Search

Silvia Moga,1,2 Andreea Teodorescu,1,2 Petru Ifteni,1,2 Paula-Simina Petric,1,2 Ana-Aliana Miron1,2 1Transilvania University of Brasov, Brasov, Romania; 2Spitalul Clinic de Psihiatrie si Neurologie Brasov, Brasov, RomaniaCorrespondence: Petru Ifteni, Transilvania University of Brasov, Brasov, Romania, Tel +40 (724) 993329, Email petru_ifteni@yahoo.com Paula-Simina Petric, Spitalul Clinic de Psihiatrie si Neurologie Brasov, Brasov, Romania, Tel +40 (747) 629883, Email paula_petric@yahoo.comBackground: Clozapine (CLZ) is used for treatment-resistant schizophrenia (TRS). Adverse reactions to clozapine include neutropenia. In March 2020, WHO declared the COVID-19 pandemic and after, psychiatrists raised concerns regarding continuation of clozapine, due to multiple restrictions. We aimed to provide a study on the association between neutropenia and clozapine in patients with schizophrenia and COVID-19.Aim: To assess the neutrophil count in patients with schizophrenia treated with clozapine and infected with COVID-19.Methods: The study patients with schizophrenia, according to DSM-5, admitted to the Clinical Hospital of Psychiatry and Neurology Brasov, Romania, between April 2020 and October 2021. The inclusion criteria included positive RT-PCR (real-time PCR) test for COVID-19 and treatment with clozapine. We assessed three values of ANC (absolute neutrophil count): before COVID-19 infection (last ANC obtained at mandatory check), during infection and 1 month after resolution (first negative PCR test).Results: Of the 105 cases, 95 did not have neutropenia. Fifty-nine patients were males (62.1%), mean age was 43.5 years (SD = 12.1) with an average of clozapine treatment of 52.4 months (SD = 11.9). At baseline, they had a small reduction in the ANC mean value (4.41 × 109/l; SD = 2.22) which did not constitute a statistically significant decline from the prior to COVID-19 mean value of 4.66 × 109/l (SD = 2.34; p = 0.45). Values were also normal in the first month after negative PCR testing (4.45 × 109/l; SD = 2.35; p = 0.91). A total of 10 patients (9.5%) had neutropenia. The age, dose of clozapine and duration of treatment were not statistically different compared to the group without neutropenia.Conclusion: Psychiatrists and other health professionals should keep in mind that neutrophil count may decrease during COVID-19 infection in patients taking clozapine and in some cases, neutropenia may even occur. We assumed that neutropenia could be caused by COVID-19 and clozapine interaction.Keywords: clozapine, SARS-CoV-2, schizophrenia, agranulocytosis, neutropenia

Silvia Moga, Andreea Teodorescu, Petru Ifteni, Claudia Gavris, Paula-Simina Petric Faculty of Medicine, Transilvania University of Brasov, Brasov, RomaniaCorrespondence: Petru IfteniFaculty of Medicine, Transilvania University of Brasov, Romania, 29th Eroilor Boulevard, Brasov, 500036, RomaniaTel +40 724 993329Email petru_ifteni@yahoo.comBackground: Schizophrenia patients are a population at particular risk of poor outcomes in COVID-19 infection. They have multiple comorbidities that have been identified as risk factors for severe COVID-19: diabetes, hypertension, chronic obstructive respiratory disease, and end-stage renal disease.Aim: The aim of this research was to evaluate the inflammatory response and in-hospital mortality in schizophrenia patients compared to a control group without mental illness.Methods: A total of 101 consecutive individuals with schizophrenia tested positive for COVID-19 was compared with 101 individuals without schizophrenia admitted in the same hospital. The number of severe cases and the number of deaths caused by SARS-CoV-2 were evaluated between April 2020 and April 2021.Results: There were no deaths in the group of patients with schizophrenia. Although the group had a higher number of cases with pulmonary and metabolic comorbidities, in the group with SCZ there were fewer severe cases compared to the control group. The values of some markers of inflammation (CRP and fibrinogen) were significantly lower in SCZ patients. The duration from infection to diagnosis and the start of symptomatic treatment was shorter for the group with SCZ (4.2± 3.2 vs 5.3± 4.6, p < 0.05).Conclusion: The main findings of the study were that vulnerable schizophrenia individuals on antipsychotic treatment showed a lower risk of SARS-CoV-2 severe infection and a likely better COVID-19 prognosis in a protective environment. Rapid access to specialists in case of need are factors that have determined the favorable evolution in a group considered high risk. It could be speculated that antipsychotics could play an important role in preventing SARS-CoV-2 severe manifestation and may exert protective effects against detrimental courses of COVID-19.Keywords: schizophrenia, COVID-19, inflammation, antipsychotics

This paper presents the MPI parallelization of a new algorithm--DPD-B thermostat--for molecular dynamics simulations. The presented results are using Martini Coarse Grained Water System. It should be taken into account that molecular dynamics simulations are time consuming. In some cases the running time varies from days to weeks and even months. Therefore, parallelization is one solution for reducing the execution time. The paper describes the new algorithm, the main characteristics of the MPI parallelization of the new algorithm, and the simulation performances. [ABSTRACT FROM AUTHOR]

This paper proposes a neural architecture for a robot in order to learn how to imitate a sequence ofmovements performed by another robot or by a human. The main idea is that the imitation process does not need to be given to the system but can emerge from a misinterpretation ofthe perceived situation at the level of a simple sensory-motor system. The robot controller is based on a Perception-Action (PerAc) architecture. This architecture allows an autonomous robot to learn by itself sensory-motor associations with a delayed reward. Here, we show how the same architecture can also be used by a ''student'' robot to learn to imitate another robot, allowing the student robot to discover by itselfsolutions to a particular problem or to learn from another robot what to do. We discuss the difficulty linked to the segmentation ofthe actions to imitate. This imitation problem is demonstrated by a task oflearning a sequence ofmovements and their precise timing. Another interesting aspect ofthis work is that the neural network (NN) used for sequence learning is directly inspired from a brain structure named the hippocampus and mainly involved in memory processes (Banquetet al., 1997). We discuss the importance of imitation processes for the understanding of our high-level cognitive abilities linked to self-recognition and to the recognition ofthe other as something similar to me. [ABSTRACT FROM AUTHOR]

This paper is an overview of the recent literature regarding the cerebral abnormalities determined by congenital CMV infection and their detection by ultrasound examination. Ultrasound may detect cerebral abnormalities in fetuses with presumed or confirmed congenital CMV infection, although these findings are not always so obvious and are not specifically for CMV infection. [Extracted from the article]

The interest in the unique properties associated with materials having structures on a nanometer scale has been increasing at an exponential rate in last decade. Transition metal oxides are preferred materials for catalytic applications due to their half-filled d orbitals that make them exist in different oxidation states. Transition metal oxides show a broad structural variety due to their ability to form phases of varying metal to oxygen ratios reflecting multiple stable oxidation states of the metal ions. The Solar Physical Vapor Deposition (SPVD) presented in the paper as elaboration method is an original process to prepare nanopowders working under concentrated sunlight in 2 kW solar furnaces. The influence of the synthesis parameters on the chemical and microstructural characteristics of zinc and manganese oxides synthesized nanophases has been systematically studied using XRD, SEM and EDX.

The SONAR images are perturbed by speckle noise. The use of speckle reduction filters is necessary to optimize the image exploitation procedures. This paper presents a new denoising method in the wavelet domain, which tends to reduce the speckle, preserving the structural features and textural information of the scene. Shift-invariance associated with good directional selectivity is important for the use of a wavelet transform (WT) in many fields of image processing. Generally, complex wavelet transforms, for example, the Double Tree Complex Wavelet Transform (DT-CWT) have these useful properties. In this paper, we propose the use of the DT-CWT in association with Maximum A Posteriori (MAP) filters. Such systems carry out different quality denoising in regions with different homogeneity degree. We propose a solution for the reduction of this unwanted effect based on diversity enhancement. The corresponding denoising algorithm is simple and fast. Some simulation results prove the performance obtained.

Objectives: To assess tuberculosis (TB) and associated factors among patients with presumptive TB with chronic kidney disease (CKD)., Methods: A prospective cross-sectional study was conducted from January to December 2023 among 381 patients with CKD attending six hospitals found in five regions of Ethiopia. Sputum and urine specimens were collected and examined for TB using smear microscopy, culture, and Xpert MTB/RIF Ultra assay. Data were analyzed using SPSS version 27. Descriptive statistics and logistic regression models were executed., Results: More than half (206, 54.1%) were male, with a mean age of 45.08 years. A total of 94.0% (358) were pre-dialysis patients with CKD, and 90% (343) had additional comorbidity. TB was detected in 12.9% (49), with 10.5% (40) bacteriologically confirmed and 2.4% (9) clinically diagnosed TB. Previous or current cigarette smoking (adjusted odds ratio [aOR]; 2.82), decreased appetite (aOR; 5.97), night sweats (aOR; 2.21), diabetes comorbidity (aOR; 3.01), positive dipstick albuminuria (aOR; 5.55), less than 1-year follow-up in the renal unit (aOR; 9.49), body mass index <18.5 kg/m 2 (aOR; 6.69), and hemodialysis (aOR; 4.41) were all associated with TB., Conclusions: TB is a substantial cause of morbidity among patients with CKD in Ethiopia, necessitating programmatic intervention. Thus, active TB screening and surveillance among patients with CKD in Ethiopia is important., Competing Interests: The authors have no competing interests to declare., (© 2024 The Author(s).)

Globally, drug-resistant tuberculosis (DR-TB) is responsible for 13% of mortality attributable to antimicrobial resistance. In Ethiopia, extrapulmonary tuberculosis (EPTB) is a significant public health challenge, and drug resistance (DR) in EPTB is often overlooked. In a cross-sectional study conducted between August 2022 and October 2023, we aimed to explore the magnitude of phenotypic drug resistance and identify genetic mutations linked to resistance using 189 Mycobacterium tuberculosis (MTB) isolates cultured from extrapulmonary clinical specimens. Additionally, we assessed the agreement of the phenotypic and whole genome sequencing (WGS) based genotypic drug resistance detection. We performed phenotypic drug sensitivity testing (pDST) using liquid culture BD BACTECTM MGITTM 960 system and WGS using Illumina NextSeq500/550. The genomic data analysis pipelines MTBSeq and TBProfiler were used to predict drug resistance-conferring mutations. The agreement between the pDST and WGS was analyzed using SPSS version 29.0 software. Our result demonstrated phenotypic resistance to at least one anti-TB drug was detected in 16.9% (32/189) of the study participants. Isoniazid-resistant rifampicin-susceptible-TB (Hr-TB) and multi-drug-resistant TB (MDR-TB) phenotypes accounted for 2.6% (5/189) and 4.2% (8/189) respectively. Prevalence of MDR-TB was 2.4% (4/170) among newly diagnosed and 21.1% (4/19) among previously treated cases. WGS identified more (14/160, 8.75%) rifampicin-resistant genotypes (RR-TB) compared to pDST (8/189, 4.2%). We have identified a putative compensatory mutation for rifampicin (rpoBSer450Leu, rpoCAsp747Ala) for the first time from an EPTB clinical specimen in Ethiopia. Overall, there was a 3.75% rifampicin mono-resistant-TB(RMR-TB) genotype, which remains undetected using the conventional pDST and represented 42.9% (6/14) of the identified RR-TB genotypes. Mutations conferring rifampicin resistance-interim (rpoB.Ser450Ala) represented the majority (83.3%) of RMR-TB. Changes in ethA genes associated with ethionamide resistance were the most common resistance (n=7, 87.5%) in MDR-TB cases. There was a strong agreement between the pDST and WGS-TB Profiler pipeline to detect RR-TB (kappa=0.8) compared to the MTBSeq pipeline (k=0.58). In conclusion, MDR-TB, Hr-TB, and interim-RMR-TB are equally important public health challenges in the realm of EPTB in Ethiopia. The role of WGS is tremendous in detecting borderline/interim RMR-TB, which will help for tailored, personalized treatment strategies.

Introduction: The TriAD study will assess the Xpert MTB/XDR (Xpert XDR; Cepheid) assay to detect tuberculosis (TB) drug resistance in sputum testing positive for TB to rapidly triage and treat patients with a short all-oral treatment regimen., Methods and Analysis: In this study, approximately 4800 Xpert MTB/RIF or Ultra MTB-positive patients (irrespective of rifampicin (RIF) resistance (RR) status) from several clinical sites across South Africa, Nigeria and Ethiopia will be enrolled over 18-24 months and followed-up for approximately 6 months post-TB treatment completion. Participants will be enrolled into one of two cohorts based on Xpert MTB/RIF and Xpert XDR results: Mycobacterium tuberculosis ( M.tb ) positive participants with RR in Cohort 1 (n=880) and M.tb positive RIF susceptible TB patients with isoniazid mono-resistance irrespective of presence of resistance to fluoroquinolones, second-line injectable drugs or ethionamide in Cohort 2 (n=400). Cohort 1 will be compared with historical cohorts from each implementing sites. The primary study outcomes include time to initiation of an appropriate treatment regimen by resistance profile and the proportion of patients with favourable treatment outcomes compared with historical cohorts from each of the implementing sites. Secondary outcomes include feasibility, acceptability and cost-effectiveness of this approach to inform policies and guidelines for programmatic implementation of this triage and treat model for drug-resistant tuberculosis management. Utility of the tuberculosis molecular bacterial load assay (TB-MBLA) for real-time treatment response assessment will also be evaluated., Ethics and Dissemination: The University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC) and local research committees have provided ethical review and approval (BREC/00002654/2021, HREC 210805, NHREC/01/01/2007 and EPHI-IRB-459-2022). The South African Health Products Regulatory Authority (SAHPRA) have granted regulatory approval for the TRiAD Study (SAHPRA MD20211001). Trial results will be disseminated through conference presentations, peer-reviewed publications and the clinical trial registry., Trial Registration Number: Clinicaltrials.gov; Trial registration number: NCT05175794; South African National Clinical Trials Register (SANCTR DOH-27-012022-4720)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Bedaquiline (BDQ) is an effective drug currently used for multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB) and pre-extensively drug-resistant TB (pre-XDR-TB) treatment. However, resistance to this new drug is emerging. We discussed the characteristics of the first patient in Ethiopia who acquired BDQ and fluoroquinolones (FQs) resistance during treatment follow-up., Case Report: In this case report, we present the case of a 28-year-old male pulmonary TB patient diagnosed with MDR-TB who is a resident of the Oromia Region of North Shewa, Mulona Sululta Woreda, Ethiopia. Sputum specimen was collected initially and for treatment monitoring using culture and for phenotypic drug susceptibility testing (DST) to first-line and second-line TB drugs. Initially, the patient was infected with a mycobacterial strain resistant to the first-line anti-TB drugs Rifampicin (RIF), Isoniazid (INH), and Pyrazinamide (PZA). Later, during treatment, he acquired additional drug resistance to ethambutol (EMB), ofloxacin (OFX), levofloxacin (LFX), moxifloxacin (MFX), and BDQ. The patient was tested with MTBDR plus and MTBDR sl to confirm the presence of resistance-conferring mutation and mutation was detected in rpoB, katG, and gyrA genes. Finally, the patient was registered as having extensively drug-resistant tuberculosis (XDR-TB) and immediately started an individualized treatment regimen., Conclusion: This case report data has revealed the evolution of BDQ resistance during treatment with a BDQ-containing regimen in Ethiopia. Therefore, there is a need for DST to new second-line drugs to monitor and prevent the spread of DR-TB., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: There is a global gap between tuberculosis incident cases and the notified cases. Active household contact investigation is one of the strategies to narrow this gap. It has the advantage of giving early diagnosis and preventive treatment to vulnerable and eligible groups. This study assessed the practice of contact investigation and tuberculosis preventive treatment adherence in central Ethiopia., Method: A cross-sectional study covering all registered bacteriologically confirmed pulmonary tuberculosis patients and their close contacts was conducted in central Ethiopia from January 1, 2022, to December 30, 2022., Result: A total of 1372 household contacts were declared by the index cases. From these 79.44 % (1090) contacts received a one-time tuberculosis screening giving a total of four (0.36 %) active TB cases. Among 484 household contacts of drug-resistant tuberculosis index cases, 5.53 % (14) had presumptive tuberculosis and 0.79 % (2) had active tuberculosis. While among 837 household contacts of drug-susceptible tuberculosis index cases presumptive TB cases were 1.91 % (16) and active TB cases were 0.23 % (2). Of the 142 eligible under 15 children 81.69 % (116) had started tuberculosis preventive treatment and 84.48 % (98) completed the treatment. On multivariable logistic regression, the associated factor for tuberculosis preventive treatment non-adherence was age 2-5 years (aOR, 0.02, 95 % CI (0.002-0.20) and age 5-15 years (aOR, 0.04,95 % CI (0.002-0 0.95)) P=<0.05)., Conclusion: There was low contact screening practice in the DR-TB index cases as compared to national and global targets. The yield of routine contact investigation was low and it indicates the quality of screening. Tuberculosis preventive treatment initiation and completion rates were also low as compared to those of many other countries and global achievements which need further improvement, especially for completion. Alternative mechanisms should be planned to increase the yield of tuberculosis screening and tuberculosis preventive treatment adherence., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The Mycobacterium tuberculosis complex (MTBC) includes several human- and animal-adapted pathogens. It is thought to have originated in East Africa from a recombinogenic Mycobacterium canettii-like ancestral pool. Here, we describe the discovery of a clinical tuberculosis strain isolated in Ethiopia that shares archetypal phenotypic and genomic features of M. canettii strains, but represents a phylogenetic branch much closer to the MTBC clade than to the M. canettii strains. Analysis of genomic traces of horizontal gene transfer in this isolate and previously identified M. canettii strains indicates a persistent albeit decreased recombinogenic lifestyle near the emergence of the MTBC. Our findings support that the MTBC emergence from its putative free-living M. canettii-like progenitor is evolutionarily very recent, and suggest the existence of a continuum of further extant derivatives from ancestral stages, close to the root of the MTBC, along the Great Rift Valley., (© 2023. The Author(s).)

CD34 has spear-headed the field of basic research and clinical transplantation since the first reports of its expression on hematopoietic stem cells (HSCs). Expressed in mice, humans, rats and other species, CD34 has been used for more than 40 years as a hematopoietic stem and progenitor cell marker. It was later found that muscle satellite cells and epidermal precursors can also be identified with the aid of CD34. Despite the usefulness of CD34 as a marker of HSCs, its overall purpose in animal physiology has remained unclear. This review recaptures CD34 structure, evolutionary conservation, proposed functions, and role in lung inflammation, to describe current research findings and to provide guidance for future studies on CD34., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To date, isoniazid mono-resistant tuberculosis (TB) is becoming an emerging global public health problem. It is associated with poor treatment outcome. Different studies have assessed the treatment outcome of isoniazid mono-resistant TB cases, however, the findings are inconsistent and there is limited global comprehensive report. Thus, this study aimed to assess the poor treatment outcome and its associated risk factors among patients with isoniazid mono-resistant TB., Methods: Studies that reported the treatment outcomes and associated factors among isoniazid mono-resistant TB were searched from electronic databases and other sources. We used Joana Briggs Institute critical appraisal tool to assess the study's quality. We assessed publication bias through visual inspection of the funnel plot and confirmed by Egger's regression test. We used STATA version 17 for statistical analysis., Results: Among 347 studies identified from the whole search, data were extracted from 25 studies reported from 47 countries. The pooled successful and poor treatment outcomes were 78% (95%CI; 74%-83%) and 22% (95%CI; 17%-26%), respectively. Specifically, complete, cure, treatment failure, mortality, loss to follow-up and relapse rates were 34%(95%CI; 17%-52%), 62% (95%CI; 50%-73%), 5% (95%CI; 3%-7%), 6% (95%CI; 4%-8%), 12% (95%CI; 8%-17%), and 1.7% (95%CI; 0.4%-3.1%), respectively. Higher prevalence of pooled poor treatment outcome was found in the South East Asian Region (estimate; 40%, 95%C; 34%-45%), and African Region (estimate; 33%, 95%CI; 24%-42%). Previous TB treatment (OR; 1.74, 95%CI; 1.15-2.33), having cancer (OR; 3.53, 95%CI; 1.43-5.62), and being initially smear positive (OR; 1.26, 95%CI; 1.08-1.43) were associated with poor treatment outcome. While those patients who took rifampicin in the continuation phase (OR; 0.22, 95%CI; 0.04-0.41), had extrapulmonary TB (OR; 0.70, 95%CI; 0.55-0.85), and took second-line injectable drugs (OR; 0.54, 95%CI; 0.33-0.75) had reduced risk of poor treatment outcome., Conclusion: Isoniazid mono-resistant TB patients had high poor treatment outcome. Thus, determination of isoniazid resistance pattern for all bacteriologically confirmed TB cases is critical for successful treatment outcome. PROSPERO registration number: CRD42022372367., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Alemu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To estimate the pooled proportion of extensively drug-resistant tuberculosis (XDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) in patients with multidrug-resistant TB (MDR-TB)., Methods: We systematically searched articles from electronic databases: MEDLINE (PubMed), ScienceDirect, and Google Scholar. We also searched gray literature from the different literature sources main outcome of the review was either XDR-TB or pre-XDR-TB in patients with MDR-TB. We used the random-effects model, considering the substantial heterogeneity among studies. Heterogeneity was assessed by subgroup analyses. STATA version 14 was used for analysis., Results: A total of 64 studies that reported on 12,711 patients with MDR-TB from 22 countries were retrieved. The pooled proportion of pre-XDR-TB was 26% (95% confidence interval [CI]: 22-31%), whereas XDR-TB in MDR-TB cases was 9% (95% CI: 7-11%) in patients treated for MDR-TB. The pooled proportion of resistance to fluoroquinolones was 27% (95% CI: 22-33%) and second-line injectable drugs was 11% (95% CI: 9-13%). Whereas the pooled resistance proportions to bedaquiline, clofazimine, delamanid, and linezolid were 5% (95% CI: 1-8%), 4% (95% CI: 0-10%), 5% (95% CI; 2-8%), and 4% (95% CI: 2-10%), respectively., Conclusion: The burden of pre-XDR-TB and XDR-TB in MDR-TB were considerable. The high burdens of pre-XDR-TB and XDR-TB in patients treated for MDR-TB suggests the need to strengthen TB programs and drug resistance surveillance., Competing Interests: Declaration of competing interests The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To estimate the prevalence of latent tuberculosis infection (LTBI) in chronic kidney disease (CKD) patients ., Methods: This study was conducted following the PRISMA guidelines. We identified, 3694 studies from the whole search, and 59 studies were included. Each study's quality was assessed using JBI checklist. We employed STATA version 17 for statistical analysis. We assessed heterogeneity using I 2 heterogeneity test. Publication bias was assessed using funnel plot and Egger's test. We estimated the pooled LTBI prevalence in CKD patients along with 95%CI., Results: The pooled prevalence of LTBI among CKD patients using data collected from 53 studies having 12,772 patients was 30.2% (95%CI; 25.5, 34.8). The pooled prevalence among pre-dialysis, hemodialysis, peritoneal dialysis, and renal transplanted patients was 17.8% (95%CI; 3.3, 32.4), 34.8% (95%CI; 29.1, 40.5), 25% (95%CI; 11, 38), and 16% (95%CI; 7, 25), respectively. The pooled prevalence of LTBI stratified by the laboratory screening methods was 25.3% (95%CI: 20.3-30.3) using TST, 28.0% (95%CI; 23.9-32.0) using QFT, and 32.6%, (95%CI: 23.7-41.5) using T-SPOT., Conclusion: There is high prevalence of LTBI among CKD patients mainly in patients on dialysis. Thus, early diagnosis and treatment of LTBI in CKD patients should be performed to prevent active TB in CKD patients. PROSPERO registration number: CRD42022372441., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had multiple consequences for the health care system, especially for patients with mental illnesses. Schizophrenia patients particularly appear to have a higher risk of complications due to coronavirus-19 (COVID-19). Clozapine remains the gold standard for treatment-resistant schizophrenia (TRS). However, the COVID-19 pandemic had an important negative impact on clozapine treatment, mainly because of its administration protocol, which was very difficult to follow during the restrictions imposed in the pandemic, and its side effects in patients with COVID-19 infection. Vaccination is an effective method of avoiding SARS-CoV-2 infection or its severe complications, especially in susceptible populations. Data on adverse events after vaccination against COVID-19 are limited, both in the general population and in schizophrenia patients., Study Question: The study aimed to investigate the safety of COVID-19 vaccination in patients treated with clozapine for hematological parameters., Study Design: We conducted an analytical cross-sectional study between July 1, 2021, and June 30, 2022. We compared 2 groups of COVID-19 vaccinated patients who had previously experienced SARS-CoV-2 infection: The first group was treated with clozapine, whereas the second group was treated with other antipsychotics., Measures and Outcomes: The primary objective was to identify granulocytopenia, leukocytopenia, and lymphocytopenia. The results were measured after the second dose of the Pfizer-BioNTech vaccine., Results: This study included 100 patients. White blood cell count changes were limited to a few cases of mild granulocytopenia (8.16% in the clozapine group and 3.92% in the nonclozapine group, P = 0.37) with no cases of severe granulocytopenia or agranulocytosis., Conclusions: As far as leukocyte counts are concerned, mRNA COVID-19 vaccination seems to be safe in patients treated with clozapine who previously had SARS-CoV-2 infection. Leukocyte changes had no clinical implications., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Isoniazid (INH) resistant Mycobacterium tuberculosis (Hr-TB) is the most common type of drug resistant TB, and is defined as M tuberculosis complex (MTBC) strains resistant to INH but susceptible to rifampicin (RIF). Resistance to INH precedes RIF resistance in almost all multidrug resistant TB (MDR-TB) cases, across all MTBC lineages and in all settings. Therefore, early detection of Hr-TB is critical to ensure rapid initiation of appropriate treatment, and to prevent progression to MDR-TB. We assessed the performance of the GenoType MTBDRplus VER 2.0 line probe assay (LPA) in detecting isoniazid resistance among MTBC clinical isolates., Methods: A retrospective study was conducted among M. tuberculosis complex (MTBC) clinical isolates obtained from the third-round Ethiopian national drug resistance survey (DRS) conducted between August 2017 and December 2019. The sensitivity, specificity, positive predictive value, and negative predictive value of the GenoType MTBDRplus VER 2.0 LPA in detecting INH resistance were assessed and compared to phenotypic drug susceptibility testing (DST) using the Mycobacteria Growth Indicator Tube (MGIT) system. Fisher's exact test was performed to compare the performance of LPA between Hr-TB and MDR-TB isolates., Results: A total of 137 MTBC isolates were included, of those 62 were Hr-TB, 35 were MDR-TB and 40 were INH susceptible. The sensitivity of the GenoType MTBDRplus VER 2.0 for detecting INH resistance was 77.4% (95% CI: 65.5-86.2) among Hr-TB isolates and 94.3% (95% CI: 80.4-99.4) among MDR-TB isolates (P = 0.04). The specificity of the GenoType MTBDRplus VER 2.0 for detecting INH resistance was 100% (95% CI: 89.6-100). The katG 315 mutation was observed in 71% (n = 44) of Hr-TB phenotypes and 94.3% (n = 33) of MDR-TB phenotypes. Mutation at position-15 of the inhA promoter region alone was detected in four (6.5%) Hr-TB isolates, and concomitantly with katG 315 mutation in one (2.9%) MDR-TB isolate., Conclusions: GenoType MTBDRplus VER 2.0 LPA demonstrated improved performance in detecting INH resistance among MDR-TB cases compared to Hr-TB cases. The katG315 mutation is the most common INH resistance conferring gene among Hr-TB and MDR-TB isolates. Additional INH resistance conferring mutations should be evaluated to improve the sensitivity of the GenoType MTBDRplus VER 2.0 for the detection of INH resistance among Hr-TB cases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Objective: This study aimed to determine the frequencies and trends of Mycobacterium tuberculosis and rifampicin resistance among presumptive tuberculosis patients in Ethiopia, who were tested using the Xpert MTB/RIF assay between 2014 and 2021., Methods: Data were collected retrospectively from patient registries. Laboratory-based data were extracted from the national tuberculosis (TB) referral laboratory database. All patients referred to the National Tuberculosis Reference Laboratory (NTRL) for TB diagnosis from all over the country between March 1, 2014 and September 30, 2021, and tested using the Xpert MTB/RIF assay, were included. The extracted data were entered into a Microsoft Excel sheet and analyzed by Statistical Package for Social Sciences (SPSS) version 23., Results: Among a total of 13 772 individuals tested using the Xpert MTB/RIF assay, the majority (8223; 59.7%) were males, and 48.5% (6678) of the individuals were aged between 15 and 39 years. Mycobacterium tuberculosis (MTB) was detected in 17.0% (2347) of the examined individuals. Of the detected MTB cases, nearly 9.9% (233) were rifampicin resistant (RR-TB), while 24 (1.0%) were RR-intermediate. Among all RR-TB cases, more than half (125; 53.6%) were detected in males, and 105 were new TB cases. Extrapulmonary (EPTB) patients had a greater rate of rifampicin resistance (11.0%) than pulmonary (PTB) patients (9.6%)., Conclusion: The frequency of TB and RR-TB remains high in the study setting. RR-TB was found to have a statistically significant association with previous anti-TB medication treatment. As a result, improving treatment adherence in recognized instances could assist in preventing MTB and RR-TB cases., (© 2022 The Author(s).)

Background: Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia. Despite its therapeutic benefits, it is still widely underused, mainly because of its potential to cause agranulocytosis and neutropenia. Prescribing clozapine in COVID-19-positive patients became more challenging because of this potential side effect. This article is a review of literature on the risk of neutropenia associated with clozapine treatment in patients with COVID-19., Areas of Uncertainty: In clozapine-treated COVID-19-positive patients, neutropenia was reported in some cases; is it a consequence of clozapine treatment or of SARS-Co2 infection?, Data Sources: Data were extracted from 2 databases: PubMed/MEDLINE and Google Scholar. We selected all original reports, from March 2020 until May 2022, on neutropenia associated with clozapine treatment in positive COVID-19 patients. Eleven studies were selected for the final analysis., Therapeutic Advances: Before the COVID-19 pandemic, neutropenia in clozapine-treated patients was reported in 3.8% of cases. During the pandemic, neutropenia rates seemed to be higher. As per the cause of neutropenia, studies reported contradictory results. We aim to clarify rates and causes of neutropenia in clozapine-treated COVID-19-positive patients., Results: Three hundred eighty-eight articles were initially selected from the 2 databases. After excluding duplicates, unrelated articles, reviews, and guidelines, 11 studies were analyzed, all centered on clozapine treatment, COVID-19 infection, and associated neutropenia., Conclusions: Clozapine treatment in COVID-19-positive patients may be associated with a transient reduction of absolute neutrophils count, in some cases reaching neutropenia levels. Neutropenia rates reported in SARS-CoV-2-infected patients are higher than the prepandemic reports; therefore, we assume that the cause might be a result of the immunological interference between clozapine and SARS-CoV-2. Clozapine treatment needs to be continued whenever possible, with dose adjustments in relation to blood test results., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The rise of drug-resistant tuberculosis (DR-TB) has presented a substantial challenge to the national tuberculosis (TB) control program. Understanding the epidemiology of pre-extensively drug-resistant tuberculosis (pre-XDR-TB) could help clinicians to adapt MDR-TB treatment regimens at an earlier stage. This study aimed to assess second-line anti-TB drug resistance among MDR-TB patients in Ethiopia using routine laboratory-based data., Methods: Laboratory-based cross-sectional data were collected from the national TB reference laboratory and seven regional tuberculosis culture laboratories in Ethiopia from July 2019 to March 2022. The required data, such as drug-susceptibility testing (DST) results and sociodemographics, were collected on a structured checklist from laboratory registration books and electronic databases. Data were entered into a Microsoft Excel spreadsheet and analyzed using SPSS version 23. Descriptive statistics were performed to show the distribution and magnitude of drug resistance., Results: Second-line drugs (SLDs) susceptibility testing was performed for 644 MDR isolates, of which 19 (3%) were found to be pre-XDR-TB cases. Of the total MDR-TB isolates, 19 (3%) were resistant to at least one fluoroquinolone drug, while 11 (1.7%) were resistant to at least one injectable second-line drug. Of the 644 MDR-TB isolates, 1.9% (5/261) pre-XDR were from new MDR-TB cases, while 3.7% (14/383) were from previously treated MDR-TB patients. The most frequently identified mutations, based on MTBDR sl results, were in codon A90V of the gyrA gene (77.3%) and A1401G of the rrs gene (45.5%)., Conclusion: The overall prevalence of pre-XDR-TB in Ethiopia is considerable. The majority of SLD resistance mutations were in the gyrA gene at position A90V . Modern, rapid DST is necessary to enable identification of pre-XDR-TB and XDR-TB in supporting proper regimen administration for patients., (© 2022 The Author(s).)

Introduction: Molecular tests allow rapid detection of Mycobacterium tuberculosis and drug resistance in a few days. Identifying the mutations in genes associated with drug resistance may contribute to the development of appropriate interventions to improve tuberculosis control. So far, there is little information in Ethiopia about the diagnostic performance of line probe assay (LPA) and the M. tuberculosis common gene mutations associated with drug resistance in extrapulmonary tuberculosis. Thus, this study aimed to assess the frequency of drug resistance-associated mutations in patients with extrapulmonary tuberculosis (EPTB) and to compare the agreement and determine the utility of the genotypic in the detection of drug resistance in Addis Ababa, Ethiopia., Methods: A cross-sectional study was conducted on stored M. tuberculosis isolates. The genotypic and phenotypic drug susceptibility tests were performed using LPA and BACTEC-MGIT-960, respectively. The common mutations were noted, and the agreement and the utility of the LPA were determined using the BACTEC-MGIT-960 as a gold standard., Results: Of the 151 isolates, the sensitivity and specificity of MTBDR plus in detecting isoniazid resistance were 90.9% and 100%, respectively. While for rifampicin, it was 100% and 99.3% for sensitivity and specificity, respectively. The katG S315Tl was the most common mutation observed in 85.7% of the isoniazid-resistant isolates. In the case of rifampicin, the most common mutation (61.9%) was observed at position rpoB S531L . Mutations in the gyrA promoter region were strongly associated with Levofloxacin and Moxifloxacin resistance., Conclusion: Line probe assay has high test performance in detecting resistance to anti-TB drugs in EPTB isolates. The MTBDR plus test was slightly less sensitive for the detection of isoniazid resistance as compared to the detection of rifampicin. The most prevalent mutations associated with isoniazid and rifampicin resistance were observed at katG S315Tl and rpoB S531L respectively. Besides, all the fluoroquinolone-resistant cases were associated with gyrA gene. Finally, a validation study with DNA sequencing is recommended., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Rapid and sensitive Tuberculosis (TB) diagnosis closer to patients is a key global TB control priority. Truenat assays (MTB, MTB Plus, and MTB-RIF Dx) are new TB molecular diagnostic tools for the detection of TB and Rifampicin (RIF)-resistance from sputum samples. The diagnostic accuracy of the assays is needed prior to implementation in clinical use in Ethiopia. This study aimed to determine the sensitivity and specificity of Truenat assays; and aimed to compare the assays to the Xpert MTB/RIF assay., Methods: A prospective evaluation study was conducted among 200 presumptive TB patients in microscopy centers in Addis Ababa, Ethiopia from May 2019 to December 2020. Culture (Solid and Liquid methods) and phenotypic (liquid method) drug susceptibility testing (DST) were used as a reference standard., Results: Of 200 adult participants, culture confirmed TB cases were 25 (12.5%), and only one isolate was resistant to RIF by phenotypic DST. The sensitivity of Truenat MTB was 88.0% [95% CI 70.1, 95.8], while 91.7 [95% CI 74.2, 97.7] for Truenat MTB Plus at the microscopy centers. The specificity of Truenat MTB was 97.2% [95% CI 93.1, 98.9], while for Truenat MTB Plus was 97.2% [95% CI 93.0, 99.0]. The sensitivity of Truenat MTB was 90.5% while for MTB Plus, 100% compared to the Xpert MTB/RIF assay., Conclusion: Truenat assays were found to have high diagnostic accuracy. The assays have the potential to be used as a point of care (POC) TB diagnostic tests., Competing Interests: The authors have declared that no competing interests exist.

Background: In Ethiopia, tuberculosis (TB) is one of the most common causes of illness and death. However, there is limited information available on lineages associated with drug resistance among extrapulmonary tuberculosis patients in Ethiopia. In this study, researchers looked into Mycobacterium tuberculosis lineages linked to drug resistance in patients with extrapulmonary tuberculosis in Addis Ababa, Ethiopia., Methods: On 151 Mycobacterium tuberculosis isolates, a cross-sectional analysis was performed. Spoligotyping was used to characterize mycobacterial lineages, while a phenotypic drug susceptibility test was performed to determine the drug resistance pattern. Data were analyzed using SPSS version 23., Results: Among 151 Mycobacterium tuberculosis complex (MTBC) genotyped isolates, four lineages (L1-L4), and Mycobacterium bovis were identified. The predominantly identified lineage was Euro-American (73.5%) followed by East-African-Indian (19.2%). Any drug resistance (RR) and multidrug-resistant (MDR) tuberculosis was identified among 16.2% and 7.2% of the Euro-American lineage, respectively, while it was 30.8% and 15.4% among the East-African-Indian lineages. Among all three preextensively drug-resistance (pre-XDR) cases identified, two isolates belong to T3-ETH, and the other one strain was not defined by the database. There was no statistically significant association between any type of drug resistance and either lineage or sublineages of Mycobacterium tuberculosis ., Conclusion: A higher proportion of any type of drug resistance and MDR was detected among the East-African-Indian lineage compared to others. However, there was no statistically significant association between any type of drug resistance and either lineages or sublineages. Thus, the authors recommend a large-scale study., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Getu Diriba et al.)

This scientific research focused on the production of hydroethanolic extract of the plant species Lycopodium selago L. ( L. selago ) by the ultrasound-assisted extraction (USAE) and the identification of biocompounds with high antioxidant activity is of interest for possible phytotherapeutic treatment against Alzheimer's disease (AD). The extract was phytochemically analyzed to investigate polyphenols, flavonoids, and identify the sesquiterpenoid alkaloid huperzine A (HupA), which is known in the literature for its great relevance in AD. Evaluation and comparison of the antioxidant activity of the extract were performed by four complementary spectrophotometric methods (DPPH, FRAP, ABTS, ORAC). In vitro tests of the extract showed an excellent reciprocal link between the concentration of polyphenols and the measurement of the antioxidant activity of the extract with the sesquiterpenoid HupA. To confirm the antioxidant activity, L. selago hydroethanolic extract was administered in vivo to zebrafish ( Danio rerio) with a pattern of scopolamine-induced cognitive impairment. Moreover, this study explored a possible correlation between the expression of oxidative stress markers in the brain tissue with the behavior of the scopolamine zebrafish model. In vivo tests showed that this fern could be used as a nutritional supply and as a phytotherapeutic method to prevent or treat various neurodegenerative diseases that call for high-nutritive-value medications.

Hericium erinaceus ( H. erinaceus ) is a rare and appreciated fungal species belonging to the division Basidiomycota used for centuries in traditional Chinese medicine for its medicinal value. This species of mushrooms brings the most diverse benefits for the human body, and can have beneficial effects for treating Alzheimer's disease (AD). This study investigated whether ethanolic extract from the fungal biomass of H. erinaceus enhances cognitive function via the action on cholinergic neurons using the scopolamine (SCOP)-induced zebrafish ( Danio rerio ) model of memory impairment. The ethanolic extract from the fungal biomass of H. erinaceus was previously obtained using an ultrasonic extraction method (UE). The administration of H. erinaceus extract to zebrafish, with a pattern of AD induced by scopolamine, showed an improvement in memory evaluated by behavioral and biochemical tests on brain tissue. These results suggest that H. erinaceus has preventive and therapeutic potentials in managing memory deficits and brain oxidative stress in zebrafish with AD.

Background: The Oropharyngeal squamous cell carcinoma is the second most common head and neck malignancy. Bcl-2 expression alterations have been reported invariably in different cancers. It plays a part in carcinogenesis by inhibiting programmed cell death and thus increasing cell survival., Materials and Methods: The present study was conducted in Department of Pathology, S.G.T. Medical College and University, Gurugram over a period of one year (2019-20) on biopsy proven cases of squmaous cell carcinoma of oropharynx. Grading of the tumor was done using Anneroth's multifactorial grading system. The Bcl-2 scoring was done., Results: In the present study, a total of 75 cases of oropharyngeal SCC constituted the study group, with the mean age at presentation of 56.63 years. The correlation between Anneroth's grading system and WHO grade was found to be statistically significant, while correlation between WHO grade with lymph node status was found to be statistically non significant., Conclusion: There was significant correlation between Anneroth's grading system and WHO grading system in SCC of oropharynx and it was found to be more relevant in predicting the stage of tumor. Bcl-2 expression did not correlate with the grading of tumor., Competing Interests: We do not have any conflict of interest., (© 2021 The Authors.)

Hericium erinaceus is a medicinal fungal species that produces the active biological metabolite erinacine A with strong antioxidant activity. The classical extraction techniques used to date to obtain metabolites from this fungal species require high consumption of resources and energy and, in the end, prove to be expensive and inefficient, especially on a biomedical scale. The aim of this research is based on the development of an ultrasonic extraction (UE) method for the identification and extraction of biological compounds with high antioxidant activity from the mycelia of H. erinaceus biomass developed through a solid cultivation process. The extraction process was optimized by varying parameters to determine the best extraction yield of metabolites involved in such antioxidant activity, using the response surface methodology (RSM). The physicochemical analyses were oriented towards the investigation of polyphenols, flavonoids, and the diterpenoid erinacine A. It is highlighted that there is a very good mutual connection between the concentration of polyphenols and flavonoids in the extracts studied and the diterpenoid erinacine A. Also, this study describes an efficient and qualitative extraction method for extracting natural antioxidants from the H. erinaceus mushroom, since toxic solvents were not used in the developed extraction procedure. This biomass can be used both as a food source and as a possible phytotherapeutic tool in the prevention or treatment of various neurodegenerative disorders that require drugs with strong antioxidant activity.