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Global Health, Science and Practice Jun 2024Barriers to achieving and sustaining access to water, sanitation, hygiene, cleaning, and waste management (WASH) in health care facilities include a lack of supportive...
Barriers to achieving and sustaining access to water, sanitation, hygiene, cleaning, and waste management (WASH) in health care facilities include a lack of supportive policy environment and adequate funding. While guidelines exist for assessing needs and making initial infrastructure improvements, there is little guidance on how to develop budgets and policies to sustain WASH services. We conducted costing and advocacy activities in Thakurbaba municipality, Nepal, to develop a budget and operations and maintenance policy for WASH in health care facilities in partnership with the municipal government. Our objectives for this study were to (1) describe the process and methods used for costing and advocacy, (2) report the costs to achieve and maintain basic WASH services in the 8 health care facilities of Thakurbaba municipality, and (3) report the outcomes of advocacy activities and policy development. We applied bottom-up costing to enumerate the resources necessary to achieve and maintain basic WASH services and their costs. The annual costs to achieve, operate, and maintain basic access to WASH services ranged from US$4881-US$9695 per facility. Cost findings were used to prepare annual budgets recommended to achieve, operate, and maintain basic services, which were presented to the municipal government and incorporated into an operations and maintenance policy. To date, the municipality has adopted the policy and established a recovery fund of US$3831 for repair and maintenance of infrastructure and an additional US$153 per facility for discretionary WASH spending, which were to be replenished as they were spent. Advocacy at the national level for WASH in health care facilities is currently being championed by the municipality, and findings from this project have informed the development of a nationally costed plan for universal access. This study is intended to provide a roadmap for how cost data can be collected and applied to inform policy.
Topics: Nepal; Sanitation; Humans; Hygiene; Health Facilities; Budgets; Water Supply; Waste Management
PubMed: 38936959
DOI: 10.9745/GHSP-D-23-00491 -
Cell Reports Jun 2024In contrast to most hematopoietic lineages, megakaryocytes (MKs) can derive rapidly and directly from hematopoietic stem cells (HSCs). The underlying mechanism is...
In contrast to most hematopoietic lineages, megakaryocytes (MKs) can derive rapidly and directly from hematopoietic stem cells (HSCs). The underlying mechanism is unclear, however. Here, we show that DNA damage induces MK markers in HSCs and that G2 arrest, an integral part of the DNA damage response, suffices for MK priming followed by irreversible MK differentiation in HSCs, but not in progenitors. We also show that replication stress causes DNA damage in HSCs and is at least in part due to uracil misincorporation in vitro and in vivo. Consistent with this notion, thymidine attenuated DNA damage, improved HSC maintenance, and reduced the generation of CD41 MK-committed HSCs. Replication stress and concomitant MK differentiation is therefore one of the barriers to HSC maintenance. DNA damage-induced MK priming may allow rapid generation of a lineage essential to immediate organismal survival, while also removing damaged cells from the HSC pool.
PubMed: 38935497
DOI: 10.1016/j.celrep.2024.114388 -
Indian Journal of Public Health Oct 2023The augmentation of precautionary behaviors through the application of health belief model (HBM) constructs could help in curbing the current pandemic.
BACKGROUND
The augmentation of precautionary behaviors through the application of health belief model (HBM) constructs could help in curbing the current pandemic.
OBJECTIVES
The objectives are to assess adherence to CAB and to evaluate its predictors using the constructs of HBM among COVID-19 vaccinees in Himachal Pradesh.
MATERIALS AND METHODS
A cross-sectional study using a telephone survey, with two-step stratified random sampling, was employed to acquire a sample of 441 respondents from Himachal Pradesh. Formal interviews were conducted using pretested, structured, self-administered questionnaires.
RESULTS
The mean age of respondents was 32.16 years (standard deviation = 12.77; range = 18-78 years). Maximum adherence was seen for wearing masks at 83% (95% confidence interval [CI]: 79.3%-86.3%), followed by maintenance of respiratory hygiene at 72.3% (95% CI 68%-78.4%). Nearly 42.2% (95% CI 37.6%-47.8%) conformed to social distancing norms. We observed minimum adherence for handwashing practices of 12.9% (95% CI 10%-16.3.0%). On bivariate analyses, except for perceived severity, all HBM constructs were significantly associated with CAB. However, after adjusting for gender, age, education, area of residence, and reduced income in multivariate analysis, perceived susceptibility, perceived barriers, and exposure to cues to action remained significant predictors of CAB.
CONCLUSIONS
The study highlights the empirical evidence of the application of HBM constructs to enhance behavioral adherence to COVID-19 precautionary measures.
Topics: Humans; COVID-19; India; Adult; Cross-Sectional Studies; Male; Female; Middle Aged; Health Belief Model; Adolescent; Young Adult; Aged; SARS-CoV-2; Health Behavior; Health Knowledge, Attitudes, Practice; Socioeconomic Factors; Hand Disinfection
PubMed: 38934832
DOI: 10.4103/ijph.ijph_1525_22 -
Haematologica Jun 2024To evaluate the efficacy and safety of flumatinib in the later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid...
To evaluate the efficacy and safety of flumatinib in the later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CP-CML previously treated with tyrosine kinase inhibitors (TKIs). Patients with CML-CP were evaluated for the probabilities of responses including complete hematologic response (CHR), cytogenetic response, and molecular response (MR) and adverse events (AEs) after the later-line flumatinib therapy. Of 336 enrolled patients with median age 50 years, median duration of treatment with flumatinib was 11.04 (2-25.23) months. Patients who achieved clinical responses at baseline showed maintenance of CHR, complete cytogenetic response (CCyR)/2-log molecular response (MR2), major molecular response (MMR), and 4-log molecular response or deep molecular response (MR4/DMR) in 100%, 98.9%, 98.6%, and 92.9% patients, respectively. CHR, CCyR/MR2, MMR, and MR4/DMR responses were achieved in 86.4%, 52.7%, 49.6%, and 23.5% patients respectively, which showed the lack of respective clinical responses at baseline. The patients without response at baseline, treated with flumatinib as 2L TKI, having no resistance to prior TKI or only resistance to imatinib, with response to last TKI, and with BCR::ABL ≤10% had higher CCyR/MR2, MMR, or MR4/DMR. The AEs observed during the later-line flumatinib treatment were tolerable and consistent with those reported with the first-line therapy. Flumatinib was effective and safe in patients who are resistant or intolerant to other TKIs. In particular, 2L flumatinib treatment induced high response rates and was more beneficial to patients without previous 2G TKI resistance, thus serving as a probable treatment option for these patients.
PubMed: 38934064
DOI: 10.3324/haematol.2023.284892 -
Frontiers in Cell and Developmental... 2024Lipids, the primary constituents of the cell membrane, play essential roles in nearly all cellular functions, such as cell-cell recognition, signaling transduction, and... (Review)
Review
Lipids, the primary constituents of the cell membrane, play essential roles in nearly all cellular functions, such as cell-cell recognition, signaling transduction, and energy provision. Lipid metabolism is necessary for the maintenance of life since it regulates the balance between the processes of synthesis and breakdown. Increasing evidence suggests that cancer cells exhibit abnormal lipid metabolism, significantly affecting their malignant characteristics, including self-renewal, differentiation, invasion, metastasis, and drug sensitivity and resistance. Prominent oncogenic signaling pathways that modulate metabolic gene expression and elevate metabolic enzyme activity include phosphoinositide 3-kinase (PI3K)/AKT, MAPK, NF-kB, Wnt, Notch, and Hippo pathway. Conversely, when metabolic processes are not regulated, they can lead to malfunctions in cellular signal transduction pathways. This, in turn, enables uncontrolled cancer cell growth by providing the necessary energy, building blocks, and redox potentials. Therefore, targeting lipid metabolism-associated oncogenic signaling pathways could be an effective therapeutic approach to decrease cancer incidence and promote survival. This review sheds light on the interactions between lipid reprogramming and signaling pathways in cancer. Exploring lipid metabolism as a target could provide a promising approach for creating anticancer treatments by identifying metabolic inhibitors. Additionally, we have also provided an overview of the drugs targeting lipid metabolism in cancer in this review.
PubMed: 38933330
DOI: 10.3389/fcell.2024.1399065 -
Fundamental Research Sep 2023Tumorigenesis is a complicated process in which numerous modulators are involved in different ways. Previous studies have focused primarily on tumor-associated... (Review)
Review
Tumorigenesis is a complicated process in which numerous modulators are involved in different ways. Previous studies have focused primarily on tumor-associated protein-coding genes such as oncogenes and tumor suppressor genes, as well as their associated oncogenic pathways. However, noncoding RNAs (ncRNAs), rising stars in diverse physiological and pathological processes, have recently emerged as additional modulators in tumorigenesis. In this review, we focus on two typical kinds of ncRNAs: long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs). We describe the molecular patterns of ncRNAs and focus on the roles of ncRNAs in cancer stem cells (CSCs), tumor cells, and tumor environmental cells. CSCs are a small subset of tumor cells and are generally considered to be cells that initiate tumorigenesis, and dozens of ncRNAs have been defined as critical modulators in CSC maintenance and oncogenesis. Moreover, ncRNAs are widely involved in oncogenetic processes, including sustaining proliferation, resisting cell death, genome instability, metabolic disorders, immune escape and metastasis. We also discuss the potential applications of ncRNAs in tumor diagnosis and therapy. The progress in ncRNA research greatly improves our understanding of ncRNAs in oncogenesis and provides new potential targets for future tumor therapy.
PubMed: 38933287
DOI: 10.1016/j.fmre.2023.05.014 -
Viruses Jun 2024Experimental evolution studies, in which biological populations are evolved in a specific environment over time, can address questions about the nature of spontaneous... (Review)
Review
Experimental evolution studies, in which biological populations are evolved in a specific environment over time, can address questions about the nature of spontaneous mutations, responses to selection, and the origins and maintenance of novel traits. Here, we review more than 30 years of experimental evolution studies using the bacteriophage (phage) Φ6 cystovirus. Similar to many lab-studied bacteriophages, Φ6 has a high mutation rate, large population size, fast generation time, and can be genetically engineered or cryogenically frozen, which facilitates its rapid evolution in the laboratory and the subsequent characterization of the effects of its mutations. Moreover, its segmented RNA genome, outer membrane, and capacity for multiple phages to coinfect a single host cell make Φ6 a good non-pathogenic model for investigating the evolution of RNA viruses that infect humans. We describe experiments that used Φ6 to address the fitness effects of spontaneous mutations, the consequences of evolution in the presence of coinfection, the evolution of host ranges, and mechanisms and consequences of the evolution of thermostability. We highlight open areas of inquiry where further experimentation on Φ6 could inform predictions for pathogenic viruses.
Topics: Bacteriophage phi 6; Mutation; Host Specificity; Evolution, Molecular; Cystoviridae; Genome, Viral; Humans; Directed Molecular Evolution; Biological Evolution
PubMed: 38932268
DOI: 10.3390/v16060977 -
Viruses Jun 2024Quantification of Torquetenovirus (TTV) viremia is becoming important for evaluating the status of the immune system in solid organ transplant recipients, monitoring the...
Quantification of Torquetenovirus (TTV) viremia is becoming important for evaluating the status of the immune system in solid organ transplant recipients, monitoring the appearance of post-transplant complications, and controlling the efficacy of maintenance immunosuppressive therapy. Thus, diagnostic approaches able to scale up TTV quantification are needed. Here, we report on the development and validation of a real-time PCR assay for TTV quantification on the Hologic Panther Fusion System by utilizing its open-access channel. The manual real-time PCR previously developed in our laboratories was optimized to detect TTV DNA on the Hologic Panther Fusion System. The assay was validated using clinical samples. The automated TTV assay has a limit of detection of 1.6 log copies per ml of serum. Using 112 samples previously tested via manual real-time PCR, the concordance in TTV detection was 93% between the assays. When the TTV levels were compared, the overall agreement between the methods, as assessed using Passing-Bablok linear regression and Bland-Altman analyses, was excellent. In summary, we validated a highly sensitive and accurate method for the diagnostic use of TTV quantification on a fully automated Hologic Panther Fusion System. This will greatly improve the turnaround time for TTV testing and better support the laboratory diagnosis of this new viral biomarker.
Topics: Real-Time Polymerase Chain Reaction; Viremia; Humans; Viral Load; DNA Virus Infections; Sensitivity and Specificity; Torque teno virus; DNA, Viral; Limit of Detection; Reproducibility of Results; Automation, Laboratory
PubMed: 38932255
DOI: 10.3390/v16060963 -
Pharmaceutics May 2024Most infectious diseases of the gastrointestinal tract can easily be treated by exploiting the already available antibiotics with the change in administration approach...
Most infectious diseases of the gastrointestinal tract can easily be treated by exploiting the already available antibiotics with the change in administration approach and delivery system. Ciprofloxacin (CIP) is used as a drug of choice for many bacterial infections; however, long-term therapy and off-site drug accumulation lead to an increased risk of tendinitis and peripheral neuropathy. To overcome this issue, nanotechnology is being exploited to encapsulate antibiotics within polymeric structures, which not only facilitates dose maintenance at the infection site but also limits off-site side effects. Here, sodium alginate (SA) and thiol-anchored chitosan (TC) were used to encapsulate CIP via a calcium chloride (CaCl) cross-linker. For this purpose, the B-390 encapsulator was employed in the preparation of nanobeads using a simple technique. The hydrogel-like sample was then freeze-dried, using trehalose or mannitol as a lyoprotectant, to obtain a fine dry powder. Design of Experiment (DoE) was utilized to optimize the nanobead production, in which the influence of different independent variables was studied for their outcome on the polydispersity index (PDI), particle size, zeta potential, and percentage encapsulation efficiency (% EE). In vitro dissolution studies were performed in simulated saliva fluid, simulated gastric fluid, and simulated intestinal fluid. Antibacterial and anti-inflammatory studies were also performed along with cytotoxicity profiling. By and large, the study presented positive outcomes, proving the advantage of using nanotechnology in fabricating new delivery approaches using already available antibiotics.
PubMed: 38931815
DOI: 10.3390/pharmaceutics16060691 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Ovarian cancer (OC) is a significant cause of cancer-related mortality in women globally, with a five-year survival rate of approximately 49%. Standard therapy involves... (Review)
Review
BACKGROUND
Ovarian cancer (OC) is a significant cause of cancer-related mortality in women globally, with a five-year survival rate of approximately 49%. Standard therapy involves cytoreductive surgery followed by chemotherapy. Its poor prognosis has driven interest in alternative therapies such as targeted molecular agents like bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi).
MATERIALS AND METHODS
This review systematically searched PubMed from January 2018 to December 2023 for studies on PARPi in OC. Emphasis was on identifying relevant Phase III trials, extracting data on study design, patient demographics, and outcomes. Special focus was on assessing PARPi efficacy, safety, impact on quality of life, and ongoing trials, including those on Clinicaltrials.gov.
RESULTS
The efficacy of PARPi in first-line therapy for OC has been extensively studied. Trials like SOLO-1, PRIMA, and ATHENA-MONO have demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS), particularly in patients with BRCA mutations. Additionally, the combination of PARPi with other agents like bevacizumab has shown promising results in extending PFS. However, PARPi treatment is associated with various adverse effects, including hematologic toxicities like anemia, thrombocytopenia, and neutropenia. While most adverse events are manageable, some patients may require dose adjustments or discontinuation of treatment. Importantly, PARPi maintenance therapy has not adversely affected health-related quality of life (HRQoL), with studies reporting similar HRQoL scores between PARPi-treated and placebo-treated patients.
CONCLUSIONS
PARPi offer effective treatment with manageable side effects, suitable even for medically fragile patients. Individualized dosing can optimize benefits while minimizing adverse events. Exploring diverse treatment approaches, particularly in patients with limited life expectancy or high disease burden, could improve outcomes. Ongoing research is investigating alternative therapies and combinations to broaden treatment options. Combining bevacizumab with PARPi may be justified for first-line and recurrent maintenance therapy. Regardless of mutational status, PARPi should be considered for maintenance therapy in newly diagnosed advanced OC. Platinum sensitivity remains crucial for treatment decisions and predicting survival outcomes.
PubMed: 38931448
DOI: 10.3390/ph17060778