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Background: Posterior reversible encephalopathy syndrome (PRES) is clinicoradiological disease entity characterized by headache, seizures, altered sensorium and corticalvisual loss with characteristic MRI features of subcortical white matter hyperintensities on T2W imaging. Though hypertension is a traditional hallmark of PRES, uncommon causes without hypertension have been described. We report an unusual such case without hypertension, precipitated by red cell transfusion. Case Presentation: A 40 years female received six units of packed cell transfusion for severe anemia (Hemoglobin 3.0 Gm %) transfused over 8 hours. She was having menorrhagia and was operated on for a hysterectomy. She developed a headache on the second postoperative day for five days and no cause was revealed in spite of extensive workup, including MRI brain and CSF study. On the sixth day, she had recurrent seizures followed by altered sensorium in the absence of hypertension. Her repeat MRI brain findings were consistent with PRES. Conclusion: We reviewed 25 cases, including the present one as PRES after the blood transfusion. 24 were females, and 16 of 19 developed PRES in the course of chronic anemia lasting over 1 month. Anemia was severe in 18 of 25 cases, with haemoglobin (Hb) levels < 4.0 Gm%. In 16 of 20 cases, Hb levels increased to 5 g/dl by red cell blood transfusion until the onset of PRES. On MRI brain, 23 of 25 cases showed vasogenic edema and 3 of 25 cases showed an irreversible neurological deficit. When treating severe chronic anemia rapid correction of Hb with blood transfusion, one should consider a possibility of PRES in post-transfusion neurological symptoms in spite of normal diagnostic workup.

PURPOSE Visual outcomes after postinjection endophthalmitis have been well-studied, but the effect of endophthalmitis on the underlying exudative disease process remains unclear. We investigate the need for continued anti-vascular endothelial growth factor injections after endophthalmitis. METHODS Eyes that developed endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor between January 1, 2016, and May 31, 2018, at a single academic retina practice were identified. Retrospective chart review was performed to determine 1) the proportion of eyes without recurrence of macular edema or subretinal fluid after endophthalmitis and 2) the proportion achieving a 12-week or greater interval between anti-vascular endothelial growth factor injections or exudation after endophthalmitis compared with internal controls before endophthalmitis. RESULTS Of 50 eyes with endophthalmitis, seven (14.0%) had no fluid recurrence at a mean of 98.1 week. Of 43 eyes with recurrence, 48.0% achieved a >12-week recurrence-free interval after endophthalmitis (vs. 8.3% before endophthalmitis; P < 0.0001). Eyes with compared to those without choroidal neovascularization were more likely to achieve this interval (60.5% vs. 8.3%, respectively; P = 0.002). CONCLUSION Endophthalmitis after anti-vascular endothelial growth factor injection is associated with relative stability of the underlying exudation. Further research is necessary to elucidate the mechanism, which may be useful in developing strategies and targets for the treatment of exudative macular diseases.

To compare 2 mg intravitreal triamcinolone (IVT) versus 40 mg posterior sub-Tenon triamcinolone acetonide (STT) for the treatment of eyes with pseudophakic cystoid macular edema.A retrospective, single-center review of eyes receiving 2 mg IVT between 3/1/2012-3/1/2017 and 40 mg STT between 1/1/2015-3/1/2017. Visual acuity (VA) and central macular thickness (CMT) were recorded at baseline, 1-, 3-, and 6-month follow-up visits.Forty-five eyes were included in the IVT group and 50 eyes in the STT group. Change in VA from baseline to 1, 3, and 6 months was not significantly different between IVT and STT (6 months: 2.3 lines vs. 2.4 lines,2 mg IVT and 40 mg STT both achieved significant improvement in vision and CMT with no significant difference between interventions at 3- and 6-month follow-up.

To compare rates of ocular hypertension (OHT) in eyes receiving 40 mg sub-Tenon triamcinolone (STT), 0.7 mg dexamethasone implant (DEX), and 2 mg intravitreal triamcinolone (IVT).This study is a single-centre, retrospective case series. All patients receiving STT and DEX between 4/1/2014 and 3/1/2017 and IVT between 3/1/2012 and 3/1/2017 with a minimum of 3 months' follow-up were included. OHT was defined as an intraocular pressure (IOP)24 mm Hg. Patients receiving any other form of topical, oral, or intravitreal steroid were excluded.113 eyes from 104 patients in the STT group, 122 eyes from 109 patients in the DEX group, and 109 eyes from 103 patients in the IVT group were included. The mean number of injections for each eye was 1.7 in the STT group, 2.6 for the DEX group, and 2.8 for the IVT group (p0.001). Twenty eyes (17.7%) developed OHT in the STT group, 19 eyes (15.6%) developed OHT in the DEX group, and 14 eyes (12.8%) developed OHT in the IVT group (p = 0.60). IOP was controlled in all eyes with observation, topical IOP-lowering medication, or surgical intervention. The rate of incisional glaucoma surgery was 1.7% in the STT group, 1.6% in the DEX group, and 0% in the IVT group (p = 0.55).The rate of OHT was similar across treatment groups. The proportion of OHT in patients with a history of glaucoma was no different from that in patients without a history of glaucoma. All cases were successfully managed with observation, medical treatment, or incisional surgery.

Nasal mucociliary clearance (NMC) system is an important defence mechanism in respiratory tract. The contents present in the smoke are found to be toxic to cilia in vitro. Our study aims at evaluating the NMC in smokers so as to know effect of tobacco smoke on ciliary function and also comparing it with non smokers. We also studied effect of duration, intensity and pattern of smoking on the NMC. A total of 60 participants in the age group 21–40 years (30 smokers and 30 non smokers) were included in the study. Saccharin test was performed in all participants. A 0.5 mm diameter particle of saccharin was placed 1 cm from the anterior end of the inferior nasal turbinate. The time duration was noted for the first appearance of sweet taste. The mean NMC in smoker group was 16.53 min and in nonsmoker group was 9.28 min On comparison it was found that NMC time in smoker group was significantly higher than nonsmoker group p

Purpose: This article compares 2-mg intravitreal triamcinolone (IVT) and 0.7-mg dexamethasone (DEX) implant for the treatment of diabetic macular edema in eyes that had a suboptimal response to antivascular endothelial growth factor therapy. Methods: A single-center, retrospective review was conducted of patients receiving either IVT between January 1, 2013, and January 1, 2018, or patients receiving DEX between October 1, 2015, and January 1, 2018. Visual acuity and central macular thickness (CMT) were recorded at visit of first injection and all subsequent visits. Results: Twenty-five eyes were included in the DEX group and 32 eyes were included in the IVT group. Change in vision from baseline was similar between DEX and IVT at 6-month follow-up (1.1 lines vs 2.3 lines, respectively; P = .24). Mean decrease in CMT from baseline was not different at 6-month follow-up (DEX: 120 µm vs IVT: 185 µm; P = .17). Conclusions: DEX and 2-mg IVT both achieved improvement in vision and CMT with no significant differences between treatment groups at 6-month follow-up.

Objectives: Health status is associated with socioeconomic status (SES) of the individuals. The aim of this study was to identify any link between the SES and influenza-like illness (ILI). Materials and Methods: This observational case-control study was done on 18–70 years old patients presented with ILI (cases) at tertiary care hospital of western India. Controls were selected from demographically matched elective surgery patients except the SES. SES was evaluated as per the Modified B G Prasad 2017 scale and participants were further classified in lower SES (per capita income

Purpose To report the incidence and course of ocular hypertension after intravitreal injection of 2-mg triamcinolone acetonide (IVT). Methods In a retrospective, consecutive series, all patients receiving 2-mg IVT at a single institution between March 1, 2012, and March 1, 2017, with a minimum of 3-month follow-up were reviewed. Ocular hypertension was defined as an intraocular pressure (IOP) measurement over 24 mmHg at any follow-up visit after IVT. Patients receiving topical, periocular, or intravitreal corticosteroid other than 2-mg IVT were excluded. Results A total of 106 eyes in 100 patients receiving at least one injection of 2-mg IVT were included. Eyes received an average of 2.9 injections (range 1-17), and average patient follow-up was 15.1 months (range 3.0-52.5 months). A total of 14 eyes (13.2%) in 14 patients developed ocular hypertension after a median of 1.5 injections (range 1-9) with an average peak IOP of 29 mmHg (range 25-38 mmHg). Overall, a total of 11 eyes (10.4%) had an IOP elevation ≥10 mmHg above baseline at any point after first IVT. In all cases of ocular hypertension, IOP was successfully managed with observation or topical IOP-lowering medication alone; no patients required surgical intervention. Conclusion Ocular hypertension developed in 13.2% of eyes receiving intravitreal injection of 2-mg triamcinolone acetonide. Incidence of ocular hypertension after 2-mg IVT compares favorably with other intravitreally administered corticosteroids.

BACKGROUND: Ketogenic diet is now in trend. But very less researches were conducted in India to check signicant effects on weight loss of Ketogenic Diet among overweight/obese adults compared to calorie restricted Low Fat diet. OBJECTIVE:To compare the effect of Very Low Carbohydrate Ketogenic (VLCK) diet and energy restricted Low-Fat (LF) diets on weight loss in overweight/obese healthy adults. Design: An interventional randomized controlled trial of 6 months was initiated. PARTICIPANTS: 113 overweight/obese adults with a body mass index of 25 kg/m2 or greater; with no abnormalities and more than 20 years of age. INTERVENTION: Among 113 overweight/obese adults, we conducted a six-month randomized controlled trial of two sets of dietary advice, each providing approximately 12,00-1500 calories per day but differing in protein, ber, fat and carbohydrate content. RESULTS: We found that dieters given VLCK advice tended to lose more weight than those given a LF diet. CONCLUSION: For short period of time VLCK diet is more effective than conventional LF diet for weight loss. But for long term effects further studies are required.

BACKGROUND & AIMS: Chromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer-associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic.METHODS: We performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, gamma-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2'-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients.RESULTS: High expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients.CONCLUSIONS: We found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors.

The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA CCAT2 in the highly amplified 8q24.21 region have been implicated in cancer predisposition, although causality has not been established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate that CCAT2 overexpression leads to spontaneous myeloid malignancies. We further identified that CCAT2 is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2 induces global deregulation of gene expression by down-regulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel non-APOBEC, non-ADAR, RNA editing at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and CCAT2 in myeloid malignancies.

Background: Hypoglycemia may rarely present as hemiparesis and sometimes it is difficult to differentiate from ischemic stroke. When random blood sugar (RBS) value is between 50 and 80 mg % in patients presenting with focal neurological deficit, no guideline exists to consider the possibility of hypoglycemia before initiating thrombolytic therapy. Clinical Case: A 58-year-old male, who was a known case of diabetes and hypertension, was brought to the emergency room with acute onset of right hemiparesis and dysarthria of 90 minutes duration. His NIHSS Score was 9, blood pressure was 150/90 mm of Hg and RBS was 79 mg% on admission. His CT scan brain was normal and was considered for thrombolysis. Resident doctor not aware of previous sugar repeated RBS before thrombolysis which was surprisingly 60 mg% 60 minutes after the first RBS. Even though he was a candidate for thrombolysis, intravenous 25 % dextrose was administered considering the possibility of hypoglycemia. He made a complete recovery within 20 minutes and thrombolytic therapy was withheld. In Diabetic patients with focal neurological deficit and RBS less than 80 mg% on admission, RBS should be rechecked and in appropriate cases should be challenged with IV dextrose considering the possibility of hypoglycemia before commencing thrombolytic therapy.

To determine the prevalence and risk factors of under-nutrition amongst under-five children living in Jhadol Block of Udaipur, a cross-sectional survey of 350 randomly selected under-five children was carried out. The selected samples were taken out of the total 48426 children living in Jhadol Block. The findings reveal that 41.1% of the children were found to be stunted, 26% of them wasted and 20.3% of them were under-weight. Female children, children aged 48-59 months, children born to older mothers aged 20-29years, children with 1-2 siblings, low-birth-weight, having an illiterate mother or unskilled labourer father were observed to be at the highest risk of being under-nourished. Birth spacing of

Background The optimal management of progressive brain metastases in patients with germ cell tumors (GCTs) remains unsettled. This study reports the management of 25 consecutive patients with relapsed GCTs and progressive brain metastases undergoing high-dose chemotherapy (HDCT) with peripheral blood stem cell transplantation (PBSCT) at Indiana University from 2006 to 2016. Methods All patients were planned to undergo HDCT, which consisted of carboplatin at 700 mg/m2 on days 1 to 3 plus etoposide at 750 mg/m2 on days 1 to 3, followed by PBSCT on day 5 for 2 cycles. Patients were treated with brain metastectomy, stereotactic radiotherapy or whole-brain radiotherapy, HDCT alone, or a combination thereof. All 25 patients had progressive brain metastases at the time of initiating HDCT. Patient and disease characteristics, management of brain metastases, and outcomes were measured. Platelet transfusions were given to maintain platelet counts > 30,000/µL; the goal was >50,000/µL when there were signs of prior or active hemorrhaging. Results Twenty-two of 25 patients completed both courses of HDCT. The median α-fetoprotein level was 7.5 ng/mL (range, 1.6-1130 ng/mL), and the human chorionic gonadotropin level was 31.3 IU/mL (range, 0.5-25,601 IU/mL). At a median follow-up of 24.5 months (range, 0.4-117 months), 11 patients (44%) were alive with no evidence of disease, 2 patients were alive with relapsed disease, and 12 patients had died of disease progression or complications from HDCT. Fifteen patients developed progressive brain metastases despite radiation and/or craniotomy before HDCT, and 8 of these patients were alive without evidence of disease. There were no intracranial hemorrhagic events leading to death. Conclusions Patients with relapsed GCTs and progressive brain metastases are curable with multimodality therapy that includes HDCT and peripheral blood stem cell transplantation.

Purpose To compare the rates of infectious endophthalmitis following intravitreal injection of ranibizumab using prefilled syringes vs conventional preparation. Design Multicenter retrospective cohort study. Methods All eyes receiving intravitreal injection of 0.5 mg ranibizumab for retinal vascular diseases at 10 retina practices across the United States (2016 to 2017) and Japan (2009 to 2017) were included. The total numbers of eyes and injections were determined from billing codes. Endophthalmitis cases were determined from billing records and evaluated with chart review. Primary outcome was the rate of postinjection acute endophthalmitis. Secondary outcomes were visual acuity and microbial spectrum. Results A total of 243 754 intravitreal 0.5 mg ranibizumab injections (165 347 conventional and 78 407 prefilled) were administered to 43 132 unique patients during the study period. In the conventional ranibizumab group, a total of 43 cases of suspected endophthalmitis occurred (0.026%; 1 in 3845 injections) and 22 cases of culture-positive endophthalmitis occurred (0.013%; 1 in 7516 injections). In the prefilled ranibizumab group, 12 cases of suspected endophthalmitis occurred (0.015%; 1 in 6534 injections) and 2 cases of culture-positive endophthalmitis occurred (0.0026%; 1 in 39 204 injections). Prefilled syringes were associated with a trend toward decreased risk of suspected endophthalmitis (odds ratio 0.59; 95% confidence interval 0.31-1.12; P = .10) and a statistically significant decreased risk of culture-positive endophthalmitis (odds ratio 0.19; 95% confidence interval 0.045-0.82; P = .025). Average logMAR vision loss at final follow-up was significantly worse for eyes that developed endophthalmitis from the conventional ranibizumab preparation compared to the prefilled syringe group (4.45 lines lost from baseline acuity vs 0.38 lines lost; P = .0062). Oral-associated flora was found in 27.3% (6/22) of conventional ranibizumab culture-positive endophthalmitis cases (3 cases of Streptococcus viridans, 3 cases of Enterococcus faecalis) compared to 0 cases in the prefilled ranibizumab group. Conclusion In a large, multicenter, retrospective study the use of prefilled syringes during intravitreal injection of ranibizumab was associated with a reduced rate of culture-positive endophthalmitis, including from oral flora, as well as with improved visual acuity outcomes.

Patients with triple-negative breast cancer (TNBC) who have residual disease after neoadjuvant therapy have a high risk of recurrence. We tested the impact of DNA-damaging chemotherapy alone or with PARP inhibition in this high-risk population. Patients with TNBC or deleterious BRCA mutation (TNBC/BRCAmut) who had >2 cm of invasive disease in the breast or persistent lymph node (LN) involvement after neoadjuvant therapy were assigned 1:1 to cisplatin alone or with rucaparib. Germline mutations were identified with BROCA analysis. The primary endpoint was 2-year disease-free survival (DFS) with 80% power to detect an HR 0.5. From Feb 2010 to May 2013, 128 patients were enrolled. Median tumor size at surgery was 1.9 cm (0–11.5 cm) with 1 (0–38) involved LN; median Residual Cancer Burden (RCB) score was 2.6. Six patients had known deleterious BRCA1 or BRCA2 mutations at study entry, but BROCA identified deleterious mutations in 22% of patients with available samples. Toxicity was similar in both arms. Despite frequent dose reductions (21% of patients) and delays (43.8% of patients), 73% of patients completed planned cisplatin. Rucaparib exposure was limited with median concentration 275 (82–4694) ng/mL post-infusion on day 3. The addition of rucaparib to cisplatin did not increase 2-year DFS (54.2% cisplatin vs. 64.1% cisplatin + rucaparib; P = 0.29). In the high-risk post preoperative TNBC/BRCAmut setting, the addition of low-dose rucaparib did not improve 2-year DFS or increase the toxicity of cisplatin. Genetic testing was underutilized in this high-risk population.

ObjectivesSensory impairments are associated with worse mental health and poorer quality of life, but few studies have investigated whether sensory impairment is associated with suicidal behaviour in a population sample. We investigated whether visual and hearing impairments were associated with suicidal ideation and attempt.DesignNational cross-sectional study.SettingHouseholds in England.ParticipantsWe analysed data for 7546 household residents in England, aged 16 and over from the 2014 Adult Psychiatric Morbidity Survey.ExposuresSensory impairment (either visual or hearing), Dual sensory impairment (visual and hearing), visual impairment, hearing impairment.Primary outcomeSuicidal ideation and suicide attempt in the past year.ResultsPeople with visual or hearing sensory impairments had twice the odds of past-year suicidal ideation (OR 2.06; 95% CI 1.17 to 2.73; pConclusionsWe found evidence that individuals with sensory impairments are more likely to have thought about or attempted suicide in the past year than individuals without.

Growing organizations, institutions, and SMEs demand for transformation in all the aspects of their businesses along with the progression in time and technology. When it comes to healthcare, the growth should be heightened to higher levels with necessity. The need of providing quality of service (QoS) in healthcare is taking significant place, allowing health institutions and medical compliances to develop an ecosystem with cutting-edge technology with the same reliability but better productivity and performance. Moreover, the healthcare systems are aiming for a more patient-centric strategy. Healthcare systems work on complicated and traditional methods, oftentimes administered via teams of professionals who manage data and supportive mechanisms of the system. Blockchain could streamline and automate those methods, conserving weeks of effort in the company's production line to increase the overall revenue and discover new opportunities. This chapter aims to illustrate blockchain technology along with its state-of-the-art applications in healthcare.

BACKGROUND:In recent outbreak of COVID-19 infection,the risk of thrombosis should be concerned.We observed dynamic changes of D-Dimer level,C-Reactive Protein(CRP) level and Venous Thromboembolism risk assessment score(VTE score) during active disease.We included patients of conrmed covid-19 patients who were RT-PCR positive and patients of community acquired pneumonia(CAP) who were conrmed by CT-SCAN ndings.We observed correlation of D-dimer level with both CRP level & VTE score. METHOD:We examined the clinical laboratory result of 50 patients with conrmed COVID-19 positive patients and 50 patients with community acquired pneumonia(CAP).We analysed D-dimer level of this patients by Automated Coagulometer-STAGO in our hematological laboratory and CRP level by latex method.We use pauda prediction score to identify patients at high risk for venous thrombo embolism.We observed D-dimer level of all patients with their correlation to CRP level & VTE score.S RESULT:On admission,Both COVID-19 and CAP patients,D-dimer level were increased,more increased in COVID-19 patient compare to CAP patient. D-dimer level were related to inammatory marker,mainly with CRP level.There was low correlation between VTE score & Ddimer levels weakened the role of D-dimer in the prediction of thrombosis. CONCLUSION:Elevated baseline D-dimer levels are associated with inammation but not with VTE score in COVID patients,So we can't judge whether anticoagulation is needed only according to D-dimer levels. Abnormal D-dimer level with inammatory factors suggest that anticoagulant therapy might be needed.

Introduction Bronchiolitis obliterans syndrome (BOS) after allogeneic haemopoietic stem cell transplant (HSCT) is an under-recognised and difficult to treat disease. This occurs in the context of limited clinical research and inconsistent diagnostic criteria. Method Retrospective data was collected on 275 patients who underwent allogeneic HSCT at an Australian tertiary hospital between 2007 and 2017. The prevalence of BOS, defined by 2014 National Institute of Health criteria, as well as predictors for BOS and mortality were determined. Treatment outcomes, using serial spirometry, were compared between patients who received early versus late immunosuppression for BOS. Results The prevalence of BOS was 9.1%. Myeloablative conditioning (OR: 2.7, 95%CI: 1.13–6.50, p = 0.03) and extra-pulmonary chronic graft-versus-host disease (OR 2.62, 95% CI: 1.04–6.60, p = 0.04) were associated with BOS. There was reduced median survival in the BOS group compared with the non-BOS group, but this was not statistically significant (4.1years (IQR: 2.8, 6.8) versus 4.6years (IQR: 2.4, 7.8), respectively, p = 0.33). The vast majority (87.5%) of BOS patients failed to attain improvement in FEV1 at 12 months, regardless of treatment strategy. Patients who underwent a late immunosuppression strategy had worse mean FEV1 decline compared to those who received early immunosuppression (−36.3% versus −1.6%, respectively, p = 0.03). Conclusion BOS is a common and progressive disease following HSCT and is largely refractory to current treatment strategies. Compared to late immunosuppression, early augmentation of immunosuppression may slow lung function deterioration in the short term. However, further research is urgently needed to identify effective prevention and treatment strategies for BOS.

Tracheostomy in patients with COVID-19 requires significant decision making and procedural planning. Use of tracheostomy can facilitate weaning from ventilation and potentially increase the availability of much needed intensive care unit (ICU) beds, however this being a high aerosol generating procedure it does put the health care worker to risk of transmission. Here we present our experience and protocols for performing tracheostomy in COVID-19 positive patients. Eleven tracheostomies were performed in COIVD-19 patients over a period of 2 months (May-June 2020) at this tertiary care hospital dedicated to manage COVID patients. All patients underwent open surgical tracheostomy, the specific indication, preoperative protocols, surgical steps and precautions taken have been discussed. Tracheostomy was done not before 10 days after initiation of mechanical ventilation. Patient's cardiovascular vitals should show recovery with some spontaneous effort. There should be reduction in need for FiO2 and ventilator requirements. Of total 11 tracheostomies performed only one patient had post procedure bleeding which was controlled conservatively. We have summarized our experience in performing tracheostomies in 11 such patients. Our guidelines and recommendations on tracheostomy during the COVID-19 pandemic are presented in this study. We suggest tracheostomies to be done after 10 days of intubation with precautions and given indications with the idea of early weaning off of patient from ventilator and more availability of ICU beds which is already overwhelmed by patient load.

COVID-19 outbreak is major pandemic affecting lakhs of people all across the globe. Along with other nonspecific clinical features, reports mention anosmia to be an important symptom in COVID-19 positive patients. To study the prevalence of anosmia in confirmed COVID-19 patients, in Indian population and to ascertain its significance as a symptom of COVID 19. Study was done at a tertiary care COVID treating hospital. While eliciting detailed history from Covid-19 positive patients, all patients were asked about symptom of anosmia. Same was asked from control group of subjects who were COVID-19 negative. The history of anosmia was also elicited on discharge after the patients tested negative for COVID-19. 74 patients formed part of the study. 11 of 74 (14.8%) patients had anosmia. On using the chi square test for significance the difference was significant (p

Purpose To assess the utility of microbiologic culture data for the management of endophthalmitis after cataract surgery. Design Retrospective, single-center, cohort study. Participants All patients treated for endophthalmitis after cataract surgery between January 1, 2014, and December 31, 2017, at a single institution. Methods Endophthalmitis cases were determined from billing records and confirmed with chart review. A change in clinical management was defined as additional intravitreal antibiotic injections or pars plana vitrectomy. Main Outcome Measures A change in clinical management within 2 weeks of initial endophthalmitis culture and treatment; visual acuity (VA). Results A total of 111 eyes of 111 patients were treated for endophthalmitis after cataract surgery, of which 57 (51%) were culture-positive. After initial treatment of endophthalmitis, a change in clinical management after vitreous culture occurred in 9 of 111 eyes (8%), including 6 of 57 (11%) culture-positive eyes compared with 3 of 54 (6%) culture-negative eyes (P = 0.49). Change in clinical management for culture-positive eyes was based on declining vision (3 eyes), worsening clinical examination results (2 eyes), and retinal detachment (1 case). Change in clinical management for culture-negative endophthalmitis eyes was based on worsening clinical examination results (2 eyes) and declining vision (1 eye). No additional interventions were initiated on the basis of positive culture results. At final follow-up, mean logarithm of the minimum angle of resolution (logMAR) VA was 1.09 (∼20/250) for the culture-positive eyes compared with 0.59 (∼20/80) for culture-negative eyes (adjusted difference, 0.394; 95% confidence interval, 0.02–0.77, P = 0.03). Rhegmatogenous retinal detachments (RRDs) or retinal tears occurred in 19 of 111 eyes (17%) after developing endophthalmitis, and culture-positive eyes developed a secondary RRD in 11 of 57 eyes (19%) compared with 3 of 54 (6%) culture-negative eyes (P = 0.03). Conclusions After endophthalmitis related to cataract surgery, vitreous cultures may have prognostic value for final visual outcomes but have a limited effect on clinical management.

PurposeResearch on the impact of social distancing on mental health during epidemics is limited, especially in India. The purpose of this study is to scale the association between anxiety and socio-demographic factors during Covid19 lockdown among the general Indian population.Design/methodology/approachA descriptive cross-sectional nationwide study was designed to enrol the general population. The inclusion criteria for this study were Indian citizens aged 18 years and above. The study was conducted from 29th March to 12th April 2020, using an online google questionnaire. The anxiety among respondents was detected and measured using a Generalised Anxiety Disorder Scale which consists of 7 questions (in English), i.e. GAD-7.FindingsRespondees were 392, and from these participants, the prevalence of anxiety was 25.3 per cent. Based on the bivariate logistic regression analysis, the predictors of anxiety were gender, religion, occupation as business/self-employed, marital status, family size, health status and sleep deprivation.ConclusionThis study reports the prevalence of anxiety among Indian population who were grounded at their homes during lockdown due to coronavirus pandemic in the country.Limitations(1) The selection of participants through non-random sampling. (2) Because of the cross-sectional character of the study, causal conclusions cannot be drawn.Originality/ValueThis paper fulfils an identified need to study the mental health status of the population under situations like lockdown, thereby helping fill a persistent gap in Indian research on this issue.

Laryngopharyngeal Reflux Disease (LPRD) is form of extra-oesophageal reflux due to the backflow of gastric contents into the upper aero digestive tract leading to throat symptoms. World over, the prevalence rate of LPRD, ranges from 5 to 30%. The aim of this study was to find the prevalence rate of LPRD in Indian population. This was an observational study whereby the RSI questionnaire was circulated amongst the population and records collected. All subjects who had RSI score more than 13 were considered to be suffering from LPRD. 2300 responses were collected from almost all strata of population. Out of 2300 people who responded 253 had RSI score > 13, and were considered as suffering from LPRD. Thus the prevalence rate of LPRD in population was 11%. The prevalence rate of LPRD in females was 11.2% and in males was 10.6%. The difference in prevalence among both the genders was not significant.The most common symptom of LPR reported by subjects was heartburn followed by clearing of throat and excess throat mucous. The prevalence of LPRD in Indian population as assessed by RSI score > 13 was 11%. The prevalence is same in males and females.

Background: To compare the incidence and outcomes of ocular hypertension (OHT) after intravitreal injection of 0.7 mg dexamethasone (DEX) and 2 mg triamcinolone acetonide (IVT).Methods: In a single...

Cinnamomum verum plant is widely used in traditional medicine to reduce inflammation. In the present study, water-soluble polysaccharides were isolated from Cinnamomum verum bark followed by sequential separation from four solvent extracts (hexane, dichloromethane, chloroform and methanol) and analysed for the presence of sugar, protein and different phytochemicals. Crude and purified ethyl acetate fractions of soluble polysaccharides were analysed in vitro using mouse leukemic macrophage (RAW 264.7) cell line and human peripheral blood mononuclear cells (PBMCs). Water-soluble (crude and ethyl acetate purified fractionation) polysaccharides contained glucose, whereas proteins and phytochemicals were absent. Water-soluble polysaccharide fraction had less antioxidant activity as compared to all four solvent extracts. Also, water-soluble polysaccharides (250 μg/ml) did not affect the cell growth, while all other four extracts (250 μg/ml) inhibited the growth of RAW 264.7 cells. Cell growth inhibition was detected when concentration of crude and ethyl acetate fraction polysaccharides was increased, where IC50 values were 1120 ± 27 and 1780 ± 227 μg/mL, respectively. Interestingly, crude and ethyl acetate polysaccharides showed concentration-dependent increase of the cell growth in PBMCs, indicating immunostimulating effect. Our data suggests that the immunological properties of cinnamon may be associated with the presence of polysaccharides.

Introduction:Tumor boards (TB) at National Cancer Institute Designated Comprehensive Cancer Centers (NCI-CCC) are an important source of multidisciplinary education. Unfortunately, expert knowledge from NCI-CCCs is not systematically documented and made accessible to oncologists in the community. This represents a lost opportunity to capture and share clinical expertise that can impact patient care in community centers. Using an online oncologist-only social network, we sought to demonstrate the feasibility of systematically documenting expert insights from TBs and department conferences at NCI-CCCs in order to expand their reach and provide educational benefit to the greater oncology community. Methods: A pilot program was developed at the University of Texas MD Anderson Cancer Center (MDACC) to design a process in which discussions at departmental breast cancer conferences would be distilled down to clinical questions and answers (Q&A) and posted on theMednet.org, an online social Q&A website of over 3,800 US oncologists. An educational breast cancer conference was selected during a site visit. A faculty member was selected to distil discussions about patient management from the selected conference into a question that addressed the clinical situation being discussed. After the question was posted, the oncologist leading the discussion answered the question on theMednet. The Q&A was then indexed and stored for easy search retrieval and disseminated in a weekly newsletter to all registered medical oncologists. A detailed manual was created to document operating procedures for implementation at additional institutions. Results: After developing the process at MDACC, the program was expanded to 2 additional NCI-CCCs- University of Pittsburgh (UPMC) and UCLA. The educational breast cancer conferences selected varied by site and were the new patient planning conference at MDACC, tumor board at UPMC, and multidisciplinary clinic at UCLA. The most significant factor for success was involvement of one faculty member who regularly identified educational questions and additional faculty who posted their answers. Between December 2016 and May 2017, 17 answers to 17 questions were posted and shared with over 1,200 medical oncologists via an email newsletter. All questions were focused on topics not answered by NCCN or ASCO guidelines. The majority of questions focused on management decisions around chemotherapy and endocrine therapy. Answers were viewed by 339 oncologists at 260 institutions in 47 states. This included 190 community practices and 70 academic medical centers. Conclusion: We developed a process of capturing and sharing expert knowledge at NCI-CCC breast cancer conferences on questions not answered by current guidelines. These discussions are otherwise not documented or shared outside of academic centers. By translating discussions into actionable Q&A on an online oncologist network, we made them easily accessible to oncologists at nearly 200 community practices. Future efforts will be aimed at implementing the program into the breast cancer programs at additional NCI-CCCs. Citation Format: Kalra M, Karuturi M, Tripathy D, Jankowitz R, McCann K, Brufsky A, Hurvitz S, Bogler O, Housri S, Housri N. Documenting and sharing breast cancer knowledge from National Cancer Institute designated comprehensive cancer centers (NCI-CCCs) with community oncologists [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-16-01.

Tablet splitting or breaking of tablets into multiple strengths has been a common practice across the world. Splitting of tablet offers various advantages such as dose flexibility and ease of swallowing in different population including geriatric and pediatric patients (wide patient acceptance) and cost saving on medications (economic advantage) The tablet products that are meant to be split and approved by the Food and Drug Administration (FDA) will have a scored line indicating the split location to ensure patient can adjust the dose by splitting and such splitting information will be included in the patient package insert. Having a consistent scored reduces difficulty in dose related problems especially when using products made by different manufacturers such as Generic compared to Reference Listed Drugs (RLD). Physical characteristics such as shape, size and tablet score may affect tablet splitability. Currently, various regulatory bodies (FDA, USP, and EP) provide consistent and useful information to the pharmaceutical industry. In this review, authors have compiled information from currently available resources on tablet scoring.

Objective: The present study was conducted to assess the validity of symptom score and Genital Health Clinical Evaluation (GHCE) score as diagnostic tools for urogenital atrophy in females of 40–75 years of age group. Materials and Methods: A cross-sectional study including 600 females in the age group of 40–75 years attending gynecology outpatient department was conducted. They were given a symptom score based on their history. GHCE score and smears for vaginal maturation index (VMI) were taken and percentages of superficial cells were counted. Statistical tests of significance such as Karl Pearson's coefficient of correlation were applied. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy of GHCE score, and symptom score with VMI score were calculated. Results: The prevalence of urogenital atrophy in females of 40–75 years of age group using VMI scoring was 38.1%. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of total symptom score for diagnosing urogenital atrophy were 66.4%, 75.3%, 56.3%, 82.4%, and 72.5%, respectively. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of GHCE score for diagnosing urogenital atrophy were 43.4%, 80.7%, 75.3%, 51.3%, and 59.3%, respectively. Conclusion: Both symptom score and GHCE score can be used as valid alternatives to VMI as diagnostic tools for urogenital atrophy in females of 40–75 years of age group at least in resource-poor settings.

Background:Calciphylaxis is a complex dermatological lesion of micro vascular calcification that is typically presented as panniculitis with gangrenous painful lesions having uremic and non-uremic causes.Case Report:We present a case of a 48-year old male with a history of paroxysmal atrial fibrillation and hypertension taking amlodipine 5 mg and warfarin 5 mg daily for the last 26 months. The patient had a 6- months history of painful swelling followed by necrotic skin ulcer over the right leg. His remarkable examination findings were right leg tender ulcer with surrounding erythema and secondary sepsis. His hemogram, metabolic profile and connective tissue diseases work up were unremarkable except leucocytosis and raised inflammatory markers. His local part radiological and skin biopsy findings were suggestive of calciphylaxis.Results and Conclusion:In our case, warfarin and amlodipine were culprit drugs for the lesion, but Naranjo score (warfarin 7and amlodipine 1) speculate warfarin as a probable adverse reaction of warfarin. The lesion was cured with local wound treatment after discontinuation of warfarin. The physician should be aware of this rare cutaneous disorder of systemic origin for proper management.

Food security is one of the burning issues at present. The elevated levels of atmospheric carbon dioxide ( $$\hbox {CO}_2$$ ) and temperature are anticipated to affect the yield of staple food crops. In this paper, we have formulated a nonlinear mathematical model to study the crop response to the elevated levels of $$\hbox {CO}_2$$ and temperature. Qualitative analysis of the model is performed to assess the long-term behavior of the system. The model analysis provides a condition under which the increase in anthropogenic $$\hbox {CO}_2$$ emission leads to decrease in the equilibrium level of crop yield. The analytical results are validated through numerical simulation for the case of wheat yield in India. The future projections of wheat yield in India are depicted in various scenarios. Sensitivity analysis is performed to explore the effect of changes in the key parameters on the wheat yield.

Objectives: To measure the effect of vaginal estrogen cream in the treatment of vaginal atrophy in menopausal Indian women. Methods: A total of 50 menopausal women aged between 40 and 80 years old with symptoms of vaginal atrophy were selected and treated with 0.5 g vaginal estrogen cream, twice weekly for 12 weeks. The women were followed-up monthly where symptom score, Genital Health Clinical Evaluation (GHCE) score, vaginal pH, and vaginal maturation index (VMI) were assessed and compared to baseline data. Any adverse events were recorded. Results: There was a significant improvement (p < 0.010) in complaints such as vaginal dryness, itching, burning, and dyspareunia at the end of the study period. The clinical improvement of these patients was reflected in a decrease in GHCE score on every visit. Vaginal pH and VMI score also showed statistically significant improvements (p < 0.010). No side effects with the drugs used were recorded during the study period. Conclusions: Vaginal estrogen cream causes symptomatic relief in women of menopausal age in India suffering from vaginal atrophy.

Objectives The epidemiology, clinical characteristics and outcomes of antimicrobial-associated anaphylaxis remain ill-defined. We sought to examine antimicrobial anaphylaxis with regard to: (i) the frequency of implicated antimicrobials; (ii) attributable mortality; and (iii) referral for definitive allergy assessment. Methods This was conducted through a national retrospective multicentre cohort study at five Australian tertiary hospitals (January 2010 to December 2015). Cases of antimicrobial anaphylaxis were identified from ICD-10 coding and adverse drug reaction committee databases. Results There were 293 participants meeting the case definition of antimicrobial anaphylaxis and 310 antimicrobial anaphylaxis episodes. Of 336 implicated antimicrobials, aminopenicillins (62/336, 18.5%) and aminocephalosporins (57/336, 17%) were implicated most frequently. ICU admission occurred in 43/310 (13.9%) episodes; however, attributable mortality was low (3/310, 1%). The rate of anaphylaxis to IV antibiotics was 3.5 (95% CI = 2.9–4.3) per 100 000 DDDs and the rate of hospital-acquired anaphylaxis was 1.9 (95% CI = 2.1–3.3) per 100 000 occupied bed-days. We observed overall low rates of hospital discharge documentation (222/310, 71.6%) and follow-up by specialist allergy services (73/310, 23.5%), which may compromise medication safety and antimicrobial prescribing in future. Conclusions This study demonstrated that a high proportion of severe immediate hypersensitivity reactions presenting or acquired in Australian hospitals are secondary to aminopenicillins and aminocephalosporins. Overall rates of hospital-acquired anaphylaxis, predominantly secondary to cephalosporins, are low, and also associated with low inpatient mortality.

We report the first case of hypotensive episodes associated with intravenous (IV) azithromycin. This is a potentially fatal adverse drug reaction (ADR), with the risk of irreversible end-organ damage, and therefore must be recognized and treated immediately. In our case, the reaction was successfully managed by immediate cessation of the azithromycin infusion. It is important for clinicians to be aware of this ADR as azithromycin is a commonly prescribed medication worldwide.

It is important to assess the prevalence of hypogonadism and to identify the correlation between hypogonadism and cancer treatment with quality of life (QoL) in germ cell tumor (GCT) survivors. This is a single-center, non-randomized, prospective observational study in GCT survivors 18–50 years of age previously treated with surgery and chemotherapy (S+C) or surgery alone (S). Patients completed a validated QoL questionnaire at baseline, 3, and 6 months. Patients received supplemental testosterone as clinically indicated. Mean QoL scores were compared between two treatment groups (S+C vs. S) and within each group between survivors with hypogonadism (serum testosterone level

Metacaspases are distant relatives of animal caspases found in plants, protozoa and fungi. Some recent studies have demonstrated that metacaspases are involved in regulating the developmental and environmentally induced programmed cell death in plants. In this study, we identified metacaspase gene family in potato (Solanum tuberosum L.) and analyzed their expression pattern in various developmental tissues and stress responses of plants. There were eight metacaspase genes identified in the Peptidase (Cysteine protease) C14 family and based upon sequence alignment and phylogenetic analysis, a systematic nomenclature of potato metacaspases (SotubMCs) has been proposed. Three of the eight candidate genes showing homology with Arabidopsis thaliana type I metacaspase, AtMC1 were given name SotubMC1, SotubMC2 and SotubMC3 as per the degree of relatedness. Similarly, the next three being homologous to A. thaliana type I metacaspase, AtMC3 were named SotubMC4, SotubMC5, and SotubMC6. The remaining two were named SotubMC7 and SotubMC8, showing significant similarity with type II metacaspases of A. thaliana, AtMC4 and AtMC9, respectively. Evolutionary divergence analysis of SotubMCs from its orthologs in seven other members of Solanaceae family as well as with A. thaliana, Vitis vinifera and Oryza sativa was also carried out. The dN/dS ratios of the orthologous pairs suggested the SotubMCs were under purifying (negative) selection in course of plant evolution. Splicing patterns of potato metacaspases were also analyzed. Amongst all SotubMCs, SotubMC2, SotubMC4, SotubMC6 and SotubMC7 genes appeared to produce multiple alternative spliced variants of different lengths. Furthermore using protein modeling tools, we have predicted the protein structure of identified metacaspases. The cis-regulatory elements analysis was also performed exhibiting the presence of development, stress and hormones related cis-elements in the promoter regions of the SotubMCs. This indicates that potato metacaspases might be playing important roles in the development, stress and hormone responsive pathways. Moreover, relative expression analysis of identified genes was carried out using qRT-PCR in various developmental tissues that also include stolons and tubers. The eight metacaspases showed differential expression in different tissues. Some of the tissues such as leaf undergoing senescence among different leaf developmental stages (immature, mature and senescent) displayed higher relative expression of some of the metacaspases, implying their involvement in leaf senescence. The expression pattern of SotubMCs under various abiotic, biotic and hormonal stresses was also analysed. The results showed that many members of the potato metacaspase gene family displayed differential expression patterns under various stress conditions. Taken together, the study could provide crucial resources for further investigations to understand the functional roles of the identified metacaspases in potato.

Purpose: To compare the visual outcomes and complications between the eyes receiving retropupillary iris claw intraocular lens (IOL) and scleral-fixated IOL (SFIOL) for post-cataract aphakia. Methods: Medical records of consecutive patients who had iris claw IOL and SFIOL surgery from January 2010 to March 2015, with > 1 year of follow up were retrospectively analyzed. The surgical technique was based on individual surgeon preference. The best-corrected distance visual acuity (BCDVA), previous surgery, surgical technique, and complications were analyzed. Results: Retropupillary iris claw IOL was fixated in 48 eyes (46%) and SFIOL was performed in 56 eyes. Iris claw was performed more frequently at the time of primary cataract surgery (56%) compared to SFIOL (14%) (P < 0.001). At 1 month postoperative, BCDVA was significantly better in the SFIOL group [0.7 ± 0.5 logarithm of minimum angle of resolution (logMAR) in iris claw vs. 0.3 ± 0.2 logMAR in SFIOL, P < 0.001] but this difference did not persist at 1 year (0.4 ± 0.4 logMAR in iris claw vs. 0.3 ± 0.2 logMAR in SFIOL, P = 0.56). Eyes with iris claw IOL experienced significantly more postoperative iritis (17%), intraocular pressure spikes (10%), and ovalization of the pupil (16%). Conclusion: Retropupillary iris claw IOL fixation is as safe as SFIOL for visual rehabilitation of post-cataract aphakia. Visual rehabilitation following iris claw IOL might take longer than SFIOL. Ovalization of the pupil is the commonest adverse effect reported with this type of IOL design.

Previous studies have shown that volatile organic compounds (VOCs) are potential biomarkers of breast cancer. An unanswered question is how urinary VOCs change over time as tumors progress. To explore this, BALB/c mice were injected with 4T1.2 triple negative murine tumor cells in the tibia. This typically causes tumor progression and osteolysis in 1–2 weeks. Samples were collected prior to tumor injection and from days 2–19. Samples were analyzed by headspace solid phase microextraction coupled to gas chromatography–mass spectrometry. Univariate analysis identified VOCs that were biomarkers for breast cancer, some of these varied significantly over time and others did not. Principal component analysis was used to distinguish Cancer (all Weeks) from Control and Cancer Week 1 from Cancer Week 3 with over 90% accuracy. Forward feature selection and linear discriminant analysis identified a unique panel that could identify tumor presence with 94% accuracy and distinguish progression (Cancer Week 1 from Cancer Week 3) with 97% accuracy. Principal component regression analysis also demonstrated that a VOC panel could predict number of days since tumor injection (R2 = 0.71 and adjusted R2 = 0.63). VOC biomarkers identified by these analyses were associated with metabolic pathways relevant to breast cancer.

MicroRNAs (miRNAs) are an evolutionarily conserved class of small, regulatory non-coding RNAs that negatively regulate protein coding gene and other non-coding transcripts expression. miRNAs have been established as master regulators of cellular processes, and they play a vital role in tumor initiation, progression and metastasis. Further, widespread deregulation of microRNAs have been reported in several cancers, with several microRNAs playing oncogenic and tumor suppressive roles. Based on these, miRNAs have emerged as promising therapeutic tools for cancer management. In this review, we have focused on the roles of miRNAs in tumorigenesis, the miRNA-based therapeutic strategies currently being evaluated for use in cancer, and the advantages and current challenges to their use in the clinic., Highlights • miRNAs can act as oncogenes or tumor suppressors depending on the specific tissue/cancer targets. • miRNAs can be used as drugs or can be targets for drugs. • Clinical trials using miRNA mimetics or anti-miRNAs as therapeutic targets are currently underway and show promising results.

Altered energy metabolism is a cancer hallmark as malignant cells tailor their metabolic pathways to meet their energy requirements. Glucose and glutamine are the major nutrients that fuel cellular metabolism, and the pathways utilizing these nutrients are often altered in cancer. Here, we show that the long ncRNA CCAT2, located at the 8q24 amplicon on cancer risk-associated rs6983267 SNP, regulates cancer metabolism in vitro and in vivo in an allele-specific manner by binding the Cleavage Factor I (CFIm) complex with distinct affinities for the two subunits (CFIm25 and CFIm68). The CCAT2 interaction with the CFIm complex fine-tunes the alternative splicing of Glutaminase (GLS) by selecting the poly(A) site in intron 14 of the precursor mRNA. These findings uncover a complex, allele-specific regulatory mechanism of cancer metabolism orchestrated by the two alleles of a long ncRNA., G.A.C. is The Alan M. Gewirtz Leukemia & Lymphoma Society Scholar. Work in G.A.C.’s laboratory is supported in part by the NIH/NCI grants 1UH2TR00943-01 and 1 R01 CA182905-01, the UT MD Anderson Cancer Center SPORE in Melanoma grant from NCI (P50 CA093459), Aim at Melanoma Foundation and the Miriam and Jim Mulva research funds, the Brain SPORE (2P50CA127001), the Center for Radiation Oncology Research Project, the Center for Cancer Epigenetics Pilot project, a 2014 Knowledge GAP MDACC grant, a CLL Moonshot pilot project, the UT MD Anderson Cancer Center Duncan Family Institute for Cancer Prevention and Risk Assessment, a SINF grant in colon cancer, the Laura and John Arnold Foundation, the RGK Foundation, and the Estate of C.G. Johnson, Jr. I.B.-N. was financed by a grant entitled Non-Invasive Intelligent Systems for Colorectal Cancer Diagnosis and Prognosis Based on circulating miRNAs Integrated in the Clinical Workflow – INTELCOR. S.M.G.D., A.L.B.A., and D.A. are supported by the São Paulo Research Foundation FAPESP under grants 2014/15968-3, 2014/20673-2, and 2014/17820-3, respectively. W.L. was partly supported by grants from The University of Texas MD Anderson Cancer Center Sheikh Ahmed Bin Zayed Al Nahyan Center for Pancreatic Cancer Research. J.A.B. was supported by the Cancer Center Support Grant (P30 CA016672), and the HP imaging program of the Small Animal Facility (SAIF) was supported by the Cancer Prevention and Research Institutes of Texas grant RP-101243P5. H.L. was supported by NIH/NCI grant R01CA175486, a grant (RP140462) from the Cancer Prevention and Research Institute of Texas, and the R. Lee Clark Fellow Award from The Jeanne F. Shelby Scholarship Fund. I.B.-N. was financed by a Fulbright fellowship and by a grant entitled Non-Invasive Intelligent Systems for Colorectal Cancer Diagnosis and Prognosis Based on circulating miRNAs Integrated in the Clinical Workflow – INTELCOR.

Background: In spite of a few shortcomings such as over diagnosis and over treatment, syndromic management is a recommended practice in India for sexually transmitted infections (STIs). This study tries to find out the efficacy of syndromic management measured as symptomatic improvement in females with vaginal discharge syndrome. Objective: The objective of the study is to find out the effectiveness of syndromic management in terms of symptomatic improvement among females with vaginal discharge syndrome. Materials and Methods: A longitudinal study was conducted in Gynecology Department of Tertiary Care Hospital including 180 symptomatic females having vaginal discharge syndrome. Demographic profile, presenting complaints, menstrual history, obstetric history, partner history, and contraceptive history were noted. This was followed by clinical examination and specimen collection for laboratory tests and blood tests to find out type of STI including viral STI such as human immunodeficiency virus (HIV), herpes simplex virus (HSV), and hepatitis B surface antigen (HBsAg). Treatment was given according to syndromic management on the same day. All the participants were asked to come for follow-up after 15 days and their improvement in symptoms was noted as complete improvement, some improvement or no improvement on a five point scale. Results: 63.9% cases showed complete improvement, while 36.1% showed some improvement. None of the patients was without any improvement. Vaginal discharge syndrome was most common between 20 and 30 years (43.4%), and 67.8% of symptomatic females with vaginal discharge syndrome belonged to the lower socioeconomic group. HSV infection was the most common (15%) associated viral infection with vaginal discharge syndrome, while hepatitis B infection was the least common (0.5%). HIV was reactive in 2.8% cases only. Conclusion: Syndromic management was found to be effective in relieving symptoms in most of the cases of vaginal discharge syndrome.

The prime minister of India has declared a three-week nationwide lock-down starting from midnight the 25th of March 2020 to the 14th of April 2020, explaining that it was an essential and effective measure for breaking the COVID-19 infection cycle. Social distancing is a critical means to break the cycle of infection. There is a significant decrease in growth rate and increased doubling time of cases because of the lockdown (Lau et al., 2020)

Simvastatin is an Antilipidemic agent. The aim is to formulate and evaluate immediate release Simvastatin tablets prepared by wet granulation method. Sodium starch glycolate and crosscarmellose sodium were used as superdisintegrants. Formulations were prepared by Simvastatin with different concentration (1%, 2% and 3%) of crosscarmellose sodium and sodium starch glycolate. Formulations were evaluated for different pre and post compression parameter and in vitro drug release studies. The FTIR studies showed that there is no interaction between the drug and polymer. The results of pre compression parameters of batch I1 to I6 were compared with prescribed limits. It showed that batch I1 to I6 powder blend exhibit good flow property and compressibility property. In formulation I1-I6, disintegration time was observed 3–8 min and 100% drug released within 10–60 min time interval. Thus, based on evaluation of different parameters it was concluded that formulation of immediate release tablets of Simvastatin was successfully done and I2 showed almost 100% drug release at 10 min.

BACKGROUND: The new anti-fibrotics pirfenidone and nintedanib are now in widespread use for idiopathic pulmonary fibrosis (IPF), but they may have an adverse impact on pathways involved in wound-healing. This study aimed to establish the safety of anti-fibrotic therapy in the peri-transplant period, particularly with regard to healing of the bronchial anastomosis. METHODS: In this work we assessed a retrospective cohort of patients who had undergone lung transplantation with a diagnosis of pulmonary fibrosis between January 2012 and December 2017. Pre-transplant use of pirfenidone and nintedanib was identified. Anastomotic dehiscence of any extent was determined at bronchoscopy. Known risk factors for anastomotic dehiscence were evaluated in both anti-fibrotic and control groups. RESULTS: Two hundred twenty-six patients (160 males; mean age 59.7 ± 7.8 years) underwent transplantation in Australia for pulmonary fibrosis during the study period. Forty (17.7%) were receiving anti-fibrotics at the time of transplantation (29 with pirfenidone and 11 with nintedanib). There were 7 anastomotic dehiscence events, with overall incidence rates of 7.5% and 2.2% in the anti-fibrotic and control groups, respectively (p = 0.08). All episodes of dehiscence in the anti-fibrotic group and 2 of 4 in the comparator group occurred

The pervasive role of microRNAs (miRNAs) in cancer pathobiology drives the introduction of new drug development approaches such as miRNA inhibition. In order to advance miRNA-therapeutics, meticulous screening strategies addressing specific tumor targets are needed. Small molecule inhibitors represent an attractive goal for these strategies. In this study, we devised a strategy to screen for small molecule inhibitors that specifically inhibit, directly or indirectly, miR-10b (SMIRs) which is overexpressed in metastatic tumors. We found that the multi-tyrosine kinase inhibitor linifanib could significantly inhibit miR-10b and reverse its oncogenic function in breast cancer and liver cancer both in vitro and in vivo. In addition, we showed that the efficacy of linifanib to inhibit tyrosine kinases was reduced by high miR-10b levels. When the level of miR-10b is high, it can “hijack” the linifanib and reduce its kinase inhibitory effects in cancer resulting in reduced anti-tumor efficacy. In conclusion, our study describes an effective strategy to screen for small molecule inhibitors of miRNAs. We further propose that miR-10b expression levels, due to the newly described “hijacking” effect, may be used as a biomarker to select patients for linifanib treatment.

Information sharing is one of the main supply chain strategies for reducing uncertainty and is vital for supply chain efficiency. For decades, whitefish industries in Iceland and Norway have produced similar products and have exported to the same global markets. However, the differences in the supply chain integration in the two countries affects the information sharing between the fishing vessels and processors that in turn has an impact on supply chain decision making. In this paper, the information sharing practices in the whitefish supply chains in Norway and Iceland are compared. Vertical integration in the Icelandic industry enables information sharing between the fishing vessels and processors which is not the case in Norway. However, Iceland is still not taking full advantage of the available information. The use of the available information in supply chain planning, specifically production planning is discussed and suggestion for improved exchange and use of information is provided., International Journal on Food System Dynamics, Vol 9, No 3 (2018)

Background Studies find that economic, political, and social globalization – as well as trade liberalization specifically – influence the prevalence of overweight and obesity in countries through increasing the availability and affordability of unhealthful food. However, what are the mechanisms that connect globalization, trade liberalization, and rising average body mass index (BMI)? We suggest that the various sub-components of globalization interact, leading individuals in countries that experience higher levels of globalization to prefer, import, and consume more imported sugar and processed food products than individuals in countries that experience lower levels of globalization. Method This study codes the amount of sugar and processed food imports in 172 countries from 1995 to 2010 using the United Nations Comtrade dataset. We employ country-specific fixed effects (FE) models, with robust standard errors, to examine the relationship between sugar and processed foods imports, globalization, and average BMI. To highlight further the relationship between the sugar and processed food import and average BMI, we employ a synthetic control method to calculate a counterfactual average BMI in Fiji. Conclusion We find that sugar and processed food imports are part of the explanation to increasing average BMI in countries; after controlling for globalization and general imports and exports, sugar and processed food imports have a statistically and substantively significant effect in increasing average BMI. In the case of Fiji, the increased prevalence of obesity is associated with trade agreements and increased imports of sugar and processed food. The counterfactual estimates suggest that sugar and processed food imports are associated with a 0.5 increase in average BMI in Fiji. Electronic supplementary material The online version of this article (10.1186/s12992-018-0344-y) contains supplementary material, which is available to authorized users.

Structural stability is a major constraint on the evolution of protein sequences. However, under strong directional selection, mutations that confer novel phenotypes but compromise structural stability of proteins may be permissible. During the evolution of antibiotic resistance, mutations that confer drug resistance often have pleiotropic effects on the structure and function of antibiotic-target proteins, usually essential metabolic enzymes. In the present study, we show that trimethoprim (TMP)-resistant alleles of dihydrofolate reductase from Escherichia coli (EcDHFR) harboring the Trp30Gly, Trp30Arg or Trp30Cys mutations are significantly less stable than the wild-type, making them prone to aggregation and proteolysis. This destabilization is associated with a lower expression level, resulting in a fitness cost and negative epistasis with other TMP-resistant mutations in EcDHFR. Using structure-based mutational analysis, we show that perturbation of critical stabilizing hydrophobic interactions in wild-type EcDHFR enzyme explains the phenotypes of Trp30 mutants. Surprisingly, though crucial for the stability of EcDHFR, significant sequence variation is found at this site among bacterial dihydrofolate reductases (DHFRs). Mutational and computational analyses in EcDHFR and in DHFR enzymes from Staphylococcus aureus and Mycobacterium tuberculosis demonstrate that natural variation at this site and its interacting hydrophobic residues modulates TMP resistance in other bacterial DHFRs as well, and may explain the different susceptibilities of bacterial pathogens to TMP. Our study demonstrates that trade-offs between structural stability and function can influence innate drug resistance as well as the potential for mutationally acquired drug resistance of an enzyme.