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Olfactory dysfunction (OD) has been described in patients with antineutrophil cytoplasmic antibody-associated vasculitides (AAV), but the underlying mechanisms are not completely understood. The causes of altered smell function can generally be divided into conductive, sensorineural or others. To date no specific treatment is available for AAV-related OD and the efficacy of currently available options has not been explored. The aim of this review is to provide an overview of the causes that may lead to OD in patients with AAV. Current available treatments for OD and possible options in patients with AAV presenting with smell impairment are also mentioned.

Stroke is a major cause of death and long-term disability. Recent evidence suggests that hypoxia-inducible factor 1α (HIF-1α), a transcription factor that regulates oxygen levels, plays a key role in neurological outcomes after ischemic stroke. Accordingly, we investigated the mechanism of HIF-1α on pyroptotic and apoptotic cells during ischemia/reperfusion (I/R). Adult Sprague-Dawley rats underwent 2 h of middle cerebral artery occlusion (MCAO). The rats were then exposed to 6 or 24 h of reperfusion, with or without YC-1 (HIF-1α inhibitor, 5 mg/kg). Infarct volumes, along with mRNA and protein quantities of HIF-1α, NLRP3, IL-1β, IL-18, Caspase-1, and co-localization of HIF-1α, and NLRP3, were assessed. We measured apoptotic and pyroptotic cell death, gasdermin D (GSDMD) activation and lactate dehydrogenase (LDH) activity, and the infiltration of neutrophils and macrophages after ischemic stroke. HIF-1α mRNA and NLRP3 inflammasome components were increased after 24 h of reperfusion. YC-1 significantly reduced the mRNA and protein expression of NLRP3, IL-1β, IL-18, and caspase-1; significantly decreased infarction and pyroptotic cell death after 24 h of reperfusion; attenuated the neuroinflammatory response by reducing infiltration of CD68- and MPO-positive cells after 24 h of reperfusion; and reduced apoptotic cell death following ischemic stroke. We found that HIF-1α likely regulates inflammatory responses through the NLRP3 inflammasome complex, thus influencing both apoptotic and pyroptotic cell death after stroke. These findings suggest that future investigations are needed regarding HIF-1α and its role as a potential molecular target in the treatment of acute ischemic stroke.

Background Previous trials suggest lower long-term risk of mortality after invasive rather than non-invasive management of patients with non-ST elevation myocardial infarction (NSTEMI), but the trials excluded very elderly patients. We aimed to estimate the effect of invasive versus non-invasive management within 3 days of peak troponin concentration on the survival of patients aged 80 years or older with NSTEMI. Methods Routine clinical data for this study were obtained from five collaborating hospitals hosting NIHR Biomedical Research Centres in the UK (all tertiary centres with emergency departments). Eligible patients were 80 years old or older when they underwent troponin measurements and were diagnosed with NSTEMI between 2010 (2008 for University College Hospital) and 2017. Propensity scores (patients' estimated probability of receiving invasive management) based on pretreatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days of peak troponin concentration without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and compared the rate of hospital admissions for heart failure. Findings Of the 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin concentration and 375 were excluded because of extreme propensity scores. The remaining 1500 patients had a median age of 86 (IQR 82–89) years of whom (845 [56%] received non-invasive management. During median follow-up of 3·0 (IQR 1·2–4·8) years, 613 (41%) patients died. The adjusted cumulative 5-year mortality was 36% in the invasive management group and 55% in the non-invasive management group (adjusted hazard ratio 0·68, 95% CI 0·55–0·84). Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0·67, 95% CI 0·48–0·93). Interpretation The survival advantage of invasive compared with non-invasive management appears to extend to patients with NSTEMI who are aged 80 years or older. Funding NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative.

Background Until recently, the mechanism for the malignant hyperthermia crisis has been attributed solely to sustained massive Ca2+ release from the sarcoplasmic reticulum on exposure to triggering agents. This study tested the hypothesis that transient receptor potential cation (TRPC) channels are important contributors to the Ca2+ dyshomeostasis in a mouse model relevant to malignant hyperthermia. Methods This study examined the mechanisms responsible for Ca2+ dyshomeostasis in RYR1-p.G2435R mouse muscles and muscle cells using calcium and sodium ion selective microelectrodes, manganese quench of Fura2 fluorescence, and Western blots. Results RYR1-p.G2435R mouse muscle cells have chronically elevated intracellular resting calcium and sodium and rate of manganese quench (homozygous greater than heterozygous) compared with wild-type muscles. After exposure to 1-oleoyl-2-acetyl-sn-glycerol, a TRPC3/6 activator, increases in intracellular resting calcium/sodium were significantly greater in RYR1-p.G2435R muscles (from 153 ± 11 nM/10 ± 0.5 mM to 304 ± 45 nM/14.2 ± 0.7 mM in heterozygotes P < 0.001] and from 251 ± 25 nM/13.9 ± 0.5 mM to 534 ± 64 nM/20.9 ± 1.5 mM in homozygotes [P < 0.001] compared with 123 ± 3 nM/8 ± 0.1 mM to 196 ± 27 nM/9.4 ± 0.7 mM in wild type). These increases were inhibited both by simply removing extracellular Ca2+ and by exposure to either a nonspecific (gadolinium) or a newly available, more specific pharmacologic agent (SAR7334) to block TRPC6- and TRPC3-mediated cation influx into cells. Furthermore, local pretreatment with SAR7334 partially decreased the elevation of intracellular resting calcium that is seen in RYR1-p.G2435R muscles during exposure to halothane. Western blot analysis showed that expression of TRPC3 and TRPC6 were significantly increased in RYR1-p.G2435R muscles in a gene–dose–dependent manner, supporting their being a primary molecular basis for increased sarcolemmal cation influx. Conclusions Muscle cells in knock-in mice expressing the RYR1-p.G2435R mutation are hypersensitive to TRPC3/6 activators. This hypersensitivity can be negated with pharmacologic agents that block TRPC3/6 activity. This reinforces the working hypothesis that transient receptor potential cation channels play a critical role in causing intracellular calcium and sodium overload in malignant hyperthermia–susceptible muscle, both at rest and during the malignant hyperthermia crisis. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

BACKGROUND Patients with existing or anticipated indications for cardiac resynchronisation therapy (CRT), bradycardia, or anti-tachycardia pacing should not be offered subcutaneous defibrillators (SQIDs) but it remains unclear how clinicians should predict future need for these therapies. METHODS We applied three SQID selection policies to data collected retrospectively from transvenous implantable cardioverter defibrillator (TV-ICD) implants: (a) approach A, SQID used in inherited channelopathies and idiopathic ventricular fibrillation only; (b) approach B, as above, plus all hypertrophic cardiomyopathy and grown-up congenital heart disease patients; (c) approach C, as above, plus primary and secondary prevention (for ventricular fibrillation only) of SCD in patients with QRS

Background Oral health is associated with diabetes, but the chances of experiencing acute or chronic diabetes complications as per this association is unknown in Canada’s most populous province, Ontario. This study assesses the impact of self-reported oral health on the likelihood of experiencing acute and chronic complications among a cohort of previously diagnosed diabetics. Methods A retrospective cohort study was conducted of diabetics (n = 5183) who participated in the Canadian Community Health Survey 2003 and 2007–08. Self-reported oral health status was linked to health encounters in electronic medical records until March 31, 2016. Multinomial regression models determined the odds of the first acute or chronic complication after self-report of oral health status. Results Thirty-eight percent of diabetics reporting “poor to fair” oral health experienced a diabetes complication, in comparison to 34% of those reporting “good to excellent” oral health. The odds of an acute or chronic complication among participants reporting “poor to fair” oral health status was 10% (OR 1.10; 95% CI 0.81, 1.51) and 34% (OR 1.34; 95% CI 1.11, 1.61) greater respectively, than among participants experiencing no complications and reporting “good to excellent” oral health. Conclusion Self-reporting “poor to fair” oral health status is associated with a greater likelihood of chronic complications than acute complications. Further research regarding the underlying causal mechanisms linking oral health and diabetes complications is needed.

Objective: Our aim was to validate the prognostic relevance in NSCLC of potential residual tumor (R) descriptors, including the proposed International Association for the Study of Lung Cancer definition for uncertain resection, referred to as R(un). Methods: A total of 14,712 patients undergoing resection with full R status and survival were analyzed. The following were also evaluated: whether fewer than three N2 stations were explored, lobe-specific nodal dissection, extracapsular extension, highest lymph node station status, carcinoma in situ at the bronchial resection margin, and pleural lavage cytologic examination result. Revised categories of R0, R(un), R1, and R2 were tested for survival impact. Results: In all, 14,293 cases were R0, 263 were R1, and 156 were R2 (median survivals not reached, 33 months, and 29 months, respectively). R status correlated with T and N categories. A total of 9290 cases (63%) had three or more N2 stations explored and 6641 cases (45%) had lobespecific nodal dissection, correlated with increasing pN2. Extracapsular extension was present in 62 of 364 cases with available data (17%). The highest station was positive in 942 cases (6.4%). The pleural lavage cytologic examination result was positive in 59 of 1705 cases (3.5%): 13 had carcinoma in situ at the bronchial resection margin. After reassignment because of inadequate nodal staging in 56% of cases, 6070 cases were R0, 8185 were R(un), 301 were R1, and 156 were R2. In node-positive cases, the median survival times were 70, 50, and 30 months for RO, R(un) (p < 0.0001), and R1 (p < 0.001), respectively, with no significant difference between RO and R(un) in pN0 cases. Conclusions: R descriptors have prognostic relevance, with R(un) survival stratifying between R0 and R1. Therefore, a detailed evaluation of R factor is of particular importance in the design and analyses of clinical trials of adjuvant therapies. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Background & Objectives: Understanding the distribution and prevalence of three major mosquito borne diseases in an area is critical for the development of effective vector control strategies and public health interventions. The present study is therefore aimed to explore the epidemiological trend of malaria, dengue and chikungunya from 2012 to 2018 in Punjab. Methods: Quantitatively retrospective data was collected from Department of Health and Family Welfare, the National Vector Borne Disease Control Programme (NVBDCP), Punjab from 2012 to March 2018. The collected data was statistically analysed. Results: In case of malaria highest prevalent districts in Punjab are Mansa and Bathinda, for dengue Patiala, Ludhiana and S.A.S. Nagar and Patiala for chikungunya. Malaria was reported mainly from rural areas while dengue and chikungunya were found more in urban areas. For all three mosquito borne diseases, males were infected more as compared to females. Malaria cases were reported in months of August and September while dengue cases increased from July to November whereas chikungunya cases were highest in months of August to October. Conclusions: These findings help in concluding the trend analysis which in turn helps us to increase our focus on disease endemic districts along with boosting the vector control strategies in respective districts. Further the control of these mosquito borne diseases can be solved by employing adequate human resources, by increasing awareness in the community by conducting health camps and strengthening the entomological surveillance for timely reduction in the breeding of the vectors, especially before the repeated rise in cases during the period from July to November each year.

Aims Operability of type A acute aortic dissections (TAAAD) is currently based on non-standardized decision-making process, and it lacks a disease-specific risk evaluation model that can predict mortality. We investigated patient, intraoperative data, surgeon, and centre-related variables for patients who underwent TAAAD in the UK. Methods and results We identified 4203 patients undergoing TAAAD surgery in the UK (2009–18), who were enrolled into the UK National Adult Cardiac Surgical Audit dataset. The primary outcome was operative mortality. A multivariable logistic regression analysis was performed with fast backward elimination of variables and the bootstrap-based optimism-correction was adopted to assess model performance. Variation related to hospital or surgeon effects were quantified by a generalized mixed linear model and risk-adjusted funnel plots by displaying the individual standardized mortality ratio against expected deaths. Final variables retained in the model were: age [odds ratio (OR) 1.02, 95% confidence interval (CI) 1.02–1.03; P, Graphical Abstract

Background & objectives: The state of Punjab, India is highly endemic for dengue fever as high number of confirmed dengue cases have been reported since 2013. A better understanding of vectors distribution and their seasonal variation is necessary to control the disease. Therefore, the present study was conducted in both rural and urban areas of 11 out of 22 districts of Punjab to highlight seasonal prevalence of Aedes vector mosquitoes. Methods: Entomological surveys were carried out in different seasons and all kinds of indoor and outdoor breeding habitats were examined and Aedes immatures were collected. The Stegomyia indices were calculated and compared from urban and rural areas in different seasons. Results: Both vectors of dengue, i.e. Aedes aegypti and Ae. albopictus were recorded to be prevalent. Ae. aegypti mosquitoes were observed in all districts surveyed while Ae. albopictus were found only in seven districts of Punjab. The Stegomyia indices were significantly high during monsoon as compared to pre- and post- monsoon periods. Occurrence of dengue cases were found to be correlated with the Stegomyia indices. Interpretation & conclusion: This is the first detailed study of prevalence of dengue mosquito vectors in Punjab showing the presence of Ae. aegypti and Ae. albopictus in both urban and rural areas of the state, thereby demonstrating wide distribution of this vector. Different breeding habitats identified in the study should be subjected to targeted intervention such as source reduction in order to achieve effective control of dengue cases.

Results of trial and registry studies have shown lower long-term mortality after invasive management than after conservative management among patients with non-ST elevation myocardial infarction (NSTEMI). Elderly patients were majorly underrepresented in these previous studies. Using data from the

The clinical importance of troponin level in patients presenting with atrial fibrillation (AF) is uncertain. We investigated the relationship between troponin level, angiography and mortality in patients undergoing troponin testing with a primary diagnosis of AF. We used the National Institute for

Decompressive craniectomy is an increasingly implemented intervention for relief of intracranial hypertension refractory to medical therapy. Despite its therapeutic benefit, a myriad of short and long-term complications may arise when the once fixed-volume cranial vault remains decompressed. The authors present a case of recurrent Syndrome of the Trephined in a patient undergoing repeated craniectomy and cranioplasty.A 70-year old male with history significant for smoking and chronic obstructive pulmonary disease presented with frontoparietal subdural hematoma with midline shift following a ground level fall necessitating craniotomy and hematoma evacuation. Three months postoperatively, the patient developed an infection of his craniotomy bone flap necessitating craniectomy without cranioplasty. Six weeks post-craniectomy the patient began demonstrating right sided sensorimotor deficits with word finding difficulties. Alloplastic cranioplasty was performed following resolution of infection, with resolution of neurologic symptoms 6 weeks post cranioplasty. Due to recurrent cranioplasty infections, multiple alloplastic cranioplasties were performed, each with reliable re-demonstration of neurologic symptoms with craniectomy, and subsequent resolution following each cranioplasty. Final cranioplasty was successfully performed using a new alloplastic implant in combination with latissimus muscle flap, with subsequent return of neurologic function.Decompressive craniectomy is a life-saving procedure, but carries many short- and long-term complications, including the Syndrome of the Trephined. Our case is the first published report, to our knowledge, to demonstrate recurrent Syndrome of the Trephined as a complication of craniectomy, with reliable resolution of the syndrome with restoration of the cranial vault.

Objectives: To validate the use of neck dissection as part of the management of parotid carcinoma. Design, setting, participants: Retrospective pathological and clinical data were retrieved from the Guy’s and St Thomas’ Hospital Head and Neck pathology archive for all primary parotid carcinoma resected at the centre between 1992 and 2014. Main outcome measure: The main outcome measure was the incidence of metastatic disease. Results: 54 of the 82 cases identified underwent a neck dissection. Nodal metastases were detected in 10 cases of carcinomas ex-pleomorphic adenoma (high grade, invasive), 2 salivary duct carcinomas, 1 adenocarinoma not otherwise specified (NOS) (high grade), 1 adenoid cystic carcinoma and 1 acinic cell carcinoma (high grade). No metastases were found in cases of acinic cell carcinoma (low grade), mucoepidermoid carcinoma (low grade), epithelial-myoepithelial carcinoma and non-invasive carcinoma ex-pleomorphic adenoma. Conclusions: The findings of this study support the use of routine neck dissection in treating carcinoma ex-pleomorphic adenoma (high grade, invasive), salivary duct carcinoma, adenocarcinoma NOS (high grade), adenoid cystic carcinoma and acinic cell carcinoma (high grade).

Background Cardioembolism in paroxysmal atrial fibrillation (PAF) is a preventable cause of transient ischaemic attack (TIA) or ischaemic stroke; however, due to its transient nature, a short-duration Holter monitor may miss a significant proportion of events. Methods We conducted an open-label randomised controlled trial of cardiac monitoring after a TIA or ischaemic stroke comparing a 14-day ECG monitoring patch (Zio® Patch, iRhythm Technologies) with short-duration Holter monitoring for the detection of PAF. The primary outcome was the detection of one or more episodes of ECG-documented PAF lasting at least 30 s within 90 days in each of the study arms. A budget impact analysis from the healthcare perspective was performed. Results From February 2016 through February 2017, 43 (76.8%) of the 56 patients assigned to the patch-based monitoring group and 47 (78.3%) of the 60 patients assigned to short-duration Holter monitoring group had successful monitor placement with 90 days of follow-up. Of the 26 protocol failures between the two groups, 23 (88.5%) were due to patient refusal for outpatient short-duration ECG monitor placement, whilst only 1 (3.8%) was due unsuccessful ZioPatch placement. The rate of detection of PAF at 90 days was 16.3% in the patch-based monitoring group (seven patients) compared to 2.1% in the short-duration Holter monitoring group (1 patient), with an odds ratio of 8.9 (95% CI 1.1–76.0; P = 0.026). An economic model demonstrated that implementation of the Zio Patch service would result in 10.8 more strokes avoided per year compared to current practice with Holter monitoring with an associated yearly saving in direct medical costs of £113,630, increasing to £162,491 over 5 years. Conclusions Early, prolonged, patch-based monitoring after an index stroke or TIA is superior to short-duration Holter monitoring in the detection of PAF and likely cost-effective for preventing recurrent strokes. Trial registrationhttp://www.isrctn.com. Unique identifier: ISRCTN 50253271. Registered 21 January 2016

ObjectivesCongestion is associated with worse outcomes in critically ill surgical patients but can be difficult to quantify noninvasively. We hypothesised that plasma volume status (PVS), estimated preoperatively using a validated formula that enumerates percentage change from ideal plasma volume (PV), would provide incremental prognostic utility after coronary artery bypass graft (CABG) surgery.MethodsIn this retrospective cohort study, patients who underwent CABG surgery (1999–2010) were identified from a prospectively collected database. Actual ([1-haematocrit] x [a+(b x weight [kg])]) and ideal (c x weight [kg]) PV were obtained from equations where a, b and c are sex-dependent constants. Calculated PVS was then derived (100% x [(actual−ideal)/ideal]).ResultsIn 1887 patients (mean age 67±10 years; 79% male; median European System for Cardiac Operative Risk Evaluation [EuroSCORE] 4), mean PVS was −8.2±9%. While 8% of subjects had clinical evidence of congestion, a relatively increased PV (PVS >0%) was estimated in 17% and correlated with lower serum sodium, higher EuroSCORE and a diagnosis of diabetes mellitus. A PVS≥5.6% was optimally prognostic and associated with greater mortality (HR: 2.31, p=0.009), independently of, and incremental to, EuroSCORE, New York Heart Association class and serum sodium. A PVS≥5.6% also independently predicted longer intensive care (β: 0.65, p=0.007) and hospital (β: 2.01, p=0.006) stays, and greater postoperative renal (OR: 1.61, p=0.008) and arrhythmic (OR: 1.29, p=0.03) complications.ConclusionsHigher PVS values, calculated simply from weight and haematocrit, are associated with worse inpatient outcomes after CABG. PVS could help refine risk stratification and further investigations are warranted to evaluate the potential clinical utility of PVS-guided management in patients undergoing CABG.

Background Per-oral pancreatoscopy (POP) plays a role in the diagnosis and therapy of pancreatic diseases. With recent technological advances, there has been renewed interest in this modality. Aim To evaluate the efficacy and safety of POP in management of pancreatic stone disease and pancreatic ductal neoplasia. Methods To determine the safety and efficacy of POP in the management of pancreatic diseases, a systematic search was conducted in MEDLINE, EMBASE and Ovid. Articles in languages other than English and case reports were excluded. All published case series were eligible. Data specific to POP were extracted from studies, which combined cholangiopancreatoscopy. Ten studies were included in the analysis of POP therapy for pancreatic stone disease, and 15 case series satisfied the criteria for inclusion for the role of POP in the management of pancreatic ductal neoplasia. The examined data were subcategorized according to adjunctive modalities, such as direct tissue sampling, cytology, the role of intraoperative POP, intraductal ultrasound (IDUS) and POP combined with image-enhancing technology. Results The success rate for complete ductal stone clearance ranged from 37.5%-100%. Factors associated with failure included the presence of strictures, multiple stones and the inability to visualize the target area. Although direct visualization can identify malignant and premalignant conditions, there is significant overlap with benign diseases. Visually-directed biopsies provide a high degree of accuracy, and represent a unique approach for tissue acquisition in patients with ductal abnormalities. Addition of pancreatic fluid cytology increases diagnostic yield for indeterminate lesions. Protrusions larger than 3 mm noted on IDUS are significantly more likely to be associated with malignancy. The rate of adverse events associated with POP ranged from 0%-35%. Conclusion Current evidence supports wider adoption of pancreatoscopy, as it is safe and effective. Improved patient selection and utilization of novel technologies may further enhance its role in managing pancreatic disease.

Background CT coronary angiography (CTCA)-derived low attenuation plaque has recently been identified as the strongest predictor of future myocardial infarction. Antibodies against oxidized low-density lipoprotein (oxLDL)/ malondialdehyde-modified LDL (MDA-LDL) are related to freedom from cardiovascular events. Objectives To investigate possible relationships between CTCA-derived atherosclerotic plaque subtypes and anti-oxLDL antibodies. Methods In a post-hoc analysis of the multicentre randomised controlled SCOT-HEART trial (Scottish COmputed Tomography of the HEART), we investigated the association between quantitatively assessed atherosclerotic plaque types on CTCA and IgM/ IgG anti-MDA-LDL or oxLDL. Serological biomarkers were measured using laboratory-developed enzyme-linked immunosorbent assays, and assessed versus imaging parameters. Results In 830 patients (52.8% male, 57.6±9.8 years), IgM anti-MDA-LDL was significantly inversely associated with coronary artery calcium score (p=0.0099) and obstructive coronary artery disease (OR 0.63 ([95% CI, 0.42-0.95], p=0.028). IgG anti-MDA-LDL strongly indicated protection from greater number of obstructed coronary arteries (OR 0.20 [95% CI 0.07-0.62], p=0.0048). Increasing tertiles of IgG anti-MDA-LDL related to less low attenuation plaque (p value for trend; unadjusted, p=0.021; adjusted for cardiovascular risk score, p=0.023). When using a predefined threshold of low attenuation plaque burden >4%, the highest tertile of IgG anti-MDA-LDL was significantly associated with low attenuation plaque at a threshold that confers a reduced likelihood of fatal or non-fatal myocardial infarction, withstanding adjustment for cardiovascular risk score (OR 0.58 [95% CI 0.34-0.96], p=0.037), p=0.027 for trend. Conclusions Both IgM and IgG anti-MDA-LDL antibodies are associated with protection from various atherosclerotic plaque characteristics. For the first time we provide evidence linking IgG anti-MDA-LDL antibodies with protection from low attenuation plaque, which is the strongest predictor of future fatal and non-fatal myocardial infarction. Conflict of Interest None

Objectives To determine the extent to which living conditions and individual behaviors influence the association between oral health status and systemic disease outcomes in Ontario, Canada's most populated province. Methods A secondary data analysis of Ontario data from the Canadian Community. Health Survey 2013/14 was undertaken. Separate analyses were conducted for participants aged 35-59 years (n = 11,858) and 60+ years (n = 11,273). A series of regression models were constructed to examine the association between self-reported oral health status and systemic disease outcomes (arthritis, diabetes, hypertension, heart disease, chronic obstructive pulmonary disease, and stroke). Models were adjusted by proxies of living conditions (income, education, ethnicity, country of birth, employment, and food security) and individual behaviors (smoking status, alcohol use, tooth brushing, life stress, physical activity, sense of belonging). Percent attenuation between models was calculated to determine the extent of the living condition-behavior impact. Results In both age groups, the prevalence of arthritis and high blood pressure was the highest, followed by heart disease. There was variation in percent attenuation by age group and outcome. Among participants aged 35-59 years, living conditions had a greater impact on the oral-systemic relationship, while individual behaviors played a greater role in this association among adults aged 60+ years. Conclusion There is an association between oral and systemic diseases; however, after accounting for living conditions and individual behaviors, this relationship was attenuated. This highlights the need to address upstream and midstream factors that are common to oral and systemic conditions.

Background The state of Punjab in India qualifies for malaria elimination because the number of cases reported through routine surveillance is in decline. However, surveillance system prevalence mainly provides malaria trends. Therefore, a prospective epidemiological study was designed to estimate the malaria burden in the state. Methods District-wise annual parasite incidence (API) was used for identification of three strata, representing high, moderate and low API zones. A total of 0.9 million people from nine districts was under malaria surveillance for 1 y. The weighted estimates of API for the three regions was calculated and combined to give an estimate of API for the total population of the state. Results Based upon the primary data generated, malaria cases from high, moderate and low malaria-endemic areas were estimated to be 3727, 904 and 106, respectively. Further, the total number of malaria cases in the state was estimated to be 4737 (95% CI 4006 to 5469) cases per annum. Conclusion Actual burden of malaria in the state of Punjab, India, is about seven to eight times higher than that reported by routine surveillance activities. However, the state still qualifies for malaria elimination but needs vigorous efforts to strengthen the active surveillance and reporting system along with implementation of effective control strategies to achieve malaria elimination.

Description, RyR1 Ca2+ leak causes a cascade of events that shifts Ca2+ to the cytoplasm and mitochondria, supporting force generation., Muscle contraction depends on tightly regulated Ca2+ release. Aberrant Ca2+ leak through ryanodine receptor 1 (RyR1) on the sarcoplasmic reticulum (SR) membrane can lead to heatstroke and malignant hyperthermia (MH) susceptibility, as well as severe myopathy. However, the mechanism by which Ca2+ leak drives these pathologies is unknown. Here, we investigate the effects of four mouse genotypes with increasingly severe RyR1 leak in skeletal muscle fibers. We find that RyR1 Ca2+ leak initiates a cascade of events that cause precise redistribution of Ca2+ among the SR, cytoplasm, and mitochondria through altering the Ca2+ permeability of the transverse tubular system membrane. This redistribution of Ca2+ allows mice with moderate RyR1 leak to maintain normal function; however, severe RyR1 leak with RYR1 mutations reduces the capacity to generate force. Our results reveal the mechanism underlying force preservation, increased ATP metabolism, and susceptibility to MH in individuals with gain-of-function RYR1 mutations.

Arboviruses are of public health concern globally. Zika virus (ZIKV) is one of the recent emerging arboviruses that caused a great fear worldwide because of its quick spread and complicated clinical manifestations. The primary vector responsible for transmission of this arbovirus is the mosquito species Aedes aegypti L. Unfortunately, neither effective vaccines nor specific drugs are available against these viruses; therefore direct targeting of mosquitoes is required to control the spread of this disease. In recent years, various plant-derived products are being used to check their effectiveness against mosquitoes. Plant essential oils (EOs) are used as bioinsecticide and are considered environment- and user-friendly with minimal development of resistance. Even though EOs are considered safe, few side effects like skin irritation are associated with some EOs. Therefore development of plant EOs with better repellent properties, long activity, target selectivity, and low toxicity to humans and environment is required.

In developing countries, typhoid fever is a common cause of febrile illness accompanied by abdominal pain and weakness. It is caused by Salmonella enterica serovar Typhi. Humans are the only known reservoir of infection, and typhoid fever is common in regions where access to clean water and sanitation is limited. The antimicrobials of choice for a case of typhoid fever acquired outside Pakistan are third generation cephalosporins. Lately, cases of extensively drug-resistant (XDR) Salmonella Typhi have been reported in people with a travel history to Pakistan. We present a case of XDR typhoid fever which relapsed after treatment with meropenem.

This review examines the latest evidence for photodynamic therapy (PDT) in treating chronic rhinosinusitis. MedLine, EMBASE and TRIP Database searches were conducted using the terms: "photodynamic" or "phototherapy" or "photo" and "sinusitis" or "rhinosinusitis," date range January 2000 to May 2020. A total of 192 records were initially identified, after duplicates and exclusions, 9 full papers and 3 abstracts were included. All study types including in-vitro, animal and human studies were evaluated. Whilst there is in-vitro evidence for the efficacy of PDT's bactericidal effect on drug resistant bacteria and biofilm viability, there are few clinical studies. PDT is a promising area of research, but larger, focused studies looking at the safety, delivery, efficacy, and patient selection are required before it can be considered a viable treatment for CRS.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. The natural history of COPD is punctuated by exacerbations, which have major short- and long-term implications on the patient and health care system. Evidence-based guidelines stipulate that early detection and prompt treatment of exacerbations are essential to ensure optimal outcomes and to reduce the burden of COPD. In this review, we provide a concise overview of COPD exacerbations and their risk factors and etiology (infection vs noninfectious), outlining the initial evaluation, triaging, and current management including invasive and noninvasive ventilation, in addition to the prognosis and the preventive strategies.

10% of pleomorphic adenomas occur in the minor salivary glands with the palate being the most common site. Pleomorphic adenomas account for the majority of palatal tumours; however, minor salivary gland tumours have a higher risk of malignancy compared to tumours of the major salivary glands, so definite diagnostic evaluation should be executed. A case of 26-year-old man with a longstanding history of a soft palate pleomorphic adenoma which required excision under general anaesthetia We discuss the appropriate preoperative investigations, operative technique for surgical excision, histopathologic interpretation for this patient and brief review of literature for pleomorphic adenoma.

Background: Microtia is one of the forms of ear loss and deformity. It is a congenital anomaly of the external ear. Social and psychological rehabilitation of such patients requires a prosthesis that is esthetic as well as has enough strength and texture to represent the natural ear. Because of financial constraints, some patients cannot afford the surgical procedure of grafting. Case report: This is a case of 17 year old female with congenital missing right ear along with facial deformity due to Lower Motor Neuron facial nerve palsy. Treatment plan: Prosthetic replacement of the missing ear was planned to improve the esthetic and social well being of the patient in an economical way. Conclusion: a definitive management of the missing ear can be done using dental implants and bar attachment if the financial condition and social acceptance with interim prosthesis is satisfactory.

Objective To determine the relation between age and troponin level and its prognostic implication. Design Retrospective cohort study. Setting Five cardiovascular centres in the UK National Institute for Health Research Health Informatics Collaborative (UK-NIHR HIC). Participants 257 948 consecutive patients undergoing troponin testing for any clinical reason between 2010 and 2017. Main outcome measure All cause mortality. Results 257 948 patients had troponin measured during the study period. Analyses on troponin were performed using the peak troponin level, which was the highest troponin level measured during the patient’s hospital stay. Troponin levels were standardised as a multiple of each laboratory’s 99th centile of the upper limit of normal (ULN). During a median follow-up of 1198 days (interquartile range 514-1866 days), 55 850 (21.7%) deaths occurred. A positive troponin result (that is, higher than the upper limit of normal) signified a 3.2 higher mortality hazard (95% confidence interval 3.1 to 3.2) over three years. Mortality varied noticeably with age, with a hazard ratio of 10.6 (8.5 to 13.3) in 18-29 year olds and 1.5 (1.4 to 1.6) in those older than 90. A positive troponin result was associated with an approximately 15 percentage points higher absolute three year mortality across all age groups. The excess mortality with a positive troponin result was heavily concentrated in the first few weeks. Results were analysed using multivariable adjusted restricted cubic spline Cox regression. A direct relation was seen between troponin level and mortality in patients without acute coronary syndrome (ACS, n=120 049), whereas an inverted U shaped relation was found in patients with ACS (n=14 468), with a paradoxical decline in mortality at peak troponin levels >70×ULN. In the group with ACS, the inverted U shaped relation persisted after multivariable adjustment in those who were managed invasively; however, a direct positive relation was found between troponin level and mortality in patients managed non-invasively. Conclusions A positive troponin result was associated with a clinically important increased mortality, regardless of age, even if the level was only slightly above normal. The excess mortality with a raised troponin was heavily concentrated in the first few weeks. Study registration ClinicalTrials.gov NCT03507309 .

Background Patients presenting with atrial fibrillation ( AF ) often undergo a blood test to measure troponin, but interpretation of the result is impeded by uncertainty about its clinical importance. We investigated the relationship between troponin level, coronary angiography, and all‐cause mortality in real‐world patients presenting with AF . Methods and Results We used National Institute of Health Research Health Informatics Collaborative data to identify patients admitted between 2010 and 2017 at 5 tertiary centers in the United Kingdom with a primary diagnosis of AF . Peak troponin results were scaled as multiples of the upper limit of normal. A total of 3121 patients were included in the analysis. Over a median follow‐up of 1462 (interquartile range, 929–1975) days, there were 586 deaths (18.8%). The adjusted hazard ratio for mortality associated with a positive troponin (value above upper limit of normal) was 1.20 (95% CI , 1.01–1.43; P CI , 1.9–3.4) at ≈250 multiples of the upper limit of normal. There was an exponential relationship between higher troponin levels and increased odds of coronary angiography. The mortality risk was 36% lower in patients undergoing coronary angiography than in those who did not (adjusted hazard ratio, 0.61; 95% CI , 0.42–0.89; P =0.01). Conclusions Increased troponin was associated with increased risk of mortality in patients presenting with AF . The lower hazard ratio in patients undergoing invasive management raises the possibility that the clinical importance of troponin release in AF may be mediated by coronary artery disease, which may be responsive to revascularization.

Life-threatening arrhythmias (LTAs) can trigger sudden cardiac death or provoke implantable cardioverter-defibrillator (ICD) discharges that escalate morbidity and mortality. Longitudinal myofibrils predominate in the subendocardium, which is uniquely sensitive to arrhythmogenic triggers. In this study, we test the hypothesis that mitral annular systolic velocity (S'), a simple routinely obtained tissue Doppler index of LV long-axis systolic function, might predict lethal arrhythmias irrespective of left ventricular ejection fraction (LVEF).This is a retrospective analysis of data from 302 patients (mean age, 68 years; LVEF, 32%; 77% male; 52% ischemic; 35% primary prevention; and 53% cardiac resynchronization therapy defibrillator [CRT-D]) who were followed up (median, 15 months) at two centers after receipt of an ICD or CRT-D for diverse indications. S', averaged from tissue Doppler-derived medial and lateral mitral annular velocities, was correlated with the primary outcome of time to sustained ventricular tachycardia (VT) or fibrillation (VF) needing device therapy.The median S' was 5.1 (interquartile range, 4.0-6.2) cm/sec and lower in CRT-D than ICD subjects (4.5 [3.8-5.6] cm/sec vs 5.5 [4.8-6.8] cm/sec, P .001). Fifty-six (19%) subjects had LTA. Each 1 cm/sec higher S' correlated to a 30% decreased risk of LTA (hazard ratio = 0.70; 95% CI, 0.57-0.87; P = .001) independently of age, sex, β-blocker use, center, ICD use, and LVEF. Adding S' to the baseline Cox model improved net reclassification (P = .02). An S'5.6 cm/sec was the best cutoff and linked to a 58% lower LTA risk than an S' ≤ 5.6 cm/sec (95% CI, 0.23-0.85; P = .02).A higher S' is associated with a reduced probability of LTA in cardiac device recipients irrespective of LVEF and may have the potential to be used clinically to titrate medical, device, and ablative therapies to mitigate future arrhythmic risk.

Objective: Cerebrovascular accidents are the second leading cause of death and the third leading cause of disability worldwide. We hypothesized that cerebellar transcranial direct current stimulation (ctDCS) of the dentate nuclei and the lower-limb representations in the cerebellum can improve functional reach during standing balance in chronic (&gt, 6 months&rsquo, post-stroke) stroke survivors. Materials and Methods: Magnetic resonance imaging (MRI) based subject-specific electric field was computed across a convenience sample of 10 male chronic (&gt, 6 months) stroke survivors and one healthy MRI template to find an optimal bipolar bilateral ctDCS montage to target dentate nuclei and lower-limb representations (lobules VII&ndash, IX). Then, in a repeated-measure crossover study on a subset of 5 stroke survivors, we compared 15minutes of 2mA ctDCS based on the effects on successful functional reach (%) during standing balance task. Three-way ANOVA investigated the factors of interest&ndash, brain regions, montages, stroke participants, and their interactions. Results: &ldquo, One-size-fits-all&rdquo, bipolar ctDCS montage for the clinical study was found to be PO9h&ndash, PO10h for dentate nuclei and Exx7&ndash, Exx8 for lobules VII&ndash, IX with the contralesional anode. PO9h&ndash, PO10h ctDCS performed significantly (alpha = 0.05) better in facilitating successful functional reach (%) when compared to Exx7&ndash, Exx8 ctDCS. Furthermore, a linear relationship between successful functional reach (%) and electric field strength was found where PO9h&ndash, PO10h montage resulted in a significantly (alpha = 0.05) higher electric field strength when compared to Exx7&ndash, Exx8 montage for the same 2mA current. Conclusion: We presented a rational neuroimaging based approach to optimize deep ctDCS of the dentate nuclei and lower limb representations in the cerebellum for post-stroke balance rehabilitation. However, this promising pilot study was limited by &ldquo, one-size-fits-all&rdquo, bipolar ctDCS montage as well as a small sample size.

Background The durability of TAVR prostheses has come under major scrutiny since the move towards lower risk patients. We sought to compare the rate of structural valve deterioration (SVD) over time between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). Methods We included all TAVR and SAVR patients (age ≥ 75 years) that were performed in our centre from 2005 until 2015. Applying the internationally “agreed on” definitions of SVD, we surveyed all available serial echocardiographic follow-ups. Results We included 269 TAVR and 174 SAVR cases. Post-intervention, TAVR patients had lower mean and peak gradients but higher rate of mild aortic regurgitation. SAVR patients had longer follow-up (in months, SAVR: 53 (30, 85) Vs TAVR: 33.4 (23, 52)). SVD as per Valve Academic Research Consortium-2 (VARC-2) was similar between the two groups (TAVR 28% Vs SAVR 31%; P = 0.593) but moderate haemodynamic SVD (European Association of Percutaneous Cardiovascular Intervention (EAPCI) criteria) was more common among SAVR cases (TAVR 11.5% Vs SAVR 20.7%; P = 0.007). Using Kaplan-Meier estimates, the rate of SVD over time was not different between the two groups as per VARC-2 criteria but different when moderate haemodynamic SVD criteria were applied (Log Rank P = 0.022) in favour of TAVR. The mean gradient rose steadily over time but more so post-SAVR (β = 0.52 ± 0.24 in comparison to TAVR at every given time point; P = 0.032). Conclusion Structural valve deterioration is common on long-term follow-up post-TAVR. The rate is similar to post-SAVR cases according to VARC-2 criteria but less according to the moderate haemodynamic SVD criteria.

Background Surgical subspecialization has resulted in mastitis and breast abscesses being managed with unnecessary admission to hospital, prolonged inpatient stay, variable antibiotic prescribing, incision and drainage rather than percutaneous aspiration, and loss to specialist follow-up. The objective was to evaluate a best-practice algorithm with the aim of improving management of mastitis and breast abscesses across a multisite NHS Trust. The focus was on uniformity of antibiotic prescribing, ultrasound assessment, admission rates, length of hospital stay, intervention by aspiration or incision and drainage, and specialist follow-up. Methods Management was initially evaluated in a retrospective cohort (phase I) and subsequently compared with that in two prospective cohorts after introduction of a breast abscess and mastitis pathway. One prospective cohort was analysed immediately after introduction of the pathway (phase II), and the second was used to assess the sustainability of the quality improvements (phase III). The overall impact of the pathway was assessed by comparing data from phase I with combined data from phases II and III; results from phases II and III were compared to judge sustainability. Results Fifty-three patients were included in phase I, 61 in phase II and 80 in phase III. The management pathway and referral pro forma improved compliance with antibiotic guidelines from 34 per cent to 58·2 per cent overall (phases II and III) after implementation (P = 0·003). The improvement was maintained between phases II and III (54 and 61 per cent respectively; P = 0·684). Ultrasound assessment increased from 38 to 77·3 per cent overall (P < 0·001), in a sustained manner (75 and 79 per cent in phases II and III respectively; P = 0·894). Reductions in rates of incision and drainage (from 8 to 0·7 per cent overall; P = 0·007) were maintained (0 per cent in phase II versus 1 per cent in phase III; P = 0·381). Specialist follow-up improved consistently from 43 to 95·7 per cent overall (P < 0·001), 92 per cent in phase II and 99 per cent in phase III (P = 0·120). Rates of hospital admission and median length of stay were not significantly reduced after implementation of the pathway. Conclusion A standardized approach to mastitis and breast abscess reduced undesirable practice variation, with sustained improvements in process and patient outcomes.

BACKGROUND: Narrow-band UVB (NB-UVB) has been shown to be one of the most effective treatment modalities for psoriasis. Tazarotene, a known effective anti-psoriatic modality, when combined with NB-UVB may enhance the therapeutic success. OBJECTIVE: To study clinical efficacy and safety of combination of NB-UVB with topical tazarotene 0.05% gel in psoriasis. METHOD: Thirty patients with plaque psoriasis having symmetrical lesions were enrolled for 12 weeks. All patients were instructed to apply tazarotene gel on target plaque on left side of body once daily. In addition, the whole body was irradiated with NB-UVB twice weekly. Efficacy was assessed by target plaque scoring and number of treatment sessions for clearance. RESULT: Our study resulted in 3 key findings: Firstly, therapeutic efficacy of NB-UVB was enhanced by addition of tazarotene. This enhanced efficacy was more apparent in decreasing scaling and thickness as compared to decrease in erythema. Secondly, combination therapy showed faster clearance of target plaques, with reduction in mean number of treatment sessions. Thirdly, mean cumulative NB-UVB dose needed to achieve clearance of target plaques was significantly reduced with combination therapy. STUDY LIMITATIONS: The study was not randomized or controlled, but an open-label trial. The study period was relatively short, i.e., 12 weeks, without any follow-up period. CONCLUSION: Tazarotene gel significantly enhances the therapeutic efficacy of NB-UVB irradiation with faster clearance and without serious side effects.

Purpose Early treatment of heterotopic ossification (HO) is currently limited by delayed diagnosis due to limited visualization at early time points. In this study, we validate the use of spectral ultrasound imaging (SUSI) in an animal model to detect HO as early as one week after burn tenotomy. Methods Concurrent SUSI, micro CT, and histology at 1, 2, 4, and 9 weeks post-injury were used to follow the progression of HO after an Achilles tenotomy and 30% total body surface area burn (n = 3–5 limbs per time point). To compare the use of SUSI in different types of injury models, mice (n = 5 per group) underwent either burn/tenotomy or skin incision injury and were imaged using a 55 MHz probe on VisualSonics VEVO 770 system at one week post injury to evaluate the ability of SUSI to distinguish between edema and HO. Average acoustic concentration (AAC) and average scatterer diameter (ASD) were calculated for each ultrasound image frame. Micro CT was used to calculate the total volume of HO. Histology was used to confirm bone formation. Results Using SUSI, HO was visualized as early as 1 week after injury. HO was visualized earliest by 4 weeks after injury by micro CT. The average acoustic concentration of HO was 33% more than that of the control limb (n = 5). Spectroscopic foci of HO present at 1 week that persisted throughout all time points correlated with the HO present at 9 weeks on micro CT imaging. Conclusion SUSI visualizes HO as early as one week after injury in an animal model. SUSI represents a new imaging modality with promise for early diagnosis of HO.

Introduction: All antiretroviral therapies (ARTs) are potentially toxic to the liver. In sub-Saharan Africa, the rising incidence of ART induced adverse events has complicated treatment leading to recent revisions of Namibian ART guidelines. Unfortunately there have been limited studies to date evaluating ART induced liver injury in Namibia to guide further revisions if needed.Objective: Determine the current patterns and grades of ALT elevation in Namibia’s HIV/AIDS.Methods: Retrospective cohort analysis. Patterns of alanine amino transferase (ALT) liver enzyme elevation were determined in a cohort of ART naïve HIV patients on firstline ART regimen in a referral hospital in Namibia over a 1 year treatment period. Patterns of ALT changes at baseline, 3 months and 6 months were analyzed using ANOVA and Bonferroni test for pairwise comparisons.Results: Of 79 eligible patients, 72 developed significant ALT elevation within 3 months of ART initiation (F (3, 76) = 6.4, p = 0.002, ƞ2 = 0.193). Four 4 (5.6%) and 1 (1.38%) patient respectively developed grade 2 and grade 3 ALT elevation by month 3. There was no significant difference between mean ALT levels at baseline and month 6. A CD4 count of

Obesity is a highly prevalent public health concern, attributed to multifactorial causes and limited in treatment options. Several comorbidities are closely associated with obesity such as the development of type 2 diabetes mellitus (T2DM), cardiovascular and cerebrovascular diseases, and nonalcoholic fatty liver disease (NAFLD). Bariatric surgery, which can be delivered in multiple forms, has been remarked as an effective treatment to decrease the prevalence of obesity and its associated comorbidities. The different types of bariatric surgery create a variety of new pathways for food to metabolize in the body and truncate the stomach’s caliber. As a result, only a small quantity of food is tolerated, and the body mass index noticeably decreases. This review describes the improvements of obesity and its comorbidities following bariatric surgery and their mechanism of improvement. Additionally, endocrine function improvements after bariatric surgery, which contributes to the patients’ health improvement, are described, including the role of glucagon-like peptide-1 (GLP-1), fibroblast growth factors 19 and 21 (FGF-19, FGF-21), and pancreatic peptide YY (PYY). Lastly, some of the complications of bariatric surgery, including osteoporosis, iron deficiency/anemia, and diarrhea, as well as their potential mechanisms, are described.

Efficacy of chemotherapeutic treatment continues to vary drastically from patient to patient because of the complex development and progression of cancer. The standard treatment procedures involve identification of the types and stages of cancer, followed by a plethora of therapies, however, with little or no room for personalizing the treatment. The objective of the current study is to develop a biologically consistent mathematical model of an avascular tumor, considering the mass transfer, pharmacological and pharmacodynamic characteristics of chemotherapy drugs and nutrients. The model simulation results are used to study progression of the tumor growth, while monitoring efficacy of the chemotherapeutic drugs, namely, cisplatin and paclitaxel. The simulations are performed using CompuCell3D, a Glazier-Graner-Hogeweg (GGH) model-based software integrated with partial differential solver, FiPy. Specifically, the developed model in this study considers the individual and combinatorial administration of the drugs. The model simulation results, with GGH as the underlying principle, allow studying the dynamics of the tumor at an individual cell-scale, while monitoring the cell-cycle phase, nutrient and drug uptakes, and cell repair. The simulation results reveal that paclitaxel is more potent than cisplatin when both drugs are administered combinatorically.

Background Little is known about variations in care and outcomes of patients undergoing surgical repair for type A aortic dissection(TAAD). We aim to investigate decade-long trends in TAAD surgical repair in England. Methods Retrospective review of the National Adult Cardiac Surgery Audit, which prospectively collects demographic and peri‑operative information for all major adult cardiac surgery procedures performed in the UK. We identified patients undergoing surgery for TAAD from January 2009-December 2018, reviewed trends in operative frequency, patient demographics, and mortality. Findings Over the 10-year period,3,680 TAAD patients underwent surgical repair in England. A doubling in the overall number of operations conducted in England was observed (235 cases in 2009 to 510 in 2018). Number of procedures per hospital per year also doubled(9 in 2009 to 23 in 2018). Overall, in-hospital mortality was 17.4% with a trend toward lower mortality in recent years(23% in 2009 to 14.7% in 2018). There was a significant variation in operative mortality between hospitals and surgeons. We also found that most patients presented towards the middle of the week and during winter. Interpretation Surgery is the only treatment for acute TAAD but is associated with high mortality. Prompt diagnosis and referral to a specialist center is paramount. The number of operations conducted in England has doubled in 10 years and the associated survival has improved. Variations exist in service provision with a trend towards better survival in high volume centers. Funding British Heart Foundation and NIHR Biomedical Research center(University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol).

The present work was conducted to isolate and detect by PCR three important bacterial pathogens (Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus uberis) associated with bovine mastitis. A total of 36 clinical mastitic milk samples were collected from various cross bred cattle presented in the Veterinary Clinical complex centre, Bikaner, Rajasthan. Out of 36 milk samples processed, we recovered 51 isolates belonging to Staphylococcus aureus (18), Streptococcus uberis (5), Streptococcus agalactiae (2), Staphylococcus intermedius (8), Staphylococcus chromogens (4), Bacillus sp. (2) and Escherichia coli (12). The PCR conducted directly on milk samples with species-specific primers of Staphylococcus aureus, Streptococcus agalactiae and Streptococcus uberis revealed 19, 7 and 2 samples respectively positive for these pathogens. The study showed highest incidence of Staphylococcus aureus (50.0%) followed by Streptococcus uberis, (13.89%) and Streptococcus agalactiae (5.5%) by culture-based method while incidence rate recorded by PCR of Staphylococcus aureus (52.77%) followed by Streptococcus uberis, (19.44%) and Streptococcus agalactiae (5.5%) associated with bovine mastitis. Thus, PCR was found to have a good correlation with cultural method for diagnosis of the causative agent of mastitis in a short span of time.

Tracking world cases of breast implant-associated anaplastic large cell lymphoma (ALCL) is currently limited to patient registries at a few academic centers, dependent upon patient referral and case reports in the literature. The purpose of this study was to review and compare federal database adverse event reports of breast implant-associated ALCL encompassing the major breast implant markets worldwide.Federal implantable device regulatory bodies were contacted and database queries were performed for 40 countries. Demographics, device characteristics, pathology, treatment modalities, and outcomes were assessed when available.For the countries queried, 363 unique cases were reported for breast implant-associated ALCL. Search terms "anaplastic" and "ALCL" were queried of the U.S. Manufacturer and User Facility Device Experience (MAUDE) database and yielded 258 unique cases as of September 2015, of which only 130 had pathologic markers performed. Implant surface was textured significantly more than smooth (50 percent versus 4.2 percent; p = 0.0001). Treatment, when reported (n = 136), included explantation [n = 125 (91.9 percent)], chemotherapy [n = 42 (30.8 percent)], radiation therapy [n = 25 (18.4 percent)], and/or stem cell transplant [n = 9 (6.6 percent)], and five deaths were reported.Federal reporting of breast implant-associated ALCL has limitations in providing clinical history, treatment, and oncologic follow-up. Worldwide and country-specific total and textured implant sales data are needed to determine critical incidence and prevalence analysis. International multi-institutional collaborations and centralized tissue consortiums working in concert with federal authorities are necessary to acquire accurate complete data on breast implant-associated ALCL.

Metastatic pancreatic cancer (mPC) is associated with low survival, with less than 10% of patients surviving 5 years. Recent therapies improve survival outcomes where few alternative therapies exist, but few economic analyses measure the value of survival gains attributable to new therapies.To estimate the value of survival gains in advanced or mPC attributable to the introduction of novel treatment regimens.Multivariate Cox proportional hazards models were used to estimate real-world survival gains associated with the introduction of gemcitabine (GEM) for patients diagnosed with stage IV or unstaged mPC in the Surveillance, Epidemiology, and End Results Program cancer registries. Then, evidence from clinical trials was used to evaluate the survival gains associated with nab-paclitaxel + gemcitabine (nP +GEM) and FOLFIRINOX (FFX) relative to GEM. The survival estimates and clinical trial evidence were used to calibrate an economic model and assess the cumulative value of survival gains in mPC to patients. Costs of treatment were calculated based on published cost-effectiveness studies.We estimated that the introduction of GEM in 1996 was associated with a hazard ratio of 0.920 (P0.05) and an increase in median survival from 3.1 to 4.5 months. Results suggested that the value of survival gains attributable to GEM equaled about $71,000 per patient, while the value attributable to nP + GEM was an additional $56,700. Estimates for the value of survival gains per patient, net of total incremental lifetime treatment costs (drugs, adverse events, and other costs), were $50,294 for GEM and an additional $31,900 for nP + GEM. Clinical trials and cost-effectiveness studies reported an overall survival gain from FFX that was larger than, but statistically similar to, nP + GEM and had greater risk of adverse events and total incremental costs. We estimated that the total value of survival gains to mPC patients, net of total costs, associated with GEM was up to $47.6 billion, and the additional values attributable to nP+GEM and FFX were up to $39.0 billion and $26.3 billion, respectively.Historically, mPC patients have faced high disease burden and had few treatment options. Treatments introduced since 1996 have led to improved survival, with varying costs associated with treatment and adverse events. Accounting for total incremental costs, the majority of the value of survival gains from GEM and nP+GEM was retained by mPC patients, highlighting the value of innovation in settings where survival is low and few alternative therapies exist.Support for this research was provided by Celgene. Precision Health Economics was compensated by Celgene for work on this study. MacEwan is an employee of, and Yin is a consultant to, Precision Health Economics. Kaura and Khan are employees of Celgene. Study concept and design were contributed primarily by Yin and MacEwan, along with Kaura and Khan. MacEwan collected the data, and data interpretation was performed primarily by MacEwan and Yin, along with Kaura and Khan. The manuscript was written and revised by MacEwan, Yin, Kaura, and Khan.

Background: Hepatitis B is highly infectious, but preventable diseases and dentists are at increased risk of exposure to saliva and blood of patients during their clinical practice, and so it is of utmost importance that they follow standard guidelines for infection control. Aims: To assess knowledge, attitude, and practices regarding infection control measures among dental students of Government Dental College in Punjab. Materials and Methods: A cross-sectional survey using a self-administered pretested questionnaire to dental students and responses were statistically analyzed. The analysis of variance was used to compare means of knowledge, attitude, and practice scores between four groups of study subjects and P < 0.05 is considered statistically significant. Results: Although the students have sufficient knowledge regarding hepatitis B, still there are gaps in putting their knowledge into practice. Third and final year students have significantly less mean knowledge and practice scores compared to interns and postgraduate students. The majority of students have a positive attitude and were willing to perform any procedure on hepatitis B-infected patients. Conclusions: Dental students have adequate knowledge and good attitude but still there are some misconceptions. There is poor implementation of standard infection control measures in their practice. Rigorous training programs on preventive practices and regular workshops must be organized on an annual basis in dental colleges. Moreover, hepatitis B vaccination must be made mandatory for students before they start their clinical practice.

Hepatic infarction is rare due to the unique dual hepatic blood supply from the hepatic artery and the portal vein. Herein, we report a case of hepatic infarction that occurred as a complication of acute pancreatitis. The patient was a 58-year-old male with past medical history of chronic alcoholism, who presented with epigastric abdominal pain, nausea, and vomiting. Hepatic infarction was diagnosed with computed tomography of the abdomen and pelvis without contrast, which revealed suspicion of splenic vein thrombosis and peripancreatic fat stranding along with a wedge-shaped, peripheral hypo density in the right hepatic lobe with typical morphology for hepatic infarction.