Miracle-dz/UniFAR-FTUs huggingface dataset:
Managing the complexity of change in postgraduate surgical education and training

Pressure of workforce shortages, educational reform, heightened regulatory requirements and increased community expectations and scrutiny, has led to demand for substantial change in the provision of surgical education and training. The Royal Australasian College of Surgeons has responded positively to these external factors through an extensive review of local and worldwide practice and opinion, providing ongoing realignment of its governance and committee structure, substantially adjusting the structure of its educational program and increasing the educational support to trainees and supervisors. The College looks to the Council and its senior Fellows to create the direction and drive, but these changes need to be supported and implemented with care by the management and administrative staff of the College and specialist societies. This is in an opinion‐rich zone with substantial regulatory scrutiny.
Emergence of 2.1. subgenotype of classical swine fever virus in pig population of India in 2011

Background: Limited studies are available on molecular epidemiology of classical swine fever virus (CSFV) in India and are restricted to domestic pigs. These studies show the presence of 1.1. genotype. Hypothesis/objectives: The aim of the present study was to subgenotype four CSFV isolates, two each from the outbreaks of CSF in wild (Sus scrofa) and domestic pigs of Mizoram state, India, in 2011. Animals and methods: CSFV isolates were subjected to nucleotide sequencing in E2 and NS5B genomic regions. Phylogenetic analysis of the isolates in both genomic regions was carried out with 39 Indian isolates (4 isolates from the present study of Mizoram state and 35 isolates from the other states of India) and 57 reference sequences retrieved from the GenBank database. Two of the 39 isolates from India were collected from wild boar and were subgenotyped as 2.1. Out of 37 isolates from domestic pigs, only two were subgenotyped as 2.1. Results: The analysis revealed the emergence of 2.1. subgenotype of CSFV in both wild and domestic pigs in India. Conclusions and clinical importance: The isolates from domestic pigs of Mizoram state (CSF/MZ/KOL/73 and CSF/MZ/AIZ/115) were grouped in genotype 1 and subgenotype 1.1. , thus confirming that the source of CSF outbreaks in domesticated pigs in Mizoram was not from wild pigs. The current study forms an essential step for better understanding of the epidemiology of 2.1 subgroup as well as the movement and spread of the disease in India.
Mild gentamicin nephrotoxicity reduces the progression of chronic adriamycin nephrosis

The effect of mild acute tubular injury on the progression of tubulointerstitial fibrosis was studied in pair‐fed uninephrectomized male Wistar rats with established adriamycin nephrosis (n=34). Rats were stratified into three groups according to endogenous creatinine clearance (CrCl), proteinuria (Upr) and body weight (BW): (i) group 1 (Fe, n=12) received a single intraperitoneal injection of ferric nitrilotriacetate (5 mg Fe/kg BW); (ii) group 2 (G, n=10) three daily subcutaneous injections of gentamicin (60 mg/kg BW) and; (iii) group 3 (C, n=12) saline injections. Serial CrCl (day 2, day 5, weeks 2, 4, 6 and 8) and renal histology (week 8) were examined following administration of nephrotoxin. CrCl was reduced on d2 (Fe: 0.78±0.23 mL/min; mean±SD) and day 5 (G: 0.91±0.36 mL/min) as compared with C (1.22±0.12 mL/min; P<0.05). There was no change in the serum creatinine and functional recovery occurred by d5 (Fe) and week 2 (G). Upr decreased transiently in G at week 2 (G: 482±208 mg/day vs C: 716±233; P=0.05) despite similar food intake, baseline Upr and CrCl. At week 8, CrCl in Fe (0.84±0.40 mL/min) was similar to C (0.84±0.58 mL/min), whereas in G it remained stable (1.27±0.39 mL/min; P<0.05). By morphometric analysis, mean relative interstitial volume (RIV) and glomerulosclerosis (GS) in Fe (RIV: 28.5±13.4%; GS: 10.3±12.3%) was no different to C (RIV: 24.5±12.5%; GS: 20.9±20.0%), whereas both parameters were reduced in G (RIV: 14.1±8.1%; GS: 4.0±4.8%; P<0.05). Mild gentamicin nephrotoxicity therefore reduced the progression of adriamycin nephrosis. The mechanism of this finding is unclear, but it may relate to altered glomerular and tubular cell handling of protein.
Early mobilization after total knee replacement reduces the incidence of deep venous thrombosis

Both chemical and mechanical methods of prophylaxis have reduced the incidence of thromboembolic complications following total knee replacement (TKR). Only a few studies have shown that mobilization on the first post‐operative day further reduces the incidence of thromboembolic phenomena. We conducted a prospective study to verify not only if early mobilization but also whether the distance mobilized on the first post‐operative day after TKR reduced the incidence of thromboembolic complications.
Prenatal Exposure to Maternal Cigarette Smoke and Offspring Risk of Excess Weight Is Independent of Both Birth Weight and Catch-Up Growth

Prenatal exposure to maternal cigarette smoke (PEMCS) is one of the most common insults to the developing fetus and has consistently emerged as an important risk factor for excess weight in the offspring. However, no consensus exists on the mechanism of action or duration of impact. This study seeks to further examine the role of PEMCS on overweight status of children up to age 10. Mother and child pairs (𝑛=1183) were analysed from the Quebec Longitudinal Study of Child Development (QLSCD) (1998–2010). Multivariable logistic regression models were used to control for confounders and assess mediation. PEMCS was associated with overweight status at age 10 (OR: 1.70; 95% CI: 1.20–2.43) after adjustment for early life exposures and childhood behaviours. This relationship remained robust after adjustment for birth weight and catch-up growth. Other significant predictors included APGAR score, mother’s immigrant and weight status, family type and child energy intake. The elevated risk of excess weight among the offspring of smoking mothers was not accounted for by other known determinants, and PEMCS appears to play a role independent of birth weight and catch-up growth. Our research suggests that young mothers may be an important audience for targeting preventive strategies.
Zika virus – emergence, evolution, pathology, diagnosis, and control: current global scenario and future perspectives – a comprehensive review

ABSTRACT This review converses the Zika virus which has attained global concern due to its rapid pandemic potential and impact on humans. Though Zika virus was first isolated in 1947, till the recent large-scale outbreak which occurred in Micronesia, in 2007, the virus was placed into the innocuous pathogen category. The World Health Organization on 1 February 2016 declared it as a ‘Public Health Emergency of International Concern. ’ Of the note, American as well as Pacific Island strains/isolates is relatively closer to Asian lineage strains. The African and American strains share more than 87.5% and 95% homologies with Asian strains/isolates, respectively. Asian strains form independent clusters, except those isolated from China, suggesting relatively more diversity than African strains. Prevention and control are mainly aimed at the vector population (mosquitoes) with Aedes aegypti being the main species. Surveys in Africa and Asia indicated seropositivity in various animal species. However, so far its natural reservoir is unknown. There is an urgent need to understand why Zika virus has shifted from being a virus that caused mild illness to unforeseen birth defects as well as autoimmune-neurological problems. Unfortunately, an effective vaccine is not available yet. Availability of cryo-electron microscopy based on 3.8 Å resolution revealing mature Zika virus structure and the probable virus attachment site to host cell would provide critical insights into the development of antiviral treatments and vaccines.
Neurotrophic factors as a therapeutic target for Parkinson's disease

Background: The search for therapeutic agents that might alter the disease course in Parkinson's disease (PD) is ongoing. One area of particular interest involves neurotrophic factors (NTFs), with those of the glial cell line-derived neurotrophic factor (GDNF) family showing greatest promise. The safety and efficacy of these therapies has recently come into question. Furthermore, many of the key questions pertaining to such therapies, such as the optimal method of delivery, timing of treatment and selection of patients most likely to benefit, remain unanswered. Objective: In this review we sought to evaluate the therapeutic potential of NTFs in the treatment of PD. We appraised the evidence provided by both in vitro and in vivo work before proceeding to a critical assessment of the relevant clinical trial data. Methods: Relevant literature was identified using a PubMed search of articles published up to October 2007. Search terms included: ‘Parkinson's disease’, ‘Neurotrophic factors’, ‘BDNF’ (Brain-derived neurotrophic factor), ‘GDNF’ and ‘Neurturin’. Original articles were reviewed, and relevant citations from these articles were also appraised. Conclusion: NTF therapy has potential in the treatment of nigrostriatal dysfunction in PD but numerous methodological and safety issues will need to be addressed before this approach can be widely adopted. Furthermore PD is now recognized as being more than a pure motor disorder, and one in which neuronal loss is not just confined to the dopaminergic nigrostriatal system. Non-motor symptomatology in PD is unlikely to benefit from therapies that target only the nigrostriatal system, and this must inform our thinking as to the maximal achievable benefit that NTFs are ever likely to provide.
Parents' mental health after the birth of an extremely preterm child: A comparison between bereaved and non-bereaved parents

Objective. To assess the impact of extremely preterm birth (24–26 weeks of gestation) on the mental health of parents two to six years after delivery, and to examine potential differences in post-traumatic growth between parents whose newborn infant died and those whose child survived. Method. A total of 54 parents who had lost their newborn and 38 parents whose preterm child survived were assessed by questionnaires with regard to depression and anxiety (HADS) and post-traumatic growth (PTGI). Results. Neither group of parents had clinically relevant levels of depression and anxiety. Mothers showed higher levels of anxiety than fathers. Bereaved parents with no other, living child reported higher levels of depression than bereaved parents with one or more children. Mothers reported higher post-traumatic growth compared to fathers. In particular, bereaved mothers experienced the value and quality of their close social relationships more positively compared to the non-bereaved parents. Conclusion. In the long term, bereaved and non-bereaved parents cope reasonably well with an extremely preterm birth of a child. Post-traumatic growth appears to be positively related to bereavement, particularly in mothers.
Complete anaerobic mineralization of pentachlorophenol (PCP) under continuous flow conditions by sequential combination of PCP‐dechlorinating and phenol‐degrading consortia

Complete mineralization of 50 µM of pentachlorophenol (PCP) was achieved anaerobically under continuous flow conditions using two columns connected in series with a hydraulic retention time of 14.2 days, showing the highest reported mineralization rate yet of 3.5 µM day−1. The first column, when injected with a reductive PCP dechlorinating consortium, dechlorinated PCP to mainly phenol and traces of 3‐chlorophenol (3‐CP) using lactate supplied continuously as an electron donor. The second column, with an anaerobic phenol degrading consortium, decomposed phenol and 3‐CP under iron‐reducing conditions with substantial fermentative degradation of organic compounds. When 20 mM of lactate was introduced into the first column, the phenol degradation activity of the second column was lost in a short period of time, because the amorphous Fe(III) oxide (FeOOH) that had been packed in the column before use was depleted by lactate metabolites, such as acetate and propionate, flowing into the second column from the first column. The complete mineralization of PCP was maintained for a long period by reducing the lactate concentration to 4 mM, effectively extending the longevity of second‐column activity with no depletion of FeOOH for more than 200 pore volumes (corresponding to 3,000 days). The carbon balance showed that 50 µM PCP and 4 mM lactate in the influent had transformed to CO2 (81%) and CH4 (3%) and had contributed to biomass growth (8%). A comparison of the microbial consortia introduced into the columns and those flowing out from the columns suggested that the introduced population did not flow out during the experiments, although the microbial composition of the phenol column was considered to be affected by the inflow of microbes from the PCP dechlorination column. These results suggest that a sequential combination of reductive dechlorinating and anaerobic oxidizing consortia is useful for anaerobic remediation of chlorinated aromatic compounds in a microbial permeable reactive barrier. Biotechnol. Bioeng. 2010;107: 775–785. © 2010 Wiley Periodicals, Inc.
Production of succinic acid at low pH by a recombinant strain of the aerobic yeast Yarrowia lipolytica

Biotechnological production of weak organic acids such as succinic acid is most economically advantageous when carried out at low pH. Among naturally occurring microorganisms, several bacterial strains are known to produce considerable amounts of succinic acid under anaerobic conditions but they are inefficient in performing the low‐pH fermentation due to their physiological properties. We have proposed therefore a new strategy for construction of an aerobic eukaryotic producer on the basis of the yeast Yarrowia lipolytica with a deletion in the gene coding one of succinate dehydrogenase subunits. Firstly, an original in vitro mutagenesis‐based approach was proposed to construct strains with Ts mutations in the Y. lipolytica SDH1 gene. These mutants were used to optimize the composition of the media for selection of transformants with the deletion in the Y. lipolytica SDH2 gene. Surprisingly, the defects of each succinate dehydrogenase subunit prevented the growth on glucose but the mutant strains grew on glycerol and produced succinate in the presence of the buffering agent CaCO3. Subsequent selection of the strain with deleted SDH2 gene for increased viability allowed us to obtain a strain capable of accumulating succinate at the level of more than 45 g L−1 in shaking flasks with buffering and more than 17 g L−1 without buffering. The possible effect of the mutations on the utilization of different substrates and perspectives of constructing an industrial producer is discussed. Biotechnol. Bioeng. 2010;107:673–682. © 2010 Wiley Periodicals, Inc.
Sudden Appearance of New Upper Extremity Motor Function While Performing Neurophysiologic Intraoperative Monitoring During Tethered Cord Release: A Case Report

&NA; Tethered cord syndrome occurs when the distal spinal cord or filum adheres to adjacent structures resulting in progressive sensorimotor deficits in the lower extremities, fecal and/or urinary incontinence, and musculoskeletal deformities. Tethering of the distal cord may be idiopathic, may be associated with an intraspinal abnormality such as a lipoma, but most commonly the distal spinal cord remnant is adherent to the area of the original dysraphism repair in patients with myelodysplasia. Surgery to untether the cord is indicated in patients with worsening pain symptoms, progressive limb deformity or spasticity, or before any acute correction of an associated spinal deformity. Neurophysiologic intraoperative monitoring is used to minimize the risk of inadvertent nerve root or spinal cord injury during the untethering procedure and to assess any changes in cord function at the time of an associated spinal deformity correction. We present a patient with a lumbar level myelodysplasia, Chiari II malformation, severe scoliosis, and tethered cord that underwent concurrent scoliosis correction and tethered cord syndrome surgery, who demonstrated immediate intraoperative improvement in neurophysiologic responses in a previously flaccid upper extremity after untethering. These monitoring changes correlated with clinical improvements noted by physicians and family postoperatively. Level of Evidence Level IV.
Defining process design space for a hydrophobic interaction chromatography (HIC) purification step: Application of quality by design (QbD) principles

The concept of design space has been taking root under the quality by design paradigm as a foundation of in‐process control strategies for biopharmaceutical manufacturing processes. This paper outlines the development of a design space for a hydrophobic interaction chromatography (HIC) process step. The design space included the impact of raw material lot‐to‐lot variability and variations in the feed stream from cell culture. A failure modes and effects analysis was employed as the basis for the process characterization exercise. During mapping of the process design space, the multi‐dimensional combination of operational variables were studied to quantify the impact on process performance in terms of yield and product quality. Variability in resin hydrophobicity was found to have a significant influence on step yield and high‐molecular weight aggregate clearance through the HIC step. A robust operating window was identified for this process step that enabled a higher step yield while ensuring acceptable product quality. Biotechnol. Bioeng. 2010;107: 985–997. © 2010 Wiley Periodicals, Inc.
Previous pregnancy outcomes and subsequent pregnancy anxiety in a Quebec prospective cohort

Abstract Introduction: Pregnancy anxiety is an important psychosocial risk factor that may be more strongly associated with adverse birth outcomes than other measures of stress. Better understanding of the upstream predictors and causes of pregnancy anxiety could help to identify high-risk women for adverse maternal and infant outcomes. The objective of the present study was to measure the associations between five past pregnancy outcomes (live preterm birth (PTB), live term birth, miscarriage at <20 weeks, stillbirth at ≥20 weeks, and elective abortion) and pregnancy anxiety at three trimesters in a subsequent pregnancy. Methods: Analyses were conducted using data from the 3D Cohort Study, a Canadian birth cohort. Data on maternal demographic characteristics and pregnancy history for each known previous pregnancy were collected via interviewer-administered questionnaires at study entry. Pregnancy anxiety for the index study pregnancy was measured prospectively by self-administered questionnaire following three prenatal study visits. Results: Of 2366 participants in the 3D Study, 1505 had at least one previous pregnancy. In linear regression analyses with adjustment for confounding variables, prior live term birth was associated with lower pregnancy anxiety in all three trimesters, whereas prior miscarriage was significantly associated with higher pregnancy anxiety in the first trimester. Prior stillbirth was associated with greater pregnancy anxiety in the third trimester. Prior elective abortion was significantly associated with higher pregnancy anxiety scores in the first and second trimesters, with an association of similar magnitude observed in the third trimester. Discussion: Our findings suggest that the outcomes of previous pregnancies should be incorporated, along with demographic and psychosocial characteristics, into conceptual models framing pregnancy anxiety.
Reaction–diffusion constraints in living tissue: Effectiveness factors in skeletal muscle design

A mathematical model was developed to analyze the effects of intracellular diffusion of O2 and high‐energy phosphate metabolites on aerobic energy metabolism in skeletal muscle. We tested the hypotheses that in a range of muscle fibers from different species (1) aerobic metabolism was not diffusion limited and (2) that fibers had a combination of rate and fiber size that placed them at the brink of substantial diffusion limitation. A simplified chemical reaction rate law for mitochondrial oxidative phosphorylation was developed utilizing a published detailed model of isolated mitochondrial function. This rate law was then used as a boundary condition in a reaction–diffusion model that was further simplified using the volume averaging method and solved to determine the rates of oxidative phosphorylation as functions of the volume fraction of mitochondria, the size of the muscle cell, and the amount of oxygen delivered by the capillaries. The effectiveness factor, which is the ratio of reaction rate in the system with finite rates of diffusion to those in the absence of any diffusion limitations, defined the regions where intracellular diffusion of metabolites and O2 may limit aerobic metabolism in both very small, highly oxidative fibers as well as in larger fibers with lower aerobic capacity. Comparison of model analysis with experimental data revealed that none of the fibers was strongly limited by diffusion, as expected. However, while some fibers were near substantial diffusion limitation, most were well within the domain of reaction control of aerobic metabolic rate. This may constitute a safety factor in muscle that provides a level of protection from diffusion constraints under conditions such as hypoxia. Biotechnol. Bioeng. 2011; 108:104–115. © 2010 Wiley Periodicals, Inc.
An active intracellular device to prevent lethal disease outcomes in virus‐infected bacterial cells

Synthetic biology includes an effort to logically control cellular behavior. One long‐term goal is to implement medical interventions inside living cells, creating intracellular “disease fighters”; one may imagine a system that detects viral infection and responds to halt the spread of the virus. Here, we explore a system designed to display some of the qualitative features that such disease prevention systems should have, while not claiming that the system itself has any medical application. An intracellular disease prevention mechanism should: lie dormant in the absence of the disease state; detect the onset of a lethal disease pathway; respond to halt or mitigate the disease's effects; and be subject to external deactivation when required. We have created a device that displays these properties, in the highly simplified case of a bacterial viral disease. Our system detects the onset of the lytic phase of bacteriophage lambda in Escherichia coli, responds by preventing this lethal pathway from being followed, and is deactivated by a temperature shift. We have formulated a mathematical model of the engineered system, using parameters obtained from the literature and by local experimental measurement, and shown that the model captures the essential experimental behavior of the system in most parameter regimes. Biotechnol. Bioeng. 2011; 108:645–654. © 2010 Wiley Periodicals, Inc.