Awareness and Attitude Regarding Contact Lens Use Among Female Students at the University of Bisha: A Cross-Sectional Study.

INTRODUCTION: Given the growing popularity of contact lenses among female students in Saudi Arabia for various reasons including vision correction as well as aesthetic and therapeutic purposes, it is essential to understand the knowledge about them, their uses, and how to handle them, given their significance in healthcare. METHODS: A cross-sectional study design was utilized in this research, employing data from a sample of 413 female students at the University of Bisha. The participants completed a self-administered questionnaire and were ensured anonymity. RESULTS: The study results showed that 52.9% (n=218) had a good knowledge level while 47.1% (n=195) had poor knowledge about contact lenses use. The results established a statistically significant association between region, faculty, and study year (p<0.005) with p-values of 0.002, 0.001, and 0.005, respectively, and level of knowledge about contact lens use. There was no statistically significant association between the age of the participants and the level of knowledge about contact lens use. CONCLUSION: Although there was a generally good level of awareness about contact lens use among female students, there is still insufficiency in knowledge with regard to particular aspects such as cleaning the contact lenses and contact lens cover. The study finds the need for more ocular educational sessions with ophthalmologists to increase awareness about contact lenses.

Biotic Ligand Modeling for the Effect of Major Cations on the Uptake of Cadmium in Folsomia candida Exposed in a Sand-Solution Medium.

Biotic ligand modeling (BLM) approaches are already applied to predict the bioavailability and possible risk of metals in surface water, but need further development for soils. The present study investigated the effect of major cations (Ca2+, Mg2+, Na+, K+, and H+) on cadmium bioaccumulation in the springtail Folsomia candida. To avoid the complexity of real soils and enable control of elemental speciation in the exposure medium, the animals were exposed to different cadmium concentrations in an inert quartz sand-solution medium. Accumulation of cadmium in the animals was measured after 7 days exposure at different cation concentrations. Among the cations, only Ca2+ significantly affected the uptake of cadmium in the springtails. Mg2+ also had higher effects compared with other selected cations. Using a BLM approach, the uptake of cadmium in the animals predicted by taking into account both Ca2+ and Mg2+ activities correlated well with the measured values (R2 = 0.68). The final estimated conditional binding constants for cadmium (log KCd-BL), Ca (log KCa-BL), and Mg (log KMg-BL) of 1.06, 2.14, and 1.23 L/mol, respectively, were in agreement with previously reported values. The match between predicted and measured uptake data confirms the applicability and usefulness of the BLM for predicting the bioavailability of cadmium to springtails and opens the way for its application in soil. Environ Toxicol Chem 2024;43:1090-1096. © 2024 SETAC.

Evaluation of the DN-Mini (miniaturized double net) trap for sampling host-seeking Anopheles mosquitoes in malaria-endemic villages of southern Tanzania.

BACKGROUND: Surveillance of malaria vectors is crucial for assessing the transmission risk and impact of control measures. Human landing catches (HLC) directly estimate the biting rates but raise ethical concerns due to the exposure of volunteers to mosquito-borne pathogens. A common alternative is the CDC-light trap, which is effective for catching host-seeking mosquitoes indoors but not outdoors. New, exposure-free methods are needed for sampling mosquitoes indoors and outdoors in ways that reflect their natural risk profiles. The aim of this study was therefore to evaluate the efficacy of the miniaturized double net trap (DN-Mini) for sampling host-seeking mosquitoes in south-eastern Tanzania, where malaria transmission is dominated by Anopheles funestus. METHODS: Adult mosquitoes were collected from 222 randomly selected houses across three villages (74 per village) in Ulanga district, south-eastern Tanzania, using the DN-Mini traps, CDC-Light traps, and Prokopack aspirators. First, we compared CDC-light and DN-Mini traps for collecting indoor host-seeking mosquitoes, while Prokopack aspirators were used for indoor-resting mosquitoes. Second, we deployed the DN-Mini and Prokopack aspirators to collect host-seeking and resting mosquitoes indoors and outdoors. Generalized linear mixed models (GLMM) with a negative binomial distribution were used to compare the effectiveness of the traps for catching different mosquito species. RESULTS: The DN-Mini was 1.53 times more efficient in collecting An. funestus indoors (RR = 1.53, 95% CI: 1.190-1.98) compared to the CDC-Light trap. However, for Anopheles arabiensis, the DN-Mini caught only 0.32 times as many mosquitoes indoors as the CDC-Light traps (RR = 0.32, 95% CI: 0.183-0.567). Both An. funestus and An. arabiensis were found to be more abundant indoors than outdoors when collected using the DN-Mini trap. Similarly, the Prokopack aspirator was greater indoors than outdoors for both An. funestus and An. arabiensis. CONCLUSION: The DN-Mini outperformed the CDC-light trap in sampling the dominant malaria vector, An. funestus species, but was less effective in capturing An. arabiensis, and for both vector species, the biting risk was greater indoors than outdoors when measured using the DN-Mini trap. These findings highlight the importance of selecting appropriate trapping methods based on mosquito species and behaviors.

Enriched Environment Contributes to the Recovery from Neurotoxin-Induced Parkinson's Disease Pathology.

Parkinson's disease (PD) is a neurological disorder that affects dopaminergic neurons. The lack of understanding of the underlying molecular mechanisms of PD pathology makes treating it a challenge. Several pieces of evidence support the protective role of enriched environment (EE) and exercise on dopaminergic neurons. The specific aspect(s) of neuroprotection after exposure to EE have not been identified. Therefore, we have investigated the protective role of EE on dopamine dysregulation and subsequent downregulation of DJ1 protein using in vitro and in vivo models of PD. Our study for the first time demonstrated that DJ1 expression has a direct correlation with dopamine downregulation in PD models and exposure to EE has a significant impact on improving the behavioral changes in PD mice. This research provides evidence that exercise in EE has a positive effect on PD without interfering with the current line of therapy.

Leveraging Bayesian deep learning and ensemble methods for uncertainty quantification in image classification: A ranking-based approach.

Bayesian deep learning (BDL) has emerged as a powerful technique for quantifying uncertainty in classification tasks, surpassing the effectiveness of traditional models by aligning with the probabilistic nature of real-world data. This alignment allows for informed decision-making by not only identifying the most likely outcome but also quantifying the surrounding uncertainty. Such capabilities hold great significance in fields like medical diagnoses and autonomous driving, where the consequences of misclassification are substantial. To further improve uncertainty quantification, the research community has introduced Bayesian model ensembles, which combines multiple Bayesian models to enhance predictive accuracy and uncertainty quantification. These ensembles have exhibited superior performance compared to individual Bayesian models and even non-Bayesian counterparts. In this study, we propose a novel approach that leverages the power of Bayesian ensembles for enhanced uncertainty quantification. The proposed method exploits the disparity between predicted positive and negative classes and employes it as a ranking metric for model selection. For each instance or sample, the ensemble's output for each class is determined by selecting the top 'k' models based on this ranking. Experimental results on different medical image classifications demonstrate that the proposed method consistently outperforms or achieves comparable performance to conventional Bayesian ensemble. This investigation highlights the practical application of Bayesian ensemble techniques in refining predictive performance and enhancing uncertainty evaluation in image classification tasks.

Parents' Awareness, Knowledge, and Perception of Amblyopia in Children: A Study in Jazan Region, Saudi Arabia.

Background Amblyopia is a vision disorder that results from a development problem in the brain rather than a neurological disease in the eye. The condition causes reduced visual acuity in one or both eyes due to the brain's inability to process inputs, rather than a structural abnormality. This study aims to assess parents' awareness, knowledge, and perception of amblyopia in their children in the Jazan region, Saudi Arabia. Methods This is a cross-sectional study that used an electronic questionnaire consisting of five main sections to assess the level of awareness of amblyopia among parents in the Jazan region. The Statistical Package for Social Sciences (SPSS v.25, IBM Corp., Armonk, NY, USA) was utilized to input the data. The degree to which participants' level of awareness was related to variables such as age, gender, and educational level was assessed through the chi-square test (χ2), and any values that scored p-values under 0.05 were deemed statistically significant. Results The analysis included 572 participants, 395 mothers (69.0%) and 177 fathers (31.0%). The age groups of the participants were divided into 36-45 years (38.0%), 26-35 years (36.0%), and above 46 years (17.0%). Out of the total, 36 participants (6.0%) had a history of amblyopia, and 73 (13.0%) had a child who suffered from amblyopia. The findings showed that only 18 participants (3.1%) had a good awareness of amblyopia, while 242 (42.3%) had a fair level of awareness. Most participants, 312 (54.5%), were classified as having a poor awareness level of amblyopia. Parents with postgraduate degrees, those with prior awareness, and parents whose children had eye diseases demonstrated higher levels of good awareness. However, gender, age, and residency did not have significant associations with awareness levels. Conclusion While parents must be involved in managing amblyopia, our research found that more than half of the parents surveyed had a limited understanding of various aspects of the disease, which can cause permanent damage to their child's vision. Therefore, we recommend implementing health education programs to increase awareness and knowledge about amblyopia in Jazan.

Knowledge and Attitudes of Parents Regarding Neonatal Jaundice in Bisha City, Saudi Arabia.

Background Neonatal jaundice (NNJ) is one of the most common neonatal illnesses around the world. It continues to be a leading cause of avoidable brain damage, physical and mental impairment, and death in neonates. Neonatal morbidity due to NNJ has a significant impact and cost on families and healthcare resources. The majority of instances are addressed without intervention, but others require assessment and assistance in the form of follow-up or treatment. Inadequate family awareness and understanding of this frequent newborn condition can contribute to delays and difficulties. Aim This study aimed to assess the knowledge and attitudes of parents regarding NNJ in Bisha City, Saudi Arabia. Methodology A cross-sectional study involving 242 participants was carried out. Data were collected using an online questionnaire. The knowledge score differences between groups were analyzed using a Wilcoxon rank sum test and the Kruskal-Wallis rank test. Results In this study of 242 participants from Bisha, we found that the majority were female (155, 64.0%), employed (129, 53.3%), and held a postgraduate degree (150, 62.0%). Regarding knowledge of NNJ, 109 (45.0%) have correctly defined it as yellow pigmentation in the sclera and 64 (26.4%) as yellow pigmentation of the skin. Of most participants, 132 (54.5%) recognized that NNJ could cause complications, but 53 (40.2%) of these were unaware of what these complications might be. Notably, only 89 (36.8%) of respondents believed they had sufficient knowledge about NNJ. The median knowledge score was 3.0 (IQR, 1.0-4.0), and higher scores were significantly associated with being female and reporting sufficient knowledge about the disease. Strategies suggested for improving awareness included campaigns (98, 40.5%) and social networking programs (81, 33.5%). The data suggest a need for enhanced public education regarding NNJ. Conclusion The study highlights the need for increased awareness and education among parents in Bisha, Saudi Arabia, about NNJ. The findings suggest that campaigns and social networking programs could effectively educate people about the condition. Additionally, the study provides insights into the factors associated with higher knowledge scores, such as gender and having a child with NNJ. The results of this study may help healthcare professionals develop effective educational programs and interventions to improve parents' knowledge and attitudes toward NNJ.

Efficiency of plant-based acaricide gels compared to fluvalinate-impregnated strips for control of Varroa destructor in honey bee colonies.

The Varroa mite is one of the most important pests of honey bee colonies. This study compares the efficiency of thymol-based acaricides with the tau-fluvalinate-based commercial treatment to control this mite species. Two experiments were conducted: (1) in the Fall, thymol-based gel was compared with a widely used acaricide, fluvalinate-impregnated strips (Apistan®), and (2) in the Spring, gels containing thymol-only, thymol + menthol + eucalyptus essential oil, and thymol + thyme essential oil were compared with fluvalinate-impregnated strips. In the first experiment, both treatments reduced Varroa mite infestation levels significantly after 70 days of their application compared to the control treatment. The results of the second experiment showed that thymol + thyme essential oil gel, thymol + menthol + eucalyptus essential oil gel, and Apistan strips had always higher efficiency on decreasing mite infestation levels of the selected colonies compared to the control treatment and thymol-only gel during their 7-week application. The results of this study demonstrate that plant-based acaricides for controlling Varroa mites in honey bee colonies have similar efficiency compared to the chemical control methods. Therefore, it is better to use these selected acaricides to reduce mite resistance to chemical control treatments in honey bee colonies.

Parents' Knowledge, Attitude, and Practice Regarding Traditional Medicine on Their Children: A Community-Based Cross-Sectional Study in Bisha City, Saudi Arabia.

Background The use of traditional medicine (TM) in children is widespread, particularly in developing countries. Parents often rely on TM to treat their children's illnesses or maintain their health. However, the safety and efficacy of TM are often unclear, and there is a need to assess parents' knowledge, attitudes, and practices toward its use. Methods This is a community-based cross-sectional study conducted in Bisha, Saudi Arabia, with a sample size of 555. The study used a modified questionnaire to collect data. The data were collected from March to June 2023. This study involved both descriptive and inferential statistics.  Results The study included 555 participants, most of whom were female, Saudi nationals, and married and had a bachelor's degree. More than half of the participants reported using TM, and most believed that it had fewer side effects and could be taken with allopathic medicines. However, many participants did not believe that TM could prevent or cure all diseases or that it was always safe. The median knowledge score was 4.0, with higher scores associated with older age and higher educational level. Most participants had a positive attitude toward TM, with higher attitude scores associated with younger age, male gender, lower educational level, and healthcare-related occupation. The median practice score was 31.0, with higher scores associated with younger age, male gender, illiteracy, and healthcare-related occupation. Overall, the study highlights the importance of understanding the patterns of use, knowledge, attitudes, and practices of TM in the population, particularly among different demographic groups. Conclusions This study highlights the need for better regulation and supervision of TM outlets to ensure the safety and efficacy of the products. It also emphasizes the importance of consulting healthcare professionals before using TM on children. The findings suggest that healthcare providers should be knowledgeable about TM and provide guidance to parents on its appropriate use.

Effect of a 3.5% NaCl-10% HCl Corrosive Environment on the Fatigue Behavior of Hot Rolled Aluminum 5083-H111.

This study deals with the microstructure of rolled Al5083-H111 materials, their hardness, corrosion in different solutions, and rotary bending fatigue properties of non-corroded and corroded samples in different solutions. This study is the first to report the fatigue behavior of corroded samples in different aggressive corrosion environments of Al5083. The microstructure of the Al5083-H111 material is in the form of grains oriented towards the rolling direction and it consists of binary Al-Mg, Al-Mn, and Mg-Si; ternary Al-Mg-Si; and quaternary Al-Mn-Fe-Si and Al-Cr-Mn precipitated randomly at the grain boundary. The Brinell hardness of the Al5083-H111 material is 68.67 HB. According to the results of the immersion corrosion, while the sample was more resistant to corrosion in a 3.5% NaCl environment, it showed a less resistant behavior in a 3.5% NaCl + 10% HCl environment. As a result of the fatigue test, it was observed that the sample that did not undergo corrosion showed a higher fatigue life than the samples that were exposed to corrosion. The fatigue rate of the 3.5% NaCl corrosion sample was 3.5 times lower than the fatigue rate of the 3.5% NaCl + 10% HCl corrosion sample.

Return to Sport After Anterior Cruciate Ligament Reconstruction Among Physically Active Adults.

An anterior cruciate ligament (ACL) is one of athletes' most severe and frequent knee ligament injuries. The primary function of the ACL is preventing excessive anterior tibial translation, and it limits varus/valgus stress when the knee is in full extension and rotatory movements. Returning to sport after an ACL injury is a crucial aim of ACL reconstruction (ACLR). Multiple factors, modifiable and nonmodifiable, can influence the time to return to sport. This study aimed to discuss factors that affect optimal return-to-play (RTP) timing, symptom recurrence, and long-term consequences of an ACL injury. This is a cross-sectional study involving patients who are following in orthopedic surgery outpatient clinics with a history of ACLR at least six months before surgery and not beyond six years after surgery. Participants received a survey about their sociodemographic data, details of the type and site of injury, and ACL return to sport before and after reconstruction scale. Full data description and testing of dependent variables against participant variables using two-sided tests were performed with a significance level of P ≤ 0.05. The study involved 129 participants, of which the majority were male Bisha residents aged 20 to 29 years. The study found that the right leg was the most commonly injured, with the dominant leg being the most frequently reconstructed due to problems with knee function. Before the injury, most participants ran, cut (quick changes of direction during running), decelerated, and pivoted activities four or more times per month. However, physical activities notably reduced after ACLR. Age and body mass index (BMI) showed statistical significance related to the likelihood of returning to physical activities.  The study found a significant reduction in the frequency of activities such as cutting, deceleration, and running after ACLR. Age was identified as a predictor affecting the likelihood of returning to the sport, with older patients being less likely to return than younger ones.

Lightweight deep CNN-based models for early detection of COVID-19 patients from chest X-ray images.

Hundreds of millions of people worldwide have recently been infected by the novel Coronavirus disease (COVID-19), causing significant damage to the health, economy, and welfare of the world's population. Moreover, the unprecedented number of patients with COVID-19 has placed a massive burden on healthcare centers, making timely and rapid diagnosis challenging. A crucial step in minimizing the impact of such problems is to automatically detect infected patients and place them under special care as quickly as possible. Deep learning algorithms, such as Convolutional Neural Networks (CNN), can be used to meet this need. Despite the desired results, most of the existing deep learning-based models were built on millions of parameters (weights), which are not applicable to devices with limited resources. Inspired by such fact, in this research, we developed two new lightweight CNN-based diagnostic models for the automatic and early detection of COVID-19 subjects from chest X-ray images. The first model was built for binary classification (COVID-19 and Normal), whereas the second one was built for multiclass classification (COVID-19, viral pneumonia, or normal). The proposed models were tested on a relatively large dataset of chest X-ray images, and the results showed that the accuracy rates of the 2- and 3-class-based classification models are 98.55% and 96.83%, respectively. The results also revealed that our models achieved competitive performance compared with the existing heavyweight models while significantly reducing cost and memory requirements for computing resources. With these findings, we can indicate that our models are helpful to clinicians in making insightful diagnoses of COVID-19 and are potentially easily deployable on devices with limited computational power and resources.

The Effect of Microbial Diversity and Biomass on Microbial Respiration in Two Soils along the Soil Chronosequence.

Microbial diversity plays an important role in the decomposition of soil organic matter. However, the pattern and drivers of the relationship between microbial diversity and decomposition remain unclear. In this study, we followed the decomposition of organic matter in soils where microbial diversity was experimentally manipulated. To produce a gradient of microbial diversity, we used soil samples at two sites of the same chronosequence after brown coal mining in Sokolov, Czech Republic. Soils were X-ray sterilized and inoculated by two densities of inoculum from both soils and planted with seeds of six local plant species. This created two soils each with four levels of microbial diversity characterized by next-generation sequencing. These eight soils were supplied, or not, by litter of the bushgrass Calamagrostis epigejos, and microbial respiration was measured to assess the rate of decomposition. A strong positive correlation was found between microbial diversity and decomposition of organic matter per gram of carbon in soil, which suggests that microbial diversity supports decomposition if the microbial community is limited by available carbon. In contrast, microbial respiration per gram of soil negatively correlated with bacterial diversity and positively with fungal biomass, suggesting that in the absence of a carbon limitation, decomposition rate is controlled by the amount of fungal biomass. Soils with the addition of grass litter showed a priming effect in the initial stage of decomposition compared to the samples without the addition of litter. Thus, the relationship between microbial diversity and the rate of decomposition may be complex and context dependent.

COVID-19 vaccine breakthrough infection among fully vaccinated healthcare workers in Duhok governorate, Iraqi Kurdistan: A retrospective cohort study.

The aims of this study were: to determine the incidence of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection among vaccinated healthcare workers (HCWs), assess risk factors associated with the vaccine breakthrough (BT), and compare the effectiveness of vaccine manufacturers against SARS-CoV-2 variant of concern among HCWs in Duhok governorate. It is a multicenter retrospective cohort study, which enrolled 944 HCWs through March 2022. COVID-19 vaccinated HCWs aging 18 and above were included. A random sampling process was performed by asking the participants to fill out a standardized questionnaire by means of interviews or participant-completed surveys. Fully vaccinated HCWs with positive polymerase chain reaction tests were considered to have vaccine BT infection. Two hundred and eighty-four (30.1%) out of 944 vaccinated HCWs had SARS-CoV-2 infection postvaccination, of whom 241 (84.9%) were fully vaccinated, concluding that the incidence of BT infection is 25.5%. There were 422 (44.7%) males and 522 (55.3%) females. Most vaccine BT infections had developed in SARS-CoV-2 Omicron variant (53.5%). The majority of BT infections were mild to moderate (95.5%). Occupation, namely dentist was a significant risk factor, with a p value of 0.001. HCWs with a history of SARS-CoV-2 infection prevaccination were more prone to a vaccine BT infection (p value =0.002). Pfizer vaccine manufacturers revealed the highest effectiveness against BT infection (p value =0.0001). Paramedics showed a significant association with the disease severity (p value =0.02). The three available vaccine manufacturers in the Duhok governorate are effective against COVID-19 BT infections. Dentists and paramedics were significantly associated with poor COVID-19 outcomes.

Mango performance as affected by the soil application of zeolite and biochar under water salinity stresses.

This study was carried out during two consecutive seasons, 2020 and 2021, on 12-year-old mango (Mangifera indica L.). cv. Ewaise grown in region Idku, El Beheira Governorate, Egypt. The trees were planted at 5 × 4 m apart and grafted on "Sokary" root stock to study the influence of zeolite and biochar on growth, yield, and fruit quality of "Ewaise" mango cultivar irrigated by agricultural drainage water. The trees were treated by the following treatments: zeolite or biochar solely at 1, 2, and 3 kg for tree and their different combinations such as 1 kg zeolite + 1 kg biochar; 1 kg zeolite + 2 kg biochar; 1 kg zeolite + 3 kg biochar; 2 kg zeolite + 1 kg biochar; 2 kg zeolite + 2 kg biochar; 2 kg zeolite + 3 kg biochar; 3 kg zeolite + 1 kg biochar; 3 kg zeolite + 2 kg biochar; and 3 kg zeolite + 3 kg biochar as well as control zero soil application. The obtained results showed that the soil application of zeolite or biochar gave a positive effect on improving the soil characteristics which reflects on the tree trunk thickness, shoot length and thickness, number of inflorescences, yield in kg per tree, and fruit quality. The greatest positive effect on the previous mentioned parameters was obtained by the combined application of the soil application of 2 kg zeolite + 3 kg biochar; 2 kg zeolite + 2 kg biochar; 3 kg zeolite + 2 kg biochar; and 3 kg zeolite + 3 kg biochar over the rest-applied treatments or control in the two seasons.

A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus.

There is an urgent need for an effective, oral, direct-acting therapeutic to block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent progression to severe coronavirus disease 2019 (COVID-19). In a phase 2a double-blind, placebo-controlled, randomized, multicenter clinical trial, we evaluated the safety, tolerability, and antiviral efficacy of the nucleoside analog molnupiravir in 202 unvaccinated participants with confirmed SARS-CoV-2 infection and symptom duration <7 days. Participants were randomized 1:1 to receive molnupiravir (200 mg) or placebo and then 3:1 to receive molnupiravir (400 or 800 mg) or placebo, orally twice daily for 5 days. Antiviral activity was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 RNA in nasopharyngeal swabs. Infectious virus was assessed by inoculation of cultured Vero cells with samples from nasopharyngeal swabs and was detected by RT-PCR. Time to viral RNA clearance (primary endpoint) was decreased in the 800-mg molnupiravir group (median 14 days) compared to the placebo group (median 15 days) (log rank P value = 0.013). Of participants receiving 800 mg of molnupiravir, 92.5% achieved viral RNA clearance compared with 80.3% of placebo recipients by study end (4 weeks). Infectious virus (secondary endpoint) was detected in swabs from 1.9% of the 800-mg molnupiravir group compared with 16.7% of the placebo group at day 3 of treatment (P = 0.016). At day 5 of treatment, infectious virus was not isolated from any participants receiving 400 or 800 mg of molnupiravir compared with 11.1% of placebo recipients (P = 0.034 and 0.027, respectively). Molnupiravir was well tolerated across all doses.

Efficacy and Safety of Tofacitinib for Treatment of Moderate to Severe Active Ulcerative Colitis: First Report from Iran.

BACKGROUND: Tofacitinib, a selective inhibitor of JAK/STAT pathway, has recently become available in our region. Here, we examined the safety and efficacy of tofacitinib in active ulcerative colitis (UC). METHODS: In a prospective, non-randomized, placebo-free, 52-week clinical trial defined in two phases of induction and maintenance, adult patients with active UC and no response or loss of response to previous conventional treatments, or anti-TNF were recruited (IRCT20181217042020N2). Patients received 10 mg/BID of tofacitinib for 8 weeks. Clinically responding patients were entered into the maintenance phase and received tofacitinib 5 mg/BID for 44 weeks. Clinical evaluation, biochemical tests and endoscopy at time points of baseline, 8, 24 and 52 weeks were performed. The primary outcome was clinical remission at 8 and 52 weeks. RESULTS: Fifty out of 53 enrolled patients completed the induction phase. Clinical response and clinical remission at 8 weeks occurred in 84% and 9.5%, respectively. Forty-two patients who had clinical response entered the maintenance phase. Clinical remission based on the total Mayo score and the partial Mayo score occurred in 38.9% and 55.3% at 24 weeks and in 61.1% and 72.2% at 52 weeks, respectively. There was significant correlation between the total and partial Mayo score with regard to clinical remission in both 24 and 52 weeks. No serious adverse events, no case of herpes zoster, but two cases of deep vein thrombosis were seen. CONCLUSIONS: Our study showed acceptable efficacy and safety for tofacitinib and suggested a correlation between the total Mayo score with partial Mayo score with regard to clinical remission.

Molnupiravir, an Oral Antiviral Treatment for COVID-19.

BACKGROUND: Easily distributed oral antivirals are urgently needed to treat coronavirus disease-2019 (COVID-19), prevent progression to severe illness, and block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the results of a Phase 2a trial evaluating the safety, tolerability, and antiviral efficacy of molnupiravir in the treatment of COVID-19 ( ClinicalTrials.gov NCT04405570 ). METHODS: Eligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days. Participants were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 or 800 mg) or placebo, twice-daily for 5 days. Antiviral activity was assessed as time to undetectable levels of viral RNA by reverse transcriptase polymerase chain reaction and time to elimination of infectious virus isolation from nasopharyngeal swabs. RESULTS: Among 202 treated participants, virus isolation was significantly lower in participants receiving 800 mg molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p = 0.02). At Day 5, virus was not isolated from any participants receiving 400 or 800 mg molnupiravir, versus 11.1% of those receiving placebo (p = 0.03). Time to viral RNA clearance was decreased and a greater proportion overall achieved clearance in participants administered 800 mg molnupiravir versus placebo (p = 0.01). Molnupiravir was generally well tolerated, with similar numbers of adverse events across all groups. CONCLUSIONS: Molnupiravir is the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile.

Molnupiravir, an Oral Antiviral Treatment for COVID-19

BackgroundEasily distributed oral antivirals are urgently needed to treat coronavirus disease-2019 (COVID-19), prevent progression to severe illness, and block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the results of a Phase 2a trial evaluating the safety, tolerability, and antiviral efficacy of molnupiravir in the treatment of COVID-19 (ClinicalTrials.gov NCT04405570). MethodsEligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days. Participants were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 or 800 mg) or placebo, twice-daily for 5 days. Antiviral activity was assessed as time to undetectable levels of viral RNA by reverse transcriptase polymerase chain reaction and time to elimination of infectious virus isolation from nasopharyngeal swabs. ResultsAmong 202 treated participants, virus isolation was significantly lower in participants receiving 800 mg molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p = 0.02). At Day 5, virus was not isolated from any participants receiving 400 or 800 mg molnupiravir, versus 11.1% of those receiving placebo (p = 0.03). Time to viral RNA clearance was decreased and a greater proportion overall achieved clearance in participants administered 800 mg molnupiravir versus placebo (p = 0.01). Molnupiravir was generally well tolerated, with similar numbers of adverse events across all groups. ConclusionsMolnupiravir is the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile.

Methanogenesis in the Digestive Tracts of the Tropical Millipedes Archispirostreptus gigas (Diplopoda, Spirostreptidae) and Epibolus pulchripes (Diplopoda, Pachybolidae).

Methanogens represent the final decomposition step in anaerobic degradation of organic matter, occurring in the digestive tracts of various invertebrates. However, factors determining their community structure and activity in distinct gut sections are still debated. In this study, we focused on the tropical millipede species Archispirostreptus gigas (Diplopoda, Spirostreptidae) and Epibolus pulchripes (Diplopoda, Pachybolidae), which release considerable amounts of methane. We aimed to characterize relationships between physicochemical parameters, methane production rates, and methanogen community structure in the two major gut sections, midgut and hindgut. Microsensor measurements revealed that both sections were strictly anoxic, with reducing conditions prevailing in both millipedes. Hydrogen concentration peaked in the anterior hindgut of E. pulchripes. In both species, the intestinal pH was significantly higher in the hindgut than in the midgut. An accumulation of acetate and formate in the gut indicated bacterial fermentation activities in the digestive tracts of both species. Phylogenetic analysis of 16S rRNA genes showed a prevalence of Methanobrevibacter spp. (Methanobacteriales), accompanied by a small fraction of so-far-unclassified "Methanomethylophilaceae" (Methanomassiliicoccales), in both species, which suggests that methanogenesis is mostly hydrogenotrophic. We conclude that anoxic conditions, negative redox potential, and bacterial production of hydrogen and formate promote gut colonization by methanogens. The higher activities of methanogens in the hindgut are explained by the higher pH of this compartment and their association with ciliates, which are restricted to this compartment and present an additional source of methanogenic substrates. IMPORTANCE Methane (CH4) is the second most important atmospheric greenhouse gas after CO2 and is believed to account for 17% of global warming. Methanogens are a diverse group of archaea and can be found in various anoxic habitats, including digestive tracts of plant-feeding animals. Termites, cockroaches, the larvae of scarab beetles, and millipedes are the only arthropods known to host methanogens and emit large amounts of methane. Millipedes are ranked as the third most important detritivores after termites and earthworms, and they are considered keystone species in many terrestrial ecosystems. Both methane-producing and non-methane-emitting species of millipedes have been observed, but what limits their methanogenic potential is not known. In the present study, we show that physicochemical gut conditions and the distribution of symbiotic ciliates are important factors determining CH4 emission in millipedes. We also found close similarities to other methane-emitting arthropods, which might be associated with their similar plant-feeding habits.