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IntroductionThe aim of this research was to evaluate the impact of a novel tele-rehabilitation system on self-reported functional outcomes compared to usual care during the first three months after stroke.MethodsA parallel, two-arm, evaluator-blinded, randomised controlled trial was conducted. Adults aged ≥40 years who had suffered a stroke within four weeks of the start of the study were recruited from the general community. The intervention group received access to a novel tele-rehabilitation system and programme for three months. The primary outcome measures utilised were the frequency and limitation total scores of the Late-Life Function and Disability Instrument (LLFDI) at three months.ResultsA total of 124 individuals were recruited. The mean differences in the LLDFI frequency and limitation total scores at three months comparing the intervention and control groups were –3.30 (95% confidence interval (CI) –7.81 to 1.21) and –6.90 (95% CI –15.02 to 1.22), respectively. Adjusting for the respective baseline covariates and baseline Barthel Index also showed no significant difference between interventions in the LLFDI outcomes.DiscussionThe intervention and control groups self-reported similar improvements in functional outcomes. Tele-rehabilitation may be a viable option to provide post-stroke rehabilitation services in Singapore while reducing barriers to continue rehabilitation conventionally after discharge from hospital and encouraging more participation.

Introduction With the latest addition from Re-evaluation of Systemic Early Neuromuscular Blockade (ROSE) trial result, the question of mortality benefit from neuromuscular blocking agents (NMBAs) in different studies, remained unanswered. We hypothesize that NMBAs use in moderate to severe acute respiratory distress syndrome (ARDS) does not influence intensive care unit (ICU) mortality. Evidence acquisition Pubmed, Embase and the Cochrane Library were searched for randomized controlled trials (RCTs) related to NMBAs infusion in patients with ARDS. The primary outcome was ICU mortality. Secondary outcomes were mortality at day 28 and day 90, oxygenation response to NMBA, ICU length of stay (LOS), ICU Acquired weakness (ICU-AW) and ventilator-free days (VFDs). Meta-analysis was conducted to re-evaluate the effect of NMBAs on patients with ARDS with all randomised controlled trials available. Evidence synthesis NMBAs infusion was associated with reduced ICU mortality [relative ratio (RR) : 0.69; 95% confidence-interval (CI): 0.55-0.88; I2 = 0 %], but not 28 days mortality (RR: 0.76; 95% CI: 0.57-1.0; I2 = 49%) and 90-day mortality (RR: 0.87; 95% CI: 0.70-1.08; I2 = 46%). NMBA use was not associated with increased risk of ICU-AW (RR, 1.21; 95% CI, 0.84 to 1.76; I2 = 34%). Conclusions Early 48-hour NMBAs infusion in patients with moderate to severe ARDS was associated with reduced ICU mortality without improvement in oxygenation, VFDs, 28-day and 90-day mortality. It did not contribute significantly to ICU-AW. Based on these results, NMBAs infusion is recommended for moderate to severe ARDS for its short-term benefit in early phase of disease. Prolonged use of NMBAs beyond 48 hours requires further study.

Background International guidelines recommend the fallopian tubes be removed at the time of hysterectomy, to lower the incidence of ovarian cancer in women. Aims To determine the rate of salpingectomy at the time of hysterectomy at our institution and to discuss a standard rate. Materials and methods Hysterectomies (n = 200) performed for benign indications from 13 January 13, 2015 until 26 April 26, 2016 were reviewed. Results The overall rate of salpingectomy was 76.0%. Factors associated with non-completion were uterovaginal prolapse indication and vaginal surgical approach. Conclusions Rates of completing salpingectomy with hysterectomy are high. There may be additional opportunity for ovarian cancer reduction. No standard rate has been published but considering difficulty with removal of fallopian tubes in certain cases, it may not be 100%. Our data allows for comparison by other units performing similar studies. We recommend the formal adoption of local guidelines regarding salpingectomy at the time of hysterectomy for benign indications in order to keep local practice up to date with international recommendations.

Malaria is a life-threatening disease and one of the main causes of morbidity and mortality in the human population. The disease also results in a major socio-economic burden. The rapid spread of malaria epidemics in developing countries is exacerbated by the rise in drug-resistant parasites and insecticide-resistant mosquitoes. At present, malaria research is focused mainly on the development of drugs with increased therapeutic effects against Plasmodium parasites. However, a vaccine against the disease is preferable over treatment to achieve long-term control. Trials to develop a safe and effective immunization protocol for the control of malaria have been occurring for decades, and continue on today; still, no effective vaccines are available on the market. Recently, peptide-based vaccines have become an attractive alternative approach. These vaccines utilize short protein fragments to induce immune responses against malaria parasites. Peptide-based vaccines are safer than traditional vaccines, relatively inexpensive to produce, and can be composed of multiple T- and B-cell epitopes integrated into one antigenic formulation. Various combinations, based on antigen choice, peptide epitope modification and delivery mechanism, have resulted in numerous potential malaria vaccines candidates; these are presently being studied in both preclinical and clinical trials. This review describes the current landscape of peptide-based vaccines, and addresses obstacles and opportunities in the production of malaria vaccines.

Medically important arboviruses such as dengue, Zika, and chikungunya viruses are primarily transmitted by the globally distributed mosquito Aedes aegypti. Increasing evidence suggests that transmission can be influenced by mosquito viromes. Herein RNA-Seq was used to characterize RNA metaviromes of wild-caught Ae. aegypti from Bangkok (Thailand) and from Cairns (Australia). The two mosquito populations showed a high degree of similarity in their viromes. BLAST searches of assembled contigs suggest up to 27 insect-specific viruses may infect Ae. aegypti, with up to 23 of these currently uncharacterized and up to 16 infecting mosquitoes from both Cairns and Bangkok. Three characterized viruses dominated, Phasi Charoen-like virus, Humaita-Tubiacanga virus and Cell fusing agent virus, and comparisons with other available RNA-Seq datasets suggested infection levels with these viruses may vary in laboratory-reared mosquitoes. As expected, mosquitoes from Bangkok showed higher mitochondrial diversity and carried alleles associated with knock-down resistance to pyrethroids. Blood meal reads primarily mapped to human genes, with a small number also showing homology with rat/mouse and dog genes. These results highlight the wide spectrum of data that can be obtained from such RNA-Seq analyses, and suggests differing viromes may need to be considered in arbovirus vector competence studies.

ContextBardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder in which previous reports have described obesity and a metabolic syndrome.ObjectiveWe describe the endocrine and metabolic characteristics of a large BBS population compared with matched control subjects.DesignWe performed a case-control study.SettingThis study was performed at a hospital clinic.PatientsStudy patients had a clinical or genetic diagnosis of BBS.Main Outcome MeasurementsOur study determined the prevalence of a metabolic syndrome in our cohort.ResultsA total of 152 subjects were studied. Eighty-four (55.3%) were male. Mean (± standard deviation) age was 33.2 ± 1.0 years. Compared with age-, sex-, and body mass index–matched control subjects, fasting glucose and insulin levels were significantly higher in subjects with BBS (glucose: BBS, 5.2 ± 1.2 mmol/L vs control, 4.9 ± 0.9 mmol/L, P = 0.04; insulin: BBS, 24.2 ± 17.0 pmol/L vs control, 14.2 ± 14.8 pmol/L, P < 0.001). Serum triglycerides were significantly higher in subjects with BBS (2.0 ± 1.2 mmol/L) compared with control subjects (1.3 ± 0.8 mmol/L; P < 0.001), but total cholesterol, high-density lipoprotein, and low-density lipoprotein were similar in both groups. Systolic blood pressure was higher in the BBS group (BBS, 135 ± 18 mm Hg vs control subjects, 129 ± 16 mm Hg; P = 0.02). Alanine transaminase was raised in 34 (26.8%) subjects with BBS, compared with five (8.9%) control subjects (P = 0.01). The rate of metabolic syndrome, determined using International Diabetes Federation criteria, was significantly higher in the BBS group (54.3%) compared with control subjects (26% P < 0.001). Twenty-six (19.5%) of male subjects with BBS were hypogonadal (serum testosterone, 9.9 ± 5.3 mmol/L), but significant pituitary abnormalities were uncommon. Subclinical hypothyroidism was present in 24 of 125 (19.4%) patients with BBS, compared with 3 of 65 (4.6%) control subjects (P = 0.01).ConclusionsInsulin resistance and the metabolic syndrome are increased in adult patients with BBS compared with matched control subjects. Increased subclinical hypothyroidism in the BBS cohort needs further investigation.

SUMMARY Previous studies have shown that people infected with schistosomiasis have lower levels of serum cholesterol than uninfected controls. To better understand the impact of this parasitic infection on serum cholesterol levels and on atherosclerotic lesion development induced by hypercholesterolemia, apolipoprotein E (ApoE)-deficient mice were chronically exposed to the eggs of Schistosoma mansoni over a period of 16 weeks. Total serum cholesterol and low-density lipoprotein (LDL) were reduced in egg-exposed ApoE-deficient mice fed a diet high in cholesterol compared to unexposed controls. However, exposure to eggs had no effect on atherosclerotic lesion size or progression in ApoE-deficient mice. Macrophages isolated from egg-exposed mice had an enhanced ability to take up LDL but not acetylated LDL (acLDL). This study suggests that schistosome eggs alone may alter serum lipid profiles through enhancing LDL uptake by macrophages, but these changes do not ultimately affect atherosclerotic lesion development.

Introduction and Objectives: A total of 456 patients were recruited globally for the ULIS II study. To compare the data from South Asia (SA) with the global (GLB) results, a subanalysis was performed.Methods: A total of 51 patients from Hong Kong, Philippines, Thailand, Taiwan, Malaysia, and Singapo

Bone marrow transplantation has become a beneficial and curative technique used in treatment of patients with different hematologic conditions. It has become widely used at our institution for hematologic malignancies and certain resistant solid tumors. However, this treatment can result in immunosuppression, with an increased chance of infection. The purpose of this study was to review the causes of infections and determine the number of patients diagnosed with sinusitis. In the retrospective study, we evaluated the cases of bone marrow transplant patients for incidence and cause of fever. Sixty-eight percent of patients had fever after transplant; of these, 59% had fever of unknown origin. Only 1% of the patients with fever were diagnosed with sinusitis. In the evaluation of fever, sinusitis was not usually suspected and therefore was not included in the differential diagnosis. With such a high percentage of fever of unknown origin in this growing patient population, appropriate pretreatment evaluation of each case to rule out sinusitis should be considered.

Fetal macrosomia in human diabetic pregnancy has long been recognized. However, an animal model suitable for studying fetal macrosomia and other fetal anomalies in diabetic pregnancy has been lacking. In the present study the visually recognizable macrosomic fetus was compared with its normal weight litter mates obtained on the 19.5 day of gestation from mildly diabetic Sprague-Dawley rats. The mean body weights of macrosomic fetuses and the normal litter mates were 4.72 ± 0.45 g (mean ± SE) and 2.76 ± 0.18 g, respectively. The rate of [ 3 H]AIB influx from the maternal to fetal side for the macrosomic fetuses was approximately 50 times greater than the corresponding rate for the normal litter mates. The visual identification of macrosomia is thus verified by two different parameters (e.g., body weight and rate of metabolite influx). These results provide a rationale for comparing macrosomic fetuses with their litter mates for studying pathogenesis of macrosomia in diabetic pregnancies in an animal system. This model mimics the human fetal macrosomia more closely than those reported heretofore.

Data are now available on 9 pedigrees in detail and 4 pedigrees as lod scores only. Linkage to HLA is significant (Z = 5.53 at recombination rates of 0.223 in males and 0.327 in females). Tight linkage is excluded. Nine pedigrees which appear to be typical olivopontocerebellar atrophy (OPCA I) have recombination rates of 0.150 in males and 0.300 in females. The remaining 4 pedigrees are clinically atypical or include discrepant data and give no evidence for linkage. The symbol SCA1 is proposed for a locus on chromosome 6 (loosely linked to HLA), at which at least one allele produces OPCA I (Menzel type). It is not yet clear whether other clinical types are determined by alleles at different loci, although this is suggested by several pedigrees, including a Danish pedigree of OPCA with dementia. Linkage evidence will be decisive in delineating the ataxias.

We have recently demonstrated that 48 hour exposure of ROS 17/2 cells to low concentrations of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) (1.0 pg/ml) stimulated the cellular accumulation of45Ca, and exposure to high concentrations (160 pg/ml) inhibited such accumulation. In the present study, short-term (15 min) effects of the sterol on45Ca accumulation in ROS 17/2 cells were compared with the long-term (48 hours) effects in order to clarify mechanisms responsible for 1,25(OH)2D3 control of calcium metabolisms in ROS 17/2 cells. ROS 17/2 cells were grown for 48 hours in the presence and absence of 1,25(OH)2D3 and then incubated for an additional 15 min in the presence and absence of 1,25(OH)2D3 immediately before measuring45Ca accumulation. Cellular45Ca was measured after incubating the cells in the medium containing 0.5 μCi/ml of45CaCl2 for 4 min at 25°C. The effect of actinomycin D was determined by preincubating the cells in 0.1 μg/ml of actinomycin D for 45 min at 25°C. Exposure to low concentrations (1.0 pg/ml) of 1,25(OH)2D3 for either 48 hours or 15 min increased45Ca in the cells by 10–20%. An additional 15 min exposure following 48 hour exposure yielded an increase in the cellular45Ca similar to that after 48 hours or 15 min exposure. Exposure to high concentrations (160 pg/ml) for either 48 hour or 15 min decreased cell45Ca by approximately 20%.An additional 15 min exposure to the high concentrations did not change the 48 hour effect. Actinomycin D reversed early inhibitory effects of high concentrations, but had no effect on the early stimulatory effects of low concentrations. These results suggest that the mechanisms underlying the 15 min and 48 hour effects of 1,25(OH)2D3 are the same. Moreover, the mechanism responsible for the inhibitory effect of high concentrations is dependent onde novo protein synthesis whereas that for the stimulatory effects of low concentrations is not.

Fetal macrosomia in diabetic pregnancy has been shown to accompany increases in the fetal levels of deoxyribonucleic acid (DNA) and proteins in animal model systems. In order to elucidate the underlying mechanisms of this macrosomia, the synthesis of DNA and proteins, the transport of the precursors, and the tissue level of DNA polymerase activities in macrosomic fetuses from mildly diabetic rats were compared with those in normal fetuses on 20.5 and 19.5 days of gestation. Increases in the influx of precursors and stimulation of synthesis of the macromolecules were observed in macrosomic fetuses as early as 19.5 days of gestation. However, stimulation of DNA polymerase activities in macrosomic fetuses did not occur until 20.5 days of gestation. Therefore, stimulation of DNA polymerase may participate in maintenance of macrosomia but does not initiate macrosomia. Whether or not increases in both the influx of substrates and the synthesis activities precede the macrosomia has yet to be determined.

Chikungunya virus (CHIKV) belongs to a group of mosquito-borne alphaviruses associated with acute and chronic arthropathy, with peripheral and limb joints most commonly affected. Using a mouse model of CHIKV infection and arthritic disease, we show that CHIKV replication and the ensuing foot arthropathy were dramatically reduced when mice were housed at 30°C, rather than the conventional 22°C. The effect was not associated with a detectable fever, but was dependent on type I interferon responses. Bioinformatics analyses of RNA-Seq data after injection of poly(I:C)/jetPEI suggested the unfolded protein response and certain type I interferon responses are promoted when feet are slightly warmer. The ambient temperature thus appears able profoundly to effect anti-viral activity in the periphery, with clear consequences for alphaviral replication and the ensuing arthropathy. These observations may provide an explanation for why alphaviral arthropathies are largely restricted to joints of the limbs and the extremities., Author summary Chikungunya virus (CHIKV) and Ross River virus are mosquito-borne alphaviruses that cause epidemics of human arthritic disease that usually last from weeks to months. Arthropathy predominantly manifests in the joints of limbs and the joints at the extremities (e.g. hand and feet). Herein we show a surprisingly large reduction in viral loads and foot arthropathy in mice when animals were housed at 30°C rather than the conventional 22°C, with the feet of the former mice being ≈3–4°C warmer. Using RNA-Seq analyses of mice feet, we illustrate that this small increase in temperature results in a significant increase in both the unfolded protein response and anti-viral type I interferon responses. Taken together these results suggest that the predominantly peripheral alphaviral arthropathy is due to the usually slightly lower temperature of limbs and extremities, which results in less effective type I interferon responses and a subsequent increase in viral loads and ensuing arthritic disease.