tested. The manufactured particles showed a remarkable ability to eliminate pathogenic bacteria in real sewage samples. The results obtained endorsed that the manufactured magnetic nanoparticles (MNPs) are powerful nano-weapons with an excellent anticipated output for the deactivation of pathogenic microbes during sewage treatment, with, nickel-zinc-cerium ferrite being more effective in inhibiting microbial growth than nickel-zinc-cerium ferrite.

Factors influencing dialysis withdrawal: a scoping review.

BACKGROUND: Research on factors associated with dialysis withdrawal is scarce. This study examined the predictors that might influence rate of dialysis withdrawal. Existing literature is summarized, analyzed and synthesized to identify gaps in the literature with regard to the factors associated with dialysis withdrawal. METHODS: This scoping review used a systematic search to synthesize research findings related to dialysis withdrawal and identified gaps in the literature. The search strategy was developed and applied using PubMed, EMBASE and CINHAL databases. The selection criteria included articles written in English and published between 1997 and 2016 that examined dialysis withdrawal and associated factors in patients with any modality of renal dialysis.. Case reports and studies only including renal transplant patients were excluded. Fifteen articles were selected in accordance with these selection criteria. RESULTS: The literature review revealed a scarcity of research on dialysis withdrawal and associated factors. Furthermore, the study findings were inconsistent and inconclusive. Authors have defined dialysis withdrawal in terms of dialysis discontinuation, withholding, death, withdrawal, treatment refusal/cessation, or technique failure. Authors have selected homogeneous patient population on either hemodialysis (HD) or peritoneal dialysis (PD) patients, thus making comparisons of studies and generalization of findings difficult. CONCLUSION: Future studies should explore the influence of both HD and PD on patient-elected dialysis withdrawal using a large a priori calculated sample size.

Rates of exponential decay in systems of discrete energy levels by Stieltjes imaging.

An isolated bound state coupled to a continuum shows an exponential decay of its survival probability. Rates of the exponential decay occurring due to the bound-continuum coupling can be recovered from discretized continuum (L(2)) calculations using a computational technique known as Stieltjes-Chebyshev moment theory or Stieltjes imaging. At the same time, some genuinely discrete level systems, e.g., Bixon-Jortner model, also show an exponential (or approximately exponential) decay of the initially populated level before the onset of quantum revivals. Here, we demonstrate numerically that Stieltjes imaging can be used for calculation of the rates of the exponential decay in such discrete level systems. We apply the Stieltjes imaging technique to the approximately exponential decay of inner-valence vacancies in trans-butadiene in order to show that the breakdown of the molecular orbital picture of ionization in the inner valence region can be physically interpreted as an energy-forbidden Coster-Kronig transition.