Amongst the neglected tropical diseases, leishmaniasis alone causes 30 000 deaths annually due to the protozoan parasite genus Leishmania . Existing therapies have serious drawbacks in safety, drug ...resistance, field-adapted application and cost. Therefore, new safer and shorter treatments are an urgent need of the time. Herein, we report the synthesis of fifteen novel diphenyl triazine and diphenyl triazine pyrimidine derivatives and their antileishmanial properties against Leishmania donovani , that causes fatal visceral leishmaniasis. Most of the synthesized analogues exhibited more than 90% inhibition against the promastigote stage of the parasite. Moreover, compounds T4 and T7 showed potent activity against extracellular promastigote (IC 50 = 1.074 μM and IC 50 = 1.158 μM) as compared to miltefosine (IC 50 = 1.477 μM) and is nontoxic towards the host THP-1 macrophage cell line. Interestingly, compound T4 exhibited significant activity against amastigotes (7.186 μM) and induced the macrophages to prevent the survival of the parasite. Our results indicate that T4 represents a new structural lead for this serious and neglected disease.
The extraction of berberine was carried out from
Berberis vulgaris
,
Berberis aquifolium
, and
Hydrastis canadensis
plants using ethanol and water (70:30, v/v). The extracted berberine was ...characterized by ultraviolet‐visible and Fourier‐transform infrared spectroscopy. The purity of berberine was ascertained by thin‐layer chromatography using
n
‐propanol‐formic acid‐water (95:1:4) and (90:1:9) solvents. h
R
f
values were in the range of 44–49 with compact spots (diameter 0.2–0.4 cm). HPLC was carried out using ammonium acetate buffer and acetonitrile in gradient mode with Zodiac (4.6 × 150 mm, 3 μm) column. The flow rate was 1.0 mL/min and detection was at 220 nm. The values of separation and resolution factors of the standard and the extracted berberine were in the range of 1.13–1.16 and 1.40–1.71, respectively. A comparison has shown that both thin‐layer chromatography and high‐performance liquid chromatography (HPLC) methods found applications in different situations and requirements. The extracted berberine samples were used to treat Leishmaniosis and the results showed better activity of berberine in comparison to the standard drug Amphotericin B. Briefly, the reported research is a novel and may be used to extract berberine from plants, separation and identification of berberine by thin layer chromatography and HPLC and to treat Leishmaniosis.
The current research aims to develop a carrier system for the delivery of a matrix metalloproteinase (MMP) inhibitor along with a bioceramic agent to the periodontal pocket. It is proposed that the ...present system, if given along with a systemic antibiotic, would be a fruitful approach for periodontitis amelioration. To fulfill the aforementioned objective, a doxycycline hyclate- and hydroxyapatite-adsorbed composite was prepared by a physical adsorption method and successfully loaded inside sodium alginate–chitosan nanoparticles and optimized based on particle size and drug content. Optimized formulation was then subjected to different evaluation parameters like encapsulation efficiency, hydroxyapatite content, ζ potential, surface morphology, in vitro drug release, cell line studies, and stability studies. For the optimized formulation, particle size, polydispersity index (PDI), entrapment efficiency, ζ potential, and drug content were found to be 336.50 nm, 0.23, 41.77%, −13.85 mV, and 14.00%, respectively. The surface morphology of the placebo and adsorbed composite-loaded nanoparticles as observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed the spherical shape and rough surface of the particles. In gingival crevicular fluid (GCF) 7.6, a sustained drug release profile was obtained up to 36 h. In vitro % viability studies performed on murine fibroblast cells (NIH3T3) and human periodontal ligament (hPDL) cell lines confirmed the proliferative nature of the formulation. Also, when subjected to stability studies for 4 weeks, particle size, PDI, and drug content did not vary considerably, thereby ensuring the stable nature of nanoparticles. Henceforth, sodium alginate–chitosan nanoparticles appeared to be a good carrier system for doxycycline hyclate and hydroxyapatite for periodontal therapy. If given along with a system antibiotic, the system will serve as a fruitful tool for infection-mediated periodontal regeneration and healing.
In low-incidence countries, tuberculosis mainly affects migrants, mostly resulting from reactivation of latent tuberculosis infection (LTBI) acquired in high-incidence countries before migration. A ...nationwide primary care-based LTBI testing and treatment programme for migrants from high-incidence countries was therefore established in high tuberculosis incidence areas in England. We aimed to assess the effectiveness of this programme.
We did a retrospective, population-based cohort study of migrants who registered in primary care between Jan 1, 2011, and Dec 31, 2018, in 55 high-burden areas with programmatic LTBI testing and treatment. Eligible individuals were aged 16–35 years, born in a high-incidence country, and had entered England in the past 5 years. Individuals who tested interferon-γ release assay (IGRA)-negative were advised about symptoms of tuberculosis, whereas those who tested IGRA-positive were clinically assessed to rule out active tuberculosis and offered preventive therapy. The primary outcome was incident tuberculosis notified to the national Enhanced Tuberculosis Surveillance system.
Our cohort comprised 368 097 eligible individuals who had registered in primary care, of whom 37 268 (10·1%) were tested by the programme. 1446 incident cases of tuberculosis were identified: 166 cases in individuals who had IGRA testing (incidence 204 cases 95% CI 176–238 per 100 000 person-years) and 1280 in individuals without IGRA testing (82 cases 77–86 per 100 000 person-years). Overall, in our primary analysis including all diagnosed tuberculosis cases, a time-varying association was identified between LTBI testing and treatment and lower risk of incident tuberculosis (hazard ratio HR 0·76 95% CI 0·63–0·91) when compared with no testing. In stratified analysis by follow-up period, the intervention was associated with higher risk of tuberculosis diagnosis during the first 6 months of follow-up (9·93 7·63–12·9) and a lower risk after 6 months (0·57 0·41–0·79). IGRA-positive individuals had higher risk of tuberculosis diagnosis than IGRA-negative individuals (31·9 20·4–49·8). Of 37 268 migrants who were tested, 6640 (17·8%) were IGRA-positive, of whom 1740 (26·2%) started preventive treatment. LTBI treatment lowered the risk of tuberculosis: of 135 incident cases in the IGRA-positive cohort, seven cases were diagnosed in the treated group (1·87 cases 95% CI 0·89–3·93 per 1000 person-years) and 128 cases were diagnosed in the untreated group (10·9 cases 9·16–12·9 per 1000 person-years; HR 0·14 95% CI 0·06–0·32).
A low proportion of eligible migrants were tested by the programme and a small proportion of those testing positive started treatment. Despite this, programmatic LTBI testing and treatment of individuals migrating to a low-incidence region is effective at diagnosing active tuberculosis earlier and lowers the long-term risk of progression to tuberculosis. Increasing programme participation and treatment rates for those testing positive could substantially impact national tuberculosis incidence.
National Institute for Health Research Health Protection Research Unit in Respiratory Infections.
Menstruation-related school absenteeism significantly affects girls’ academic progress and general wellbeing. This study aimed to assess menstruation-related school absenteeism in an urban population ...in the Northern Region of Ghana. A school-based cross-sectional study was conducted to determine the prevalence of school absenteeism among girls using a structured questionnaire, which was pretested. The data were analyzed using Stata 16. Descriptive and inferential statistics, including cross-tabulation, the chi-square test, and binary logistic regression, were performed. The majority (59%) was between the ages of 15 and 19 years. Approximately one fifth of all respondents missed school during menstruation. Reasons assigned to missing school were menstrual pains (57%), stained clothes (43%), heavy bleeding (40%), and self-stigmatization (2%). The majority (95%) of respondents used some form of materials to absorb menstrual blood. About 88% of respondents used sanitary pads, 11% used cloth, and 1% used tissues to absorb their menstrual blood. The multivariable analysis showed that school girls < 15 years old (AOR: 3.69, 95% CI: 2.02–6.73), first year of Junior High School (AOR: 4.68, 95% CI: 2.14–10.22), and public school (AOR: 3.57, 95% CI: 1.83–6.94) were associated with increased odds of menstruation-related school absenteeism. Menstruation-related school absenteeism is considered high and could affect girls’ educational attainment. School absenteeism due to menstruation, particularly in public schools, warrants attention by the Ghana Education Service.
Abstract Background Quality sleep is vital for well-being, especially for healthcare workers facing high risks of fatigue and burnout. Sleep deprivation impairs cognitive and motor functions, ...contributing to medical errors. Addressing sleep disorders among healthcare professionals is crucial for enhancing patient care. Tailored interventions are needed to support their well-being and improve healthcare outcomes. Objective To evaluate the effect of Sleep Quality and its Deprivation on Sudanese Healthcare Professionals amidst conflict in Sudan. Methods A cross-sectional online survey of Sudanese doctors was conducted using convenience sampling. The questionnaire covered sleep quality, daytime sleepiness, and psychological well-being. Pilot testing ensured questionnaire clarity. Data collection utilized Google Forms distributed through social media and professional networks. A minimum sample size of 384 was calculated. Statistical analysis included descriptive statistics and various tests for significance. Data were securely stored and analyzed using SPSS and R software. Results Among 649 participants, 404 (62.2%) were women, with a mean age of 30.34 years. Most were single (434, 66.9%). General practitioners constituted the largest professional group (267, 41.1%), followed by registrars/residents (142, 21.9%). Participants took an average of 43.70 minutes to fall asleep and slept an average of 5.90 hours per night. According to the PSQI, 300 (46.2%) reported mild sleep disturbance, 287 (44.2%) moderate, 42 (6.5%) severe, and only 20 (3.1%) normal sleep. The ESS revealed 285 (43.9%) with lower normal daytime sleepiness, 188 (29.0%) with higher normal, and various levels of excessive daytime sleepiness. Stress levels varied, with 398 (61.3%) reporting normal stress, while anxiety ranged from 248 (38.2%) normal to 148 (22.8%) extremely severe. Conclusion This study emphasizes the importance of addressing sleep quality, mental health, and performance challenges among Sudanese healthcare professionals. It highlights the need for hospitals to implement measures enabling more time off, adequate sleep, and reduced on-call service days. Healthcare workers must recognize the significance of these factors for their well-being and patient care quality. The research outcomes can raise awareness about the necessity of regulating healthcare practitioners' working hours and ensuring adequate sleep.
Background:
Chronic myeloid leukemia (CML) is a hematological disorder caused by fusion of
BCR
and
ABL
genes.
BCR-ABL
dependent and independent pathways play equally important role in CML. TGFβ-Smad ...pathway, an important
BCR -ABL
independent pathway, has scarce data in CML. Present study investigate the association between TGFβ-Smad pathway and CML.
Materials and Methods:
Sixty-four CML patients and age matched healthy controls (n=63) were enrolled in this study. Patients were segregated into responder and resistant groups depending on their response to Imatinib mesylate (IM).
TGFβ1
serum levels were evaluated by ELISA and transcript levels of
TGFβ1
receptors,
SMAD4
and
SMAD7
were evaluated by Real-Time PCR. Sequencing of exons and exon-intron boundaries of study genes was performed using Next Generation Sequencing (NGS) in 20 CML patients. Statistical analysis was performed using SPSS version 16.0.
Results:
TGFβ1
serum levels were significantly elevated (
p
= 0.02) and
TGFβR2
and
SMAD4
were significantly down-regulated (
p
= 0.012 and
p
= 0.043 respectively) in the patients. c.69A>G in
TGFβ1
, c.1024+24G>A in
TGFβR1
and g.46474746C>T in
SMAD7
were the most important genetic variants observed with their presence in 10/20, 8/20 and 7/20 patients respectively. In addition,
TGFβR1
transcript levels were reduced in CML patients with c.69A>G mutation. None of the genes differed significantly in terms of expression or genetic variants between responder and resistant patient groups.
Conclusion:
Our findings demonstrate the role of differential expression and genetic variants of TGFβ-Smad pathway in CML. Decreased
TGFβR2
and
SMAD4
levels observed in the present study may be responsible for reduced tumor suppressive effects of this pathway in CML.
A considerable epidemiological and pathogenetic overlap exists between tuberculosis (TB) and cardiovascular diseases (CVD). The objective of this study was to establish the prevalence of CVD in the ...TB population. A systematic literature search was performed using Scopus, PubMed, EBSCO, ProQuest, Web of Science on January 25, 2023 using the keywords: “Tuberculosis,” “TB,” “mycobacterium tuberculosis,” and “cardiovascular disease,” “CVD” and with individual terms of various CVDs. Observational Studies were included if they reported the prevalence of CVD in the presence of TB in an adult population. The Newcastle-Ottawa Scale was used for quality evaluation. Statistical analyses were performed using STATA version 17. From 10 studies involving 46715 TB patients, a combined prevalence of CVDs was found to be 11% (CI: 95%, 5-16) with significant heterogeneity across studies (I2 = 96.72%). This study showed a considerable prevalence of CVD among TB patients suggesting TB patients to consider cardiac examination.
Our developed cell division-specific ‘centrin’ gene deleted Leishmania donovani (LdCen1−/−) the causative parasite of the fatal visceral-leishmaniasis (VL), exhibits a selective growth arrest at the ...intracellular stage and is anticipated as a live attenuated vaccine candidate against VL. LdCen1−/− immunization in animals has shown increased IFN-γ secreting CD4+ and CD8+ T cells along with protection conferred by a protective proinflammatory immune response. A label-free proteomics approach has been employed to understand the physiology of infection and predict disease interceptors during Leishmania-host interactions. Proteomic modulation after infection of human macrophage cell lines suggested elevated annexin A6, implying involvement in various biological processes such as membrane repair, transport, actin dynamics, cell proliferation, survival, differentiation, and inflammation, thereby potentiating its immunological protective capacity. Additionally, S100A8 and S100A9 proteins, known for maintaining homeostatic balance in regulating the inflammatory response, have been upregulated after infection. The inhibitory clade of serpins, known to inhibit cysteine proteases (CPs), was upregulated in host cells after 48 h of infection. This is reflected in the diminished expression of CPs in the parasites during infection. Such proteome analysis confirms LdCen1−/− efficacy as a vaccine candidate and predicts potential markers in future vaccine development strategies against infectious diseases.
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