Development of hybrid polyvinylpyrrolidone/carboxymethyl cellulose/collagen incorporated oregano scaffolds via direct ink write printing for potential wound healing applications.

Additive manufacturing can develop regenerative scaffolds for wound healing. 3D printing offers meticulous porosity, mechanical integrity, cell adhesion and cost-effectiveness. Herein, we prepared ink composed of carboxymethyl cellulose (CMC), polyvinylpyrrolidone (PVP), collagen, and oregano extract for the fabrication of tissue constructs. The blend was optimized to form a homogeneous ink and rheological characterization demonstrated shear thinning behavior. The scaffolds were printed using Direct Ink Write (DIW) at a flow speed of 4 mm3/s and a layer height of 0.18 mm. The fabricated scaffolds demonstrated an ultimate tensile strength (UTS) and toughness of 730 KPa and 2.72 MJ/m3, respectively. Scanning Electron Microscopy (SEM) revealed an average pore size of 300 ± 30 µm. Fourier transform infrared spectroscopy (FTIR) analysis confirmed that all materials were present. The contact angle of the composite scaffold was 68° ± 1°. Moreover, the scaffolds presented 82 % mass loss (degradation) in phosphate buffer saline (PBS) over 14 days. The composite scaffold exhibited inhibition zones of 9 mm and 12 mm against Staphylococcus aureus and Escherichia coli, respectively. The PVP/CMC/collagen/oregano 3D printed scaffolds exhibited excellent biocompatibility with the mesenchymal stem cells and humman dermal fibroblast cells, confirmed by water-soluble tetrazolium - 8 (WST-8) assay (test conducted for 7 days). The enhanced angiogenic potential of said scaffold was assesed by release of vascular endothelial growth factor followed by further validation through in-vivo CAM assay. Thus, confirming suitability for the potential wound healing application.

Electrophoretically deposited Asphaltum punjabianum (Shilajit) coatings on polyvinylalcohol/carboxymethylcellulose hydrogels.

The present study aims to develop Asphaltum punjabianum (namely Shilajit) coated Polyvinyl alcohol (PVA)/Carboxymethyl cellulose (CMC) hydrogels and examine their structural, morphological, degradation, and biological properties. Hydrogels were produced at two different concentrations: 70:30 PVA/CMC and 90:10 PVA/CMC. Following that, Shilajit was applied to the synthesized hydrogels using electrophoretic deposition for a duration of 3 min at 30 V. The scanning electron microscopy images showed that the hydrogel's surface had a regular distribution of irregular Shilajit particles. Fourier transform infrared spectroscopy (FTIR) analysis demonstrated the presence of hydrogen bonding between PVA and CMC hydrogels and Shilajit, indicating the successful deposition of Shilajit on the hydrogel. The hydrogels coated with Shilajit exhibited a strong antimicrobial activity, resulting in an inhibition zone measuring 34 mm against Escherichia coli (E. coli) and 41 mm against Staphylococcus aureus (S. aureus). The hydrogels exhibited a cell viability of 80 % with mesenchymal stem cells (MSCs), and release of the collagen II also increased. Furthermore, the PVA/CMC/Shilajit hydrogel exhibited a lower degradation rate compared to the PVA/CMC hydrogel. The results of the swelling, degradation, and drug release studies indicate that the shilajit coating is appropriate for the long-term process of tissue/cartilage regeneration.

Patients' knowledge, attitude, and practices toward unused medications in Qatar: A cross-sectional survey.

Background: Global evidence has linked unused medications and their inappropriate disposal to adverse health, economic, environmental, and ethical impacts. However, such evidence is scarce in Qatar. This study explored patients' knowledge and attitude toward unused medications and their practices toward medication supply and disposal (KAP) in Qatar.Materials and methods. Study design: A cross-sectional survey using a pretested questionnaire was performed between February 2020 and October 2020. Descriptive statistics, Man Whitney U, and Kruskal-Wallis Rank-Sum tests were applied. The Chi square test assessed the association between socio-demographic characteristics and KAP scores. Characteristics that were found significantly associated with KAP (i.e., p-values <0.05) were further included as predictor variables in the multiple linear regression model. Results: All items pertaining to patients' knowledge were found to be good (mean score > 3), except for "awareness of unwanted medication return policy" (mean score < 3), i.e., the lowest level of patient agreement (31 %) (median (M) = 3, Interquartile Range (IQR) = 3). Their attitude was generally good (mean score > 3). Conversely, their practice toward medication supply was poor (mean score < 3). Possible future use was the most reported reason (79 %) for keeping medications at home, and home trash was the most widely disposing place of unused ones (76 %). Knowledge was significantly higher among non-laborers and other occupations than among patients with no work (p < 0.001) and (p = 0.005), respectively. The attitude was significantly lower among patients with healthcare providers (HCPs) in their household than among those without (p = 0.001). Practices were also significantly lower among those aged 40-49 years and those with HCPs in their household than those aged 18-29 years (p = 0.012) and those without HCPs, (p < 0.001), respectively. Conclusions: Overall, patients' knowledge and attitude toward unused medications seem good, while their practices toward medication supply and disposal are bad. To mitigate the health, economic, and environmental impacts of unused medications, interventions including rationalizing drug supply, use, disposal, prescribing, manufacturing, and promotion are recommended.

Impact of bevacizumab on clinical outcomes and its comparison with standard chemotherapy in metastatic colorectal cancer patients: a systematic review and meta-analysis.

Background: Advances in targeted therapies have expanded the treatment options for colorectal cancer (CRC), allowing for more tailored and effective approaches to managing the disease. In targeted therapy, Bevacizumab is a commonly prescribed anti-VEGF monoclonal antibody that has a direct anti-vascular impact in cancer patients. Vascular Endothelial Growth Factors (VEGFs), especially VEGF-A, are significant agents in promoting tumour angiogenesis. Objective: To assess the impact of adding Bevacizumab to chemotherapy on progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer. Methodology: Comprehensive searches have been performed on electronic databases such as PubMed, and Google Scholar using the following terms: colorectal cancer, adenocarcinoma, Bevacizumab, chemotherapy, and monoclonal antibody. Results: In the meta-analysis, 16 out of the 24 included studies were analysed. In the final analysis, incorporating Bevacizumab with chеmothеrapy demonstrated favourable outcomes for OS with a hazard ratio (HR = 0.689,95%CI: 0.51-0.83, I² = 39%, p <0.01) and for PFS with a hazard ratio (HR = 0.77 95% CI: 0.60-0.96, I² = 54%, p < 0.01). The subgroup analysis of PFS, categorised by study dеsign (prospеctivе vs rеtrospеctivе), reveals that the Hazard Ratio (HR = 0.82, 95% CI: 0.62-0.97, I² = 21%, p < 0.01) and for OS with a hazard ratio (HR = 0.73, 95% CI: 0.52-0.86, I² = 17%, p < 0.01). Conclusion: Our findings indicate that combining Bevacizumab with chemotherapy enhances clinical outcomes and results in a significant increase in PFS and OS in patients with metastatic colorectal cancer. Positive outcomes are demonstrated by a substantial 23% increase in PFS and 31% increase in OS in patients with metastatic colorectal cancer who undergo Bevacizumab in conjunction with chemotherapy.

BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population.

BACKGROUND: Pakistan is endemic to a diverse set of parasitic, mycobacterial and viral diseases. The recognition of BCG Trained Immunity (TI) led us to postulate that the continued presence of BCG-TI may play a protective role, previously reported for both infectious and noninfectious conditions. Most of the previous studies have addressed the issue of BCG-TI in the paediatric populations. This study addressed the key issue of maintenance of BCG-TI in a wider age range (adolescent and adults) to identify the strength and quality of the immune responses. OBJECTIVE: To assess the BCG-induced recall responses in healthy individuals by cytokines secreted from the TI network and its potential role in providing cross-protection against COVID-19 and other viral infections. STUDY DESIGN: In this cross-sectional study, healthy young adults and adolescents (n = 20) were recruited from 16-40 years of age, with no prior history of TB treatment, autoimmune, or chronic inflammatory condition. METHODS: BCG-induced cytokine responses were assessed using prototypic markers for cells of the TI network [macrophages [M1 (TNFα, IFNγ), M2 (IL10)], NK (IL2), Gamma delta (γδ) T (IL17, IL4)] and SARS CoV2 IgG antibodies against RBD using short-term (12 hrs.) cultures assay. RESULTS: Significant differences were observed in the magnitude of recall responses to BCG with macrophage cytokines showing the highest mean levels of TNFα (9148 pg/ml) followed by IL10 (488 pg/ml) and IFNγ (355 pg/ml). The ratio of unstimulated vs.BCG-stimulated cytokines was 132 fold higher for TNFα, 40 fold fo r IL10, and 27 fold for IFNγ. Furthermore, SARS-CoV-2 antibodies were also detected in unstimulated plasma which showed cross reactivity with BCG. CONCLUSION: The presence of cross reactive antibodies to SARS-CoV-2 and the relative ratio of pro- and anti-inflammatory cytokines secreted by activated TI cellular network may play a pivotal role in protection in the early stages of infection as observed during the COVID-19 pandemic in the younger age groups resulting in lower morbidity and mortality.

3D-printed polyether-ether ketone/carboxymethyl cellulose scaffolds coated with Zn-Mn doped mesoporous bioactive glass nanoparticles.

Patient-specific fabrication of scaffold/implant requires an engineering approach to manufacture the ideal scaffold. Herein, we design and 3D print scaffolds comprised of polyether-ether-ketone (PEEK) and sodium-carboxymethyl cellulose (Na-CMC). The fabricated scaffold was dip coated with Zn and Mn doped bioactive glass nanoparticles (Zn-Mn MBGNs). The synthesized ink exhibit suitable shear-thinning behavior for direct ink write (DIW) 3D printing. The scaffolds were crafted with precision, featuring 85% porosity, 0.3 mm layer height, and 1.5 mm/s printing speed at room temperature. Scanning electron microscopy images reveal a well-defined scaffold with an average pore size of 600 ± 30 µm. The energy dispersive X-ray spectroscopy analysis confirmed a well dispersed/uniform coating of Zn-Mn MBGNs on the PEEK/Na-CMC scaffold. Fourier transform infrared spectroscopy approved the presence of PEEK, CMC, and Zn-Mn MBGNs. The tensile test revealed a Young's modulus of 2.05 GPa. Antibacterial assays demonstrate inhibition zone against Staphylococcus aureus and Escherichia Coli strains. Chick Chorioallantoic Membrane assays also present significant angiogenesis potential, owing to the antigenic nature of Zn-Mn MBGNs. WST-8 cell viability assays depicted cell proliferation, with a 103% viability after 7 days of culture. This study suggests that the PEEK/Na-CMC scaffolds coated with Zn-Mn MBGNs are an excellent candidate for osteoporotic fracture treatment. Thus, the fabricated scaffold can offer multifaceted properties for enhanced patient outcomes in the bone tissue regeneration.

Management, risk factors and treatment outcomes of rhegmatogenous retinal detachment associated with giant retinal tears: scoping review.

BACKGROUND: Rhegmatogenous retinal detachment (RRD) is a serious condition that occurs when the retina detaches from its underlying retinal pigment epithelium. RRDs associated with giant retinal tears (GRTs) are caused by retinal tears at least 90° or one-quarter of the circumferential extent. This scoping review systematically identifies and summarizes clinical studies evaluating surgical techniques for the management of GRT-related RRDs, discusses functional and visual outcomes and the risk factors affecting treatment outcomes. METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, Google Scholar, and Springer Link databases were searched for relevant papers (from January 2001 to March 2023). Studies that were published in the English language and reported the risk factors, management, and treatment outcomes of GRT-related RRDs were included in the review. The outcome measures included anatomic success rates, changes in BCVA (logMAR) from baseline to the final follow-up, and adverse events. RESULTS: A total of 11,982 articles were identified. After the title and abstract review, 71 studies were deemed eligible for full-text review. Thirty-six studies that met the eligibility criteria were included in the final review. Four surgical techniques were identified: pars plana vitrectomy (PPV), combined PPV and scleral buckling, scleral buckling alone, and pneumatic retinopexy. Various types of tamponades, including gas, silicone oil, and air, have been used. PPV was the most commonly used surgical technique in 33.1-100% of patients. Among the 20 studies that used PPV alone, 17 were associated with preoperative PVR. In addition, scleral buckling alone or in combination with PPV was reported as a treatment option in 10 studies, with 2-100% of patients experiencing scleral buckling alone and 13.6-100% experiencing combined PPV and complementary scleral buckling. Primary anatomic success (PAS) was achieved with retinal reattachment via a single operation with no residual tamponade, whereas final anatomic success (FAS) was achieved via more than one operation with no residual tamponade. Reported single surgery anatomic success (SSAS) rates range from 65.51 to 100%. The preoperative best-corrected visual acuity (BCVA) ranged from 0.067 to 2.47 logMAR, whereas the postoperative BCVA ranged from 0.08 to 2.3 logMAR. An improvement in visual acuity was observed in 29 studies. Cataracts (3.9-28.3%) were the most common postoperative complication, followed by high IOP (0.01-51.2%) and PVR (0.8-31.57%). CONCLUSION: PPV is the most common surgical technique, and currently microincision vitrectomy surgery (MIVS) systems are commonly employed. Silicone oil is the most frequently used tamponade in RRD repair. Risk factors for GRT-related RRD include age, sex, lens status, high myopia status, proliferative vitreoretinopathy (PVR), presenting visual acuity, the extent of the GRT and retinal detachment, and macular involvement. Future research areas include guidelines to reduce variability in the reporting of surgical methodology, choice of tamponades, and reporting of functional and visual outcomes to inform the best therapeutic interventions in GRT-related RRD.

Oxidized alginate-gelatin (ADA-GEL)/silk fibroin/Cu-Ag doped mesoporous bioactive glass nanoparticle-based hydrogels for potential wound care treatments.

The present work focuses on developing 5% w/v oxidized alginate (alginate di aldehyde, ADA)-7.5% w/v gelatin (GEL) hydrogels incorporating 0.25% w/v silk fibroin (SF) and loaded with 0.3% w/v Cu-Ag doped mesoporous bioactive glass nanoparticles (Cu-Ag MBGNs). The microstructural, mechanical, and biological properties of the composite hydrogels were characterized in detail. The porous microstructure of the developed ADA-GEL based hydrogels was confirmed by scanning electron microscopy, while the presence of Cu-Ag MBGNs in the synthesized hydrogels was determined using energy dispersive x-ray spectroscopy. The incorporation of 0.3% w/v Cu-Ag MBGNs reduced the mechanical properties of the synthesized hydrogels, as investigated using micro-tensile testing. The synthesized ADA-GEL loaded with 0.25% w/v SF and 0.3% w/v Cu-Ag MBGNs showed a potent antibacterial effect againstEscherichia coliandStaphylococcus aureus. Cellular studies using the NIH3T3-E1 fibroblast cell line confirmed that ADA-GEL films incorporated with 0.3% w/v Cu-Ag MBGNs exhibited promising cellular viability as compared to pure ADA-GEL (determined by WST-8 assay). The addition of SF improved the biocompatibility, degradation rate, moisturizing effects, and stretchability of the developed hydrogels, as determinedin vitro. Such multimaterial hydrogels can stimulate angiogenesis and exhibit desirable antibacterial properties. Therefore further (in vivo) tests are justified to assess the hydrogels' potential for wound dressing and skin tissue healing applications.

Tuberculosis (TB) treatment challenges in TB-diabetes comorbid patients: a systematic review and meta-analysis.

BACKGROUND: The Directly Observed Treatment-Short Course (DOTS) Programme was implemented by WHO and includes a combination of four anti-tuberculosis (TB) drugs (isoniazid, pyrazinamide, ethambutol and rifampicin) for a period of six months to eradicate the TB infection completely. Diabetes mellitus (DM) is recognized as one of a strong contributor of TB according to World Health Organization (WHO). The presence of diabetes mellitus type 2 (DM type 2) makes TB treatment complicated. Thus, the objective of the current meta-analysis was to identify and quantify the impact of type 2 DM on treatment outcomes of TB patients treated under the DOTS Programme. METHODS: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Through a systematic review of relevant literature, we focused on studies investigating treatment outcomes including extended treatment duration and recurrence for individuals with both TB and DM undergoing DOTS therapy. The extracted information included study designs, sample sizes, patient characteristics and reported treatment results. RESULTS: In 44 studies from different parts of the world, the pooled HR for the impact of DM on extended treatment duration and reoccurrence were HR 0.72, 95% CI 0.56-0.83, p < .01 and HR 0.93, 95% CI 0.70-1.04, p = .08, respectively. The pooled HR for impact of DM on composite TB treatment outcomes was calculated as 0.76 (95% CI 0.60-0.87), p < .01 with an effect size of 41.18. The heterogeneity observed among the included studies was moderate (I2 = 55.79%). CONCLUSIONS: A negative impact of DM was found on recurrence and extended treatment duration in TB patients treated with DOTS therapy. DM type 2 is responsible for the TB treatment prolongation and TB recurrence rates. By implementing effective management strategies and advancing research, the challenges can be mitigated, arising due to the complex interaction between DM and TB.

A qualitative study exploring community pharmacists' awareness, attitudes and perceptions about drive-thru community pharmacy service in Malaysia during COVID-19.

Introduction: Drive-thru services are not given sufficient focus in the community pharmacy setting which was highlighted during COVID-19, particularly in Malaysia. This study aimed to explore the community pharmacists' perspectives regarding drive-thru community pharmacy service during COVID-19 in Malaysia. Methods: In-depth online semi-structured individual interviews were conducted among 25 community pharmacists working in Malaysia. All interviews were conducted between March 2022 and May 2022 and were audio-recorded and transcribed verbatim, and then analysed by thematic analysis. Results: Thematic analysis yielded seven major themes, 1-familiarity with drive-thru community pharmacy service during COVID-19, 2-willingness toward this service during COVID-19, 3-perceived benefits toward drive-thru community pharmacy service during COVID-19, 4-perceived disadvantages toward this service, 5-barriers toward drive-thru community pharmacy service, 6-factors affecting the preference toward this service, and 7-facilitators to drive-thru community pharmacy service. Enhancing social distancing and preventing the spread of COVID-19 were the major perceived benefits of this service during COVID-19 as reported by participants. Conclusion: Overall, community pharmacists reported positive attitudes toward drive-thru community pharmacy service during COVID-19. However, concerns about poor communication between the pharmacist and the patient, limited counselling, and dispensing errors were acknowledged. These concerns would need to be addressed to improve the provision of drive-thru community pharmacy service.

Low serum HDL-cholesterol is associated with raised tumor necrosis factor-alpha during ENL reactions

The concentrations of serum lipids and tumor necrosis factor (TNF) were measured in leprosy patients across the spectrum of the disease and in erythema nodosum leprosum (ENL) patients at the onset of the reaction and after the reaction had clinically subsided. Lepromatous/borderline lepromatous (LL/BL) patients had significantly higher serum triglyceride and lower HDL-cholesterol levels; there was no such change in the tuberculoid/borderline tuberculoid (TT/BT) patients. The household contacts (HC) of the LL/BL patients also had significantly lower serum HDL levels. ENL patients during the acute phase of the reaction had significantly lower total, LDL-, HDL-cholesterol levels compared to the stable LL/BL patients, and these changes were reversible to pre-ENL levels after the reaction had subsided. Serum TNF levels were significantly higher in household contacts and in LL/BL patients but were not statistically different in TT/BT patients. Serum TNF levels were also significantly higher during the acute phase of ENL, and declined after the clinical remission of the reaction to levels comparable with those of LL/BL patients. There was a significant negative correlation between serum TNF and HDL-cholesterol levels during and after ENL reaction. However, there was no such correlation between TNF and total or LDL-cholesterol levels in ENL patients. Our results suggest that the changes in HDL-cholesterol metabolism are a specific part of the host response to lepromatous leprosy and to the ENL reaction and may be mediated by increased TNF production.

Quantitative antibody ELISA for leprosy

Quantitative enzyme-linked immunosorbent assays (ELISAs) were established to measure IgM and IgG antibody levels to soluble Mycobacterium leprae sonicate (CD60) and to the synthetic disaccharide antigen based on the phenolic glycolipid-I antigen of M. leprae coupled to bovine serum albumin in 46 leprosy patients. Separate reference pools for IgM and IgG antibody were established. The reciprocal of the antibody titer was expressed as the number of arbitrary units in the reference pools which was subsequently used as the calibrator for assessment of units in individual test sera. The dose-response relationship for both IgM and IgG was highly specific and reproducible for both isotypes, as indicated by the intra- and inter-assay coefficients of variation. The distribution of antibody levels are in general agreement with the results from previous studies against different M. leprae antigens. The lepromatous group showed 10- to 100-fold higher IgM antibodies to both the soluble sonicate antigen and the disaccharide as compared to the control group. Very low to undetectable levels of IgM antibodies were observed in the tuberculoid group of leprosy patients. IgG antibodies, on the other hand, were not only present but showed considerable overlap with the lepromatous patient group. Optimized ELISAs, such as the one described in this study, would allow one to address issues such as antibody changes with treatment, antigen clearance, and correlation with other immune parameters associated with disease pathogenesis and protection