Prospective exploratory evaluation of Cepheid Xpert Mycobacterium tuberculosis host response cartridge: a focus on adolescents and young adults.

BACKGROUND: An accurate, rapid, non-sputum-based triage test for diagnosing tuberculosis (TB) is needed. METHODS: A prospective evaluation of the Xpert-MTB-HR cartridge, a prototype blood-based host-response mRNA signature assay, among individuals presenting with TB-like symptoms was performed in Pakistan and results were compared to three reference standards: Xpert MTB/RIF Ultra, bacteriological confirmation (Xpert MTB/RIF Ultra and/or culture positivity), and composite clinical diagnosis (clinician diagnosis, treatment initiation, Xpert MTB/RIF Ultra, and/or culture positivity). Analyses were conducted both for the entire study cohort and separately in the adolescent and young adult cohort (ages 10-24). RESULTS: A total of 497 participants, ages 6-83, returned valid Xpert-MTB-HR results. When a diagnostic threshold was set for a sensitivity of >90%, specificity was 32% (95%CI 28-37) when compared to Xpert MTB/RIF Ultra, 29% (95%CI 25-34) when compared to a bacteriological confirmation, and 22% (95%CI 18-26) when compared to a composite clinical diagnosis. However, when evaluating only the adolescent and young adult cohort with a diagnostic threshold set for sensitivity of >90%, specificity was 82% (95%CI 74-89) when compared to Xpert MTB/RIF Ultra, 84% (95%CI 75-90) when compared to a bacteriological confirmation, and 54% (95%CI 44-64) when compared to a composite clinical diagnosis. CONCLUSIONS: While the Xpert-MTB-HR does not meet World Health Organization minimum criteria in the general population, in our study it does meet the minimum sensitivity and specificity requirements for a non-sputum-based triage test among adolescents and young adults when compared to Xpert MTB/RIF Ultra or bacteriological confirmation.

Suture closure AFtEr large bore vein access (SAFE-VEIN): A randomized, prospective study of the efficacy and safety of venous closure device.

BACKGROUND: Perclose ProGlide (PPG) Suture-Mediated Closure System™ is safe and can reduce time to hemostasis following procedures requiring arterial access. AIMS: We aimed to compare PPG to figure of 8 suture in patients who underwent interventional catheter procedures requiring large bore venous access (LBVA) (≥13 French). METHODS: In this physician-initiated, randomized, single-center study [clinicaltrials.gov ID: NCT04632641], single-stick venous access was obtained under ultrasound guidance. Eligible patients were randomized 1:1, and 100 subjects received allocated treatment to either PPG (n = 47) or figure of 8 suture (n = 53). No femoral arterial access was used in any patient. Primary outcomes were time to achieve hemostasis (TTH) and time to ambulation (TTA). Secondary outcomes were time to discharge (TTD) and vascular-related complications and mortality. Wilcoxon rank-sum test was used to compare TTH, TTA, and TTD. RESULTS: TTH (minutes) was significantly lower in PPG versus figure of 8 suture [median, (Q1, Q3)] [7 (2,10) vs. 11 (10,15) respectively, p < 0.001]. TTA (minutes) was significantly lower in PPG compared to figure of 8 suture [322 (246,452) vs. 403 (353, 633) respectively, p = 0.005]. TTD (minutes) was not significantly different between the PPG and figure of 8 suture arms [1257 (1081, 1544) vs. 1338 (1171,1435), p = 0.650]. There was no difference in minor bleeding or access site hematomas between both arms. No other vascular complications or mortality were reported. CONCLUSION: PPG use had lower TTH and TTA than figure of 8 suture in a population of patients receiving LBVA procedures. This may encourage same-day discharge in these patients.

Efficacy and safety of combination of empagliflozin and metformin with combination of sitagliptin and metformin during Ramadan: an observational study.

BACKGROUND: Management of diabetes during fasting is a clinical challenge. Sodium glucose co-transporter -2 inhibitors (SGLT2i) are considered safe with a low risk of hypoglycemia. However, studies on SGLT2i are scarce. This study was designed to compare the efficacy, safety, and tolerability of empagliflozin with metformin during Ramadan in comparison with sitagliptin and metformin. METHODS: It was a prospective, observational study, conducted at 11 different sites all across Pakistan on an outpatient basis during Ramadan (May 2021-June 2021). including 132 patients, 88 who received metformin and sitagliptin, and 44 patients who received metformin and empagliflozin. RESULTS: Patients of the SGLT-2i group experienced similar symptomatic hypoglycemic episodes (15.9%) as the sitagliptin group. There was an improvement in blood sugar levels after the use of SGLT-2i (RBS 181 ± 64 before Ramadan vs 162 ± 53 after Ramadan). HbA1c also improved after the use of SGLT-2i before and after Ramadan (7.2 ± 0.8 vs 6.9 ± 0.9 for Metformin + Empagliflozin and 7.8 ± 1.5 vs 7.6 ± 1.6 for Metformin and sitagliptin). Weight and BMI improved after the use of SGLT-2i (BMI 36.5 ± 4.8 before Ramadan and 33.7 ± 2.4 after Ramadan). There were no reported cases of urinary tract infection in the empagliflozin group. CONCLUSION: SGLT-2 inhibitors combined with metformin for patients with diabetes during Ramadan fasting is as effective, safe and well tolerated as DPP4 combined with metformin.

Complications and Management of Eptifibatide-Induced Thrombocytopenia.

BACKGROUND: Eptifibatide is used in acute coronary syndromes to reversibly block platelet aggregation by inhibiting the platelet glycoprotein IIb/IIIa receptor. A serious adverse effect of eptifibatide is a profound drop in platelet count, termed eptifibatide-induced thrombocytopenia (EIT). OBJECTIVE: To provide insight into the types of complications and management of EIT. METHODS: Cases of EIT submitted to the Food and Drug Administration adverse event reporting system were evaluated. Data analyses included management of EIT, complications of thrombocytopenia, initial platelets, and platelet nadir following eptifibatide. RESULTS: 103 cases of EIT were reported from January 2010 to 2019; 57 cases met the Naranjo scale and were included. Only 37 of those cases contained information on how EIT was managed. Eptifibatide administration was withheld in all 37 of those cases. Platelet transfusions were administered in 20 cases (54%). Two cases were managed with steroids (5.4%), and 1 case used intravenous immunoglobulin G to reverse EIT (2%). The median initial platelet count prior to administration of eptifibatide was 207 000 cells/mm3 (SD = 69 000; n = 27), and median platelet nadir was 9000 cells/mm3 (SD = 19 000; n = 35) The majority of complications of EIT included bleeding events (16/28, 57%). Delayed procedures, prolonged stay, allergic reactions, and thrombosis were each reported in 3 patients (10.75%). CONCLUSION AND RELEVANCE: Most cases of EIT were managed by withholding eptifibatide with platelet transfusion if necessary. The majority of complications included bleeding. However, significant procedure delays, prolonged hospital stay, thrombosis, and allergic reactions were also reported.

Profiling and identification of novel rpoB mutations in rifampicin-resistant Mycobacterium tuberculosis clinical isolates from Pakistan.

INTRODUCTION: Rifampicin (RIF) is one of the most effective anti-tuberculosis first-line drugs prescribed along with isoniazid. However, the emergence of RIF resistance Mycobacterium tuberculosis (MTB) isolates is a major issue towards tuberculosis (TB) control program in high MDR TB-burdened countries including Pakistan. Molecular data behind phenotypic resistance is essential for better management of RIF resistance which has been linked with mutations in rpoB gene. Since molecular studies on RIF resistance is limited in Pakistan, the current study was aimed to investigate the molecular data of mutations in rpoB gene behind phenotypic RIF resistance isolates in Pakistan. METHOD: A total of 322 phenotypically RIF-resistant isolates were randomly selected from National TB Reference Laboratory, Pakistan for sequencing while 380 RIF resistance whole-genome sequencing (WGS) of Pakistani isolates (BioProject PRJEB25972), were also analyzed for rpoB mutations. RESULT: Among the 702 RIF resistance samples, 675 (96.1%) isolates harbored mutations in rpoB in which 663 (94.4%) were detected within the Rifampicin Resistance Determining Region (RRDR) also known as a mutation hot spot region, including three novel. Among these mutations, 657 (97.3%) were substitutions including 603 (89.3%) single nucleotide polymorphism, 49 (7.25%) double and five (0.8%) triple. About 94.4% of Phenotypic RIF resistance strains, exhibited mutations in RRDR, which were also detectable by GeneXpert. CONCLUSION: Mutations in the RRDR region of rpoB is a major mechanism of RIF resistance in MTB circulating isolates in Pakistan. Molecular detection of drug resistance is a faster and better approach than phenotypic drug susceptibility testing to reduce the time for transmission of RIF resistance strains in population. Such insights will inform the deployment of anti-TB drug regimens and disease control tools and strategies in high burden settings, such as Pakistan.

Dietary Genistein Rescues Reduced Basal Chloride Secretion in Diabetic Jejunum via Sex-Dependent Mechanisms.

BACKGROUND/AIMS: The goal of this study was to determine the effect of dietary genistein (naturally occurring phytoestrogen) on jejunal secretory function in a clinically relevant model of diabetes and obesity, the leptin-defIcient ob/ob mouse. METHODS: We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum from 12-week old male and female ob/ob and lean C57Bl/6J mice fed a genistein diet (600 mg genistein/kg diet) for 4-weeks. Separate segments of jejunum were frozen for western blot determination of key proteins involved in secretory transport. RESULTS: Basal Isc was signifIcantly decreased (by 33%, P<0.05) in ob/ob females versus leans, and genistein-diet reversed this. Similarly, in males, basal Isc was decreased (by 47%, P<0.05) in ob/ob mice versus leans, and genistein-diet reversed this. Inhibition with either clotrimazole (100 µM, bilateral) or ouabain (100 µM, basolateral) was signifIcantly reduced in ob/ob mice compared to leans (P<0.05), and genistein-diet reversed clotrimazole-sensitive inhibition in ob/ob females, and reversed the ouabain-sensitive inhibition in males (indicating sex-dependent mechanisms). Our data suggested that PDE3 levels were dysregulated in ob/ob females and genistein reversed this. Expression of total CFTR (normalized to actin) was signifIcantly decreased ∼80% (P<0.05) in all ob/ob mice compared to leans, and genistein-diet was without effect. Expression of total NKCC1 (normalized to actin) was signifIcantly decreased ∼80% (P<0.05) in ob/ob male mice versus leans, and genistein-diet reversed this. CONCLUSIONS: Our data suggests that the reduced basal jejunal Isc in ob/ob female mice is a consequence of reduced CFTR expression, decreased activities of the basolateral KCa channel and Na+/K+-ATPase, and in male mice reduced basal jejunal Isc is a consequence of reduced CFTR and NKCC1 expression, along with decreased activities of the basolateral KCa channel and Na+/K+-ATPase. Genistein-diet has beneficial effects on basal Isc mediated by sex-dependent mechanisms in diabetic mice: in females via increased KCa-sensitive Isc and in males via increased Na+/K+-ATPase activity and increased NKCC1 expression. Improved understanding of intestinal dysfunctions in the ob/ob jejunum, may allow for the development of novel drug targets to treat obesity and diabetes, and may also be of benefit in CF-related diabetes.

Improvement in Harris Hip Score after cementless total hip arthroplasty in young active adults with secondary hip arthritis- A short-term follow-up result.

OBJECTIVE: To determine the improvement in Harris Hip Score after non-cemented total hip replacement in younger patients with secondary hip joint arthritis. METHODS: The quasi-experimental study was conducted at Unit I, Department of Orthopaedic Surgery and Traumatology, Mayo Hospital, Lahore, and comprised patients diagnosed clinically and radiologically as secondary hip joint arthritis from September 2009 to December 2014. Harris Hip Score was calculated pre-operatively. All patients were operated by the same surgical team. One dose of second-generation intravenous cephalosporin after test dose was given at induction of anaesthesia followed by 3 times daily postoperatively along with aminoglycosides twice daily for three days followed by oral quinolones for 2 weeks. Patients were followed up for 6 months. The improvement in hip score was classified as poor, fair, good and excellent. Data entry and analysis was done using SPSS 11.5. RESULTS: Of the 65 patients in the study, 43(66%) were male and 22(34%) were females. Right hip was involved in 40(62%) patients and 25(38%) had pathology in the left hip. Overall mean age of male and female patients was 35.69±5.55 years and 35.72±5.95 years respectively. Harris Hip score improved over 6 months from poor to fair. CONCLUSIONS: The use of non-cemented total hip arthroplasty conferred a significant improvement in function in young patients with arthritis of the hip joint.

Case Report: Vasospastic angina presenting as phantom odor perception.

Background: Vasospastic angina usually presents with intermittent episodes of chest pain. It can rarely be associated with the perception of phantom odors. Case summary: A 69-year-old woman presented for evaluation of intermittent shortness of breath and chest pain. She reported that she often experienced an abnormal smell sensation just prior to the event. The patient had abnormal smell sensation and shortness of breath at the initiation of exercise stress echocardiography with transient electrocardiographic changes and new regional wall motion abnormalities. Subsequent invasive coronary angiography showed no obstructive epicardial coronary artery disease. The patient was started on calcium channel blocker therapy with resolution of symptoms. Conclusion: Phantom odor perception has been rarely reported as an angina-equivalent symptom. Clinicians should have a high index of suspicion in patients presenting with atypical anginal symptoms.

Lymphangiogenesis Guidance Mechanisms and Therapeutic Implications in Pathological States of the Cornea.

Corneal lymphangiogenesis is one component of the neovascularization observed in several inflammatory pathologies of the cornea including dry eye disease and corneal graft rejection. Following injury, corneal (lymph)angiogenic privilege is impaired, allowing ingrowth of blood and lymphatic vessels into the previously avascular cornea. While the mechanisms underlying pathological corneal hemangiogenesis have been well described, knowledge of the lymphangiogenesis guidance mechanisms in the cornea is relatively scarce. Various signaling pathways are involved in lymphangiogenesis guidance in general, each influencing one or multiple stages of lymphatic vessel development. Most endogenous factors that guide corneal lymphatic vessel growth or regression act via the vascular endothelial growth factor C signaling pathway, a central regulator of lymphangiogenesis. Several exogenous factors have recently been repurposed and shown to regulate corneal lymphangiogenesis, uncovering unique signaling pathways not previously known to influence lymphatic vessel guidance. A strong understanding of the relevant lymphangiogenesis guidance mechanisms can facilitate the development of targeted anti-lymphangiogenic therapeutics for corneal pathologies. In this review, we examine the current knowledge of lymphatic guidance cues, their regulation of inflammatory states in the cornea, and recently discovered anti-lymphangiogenic therapeutic modalities.

Synergy of silica sand and waste plastics as thermoplastic composites on abrasive wear characteristics under conditions of different loads and sliding speeds.

The diverse nature of polymers with attractive properties has replaced the conventional materials with polymeric composites. The present study was sought to evaluate the wear performance of thermoplastic-based composites under the conditions of different loads and sliding speeds. In the present study, nine different composites were developed by using low-density polyethylene (LDPE), high-density polyethylene (HDPE) and polyethylene terephthalate (PET) with partial sand replacements i.e., 0, 30, 40, and 50 wt%. The abrasive wear was evaluated as per the ASTM G65 standard test for abrasive wear through a dry-sand rubber wheel apparatus under the applied loads of 34.335, 56.898, 68.719, 79.461 and 90.742 (N) and sliding speeds of 0.5388, 0.7184, 0.8980, 1.0776 and 1.4369 (m/s). The optimum density and compressive strength were obtained to be 2.0555 g/cm3 and 46.20 N/mm2, respectively for the composites HDPE60 and HDPE50 respectively. The minimum value of abrasive wear were found to 0.02498, 0.03430, 0.03095, 0.09020 and 0.03267 (cm3) under the considered loads of 34.335, 56.898, 68.719, 79.461 and 90.742 (N), respectively. Moreover, the composites LDPE50, LDPE100, LDPE100, LDPE50PET20 and LDPE60 showed a minimum abrasive wear of 0.03267, 0.05949, 0.05949, 0.03095 and 0.10292 at the sliding speeds of 0.5388, 0.7184, 0.8980, 1.0776 and 1.4369 (m/s), respectively. The wear response varied non-linearly with the conditions of loads and sliding speeds. Micro-cutting, plastic deformations, fiber peelings, etc. were included as the possible wear mechanism. The possible correlations between wear and mechanical properties, and throughout discussions for wear behaviors through the morphological analyses of the worn-out surfaces were provided.

Lymphatic Vessel Regression and Its Therapeutic Applications: Learning From Principles of Blood Vessel Regression.

Aberrant lymphatic system function has been increasingly implicated in pathologies such as lymphedema, organ transplant rejection, cardiovascular disease, obesity, and neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. While some pathologies are exacerbated by lymphatic vessel regression and dysfunction, induced lymphatic regression could be therapeutically beneficial in others. Despite its importance, our understanding of lymphatic vessel regression is far behind that of blood vessel regression. Herein, we review the current understanding of blood vessel regression to identify several hallmarks of this phenomenon that can be extended to further our understanding of lymphatic vessel regression. We also summarize current research on lymphatic vessel regression and an array of research tools and models that can be utilized to advance this field. Additionally, we discuss the roles of lymphatic vessel regression and dysfunction in select pathologies, highlighting how an improved understanding of lymphatic vessel regression may yield therapeutic insights for these disease states.

State of the art review: coronary artery disease in patients with inflammatory bowel disease: mechanisms, prevalence, and outcomes.

Extraintestinal disease manifestations of inflammatory bowel disease (IBD), such as arthritis and uveitis, have been well described in the medical literature. However, there has been growing evidence suggesting an association between IBD and both coronary artery disease (CAD) and acute myocardial infarctions (AMI). In this critical review, the pathogenesis of proatherogenic inflammatory markers (CD40-CD40L, IL-6, and TNF-α) are summarised along with clinical evidence that supports the association of these makers with CAD. Moreover, clinical data are examined that suggest an increased risk of AMI and CAD in IBD patients along with recent analyses of in-hospital and post-MI outcomes of AMI in IBD patients. This comprehensive review summarises and expands upon our understanding of the growing association between both CAD and AMI in IBD patients that potentially identifies IBD as a risk factor for developing CAD.

Therapeutic Strategies for Restoring Perturbed Corneal Epithelial Homeostasis in Limbal Stem Cell Deficiency: Current Trends and Future Directions.

Limbal stem cells constitute an important cell population required for regeneration of the corneal epithelium. If insults to limbal stem cells or their niche are sufficiently severe, a disease known as limbal stem cell deficiency occurs. In the absence of functioning limbal stem cells, vision-compromising conjunctivalization of the corneal epithelium occurs, leading to opacification, inflammation, neovascularization, and chronic scarring. Limbal stem cell transplantation is the standard treatment for unilateral cases of limbal stem cell deficiency, but bilateral cases require allogeneic transplantation. Herein we review the current therapeutic utilization of limbal stem cells. We also describe several limbal stem cell markers that impact their phenotype and function and discuss the possibility of modulating limbal stem cells and other sources of stem cells to facilitate the development of novel therapeutic interventions. We finally consider several hurdles for widespread adoption of these proposed methodologies and discuss how they can be overcome to realize vision-restoring interventions.

High throughput interrogation of human liver stellate cells reveals microenvironmental regulation of phenotype.

Liver fibrosis is a common feature of progressive liver disease and is manifested as a dynamic series of alterations in both the biochemical and biophysical properties of the liver. Hepatic stellate cells (HSCs) reside within the perisinusoidal space of the liver sinusoid and are one of the main drivers of liver fibrosis, yet it remains unclear how changes to the sinusoidal microenvironment impact HSC phenotype in the context of liver fibrosis. Cellular microarrays were used to examine and deconstruct the impacts of bio-chemo-mechanical changes on activated HSCs in vitro. Extracellular matrix (ECM) composition and stiffness were found to act individually and in combination to regulate HSC fibrogenic phenotype and proliferation. Hyaluronic acid and collagen III promoted elevated collagen I expression while collagen IV mediated a decrease. Previously activated HSCs exhibited reduced lysyl oxidase (Lox) expression as array substrate stiffness increased, with less dependence on ECM composition. Collagens III and IV increased HSC proliferation, whereas hyaluronic acid had the opposite effect. Meta-analysis performed on these data revealed distinct phenotypic clusters (e.g. low fibrogenesis/high proliferation) as a direct function of their microenvironmental composition. Notably, soft microenvironments mimicking healthy tissue (1 kPa), promoted higher levels of intracellular collagen I and Lox expression in activated HSCs, compared to stiff microenvironments mimicking fibrotic tissue (25 kPa). Collectively, these data suggest potential HSC functional adaptations in response to specific bio-chemo-mechanical changes relevant towards the development of therapeutic interventions. These findings also underscore the importance of the microenvironment when interrogating HSC behavior in healthy, disease, and treatment settings. STATEMENT OF SIGNIFICANCE: In this work we utilized high-throughput cellular microarray technology to systematically interrogate the complex interactions between HSCs and their microenvironment in the context of liver fibrosis. We observed that HSC phenotype is regulated by ECM composition and stiffness, and that these phenotypes can be classified into distinct clusters based on their microenvironmental context. Moreover, the range of these phenotypic responses to microenvironmental stimuli is substantial and a direct consequence of the combinatorial pairing of ECM protein and stiffness signals. We also observed a novel role for microenvironmental context in affecting HSC responses to potential fibrosis therapeutics.

Design and Evaluation of a Button Sensor Antenna for On-Body Monitoring Activity in Healthcare Applications.

A button sensor antenna for on-body monitoring in wireless body area network (WBAN) systems is presented. Due to the close coupling between the sensor antenna and the human body, it is highly challenging to design sensor antenna devices. In this paper, a mechanically robust system is proposed that integrates a dual-band button antenna with a wireless sensor module designed on a printed circuit board (PCB). The system features a small footprint and has good radiation characteristics and efficiency. This was fabricated, and the measured and simulated results are in good agreement. The design offers a wide range of omnidirectional radiation patterns in free space, with a reflection coefficient (S11) of −29.30 (−30.97) dB, a maximum gain of 1.75 (5.65) dBi, and radiation efficiency of 71.91 (92.51)% in the lower and upper bands, respectively. S11 reaches −23.07 (−27.07) dB and −30.76 (−31.12) dB, respectively, with a gain of 2.09 (6.70) dBi and 2.16 (5.67) dBi, and radiation efficiency of 65.12 (81.63)% and 75.00 (85.00)%, when located on the body for the lower and upper bands, respectively. The performance is minimally affected by bending, movement, and fabrication tolerances. The specific absorption rate (SAR) values are below the regulatory limitations for the spatial average over 1 g (1.6 W/Kg) and 10 g of tissues (2.0 W/Kg). For both indoor and outdoor conditions, experimental results of the range tests confirm the coverage of up to 40 m.

Development and Implementation of a Virtual Cell Culture Lab Practical for an Introductory BME Lab Course.

The transition to remote learning in response to the COVID-19 pandemic necessitated the adaptation of an in-person cell culture lab practical to a virtual assessment in an introductory biomedical engineering lab course. The virtual lab practical was administered in the course LMS and implemented video, data analysis, and multiple-choice questions. Average student scores and grade distributions were comparable across in-person and virtual lab practical formats. Instructors observed fewer grading concerns for the virtual practical compared to previous in-person offerings. The virtual lab practical may be preferred over in-person lab practical in future offerings due to decreased student stress, lower cost, reduced required instructor time, and limited availability of equipment. Resources developed for the virtual practical, including video tutorials and a hemocytometer simulator to practice calculations, can be used by other educators and as supplements to existing course material.

Laboratory Exercise to Measure Plasmid Copy Number by qPCR.

Quantitative PCR (qPCR) has numerous applications in biology. In an educational setting, qPCR provides students an opportunity to better understand the PCR mechanism by providing both quantitative information about the reactions and also data to troubleshoot PCRs (e.g., melt curves). Here, we present a relatively short (2-h) laboratory activity to demonstrate qPCR to quantify plasmid copy number (CN) by measuring the cycle threshold (CT ) values for a genomic gene and a plasmid gene using transformed cells as a template. The activity can be combined with additional laboratory exercises, including bacterial transformation, to create the template to be used in the qPCRs. This lab activity is ideal for undergraduate laboratory courses that include recombinant DNA technology. (This work was presented at the 2020 Biomedical Engineering Society annual meeting).

Comparison of Functional Outcome Between Intra-Articular Injection of Corticosteroid Versus Platelet-Rich Plasma in Frozen Shoulder: A Randomized Controlled Trial.

Background In this study, we compared the functional outcome of intra-articular injection of corticosteroid versus platelet-rich plasma (PRP) in patients with frozen shoulder (FS). Methodology This randomized controlled trial was conducted in the Department of Orthopedics, Mayo Hospital, Lahore, from January 2018 to December 2018.A total of 202 patients with FS aged 40 to 70 years were included. Patients with medical comorbidities such as chronic liver disease (assessed on history and serum bilirubin >2.0 mg/dl), chronic renal failure (assessed on history and serum creatinine >1.5 mg/dL), and chronic steroid use were excluded. Employing an anterior approach, subjects in groups A and B received one intra-articular injection of 2 mL PRP and 2 mL (80 mg) methylprednisolone acetate, respectively. Age, gender, duration of disease, and pre-injection and post-injection range of motion (ROM) (flexion, extension, abduction, external rotation, and internal rotation) were assessed. The University of California at Los Angeles Shoulder Score (UCLA) and visual analog scale (VAS) scores were measured and compared before and after the injection. All patients were followed at regular intervals post-therapy and the final functional outcome was measured after 12 weeks of therapy. Results Data were analyzed using SPSS version 20 (IBM Corp., Armonk, NY, USA). A p-value of 0.05 was considered significant when comparing flexion, abduction, external rotation, and internal rotation in both groups using the independent t-test. The ROM in group A (intra-articular PRP) improved significantly (p < 0.05) after injection compared to group B (intra-articular corticosteroid). The ROM after PRP for abduction was 147.09 ± 7.78, forward flexion 154.52 ± 6.48, external rotation 71.59 ± 7.43, and internal rotation 59.20 ± 3.96. The ROM in the steroid injection group for abduction was 129.07 ± 4.72, forward flexion 127.14 ± 7.87, external rotation 56.27 ± 5.93, and internal rotation 48.86 ± 4.90. Conclusions Intra-articular injection of PRP resulted in a substantial improvement in the VAS score, UCLA, and ROM when compared to intra-articular corticosteroid injection in patients with FS.

De-novo acute myeloid leukemia in a BRCA positive female with locally treated ductal carcinoma In Situ.

Acute myeloid leukemia (AML) is primarily a disease of older adults and can arise de novo, in relation to previous treatment or in the setting of underlying hematological disease. While it is known to arise from chemoradiation in the setting of breast cancer, little is known about the association between BRCA carriers and AML. We report a case of a young female BRCA carrier who develops de novo AML without prior chemoradiation treatment, and examine if there is a link between BRCA and developing leukemia.

Modeling, Optimization and Performance Evaluation of TiC/Graphite Reinforced Al 7075 Hybrid Composites Using Response Surface Methodology.

The tenacious thirst for fuel-saving and desirable physical and mechanical properties of the materials have compelled researchers to focus on a new generation of aluminum hybrid composites for automotive and aircraft applications. This work investigates the microhardness behavior and microstructural characterization of aluminum alloy (Al 7075)-titanium carbide (TiC)-graphite (Gr) hybrid composites. The hybrid composites were prepared via the powder metallurgy technique with the amounts of TiC (0, 3, 5, and 7 wt.%), reinforced to Al 7075 + 1 wt.% Gr. The microstructural characteristics were investigated by optical microscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDS) elemental mapping. A Box Behnken design (BBD) response surface methodology (RSM) approach was utilized for modeling and optimization of density and microhardness independent parameters and to develop an empirical model of density and microhardness in terms of process variables. Effects of independent parameters on the responses have been evaluated by analysis of variance (ANOVA). The density and microhardness of the Al 7075-TiC-Gr hybrid composites are found to be increased by increasing the weight percentage of TiC particles. The optimal conditions for obtaining the highest density and microhardness are estimated to be 6.79 wt.% TiC at temperature 626.13 °C and compaction pressure of 300 Mpa.