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Introduction: The protective factors against urinary tract infections (UTIs) in the setting of vesicoureteric reflux (VUR) remain poorly defined. Breastfeeding was suggested as a protective factor against UTI, but its role remains undetermined in this highly susceptible population. Objectives: The objective of the study was to identify the pattern and risk factors of UTI and investigate the effect of breastfeeding on UTI occurrence in VUR children. Materials and Methods: This was a mixed-method design, whereby the first part was a cross-sectional study that included children who were diagnosed with VUR and were assessed for their UTI pattern. The second part was a case-control study, which involved contacting the mothers of the children enrolled and questioning them about their breastfeeding pattern, and UTI development was assessed. Results: Our study included 62 children with a median age of 4.4 (interquartile range = 21) months at diagnosis. Of those, 37 (60%) were male and 25 (40%) were female. Most UTIs occurred in the first 3 months of life, and the first episodes were more frequent in males. Constipation was significantly associated with the occurrence of UTI (relative risk [RR] =1.750 [95% confidence interval (CI): 1.231-2.489], P = 0.003). Children with breakthrough UTIs were more likely to have been breastfed for <9 months (odds ratio [OR] = 4.091 [95% CI: 1.287-13.002], P = 0.015) and to have been exclusively breastfed for <2 months (OR = 4.600 [95% CI: 1.337-15.823], P = 0.012). Conclusion: Children with VUR are more susceptible to UTIs in their 1st year of life. Constipation is a major risk factor for UTI occurrence in VUR children and should be aggressively managed. Breastfeeding for longer durations showed promising protective features against breakthrough UTIs.
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BACKGROUND: The incidence of anal cancer, largely associated with anal human papillomavirus (HPV) infection, is increasing among men who have sex with men (MSM), and transgender women living with or without HIV. Screening for anal cancer to detect anal precancerous lesions in high-risk groups is an important opportunity for prevention but still lacking in many low-and-middle-income countries. The aim of this study was to explore the readiness of Pakistan's healthcare system to integrate anal cancer and HPV screening into a national HIV program, as perceived by policymakers, health managers, and healthcare providers. DESIGN: This qualitative study using key-informant interviews with participants influence in policy making, implementation and advocacy from public and private sector were conducted between March 2021 to August 2021 in Karachi Pakistan. METHODS: Key informants were purposely selected from different domains of the healthcare system responsible for the target group of interest, MSM and transgender-women in general and people living with HIV in particular. A total of 18 key informants, at different levels of seniority were recruited from governmental and non-governmental organizations, high-level infectious disease healthcare managers, and United Nations Program representatives. Qualitative content analysis was used to identify the manifest and latent themes, based on socioecological framework. RESULTS: The results were grouped into five major themes; (1) The policy context and priorities, (2) Health systems factors, (3) Community environment, (4) Healthcare setting & providers and (5) Individual-level obstacles. The policy actors expressed their concerns about their limited voice in country's health and health related priority setting. Informants reported a lack of political will and suggested that government should bring a change in the paradigm of healthcare service delivery from reactive to proactive approach. Although, participants unanimously favored integration of HPV preventive services into existing HIV program, they also identified several service delivery barriers including trained workforce shortage, limited capacity of information technology, lack of supplies needed for screening, lack of financing, and lack of services that could meet key-populations needs. Participants also predicted other implementation challenges such as stigma, social victimization, and systemic discrimination against at-risk groups at healthcare facilities. CONCLUSION: Although policy makers and health providers in Pakistan saw a clear need to scale-up and integrate anal cancer screening for key populations, the feasibility of this is dependent on political will, financing, anti-stigma and discrimination interventions and health system efficiency.
Subject(s)
Anus Neoplasms , HIV Infections , Papillomavirus Infections , Sexual and Gender Minorities , Male , Humans , Female , Homosexuality, Male , Human Papillomavirus Viruses , HIV Infections/diagnosis , HIV Infections/prevention & control , HIV Infections/epidemiology , Papillomavirus Infections/complications , Papillomavirus Infections/diagnosis , Papillomavirus Infections/prevention & control , Pakistan , Early Detection of Cancer , Anus Neoplasms/diagnosis , Anus Neoplasms/prevention & controlABSTRACT
Hodgkin's Lymphoma is a cancer affecting the lymphatic system. There are two subtypes of Hodgkin's Lymphoma: Nodular lymphocyte predominant (NLPHL) and classical Hodgkin's Lymphoma which has further four types. It has a bimodal distribution and is more common among males. The most common presentation is painless swelling in the neck, armpit or groin region. Associated Symptoms include night sweats, unintentional weight loss, fever, persistent cough or dyspnea. Involvement of the gastrointestinal tract is a rare occurrence. Diagnosis is based on hematological, radiological and histochemical studies. Here we report a rare presentation of a 47-year-old male who presented with symptoms of loose stools, weight loss and fever. CT scan and abdominal lymph node biopsy findings were consistent with a lymphoproliferative disorder Patient was being managed in the line of malabsorption syndrome with possible underlying malignancy but his condition deterioted before the histological diagnosis was confirmed. Thus, this report highlights the importance having a consideration for Hodgkin's lymphoma in the management of chronic diarrhea.
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Primary Thyroid Lymphoma (PTL) is a rare disease, mostly affecting middle-to-old aged females. It has a strong association with pre-existing thyroiditis, which increases the risk of its development. The disease has been studied in detail in the Western populations. However, there is lack of data for south Asians, especially in Pakistani population. This study was carried out to learn more about the disease characteristics in our area. This was a retrospective study where we reviewed four diagnosed and/or treated cases of primary thyroid Lymphoma at tertiary care hospital of Pakistan (Aga Khan University Hospital), Karachi, Pakistan. Each patient's medical record was reviewed and studied. The participants' average age was 62.8±10.12 years,, with two males and two females. The histology of all of the patients was compatible with the Diffuse B cell Lymphoma subtype. One patient died as a result of complications, one patient was lost to follow up, and the remaining two patients are doing well with no active complaints and are being followed up on a regular basis.
Subject(s)
Lymphoma , Thyroid Neoplasms , Aged , Female , Humans , Male , Middle Aged , Developing Countries , Lymphoma/epidemiology , Lymphoma/therapy , Retrospective Studies , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/therapyABSTRACT
Constitutively activated B cell receptor (BCR) signaling is a primary biological feature of chronic lymphocytic leukemia (CLL). The biological events controlled by BCR signaling in CLL are not fully understood and need investigation. Here, by analysis of the chromatin states and gene expression profiles of CLL B cells from patients before and after Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib treatment, we show that BTKi treatment leads to a decreased expression of APOBEC3 family genes by regulating the activity of their enhancers. BTKi treatment reduces enrichment of enhancer marks (H3K4me1 and H3K27ac) and chromatin accessibility at putative APOBEC3 enhancers. CRISPR-Cas9 directed deletion or inhibition of the putative APOBEC3 enhancers leads to reduced APOBEC3 expression. We further find that transcription factor NFATc1 couples BCR signaling with the APOBEC3 enhancer activity to control APOBEC3 expression. We also find that enhancer-regulated APOBEC3 expression contributes to replication stress in malignant B cells. In total we demonstrate a novel mechanism for BTKi suppression of APOBEC3 expression via direct enhancer regulation in an NFATc1-dependent manner, implicating BCR signaling as a potential regulator of leukemic genomic instability.
Subject(s)
APOBEC Deaminases , Leukemia, Lymphocytic, Chronic, B-Cell , Receptors, Antigen, B-Cell , APOBEC Deaminases/biosynthesis , APOBEC Deaminases/genetics , APOBEC Deaminases/metabolism , Chromatin , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Protein Kinase Inhibitors/pharmacology , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Receptors, Antigen, B-Cell/genetics , Receptors, Antigen, B-Cell/metabolismABSTRACT
Background: lack of medical practitioners' knowledge about oral cancer has contributed to delays in referral and treatment. Oral cancer is amenable to treatment when detected early, which leads to better prognosis and survival rates. In this study, we aimed to assess the knowledge of the Syrian medical students about the risk factors of oral cancer, oral cavity changes associated with oral cancer, and the relation between the relation with Human Papilloma Virus (HPV) and oral cancer. Methods: This is a cross-sectional study conducted at the Syrian Private University. Data were collected through self-administered questionnaires, which targeted social demographic information, general knowledge, risk factors, oral changes and HPV knowledge associated with oral cancer. Data was categorized and analyzed to assess and compare the levels of knowledge between clinical and preclinical students. Results: 301 out of 401 medical students responded to the questionnaires bringing the response rate to 75.25%. The study revealed adequate knowledge about oral cancer, general information, clinical features, risk factors and relation to HPV. Clinical students showed higher levels of awareness compared to pre-clinical students. No significance in knowledge was found between the genders. Conclusion: The findings of the present study suggest that there is a need to reinforce the medical curriculum concerning oral cancer education, particularly in prevention and early detection to improve practices.
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A pathogenic strain of Macrococcus caseolyticus (M. caseolyticus) was isolated from wounds infection during an investigation on donkeys in Khartoum State. (122) samples were collected from external wounds (head, abdomen, back and leg) during different seasons. One isolate (124B) was identified using whole-genome sequence analysis. RAST software identified 31 virulent genes of disease and defense, including methicillin-resistant genes, TatR family and ANT(4')-Ib. Plasmid rep22 was identified by PlasmidFindet-2.0 Server and a CRISPR. MILST-2.0 predicted many novel alleles. NCBI notated the genome as a novel M. caseolyticus strain (DaniaSudan). The MLST-tree-V1 revealed that DaniaSudan and KM0211a strains were interrelated. Strain DaniaSudan was resistant to ciprofloxacin, ceftazidime, erythromycin, oxacillin, clindamycin and kanamycin. Mice modeling showed bacteremia and many clinical signs (swelling, allergy, wounds, and hair loss). Enlargement, hyperemia, adhesions and abscesses were observed in many organs.Constructive conclusionThe prevalence of the strain was 4.73%, with significant differences between collection seasons and locations of wounds. A highly significant association between doses (105 CFU/ml, 102 CFU/ml, Intra-peritoneum and sub-cutaneous) and swelling, developing of allergy and loss of hair (p = 0.001, p = 0.000 and p = 0.005) respectively were seen.This result represents the first report of pathogenic strains of M. caseolyticus worldwide.
Subject(s)
Rodent Diseases , Staphylococcaceae , Wounds and Injuries , Animals , Anti-Bacterial Agents/pharmacology , Equidae/microbiology , Hypersensitivity/etiology , Hypersensitivity/veterinary , Mice , Microbial Sensitivity Tests/veterinary , Multilocus Sequence Typing/veterinary , Prevalence , Staphylococcaceae/genetics , Sudan , Wounds and Injuries/microbiologyABSTRACT
BACKGROUND: Globally, just 21% of the estimated 58 million people living with hepatitis C virus (HCV) know their status. Thus, there is considerable need to scale-up HCV testing if the World Health Organization (WHO) 2030 hepatitis elimination goals are to be achieved. HCV self-testing may assist with this; however, there are currently no data on the real-world impact of HCV self-testing. With an estimated 5% of the general population living with HCV, Pakistan has the second highest HCV burden in the world. This study aims to evaluate the acceptability and impact of home delivery of HCV self-testing for secondary distribution in the context of a house-to-house HCV micro-elimination programme in Pakistan. METHODS: This is a parallel group, non-blinded, cluster randomised trial comparing secondary distribution of HCV self-testing with secondary distribution of information pamphlets encouraging individuals to visit a testing facility for HCV screening. The cluster allocation ratio is 1:1. Clusters will be randomised either to HCV self-testing distributed via study staff or control clusters where information on HCV will be given and the participant will be requested to attend their local hospital for HCV screening. In both clusters, only households with a member who has not yet been screened as part of the larger micro-elimination project will be included. The primary outcome is the number and proportion of participants who report completion of testing. Secondary outcomes include the number and proportion of participants who a) receive a positive result and are made aware of their status, b) are referred to and complete HCV RNA confirmatory testing, and c) start treatment. Acceptability, feasibility, attitudes towards HCV testing, and cost will also be evaluated. The target sample size is 2,000 participants. DISCUSSION: This study will provide the first ever evidence regarding secondary distribution of HCV self-testing. By comparing HCV self-testing with facility-based testing, we will assess whether HCV self-testing increases the uptake of HCV testing. The findings will inform micro-elimination programmes and determine whether HCV self-testing can enable individuals to be reached who may otherwise be missed. TRIAL REGISTRATION: This study and was registered on clinicaltrials.gov ( NCT04971538 ) 21 July 2021.
Subject(s)
Hepacivirus , Hepatitis C , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Hepatitis C/prevention & control , Humans , Pakistan/epidemiology , Randomized Controlled Trials as Topic , Self-Testing , Serologic TestsABSTRACT
OBJECTIVES: Men who have sex with men (MSM) and transgender individuals are at higher risk of genital warts and anal cancer due to sexually transmitted human papillomavirus infection. This study explores MSM and transgender women's perceptions of Human papillomavirus (HPV) infection and HPV prevention strategies (screening and vaccination) in Pakistan. DESIGN: A qualitative study using focus group discussions (FGD) with self-identified MSM, male sex workers and transgender women were conducted between March 2019 to August 2019 in Karachi, Pakistan. METHODS: Participants were recruited from community-based organization (CBO) working for MSM and transgender women. A total of 38 men and 10 transgender women took part in 6 FGDs. Discussions were recorded, translated, transcribed verbatim and analyzed using content analysis. RESULTS: Three themes were identified from the emerging analysis. These are, 1) Knowledge and risk perceptions about STIs and HPV, 2) Beliefs and attitudes towards HPV prevention, 3) Participant's recommendations for HPV vaccination and anal Pap screening. Participants described lack of knowledge of HPV and its health consequences as HIV is the only focus of attention of the government and the local CBOs. None of participants had heard about HPV prevention including vaccination and anal Pap screening for men but expressed a positive attitude towards prevention. Genital warts and anal cancer were perceived as severe potential consequences of a known risk behaviors. All participants stated they would be interested in taking an HPV vaccine but acknowledged that the provision of services for sexually transmitted infections (STI) are inadequate to meet the needs of key populations and are not prioritized by the government. The main perceived barriers to access HPV prevention included cost and challenges to access public health care services or openly discussing one's sexual orientation with health care providers. Participants generally preferred the CBO for more professional, unbiased staff attitudes that respect patients' integrity, confidentiality and privacy. Most participants thought that in case the government is non-cooperative, CBOs should work in the interest of HPV eradication and generate funds through international funding. CONCLUSIONS: The findings from this study can help public health policy and researchers to understand this minority's perspective on HPV prevention. Given the low level of knowledge about HPV infection and its negative health consequences there is a need of HPV education combined with STI education and awareness through HPV brochures to educate the target population effectively.