Saraiki language characters dataset (SLCD).

About 26 million people worldwide use the Saraiki language [1]. In the southern part of Punjab and Sindh, Saraiki language is extensively spoken. One of the most important Saraiki cultural hubs is Dera Ghazi Khan. In Dera Ghazi Khan, the Saraiki language is spoken by over 90 % of the population. Calligraphers use a sophisticated script to write this language. Despite the vast body of Optical Character Recognition (OCR) literature and research dedicated to other languages, a fully functional OCR system is still needed for Saraiki language [2,3]. This work presents a genuine dataset of Saraiki handwritten characters, consisting of 50,000 scanned photos, and makes it accessible to the public for use. All of the photographs include handwritten text contributed by teachers and students from Pak-Austria Fachhochschule for Applied Sciences and Technology, Pakistan. Around 1000 people, roughly half men and half women, contributed in writing this text. For scientific research, the dataset will be made accessible to the general public.

Factors necessary for entrustment decision-making in surgical operating rooms: A modified Delphi study.

Objective: Resident autonomy in an operation theatre has been directly linked with patient safety in healthcare. The objective of this study was to identify the factors necessary for making resident-entrustment decisions from the perspective of a supervisor/consultant viewpoint. The second objective was to develop a checklist for assessing resident readiness for independent work. Materials and methods: This study employed a mixed-method Delphi approach. In the first stage, a comprehensive literature review and a qualitative exploratory study produced a list of factors related to residents. The second phase involved content validation by a panel of experts, followed by a two-round Delphi study with 20 expert panelists. Results: A total of 49 resident-related factors for entrustment were identified, which were reduced to 46 after content validation. During Delphi Round I, 17 factors were fully accepted, 7 were rejected and 22 items were partially accepted. Out of the 39 items sent to Delphi Round II, 23 items were accepted and 16 were rejected. A final 23-item checklist was formed based on the following factors; 6 Cognitive (knowledgeable, risk manager, safe doctor, general manager, field of interest, communicator), 5 Psychomotor (past performer, competent, ability to pick critical findings, ability to act situationally, decision maker) and 12 affective (responsible, leader, honest, empathetic, ethical, receptive, humble, emotionally intelligent, motivated, accountable, team player, disciplined) factors. Conclusion: The study resulted in the formation of a checklist based on the factors necessary for entrustment decision-making in surgical operating rooms. Some of the novel contextual factors were 'general manager', 'field of interest', 'ability to pick critical findings', 'accountable', 'risk manager', and 'past performer'. This framework offers a guideline for supervisors and residents to evaluate progress throughout the residency program. The developed tool demonstrates good content validity and is suitable for entrustment assessment following construct validation.

A bioactive and biodegradable vitamin C stearate-based injectable hydrogel alleviates experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory joint disorder affecting nearly 1% of the global population. In RA, synovial joints are infiltrated by inflammatory mediators and enzymes, leading to articular cartilage deterioration, joint damage, and bone erosion. Herein, the 9-aminoacridine-6-O-stearoyl-L-ascorbic acid hydrogel (9AA-SAA hydrogel) was formulated by the heat-cool method and further characterized for surface charge, surface morphology, rheology, and cytocompatibility. Furthermore, we evaluated the therapeutic efficacy of the 9AA-SAA hydrogel, an enzyme-responsive drug delivery system with on-and-off switching capabilities based on disease severity against collagen-induced experimental arthritis in Wistar rats. The anti-inflammatory action of the US FDA-approved drug 9-aminoacridine (9AA) was revealed which acted through nuclear receptor subfamily 4 group A member 1 (NR4A1), an anti-inflammatory orphan nuclear receptor that inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Furthermore, we have explored the role of ascorbic acid, an active moiety of 6-O-stearoyl-L-ascorbic acid (SAA), in promoting the production of collagen production through ten-eleven translocation-2 (TET2) upregulation. Targeting through NR4A1 and TET2 could be the probable mechanism for the treatment of experimental arthritis. The combination of 9AA and ascorbic acid demonstrated enhanced therapeutic efficacy in the 9AA-SAA hydrogel, significantly reducing the severity of experimental arthritis. This approach, in contrast to existing treatments with limited effectiveness, presents a promising and more effective strategy for RA treatment by mitigating inflammation in experimental arthritis.

Experimental Verification of Geometric Changes Caused by the Release of Residual Stresses for Large-Scale Welded Frames.

This paper presents geometric analyses of welded frames after free relaxing and vibratory stress relief (VSR). The tested frames were components of a prototype packaging machine. Two types of relaxation were carried out to remove stresses introduced as a result of the welding process. One of the frames was subjected to free relaxation, while the other one was subjected to accelerated vibration relaxation. Detection of the frame geometry changes was performed using a photogrammetric system. In addition, an evaluation of the geometry change was conducted for fifteen variants of a steel frame support. A comparative analysis of the geometric deviations of the frames after free and vibratory stress relief confirmed the assumption that the frame post vibration stress relief better reproduces the nominal dimensions. Nevertheless, it should be emphasized that after vibratory stress relief, the frame is not subject to further deformation, which is a desirable effect. In the case of free relaxing, the frame undergoes dimensional changes in a random manner. In summary, carrying out accelerated vibratory stress relief allows for control of spontaneous dimensional changes in the designed frame of a packaging machine resulting from spontaneous relaxation of stresses arising from the welding process. The shortening of the relaxation process of the welded frame is also an unquestionable advantage.

A chlorogenic acid-conjugated nanomicelle attenuates disease severity in experimental arthritis.

Rheumatoid arthritis (RA) is a systemic immune disorder marked by synovitis, bone damage, and cartilage erosion, leading to increased socio-economic burdens and reduced quality of life. Despite its unknown cause, advancements in understanding its pathophysiology have facilitated novel therapeutic approaches. Current treatments, including disease-modifying anti-rheumatic drugs (DMARDs) and biologics, often result in low efficacy and unnecessary side effects. To address the limitations of these drugs, carrier-based drug delivery systems, such as nanomicelles, have emerged as a promising solution. In this study, nanomicelles were synthesised utilizing PLGA (poly(lactic-co-glycolic acid)) as a backbone; this backbone is conjugated with chlorogenic acid (CGA), which is known for suppressing inflammation, and incorporates methotrexate (MTX), a model drug that is established for RA treatment. The nanomicelles were extensively characterized in terms of size, charge, drug loading, and drug-release behaviour. The in vivo assessment of MTX-PLGA-b-CGA nanomicelles in a collagen-induced arthritis model demonstrated a remarkable reduction in joint swelling, cartilage erosion, and disease severity. Furthermore, histological findings confirmed cartilage integrity and reduced expression of key pro-inflammatory markers, including receptor activator of nuclear factor kappa beta ligand (RANKL) and tumor necrosis factor (TNF-α). The approach based on the MTX-PLGA-b-CGA nanomicelles presents a biocompatible and potentially effective therapeutic strategy for management of the severity and progression of RA, providing a hopeful alternative for RA treatment.

Sophorin mitigates flutamide-induced hepatotoxicity in wistar rats.

Flutamide is frequently used in the management of prostate cancer, hirsutism, and acne. It is a non-steroidal anti-androgenic drug and causes hepatotoxicity. The current study's objective is to evaluate sophorin's hepatoprotective effectiveness against flutamide-induced hepatotoxicity in Wistar rats. Sophorin is a citrus flavonoid glycoside, also known as rutin, which is a low molecular weight polyphenolic compound with natural antioxidant properties and reported to have promising hepatoprotective efficacy. In this study, sophorin was used at a dose of 100 mg/kg body weight in purified water via oral route for 4 week daily whereas, flutamide was used at a dose of 100 mg kg/b.wt for 4 weeks daily in 0.5% carboxy methyl cellulose (CMC) through the oral route for the induction of hepatotoxicity. Flutamide administration leads to enhanced reactive oxygen species (ROS) generation, an imbalance in redox homeostasis and peroxidation of lipid resulted in reduced natural antioxidant level in liver tissue. Our result demonstrated that sophorin significantly abrogate flutamide induced lipid peroxidation, protein carbonyl (PC), and also significantly increasesed in enzymatic activity/level of tissue natural antioxidant such as reduced glutathione(GSH), glutathione reductase(GR), catalase, and superoxide dismutase(SOD). Additionally, sophorin reduced the activity of cytochrome P450 3A1 in liver tissue which was elevated due to flutamide treatment. Furthermore, sophorin treatment significantly decreased the pro-inflammatory cytokines (TNF-α and IL-6) level. Immunohistochemical analysis for the expression of inflammatory proteins (iNOS and COX-2) in hepatic tissue was decreased after sophorin treatment against flutamide-induced hepatotoxicity. Moreover, sophorin suppressed the infiltration of mast cells in liver tissue which further showed anti-inflammatory potential of sophorin. Our histological investigation further demonstrated sophorin's hepatoprotective function by restoring the typical histology of the liver. Based on the aforementioned information, we are able to come to the conclusion that sophorin supplementation might benefit wistar rats with flutamide-induced hepatic damage by reducing oxidative stress and hepatocellular inflammation.

Biomaterial-based combinatorial approach of aescin-comprised zein-coated gelatin nanoparticles alleviates synovial inflammation in experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that mostly affects joints. Although RA therapy has made significant progress, difficulties including extensive medication metabolism and its quick clearance result in its inadequate bioavailability. The anti-inflammatory effect of zein was reported with other medications, but it has certain limitations. There are reports on the anti-oxidant and anti-inflammatory effect of aescin, which exhibits low bioavailability for the treatment of rheumatoid arthritis. Also, the combinatorial effect of zein with other effective drug delivery systems is still under investigation for the treatment of experimental collagen-induced rheumatoid arthritis. The focus of this study was to formulate and define the characteristics of zein-coated gelatin nanoparticles encapsulated with aescin (Ze@Aes-GNPs) and to assess and contrast the therapeutic effectiveness of Ze@Aes-GNPs towards collagen-induced RA in Wistar rats. Nanoprecipitation and the layer-by-layer coating process were used to fabricate Ze@Aes-GNPs and their hydrodynamic diameter was determined to be 182 nm. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to further validate the size, shape, and surface morphology of Ze@Aes-GNPs. When tested against foreskin fibroblasts (BJ), these nanoparticles demonstrated significantly high cytocompatibility. Both Aes and Ze@Aes-GNPs were effective in treating arthritis, as shown by the decreased edoema, erythema, and swelling of the joints, between which Ze@Aes-GNPs were more effective. Further, it was demonstrated that Aes and Ze@Aes-GNPs reduced the levels of oxidative stress (articular elastase, lipid peroxidation, catalase, superoxide dismutase and nitric oxide) and inflammatory indicators (TNF-α, IL-1ß and myeloperoxidase). The histopathology findings further demonstrated that Ze@Aes-GNPs considerably reduced the infiltration of inflammatory cells at the ankle joint cartilage compared to Aes. Additionally, immunohistochemistry examination showed that treatment with Ze@Aes-GNPs suppressed the expression of pro-inflammatory markers (COX-2 and IL-6) while increasing the expression of SOD1. In summary, the experiments indicated that Aes and Ze@Aes-GNPs lowered the severity of arthritis, and critically, Ze@Aes-GNPs showed better effectiveness in comparison to Aes. This suppression of oxidative stress and inflammation was likely driven by Aes and Ze@Aes-GNPs.

Evaluation of the Efficacy of LASER, Desensitizing Agents, and their Combined Effect on Dentinal Hypersensitivity in Bicuspids: In Vitro Study.

Aim: This study aimed to know the potential of diode light amplification by stimulated emission of radiation (LASER) and desensitizing agents on blocking the dentinal tubules, which may further help in reducing the most common dental problem named dentinal hypersensitivity (DH). Materials and Methods: Sixty human permanent bicuspids were selected, and preparation was performed in the cervical region measuring 2.5 mm × 2.5 mm × 2.5 mm, followed by acid etching for 15 seconds. These are then divided according to the groups mentioned: group 1-nano-hydroxyapatite (HA) was applied for 15 minutes; group 2-biosilicate was applied for 15 minutes; group 3-diode LASER application was performed twice for 60 seconds in noncontact mode; group 4-nano-HA plus diode LASER application; and group 5-biosilicate plus diode LASER application. The same procedure was followed on the 1st, 7th, and 14th days and then rinsed and stored in artificial saliva, and the saliva was changed every 24 hours. The dentinal tubular occlusion was observed under a scanning electron microscope (SEM) after the 14th day. Result: The maximum dentinal tubular occlusion was observed in group 4, where nano-HA and diode LASER application was performed. Conclusion: All the investigated treatment groups have promising occluding potential, but the maximum was found in group 4 >group 5 >group 3 >group 1 >group 2. LASER plus desensitizing together prove to be potent and effective in reducing dentinal tubular diameter.

Resilience and academic performance: Exploring the link in dental students.

This study aims to assess the correl ation between t he resilience level of dental students (preclinical and clinical years) and its effects on their academic performance. It is a correlational research study that was carried out on second, third, and final-yea r denta l students at Lahore Medical & Dental College, Lahore. Academic resilience was judged by using the academic resilience scale (ARS-30). The correlation between resilience and academic performance was e s tablished by appl ying the bivar iate Pea rso n correlation. The mean age of the stude nt s was 2 1.49±1.39 years. Among 196 dental students from different years, 132 (67.35%) were females and 64(32.65%) were males. A strong p ositive co rrelati on was obser ved bet ween the academic performance and resilience of denta l students, i.e. r=0.774. From the results, it can be concluded that there is a positive correlation between academic resilience and academic performance among dental students.

Effect of the shape of flapping airfoils on aerodynamic forces.

The rapid exhaustion of fossil fuels and the ozone depletion caused by the excessive usage of the fossil fuels has prompted researchers to look towards bioinspired designs for both propulsion and energy extraction purposes. Limited amount of work has been done to present the effects of airfoil shape on the aerodynamic forces on flapping foils. In this paper, we examine in detail the effect of airfoil camber and its position on flapping foil performance in both energy extraction and propulsion regimes. We also examine the effect of reflex camber on flapping foil performance in both flow regimes. In total, 42 airfoils are analyzed using the NACA 4 and 5-series cross-sections. The man objective of this research is to identify a trend, between airfoil shape and aerodynamic forces. The database created as a result will be used in the future work for designing a hydrokinetic turbine and a bio-inspired unmanned aerial vehicle. The results from the numerical simulations indicate that the airfoil shape has significant effects on the time averaged drag force on the airfoil in both flow regimes. However, the time averaged lift force remains negligible for all cases.

Virtual patients versus standardized patients for improving clinical reasoning skills in ophthalmology residents. A randomized controlled trial.

BACKGROUND: History taking and clinical reasoning are important skills that require knowledge, cognition and meta-cognition. It is important that a trainee must experience multiple encounters with different patients to practice these skills. However, patient safety is also important, and trainees are not allowed to handle critically ill patients. To address this issue, a randomized controlled trial was conducted to determine the effectiveness of using Virtual Patients (VP) versus Standardized Patients (SP) in acquiring clinical reasoning skills in ophthalmology postgraduate residents. METHODS: Postgraduate residents from two hospitals in Lahore, Pakistan, were randomized to either the VP group or the SP group and were exposed to clinical reasoning exercise via the VP or SP for 30 min after the pretest. This was followed by a posttest. One month after this activity, a follow-up posttest was conducted. The data were collected and analysed using IBM-SPSS version 25. Repeated measures ANOVA was used to track the effect of learning skills over time. RESULTS: The mean age of the residents was 28.5 ± 3 years. The male to female ratio was 1:1.1. For the SP group, the mean scores were 12.6 ± 3.08, 16.39 ± 3.01 and 15.39 ± 2.95, and for the VP group, the mean scores were 12.7 ± 3.84, 16.30 ± 3.19 and 15.65 ± 3.18 for the pretest, posttest and follow-up posttest, respectively (p value < 0.00). However, the difference between the VP and SP groups was not statistically significant (p = 0.896). Moreover, there was no statistically significant difference between the VP and SP groups regarding the retention of clinical reasoning ability. In terms of learning gain, compared with the VP group, the SP group had a score of 51.46% immediately after clinical reasoning exercise as compared to VP group, in which it was 49.1%. After one month, it was 38.01 in SP and 40.12% in VP group. CONCLUSION: VPs can be used for learning clinical reasoning skills in postgraduate ophthalmology residents in a safe environment. These devices can be used repeatedly without any risk to the real patient. Although similarly useful, SP is limited by its nonavailability for repeated exercises.

Formulation of Folate Receptor-Targeted Silibinin-Loaded Inhalable Chitosan Nanoparticles by the QbD Approach for Lung Cancer Targeted Delivery.

Aim: Targeted delivery of chemotherapeutics by functionalized nanoparticles exhibits a wonderful prospect for cancer treatment. The main objective of this research was to develop folate receptor-targeted silibinin (SB)-loaded inhalable polymeric nanoparticles (FA-CS-SB-NPs) for the treatment of lung cancer. Method: The qbD approach was implemented to prepare SB-loaded nanoparticles. Folic acid was conjugated by electrostatic conjugation in an optimized batch. The therapeutic potentials of formulations were determined using a lung cancer cell-bearing rat model. Result: Optimized formulation exhibited a spherical surface with a mean particle size of 275 ± 1.20 nm, a PDI of 0.234 ± 0.07, a ζ-potential of 32.50 ± 0.21, an entrapment efficiency of 75.52 ± 0.87%, and a CDR of 63.25 ± 1.21% at 48 h. Aerodynamic behaviors such as the mass median aerodynamic diameter (MMAD) and geometric size distribution (GSD) were found to be 2.75 ± 1.02 and 3.15 ± 0.88 µm, respectively. After 24 h of incubation with FA-CS-SB-NPs, the IC50 value was found to be 24.5 g/mL. FA-SB-CS-NPs maintained a significantly higher deposition of SB in lung tissues. Conclusions: Thus, the noninvasive nature and target specificity of FA-CS-SB-NPs pave the way for pulmonary delivery for treating lung cancer.

Impact of emotional intelligence in resolving clinical conflicts among postgraduate residents of surgery.

Background & Objective: Emotional intelligence (EI) can become a vital tool for resolving clinical conflicts (CC) in surgery. The postgraduate residents focus on the technical skills and undermine the soft skills required for their better training. Our aim was to determine the EI of postgraduate resident (PGR) years one & two in General and Orthopedic Surgery. The CC in their workplace and how they use their EI to resolve these conflicts. Methods: This mixed-method study was conducted from March 10, 2019 to May 28, 2020 at Departments of General and Orthopedic Surgery, Mayo Hospital, Lahore. The study was conducted in two phases 1 & 2. In Phase-1, one hundred PGR years one & two were administered the Mayor-Salovey-Caruso Emotional Intelligence test (MSCEIT) to measure EI. In phase-2, semi-structured in-depth interviews of 10 PGRs five with high and five with low EI were conducted to determine the CC and use of EI to resolve the CC at the workplace. A thematic analysis was done. Results: Out of 100 PGR, the mean EI score was 46.25±14.8 with a maximum score of 75.4, and a minimum score of 18.16 (p-value =0.775). Ninety-one (91%) have not improving EI, and 09 (09%) have considered developing EI. Five themes in four settings, including emergency, ward, elective operation theatre, and outpatient department (OPD) were determined. The emerged themes for the CC were nepotism, gender biases, burnout, lack of professionalism, and toxic culture. The following were CC management strategies: self-study, deceit, gender affinity, performing attention-attaining work, aggrieved reaction and being disgruntled when alone. Conclusion: None of the PGR was emotionally intelligent in overall grades, as well as a particular aspect of MSCEIT.

Digital teaching: Developing a structured digital teaching competency framework for medical teachers.

AIM: To explore the core competencies needed on part of the medical and dental teachers to carry out effective digital teaching for their students. METHODS: It was a qualitative study which employed phenomenological approach. The data were collected from 12 teachers who were purposively selected for semi-structured interviews. They were all expert digital teachers. The data were transcribed verbatim, coded and analyzed thematically. Textural and structural description of the themes helped to develop a new competency framework. RESULTS: The data yielded 47 selective codes with 15 sub-themes and five themes. The emergent themes included general digital competencies, specific digital teaching competencies, mastery of the subject matter, mastery of pedagogical strategies and proficiency in using innovative digital technologies for teaching. The themes 1, 2 and 5 relate to digital competencies only whereas the themes 3 and 4 are generic competencies which apply to both digital and non-digital teaching. These generic competencies form the basis of all kinds of teaching, hence equally important for digital teaching. CONCLUSION: Medical teachers should possess diverse digital competencies. The competency framework that emerged in the current research encompasses the essential attributes that should be included in any future training program aiming at the digital capacity building of the teachers. This will keep them primed for effective digital teaching. Given its crucial importance, the digital teaching competency should be considered as a cross-cutting competency that applies to almost all of the famous eight roles of medical teacher.

Oral delivery of aescin-loaded gelatin nanoparticles ameliorates carbon tetrachloride-induced hepatotoxicity in Wistar rats.

AIM: The liver plays a crucial role in biotransformation but it is susceptible to chemical-induced damage, known as hepatotoxicity. Traditional therapies for protecting the liver face significant challenges, including poor bioavailability, off-target effects, adverse reactions, drug breakdown, and inadequate uptake. These issues emphasize the need for precise, targeted therapeutic approaches against hepatotoxicity. MATERIALS AND METHODS: The objective of our research was to develop a customized, biocompatible, and biodegradable nanodrug delivery system for hepatoprotection. We chose collagen hydrolyzed protein, or gelatin, as the base material and utilized solvent evaporation and nanoprecipitation methods to create nanoparticles with size ranging from 130 to 155 nm. The resulting nanoparticles exhibited a spherical and smooth surface, as confirmed by scanning and transmission electron microscopy. KEY FINDINGS: Bioactive aescin (AES), into these gelatin nanoparticles (AES-loaded gel NPs), we tested these nanoparticles using a hepatotoxicity model. The results were indicating a significant reduction in the levels of key biomolecules, including NF-κB, iNOS, BAX, and COX-2 and decreased serum levels of enzymes ALT and AST. This reduction correlated with a notable alleviation in the severity of hepatotoxicity. Furthermore, the treatment with AES-loaded gel NPs resulted in the downregulation of several inflammatory and liver-specific biomarkers, including nitrite, MPO, TNF-α, and IL-6. SIGNIFICANCE: In summary, our study demonstrates that the AES-loaded gel NPs were markedly more effective in mitigating experimental hepatotoxicity when compared to the free aescin. The nanoparticles exhibited a propensity for suppressing liver damage, showcasing the potential of this targeted therapeutic approach for safeguarding the liver from harmful chemical insults.

A genetically modulated Toll-like-receptor-tolerant phenotype in peripheral blood cells of children with multisystem inflammatory syndrome.

Dysregulated innate immune responses contribute to multisystem inflammatory syndrome in children (MIS-C), characterized by gastrointestinal, mucocutaneous, and/or cardiovascular injury occurring weeks after SARS-CoV-2 exposure. To investigate innate immune functions in MIS-C, we stimulated ex vivo peripheral blood cells from MIS-C patients with agonists of Toll-like receptors (TLR), key innate immune response initiators. We found severely dampened cytokine responses and elevated gene expression of negative regulators of TLR signaling. Increased plasma levels of zonulin, a gut leakage marker, were also detected. These effects were also observed in children enrolled months after MIS-C recovery. Moreover, cells from MIS-C children carrying rare genetic variants of lysosomal trafficking regulator (LYST) were less refractory to TLR stimulation and exhibited lysosomal and mitochondrial abnormalities with altered energy metabolism. Our results strongly suggest that MIS-C hyperinflammation and/or excessive or prolonged stimulation with gut-originated TLR ligands drive immune cells to a lasting refractory state. TLR hyporesponsiveness is likely beneficial, as suggested by excess lymphopenia among rare LYST variant carriers. Our findings point to cellular mechanisms underlying TLR hyporesponsiveness; identify genetic determinants that may explain the MIS-C clinical spectrum; suggest potential associations between innate refractory states and long COVID; and highlight the need to monitor long-term consequences of MIS-C.

Fetal loss and long-term maternal morbidity and mortality: A systematic review and meta-analysis.

BACKGROUND: Evidence suggests common pathways between pregnancy losses and subsequent long-term maternal morbidity, rendering pregnancy complications an early chronic disease marker. There is a plethora of studies exploring associations between miscarriage and stillbirth with long-term adverse maternal health; however, these data are inconclusive. METHODS AND FINDINGS: We systematically searched MEDLINE, EMBASE, AMED, BNI, CINAHL, and the Cochrane Library with relevant keywords and MeSH terms from inception to June 2023 (no language restrictions). We included studies exploring associations between stillbirth or miscarriage and incidence of cardiovascular, malignancy, mental health, other morbidities, and all-cause mortality in women without previous pregnancy loss. Studies reporting short-term morbidity (within a year of loss), case reports, letters, and animal studies were excluded. Study selection and data extraction were performed by 2 independent reviewers. Risk of bias was assessed using the Newcastle Ottawa Scale (NOS) and publication bias with funnel plots. Subgroup analysis explored the effect of recurrent losses on adverse outcomes. Statistical analysis was performed using an inverse variance random effects model and results are reported as risk ratios (RRs) with 95% confidence intervals (CIs) and prediction intervals (PIs) by combining the most adjusted RR, odds ratios (ORs) and hazard ratios (HRs) under the rare outcome assumption. We included 56 observational studies, including 45 in meta-analysis. There were 1,119,815 women who experienced pregnancy loss of whom 951,258 had a miscarriage and 168,557 stillbirth, compared with 11,965,574 women without previous loss. Women with a history of stillbirth had a greater risk of ischaemic heart disease (IHD) RR 1.56, 95% CI [1.30, 1.88]; p < 0.001, 95% PI [0.49 to 5.15]), cerebrovascular (RR 1.71, 95% CI [1.44, 2.03], p < 0.001, 95% PI [1.92, 2.42]), and any circulatory/cardiovascular disease (RR 1.86, 95% CI [1.01, 3.45], p = 0.05, 95% PI [0.74, 4.10]) compared with women without pregnancy loss. There was no evidence of increased risk of cardiovascular disease (IHD: RR 1.11, 95% CI [0.98, 1.27], 95% PI [0.46, 2.76] or cerebrovascular: RR 1.01, 95% CI [0.85, 1.21]) in women experiencing a miscarriage. Only women with a previous stillbirth were more likely to develop type 2 diabetes mellitus (T2DM) (RR: 1.16, 95% CI [1.07 to 2.26]; p < 0.001, 95% PI [1.05, 1.35]). Women with a stillbirth history had an increased risk of developing renal morbidities (RR 1.97, 95% CI [1.51, 2.57], p < 0.001, 95% [1.06, 4.72]) compared with controls. Women with a history of stillbirth had lower risk of breast cancer (RR: 0.80, 95% CI [0.67, 0.96], p-0.02, 95% PI [0.72, 0.93]). There was no evidence of altered risk of other malignancies in women experiencing pregnancy loss compared to controls. There was no evidence of long-term mental illness risk in women with previous pregnancy losses (stillbirth: RR 1.90, 95% CI [0.93, 3.88], 95% PI [0.34, 9.51], miscarriage: RR 1.78, 95% CI [0.88, 3.63], 95% PI [1.13, 4.16]). The main limitations include the potential for confounding due to use of aggregated data with variable degrees of adjustment. CONCLUSIONS: Our results suggest that women with a history of stillbirth have a greater risk of future cardiovascular disease, T2DM, and renal morbidities. Women experiencing miscarriages, single or multiple, do not seem to have an altered risk.

Curriculum implementation challenges: Development and validation of an integrated curriculum implementation challenges tool.

Objective: To develop an instrument to identify the challenges faced by faculty while implementing an integrated curriculum in an undergraduate dentistry program. Methods: The study was conducted between September 2020 and October 2021 at the University College of Medicine and Dentistry (UCMD), University of Lahore (UOL). A preliminary questionnaire, developed through literature review and faculty interviews was sent to 10 medical education experts for content validation via the Delphi technique. Content Validity Index (CVI) was calculated for individual items (I-CVI) as well as for the composite scale (S-CVI). A panel agreement of more than 75% was considered as the criterion for the inclusion of items in the questionnaire. Cognitive pretesting of five faculty members was conducted and pilot testing was subsequently done with 27 faculty members. The reliability of the tool was determined by Cronbach's alpha. Results: After the Delphi process, the final Integrated Curriculum Implementation Challenges (ICIC) questionnaire had 42 items. S-CVI was 0.87 and the cut-off value for I-CVI was taken as 0.78 as the criterion for item deletion. Cognitive interviews and pretesting revealed good item interpretation. Cronbach's alpha for this tool was 0.87. Conclusion: ICIC is a useful instrument with good reliability and content validity. It can be used to identify the presence and extent of challenges faced by the faculty while implementing an integrated curriculum.

Achieving Benchmarks for National Quality Indicators Reduces Recurrence and Progression in Non-muscle-invasive Bladder Cancer.

BACKGROUND: Noncompliance with evidence-based interventions and guidelines contributes to significant and variable recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC). The implementation of a quality performance indicator (QPI) programme in Scotland's National Health Service (NHS) aimed to improve cancer outcomes and reduce nationwide variance. OBJECTIVE: To evaluate the effect of hospitals achieving benchmarks for two specific QPIs on time to recurrence and progression in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: QPIs for bladder cancer (BC) were enforced nationally in April 2014. NHS health boards collected prospective data on all new BC patients. Prospectively recorded surveillance data were pooled from 12 collaborating centres. INTERVENTION: QPIs of interest were (1) hospitals achieving detrusor muscle (DM) sampling target at initial transurethral resection of bladder tumour (TURBT) and (2) use of single instillation of mitomycin C after TURBT (SI-MMC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary endpoints were time to recurrence and progression, respectively. Kaplan-Meier and Cox multivariable regression analyses were performed. KEY FINDINGS AND LIMITATIONS: Between April 1, 2014 and March 31, 2017, we diagnosed 3899 patients with new BC, of which 2688 were NMIBC . With a median follow up of 60.3 mo, hospitals achieving the DM sampling target had a 5.4% lower recurrence rate at 5 yr than hospitals not achieving this target (442/1136 [38.9%] vs 677/1528 [44.3%], 95% confidence interval [CI] = 1.6-9.2, p = 0.005). SI-MMC was associated with a 20.4% lower recurrence rate (634/1791 [35.4%] vs 469/840 [55.8%], 95% CI = 16.4-24.5, p < 0.001). On Cox multivariable regression, meeting the DM target and SI-MMC were associated with significant improvement in recurrence (hazard ratio [HR] 0.81, 95% CI = 0.73-0.91, p = 0.0002 and HR 0.66, 95% CI = 0.59-0.74, p < 0.004, respectively) as well as progression-free survival (HR 0.62, 95% CI = 0.45-0.84, p = 0.002 and HR 0.65, 95% CI = 0.49-0.87, p = 0.004, respectively). We did not have a national multicentre pre-QPI control. CONCLUSIONS: Within a national QPI programme, meeting targets for sampling DM and SI-MMC in the real world were independently associated with delays to recurrence and progression in NMIBC patients. PATIENT SUMMARY: Following the first 3 yr of implementing a novel quality performance indicator programme in Scotland, we evaluated compliance and outcomes in non-muscle-invasive bladder cancer. In 2688 patients followed up for 5 yr, we found that achieving targets for sampling detrusor muscle and the single instillation of mitomycin C during and after transurethral resection of bladder tumour, respectively, were associated with delays in cancer recurrence and progression.

Provenance, diagenesis, and depositional environment of Miocene Kamlial Formation, Azad Jammu and Kashmir, Sub Himalayas, Pakistan: Evidences from field observations and petrography.

Petrographical characterization and field observations were caried out to evaluate Kamlial Formation in Bagh district, Azad Jammu and Kashmir. Based on detailed petrography, the lithic arenite consisted of quartz (20-25%), feldspar (7-11%), rock fragments (20-37%), cementing materials (11-21%), and accessory minerals. Grains are mostly angular to subrounded and poorly to moderately sorted. The analysis revealed that the lithic arenite is mineralogically immature; also, the current activity during the time of deposition was low. Polycrystalline quartz indicates that the sandstone was derived from metamorphic source, while monocrystalline quartz indicates a granitic origin. Quartz having an angular shape suggests the source rock was near the depositional site, while quartz having a rounded shape represents long transportation. The presence of feldspar in the lithic arenite suggests the rocks were deposited at high relief or cold temperatures. Primary porosity in sandstone was reduced by calcite cements around the grain, while secondary porosity was developed by fracturing of quartz and feldspar. Tectonic uplift in the study area was demonstrated by fractured quartz and mica in thin sections. Field observations of various sedimentary structures were observed such as load casts, ripple marks, and mud cracks, etc. The presence of conglomerates and load casts in the study area indicates that the Kamlial sandstone was deposited by fluvial and shallow marine environment. Furthermore, the ripple marks indicate that the tidal flat environment controlled the deposition of the sediments.