Quantitative and functional abnormalities of total T lymphocytes in relatives of patients with Hodgkin's disease.
Seven patients, long-term survivors of Hodgkin's disease, and 24 of their relatives (parents, siblings and children), together with normal controls were studied for percentages, absolute counts and mitogen-proliferative responses by means of monoclonal antibodies, E rosette technique and in vitro cultures with PHA, ConA and PWM. The aim of the study was to ascertain whether the impaired cell-mediated immunity of Hodgkin's patients was also present in relatives in order to elucidate the still debated etiology of the defect and of the disease (congenital? environmental? infectious?). The results show that both Hodgkin's patients and their relatives have a significant decrease of total T cells (as T3+, T11+ and E rosette-forming cells) in peripheral blood and a significant impairment of polyclonal responses to all the mitogens employed. The Leu-7+ cells (i.e. a consistent amount of natural killer cells) are significantly increased only in the Hodgkin's patients but not in their relatives. The T cell subpopulations (T4 and T8), B cells and monocytes do not show any difference between the patients, their relatives and normal controls. Our results seem to support, at least in part, the presence of a common defect of T cell lineage both in patients and in their relatives, but its etiology still remains uncertain (genetic? environmental?).


Noninvasive assessment of coronary flow dynamics before and after coronary angioplasty using transesophageal Doppler.
Recent invasive studies using intracoronary Doppler catheters or guide wires reported improved coronary flow dynamics after successful percutaneous transluminal coronary angioplasty. Transesophageal Doppler enables the measurement of coronary flow velocities within the left anterior descending artery. The present study was designed to test: (1) whether transesophageal Doppler may detect coronary flow velocity changes in patients undergoing angioplasty for left anterior descending artery stenosis, and (2) whether this technique may help to evaluate non-invasively the results of the procedure. Twenty-three patients undergoing angioplasty of the left anterior descending artery were studied by transesophageal Doppler before and < or = 24 hours after the interventional procedure. Coronary flow velocities were measured in the proximal part of the left anterior descending artery with the use of pulsed Doppler guided by color flow imaging. The degree of stenosis was measured by computerized quantitative coronary arteriography. Coronary flow velocity signals were successfully obtained in 19 of 23 patients (83%). In 16 successful angioplasty procedures, peak diastolic velocity increased from 37 +/- 14 cm/s before angioplasty to 51 +/- 16 cm/s after (p = 0.0001). In the 3 patients in whom angioplasty was unsuccessful, transesophageal Doppler showed no significant increase in peak diastolic coronary flow velocity. In a total of 19 angioplasty procedures, a good linear relation was found between the percent changes in coronary flow diastolic velocity and the reduction in the degree of stenosis (r = 0.85; p = 0.0001). All patients with > 20% increase in peak diastolic velocity had > 40% stenosis reduction.(ABSTRACT TRUNCATED AT 250 WORDS)


Steam activation of chars produced from oat hulls and corn stover.
Oat hulls and corn stover were used to produce chars at approximately 500 degrees C. The carbon concentrations of oat hull char and corn stover chars produced were 72.3 and 68.0 wt.%, respectively. Both activation burn-off and Brunauer-Emmett-Teller (BET) surface area appear to exhibit a linear relationship with respect to activation time of oat hulls. As to corn stover activated carbons, there is no linear relationship between activation time and BET surface area. However, activation burn-off of and activation time appear to relate in a linear manner for the activated carbons produced from corn stover chars. Oat hull is better than corn stover as a raw material for the production of activated carbon.


Cholangiocarcinoma complicating primary sclerosing cholangitis: a 24-year experience.
To report the prevalence and outcome of cholangiocarcinoma arising in primary sclerosing cholangitis for a British tertiary referral centre. All patients diagnosed with primary sclerosing cholangitis and concurrent cholangiocarcinoma were identified from a prospectively maintained departmental database, and the mode of presentation, management and outcome were determined. Of 370 patients with primary sclerosing cholangitis, 48 patients (13%) were diagnosed with a cholangiocarcinoma within a median time of 0.51 months (range: 0-73.12) from presentation to the unit. Mode of presentation included: inoperable tumours (n = 14); incidental findings in transplant hepatectomy specimens (n = 13); primary sclerosing cholangitis follow-up (n = 9); transplant work-up (n = 5); transplant waiting list (n = 5); suspected tumour confirmed at transplant (n = 1), and incidental finding at cholecystectomy (n = 1). The diagnosis was confirmed by: radiology-guided biopsy (n = 27); MRI (n = 3); CT (n = 2); laparoscopy or laparotomy (n = 2), and frozen section at transplant (n = 1). Management consisted of: transplantation (n = 14, including 1 abandoned); hepatic resection (n = 8), and palliation through stenting (n = 26). The overall median survival of the cohort was 4.9 months (range: 0.09-104.5). Median survival ranged from 2.6 months (range: 0.09-35.3) for palliation to 7.6 months (range: 0.6-99.6) for transplantation and 52.8 months (range: 3.7-104.5) for resection. There was no difference in survival between the transplant and resection groups (p = 0.14). Cholangiocarcinoma is a common finding in primary sclerosing cholangitis and regular screening of this cohort of patients at referring centres is advocated to detect early tumours, as surgical treatment at an early stage offers significantly better outcomes for this cohort of patients.


Climate change and health care facilities: A risk analysis framework through a mapping review.
Climate change (CC) has been identified as the biggest global health threat of the 21st century. Although health care facilities (HCF) play a central role in the care of populations, there has been no comprehensive assessment of the impact of CC on HCF. The objective of our study was to highlight the components of HCFs affected by CC through a mapping review of the literature. To meet our objective, we first assessed the place of HCFs in relation to CC in the scientific literature and in the Intergovernmental Panel on Climate Change (IPCC) reports. Bibliometric data from the PubMed database were analyzed between 1979 and 2021 to assess the penetration of keywords on CC alone, and in relation to health and HCF in particular. Second, we analyzed the changes in HCF keywords in the IPCC reports. Finally, we conducted a mapping review in five databases, of the international scientific literature published between 1979 and 2019, and identified the components of HCF affected by CC using the Ishikawa diagram. From the 2000s, the number of publications on CC and HCF increased gradually with 137 articles in 2005, and even more sharply since 2008 with 358 articles published and 813 in 2021. Even though CC is only recently present in the biomedical literature, all climatic events (warming and heatwaves, droughts, wildfires, storms, hurricanes and cyclones, floods and sea-level rise, and other indirect effects) have had an impact on at least one component of HCF. HCFs are already impacted, in all their components, by CC. By enhancing our understanding of the impacts of CC on HCF, this work could contribute to the engagement of health professionals in the implementation of mitigation and adaptation actions, thereby limiting the consequences of CC on patient care.


Evidence that informs feeding practices in very low birthweight and very preterm infants in sub-Saharan Africa: an overview of systematic reviews.
Optimal feeding of very low birthweight (VLBW <1500 g)/very preterm (gestation <32 weeks) infants in resource-limited settings in sub-Saharan Africa (sSA) is critical to reducing high mortality and poor outcomes. To review evidence on feeding of VLBW/very preterm infants relevant to sSA. We searched the Cochrane Database of Systematic Reviews, Embase, PubMed and Cumulative Index to Nursing and Allied Health Literature (CINAHL) from inception to July 2019 to identify reviews of randomised and quasi-randomised controlled trials of feeding VLBW/very preterm infants. We focused on interventions that are readily available in sSA. Primary outcomes were weight gain during hospital stay and time to achieve full enteral feeds (120 mL/kg/day). Secondary outcomes were growth, common morbidities, mortality, duration of hospital stay and cognitive development. Quality of evidence (QOE) was assessed using the Measurement Tool to Assess Systematic Reviews (AMSTAR2). Eight systematic reviews were included. Higher feed volume of day 1 (80 mL/kg) reduced late-onset sepsis and time to full enteral feeds, and higher feed volume (up to 300 mL/kg/day) improved weight gain without adverse events (QOE: low-moderate). Rapid advancement of feeds (30-40 mL/kg/day) was not associated with harm. Breast milk fortification with energy and protein increased growth and with prebiotics increased growth and reduced duration of admission (QOE: low-very low) and did not result in harm. Evidence regarding feeding tube placement and continuous versus bolus feeds was insufficient to draw conclusions. We found no reviews meeting our selection criteria regarding when to start feeds, use of preterm formula, cup-and-spoon feeding or gravity versus push feeds and none of the reviews included trials from low-income countries of sSA. The evidence base informing feeding of VLBW/very preterm babies in resource-limited settings in sSA is extremely limited. Pragmatic studies are needed to generate evidence to guide management and improve outcomes for these highly vulnerable infants. CRD42019140204.


Construction trade and extraction workers: A population at high risk for drug use in the United States, 2005-2014.
To estimate prevalence of past-month marijuana, cocaine, and nonmedical prescription opioid (NPO) use and determine employment-related correlates of drug use among construction trade/extraction workers (CTEW). We analyzed ten years of data (2005-2014) from 293,492 adults (age≥18) in the National Survey on Drug Use and Health, comparing CTEW and non-CTEW. CTEW were 5.6% (n = 16,610) of the sample. Compared to non-CTEW, CTEW were significantly more likely to report past-month marijuana (12.3% vs. 7.5%), cocaine (1.8% vs. 0.8%), and/or NPO use (3.4% vs. 2.0%; Ps<.001). Among CTEW, past-week unemployment and working for >3 employers was associated with increased odds of marijuana and NPO use. Missing 1-2 days in the past month because the participant did not want to go into work was associated with increased odds for use of marijuana, cocaine, and NPO use. Missing 3-5 days of work in the past month because sick or injured was associated with double the odds (aOR = 2.00 [95% CI: 1.33-3.02]) of using NPO. Having written drug policies was associated with reduced odds for cocaine use, and workplace tests for drug use during hiring and random drug testing were also associated with lower odds of marijuana use. CTEW are a high-risk population for drug use. Precarious employment is associated with higher prevalence of drug use while some workplace drug policies were associated with lower prevalence. Coupled with reports of high overdose mortality among CTEW, these findings suggest that prevention and harm reduction programming is needed to prevent drug-related morbidity and mortality among CTEW.


A study of the combination of gemcitabine hydrochloride (LY188011) and cisplatin in non-small-cell lung cancer: 3-week schedule.
It has been reported that the combination of gemcitabine (LY188011; GEM) and cisplatin (CDDP) in a 4-week schedule showed a high response rate for patients with non-small-cell lung cancer (NSCLC), but GEM could not be administered on day 15 because of increased myelosuppression in many patients. The present study was performed to evaluate the efficacy and safety of GEM and CDDP in a 3-week schedule. Patients with unresectable NSCLC without prior chemotherapy were enrolled. We administered 1000 mg/m2 of GEM on days 1 and 8, and 80 mg/m2 of CDDP on day 1. The feasibility of the combination therapy was confirmed in 8 patients, and then 20 more patients were enrolled, to evaluate the efficacy and safety of this combination therapy for all 28 patients. The response rate was 42.9% (12/28) and the median survival time was 12.6 months. Neutropenia, leukopenia, anemia, thrombocytopenia or lymphocytopenia of grade 3 or higher were observed as hematological toxicity, and anorexia, nausea, fatigue, or vomiting of grade 3 were the nonhematological toxicities, but most of these toxicities were of grade 2 or less. For GEM and CDDP, 89% and 91% of the scheduled doses, respectively, were administered. This is the first study of the combination of GEM and CDDP with a 3-week schedule in Japan, and the results showed a low level of myelosuppression, high dose intensity, and high response rate, similar to the results reported in other countries. Accordingly, the combination of GEM and CDDP with a 3-week schedule may be a promising regimen for the treatment of NSCLC in Japan.


Biologically selective potassium channel openers having 1,1-diethylpropyl group.
To find out selective potassium channel openers (PCOs), we synthesized several 3,5-disubstituted phenylcyanoguanidine derivatives and investigated their structure-activity relationships (SAR). As a result, we discovered selective PCOs having 1,1-diethylpropyl group toward antihypertensive activity.


A serologic survey for Coxiella burnetii in semi-wild ungulates in the Emirate of Dubai, United Arab Emirates.
Q fever, a highly infectious zoonotic disease caused by Coxiella burnetii, has not been officially reported in the United Arab Emirates (UAE). This first serosurvey of a large group of semi-free-ranging animals in the UAE indicates that a wide range of ungulates have been exposed C. burnettii in the region.


Translation and psychometric evaluation of the Persian version of Knee Outcome Survey-Activities of Daily Living Scale (KOS-ADLS).
The present study aimed to translate and validate the Knee Outcome Survey-Activities of Daily Living Scale (KOS-ADLS) in Iran. Following standard forward and backward translation procedure, content and face validity were tested by specialists and a sample of 32 patients. Then, in a cross sectional study, a sample of patients with knee disorders, recruited through simple sampling, completed the KOS-ADLS and the Short-Form Health Survey (SF-36) in their first visit to physiotherapy clinics in Tehran. Regarding construct validity, the Spearman's correlation (rs) and one-way ANOVA were employed to evaluate the correlations between the Persian KOS-ADLS and SF-36 subscales (convergent validity) and known groups comparison, respectively. Test-retest reliability and internal consistency were evaluated by intraclass correlation coefficient (ICC) and the Cronbach's α coefficient. In total 101 patients were included in the study. The mean age of patients was 42.39 (SD = 9.2). The finding indicated that the KOS-ADLS had strong correlations with SF-36 physical functioning, bodily pain subscales, and also physical component summary while it had lower correlations with other subscales of the SF-36 as expected. The KOS-ADLS was able to differentiate between the subgroups of patients who differed in BMI. The acceptable level of intraclass correlation coefficient (ICC = 0.91) and Cronbach's α coefficient (α = 0.91) was obtained for the Persian KOS-ADLS. Also no floor and ceiling effects were observed for the questionnaire. The Persian version of KOS-ADLS was found to be a reliable and valid outcome measure for assessing daily living activities in patients who suffer from knee pathological conditions.


Temporal associations for spatial events: the role of the dentate gyrus.
Previous research suggests that the dorsal dentate gyrus (DG) hippocampal subregion mediates spatial processing functions. However, a novel role for the DG in temporal processing for spatial information has begun to emerge based on the development of a computational model of neurogenesis. According to this model, adult born granule cells in the DG contribute to a temporal associative integration process for events presented closer in time. Currently, there is a paucity of behavioral evidence to support the temporal integration theory. Therefore, we developed a novel behavioral paradigm to investigate the role of the dDG in temporal integration for proximal and distal spatial events. Male Long-Evans rats were randomly assigned to a control group or to receive bilateral intracranial infusions of colchicine into the dDG. Following recovery from surgery, each rat was tested on a cued-recall of sequence paradigm. In this task, animals were allowed to explore identical objects placed in designated spatial locations on a cheeseboard maze across 2 days (e.g., Day 1: A and B; Day 2: C and D). One week later, animals were given a brief cue (A or C) followed by a preference test between spatial location B and D. Control animals had a significant preference for the spatial location previously paired with the cue (the temporal associate) whereas dDG lesioned animals failed to show a preference. These findings suggest that selective colchicine-induced dDG lesions are capable of disrupting the formation of temporal associations between spatial events presented close in time.


Efficacy and safety of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy: Results from a randomized phase II trial.
This phase II, dose-ranging, double-blind, placebo-controlled, randomized study (NCT01463059) evaluated efficacy and safety of olokizumab (OKZ), a humanized anti-interleukin 6 monoclonal antibody, in Asian patients with moderately-to-severely active rheumatoid arthritis (RA) who had previously failed anti-TNF therapy. Patients were randomized to one of six treatment arms: placebo or OKZ (60 mg/120 mg/240 mg every four weeks [Q4W]; or 60 mg/120 mg every two weeks [Q2W]); stratified by country and number of prior anti-TNFs. Primary efficacy variable was Week 12 change from baseline (CFB) in DAS28 CRP for 4-week cumulative dose groups of OKZ and placebo; secondary efficacy variables were Week 12 ACR20/ACR50/ACR70 response rates. Patients continued MTX treatment from baseline, without additional csDMARDs. Of 119 randomized patients, 88.2% completed the study. Greater improvements in DAS28(CRP) mean CFB at Week 12 were observed in all OKZ 4-week cumulative dose groups (60 mg/120 mg/240 mg) versus placebo (p < 0.0001). Week 12 ACR20/ACR50 response rates were higher in all OKZ cumulative dose groups versus PBO (p < 0.05). Incidences of adverse events were similar across OKZ 4-week cumulative dose groups (76.9-84.4%) and placebo (82.8%) with no deaths. OKZ demonstrated improvements in efficacy variables versus placebo in Asian patients with moderately-to-severely active RA who had previously failed anti-TNF therapy. The safety profile was as expected for this class of drug.


Ultrasound assessment of the prevalence of increased gastric contents and volume in elective pediatric patients: A prospective cohort study.
Though pulmonary aspiration of gastric contents occurs mainly in the setting of emergency surgery, it may also occur in children scheduled for elective surgery without any obvious clinical risk factor. Increased gastric content volume is one the predisposing factors for pulmonary aspiration that could affect such children and may be identified using ultrasound examination of the gastric antrum. We aimed to assess the prevalence of "at-risk stomach" defined by ultrasound visualization of any solid content in the antrum and/or by calculated gastric fluid volume > 1.25 mL/kg, in children scheduled for elective surgery. Children scheduled for elective surgery were consecutively included into this prospective cohort study. Preoperative ultrasound examination of the antrum was performed in both the supine and the right lateral decubitus positions. Gastric fluid content was assessed using a 0-2 qualitative grading scale. The antral cross-sectional area was also measured in both the supine and the right lateral decubitus positions, allowing the calculation of the gastric fluid volume according to a formula previously described. We analyzed 200 elective children. Median duration of fasting was 4 hours for liquids and >13 hours for solids. None of the children included in this study had evidence of solid content. Six (3%) children had a Grade 2 antrum (fluid content seen in both the supine and the right lateral decubitus positions). Two children had a gastric fluid volume >1.25 mL/kg. The prevalence of "at-risk stomach" was 1% (95% confidence interval: 0.2%-3.9%). According to our results, only 1% of elective children had potentially increased risk for pulmonary aspiration. Further studies should be performed in order to define the target population of elective children for which ultrasound assessment of gastric content should be performed prior to general anesthesia.


Biceps and triceps injuries of the elbow.
In this article, the common biceps and triceps injuries about the elbow are reviewed. The relevant anatomy, presenting signs, symptoms, and treatment of these injuries are discussed.


Visual screening versus transcutaneous bilirubinometry for predischarge jaundice assessment.
Comparison of visual screening with transcutaneous bilirubinometry (TcB) in identifying neonates with plasma total bilirubin (PTB) > or =75th percentile. In 100 paired readings PTB was 34 +/- 24 micromol/L higher than the TcB counterpart. A TcB reading of 154 micromol/L was therefore regarded as equivalent to a PTB of 188 micromol/L, corresponding to the 75th percentile at 48 h. Predischarge, all newborns were evaluated for jaundice, first by visual inspection and then transcutaneously. PTB was ordered as indicated by visual assessment or if the TcB reading was > or =154 micromol/L. Of 346 newborns tested, 25 (7.2%) had a PTB concentration > or =75th percentile. Forty-nine had PTB determinations based on TcB compared with 83 by visual assessment. However, a similar number of affected newborns was identified by each method (21/25 (84%) by visual screening vs. 18/25 (72%) by TcB). PTB concentrations of those who had been chosen by TcB were higher than those selected visually (202 +/- 24 micromol/L vs. 186 +/- 31 micromol/L). A practical method for predischarge detection of neonates with plasma total bilirubin concentration > or = 75th percentile, implementing transcutaneous bilirubinometry, is described. The transcutaneous technique required fewer blood tests than visual assessment for similar yield.


Perioperative Management of Patients with Glioblastoma.
The clinical presentation of glioblastomas is varied, and definitive diagnosis requires pathologic examination and study of the tissue. Management of glioblastomas includes surgery and adjuvant chemotherapy and radiotherapy, with surgery playing an important role in the prognosis of these patients. Awake craniotomy plays a crucial role in tumors in or adjacent to eloquent areas, allowing surgeons to maximize resection, while minimizing iatrogenic deficits. However, the prognosis remains dismal. This article presents the perioperative management of patients with glioblastoma including tools and surgical adjuncts to maximize extent of resection and minimize poor outcomes.


Application Value of Serum Neurofilament Light Protein for Disease Staging in Huntington's Disease.
Neurofilament light protein (NfL) has been proven to be a sensitive biomarker for Huntington's disease (HD). However, these studies did not include HD patients at advanced stages or with larger CAG repeats (>50), leading to a knowledge gap of the characteristics of NfL. Serum NfL (sNfL) levels were quantified using an ultrasensitive immunoassay. Participants were assessed by clinical scales and 7.0 T magnetic resonance imaging. Longitudinal samples and clinical data were obtained. Baseline samples were available from 110 controls, 90 premanifest HD (pre-HD) and 137 HD individuals. We found levels of sNfL significantly increased in HD compared to pre-HD and controls (both P < 0.0001). The increase rates of sNfL were differed by CAG repeat lengths. However, there was no difference in sNfL levels in manifest HD from early to late stages. In addition, sNfL levels were associated with cognitive measures in pre-HD and manifest HD group, respectively. The increased levels of sNfL were also closely related to microstructural changes in white matter. In the longitudinal analysis, baseline sNfL did not correlate with subsequent clinical function decline. Random forest analysis revealed that sNfL had good power for predicting disease onset. Although sNfL levels are independent of disease stages in manifest HD, it is still an optimal indicator for predicting disease onset and has potential use as a surrogate biomarker of treatment effect in clinical trials. © 2023 International Parkinson and Movement Disorder Society.


Effects of Cr(VI) on the performance and kinetics of the activated sludge process.
The substrates removal performance, removal kinetics and the electron transport system (ETS) of sludge were investigated by sequencing batch reactors (SBR) and batch assays, respectively. Compared to the control system, significant decreases were observed in substrate removal efficiency with the Cr(VI)-feeding concentration up to 5 mg L(-1) in SBR system. And the recovery for NH4+-N removal were more difficult than that of COD after the termination of Cr(VI)-feeding. Significant inhibitory effects of Cr(VI) on the ETS activity and substrate removal kinetics were observed in the batch assays. The inhibitory effects of Cr(VI) would be overestimated on COD removal and underestimated on NH4+-N removal by the short-term batch assay as compared to the long-term operations. Additionally, significant correlations between the ETS activity and the inhibitory rates of Cr(VI) on substrate removal indicated the ETS activity can provide effective predictions on the potential performance of substrate removal in activated sludge.


Specific regulatory role of phosphorylation of calf thymus DNA-topoisomerase I smaller forms on the relaxational activity expression. Phosphorylation role on Topo I smaller forms activity.
Calf thymus Topo I is found to be associated with three active breakdown products, resolved from intact enzyme, which do not appear to be unique to one extraction procedure. They are phosphoproteins, whose enzymatic activity can be modulated through changes in phosphorylation, and which can be phosphorylated 'in vitro', by N II protein kinase, in the same five sites as the intact enzyme. Different amounts of 32P incorporated are observed however, in the corresponding sites. We conclude: 1. proteolysis is probably an 'in vivo' phenomenon, as the Topo I smaller species are observed, during isolation from the earlier crude fractions, and as a minimum of them is always present, even if precautions are taken to minimize proteolysis; 2. a specific regulatory role in the DNA relaxational activity might be played by N II protein kinase phosphorylation, indeed, in the smaller species; 3. the different degrees of 32P incorporation, in analogous phosphorylation sites, might represent a different signal for modulating the gene expression.


Does First Nations ancestry modify the association between gestational diabetes and subsequent diabetes: a historical prospective cohort study among women in Manitoba, Canada.
Over the past 30 years, the prevalence of diabetes has steadily increased among Canadians, and is particularly evident among First Nations (FN) women. The interplay between FN ancestry, gestational diabetes and the development of subsequent diabetes among mothers remains unclear. After excluding known pre-existing diabetes, we explored whether FN ancestry may modify the association between gestational diabetes and post-partum diabetes among women in Manitoba (1981-2011) via a historical prospective cohort database study. We analysed administrative data in the Population Health Research Data Repository using Kaplan-Meier survival analysis and Cox proportional hazards regression. Gestational diabetes was diagnosed in 11 906 of 404 736 deliveries (2.9%), 6.7% of FN and 2.2% of non-FN pregnant women (P < 0.0001). Post-partum diabetes during ≤ 30 years follow-up was more than three times higher among FN women than among non-FN women (P < 0.0001). Diabetes developed in 76.0% of FN and 56.2% of non-FN women with gestational diabetes within the follow-up period. The hazard ratio of gestational diabetes for post-partum diabetes was 10.6 among non-FN women and 5.4 among FN women. Other factors associated with a higher risk of diabetes included lower family income among FN and non-FN women and rural/remote residences among FN women. Among non-FN women, urban residence was associated with a higher risk of diabetes. Gestational diabetes increases post-partum diabetes in FN and non-FN women. FN women had substantially more gestational diabetes or post-partum diabetes than non-FN women, partially due to socio-economic and environmental barriers. Reductions in gestational diabetes and socio-economic inequalities are required to prevent diabetes in women, particularly in FN population.


Ecological rationale for H2 metabolism during aquatic blooms of the cyanobacterium Anabaena.
Nitrogenase-produced H2 serves to remove excess intracellular O2 during vigorous growth periods (blooms) of the nuisance cyanobacterium Anabaena. In two naturally-occurring species, A. oscillarioides and A. spiroides, nitrogen fixation (acetylene reduction) showed a high degree of resistance to O2 inactivation. Under the influence of supersaturated O2 concentrations, commonly encountered in lake blooms, elevated cellular ATP levels and enhanced uptake hydrogenase and nitrogenase activities were observed in actively growing filaments. Oxygen enhancement of nitrogenase activity appears mediated through localized uptake hydrogenase reactions. Hydrogen assimilated by hydrogenase is combined with O2 in a "Knallgas" reaction, leading to the formation of H2O and ATP via a respiratory chain. This combination of activities appears poised at O2 removal and allows Anabaena to dominate O2 supersaturated surface waters while maintaining optimal nitrogenase activity. Hence, instead of being a wasteful dissipation of reducing power, H2 evolution via nitrogenase ultimately affords protection from O2 while constituting a source of ATP through subsequent H2 metabolism.


Barriers and facilitators of older adults for professional mental health help-seeking: a systematic review.
Older adults are at an increased risk for mental health issues, yet they are less likely to seek professional help. This systematic review aims to identify and summarize literature on the barriers and facilitators that older adults face when seeking professional mental health help. A comprehensive literature search was conducted using multiple databases including PubMed-Medline, EMBASE, ProQuest central, CINAHL and Scopus to identify relevant studies published between 2010 and 2021 that focused on barriers and/or facilitators to seeking help for depression, anxiety, and psychological distress among older adults aged 65 years or older. Studies' risk of bias was assessed using the Newcastle-Ottawa Scale and results of studies were synthesized guided by the methodological framework of Rodgers and colleagues. A total of eight cross-sectional studies, from Australia, United States, Mexico, Netherlands, and Malaysia met the inclusion criteria for this review. Included studies reported that the majority of their participants had anxiety or depression, yet they exhibited a preference for informal mental health help over professional help. Stigma, negative beliefs about mental health professional services, and cost were the most reported barriers. Main reported facilitators were prior positive experience with mental health services and high socioeconomic status. Older adults are in need of interventions normalizing mental health help seeking and ensuring these services are accessible in terms of costs. This should be the focus of policy makers, healthcare providers, and public health practitioners working with older adults. PROSPERO 2021 CRD42021238853.


Straightforward Access to Block and Gradient Light-Responsive Poly(2-Oxazoline)S via Cationic Ring Opening Polymerization Of 2-Azobenzenyl-2-Oxazoline.
Light-responsive polymers are a prospective area of smart materials. The increasing number of potential applications of these materials require the development of new polymers sensitive to external irradiation. However, most of the polymers reported so far are represented by poly(meth)acrylates. In this work, the straightforward approach is proposed to the synthesis of light-responsive poly(2-oxazoline)s via cationic ring-opening polymerization of 2-azobenzenyl-2-oxazoline (2-(4-(phenyldiazenyl)phenyl)-2-oxazoline). Polymerization kinetics studies reveal significant activity of the new monomer in both homopolymerization and copolymerization with 2-ethyl-2-oxazoline. The difference in monomer reactivity allows obtaining both gradient and block copolymers via simultaneous or subsequent one-pot polymerization, respectively, leading to a set of well-defined gradient and block copoly(2-oxazoline)s with 10-40% of azobenzene units. Due to their amphiphilic nature, the materials self-assemble in water, which is proven by dynamic light scattering and transmission electron microscopy. The change in polarity caused by the isomerization of azobenzene fragments in response to UV light irradiation results in a change of nanoparticle size. The obtained results provide a new impulse for the development of light-responsive materials based on poly(2-oxazoline)s.


Commentary: On the reliability of causal claims.
Causal assessments in epidemiology are a complex process due to the many methods involved. The general scientific method lords over the process joined by study designs and statistical methods. Other methods include those that evaluate quality and bias along with the research synthesis methods such as the systematic narrative review, meta-analysis, and the criteria-based methods. When different investigators apply these methods to the same evidence and come up with different causal assessments, as described in the review by Goodman et al. in this issue, a key question becomes, how can the differences be explained? A prime candidate involves different methodologic choices. A deeper question emerges from this same situation: are the methods used for causal assessments reliable? Reliability is a hallmark of scientific practice. The methods used to make claims about causality should be reliable. Given the complexity of the causal assessment process, an objective evaluation of reliability is challenging but clearly worth the effort. Fortunately, Hill's criterion of analogy, much maligned in epidemiology, provides a clue. This commentary explores the issue of the reliability of causal claims using the Goodman et al. systematic review as its foil along with the claims by EPA, IARC, and ATSDR about the relationship between perchloroethylene and non-Hodgkin lymphoma, the claims Goodman et al. believe are wrong.


The role of Superior Capsule Reconstruction in the irreparable rotator cuff tear - A systematic review.
Irreparable rotator cuff tears in active patients provide a significant challenge and a consensus on the gold standard treatment is currently lacking. Superior capsule reconstruction (SCR) has recently been advocated and functions by providing a passive biological constraint to superior humeral head migration. The aim of this study is to systematically review the literature to evaluate the role of SCR in terms of functional outcome scores and failure rates. A review of the online databases Medline and EMBASE was conducted in accordance with the PRISMA guidelines on the 28th January 2019. Clinical studies reporting SCR using any type of graft or surgical technique were included if reporting either functional outcome scores or rate of secondary surgery. The studies were appraised using the Methodological index for non-randomised studies tool. The search strategy identified nine studies eligible for inclusion; five reported on fascia lata autografts and four studies reported on dermal allografts. All nine studies reported significant improvement in functional scores after SCR. Rates of secondary surgery were only provided in the dermal allograft studies at short-term follow-up (mean 10.9 to 32.4months) and ranged from 0 to 18.6%. Radiological assessment revealed graft failure in 5.5 to 55% of dermal allografts and 4.2 to 36.1% of fascia lata autografts. This review demonstrates that SCR is a useful treatment modality for patients with irreparable rotator cuff tears. SCR was associated with significantly improved functional outcome scores in all studies. All studies reported a preserved or increased mean AHD. The radiological graft failure rate ranged from 4.2 to 55% and the short duration of follow-up in most studies means that this remains an important concern that requires longer-term evaluation. IV, systematic review.


Wall composition analysis of the human hepatic artery by intravascular ultrasound.
The purpose of this study was to elucidate the wall layer appearance of the human hepatic artery shown by intravascular ultrasound (IVUS). We evaluated the wall layer appearance of 57 human hepatic arteries from 36 cadavers. The thickness of the inner high-echoic layer and the second low-echoic layer of the arteries was measured by IVUS, and it was compared with that of the arterial intima and media, respectively. The thickness of the inner high-echoic layer was 0.2 ± 0.1 mm and that of the second low-echoic layer was 0.4 ± 0.1 mm, on IVUS. However, the histological thickness of the intima was 120 ± 45 μm and that of the media was 258 ± 71 μm. The media of the hepatic artery correlated significantly with the second low-echoic layer on IVUS (r = 0.62, P < 0.01). The diameter of the vessels measured on IVUS correlated significantly with that of the histological specimens (r = 0.89, P < 0.01). From our results, the three layers of the hepatic artery detected with IVUS may correspond to the intima, media, and adventitia, respectively.


[Exercise. Prevention and health promotion--pathways to innovation in public health?].
Besides appropriate nutrition, adequate exercise is the universal remedy. Regular endurance training elicits positive effects in numerous organs and tissue systems in the sense of primary prevention. Nevertheless, a lack of exercise and obesity are widespread among the German population. In addition to the individual's own responsibility, measures for disease-oriented prevention as well as for preserving health should be improved based on broad social consensus. To begin with, improved research on treatment and prevention should be required. This national challenge should not only be financed by health insurance funds but also by taxes and levies (e.g., tobacco tax). Only then can the constantly spiralling costs of public health be met.


The use of natural herbal extracts for improving the lipid stability and sensory characteristics of irradiated ground beef.
Ground Longissimus dorsi of beef were treated with herbal extracts of marjoram, rosemary and sage at concentration of 0.04% (v/w), radiation (2 or 4.5 kGy) or their combination. Treated samples were stored at 5°C and analyzed periodically for thiobarbituric acid reactive substances (TBARS), sensory characteristics and psychrotrophic bacterial counts during storage for 41 and 48 days for samples treated at 2 and 4.5 kGy respectively. Results demonstrated a significant benefit of the addition of herbal extracts to the ground beef prior to irradiation. All three extracts significantly (P<0.05) lowered the TBARS values and off-odor scores and significantly (P<0.05) increased color and acceptability scores in all samples with marjoram being the most effective. The combination treatment with herbal extracts plus irradiation resulted in extension of the shelf life of samples treated with 2 kGy by one week and samples treated with 4.5 kGy by two weeks, over that treated with irradiation alone. In conclusion, the addition of herbal extracts can minimize lipid oxidation, improve color and decrease off-odor production in irradiated ground beef.


Challenges in telemedicine for adult patients with drug-resistant epilepsy undergoing ketogenic diet treatment during the COVID-19 pandemic in the public healthcare system in Brazil.
Hygienic and sanitary measures and social distancing policies implemented during the new coronavirus disease - COVID-19 - pandemic have altered the care and follow-up provided by healthcare professionals for patients with chronic diseases, including patients with epilepsy (PWEs). Telemedicine has become a solution for the healthcare of PWEs in many developed countries. In this short communication, we trace a particular perspective for the application of telemedicine for PWEs undergoing ketogenic diet (KD) treatment, considering the social and economic difficulties faced by healthcare teams in resource-poor countries, such as Brazil. During the pandemic, financial strain was the main impediment to following KD. The pandemic increased socioeconomic insecurity and access to KD-related products, as well as increasing anxiety in 71% of PWE, impacting their KD treatment follow-up. The challenges of telemedicine in Brazil include not only social and economic issues but also access to food, healthcare services, and education for the population, in addition to digital inclusion.


Results of a questionnaire in 100 ALS patients and 100 control cases.
A questionnaire with 54 relevant questions was studied in 100 ALS patients and 100 age and sex matched control cases. The findings were discussed in relation to 7 questionnaires in the literature. No differences were found between ALS patients and controls. Especially the increase of frequency of gastrointestinal operations, previous poliomyelitis, toxic metal exposure frequency, antecedent fractures and excess milk drinking as described in the literature were not confirmed.


Successful treatment of cold-induced neck pain and jaw claudication with revascularization of severe atherosclerotic external carotid artery stenoses.
To present a patient whose cold-triggered neck pain and jaw claudication remitted after revascularization of severe atherosclerotic stenoses of both external carotid arteries (ECA). A 60-year-old vintner presented with jaw claudication and neck pain that increased in severity while he worked in cold temperatures. Angiography showed severe atherosclerotic narrowing of both ECAs. The symptoms disappeared after staged, bilateral percutaneous transluminal angioplasty procedures. However, the pain recurred together with severe bilateral ECA restenoses 6 months later; once again, the pain remitted after redilation. Right-sided neck pain and severe ECA narrowing recurred 5 months later and resolved after carotid endarterectomy. The patient remained asymptomatic and showed no ECA stenosis during a 3-year follow-up. Cold-triggered neck pain may be a symptom of atherosclerotic ECA stenoses, and carotid revascularization may be an efficient and safe treatment.


Changes in resting connectivity with age: a simultaneous electroencephalogram and functional magnetic resonance imaging investigation.
Resting fluctuations in the blood oxygenation level-dependent signal have attracted considerable interest for their sensitivity to pathological brain processes. However, these analyses are susceptible to confound by nonneural physiological factors such as vasculature, breathing, and head movement which is a concern when investigating elderly or pathological groups. Here, we used simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) (EEG/fMRI) to constrain the analysis of resting state networks (RSNs) and identify aging differences. Four of 26 RSNs showed fMRI and EEG/fMRI group differences; anterior default-mode network, left frontal-parietal network, bilateral middle frontal, and postcentral gyri. Seven RSNs showed only EEG/fMRI differences suggesting the combination of these 2 methods might be more sensitive to age-related neural changes than fMRI alone. Five RSNs showed only fMRI differences and might reflect nonneural group differences. Activity within some EEG/fMRI RSNs was better explained by neuropsychological measures (Mini Mental State Examination and Stroop) than age. These results support previous studies suggesting that age-related changes in specific RSNs are neural in origin, and show that changes in some RSNs relate better to elderly cognition than age.


NMR relaxation study of the protonated form of 1,8-Bis(dimethylamino)naphthalene in isotropic solution: anisotropic motion outside of extreme narrowing and ultrafast proton transfer.
The protonated form of 1,8-bis(dimethylamino)naphthalene (DMANH(+)) consists of a rigid, aromatic framework, substituted by two amino groups that are connected by a strong, symmetric (on the NMR time-scale) hydrogen bond bridge. The reorientational motion of the molecule in dimethylformamide-d7 solution was characterized by T(1) and NOE measurements for aromatic (13)C nuclei. Treating the reorientation of DMANH(+) as anisotropic rotational diffusion of a rigid body, the diffusion tensor was determined with good accuracy. Measurements and interpretation of (15)N T(1) and NOE indicate that the proton transfer between potential minima in the hydrogen bond bridge is faster than the molecular reorientation.


Analysis of yeast RNA polymerases with subunit-specific antibodies.
Specific antibodies directed against each polypeptide component of yeast RNA polymerases A or B were prepared and their affinity spectrum determined by protein blot immunodetection. The majority of enzyme A or B subunits were specifically recognized by their respective antiserum. A direct correspondence was established between the polypeptides immunologically related in the three forms of RNA polymerases A, B, and C by reacting the different antibodies with enzymes subunits transferred to a nitrocellulose membrane. Subunit-specific antibodies and antibodies to native enzymes A and B were used to probe the activity of RNA polymerases A, B, and C. Based on DNA protection experiments, the largest subunit of enzymes A and B as well as the common subunit ABC23 appear to be involved in DNA binding.


Different Patterns of Foxp3 Gene Expression in Pre-and Post-Transplantation Kidney Biopsies and the Effect of Use Mammalian Target of Rapamycin Inhibitors.
Trafficking of regulatory T cells (Tregs) modulates the inflammatory response after kidney transplantation (KTx). There is scarce information on whether circulating and intragraft Tregs are similarly affected by immunosuppressive drugs and the type of deceased kidney donor. FOXP3 gene expression was measured in the pretransplant kidney biopsies (PIBx) from donors who met extended (ECD) and standard (SCD) criteria donors. In the third month after KTx, the patients were divided according to tacrolimus (Tac) or everolimus (Eve) and the type of kidney they had received. FOXP3 gene expression in the peripheral blood (PB) and kidney biopsies (Bx) was analyzed using real-time polymerase chain reaction. FOXP3 gene expression in the PIBx was higher in ECD kidneys. FOXP3 gene expression in the PB and Bx was greater in Eve- than in Tac-treated patients. However, SCD recipients treated with Eve (SCD/Eve) had higher FOXP3 expression than ECD/Eve. Pretransplant kidney biopsies from ECD kidneys had higher FOXP3 gene expression than SCD, and the use of Eve may affect the expression of the FOXP3 gene only in SCD kidneys.


Regioisomers of phosphatidylcholine containing DHA and their potential to deliver DHA to the brain: role of phospholipase specificities.
Because neurons cannot synthesize docosahexaenoic acid (DHA), a dietary supplement of DHA in the form of phospholipids is recommended for maintaining proper brain functions. A model for delivering dietary sn-2-DHA phosphatidylcholine (PtdCho) to the brain involves phospholipase A2 based deacylation/reacylation cycle followed by delivery of DHA through high-density lipoproteins that bind to the brain capillary endothelial cells in the blood-brain barrier (BBB). Our previous study demonstrated preference of endothelial lipase (EL) for PtdCho species that contain sn-2-DHA, resulting in production of sn-2-DHA lysoPtdCho that is preferentially taken up by the brain. However, since CoA-dependent reacylation of lysoPtdCho with DHA at the sn-2 position is not favored in vivo, we proposed that sn-1-DHA PtdCho in the diet may be a superior source of DHA for the brain. To test this hypothesis, DHA PtdCho regioisomers were prepared, and their hydrolysis by physiologically relevant phospholipases was determined. The data presented here show that: (1) group X secretory PLA2 (sPLA2) is about threefold more active than group V sPLA2 in releasing sn-2 fatty acids from DHA regioisomers, and (2) EL shows its specificity for DHA PtdCho species in a concentration independent manner, suggesting that the enzyme could play a major role in generating free sn-1-DHA or/and sn-2-DHA lysoPtdCho from the regioisomers in the BBB. We propose that PtdCho species containing sn-1-DHA may have the advantages of both "preserving" DHA in deacylation/reacylation cycle and releasing free DHA in the BBB for uptake by the brain.


Appraisal of intraoperative ultrasonography during laparoscopic cholecystectomy.
The usefulness of intraoperative ultrasonography during laparoscopic cholecystectomy (LC) has yet to be evaluated fully. In 50 patients who underwent LC, the intraoperative ultrasonography findings were compared with those of preoperative ultrasonography, intraoperative cholangiography, and histology, and then its usefulness for examining anatomic relationships in the hepatoduodenal ligament, detecting bile duct stones, diagnosing gallbladder polyps and abnormally thickened walls, and determining the propriety of LC was appraised. The preoperative ultrasonography diagnoses were gallstones in 38 patients, polyps in 10, and cancer and adenomyomatosis in one each. In four patients endoscopic retrograde cholangiography showed bile duct stones. In all 50 patients intraoperative ultrasonography was useful for examining the anatomic relationships between the bile duct and vessels, such as the portal vein and hepatic artery, and showing the presence or absence of bile duct stones. On the basis of the intraoperative ultrasonography findings, gallstones were diagnosed in 38 patients, in five of whom bile duct stones were shown clearly, cholesterol polyps in eight, early-stage cancer or adenoma in two, and adenomyomatosis in two, and subsequently LC was performed. Histologic diagnoses of cholesterol polyps were made in eight of ten patients with polyps, and intramucosal cancer and an inflammatory polyp in one each. In one patient with a preoperative diagnosis of cancer the apparently elevated flat lesion was found to be partial thickening of the gallbladder wall, which was diagnosed as adenomyomatosis, and LC was chosen as the operative procedure. Intraoperative ultrasonography during LC is useful for detecting bile duct stones, diagnosing gallbladder polyps and abnormally thickened walls, and deciding whether LC is adequate for resection of the gallbladder.


The composition and capacity of the clinical genetics workforce in high-income countries: a scoping review.
As genetics becomes increasingly integrated into all areas of health care and the use of complex genetic tests continues to grow, the clinical genetics workforce will likely face greatly increased demand for its services. To inform strategic planning by health-care systems to prepare to meet this future demand, we performed a scoping review of the genetics workforce in high-income countries, summarizing all available evidence on its composition and capacity published between 2010 and 2019. Five databases (MEDLINE, Embase, PAIS, CINAHL, and Web of Science) and gray literature sources were searched, resulting in 162 unique studies being included in the review. The evidence presented includes the composition and size of the workforce, the scope of practice for genetics and nongenetics specialists, the time required to perform genetics-related tasks, case loads of genetics providers, and opportunities to increase efficiency and capacity. Our results indicate that there is currently a shortage of genetics providers and that there is a lack of consensus about the appropriate boundaries between the scopes of practice for genetics and nongenetics providers. Moreover, the results point to strategies that may be used to increase productivity and efficiency, including alternative service delivery models, streamlining processes, and the automation of tasks.


Influence of environmental temperature on energy balance, diet-induced thermogenesis and brown fat activity in 'cafeteria'-fed rats.
1. Young male rats were fed on a pelleted stock diet or a variety of palatable food items ('cafeteria' diet) and housed at 24 degrees or 29 degrees. 2. 'Cafeteria' feeding at the lower temperature stimulated energy intake, gain and expenditure, but reduced energetic efficiency such that over 70% of the excess intake was expended. 3. Housing at 29 degrees suppressed intake and expenditure in animals on both diets, but to a greater extent in 'cafeteria'-fed rats and energetic efficiency was greater than control values at this higher temperature. 4. The thermogenic capacity of brown fat (mitochondrial purine nucleotide binding) was increased by 'cafeteria' feeding, but was suppressed in animals kept at 29 degrees. 5. The results demonstrate that diet-induced thermogenesis is inhibited by high environmental temperatures.


Setting up of teeth in the neutral zone and its effect on speech.
Rational goals for denture construction are basically directed at the restoration of esthetics and masticatory function and the healthy preservation of the remaining natural tissues. Little concern has been given to the perfection and optimization of the phonetic quality of denture users. However, insertion of prosthodontic restorations may lead to speech defects. Most such defects are mild but, nevertheless, can be a source of concern to the patient. For the dental practitioner, there are few guidelines for designing a prosthetic restoration with maximum phonetic success. One of these guidelines involves the setting up of teeth within the neutral zone. The aim of this study was to evaluate, subjectively and objectively, the effect on speech of setting up teeth in the neutral zone. Three groups were examined: group I (control) included 10 completely dentulous subjects, group II included 10 completely edentulous patients with conventional dentures, and group III included the same 10 edentulous patients with neutral zone dentures. Subjective assessment included patient satisfaction. Objective assessment included duration taken for recitation of Al-Fateha and acoustic analysis. Subjectively, patients were more satisfied with their neutral zone dentures. Objectively, speech produced with the neutral zone dentures was closer to normal than speech with conventional dentures.


Behavioural effects of hashish in mice in comparison with other psychoactive drugs.
1. The behavioural effects of hashish extract (10 mg delta 9-THC/kg) were compared to those of morphine (20 mg/kg), diazepam (10 mg/kg), imipramine (10/kg), amphetamine (10 mg/kg) and chlorpromazine (10 mg/kg) by testing male mice in a resident-intruder situation. 2. The drugs were given either to the resident or to the intruder male. 3. Hashish extract similar to diazepam and chlorpromazine reduced social activities in resident and intruder males. 4. Intruder males treated with hashish or diazepam were more frequently attacked and submission and light was increased. 5. Amphetamine and morphine stimulated locomotion and non-social activities but impaired social behaviour especially in residents. 6. Imipramine increased aggressive behaviour in resident and intruder males.


Plasma clot retraction assay with standard platelet count.
After classifying the phases of blood clot retraction within the mechanism of blood coagulation and the factors on which this phenomenon is depending, the authors briefly review the methods employed for its investigation. An improvement based on the determination of plasma clot retraction, performed in a plasma with a standard count of platelets (100,000/mm3) is presented. The authors have employed it for the investigation of 100 normal subjects and 25 patients with platelet dysfunctions, and have obtained very good results.


[Intraoperative exchange of the endotracheal tube using the Cook C-CAE airway exchange catheter].
The Cook airway exchange catheter is mainly used in ICU patients to exchange endotracheal tubes. We report three cases where this device was used during anaesthesia in patients with damaged tubes in critical circumstances (oropharyngeal bleeding, head and neck surgery). It allowed a fast and atraumatic exchange of the tubes.


SARS-CoV-2 infection causes intestinal cell damage: Role of interferon's imbalance.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of the newly emerging lung disease pandemic COVID-19. This viral infection causes a series of respiratory disorders, and although this virus mainly infects respiratory cells, the small intestine can also be an important site of entry or interaction, as enterocytes highly express in angiotensin-2 converting enzyme (ACE) receptors. There are countless reports pointing to the importance of interferons (IFNs) with regard to the mediation of the immune system in viral infection by SARS-CoV-2. Thus, this review will focus on the main cells that make up the large intestine, their specific immunology, as well as the function of IFNs in the intestinal mucosa after the invasion of coronavirus-2.


Distribution of lymphatic vessel network in normal urinary bladder.
The lymphatic vessel endothelial hyaluronan receptor (LYVE-1) is a novel lymphatic vessel marker that is expressed on lymph vessel endothelial cells. The objective of this study was to determine the LYVE-1 expression patterns in normal urothelium and to compose the geometric topography of the lymphatic network. Immunohistochemical staining for LYVE-1 and von Willebrand factor was performed to assess the differences in the distribution of lymphatic vessels between the components in the urinary bladder. The sizes of the individual lymphatic vessels were categorized as small, medium, and large. To compare the lymphatic density (counts per square millimeter), the number of lymphatic vessels of the five random areas was counted in each specimen. LYVE-1 expression and the lymphatic density of the muscularis propria were significantly greater than those of other layers, including the epithelium, lamina propria, perivesical fat, and serosa (P <0.0001). The size of the lymphatic vessels in the muscularis propria was significantly smaller than that in the other layers (P <0.0001). The greatest distribution of the lymphatic vessels was identified in the border areas consisting of the lamina propria and muscular propria or the muscular propria and adventitia, including the perivesical fat and serosa. We have developed a new type of color geometric topography to accurately exhibit the distribution of that complex network. Lymphatic vessels, although small, are predominately distributed in the muscularis propria in the normal urothelium compared with that in the other layers. The LYVE-1 antibody was a useful specific marker for the illustration of the lymphatic vessel in conventional paraffin-embedded specimens of the urinary bladder.


Increase of Severe Pulmonary Infections in Adults Caused by M1UK Streptococcus pyogenes, Central Scotland, UK.
We characterized the epidemiology, host-pathogen characteristics, and outcomes of severe adult pulmonary Streptococcus pyogenes infections that coincided with a high community caseload in central Scotland, UK. The pulmonary infections had high illness and death rates and were associated with socioeconomic deprivation, influenza A co-infection, and the M1UK lineage of S. pyogenes.


Hydrocortisone versus vasopressin for the management of adult patients with septic shock refractory to norepinephrine: A multicenter retrospective study.
Significant practice variation exists when selecting between hydrocortisone and vasopressin as second line agents in patients with septic shock in need of escalating doses of norepinephrine. The goal of this study was to assess differences in clinical outcomes between these two agents. Multicenter, retrospective, observational study. Ten Ascension Health hospitals. Adult patients with presumed septic shock receiving norepinephrine prior to study drug initiation between December 2015 and August 2021. Vasopressin (0.03-0.04 units/min) or hydrocortisone (200-300 mg/day). A total of 768 patients were included with a median (interquartile range) SOFA score of 10 (8-13), norepinephrine dose of 0.3 mcg/kg/min (0.1-0.5 mcg/kg/min), and lactate of 3.8 mmol/L (2.4-7.0 mmol/L) at initiation of the study drug. A significant difference in 28-day mortality was noted favoring hydrocortisone as an adjunct to norepinephrine after controlling for potential confounding factors (OR 0.46 [95% CI, 0.32-0.66]); similar results were seen following propensity score matching. Compared to vasopressin, hydrocortisone initiation was also associated with a higher rate of hemodynamic responsiveness (91.9% vs. 68.2%, p < 0.01), improved resolution of shock (68.8% vs. 31.5%, p < 0.01), and reduced recurrence of shock within 72 h (8.7% vs. 20.7%, p < 0.01). Addition of hydrocortisone to norepinephrine was associated with a lower 28-day mortality in patients with septic shock, compared to the addition of vasopressin.


RAPD for the typing of coagulase-negative staphylococci implicated in catheter-related bloodstream infection.
A rapid random amplification of polymorphic DNA (RAPD) technique was developed to distinguish between strains of coagulase-negative staphylococci (CoNS) involved in central venous catheter (CVC)-related bloodstream infection. Its performance was compared with that of pulsed-field gel electrophoresis (PFGE). Patients at the University Hospital Birmingham NHS Foundation Trust, U.K. who underwent stem cell transplantation and were diagnosed with CVC-related bloodstream infection due to CoNS whilst on the bone marrow transplant unit were studied. Isolates of CoNS were genotyped by PFGE and RAPD, the latter employing a single primer and a simple DNA extraction method. Both RAPD and PFGE were highly discriminatory (Simpson's diversity index, 0.96 and 0.99, respectively). Within the 49 isolates obtained from blood cultures of 33 patients, 20 distinct strains were identified by PFGE and 25 by RAPD. Of the 25 strains identified by RAPD, nine clusters of CoNS contained isolates from multiple patients, suggesting limited nosocomial spread. However, there was no significant association between time of inpatient stay and infection due to any particular strain. The RAPD technique presented allows CoNS strains to be genotyped with high discrimination within 4h, facilitating real-time epidemiological investigations. In this study, no single strain of CoNS was associated with a significant number of CVC-related bloodstream infections.


GM-1 ganglioside administration combined with physical therapy restores ambulation in humans with chronic spinal cord injury.
In a randomized double-blind cross-over study, humans with chronic spinal cord injury received ganglioside GM-1 or placebo for 2 months. GM-1, administered intravenously at a dose of 100 mg, 6 days a week, resulted in a statistically significant improvement of motor scores (P < 0.05), whether administered before or after 2 months of placebo. There was no placebo effect on motor scores. Subjects who received GM-1 before placebo maintained their improvement during the placebo phase. Subjects who received GM-1 ambulated with a reciprocal gait, using orthotics, for longer distances and at a faster rate whether the drug was administered before or after placebo. These results constitute the first finding that any chemical substance improves locomotion in human chronic spinal cord injury.


The impact of the COVID-19 pandemic on mortality in people with dementia without COVID-19: a systematic review and meta-analysis.
Significant mortality amongst vulnerable populations, such as people living with dementia, might go undetected during pandemic conditions due to refocus of care efforts. There is an urgent need to fully evaluate the pandemic impact on mortality amongst people living with dementia in order to facilitate future healthcare reforms and prevent deaths. The purpose of this study was to determine whether there was any significant difference in mortality amongst people with dementia without COVID-19 during the COVID-19 pandemic compared to previous years. A literature search was conducted in 5 databases. The relative risk ratio and confidence interval was used to estimate the change in mortality rates amongst people with dementia during the COVID-19 pandemic. The I2 value was used to assess heterogeneity, publication bias, and sensitivity analyses were performed. Pooled analysis of 11 studies showed that mortality amongst people living with dementia was significantly increased during the COVID-19 pandemic for people with dementia without COVID-19. Mortality risk increased by 25% during the time period studied. Subgroup analysis was not performed due the low number of included studies. The results of this study suggest that people with dementia had a significant increased mortality during the pandemic even if they did not have COVID-19. People with dementia should participate in efforts that reduce general social spread and pandemic impact on healthcare system such as vaccinations, mask mandates, and testing. These results have clinical implications as preventing direct COVID-19 infection is not enough to adequately protect people living with dementia from increased mortality. Measures to limit social spread of infections and help support patients should also be a focus for clinicians. Further research should focus on the identification of mechanisms and other explanations for increased mortality as well as contributing factors such as living in care homes and differences between countries with various pandemic strategies.


Violence, conflict and health in Africa.
This study attempts to examine the impact of incessant violence and political conflicts on the development of health services in Africa. Specifically, how do violent activities and conflicts, such as wars, affect health care infrastructures and health policies in Africa? The paper further examines the consequences of violence and conflicts on the health of refugees. The paper concludes that African states would develop better health policies for their citizens in the absence of violence and conflicts.


Concomitant rotator cuff and capsuloligamentous lesions of the shoulder: a cadaver study.
Rotator cuff lesions have not yet been evaluated in association with capsuloligamentous lesions in an otherwise intact shoulder model. Our hypothesis was that less extensive capsuloligamentous lesions are necessary to allow dislocation in the presence of rotator cuff lesions. The supraspinatus and infraspinatus, or the subscapularis, or all 3 tendons were carefully detached from their insertion without damage to the underlying capsule. Adjacent combinations of 4 zones of the capsuloligamentous complex were then sequentially detached from the glenoid or from the humerus in 80 cadaver shoulders. Stability was tested before and after each resection step; this included testing of inferior stability with a sulcus test, and of anterior stability with a drawer test and with an apprehension maneuver. Findings from these specimens were statistically compared with those from the same types of tests in specimens with intact rotator cuffs. Subluxation during the drawer and sulcus tests is already reached after the tendon lesion has been created, or after only 1 ligamentous zone has been cut. In the presence of a tendon lesion, at least 1 less cutting step is necessary for dislocation to occur in the apprehension position. There is a difference, however, between glenoid- and humerus-based lesions. The humeral head dislocates easily with less extensive capsuloligamentous lesions when rotator cuff lesions are present. In the present experimental model, passive stabilization provided by the rotator cuff appears more easily disrupted when associated with ligamentous lesions on the humeral side than with lesions on the glenoid side. This may be so because interdigitation of the cuff tendons with each other and with the capsule through the rotator cable is maintained with glenoid-sided lesions. Rotator cuff lesions destabilize the glenohumeral joint. This effect is less pronounced when cuff tendons continue to interact with underlying capsuloligamentous structures. This finding may be relevant for small cuff tears and for partial cuff tears, especially those seen after dislocation.


Synergistic activation of transcription by UNC-86 and MEC-3 in Caenorhabditis elegans embryo extracts.
The nematode Caenorhabditis elegans has been a choice organism for the study of developmental regulation using classical and molecular genetic approaches. Consequently, many genetically defined pathways have been described and numerous regulatory genes have been identified. However, the biochemical and functional properties of these putative transcription factors have remained uncharacterized, partly because C.elegans cell-free transcription reactions have not been developed. Here we describe the in vitro transcriptional activation properties of two C.elegans homeodomain proteins, UNC-86 and MEC-3, in nuclear extracts derived from C.elegans embryos. Whereas the POU homeodomain protein, UNC-86, alone was able to activate transcription of the mec-3 promoter in vitro, the LIM homeodomain protein, MEC-3, failed to bind DNA or activate transcription on its own. However, in the presence of both UNC-86 and MEC-3, we observed cooperative binding to the mec-3 promoter and synergistic activation of transcription in vitro. Protein-protein interaction assays revealed that UNC-86 can bind directly to MEC-3, and in vitro transcription studies indicate that both proteins contain a functional activation domain. Thus, formation of a heteromeric complex containing two activation domains results in a highly potent activator. These studies provide direct functional evidence for coordinated transcriptional activation by two C.elegans DNA binding proteins that have been defined genetically as regulators of gene expression during embryogenesis.


Topotecan-induced topoisomerase IIalpha expression increases the sensitivity of the CML cell line K562 to subsequent etoposide plus mitoxantrone treatment.
A new chemotherapy regimen was designed for leukemia to improve response to therapy and elucidate the possible underlying mechanisms responsible for its efficacy. Cells of the chronic myelogenous leukemia (CML) cell line, K562, were treated singly, in combination, and in sequence with clinically equivalent dosages of topotecan, which targets topoisomerase I (Topo I), and etoposide and mitoxantrone, which target topoisomerase II (Topo II), to determine the best treatment. Apoptosis, early cell deaths, and cell cytotoxicities in drug-treated cells were determined with annexin V and propidium iodide staining and MTT assays, respectively. Confocal microscopy and RT-PCR showed the cellular locations and relative increases in Topo IIalpha in topotecan-treated cells. The double comet assay of individual cells showed simultaneously free Topo proteins, non-Topo-associated DNA, and Topo-DNA complexes in drug-induced DNA fragments. Sequential treatment with topotecan on days 1-3, followed by etoposide+mitoxantrone on days 4, 5, 9 and 10 resulted in 100% cell death whereas treatments involving administration of drugs singly or simultaneously resulted in less cell kill. The cytotoxicity results in cells treated for fewer days with the same sequential chemotherapy regimen showed the same trend, and adequate surviving cells for the experiments on the cellular and molecular mechanisms of drug action were produced. An increase in Topo IIalpha mRNA from RT-PCR 1 h after topotecan treatment was observed. Observations on K562 cells treated sequentially with topotecan followed by etoposide, mitoxantrone or etoposide+mitoxantrone were as follows: (1) Topo IIalpha protein levels increased and relocated from the cytoplasm into the nucleus as detected by confocal microscopy, (2) Topo IIalpha-DNA complexes increased and were associated with fragmented DNA (positive double comets) as detected by protein-DNA double comet assay, and (3) Topo I and Topo IIbeta proteins were not associated with fragmented DNA. Topotecan-induced Topo IIalpha protein levels correlated with increased numbers of positive double comets and reduction of cell viability. Our results showed that Topo IIalpha protein induction after Topo I-directed drug treatment enhanced the sensitivity of cells to subsequent exposure to Topo II-directed drugs. Timed sequential chemotherapy with topotecan followed by etoposide+mitoxantrone is an effective regimen to ablate CML cancer cells.


Forensic implications of the foot and ankle.
To clinicians, forensic medicine and the foot and ankle complex may appear to have little connection. However, if decomposed, burned, fragmented, or skeletonized human remains are recovered, the foot and ankle can provide information leading to identification and incident analysis. Furthermore, analysis of data collected at accidents can lead to safety modifications. This article reviews common elements of forensic medicine applied to the foot and ankle in 2 areas: establishing positive identification by using radiographic comparisons and analyzing aviation incidents. An understanding of these cases will enhance clinicians' awareness of the potential forensic value of the foot and ankle.


[Digital subtraction myelography--a preliminary report on the use of the digital subtraction technic in myelography].
Preliminary examinations with digital subtraction myelography revealed the possibility of saving up to 70% of water soluble contrast medium compared with usual myelographic procedures, thereby reducing the risk of neurotoxic adverse reactions.


Structure based virtual screening of natural product molecules as glycosidase inhibitors.
Objective of the present investigation comprised of the application of in silico methods to discover novel natural product (NP) based potential inhibitors for carbohydrate mediated diseases. Structure based drug design studies (molecular docking and structure based pharmacophore analysis) were carried out on a series of natural product compounds to identify significant bioactive molecules to inhibit α-mannosidase (I and II) and β-galactosidase enzymes. Furthermore, protein ligand interaction fingerprint analysis, molecular dynamics simulations and molecular access system (MACCS) fingerprint analysis were performed to understand the binding behaviors of the studied molecules. The results derived from these analyses showed that the identified compounds exhibit significant binding interactions with the active site residues. The compounds, NP-51, NP-81 and NP-165 have shown significant docking score against the studied enzymes (α-mannosidases-I, α-mannosidases-II and β-galactosidases). The fingerprint studies showed that the presence of rings (aromatic or aliphatic) with sulfur atoms, nitrogen atoms, methyl groups, etc. have favorable effects on the α-mannosidase II inhibitory activity. However, the presence of halogen atoms substituted in the molecules have reduced inhibitory ability against α-mannosidase II. The compound, NP-165 has significant activity against both enzymes (α-mannosidases and β-galactosidases). These studies accomplished that the compounds identified through in silico methodologies can be used to develop semisynthetic derivatives of the glycosidase inhibitors and can be screened for the treatment of different carbohydrate mediated diseases. The online version contains supplementary material available at 10.1007/s40203-021-00115-9.


Clinical characteristics and prognostic factors of prostate cancer with liver metastases.
Liver metastasis from prostate cancer is uncommon and remains poorly understood. We computer searched the clinical records of all our patients registered into a database to identify patients that presented or developed liver metastases. A total of 27 prostate cancer patients with ultrasound or CT/MR imaging evidence of liver metastases were included in our analysis. The liver metastasis rate from metastatic prostate cancer was 4.29%. Eight (29.63%) patients had previously untreated, hormone-naive prostate cancer (synchronous liver metastases at diagnosis of prostate cancer), whereas 19 (70.37%) patients had already been diagnosed as having hormone-refractory prostate cancer. In the hormone-naive group, the median overall survival after liver metastases diagnosis was 38 months and half of the patients were still alive at the latest follow-up, whereas only 6 months in the hormone-refractory group (p = 0.003). High concentration of serum neuron-specific enolase and previous chemotherapy were associated with a significantly poor overall survival after liver metastases in the hormone-refractory group using Kaplan–Meier curves and logrank tests for univariate analysis.


[New species of microsporidian Issia globulifera sp. n. (Nosematidae) in the malarial mosquito Anopheles maculipennis].
A microsporidia, Issia globulifera sp. n., which has diplocaryotic stages during its whole developmental cycle and disporoblastic sporogony, is described. Spores are eggshaped, 3.6 X 2.4 mu in size. During sporogenesis at the hind pole of spores in the place of their contact a globule holding spores together is formed. Spores and globule are covered by a compact pansporoblastic membrane.


The clot burden score, the Boston Acute Stroke Imaging Scale, the cerebral blood volume ASPECTS, and two novel imaging parameters in the prediction of clinical outcome of ischemic stroke patients receiving intravenous thrombolytic therapy.
Recently two classification methods based on the location and the extent of thrombosis detected with CT angiography have been introduced: the Boston Acute Stroke Imaging Scale (BASIS) and the clot burden score (CBS). We studied the performance of BASIS and CBS in predicting good clinical outcome (mRS ≤ 2 at 90 days) in an acute (< 3 h) stroke cohort treated with intravenous thrombolytic therapy. Eighty-three consecutive patients who underwent multimodal CT were analyzed. Binary logistic regression model was used to assess how BASIS, CBS, and cerebral blood volume (CBV) ASPECTS predict favorable clinical outcome. Diagnostic sensitivities and specificities were calculated and compared. Patients with low CBS and CBV ASPECTS scores and major strokes according to BASIS had significantly higher admission NIHSS scores, larger perfusion defects, and more often poor clinical outcome. In logistic regression analysis, CBV ASPECTS, CBS and BASIS were significantly associated with the clinical outcome. The performance of BASIS improved when patients with thrombosis of the M2 segment of the middle cerebral artery were classified as having minor stroke (M1-BASIS). In the anterior circulation, the sum of CBS and CBV ASPECTS (CBSV) proved to be the most robust predictor of favorable outcome. CBV ASPECTS and CBS had high sensitivity but moderate to poor specificity while BASIS was only moderately sensitive and specific. CBS, BASIS, and CBV ASPECTS are statistically robust and sensitive but unspecific predictors of good clinical outcome. Two new derived imaging parameters, CBSV and M1-BASIS, share these properties and may have increased prognostic value.


Co-chairman's remarks: before the double helix.
In the nineteen-thirties and -forties, genes were universally believed to be made of protein. Biochemists met Avery, MacLeod and McCarty's discovery, that the transforming factor of pneumococci consists of DNA, with disbelief, and the notion that this was true of genes took a long time to be generally accepted even after Watson and Crick's discovery of its double helical structure. Until Watson's arrival, Kendrew, Crick and I were interested mainly in solving the structure of proteins, but Watson made us think about the structure of genes which determine protein structure.


Intradermal administration of fractional doses of the inactivated poliovirus vaccine in a campaign: a pragmatic, open-label, non-inferiority trial in The Gambia.
A rapid increase in circulating vaccine-derived poliovirus type 2 outbreaks, and the need to reserve inactivated poliovirus vaccine (IPV) for routine immunisation, has increased the value of fractional dose IPV (fIPV) as a measure to prevent acute flaccid paralysis. However, the intradermal route of administration has been viewed as prohibitive to outbreak response campaigns. We aimed to establish the immunogenicity and safety of administering intradermal fIPV with a disposable syringe jet injector (DSJI) or an intradermal adaptor (IDA) compared with standard administration with a BCG needle and syringe (N&S). This pragmatic, non-inferiority trial was undertaken in a campaign setting in communities in The Gambia. Children aged 4-59 months without contraindication to vaccination were eligible. Children were not individually randomly assigned; instead, the vaccination teams were randomly assigned (1:1:1) to one of three administration methods. Parents and the field team were not masked, but laboratory personnel were masked. Baseline demographic and anthropometric data were collected from the participants. Public health officers experienced at intradermal immunisation, and nurses without experience, had 2 h of training on each of the administration methods before the campaign. Participants were vaccinated using the administration method in use by the vaccination team in their community. Poliovirus serum neutralising antibodies (SNA) were measured in children aged 24-59 months before and 4 weeks after vaccination. Adverse events and data on injection quality were collected from all participants. The primary outcome was the type 2 immune response rate (seroconversion in seronegative [SNA titre <8] children plus a 4-fold titre rise in seropositive children). Adjusted differences in the immune response between the DSJI or IDA group versus the N&S group were calculated with 97·5% CIs. A margin of -10% was used to define the non-inferiority of DSJI or IDA compared to N&S. Immunogenicity analysis was done per protocol. The trial is registered with ClinicalTrials.govNCT02967783 and has been completed. Between Oct 28 and Dec 29, 2016, 3189 children aged 4-59 months were recruited, of whom 3170 were eligible. Over 3 days, 2720 children were vaccinated (N&S, 917; IDA, 874; and DSJI, 929). Among 992 children aged 25-59 months with a baseline SNA available, 90·1% (95% CI 86·1-92·9; 281/312) of those vaccinated using the DSJI had an immune response to type 2 compared with 93·8% (90·6-95·8; 331/353) of those vaccinated with N&S and 96·6% (94·0-98·0; 316/327) of those vaccinated with IDA. All (53/53) type 2 seronegative children seroconverted. For polio type 2, non-inferiority was shown for both the IDA (adjusted difference 0·7% [97·5% CI -3·3 to 4·7], unadjusted difference 2·9% [-0·9 to 6·8]) and DSJI (adjusted difference -3·3% [-8·3 to 1·5], unadjusted difference -3·7% [-8·7 to 1·1]) compared with N&S. Non-inferiority was shown for type 1 and 3 for the IDA and DSJI. Neither injection quality nor the training and experience of the vaccinators had an effect on immune response. No safety concerns were reported. In a campaign, intradermal fIPV is safe and generates consistent immune responses that are not dependent on vaccinator experience or injection quality when administered using an N&S, DSJI, or IDA. Countries facing vaccine-derived poliovirus type 2 outbreaks should consider fIPV campaigns to boost population immunity and prevent cases of acute flaccid paralysis. World Health Organization and the Medical Research Council.


Effects of diesel oil spill on macrobenthic assemblages at the intertidal zone: A mesocosm experiment in situ.
The oil spill accidents may drastically impact the environment and ecosystem at intertidal zones. The spilled oil will penetrate the sediments and accumulate to cause lethal or sublethal effects on the benthic invertebrates. An M-BACI experiment was manipulated in situ to assess the ecological responses of benthic macrofauna to different degrees of diesel oil spill. Both biotic and abiotic parameters were studied for 126 days, subjected to both "pulse" and "press" oil contaminations. The content of aliphatic hydrocarbons (displayed as ratios of n-C17/Pr and n-C18/Ph) slightly dropped then continuously existed in the sediment during the experiment time. The macrofaunal assemblage structures were dramatically altered in species number, abundance and biomass. In general, it takes longer time for the macrofauna assemblages to recover under high concentration oil spill than that under low concentration. Our results highlight the diversified strategies for survival and recolonization among dominant species, which distinguish themselves between: i) tolerant species, ii) opportunistic species, and iii) equilibrium species.


Construction of an infectious bronchitis virus vaccine strain carrying chimeric S1 gene of a virulent isolate and its pathogenicity analysis.
Infectious bronchitis virus (IBV) is a member of genus gamma-coronavirus in the family Coronaviridae, causing serious economic losses to the poultry industry. Reverse genetics is a common technique to study the biological characteristics of viruses. So far, there is no BAC reverse genetic system available for rescue of IBV infectious clone. In the present study, a new strategy for the construction of IBV infectious cDNA clone was established. The full-length genomic cDNA of IBV vaccine strain H120 was constructed in pBAC vector from four IBV fragment subcloning vectors by homologous recombination, which contained the CMV promoter at the 5' end and the hepatitis D virus ribozyme (HDVR) sequence and bovine growth hormone polyadenylation (BGH) sequence after the polyA tail at the 3' end of the full-length cDNA. Subsequently, using the same technique, another plasmid pBAC-H120/SCS1 was also constructed, in which S1 gene from IBV H120 strain was replaced with that of a virulent SC021202 strain. Recombinant virus rH120 and rH120/SCS1 were rescued by transfecting the plasmids into BHK cells and passaged in embryonated chicken eggs. Finally, the pathogenicity of both the recombinant virus strains rH120 and rH120/SCS1 was evaluated in SPF chickens. The results showed that the chimeric rH120/SCS1 strain was not pathogenic compared with the wild-type IBV SC021202 strain and the chickens inoculated with rH120/SCS1 could resist challenge infection by IBV SC021202. Taken together, our results indicate that BAC reverse genetic system could be used to rescue IBV in vitro and IBV S1 protein alone might not be the key factor for IBV pathogenicity. KEY POINTS: • BAC vector was used to construct IBV full-length cDNA by homologous recombination. • Based on four subcloning vectors, a recombinant chimeric IBV H120/SCS1 was constructed and rescued. • Pathogenicity of H120/SCS1 was similar to that of H120, but different to that of SC021202.


Persistence of long-term immunity to hepatitis B among adolescents immunized at birth.
The long-term duration of recombinant hepatitis B vaccine-induced immunity among persons vaccinated starting at birth is still not well understood. Waning of vaccine-induced immunity could leave young adults at risk of hepatitis B virus infection due to behavioral or occupational exposures. We followed a cohort of children immunized starting at birth with a 3-dose regimen of recombinant hepatitis B vaccine (5 mcg, 2.5 mcg, 2.5 mcg). They were challenged with a booster dose of the hepatitis B vaccine 10 and 15 years after vaccination to assess anamnestic response as a measure of persistence of protection. Among 108 participants who had lost protective antibody levels against hepatitis B, the majority (>70%) had an anamnestic response to the booster dose; response rates did not decline significantly between 10 and 15 years follow-up periods. A high antibody concentration following primary vaccination was independently associated with an anamnestic response later on in life. Nonetheless, ~20-30% of participants were unable to mount an immune response after boosting. Hepatitis B revaccination might be required for persons vaccinated starting at birth if opportunities for hepatitis B virus exposure exist. Future vaccine recommendations should be based on studies ascertaining protection against clinically significant disease.


Adolescence exposure to China's great famine period and the association of metabolic syndrome in adulthood: a retrospective study.
Exposure to famine during early life is related to several adverse health outcomes in adulthood, but the effect of famine exposure during adolescence is unclear. This study aims to examine whether exposure to famine in adolescence is associated with metabolic syndrome (MetS) in adulthood. This study included 4130 Chinese adults (2059 males and 2071 females) aged 59-71 from the 2011 China Health and Retirement Longitudinal Study (CHARLS). All the selected participants were exposed to the three-year time period (1959-1961) of China's Great Famine. Participants were categorized into an adolescent-exposed group (born 01/01/1944-12/31/1948) and a non-adolescent-exposed group (born 01/01/1940-12/31/1941 and 01/01/1951-12/31/1952). Sex-stratified multiple logistic regression models were used to estimate the association between exposure to famine in adolescence and MetS. Participants exposed to famine during adolescence were more likely to report MetS (aOR = 1.35; 95%CI 1.01-1.78) compared to the non-adolescent-exposed group. Further, males were 45% less likely to report MetS than females (aOR = 0.55; 95%CI 0.36-0.83). After stratification by sex, the effects of famine exposure during adolescence on MetS were detected among males only (aOR = 1.97; 95%CI 1.20-3.24). Additionally, males with a history of drinking were more likely to report MetS compared to those with no history of drinking (aOR = 2.63; 95%CI 1.41-4.90). Our findings reveal that exposure to famine during adolescence is associated with higher odds of MetS in adulthood overall, and this association is only pronounced among males. This study emphasizes that undernutrition in early life, including adolescence, may have a long-term effect and be associated with adverse health events in middle-to-late life. Targeting those elderly people who suffered famine during adolescence may help prevent the development of MetS in later life.


Facilitating access to glucometer reagents increases blood glucose self-monitoring frequency and improves glycaemic control: a prospective study in insulin-treated diabetic patients.
To investigate whether availability of glucometer reagents increases the frequency of self-blood glucose monitoring (SBGM) and improves glycaemic control in diabetic patients. Sixty-two insulin-treated diabetic patients were randomized to two groups, matched for age, gender, education, income, type and duration of diabetes, years of insulin treatment, number of daily insulin injections, and haemoglobin (Hb)A1c. All patients were given a glucometer, but one group (no cost, NC) was provided glucometer test strips free of charge. The other group (control, C) had to purchase strips as they found it necessary. Both groups of patients were followed longitudinally at 2-monthly intervals for 12 months with measurement of blood glucose and HbA1c, and the frequency of SBGM was determined by downloading the glucometer memory. The SBGM frequency was significantly higher in the NC group vs. the C group during the first 4 months (2.0 +/- 0.2 tests/day vs. 1.4 +/- 0.1 tests/day, P<0.025). Mean HbA1c remained stable over the 12 months in the NC group, whereas an increase with time was observed in the C group. The difference in HbA1c between the two groups was significant (P<0.002) after 6 months. Random blood glucose measured at each visit and average glucose recorded by the glucometer were also lower in the NC group vs. the C group (P<0.005). There was a negative correlation between HbA1c and SBGM frequency, and HbA1c in patients testing at least twice a day was lower than in those testing less than twice a day (8.8 +/- 0.2% vs. 9.6 +/- 0.2%, P<0.001). In this prospective study, having easy access to glucometer strips provided free of charge to patients increased SBGM frequency. The relationship between HbA1c and SBGM frequency supports the view that SBGM is an essential tool in diabetes management.


Transient expression of cauliflower mosaic virus (CaMV) P6-GFP complements a defective CaMV replicon to facilitate viral gene expression, replication and virion formation.
Over the past decades, several studies have examined the subcellular localization of the cauliflower mosaic virus (CaMV) P6 protein by tagging it with GFP (P6-GFP). These investigations have been essential in the development of models for inclusion body formation, nuclear transport, and microfilament-associated intracellular movement of P6 inclusion bodies for delivery of virions to plasmodesmata. Although it was shown early on that the translational transactivation function of P6-GFP was comparable to wild type P6, it has not been possible to incorporate a P6-GFP gene into an infectious clone of CaMV. Consequently, it has not been possible to formally prove that a P6-GFP fusion is comparable in function to the unmodified P6 protein. Here we show that transient expression of P6-GFP can complement a defective CaMV replicon through gene expression, replication and encapsidation, which validates the relevance of P6-GFP subcellular localization studies for understanding the development of CaMV infections.


Anti-tissue transglutaminase (tTG) screening using relative light units to identify IgA deficiency.
IgA deficiency is more common in patients with coeliac disease (CD). Total IgA levels are often recommended as part of first line coeliac testing along with anti-tissue transglutaminase (tTG) IgA, to identify these patients and reduce falsely negative results. This study aimed to identify patients with complete IgA deficiency by determining a cut-off threshold on chemiluminescent tTG IgA testing. A chemiluminescent assay QUANTA Flash h-tTG was reviewed using the BIO-FLASH automated platform. tTG relative light units (RLU) were analysed in relation to total IgA levels. Correlation analysis was performed and distributions of tTG RLU were compared between the IgA deficient and IgA detectable groups, and ROC analysis was performed to identify a suitable threshold. A total of 203 samples were reviewed in our initial cohort. There was a strong correlation between IgA and tTG RLU levels (Pearson correlation coefficient 0.495, p<0.001). There was a statistically significant difference of 170.57 RLU between the means of the IgA deficient and IgA detectable group (p<0.001, 156.50-184.64). A receiver operating characteristic (ROC) curve was generated with area under the curve of 0.997. A cut-off of less than 300 tTG RLU for identification of IgA deficiency was chosen, which had a sensitivity and specificity of 100% and 98.9%, respectively. A prospective validation cohort was conducted which confirmed the initial results. Our study has validated an algorithm to identify complete IgA deficiency by implementing a threshold of 300 RLU during tTG IgA testing by chemiluminescent immunoassay. This approach resulted in a sensitivity of 100% to detect patients with complete IgA deficiency. Widespread uptake would result in improved workflow, workload and turnaround time, and reduce the need for unnecessary blanket testing of total IgA in the screening for coeliac disease.