General loss of proteostasis links Huntington disease to Cockayne syndrome.

Cockayne syndrome (CS) is an autosomal recessive disorder of developmental delay, multiple organ system degeneration and signs of premature ageing. We show here, using the RNA-seq data from two CS mutant cell lines, that the CS key transcriptional signature displays significant enrichment of neurodegeneration terms, including genes relevant in Huntington disease (HD). By using deep learning approaches and two published RNA-Seq datasets, the CS transcriptional signature highly significantly classified and predicted HD and control samples. Neurodegeneration is one hallmark of CS disease, and fibroblasts from CS patients with different causative mutations display disturbed ribosomal biogenesis and a consecutive loss of protein homeostasis - proteostasis. Encouraged by the transcriptomic data, we asked whether this pathomechanism is also active in HD. In different HD cell-culture models, we showed that mutant Huntingtin impacts ribosomal biogenesis and function. This led to an error-prone protein synthesis and, as shown in different mouse models and human tissue, whole proteome instability, and a general loss of proteostasis.

Un/met: a mixed-methods study on primary healthcare needs of the poorest population in Khyber Pakhtunkhwa province, Pakistan.

BACKGROUND: Access of all people to the healthcare they need, without financial hardship is the goal of Universal Health Coverage (UHC). As UHC initiatives expand, assessing the needs of vulnerable populations can reveal gaps in the system which may be covered by relevant policies. In this study we (i) identify the met and unmet primary healthcare needs of the poorest population of Khyber Pakhtunkhwa province (KP), Pakistan, and (ii) explore why the gaps exist. METHODS: We used Leveque's Framework of Patient-centred Access to Healthcare to examine unmet primary healthcare (PHC) needs and their underlying causes for the poorest population in four districts of Khyber Pakhtunkhwa province, Pakistan. Using a triangulation mixed methods design, we analysed data from a quantitative household survey of744 households, 17 focus group discussions with household members and, 11 interviews with healthcare providers. RESULTS: Our results show that indicate that despite service utilization, PHC needs were not met, primarily due to prohibitively high costs at each stage of access. Furthermore, gaps in outreach and information (approachability), and varying availability of medicines and diagnostics at facilities (appropriateness) the supply side as well as difficulties in navigating the system (inability to perceive) and adhering to prescriptions (inability to engage) on the demand side, also led to unmet PHC needs. Going beyond utilization, our findings highlight that engagement with care is an important determinant of met needs for vulnerable populations. CONCLUSION: Social health protection policies can contribute to advancing UHC for primary care. However, in our setting, enhancing communication and outreach, addressing gender and age disparities, and improving quality of care and health infrastructure are necessary to fully meet the needs of the poorest populations.

Knowledge, Attitude, and Practice of Healthcare Professionals and Medical Students Regarding Probiotics and Prebiotics in Lahore, Pakistan: A Cross-Sectional Study.

Objective This study aims to explore healthcare professionals' and medical students' knowledge and attitudes toward probiotics and prebiotics in various health conditions. It seeks to identify any obstacles associated with their use and gain insight into the healthcare community's perspectives on these supplements. Methods A descriptive cross-sectional study was conducted using a preformed questionnaire. Data was collected by a convenience sampling technique during October and November 2023. A total of 417 responses were collected, and the data analysis was performed using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, NY, USA). Results In the study, 198 participants (47.5%) were doctors, and 219 (52.5%) were medical students. Only 81 (37%) students had good knowledge about probiotics, while 36 (16.4%) had good knowledge about prebiotics. Poor knowledge was associated with a poor knowledge, attitude, and practice (KAP) score, indicating a link between knowledge, attitude, and practice. Similarly, only 96 (48.5%) doctors had good knowledge about probiotics, while 45 (22.7%) of them had good knowledge about prebiotics. The study found that a lack of knowledge was the primary barrier to the use of prebiotics and probiotics, as reported by 226 (54.4%) participants. The chi-square test showed no significant correlation between participants' demographics and their KAP. Conclusion The majority of respondents demonstrated poor knowledge and practices regarding probiotics and prebiotics, which can be attributed to insufficient awareness of their benefits. Education tools like curriculum and training programs should include evidence-based information to raise awareness among healthcare professionals about their benefits and address concerns associated with their use in treating patients.

Anticoagulants versus Antiplatelet Treatment in the Medical Management of Carotid Floating Thrombus.

BACKGROUND: Carotid free-floating thrombus (CFT) is a rare cause of stroke describing an intraluminal thrombus that is loosely associated with the arterial wall and manifesting as a filling defect fully surrounded by flow on vascular imaging. Unfortunately, there is no clear consensus among experts on the ideal treatment for this pathology. METHODS: Retrospective analysis of acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients diagnosed with CFT on computed tomography angiogram (CTA) between January 2015-March 2023. We aimed to compare two treatment regimens: anticoagulation (ACT) and antiplatelet (APT) in the treatment of CFT. APT regimens included the use of dual or single antiplatelets (DAPT or SAPT; aspirin, clopidogrel and ticagrelor) and ACT regimens included the use of direct oral anticoagulants, warfarin, heparin or low molecular weight heparin +/- ASA. Patients that underwent mechanical thrombectomy were excluded. RESULTS: During study time there were 8252 acute ischemic stroke hospitalizations, of which 135 (1.63 %) patients were diagnosed with CFT. Sixty-six patients were included in our analysis. Patients assigned to APT were older (60.41years ± 12.82;p < 0.01). Other demographic variables were similar between ACT and APT groups. Complete CFT resolution on repeat vascular imaging was numerically higher at 30 days (58.8 vs 31.6 %, respectively; p = 0.1) and at latest follow-up (70.8 vs 50 %; p = 0.1) on ACT vs APT, respectively without reaching statistical significance. Similarly, there was numerically higher rates of any ICH with ACT compared to APT but it did not achieve statistical significance (27.6 % vs 13.5 %; p = 0.5). There were similar rates of PH1/2 hemorrhagic transformation, independence at discharge and similar hospital length of stay between ACT and APT groups. Patients assigned to APT were more likely to be discharged on their assigned treatment compared to those assigned to ACT (86.5 vs 55.2 %; p < 0.001). The rate of 30-day recurrent stroke was comparable among ACT and APT at 30 days (3.4 vs 0 %; p = 0.1, respectively). Subgroup analysis comparing exclusive ACT vs Dual APT lead to similar results. CONCLUSION: Our study showed comparable efficacy and safety outcomes in CFT patients who were exclusively managed medically with ACT vs APT. Larger prospective studies are needed.

Process evaluation of a pragmatic feasibility trial on smokeless tobacco cessation intervention delivered in dental hospitals.

BACKGROUND: Article 14 of the WHO 'Framework Convention on Tobacco Control' recommends, that all oral healthcare providers provide support for tobacco cessation, to all patients. Despite evidence on the effectiveness of tobacco cessation interventions in dental settings, implementation remains low in most high-burden countries like Pakistan. A pragmatic pilot trial of a dentist-delivered behavioural support intervention for smokeless tobacco (ST) cessation, was conducted in dental hospitals in Pakistan. This paper presents the findings of the process evaluation of the trial. METHODS: A mixed-method process evaluation of a multi-centre randomised control pilot trial of dentist-delivered behavioural support intervention ST cessation was conducted. The intervention included three sessions namely: pre-quit, quit and post-quit sessions. The process evaluation involved: semi-structured interviews with trial participants (n = 26, of which dental patients were n = 13 and participating dentists were n = 13 conducted from June-August 2022); and fidelity assessment of audio recordings of the intervention sessions (n = 29). The framework approach was used to thematically analyse the interview data. RESULTS: Overall the trial procedures were well accepted, however, young patients expressed uneasiness over revealing their ST use status. The intervention was received positively by dentists and patients. Dentists identified some challenges in delivering behavioural support to their patients. Of these, some were related to the contents of the intervention whereas, others were related to the logistics of delivering the intervention in a clinical setting (such as workload and space). Acceptability of the intervention resources was overall low amongst young patients as they did not take the intervention resources home due to fear of their family members finding out about their ST use. The intervention was successful in achieving the intended impact (in those who engaged with the intervention), i.e., change in the patients' ST use behaviour. Giving up ST with the aid of behavioural support also had an unintended negative effect i.e., the use of harmful substances (cannabis, cigarettes) to give up ST use. Patients' satisfaction with their dental treatment seemed to influence the intervention outcome. CONCLUSION: While there are many variables to consider, but for the participants of this study, behavioural support for abstinence delivered through dentists during routine dental care, appears to be an acceptable and practical approach in helping patients give up ST use, in a country like Pakistan, where negligible support is offered to ST users.

Improving broiler health through cecal microbiota transplantation: a comprehensive study on growth, immunity, and microbial diversity.

Cecal microbiota has emerged as a prominent intervention target for improving the production and welfare of poultry. This is essential for the overall health and performance of broiler chickens. The current study focused on investigating the effect of cecal microbiota transplantation (CMT) from healthy donor chickens on the growth performance, immunity, and microbial composition of newly hatched chicks and evaluated the effect of sample storage on the microbial diversity of the cecal samples. A healthy "Wannan Yellow Chicken line" was selected as the donor, and 180 1-d-old chicks from the same line were used as recipients for a 60-d feed trial. The chicks were randomly allocated to three groups (60 birds per group) with three replicates in each group. The three treatment groups were CMT-0 (control, normal saline solution), CMT-I (1:12 cecal content, normal saline supplemented with 10% glycerol), and CMT-II (1:6 cecal content, normal saline supplemented with 10% glycerol). The results of weight gain and absolute organ weight showed significant improvements in the CMT-II group compared with the CMT-0 group. Serum IgG level was significantly improved (P < 0.05) in CMT-I compared with that in the CMT-0. However, IL-6 levels increased in CMT-I and then significantly decreased in CMT-II. The cecal microbial diversity of CMT treatment was compared between two groups, fresh samples (FS) and stored samples at-80 °C (SS). The results showed that beneficial taxa, such as Firmicutes and Verrucomicrobiota, were substantially more abundant in both CMT-I and CMT-II than in CMT-0 in both FS and SS. Microbial function analysis at levels 1, 2, and 3 showed improved metabolism, genetic information processing, cellular processes, environmental information processing, and organismal systems in CMT-I and CMT-II for both FS and SS groups. However, the SS group showed decreased microbial diversity and function. To conclude, cecal microbiota transplantation is a promising strategy for enhancing the productivity and health of broiler chickens.

The cecal microbiota refers to a diverse community of microorganisms that play a crucial role in digestion, nutrient absorption, and overall gut health, influencing the well-being and performance of the host bird. In this study, we aimed to improve the health and growth of broiler chickens by exploring a unique approach called cecal microbiota transplantation. A thorough investigation was conducted by transplanting the microbiota from healthy Wannan Yellow Chicken line donors into newly hatched chicks in a 60-d feeding trial. After dividing the chicks into three groups, each receiving different treatments, we found significant enhancements in WG and organ health in the groups that received cecal microbiota transplants. The results also showed improvements in Serum IgG levels in the treatment groups. Furthermore, the analysis of microbial diversity indicated that beneficial microorganisms were more abundant in the treated groups, suggesting a positive effect on chicken digestive health. To summarize, our findings suggest that transferring healthy gut microorganisms from mature parent chickens to young chicks can lead to improved growth, immune system function, microbial diversity, and overall health. This approach is a promising strategy for enhancing the productivity and well-being of broiler chickens.

Global trends in hepatitis C-related hepatocellular carcinoma mortality: A public database analysis (1999-2019).

BACKGROUND: Hepatitis C is the leading cause of chronic liver disease worldwide and it significantly contributes to the burden of hepatocellular carcinoma (HCC). However, there are marked variations in the incidence and mortality rates of HCC across different geographical regions. With the advent of new widely available treatment modalities, such as direct-acting antivirals, it is becoming increasingly imperative to understand the temporal and geographical trends in HCC mortality associated with Hepatitis C. Furthermore, gender disparities in HCC mortality related to Hepatitis C are a crucial, yet underexplored aspect that adds to the disease's global impact. While some studies shed light on gender-specific trends, there is a lack of comprehensive data on global and regional mortality rates, particularly those highlighting gender disparities. This gap in knowledge hinders the development of targeted interventions and resource allocation strategies. AIM: To understand the global and regional trends in Hepatitis C-related HCC mortality rates from 1990 to 2019, along with gender disparities. METHODS: We utilized the Global Burden of Disease database, a comprehensive repository for global health metrics to age-standardized mortality rates due to Hepatitis C-related HCC from 1999 to 2019. Rates were evaluated per 100000 population and assessed by World Bank-defined regions. Temporal trends were determined using Joinpoint software and the Average Annual Percent Change (AAPC) method, and results were reported with 95% confidence intervals (CI). RESULTS: From 1990 to 2019, overall, there was a significant decline in HCC-related mortality rates with an AAPC of -0.80% (95%CI: -0.83 to -0.77). Females demonstrated a marked decrease in mortality with an AAPC of -1.06% (95%CI: -1.09 to -1.03), whereas the male cohort had a lower AAPC of -0.52% (95%CI: -0.55 to -0.48). Regionally, East Asia and the Pacific demonstrated a significant decline with an AAPC of -2.05% (95%CI: -2.10 to -2.00), whereas Europe and Central Asia observed an uptrend with an AAPC of 0.72% (95%CI: 0.69 to 0.74). Latin America and the Caribbean also showed an uptrend with an AAPC of 0.06% (95%CI: 0.02 to 0.11). In the Middle East and North Africa, the AAPC was non-significant at 0.02% (95%CI: -0.09 to 0.12). North America, in contrast, displayed a significant upward trend with an AAPC of 2.63% (95%CI: 2.57 to 2.67). South Asia (AAPC -0.22%, 95%CI: -0.26 to -0.16) and Sub-Saharan Africa (AAPC -0.14%, 95%CI: -0.15 to -0.12) trends significantly declined over the study period. CONCLUSION: Our study reports disparities in Hepatitis C-related HCC mortality between 1999 to 2019, both regionally and between genders. While East Asia and the Pacific regions showed a promising decline in mortality, North America has experienced a concerning rise in mortality. These regional variations highlight the need for healthcare policymakers and practitioners to tailor public health strategies and interventions. The data serves as a call to action, particularly for regions where mortality rates are not improving, emphasizing the necessity for a nuanced, region-specific approach to combat the global challenge of HCC secondary to Hepatitis C.

Site-Directed Mutagenesis: Improving the Acid Resistance and Thermostability of Bacillus velezensis α-Amylase and Its Preliminary Feed Application.

The current study aimed to improve the acid resistance and thermostability of Bacillus velezensis α-amylase through site-directed mutagenesis, with a specific focus on its applicability to the feed industry. Four mutation sites, P546E, H572D, A614E, and K622E, were designed in the C domain of α-amylase, and three mutants, Mut1 (E), Mut2 (ED), and Mut3 (EDEE), were produced. The results showed that the specific activity of Mut3 was 50 U/mg higher than the original α-amylase (Ori) after incubation at 40 °C for 4 h. Compared to Ori, the acid resistance of Mut3 showed a twofold increase in specific activity at pH 2.0. Moreover, the results of preliminary feed hydrolysis were compared between Ori and Mut3 by designing three factors, three levels of orthogonal experiment for enzymatic hydrolysis time, feed quantity, and amount of amylase. It was observed that the enzymatic hydrolysis time and feed quantity showed an extremely significant difference (p < 0.01) in Mut3 compared to Ori. However, the amount of enzyme showed significant (p < 0.05) improvement in the enzymatic hydrolysis in Mut3 as compared to Ori. The study identified Mut3 as a promising candidate for the application of α-amylase in the feed industry.

CDCA8, a mitosis-related gene, as a prospective pan-cancer biomarker: implications for survival prognosis and oncogenic immunology.

BACKGROUND: Human cell division cycle-associated protein 8 (CDCA8), a critical regulator of mitosis, has been identified as a prospective prognostic biomarker in several cancer types, including breast, colon, and lung cancers. This study analyzed the diagnostic/prognostic potential and clinical implications of CDCA8 across diverse cancers. METHODS: Bioinformatics and molecular experiments. RESULTS: Analyzing TCGA data via TIMER2 and GEPIA2 databases revealed significant up-regulation of CDCA8 in 23 cancer types compared to normal tissues. Prognostically, elevated CDCA8 expression correlated with poorer overall survival in KIRC, LUAD, and SKCM, emphasizing its potential as a prognostic marker. UALCAN analysis demonstrated CDCA8 up-regulation based on clinical variables, such as cancer stage, race, and gender, in these cancers. Epigenetic exploration indicated reduced CDCA8 promoter methylation levels in Kidney Renal Clear Cell Carcinoma (KIRC), Lung Adenocarcinoma (LUAD), and Skin Cutaneous Melanoma (SKCM) tissues compared to normal controls. Promoter methylation and mutational analyses showcased a hypomethylation and low mutation rate for CDCA8 in these cancers. Correlation analysis revealed positive associations between CDCA8 expression and infiltrating immune cells, particularly CD8+ and CD4+ T cells. Protein-protein interaction (PPI) network analysis unveiled key interacting proteins, while gene enrichment analysis highlighted their involvement in crucial cellular processes and pathways. Additionally, exploration of CDCA8-associated drugs through DrugBank presented potential therapeutic options for KIRC, LUAD, and SKCM. In vitro validation using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) confirmed elevated CDCA8 expression in LUAD cell lines (A549 and H1299) compared to control cell lines (Beas-2B and NL-20). CONCLUSION: This study provides concise insights into CDCA8's multifaceted role in KIRC, LUAD, and SKCM, covering expression patterns, diagnostic and prognostic relevance, epigenetic regulation, mutational landscape, immune infiltration, and therapeutic implications.

Percutaneous Electrical Nerve Field Stimulation in Children and Adolescents With Functional Dyspepsia-Integrating a Behavioral Intervention.

OBJECTIVES: Functional dyspepsia (FD) includes postprandial distress and epigastric pain syndrome. Percutaneous electrical nerve field stimulation (PENFS) in addition to behavioral interventions (BI) has shown benefits in children with functional abdominal pain but not specifically in FD. We aimed to assess the efficacy of PENFS for treating FD and compare the outcomes with those who received the combination of PENFS + BI. MATERIALS AND METHODS: Charts of patients with FD who completed four weeks of PENFS were evaluated. A subset of patients received concurrent BI. Demographic data, medical history, and symptoms were documented. Outcomes at different time points included subjective symptom responses and validated questionnaires collected clinically (Abdominal Pain Index [API], Nausea Severity Scale [NSS], Functional Disability Inventory [FDI], Pittsburgh Sleep Quality Index [PSQI], Children's Somatic Symptoms Inventory [CSSI], Patient-Reported Outcomes Measurement Information Systems [PROMIS] Pediatric Anxiety and Depression scales). RESULT: Of 84 patients, 61% received PENFS + BI, and 39% received PENFS alone. In the entire cohort, API (p < 0.0001), NSS (p = 0.001), FDI (p = 0.001), CSSI (p < 0.0001), PSQI (p = 0.01), PROMIS anxiety (p = 0.02), and depression (p = 0.01) scores improved from baseline to three weeks and at three months. Subjective responses showed nausea improvement (p = 0.01) and a trend for improvement in abdominal pain (p = 0.07) at week three. Abdominal pain subjectively improved at week three and three months (p = 0.003 and 0.02, respectively), nausea at week three and three months (p = 0.01 and 0.04, respectively), and a trend for improvement in sleep disturbances at week three and three months (p = 0.08 and p = 0.07, respectively) in the PENFS + BI group vs PENFS alone. CONCLUSION: Abdominal pain, nausea, functioning, somatization, sleep disturbances, anxiety, and depression improved at three weeks and three months after PENFS in pediatric FD. Subjective pain and nausea improvement were greater in the PENFS + BI group than in the group with PENFS alone, suggesting an additive effect of psychologic therapy.

In silico designing and characterization of outer membrane protein K (OmpK) from Vibrio anguillarum and its expression in Nicotiana tabacum for the development of a plant-based vaccine against fish vibriosis.

Vibriosis is caused by Vibrio anguillarum in various species of aquaculture. A novel, secure, and stable vaccine is needed to eradicate vibriosis. Here, for reverse vaccinology and plant-based expression, the outer membrane protein K (OmpK) of V. anguillarum was chosen due to its conserved nature in all Vibrio species. OmpK, an ideal vaccine candidate against vibriosis, demonstrated immunogenic, non-allergic, and non-toxic behavior by using various bioinformatics tools. Docking showed the interaction of the OmpK model with TLR-5. In comparison to costly platforms, plants can be used as alternative and economic bio-factories to produce vaccine antigens. We expressed OmpK antigen in Nicotiana tabacum using Agrobacterium-mediated transformation. The expression vector was constructed using Gateway® cloning. Transgene integration was verified by polymerase chain reaction (PCR), and the copy number via qRT-PCR, which showed two copies of transgenes. Western blotting detected monomeric form of OmpK protein. The total soluble protein (TSP) fraction of OmpK was equivalent to 0.38% as detected by ELISA. Mice and fish were immunized with plant-derived OmpK antigen, which showed a significantly high level of anti-OmpK antibodies. The present study is the first report of OmpK antigen expression in higher plants for the potential use as vaccine in aquaculture against vibriosis, which could provide protection against multiple Vibrio species due to the conserved nature OmpK antigen.

Subspeciality Interests Among the Ophthalmology Residents: A Mixed-Methods Study.

OBJECTIVE: To determine the popular subspeciality choices among ophthalmology residents, to explore the factors affecting that choice, and to identify the obstacles that they face while selecting a subspeciality fellowship. STUDY DESIGN: Mixed-methods study. Place and Duration of the Study: Department of Ophthalmology of Hayatabad Medical Complex and Lady Reading Hospital, Peshawar, from 1st September to 30th November, 2021. METHODOLOGY: The qualitative (1st) phase comprised of focussed group discussion (FGD) followed by an online in-depth interview (IDI). Quantitative (2nd) phase was conducted as online survey and consisted of currently enrolled FCPS-ophthalmology residents. Themes were generated and used to modify the pre-designed questionnaire. Questionnaire was piloted and necessary adjustments were made. In the 2nd phase, the online link of the questionnaire was shared with the eligible participants all over the country. For the association between categorical variables, the Pearson Chi-square test was used with significance at p-value <0.05.   Results: Nine participants were recruited in the first phase and three themes were generated. In the second phase, a total of 138 responses were received, among which mean age was 29.37 + 3.9 years, and 74 (53.6%) participants were males. The top three subspeciality choices were cataract and refractive surgery (n = 31, 22.5%), vitreoretinal surgery (n = 30, 21.7%) and orbit and oculoplasty (n = 13, 9.4%). Sixty-two (48.8%) participants stated interest in the career to be the main reason to choose a particular fellowship, and 54 (42.5%) participants identified challenging subspeciality as the main obstacle. An association between gender and the intended subspeciality showed significant results (p = 0.029). CONCLUSION: Ophthalmology residents of Pakistan have different approaches and motivations for selecting a fellowship programme. Professional needs and scientific reasons are their main motivations. KEY WORDS: Ophthalmology, Fellowship, Motivations, Career choices, Mentor, Pakistan.

Analysis of Cervix Intraepithelial Neoplasia Prevalence in the Kurdistan Region, Iraq.

BACKGROUND:  Cervix intraepithelial neoplasia (CIN) refers to abnormal changes in the squamous cells of the cervix, with more significant changes known as high-grade squamous intraepithelial lesions (HSIL) occurring in grades II and III. AIM:  The study aimed to estimate the prevalence of cervical intraepithelial neoplasia and explore potential risk factors for HSIL among women living in the Kurdistan region, Iraq. MATERIALS AND METHODS:  The research encompassed a sample size of 1300 female participants whose Papanicolaou (pap) smears were taken in several hospitals located within the Kurdistan region. The objective of the study was to determine the prevalence of cervical infection among these women. This was a multi-centre study conducted from January 2021 to the end of December 2021 for the determination of pap smears and the relationship between CIN and cervical cancer. Only 120 (9.23%) of those 1300 participants suffered from cervical or vaginal problems. A pap smear, also known as a pap test, is a routine screening procedure used to detect abnormal cervical cells that may indicate cervical cancer or precancerous conditions. The procedure involves collecting a sample of cells from the cervix. RESULTS:  The most important details in this study are the age groups and percentages of women who have undergone a pap smear. There were four women who tested positive for cervical cancer, accounting for 3.33% of the 120 participants with cervical or vaginal problems. However, there were 116 (96.67%) women who tested negative. With regard to the distribution of inflammation rates among the participants with cervical or vaginal problems, there were 114 (95%) women who suffered inflammation, whereas there were six (5%) women without inflammation. In each age group, the numbers of women with and without cervical cancer, as well as the corresponding percentages, were considered. The data suggest that the incidence of cervical cancer tends to increase with age since higher percentages were observed in older age groups. The study highlights the importance of regular screenings and age-specific cervical cancer prevention and detection strategies to ensure early diagnosis and effective medical interventions. CONCLUSION:  The prevalence of cervical cancer cases was relatively low, with only 0.31% of the total participants diagnosed with cervical cancer. The majority, accounting for 99.69%, did not have cervical cancer. These results highlight the importance of pap smear screenings as a valuable tool for early detection and prevention of cervical cancer. They also highlight the importance of regular screenings, especially for younger women, to detect and treat cervical abnormalities at an early stage.

Cholera outbreak in 2022 among children in Karachi: Study of cases attending to a Tertiary Care Hospital.

Objective & Background: Repeated outbreaks of cholera have occurred in Karachi. Changing patterns in seasonality, serotypes and antibiotic resistance have been observed in these outbreaks. Recently, in the year 2022, a surge of cholera cases has been reported from Karachi during the months of April-June. This study aimed to identify clinical features, antibiotic susceptibility, complications, and response to treatment of V. cholerae infection among children attending Indus hospital, Karachi. Methods: A retrospective chart review of pediatric patients was conducted for children aged 0-16 years. All children treated for culture-proven cholera infection at Indus Hospital from March to June 2022 were included. Details of clinical features, complications, antibiotic susceptibility, and response to treatment were retrieved from the health management information system (HMIS) of the hospital. Results: Twenty children were included. The median age was 01 (0.50-3.75) years. There were 9 (45%) males and 11 (55%) females. All the culture isolates belonged to serogroup O1 Ogawa of the Vibrio cholerae. Vomiting and diarrhea were the most common symptoms. Dehydration, acute kidney injury, and shock were seen in 19 (95%), 6 (30%), and 2 (10%) children respectively. Eleven children were admitted with an average hospital stay of 5 (Median-IQR 3-6) days. The isolates were completely susceptible to tetracycline, ciprofloxacin, and azithromycin. Different antibiotics were given which included cefotaxime, ceftriaxone, doxycycline, and ciprofloxacin. All children responded completely to the antibiotics. Conclusion: In present study all V. cholerae isolates belonged to the O1 Ogawa serotype that showed complete susceptibility to tetracycline, ciprofloxacin, and azithromycin. Dehydration, electrolyte imbalance, and renal impairment were the most common complications observed. Drinking unboiled water was identified as a potential source of cholera in most children. Therefore, advocacy of hygienic practices and disinfection of water supplies is recommended to prevent future cholera outbreaks.

Effect of Bacillus subtilis Supplemented Diet on Broiler's Intestinal Microbiota and TLRs Gene Expression.

This study aimed to investigate the effects of dietary Bacillus subtilis supplementation on gut microbiota diversity, digestive enzyme activity, and Toll-like receptor (TLR) expression in broiler chickens. A total of 240 "817" crossbred broiler chickens were randomly assigned to four groups: control (basal diet, BD), group I (BD + 300 g/d B. subtilis at 1.08 × 107 CFU/kg), group II (BD + 600 g/d B. subtilis at 2.16 × 107 CFU/kg), and group III (BD + 900 g/d B. subtilis at 3.24 × 107 CFU/kg). Gut microbiota analysis revealed significant improvements in the abundance of specific microorganisms in the treatment groups, with distinct variations in the core microorganisms between the groups. Notably, protease activity in the ileum was significantly increased in groups II (22.59%; p < 0.01) and III (14.49%; p < 0.05) compared to that in the control group. Moreover, significant up-regulation of TLR1A and TLR7 expression was observed in jejunum and cecum of the treated groups. Additionally, the TLR1B expression in the ileum was significantly increased. Furthermore, TLR2A and MyD88 transcription levels were significantly elevated in the jejunum, liver, spleen, and kidneys of experimental groups. Modulations in the expression of various TLR's (TLR2B, TLR3, TLR4, TLR15, and TLR21) were also observed in different organs. The spleen and kidney of B. subtilis-supplemented chickens exhibited upregulated expression of the proinflammatory cytokine IL-1ß. Dietary supplementation with B. subtilis in broiler chickens improved the gut microbiota diversity and significantly upregulated TLR's expression in various organs. B. subtilis could be a valuable feed additive, contributing to improved disease management and overall health in broiler chickens.

Detection of dengue virus serotype 4 in Sudan.

Background: Dengue virus infection is spreading globally and most parts of Sudan have witnessed repeated dengue outbreaks, with the detection of DENV-1, DENV-2 and DENV-3 serotypes. Aims: In this report we describe the dengue fever outbreaks that occurred in eastern Sudan (Kassala and Port Sudan cities) from August to November 2019. Methods: We enrolled 79 (29.8%) suspected cases from Kassala and 186 (70.2%) from Port Sudan who presented with fever. The participants were medically examined and their clinical signs recorded. Blood samples were collected for complete blood count, detection of anti-dengue virus IgM, detection of NS1 dengue antigen and identification of the virus serotype using RT-PCR. Results: The main clinical presentations were fever, abdominal pain, joint pain and vomiting, and thrombocytopenia was the main laboratory finding. One hundred and twenty-five blood samples tested positive for the anti-dengue IgM antibody, and 145 were positive for the NS1 antigen. Using RT-PCR, we identified 35 (24%) infections with DENV-2, 100 (69%) with DENV-3 and 10 (7%) with DENV-4 serotypes. Conclusions: We identified multiple serotypes - DENV-2, DENV-3 and DENV-4 - as the causes of the outbreak. The presence of DENV-4 serotype was documented for the first time in Sudan.

Ribosomal Dysfunction Is a Common Pathomechanism in Different Forms of Trichothiodystrophy.

Mutations in a broad variety of genes can provoke the severe childhood disorder trichothiodystrophy (TTD) that is classified as a DNA repair disease or a transcription syndrome of RNA polymerase II. In an attempt to identify the common underlying pathomechanism of TTD we performed a knockout/knockdown of the two unrelated TTD factors TTDN1 and RNF113A and investigated the consequences on ribosomal biogenesis and performance. Interestingly, interference with these TTD factors created a nearly uniform impact on RNA polymerase I transcription with downregulation of UBF, disturbed rRNA processing and reduction of the backbone of the small ribosomal subunit rRNA 18S. This was accompanied by a reduced quality of decoding in protein translation and the accumulation of misfolded and carbonylated proteins, indicating a loss of protein homeostasis (proteostasis). As the loss of proteostasis by the ribosome has been identified in the other forms of TTD, here we postulate that ribosomal dysfunction is a common underlying pathomechanism of TTD.

Invasive Micropapillary Carcinoma of the Breast With Solid Papillary Carcinoma: A Case Report.

Invasive micropapillary carcinoma and Solid papillary carcinomas are rare histologic subtypes of breast cancer. Co-existence of tumors of the breast like invasive ductal and lobular carcinomas, or invasive ductal carcinoma and mucinous carcinomas have been reported before. But the existence of invasive micropapillary carcinoma with solid papillary carcinoma is a rare occurrence. Here, we are reporting a rare case of a 60-year-old female with a mass in her left breast. The histopathology report showed a tumor containing these two histologic subtypes. Recognition of all tumor subtypes is necessary, as this can impact the treatment strategy.

Corrigendum: Plants in vitro propagation with its applications in food, pharmaceuticals and cosmetic industries; current scenario and future approaches.

[This corrects the article DOI: 10.3389/fpls.2022.1009395.].