Vitamin D supplementation modulates glycated hemoglobin (HBA1c) in diabetes mellitus.

Diabetes is a metabolic illness that increases protein glycosylation in hyperglycemic conditions, which can have an impact on almost every organ system in the body. The role of vitamin D in the etiology of diabetes under RAGE (receptor for advanced glycation end products) stress has recently received some attention on a global scale. Vitamin D's other skeletal benefits have generated a great deal of research. Vitamin D's function in the development of type 1 and type 2 diabetes is supported by the discovery of 1,25 (OH)2D3 and 1-Alpha-Hydroylase expression in immune cells, pancreatic beta cells, and several other organs besides the bone system. A lower HBA1c level, metabolic syndrome, and diabetes mellitus all seems to be associated with vitamin D insufficiency. Most of the cross-sectional and prospective observational studies that were used to gather human evidence revealed an inverse relationship between vitamin D level and the prevalence or incidence of elevated HBA1c in type 2 diabetes. Several trials have reported on the impact of vitamin D supplementation for glycemia or incidence of type 2 diabetes, with varying degrees of success. The current paper examines the available data for a relationship between vitamin D supplementation and HBA1c level in diabetes and discusses the biological plausibility of such a relationship.

Investigating In Situ Expression of Neurotrophic Factors and Partner Proteins in Irreversible Pulpitis.

INTRODUCTION: In situ assessments of neurotrophic factors and their associated molecular partners have not been explored to date, particularly in humans. The present investigation aimed to explore the expressional dysregulation of neurotrophic factors (nerve growth factor [NGF], brain derived neurotrophic factor [BDNF], and NT4/5), their receptors (TrkA and TrkB), and their modulators (USP36 and Nedd4-2) directly in irreversibly inflamed human pulp tissues. METHODS: Forty samples each of healthy and irreversibly inflamed pulp were extirpated for the study. Immunohistochemical examinations were carried out for the anatomic changes and expression of neurotrophic factors and partner proteins. Expression was digitally quantified using the IHC profiler module of ImageJ and deduced as optical density. Statistical analyses were carried out by GraphPad Prism. RESULTS: Decrease in nuclear and vessel diameters was observed in irreversibly inflamed pulp tissues. NGF and BDNF were found to be significantly upregulated in symptomatic irreversible pulpitis (SIP), whereas no significant difference was observed in the expression of TrkA and TrkB. Expression of Nedd4-2, USP36, and TrkA was found positively correlated with the NGF in healthy pulp tissues. However, in SIP, positive correlation was only observed between the expression of USP36 and NGF. Among the ligands, BDNF expression was found positively correlated with NGF in healthy pulp but not with NT4/5. In the case of SIP, no correlation was observed between any neurotrophic factors. CONCLUSIONS: Upregulation of NGF, BDNF, USP36 and Nedd4-2 in SIP indicates dysregulation in the molecular events underlying the disease biology and could be exploited as potential markers for the disease diagnosis.

South Asian medical cohorts reveal strong founder effects and high rates of homozygosity.

The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of rare homozygotes that reach 100 times that seen in outbred populations. Founder effects increase the power to associate functional variants with disease processes and make South Asia a uniquely powerful place for population-scale genetic studies.

Comparative evaluation of Sapindus Mukorossi extract with 17% EDTA on smear layer removal in various parts of the tooth root.

OBJECTIVES: This study aimed to compare the effectiveness of an experimental root canal irrigant and 17% Ethylene-di-amine tetra acetic acid for removal of the smear layer in the coronal, middle and apical portions of the root canal. MATERIALS AND METHODS: Ninety human single rooted maxillary and mandibular teeth were selected for this study. The teeth were randomly divided into two experimental groups and one control group as follows: Group A (Ethanolic extract of Sapindus Mukorossi), Group B (17% EDTA), and Group C (Distilled water). The root canals of all three groups were prepared with stainless steel K-files by means of the standard step-back technique and irrigated with 5.25% sodium hypo chloride. The teeth were decoronated, following the irrigation and divided longitudinally into two-halves and visualized using scanning electron microscope (SEM) for the amount of smear layer present utilizing the three-point score system. The observations were noted both before and after the treatment. Nonparametric tests were applied for the comparison and p-value ⩽ 0.05 was considered as statistically significant. RESULTS: It was evident from that smear layer was completely removed in coronal portion of 27 out of 30 teeth in-group A. For middle and apical areas of group A, 24 and 19 teeth showed complete smear layer removal. In-group B it was found that there were 24, 21, and 3 teeth at coronal, middle and apical, areas respectively where smear layer were completely absent. Intra group comparison showed a significant difference (p = 0.002) in smear layer removal was found for group A at coronal, middle and apical thirds. Similarly, a significant difference (p = 0.001) was also found for group B; however heavy smear layer was found among the three parts of the canal for group C. CONCLUSIONS: Ethanolic extract of Sapindus Mukorossi have higher effectiveness in removing the smear layer from the root canal in comparison to 17% EDTA.

Development of extended-release metformin core tablet and synergistic coating of sitagliptin for the treatment of type-II diabetes mellitus - A comparative drug release evaluation with reference product.

Diabetes is getting a common disease and is spreading rapidly, affecting 6.6 percent world's population. Metformin HCl is an effective pharmacological treatment for type 2 diabetic patients because of its lowering blood glucose level ability, better weight-neutral effects and reduced risk of hypoglycemia. Nevertheless, gastrointestinal (GI) sensitivities are a concern in many patients using its immediate-release formulations. This study aimed to develop extended-release (ER) formulations to control the release into the body and minimize the dosage-related side effects of metformin and to develop an effective method of coating Sitagliptin immediate-release (IR) formulation over the core tablet. This study evaluated different formulations of Metformin HCl ER tablet using hydrophilic polymers. Different concentrations of Sitagliptin were used to develop immediate release coating. The dissolution profile of the designed formulation was compared with the reference 50/500mg tablet. In vitro dissolution of Metformin HCl (MT5), containing Methocel K4M and Methocel K100 polymer, showed 37.62% release at 1hr, 53.46% at 2hr, 84.75% at 6hr and 94.81% at 10hr. The Sitagliptin (ST8) with 10% excess released 103.64% in 30min. Similarity factor values suggested that developed Metformin ER and Sitagliptin IR formulation were like the reference product.

GGA and GGA + U Study of ThMn2Si2 and ThMn2Ge2 Compounds in a Body-Centered Tetragonal Ferromagnetic Phase.

Our study used the full-potential linearized augmented plane waves (FP-LAPW) method to conduct a first-principles evaluation of the structural, electronic, and magnetic properties of ThMn2X2 (X = Si and Ge) compounds. To establish theoretical dependability with the currently available experimental results, computations for the structural findings of ternary intermetallic thorium (Th)-based compounds were achieved using the generalized gradient approximation in the scheme of Perdew-Burke-Ernzerhof (PBE-GGA) potential, while the generalized gradient approximation plus the Hubbard U (GGA + U) approach was employed to improve the electrical and magnetic properties. In contrast with both the paramagnetic (PM) and antiferromagnetic (AFM) phases, the ThMn2X2 compounds were optimized in a stable ferromagnetic (FM) phase, which was more suited for studying and analyzing magnetic properties. The electronic band structures (BS) and the density of state (DOS) were computed using the two PBE-GGA and GGA + U approximations. The thorium (Th)-based ThMn2X2 compound has full metallic character, due to the crossing and overlapping of bands across the Fermi level of energy, as well as the absence of a gap through both spin (up and down) channels. There was a significant hybridization between (Mn-d and (X = Si and Ge)-p states of conduction band with Th-f states in the valence band. The total magnetic moment of ThMn2Si2 in the ferromagnetic phase was 7.94534 µB, while for ThMn2Ge2 it was 8.73824 µB with a major contribution from the Mn atom. In addition, the ThMn2Ge2 compound's total magnetic moment confirmed that it exhibits higher ferromagnetism than does the ThMn2Si2 compound.

Characterization of Non-Invasively Induced Post-Traumatic Osteoarthritis in Mice.

The pathophysiology of post-traumatic arthritis (PTOA) is not fully understood. This study used non-invasive repetitive mechanical loading (ML) mouse models to study biochemical, biomechanical, and pain-related behavioral changes induced in mice. Mouse models reflected the effects of the early stages of PTOA in humans. For the PTOA model, cyclic comprehensive loading (9N) was applied to each mouse's left knee joint. ML-induced biochemical and molecular changes were analyzed after loading completion. Cartilage samples were examined using gene expression analysis. Tissue sections were used in subsequent OA severity scoring. Biomechanical features and pain-related behavior were studied after 24 h and three weeks post-ML sessions to examine the development of PTOA. The loaded left knee joint showed a greater ROS/RNS signal than the right knee, which was not loaded. There was a significant increase in cartilage damage and MMP activity in the mechanically loaded joints relative to non-loaded control knee joints. Similarly, we found a difference in the viscoelastic tangent, which highlights significant changes in mechanical properties. Biochemical analyses revealed significant increases in total NO, caspase-3 activity, H2O2, and PGE2 levels. Gene expression analysis highlighted increased catabolism (MMP-13, IL-1ß, TNF-α) with a concomitant decrease in anabolism (ACAN, COL2A1). Histopathology scores clearly indicated increases in OA progression and synovitis. The gait pattern was significantly altered, suggesting signs of joint damage. This study showed that biomechanical, biochemical, and behavioral characteristics of the murine PTOA groups are significantly different from the control group. These results confirm that the current mouse model can be considered for translational PTOA studies.

Effect of Erosive Agents on Surface Characteristics of Nano-Fluorapatite Ceramic: An In-Vitro Study.

Erosive beverages cause dissolution of natural teeth and intra-oral restorations, resulting in surface characteristic changes, particularly roughness and degradation. The purpose of this study was to evaluate the surface roughness and topography of a dental ceramic following immersion in locally available erosive solutions. A total of 160 disc specimens of a nano-fluorapatite type ceramic (12 mm diameter and 2 mm thickness) were fabricated and equally distributed into two groups (n = 80) and then evenly distributed among the following five testing groups (n = 16): lemon juice, citrate buffer solution, 4% acetic acid, soft cola drink, and distilled water which served as a control. The surface roughness (Ra) and topography were evaluated using a profilometer and scanning electron microscope at baseline, 24 h, 96 h, and 168 h respectively. Data were analyzed using ANOVA and Tukey's multiple comparisons (p ≤ 0.05). Surface changes were observed upon exposure to all acidic beverages except distilled water. Amongst all immersion media, 4% acetic acid produced the most severe surface roughness across all time periods (i.e., baseline, 24 h, 96 h, and 168 h). A statistically significant difference in the surface roughness values between all immersion media and across all four time intervals was observed. Erosive agents had a negative effect on the surface roughness and topography of the tested ceramic. The surface roughness increased with increased storage time intervals.

Physicians' Response and Preparedness of Terrorism-Related Disaster Events in Quetta City, Pakistan: A Qualitative Inquiry.

Background: Besides catastrophes, infrastructural damages, and psychosocial distress, terrorism also imposes an unexpected burden on healthcare services. Considerably, adequately-prepared and responsive healthcare professionals affirms effective management of terrorism-related incidences. Accordingly, the present study aimed to evaluate physicians' preparedness and response toward terrorism-related disaster events in Quetta city, Pakistan. Methods: A qualitative design was adopted. Physicians practicing at the Trauma Center of Sandeman Provincial Hospital (SPH), Quetta, were approached for the study. We conducted in-depth interviews; all interviews were audio-taped, transcribed verbatim, and analyzed for thematic contents by a standard content analysis framework. Results: Fifteen physicians were interviewed. The saturation was achieved at the 13th interview however we conducted another two to validate the saturation. The thematic content analysis revealed five themes and 11 subthemes. All physicians have experienced, responded to, and managed terrorism-related disaster events. They were prepared professionally and psychologically in dealing with a terrorism-related disaster. Physicians identified lack of disaster-related curricula and training, absence of a standardized protocol, recurrence of the disaster, and hostile behavior of victim's attendants during an emergency as critical barriers to effective terrorism-related disaster management. Among limitations, all respondents mentioned workspace, and resources as a foremost constraint while managing a terrorism-related disaster event. Conclusion: Although physicians understood the abilities and had the required competencies to mitigate a terrorism-related disaster, lack of workspace and resources were identified as a potential barrier to effective disaster management. Based on the results, we propose reconsideration and integration of the medical curriculum, particularly for terrorism-related disaster management, collaboration, and communication among various stakeholders to manage terrorism-related disaster events competently.

Analyzing human knockouts to validate GPR151 as a therapeutic target for reduction of body mass index.

Novel drug targets for sustained reduction in body mass index (BMI) are needed to curb the epidemic of obesity, which affects 650 million individuals worldwide and is a causal driver of cardiovascular and metabolic disease and mortality. Previous studies reported that the Arg95Ter nonsense variant of GPR151, an orphan G protein-coupled receptor, is associated with reduced BMI and reduced risk of Type 2 Diabetes (T2D). Here, we further investigate GPR151 with the Pakistan Genome Resource (PGR), which is one of the largest exome biobanks of human homozygous loss-of-function carriers (knockouts) in the world. Among PGR participants, we identify eleven GPR151 putative loss-of-function (plof) variants, three of which are present at homozygosity (Arg95Ter, Tyr99Ter, and Phe175LeufsTer7), with a cumulative allele frequency of 2.2%. We confirm these alleles in vitro as loss-of-function. We test if GPR151 plof is associated with BMI, T2D, or other metabolic traits and find that GPR151 deficiency in complete human knockouts is not associated with clinically significant differences in these traits. Relative to Gpr151+/+ mice, Gpr151-/- animals exhibit no difference in body weight on normal chow and higher body weight on a high-fat diet. Together, our findings indicate that GPR151 antagonism is not a compelling therapeutic approach to treatment of obesity.

Medication Errors and Type 2 Diabetes Management: A Qualitative Exploration of Physicians' Perceptions, Experiences and Expectations From Quetta City, Pakistan.

Background: Type 2 Diabetes-related medication errors are frequently reported from the hospitals and consequently are of major concern. However, such reports are insufficient when developing healthcare settings are pursued in literature. Keeping this inadequacy in mind, we therefore aimed to explore physicians' perceptions, experiences and expectations of medication errors when managing patients with Type 2 Diabetes Mellitus. Methods: A qualitative design was adopted. By using a semi-structured interview guide through the phenomenology-based approach, in-depth, face-to-face interviews were conducted. Physicians practicing at the medicine ward of Sandeman Provincial Hospital, Quetta, were purposively approached for the study. All interviews were audio-taped, transcribed verbatim, and were then analyzed for thematic contents by the standard content analysis framework. Results: Although the saturation was reached at the 13th interview, we conducted additional two interviews to ensure the saturation. Fifteen physicians were interviewed, and thematic content analysis revealed six themes and nine subthemes. Mixed conceptualization and characterization of medication errors were identified. Medication errors were encountered by all physicians however poor understanding of the system, deficiency of logistics and materials were rated as barriers in reporting medication errors. Among contributors of medication errors, physicians themselves as well as dispensing and patient-related factors were identified. Physicians suggested targeted training sessions on medication error-related guidelines and reporting system. Parallel, establishment of an independent unit, involving the pharmacists, and strict supervision of paramedics to minimize medication errors was also acknowledged during data analysis. Conclusion: With a longer life expectancy and a trend of growing population, the incidences of medication errors are also expected to increase. Our study highlighted prescribing, dispensing and administration phases as contributing factors of medication errors. Although, physicians had poor understanding of medication errors and reporting system, they believed getting insights on guidelines and reporting system is essential. A review of admission and discharge reconciliation must be prioritized and a culture of teamwork, communication and learning from mistakes is needed.

Indirect effects of COVID-19 pandemic on reproductive, maternal, newborn and child health services in Pakistan

Background: COVID-19 is having many impacts on health, economy and social life; some due to the indirect effects of closure of health facilities to curb the spread. Closures were implemented in Pakistan from March 2020, affecting provision of reproductive, maternal, newborn and child health (RMNCH) services. Aim: To appraise the effects of containment and lockdown policies on RMNCH service utilization in order to develop an early response to avoid the catastrophic impact of COVID-19 on RMNCH in Pakistan. Methods: Routine monitoring data were analysed for indicators utilization of RMNCH care. The analysis was based on Period 1 (January–May 2020, first wave of COVID-19); Period 2 (June–September 2020, declining number of cases of COVID-19); and Period 3 (October–December 2020, second wave of COVID-19). We also compared data from May and December 2020 with corresponding months in 2019, to ascertain whether changes were due to COVID-19. Results: Reduced utilization was noted for all RMNCH indicators during Periods 1 and 3. There was a greater decline in service utilization during the first wave, and the highest reduction (~82%) was among children aged < 5 years, who were treated for pneumonia. The number of caesarean sections dropped by 57%, followed by institutional deliveries and first postnatal visit (37% each). Service utilization increased from June to September, but the second wave of COVID-19 led to another decrease. Conclusion: To reinstate routine services, priority actions and key areas include continued provision of family planning services along with uninterrupted immunization campaigns and routine maternal and child services.

An In-Vitro Evaluation of Microleakage in Resin-Based Restorative Materials at Different Time Intervals.

A vital feature of conservative dentistry is the adhesion of the restorative material to the tooth structure for restoration of the tooth substance lost due to dental decay, trauma, or dental imperfections. In a perfect world, a restorative material should generate a lasting adhesion by bonding the restoration with tooth tissues. The ingress of micro-organisms, oral fluids, molecules, and ions through microscopic spaces due to faulty adhesion between restoration and tooth structure is known as microleakage. This study is focuses on the evaluation of adhesive failures between the restorative materials. In the past, studies have focused more on the bonding potential of a restorative material with the tooth surface. Therefore, there is need to carry out a study that compares the microleakage between resin-based restorative materials in a sandwich manner with and without the intermediate bonding layer after immersion in 2% methylene blue dye at different time intervals. The restorative materials used were composite Ceram X Mono plus (DENTSPLY) and Z350 (3M ESPE), Vitremer resin modified glass ionomer cement (RMGIC) (3M ESPE), smart dentine replacement SDR (3M ESPE), Bond NT (DENTSPLY), and Universal Bond (3M ESPE). A light emitting diode (LED) was used to cure the specimens. Artificial saliva was used as a storage medium for the specimens. Thermocycling of specimens was carried out at 500 cycles/30 s and 1000 cycles/30 s. The world health organization (WHO) grading tool for microleakage was used to analyze fluid ingress in the specimens through disclosing by 2% methylene blue dye. The statistical analysis was carried out with one-way analysis of variance (ANOVA) and Tukey post hoc test, keeping the level of significance at p ≤ 0.05. In Grade 0 = 85 samples, Grade 1 = 10 samples, Grade 2 = 7 samples, Grade 3 = 16 samples, and in Grade 4 = 2 samples were identified. This study describes that no microleakage was observed in SDR and resin composite groups as compared to Vitremer and resin composite groups.

The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice.

Angiogenesis is critical for successful fracture healing. Age-related alterations in endothelial cells (ECs) may cause impaired bone healing. Therefore, examining therapeutic treatments to improve angiogenesis in aging may enhance bone healing. Sirtuin 1 (SIRT1) is highly expressed in ECs and its activation is known to counteract aging. Here, we examined the effects of SRT1720 treatment (SIRT1 activator) on the growth and function of bone marrow and lung ECs (BMECs and LECs, respectively), derived from young (3-4 month) and old (20-24 month) mice. While aging did not alter EC proliferation, treatment with SRT1720 significantly increased proliferation of all LECs. However, SRT1720 only increased proliferation of old female BMECs. Vessel-like tube assays showed similar vessel-like structures between young and old LECs and BMECs from both male and female mice. SRT1720 significantly improved vessel-like structures in all LECs. No age, sex, or treatment differences were found in migration related parameters of LECs. In males, old BMECs had greater migration rates than young BMECs, whereas in females, old BMECs had lower migration rates than young BMECs. Collectively, our data suggest that treatment with SRT1720 appears to enhance the angiogenic potential of LECs irrespective of age or sex. However, its role in BMECs is sex- and age-dependent.

Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci.

BACKGROUND: Genetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies. METHODS: We characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci. RESULTS: We identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci. CONCLUSIONS: Our findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci.

The effects of bone morphogenetic protein 2 and thrombopoietin treatment on angiogenic properties of endothelial cells derived from the lung and bone marrow of young and aged, male and female mice.

With an aging world population, there is an increased risk of fracture and impaired healing. One contributing factor may be aging-associated decreases in vascular function; thus, enhancing angiogenesis could improve fracture healing. Both bone morphogenetic protein 2 (BMP-2) and thrombopoietin (TPO) have pro-angiogenic effects. The aim of this study was to investigate the effects of treatment with BMP-2 or TPO on the in vitro angiogenic and proliferative potential of endothelial cells (ECs) isolated from lungs (LECs) or bone marrow (BMECs) of young (3-4 months) and old (22-24 months), male and female, C57BL/6J mice. Cell proliferation, vessel-like structure formation, migration, and gene expression were used to evaluate angiogenic properties. In vitro characterization of ECs generally showed impaired vessel-like structure formation and proliferation in old ECs compared to young ECs, but improved migration characteristics in old BMECs. Differential sex-based angiogenic responses were observed, especially with respect to drug treatments and gene expression. Importantly, these studies suggest that NTN1, ROBO2, and SLIT3, along with angiogenic markers (CD31, FLT-1, ANGPT1, and ANGP2) differentially regulate EC proliferation and functional outcomes based on treatment, sex, and age. Furthermore, treatment of old ECs with TPO typically improved vessel-like structure parameters, but impaired migration. Thus, TPO may serve as an alternative treatment to BMP-2 for fracture healing in aging owing to improved angiogenesis and fracture healing, and the lack of side effects associated with BMP-2.

Effect of pre-cooling agent on intensity of pricking pain at intraoral injection site in adults: An experimental study.

OBJECTIVE: To determine the effect of pre-cooling agent on the intensity of pricking pain at the intraoral injection site in adult patients. METHODS: The in-vivo interventional study was conducted at the Department of Operative Dentistry, Dr. Ishrat-ul-Ebad Khan Institute of Oral Health Sciences, Dow University of Health Sciences, Karachi, from September 2018 to August 2019, and comprised adult patients of either gender. The pricking pain perception during needle administration was assessed using split-mouth technique. Topical anaesthesia benzocaine gel was applied on the left side, which was treated as controls, for 1 min, while on the right side, which was treated as the experimental side, refrigerated cartridge was placed for 2 min. Infiltration anaesthesia was then administered on both sides. Pain perception ratings were measured through visual analogue scale. After profound anaesthesia was achieved, restorative treatment was performed under rubber dam isolation. Data was analysed using SPSS 24. RESULTS: Of the 152 subjects, 77(50.65%) were females and 75(49.34%) were males. The overall mean age was 35.97±8.669 years (range: 21-50 years). The effect of refrigerated cartridge was significant on the intensity of pricking pain at the intraoral injection site in patients aged 41-50 years, and in female patients aged 21-30 years (p<0.05), whereas its effect was non-significant in males aged 21-30 years and patients aged 31-40 years (p>0.05). CONCLUSIONS: Pre-cooling agent was found to be effective in decreasing pricking pain felt by patients.

Comparison of gingival biotype in smokeless tobacco users (Gutka and Paan) and non-tobacco users.

OBJECTIVE: To assess the gingival biotypes in smokeless tobacco (Gutka and Paan) users and compare it with non-tobacco users in Karachi sub-population using trans-gingival probing method (TRAN). METHODS: This in-vivo, cross sectional study was conducted in the department of Operative Dentistry from 20th February 2019 to 25th June 2019 Dow University of Health Sciences, Karachi after obtaining ethical approval from the Institutional review board of DUHS (Ref: IRB-1207/DUHS/Approval/2019/21). A total of 70 participants, 35 subjects currently using smokeless tobacco (Gutka and Paan) and 35 non-tobacco users from both genders were included in the study after taking informed consent. Gingival biotype was recorded using probe transparency method. Probing of the gingival sulcus was performed at the mid-buccal aspect of both maxillary incisors. Depending on the visibility of the underlying probe gingiva was categorized as thin or thick. RESULTS: Statistically significant differences in gingival biotype was observed of both groups (p=0.005). Males were recorded with a higher percentage of thick gingiva in both groups (81% in smokeless tobacco and 65% in non-tobacco) while in females thick gingiva was more prevalent in smokeless tobacco group (85.7%) whereas thin gingiva was noted in non-tobacco group (66.7%); although the results between genders was statistically insignificant. The comparison between different age groups, genders and both groups was statistically insignificant. CONCLUSIONS: Significant difference was observed between gingival biotype of smokeless tobacco and non-tobacco user groups. No statistically significant results were observed between genders and age groups.

"Expecting the Unexpected:" Nurses' Response and Preparedness of Terrorism-Related Disaster Events in Quetta City, Pakistan.

Background: In addition to the psychiatric and societal misery, terrorism places an exceptional burden while delivering healthcare services. Accordingly, a responsive and well-prepared healthcare system ensures effective management of terrorism-related events. Within this context, with a strong historic grounding in addressing situations of societal crisis nurses are well-placed in contributing to the global arena of humanitarian policy and social research. Therefore, assessing their response and preparedness is vital in effective management of a terrorism-related disaster. For that very reason, we aimed to evaluate nurses' preparedness and response toward terrorism-related disaster events in Quetta city, Pakistan. Methods: A qualitative design was adopted to explore nurses' response and preparedness of terrorism-related disaster events. By using a semi-structured interview guide through the phenomenology-based approach, in-depth, face-to-face interviews were conducted. Nurses practicing at the Trauma Center of Sandeman Provincial Hospital (SPH), Quetta, were approached for the study. All interviews were audio-taped, transcribed verbatim, and were then analyzed for thematic contents by the standard content analysis framework. Results: Fifteen nurses were interviewed and thematic content analysis revealed five themes. All nurses have experienced, responded to, and managed terrorism-related disaster events. They were prepared both professionally and psychologically in dealing with a terrorism-related disaster. Among limitations, space and workforce were highlighted by almost all the respondents. Lack of disaster-related curricula, absence of a protocol, recurrence of the disaster, and hostile behavior of victim's attendants during an emergency were highlighted as a key barrier toward terrorism-related disaster management. Conclusion: The skills and expertise needed to address a terrorism-related disaster are well-understood by the nurses but are lacking for various reasons. In addition to the review and adaption of the nursing curriculum specifically for terrorism-related disaster management, collaboration and dialogue between various stakeholders is required to efficiently manage terrorism-related disaster events.

The effects of high fat diet, bone healing, and BMP-2 treatment on endothelial cell growth and function.

Angiogenesis is a vital process during the regeneration of bone tissue. The aim of this study was to investigate angiogenesis at the fracture site as well as at distal locations from obesity-induced type 2 diabetic mice that were treated with bone morphogenetic protein-2 (BMP-2, local administration at the time of surgery) to heal a femoral critical sized defect (CSD) or saline as a control. Mice were fed a high fat diet (HFD) to induce a type 2 diabetic-like phenotype while low fat diet (LFD) animals served as controls. Endothelial cells (ECs) were isolated from the lungs (LECs) and bone marrow (BMECs) 3 weeks post-surgery, and the fractured femurs were also examined. Our studies demonstrate that local administration of BMP-2 at the fracture site in a CSD model results in complete bone healing within 3 weeks for all HFD mice and 66.7% of LFD mice, whereas those treated with saline remain unhealed. At the fracture site, vessel parameters and adipocyte numbers were significantly increased in BMP-2 treated femurs, irrespective of diet. At distal sites, LEC and BMEC proliferation was not altered by diet or BMP-2 treatment. HFD increased the tube formation ability of both LECs and BMECs. Interestingly, BMP-2 treatment at the time of surgery reduced tube formation in LECs and humeri BMECs. However, migration of BMECs from HFD mice treated with BMP-2 was increased compared to BMECs from HFD mice treated with saline. BMP-2 treatment significantly increased the expression of CD31, FLT-1, and ANGPT2 in LECs and BMECs in LFD mice, but reduced the expression of these same genes in HFD mice. To date, this is the first study that depicts the systemic influence of fracture surgery and local BMP-2 treatment on the proliferation and angiogenic potential of ECs derived from the bone marrow and lungs.