Background: TeleStroke can improve access to stroke care in rural areas. We aim to evaluate the safety and effectiveness of intravenous thrombolysis in our TeleStroke system. Methods: The Manitoba TeleStroke program was rolled out across 7 sites between November 2014 and January 2019. We retrospectively analyzed prospectively collected consecutive acute stroke patients’ data in this duration. The primary outcome was safety and effectiveness measured in terms of 90-day modified Rankin score (mRs). The number of acute ischemic stroke (AIS) patients receiving thrombolysis and endovascular thrombectomy [EVT] and process metrics were also analyzed. R/RStudio version-4.3.2 was used (p<0.05). Results: Of the 1,748 TeleStroke patients (age 71 years [IQR 58-81], female 810[46.3%]), 696 were identified as AIS. Of these, 265(38.1%) received thrombolysis and 48(6.9%) EVT. Ninety-day mortality was 53(20.0%) among those receiving thrombolysis and 117(44.2%) had a favorable outcome (mRs ≤2). Of those who received intravenous thrombolysis, 9 patients (4.2%) were found to have symptomatic intracranial hemorrhage. The median last-seen-normal (LSN)-to-door was121 minutes and the median door-to-needle, 55 minutes. Conclusions: Intravenous thrombolysis was found to be effective with acceptable safety. TeleStroke improved overall access to stroke care and played an important role in identifying AIS patients eligible for thrombolysis and EVT.

Each day a venous catheter is retained poses unnecessary safety risks. In a retrospective evaluation of central/peripheral lines in nursing home residents receiving antibiotics, 80% were retained beyond antibiotic treatment end and nearly one third were retained longer than a week. Interventions for timely catheter removal are urgently needed.

Adequate nutrition is necessary during childhood and early adolescence for adequate growth and development. Hence, the objective of the study was to assess the association between dietary intake and blood levels of minerals (calcium, iron, zinc, and selenium) and vitamins (folate, vitamin B12, vitamin A, and vitamin D) in urban school going children aged 6–16 years in India, in a multicentric cross-sectional study. Participants were enrolled from randomly selected schools in ten cities. Three-day food intake data was collected using a 24-h dietary recall method. The intake was dichotomised into adequate and inadequate. Blood samples were collected to assess levels of micronutrients. From April 2019 to February 2020, 2428 participants (50⋅2 % females) were recruited from 60 schools. Inadequate intake for calcium was in 93⋅4 % (246⋅5 ± 149⋅4 mg), iron 86⋅5 % (7⋅6 ± 3⋅0 mg), zinc 84⋅0 % (3⋅9 ± 2⋅4 mg), selenium 30⋅2 % (11⋅3 ± 9⋅7 mcg), folate 73⋅8 % (93⋅6 ± 55⋅4 mcg), vitamin B12 94⋅4 % (0⋅2 ± 0⋅4 mcg), vitamin A 96⋅0 % (101⋅7 ± 94⋅1 mcg), and vitamin D 100⋅0 % (0⋅4 ± 0⋅6 mcg). Controlling for sex and socioeconomic status, the odds of biochemical deficiency with inadequate intake for iron [AOR = 1⋅37 (95 % CI 1⋅07–1⋅76)], zinc [AOR = 5⋅14 (95 % CI 2⋅24–11⋅78)], selenium [AOR = 3⋅63 (95 % CI 2⋅70–4⋅89)], folate [AOR = 1⋅59 (95 % CI 1⋅25–2⋅03)], and vitamin B12 [AOR = 1⋅62 (95 %CI 1⋅07–2⋅45)]. Since there is a significant association between the inadequate intake and biochemical deficiencies of iron, zinc, selenium, folate, and vitamin B12, regular surveillance for adequacy of micronutrient intake must be undertaken to identify children at risk of deficiency, for timely intervention.

Anthracnose caused by Colletotrichum truncatum is a major soybean disease in India. Genetic resistance is the viable option to combat yield losses due to this disease. In the current study, 19 soybean genotypes were evaluated for anthracnose disease resistance at five locations (Medziphema, Palampur, Dharwad, Jabalpur and Indore) for three consecutive years (2017–2019) to identify stable and superior genotypes as resistant sources and to elucidate genotype (G) × environment (E) interactions. Genotype effect, environment effect and G × E interactions were found significant (P < 0.001) where G × E interactions contributed highest (42.44) to the total variation followed by environment (29.71) and genotype (18.84). Through Weighted Average of Absolute Scores (WAASB) stability analysis, PS 1611 (WAASB score = 0.33) was found to be most stable and through WAASBY superiority analysis NRC 128 (WAASBY score = 94.31) and PS 1611 (WAASBY score = 89.43) were found to be superior for mean performance and stability. These two genotypes could be candidate parents for breeding for durable and stable anthracnose resistance. Through principal component analysis, disease score was found to be positively associated with relative humidity, wind speed at 2 m above ground level, effect of temperature on radiation use efficiency and global solar radiation based on latitude and Julian day. Among the five locations, Indore was found to be highly discriminative with the highest mean disease incidence and could differentiate anthracnose-resistant and susceptible genotypes effectively, therefore can be considered an ideal location for breeding for field resistance against anthracnose disease.

Background: Thrombus embolization during endovascular treatment (EVT) occurs in up to 9% of cases, making secondary medium-vessel occlusions (MeVOs) of particular interest to neurointerventionalists. We sought to gain insight into the current EVT approaches for secondary MeVO stroke in an international case-based survey as there are currently no clear recommendations for EVT in these patients. Methods: Participants were presented with three secondary MeVO cases, each consisting of three case-vignettes with changes in patient neurological status (improvement, no change, unable to assess). Clustered multivariable logistic regression analyses were used to assess factors influencing the decision to treat. Results: 366 physicians from 44 countries took part. The majority (54.1%) were in favor of EVT. Participants were more likely to treat occlusions in the anterior M2/3 (74.3%; risk ratio [RR]2.62, 95%CI:2.27-3.03) or A3 (59.7%; RR2.11, 95%CI:1.83-2.42) segment, compared to the M3/4 segment (28.3%;reference). Physicians were less likely to pursue EVT in patients with neurological improvement (49.9% versus 57.0%; RR0.88, 95%CI:0.83-0.92). Interventionalists and more experienced physicians were more likely to treat secondary MeVOs. Conclusions: Physician’s willingness to treat secondary MeVOs endovascularly is limited and varies per occlusion location and change in neurological status. More evidence on the safety and efficacy of EVT for secondary MeVO stroke is needed.

A cross-sectional study was conducted from 2014 to 2017 in 13 organised pig farms located in eight states of India (Northern, North-Eastern and Southern regions) to identify the risk factors, pathotype and antimicrobial resistance of Escherichia coli associated with pre- and post-weaning piglet diarrhoea. The data collected through questionnaire survey were used to identify the risk factors by univariable analysis, in which weaning status, season, altitude, ventilation in the shed, use of heater/cooler for temperature control in the sheds, feed type, water source, and use of disinfectant, were the potential risk factors. In logistic regression model, weaning and source of water were the significant risk factors. The piglet diarrhoea prevalence was almost similar across the regions. Of the 909 faecal samples collected (North – 310, North-East – 194 and South – 405) for isolation of E. coli, pathotyping and antibiotic screening, 531 E. coli were isolated in MacConkey agar added with cefotaxime, where 345 isolates were extended spectrum β-lactamase (ESBL) producers and were positive for blaCTX-M-1 (n = 147), bla TEM (n = 151), qnrA (n = 98), qnrB (n = 116), qnrS (n = 53), tetA (n = 46), tetB (n = 48) and sul1 (n = 54) genes. Multiple antibiotic resistance (MAR) index revealed that 14 (2.64%) isolates had MAR index of 1. On the virulence screening of E. coli, 174 isolates harboured alone or combination of Stx1, Stx2, eaeA, hlyA genes. The isolates from diarrhoeic and post-weaning samples harboured higher number of virulence genes than non-diarrhoeic and pre-weaning. Alleviating the risk factors might reduce the piglet diarrhoea cases. The presence of multidrug-resistant and ESBL-producing pathogenic E. coli in piglets appears a public health concern.

A series of Cu-substituted goethites, single and co-substituted with Cr, Zn, Cd and/or Pb was prepared, having molar ratios equal to 2.00, 3.33 and 5.00 mol%. All the samples contained only goethite, except Cu-, (Cu,Zn)- and (Cu,Pb)-samples synthesized at 5.00 mol% where hematite was also formed. The presence of Cr/Cd suppressed the hematite-forming effects of Cu. The general sequence of metal entry into the single-metal-substituted goethites was Zn = Cr > Cd > Cu > Pb and in di- (5.00 mol%) and tri- (3.33 mol%) metal-substituted goethites was Cu > Zn > Cd > Cr >> Pb. Cu incorporation increased all the unit-cell parameters in single-metal-substituted goethite, and these parameters increased in combination with other metals as follows: Cd > Zn > Cr > Pb in the multimetal-substituted goethites. The Cu-substituted goethite dissolved faster than pure goethite. Co substitutions of Cr/Pb reduced the dissolution rate (k Fe), while substitutions of Cd/Zn increased k Fe.

Rice has the lowest grain protein content (GPC) among cereals. Efforts have been made to improve GPC through the modified bulk-pedigree method of selection. A total of 1780 F8 recombinant lines were derived in the year 2013 from five different cross combinations involving two high-GPC landraces, namely ARC10075 and ARC10063, three high-yielding parents, namely Swarna, Naveen and IR64, and one parent, namely Sharbati, known for superior grain quality with high micronutrient content. Near-infrared spectroscopy was used to facilitate high-throughput selection for GPC. Significant selection differential, response to selection and non-significant differences between the predicted and observed response to selection for GPC and protein yield indicated the effectiveness of this selection process. This resulted in lines with high GPC, protein yield and desirable levels of amylose content. Further, based on high mean and stability for GPC and protein yield over the environments in the wet seasons of 2013, 2014 and the dry season of 2014, 12 elite lines were identified. Higher accumulation of glutelin fraction and non-significant change in prolamin/glutelin ratio in the grain suggested safe guarding of the nutritional value of rice grain protein of most of these identified lines. Since rice is the staple food of millions, the output of breeding for high GPC could have a significant role in alleviating protein malnutrition, especially in the developing world.

Bovine calf scours reported to be caused by multiple aetiologies resulting in heavy mortality in unweaned calves and huge economic loss to the dairy farmers. Among these, cryptosporidiosis is an emerging waterborne zoonoses and one of the important causes of neonatal calf diarrhoea. Poor immune response coupled with primary cryptosporidial infections predispose neonatal calves to multiple secondary infections resulting in their deaths. In the present study, faecal samples from 100 diarrhoeic calves randomly picked up out of 17 outbreaks of bovine calf diarrhoea in periurban Ludhiana, Punjab in Northern India were subjected to conventional (microscopy, modified Zeihl–Neelsen (mZN) staining) and immunological and molecular techniques (faecal antigen capture ELISA and PCR) for detection of primary Cryptosporidium parvum infection as well as other frequently reported concurrent pathogens, viz. rotavirus and coronavirus, Salmonella spp., Escherichia coli, Clostridium perfringens and Eimeria spp. The faecal antigen capture ELISA and PCR revealed 35% prevalence of C. parvum in contrast to 25% by mZN staining with a relatively higher prevalence (66·7%) in younger (8–14-day-old) calves. The detection rate of the other enteropathogens associated with C. parvum was 45·71% for C. perfringens followed by Salmonella spp (40·0%), rotavirus (36·0%), coronavirus (16·0%), E. coli (12·0%) and Eimeria spp (4·0%) The sensitivity for detection of C. parvum by ELISA and mZN staining in comparison to PCR was 97·14% and 72·72%, respectively. An important finding of the study was that C. parvum alone was found in only 10% of the diarrhoeic faecal samples, whereas, majority of the samples (90%) showed mixed infections ranging from a combination of two to five agents. This is the first documentary proof of C. parvum and associated pathogens responsible for severe periurban outbreaks of bovine calf diarrhoea culminating in heavy mortality from Northern India.

An estimation of the critical period of weed control is helpful in formulating appropriate weed-control strategies. A regression approach is presented to estimate the thresholds of critical period of weed control and time of equal interference (or time of onset of competition). In this approach, yields were either a linear or logistic function of the duration of weed-free and weed-infested periods. Confidence intervals of the thresholds of critical period and time of equal interference were determined for the linear model. An approximation to the standard error of critical period and associated confidence interval were given for any general form of the model. The method was applied to estimate the critical period of weed control in rainfed lentil using data from four field experiments conducted in Jordan. The relationship of yield with the duration of weed-free period was described by a linear function, whereas the relationship with the duration of weed-infested period showed a better fit with a logistic function. To maintain 90% of maximum seed yield, the maximum time allowed to let weeds grow after the crop emergence varied over locations from 4.8 to 5.8 wk. The same level could be achieved if the crop is kept free of weeds from its emergence until 12.1 to 14.1 wk; while the time when the same amount of yield would be achieved under both approaches varied from 7.7 to 9.3 wk after crop emergence. For straw yield, the time to get 90% of the maximum yield could vary over location from a maximum of 4.5 to 8.0 wk under weed-infestation and from at least 11.5 to 13.5 wk when weed-free. The time to achieve the same amount of straw under two systems of competition varied from 6.5 to 9.9 wk after crop emergence. One of the four experiments showed a longer critical period than the others for seed and straw yields.

Background: The surgical risk factors and neuro-imaging characteristics associated with cerebellar mutism (CM) remain unclear and require further investigation. We aimed to examine surgical and MRI findings associated with CM in children following posterior fossa tumor resection. Methods: Using our data registry, we retrospectively collected data from pediatric patients who acquired CM and were matched based on age and pathology type with patients not acquiring CM after posterior fossa surgery. The strength of association between surgical and MRI variables and CM were examined using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results: A total of 22 patients were included. Medulloblastoma was the most common pathology among CM patients (91%). Tumor attachment to the floor of the fourth ventricle (OR, 6; 95% CI, 0.7-276), calcification/hemosiderin deposition (OR 7; 95% CI 0.9-315.5), and post-operative peri-ventricular ischemia on MRI (OR, 5; 95% CI, 0.5-236.5) were found to have the highest association with CM. Conclusions: Our results may suggest that tumor attachment to the floor of the fourth ventricle, pathological calcification, and post-operative ischemia are relatively more prevalent in patients with CM. Collectively, our work calls for a larger multi-institutional study of CM patients to further investigate the determinants and management of CM to potentially minimize its development and predict onset.

Medulloblastoma (MB) is the most common malignant pediatric brain tumour, and is categorized into four molecular subgroups, with Group 3 MB having the worst prognosis due to the highest rate of metastatic dissemination and relapse. In this work, we describe the epigenetic regulator Bmi1 as a novel therapeutic target for treatment of recurrent Group 3 MB. Through comparative profiling of primary and recurrent MB, we show that Bmi1 defines a treatment-refractory cell population that is uniquely targetable by a novel class of small molecule inhibitors. We have optimized an in vivo mouse-adapted therapy model that has the advantage of generating recurrent, human, treatment-refractory MBs. Our preliminary studies showed that although chemoradiotherapy administered to mice engrafted with human MB showed reduction in tumour size, Bmi1 expression was enriched in the post-treatment residual tumour. Furthermore, we found that knockdown of Bmi1 in human recurrent MB cells decreases proliferation and self-renewing capacities of MB cells in vitro as well as both tumour size and extent of spinal leptomeningeal metastases in vivo. Oral administration of a potent Bmi1 inhibitor, PTC 028, resulted in a marked reduction in tumour burden and an increased survival in treatment cohort. Bmi1 inhibitors showed high specificity for MB cells and spared normal human neural stem cells, when treated with doses relevant for MB cells. As Group 3 medulloblastoma is often metastatic and uniformly fatal at recurrence, with no current or planned trials of targeted therapy, an efficacious agent such as Bmi1 inhibitor could be rapidly transitioned to clinical trials.

Medulloblastoma (MB), the most common malignant pediatric brain tumor, is categorized into four molecular subgroups. Given the high rate of metastatic dissemination at diagnosis and recurrence in Group 3 MBs, these patients have the worst clinical outcome with a 5-year survivorship of approximately 50%. By adapting the existing COG (Children’s Oncology Group) Protocol for children with newly diagnosed high-risk MB, for treatment of immuno-deficient mice intracranially engrafted with human MB brain tumour initiating cells we aim to identify and characterize the treatment-refractory cell population in Group 3 MBs. Mice were sacrificed at multiple time points during the course of tumor development and therapy: (i) at engraftment; (ii) post-radiation; (iii) post-radiation and chemotherapy; and (iv) at MB recurrence. MB cell populations recovered separately from brains and spines were comprehensively profiled for gene expression analysis, stem cell and molecular features to generate a global, comparative profile of MB cells through therapy. We report a higher expression of CD133, Sox2 and Bmi1 in addition to increased self-renewal capacity following chemoradiotherapy treatment. The enrichment map constructed from global gene expression analysis showed an increase in pathways regulating self-renewal, DNA repair and chemoresistance post-therapy despite the apparent decrease in tumour size and vascularity. Additionally, from gene expression at MB recurrence, we identified a list of genes that negatively correlate with survival in patients diagnosed with Group 3 MB. A differential genomic profile of the “treatment-responsive” tumors against those that fail therapy may contribute to discovery of novel therapeutic approaches for the most aggressive subgroup of MB.

Brain Metastases (BM) represent a leading cause of cancer mortality. While metastatic lesions contain subclones derived from their primary lesion, their functional characterization has been limited by a paucity of preclinical models accurately recapitulating the stages of metastasis. This work describes the isolation of a unique subset of metastatic stem-like cells from primary human patient samples of BM, termed brain metastasis initiating cells (BMICs). Utilizing these BMICs we have established a novel patient-derived xenograft (PDX) model of BM that recapitulates the entire metastatic cascade, from primary tumor initiation to micro-metastasis and macro-metastasis formation in the brain. We then comprehensively interrogated human BM to identify genetic regulators of BMICs using in vitro and in vivo RNA interference screens, and validated hits using both our novel PDX model as well as primary clinical BM specimens. We identified SPOCK1 and TWIST2 as novel BMIC regulators, where in our model SPOCK1 regulated BMIC self-renewal and tumor initiation, and TWIST2 specifically regulated cell migration from lung to brain. A prospective cohort of primary lung cancer specimens was used to establish that SPOCK1 and TWIST2 were only expressed in patients who ultimately developed BM, thus establishing both clinical and functional utility for these gene products. This work offers the first comprehensive preclinical model of human brain metastasis for further characterization of therapeutic targets, identification of predictive biomarkers, and subsequent prophylactic treatment of patients most likely to develop BM. By blocking this process, metastatic lung cancer would effectively become a localized, more manageable disease.

A method has been developed for calculating the load distribution, overall forces and moments on a thin wing of arbitrary shape undergoing small amplitude simple harmonic motion in inviscid, incompressible flow. The method is compared with experimental data and other theoretical methods for wings and control surfaces in pitching oscillation and wings going through a sinusoidal vertical gust.