Integrated Safety Update of Abrocitinib in 3802 Patients with Moderate-to-Severe Atopic Dermatitis: Data from More than 5200 Patient-Years with Up to 4 Years of Exposure.

BACKGROUND: Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile. OBJECTIVE: We aimed to provide updated integrated long-term safety results for abrocitinib from available data accrued up to a maximum of almost 4 years in patients with moderate-to-severe atopic dermatitis from the JADE clinical development program. METHODS: Analysis included 3802 patients (exposure: 5213.9 patient-years) from the phase II monotherapy study (NCT02780167) and the phase III studies JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only), JADE REGIMEN (NCT03627767), and JADE EXTEND (NCT03422822; data cutoff 25 September, 2021). Data from patients receiving one or more doses of abrocitinib 200 mg or 100 mg were pooled in a consistent-dose cohort (patients were allocated to receive the same abrocitinib dose throughout exposure in the qualifying parent study and/or long-term study) or a variable-dose cohort (patients received open-label abrocitinib 200 mg; responders were randomized to abrocitinib 200 mg, 100 mg, or placebo, and could then receive abrocitinib 200 mg plus topical corticosteroids as rescue therapy). Incidence rates of adverse events of special interest were assessed. Cox regression analysis of risk factors for herpes zoster and serious infections was performed. RESULTS: Overall, this safety analysis of long-term data up to a maximum of ~ 4 years of abrocitinib exposure does not indicate any changes from the previously reported risk profile. The most frequent serious infections (per Medical Dictionary for Regulatory Activities preferred term) with consistent-dose abrocitinib 200 mg and 100 mg were herpes zoster (0.5% and 0.2%), pneumonia (0.2% with either dose), and herpes simplex (0.1% with either dose). Risk factors for herpes zoster were a history of herpes zoster, abrocitinib 200-mg dose, age ≥ 65 years, absolute lymphocyte count < 1 × 103/mm3 before the event, and residing in Asia. For serious infections, > 100 kg body weight was a risk factor. Incidence rate/100 patient-years (95% confidence interval) with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in older (aged ≥ 65 years) patients versus younger (aged 18 to < 65 years) patients for serious adverse events (17.6 [11.7‒25.4] vs 6.7 [5.8‒7.8]), malignancy excluding non-melanoma skin cancer (2.4 [0.6‒6.0] vs 0.1 [0.0‒0.4]), non-melanoma skin cancer (2.4 [0.6‒6.1] vs 0.2 [0.1‒0.4]), lymphopenia (3.5 [1.3‒7.6] vs 0.1 [0.0‒0.3]), and venous thromboembolism (1.7 [0.4‒5.1] vs 0.1 [0.0‒0.3]). Incident rate/100 patient-years (95% confidence interval) of non-melanoma skin cancer with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in current/former smokers (0.9 [0.4‒1.6]) vs never-smokers (0.0 [0.0‒0.1]). CONCLUSIONS: This safety update showed a consistent profile for abrocitinib with no new safety signals and continues to support that abrocitinib has a manageable long-term safety profile in patients with moderate-to-severe atopic dermatitis. Risk of specific adverse events was higher in certain patient populations, especially those aged ≥ 65 years. [Video abstract available.] CLINICAL TRIAL REGISTRATION: NCT02780167; study start date: April, 2016; primary completion date: March, 2017; study completion date: April, 2017. NCT03349060; study start date: 7 December, 2017; study completion date: 26 March, 2019. NCT03575871; study start date: 29 June, 2018; study completion date: 13 August, 2019. NCT03720470; study start date: 29 October, 2018; primary completion date: 27 December, 2019; study completion date: 6 March, 2020. NCT03796676; study start date: 18 February, 2019; study completion date: 8 April, 2020. NCT03627767; study start date: 11 June, 2018; primary completion date: 2 September, 2020; study completion date: 7 October, 2020. NCT04345367; study start date: 11 June, 2020; primary completion date: 16 December, 2020; study completion date: 13 July, 2021. NCT03422822; study start date: 8 March, 2018; study completion date: ongoing (estimated completion date: 31 January, 2026).

Abrocitinib is an approved treatment for people with moderate or severe atopic dermatitis, also known as AD or atopic eczema. Abrocitinib is a tablet that is taken by mouth once a day. This safety analysis looked at the side effects of treatment in a large group of adults and adolescents with moderate or severe AD who took abrocitinib up to a maximum of almost 4 years. This analysis also looked at which people were more likely to have certain side effects after taking abrocitinib. The results from this analysis were similar to those of previous safety analyses with abrocitinib, with no new side effects. Infections such as shingles, pneumonia, or herpes simplex can occur during treatment with abrocitinib. Shingles was more likely to occur in people who previously had shingles before taking abrocitinib, or who took the higher dose of abrocitinib (200 mg), or were 65 years of age or older, or had certain blood test results, or lived in Asia. People who are 65 years of age or older and took abrocitinib were more likely to develop some types of cancer, have certain abnormal blood test results, or develop blood clots in the veins than people with AD who were younger and took abrocitinib. Current or former smokers with AD who took abrocitinib were more likely to develop skin cancer (but not melanoma) than people with AD who took abrocitinib but have never smoked. This analysis further shows that abrocitinib had manageable safety in patients with moderate-to-severe AD. Video abstract: Integrated safety update of abrocitinib in 3802 patients with moderate-to-severe atopic dermatitis: data from more than 5200 patient-years with up to 4 years of exposure (MP4 63720 KB).

Exploring associations between pregnancy cravings and sociodemographic, lifestyle and health factors: insights from a cross-sectional population study in Jordan.

OBJECTIVE: To explore the potential associations between pregnancy cravings and various sociodemographic, lifestyle and health factors. DESIGN: Cross-sectional study. SETTING: Population-based study in Jordan. PARTICIPANTS: A total of 500 women who had children and experienced pregnancy cravings were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Pregnancy cravings are prevalent among Jordanian women and associated with some sociodemographic, lifestyle and health factors. RESULTS: The results showed that 75.40% (377/500) of women experienced food cravings, with 40.6% and 29.1% of them having iron deficiency and vitamin D deficiency, respectively. The most commonly craved food items were sweets (17.2%, 86/500) and salts (22.2%, 115/500), while less than 1.0% of women craved non-food items. No significant correlation (p>0.05) was found between food cravings and the gender of the babies. Significant associations were found between food cravings and the mother's educational level (p=0.023), weight loss (p<0.001) and diseases such as anaemia (p=0.01). CONCLUSION: Pregnancy cravings, particularly for food items, with sweets and salts being the most commonly craved, are prevalent among Jordanian women and are associated with the mother's educational level, changes in weight and the presence of anaemia. Additionally, the study found that iron and vitamin D deficiencies are prevalent health issues among women experiencing these cravings in Jordan. This research has important implications, emphasising the pressing need for targeted nutritional interventions and healthcare strategies to address identified deficiencies and improve maternal health outcomes in the region.

Effect of red osier dogwood extract on in vitro gas production, dry matter digestibility, and fermentation characteristics of forage-based diet or grain-based diet.

This in vitro batch culture study investigated the effects of red osier dogwood (ROD) extract supplementation on gas production (GP), dry matter disappearance (DMD), and fermentation characteristics in high forage (HF) and high grain (HG) diets with varying media pH level. The experiment was a factorial arrangement of treatments in a completely randomized design with 2 media pH (5.8 and 6.5) × 4 dose rates of ROD extract (0, 1, 3, and 5% of DM substrate). An additional treatment of monensin was added as a positive control for each pH level. The HF substrate consisted of 400 and 600 g/kg DM barley-based concentrate and barley silage, respectively, while the HG substrate contained 100 and 900 g/kg DM barley silage and barley-based concentrate, respectively. Treatments were incubated for 24 h with GP, DMD and fermentation parameters determined. No interaction was detected between the media pH level and ROD extract dose rate on GP, DMD and most of the fermentation parameters. The GP, DMD, and total volatile fatty acid (VFA) concentration were greater (P = 0.01) with media pH of 6.5 in both HF and HG diets. The GP were not affected by increasing ROD dose rate, except that GP linearly decreased in the HF (P = 0.04) and HG (P = 0.01) diets at 24 h; the DMD tended to linearly decrease at pH 6.5 (P = 0.06) for both HF and HG diets and at pH 5.8 (P = 0.02) for the HG diet. Adding ROD extract to the HF and HG diets linearly (P = 0.01) increased the acetate molar proportion at high or low media pH and consequently, the acetate to propionate (A:P) ratio linearly (P ≤ 0.04) increased. Supplementation of ROD extract to the HF diet linearly (P = 0.04) decreased the molar proportion of propionate at pH 6.5 (interaction between pH and ROD extract; P = 0.05), but had no effect on propionate proportion when added to the HG diet. Moreover, the proportion of branched-chain fatty acids linearly (P = 0.03) decreased with ROD extract supplementation at low pH (interaction, P < 0.05) for HF diet and linearly decreased (P = 0.05) at pH 6.5 for HG diet (interaction, P < 0.05). The NH3-N concentration was not affected by ROD supplementation in the HF diet but it linearly (P = 0.01) decreased with increasing dose rate in the HG diet. Methane concentration tended to linearly (P = 0.06) increase with ROD extract supplementation at high pH for HF diet and linearly increased at pH 5.8 (P = 0.06) and pH 6.5 (P = 0.02) for HG diet. These results indicate that the decreased DMD and increased A:P ratio observed with addition of ROD extract may be beneficial to HG-fed cattle to reduce the risk of rumen acidosis without negatively impacting fiber digestion.

Assessment of land use cover changes, carbon sequestration and carbon stock in dry temperate forests of Chilas watershed, Gilgit-Baltistan

Abstract Land use and land cover change are affecting the global environment and ecosystems of the different biospheres. Monitoring, reporting and verification (MRV) of these changes is of utmost importance as they often results in several global environmental consequences such as land degradation, mass erosion, habitat deterioration as well as micro and macro climate of the regions. The advance technologies like remote sensing (RS) and geographical information system (GIS) are helpful in determining/ identifying these changes. In the current study area, changes in carbon stocks, notably in forest areas, are resulting in considerable dynamics of carbon stocks as a result of climate change and carbon sequestration. This study was carried out in the Diamer district of the Gilgit Baltistan (GB) Pakistan to investigate the change in cover change/land use change (particularly Forest Land use) as well as carbon sequestration potential of the forests in the district during almost last 25years. The land cover, temporal Landsat data (level 1, LIT) were downloaded from the USGS EROS (2016), for 1979-1989, 1990-2000 and 2001-2012. Change in land uses, particularly forest cover was investigated using GIS techniques. Forest inventory was carried out using random sampling techniques. A standard plot of size 0.1 ha (n=80) was laid out to determine the tree density, volume, biomass and C stocks. Simulation of C stocks was accomplished by application of the CO2FIX model with the data input from inventory. Results showed a decrease in both forest and snow cover in the region from 1979-2012. Similarly decrease was seen in tree volume, tree Biomass, dynamics of C Stocks and decrease was in occur tree density respectively. It is recommended we need further more like project such as BTAP (Billion Tree Afforestation Project) and green Pakistan project to increase the forest cover, to control on land use change, protect forest ecosystem and to protect snow cover.

Resumo O uso e as mudanças na cobertura da terra estão afetando o meio ambiente global e os ecossistemas das diferentes biosferas. O monitoramento, relatório e verificação (MRV) dessas mudanças são de extrema importância, pois muitas vezes resultam em várias consequências ambientais globais, como degradação da terra, erosão em massa, deterioração do hábitat, bem como micro e macroclima das regiões. As tecnologias avançadas, como sensoriamento remoto (RS) e sistema de informações geográficas (SIG), são úteis para determinar / identificar essas mudanças. Na área de estudo atual, as mudanças nos estoques de carbono, principalmente em áreas florestais, estão resultando em uma dinâmica considerável dos estoques de carbono como resultado das mudanças climáticas e do sequestro de carbono. Este estudo foi realizado no distrito de Diamer de Gilgit Baltistan (GB), Paquistão, para investigar a mudança na mudança de cobertura / mudança de uso da terra (particularmente uso de terras florestais), bem como o potencial de sequestro de carbono das florestas no distrito durante quase os últimos 25 anos. A cobertura da terra, os dados temporais do Landsat (nível 1, LIT), foram baixados do USGS EROS (2016), para 1979-1989, 1990-2000 e 2001-2012. Mudanças nos usos da terra, particularmente na cobertura florestal, foram investigadas usando técnicas de SIG. O inventário florestal foi realizado por meio de técnicas de amostragem aleatória. Um lote padrão de 0,1 ha (n = 80) foi estabelecido para determinar a densidade das árvores, volume, biomassa e estoques de C. A simulação dos estoques de C foi realizada pela aplicação do modelo CO2FIX com a entrada de dados do inventário. Os resultados mostraram uma diminuição na cobertura florestal e de neve na região de 1979 a 2012. Da mesma forma, diminuição foi observada no volume da árvore, biomassa das árvores, dinâmica dos estoques de C e diminuição na densidade das árvores, respectivamente. É recomendado que precisemos de mais projetos como o BTAP (Billion Tree Afforestation Project) e o projeto Green Pakistan para aumentar a cobertura florestal, controlar as mudanças no uso da terra, proteger o ecossistema florestal e proteger a cobertura de neve.

Side chain inset of neurogenerative amino acids to metalloproteins: a therapeutic signature for huntingtin protein in Huntington's disease.

OBJECTIVE: Huntington's disease is a dominant autosomal inherited neurodegenerative disease that results in progressive impairment, characterized by dementia, chorea, and behavioral and cognitive decline. The objective of this study was to investigate the potential activity of metalloproteins against the huntingtin protein using various insertion-based engineering computational methods. Metalloproteins, metal protein complexes involved in important biochemical and physiological processes, were explored as potential drug candidates for Huntington's disease. MATERIALS AND METHODS: A total of 18 metalloproteins were selected as drug candidates and studied to assess their potential inhibitory effects on the huntingtin protein. The screening process was based on the lowest binding energy. The metalloprotein with the lowest docking score was chosen for side chain insertion of neurogenerative amino acids. The engineered metalloprotein was then evaluated based on physiochemical properties, allergenicity, toxicity, and surface accessibility. Cloning and expression analysis was performed to further investigate its potential as a therapeutic agent. RESULTS: The metalloprotein chosen for side chain insertion, cytochrome C oxidase, showed promising results. It was computed as a probable non-allergen and exhibited no toxic domains, indicating its non-toxic nature. Additionally, it demonstrated a strong binding affinity with the huntingtin protein, with a binding energy of -1,253.3 Kcal/mol. CONCLUSIONS: Metal-based proteins, when engineered with additional neurogenerative amino acids, hold potential as drug candidates for treating neurodegenerative diseases such as Huntington's disease. The successful development of these engineered metalloproteins could offer therapeutic advantages. Further testing, both in vitro and in vivo, is necessary to evaluate their efficacy and validate their potential activity as novel drugs for the treatment of neurodegenerative diseases.

Abrocitinib efficacy and safety in patients with moderate-to-severe atopic dermatitis: Results from phase 3 studies, including the long-term extension JADE EXTEND study.

BACKGROUND: Abrocitinib improved signs and symptoms of moderate-to-severe atopic dermatitis (AD) at 12 or 16 weeks in phase 3 studies with a manageable safety profile. Further understanding of the abrocitinib long-term efficacy and safety profile is important for its appropriate use in treating chronic AD. OBJECTIVE: To evaluate the abrocitinib efficacy up to 48 weeks and long-term safety in patients with moderate-to-severe AD. METHODS: JADE EXTEND (NCT03422822) is an ongoing, phase 3, long-term extension study that enrolled patients from previous abrocitinib AD trials. This analysis focusses on patients from the phase 3 JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871) and JADE COMPARE (NCT03720470) studies who completed the full treatment period of placebo or abrocitinib (200 mg or 100 mg once daily) and subsequently entered JADE EXTEND. Efficacy endpoints included the proportion of patients achieving skin clearance (Investigator's Global Assessment [IGA] 0/1 [clear/almost clear]; ≥75% improvement in Eczema Area and Severity Index [EASI-75]) and itch response (Peak Pruritus Numerical Rating Scale [PP-NRS] severity ≥4-point improvement). Safety endpoints included treatment-emergent adverse events (TEAEs), serious TEAEs and TEAEs leading to discontinuation. Data cut-off: April 22, 2020. RESULTS: As of the data cut-off, ~70% and ~45% of patients received abrocitinib for ≥36 and ≥48 weeks, respectively. Nasopharyngitis, atopic dermatitis, nausea and upper respiratory tract infections were the most frequent TEAEs. Serious TEAEs occurred in 7% and 5% and TEAEs leading to study discontinuation occurred in 9% and 7% of patients receiving abrocitinib 200 mg and 100 mg, respectively. Week 48 efficacy responses with abrocitinib 200 mg and 100 mg were as follows: IGA 0/1 52% and 39%; EASI-75 82% and 67%, and PP-NRS severity ≥4-point improvement 68% and 51%. CONCLUSIONS: In patients with moderate-to-severe AD, long-term abrocitinib treatment resulted in clinically meaningful skin and pruritus improvement. The long-term safety profile was manageable and consistent with previous reports.

Influence of Disorder on the Bad Metal Behavior in Polar Amalgams.

The two new ternary amalgams K1-xRbxHg11 [x = 0.472(7)] and Cs3-xCaxHg20 [x = 0.20(3)] represent two different examples of how to create ternary compounds from binaries by statistical atom substitution. K1-xRbxHg11 is a Vegard-type mixed crystal of the isostructural binaries KHg11 and RbHg11 [cubic, BaHg11 structure type, space group Pm3̅m, a = 9.69143(3) Å, Rietveld refinement], whereas Cs3-xCaxHg20 is a substitution variant of the Rb3Hg20 structure type [cubic, space group Pm3̅n, a = 10.89553(14) Å, Rietveld refinement] for which a fully substituted isostructural binary Ca phase is unknown. In K1-xRbxHg11, the valence electron concentration (VEC) is not changed by the substitution, whereas in Cs3-xCaxHg20, the VEC increases with the Ca content. Amalgams of electropositive metals form polar metal bonds and show "bad metal" properties. By thermal analysis, magnetic susceptibility and resistivity measurements, and density functional theory calculations of the electronic structures, we investigate the effect of the structural disorder introduced by creating mixed-atom occupation on the physical properties of the two new polar amalgam systems.

Global epidemiology of Equine Influenza viruses: "A possible emerging zoonotic threat in future" an extensive systematic review with evidence / Epidemiologia global dos vírus da Gripe Equina: "Uma possível ameaça zoonótica emergente no futuro" uma extensa revisão sistemática com evidências

There are different opinions around the World regarding the zoonotic capability of H3N8 equine influenza viruses. In this report, we have tried to summarize the findings of different research and review articles from Chinese, English, and Mongolian Scientific Literature reporting the evidence for equine influenza virus infections in human beings. Different search engines i.e. CNKI, PubMed, ProQuest, Chongqing Database, Mongol Med, and Web of Knowledge yielded 926 articles, of which 32 articles met the inclusion criteria for this review. Analyzing the epidemiological and Phylogenetic data from these articles, we found a considerable experimental and observational evidence of H3N8 equine influenza viruses infecting human being in different parts of the World in the past. Recently published articles from Pakistan and China have highlighted the emerging threat and capability of equine influenza viruses for an epidemic in human beings in future. In this review article we have summarized the salient scientific reports published on the epidemiology of equine influenza viruses and their zoonotic aspect. Additionally, several recent developments in the start of 21st century, including the transmission and establishment of equine influenza viruses in different animal species i.e. camels and dogs, and presumed encephalopathy associated to influenza viruses in horses, have documented the unpredictable nature of equine influenza viruses. In sum up, several reports has highlighted the unpredictable nature of H3N8 EIVs highlighting the need of continuous surveillance for H3N8 in equines and humans in contact with them for novel and threatening mutations.

Existem diferentes opiniões em todo o mundo a respeito da capacidade zoonótica dos vírus da influenza equina H3N8. Neste relatório, tentamos resumir os resultados de diferentes pesquisas e artigos de revisão da literatura científica chinesa, inglesa e mongol relatando as evidências de infecções pelo vírus da influenza equina em seres humanos. Diferentes mecanismos de busca, como CNKI, PubMed, ProQuest, Chongqing Database, Mongol Med e Web of Knowledge geraram 926 artigos, dos quais 32 atenderam aos critérios de inclusão para esta revisão. Analisando os dados epidemiológicos e filogenéticos desses artigos, encontramos uma considerável evidência experimental e observacional de vírus da influenza equina H3N8 infectando seres humanos em diferentes partes do mundo no passado. Artigos publicados recentemente no Paquistão e na China destacaram a ameaça emergente e a capacidade dos vírus da influenza equina para uma epidemia em seres humanos no futuro. Neste artigo de revisão, resumimos os relatórios científicos relevantes publicados sobre a epidemiologia dos vírus da influenza equina e seu aspecto zoonótico. Além disso, vários desenvolvimentos recentes no início do século 21, incluindo a transmissão e estabelecimento de vírus da influenza equina em diferentes espécies animais, ou seja, camelos e cães, e presumida encefalopatia associada aos vírus da influenza em cavalos, documentaram a natureza imprevisível dos vírus da influenza equina. Em suma, vários relatórios destacaram a natureza imprevisível de H3N8 EIVs destacando a necessidade de vigilância contínua para H3N8 em equinos e humanos em contato com eles para novas mutações ameaçadoras.

Global epidemiology of Equine Influenza viruses; A possible emerging zoonotic threat in future an extensive systematic review with evidence

Abstract There are different opinions around the World regarding the zoonotic capability of H3N8 equine influenza viruses. In this report, we have tried to summarize the findings of different research and review articles from Chinese, English, and Mongolian Scientific Literature reporting the evidence for equine influenza virus infections in human beings. Different search engines i.e. CNKI, PubMed, ProQuest, Chongqing Database, Mongol Med, and Web of Knowledge yielded 926 articles, of which 32 articles met the inclusion criteria for this review. Analyzing the epidemiological and Phylogenetic data from these articles, we found a considerable experimental and observational evidence of H3N8 equine influenza viruses infecting human being in different parts of the World in the past. Recently published articles from Pakistan and China have highlighted the emerging threat and capability of equine influenza viruses for an epidemic in human beings in future. In this review article we have summarized the salient scientific reports published on the epidemiology of equine influenza viruses and their zoonotic aspect. Additionally, several recent developments in the start of 21st century, including the transmission and establishment of equine influenza viruses in different animal species i.e. camels and dogs, and presumed encephalopathy associated to influenza viruses in horses, have documented the unpredictable nature of equine influenza viruses. In sum up, several reports has highlighted the unpredictable nature of H3N8 EIVs highlighting the need of continuous surveillance for H3N8 in equines and humans in contact with them for novel and threatening mutations.

Resumo Existem diferentes opiniões em todo o mundo a respeito da capacidade zoonótica dos vírus da influenza equina H3N8. Neste relatório, tentamos resumir os resultados de diferentes pesquisas e artigos de revisão da literatura científica chinesa, inglesa e mongol relatando as evidências de infecções pelo vírus da influenza equina em seres humanos. Diferentes mecanismos de busca, como CNKI, PubMed, ProQuest, Chongqing Database, Mongol Med e Web of Knowledge geraram 926 artigos, dos quais 32 atenderam aos critérios de inclusão para esta revisão. Analisando os dados epidemiológicos e filogenéticos desses artigos, encontramos uma considerável evidência experimental e observacional de vírus da influenza equina H3N8 infectando seres humanos em diferentes partes do mundo no passado. Artigos publicados recentemente no Paquistão e na China destacaram a ameaça emergente e a capacidade dos vírus da influenza equina para uma epidemia em seres humanos no futuro. Neste artigo de revisão, resumimos os relatórios científicos relevantes publicados sobre a epidemiologia dos vírus da influenza equina e seu aspecto zoonótico. Além disso, vários desenvolvimentos recentes no início do século 21, incluindo a transmissão e estabelecimento de vírus da influenza equina em diferentes espécies animais, ou seja, camelos e cães, e presumida encefalopatia associada aos vírus da influenza em cavalos, documentaram a natureza imprevisível dos vírus da influenza equina. Em suma, vários relatórios destacaram a natureza imprevisível de H3N8 EIVs destacando a necessidade de vigilância contínua para H3N8 em equinos e humanos em contato com eles para novas mutações ameaçadoras.

Men with oligozoospermia had lower level of seminal plasma pyridoxine compared to normozoospermic men.

The contribution of pyridoxine on various human disorders has been revealed in so many studies; however, this contribution on poor semen quality has yet to be investigated. Here, we intended to measure the level of seminal plasma pyridoxine (SPP) in men with oligozoospermia compared to normozoospermic men. Thirty-three men with oligozoospermia and forty-three normozoospermic men were randomly enrolled in this study. Collected semen were tested for sperm motility, sperm concentration, semen volume, and pyridoxine status. Liquid chromatography with tandem mass spectrometry was used to measure SPP in the collected samples. There was a significant reduction (p < 0.0001) in the concentrations of SPP in men with oligozoospermia (0.79 ± 0.41 µg L-1) compared to normozoospermic men (3.17 ± 0.96 µg L-1). Besides, SPP was not significantly correlated (p > 0.05) with sperm motility, sperm concentration, and semen volume in both tested groups, but, independently, it was found to be positively correlated (p = 0.0154) with male age in oligozoospermic group. Men with oligozoospermia had lower level of SPP compared to normozoospermic men. These results may open a new research gate for the use of pyridoxine in the management of male infertility.

Level of Awareness and Attitude Toward Cerebral Palsy Among Parents in Al-Baha City, Saudi Arabia.

Background Cerebral palsy (CP) is a chronic disorder of motion, posture, and tone which occurs due to brain insult during the period of brain growth. It is a disabling disorder in both motor and intellectual aspects. Fortunately, CP is a manageable disease that can be managed in part by increasing the knowledge and understanding of the parents. Methodology This cross-sectional, prospective, community-based study aimed to assess the level of parents' knowledge and their attitude toward CP using an electronic questionnaire. The parents' knowledge was classified as good or poor based on an adopted scoring system. The parents' attitude was categorized as positive or negative. Results Our study results showed that good knowledge (those with a score more than 60% of the total score) was noted in 275 (61.1%) participants, whereas 175 of the participants had poor knowledge (38.9%), especially regarding awareness of the diagnosis of CP. Conclusions Most participants had an overall good knowledge of CP although they had insufficient knowledge of some aspects of the disease such as causes, disease course, clinical presentations, diagnosis, and prognosis. Although the results showed a positive attitude concerning playing with a child with CP, unfortunately, there was a negative attitude toward hiring a CP patient and a strongly negative attitude toward marrying a patient with CP.

Abrocitinib monotherapy in Investigator's Global Assessment nonresponders: improvement in signs and symptoms of atopic dermatitis and quality of life.

BACKGROUND: Abrocitinib, a once-daily, oral Janus kinase 1 selective inhibitor, was shown to be an effective treatment for moderate-to-severe atopic dermatitis in phase 2 b/3 monotherapy trials. METHODS: These analyses included data for Investigator's Global Assessment responder (clear [0] or almost clear [1] with ≥2-grade improvement) and nonresponder patients with moderate-to-severe atopic dermatitis who received abrocitinib (200 mg or 100 mg) or placebo in three abrocitinib monotherapy trials (phase 2 b, NCT02780167; two phase 3, NCT03349060/JADE MONO-1 and NCT03575871/JADE MONO-2). Outcomes measuring skin clearance, itch, and quality of life were evaluated. RESULTS: Both nonresponders (n = 548) and responders (n = 260) treated with abrocitinib had rapid and clinically meaningful improvement in skin clearance, itch, and quality of life compared with placebo. CONCLUSION: Patients with moderate-to-severe atopic dermatitis treated with abrocitinib who did not achieve an Investigator's Global Assessment 0/1 response at week 12 still experienced rapid, clinically meaningful improvements across several other validated measures of efficacy and quality of life. CLINICALTRIALS.GOV: NCT02780167, NCT03349060, NCT03575871.

The Effect of Alcoholic Extract of Anabasis syriaca Iljin on Biochemical and Histological Parameters in Rats.

This work investigates the effect of the alcoholic extract of Anabasis syriaca Iljin on biochemical and histological parameters in male rats. The lethal dose (50% of the plant extract) was assessed, and three separate doses (1/10th, 1/15th, and 1/20th) were orally gavaged for two weeks into three study groups of animals (five rats in each group), with one group used as a control and gavaged normal saline via the same route. Blood was collected after overnight fasting, and 24 biochemical parameters were evaluated. The gross and microscopic findings were reported after the collection of specimens from the animals and processed routinely for standard histological procedures. Among all tested biochemical parameters, a significant increase was noted in fasting serum glucose (p ≤ 0.010), troponin (p ≤ 0.001), and creatine kinase (p ≤ 0.001), while a significant decrease was found in triglycerides (p ≤ 0.001) and low-density lipoprotein (p=0.001). On the other hand, no significant histopathological lesions were present within the examined tissues of all groups. In conclusion, ethanolic extract of Anabasis syriaca negatively affected the cardiac function of male rats and increased their serum glucose but reduced their serum triglycerides and low-density lipoprotein.

Ischemic Priapism Progressing to Penile Gangrene in a Patient with COVID-19 Infection: A Case Report with Literature Review.

Priapism is considered a rare disorder and even more rare when it occurs as a complication of COVID-19. To the best of our knowledge, only eight studies have reported priapism as a complication of COVID-19. Here, we report the case of a 66-year-old male with COVID-19 who presented with neglected priapism for three days. On local examination, penile erection was apparent in association with blackened areas on the glans penis extending to the midpenile shaft denoting penile gangrene. A clear line of demarcation was noticed at the midpenile shaft. Penile duplex was performed, showing no blood flow in both cavernosal arteries. Penile aspiration was performed, and the cavernosal blood sample showed evidence of ischemic priapism. Given the presence of penile gangrene extending to the midshaft of the penis and the poor general condition of the patient, the decision was made to perform partial penectomy and suprapubic tube placement. We recommend the establishment of a guideline for the diagnosis and prevention of thrombotic diseases in patients with COVID-19 infection as there is increasing evidence of COVID-19-related thrombotic manifestations.

Reactivity of allyl methyl sulphide, the in-vitro metabolite of garlic, with some amino acids and with phospholipid involved in viral infections.

Garlic, as well as several natural food ingredients such as basil, ginger, turmeric, cinnamon, clove, pepper etc., has long been traditionally used as routine anti-viral and anti-bacterial remedy. Allyl methyl sulfide (AMS) is reportedly a persistent main active metabolite component of allicin after garlic ingestion accounting for at least 90% of the allicin consumed. Several studies have reported the presence of AMS in organs such as lung, kidney etc. and body fluids such as mucous, and blood-plasma. Glycoproteins of enveloped viruses are actively involved in viral pathogenesis. N-acetylneuraminic acid (sialic acid) and N-Acetylglucosamine, are some of the vital amino acids involved in several viral infections using glycoproteins via glycosylation. Simulations studies based on First-principles density functional theory show that these amino acids attach with AMS, and the reactions are thermodynamically spontaneous (ΔG and ΔS negative are at 310.15 K as well as lower and higher temperatures). Further, phospholipid phosphatidylethanolamine (a component of some viral envelops) also attaches readily with AMS and the reaction is spontaneous. AMS molecules attachment with viral phospholipids and amino-acids involved in viral infection would denature the virus and prevent its attachment to the host cell.Communicated by Ramaswamy H. Sarma.

Knowledge and awareness of human papillomavirus infection and human papillomavirus vaccine among Kazakhstani women attending gynecological clinics.

Cervical cancer remains one of the top causes of cancer-related morbidity and mortality all over the world. Currently, however, there are no published studies to assess the knowledge of HPV and cervical cancer in Kazakhstan. This study aimed to assess the awareness of HPV, the knowledge of HPV as a cause of cervical cancer, and the awareness of HPV vaccination among Kazakhstani women visiting gynecological clinics across the country. In addition, the study aimed to identify the factors associated with the awareness of HPV and the HPV vaccine and knowledge of HPV as a major cause of cervical cancer. This was a cross-sectional survey-based study with 2,272 women aged between 18-70 years attending gynecological clinics, who were administered paper-based questionnaires. Data analysis included descriptive statistics consisting of mean values, standard deviations, and frequencies, where applicable. Differences in categorical variables between groups were analyzed using the Chi-square test with a significance value of <0.005. Crude odds ratio (OR) and adjusted odds ratio (AOR) with 95% corresponding confidence intervals were calculated in regression analysis using univariate and multivariable logistic regression models. The mean age of participants was 36.33±10.09 years. More than half (53%) of the participants had been screened for cervical cancer. Among those who were aware of HPV, 46% knew that HPV causes cervical cancer and 52% were aware of the HPV vaccine. The key factors related to outcome variables were age, ethnicity, education, family, number of deliveries, and menarche. From a subgroup analysis, results from the HPV test and Pap smear test were factors related to dependent variables such as awareness of HPV and awareness of HPV vaccination.

Melatonin serum level, sleep functions, and depression level after bilateral anodal transcranial direct current stimulation in patients with Parkinson's disease: a feasibility study.

OBJECTIVE: Parkinson's disease (PD) is associated with non-motor complications such as sleep disturbance and depression. Transcranial direct current stimulation (tDCS) showed therapeutic effects on the motor dysfunctions. However, the potential effects of tDCS therapy on melatonin hormone, sleep dysfunctions, and depression in patients with PD still unclear. This feasibility study aimed to identify any potential changes in melatonin serum level, sleep functions and depression after the bilateral anodal tDCS in patients with PD. MATERIAL AND METHODS: Tensessions of bilateral anodal tDCS stimulation applied over left and right prefrontal and motor areas were given to twenty-five patients with PD. Melatonin serum level, Pittsburgh sleep quality index, and geriatric depression scale examined before and after tDCS stimulation. RESULTS: After bilateral anodal tDCS, there was a significant reduction in melatonin serum level, improvement in depression, improvements in overall sleep quality, and sleep latency. Correlations test showed significant associations between melatonin serum level reduction and changes in subjective sleep quality, and sleep duration, as well as between improvements in depression and overall sleep quality, sleep latency, and sleep disturbance. CONCLUSION: Bilateral anodal tDCS therapy was a feasible and safe tool that showed potential therapeutic effects on melatonin serum level, sleep quality, and depression level in patients with PD. Although the further large scale and randomized-control trial studies are crucially needed, there is still a need for such a feasibility study to be established before such trials can be implemented as is recommended in the new medical research council guidelines.

Global epidemiology of Equine Influenza viruses; "A possible emerging zoonotic threat in future" an extensive systematic review with evidence.

There are different opinions around the World regarding the zoonotic capability of H3N8 equine influenza viruses. In this report, we have tried to summarize the findings of different research and review articles from Chinese, English, and Mongolian Scientific Literature reporting the evidence for equine influenza virus infections in human beings. Different search engines i.e. CNKI, PubMed, ProQuest, Chongqing Database, Mongol Med, and Web of Knowledge yielded 926 articles, of which 32 articles met the inclusion criteria for this review. Analyzing the epidemiological and Phylogenetic data from these articles, we found a considerable experimental and observational evidence of H3N8 equine influenza viruses infecting human being in different parts of the World in the past. Recently published articles from Pakistan and China have highlighted the emerging threat and capability of equine influenza viruses for an epidemic in human beings in future. In this review article we have summarized the salient scientific reports published on the epidemiology of equine influenza viruses and their zoonotic aspect. Additionally, several recent developments in the start of 21st century, including the transmission and establishment of equine influenza viruses in different animal species i.e. camels and dogs, and presumed encephalopathy associated to influenza viruses in horses, have documented the unpredictable nature of equine influenza viruses. In sum up, several reports has highlighted the unpredictable nature of H3N8 EIVs highlighting the need of continuous surveillance for H3N8 in equines and humans in contact with them for novel and threatening mutations.

Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program.

BACKGROUND: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy. OBJECTIVE: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study. METHODS: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported. RESULTS: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19. CONCLUSION: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD. TRIAL REGISTRIES: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.