UPDATE ON THE USE OF METHOTREXATE IN THE MANAGEMENT OF RHEUMATOID ARTHRITIS.

Rheumatoid arthritis (RA) is an auto-immune disorder described by permanent inflammation of the articular synovial membrane. Non-treated RA can cause gradual joint damage, ending in complaint, poor lifestyle, and an upright ratio of death. Approximately one percent of the people are involved, and the disorder begins, in general, appears during the third and fifth decades of age, with more occurrences in females. The treatment is complicated as well as involves various stages of medications with variable methods of application as well as non-pharmacologic methods. The extra prevalent are disease person's culture, then, sports and mechanical and behavioral therapy. Due to more chance of ischemic heart disease, trials should be increased to lessen the assisting behaviors such as cigarette smoking, high lipid profile, elevation of blood pressure, and high body mass index.

The impact of ketogenic diet on some metabolic and non-metabolic diseases: Evidence from human and animal model experiments.

The ketogenic diet (KD) is recognized as minimum carbohydrate and maximum fat intakes, which leads to ketosis stimulation, a state that is thought to metabolize fat more than carbohydrates for energy supply. KD has gained more interest in recent years and is for many purposes, including weight loss and managing serious diseases like type 2 diabetes. On the other hand, many believe that KD has safety issues and are uncertain about the health drawbacks. Thus, the outcomes of the effect of KD on metabolic and non-metabolic disease remain disputable. The current narrative review aims to evaluate the effect of KD on several diseases concerning the human health. To our best knowledge, the first report aims to investigate the efficacy of KD on multiple human health issues including type 2 diabetes and weight loss, cardiovascular disease, kidney failure and hypertension, non-alcoholic fatty liver, mental problem, oral health, libido, and osteoporosis. The literature searches were performed in Databases, PubMed, Scopus, and web of Science looking for both animal and human model designs. The results heterogeneity seems to be explained by differences in diet composition and duration. Also, the available findings may show that proper control of carbohydrates, a significant reduction in glycemic control and glycated hemoglobin, and weight loss by KD can be an approach to improve diabetes and obesity, hypertension, non-alcoholic fatty liver, PCOS, libido, oral health, and mental problem if isocaloric is considered. However, for some other diseases like cardiovascular disease and osteoporosis, more robust data are needed. Therefore, there is robust data to support the notion that KD can be effective for some metabolic and non-metabolic diseases but not for all of them. So they have to be followed cautiously and under the supervision of health professionals.

Environmental pollutants PM2.5, PM10, carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3) impair human cognitive functions.

OBJECTIVE: Environmental pollution is an emerging global public health problem across the world and causes serious threats to ecosystems, human health, and the planet. This study is designed to explore the impact of environmental pollution particulate matter PM2.5, PM10, carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3) on cognitive functions in students from schools located in or away from air-polluted areas. SUBJECTS AND METHODS: In this study, two schools were selected: one was located near a traffic-polluted area (school #1), and the second was in an area away from the traffic-polluted area (school #2). In this study, a total of 300 students were recruited: 150 (75 male and 75 female) students from school #1 located in a traffic-polluted area, and 150 students (75 male and 75 female) from school #2 located away from a traffic polluted area. The overall average age of students was 13.53±1.20 years. The students were selected based on age, gender, health status, height, weight, BMI, ethnicity, and homogenous socio-economic and educational status. The pollutants PM2.5, PM10, CO, NO2, O3, and SO2 were recorded in the surrounding environment. The overall mean concentration of environmental pollutants in school #1 was 35.00±0.65 and in school #2 was 29.95±0.32. The levels of airborne particles were measured, and the cognitive functions were recorded using the Cambridge Neuropsychological Test Automated Battery (CANTAB). The students performed the cognitive functions tasks, including the attention switching task (AST), choice reaction time (CRT), and motor screening task (MOT). RESULTS: The results revealed that the AST-Mean 928.34±182.23 vs. 483.79±146.73 (p=0.001), AST-mean congruent 889.12±197.12 vs. 473.30±120.11 (p=0.001), AST-mean in-congruent 988.98±201.27  vs. 483.87±144.57 (p=0.001), CRT-Mean 721.36±251.72  vs. 418.17±89.71 (p=0.001), and MOT-Mean 995.07±394.37 vs. 526.03±57.83 (p=0.001) were significantly delayed among the students who studied in school located in the traffic polluted area compared to students who studied in school which was located away from the traffic-polluted area. CONCLUSIONS: Environmental pollution was significantly higher in motor vehicle-congested areas. Cognitive functions were impaired among the students who were studying in a school located in a polluted area. The results further revealed that the students studying in schools located in environmentally polluted areas have attention, thinking, and decision-making abilities related to cognitive function impairment.

Higher beta-hydroxybutyrate ketone levels associated with a slower kidney function decline in ADPKD.

BACKGROUND AND HYPOTHESIS: Dysregulated energy metabolism is a recently discovered key feature of Autosomal Dominant Polycystic Kidney Disease (ADPKD). Cystic cells depend on glucose and are poorly able to use other energy sources such as ketone bodies. Raising ketone body concentration reduced disease progression in animal models of polycystic kidney diseases. Therefore, we hypothesized that higher endogenous plasma beta-hydroxybutyrate concentrations are associated with reduced disease progression in patients with ADPKD. METHODS: We analyzed data from 670 patients with ADPKD participating in the DIPAK cohort, a multi-center prospective observational cohort study. Beta-hydroxybutyrate was measured at baseline using nuclear magnetic resonance spectroscopy. Participants were excluded if they had type 2 diabetes, were using disease-modifying drugs (e.g. tolvaptan, somatostatin analogs), were not fasting, or had missing beta-hydroxybutyrate levels, leaving 521 participants for the analyses. Linear regression analyses were used to study cross-sectional associations and linear mixed-effect modeling for longitudinal associations. RESULTS: Of the participants, 61% were female, with an age of 47.3 ± 11.8 years, a height-adjusted total kidney volume (htTKV) of 834 (IQR 495-1327) ml/m, and an estimated glomerular filtration rate (eGFR) of 63.3 ± 28.9 mL/min/1.73m2. The median concentration of beta-hydroxybutyrate was 94 (IQR 68-147) µmol/L. Cross-sectionally, beta-hydroxybutyrate was neither associated with eGFR nor with htTKV. Longitudinally, beta-hydroxybutyrate was positively associated with eGFR slope (B = 0.35 ml/min/1.73m2 (95% CI 0.09 to 0.61), p = 0.007), but not with kidney growth. After adjustment for potential confounders, every doubling in beta-hydroxybutyrate concentration was associated with an improvement in the annual rate of eGFR by 0.33 ml/min/1.73m2 (95% CI 0.09 to 0.57, p = 0.008). CONCLUSION: These observational analyses support the hypothesis that interventions that raise beta-hydroxybutyrate concentration could reduce the rate of kidney function decline in patients with ADPKD.

Toxicity, arsenic speciation and characteristics of hyphenated techniques used for arsenic determination in vegetables. A review.

Arsenic (As) speciation is an interesting topic because it is well recognized that the toxicity of this metalloid ultimately depends on its chemical form. More than 300 arsenicals exist naturally. However, As can be present in four oxidation states: As-III, As0, AsIII and AsV. Long-term exposure to As from different sources, such as anthropogenic processes, or water, fauna and flora contaminated with As, has put human health at risk for decades. There are many side-effects correlated with exposure to InAs species, such as skin problems, respiratory diseases, kidney problems, cardiovascular diseases and even cancer. There are different levels and types of As in foods, particularly in vegetables. Furthermore, different chemical methods and techniques have been developed. Therefore, this review focuses on the general properties of various approaches used to identify As species in vegetation samples published worldwide. This includes various approaches (different solvents and techniques) used to extract As species from the matrix. Then, versatile chromatographic and non-chromatographic systems to separate different forms of As are reviewed. Finally, the general properties of the most common instruments used to detect As species from samples of interest are listed.

Amlodipine downregulates gene expression that involved in the signaling pathways of coagulation process in COVID-19 patients: An observational clinical study.

The SARS-CoV-2 virus has the property of activating the coagulation process, which is responsible for producing thrombotic events which is considered as one of the most serious COVID-19 complications. Hypertension is a hazard factor for COVID-19 complications, and people who are treated with calcium entry blockers may halt the occurrence of thrombotic events. to evaluate the effect of amlodipine on some genes involved in the activation of the coagulation procedure in COVID-19 patients with hypertensive. observational, cross-sectional study. This study was carried out in the Department of Pharmacy at Al-Kut University College in Wasit, Iraq, in conjunction with Al Zahraa Hospital from June 2021 to March 2022. A total of 45 COVID-19 patients participated in this study who were grouped into as follows: Group I (n = 23) who had no previous history of hypertension and Group II (n = 22) who had previous hypertension and were treated with amlodipine. Expression of the calcium-sensing receptor (CaSR), coagulation factor V (F5), and methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 Like (MTHFD1L) genes was determined. P values were calculated by Chi-square test for categorized facts and the Mann-Whitney test for incessant data. P ≤ 0.05 was considered statistically significant. Group II patients had significantly lower levels of CaSR, F5, and MTHFD1L gene expression compared with the corresponding levels in Group I patients. The expression level of MTHFD1L was elevated significantly in patients who had currently high blood pressure compared with normotensive patients in both the groups. Amlodipine is preferred in hypertensive patients who have COVID-19 because it attenuates the levels of gene expression that have an impact on the coagulation process.

Embryo selection through artificial intelligence versus embryologists: a systematic review.

STUDY QUESTION: What is the present performance of artificial intelligence (AI) decision support during embryo selection compared to the standard embryo selection by embryologists? SUMMARY ANSWER: AI consistently outperformed the clinical teams in all the studies focused on embryo morphology and clinical outcome prediction during embryo selection assessment. WHAT IS KNOWN ALREADY: The ART success rate is ∼30%, with a worrying trend of increasing female age correlating with considerably worse results. As such, there have been ongoing efforts to address this low success rate through the development of new technologies. With the advent of AI, there is potential for machine learning to be applied in such a manner that areas limited by human subjectivity, such as embryo selection, can be enhanced through increased objectivity. Given the potential of AI to improve IVF success rates, it remains crucial to review the performance between AI and embryologists during embryo selection. STUDY DESIGN SIZE DURATION: The search was done across PubMed, EMBASE, Ovid Medline, and IEEE Xplore from 1 June 2005 up to and including 7 January 2022. Included articles were also restricted to those written in English. Search terms utilized across all databases for the study were: ('Artificial intelligence' OR 'Machine Learning' OR 'Deep learning' OR 'Neural network') AND ('IVF' OR 'in vitro fertili*' OR 'assisted reproductive techn*' OR 'embryo'), where the character '*' refers the search engine to include any auto completion of the search term. PARTICIPANTS/MATERIALS SETTING METHODS: A literature search was conducted for literature relating to AI applications to IVF. Primary outcomes of interest were accuracy, sensitivity, and specificity of the embryo morphology grade assessments and the likelihood of clinical outcomes, such as clinical pregnancy after IVF treatments. Risk of bias was assessed using the Modified Down and Black Checklist. MAIN RESULTS AND THE ROLE OF CHANCE: Twenty articles were included in this review. There was no specific embryo assessment day across the studies-Day 1 until Day 5/6 of embryo development was investigated. The types of input for training AI algorithms were images and time-lapse (10/20), clinical information (6/20), and both images and clinical information (4/20). Each AI model demonstrated promise when compared to an embryologist's visual assessment. On average, the models predicted the likelihood of successful clinical pregnancy with greater accuracy than clinical embryologists, signifying greater reliability when compared to human prediction. The AI models performed at a median accuracy of 75.5% (range 59-94%) on predicting embryo morphology grade. The correct prediction (Ground Truth) was defined through the use of embryo images according to post embryologists' assessment following local respective guidelines. Using blind test datasets, the embryologists' accuracy prediction was 65.4% (range 47-75%) with the same ground truth provided by the original local respective assessment. Similarly, AI models had a median accuracy of 77.8% (range 68-90%) in predicting clinical pregnancy through the use of patient clinical treatment information compared to 64% (range 58-76%) when performed by embryologists. When both images/time-lapse and clinical information inputs were combined, the median accuracy by the AI models was higher at 81.5% (range 67-98%), while clinical embryologists had a median accuracy of 51% (range 43-59%). LIMITATIONS REASONS FOR CAUTION: The findings of this review are based on studies that have not been prospectively evaluated in a clinical setting. Additionally, a fair comparison of all the studies were deemed unfeasible owing to the heterogeneity of the studies, development of the AI models, database employed and the study design and quality. WIDER IMPLICATIONS OF THE FINDINGS: AI provides considerable promise to the IVF field and embryo selection. However, there needs to be a shift in developers' perception of the clinical outcome from successful implantation towards ongoing pregnancy or live birth. Additionally, existing models focus on locally generated databases and many lack external validation. STUDY FUNDING/COMPETING INTERESTS: This study was funded by Monash Data Future Institute. All authors have no conflicts of interest to declare. REGISTRATION NUMBER: CRD42021256333.

Wastewater-based epidemiology for tracking bacterial diversity and antibiotic resistance in COVID-19 isolation hospitals in Qatar.

BACKGROUND: Hospitals are hotspots for antimicrobial resistance genes (ARGs), and play a significant role in their emergence and spread. Large numbers of ARGs will be ejected from hospitals via wastewater systems. Wastewater-based epidemiology has been consolidated as a tool to provide real-time information, and represents a promising approach to understanding the prevalence of bacteria and ARGs at community level. AIMS: To determine bacterial diversity and identify ARG profiles in hospital wastewater pathogens obtained from coronavirus disease 2019 (COVID-19) isolation hospitals compared with non-COVID-19 facilities during the pandemic. METHODS: Wastewater samples were obtained from four hospitals: three assigned to patients with COVID-19 patients and one assigned to non-COVID-19 patients. A microbial DNA quantitative polymerase chain reaction was used to determine bacterial diversity and ARGs. FINDINGS: The assay recorded 27 different bacterial species in the samples, belonging to the following phyla: Firmicutes (44.4%), Proteobacteria (33.3%), Actinobacteria (11%), Bacteroidetes (7.4%) and Verrucomicrobiota (3.7%). In addition, 61 ARGs were detected in total. The highest number of ARGs was observed for the Hazem Mebaireek General Hospital (HMGH) COVID-19 patient site (88.5%), and the lowest number of ARGs was found for the HMGH non-patient site (24.1%). CONCLUSION: The emergence of contaminants in sewage water, such as ARGs and high pathogen levels, poses a potential risk to public health and the aquatic ecosystem.

Directed delivery of terahertz frequency radiation from quantum cascade lasers within a dry 3He dilution refrigerator.

We present a scheme for the full integration of terahertz (THz) frequency quantum cascade lasers (QCLs) within a dilution refrigerator in order to provide a directed delivery of THz power into the sample space. We describe a successful operation of a 2.68 THz QCL located on the pulse tube cooler stage of the refrigerator, with its output coupled onto a two-dimensional electron gas (2DEG) located on a milli-kelvin sample stage via hollow metal waveguides and Hysol thermal isolators, achieving a total loss from QCL to the sample of ∼-9 dB. The thermal isolators limit heat leaks to the sample space, with a base temperature of ∼210 mK being achieved. We observe cyclotron resonance (CR) induced in the 2DEG by the QCL and explore the heating impact of the QCL on all stages of the refrigerator. The CR effect induced by the THz QCL is observable at electron temperatures as low as ∼430 mK. The results show a viable route for the exploitation of THz QCLs within the environment of a dilution refrigerator and for the THz power delivery in very low-temperature (<0.5 K) condensed matter experiments.

Quality of Victim Statement in Child Sexual Abuse in Turkey.

Child sexual abuse is the most challenging type of abuse to detect. Moreover, there are difficulties in gathering evidence, apprehending, and prosecuting the perpetrator. The trial is often based on the contradiction of the suspect's and the child's statements. The aim of this study is to identify the difficulties encountered during the entire trial in cases of sexual assault against the child in Turkey starting from the investigation phase, to determine the auditability of taking a child's statement, which is the basis of the judicial decision, and to evaluate the effectiveness of the principles set by the Supreme Court, which oversees the local court decision. It was determined that the trial was continued on abstract allegations, the Supreme Court's approval of the decision of the local court was based on "the slander of a person who wants to harm another person over the sexuality of a minor is contrary to the usual flow of life." Furthermore, the reason wassuggestive of subjective interpretations rather than material truths. This study, which is a master's thesis, has been submitted to the Turkish Ministry of Justice.

Prevalence of Y chromosome microdeletion in azoospermic infertile males of Iraqi population.

In human gamete development, the important period is spermatogenesis, which is organized by specific genes on Y chromosome. In some cases, the infertile men have shown microdeletions on Y chromosome, which seemed as if the structural chromosome variance is linked to the reduction of sperm count. This study aimed to determine the frequency and patterns of Y chromosome microdeletions in azoospermia factor (AZF) of Iraqi infertile males. Here, 90 azoospermic infertile males as a study group and 95 normal fertile males as control group were investigated for the microdeletion of AZF loci using numerous sequence-tagged sites. Of these 90 infertile male patients, 43 (47.8%) demonstrated Y chromosome microdeletions, in which AZFb region was the most deleted section inazoospermia patients (33.3%) followed by deletions in the AZFc region (23%), while there were no microdeletion in the AZFa region. The largest microdeletion involved in both AZFb and AZFc was detected in six azoospermic patients (6.7%). The present study demonstrated a high frequency of Y chromosome microdeletions in the infertile Iraqi patients which is not reported previously. The high frequency of deletions may be due to the association of ethnic and genetic factors. PCR-based Y chromosome screening for microdeletions has a potential to be used in infertility clinics for genetic counselling and assisted reproduction.

Genetic and phenotypic characterization of NKX6-2-related spastic ataxia and hypomyelination.

BACKGROUND AND PURPOSE: Hypomyelinating leukodystrophies are a heterogeneous group of genetic disorders with a wide spectrum of phenotypes and a high rate of genetically unsolved cases. Bi-allelic mutations in NKX6-2 were recently linked to spastic ataxia 8 with hypomyelinating leukodystrophy. METHODS: Using a combination of homozygosity mapping, exome sequencing, and detailed clinical and neuroimaging assessment a series of new NKX6-2 mutations in a multicentre setting is described. Then, all reported NKX6-2 mutations and those identified in this study were combined and an in-depth analysis of NKX6-2-related disease spectrum was provided. RESULTS: Eleven new cases from eight families of different ethnic backgrounds carrying compound heterozygous and homozygous pathogenic variants in NKX6-2 were identified, evidencing a high NKX6-2 mutation burden in the hypomyelinating leukodystrophy disease spectrum. Our data reveal a phenotype spectrum with neonatal onset, global psychomotor delay and worse prognosis at the severe end and a childhood onset with mainly motor phenotype at the milder end. The phenotypic and neuroimaging expression in NKX6-2 is described and it is shown that phenotypes with epilepsy in the absence of overt hypomyelination and diffuse hypomyelination without seizures can occur. CONCLUSIONS: NKX6-2 mutations should be considered in patients with autosomal recessive, very early onset of nystagmus, cerebellar ataxia with hypotonia that rapidly progresses to spasticity, particularly when associated with neuroimaging signs of hypomyelination. Therefore, it is recommended that NXK6-2 should be included in hypomyelinating leukodystrophy and spastic ataxia diagnostic panels.

Large Rhinophyma Treated by Surgical Excision and Electrocautery.

Rhinophyma is a benign condition characterized by a large, bulbous nose with prominent pores. It is commonly associated with untreated cases of rosacea. The disease can carry a substantial psychological impact that causes patients to seek advice about how to improve their physical appearance. Many treatment options are available for rhinophyma, but there is no standard treatment protocol. Here, we describe the case of a 65-year-old man with a large rhinophyma that caused him cosmetic and psychosocial embarrassment. The condition was treated by surgical excision and bipolar electrocautery. No complications occurred after the procedures, and healing was completed 2 weeks later by secondary intention and reepithelialization. A simple surgical removal using a scalpel to shave off the abnormal tissue with electrocauterization of the bleeding points can be considered as a good treatment option for rhinophyma, as it results in an excellent cosmetic outcome and has short recovery time.

Rare variant in LAMA2 gene causing congenital muscular dystrophy in a Sudanese family. A case report.

Congenital muscular dystrophies (CMD) are a heterogeneous group of disorders caused by mutations in musculoskeletal proteins. The most common type of CMD in Europe is Merosin-deficient CMD caused by mutations in laminin-α2 protein. Very few studies reported pathogenic variants underlying these disorders especially from Africa. In this study we report a rare variant (p.Arg148Trp, rs752485547) in LAMA2 gene causing a mild form of Merosin-deficient CMD in a Sudanese family. The family consisted of two patients diagnosed clinically with congenital muscular dystrophy since childhood and five healthy siblings born to consanguineous parents. Whole exome sequencing was performed for the two patients and a healthy sibling. A rare missense variant (p.Arg148Trp, rs752485547) in LAMA2 gene was discovered and verified using Sanger sequencing. The segregation pattern was consistent with autosomal recessive inheritance. The pathogenicity of this variant was predicted using bioinformatics tools. More studies are needed to explore the whole spectrum of mutations in CMD in patients from Sudan and other parts of the world.

Genetic polymorphisms of fecundity genes in Watish Sudanese desert sheep.

BACKGROUND AND AIM: The Watish sheep is a strain of desert sheep of smaller size compared to other desert sheep ecotypes, and there is anecdotal evidence that it is endowed with high litter size. The present study was designed for screening for polymorphisms in the known fecundity genes (bone morphogenetic protein receptor type 1B A

Clinical predictors of escalating care in hepatic and renal cyst infection in autosomal dominant polycystic kidney and liver disease.

BACKGROUND: Cyst infection may occur in autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD). Antimicrobial agents often fail to control infection, leading to invasive action. We aimed to identify factors predicting escalation of care. METHODS: ADPKD and ADPLD patients were identified from local/national databases (2001-2013). Records were screened for patients meeting criteria for cyst infection (positive cyst aspirate and/or clinical findings). Factors that predict escalated care were identified with multivariate modified Poisson regression. RESULTS: We screened 1773 patients. A total of 77 patients with cyst infection (4.3%) were included for analysis (hepatic 36%; male 49%; age 54 ±; 13 years; ADPKD 95%; dialysis 9%, diabetes 18%, renal transplant 56%, eGFR [IQR 24-78] ml/min/1.73 m2 (excluding patients with a history of renal transplant or receiving dialysis)). A pathogen was identified in 71% of cases. Escherichia coli was the most common pathogen and accounted for 69% of cases. Initial treatment was limited to antibiotics in 87% of patients (n = 67), 40% included a fluoroquinolone. Ultimately, 48% of patients underwent some form of invasive action (escalation of care). Increasing white blood cell count (WBC) (RR 1.04 95%-CI 1.01-1.07, p = 0.008) was associated with escalating care, whereas an increase in time between transplant and infection (RR 0.92 95% CI 0.86-0.97, p = 0.005) and E. coli isolation (RR 0.55 95% CI 0.34-0.89, p = 0.02) were protective. CONCLUSION: High serum WBC, isolation of atypical pathogens and early infection after transplantation are factors that increase the risk of escalation of care in hepatic and renal cyst infection patients.

Genetic investigation of 93 families with microphthalmia or posterior microphthalmos.

Microphthalmia is a developmental eye defect that is highly variable in severity and in its potential for systemic association. Despite the discovery of many disease genes in microphthalmia, at least 50% of patients remain undiagnosed genetically. Here, we describe a cohort of 147 patients (93 families) from our highly consanguineous population with various forms of microphthalmia (including the distinct entity of posterior microphthalmos) that were investigated using a next-generation sequencing multi-gene panel (i-panel) as well as whole exome sequencing and molecular karyotyping. A potentially causal mutation was identified in the majority of the cohort with microphthalmia (61%) and posterior microphthalmos (82%). The identified mutations (55 point mutations, 15 of which are novel) spanned 24 known disease genes, some of which have not or only very rarely been linked to microphthalmia (PAX6, SLC18A2, DSC3 and CNKSR1). Our study has also identified interesting candidate variants in 2 genes that have not been linked to human diseases (MYO10 and ZNF219), which we present here as novel candidates for microphthalmia. In addition to revealing novel phenotypic aspects of microphthalmia, this study expands its allelic and locus heterogeneity and highlights the need for expanded testing of patients with this condition.