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OBJECTIVE: To investigate the short-term effects of 3D-printed and prefabricated foot orthoses on the management of flat feet. DESIGN: In this single-blinded study, 63 patients with flat feet were enrolled via convenience sampling. They were randomly assigned to the control and experimental groups, receiving prefabricated and customized 3D-printed foot orthoses, respectively. The assessment tools included a Visual analog scale (VAS) and a modified Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) questionnaire. The patients scored their pain at weeks 0 and 4 using the VAS. At the end of week 4, patients completed the modified version of the QUEST questionnaire to record their satisfaction with the orthosis. RESULTS: VAS scores at week 0 for the two groups were not statistically significant (p > 0.05). At week 4, the VAS scores of the experimental group reduced significantly (p < 0.001), whereas the VAS scores of the control group remained statistically insignificant (p > 0.05). Modified QUEST questionnaire analysis revealed higher satisfaction with orthosis comfort and effectiveness in the experimental group than in the control, while factors like orthosis dimensions, weight, and durability did not differ significantly between groups. CONCLUSIONS: Customized 3D-printed orthoses effectively reduced pain and enhanced patient satisfaction with comfort and effectiveness in 4 weeks.
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Background: The method currently available to diagnose shigellosis is insensitive and has many limitations. Thus, this study was designed to identify specific antigenic protein(s) among the cell surface associated proteins (SAPs) of Shigella that would be valuable in the development of an alternative diagnostic assay for shigellosis, particularly one that could be run using a stool sample rather than serum. Methods: The SAPs of clinical isolates of S. dysenteriae, S. boydii, Shigella flexneri, and S. sonnei were extracted from an overnight culture grown at 37 °C using acidified-glycine extraction methods. Protein profiles were observed by SDS-PAGE. To determine if antibodies specific to certain Shigella SAPs were present in both sera and stool suspensions, Western blot analysis was used to detect the presence of IgA, IgG, and IgM. Results: Immunoblot analysis revealed that sera from patients infected with S. flexneri recognized 31 proteins. These SAP antigens are recognized by the host humoral response during Shigella infection. Specific antibodies against these antigens were also observed in intestinal secretions of shigellosis patients. Of these 31 S. flexneri proteins, the 35 kDa protein specifically reacted against IgA present in patients' stool suspensions. Further study illustrated the immunoreactivity of this protein in S. dysenteriae, S. boydii, and S. sonnei. This is the first report that demonstrates the presence of immunoreactive Shigella SAPs in stool suspensions. The SAPSs could be very useful in developing a simple and rapid serodiagnostic assay for shigellosis directly from stool specimens.
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Bacterial Proteins , Dysentery, Bacillary , Feces , Shigella flexneri , Humans , Feces/microbiology , Feces/chemistry , Dysentery, Bacillary/diagnosis , Dysentery, Bacillary/immunology , Dysentery, Bacillary/microbiology , Shigella flexneri/immunology , Shigella flexneri/isolation & purification , Bacterial Proteins/immunology , Bacterial Proteins/analysis , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Antigens, Bacterial/immunology , Antigens, Bacterial/analysis , Blotting, Western , Electrophoresis, Polyacrylamide Gel , Immunoglobulin A/immunology , Immunoglobulin A/blood , Immunoglobulin A/analysisABSTRACT
OBJECTIVES: This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel. METHODS: Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed. RESULTS: The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery. CONCLUSION: This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.
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Administration, Cutaneous , Anti-Bacterial Agents , Cefepime , Chitosan , Gels , Particle Size , Skin Absorption , Skin , Chitosan/chemistry , Cefepime/administration & dosage , Cefepime/pharmacokinetics , Cefepime/chemistry , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Gels/chemistry , Animals , Skin Absorption/drug effects , Skin/metabolism , Rats , Drug Delivery Systems/methods , Drug Liberation , Microbial Sensitivity Tests , Male , Drug Carriers/chemistry , Nanoparticles/chemistry , Rats, WistarABSTRACT
Background: Rigorous data management systems and planning are essential to successful research projects, especially for large, multicountry consortium studies involving partnerships across multiple institutions. Here we describe the development and implementation of data management systems and procedures for the Enterics For Global Health (EFGH) Shigella surveillance study-a 7-country diarrhea surveillance study that will conduct facility-based surveillance concurrent with population-based enumeration and a health care utilization survey to estimate the incidence of Shigella--associated diarrhea in children 6 to 35 months old. Methods: The goals of EFGH data management are to utilize the knowledge and experience of consortium members to collect high-quality data and ensure equity in access and decision-making. During the planning phase before study initiation, a working group of representatives from each EFGH country site, the coordination team, and other partners met regularly to develop the data management systems for the study. Results: This resulted in the Data Management Plan, which included selecting REDCap and SurveyCTO as the primary database systems. Consequently, we laid out procedures for data processing and storage, study monitoring and reporting, data quality control and assurance activities, and data access. The data management system and associated real-time visualizations allow for rapid data cleaning activities and progress monitoring and will enable quicker time to analysis. Conclusions: Experiences from this study will contribute toward enriching the sparse landscape of data management methods publications and serve as a case study for future studies seeking to collect and manage data consistently and rigorously while maintaining equitable access to and control of data.
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Background: Shigella is a leading cause of acute watery diarrhea, dysentery, and diarrhea-attributed linear growth faltering, a precursor to stunting and lifelong morbidity. Several promising Shigella vaccines are in development and field efficacy trials will require a consortium of potential vaccine trial sites with up-to-date Shigella diarrhea incidence data. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study will employ facility-based enrollment of diarrhea cases aged 6-35 months with 3 months of follow-up to establish incidence rates and document clinical, anthropometric, and financial consequences of Shigella diarrhea at 7 country sites (Mali, Kenya, The Gambia, Malawi, Bangladesh, Pakistan, and Peru). Over a 24-month period between 2022 and 2024, the EFGH study aims to enroll 9800 children (1400 per country site) between 6 and 35 months of age who present to local health facilities with diarrhea. Shigella species (spp.) will be identified and serotyped from rectal swabs by conventional microbiologic methods and quantitative polymerase chain reaction. Shigella spp. isolates will undergo serotyping and antimicrobial susceptibility testing. Incorporating population and healthcare utilization estimates from contemporaneous household sampling in the catchment areas of enrollment facilities, we will estimate Shigella diarrhea incidence rates. Conclusions: This multicountry surveillance network will provide key incidence data needed to design Shigella vaccine trials and strengthen readiness for potential trial implementation. Data collected in EFGH will inform policy makers about the relative importance of this vaccine-preventable disease, accelerating the time to vaccine availability and uptake among children in high-burden settings.
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Background: Quantitative polymerase chain reaction (qPCR) targeting ipaH has been proven to be highly efficient in detecting Shigella in clinical samples compared to culture-based methods, which underestimate Shigella burden by 2- to 3-fold. qPCR assays have also been developed for Shigella speciation and serotyping, which is critical for both vaccine development and evaluation. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study will utilize a customized real-time PCR-based TaqMan Array Card (TAC) interrogating 82 targets, for the detection and differentiation of Shigella spp, Shigella sonnei, Shigella flexneri serotypes, other diarrhea-associated enteropathogens, and antimicrobial resistance (AMR) genes. Total nucleic acid will be extracted from rectal swabs or stool samples, and assayed on TAC. Quantitative analysis will be performed to determine the likely attribution of Shigella and other particular etiologies of diarrhea using the quantification cycle cutoffs derived from previous studies. The qPCR results will be compared to conventional culture, serotyping, and phenotypic susceptibility approaches in EFGH. Conclusions: TAC enables simultaneous detection of diarrheal etiologies, the principal pathogen subtypes, and AMR genes. The high sensitivity of the assay enables more accurate estimation of Shigella-attributed disease burden, which is critical to informing policy and in the design of future clinical trials.
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Introduction: The periodic evaluation of knowledge, attitudes, and practices (KAP) of healthcare workers, including vaccinators, concerning expanded programs on immunization (EPI) is very crucial for a better healthcare system. This study was carried out to assess the KAP of vaccinators about the EPI, including cold storage of vaccines and their practices related to vaccine cold chain management. Method: A cross-sectional study was conducted from January 2022 to June 2022 among registered vaccinators in the twin cities (Islamabad and Rawalpindi) of Pakistan. A structured self-administered questionnaire (English and Urdu) was developed as per the Pakistan national EPI policy and strategic guidelines 2022 and World Health Organization (WHO) guidelines, as well as from earlier studies (Cronbach's alpha value of 0.734). The final questionnaire consisted of closed-ended questions in four sections, including sociodemographic information, knowledge (with dichotomous variables of yes/no), attitudes (with a 5-point Likert scale ranging from strongly agree to strongly disagree), and handling of vaccines and cold chain management. Completed questionnaires were entered into Microsoft Excel and then imported into SPSS version 25 for statistical analysis. Results: A total of 186 vaccinators completely filled out their questionnaires, with a 97.9% response rate. More than half of the participants (57.5%) had no training related to EPI. Most of the respondents had a moderate to poor level of knowledge regarding EPI. The overall attitude was positive, and 57% of the participants strongly agreed that the national immunization programs can significantly contribute to the decrease in morbidity and mortality rates among children. In the current study, participants showed good practices toward EPI, vaccine storage, and cold chain management. The majority (93.5%) of the participants checked the expiry of vaccines at regular intervals to maintain the first expiry first out (FEFO) in their healthcare setting. Discussion: In conclusion, most of the vaccinators had moderate to poor knowledge, a positive attitude, and good practices toward EPI, vaccine cold storage, and cold chain management. Lack of training among vaccinators on EPI was also observed. These findings have suggested that continuous training, education, and regular supervision of vaccinators in EPI are important for maximum immunization effectiveness and coverage.
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Health Knowledge, Attitudes, Practice , Vaccines , Child , Humans , Cross-Sectional Studies , Immunization , Immunization ProgramsABSTRACT
Background: The Enterics for Global Health (EFGH) Shigella surveillance study is a longitudinal multicountry study that aims to estimate incidence rates and document consequences of Shigella diarrhea within 7 countries in Africa, Asia, and Latin America. In addition to a high incidence of childhood diarrhea, Pakistan is facing a problem of antimicrobial resistance in urban and peri-urban areas of Karachi. Methods: In Pakistan, EFGH will be conducted in Karachi, which is one of the metropolitan cities bordering the Arabian Sea and has a diverse population of 1.6 million according to the 2017 population census. The study aims to enroll 1400 children aged 6-35 months over 2 years (2022-2024) from 6 health care facilities (Abbasi Shaheed Hospital, Khidmat-e-Alam Medical Centre, Sindh Government Hospital Korangi 5, Sindh Government Hospital Ibrahim Hyderi, Ali Akbar Shah VPT Center, and Bhains Colony VPT Center) situated in Nazimabad and Bin-Qasim town. Moreover, population enumeration and health care utilization surveys from a defined catchment area of health facilities will be conducted to estimate the Shigella diarrhea incidence rates. Conclusions: The study will provide critical data to policy-makers about the burden of Shigella and antimicrobial resistance, which is essential for planning Shigella vaccine trials.
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Background: Comparative costs of public health interventions provide valuable data for decision making. However, the availability of comprehensive and context-specific costs is often limited. The Enterics for Global Health (EFGH) Shigella surveillance study-a facility-based diarrhea surveillance study across 7 countries-aims to generate evidence on health system and household costs associated with medically attended Shigella diarrhea in children. Methods: EFGH working groups comprising representatives from each country (Bangladesh, Kenya, Malawi, Mali, Pakistan, Peru, and The Gambia) developed the study methods. Over a 24-month surveillance period, facility-based surveys will collect data on resource use for the medical treatment of an estimated 9800 children aged 6-35 months with diarrhea. Through these surveys, we will describe and quantify medical resources used in the treatment of diarrhea (eg, medication, supplies, and provider salaries), nonmedical resources (eg, travel costs to the facility), and the amount of caregiver time lost from work to care for their sick child. To assign costs to each identified resource, we will use a combination of caregiver interviews, national medical price lists, and databases from the World Health Organization and the International Labor Organization. Our primary outcome will be the estimated cost per inpatient and outpatient episode of medically attended Shigella diarrhea treatment across countries, levels of care, and illness severity. We will conduct sensitivity and scenario analysis to determine how unit costs vary across scenarios. Conclusions: Results from this study will contribute to the existing body of literature on diarrhea costing and inform future policy decisions related to investments in preventive strategies for Shigella.
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Background: Accurate estimation of diarrhea incidence from facility-based surveillance requires estimating the population at risk and accounting for case patients who do not seek care. The Enterics for Global Health (EFGH) Shigella surveillance study will characterize population denominators and healthcare-seeking behavior proportions to calculate incidence rates of Shigella diarrhea in children aged 6-35 months across 7 sites in Africa, Asia, and Latin America. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study will use a hybrid surveillance design, supplementing facility-based surveillance with population-based surveys to estimate population size and the proportion of children with diarrhea brought for care at EFGH health facilities. Continuous data collection over a 24 month period captures seasonality and ensures representative sampling of the population at risk during the period of facility-based enrollments. Study catchment areas are broken into randomized clusters, each sized to be feasibly enumerated by individual field teams. Conclusions: The methods presented herein aim to minimize the challenges associated with hybrid surveillance, such as poor parity between survey area coverage and facility coverage, population fluctuations, seasonal variability, and adjustments to care-seeking behavior.
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This article discusses the modal behavior of elastically constrained beams under various types of foundations and provides insights into the effects of different factors on the eigenfrequencies of beams. Numerical and analytical techniques, specifically the Galerkin finite element method (GFM) and the separation of variables, are utilized to determine the eigenfrequencies and mode shapes of beams. Modal analysis of Timoshenko, shear, Rayleigh, and Euler-Bernoulli beams that are elastically constrained and resting on Winkler, Pasternak, and Hetényi foundations, considering non-classical boundary conditions, is included in the study. The effects of factors such as flexural rigidity, transverse modulus, and Winkler foundation constant on natural frequencies of different beam models are investigated. The proposed method efficiently converges to the exact solution without shear locking in the stiffness element. The results demonstrate that the natural frequencies of the beam rise because of the shear layer, flexural rigidity, and foundation constant. Furthermore, the Hetényi elastic foundation affects the natural frequency of the beam, depending on the relative values of beam stiffness and foundation stiffness. Additionally, incorporating both shear deformation and rotary inertia has a greater impact on the eigenfrequencies of Euler-Bernoulli beams compared to incorporating only one of these effects. The findings of this work provide valuable insights into the behavior of beams under different foundation conditions and have potential applications in the design and optimization of structures incorporating beams, thereby enhancing the understanding of beam analysis.
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Introduction: Silver nanoparticles (AgNPs) have been found to exhibit unique properties which show their potential to be used in various therapies. Green synthesis of AgNPs has been progressively gaining acceptance due to its cost-effectiveness and energy-efficient nature. Objective: In the current study, aqueous extract of Thymus vulgaris (T. vulgaris) was used to synthesize the AgNPs using green synthesis techniques followed by checking the effectiveness and various biological activities of these AgNPs. Methods: At first, the plant samples were proceeded for extraction of aqueous extracts followed by chromatography studies to measure the phenolics and flavonoids. The synthesis and characterization of AgNPs were done using green synthesis techniques and were confirmed using Fourier transform infra-red (FT-IR) spectroscopy, UV-visible spectroscopy, scanning electron microscope (SEM), zeta potential, zeta sizer and X-Ray diffraction (XRD) analysis. After confirmation of synthesized AgNPs, various biological activities were checked. Results: The chromatography analysis detected nine compounds accounting for 100% of the total amount of plant constituents. The FT-IR, UV-vis spectra, SEM, zeta potential, zeta sizer and XRD analysis confirmed the synthesis of AgNPs and the variety of chemical components present on the surface of synthesized AgNPs in the plant extract. The antioxidant activity of AgNPs showed 92% inhibition at the concentration of at 1000 µg/mL. A greater inhibitory effect in anti-diabetic analysis was observed with synthesized AgNPs as compared to the standard AgNPs. The hemolytic activity was low, but despite low concentrations of hemolysis activity, AgNPs proved not to be toxic or biocompatible. The anti-inflammatory activity of AgNPs was observed by in-vitro and in-vivo approaches in range at various concentrations, while maximum inhibition occurs at 1000 µg (77.31%). Conclusion: Our data showed that the potential biological activities of the bioactive constituents of T. vulgaris can be enhanced through green synthesis of AgNPs from T. vulgaris aqueous extracts. In addition, the current study depicted that AgNPs have good potential to cure different ailments as biogenic nano-medicine.
Subject(s)
Metal Nanoparticles , Thymus Plant , Silver/pharmacology , Spectroscopy, Fourier Transform Infrared , Cell Death , HemolysisABSTRACT
Diabetes and depression are both serious health conditions. While their relationship is bidirectional and each condition adversely affects outcomes for the other, they are treated separately. In low and middle income countries, such as Bangladesh and Pakistan, health systems are already stretched and the integration of diabetes and depression care is rarely a priority. Within this context through interviews with patients, healthcare workers and policy makers the study explored: lived experiences of people living with depression and diabetes, current practice in mental health and diabetes care and barriers and perspectives on integrating a brief psychological therapy into diabetes care. The findings of the study included: differing patient and practitioner understandings of distress/depression, high levels of stigma for mental health and a lack of awareness and training on treating depression. While it was apparent there is a need for more holistic care and the concept of a brief psychological intervention appeared acceptable to participants, many logistical barriers to integrating a mental health intervention into diabetes care were identified. The study highlights the importance of context and of recognising drivers and understandings of distress when planning for more integrated mental and physical health services, and specifically when adapting and implementing a new intervention into existing services.
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BACKGROUND: The COG complex is implicated in the tethering of retrograde intra-Golgi vesicles, which involves vesicular tethering and SNAREs. SNARE complexes mediate the inva-sion and metastasis of cancer cells through MMPs which activate growth factors for ECM frag-ments by binding to integrin receptors. Increasing MMPs is in line with YKL40 since YKL40 is linked to promoting angiogenesis through VEGF and can increase ovarian cancer (OC) resistance to chemotropic and cell migration. OBJECTIVE: The aim of this study is an assessment of siRNA-COG3 on proliferation, invasion, and apoptosis of OC cells. In addition, siRNA-COG3 may prevent the growth of OC cancer in mice with tumors. METHODS: Primary OC cell lines will be treated with siRNA-COG3 to assay YKL40 and identified angiogenesis by Tube-like structure formation in HOMECs. The Golgi morphology was analyzed using Immunofluorescence microscopy. Furthermore, the effects of siRNA-COG3 on the prolifer-ation and apoptosis of cells were evaluated using MTT and TUNEL assays. Clones of the HOSEpiC OC cell line were subcutaneously implanted in FVB/N mice. Mice were treated after two weeks of injection of cells using siRNA-COG3. Tumor development suppression was detected by D-luciferin. RT-PCR and western blotting analyses were applied to determine COG3, MT1-MMP, SNAP23, and YKL40 expression to investigate the effects of COG3 gene knockdown. RESULTS: siRNA-COG3 exhibited a substantial effect in suppressing tumor growth in mice. It dra-matically reduced OC cell proliferation and triggered apoptosis (all p < 0.01). Inhibition of COG3, YKL-40, and MT1-MPP led to suppression of angiogenesis and reduction of microvessel density through SNAP23 in OC cells. CONCLUSION: Overall, by knockdown of the COG3 gene, MT1-MMP and YKL40 were dropped, leading to suppressed angiogenesis along with decreasing migration and proliferation. SiRNA-COG3 may be an ideal agent to consider for clinical trial assessment therapy for OC, especially when an antiangiogenic SNAR-pathway targeting drug.
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Inflammatory cell infiltration, particularly macrophages, plays a major contribution to the pathogenesis of Rheumatoid Arthritis (RA). Exploiting the overexpression of folate receptors (FR-ß) on these recruited macrophages has gained significant attraction for ligand-targeted delivery. Leflunomide (LEF), being an immunomodulatory agent is considered the cornerstone of the therapy, however, its oral efficacy is impeded by low solubility and escalating adverse effects profile. Therefore, in the present work, we developed Folate-conjugated chitosan-chondroitin sulfate nanoparticles encapsulating LEF for selective targeting at inflammatory sites in RA. For this purpose, the folate group was first conjugated with the chitosan polymer. After which, Folate Leflunomide Nanoparticles (FA-LEF-NPs) were synthesized through the ionotropic gelation method by employing FA-CHI and CHS. The polymers CHI and CHS were also presented with innate anti-inflammatory and anti-rheumatic attributes that were helpful in provision of synergistic effects to the formulation. These nanoparticles were further fabricated into a hydrogel, employing almond oil (A.O) as a permeation enhancer. The in vivo studies justified the preferential accumulation of FA-conjugated nanoparticles at inflamed joints more than any other organ in comparison to the free LEF and LEF-NPs formulation. The FA-LEF-NPs loaded hydrogel also ascertained a minimal adverse effect profile with an improvement of inflammatory cytokines expression.
Subject(s)
Arthritis, Rheumatoid , Chitosan , Nanoparticles , Humans , Folic Acid , Chondroitin Sulfates , Leflunomide , Hydrogels , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/pathology , Macrophages/metabolism , PolymersABSTRACT
In this study, we present a comprehensive analysis of the laminar time-dependent magnetohydrodynamic (MHD) flow of ethylene glycol-based aluminum oxide nanofluid through a rectangular channel with contracting/expanding porous walls. We investigate the influence of aggregation/non-aggregation of nanoparticles, as well as the presence of thermal radiation. By imposing self-similarities in space and time, we obtain a system of nonlinear ordinary differential equations governing the flow. To solve these equations, we employ a well-known semi-analytical technique known as the Method of Moments (MoM). Additionally, we compare our results with the outcomes achieved through an application of another commonly utilized numerical approach (shooting technique with the Runge-Kutta-Fehlberg scheme). The comparison shows an excellent agreement that endorses the accuracy of the calculated solutions. The velocity and temperature profiles obtained from our analysis exhibit variations due to the changes in involved dimensionless parameters. We present these variations through graphical representations along with their explanations. Interestingly, our study reveals that the aggregation of nanoparticles influences the fluctuations caused by other parameters, and to some extent, suppresses them. Consequently, we observe less deviation among the velocity and temperature curves for the aggregation case compared to the non-aggregation case. These findings have significant implications in real-world engineering and industry. The understanding of the flow behavior of nanofluids through expanding/contracting rectangular channels can aid in the design and optimization of various engineering systems, such as heat exchangers and microfluidic devices. Additionally, our study provides valuable insights into the effects of nanoparticle aggregation and thermal radiation in such systems, offering opportunities for enhancing their efficiency and performance.
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Streptococcus pneumoniae (S. pneumoniae) is a bacterial species often associated with the occurrence of community-acquired pneumonia (CAP). CAP refers to a specific kind of pneumonia that occurs in individuals who acquire the infection outside of a healthcare setting. It represents the leading cause of both death and morbidity on a global scale. Moreover, the declaration of S. pneumoniae as one of the 12 leading pathogens was made by the World Health Organization (WHO) in 2017. Antibiotics like ß-lactams, macrolides, and fluoroquinolones are the primary classes of antimicrobial medicines used for the treatment of S. pneumoniae infections. Nevertheless, the efficacy of these antibiotics is diminishing as a result of the establishment of resistance in S. pneumoniae against these antimicrobial agents. In 2019, the WHO declared that antibiotic resistance was among the top 10 hazards to worldwide health. It is believed that penicillin-binding protein genetic alteration causes ß-lactam antibiotic resistance. Ribosomal target site alterations and active efflux pumps cause macrolide resistance. Numerous factors, including the accumulation of mutations, enhanced efflux mechanisms, and plasmid gene acquisition, cause fluoroquinolone resistance. Furthermore, despite the advancements in pneumococcal vaccinations and artificial intelligence (AI), it is not feasible for individuals to rely on them indefinitely. The ongoing development of AI for combating antimicrobial resistance necessitates more research and development efforts. A few strategies can be performed to curb this resistance issue, including providing educational initiatives and guidelines, conducting surveillance, and establishing new antibiotics targeting another part of the bacteria. Hence, understanding the resistance mechanism of S. pneumoniae may aid researchers in developing a more efficacious antibiotic in future endeavors.
Subject(s)
Anti-Infective Agents , Community-Acquired Infections , Pneumonia , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Streptococcus pneumoniae , Fluoroquinolones/pharmacology , Fluoroquinolones/therapeutic use , beta-Lactams/pharmacology , beta-Lactams/therapeutic use , Macrolides/pharmacology , Macrolides/therapeutic use , Artificial Intelligence , Drug Resistance, Bacterial , Pneumonia/drug therapy , Community-Acquired Infections/drug therapy , Community-Acquired Infections/microbiologyABSTRACT
Background: Nab-paclitaxel is formulated to address several limitations of paclitaxel. Methods: A systematic review was done of several databases and a meta-analysis with a random-effects model was conducted to assess the efficacy and safety of nab-paclitaxel in metastatic gastric cancer (MGC). Results: Included studies revealed that nab-paclitaxel provides a 30.4% overall response rate and 65.7% disease control rate in MGC patients. The overall survival was 9.65 months and progression-free survival was 4.48 months, associated with the treatment line and regimen. The highest incidence of grade 3 and higher treatment-related adverse events was for neutropenia (29.9%). Conclusion: Nab-paclitaxel provides better disease response and longer survival with manageable side effects in MGC compared with paclitaxel.
Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Paclitaxel/adverse effects , Albumins/adverse effects , Antineoplastic Combined Chemotherapy Protocols , Treatment OutcomeABSTRACT
We evaluate the effectiveness of psychological interventions for depression in people with NCDs in South Asia and explore the individual, organizational, and policy-level barriers and facilitators for the implementation and scaling up of these interventions. Eight databases (and local web pages) were searched in May 2022. We conducted random effects models to evaluate the pooled effect of psychological interventions on depression in people with NCDs. We extracted the individual, organizational, and policy level barriers and facilitators. We found five randomized control trials, nine qualitative studies, and 35 policy documents that fitted the inclusion criteria. The pooled standardized mean difference in depression comparing psychological interventions with usual care was -2.31 (95% CI, -4.16 to -0.45; p = .015, I2 = 96.0%). We found barriers and facilitators to intervention delivery, mental health appears in the policy agenda in Bangladesh and Pakistan. However, there is a lack of policies relating to training in mental health for NCD health providers and a lack of integration of mental health care with NCD care. All of the psychological interventions reported to be effective in treating depression in this population. There are important delivery and policy barriers to the implementation and scaling up of psychological interventions for people with NCDs.