Accelerating Implementation of Virtual Care in an Integrated Health Care System: Future Research and Operations Priorities.
Virtual care is critical to Veterans Health Administration (VHA) efforts to expand veterans' access to care. Health care policies such as the Veterans Access, Choice, and Accountability (CHOICE) Act and the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act impact how the VHA provides care. Research on ways to refine virtual care delivery models to meet the needs of veterans, clinicians, and VHA stakeholders is needed. Given the importance of virtual approaches for increasing access to high-quality VHA care, in December 2019, we convened a Think Tank, Accelerating Implementation of Virtual Care in VHA Practice, to consider challenges to virtual care research and practice across the VHA, discuss novel approaches to using and evaluating virtual care, assess perspectives on virtual care, and develop priorities to enhance virtual care in the VHA. We used a participatory approach to develop potential priorities for virtual care research and activities at the VHA. We refined these priorities through force-ranked prioritization and group discussion, and developed solutions for selected priorities. Think Tank attendees (n = 18) consisted of VHA stakeholders, including operations partners (e.g., Office of Rural Health, Office of Nursing Services, Health Services Research and Development), clinicians (e.g., physicians, nurses, psychologists, physician assistants), and health services researchers. We identified an initial list of fifteen potential priorities and narrowed these down to four. The four priorities were (1) scaling evidence-based practices, (2) centralizing virtual care, (3) creating high-value care within the VHA with virtual care, and (4) identifying appropriate patients for virtual care. Our Think Tank took an important step in setting a partnered research agenda to optimize the use of virtual care within the VHA. We brought together research and operations stakeholders and identified possibilities, partnerships, and potential solutions for virtual care.


Personal dust exposures at a food processing facility.
A field study was performed to quantify personal dust exposures at a food processing facility. A review of the literature shows very little exposure information in the food processing industry. The processing area consisted of a series of four rooms, connected by a closed-loop ventilation system, housed within a larger warehouse-type facility. Workers were exposed to various fruit and vegetable dusts during the grinding, sieving, mixing and packaging of freeze-dried or air-dried products. Eight two-hour periods were monitored over two days. Personal total suspended particulate samples were collected on 37 mm PVC filters with 5 microm pore size according to National Institute for Occupational Safety and Health (NIOSH) Method 0500. The filters were analyzed gravimetrically. The two-hour task sampling personal dust exposures ranged from 0.33-103 mg/m3. For each worker, an eight-hour time weighted average (TWA) concentration was calculated, and these ranged from 3.08-59.8 mg/m3. Although there are no directly appropriate occupational exposure limits that may be used for comparison, we selected the Threshold Limit Value (TLV) for particulates not otherwise classified (PNOC) of 10 mg/m3 for inhalable particles. Neglecting the respiratory protection used, five out of eight of the worker time-weighted averages exceeded the TLV. It should be noted that the TLV is based on the inhalable fraction and in this study total suspended particulate was measured; additionally, the TLV is applicable for dusts that are insoluble or poorly soluble, and have low toxicity, which may have limited protective ability in this case due to the irritant nature of certain dusts (e.g., jalapeno peppers, aloe vera). Sieving resulted in significantly higher exposure than grinding and blending. Measuring area concentrations alone in this environment is not a sufficient method of estimating personal exposures due to work practices for some operations.


The changing epidemiology of chickenpox in Alberta.
Varicella vaccine was licensed in Canada in 1998. The province of Alberta introduced a universal publicly funded varicella vaccination program in 2001. To describe the epidemiology of non-fatal cases of chickenpox for which publicly funded health services were utilized for the period 1986-2002. We used the records of Alberta's universal, publicly funded health care insurance system to identify cases of chickenpox for the period 1986-2002. The earliest dated utilization of a health service for which there was an ICD9-CM code of 052.xx or an IC10-CA code of B01.xx was used as the date of illness onset. Denominators for rates were estimated using mid-year population estimates from the Alberta Health Care Insurance Registry. Age-specific rates were estimated for each year. The crude incidence of chickenpox significantly declined over the period 1994-2002, most steeply after the year 2000. The incidence of chickenpox varied by age group and year and there was evidence of age-group-year interaction. Among those aged 5-19 years, chickenpox incidence began to decline prior to vaccine licensure in Canada. Among those aged less than one year and those aged 1-4 years, the incidence increased until 1999 when a decline began. Over the period 0.8% of cases were hospitalized. Chickenpox rates began to decline prior to the introduction of the publicly funded vaccination program; however the declines in rates among the youngest age-groups are consistent with a vaccination program effect.


Low-Value Surgical Procedures in Low- and Middle-Income Countries: A Systematic Scoping Review.
Overuse of surgical procedures is increasing around the world and harms both individuals and health care systems by using resources that could otherwise be allocated to addressing the underuse of effective health care interventions. In low- and middle-income countries (LMICs), there is some limited country-specific evidence showing that overuse of surgical procedures is increasing, at least for certain procedures. To assess factors associated with, extent and consequences of, and potential solutions for low-value surgical procedures in LMICs. We searched 4 electronic databases (PubMed, Embase, PsycINFO, and Global Index Medicus) for studies published from database inception until April 27, 2022, with no restrictions on date or language. A combination of MeSH terms and free-text words about the overuse of surgical procedures was used. Studies examining the problem of overuse of surgical procedures in LMICs were included and categorized by major focus: the extent of overuse, associated factors, consequences, and solutions. Of 4276 unique records identified, 133 studies across 63 countries were included, reporting on more than 9.1 million surgical procedures (median per study, 894 [IQR, 97-4259]) and with more than 11.4 million participants (median per study, 989 [IQR, 257-6857]). Fourteen studies (10.5%) were multinational. Of the 119 studies (89.5%) originating from single countries, 69 (58.0%) were from upper-middle-income countries and 30 (25.2%) were from East Asia and the Pacific. Of the 42 studies (31.6%) reporting extent of overuse of surgical procedures, most (36 [85.7%]) reported on unnecessary cesarean delivery, with estimated rates in LMICs ranging from 12% to 81%. Evidence on other surgical procedures was limited and included abdominal and percutaneous cardiovascular surgical procedures. Consequences of low-value surgical procedures included harms and costs, such as an estimated US $3.29 billion annual cost of unnecessary cesarean deliveries in China. Associated factors included private financing, and solutions included social media campaigns and multifaceted interventions such as audits, feedback, and reminders. This systematic review found growing evidence of overuse of surgical procedures in LMICs, which may generate significant harm and waste of limited resources; the majority of studies reporting overuse were about unnecessary cesarean delivery. Therefore, a better understanding of the problems in other surgical procedures and a robust evaluation of solutions are needed.


[Microsporous infection of the scalp in an adult (author's transl)].
Infection of the scalp in an elderly woman due to Microsporum canis (zoophilic, long-lived fungus) after repeated direct contact with infected cats. We think that the infection could occur because of an age-induced decrease in some of the organic functions which govern the healing process of microsporous infections during puberty.


Patterns of type 2 diabetes monitoring in rural towns: How does frequency of HbA1c and lipid testing compare with existing guidelines?
To indicate levels of monitoring of type 2 diabetes in rural and regional Australia by examining patterns of glycated haemoglobin (HbA1c) and blood lipid testing. Retrospective analysis of pathology services data from twenty regional and rural towns in eastern Australia over 24 months. Of 13 105 individuals who had either a single HbA1c result ≥7.0% (53 mmol mol-1 ); or two or more HbA1c tests within the study period. Frequency of testing of HbA1c and blood lipids (cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides) were compared with guideline recommendations. About 58.3% of patients did not have the recommended 6-monthly HbA1c tests and 30.6% did not have annual lipid testing. For those who did not receive tests at the recommended interval, the mean between-test interval was 10.5 months (95% CI = 7.5-13.5) rather than 6 months for HbA1c testing; and 15.7 (95% CI = 13.3-18.1) months rather than annually for blood lipids. For those with at least one out-of-range test result, 77% of patients failed to receive a follow-up HbA1c test and 86.5% failed to receive a follow-up blood lipid test within the recommended 3 months. Patients less than 50 years of age, living in a more remote area and with poor diabetes control were less likely to have testing at the recommended intervals (P < 0.0001). Although poor diabetes testing is not limited to rural areas, more intensive diabetes monitoring is likely to be needed for patients living in non-metropolitan areas, particularly for some subgroups.


SmartMal: a service-oriented behavioral malware detection framework for mobile devices.
This paper presents SmartMal--a novel service-oriented behavioral malware detection framework for vehicular and mobile devices. The highlight of SmartMal is to introduce service-oriented architecture (SOA) concepts and behavior analysis into the malware detection paradigms. The proposed framework relies on client-server architecture, the client continuously extracts various features and transfers them to the server, and the server's main task is to detect anomalies using state-of-art detection algorithms. Multiple distributed servers simultaneously analyze the feature vector using various detectors and information fusion is used to concatenate the results of detectors. We also propose a cycle-based statistical approach for mobile device anomaly detection. We accomplish this by analyzing the users' regular usage patterns. Empirical results suggest that the proposed framework and novel anomaly detection algorithm are highly effective in detecting malware on Android devices.


The kinetic properties and reaction mechanism of histamine methyltransferase from human skin.
The substrate kinetic properties of histamine methyltransferase from human skin were studied at limiting concentrations of both histamine and S-adenosylmethionine. Substrate inhibition by histamine was observed at concentrations above 10 microM. Primary plots showed evidence of a sequential reaction mechanism. The Michaelis constants were derived from secondary plots of slopes from the primary plots ([S]/v versus [S]) versus reciprocal of the second substrate concentration. The mean Km values for histamine and S-adenosylmethionine were 4.2 and 1.8 microM respectively. Histamine in concentrations of 25-100 microM inhibited enzyme activity uncompetitively with respect to S-adenosylmethionine. No substrate inhibition was observed with S-adenosylmethionine. To elucidate the reaction mechanism further, inhibition by the two products, S-adenosylhomocysteine and 1-methylhistamine, was studied. S-Adenosylhomocysteine inhibited non-competitively with respect to histamine and competitively with respect to S-adenosylmethionine. 1-Methylhistamine inhibited non-competitively with respect to histamine and to S-adenosylmethionine. These results are interpreted as providing evidence for an ordered sequential Bi Bi reaction mechanism, with the methyl-group donor S-adenosylmethionine as the first substrate that adds to the enzyme and histamine as the second substrate. 1-Methylhistamine is the first product to leave the enzyme and S-adenosylhomocysteine is the second. The results are discussed in terms of the possible role that this enzyme could play in the modulation of histamine-mediated reactions in skin.


Influence of Different Irrigation Solutions and Instrumentation Techniques on the Amount of Apically Extruded Debris.
The objective of the present study was to evaluate the influence of different irrigation solutions on the amount of extruded residues apically, varying the instrumentation technique in manual, continuous rotation, or reciprocation motions. The amounts of residue for each irrigation solution was also assessed. Two tests were performed. In the first test, 90 mandibular premolars were divided into nine groups (n=10). Each group was subjected to a different technique: ProTaper Universal, WaveOne Gold, or manual instruments, with different irrigation solutions [2.5% sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX) gel, or distilled water]. During the preparation of the root canal, the apically extruded material was collected in previously weighed glass vials. In the second test, irrigation solutions were weighed separately with the same weighing method. Data were analyzed using the Kolmogorov-Smirnov, one-way and two-way ANOVA, Levene, Tukey, and Games-Howell tests. Apically extruded debris was observed in all groups. ProTaper Universal with continuous rotation using 2% CHX gel resulted in the greatest amount of debris (P<0.001). There were significant differences in the amounts of residue among the different groups (P<0.001). Moreover, when the weighing of the irrigation solutions was tested, the 2.5% NaOCl solution produced the greatest amount of residues compared with other irrigation solutions. Different irrigation solutions influenced the amount of apically extruded debris during the preparation of the canal among the different instrumentation techniques. The ProTaper technique using 2% CHX gel resulted in the greatest amount of apically extruded debris.


Movement Variability Increases With Shoulder Pain When Compensatory Strategies of the Upper Body Are Constrained.
This cross-sectional study analyzed the influence of chronic shoulder pain (CSP) on movement variability/kinematics during humeral elevation, with the trunk and elbow motions constrained to avoid compensatory strategies. For this purpose, 37 volunteers with CSP as the injured group (IG) and 58 participants with asymptomatic shoulders as the control group (CG) participated in the study. Maximum humeral elevation (Emax), maximum angular velocity (Velmax), variability of the maximum angle (CVEmax), functional variability (Func_var), and approximate entropy (ApEn) were calculated from the kinematic data. Patients' pain was measured on the visual analogue scale (VAS). Compared with the CG, the IG presented lower Emax and Velmax and higher variability (i.e., CVEmax, Func_var, and ApEn). Moderate correlations were achieved for the VAS score and the kinematic variables Emax, Velmax and variability of curve analysis, Func_varm, and ApEn. No significant correlation was found for CVEmax. In conclusion, CSP results in a decrease of angle and velocity and an increased shoulder movement variability when the neuromuscular system cannot use compensatory strategies to avoid painful positions.


An El Tor cholera outbreak in Maldah district, West Bengal.
An outbreak of cholera occurred in Maldah district, West Bengal during July-August 1998. Attack rate was 34/1000. Cases were more (59.3%) amongst adults (> 15 years.). V. cholerae 01 biotype E1 Tor serotype ogawa was isolated as a single pathogen from 52.9% (9/17 samples examined). All V. cholerae strains belonged to phage type 2 (Basu and Mukherjee scheme) and type 27 (new phage type scheme). The strains were resistant to co-trimoxazole, furazolidone, ampicillin, streptomycin and nalidixic acid.


Greater than age-related changes in brain diffusion of HIV patients after 1 year.
Chronic infection with HIV is associated with neuroinflammation. Prior diffusion tensor imaging (DTI) studies demonstrated increased mean diffusion (MD) and decreased fractional anisotropy (FA) in the white matter (WM) and subcortical brain regions of HIV patients. The current study aims to detect whether there are greater than age-related brain changes in HIV patients after a 1-year follow-up period using DTI. Thirty-nine antiretroviral-stable HIV subjects and 32 HIV-seronegative (SN) controls were evaluated, with neuropsychological tests and DTI, at baseline and after 1 year. MD and FA in the genu and splenium of the corpus callosum and in six other subcortical and white matter regions were evaluated bilaterally. Compared to SN controls, HIV subjects had significantly higher MD in the frontal WM (p = 0.0104) and lower FA in the parietal WM (p = 0.006). After 1 year, HIV subjects showed increase in MD in frontal and parietal WM, putamen, and genu; HIV subjects also showed greater increased genu diffusion than SN controls (p = 0.005). Changes in global cognitive deficit score correlated with changes in MD in the genu and FA in the parietal and frontal WM and putamen (multiple regression, p = 0.0008). Lastly, normal age-dependent changes in frontal WM diffusion and FA in genu and putamen were not observed in HIV subjects. Since increased MD may reflect increased neuroinflammation, our findings suggest greater than normal age-related inflammatory changes in the genu of these HIV patients, which may contribute to the cognitive deficits. Measurements of MD in the genu may be useful for monitoring disease progression in HIV brain infection.


Verification and Utility in the Arabic Commentaries on the Canon of Medicine: Examples from the Works of Fakhr al-Dīn al-Rāzī (d. 1210) and Ibn al-Nafīs (d. 1288).
Although over two dozen Arabic commentaries on the Canon of Medicine were composed between the twelfth and fourteenth centuries, historians of medicine have paid scant attention to them. Instead, these commentaries have often been dismissed as being uncritical expositions that further entrenched the dogma of Galenic/Avicennan medical theory. In this article, I shall show that in fact the opposite was the case for at least a subset of the Canon commentaries from this period. Fakhr al-Dīn al-Rāzī developed a new style of verification commentary across his philosophical corpus that he also deployed in his Canon commentary. Even though Fakhr al-Dīn largely adhered to Galenic/Avicennan medical theory, his commitment to verification (taḥqīq) led him to challenge and critically assess many facets of medical theory based on systematic, philosophical investigations. Ibn al-Nafīs, following in Fakhr al-Dīn's footsteps, undertook a similar, systematic investigation into medical theory in his own Commentary on the Canon. However, in this case, verification led Ibn al-Nafis to challenge and modify several facets of medical theory. Moreover, as a trained, practicing physician, Ibn al-Nafīs also wanted to ensure that his commentary was useful for other practicing physicians. His commentary thus shows how a post-classical physician committed to the principles of verification and utility could employ philosophical argumentation, empirical observations and even occasional experiments to modify key aspects of Galenic/Avicennan medical theory and practice.


Expression of MHC-I and MHC-II antigens in endomyocardial biopsies from patients with viral myocarditis and cardiomyopathy.
In situ expression of major histocompatibility complex (MHC) I and II antigens were examined in endomyocardial biopsy samples from 35 patients with viral myocarditis (VMC) and dilated cardiomyopathy (DCM). Increased expressions of these 2 antigens were observed on endocardia, capillary endothelia, dentritic and mononuclear cell membranes. The expression of sarcolemma was also found in specimens of VMC and DCM. Thus the abnormal expression of MHC is a new marker of autoimmune reactivity directed against cardiac structures.


[Obtaining purified staphylococcal enterotoxin type B].
The authors elaborated a method of purification of staphylococcus enterotoxin, type B, consisting of three stages: the first stage--lyophilization and dialysis of the culture fluid against distilled water for 36 hours, the second stage--precipitation of dialyzed preparation with 2 volumes of ethanol at --15 degrees C, and the third stage--gel-chromatography of the enterotoxin preparation precipitated with alcohol on a column with Sephadex G-100 in a 0.015 M solution of NaCl (pH 7.0). Preparation isolated by the mentioned method possessed enterotoxic activity in a dose of 0.015 mg of protein per 1 kg of cat weight; by antigenic composition it represented a two-component system. In immunization of rabbits with a purified enterotoxin preparation an antiserum with the prevalence of antibodies to enterotoxin, type B, was obtained.


Longitudinal Characterization and Biomarkers of Age and Sex Differences in the Decline of Spatial Memory.
The current longitudinal study examined factors (sex, physical function, response to novelty, ability to adapt to a shift in light/dark cycle, brain connectivity), which might predict the emergence of impaired memory during aging. Male and female Fisher 344 rats were tested at 6, 12, and 18 months of age. Impaired spatial memory developed in middle-age (12 months), particularly in males, and the propensity for impairment increased with advanced age. A reduced response to novelty was observed over the course of aging, which is inconsistent with cross-sectional studies. This divergence likely resulted from differences in the history of environmental enrichment/impoverishment for cross-sectional and longitudinal studies. Animals that exhibited lower level exploration of the inner region on the open field test exhibited better memory at 12 months. Furthermore, males that exhibited a longer latency to enter a novel environment at 6 months, exhibited better memory at 12 months. For females, memory at 12 months was correlated with the ability to behaviorally adapt to a shift in light/dark cycle. Functional magnetic resonance imaging of the brain, conducted at 12 months, indicated that the decline in memory was associated with altered functional connectivity within different memory systems, most notably between the hippocampus and multiple regions such as the retrosplenial cortex, thalamus, striatum, and amygdala. Overall, some factors, specifically response to novelty at an early age and the capacity to adapt to shifts in light cycle, predicted spatial memory in middle-age, and spatial memory is associated with corresponding changes in brain connectivity. We discuss similarities and differences related to previous longitudinal and cross-sectional studies, as well as the role of sex differences in providing a theoretical framework to guide future longitudinal research on the trajectory of cognitive decline. In addition to demonstrating the power of longitudinal studies, these data highlight the importance of middle-age for identifying potential predictive indicators of sexual dimorphism in the trajectory in brain and cognitive aging.


Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation.
The effects of drug dependence on social systems has helped shape the generally held view that drug dependence is primarily a social problem, not a health problem. In turn, medical approaches to prevention and treatment are lacking. We examined evidence that drug (including alcohol) dependence is a chronic medical illness. A literature review compared the diagnoses, heritability, etiology (genetic and environmental factors), pathophysiology, and response to treatments (adherence and relapse) of drug dependence vs type 2 diabetes mellitus, hypertension, and asthma. Genetic heritability, personal choice, and environmental factors are comparably involved in the etiology and course of all of these disorders. Drug dependence produces significant and lasting changes in brain chemistry and function. Effective medications are available for treating nicotine, alcohol, and opiate dependence but not stimulant or marijuana dependence. Medication adherence and relapse rates are similar across these illnesses. Drug dependence generally has been treated as if it were an acute illness. Review results suggest that long-term care strategies of medication management and continued monitoring produce lasting benefits. Drug dependence should be insured, treated, and evaluated like other chronic illnesses. JAMA. 2000;284:1689-1695.


The demographic history and mutational load of African hunter-gatherers and farmers.
Understanding how deleterious genetic variation is distributed across human populations is of key importance in evolutionary biology and medical genetics. However, the impact of population size changes and gene flow on the corresponding mutational load remains a controversial topic. Here, we report high-coverage exomes from 300 rainforest hunter-gatherers and farmers of central Africa, whose distinct subsistence strategies are expected to have impacted their demographic pasts. Detailed demographic inference indicates that hunter-gatherers and farmers recently experienced population collapses and expansions, respectively, accompanied by increased gene flow. We show that the distribution of deleterious alleles across these populations is compatible with a similar efficacy of selection to remove deleterious variants with additive effects, and predict with simulations that their present-day additive mutation load is almost identical. For recessive mutations, although an increased load is predicted for hunter-gatherers, this increase has probably been partially counteracted by strong gene flow from expanding farmers. Collectively, our predicted and empirical observations suggest that the impact of the recent population decline of African hunter-gatherers on their mutation load has been modest and more restrained than would be expected under a fully recessive model of dominance.


A multi-omics study on quantifying antimicrobial resistance in European freshwater lakes.
The surveillance of wastewater for the Covid-19 virus during this unprecedented pandemic and mapped to the distribution and magnitude of the infected in the population near real-time exemplifies the importance of tracking rapidly changing trends of pathogens or public health problems at a large scale. The rising trends of antimicrobial resistance (AMR) with multidrug-resistant pathogens from the environmental water have similarly gained much attention in recent years. Wastewater-based epidemiology from water samples has shown that a wide range of AMR-related genes is frequently detected. Albeit sewage is treated before release and thus, the abundance of pathogens should be significantly reduced or even pathogen-free, several studies indicated the contrary. Pathogens are still measurable in the released water, ultimately entering freshwaters, such as rivers and lakes. Furthermore, socio-economic and environmental factors, such as chemical industries and animal farming nearby, impact the presence of AMR. Many bacterial species from the environment are intrinsically resistant and also contribute to the resistome of freshwater lakes. This study collected the most extensive standardized freshwater data set from hundreds of European lakes and conducted a comprehensive multi-omics analysis on antimicrobial resistance from these freshwater lakes. Our research shows that genes encoding for AMR against tetracyclines, cephalosporins, and quinolones were commonly identified, while for some, such as sulfonamides, resistance was less frequently present. We provide an estimation of the characteristic resistance of AMR in European lakes, which can be used as a comprehensive resistome dataset to facilitate and monitor temporal changes in the development of AMR in European freshwater lakes.


How embedded memory in recurrent neural network architectures helps learning long-term temporal dependencies.
Learning long-term temporal dependencies with recurrent neural networks can be a difficult problem. It has recently been shown that a class of recurrent neural networks called NARX networks perform much better than conventional recurrent neural networks for learning certain simple long-term dependency problems. The intuitive explanation for this behavior is that the output memories of a NARX network can be manifested as jump-ahead connections in the time-unfolded network. These jump-ahead connections can propagate gradient information more efficiently, thus reducing the sensitivity of the network to long-term dependencies. This work gives empirical justification to our hypothesis that similar improvements in learning long-term dependencies can be achieved with other classes of recurrent neural network axchitectures simply by increasing the order of the embedded memory. In particular we explore the impact of learning simple long-term dependency problems on three classes of recurrent neural network architectures: globally recurrent networks, locally recurrent networks, and NARX (output feedback) networks.Comparing the performance of these architectures with different orders of embedded memory on two simple long-term dependencies problems shows that all of these classes of network architectures demonstrate significant improvement on learning long-term dependencies when the orders of embedded memory are increased. These results can be important to a user comfortable with a specific recurrent neural network architecture because simply increasing the embedding memory order of that architecture will make it more robust to the problem of long-term dependency learning.


Fresh soy oil protects against vascular changes in an estrogen-deficient rat model: an electron microscopy study.
To observe the effects of consuming repeatedly heated soy oil on the aortic tissues of estrogen-deficient rats. Thirty female Sprague Dawley rats (200-250 g) were divided equally into five groups. One group served as the normal control (NC) group. The four treated groups were ovariectomized and were fed as follows: 2% cholesterol diet (OVXC); 2% cholesterol diet + fresh soy oil (FSO); 2% cholesterol diet + once-heated soy oil (1HSO); and 2% cholesterol diet + five-times-heated soy oil (5HSO). After four months, the rats were sacrificed, and the aortic tissues were obtained for histological studies. After four months of feeding, the NC, FSO and 1HSO groups had a lower body weight gain compared to the OVXC and 5HSO groups. The tunica intima/media ratio in the 5HSO group was significantly thicker (p < 0.05) compared to the NC, OVXC and FSO groups. Electron microscopy showed that endothelial cells were normally shaped in the FSO and NC groups but irregular in the 1HSO and 5HSO groups. A greater number of collagen fibers and vacuoles were observed in the 5HSO group compared to the other treatment groups. Fresh soy oil offered protection in the estrogen-deficient state, as these rats had similar features to those of the NC group. The damage to the tunica intima and the increase in the ratio of tunica intima/media thickness showed the deleterious effect of consuming repeatedly heated soy oil in castrated female rats.


So you want to be ... a maxillofacial surgeon.
Maxillofacial surgery (or to give the speciality its full title oral and maxillofacial surgery) has long had a veil of mystery associated with it. Maxillofacial surgical trainees were seen as a rare breed of people who did a dental degree followed by a medical degree before embarking on their surgical training. However, changes have been afoot for several years and there are now increasing numbers of people in the speciality whose primary qualification is medicine with a secondary degree in dentistry.


Effects of Respiratory Disorders on Smoking Cessation and Re-Initiation in an Italian Cohort Study.
The present study aims to prospectively assess the influence of respiratory disorders on smoking cessation and re-initiation. Three population-based Italian cohorts answered a questionnaire on respiratory health and smoking habits during 1998-2001 and after a mean follow-up (SD) of 9.1 (0.8) years. Out of 1874 current smokers and 1166 ex-smokers at baseline, 965 (51.5%) and 735 (63.0%) reported their smoking status at follow-up. From current smokers, 312 had stopped smoking at follow-up, while 86 ex-smokers had resumed smoking. People reporting asthma at baseline were more likely to stop smoking than the other subjects (48.6% vs. 31.7%), while people reporting allergic rhinitis or chronic cough/phlegm had a higher probability to resume smoking (16.7% vs. 10.5% and 20.7% vs. 10.4%, respectively). In the multivariable logistic model, smoking relapse strongly decreased with increasing abstinence duration in people without chronic cough/phlegm (OR for ≥7.5 years vs. <7.5 years = 0.23, 95% CI 0.20-0.27), while no effect was detected in people with chronic cough/phlegm (p for interaction = 0.039). Smoking cessation was enhanced in asthmatic subjects, while people with allergic rhinitis or chronic cough/phlegm were at higher risk to resume smoking. Chronic cough/phlegm blunted the decrease in smoking resumption associated with longer abstinence duration.


Trends in unintentional-injury deaths during the 20th century.
Since 1900 the number of deaths per 100,000 population due to unintentional injuries (accidents) was reduced by 53 percent, dropping from 72 to 34. Had this rate not decreased almost 4.2 million more people would have died from unintentional injuries over the century. Of the seven kinds of injury events that accounted for 90 percent of all unintentional injury deaths in 1998, only two experienced increases in rates. Death rates from falls, fires and burns, drowning, poisoning by gases and vapors and firearms were reduced between 61 and 90 percent. The mortality rate due to poisoning by solids and liquids, however, increased 19 percent while that from motor-vehicle crashes sky-rocketed by 7,500 percent. In 1910 there were 468,500 vehicles registered in the United States and the death rate from these crashes was 0.2 per 100,000. In 1998, however, there were 215.4 million vehicles and a death rate of 15.2. Deaths due to solid and liquid poisonings ranged between 1,500 and 2,500 until the late 1960s and now number more than 8,000 annually. The increase is greatest among persons between the ages of 25 and 44 and is largely attributed to illegal drugs. Death rates in this category were lowest in the 1950s and now are as high as in the mid-1910s. Deaths due to falls fluctuated from about 7,400 in 1910 to nearly 25,000 annually in the 1940s, to about 11,400 in 1986, and to 16,600 in 1998. Death rates for age groups under 65 years are at their lowest while those for the 65 and older age group have been increasing. Drowning and firearms deaths have decreased fairly steadily since the early 1970s. Death rates for all age groups have shown steady reductions over the century and are now at or near their lowest points. The firearms death rate for 15-24 year olds, however, was and is substantially greater than all other age groups. The number of deaths due to fires and burns and gas and vapor poisonings have been declining since the mid-1960s and late 1970s respectively. Fire and burn death rates among young children and the elderly have shown the greatest improvement.


Altered fusiform connectivity during processing of fearful faces in social anxiety disorder.
Social anxiety disorder (SAD) has been associated with hyper-reactivity in limbic brain regions like the amygdala, both during symptom provocation and emotional face processing tasks. In this functional magnetic resonance imaging study we sought to examine brain regions implicated in emotional face processing, and the connectivity between them, in patients with SAD (n=14) compared with healthy controls (n=12). We furthermore aimed to relate brain reactivity and connectivity to self-reported social anxiety symptom severity. SAD patients exhibited hyper-reactivity in the bilateral fusiform gyrus in response to fearful faces, as well as greater connectivity between the fusiform gyrus and amygdala, and decreased connectivity between the fusiform gyrus and ventromedial prefrontal cortex. Within the SAD group, social anxiety severity correlated positively with amygdala reactivity to emotional faces, amygdala-fusiform connectivity and connectivity between the amygdala and superior temporal sulcus (STS). These findings point to a pivotal role for the fusiform gyrus in SAD neuropathology, and further suggest that altered amygdala-fusiform and amygdala-STS connectivity could underlie previous findings of aberrant socio-emotional information processing in this anxiety disorder.


Reducing unnecessary preoperative blood orders and costs by implementing an updated institution-specific maximum surgical blood order schedule and a remote electronic blood release system.
Using blood utilization data acquired from the anesthesia information management system, an updated institution-specific maximum surgical blood order schedule was introduced. The authors evaluated whether the maximum surgical blood order schedule, along with a remote electronic blood release system, reduced unnecessary preoperative blood orders and costs. At a large academic medical center, data for preoperative blood orders were analyzed for 63,916 surgical patients over a 34-month period. The new maximum surgical blood order schedule and the electronic blood release system (Hemosafe; Haemonetics Corp., Braintree, MA) were introduced mid-way through this time period. The authors assessed whether these interventions led to reductions in unnecessary preoperative orders and associated costs. Among patients having surgical procedures deemed not to require a type and screen or crossmatch (n = 33,216), the percent of procedures with preoperative blood orders decreased by 38% (from 40.4% [7,167 of 17,740 patients] to 25.0% [3,869 of 15,476 patients], P < 0.001). Among all hospitalized inpatients, the crossmatch-to-transfusion ratio decreased by 27% (from 2.11 to 1.54; P < 0.001) over the same time period. The proportion of patients who required emergency release uncrossmatched blood increased from 2.2 to 3.1 per 1,000 patients (P = 0.03); however, most of these patients were having emergency surgery. Based on the realized reductions in blood orders, annual costs were reduced by $137,223 ($6.08 per patient) for surgical patients, and by $298,966 ($6.20/patient) for all hospitalized patients. Implementing institution-specific, updated maximum surgical blood order schedule-directed preoperative blood ordering guidelines along with an electronic blood release system results in a substantial reduction in unnecessary orders and costs, with a clinically insignificant increase in requirement for emergency release blood transfusions.


Multifunctional CMOS microchip coatings for protein and peptide arrays.
Complementary metal oxide semiconductor (CMOS) microelectronic chips fulfill important functions in the field of biomedical research, ranging from the generation of high complexity DNA and protein arrays to the detection of specific interactions thereupon. Nevertheless, the issue of merging pure CMOS technology with a chemically stable surface modification which further resists interfering nonspecific protein adsorption has not been addressed yet. We present a novel surface coating for CMOS microchips based on poly(ethylene glycol)methacrylate graft polymer films, which in addition provides high loadings of functional groups for the linkage of probe molecules. The coated microchips were compatible with the harshest conditions emerging in microarray generating methods, thoroughly retaining structural integrity and microelectronic functionality. Nonspecific adsorption of proteins on the chip's surface was completely obviated even with complex serum protein mixtures. We could demonstrate the background-free antibody staining of immobilized probe molecules without using any blocking agents, encouraging further integration of CMOS technology in proteome research.


Surgical approach to extensive hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is a chronic suppurative disease of skin with high recurrence. To determine factors affecting complications and recurrence of HS in patients who underwent surgery. We operated on 15 patients with HS at 36 sites between 1999 and 2009. The affected areas were classified as groin, axilla, buttocks, nuchae, perianal, and perineal. All patients were treated using wide surgical excision under general anesthesia. The methods of reconstruction varied depending on the size and location of the defect. The female:male ratio of patients was 4:11. Mean age was 41.8 ± 10.6. Twenty-eight (77%) of the lesions were Stage III according to Hurley's staging system. Mean follow-up was 42 months. Radical excision was performed on all lesions; 20 were reconstructed with primary closure, nine with fasciocutaneous flaps, and five with split-thickness skin grafts. The overall complication rate was 25% (9/36) and complications occurred mostly in perineal, perianal, and buttocks sites. Two (5.5%) recurrences were seen only in buttocks site. To prevent complication, avoid recurrence of HS, and improve patients' quality of life, early and wide surgical excision is important and effective. The recurrence and complications are mostly related to the location of the disease. The authors have indicated no significant interest with commercial supporters.


Analytic calculation and analysis of atomic polar tensors for molecules and materials using the Gaussian and plane waves approach.
The evaluation of atomic polar tensors and Born Effective Charge (BEC) tensors from Density Functional Perturbation Theory (DFPT) has been implemented in the CP2K code package. This implementation is based on a combination of the Gaussian and plane wave approach for the description of basis functions and arising potentials. The presence of non-local pseudo-potentials has been considered, as well as contributions arising from the basis functions being centered on the atoms. Simulations of both periodic and non-periodic systems have been implemented and carried out. Dipole strengths and infrared absorption spectra have been calculated for two isomers of the tripeptide Ser-Pro-Ala using DFPT and are compared to the results of standard vibrational analyses using finite differences. The spectra are then decomposed into five subsets by employing localized molecular orbitals/maximally localized Wannier functions, and the results are discussed. Moreover, group coupling matrices are employed for visualization of results. Furthermore, the BECs and partial charges of the surface atoms of a periodic (101) anatase (TiO2) slab have been investigated in a periodic framework.


Mechanistic studies of protein tyrosine phosphatases YopH and Cdc25A with m-nitrobenzyl phosphate.
Protein tyrosine phosphatases (PTPs) constitute a large family of signaling enzymes that include both tyrosine specific and dual-specificity phosphatases that hydrolyze pSer/Thr in addition to pTyr. Previous mechanistic studies of PTPs have relied on the highly activated substrate p-nitrophenyl phosphate (pNPP), an aryl phosphate with a leaving group pK(a) of 7. In the study presented here, we employ m-nitrobenzyl phosphate (mNBP), an alkyl phosphate with a leaving group pK(a) of 14.9, which mimics the physiological substrates of the PTPs. We have carried out pH dependence and kinetic isotope effect measurements to characterize the mechanism of two important members of the PTP superfamily: Yersinia PTP (YopH) and Cdc25A. Both YopH and Cdc25A exhibit bell-shaped pH-rate profiles for the hydrolysis of mNBP, consistent with general acid catalysis. The slightly inverse (18)(V/K)(nonbridge) isotope effects (0.9999 for YopH and 0.9983 for Cdc25A) indicate a loose transition state with little nucleophilic participation for both enzymes. The smaller (18)(V/K)(bridge) primary isotope effects (0.9995 for YopH and 1.0012 for Cdc25A) relative to the corresponding isotope effects for pNPP hydrolysis suggest that protonation of the leaving group oxygen at the transition state by the general acid is ahead of P-O bond fission with the alkyl substrate, while general acid catalysis of pNPP by YopH is more synchronous with P-O bond fission. The isotope effect data also confirm findings from previous studies that Cdc25A utilizes general acid catalysis for substrates with a leaving group pK(a) of >8, but not for pNPP. Interestingly, the difference in the kinetic isotope effects for the reactions of aryl phosphate pNPP and alkyl phosphate mNBP by the PTPs parallels what is observed in the uncatalyzed reactions of their monoanions. In these reactions, the leaving group is protonated in the transition state, as is the case in PTP-catalyzed reactions. Also, the phosphoryl group in the transition states of the enzymatic reactions does not differ substantially from those of the uncatalyzed reactions. These results provide further evidence that these enzymes do not change the transition state but simply stabilize it.


Sarcomatoid renal cell carcinoma. A treatable entity.
Of 920 patients with histologically confirmed renal cell carcinoma (RCC) seen at University of Texas M. D. Anderson Hospital over a 10-year period, 44 (4.8%) had the sarcomatoid variant. The authors show that, although sarcomatoid RCC has as common denominators with classic RCC in certain epidemiologic parameters such as age and sex, its biologic behavior is different. It is more malignant, has a higher metastatic rate, ultimate recurrence in localized disease which translates to a shorter survival time. Metastasis at presentation, advanced age (older than 59 years) and female sex were a associate with a worse prognosis. This entity is characterized by a high incidence of bone metastasis at presentation (48%) and by a tendency toward pathologic bone fractures. All of the untreated patients died very soon after diagnosis (median, 3.8 months), whereas all of the patients treated with the various systemic modalities initiated only in the presence of metastatic disease survived significantly longer (median, 13.0 months). Of the eight patients who were treated with doxorubicin HCI chemotherapy regimens two (on CYVADIC) showed complete responses and are the only survivors (50, 65 months). Four patients treated with interferon had the longest median survival (41.0 months). These results suggest that CYVADIC chemotherapy should be combined with interferon in this entity. Since surgery is not curative in early stages of sarcomatoid RCC, adjuvant therapy with those agents should be considered.


Controlled trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy.
Sixty-seven adults with idiopathic membranous nephropathy and the nephrotic syndrome were randomly assigned to symptomatic treatment only or to a six-month course of methylprednisolone alternated with chlorambucil every other month. Patients were followed for one to seven years. At the end of follow-up (mean of 31.4 +/- 18.2 months for the treated group and 37.0 +/- 22.0 for the control group) 23 of 32 treated patients were in complete or partial remission, as compared with 9 of 30 control patients (P = 0.001). Twelve of the treated patients were in complete remission, as compared with only two of the controls. In the treated group there were no changes in renal function during follow-up, whereas in the control group the reciprocal of the plasma creatinin level, which is proportional to the creatinine clearance, decreased significantly (P = 0.00017) after two years of follow-up. Side effects were minimal in all treated patients except two, who were dropped from the study because of peptic ulcer and gastric intolerance to chlorambucil. We conclude that steroid and chlorambucil treatment for six months favors remission of the nephrotic syndrome in adults with idiopathic membranous nephropathy and can preserve renal function for at least some years.


Human leukemia and lymphoma cell lines as models and resources.
Tumor cell lines are widely used as oncologic models and resources, forming, along with primary patient material and animal models, one of three major subjects for cancer investigation. With the advent of the Human Genome Project (HGP) and the ensuing provision of sequencing data and mapped clones, human cancer cell lines, notably those derived from leukemia-lymphoma (LL) have become increasingly productive tools for cancer gene ascertainment and characterization. Hence, the roles of putative novel cancer genes may be investigated using diverse panels of LL cell lines, both individually by PCR-based methods, and globally by transcriptional chip-profiling. Similar studies have also enabled the faithfulness with which cancer cell lines model their supposed in vivo counterparts to be quantified at last. Several recent transcriptional profiling studies indicate that of all tumor types well characterized human LL cell lines most accurately model the gene expression patterns of their corresponding primary tumors. Analysis using genomic arrays tells a similar story for the stability of chromosome rearrangements in LL cell lines. Well characterized LL cell lines also provide ideal tools for investigating the druggability of individual gene products, e.g. by measuring their transcript levels using q(uantitative)-PCR methods in cells subjected to treatments with small interfering (si)-RNAs. We provide a list of authentic, well characterized examples for prospective investigators, since many circulating cell lines have been cross-contaminated and describe DNA profiling methods which, together with classic and molecular cytogenetic analyses, inform authentication. We also review the problem of mycoplasma contamination and means for its eradication.


Immunochemistry of the surface carbohydrate antigens of Bacteroides fragilis and definition of a common antigen.
The components extracted by aqueous phenol from whole cells of Bacteroides fragilis were analysed by SDS-PAGE and immunoblotting and shown to consist of a series of strain-specific, cross-reactive and common antigens. Regularly-spaced ladder patterns on silver-stained gels indicated that in most strains the LPS was present as a predominantly smooth type, but with chain lengths of varying molecular mass, ranging within each particular strain from essentially rough forms to long chain-length smooth forms. The rough form of the LPS at the gel front possessed an antigen common to most of the strains investigated. Another antigen, which migrated behind the rough LPS on SDS gels, was common to all strains of the species. The smooth LPS forms and the other high molecular mass components were strain-specific antigens. Previously published methods are not capable of producing pure LPS or capsular polysaccharide for this organism.


A prospective randomized multicenter clinical evaluation of an anterior cervical fusion cage.
A prospective, concurrently controlled, randomized, multicenter trial of an anterior Bagby and Kuslich cervical fusion cage (BAK/C; Sulzer Spine-Tech, Minneapolis, MN) for treatment of degenerative disc disease of the cervical spine. To report clinical results with maximum 24-month follow-up of fusions performed with the BAK/C fusion cage. Threaded lumbar cages have been used during the past decade as a safe and effective surgical solution for chronic disabling low back pain. Threaded cages have now been developed for use in anterior cervical interbody fusions to obviate the need for allografts or autogenous bone grafting procedures while providing initial stability during the fusion process. Patients with symptomatic cervical discogenic radiculopathy were treated with either anterior cervical discectomy with uninstrumented bone-only fusion (ACDF) or BAK/C fusion cage(s). Independent radiographic assessment of fusion was made and patient-based outcome was assessed by visual analog pain scale and a Short Form (SF)-36 Health Status Questionnaire. Data analysis included 344 patients at 1 year and 180 at 2 years. When the two cage groups (hydroxya, patite-coated or noncoated) were compared with the ACDF group, similar outcomes were noted for duration of surgery, hospital stay, improvements in neck pain and radicular pain in the affected limb, improvements in the SF-36 Physical Component subscale and Mental Component subscale, and the patients' perception of overall surgical outcome. Symptom improvements were maintained at 2 years. A greater percentage of patients with ACDF needed an iliac crest bone harvest than did BAK/C patients (67% vs.- 3%). Successful fusion for one-level procedures at 12 months was 97.9% for the BAK/C groups and 89.7% for the ACDF group (P < 0.05). The complication rate for the ACDF group was 20.4% compared with an overall complication rate of 11.8% with BAK/C. There was no difference in complications that necessitated a second operative procedure. These results demonstrate that outcomes after a cervical fusion procedure with a threaded cage are the same as those of a conventional uninstrumented bone-only anterior discectomy and fusion with a low risk of complications and rare need for autogenous bone graft harvest.


Protection against kainate neurotoxicity by ginsenosides: attenuation of convulsive behavior, mitochondrial dysfunction, and oxidative stress.
We previously demonstrated that kainic acid (KA)-mediated mitochondrial oxidative stress contributed to hippocampal degeneration and that ginsenosides attenuated KA-induced neurotoxicity and neuronal degeneration. Here, we examined whether ginsenosides affected KA-induced mitochondrial dysfunction and oxidative stress in the rat hippocampus. Treatment with ginsenosides attenuated KA-induced convulsive behavior dose-dependently. KA treatment increased lipid peroxidation and protein oxidation and decreased the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio to a greater degree in the mitochondrial fraction than in the hippocampal homogenate. KA treatment resulted in decreased Mn-superoxide dismutase expression and diminished the mitochondrial membrane potential. Furthermore, KA treatment increased intramitochondrial Ca(2+) and promoted ultrastructural degeneration in hippocampal mitochondria. Treatment with ginsenosides dose-dependently attenuated convulsive behavior and the KA-induced mitochondrial effects. Protection appeared to be more evident in mitochondria than in tissue homogenates. Collectively, the results suggest that ginsenosides prevent KA-induced neurotoxicity by attenuating mitochondrial oxidative stress and mitochondrial dysfunction.


Switchable Novel Object Captioner.
Image captioning aims at automatically describing images by sentences. It often requires lots of paired image-sentence data for training. However, trained captioning models can hardly be applied to new domains in which some novel words exist. In this paper, we introduce the zero-shot novel object captioning task, where the machine generates descriptions about novel objects without extra training sentences. To tackle the challenging task, we mimic the way that babies talk about something unknown, i.e., using the word of a similar known object. Following this motivation, we build a key-value object memory by detection models, containing visual information and corresponding words for objects in the image. For those novel objects, we use words of most similar seen objects as proxy visual words to solve the out-of-vocabulary issue. We then propose a Switchable LSTM that incorporates knowledge from the object memory into sentence generation. The model has two switchable working modes, i.e., 1) generating the sentences like standard LSTMs and 2) retrieving proper nouns from the key-value memory. Thus our model is learned to fully disentangle language generation from training objects, and requires zero training sentence in describing novel objects. Experiments on three large-scale datasets demonstrate the ability of our method to describe novel concepts.


Multisensory integration and internal models for sensing gravity effects in primates.
Gravity is crucial for spatial perception, postural equilibrium, and movement generation. The vestibular apparatus is the main sensory system involved in monitoring gravity. Hair cells in the vestibular maculae respond to gravitoinertial forces, but they cannot distinguish between linear accelerations and changes of head orientation relative to gravity. The brain deals with this sensory ambiguity (which can cause some lethal airplane accidents) by combining several cues with the otolith signals: angular velocity signals provided by the semicircular canals, proprioceptive signals from muscles and tendons, visceral signals related to gravity, and visual signals. In particular, vision provides both static and dynamic signals about body orientation relative to the vertical, but it poorly discriminates arbitrary accelerations of moving objects. However, we are able to visually detect the specific acceleration of gravity since early infancy. This ability depends on the fact that gravity effects are stored in brain regions which integrate visual, vestibular, and neck proprioceptive signals and combine this information with an internal model of gravity effects.


Semantic querying of relational data for clinical intelligence: a semantic web services-based approach.
Clinical Intelligence, as a research and engineering discipline, is dedicated to the development of tools for data analysis for the purposes of clinical research, surveillance, and effective health care management. Self-service ad hoc querying of clinical data is one desirable type of functionality. Since most of the data are currently stored in relational or similar form, ad hoc querying is problematic as it requires specialised technical skills and the knowledge of particular data schemas. A possible solution is semantic querying where the user formulates queries in terms of domain ontologies that are much easier to navigate and comprehend than data schemas. In this article, we are exploring the possibility of using SADI Semantic Web services for semantic querying of clinical data. We have developed a prototype of a semantic querying infrastructure for the surveillance of, and research on, hospital-acquired infections. Our results suggest that SADI can support ad-hoc, self-service, semantic queries of relational data in a Clinical Intelligence context. The use of SADI compares favourably with approaches based on declarative semantic mappings from data schemas to ontologies, such as query rewriting and RDFizing by materialisation, because it can easily cope with situations when (i) some computation is required to turn relational data into RDF or OWL, e.g., to implement temporal reasoning, or (ii) integration with external data sources is necessary.


Using Hybrid Effectiveness Studies to Facilitate Implementation in Community-Based Settings: Three Case Studies in Dementia Care Research.
The pipeline from discovery to testing and then implementing evidence-based innovations in real-world contexts may take 2 decades or more to achieve. Implementation science innovations, such as hybrid studies that combine effectiveness and implementation research questions, may help to bridge the chasm between intervention testing and implementation in dementia care. This paper describes hybrid effectiveness studies and presents 3 examples of dementia care interventions conducted in various community-based settings. Studies that focus on outcomes and implementation processes simultaneously may result in a truncated and more efficient implementation pipeline, thereby providing older persons, their families, health care providers, and communities with the best evidence to improve quality of life and care more rapidly. We offer post-acute and long-term care researchers considerations related to study design, sampling, data collection, and analysis that they can apply to their own dementia and other chronic disease care investigations.


Preliminary analysis of early outcomes of a prospective, randomized trial of complete steroid avoidance in liver transplantation.
Steroids are a mainstay in liver transplantation for induction and maintenance immunosuppression but are associated with significant adverse effects. While prior studies have successfully limited the use of steroids, whether complete steroid avoidance will improve outcomes remains unclear. To further evaluate the need for steroids, consenting patients who underwent liver transplantation between June 2002 and May 2004 were entered into a prospective, randomized trial to receive either standard therapy (tacrolimus, mycophenolate mofetil, steroid induction/maintenance) or complete steroid avoidance (standard therapy without steroid induction/maintenance). Clinically suspected rejection was confirmed by biopsy and treated with pulse steroid therapy. Outcomes were compared on an intention to treat basis. Of the 72 patients enrolled, 36 (50%) were randomized to the steroid avoidance group with a mean follow up of 412 +/- 41 days. Donor and recipient characteristics were similar between groups. The steroid avoidance group was more likely to have significant infections (52% vs 28%, P = .03). There was a trend toward an increased rate of acute rejection (25% vs 14%, P = .23). Twelve of 36 recipients (33%) enrolled in the steroid avoidance group later received steroids. The incidence of recurrent hepatitis C was similar between groups. The 1-year patient (90% vs 83%, P = .44) and graft survivals (90% vs 81%, P = .27) were similar between groups. These data suggest complete steroid avoidance in liver transplantation results in acceptable patient and graft survival. However, the potential long-term benefits of steroid avoidance, including a decrease in severity of recurrent hepatitis C, remain under investigation.


Challenges facing occupational health services in the 21st century.
The mission and tasks of occupational health services are reviewed in the context of the global megatrends of productivity increase, population overgrowth, and the implications of changes in the technology of information and communication. Current trends in attempts to achieve harmonization with respect to the concept and tasks of occupational health services in the European Union are described, along with the basic features of occupational health services as a human service organization with implications for the setting of objectives and criteria for assessing quality and performance and ethics. The need to adopt a quality-focused approach to occupational health service programs is emphasized, and some of the inhibitions and obstacles to quality work are mentioned. The need for professional commitment to develop and implement quality concepts is outlined. Evidence-based health care in the setting of occupational health services and some salient aspects of professional ethics in the 21st century are commented on.


Patients and nonconsulters with irritable bowel syndrome reporting a parental history of bowel problems have more impaired psychological distress.
Little is known about the prevalence and risk factors for development of irritable bowel syndrome (IBS) in Japan. In the United States, it is reported that heredity and social learning contribute to the development of IBS. Our aims were (1) to estimate the prevalence of IBS, (2) to confirm that subjects with IBS are more likely to have parents with a history of bowel problems, (3) to confirm that gastroenteritis is a risk factor for IBS, and (4) to determine whether these two risk factors interact with psychological distress. Prevalence was estimated from a sample of 417 young adults seen for annual health screening examinations. To evaluate risk factors related to consulting physicians, the 46 subjects who fulfilled Rome II diagnostic criteria for IBS but denied ever having seen a physician about these symptoms (IBS non-consulters) were compared to the 317 subjects who did not meet the criteria for IBS (controls) and to a group of 56 patients diagnosed with IBS by gastroenterologists (IBS patients). All subjects completed the Gastrointestinal Symptoms Rating Scale, the State-Trait Anxiety Inventory, the Self-Rating Depression Scale, the Perceived Stress Scale, and the SF-36 quality of life scale. Fourteen and two-tenths percent (15.5% of females and 12.9% of males) of the community sample met the criteria for IBS diagnosis, of whom 22% consulted physicians. IBS patients and IBS nonconsulters were more likely than controls to have a parental history (33.9 vs. 12.6%, P < 0.001, for patients and 26.1 vs. 12.6%, P < 0.01, for nonconsulters) and were more likely to report an infective history compared to controls (44.6 vs. 16.1%, P < 0.001, for patients and 32.6 vs. 16.1%, P < 0.01, for nonconsulters). Two-way analysis of variance showed that the parental history was associated with a significantly greater impact on symptoms of indigestion, diarrhea, constipation, state and trait anxiety, and the SF-36 scales for social functioning and role emotional and that an infective history was associated with a greater impact on bodily pain. Both a parental history of bowel problems and a history of acute gastroenteritis are significant risk factors for development of IBS in Japan, as reported for the United States. Moreover, patients with such a family history show more psychological distress than other patients.


An Objective Perimetry Study of Central Versus Peripheral Sensitivities and Delays in Age-Related Macular Degeneration.
The purpose of this study was to compare central versus peripheral retinal sensitivities and delays in neovascular age-related macular degeneration (nAMD) using US Food and Drug Administration (FDA)-cleared multifocal pupillographic objective perimetry (mfPOP). We recruited 18 patients with nAMD and commenced Pro re nata intravitreal anti- vascular endothelial growth factor (VEGF) injection. We compared macular (±15 degrees) and wide-field (±30 degrees) mfPOP variants. We examined temporal correlations between treated and untreated fellow eyes. We fitted linear models to selected treatment patterns, and compared the ability of central versus peripheral responses to predict the need for treatment. Central sensitivity decreased by -2.23 ± 0.051 dB/month (P < 0.0002) in treated eyes, and -0.17 ± 0.07 dB/month (P = 0.033) in untreated eyes. Treated eyes showed quicker central responses by 13.08 ± 3.77 ms than untreated eyes (P = 0.001). Based on peripheral responses, we identified two eye-types. Among positive-eyes peripheral sensitivity increased by 9.88 ± 4.41 dB (P = 0.042) before treatment; delays increased by 3.49 ± 1.75 ms/month (P = 0.049). For negative-eyes peripheral delays were shorter a month before treatment by 9.38 ± 3.59 ms (P = 0.013). Correlations between treatment and peripheral sensitivities or delays peaked at 1 to 2 months post-treatment. Peripheral data significantly determined treatment frequency and final acuity (all P < 0.044). Peripheral macular function of treated and untreated eyes divided eyes into positive and negative groups. Those peripheral responses determined outcomes; changes preceding active disease by 1 to 3 months. Overall, mfPOP may provide potential biomarkers to assist nAMD management. Objective perimetry may identify the requirement for treatment in nAMD that accords with the decision of a skilled clinician based on optical coherence tomography (OCT) and clinical findings.


Population pharmacokinetics of mycophenolic acid and dose optimization in adult Chinese kidney transplant recipients.
1. This study aimed to establish a population pharmacokinetic (PPK) model of mycophenolic acid (MPA), quantify the effect of clinical factors and pharmacogenomics of MPA, and optimize the dosage for adult kidney transplant recipients.2. One-hundred and four adult renal transplant patients were enrolled. The PPK model was established using the Phoenix® NMLE software and the stepwise methods were filtered for significant covariates. Monte Carlo simulations were performed to optimize the dosage regimen.3. A two-compartment model with first-order absorption and elimination (including lag time) provided a more accurate description of MPA pharmacokinetics. Serum albumin (ALB) significantly affected the central apparent clearance (CL/F), whereas post-transplant time and creatinine clearance were associated with a central apparent volume of distribution (V/F). The estimated population values obtained by the final model were 17.5 L/h and 93.97 L for CL/F and V/F, respectively. Simulation results revealed that larger mycophenolate mofetil doses are required as the ALB concentration decreases. This study established a PPK model of MPA and validated it using various methods. ALB significantly affected CL/F and recommended optimal dose strategies were given based on the final model. These results provide a reference for the personalized therapy of MPA for kidney transplant patients.


Automated data collection and processing for a cycle ergometer.
A system is described for collection and processing of data from a cycle ergometer. Cycle pedals, specially made to withstand the extremely high forces exerted during maximal power cycling, contain transducers to measure pedal angle relative to the crank and foot forces both perpendicular and parallel to the pedal surface. An additional transducer monitors crank position. Output signals are conditioned, amplified, digitized by a 12-bit analog-to-digital converter, fed into a computer at 100 Hz/channel, and mathematically smoothed to attenuate noise. For each sample interval, foot force components perpendicular and parallel to the crank arm are calculated. Power generated on each crank revolution is determined from transducer information. Computer graphics display pedaling parameters vs. crank angle in both rectangular and circular format. Data files containing variables descriptive of pedaling force curves are produced to enable computerized statistical analysis of cycling performance.


Ergot alkaloids induce vasoconstriction of bovine uterine and ovarian blood vessels.
Fescue toxicosis is a syndrome that impairs growth and reproduction in cattle grazing endophyte-infected tall fescue [Lolium arundinaceum [(Schreb.].) Darbysh)] in the United States, resulting in approximately $1 billion in annual economic loss in species that utilize this forage resource. Approximately 90% of tall fescue contains an endophytic fungus (Epichloë coenophiala) that produces ergot alkaloids. Ergot alkaloids cause vasoconstriction and reduced blood flow to the extremities; however, it remains unknown how blood flow to the reproductive organs is affected in cattle. Therefore, the objective of this study was to determine if ergot alkaloids from endophyte-infected tall fescue reduce blood flow to the reproductive organs, thus hindering reproductive function. Angus heifers (n = 36) naïve to ergot alkaloids were placed in Calan gates and randomly assigned to receive either endophyte-infected fescue seed (E+) or noninfected fescue seed (E-; control) in a total mixed ration for 63 d. Weekly measurements were taken to monitor heifer growth and response to ergot alkaloid exposure. Reproductive measurements, including ovarian structures, uterine and ovarian vessel diameter, and hormone concentrations were determined after heifers were synchronized using the standard CO-Synch + 7 d CIDR protocol to ensure all measurements were collected at the same stages of the estrous cycle (0, 4, 10, and 17 d). Data were analyzed using repeated measures in PROC MIXED of SAS. Average daily gain was decreased for the E+ group (0.8 kg/d) compared to control heifers (1.0 kg/d). Body condition scores tended to be greater in control heifers compared to the E+ group (P = 0.053). Additionally, hair coat and hair shedding scores were greater in E+ heifers compared to controls (P < 0.05). Heart rate, rectal temperature, respiration rate, and blood pressure did not differ between treatments (P > 0.05). Vasoconstriction was observed in the caudal artery, but not the caudal vein, in heifers consuming the E+ fescue seed (P < 0.05). No differences were observed in antral follicle counts, corpus luteum area or circulating progesterone concentrations in E+ heifers compared to controls (P > 0.05). There was a significant decrease in the diameter of arteries and veins servicing the ovary and uterus on day 10 and 17 of the estrous cycle. Reduction in blood flow to the reproductive organs during critical times in the estrous cycle may contribute to the reduced ovarian function and pregnancy rates associated with fescue toxicosis.


Integrated spatial genomics reveals global architecture of single nuclei.
Identifying the relationships between chromosome structures, nuclear bodies, chromatin states and gene expression is an overarching goal of nuclear-organization studies1-4. Because individual cells appear to be highly variable at all these levels5, it is essential to map different modalities in the same cells. Here we report the imaging of 3,660 chromosomal loci in single mouse embryonic stem (ES) cells using DNA seqFISH+, along with 17 chromatin marks and subnuclear structures by sequential immunofluorescence and the expression profile of 70 RNAs. Many loci were invariably associated with immunofluorescence marks in single mouse ES cells. These loci form 'fixed points' in the nuclear organizations of single cells and often appear on the surfaces of nuclear bodies and zones defined by combinatorial chromatin marks. Furthermore, highly expressed genes appear to be pre-positioned to active nuclear zones, independent of bursting dynamics in single cells. Our analysis also uncovered several distinct mouse ES cell subpopulations with characteristic combinatorial chromatin states. Using clonal analysis, we show that the global levels of some chromatin marks, such as H3 trimethylation at lysine 27 (H3K27me3) and macroH2A1 (mH2A1), are heritable over at least 3-4 generations, whereas other marks fluctuate on a faster time scale. This seqFISH+-based spatial multimodal approach can be used to explore nuclear organization and cell states in diverse biological systems.


A Web- and Mobile-Based Intervention for Comorbid, Recurrent Depression in Patients With Chronic Back Pain on Sick Leave (Get.Back): Pilot Randomized Controlled Trial on Feasibility, User Satisfaction, and Effectiveness.
Chronic back pain (CBP) is linked to a higher prevalence and higher occurrence of major depressive disorder (MDD) and can lead to reduced quality of life. Unfortunately, individuals with both CBP and recurrent MDD are underidentified. Utilizing health care insurance data may provide a possibility to better identify this complex population. In addition, internet- and mobile-based interventions might enhance the availability of existing treatments and provide help to those highly burdened individuals. This pilot randomized controlled trial investigated the feasibility of recruitment via the health records of a German health insurance company. The study also examined user satisfaction and effectiveness of a 9-week cognitive behavioral therapy and Web- and mobile-based guided self-help intervention Get.Back in CBP patients with recurrent MDD on sick leave compared with a waitlist control condition. Health records from a German health insurance company were used to identify and recruit participants (N=76) via invitation letters. Study outcomes were measured using Web-based self-report assessments at baseline, posttreatment (9 weeks), and a 6-month follow-up. The primary outcome was depressive symptom severity (Center for Epidemiological Studies-Depression); secondary outcomes included anxiety (Hamilton Anxiety and Depression Scale), quality of life (Assessment of Quality of Life), pain-related variables (Oswestry Disability Index, Pain Self-Efficacy Questionnaire, and pain intensity), and negative effects (Inventory for the Assessment of Negative Effects of Psychotherapy). The total enrollment rate with the recruitment strategy used was 1.26% (76/6000). Participants completed 4.8 modules (SD 2.6, range 0-7) of Get.Back. The overall user satisfaction was favorable (mean Client Satisfaction Questionnaire score=24.5, SD 5.2). Covariance analyses showed a small but statistically significant reduction in depressive symptom severity in the intervention group (n=40) at posttreatment compared with the waitlist control group (n=36; F1,76=3.62, P=.03; d=0.28, 95% CI -0.17 to 0.74). Similar findings were noted for the reduction of anxiety symptoms (F1,76=10.45; P=.001; d=0.14, 95% CI -0.31 to 0.60) at posttreatment. Other secondary outcomes were nonsignificant (.06≤P≤.44). At the 6-month follow-up, the difference between the groups with regard to reduction in depressive symptom severity was no longer statistically significant (F1,76=1.50, P=.11; d=0.10, 95% CI -0.34 to 0.46). The between-group difference in anxiety at posttreatment was maintained to follow-up (F1,76=2.94, P=.04; d=0.38, 95% CI -0.07 to 0.83). There were no statistically significant differences across groups regarding other secondary outcomes at the 6-month follow-up (.08≤P≤.42). These results suggest that participants with comorbid depression and CBP on sick leave may benefit from internet- and mobile-based interventions, as exemplified with the positive user satisfaction ratings. The recruitment strategy via health insurance letter invitations appeared feasible, but more research is needed to understand how response rates in untreated individuals with CBP and comorbid depression can be increased. German Clinical Trials Register DRKS00010820; https://www.drks.de/drks_web/navigate.do? navigationId=trial.HTML&TRIAL_ID=DRKS00010820.


Phytoplasma phylogenetics based on analysis of secA and 23S rRNA gene sequences for improved resolution of candidate species of 'Candidatus Phytoplasma'.
Phytoplasma phylogenetics has focused primarily on sequences of the non-coding 16S rRNA gene and the 16S-23S rRNA intergenic spacer region (16-23S ISR), and primers that enable amplification of these regions from all phytoplasmas by PCR are well established. In this study, primers based on the secA gene have been developed into a semi-nested PCR assay that results in a sequence of the expected size (about 480 bp) from all 34 phytoplasmas examined, including strains representative of 12 16Sr groups. Phylogenetic analysis of secA gene sequences showed similar clustering of phytoplasmas when compared with clusters resolved by similar sequence analyses of a 16-23S ISR-23S rRNA gene contig or of the 16S rRNA gene alone. The main differences between trees were in the branch lengths, which were elongated in the 16-23S ISR-23S rRNA gene tree when compared with the 16S rRNA gene tree and elongated still further in the secA gene tree, despite this being a shorter sequence. The improved resolution in the secA gene-derived phylogenetic tree resulted in the 16SrII group splitting into two distinct clusters, while phytoplasmas associated with coconut lethal yellowing-type diseases split into three distinct groups, thereby supporting past proposals that they represent different candidate species within 'Candidatus Phytoplasma'. The ability to differentiate 16Sr groups and subgroups by virtual RFLP analysis of secA gene sequences suggests that this gene may provide an informative alternative molecular marker for pathogen identification and diagnosis of phytoplasma diseases.


A Nomogram for Prediction of Postoperative Pneumonia Risk in Elderly Hip Fracture Patients.
Pneumonia is one of the common complications of hip fracture. This study aimed to evaluate the risk factors and apply a nomogram to predict postoperative pneumonia in elderly hip fracture patients. From August 2014 to October 2019, 1113 hip fracture patients who were older than 65 years and underwent surgical treatment in our hospital were subjects of this study. Univariate and multivariate Cox analyses were used to identify independent risk factors. A predictive nomogram model was built, and the discrimination and calibration were determined by receiver operating characteristic and calibration plot. A total of 166 patients developed pneumonia after operation (14.91%, pneumonia group) while the remaining 947 patients did not (85.09%, non-pneumonia group). According to the results, body mass index (OR, 0.76, 95% CI, 0.70 to 0.84, P<0.001), serum albumin (OR, 0.86, 95% CI, 0.79 to 0.93, P<0.001), c-reactive protein (OR, 1.01, 95% CI, 1.00 to 1.92, P=0.011), functional status (OR, 2.94, 95% CI, 1.69 to 5.10, P<0.001) and time to surgery (OR, 4.56, 95% CI, 2.64 to 7.88, P<0.001) were identified as independent risk factors of pneumonia. The area under the curve value for postoperative pneumonia risk was 0.905, and the P-value of the Hosmer-Lemeshow calibration test was 0.529. Our nomogram model can be used to predict the risk of pneumonia in elderly hip fractures after surgery and provide clinicians with guidance for better perioperative intervention to improve prognosis and reduce mortality.


Accident and emergency medicine: content and training.
Accident and emergency medicine is a broad specialty. Its devotees are exposed to the acute aspects of all branches of medicine and surgery and the links with other agencies are extensive. Recent developments herald an interesting future for those working in this branch of medicine.


Neural cell adhesion molecule (NCAM) and myoblast fusion.
Considerable evidence points to an involvement of neural cell adhesion molecule (NCAM) in myoblast fusion. Changes in the level of NCAM expression, isoform specificity, and localization in muscle cells and tissues correspond to key morphogenetic events during muscle differentiation and repair. Furthermore, anti-NCAM antibodies have been shown by others to reduce the rate of myoblast fusion, whereas overexpression of NCAM cDNAs increases the rate of myoblast fusion compared to controls. In this study we have used a novel fusion assay based on intracistronic complementation of lacZ, in combination with fluorescent X-gal histochemistry and immunocytochemistry to assess levels of NCAM expression in individual muscle cells. Our results indicate that a substantial proportion of newly fused myoblasts have NCAM expression levels unchanged from the levels of the surrounding unfused population suggesting that increased expression of NCAM is not required for wild-type myoblasts to fuse. Moreover, pure populations of primary myoblasts isolated from mice homozygous null for NCAM and therefore lacking the molecule, when placed in differentiation medium, consistently fused to form contractile myotubes with kinetics equivalent to wild-type primary myoblasts. We conclude that the increase in expression of NCAM, although typically observed during myogenesis, is not essential to myoblast fusion to form myotubes.


Microbial and metabolomic mechanisms mediating the effects of dietary inulin and cellulose supplementation on porcine oocyte and uterine development.
Dietary fiber (DF) is often eschewed in swine diet due to its anti-nutritional effects, but DF is attracting growing attention for its reproductive benefits. The objective of this study was to investigate the effects of DF intake level on oocyte maturation and uterine development, to determine the optimal DF intake for gilts, and gain microbial and metabolomic insight into the underlying mechanisms involved. Seventy-six Landrace × Yorkshire (LY) crossbred replacement gilts of similar age (92.6 ± 0.6 d; mean ± standard deviation [SD]) and body weight (BW, 33.8 ± 3.9 kg; mean ± SD) were randomly allocated to 4 dietary treatment groups (n = 19); a basal diet without extra DF intake (DF 1.0), and 3 dietary groups ingesting an extra 50% (DF 1.5), 75% (DF 1.75), and 100% (DF 2.0) dietary fiber mixture consisting of inulin and cellulose (1:4). Oocyte maturation and uterine development were assessed on 19 d of the 2nd oestrous cycle. Microbial diversity of faecal samples was analysed by high-throughput pyrosequencing (16S rRNA) and blood samples were subjected to untargeted metabolomics. The rates of oocytes showing first polar bodies after in vitro maturation for 44 h and uterine development increased linearly with increasing DF intake; DF 1.75 gilts had a 19.8% faster oocyte maturation rate and a 48.9 cm longer uterus than DF 1.0 gilts (P < 0.05). Among the top 10 microbiota components at the phylum level, 8 increased linearly with increasing DF level, and the relative abundance of 30 of 53 microbiota components at the genus level (> 0.1%) increased linearly or quadratically with increasing DF intake. Untargeted metabolic analysis revealed significant changes in serum metabolites that were closely associated with microbiota, including serotonin, a gut-derived signal that stimulates oocyte maturation. The findings provide evidence of the benefits of increased DF intake by supplementing inulin and cellulose on oocyte maturation and uterine development in gilts, and new microbial and metabolomic insight into the mechanisms mediating the effects of DF on reproductive performance of replacement gilts.


A joystick controlled wheelchair.
A joystick based motor control for a child's wheelchair was designed and built. The design is intended to allow a child with limited strength to control a wheelchair. There is a master power switch that can be turned on and off by an instructor in a classroom situation. The joystick is made from resistors that provide the input to the pulse width modulation (PWM) circuits. The motors for each back wheel are operated by an H bridge network. The controller is built but modifications are needed for it to work properly.


Phylogeography of red muntjacs reveals three distinct mitochondrial lineages.
The members of the genus Muntiacus are of particular interest to evolutionary biologists due to their extreme chromosomal rearrangements and the ongoing discussions about the number of living species. Red muntjacs have the largest distribution of all muntjacs and were formerly considered as one species. Karyotype differences led to the provisional split between the Southern Red Muntjac (Muntiacus muntjak) and the Northern Red Muntjac (M. vaginalis), but uncertainties remain as, so far, no phylogenetic study has been conducted. Here, we analysed whole mitochondrial genomes of 59 archival and 16 contemporaneous samples to resolve uncertainties about their taxonomy and used red muntjacs as model for understanding the evolutionary history of other species in Southeast Asia. We found three distinct matrilineal groups of red muntjacs: Sri Lankan red muntjacs (including the Western Ghats) diverged first from other muntjacs about 1.5 Mya; later northern red muntjacs (including North India and Indochina) and southern red muntjacs (Sundaland) split around 1.12 Mya. The diversification of red muntjacs into these three main lineages was likely promoted by two Pleistocene barriers: one through the Indian subcontinent and one separating the Indochinese and Sundaic red muntjacs. Interestingly, we found a high level of gene flow within the populations of northern and southern red muntjacs, indicating gene flow between populations in Indochina and dispersal of red muntjacs over the exposed Sunda Shelf during the Last Glacial Maximum. Our results provide new insights into the evolution of species in South and Southeast Asia as we found clear genetic differentiation in a widespread and generalist species, corresponding to two known biogeographical barriers: The Isthmus of Kra and the central Indian dry zone. In addition, our molecular data support either the delineation of three monotypic species or three subspecies, but more importantly these data highlight the conservation importance of the Sri Lankan/South Indian red muntjac.


[CHARACTERISTICS AND DIFFERENTIAL DIAGNOSTICS OF SLEEP RELATED PATHOLOGICAL MOVEMENTS. UPDATE 2013].
Wide variety of the movements (from the physiologic body position changes to different pathologic events) can be seen during the sleep period. The most important types of these movements are the sleep related events (from the parasomnias to the restless leg related movements), the movement disorders and the epilepsy related events. To differentiate between these events is required special skill, which is based on appropriate characterisation of the events (for example timing, repetition, pattern), the polysomnographic and video-EEG examination and validated questionnaires (FLEP scale). The appropriate differential diagnostics and therapy must be based on the knowledge of the relationship of the sleep architecture and movement events. This review would like to provide guideline for the understanding and recognizing the nature of the sleep related movements.


Evaluation methods in health promotion programmes: the description of a triangulation in Brazil.
Evaluation is a key word in any health promotion programme. However, it is a challenge to choose the most appropriate method of evaluation. The purpose of this paper was to describe a triangulated methodology developed to evaluate a health promotion intervention based on intergenerational activities and to describe the theoretical framework, which guided the study. From February to December 2002 a triangulation involving a community controlled trial, focus groups technique and observation process was developed in Ceilândia, Federal District of Brazil. Samples of 253 students aged 12 to 18 years old from a secondary school and 266 elders aged 60 and over from the local area were randomly allocated to control and experimental groups. Over four months, 111 students and 32 elders had weekly meetings at school to share their life histories. Before and after the intervention, a questionnaire was administered to control and experimental groups including the outcome variables. Although the study had some limitations, it was valuable in showing for the first time that this method can be used in interventions of this kind and also to show the importance of developing a theoretical framework to understand possible mechanism of interactions in intergenerational interventions.


Osmotically relevant membrane signaling complex: association between HB-EGF, beta(1)-integrin, and CD9 in mTAL.
The integral membrane proteins cluster of differentiation-9 (CD9), beta(1)-integrin, and heparin-binding epidermal growth factor-like (HB-EGF) exist in association in many cell lines and are linked to intracellular signaling mechanisms. Two of the proteins (CD9 and beta(1)-integrin) are induced by hypertonicity, suggesting that their related signaling processes may be relevant to osmotic stress. The validity of this hypothesis rests upon coexpression and physical association between these molecules in nephron segments that are normally exposed to high and variable ambient osmolality. In this work, we show that CD9 and beta(1)-integrin are induced in rat kidney medulla after dehydration. Immunohistochemistry and immunoprecipitation studies show that CD9, HB-EGF, and beta(1)-integrin are coexpressed and physically associated in medullary thick ascending limbs (mTAL), nephron segments that are normally exposed to high and variable extracellular osmolality. Our findings are consistent with the existence of a cluster of integral membrane proteins in mTAL that may initiate or modulate osmotically relevant signaling pathways.


Impact of a disability-targeted microentrepreneurship programme in Kenya: study protocol for a randomised controlled trial of the InBusiness programme.
There is a lack of evidence on the effectiveness of livelihood interventions amongst people with disabilities. In many countries, self-employment or microentrepreneurship is a dominant source of livelihoods for people with disabilities and their caregivers. However, this group may face heightened barriers to successful microentrepreneurship, including discrimination, exclusion from training or inaccessible transport, infrastructure and communication systems. The InBusiness programme is a livelihoods programme targeted to microentrepeneurs with disabilities or their caregivers delivered by a consortium of non-governmental organisations. The programme focuses on improving the skills, practices and opportunities of microentrepreneurs while linking them with procurement opportunities with private and public institutions. This protocol describes a randomised controlled trial of the InBusiness programme in eight counties of Kenya. The randomised controlled trial will involve 495 microentrepreneurs who have been verified as eligible for InBusiness by programme implementers. Individuals will be randomised within counties, either being invited to enrol in InBusiness in March 2023 or allocated to a control group. Participants in the control arm will receive information about compliance with business-related laws and available social protection programmes. The trial will assess the impact of InBusiness on household consumption and individual economic empowerment (primary outcomes) as well as food security, well-being, social attitudes, unmet need for disability-related services and microenterprise profits (secondary outcomes). Baseline was conducted in March 2023, and follow-up will be 24 months from baseline (12 months from completion of the programme). Analysis will be through intention to treat. A process evaluation will explore fidelity, mechanisms of impact and the role of context, and complementary qualitative research with participants will be used to triangulate findings across the trial. This study will provide evidence on the impact of a large-scale disability-targeted livelihood programme on household and individual financial security and well-being. Currently, there is a lack of evidence on the effectiveness of livelihood programmes amongst people with disabilities, and so this trial can help inform the design and delivery of InBusiness as well as other livelihood programmes targeted to people with disabilities. ClinicalTrials.gov ISRCTN13693137. Registered on April 24, 2023.


Inhibition of cell proliferation and induction of apoptosis by the retinoid AHPN in human lung carcinoma cells.
In this study, we investigated the effect of the novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN/CD437) on the growth of human lung carcinoma cell lines. AHPN inhibits the proliferation of all cell lines tested, irrespective of the lung tumor type, in a concentration- and time-dependent manner. A dramatic reduction in cell number was observed in adenocarcinoma H460 cells, and was shown to be related to an induction of apoptosis. Bromodeoxyuridine (BrdU) incorporation and flow-cytometric analyses indicated that treatment of H460 cells with AHPN induces cell-cycle arrest at the G1 phase. We therefore investigated the effect of AHPN on several regulatory proteins of the G1 phase of the cell-cycle. The cell-cycle arrest induced by AHPN was accompanied by an inhibition of the hyperphosphorylation of the retinoblastoma (Rb) protein, an indication of G1 arrest. Furthermore, two cyclin-dependent kinases, cdk2 and cdk4, which are normally involved in the phosphorylation of Rb, were shown to have decreased activity. In some cell lines, the decrease in cdk activity may be partly related to an increase in p21(WAF1/Cip1) (p21), an inhibitor of cyclin-dependent kinases. No changes were observed in the cyclin-dependent kinase inhibitor p27(Kip1). The observed increase in p53 in response to AHPN could at least to some extent be responsible for the increased levels of p21. The increase in p53 expression was found to be regulated at a post-transcriptional level. Our results suggest that the growth inhibition of certain lung carcinoma cell lines by AHPN is at least partly related to an increase in p21. However, in other cell lines, different mechanisms appear to be involved. The specificity with which AHPN and other retinoids induce growth arrest and p21 expression indicates that the action of AHPN is not mediated by RAR or RXR receptors, but involves a novel signaling pathway.


Relationship between body mass index and sagittal vertical axis change as well as health-related quality of life in 564 patients after deformity surgery.
Obesity, a condition that is increasing in prevalence in the United States, has previously been associated with poorer outcomes following deformity surgery, including higher rates of perioperative complications such as deep and superficial infections. To date, however, no study has examined the relationship between preoperative BMI and outcomes of deformity surgery as measured by spine parameters such as the sagittal vertical axis (SVA), as well as health-related quality of life (HRQoL) measures such as the Oswestry Disability Index (ODI) and Scoliosis Research Society-22 patient questionnaire (SRS-22). To this end, the authors sought to clarify the relationship between BMI and postoperative change in SVA as well as HRQoL outcomes. The authors performed a retrospective review of a prospectively managed multicenter adult spinal deformity database collected and maintained by the International Spine Study Group (ISSG) between 2009 and 2014. The primary independent variable considered was preoperative BMI. The primary outcome was the change in SVA at 1 year after deformity surgery. Postoperative ODI and SRS-22 outcome measures were evaluated as secondary outcomes. Generalized linear models were used to model the primary and secondary outcomes at 1 year as a function of BMI at baseline, while adjusting for potential measured confounders. Increasing BMI (compared to BMI < 18) was not associated with change of SVA at 1 year postsurgery. However, BMIs in the obese range of 30 to 34.9 kg/m2, compared to BMI < 18 at baseline, were associated with poorer outcomes as measured by the SRS-22 score (estimated change -0.47, 95% CI -0.93 to -0.01, p = 0.04). While BMIs > 30 appeared to be associated with poorer outcomes as determined by the ODI, this correlation did not reach statistical significance. Baseline BMI did not affect the achievable SVA at 1 year postsurgery. Further studies should evaluate whether even in the absence of a change in SVA, baseline BMIs in the obese range are associated with worsened HRQoL outcomes after spinal surgery.