Ethical Review Board Approval Research Articles

Outcome of fecal incontinence in the two-staged seton fistulotomy for complex fistula in ANO.

Objective: To determine the frequency of fecal incontinence in the two-staged Seton fistulotomy in complex fistula in ano. Study Design: Prospective Cohort study. Setting: Surgical Out-patient Department at Shaikh Zayed Hospital Lahore. Period: September 2015 till March 2016. Material & Methods: After ethical review board approval, data was collected from 100 patients who fulfilled the inclusion criteria. All the procedures were conducted in the lithotomy position, under spinal or general anesthesia. A rigid sigmoidoscopy and proctoscopy was done prior to intervention. Fistula tract was marked using hydrogen peroxide (H202) for the identification of the internal opening. The external opening was gently probed using a standard 3 mm blunt-tipped probe till the internal opening was reached. The portion of the track outside the sphincter mechanism and any lateral tracts were laid open. A feeding tube of size 5 French was loosely tied around the remaining muscular portion of the sphincter complex. The seton was left in place for six weeks followed by secondary fistulotomy. Patients were evaluated for incontinence one month after the second procedure. Results: In our study, mean age was calculated as 47.38+10.96 years, 73%(n=73) were male and 27%(n=27) were females, frequency of fecal incontinence in the two-staged Seton fistulotomy in complex fistula in ano was recorded in 17%(n=17). Conclusion: The frequency of fecal incontinence in the two-staged seton fistulotomy for complex fistula in ano was acceptable in our study population and in tandem with literature. The procedure may be a suitable alternative to loose-seton placement alone.

Atrial Natriuretic Peptide in the Prevention of Postoperative Acute Renal Dysfunction in Patients Undergoing Heart Transplantation - An Investigator-Driven, Single-Center, Blinded, Randomized and Placebo-Controlled Trial

Purpose The development of acute kidney injury (AKI) and renal dysfunction is a common complication after heart transplantation (HTx) that is associated with increased morbidity and mortality. When used for treatment of AKI, infusion of atrial natriuretic peptide (ANP) has been shown to increase renal blood flow and glomerular filtration rate (GFR) after complicated cardiac surgery and in cyclosporine-induced AKI after HTx. Furthermore, it was shown that ANP reduced the probability of dialysis in cardiac surgery-associated AKI. The aim of this investigation was to evaluate whether ANP infusion could prevent or mitigate acute renal dysfunction after HTx. Methods After approval of Ethical Review Board and the Swedish Medical Products Agency, 72 adult patients undergoing HTx were included after informed consent. The patients were randomized to receive either ANP or placebo (saline) by a web-based computerized random-number generator. The anesthesia/intensive staff and physicians were blinded to the allocated treatment throughout the entire study. After induction of anesthesia, a continuous intravenous infusion of either ANP (HANP1000®, Daichii Sankyo Propharma, Japan) at a dose of 50 ng/kg/min or the equivalent volume of placebo (saline) was started. The administration of the study drugs continued for five postop days, or until the patient died or treatment with dialysis was started. Inclusion has been completed. Endpoints The primary end-point was measured mGFR at day five. mGFR was assessed by the infusion clearance of 52Cr-EDTA. The difference in mGFR between groups was estimated using intention-to-treat and per-protocol analyses. To detect a 30% higher mGFR in the ANP group, 31 patients per group would be required, assuming a 80% power and a two-sided error of 0.05. To compensate for drop-outs and for the use of nonparametric tests, we included 35 randomised patients per group. Secondary end-points were: the incidence of postoperative AKI (KDIGO criteria), daily postoperative serum creatinine, need for dialysis, intra- and postoperative diuresis, the use of diuretics, length of ICU and hospital stay, ICU mortality and 30-days mortality, length of mechanical ventilation, incidence of hypotension and arrhythmias and inotropic score.

Risk of Inflammatory Bowel Disease in HIV Patients: A Danish Cohort Study (1983-2018) with American Validation (1999-2018)

Background: HIV infection is implicated in the development of several immune mediated disorders, but the risk of inflammatory bowel disease (IBD) in people living with HIV (PLWH) remains uncertain. We aimed to study the risk of IBD among PLWH in a nationwide population-based Danish cohort study and to validate our findings with a US insurance-based database. Methods: Using Danish national patient registers (1983-2018), we identified a cohort of 8,995 PLWH who were matched to 449,750 HIV-negative individuals by age and sex, and followed for 7,154,999 person-years. Cumulative incidence of IBD in PLWH compared with matched non-HIV individuals was calculated. Cox regression analysis was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for development of IBD. Findings were validated using a US insurance-based cohort, Explorys (1999-2018), with results reported as odds ratios (OR) with 95% CI. Findings: The risk of IBD was significantly increased among PLWH in Denmark (HR: 2.24, 95% CI: 1.78-2.82) compared with the matched non-HIV population. This was seen for both Crohn’s disease (HR: 2.18, 95% CI: 1.43-3.34) and ulcerative colitis (HR: 2.22, 95% CI: 1.68-2.92) and in both the pre- and post-HAART era (pre-1996 HR: 2.30, 95% CI: 1.55-3.42; 1996-onwards HR: 2.11, 95% CI: 1.59-2.80). Risk was also increased in male (HR: 2.75, 95% CI: 2.15-3.52) but not female Danish PLWH (HR: 0.93, 95% CI: 0.48-1.79). US cohort analysis confirmed an increased risk of IBD in PLWH compared with non-HIV individuals (OR: 1.41, 95% CI: 1.35-1.49). Interpretation: This study finds a significantly increased risk of IBD among PLWH in both a Danish and US population. Further research into the interplay between HIV, IBD, and the impact of antiretroviral therapy on this relationship is required. Funding Statement: PSD is supported by the American Gastroenterology Association Research Scholar Award alongside Digestive Diseases Research Center grant and National Institue of Health grant (DK120515). Declaration of Interests: All authors declare that they have no conflict of interest. Ethics Approval Statement: TJ currently holds approval from the Danish Data Protection Agency for projects with datasets extracted from Danish national registers. Use of Explorys data does not require ethical review board approval. Ethical approval is not required for register-based research in Denmark.

A Descriptive Study of the Trends of COVID-19 in Zimbabwe from March – June 2020: Policy and Strategy Implications

Background: The first cases of COVID-19 were reported in China in December 2019. Since then, the disease has evolved to become a global pandemic. Zimbabwe reported its first case on 20 March 2020, and the number has been increasing steadily. However, Zimbabwe has not witnessed the exponential growth witnessed in other countries so far, and the trajectory seems different.Objectives: We set out to describe the epidemiological trends of COVID-19 in Zimbabwe from when the first case was confirmed to June 2020. Based on the analysis, policy and strategy implications were drawn.Methodology: Data were collected from daily situation reports that were published by the Zimbabwean Ministry of Health and Child Care from 20 March to 27 June 2020. Confirmation of COVID-19 positive cases was from daily RT-PCR and Rapid test reports conducted in various parts of the country and stratified by provinces. Missing data on the daily situation reports was not imputed. Findings: As of 27 June 2020, Zimbabwe had 567 confirmed COVID-19 cases. Eighty-two percent of these were returning residents and 18% were local transmission. The testing was heavily skewed towards returnees despite a comprehensive testing strategy. Of the confirmed cases, 142 were reported as recovered. However, demographic data for the cases were missing from the reports. It was not possible to estimate the probable period of infection of an active case, and case fatality in Zimbabwe was about 1% for the first 4 months of the pandemic.Conclusion: The epidemiological trends of COVID-19 experienced in Zimbabwe between March and June 2020 are somewhat different from what has been observed elsewhere. Further research to determine the reasons for the differences is warranted, to inform public health practice and tailor make suitable interventions.Funding Statement: No funding was sought.Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This is a description of data widely made available to the public, and therefore no ethical or institutional review board approval was necessary.

Clinical and imaging profiles of pulmonary embolism: a single-institution experience

BackgroundPulmonary embolism (PE) is a common life-threatening condition with non-specific clinical presentations. The diagnosis of PE depends highly on imaging studies, which may also provide prognostic information. This study aimed to describe the clinical and imaging profiles of patients with PE, emphasizing the differences between central and peripheral PE.MethodsAfter ethics review board approval, this retrospective observational study examined the non-negative results in adult patients who underwent computed tomography pulmonary angiography (CT-PA) at our hospital between May 2016 and December 2019. Demographic and clinical information and imaging findings were collected from the electronic medical records.ResultsThe study included 85 cases that were identified after re-interpreting the 103 non-negative CT-PA scans. Six cases were excluded for incomplete data and 12 cases were false-positive. Central PE was found in 63.5% of the cases. Obesity was the most common risk factor seen in 37.6% of the cases. Furthermore, 9.4% of the patients had sickle cell disease, which tended to be associated with peripheral PE. There was no difference between the peripheral and central PE in most clinical and imaging parameters evaluated (P > 0.05). However, patients with isolated subsegmental PE were more likely to develop hemoptysis (P = 0.04).ConclusionThis study suggests that patients with obesity and sickle cell disease constitute an important proportion of all PE cases. Furthermore, the clinical and imaging profiles in patients with peripheral PE are similar to those in patients with central PE. Future research should focus on the clinical value of peripheral PE in patients with sickle cell disease.

Urinary tract infection in pregnant females attending antenatal clinics among middle socioeconomic settings.

Objectives: To determine the frequency of Urinary tract infection (UTI) and the antibiotic sensitivity patterns of isolated uropathogens in pregnant females among middle socioeconomic settings. Study Design: Retrospective Cross Sectional study. Setting: Jinnah Medical College Hospital Karachi. Period: From Jan 2017 to Dec 2017. Material & Methods: This retrospective study was carried out in Jinnah Medical College Hospital (JMCH) Karachi after taking ethical review board approval. All the pregnant women who were registered in antenatal clinics from January 2017 to December 2017 was included. Data was taken from medical record department and information about age, parity, gravida, miscarriages, microorganisms of the urine samples and their antibiotic susceptibility pattern was noted. Results: Five hundred and sixty-four pregnant women of age 17-44 years were registered in the hospital in antenatal clinics during the year 2017. Out of 564 females, 48 (8.50%) presented with urinary tract infection some time during their pregnancy period. Majority of patients (54.2%) were infected with Escherichia coli (E coli), followed by Klebsiella pneumonia (16.77%), Pseudomonas spp. (12.5%), Enterococcus spp. (8.3%) and Staphylococus aureus (8.3%). These etiologic agents vary in their sensitivity pattern to antibiotics. Piperacillin-tazobactam had the highest overall sensitivity of (89.6%). This was followed by Meropenem (87.5%), Nitrofurantoin (87.5%) and Fosfomycin (81.3%). Cefixime, Cefotaxime and Amoxicillin/ clavulanic acid had overall sensitivities above 50%. Conclusion: E coli was the common organisms followed by others gram negative and positive organisms. Enteroococus spp. was also a significant bacterial isolates in this settings. Meropenem, Piperacillin-tazobactam, Nitrofurantoin, Fosfomycin were the highly effective antibiotics against isolated uropathogens. Amoxicillin/clavulanic acid and Cephalosporin also had a good results.

Lesional Inflammatory Profile in Hidradenitis Suppurativa Is Not Solely Driven by IL-1

Lesional Inflammatory Profile in Hidradenitis Suppurativa Is Not Solely Driven by IL-1

Gender differences in blood transfusion strategy for patients with hip fractures - a retrospective analysis.

Background: In the last decades, transfusion therapy with allogenic blood has progressively shifted to a more restrictive approach. The current study analyzed the transfusion practice and transfusion-associated factors in a regional trauma center over the course of five years.Methods: Retrospective analysis of all patients undergoing surgery for hip fractures in a level 1 trauma center of an academic teaching hospital from 2010 to 2014 (n=650). The number of transfused packed red blood cells (PRBCs), preoperative Hb concentrations, and intensive care unit (ICU) and hospital length of stay (LOS) were analyzed. A logistic regression analysis was performed to evaluate transfusion and ICU LOS-associated risk factors. (Ethical Review Board approval: 2015-497-f-S).Results: From 2010 to 2014 the average number of PRBCs transfused per patient decreased continuously despite similar preoperative Hb levels. During the same period, ICU LOS increased while hospital LOS decreased. Advanced patient age, preoperative Hb concentrations, surgical complications, and ICU LOS were associated with increased transfusion requirements. Although preoperative Hb levels were lower, females received fewer PRBCs compared to males.Conclusion: Over the course of five years, a restrictive transfusion strategy was implemented within clinical practice in patients undergoing surgery for hip fractures. In parallel, a significant reduction in the hospital LOS and an increased ICU LOS was noted. Whether there is an association between increased ICU LOS and decreasing hospital LOS and whether there is a gender effect on transfusion requirements in patients with surgery for hip fractures should be subject to further research.

Gender Disparity in Vietnamese Radiological Societies: a Preliminary Observational Study.

Introduction:The advancement of gender equality within radiology, a predominantly male profession, has currently been a significant concern.Aim:Therefore, in this original study, we aimed to investigate the gender disparity in Vietnamese radiological societies.Methods:No ethical committee or institutional review board approval was needed since the data were publicly available. In this retrospective study, we evaluated the faculties of four main radiological societies in Vietnam: Vietnamese society of radiology and nuclear medicine (VSRNM, n = 67); Radiological society of Ho Chi Minh City (RSHCM, n = 25); Vietnamese society of ultrasound in medicine (VSUM, n = 29); and Vietnamese society of interventional radiology (VSIR, n = 18).Results:There are significantly fewer women than men in faculties of four main radiological societies (15.1% vs. 84.9%). None of the women served as a professor and leader of any radiological societies. The women with a doctor of philosophy level are relatively low among the four main radiological societies. Also, female interventional and pediatric radiologists are seriously low among four main radiological societies.Conclusions:In Vietnamese radiological societies, gender disparities exist, especially about educational degrees and professorship positions. Future studies are essential to address the underlying roots of the gender gap and aid in the implementation of gender diversity programs and policies.

Dynamic expression of Slit1-3 and Robo1-2 in the mouse peripheral nervous system after injury.

The Slit family of axon guidance cues act as repulsive molecules for precise axon pathfinding and neuronal migration during nervous system development through interactions with specific Robo receptors. Although we previously reported that Slit1-3 and their receptors Robo1 and Robo2 are highly expressed in the adult mouse peripheral nervous system, how this expression changes after injury has not been well studied. Herein, we constructed a peripheral nerve injury mouse model by transecting the right sciatic nerve. At 14 days after injury, quantitative real-time polymerase chain reaction was used to detect mRNA expression of Slit1-3 and Robo1-2 in L4-5 spinal cord and dorsal root ganglia, as well as the sciatic nerve. Immunohistochemical analysis was performed to examine Slit1-3, Robo1-2, neurofilament heavy chain, F4/80, and vimentin in L4-5 spinal cord, L4 dorsal root ganglia, and the sciatic nerve. Co-expression of Slit1-3 and Robo1-2 in L4 dorsal root ganglia was detected by in situ hybridization. In addition, Slit1-3 and Robo1-2 protein expression in L4-5 spinal cord, L4 dorsal root ganglia, and sciatic nerve were detected by western blot assay. The results showed no significant changes of Slit1-3 or Robo1-2 mRNA expression in the spinal cord within 14 days after injury. In the dorsal root ganglion, Slit1-3 and Robo1-2 mRNA expression were initially downregulated within 4 days after injury; however, Robo1-2 mRNA expression returned to the control level, while Slit1-3 mRNA expression remained upregulated during regeneration from 4-14 days after injury. In the sciatic nerve, Slit1-3 and their receptors Robo1-2 were all expressed in the proximal nerve stump; however, Slit1, Slit2, and Robo2 were barely detectable in the nerve bridge and distal nerve stump within 14 days after injury. Slit3 was highly ex-pressed in macrophages surrounding the nerve bridge and slightly downregulated in the distal nerve stump within 14 days after injury. Robo1 was upregulated in vimentin-positive cells and migrating Schwann cells inside the nerve bridge. Robo1 was also upregulated in Schwann cells of the distal nerve stump within 14 days after injury. Our findings indicate that Slit3 is the major ligand expressed in the nerve bridge and distal nerve stump during peripheral nerve regeneration, and Slit3/Robo signaling could play a key role in peripheral nerve repair after injury. This study was approved by Plymouth University Animal Welfare Ethical Review Board (approval No. 30/3203) on April 12, 2014.

Responsive Asthma Care for Teens (ReACT): development protocol for an adaptive mobile health intervention for adolescents with asthma

IntroductionAsthma is a leading cause of youth morbidity in the USA, affecting >8% of youth. Adherence to inhaled corticosteroids (ICS) can prevent asthma-related morbidity; however, the typical adolescent with asthma...

Primary Palliative Care for Emergency Medicine (PRIM-ER): Protocol for a Pragmatic, Cluster-Randomised, Stepped Wedge Design to Test the Effectiveness of Primary Palliative Care Education, Training and Technical Support for Emergency Medicine

IntroductionEmergency departments (ED) care for society’s most vulnerable older adults who present with exacerbations of chronic disease at the end of life, yet the clinical paradigm focuses on treatment of...

A Risk Management Strategy for Managing Critical Human Resource Changes in a Pediatric Heart Program

BackgroundRelocation, recruitment, or retirement of critical team members may lead to changes in the expertise pool that could threaten patient outcomes in a pediatric heart program. We developed a quality initiative aimed at risk management that uses risk-stratified case complexity and outcomes to guide a program during critical fluxes in the expert staff. The Ramp Down/Up protocol is a systematic, voluntary reduction in the complexity of cases performed, followed by a transparent and intentional escalation of case complexity. MethodsInstitutional Ethics Review Board approval for this quality initiative was obtained. Patient/caregiver consent for quality data collection is obtained at the time of hospital admission. Every surgical patient having their index cardiac surgical procedure at the Izaak Walton Killam (IWK) from January 1, 2003, to December 2015 is included. The Ramp Down/Up protocol evolved to have to 4 critical elements: (1) a trigger and a reduction in case complexity; (2) an external/objective expert observer; (3) an escalation in case complexity; and (4) data (qualitative and quantitative) collection and analysis. ResultsThe Ramp Down/Up protocol was used 3 times over a 12-year period to address critical expert human resource challenges. The protocol was used for variable duration (3.5-9 months). Patient operative mortality was benchmarked to the Congenital Cardiac Surgery database, and outcomes were stable during and after protocol employment. ConclusionsA quality initiative aimed at risk management has allowed 1 pediatric heart team to ensure that patient outcomes were maintained during critical human resource changes.

A Growing Trend of Females and Dermatologists Among Top Medical Graduates in 30 Years

Background: Career outcomes of top medical graduates are seldom studied. The Tsungming Tu Foundation (TTF) has awarded the number one graduate from each medical school in Taiwan since 1981. We studied whether top medical graduates (TMG) differ from other medical graduates (OMG) in gender, specialty, and geographic regions decades in the last 30 years. Materials & Methods: Overall, 322 TMG and 40,075 OMG were identified from 1981-2017 from TTF and Taiwan healthcare public data. Subjects were further grouped by graduation year: 1981-1994, 1995-2001, 2002-2011, and after 2012. Ranges were based on implementation dates of new health policies. Results: The percentages of female OMG increased from 10•9% before 1994 to 32•6% after 2012 (linear trend, P<0•001). Similarly, the percentages of female TMG increased from 23•1% before 1994 to 42•4% after 2012 (linear trend, P=0•003). In contrast to 2% of OMG, the percentage of TMG who became dermatologists increased from 11%-20•5% (linear trend, P=0•024). TMG favored dermatology, ophthalmology, and neurology, and avoided general surgery (P<0•001). While still more likely than OMG, the percentage of TMG working in medical centers dropped significantly from 58% during 1981-1994 to 33•3% during 1995-2001 (P=0•035). This coincides with the launch of National Health Insurance in 1995. Finally, though more than half of TMG previously worked in Northern Taiwan, they have recently shifted to Mid-Taiwan. Conclusions: The percentages of female OMG and TMG reached 32•6% and 42•4%, respectively, after 2012. TMG more often chose dermatology, ophthalmology, and neurology, but avoided general surgery. Changes in health policy, reimbursement policy, and medical education affected both OMG and TMG career choices. Funding: The authors declared that the study receives no funding. Declaration of Interest: The authors declare that there are no conflicts of interest regarding the publication of this paper. Ethical Approval: The list of awardees of the Dr. Tsungming Tu Award, which represents the list of top medical graduates, is made publicly accessible as honors in the website of Tsungming Tu Foundation. Therefore, the study is exempted from ethical review board approval.

Association of seeking ophthalmic assessment in children with parental history of refractive errors.

Objective:To find out the association of seeking ophthalmic assessment in children with parental history of refractive errors.Methods:After the approval of ethical review board, an analytical cross-sectional study was conducted in eight high schools of public and private sector at Lahore during the period of seven months from August 2017 to March 2018. Multistage random sampling technique was opted and 2000 study subjects were recruited including 50% boys and 50% girls. Informed consent was obtained and data was collected on a structured questionnaire. The data was organized, entered in version 23 of IBM SPSS and analyzed by the use of statistical tools.Results:Age of the respondents ranged between nine to 18 years with a mean of 13.40 ± 1.82 SD.Parental history of wearing spectacles was present in 21.3% of the fathers and 28.6% of the mothers. Moreover, 72.4% of the participants never visited eye care professional. Among private schools, an association was found between the visit of boys to eye care professional and maternal positive history of wearing spectacles (p-value 0.019). A significant association was found between the positive paternal history of wearing spectacles and visit of the female strudy subjects to an eye care professional (p-value 0.001). In public schools, there was an association between visit of children to eye care services and positive history of mothers about the use of spectacles (p-value 0.018).Conclusions:This study concludes that positive maternal history of wearing spectacles is associated with the ophthalmic examination of children in both public and private school.

Cardiac Injuries at Estonian Major Trauma Facilities: A 23-year Perspective.

Cardiac injuries are highly lethal lesions following trauma and most of the patients decease in pre-hospital settings. However, studies on cardiac trauma in Estonia are scarce. Thus, we set out to study cardiac injuries admitted to Estonian major trauma facilities during 23 years of Estonian independence. After the ethics review board approval, all consecutive patients with cardiac injuries per ICD-9 (861.0 and 861.1) and ICD-10 codes (S.26) admitted to the major trauma facilities between 1 January 1993 and 31 July 2016 were retrospectively reviewed. Cardiac contusions were excluded. Data collected included demographics, injury profile, and in-hospital outcomes. Primary outcome was mortality. Secondary outcomes were cardiac injury profile and hospital length of stay. During the study period, 37 patients were included. Mean age was 33.1 ± 12.0 years and 92% were male. Penetrating and blunt trauma accounted for 89% and 11% of the cases, respectively. Thoracotomy and sternotomy rates for cardiac repair were 80% and 20%, respectively. Most frequently injured cardiac chamber was left ventricle at 49% followed by right ventricle, right atrium, and left atrium at 34%, 17%, and 3% of the patients, respectively. Multi-chamber injury was observed at 5% of the cases. Overall hospital length of stay was 13.5 ± 16.7 days. Overall mortality was 22% (n = 8) with uniformly fatal outcomes following left atrial and multi-chamber injuries. Overall, 37 patients with cardiac injuries were hospitalized to national major trauma facilities during the 23-year study period. The overall in-hospital mortality was 22% comparing favorably with previous reports. Risk factors for mortality were initial Glasgow Coma Scale < 9, pre-hospital cardiopulmonary resuscitation, and alcohol intoxication.

Abstract 4970: Mitochondrial trafficking in the bone marrow microenvironment promotes bioenergetic flexibility in multiple myeloma

Abstract Multiple myeloma (MM) is an incurable malignancy of terminally differentiated plasma cells which is highly dependent on the bone marrow microenvironment (BMM). MM tumor survival, proliferation and drug resistance is reliant on ATP production however the mechanisms by which the malignant cells generate ATP are poorly defined. In this study, we investigate the contributions of oxidative phosphorylation and aerobic glycolysis to tumor cell ATP generation within BMM. Furthermore, we address whether ATP generation within tumor cells is enabled by the transfer of mitochondria from the non-malignant stromal cells of the BMM to the malignant plasma cell. Bone marrow was obtained from patients under approval from the UK Health Research Authority. In-vivo experiments were performed with local Animal Welfare and Ethical Review Board approval and under license from the UK Home Office. Using Seahorse extracellular flux analysis we show that primary MM cells have high baseline rates of mitochondrial respiration compared to MM cell lines. Furthermore, mitochondrial respiration rates increased ex-vivo after co-culture with non-malignant bone marrow stromal cells (BMSC). We engrafted the malignant MM1S cell line into NSG mice and examined the mitochondrial respiration rate from isolated tumor cells compared to MM1S cells cultured in-vitro. We found increased rates of mitochondrial respiration in MM1S cells isolated from mouse BM. To determine whether the increase in tumor oxidative phosphorylation observed in the presence of micro-environment cells was a result of mitochondrial transfer from BMSC to MM, we used three methods. Firstly we stained BMSC with the mitochondrial stain MitoTracker Green and cultured these with primary MM cells. Using a combination of flow cytometry and confocal microscopy we detected MitoTracker fluorescence in the MM cells after co-culture, showing that the stained mitochondria are transferred from BMSC to MM cells in-vitro. Secondly, mitochondrial transfer was directly observed between BMSC and MM cells, visualized by the acquisition of a mCherry labeled mitochondrial protein we transfected into BMSC. Finally, using a human MM cell line engrafted into an NSG mouse xenograft model, we detected murine mitochondrial DNA in sorted human MM1S and U266 tumor cells post-transplant. Through fixed cell confocal microscopy we found that mitochondria move through tunnelling nanotubes (TNTs), and inhibition of TNT formation by treatment with cytochalasin B resulted in reduced mitochondrial transfer and tumor cell oxidative phosphorylation. Here we show that MM cellular metabolism favors oxidative phosphorylation over glycolysis, in the setting of the BMM. This is due to mitochondrial transfer occurring between non-malignant BMSC and malignant plasma cells. This process is necessary for optimum tumor growth in-vivo and forms part of the malignant phenotype of MM. Citation Format: Christopher R. Marlein, Rachel E. Piddock, Charlotte Hellmich, Lyubov Zaitseva, Martin J. Auger, Kristian M. Bowles, Stuart A. Rushworth. Mitochondrial trafficking in the bone marrow microenvironment promotes bioenergetic flexibility in multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4970.

Preprints with The Lancet: joining online research discussion platforms

Preprints with The Lancet: joining online research discussion platforms

Risk Factors of Leptospirosis in Rice Cultivators as Compared to non Rice Cultivators in Punjab, Pakistan

Leptospirosis is a global zoonotic infectious disease having alarming public health concerns. Generally this is an occupation related disease and the victims belong to animal slaughtering, owners of pet shops, farm workers, handlers of meat, sewerage and agriculture workers. Leptospirosis affect multiple organs in human body and may lead to myocarditis, renal failure, respiratory distress and hypotension. This disease is an emerging infectious problem in many developing countries like Pakistan. A total of 250 subjects were selected from five different rice growing districts of Punjab, Pakistan after the approval of institutional ethical review board (IERB), 250 subjects were selected for this comparative cross sectional study. Multiple stage probability technique was used for sampling. In the first stage one union council was selected from each district randomly. In the second stage, 25 subjects involved in rice cultivation from the last 10 years wereselected from each union council. Similarly 25 subjects who never worked in the rice paddy field were also randomly selected from each union council as controls. The serum sample of each subject was tested against each of the five antigens against the serovars. A total of 250 subjects were included in the study. Out of these, 125 subjects were exposed to the rice paddy water where as 125 were not exposed to rice paddy water. The cumulative seropositivity among the exposed is (83.2%) as compared to (42%) among the non exposed to rice paddy field water. The calculated cumulative odds ratio is 6.7 which represent a strong association of the risk for the development of disease among the exposed than the non exposed subjects. Leptospirosis is a public health zoonotic disease which is widely present in tropical and sub tropical areas. This study concludes that there is a strong association of rice cultivation with Leptospirosis. It is recommended that rice cultivators should protect their body parts with gloves or boots as prevention is the most appropriate way to control any disease.

Diffusion Properties and 3D Architecture of Human Lower Leg Muscles Assessed with Ultra-High-Field-Strength Diffusion-Tensor MR Imaging and Tractography: Reproducibility and Sensitivity to Sex Difference and Intramuscular Variability.

Purpose To demonstrate the reproducibility of the diffusion properties and three-dimensional structural organization measurements of the lower leg muscles by using diffusion-tensor imaging (DTI) assessed with ultra-high-field-strength (7.0-T) magnetic resonance (MR) imaging and tractography of skeletal muscle fibers. On the basis of robust statistical mapping analyses, this study also aimed at determining the sensitivity of the measurements to sex difference and intramuscular variability. Materials and Methods All examinations were performed with ethical review board approval; written informed consent was obtained from all volunteers. Reproducibility of diffusion tensor indexes assessment including eigenvalues, mean diffusivity, and fractional anisotropy (FA) as well as muscle volume and architecture (ie, fiber length and pennation angle) were characterized in lower leg muscles (n = 8). Intramuscular variability and sex differences were characterized in young healthy men and women (n = 10 in each group). Student t test, statistical parametric mapping, correlation coefficients (Spearman rho and Pearson product-moment) and coefficient of variation (CV) were used for statistical data analysis. Results High reproducibility of measurements (mean CV ± standard deviation, 4.6% ± 3.8) was determined in diffusion properties and architectural parameters. Significant sex differences were detected in FA (4.2% in women for the entire lower leg; P = .001) and muscle volume (21.7% in men for the entire lower leg; P = .008), whereas architecture parameters were almost identical across sex. Additional differences were found independently of sex in diffusion properties and architecture along several muscles of the lower leg. Conclusion The high-spatial-resolution DTI assessed with 7.0-T MR imaging allows a reproducible assessment of structural organization of superficial and deep muscles, giving indirect information on muscle function. ©RSNA, 2018 Online supplemental material is available for this article.