TFIIH mutations can impact on translational fidelity of the ribosome.

TFIIH is a complex essential for transcription of protein-coding genes by RNA polymerase II, DNA repair of UV-lesions and transcription of rRNA by RNA polymerase I. Mutations in TFIIH cause the cancer prone DNA-repair disorder xeroderma pigmentosum (XP) and the developmental and premature aging disorders trichothiodystrophy (TTD) and Cockayne syndrome. A total of 50% of the TTD cases are caused by TFIIH mutations. Using TFIIH mutant patient cells from TTD and XP subjects we can show that the stress-sensitivity of the proteome is reduced in TTD, but not in XP. Using three different methods to investigate the accuracy of protein synthesis by the ribosome, we demonstrate that translational fidelity of the ribosomes of TTD, but not XP cells, is decreased. The process of ribosomal synthesis and maturation is affected in TTD cells and can lead to instable ribosomes. Isolated ribosomes from TTD patients show an elevated error rate when challenged with oxidized mRNA, explaining the oxidative hypersensitivity of TTD cells. Treatment of TTD cells with N-acetyl cysteine normalized the increased translational error-rate and restored translational fidelity. Here we describe a pathomechanism that might be relevant for our understanding of impaired development and aging-associated neurodegeneration.

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.

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.

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.

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.

Emerging trends of edible vaccine therapy for combating human diseases especially COVID-19: Pros, cons, and future challenges.

The researchers are still doing efforts to develop an effective, reliable, and easily accessible vaccine candidate to protect against COVID-19. As of the August 2020, nearly 30 conventional vaccines have been emerged in clinical trials, and more than 200 vaccines are in various development stages. Nowadays, plants are also considered as a potential source for the production of monoclonal antibodies, vaccines, drugs, immunomodulatory proteins, as well as used as bioreactors or factories for their bulk production. The scientific evidences enlighten that plants are the rich source of oral vaccines, which can be given either by eating the edible parts of plants and/or by oral administration of highly refined proteins. The use of plant-based edible vaccines is an emerging trend as it possesses minimum or no side effects compared with synthetic vaccines. This review article gives insights into different types of vaccines, the use of edible vaccines, advantages of edible vaccines over conventional vaccines, and mechanism of action of edible vaccines. This review article also focuses on the applications of edible vaccines in wide-range of human diseases especially against COVID-19 with emphasis on future perspectives of the use of edible vaccines.

A Novel Method of Magnetic Nanoparticles Functionalized with Anti-Folate Receptor Antibody and Methotrexate for Antibody Mediated Targeted Drug Delivery.

Therapeutic effects of anticancer medicines can be improved by targeting the specific receptors on cancer cells. Folate receptor (FR) targeting with antibody (Ab) is an effective tool to deliver anticancer drugs to the cancer cell. In this research project, a novel formulation of targeting drug delivery was designed, and its anticancer effects were analyzed. Folic acid-conjugated magnetic nanoparticles (MNPs) were used for the purification of folate receptors through a novel magnetic affinity purification method. Antibodies against the folate receptors and methotrexate (MTX) were developed and characterized with enzyme-linked immunosorbent assay and Western blot. Targeting nanomedicines (MNP-MTX-FR Ab) were synthesized by engineering the MNP with methotrexate and anti-folate receptor antibody (anti-FR Ab). The cytotoxicity of nanomedicines on HeLa cells was analyzed by calculating the % age cell viability. A fluorescent study was performed with HeLa cells and tumor tissue sections to analyze the binding efficacy and intracellular tracking of synthesized nanomedicines. MNP-MTX-FR Ab demonstrated good cytotoxicity along all the nanocomposites, which confirms that the antibody-coated medicine possesses the potential affinity to destroy cancer cells in the targeted drug delivery process. Immunohistochemical approaches and fluorescent study further confirmed their uptake by FRs on the tumor cells' surface in antibody-mediated endocytosis. The current approach is a useful addition to targeted drug delivery for better management of cancer therapy along with immunotherapy in the future.

New-onset myocardial injury in pregnant patients with coronavirus disease 2019: a case series of 15 patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 is the new coronavirus responsible for the coronavirus disease 2019 pandemic, characterized by acute respiratory distress syndrome and atypical pneumonia. In nonpregnant women, studies have shown that severe acute respiratory syndrome coronavirus 2 causes cardiac injury, which can result in myocardial inflammation and damage. Despite many studies investigating the extent of cardiac compromise in patients with severe coronavirus disease 2019, little is known regarding its impact on pregnant women. OBJECTIVE: This study aimed to illustrate the clinical, laboratory, radiologic findings and outcomes of pregnant patients with coronavirus disease 2019 who developed myocardial injury with ventricular dysfunction. STUDY DESIGN: We retrospectively reviewed the paper records of 15 pregnant women with coronavirus disease 2019, who developed myocardial injury on a single tertiary care hospital in the Dominican Republic. Patients' baseline characteristics, clinical picture, and laboratory and radiologic findings were presented, and maternal and fetal outcomes were analyzed. RESULTS: Of 154 pregnant patients diagnosed as having coronavirus disease 2019 at our hospital during the study period, 15 (9.7%), developed myocardial injury. These patients' mean age and gestational age were 29.87±5.83 and 32.31±3.68, respectively. Furthermore, 66.7% of patients presented with shortness of breath and 16.3% with palpitations. All patients were admitted to the intensive care unit, and 86.6% needed intubation. Patients developed myocardial injury, confirmed with highly elevated troponin (34.6 [14.4-55.5 ng/mL]), and pro-B-type natriuretic peptide concentrations (209 [184-246 pg/mL]). In addition, all patients developed left ventricular dysfunction demonstrated by an echocardiogram with a mean left ventricular ejection fraction of 37.67±6.4. Unfortunately, 2 patients who presented with palpitations died a few days after admission. CONCLUSION: Our study showed coronavirus disease 2019 induced myocardial injury and left ventricular dysfunction in pregnant women with a 13.3% mortality rate, which was attributed to malignant arrhythmias.

Incidence, Predictors, and Prognosis of Acute Kidney Injury Among Cardiac Arrest Survivors.

BACKGROUND: Acute kidney injury (AKI) is common among cardiac arrest survivors. However, the outcomes and predictors are not well studied. METHODS: This is a cohort study of cardiac arrest patients enrolled from January 2012 to December 2016 who were able to survive for 24 hours post-cardiopulmonary resuscitation. Patients with anuria, chronic kidney disease (stage 5), and end-stage renal disease were excluded. Acute kidney injury (stage 1) or higher was defined using Kidney Disease: Improving Global Outcomes classification. Multivariable adjusted regression models were used to compute hazard ratio (HR) for association of AKI with risk of mortality and odds ratio (OR) with risk of poor neurological outcomes after adjusting for demographics, comorbidities, and medical therapy. Multivariable logistic regression model was used to compute OR for association of various predictors with AKI. RESULTS: Of 842 cardiac arrest survivors, 588 (69.8%) developed AKI. Among AKI patients, 69.4% died compared with 52.0% among non-AKI patients. In multivariable adjusted Cox proportional hazard model, development of AKI post-cardiac arrest was significantly associated with mortality (HR: 1.35; 95% confidence interval [CI]: 1.07-1.71, P = .01) and poor neurological outcomes defined as cerebral performance category >2 (OR: 2.27; 95% CI: 1.45-3.57, P < .001) and modified Rankin scale >3 (OR: 2.22; 95% CI: 1.43-3.45, P < .001). Postdischarge dialysis was also associated with increased risk of mortality (HR: 2.57; 95% CI: 1.57-4.23, P < .001). Use of vasopressors was strongly associated with development of AKI and continued need for postdischarge dialysis. CONCLUSIONS: Acute kidney injury was associated with increased risk of mortality and poor neurological outcomes. There is need for further studies to prevent AKI in cardiac arrest survivors.

Community pharmacist prescribing of antimicrobials: A systematic review from an antimicrobial stewardship perspective.

BACKGROUND: Pharmacist prescribing authority is expanding, while antimicrobial resistance is an increasing global concern. We sought to synthesize the evidence for antimicrobial prescribing by community pharmacists to identify opportunities to advance antimicrobial stewardship in this setting. METHODS: We conducted a systematic review to characterize the existing literature on community pharmacist prescribing of systemic antimicrobials. We searched MEDLINE, EMBASE and International Pharmaceutical Abstracts for English-language articles published between 1999 and June 20, 2019, as well as hand-searched reference lists of included articles and incorporated expert suggestions. RESULTS: Of 3793 articles identified, 14 met inclusion criteria. Pharmacists are most often prescribing for uncomplicated urinary tract infection (UTI), acute pharyngitis and cold sores using independent and supplementary prescribing models. This was associated with high rates of clinical improvement (4 studies), low rates of retreatment and adverse effects (3 studies) and decreased health care utilization (7 studies). Patients were highly satisfied (8 studies) and accessed care sooner or more easily (7 studies). Seven studies incorporated antimicrobial stewardship into study design, and there was overlap between study outcomes and those relevant to outpatient antimicrobial stewardship. Pharmacist intervention reduced unnecessary prescribing for acute pharyngitis (2 studies) and increased the appropriateness of prescribing for UTI (3 studies). CONCLUSION: There is growing evidence to support the role of community pharmacists in antimicrobial prescribing. Future research should explore additional opportunities for pharmacist antimicrobial prescribing and ways to further integrate advanced antimicrobial stewardship strategies in the community setting. Can Pharm J (Ott) 2021;154:xx-xx.

Association of genotype III of dengue virus serotype 3 with disease outbreak in Eastern Sudan, 2019.

BACKGROUND: Dengue fever (DF) is an arthropod-borne disease caused by dengue virus (DENV). DENV is a member of the genus Flavivirus in the family Flaviviridae. Recently, DENV has been reported as an important emerging infectious viral pathogen in Sudan. Multiple outbreaks and sporadic cases of DF have been frequently reported in the eastern region of Sudan. The present study was conducted to confirm DENV outbreak in Kassala State, eastern Sudan, 2019, and to provide some information on the molecular characterization of the DENV isolate associated with the disease outbreak. METHODS: A hundred serum samples were collected during the outbreak from residents of Kassala State, Sudan, 2019. ELISA was used to detect DENV non structural protein NS1 (DENV-NS1) in acute phase sera sampled during the disease outbreak. RT-PCR assays were used to amplify a fragment of the capsid/pre-membrane region (CprM) of the viral polyprotein gene. The PCR products of the amplified CprM region of the viral polyprotein gene were purified and partial sequences were generated and used to confirm the specificity of DENV sequences and to identify the virus serotype. Phylogenetic tree was constructed to determine the genotype of DENV associated with the outbreak. RESULTS: Using DENV-NS1 ELISA assay, DENV infection was confirmed in 23% sampled sera. The detection of DENV RNA was made possible using group-specific RT-PCR assay. The virus was serotyped as DENV serotype 3 (DENV-3) using DENV serotype-specific RT-PCR assay. Phylogenetic analysis of the partial CprM sequences of the viral polyprotein gene indicates that the virus belonged to genotype III of DENV-3. CONCLUSION: The scientific data presented in this investigation confirmed that genotype III of DENV-3 was associated with the disease outbreak in eastern Sudan, 2019. The study represents the first report on molecular characterization of DENV-3 in Sudan.

Recent transmission of dengue virus and associated risk Facors among residents of Kassala state, eastern Sudan.

BACKGROUND: Acute arboviral infections are distributed worldwide including Sudan, and dengue fever (DENV) is not an exception. The virus activity has recently been frequently reported in Kassala State, eastern Sudan. However, an appropriate epidemiological study would be necessary to provide accurate and precise estimates of the magnitude of recent DENV transmission in this area of endemicity. METHODS: In the present investigation, a cross sectional study was conducted to advance beyond the current knowledge of the epidemiology of the disease in Kassala State. The prevalence of the disease was estimated and associated risk factors were determined. Sampled sera were collected and screened for recent dengue transmissionas as determined by DENV-IgM enzyme-linked immunosorbent assay (ELISA). The collection of data for risk assessment was supported by a well designed structured questionnaire. RESULTS: The prevalence of recent DENV infection was estimated to be (11.42%). Potential risk factors to DENV seropsitivity include, age (OR = 3.24, CI = 1.81-5.77,p-value = 0.001); low income (OR = 3.75, CI = 1.57-8.93, p-value = 0.027); mosquito control (OR = 4.18, CI = 2.33-7.51, p-value = 0.004); and localities. CONCLUSION: The present study showed a high rate of circulating DENV IgM antibodies among the participants of the study (11.42%), suggesting recent transmission of DENV in Kassala State, eastern Sudan. The frequent occurrence of DENV infections necessitates the need for improved surveillance programs and prevention measures to combat this important arboviral disease in Sudan.

Autonomic dysfunction following traumatic brain injury: translational insights.

Although there is a substantial amount of research on the neurological consequences of traumatic brain injury (TBI), there is a knowledge gap regarding the relationship between TBI and the pathophysiology of organ system dysfunction and autonomic dysregulation. In particular, the mechanisms or incidences of renal or cardiac complications after TBI are mostly unknown. Autonomic dysfunction following TBI exacerbates secondary injury and may contribute to nonneurologial complications that prolong hospital length of stay. Gaining insights into the mechanisms of autonomic dysfunction can guide advancements in monitoring and treatment paradigms to improve acute survival and long-term prognosis of TBI patients. In this paper, the authors will review the literature on autonomic dysfunction after TBI and possible mechanisms of paroxysmal sympathetic hyperactivity. Specifically, they will discuss the link among the brain, heart, and kidneys and review data to direct future research on and interventions for TBI-induced autonomic dysfunction.

Incremental prognostic value of SPECT-MPI in chronic kidney disease: A reclassification analysis.

BACKGROUND: Traditional cardiovascular (CV) risk factors have limited predictive value of CV mortality in patients with chronic kidney disease (CKD, creatinine clearance less than 60 mL/minute per 1.73 m2). The aim of this study was to evaluate incremental and independent prognostic value of single-photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) across continuum of renal function. METHODS: We retrospectively studied 11,518 (mean age, 65 ± 12 years; 52% were men) patients referred for a clinical indication of SPECT-MPI between April 2004 and May 2009. Primary end point was composite of cardiac death and non-fatal myocardial infarction (CD/MI). We examined the relationship of total perfusion defect (TPD) and CD/MI in multiple Cox regression models for CV risk factors and GFR. The incremental predictive value of TPD was examined using Harrell's c-index, net reclassification index (NRI), and integrated discrimination index (IDI). RESULTS: Over a median follow-up of 5 years (25th to 75th percentiles, 3.0-6.5 years), 1,692 (14.5%) patients experienced CD/MI (740 MI and 1,182 CD). In a multivariable model adjusted for traditional CV risk factors and GFR, the presence of a perfusion defect was independently associated with increased risk of CD/MI (HR = 2.10; 95% CI 1.81, 2.43, p < .001). Using Cox regression, TPD improved the discriminatory ability beyond traditional CV risk factors and GFR [from AUC = 0.725, (95% CI 0.712-0.738) to 0.784, (95% CI 0.772-0.796), p < .0001]. Furthermore, TPD improves risk stratification of CKD patients over and above traditional CV risk factors and GFR [NRI = 14%, 95% CI (12%-16%, p < .001) and relative IDI = 60%, 95% CI (51%, 66%, p < .001)]. CONCLUSIONS: Across the spectrum of renal function, SPECT-MPI perfusion defects independently and incrementally reclassified patients for their risk of CD/MI, beyond traditional CV risk factors.

Prevalence of dengue fever virus antibodies and associated risk factors among residents of El-Gadarif state, Sudan.

BACKGROUND: Dengue fever, caused by dengue virus (DENV), has become one of the most important mosquito-borne viral diseases with a steady rise in global incidence, including the Sudan. Sporadic cases and frequent acute febrile illness outbreaks, compatible with Dengue fever, have been reported in El-Gadarif State, Sudan. However, diagnosis was based almost exclusively on clinical signs without confirmatory laboratory investigations. Despite the magnitude of the problem in El-Gadarif State, no information is currently available with regard to the epidemiology of the disease in this State. El-Gadarif State is one of the largest commercial centers in the Sudan. The objective of the present investigation is to estimate the prevalence of DENV antibodies, and determine the potential risk factors associated with seropositivity among residents of El-Gadarif State. METHODS: A cross sectional study was conducted in a total of 701residents randomly selected from all 10 localities in El-Gadarif State. The sera from the 701 residents were tested for the presence of DENV-specific immunoglobulin G (IgG) antibodies using a commercially available Anti-dengue IgG enzyme-linked immunosorbent assay (ELISA). RESULTS: Among the 701 residents, 334 residents (47.6%) were seropositive for DENV. Mosquito control (OR = 2.73, CI = 1.37-5.87, p-value = 0.001); low income (OR = 2.31, CI: 1.71-6.36, p value = 0.032); sleeping out-doors (OR = 3.73, CI = 2.63-6.23, p-value = 0.013), and localities were determined as potential risk factors for contracting DENV infection. CONCLUSIONS: The prevalence rate of DENV antibodies among residents of El-Gadarif State is significantly high (47.6%). Further epidemiologic studies including, distribution of mosquito vectors and implementation of improved surveillance are urgently warranted for better prediction and prevention of a possible DENV outbreak in El-Gadarif State, Sudan.

Prognostic value of extracardiac incidental findings on attenuation correction cardiac computed tomography.

BACKGROUND: Attenuation corrected computed tomography (CTAC) is often performed to improve the specificity of single-photon emission tomography imaging. Extracardiac incidental findings are frequently observed. It is unclear whether these findings have any prognostic value. METHODS: Consecutive patients (n = 1139) at a tertiary care center were retrospectively evaluated for incidental findings on CTAC. Clinically significant incidental findings were defined as findings warranting physician follow-up. Information regarding subsequent resource utilization was obtained by chart review. Cox proportional hazard model adjusted for demographic and clinical variables was used to evaluate association of these incidental findings with all-cause and cancer-specific mortality. RESULTS: A total of 135 (12%) patients with incidental findings were identified, 83 of whom (68%) were newly diagnosed. Lung nodules were the most common finding, present in 92 (68%) patients. Over a median follow-up of 468 days, incidental findings were not significantly associated with increased risk of all-cause mortality (HR 1.34; 95% CI 0.77-2.33, P = 0.29) but was significantly associated with cancer-specific mortality (HR 3.21; 95% CI 1.26-8.14, P = 0.01). This association remained statistically significant when the analysis was limited to newly diagnosed incidental findings. Among patients with incidental findings, follow-up radiographic studies were conducted in 87%, and invasive procedures performed in 32%. Physician office-based follow-up of these findings occurred in 42% of patients and incidental finding-related hospitalization occurred in 14%. CONCLUSIONS: This study shows that incidental findings are common and were associated with all-cause and cancer-specific mortality but only the later remained statistically significant after multivariable adjustment.

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.

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.

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-day-old chicks from the same line were used as recipients for a 60-day 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.