Comparing estimates of household expenditures between pictorial diaries and surveys in three low- and middle-income countries.
In most low- and middle-income countries (LMICs), household out-of-pocket (OOP) health spending constitutes a major source of healthcare financing. Household surveys are commonly used to monitor OOP health spending, but are prone to recall bias and unable to capture seasonal variation, and may underestimate expenditure-particularly among households with long-term chronic health conditions. Household expenditure diaries have been developed as an alternative to overcome the limitations of surveys, and pictorial diaries have been proposed where literacy levels may render traditional diary approaches inappropriate. This study compares estimates for general household and chronic healthcare expenditure in South Africa, Tanzania and Zimbabwe derived using survey and pictorial diary approaches. We selected a random sub-sample of 900 households across urban and rural communities participating in the Prospective Urban and Rural Epidemiology study. For a range of general and health-specific categories, OOP expenditure estimates use cross-sectional survey data collected via standardised questionnaire, and data from these same households collected via two-week pictorial diaries repeated four times over 2016-2019. In all countries, average monthly per capita expenditure on food, non-food/non-health items, health, and consequently, total household expenditure reported by pictorial diaries was consistently higher than that reported by surveys (each p<0.001). Differences were greatest for health expenditure. The share of total household expenditure allocated to health also differed by method, accounting for 2% in each country when using survey data, and from 8-20% when using diary data. Our findings suggest that the choice of data collection method may have significant implications for estimating OOP health spending and the burden it places on households. Despite several practical challenges to their implementation, pictorial diaries offer a method to assess potential bias in surveys or triangulate data from multiple sources. We offer some practical guidance when considering the use of pictorial diaries for estimating household expenditure.


Cost Effectiveness of Laminar Flow Systems for Total Shoulder Arthroplasty: Filtering Money from the OR?
Laminar flow ventilation systems were developed to reduce surgical contamination in joint arthroplasty to avoid periprosthetic joint infection (PJI). The goals of this study are to evaluate the cost-effectiveness and economic viability of installing and maintaining a laminar flow system in an operating room. A Monte Carlo simulation was used to evaluate the cost effectiveness of laminar flow. The variables included were cost to treat PJI, incidence of PJI, cost of laminar flow, years of operating room use, and arthroplasty volume as the dependent variable. Laminar flow would be financially-justified when 1,217 (SD: 319) TSA cases are performed annually with assumed 10% reduction in PJI from laminar flow and 487 (SD: 127) with assumed 25% reduction. In a high volume OR, laminar flow costs $25.24 per case (assuming 10% reduction) and $8.24 per case (assuming 25% reduction). Laminar flow would need to reduce the incidence of PJI by 35.1% (SD: 9.1) to be a cost-effective strategy. This analysis demonstrates the substantial arthroplasty volume and large reduction in PJI rates required to justify the installation and maintenance costs of this technology. This high cost of implementation should be considered prior to installing laminar flow systems.


Trends in the Use of Guideline-Directed Therapies Among Dialysis Patients Hospitalized With Systolic Heart Failure: Findings From the American Heart Association Get With The Guidelines-Heart Failure Program.
The purpose of this study was to determine the temporal trends in the adherence to heart failure (HF)-related process of care measures and clinical outcomes among patients with acute decompensated HF with reduced ejection fraction (HFrEF) and end-stage renal disease (ESRD). Previous studies have demonstrated significant underuse of evidence-based HF therapies among patients with coexisting ESRD and HFrEF. However, it is unclear if the proportional use of evidence-based medical therapies and associated clinical outcomes among these patients has changed over time. Get With The Guidelines-HF study participants who were admitted for acute HFrEF between January 2005 and June 2014 were stratified into 3 groups on the basis of their admission renal function: normal renal function, renal insufficiency without dialysis, and dialysis. Temporal change in proportional adherence to the HF-related process of care measures and incidence of clinical outcomes (1-year mortality, HF hospitalization, and all-cause hospitalization) during the study period was evaluated across the 3 renal function groups. The study included 111,846 patients with HFrEF from 390 participating centers, of whom 19% had renal insufficiency but who did not require dialysis, and 3% were on dialysis. There was a significant temporal increase in adherence to evidence-based medical therapies (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker: p trend <0.0001, β-blockers: p trend = 0.0089; post-discharge follow-up referral: p trend <0.0001) and defect-free composite care (p trend <0.0001) among dialysis patients. An improvement in adherence to these measures was also observed among patients with normal renal function and patients with renal insufficiency without a need for dialysis. There was no significant change in cumulative incidence of clinical outcomes over time among the HF patients on dialysis. In a large contemporary cohort of HFrEF patients with ESRD, adherence to the HF process of care measures has improved significantly over the past 10 years. Unlike patients with normal renal function, there was no significant change in 1-year clinical outcomes over time among HF patients on dialysis.


Optimization of treatment strategy used during shockwave lithotripsy to maximize stone fragmentation efficiency.
Previous studies have demonstrated that treatment strategy plays a critical role in ensuring maximum stone fragmentation during shockwave lithotripsy (SWL). We aimed to develop an optimal treatment strategy in SWL to produce maximum stone fragmentation. Four treatment strategies were evaluated using an in-vitro experimental setup that mimics stone fragmentation in the renal pelvis. Spherical stone phantoms were exposed to 2100 shocks using the Siemens Modularis (electromagnetic) lithotripter. The treatment strategies included increasing output voltage with 100 shocks at 12.3 kV, 400 shocks at 14.8 kV, and 1600 shocks at 15.8 kV, and decreasing output voltage with 1600 shocks at 15.8 kV, 400 shocks at 14.8 kV, and 100 shocks at 12.3 kV. Both increasing and decreasing voltages models were run at a pulse repetition frequency (PRF) of 1 and 2 Hz. Fragmentation efficiency was determined using a sequential sieving method to isolate fragments less than 2 mm. A fiberoptic probe hydrophone was used to characterize the pressure waveforms at different output voltage and frequency settings. In addition, a high-speed camera was used to assess cavitation activity in the lithotripter field that was produced by different treatment strategies. The increasing output voltage strategy at 1 Hz PRF produced the best stone fragmentation efficiency. This result was significantly better than the decreasing voltage strategy at 1 Hz PFR (85.8% vs 80.8%, P=0.017) and over the same strategy at 2 Hz PRF (85.8% vs 79.59%, P=0.0078). A pretreatment dose of 100 low-voltage output shockwaves (SWs) at 60 SWs/min before increasing to a higher voltage output produces the best overall stone fragmentation in vitro. These findings could lead to increased fragmentation efficiency in vivo and higher success rates clinically.


Insulin action on muscle protein kinetics and amino acid transport during recovery after resistance exercise.
We have determined the individual and combined effects of insulin and prior exercise on leg muscle protein synthesis and degradation, amino acid transport, glucose uptake, and alanine metabolism. Normal volunteers were studied in the postabsorptive state at rest and about 3 h after a heavy leg resistance exercise routine. The leg arteriovenous balance technique was used in combination with stable isotopic tracers of amino acids and biopsies of the vastus lateralis muscle. Insulin was infused into a femoral artery to increase the leg insulin concentrations to high physiologic levels without substantively affecting the whole-body level. Protein synthesis and degradation were determined as rates of intramuscular phenylalanine utilization and appearance, and muscle fractional synthetic rate (FSR) was also determined. Leg blood flow was greater after exercise than at rest (P<0.05). Insulin accelerated blood flow at rest but not after exercise (P<0.05). The rates of protein synthesis and degradation were greater during the postexercise recovery (65+/-10 and 74+/-10 nmol x min(-1) x 100 ml(-1) leg volume, respectively) than at rest (30+/-7 and 46+/-8 nmol x min(-1) x 100 ml(-1) leg volume, respectively; P<0.05). Insulin infusion increased protein synthesis at rest (51+/-4 nmol x min(-1) x 100 ml(-1) leg volume) but not during the postexercise recovery (64+/-9 nmol x min(-1) x 100 ml(-1) leg volume; P<0.05). Insulin infusion at rest did not change the rate of protein degradation (48+/-3 nmol x min(-1) 100 ml(-1) leg volume). In contrast, insulin infusion after exercise significantly decreased the rate of protein degradation (52+/-9 nmol x min(-1) x 100 ml(-1) leg volume). The insulin stimulatory effects on inward alanine transport and glucose uptake were three times greater during the postexercise recovery than at rest (P<0.05). In contrast, the insulin effects on phenylalanine, leucine, and lysine transport were similar at rest and after exercise. In conclusion, the ability of insulin to stimulate glucose uptake and alanine transport and to suppress protein degradation in skeletal muscle is increased after resistance exercise. Decreased amino acid availability may limit the stimulatory effect of insulin on muscle protein synthesis after exercise.


A comprehensive review of the long-term and short-term treatment of melasma with a triple combination cream.
Melasma is a common disorder of hyperpigmentation and generally involves areas of the face and neck. Hyperpigmentation is especially prevalent in darker complected patients and is often difficult to treat. Hydroquinone, tretinoin, and topical corticosteroids are well established monotherapeutic agents for treating melasma and hyperpigmentation; however, a stable, once-daily formulation triple combination cream containing 0.05% tretinoin, 4.0% hydroquinone, and 0.01% fluocinolone acetonide (Tri-Luma) represents the only commercially available combination of all three agents. This product is approved by the US FDA for the treatment of facial melasma. A number of publications have described the safety and efficacy of triple combination cream in over 2000 patients with melasma, some of whom were treated for >12 months. In the initial 8-week study, 29% of patients experienced complete clearing of melasma by week 8, and 77% were clear or almost clear by week 8. Similarly, good results were seen in the two long-term studies, with the clear/mild rate ranging from 78% to 84% of patients at month 6 and from 81% to 94% of patients at month 12. Adverse events were almost always mild in severity and typically occurred only at the application site. The primary concern for most physicians using corticosteroid-containing products on the face is skin atrophy. However, only two cases of skin atrophy were reported across the three published studies. Overall, the results of these extensive studies indicate that triple combination cream is efficacious in treating melasma and exhibits a safe profile with low potential for adverse events.


Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver.
The metabolism of imipramine by human liver microsomes was examined using a combination of five strategies. Human hepatic microsomes produced N-desmethylimipramine (84%), 2-hydroxyimipramine (10%), and 10-hydroxyimipramine (6%). Preincubation of human hepatocytes in culture with beta-naphthoflavone and macrolides exclusively induced the formation of desmethylimpramine (552%, p < 0.05, and 234%, p < 0.003, respectively). Correlations were obtained between rates of imipramine demethylation and cytochrome P-450 (P-450) 1A2 (r = 0.88, p < 0.001) and P-450 3A (r = 0.80, p < 0.02) concentrations in human liver microsomal preparations from 13 different subjects. Anti-P-450 1A2 and anti-P-450 3A antibodies selectively inhibited N-demethylation (80% and 60%, respectively). N-Demethylation was completely inhibited when anti-1A2 and anti-3A were added simultaneously. Kinetic studies with human microsomes confirm the contribution of two different enzymes in the N-demethylation. The Km of 1A2 was similar to the high affinity Km in human liver microsomes, whereas the Km of 3A was similar to the low affinity Km in human liver microsomes. P-450 1A2 was apparently more efficient than 3A4 (lower Km and higher Vmax) but was expressed in much lower concentration. Human P-450s 1A2 and 3A4 expressed in yeast efficiently produced desmethylimipramine. These results suggest that P-450 1A2 and P-450 3A4 are the major enzymes involved in imipramine N-demethylation in human hepatic microsomes. Similar experiments were conducted using P-450 2D6, and they confirmed that P-450 2D6 catalyzes imipramine 2-hydroxylation. Interindividual variations in 3A4 hepatic content may explain the large variations in imipramine blood levels observed after uniform dosages and thus may explain the variations in clinical efficacy. Caution might be advised in the clinical use of tricyclic antidepressants when drugs are also administered that induce or inhibit P-450s 3A4 and 1A2.


Wheelchair collaborative control for disabled users navigating indoors.
Mobility is of key importance for autonomous living. Persons with severe disabilities may be assisted by robotic wheelchairs when manual control is not possible. However, these persons should contribute to control as much as they can to avoid loss of residual skills and frustration. Traditionally, wheelchair shared control approaches either give control to person or robot depending on the situation. We propose a new shared control technique where robot and person contribute simultaneously to control. Their commands are weighted according to their respective local efficiencies and then combined via a reactive navigation strategy. Thus, assistance adapts to the user's needs. We refer to this approach as collaborative control. Collaborative control was tested in a home environment in Fondazione Santa Lucia (Rome) by 18 volunteers presenting different degrees of physical and cognitive disability. All of them successfully finished a complex test path with assistance. Both users and caregivers' opinion on the system was very positive. Acceptance was very good according to the psychosocial impact of assistive devices scale. Collaborative control adapts to the person's needs and assists him/her when necessary, locally compensating any problem related to specific disabilities. An ANOVA returned a p-value of 0.016, meaning that there is significant improvement in task performance when collaborative control is used.


Analysis of ROH patterns in the Noriker horse breed reveals signatures of selection for coat color and body size.
Overlapping runs of homozygosity (ROH islands) shared by the majority of a population are hypothesized to be the result of selection around a target locus. In this study we investigated the impact of selection for coat color within the Noriker horse on autozygosity and ROH patterns. We analyzed overlapping homozygous regions (ROH islands) for gene content in fragments shared by more than 50% of horses. Long-term assortative mating of chestnut horses and the small effective population size of leopard spotted and tobiano horses resulted in higher mean genome-wide ROH coverage (SROH ) within the range of 237.4-284.2 Mb, whereas for bay, black and roan horses, where rotation mating is commonly applied, lower autozygosity (SROH from 176.4-180.0 Mb) was determined. We identified seven common ROH islands considering all Noriker horses from our dataset. Specific islands were documented for chestnut, leopard spotted, roan and bay horses. The ROH islands contained, among others, genes associated with body size (ZFAT, LASP1 and LCORL/NCAPG), coat color (MC1R in chestnut and the factor PATN1 in leopard spotted horses) and morphogenesis (HOXB cluster in all color strains except leopard spotted horses). This study demonstrates that within a closed population sharing the same founders and ancestors, selection on a single phenotypic trait, in this case coat color, can result in genetic fragmentation affecting levels of autozygosity and distribution of ROH islands and enclosed gene content.


Modulation of cognitive performance and mood by aromas of peppermint and ylang-ylang.
This study provides further evidence for the impact of the aromas of plant essential oils on aspects of cognition and mood in healthy participants. One hundred and forty-four volunteers were randomly assigned to conditions of ylang-ylang aroma, peppermint aroma, or no aroma control. Cognitive performance was assessed using the Cognitive Drug Research computerized assessment battery, with mood scales completed before and after cognitive testing. The analysis of the data revealed significant differences between conditions on a number of the factors underpinning the tests that constitute the battery. Peppermint was found to enhance memory whereas ylang-ylang impaired it, and lengthened processing speed. In terms of subjective mood peppermint increased alertness and ylang-ylang decreased it, but significantly increased calmness. These results provide support for the contention that the aromas of essential oils can produce significant and idiosyncratic effects on both subjective and objective assessments of aspects of human behavior. They are discussed with reference to possible pharmacological and psychological modes of influence.


Quantitative assessment of the sensitivity of various commercial reverse transcriptases based on armored HIV RNA.
The in-vitro reverse transcription of RNA to its complementary DNA, catalyzed by the enzyme reverse transcriptase, is the most fundamental step in the quantitative RNA detection in genomic studies. As such, this step should be as analytically sensitive, efficient and reproducible as possible, especially when dealing with degraded or low copy RNA samples. While there are many reverse transcriptases in the market, all claiming to be highly sensitive, there is need for a systematic independent comparison of their applicability in quantification of rare RNA transcripts or low copy RNA, such as those obtained from archival tissues. We performed RT-qPCR to assess the sensitivity and reproducibility of 11 commercially available reverse transcriptases in cDNA synthesis from low copy number RNA levels. As target RNA, we used a serially known number of Armored HIV RNA molecules, and observed that 9 enzymes we tested were consistently sensitive to ∼1,000 copies, seven of which were sensitive to ∼100 copies, while only 5 were sensitive to ∼10 RNA template copies across all replicates tested. Despite their demonstrated sensitivity, these five best performing enzymes (Accuscript, HIV-RT, M-MLV, Superscript III and Thermoscript) showed considerable variation in their reproducibility as well as their overall amplification efficiency. Accuscript and Superscript III were the most sensitive and consistent within runs, with Accuscript and Superscript II ranking as the most reproducible enzymes between assays. We therefore recommend the use of Accuscript or Superscript III when dealing with low copy number RNA levels, and suggest purification of the RT reactions prior to downstream applications (eg qPCR) to augment detection. Although the results presented in this study were based on a viral RNA surrogate, and applied to nucleic acid lysates derived from archival formalin-fixed paraffin embedded tissue, their relative performance on RNA obtained from other tissue types may vary, and needs future evaluation.


Percutaneous ethanol injection for the treatment of axillary osmidrosis.
The development of body odour, especially in the armpits, a condition known as axillary osmidrosis, is a common condition that is annoying to patients and can cause them considerable social embarrassment. Ablation of the apocrine glands is the mainstay of treatment, and various methods have been used to achieve this; however, most involve some form of surgery or invasive treatment, and can result in complications. To evaluate the effectiveness and complications of percutaneous ethanol injection (PEI) for the treatment of axillary osmidrosis. In total, 165 patients were treated with PEI for bilateral axillary osmidrosis. After local anaesthesia, 90% ethanol was injected into the subcutaneous layer near the interface of the dermis, where the sweat glands are located. The average amount of ethanol injected per side was 8.9 mL. The mean follow-up period was 14.5 months (range 10-28). Of the 165 patients, 80 (48.5%) had their outcome rated as 'excellent', 72 patients (43.6%) as 'good', 10 (6.1%) as 'fair' and only 3 (1.8%) as 'poor'. The majority of the patients having excellent to good results considered themselves satisfied with the results [152/165 (92.1%)]. Two patients developed necrosis of the axillary skin, for which surgical repair was performed. Superficial epidermolysis or local skin necrosis occurred in 15 patients; they were treated conservatively with antibiotic ointment, and the lesions healed without sequelae. Treatment of osmidrosis with PEI seems to be a valid alternative approach to open surgery. It has advantage of minimizing recovery time and postoperative immobilization. It is also inexpensive, relatively safe, and can be performed on an outpatient basis.


Enkephalin degradation in the guinea-pig ileum: effect of aminopeptidase inhibitors, puromycin and bestatin.
Degradation of enkephalin by aminopeptidases has been established as an important functional mechanism that terminates the pharmacological action of enkephalins in the guinea-pig ileum. Aminopeptidases are a family of enzymes and little is known regarding the specificity of individual enzymes with respect to the degradation of enkephalins. Puromycin is a general inhibitor of aminopeptidases and bestatin is a more selective inhibitor of Leu-aminopeptidases and aminopeptidase B. Both agents are capable of inhibiting enkephalin degradation in broken cell preparations from brain. However, only bestatin enhanced the pharmacological response to enkephalin in the guinea-pig ileum and ileal longitudinal muscle. Bestatin enhanced the response to enkephalin in a concentration-dependent fashion. Furthermore, bestatin also decreased the formation of [3H]Tyr and increased [3H]Leu-enkephalin content after incubation of the guinea-pig ileum with [3H]Leu-enkephalin. In contrast, puromycin did not shift the concentration-response curve to Met-enkephalin in either the intact guinea-pig ileum or the ileal longitudinal muscle and, likewise, no alteration in the degradation of [3H]Leu- or Met-enkephalin occurred with puromycin. A small enhancing effect of puromycin on the duration of the inhibitory effect of enkephalin was observed only in the guinea-pig longitudinal muscle. This enhancement cannot be explained by an effect on enkephalin degradation, but may be related to some other action of puromycin. These data support the importance of aminopeptidase activity to the degradation of enkephalin and indicate that enzymes which have properties in common with Leu-aminopeptidases rather than arylamidases may be the primary aminopeptidases responsible for terminating the pharmacological actions of enkephalins in intact guinea-pig ileal preparations.


Inhibition by d-limonene of experimental hepatocarcinogenesis in Sprague-Dawley rats does not involve p21(ras) plasma membrane association.
The effects of d-limonene on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) and on membrane-associated p21(ras) and labeling and apoptotic indices of the liver were investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks, and from the beginning of experimental week 9, they received chow pellets containing 1% or 2% limonene. The preneoplastic and neoplastic liver lesions (cellular alteration foci, neoplastic nodules and hepatocellular carcinomas), and hepatic foci staining positive for glutathione-S-transferase, placental type (GST-P) were examined microscopically and histochemically. At week 16, quantitative histologic analysis showed that oral administration of 1% or 2% limonene resulted in significant reductions in the number and mean area of GST-P-positive hepatic foci and the number of cellular alteration foci, neoplastic nodules and hepatocellular carcinomas. Limonene, at both doses, also caused significant decreases in the labeling indices and significant increases in the apoptotic indices of cellular alteration foci, neoplastic nodules, hepatocellular carcinomas and adjacent liver. However, limonene, at both doses, had no significant influence on the production of membrane-associated p21(ras) in the visible liver white nodules. These findings indicate that limonene inhibits hepatocarcinogenesis and suggest that this effect may be clearly related to its effect in inhibiting cell proliferation and in enhancing apoptosis, but not through ras oncoprotein plasma membrane association.


Infection after shoulder arthroplasty.
Between 1972 and 1994, 2279 patients underwent primary shoulder arthroplasty (2512 shoulders) and 194 patients underwent revision shoulder arthroplasty (222 shoulders) at the authors' institution. Of these, 18 patients with primary shoulder arthroplasties (19 shoulders) and seven patients with revision shoulder arthroplasties (seven shoulders) were diagnosed with deep periprosthetic infection. Additionally, during this period, seven patients (seven shoulders) with primary shoulder arthroplasties and one patient (one shoulder) with a previously revised shoulder arthroplasty were referred to the authors' institution for treatment of deep periprosthetic infection. Two patients (two shoulders) were excluded because of incomplete medical records and with component removal performed elsewhere. The average time from arthroplasty to the diagnosis of infection was 3.5 years (range, 0-14.8 years). The patients were divided into four groups on the basis of treatment. Group I comprised 20 patients (21 shoulders) who underwent resection arthroplasty. Six of the 21 shoulders had additional episodes of infection. Group II comprised six patients (six shoulders) who underwent debridement and prosthetic retention. Three of the six shoulders failed this treatment with subsequent reinfection and underwent a resection arthroplasty. Group III comprised two patients (two shoulders) who had removal of the prosthesis, debridement, and immediate reimplantation. One patient underwent resection arthroplasty 9 months after direct exchange because of reinfection. Group IV comprised three patients (three shoulders) who had removal of the prosthesis, debridement, and delayed reimplantation. Reinfection has not occurred in any of these patients. At final followup, patients with a prosthesis in situ had better pain relief and shoulder function than patients treated with resection arthroplasty. Delayed reimplantation may offer the best hope for pain relief, eradication of infection, and maintenance of shoulder function.


Genetic epidemiology of rheumatoid arthritis.
We conducted family studies and segregation analyses of rheumatoid arthritis (RA) that were based on consecutive patients with RA ascertained without regard to family history or known risk factors. First-degree relatives from 135 simplex and 30 multiplex families were included in the analyses. A highly penetrant recessive major gene, with a mutant allele frequency of .005, was identified as the most parsimonious genetic risk factor. Significant evidence for heterogeneity in risk for RA was observed for proband gender but not for proband age at onset. Kaplan-Meier risk analysis demonstrated significant evidence for differences in the distribution of risk among first-degree relatives. These analyses demonstrated that both proband gender and age at onset are important risk factors but that proband gender appears to be the more important determinant of risk, with relatives of male probands having the greatest cumulative risk for RA. In addition, log-linear modeling identified proband gender, familiality (multiplex or simplex), and an interaction term between these two variables as being adequate to define the distribution of risk in families. The pattern of risk for RA among susceptible individuals and its inheritance is thus heterogeneous. For future genetic analyses, families with an excess of affected males having a young age at onset may be the most informative in identifying the putative recessive gene and its modifiers.


COVID-19 associated mortality and cardiovascular disease outcomes among US women veterans.
The burden of COVID-19 has been noted to be disproportionately greater in minority women, a population that is nevertheless still understudied in COVID-19 research. We conducted an observational study to examine COVID-19-associated mortality and cardiovascular disease outcomes after testing (henceforth index) among a racially diverse adult women veteran population. We assembled a retrospective cohort from a Veterans Affairs (VA) national COVID-19 shared data repository, collected between February and August 2020. A case was defined as a woman veteran who tested positive for SARS-COV-2, and a control as a woman veteran who tested negative. We used Kaplan-Meier curves and the Cox proportional hazards model to examine the distribution of time to death and the effects of baseline predictors on mortality risk. We used generalized linear models to examine 60-day cardiovascular disease outcomes. Covariates studied included age, body mass index (BMI), and active smoking status at index, and pre-existing conditions of diabetes, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and a history of treatment with antiplatelet or anti-thrombotic drug at any time in the 2 years prior to the index date. Women veterans who tested positive for SARS-CoV-2 had 4 times higher mortality risk than women veterans who tested negative (Hazard Ratio 3.8, 95% Confidence Interval CI 2.92 to 4.89) but had lower risk of cardiovascular events (Odds Ratio OR 0.78, 95% CI 0.66 to 0.92) and developing new heart disease conditions within 60 days (OR 0.67, 95% CI 0.58 to 0.77). Older age, obesity (BMI > 30), and prior CVD and COPD conditions were positively associated with increased mortality in 60 days. Despite a higher infection rate among minority women veterans, there was no significant race difference in mortality, cardiovascular events, or onset of heart disease. SARS-CoV-2 infection increased short-term mortality risk among women veterans similarly across race groups. However, there was no evidence of increased cardiovascular disease incidence in 60 days. A longer follow-up of women veterans who tested positive is warranted.


A neural network-based exploratory learning and motor planning system for co-robots.
Collaborative robots, or co-robots, are semi-autonomous robotic agents designed to work alongside humans in shared workspaces. To be effective, co-robots require the ability to respond and adapt to dynamic scenarios encountered in natural environments. One way to achieve this is through exploratory learning, or "learning by doing," an unsupervised method in which co-robots are able to build an internal model for motor planning and coordination based on real-time sensory inputs. In this paper, we present an adaptive neural network-based system for co-robot control that employs exploratory learning to achieve the coordinated motor planning needed to navigate toward, reach for, and grasp distant objects. To validate this system we used the 11-degrees-of-freedom RoPro Calliope mobile robot. Through motor babbling of its wheels and arm, the Calliope learned how to relate visual and proprioceptive information to achieve hand-eye-body coordination. By continually evaluating sensory inputs and externally provided goal directives, the Calliope was then able to autonomously select the appropriate wheel and joint velocities needed to perform its assigned task, such as following a moving target or retrieving an indicated object.


Cutaneous manifestations of lymphomatoid granulomatosis. Report of 44 cases and a review of the literature.
A review of records of 44 patients who had lymphomatoid granulomatosis (LYG) with skin lesions showed that cutaneous manifestations are protean and generally transient. Subcutaneous or dermal nodules were present in more than 60% of cases. A maculopapular rash or macular erythema was less common, and ulceration was rare. Skin lesions were widely distributed. Frequently, in patients who had early cutaneous involvement with LYG, associated involvement of the nervous system and joints occurred. Findings from laboratory studies were generally inconclusive. Lymphomatoid granulomatosis progressed to lymphoma in 18% of the cases, and death from respiratory failure was common. Theories on the possible cause and the pathogenesis of LYG are presented.


Theory of spontaneous vesicle formation in surfactant mixtures.
The curvature elastic energy of bilayer vesicles formed by a mixture of two surfactants, which individually form either micelles or lamellar bilayer phases is described theoretically. In the limit of large bending elastic modulus K being much greater than the temperature T, the free energy is minimized by vesicles with different concentrations of the two surfactants in each monolayer of the bilayer. Vesicles are more stable than lameliar structures only when interactions or complexing of the two surfactants is taken into account.


Familial correlations of HDL subclasses based on gradient gel electrophoresis.
We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the familial correlations of high density lipoprotein (HDL) subclasses for 150 offspring in 47 nuclear families. The absorbance of protein stain was used as an index of mass concentrations at intervals of 0.01 nm within five HDL subclasses: HDL3c (7.2-7.8 nm), HDL3b (7.8-8.2 nm), HDL3a (8.2-8.8 nm), HDL2a (8.8-9.7 nm), and HDL2b (9.7-12 nm). Parent-offspring correlations were computed for two different characterizations of the parents: 1) by sex (i.e., mother versus father) and 2) by their relative values (highest versus lowest HDL). Sibling resemblance was assessed by using the intraclass correlations coefficient. Family members were significantly related for the following subclasses: HDL3c (sibling and father-offspring), HDL3b (sibling), HDL3a (sibling and mother-offspring), HDL2a (mother-offspring), and HDL2b (sibling, father-offspring, and mother-offspring). The offsprings' HDL3c and HDL2b values were more strongly related to their fathers' than to their mothers' values, whereas their HDL2a levels were more strongly related to their mothers' than their fathers' values. In addition, fathers' HDL2b levels were inversely correlated with the offsprings' HDL3b. The parents' HDL subclass levels were more strongly related to subclass levels of their younger (< or = 20 years) than their older offspring. Among all subclasses, HDL2b showed the strongest parent-offspring relation, with the parents' HDL values accounting for over 30% of the variance in offsprings' HDL2b.(ABSTRACT TRUNCATED AT 250 WORDS)


Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies.
Autoantibodies against the extracellular domains of the voltage-gated potassium channel (VGKC) complex proteins, leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-2 (CASPR2), are found in patients with limbic encephalitis, faciobrachial dystonic seizures, Morvan's syndrome and neuromyotonia. However, in routine testing, VGKC complex antibodies without LGI1 or CASPR2 reactivities (double-negative) are more common than LGI1 or CASPR2 specificities. Therefore, the target(s) and clinical associations of double-negative antibodies need to be determined. Sera (n=1131) from several clinically defined cohorts were tested for IgG radioimmunoprecipitation of radioiodinated α-dendrotoxin (125I-αDTX)-labelled VGKC complexes from mammalian brain extracts. Positive samples were systematically tested for live hippocampal neuron reactivity, IgG precipitation of 125I-αDTX and 125I-αDTX-labelled Kv1 subunits, and by cell-based assays which expressed Kv1 subunits, LGI1 and CASPR2. VGKC complex antibodies were found in 162 of 1131 (14%) sera. 90 of these (56%) had antibodies targeting the extracellular domains of LGI1 or CASPR2. Of the remaining 72 double-negative sera, 10 (14%) immunoprecipitated 125I-αDTX itself, and 27 (38%) bound to solubilised co-expressed Kv1.1/1.2/1.6 subunits and/or Kv1.2 subunits alone, at levels proportionate to VGKC complex antibody levels (r=0.57, p=0.0017). The sera with LGI1 and CASPR2 antibodies immunoprecipitated neither preparation. None of the 27 Kv1-precipitating samples bound live hippocampal neurons or Kv1 extracellular domains, but 16 (59%) bound to permeabilised Kv1-expressing human embryonic kidney 293T cells. These intracellular Kv1 antibodies mainly associated with non-immune disease aetiologies, poor longitudinal clinical-serological correlations and a limited immunotherapy response. Double-negative VGKC complex antibodies are often directed against cytosolic epitopes of Kv1 subunits and occasionally against non-mammalian αDTX. These antibodies should no longer be classified as neuronal-surface antibodies. They consequently lack pathogenic potential and do not in themselves support the use of immunotherapies.


A Transform-Based Feature Extraction Approach for Motor Imagery Tasks Classification.
In this paper, we present a new motor imagery classification method in the context of electroencephalography (EEG)-based brain-computer interface (BCI). This method uses a signal-dependent orthogonal transform, referred to as linear prediction singular value decomposition (LP-SVD), for feature extraction. The transform defines the mapping as the left singular vectors of the LP coefficient filter impulse response matrix. Using a logistic tree-based model classifier; the extracted features are classified into one of four motor imagery movements. The proposed approach was first benchmarked against two related state-of-the-art feature extraction approaches, namely, discrete cosine transform (DCT) and adaptive autoregressive (AAR)-based methods. By achieving an accuracy of 67.35%, the LP-SVD approach outperformed the other approaches by large margins (25% compared with DCT and 6 % compared with AAR-based methods). To further improve the discriminatory capability of the extracted features and reduce the computational complexity, we enlarged the extracted feature subset by incorporating two extra features, namely, Q- and the Hotelling's [Formula: see text] statistics of the transformed EEG and introduced a new EEG channel selection method. The performance of the EEG classification based on the expanded feature set and channel selection method was compared with that of a number of the state-of-the-art classification methods previously reported with the BCI IIIa competition data set. Our method came second with an average accuracy of 81.38%.


Pediatric living donor lobar lung transplantation.
Living donor lobar lung transplantation (LDLLT) was developed in order to mitigate the growing competition for deceased donor (DD) lungs and resultant increase in waiting list mortality. Because each of the two donor lobes serves as an entire lung for the recipient, donors who are taller than the recipient are preferred. Therefore LDLLT is particularly well suited for pediatric recipients for whom adults serve as donors. Although long-term outcomes after LDLLT reported by the Organ Procurement and Transplantation Network (OPTN) are worse compared with DD recipients, overall pediatric outcomes as well as single center reports from the most experienced programs are more promising. Particularly encouraging are the findings that bronchiolitis obliterans (OB) is less frequent or less severe in LDLLT recipients in comparison to DD recipients. Moreover, outcomes may be improved by careful selection of donors to ensure adequately sized donor lobes and minimization of infectious risks. Although no donor deaths have been reported, there is a moderate risk of significant short-term complications. Long-term follow-up has not been reported. The use of LDLLT has decreased in recent years, and the recent change by the OPTN to an urgency/benefit allocation system for DD lungs in patients 12 yr and older may further reduce the demand. Nonetheless, we anticipate that LDLLT will continue to be utilized in select circumstances, particularly in children under 12 where access to DD organs remains challenging.


'Delaying' a saccade: Preparatory phase cortical hemodynamics evince the neural cost of response inhibition.
Minimally delayed (MD) saccades require inhibition of a prepotent response until a target is extinguished, and unlike the more extensively studied antisaccade task, do not require the additional cognitive component of vector inversion (i.e., 180° target spatial transposition). Here, participants completed separate blocks of MD and prepotent stimulus-driven saccades (i.e., respond at target onset) while cortical hemodynamics were measured via functional transcranial Doppler ultrasound. MD saccades produced longer and more variable reaction times (RT). In turn, MD and stimulus-driven saccade preparatory phase cortical hemodynamics increased and decreased, respectively, relative to baseline and the two conditions differed from one another throughout the preparatory phase. The longer RTs and increased cortical hemodynamics of MD saccades is taken to evince response complexity and the increased neural activity to accommodate response inhibition. To our knowledge, such findings provide the first work to examine the neural foundations of MD saccades.


Effect of glycemic exposure on the risk of microvascular complications in the diabetes control and complications trial--revisited.
The Diabetes Control and Complications Trial (Diabetes 44:968-983, 1995) presented statistical models suggesting that subjects with similar A1C levels had a higher risk of retinopathy progression in the conventional treatment group than in the intensive treatment group. That analysis has been cited to support the hypothesis that specific patterns of glucose variation, in particular postprandial hyperglycemia, contribute uniquely to an increased risk of microvascular complications above and beyond that explained by the A1C level. We performed statistical evaluations of these models and additional analyses to assess whether the original analyses were flawed. Statistically, we show that the original results are an artifact of the assumptions of the statistical model used. Additional analyses show that virtually all (96%) of the beneficial effect of intensive versus conventional therapy on progression of retinopathy is explained by the reductions in the mean A1C levels, similarly for other outcomes. Furthermore, subjects within the intensive and conventional treatment groups with similar A1C levels over time have similar risks of retinopathy progression, especially after adjusting for factors in which they differ. A1C explains virtually all of the difference in risk of complications between the intensive and conventional groups, and a given A1C level has similar effects within the two treatment groups. While other components of hyperglycemia, such as glucose variation, may contribute to the risk of complications, such factors can only explain a small part of the differences in risk between intensive and conventional therapy over time.


Rapid Endothelialization of Off-the-Shelf Small Diameter Silk Vascular Grafts.
Synthetic vascular grafts for small diameter revascularization are lacking. Clinically available conduits expanded polytetrafluorethylene and Dacron fail acutely due to thrombosis and in the longer term from neointimal hyperplasia. We report the bioengineering of a cell-free, silk-based vascular graft. In vitro we demonstrate strong, elastic silk conduits that support rapid endothelial cell attachment and spreading while simultaneously resisting blood clot and fibrin network formation. In vivo rat studies show complete graft patency at all time points, rapid endothelialization, and stabilization and contraction of neointimal hyperplasia. These studies show the potential of silk as an off-the-shelf small diameter vascular graft.


Prevalence and treatment of mental disorders in Lebanon: a national epidemiological survey.
Mental disorders are believed to account for a large portion of disease burden worldwide. However, no national studies have been undertaken to assess this assumption in the Arab world. As part of the WHO World Mental Health (WMH) Survey Initiative, a nationally representative psychiatric epidemiological survey of 2857 adults (aged 18 years) was done in Lebanon between September, 2002, and September, 2003, through a study called LEBANON (Lebanese Evaluation of the Burden of Ailments and Needs Of the Nation). 12-month prevalence and severity of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) disorders, and treatment were assessed with the WHO Composite International Diagnostic Interview (CIDI, version 3.0). Information was also obtained for sociodemographics and exposure to traumatic events in the Lebanon wars. 308 (17.0%) of respondents met criteria for at least one 12-month DSM-IV/CIDI disorder, 108 (27.0%) of whom were classified serious and an additional 112 (36.0%) moderate. Nearly half of respondents had a history of exposure to war-related traumatic events. Significantly elevated odds ratios (OR) of mood, anxiety, and impulse-control disorders were associated with two (OR 2.0-3.6) or more (2.2-9.1) war-related traumatic events, resulting in substantially higher proportions of moderate and severe 12-month mental disorders in respondents exposed to multiple war-related traumata (16.8-20.4%) compared with other respondents (3.3-3.5%). Only 47 (10.9%) respondents with 12-month disorders obtained treatment. 85% of people were treated in the general medical sector and the mental-health-care system, and the rest by religious or spiritual advisers, counsellors, herbalists, or fortune-tellers. Mental disorders are common in Lebanon, with a prevalence equivalent to that in Western Europe. However, the number of individuals with mental disorders who are not receiving treatment is considerably higher in Lebanon than in Western countries.


Rho GTPases and the actin cytoskeleton.
The actin cytoskeleton mediates a variety of essential biological functions in all eukaryotic cells. In addition to providing a structural framework around which cell shape and polarity are defined, its dynamic properties provide the driving force for cells to move and to divide. Understanding the biochemical mechanisms that control the organization of actin is thus a major goal of contemporary cell biology, with implications for health and disease. Members of the Rho family of small guanosine triphosphatases have emerged as key regulators of the actin cytoskeleton, and furthermore, through their interaction with multiple target proteins, they ensure coordinated control of other cellular activities such as gene transcription and adhesion.


Pigmented villonodular synovitis of the knee: average five-year follow-up of arthroscopic treatment.
We have reviewed the results of arthroscopic treatment of pigmented villonodular synovitis (PVNS) with reference to both recurrence and to function. Between 1985 and 1995, a single surgeon treated eight patients. At an average 5-year follow-up, all patients were interviewed and had assessment of Hospital for Special Surgery (HSS) knee score for both the affected and unaffected knees. Also recorded were age, sex, and whether disease was recurrent, localized, or diffuse. Disease recurred in 4 patients, all with diffuse PVNS, and 3 of them required a further arthroscopic synovectomy at a mean of 16 months after the index procedure. All patients had good or excellent functional results. There was no significant difference between HSS knee scores for affected and unaffected knees. Arthroscopic synovectomy is a successful treatment in patients with localized PVNS of the knee and results in a knee that is functionally not different from its unaffected partner.


Properties of low moisture composite materials consisting of oil droplets dispersed in a protein-carbohydrate-glycerol matrix: effect of continuous phase composition.
The influence of continuous phase composition on the properties of low moisture (<3% water) composite materials consisting of oil droplets dispersed in a protein-carbohydrate-glycerol matrix was investigated. These composites were produced by blending canola oil (62.3%), whey protein concentrate (1.7%, WPC), and corn syrup and glycerol together (36.0% combined) using a high speed mixer equipped with a whisk. The polyol composition was varied by changing the ratio of corn syrup to glycerol in the system while keeping the total concentration of these two polyol components constant. Some composites were analyzed directly after preparation ("unbaked"), while others were analyzed after heating at 176 degrees C for 10 min to simulate baking of a food product ("baked"). The "lightness" of the composites was greater before baking (higher L value), but the color intensity of the composites was greater after baking (higher b value), which was attributed to Maillard browning reactions. The brownness of the baked composites increased with increasing corn syrup concentration, which was attributed to Maillard browning reactions. Squeezing flow viscometry indicated that the consistency and yield stress of the composites increased with baking, which was attributed to whey protein unfolding and aggregation. These rheological parameters also increased with increasing corn syrup concentration, which was attributed to its influence on the continuous phase rheology and on the interactions between the whey proteins. This study shows that the continuous phase composition and thermal history of low moisture composite materials have a large impact on their final physicochemical properties.


Increased expression of tight junction protein occludin is associated with the protective effect of mosapride against aspirin-induced gastric injury.
Mosapride is known to affect gastric motility, however whether mosapride has anti-ulcergenic effects in gastric mucosal injury is unclear. The aim of the present study was to investigate the effects of mosapride on aspirin-induced gastric injuries. GES-1 cells were cultured and divided into 5 groups: Control group, aspirin injury group (treated with 18.2 mmol/l aspirin) and mosapride pretreatment groups (treated with 0.4, 0.5, or 0.6 µmol/l mosapride). Cell proliferation was evaluated via MTT assay and cell apoptosis was investigated via flow cytometry. The expression of occludin was determined by western blot analysis. A total of 40 male Sprague-Dawley rats were randomized into five groups: Control group, aspirin injury group (150 mg/kg) and mosapride pretreatment groups (0.25, 0.50 or 0.75 mg/kg). Gastric mucosal lesions were induced by administering 200 mg/kg aspirin daily for 4 days. Rats in the mosapride groups were pretreated with mosapride 1 h prior to aspirin administration. Histological changes were evaluated under a light microscope and gastric epithelial TJs were observed via transmission electron microscopy. The results revealed that cell apoptosis was significantly increased in the aspirin injury group compared with the control (P<0.05), whereas apoptosis was significantly decreased in the mosapride pretreatment groups compared with the aspirin group (P<0.05). Cell viability was significantly increased in the mosapride pretreatment groups compared with the aspirin injury group (P<0.05), and that of the aspirin injury group was significantly decreased compared with the control group (P<0.05). Compared with the aspirin injury group, occludin expression was significantly increased in the three mosapride pre-treatment groups (all P<0.05). It was also demonstrated that gastric damage was significantly attenuated in the mosapride pretreatment groups compared with the aspirin injury group (P<0.05). Impaired TJ integrity was observed in aspirin injury group, whereas TJs in the mosapride groups were almost intact. In conclusion, the results of the present study suggest that mosapride exerts a gastroprotective action on aspirin-induced gastric mucosal injury at least in part via attenuating cell apoptosis and increasing occludin expression.


Enhanced performance of methamphetamine lateral flow cassettes using an electronic lateral flow reader.
Surface contamination from methamphetamine in meth labs continues to be a problem. We had previously developed a lateral flow assay cassette for field detection of methamphetamine contamination that is commercially available and has been used by a number of groups to assess contamination. This cassette uses the complete disappearance of the test line as an end point for detection of 50 ng/100 cm2 of methamphetamine contamination for surface sampling with cotton swabs. In the present study, we further evaluate the response of the cassettes using an electronic lateral flow reader to measure the intensities of the test and control lines. The cassettes were capable of detecting 0.25 ng/ml for calibration solutions. For 100 cm2 ceramic tiles that were spiked with methamphetamine and wiped with cotton-tipped wooden swabs wetted in assay/sampling buffer, 1 ng/tile was detected using the reader. Semi-quantitative results can be produced over the range 0-10 ng/ml for calibration solutions and 0-25 ng/tile for spiked tiles using either a 4-parameter logistic fit of test line intensity versus concentration or spiked mass or the ratio of the control line to the test line intensity fit to concentration or spiked mass. Recovery from the tiles was determined to be about 30% using the fitted curves. Comparison of the control line to the test line was also examined as a possible visual detection end point and it was found that the control line became more intense than the test line at 0.5 to 1 ng/ml for calibration solutions or 1 to 2 ng/tile for spiked tiles. Thus the lateral flow cassettes for methamphetamine have the potential to produce more sensitive semi-quantitative results if an electronic lateral flow reader is used and can be more sensitive for detection if the comparison of the control line to the test line is used as the visual end point.


Transcriptome and proteome profiling of neural stem cells from the human subventricular zone in Parkinson's disease.
It is currently accepted that the human brain has a limited neurogenic capacity and an impaired regenerative potential. We have previously shown the existence of CD271-expressing neural stem cells (NSCs) in the subventricular zone (SVZ) of Parkinson's disease (PD) patients, which proliferate and differentiate towards neurons and glial cells in vitro. To study the molecular profile of these NSCs in detail, we performed RNA sequencing and mass spectrometry on CD271+ NSCs isolated from human post-mortem SVZ and on homogenates of the SVZ. CD271+ cells were isolated through magnetic cell separation (MACS). We first compared the molecular profile of CD271+ NSCs to the SVZ homogenate from control donors and then compared CD271+ cells to CD11b+ microglia. These results confirmed their neural stem cell identity. Finally we compared controls and PD patients to establish a specific molecular profile of NSCs and the SVZ in PD. While our transcriptome analysis did not identify any differentially expressed genes in the SVZ between control and PD patients, our proteome analysis revealed several proteins that were differentially expressed in PD. Some of these proteins are involved in cytoskeletal organization and mitochondrial function. Transcriptome and proteome analyses of NSCs from PD revealed changes in the expression of genes and proteins involved in metabolism, transcriptional activity and cytoskeletal organization. Our data suggest that NSCs may transit into a primed-quiescent state, that is in an "alert" non-proliferative phase in PD. Our results not only confirm pathological hallmarks of PD (e.g. impaired mitochondrial function), but also show that the NSCs from SVZ undergo significant changes at both transcriptome and proteome level following PD.


Association between telomere length and chromosome 21 nondisjunction in the oocyte.
Chromosome 21 nondisjunction in oocytes is the most common cause of trisomy 21, the primary chromosomal abnormality responsible for Down syndrome (DS). This specific type of error is estimated to account for over 90 % of live births with DS, with maternal age being the best known risk factor for chromosome 21 nondisjunction. The loss of telomere length and the concomitant shortening of chromosomes are considered a biological marker for aging. Thus, we tested the hypothesis that mothers who had a maternal nondisjunction error leading to a live birth with DS (n = 404) have shorter telomeres than mothers with live births without DS (n = 42). In effect, our hypothesis suggests that mothers of children with DS will appear "biologically older" as compared to the mothers of euploid children. We applied a quantitative PCR assay to measure the genome-wide relative telomere length to test this hypothesis. The results of our study support the hypothesis that young mothers of DS babies are "biologically older" than mothers of euploid babies in the same age group and supports telomere length as a biomarker of age and hence risk for chromosome nondisjunction.


Questions about intimate partner violence should be part of contraceptive counselling: findings from a community-based longitudinal study in Nicaragua.
The study aim was to examine whether exposure to intimate partner violence (IPV) was associated with reversible contraceptive use in ever-pregnant partnered women. The authors conducted a longitudinal panel study in León municipality, Nicaragua. At baseline (2002-2003), 478 pregnant women were interviewed and 398 were available for questioning about contraceptive use 40-47 months after childbirth. IPV was assessed at baseline and follow-up, with women classified as never abused, ending abuse, continued abuse or new abuse. Reversible contraceptive use was defined as women using any form of contraception apart from sterilisation. Adjusted odds ratios (AORs) were used to assess the association between reversible contraceptive use, IPV patterns and IPV exposures at follow-up. Eighty percent of the women were not pregnant and with a partner at follow-up. Half were using reversible contraceptives and 28% were sterilised. Women exposed to a continued abuse pattern (AOR 2.50, 95% CI 11.04-5.99), and those exposed to emotional (AOR 2.80, 95% CI 1.32-5.95), physical (AOR 3.60, 95% CI 1.15-11.10) or any IPV at follow-up (AOR 2.59, 95% CI 1.24-5.40) had higher odds of reversible contraceptive use than those not exposed, even after adjusting for demographic factors. No significant differences in the type of reversible contraceptive used were found between women exposed or not to IPV. IPV exposure was associated with more reversible contraceptive use. Abuse inquiring at health facilities providing contraceptives should be implemented to identify women exposed to IPV and provide adequate support.


Relations between amount and type of alcohol and colon and rectal cancer in a Danish population based cohort study.
There may be a weak association between total alcohol intake and colorectal cancer but the effect of different types of alcohol and effect on colon subsites have not been investigated satisfactorily. To investigate the relationship between amount and type of alcohol and the risk of colon and rectal cancer. A population based cohort study with baseline assessment of weekly intake of beer, wine, and spirits, smoking habits, body mass index, educational level, and leisure time physical activity in Copenhagen, Denmark. The study included a random sample of 15 491 men and 13 641 women, aged 23-95 years. Incident cases of colorectal cancer were identified in the nationwide Danish Cancer Register. During a mean follow up of 14.7 years, we observed 411 colon cancers and 202 rectal cancers. We observed a dose-response relationship between alcohol and rectal cancer. Drinkers of more than 41 drinks a week had a relative risk of rectal cancer of 2.2 (95% confidence limits 1.0-4.6) compared with non-drinkers. Drinkers of more than 14 drinks of beer and spirits a week, but not wine, had a risk of 3.5 (1.8-6.9) of rectal cancer compared with non-drinkers, while those who drank the same amount of alcohol but including more than 30% of wine had a risk of 1.8 (1.0-3.2) of rectal cancer. No relation between alcohol and colon cancer was found when investigating the effects of total alcohol, beer, wine, and spirits, and percentage of wine of total alcohol intake. Alcohol intake is associated with a significantly increased risk of rectal cancer but the risk seems to be reduced when wine is included in the alcohol intake.


Glucocorticoids induce a near-total suppression of hyaluronan synthase mRNA in dermal fibroblasts and in osteoblasts: a molecular mechanism contributing to organ atrophy.
Glucocorticoid (GC) administration induces atrophy of skin, bone, and other organs, partly by reducing tissue content of glycosaminoglycans, particularly hyaluronic acid (HA). We took advantage of the recent cloning of the three human hyaluronan synthase (HAS) enzymes (HAS1, HAS2 and HAS3), to explore the molecular mechanisms of this side effect. Northern and slot blots performed on RNA extracted from cultured dermal fibroblasts and the MG-63 osteoblast-like osteosarcoma cell line indicated that HAS2 is the predominant HAS mRNA in these cells. Incubation of both cell types for 24 h in the presence of 10(-6) M dexamethasone (DEX) resulted in a striking 97--98% suppression of HAS2 mRNA levels. Time-course studies in fibroblasts demonstrated suppression of HAS2 mRNA to 28% of control by 1 h, and to 1.2% of control by 2 h, after addition of DEX. Dose-response studies in fibroblasts indicated that the majority of the suppressive effect required concentrations characteristic of cell-surface GC receptors, a point confirmed by persistent DEX-induced suppression in the presence of RU486, an antagonist of classic cytosolic steroid hormone receptors. Nuclear run-off experiments showed a 70% suppression of HAS2 gene transcription in nuclei from DEX-treated fibroblasts, which is unlikely to fully explain the rapid 50--80-fold reduction in message levels. Experiments with actinomycin D (AMD) demonstrated that the message half-life was 25 min in cells without DEX, whereas the combination of AMD with DEX dramatically increased the half-life of HAS2 mRNA, suggesting that DEX acts by inducing a short-lived destabilizer of the HAS2 message. Direct assessment of HAS2 mRNA stability by wash-out of incorporated uridine label established a half-life of 31 min in cells without DEX, which substantially shortened in the presence of DEX. In conclusion, GCs induce a rapid and sustained, near-total suppression of HAS2 message levels, mediated through substantial decreases in both gene transcription and message stability. These effects may contribute to the loss of HA in GC-treated organs.


Deep vein thrombosis: risk factors and prevention in surgical patients.
Deep vein thrombosis (DVT) is a cause of preventable morbidity and mortality in hospitalized surgical patients. The occurrence of the disease is related to presence of risk factors, which are related primarily to trauma, venous stasis and hyper-coagulability. DVT seems not to be taken seriously by many surgeons in Nigeria. This is despite comprehensive studies that show no real differences in racial demography of the disease. To highlight the importance of physician awareness about DVT especially its risks and prevention methods. A detailed literature search was completed to extrapolate articles that described DVT risks and prevention. This involved hand and online searches. Specific search terms used included DVT/risk factors/prevention. The searches generated 468 papers. Of these 57 papers were included in the review. Predominant risk factors for DVT include middle or old age, prolonged surgery, trauma, confinement, presence of malignancy and insertion of deep venous catheters. In women, contraceptive use, hormone replacement therapy, pregnancy and the puepernum are a additional risk factors. Prophylactic measures include those directed at eliminating venous stasis and those directed at changes in blood coagulability. Deep Venous Thrombosis is a common disease with fatal and serious long term burdensome complications. We must target primary and secondary prophylaxis to improve survival and reduce morbidity from this preventable disease.


Young Zanzibari children with iron deficiency, iron deficiency anemia, stunting, or malaria have lower motor activity scores and spend less time in locomotion.
Motor activity improves cognitive and social-emotional development through a child's exploration of his or her physical and social environment. This study assessed anemia, iron deficiency, hemoglobin (Hb), length-for-age Z-score (LAZ), and malaria infection as predictors of motor activity in 771 children aged 5-19 mo. Trained observers conducted 2- to 4-h observations of children's motor activity in and around their homes. Binary logistic regression assessed the predictors of any locomotion. Children who did not locomote during the observation (nonmovers) were excluded from further analyses. Linear regression evaluated the predictors of total motor activity (TMA) and time spent in locomotion for all children who locomoted during the observation combined (movers) and then separately for crawlers and walkers. Iron deficiency (77.0%), anemia (58.9%), malaria infection (33.9%), and stunting (34.6%) were prevalent. Iron deficiency with and without anemia, Hb, LAZ, and malaria infection significantly predicted TMA and locomotion in all movers. Malaria infection significantly predicted less TMA and locomotion in crawlers. In walkers, iron deficiency anemia predicted less activity and locomotion, whereas higher Hb and LAZ significantly predicted more activity and locomotion, even after controlling for attained milestone. Improvements in iron status and growth and prevention or effective treatment of malaria may improve children's motor, cognitive, and social-emotional development either directly or through improvements in motor activity. However, the relative importance of these factors is dependent on motor development, with malaria being important for the younger, less developmentally advanced children and Hb and LAZ becoming important as children begin to attain walking skills.


Combined genetic mutations and DNA-methylated genes as biomarkers for endometrial cancer detection from cervical scrapings.
Endometrial cancer is a common gynecologic cancer. Noninvasive molecular biomarkers for triage of high-risk patients for invasive procedures are needed. Based on the success of cytological Pap smear screening, cervical scrapings are a good source of DNA for molecular testing. In addition to genetic lesions, DNA methylation is a promising biomarker. We assessed the usefulness of combining genetic and epigenetic biomarkers from cervical scrapings to detect endometrial carcinomas. We performed a retrospective case-control study of 96 consecutive cervical scrapings from patients with abnormal uterine bleeding who underwent surgery for diagnostic evaluation. Thirty and 16 cases were diagnosed with type I and type II endometrial cancers, respectively. The remaining non-cancer cases included normal endometrium (n = 12), benign uterine lesions (n = 20), and endometrial hyperplasia (n = 18). Quantitative methylation-specific PCR and mass spectrometry were used for DNA methylation and genetic mutation analysis. Logistic regression was used to evaluate the clinical performance of these candidate biomarkers. We tested the effectiveness of the methylation status of four genes (BHLHE22, CDO1, TBX5, and HAND2) in endometrial cancer detection. The area under the receiver operating characteristic curves ranged from 0.703 to 0.878, and panels of hypermethylated BHLHE22/CDO1/HAND2 (87.0% sensitivity and 86.0% specificity) and BHLHE22/CDO1/TBX5 (89.1% sensitivity and 80.0% specificity) showed significant differences and could distinguish benign from malignant endometrial lesions. The sensitivity and specificity in endometrial cancer detection for BHLHE22/CDO1 were 84.8% and 88.0%, respectively. Both type I and II endometrial carcinomas could be detected using a BHLHE22/CDO1-based methylation profile, suggesting that they may have common epigenomes. Moreover, PTEN and TP53 mutations were found in 63.3% of type I and 93.6% of type II endometrial cancers. Unexpectedly, PTEN and TP53 mutations were commonly found in cervical scrapings of the normal endometrium (25% and 33.3%, respectively) and in cases with benign uterine lesions (10% and 50%, respectively). Finally, combinations of any one mutation of PTEN and TP53 mutations had a sensitivity of 91.3%, but a specificity of only 42.0%. Adding PTEN/TP53 mutation testing to BHLHE22/CDO1-based methylation testing did not improve the detection of endometrial cancer.


The clinical and cost effectiveness of steroid injection compared with night splints for carpal tunnel syndrome: the INSTINCTS randomised clinical trial study protocol.
Patients diagnosed with idiopathic mild to moderate carpal tunnel syndrome (CTS) are usually managed in primary care and commonly treated with night splints and/or corticosteroid injection. The comparative effectiveness of these interventions has not been reliably established nor investigated in the medium and long term. The primary objective of this trial is to investigate whether corticosteroid injection is effective in reducing symptoms and improving hand function in mild to moderate CTS over 6 weeks when compared with night splints. Secondary objectives are to determine specified comparative clinical outcomes and cost effectiveness of corticosteroid injection over 6 and 24 months. A multicentre, randomised, parallel group, clinical pragmatic trial will recruit 240 adults aged ≥18 years with mild to moderate CTS from GP Practices and Primary-Secondary Care Musculoskeletal Interface Clinics. Diagnosis will be by standardised clinical assessment. Participants will be randomised on an equal basis to receive either one injection of 20 mg Depo-Medrone or a night splint to be worn for 6 weeks. The primary outcome is the overall score of the Boston Carpal Tunnel Questionnaire (BCTQ) at 6 weeks. Secondary outcomes are the BCTQ symptom severity and function status subscales, symptom intensity, interrupted sleep, adherence to splinting, perceived benefit and satisfaction with treatment, work absence and reduction in work performance, EQ-5D-5L, referral to surgery and health utilisation costs. Participants will be assessed at baseline and followed up at 6 weeks, 6, 12 and 24 months. The primary analysis will use an intention to treat (ITT) approach and multiple imputation for missing data. The sample size was calculated to detect a 15 % greater improvement in the BTCQ overall score in the injection group compared to night-splinting at approximately 90 % power, 5 % two-tailed significance and allows for 15 % loss to follow-up. The trial makes an important contribution to the evidence base available to support effective conservative management of CTS in primary care. No previous trials have directly compared these treatments for CTS in primary care populations, reported on clinical effectiveness at more than 6 months nor compared cost effectiveness of the interventions. Trial registration: EudraCT 2013-001435-48 (registered 05/06/2013), ClinicalTrials.gov NCT02038452 (registered 16/1/2014), and Current Controlled Trials ISRCTN09392969 (retrospectively registered 01/05/2014).


Antityrosinase and antimicrobial activities of trans-cinnamaldehyde thiosemicarbazone.
Tyrosinase (EC 18.104.22.168) is a key enzyme in pigment biosynthesis of organisms. trans-Cinnamaldehyde thiosemicarbazone, a derivative of benzaldehyde thiosemicarbazone, was synthesized as an inhibitor of tyrosinase. The inhibitory effects of this compound on the activity of mushroom tyrosinase were investigated. The results showed that trans-cinnamaldehyde thiosemicarbazone could potently inhibit both monophenolase activity and diphenolase activity of tyrosinase. For monophenolase activity, trans-cinnamaldehyde thiosemicarbazone could not only lengthen the lag time but also decrease the steady-state rate. For diphenolase activity, the IC(50) value was determined to be 5.72 microM. Kinetic analyses showed that trans-cinnamaldehyde thiosemicarbazone was a reversible and mixed type inhibitor on this enzyme. The inhibition constants (K(I) and K(IS)) were determined to be 4.45 and 8.85 muM, respectively. Furthermore, the antibacterial activity against Bacillus subtilis, Escherichia coli, Staphyloccocus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, and Agrobacterium tumefaciens was investigated. The results showed that trans-cinnamaldehyde thiosemicarbazone was more effective against B. subtilis and S. aureus with the same minimum inhibitory concentration (MIC) of 50 microg/mL and with the same minimum bactericidal concentration (MBC) of 50 microg/mL.


Axin expression enhances herpes simplex virus type 1 replication by inhibiting virus-mediated cell death in L929 cells.
Herpes simplex virus type 1 (HSV-1) replicates in various cell types and induces early cell death, which limits viral replication in certain cell types. Axin is a scaffolding protein that regulates Wnt signalling and participates in various cellular events, including cellular proliferation and cell death. The effects of axin expression on HSV-1 infection were investigated based on our initial observation that Wnt3a treatment or axin knockdown reduced HSV-1 replication. L929 cells expressed the axin protein in a doxycycline-inducible manner (L-axin) and enhanced HSV-1 replication in comparison to control cells (L-EV). HSV-1 infection induced cell death as early as 6 h after infection through the necrotic pathway and required de novo protein synthesis in L929 cells. Subsequent analysis of viral protein expression suggested that axin expression led to suppression of HSV-1-induced premature cell death, resulting in increased late gene expression. In analysis of axin deletion mutants, the regulators of the G-protein signalling (RGS) domain were involved in the axin-mediated enhancement of viral replication and reduction in cell death. These results suggest that viral replication enhancement might be mediated by the axin RGS domain.


Pasteurella multocida Bacteremia in an Immunocompromised Patient.
We present the case of a 61-year-old Caucasian gentleman who presented with a one-day history of fever, chills, and altered mental status. His symptoms were initially thought to be secondary to cellulitis. Blood cultures grew Pasteurella multocida, a rare pathogen to cause bacteremia. Our patient was treated with ciprofloxacin for two weeks and made a complete and uneventful recovery. Our patient's uncontrolled diabetes mellitus and chronic kidney disease put him at a higher risk for developing serious P. multocida infection. The patient's dog licking the wounds on his legs was considered as the possible source of infection. As P. multicoda bacteremia is rare, but severe with a high mortality rate, it is imperative to have a high index of suspicion for this infection especially in the vulnerable immunocompromised population.


Genic regions of a large salamander genome contain long introns and novel genes.
The basis of genome size variation remains an outstanding question because DNA sequence data are lacking for organisms with large genomes. Sixteen BAC clones from the Mexican axolotl (Ambystoma mexicanum: c-value = 32 x 10(9) bp) were isolated and sequenced to characterize the structure of genic regions. Annotation of genes within BACs showed that axolotl introns are on average 10x longer than orthologous vertebrate introns and they are predicted to contain more functional elements, including miRNAs and snoRNAs. Loci were discovered within BACs for two novel EST transcripts that are differentially expressed during spinal cord regeneration and skin metamorphosis. Unexpectedly, a third novel gene was also discovered while manually annotating BACs. Analysis of human-axolotl protein-coding sequences suggests there are 2% more lineage specific genes in the axolotl genome than the human genome, but the great majority (86%) of genes between axolotl and human are predicted to be 1:1 orthologs. Considering that axolotl genes are on average 5x larger than human genes, the genic component of the salamander genome is estimated to be incredibly large, approximately 2.8 gigabases! This study shows that a large salamander genome has a correspondingly large genic component, primarily because genes have incredibly long introns. These intronic sequences may harbor novel coding and non-coding sequences that regulate biological processes that are unique to salamanders.


Technology insight: adult mesenchymal stem cells for osteoarthritis therapy.
Despite the high prevalence and morbidity of osteoarthritis (OA), an effective treatment for this disease is currently lacking. Restoration of the diseased articular cartilage in patients with OA is, therefore, a challenge of considerable appeal to researchers and clinicians. Techniques that cause multipotent adult mesenchymal stem cells (MSCs) to differentiate into cells of the chondrogenic lineage have led to a variety of experimental strategies to investigate whether MSCs instead of chondrocytes can be used for the regeneration and maintenance of articular cartilage. MSC-based strategies should provide practical advantages for the patient with OA. These strategies include use of MSCs as progenitor cells to engineer cartilage implants that can be used to repair chondral and osteochondral lesions, or as trophic producers of bioactive factors to initiate endogenous regenerative activities in the OA joint. Targeted gene therapy might further enhance these activities of MSCs. Delivery of MSCs might be attained by direct intra-articular injection or by graft of engineered constructs derived from cell-seeded scaffolds; this latter approach could provide a three-dimensional construct with mechanical properties that are congruous with the weight-bearing function of the joint. Promising experimental and clinical data are beginning to emerge in support of the use of MSCs for regenerative applications.


[Profile of children and adolescents with autism spectrum disorders in an institution in Bogota, Colombia].
To determine the profile of children and adolescents diagnosed with autism spectrum disorder (ASD) in a comprehensive care centre in Bogota, Colombia. A descriptive-correlational study with a sample of patients who had attended the institution from 2003 to 2009. Demographic and clinical aspects were evaluated and a correlation between the diagnosis and severity being analysed in search for risk factors. A total of 138 patients were studied. The average age of onset was 21 months, and diagnosis had been made at 45 months. There was a male predominance (6.15:1). The predominant diagnosis was autistic syndrome (83%), followed by pervasive developmental disorder not otherwise specified (17%). There was no pathological background in the family history, during pregnancy or during the neonatal period. Motor development during the first year was normal but acquisition of language skills was compromised. The specific signs of ASD as regards the disorder in itself, communication skills, spontaneous speech, verbal comprehension, attention, imitation, use of objects, self-care and symbolic play were significantly related to the severity of the disease. Diagnosis of ASD is still delayed in our population and usually after referral from someone other than a health professional. The most important problems were found in communication skills and relationships with peers. The study did not show significant associated risk factors.


Structural asymmetry in the Thermus thermophilus RuvC dimer suggests a basis for sequential strand cleavages during Holliday junction resolution.
Holliday junction (HJ) resolvases are structure-specific endonucleases that cleave four-way DNA junctions (HJs) generated during DNA recombination and repair. Bacterial RuvC, a prototypical HJ resolvase, functions as homodimer and nicks DNA strands precisely across the junction point. To gain insights into the mechanisms underlying symmetrical strand cleavages by RuvC, we performed crystallographic and biochemical analyses of RuvC from Thermus thermophilus (T.th. RuvC). The crystal structure of T.th. RuvC shows an overall protein fold similar to that of Escherichia coli RuvC, but T.th. RuvC has a more tightly associated dimer interface possibly reflecting its thermostability. The binding mode of a HJ-DNA substrate can be inferred from the shape/charge complementarity between the T.th. RuvC dimer and HJ-DNA, as well as positions of sulfate ions bound on the protein surface. Unexpectedly, the structure of T.th. RuvC homodimer refined at 1.28 Å resolution shows distinct asymmetry near the dimer interface, in the region harboring catalytically important aromatic residues. The observation suggests that the T.th. RuvC homodimer interconverts between two asymmetric conformations, with alternating subunits switched on for DNA strand cleavage. This model provides a structural basis for the 'nick-counter-nick' mechanism in HJ resolution, a mode of HJ processing shared by prokaryotic and eukaryotic HJ resolvases.


The influence of maternal psychosocial characteristics on infant feeding styles.
Maternal feeding styles in infancy and early childhood are associated with children's later risk for overweight and obesity. Maternal psychosocial factors that influence feeding styles during the complementary feeding period, the time during which infants transition from a milk-based diet to one that includes solid foods and other non-milk products, have received less attention. The present study explores how maternal psychosocial factors-specifically self-esteem, parenting self-efficacy, parenting satisfaction, and depression symptoms-influence mothers' infant feeding styles at nine months of age, a time during which solid foods eating habits are being established. Participants included 160 low-income, African-American mother-infant pairs in central North Carolina who were enrolled in the Infant Care and Risk of Obesity Study. Regression models tested for associations between maternal psychosocial characteristics and pressuring and restrictive feeding styles. Models were first adjusted for maternal age, education, marital status and obesity status. To account for infant characteristics, models were then adjusted for infant weight-for-length, distress to limitations and activity level scores. Maternal self-esteem was negatively associated with pressuring to soothe. Maternal parenting self-efficacy was positively associated with restriction-diet quality. Maternal parenting satisfaction and depression symptoms were not associated with feeding styles in the final models. Focusing on strengthening maternal self-esteem and parenting self-efficacy may help to prevent the development of less desirable infant feeding styles.


Results of non-operative and operative treatment of humeral shaft fractures. A series of 104 cases.
The aim of this study was to examine the results of different modalities applied in the treatment of 104 fresh diaphyseal fractures of the adult humerus treated in the department between January 1994 and March 1997. These results were classified according to the criteria described by Stewart and Hundley. 32 patients (30.8%) were treated non-operatively using a sling and a moulded plaster splint. The type of treatment had to be changed in 12 of these patients due to 14 different complications that occurred during the course of non-operative treatment. Thus, 20 patients (62.5%) underwent non-operative treatment until fracture-union. The results in this group were: very good in 12 cases (60%), good in 5 cases (25%), fair in 3 cases (15%). 28 fractures were treated using plates and screws. 4 events (14%) occurred during in the post-operative period and, apart from 2 cases of non-union, the overall result in the 26 patients in whom the fracture united was: very good in 23 cases (88.5%) and good in 3 cases (11.5%). 22 patients (21.1%) underwent fixation using multiple flexible intramedullary wires via a supracondylar approach. Apart from one case of non-union, the final result in the 21 patients in whom the fracture united was: very good in 9 cases (42.8%), good in 9 cases (42.8%), fair in 2 cases (9.5%) and poor in 1 case (4.9%). 22 fractures were treated using an intramedullary Seidel nail. The final result in these patients was: very good in 11 cases (50%), good in 9 cases (41%) and poor in 2 cases (9%). The indications for treatment should be eclectic. Non-operative treatment remains the method of choice for undisplaced or minimally-displaced fractures or comminuted fractures with multiple parallel longitudinal fracture-lines over the middle-third, while surgical treatment is considered for displaced fractures and essentially depends upon the type and level of the fracture. Transverse and short oblique fractures are treated using a plate or a Seidel nail. Fractures with a third fragment require plate osteosynthesis. Multiple flexible intramedullary wires are used for segmental fractures or for diaphyseal fractures associated with fractures of the neck of the humerus. Comminuted fractures are realigned using an intramedullary Seidel nail or multiple flexible wires. As far as the site of fracture is concerned, those of the proximal and middle thirds of the humerus are well treated using an intramedullary nail or multiple wires or with a plate, while plating is most often the method of choice for fractures of the distal-third.


Trunk muscle strength in athletes.
Maximal voluntary strength of the trunk muscles was measured in 57 male elite athletes (soccer players, wrestlers, tennis players, and gymnasts), 14 female elite gymnasts, and in a normal group of 87 conscripts. Mean ages in the different groups ranged from 18-22 yr. An isokinetic (constant velocity) technique was used to record maximal torque produced by trunk and hip muscles during flexion, extension, and lateral flexion over the range of motion. The constant angular velocities used were 15 deg.s-1 and 30 deg.s-1, respectively. Isometric strength was measured in a straight body position (0 deg. of flexion). The measurements were made with the subjects in a horizontal position with the pivot point at the hip and at the lumbar (L2-L3) level. All male athlete groups showed higher peak torque values than the normals. The differences were largest in hip extension and trunk flexion. The male gymnasts also showed significantly higher peak values in hip flexion as compared to all other categories. There was no difference in strength per kg body weight between female gymnasts and untrained males, except in trunk extension. The position for peak torque occurred earlier in the movements for the athletes, especially for the gymnasts in extension movements and for the tennis players in flexion movements. In isometric contractions essentially the same strength differences were present as in the slow isokinetic contractions. In lateral flexion wrestlers and tennis players showed significantly higher strength in movements toward the nondominant side. Thus, differences were present between the athletes and the normals, some of which appeared to be sport specific and related to long-term systematic training.(ABSTRACT TRUNCATED AT 250 WORDS)


Non-linearities in apparent mass and transmissibility during exposure to whole-body vertical vibration.
The causes of low back pain associated with prolonged exposure to whole-body vibration are not understood. An understanding of non-linearities in the biomechanical responses is required to identify the mechanisms responsible for the dynamic characteristics of the body, to allow for the non-linearities when predicting the influence of seating dynamics, and to predict the adverse effects caused by various magnitudes of vibration. Twelve subjects were exposed to six magnitudes, 0.25-2.5ms(-2) rms, of vertical random vibration in the frequency range 0.2-20Hz. The apparent masses of the subjects were determined together with transmissibilities measured from the seat to various locations on the body surface: the upper and lower abdominal wall, at L3, over the posterior superior iliac spine and the iliac crest. There were significant reductions in resonance frequencies for both the apparent mass and the transmissibilities to the lower abdomen with increases in vibration magnitude. The apparent mass resonance frequency reduced from 5.4-4. 2Hz as the magnitude of the vibration increased from 0.25-2.5ms(-2) rms. Vertical motion of the lumbar spine and pelvis showed resonances at about 4Hz and between 8 and 10Hz. When exposed to vertical vibration, the human body shows appreciable non-linearities in its biodynamic responses. Biodynamic models should be developed to reflect the non-linearity.


Angiography-derived index of microcirculatory resistance as a novel, pressure-wire-free tool to assess coronary microcirculation in ST elevation myocardial infarction.
Immediate assessment of coronary microcirculation during treatment of ST elevation myocardial infarction (STEMI) may facilitate patient stratification for targeted treatment algorithms. Use of pressure-wire to measure the index of microcirculatory resistance (IMR) is possible but has inevitable practical restrictions. We aimed to develop and validate angiography-derived index of microcirculatory resistance (IMRangio) as a novel and pressure-wire-free index to facilitate assessment of the coronary microcirculation. 45 STEMI patients treated with primary percutaneous coronary intervention (pPCI) were enrolled. Immediately before stenting and at completion of pPCI, IMR was measured within the infarct related artery (IRA). At the same time points, 2 angiographic views were acquired during hyperaemia to measure quantitative flow ratio (QFR) from which IMRangio was derived. In a subset of 15 patients both IMR and IMRangio were also measured in the non-IRA. Patients underwent cardiovascular magnetic resonance imaging (CMR) at 48 h for assessment of microvascular obstruction (MVO). IMRangio and IMR were significantly correlated (ρ: 0.85, p < 0.001). Both IMR and IMRangio were higher in the IRA rather than in the non-IRA (p = 0.01 and p = 0.006, respectively) and were higher in patients with evidence of clinically significant MVO (> 1.55% of left ventricular mass) (p = 0.03 and p = 0.005, respectively). Post-pPCI IMRangio presented and area under the curve (AUC) of 0.96 (CI95% 0.92-1.00, p < 0.001) for prediction of post-pPCI IMR > 40U and of 0.81 (CI95% 0.65-0.97, p < 0.001) for MVO > 1.55%. IMRangio is a promising tool for the assessment of coronary microcirculation. Assessment of IMR without the use of a pressure-wire may enable more rapid, convenient and cost-effective assessment of coronary microvascular function.


The 17-residue transmembrane domain of beta-galactoside alpha 2,6-sialyltransferase is sufficient for Golgi retention.
beta-Galactoside alpha 2,6-sialyltransferase (ST) is a type II integral membrane protein of the Golgi apparatus involved in the sialylation of N-linked glycans. A series of experiments has shown that the 17-residue transmembrane domain of ST is sufficient to confer localization to the Golgi apparatus when transferred to the corresponding region of a cell surface type II integral membrane protein. Lectin affinity chromatography of chimeric proteins bearing this 17-residue sequence suggests that these chimeric proteins are localized in the trans-Golgi cisternae and/or trans-Golgi network. Further experiments suggest that this 17-residue sequence functions as a retention signal for the Golgi apparatus.


An international initiative to identify genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA).
BRCA1 and BRCA2 mutations exhibit variable penetrance that is likely to be accounted for, in part, by other genetic factors among carriers. However, studies aimed at identifying these factors have been limited in size and statistical power, and have yet to identify any convincingly validated modifiers of the BRCA1 and BRCA2 phenotype. To generate sufficient statistical power to identify modifier genes, the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) has been established. CIMBA contains about 30 affiliated groups who together have collected DNA and clinical data from approximately 10,000 BRCA1 and 5,000 BRCA2 mutation carriers. Initial efforts by CIMBA to identify modifiers of breast cancer risk for BRCA1 and BRCA2 mutation carriers have focused on validation of common genetic variants previously associated with risk in smaller studies of carriers or unselected breast cancers. Future studies will involve replication of findings from pathway-based and genome-wide association studies in both unselected and familial breast cancer. The identification of genetic modifiers of breast cancer risk for BRCA1 and BRCA2 mutation carriers will lead to an improved understanding of breast cancer and may prove useful for the determination of individualized risk of cancer amongst carriers.


An analytic model of the stereodynamics of rotationally inelastic molecular collisions.
We develop an analytic model of vector correlations in rotationally inelastic atom-diatom collisions and test it against the much examined Ar-NO (X(2)Pi) system. Based on the Fraunhofer scattering of matter waves, the model furnishes complex scattering amplitudes needed to evaluate the polarization moments characterizing the quantum stereodynamics. The analytic polarization moments are found to be in an excellent agreement with experimental results and with close-coupling calculations available at thermal energies. The model reveals that the stereodynamics is governed by diffraction from the repulsive core of the Ar-NO potential, which can be characterized by a single Legendre moment.


USP47 is a deubiquitylating enzyme that regulates base excision repair by controlling steady-state levels of DNA polymerase β.
DNA base excision repair (BER) is an essential cellular process required for genome stability, and misregulation of BER is linked to premature aging, increased rate of mutagenesis, and cancer. We have now identified the cytoplasmic ubiquitin-specific protease USP47 as the major enzyme involved in deubiquitylation of the key BER DNA polymerase (Pol β) and demonstrate that USP47 is required for stability of newly synthesized cytoplasmic Pol β that is used as a source for nuclear Pol β involved in DNA repair. We further show that knockdown of USP47 causes an increased level of ubiquitylated Pol β, decreased levels of Pol β, and a subsequent deficiency in BER, leading to accumulation of DNA strand breaks and decreased cell viability in response to DNA damage. Taken together, these data demonstrate an important role for USP47 in regulating DNA repair and maintaining genome integrity.


Unconventional Resilience: An Operational Model.
This is the third of nine planned papers drawn from the findings of our ethnographic study entitled "The Impact of Catastrophic Injury Exposure on Resilience in Special Operations Surgical Teams." Building from our strategic framework, this paper will establish that resilience is better understood as cohesive adaptation within a Special Operation Forces (SOF) cultural ecosystem. Exploring unconventional resilience as the inter-relationship across the organization, team, and individual, we will use qualitative quotes to describe the ecosystem of dynamic freedom of maneuver in ambiguity. To achieve our goals, we will: 1) compare conventional and unconventional resilience to operationalize the components of our strategic framework; 2) use qualitative quotes to show how the ecosystem of unconventional resilience functions at each level supporting our operational model; and 3) describe how the operational model of unconventional resilience links to tactical performance through five social determinants. We conclude by gesturing to how transformational change-agency applies to practical performance of all SOF medics.


The use of human experience data in the EU risk assessment process.
The incorporation of human experience data (HD) into the risk assessment process is encouraged by various authorities with the aim of improving the robustness of the subsequent findings. HD, however, can present in many forms, ranging from epidemiological studies to the accumulated experiences from poison centers. This diversity of the human experience, combined with the manner in which it may (or may not) present, creates several challenges for risk assessors if they are to give available HD due weight in the RA process. An evaluation was made of how HD has been cited and used within the 64 human health RAs published by the EU to the end of 2005. In all RAs, HD had been cited to some degree. But there was no consistency between how cited data had subsequently been taken forward and used in the evaluation of different endpoints, either between the RAs authored by the same or different EU Member States. The lack of any accepted guidance for addressing the role that HD can play within the RA process appears to lead to this situation. Recommendations are provided on the scope and focus such guidance could usefully be expected to take.