[Low-weight and weight loss as predictors of morbidity and mortality in old age].
Elderly individuals who experience weight loss are at increased risk of premature death and disability. These data contradict findings among younger populations, showing direct relationship between Body Mass Index (BMI) and chronic diseases. In the following manuscript we reviewed papers published in medical as well as in nutritional journals in the area of weight change, morbidity and mortality in old age, since 1990. Recent data indicates that among the elderly, unintentional weight loss of 5% of baseline weight during a period of 1 year marks the beginning of nutritional deterioration. As for BMI, in most studies that were reviewed for this manuscript, BMI of over 25 was protective. In a large study that was conducted in Hong Kong with 2032 participants aged 70 and older, low baseline weight was associated with mortality and was an independent predictor for the development of new diseases. In another large multicentered cohort study in the USA, 4714 participants were followed. Mortality rates among weight losers were twice as high as mortality rates among the rest of the group. Low-weight and weight loss are independent predictors for mortality among the elderly population. There is a need to develop and implement screening methods for weight loss in all the medical settings that deal with elderly people. Additionally, there is a need for developing and assessing models for intervention among elderly people who are at nutritional risk.


The appendix in endometriosis.
In the most severe stage of endometriosis, Stage IV, intestinal involvement is common. The true prevalence of endometriotic disease of the appendix in this population is not well described. A macroscopically normal looking appendix may harbour endometriosis. Our study aims to assess the role of routinely performing appendicectomy in Stage IV endometriosis surgery, and the histopathological prevalence of true appendiceal endometriosis in this population. This is a retrospective study of women undergoing surgery for Stage IV endometriosis between 2018 to 2022 in a tertiary public hospital in New South Wales, Australia. Patient demographics, age and post-operative complications were retrospectively retrieved from hospital medical records. Inclusion criteria were women with Stage IV endometriosis who underwent routine appendicectomy as part of their endometriosis surgery. Exclusion criteria were women who did not have Stage IV endometriosis, those who had cancer surgery or emergency surgery for endometriosis. The primary outcome of this study was to determine the incidence of appendiceal endometriosis. Secondary outcomes included post-operative complications and length of stay. Sixty-seven patients were included. The mean age was 36 years. All patients also underwent bowel resection for colorectal endometriosis. There were 35.8% who had confirmed appendiceal endometriosis on histopathology. Post-operative complications included port site infections, colitis, urinary tract infection and ureteric injury. There were no complications related to appendicectomy. Mean length of stay was 4.4 days. Laparoscopic appendicectomy can be safely performed at time of laparoscopic surgical excision of Stage IV endometriosis and should be routinely considered in a subset of Stage IV endometriosis patients with colorectal involvement undergoing surgery.


Smoking prevalence among perinatal women: the role of socioeconomic status, race, and ethnicity.
Baseline data were collected as part of an intervention project designed to reduce substance abuse among pregnant and postpartum women in Waterbury. Personal interviews, including questions on smoking behavior were conducted with a sample of 503 perinatal women. African American and Hispanic women represented respectively 11.8% and 10.2% of the population. Twenty-six percent of respondents reported they smoked cigarettes during pregnancy which exceeds the nationally comparable rate of 19.1%. Socioeconomic status was a stronger predictor of smoking status than other sociodemographic variables. Logistic regression analysis showed that lower socioeconomic status women were 3.7 times (P < .001) more likely to smoke during pregnancy than their higher status counterparts. Hispanics were 70% (P < .01) less likely to smoke than Whites and there were no significant differences between respondents based on race, marital status, age, or source of prenatal care. The authors conclude that smoking during pregnancy continues to be a major problem requiring multifaceted interventions and attention to underlying structural factors.


Identifying job characteristics related to employed women's breastfeeding behaviors.
For employed mothers of infants, reconciliation of work demands and breastfeeding constitutes a significant challenge. The discontinuation of breastfeeding has the potential to result in negative outcomes for the mother (e.g., higher likelihood of obesity), her employer (e.g., increased absenteeism), and her infant (e.g., increased risk of infection). Given previous research findings identifying return to work as a major risk factor for breastfeeding cessation, we investigate what types of job characteristics relate to women's intentions to breastfeed shortly after giving birth and women's actual breastfeeding initiation and duration. Using job titles and job descriptors contained in a large Australian longitudinal cohort data set (N = 809), we coded job titles using the U.S. Department of Labor (DOL)'s Occupational Information Network (O*NET) database and extracted job characteristics. Hazardous working conditions and job autonomy were identified as significant determinants of women's breastfeeding intentions, their initiation of breastfeeding, and ultimately their breastfeeding continuation. Hence, we recommend that human resource professionals, managers, and public health initiatives provide breastfeeding-supportive resources to women who, based on their job characteristics, are at high risk to prematurely discontinue breastfeeding to ensure these mothers have equal opportunity to reap the benefits of breastfeeding. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Interchangeability of conjugated Haemophilus influenzae type b vaccines in infants.
To evaluate the safety and immunogenicity of two Haemophilus influenzae type b (Hib) conjugate vaccines when administered in serial combination. These vaccines consisted of Hib capsular polysaccharide polyribosyl-ribitol phosphate (PRP) conjugated to the meningococcal outer membrane protein (OMP) complex (PRP-OMP) and H influenzae oligosaccharide conjugated to a mutant toxin (CRM197) isolated from Corynebacterium diphtheriae (HbOC). Randomized, double-blind, clinical trial evaluating five Hib vaccination regimens. Vaccine Treatment and Evaluation Units and affiliated private pediatric practices at Saint Louis (Mo) University, Vanderbilt University, Nashville, Tenn, and Baylor College of Medicine, Houston, Tex. A total of 497 healthy 2-month-old infants scheduled to receive routine immunization. Participants received either PRP-OMP or HbOC given as recommended by the manufacturer, PRP-OMP at 2 and 6 months, HbOC at 2 months, then PRP-OMP at 4 and 6 months, or PRP-OMP at 2 months and then HbOC at 4 and 6 months. Unconjugated PRP was given at 15 months to evaluate priming. Geometric mean antibody concentrations differed significantly among the groups following the second and third immunizations of the primary series and following booster immunization with unconjugated PRP. On each occasion, the groups receiving serial combinations of PRP-OMP and HbOC achieved mean antibody concentrations that equalled or exceeded those of the groups receiving a single product. Adverse reactions did not vary by group. The studied sequential combinations of Hib vaccines were safe and at least as immunogenic as either vaccine alone.


Trajectories of psychological states of women elite fencers during the final stages of international matches.
This study examined the trajectories and within-person synergies of psychological processes during the final stages of matches. A process-oriented approach was used with nine women elite fencers during an international competition. Multiple assessments of perceived control, threat and challenge appraisals, problem- and emotion-focused coping, positive and negative affects were completed after each touches using video recall method. Multilevel growth curve analyses (MGCAs) indicated that winning and losing matches were each characterised by distinct psychological processes. Specifically, perceived control, challenge appraisal, problem- and emotion-focused coping, and positive affects increased linearly and threat appraisal decreased linearly for wining matches, whereas negative affects increased linearly for losing matches. Regarding the within-person synergies of psychological processes, MGCAs indicated that (1) perceived control and challenge appraisal were significantly associated with problem- and emotion-focused coping for losing matches, the strength of these associations remaining consistent across touches; (2) problem-focused coping was significantly associated with negative affects whereas emotion-focused coping was significantly associated with positive affects for winning matches, the strength of these associations remaining consistent across touches; and (3) problem- and emotion-focused coping were significantly associated with negative affects for losing matches, the linear trajectory of negative affects accelerating at times when athletes had higher levels of emotion-focused coping. Overall, this study provided insights into transactional processes during competition.


Applied sport science and medicine of women's rugby codes: a systematic-scoping review and consensus on future research priorities protocol.
Women's rugby (rugby league, rugby union and rugby sevens) has recently grown in participation and professionalisation. There is under-representation of women-only cohorts within applied sport science and medicine research and within the women's rugby evidence base. The aims of this article are: Part 1: to undertake a systematic-scoping review of the applied sport science and medicine of women's rugby, and Part 2: to develop a consensus statement on future research priorities. This article will be designed in two parts: Part 1: a systematic-scoping review, and Part 2: a three-round Delphi consensus method. For Part 1, systematic searches of three electronic databases (PubMed (MEDLINE), Scopus, SPORTDiscus (EBSCOhost)) will be performed from the earliest record. These databases will be searched to identify any sport science and medicine themed studies within women's rugby. The Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews will be adhered to. Part 2 involves a three-round Delphi consensus method to identify future research priorities. Identified experts in women's rugby will be provided with overall findings from Part 1 to inform decision-making. Participants will then be asked to provide a list of research priority areas. Over the three rounds, priority areas achieving consensus (≥70% agreement) will be identified. This study has received institutional ethical approval. When complete, the manuscript will be submitted for publication in a peer-reviewed journal. The findings of this article will have relevance for a wide range of stakeholders in women's rugby, including policymakers and governing bodies.


Necrotizing enterocolitis in 20,822 infants: analysis of medical and surgical treatments.
Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of the neonate. Previous information about this disease has largely been gathered from limited series. We analyzed 13 years of the National Inpatient Sample (NIS) and 3 years of the Kids' Inpatient Database (KID; 1997, 2000, 2003) to generate the most comprehensive profile of outcomes to date of medically versus surgically treated NEC. We identified 20 822 infants with NEC, of whom 15,419 (74.1%) and 5403 (25.9%) were undergoing medical and surgical management, respectively. Overall, surgical patients had greater length of stay, total hospital charges, and mortality. Among infants dying during admission, there was no significant difference in length of stay or charges between the medical and surgical groups. These findings highlight the need for developing a clinically relevant risk stratification tool to identify NEC patients at high risk for death.


Synthesis and afterglow properties of MgAl2O4:Eu2+, Dy3+ nanopowders.
The MgAl2O4:Eu2+, Dy3+ nanophosphors with different particle sizes have been synthesized through a simple and inexpensive precipitate approach followed by a post-annealing process. The structure and morphology of the phosphor are characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). According to XRD and TEM results, the particle size of MgAl2O4:Eu2+, Dy3+ could be controlled via changing the ratio of MgSO4/Al2O3, and the obtained samples possess regular morphology. The afterglow properties of MgAl2O4:Eu2+, Dy3+ nanophosphors as a function of particle sizes are investigated by afterglow decay curves. Compared with the bulk phosphor, the nanophosphors exhibit longer afterglow time and higher initial afterglow intensity. In nanophosphors, there exist numerous defects on their surfaces due to the large surface to volume ratio, which generally act as luminescent killers, while some of which, however, can probably act as traps beneficial for the generation of afterglow. In the nanosized MgAl2O4:Eu2+, Dy3+ phosphor, the thermoluminescence results indeed indicate the existence of more traps which are introduced due to the large surface to volume ratio of nanoparticles and that the high temperature sintering process contributes to the longer afterglow in the nanophosphors.


Toxoplasma gondii Antibodies in Bulk Tank Milk Samples of Caprine Dairy Herds.
A major public health issue, Toxoplasma gondii infection can affect humans mainly via the consumption of animal products from certain species, including small ruminants. Therefore, a regular monitoring of the infection in ovine and caprine populations is advisable for the control of human and animal toxoplasmosis. Antibody detection in individual and bulk tank milk (BTM) may represent a valid alternative to serological analysis, in that its collection is easy and does not affect animal welfare. Many serological tools for milk analysis have already been validated for several parasites, including Apicomplexa. Thus, the aim of the present study was to obtain epidemiological data on T. gondii infection through the detection of antibodies in BTM of dairy goat herds from an important area for caprine dairy production (northern Italy). The performance of a commercial ELISA was first evaluated for analysis of caprine milk samples, using a panel of serum-milk pairs of goats naturally infected by T. gondii. The analysis of BTM confirmed the presence of anti- T. gondii antibodies in 59% of the samples. Toxoplasma gondii antibody positivity was more frequently found in goats reared on farms under extensive (64.9%) or semi-intensive systems (68.7%) in comparison with intensive farms (51.1%). Analysis of milk was a valid alternative to serological tests, being easily applied in large-scale epidemiological surveys and for continuous monitoring of T. gondii infection.


A new method for the quantitative determination of monosaccharides, amino sugars and N-acetylneuraminic acid and of 6-deoxyhexose (fucose) in the presence of other sugars.
1. Monosaccharides, amino sugars and N-acetylneuraminic acid were determined by using an original colorimetric assay procedure, based on the detection of formaldehyde released after periodate oxidation. A range of these compounds was investigated by this method and they were all found to obey Beer's law within the concentration range 0-0.6mumole/ml. 2. A simple method for the determination of 6-deoxyhexose concentration in the presence of other monosaccharides is also described. 3. The optimum pH for the release of formaldehyde from sugars by periodate oxidation was 7.0-7.5. 4. The methods described have considerable advantages over existing assay systems and their particlar value in automatic colorimetry, where the use of concentrated acids is undesirable, is discussed.


The Therapeutic Response of Gastrointestinal Stromal Tumors to Imatinib Treatment Assessed by Intravoxel Incoherent Motion Diffusion-Weighted Magnetic Resonance Imaging with Histopathological Correlation.
To exploit the intravoxel incoherent motion (IVIM) diffusion-weighted (DW) MRI when evaluating the therapeutic response of gastrointestinal stromal tumors (GIST) to Imatinib in a mouse model. Mice with xenografts bearing cells from the GIST-T1 cell line were randomly divided into a treated group receiving Imatinib and a control group. DWMRI scans with 14 b-values (0-1500 s/mm2) were performed before and after treatment (days 1, 3 and 7). IVIM related parameters perfusion fractions (fp) and perfusion-related diffusion coefficients (D*) and the conventional apparent diffusion coefficients (ADC) were calculated by fitting the DWMRI signal decay. The mean changes from baseline to each post-treatment time point for each measurement (ΔADC, Δfp and ΔD*) were calculated. The differences of mean changes between the two groups were tested for statistical significance. Histopathological analyses including Ki-67, CD31, TUNEL and H&E were conducted in conjunction with the MRI scans. Increases in ADC of the treated group were higher than those of the control group after treatment, whereas statistical significances were not observed. Compared to the control group, D* in the treated group decreased significantly (ΔD*treated = -41%, -49%, and -49% with P = 0.0001, 0.0001 and 0.0001), and fp increased significantly (Δfptreated = 79%, 82% and 110%, with P = 0.001, 0.0001 and P = 0.0007) on days 1, 3 and 7 after treatment. Histopathological analyses demonstrated different tumor tissue characteristics between the treated and control groups. IVIM measurements may serve as more sensitive imaging biomarkers than ADC when assessing GIST response to Imatinib as early as one day after treatment.


The spatial coherence of noise fields evoked by continuous source distributions.
In this work, analytic expressions for the spatial coherence of noise fields are derived in the modal domain with the aim of providing a sparse representation. For this purpose, the sound field in a region of interest is expressed in terms of a given pressure distribution on a virtual surrounding cylindrical or spherical surface. According to the Huygens-Fresnel principle, the sound pressure on this surface is represented by a continuous distribution of elementary line or point sources, where orthogonal basis functions characterize the spatial properties. To describe spatially windowed pressure distributions with arbitrary angular extensions, orthogonal basis functions of limited angular support are proposed. As special cases, circular and spherical pressure distributions with uncorrelated source modes of equal power are investigated. It is shown that these distributions result, respectively, in cylindrically isotropic and spherically isotropic, i.e., diffuse noise fields. The analytic expressions derived in this work allow for a prediction of the spatial coherence between arbitrary positions within the region of interest, such that no microphones need to be placed at the actual points of interest. Simulation results are presented to validate the derived relations.


Novel coiled-coil proteins regulate exocyst association with cortical microtubules in xylem cells via the conserved oligomeric golgi-complex 2 protein.
Xylem vessel cells develop secondary cell walls in distinct patterns. Cortical microtubules are rearranged into distinct patterns and regulate secondary cell wall deposition; however, it is unclear how exocytotic membrane trafficking is linked to cortical microtubules. Here, we show that the novel coiled-coil proteins vesicle tethering 1 (VETH1) and VETH2 recruit EXO70A1, an exocyst subunit essential for correct patterning of secondary cell wall deposition, to cortical microtubules via the conserved oligomeric Golgi complex (COG) 2 protein. VETH1 and VETH2 encode an uncharacterized domain of an unknown function designated DUF869, and were preferentially up-regulated in xylem cells. VETH1-green fluorescent protein (GFP) and VETH2-GFP co-localized at novel vesicle-like small compartments, which exhibited microtubule plus-end-directed and end-tracking dynamics. VETH1 and VETH2 interacted with COG2, and this interaction promoted the association between cortical microtubules and EXO70A1 These results suggest that the VETH-COG2 complex ensures the correct secondary cell wall deposition pattern by recruiting exocyst components to cortical microtubules.


Constipation and risk of cardiovascular diseases: a Danish population-based matched cohort study.
To assess the risks of myocardial infarction, stroke, peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter and heart failure in patients with constipation compared with a general population cohort. Population-based matched cohort study. All Danish hospitals and hospital outpatient clinics from 2004 to 2013. Patients with a constipation diagnosis matched on age, sex and calendar year to 10 individuals without constipation from the general population. Comorbidity-adjusted and medication-adjusted hazard ratios (aHRs) for cardiovascular outcomes based on Cox regression analysis. 83 239 patients with constipation were matched to 832 384 individuals without constipation. The median age at constipation diagnosis was 46.5% and 41% were men. Constipation was strongly associated with venous thromboembolism (aHR 2.04, 95% CI 1.89 to 2.20), especially splanchnic venous thrombosis (4.23, 95% CI 2.45 to 7.31). Constipation was also associated with arterial events, including myocardial infarction (1.24, 95% CI 1.14 to 1.35), ischaemic stroke (1.50, 95% CI 1.41 to 1.60), haemorrhagic stroke (1.46, 95% CI 1.26 to 1.69), peripheral artery disease (1.34, 95% CI 1.20 to 1.50), atrial fibrillation or atrial flutter (1.27, 95% CI 1.20 to 1.34) and heart failure (1.52, 95% CI 1.42 to 1.62). The associations were strongest during the first year after the constipation diagnosis and strengthened with an increased number of laxative prescriptions. Constipation was associated with an increased risk of several cardiovascular diseases, in particular venous thromboembolism.


[Characteristics of immunity in patients with destructive pulmonary tuberculosis].
Parameters of systemic immunity, activity of cation proteins of neutrophilic granulocytes and individual blood serum proteins were studied in two groups of patients: with newly diagnosed (83) and chronic destructive pulmonary tuberculosis (105). Four levels of T-lymphocytes were established per their absolute content in 1 ul of the peripheral blood, which had different interconnection with cell response intensity to mitogenic PHA stimulation and the values of the lysosomal cation++ test in both groups of patients. Indications for the prescription of immune active preparations based upon the T-cell level and, when necessary, supplemented by information related to the values of BTR with PHA and BTR with PPD were developed for both groups of patients independently of hereditary consolidated serum proteins.


G9a Regulates Cell Sensitivity to Radiotherapy via Histone H3 Lysine 9 Trimethylation and CCDC8 in Lung Cancer.
To investigate the role and underlying mechanism of G9a and CCDC8 in lung cancer radioresistance. Western blotting assays were used for G9a, CCDC8, H3K9me3 expression detection. MTT assays and clone formation assays were used for measuring cell proliferation activities. Flow cytometry assays were used for cell apoptosis detection. The enrichment of H3K9me3 in CCDC8 promoter was measured by chromatin immunoprecipitation assay. G9a and G9a-mediated H3K9me3 are upregulated in radioresistant lung cancer cells (A549/IR cell and XWLC-05/IR cell). Blocking G9a not only promotes radiosensitivity of A549/IR cell and XWLC-05/IR cell but also reduces aggressive behavior of radioresistant A549 cell/IR and XWLC-05/IR cell. In addition, G9a-controlled H3K9me3 is able to binding to the promoter of tumor suppressor gene CCDC8 and suppresses CCDC8 expression. CCDC8 dysregulation is responsible for G9a-mediated radioresistance of A549/IR cell and XWLC-05/IR cell. G9a and H3K9me3 contribute to the lung cancer radioresistance via modulating CCDC8 expression.


Sustained treatment effect in attention-deficit/hyperactivity disorder: focus on long-term placebo-controlled randomized maintenance withdrawal and open-label studies.
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that often persists throughout life. Approximately two-thirds of patients with a childhood diagnosis of ADHD continue to experience clinically significant symptoms into adulthood. Nevertheless, most of these individuals consider themselves "well," and a vast majority discontinue medication treatment during adolescence. As evidence concerning the adult presentation of ADHD becomes more widely accepted, increasing numbers of physicians and patients will face decisions about the benefits and risks of continuing ADHD treatment. The risks associated with psychostimulant pharmacotherapy, including abuse, dependence, and cardiovascular events, are well understood. Multiple clinical trials demonstrate the efficacy of psychostimulants in controlling ADHD symptoms in the short term. Recent investigations using randomized withdrawal designs now provide evidence of a clinically significant benefit with continued long-term ADHD pharmacotherapy and provide insight into the negative consequences associated with discontinuation. Because many patients lack insight regarding their ADHD symptoms and impairments, they may place a low value on maintaining treatment. Nevertheless, for patients who choose to discontinue treatment, physicians can remain a source of support and schedule follow-up appointments to reassess patient status. Medication discontinuation can be used as an opportunity to help patients recognize their most impairing symptoms, learn and implement behavioral strategies to cope with ADHD symptoms, and understand when additional supportive resources and the resumption of medication management may be necessary.


Prediabetes Screening and Treatment in Diabetes Prevention: The Impact of Physician Attitudes.
Detection and treatment of prediabetes is an effective strategy in diabetes prevention. However, most patients with prediabetes are not identified. Our objective was to evaluate the relationship between attitudes toward prediabetes as a clinical construct and screening/treatment behaviors for diabetes prevention among US family physicians. An electronic survey of a national sample of academic family physicians (n 1248) was conducted in 2016. Attitude toward prediabetes was calculated using a summated scale assessing agreement with statements regarding prediabetes as a clinical construct. Perceived barriers to diabetes prevention, current strategies for diabetes prevention, and perceptions of peers were also examined. Physicians who have a positive attitude toward prediabetes as a clinical construct are more likely to follow national guidelines for screening (58.4% vs 44.4; P < .0001) and recommend metformin to their patients for prediabetes (36.4% vs 20.9%; P < .0001). Physicians perceived a number of barriers to treatment, including a patient's economic resources (71.9%), sustaining patient motivation (83.2%), a patient's ability to modify his or her lifestyle (75.3%), and time to educate patient (75.3%) as barriers to diabetes prevention. How physicians view prediabetes varies significantly, and this variation is related to treatment/screening behaviors for diabetes prevention.


Chlamyphilone, a Novel Pochonia chlamydosporia Metabolite with Insecticidal Activity.
Metabolites from a collection of selected fungal isolates have been screened for insecticidal activity against the aphid Acyrthosiphon pisum. Crude organic extracts of culture filtrates from six fungal isolates (Paecilomyces lilacinus, Pochonia chlamydosporia, Penicillium griseofulvum, Beauveria bassiana, Metarhizium anisopliae and Talaromyces pinophilus) caused mortality of aphids within 72 h after treatment. In this work, bioassay-guided fractionation has been used to characterize the main bioactive metabolites accumulated in fungal extracts. Leucinostatins A, B and D represent the bioactive compounds produced by P. lilacinus. From P. griseofulvum and B. bassiana extracts, griseofulvin and beauvericin have been isolated, respectively; 3-O-Methylfunicone and a mixture of destruxins have been found in the active fractions of T. pinophilum and M. anisopliae, respectively. A novel azaphilone compound, we named chlamyphilone, with significant insecticidal activity, has been isolated from the culture filtrate of P. chlamydosporia. Its structure has been determined using extensive spectroscopic methods and chemical derivatization.


Wearable dry sensors with bluetooth connection for use in remote patient monitoring systems.
Cost reduction has become the primary theme of healthcare reforms globally. More providers are moving towards remote patient monitoring, which reduces the length of hospital stays and frees up their physicians and nurses for acute cases and helps them to tackle staff shortages. Physiological sensors are commonly used in many human specialties e.g. electrocardiogram (ECG) electrodes, for monitoring heart signals, and electroencephalogram (EEG) electrodes, for sensing the electrical activity of the brain, are the most well-known applications. Consequently there is a substantial unmet need for physiological sensors that can be simply and easily applied by the patient or primary carer, are comfortable to wear, can accurately sense parameters over long periods of time and can be connected to data recording systems using Bluetooth technology. We have developed a small, battery powered, user customizable portable monitor. This prototype is capable of recording three-axial body acceleration, skin temperature, and has up to four bio analogical front ends. Moreover, it is also able of continuous wireless transmission to any Bluetooth device including a PDA or a cellular phone. The bio-front end can use long-lasting dry electrodes or novel textile electrodes that can be embedded in clothes. The device can be powered by a standard mobile phone which has a Ni-MH 3.6 V battery, to sustain more than seven days continuous functioning when using the Bluetooth Sniff mode to reduce TX power. In this paper, we present some of the evaluation experiments of our wearable personal monitor device with a focus on ECG applications.


Ventricular fibrillation following removal of temporary epicardial pacemaking wires.
Temporary wires are routinely sutured to both the atrial and ventricular epimyocardium after open heart surgery. Despite their rarity, complications related to removal of such pacemaking wires may cause life threatening situations. We describe here a patient who developed ventricular fibrillation immediately after removal of temporary epicardial pacemaking wires.


COVID-19 Unmasked Global Collaboration Protocol: longitudinal cohort study examining mental health of young children and caregivers during the pandemic.
Early empirical data shows that school-aged children, adolescents and adults are experiencing elevated levels of anxiety and depression during the COVID-19 pandemic. Currently, there is very little research on mental health outcomes for young children. To describe the formation of a global collaboration entitled, 'COVID-19 Unmasked'. The collaborating researchers aim to (1) describe and compare the COVID-19 related experiences within and across countries; (2) examine mental health outcomes for young children (1 to 5 years) and caregivers over a 12-month period during the COVID-19 pandemic; (3) explore the trajectories/time course of psychological outcomes of the children and parents over this period and (4) identify the risk and protective factors for different mental health trajectories. Data will be combined from all participating countries into one large open access cross-cultural dataset to facilitate further international collaborations and joint publications. COVID-19 Unmasked is an online prospective longitudinal cohort study. An international steering committee was formed with the aim of starting a global collaboration. Currently, partnerships have been formed with 9 countries (Australia, Cyprus, Greece, the Netherlands, Poland, Spain, Turkey, the UK, and the United States of America). Research partners have started to start data collection with caregivers of young children aged 1-5 years old at baseline, 3-months, 6-months, and 12-months. Caregivers are invited to complete an online survey about COVID-19 related exposure and experiences, child's wellbeing, their own mental health, and parenting. Primary study outcomes will be child mental health as assessed by scales from the Patient-Reported Outcomes Measurement Information System - Early Childhood (PROMIS-EC) and caregiver mental health as assessed by the Depression Anxiety Stress Scale (DASS-21). The trajectories/time course of mental health difficulties and the impact of risk and protective factors will be analysed using hierarchical linear models, accounting for nested effects (e.g. country) and repeated measures.


Genomic analysis reveals that immune function genes are strongly linked to clinical outcome in the North Central Cancer Treatment Group n9831 Adjuvant Trastuzumab Trial.
To develop a genomic signature that predicts benefit from trastuzumab in human epidermal growth factor receptor 2-positive breast cancer. DASL technology was used to quantify mRNA in samples from 1,282 patients enrolled onto the Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer (North Central Cancer Treatment Group N9831 [NCCTG-N9831]) adjuvant trastuzumab trial. Cox proportional hazard ratios (HRs), adjusted for significant clinicopathologic risk factors, were used to determine the association of each gene with relapse-free survival (RFS) for 433 patients who received chemotherapy alone (arm A) and 849 patients who received chemotherapy plus trastuzumab (arms B and C). Network and pathway analyses were used to identify key biologic processes linked to RFS. The signature was built by using a voting scheme. Network and functional ontology analyses suggested that increased RFS was linked to a subset of immune function genes. A voting scheme model was used to define immune gene enrichment based on the expression of any nine or more of 14 immune function genes at or above the 0.40 quantile for the population. This model was used to identify immune gene-enriched tumors in arm A and arms B and C. Immune gene enrichment was linked to increased RFS in arms B and C (HR, 0.35; 95% CI, 0.22 to 0.55; P < .001), whereas arm B and C patients who did not exhibit immune gene enrichment did not benefit from trastuzumab (HR, 0.89; 95% CI, 0.62 to 1.28; P = .53). Enriched immune function gene expression as defined by our predictive signature was not associated with increased RFS in arm A (HR, 0.90; 95% CI, 0.60 to 1.37; P = .64). Increased expression of a subset of immune function genes may provide a means of predicting benefit from adjuvant trastuzumab.


Possible site-specific effect of an intervention combining nutrition and lifestyle counselling with consumption of fortified dairy products on bone mass: the Postmenopausal Health Study II.
The aim of the present study was to examine whether a holistic approach combining nutrition and lifestyle counselling with the consumption of milk and yoghurt enriched with calcium, vitamin D(3) and phylloquinone (vitamin K(1)) or menaquinone (vitamin K(2)) would have any additional benefit on bone mineral density (BMD) indices measured at various skeletal sites using two different techniques, dual energy X-ray absorptiometry and quantitative ultrasonography (QUS). A sample of 115 postmenopausal women were randomized to three intervention groups, receiving daily via fortified milk and yoghurt and for 12 months, 800 mg calcium and 10 μg vitamin D(3) (CaD group, n = 26); 800 mg calcium, 10 μg vitamin D(3) and 100 μg vitamin K(1) (CaDK1 group, n = 26); 800 mg calcium, 10 μg vitamin D(3) and 100 μg vitamin K(2) (CaDK2 group, n = 24); and a control group (CO group, n = 39) following their usual diet. All three intervention groups attended biweekly nutrition and lifestyle counselling sessions. Total BMD significantly increased in all three intervention groups and these changes were significantly higher compared to the CO (P < 0.001). Furthermore, the significant increases observed for L2-L4 BMD in the CaDK1 and CaDK2 groups were found to be significantly higher compared to the decrease observed in the CO (P = 0.001). No significant differences were observed for QUS parameters. The combined approach used in the current study led to favourable changes for all three intervention groups in total body BMD, while an additional benefit was observed for L2-L4 BMD in CaDK1 and CaDK2 groups. No significant differences were observed among groups in any of the QUS parameters.


Protein-ligand binding region prediction (PLB-SAVE) based on geometric features and CUDA acceleration.
Protein-ligand interactions are key processes in triggering and controlling biological functions within cells. Prediction of protein binding regions on the protein surface assists in understanding the mechanisms and principles of molecular recognition. In silico geometrical shape analysis plays a primary step in analyzing the spatial characteristics of protein binding regions and facilitates applications of bioinformatics in drug discovery and design. Here, we describe the novel software, PLB-SAVE, which uses parallel processing technology and is ideally suited to extract the geometrical construct of solid angles from surface atoms. Representative clusters and corresponding anchors were identified from all surface elements and were assigned according to the ranking of their solid angles. In addition, cavity depth indicators were obtained by proportional transformation of solid angles and cavity volumes were calculated by scanning multiple directional vectors within each selected cavity. Both depth and volume characteristics were combined with various weighting coefficients to rank predicted potential binding regions. Two test datasets from LigASite, each containing 388 bound and unbound structures, were used to predict binding regions using PLB-SAVE and two well-known prediction systems, SiteHound and MetaPocket2.0 (MPK2). PLB-SAVE outperformed the other programs with accuracy rates of 94.3% for unbound proteins and 95.5% for bound proteins via a tenfold cross-validation process. Additionally, because the parallel processing architecture was designed to enhance the computational efficiency, we obtained an average of 160-fold increase in computational time. In silico binding region prediction is considered the initial stage in structure-based drug design. To improve the efficacy of biological experiments for drug development, we developed PLB-SAVE, which uses only geometrical features of proteins and achieves a good overall performance for protein-ligand binding region prediction. Based on the same approach and rationale, this method can also be applied to predict carbohydrate-antibody interactions for further design and development of carbohydrate-based vaccines. PLB-SAVE is available at http://save.cs.ntou.edu.tw.


Repair of pre-mRNA splicing: prospects for a therapy for spinal muscular atrophy.
Recent analyses of complete genomes have revealed that alternative splicing became more prevalent and important during eukaryotic evolution. Alternative splicing augments the protein repertoire--particularly that of the human genome--and plays an important role in the development and function of differentiated cell types. However, splicing is also extremely vulnerable, and defects in the proper recognition of splicing signals can give rise to a variety of diseases. In this review, we discuss splicing correction therapies, by using the inherited disease Spinal Muscular Atrophy (SMA) as an example. This lethal early childhood disorder is caused by deletions or other severe mutations of SMN1, a gene coding for the essential survival of motoneurons protein. A second gene copy present in humans and few non-human primates, SMN2, can only partly compensate for the defect because of a single nucleotide change in exon 7 that causes this exon to be skipped in the majority of mRNAs. Thus SMN2 is a prime therapeutic target for SMA. In recent years, several strategies based on small molecule drugs, antisense oligonucleotides or in vivo expressed RNAs have been developed that allow a correction of SMN2 splicing. For some of these, a therapeutic benefit has been demonstrated in mouse models for SMA. This means that clinical trials of such splicing therapies for SMA may become possible in the near future.


Anemia associated with acute infection in children.
The pathogenesis of anemia associated with acute infection in children has not been well delineated. To characterize this type of anemia in children with acute infection, mainly in relation to iron status. These two cross-sectional studies compared the prevalence and severity of anemia between outpatient febrile children and age-matched non-febrile controls. In part 1 of the study, children with acute infection (n = 58) had a significant decrease in hemoglobin levels compared with 54 non-febrile controls. Mean corpuscular volume (MCV) did not change this association. Moreover, there was no significant difference in MCV, mean cell hemoglobin or red cell distribution width values between the two groups. Regarding part 2, of the 6534 blood counts obtained in community clinics, 229 were defined as "bacterial infection." Chart survey confirmed this diagnosis. White blood cell level was significantly inversely associated with hemoglobin level (r = -0.36, P < 0.0001). Anemia was significantly more prevalent among children with bacterial infection compared to those without: 21.4% vs. 14.1% (P = 0.002). Mean values of iron status parameters were all within normal limits. Acute illness is associated with anemia. The pathogenesis of this anemia does not appear to be associated with disruption of iron metabolism.


Clean Water for Developing Countries.
Availability of safe drinking water, a vital natural resource, is still a distant dream to many around the world, especially in developing countries. Increasing human activity and industrialization have led to a wide range of physical, chemical, and biological pollutants entering water bodies and affecting human lives. Efforts to develop efficient, economical, and technologically sound methods to produce clean water for developing countries have increased worldwide. We focus on solar disinfection, filtration, hybrid filtration methods, treatment of harvested rainwater, herbal water disinfection, and arsenic removal technologies. Simple, yet innovative water treatment devices ranging from use of plant xylem as filters, terafilters, and hand pumps to tippy taps designed indigenously are methods mentioned here. By describing the technical aspects of major water disinfection methods relevant for developing countries on medium to small scales and emphasizing their merits, demerits, economics, and scalability, we highlight the current scenario and pave the way for further research and development and scaling up of these processes. This review focuses on clean drinking water, especially for rural populations in developing countries. It describes various water disinfection techniques that are not only economically viable and energy efficient but also employ simple methodologies that are effective in reducing the physical, chemical, and biological pollutants found in drinking water to acceptable limits.


Monoclonal antibodies against chicken type IV and V collagens: electron microscopic mapping of the epitopes after rotary shadowing.
The location of the epitopes for monoclonal antibodies against chicken type IV and type V collagens were directly determined in the electron microscope after rotary shadowing of antibody/collagen mixtures. Three monoclonal antibodies against type IV collagen were examined, each one of which was previously demonstrated to be specific for only one of the three pepsin-resistant fragments of the molecule. The three native fragments were designated (F1)2F2, F3, and 7S, and the antibodies that specifically recognize each fragment were called, respectively, IA8 , IIB12 , and ID2 . By electron microscopy, monoclonal antibody IA8 recognized an epitope located in the center of fragment (F1)2F2 and in tetramers of type IV collagen at a distance of 288 nm from the 7S domain, the region of overlap of four type IV molecules. Monoclonal antibody IIB12 , in contrast, recognized an epitope located only 73 nm from the 7S domain. This result therefore provides direct visual evidence that the F3 fragment is located closest to the 7S domain and the order of the fragments must be 7S-F3-(F1)2F2. The epitope for antibody ID2 was located in the overlap region of the 7S domain, and often several antibody molecules were observed to binding to a single 7S domain. The high frequency with which antibody molecules were observed to bind to fragments of type IV collagen suggests that there is a single population of type IV molecules of chain organization [alpha 1(IV)]2 alpha 2(IV), and that four identical molecules must form a tetramer that is joined in an antiparallel manner at the 7S domain. The monoclonal antibodies against type V collagen, called AB12 and DH2 , were both found to recognize epitopes close to one another, the epitopes being located 45-48 nm from one end of the type V collagen molecule. The significance of this result still remains uncertain, but suggests that this site is probably highly immunoreactive. It may also be related to the specific cleavage site of type V collagen by selected metalloproteinases and by alpha-thrombin. This cleavage site is also known to be located close to one end of the type V molecule.


Systematic review of interventions to reduce problematic alcohol use in men who have sex with men.
Rates of heavy drinking, alcohol problems and alcohol-related disorders are high among men who have sex with men (MSM) and are an important public health issue. Associations between heavy drinking and human immunodeficiency virus (HIV) acquisition among MSM also suggest that drinking may have more severe and chronic consequences for this population relative to others. Consequently, effective interventions to reduce heavy drinking and alcohol-related risk factors among MSM are needed. We conducted a systematic review of randomised controlled trials of interventions to reduce heavy drinking and/or alcohol-related problems among MSM. We searched five electronic databases, screened 3722 records and identified 5 studies involving 1022 participants that satisfied inclusion criteria, which included having: (i) incorporated a comparison condition; (ii) randomised participants to groups; and (iii) reported quantitative outcomes. The methodological quality of studies varied, and meta-analysis was not conducted because of heterogeneity in intervention approaches and outcomes. Studies provided preliminary support for the use of motivational interviewing/motivational enhancement-based interventions (MI) and hybrid MI and cognitive behavioural therapy treatments for heavy drinking among MSM over no treatment. Perhaps the most important conclusion of this review, however, is that well-designed, theoretically informed research focused on establishing the efficacy of interventions for hazardous drinking and alcohol use disorders among MSM is alarmingly scarce. Effective interventions to reduce hazardous drinking among MSM and prevent key alcohol-related outcomes, including risk for HIV transmission and health problems among HIV-positive MSM, are needed to mitigate health disparities in this population.


Plasma CVD of hydrogenated boron-carbon thin films from triethylboron.
Low-temperature chemical vapor deposition (CVD) of B-C thin films is of importance for neutron voltaics and semiconductor technology. The highly reactive trialkylboranes, with alkyl groups of 1-4 carbon atoms, are a class of precursors that have been less explored for low-temperature CVD of B-C films. Herein, we demonstrate plasma CVD of B-C thin films using triethylboron (TEB) as a single source precursor in an Ar plasma. We show that the film density and B/C ratio increases with increasing plasma power, reaching a density of 2.20 g/cm3 and B/C = 1.7. This is attributed to a more intense energetic bombardment during deposition and more complete dissociation of the TEB molecule in the plasma at higher plasma power. The hydrogen content in the films ranges between 14 and 20 at. %. Optical emission spectroscopy of the plasma shows that BH, CH, C2, and H are the optically active plasma species from TEB. We suggest a plasma chemical model based on β-hydrogen elimination of C2H4 to form BH3, in which BH3 and C2H4 are then dehydrogenated to form BH and C2H2. Furthermore, C2H2 decomposes in the plasma to produce C2 and CH, which together with BH and possibly BH3-x(C2H5)x are the film forming species.


Extramammary Paget's disease of the vulva.
Fourteen patients with extramammary Paget's disease of the vulva treated at Yale-New Haven Medical Center from 1982 through 1993 were reviewed to evaluate the accuracy of methods used to delineate surgical margins and to determine if radical operations or surgical margin status was associated with likelihood of recurrence. These 14 patients underwent at total of 25 operations for extramammary Paget's disease. In 8 operations, a total of 44 separate frozen-section biopsies were performed to determine extent of disease with a mean of 5.5 biopsies per patient. Visual judgment alone was used to determine margin status in 17 operations. The ability to delineate free surgical margins on permanent sections was not different, whether judged visually or by frozen-section analysis. Frozen-section analysis was misleading in 3/8 (37.5%) cases, while visual judgment was in error in 6/17 (35%) cases. Moreover, permanent margin status was not found to be predictive of disease recurrence. Two of 5 (40%) patients with positive margins recurred after initial surgery compared with 3 of 9 (33%) patients with negative margins. Of the 14 primary operations, there were 8 wide local excisions, 3 simple vulvectomies, and 3 modified radical vulvectomies. The radicality of the operation as initial treatment did not statistically correlate with disease recurrence.


Triazolopyrimidines and Thiazolopyrimidines: Synthesis, Anti-HSV-1, Cytotoxicity and Mechanism of Action.
Several commercial drugs utilized in the treatment of HSV containing pyrimidine moiety. Because of the ineffectiveness of virus drugs due to the resistance of the patient's immune system, there is a pressing need to prepare new compounds that are effective in the treatment of various viruses. Merged pyrimidine derivatives were designed by one pot synthesis of pyrimidinethione derivative with halogenated compounds. The structure of all prepared compounds was characterized by their spectroscopic data and also, their ability to inhibit the in vitro replication of HSV-1 was estimated. Amongst the tested compounds 2-acetyl-3-methyl-5-(p-tolyl)indeno[1,2-d]thiazolo[3,2- a]pyrimidin-6(5H)-one (9b) and ethyl 3-methyl-6-oxo-5-(p-tolyl)-5,6-dihydroindeno[1,2-d]thiazolo- [3,2-a]pyrimidine-2-carboxylate (9c), caused viral inhibition over 90%. Furthermore, the selectivity indices of the tested compounds are high and have weak cytotoxicity (all samples were checked, not chosen on cytotoxicity basis, we only utilize secure concentrations of every compound). We succeeded in this context to synthesize a new series of potent fused pyrimidine derivatives as anti-HSV-1.


Identification of Pathogenic Mutations in Primary Microcephaly- (MCPH-) Related Three Genes CENPJ, CASK, and MCPH1 in Consanguineous Pakistani Families.
Microcephaly (MCPH) is a developmental anomaly of the brain known by reduced cerebral cortex and underdeveloped intellectual disability without additional clinical symptoms. It is a genetically and clinically heterogenous disorder. Twenty-five genes (involved in spindle positioning, Wnt signaling, centriole biogenesis, DNA repair, microtubule dynamics, cell cycle checkpoints, and transcriptional regulation) causing MCPH have been identified so far. Pakistani population has contributed in the identification of many MCPH genes. WES of three large consanguineous families revealed three pathogenic variants of MCPH1, CENPJ, and CASK. One novel (c.1254delT) deletion variant of MCPH1 and one known (c.18delC) deletion variant of CENPJ were identified in family 1 and 2, respectively. In addition to this, we also identified a missense variant (c.1289G>A) of CASK in males individuals in family 3. Missense mutation in the CASK gene is frequent in the boys with intellectual disability and autistic traits which are the common features that are associated with FG Syndrome 4. The study reports novel and reported mutant alleles disrupting the working of genes vital for normal brain functioning. The findings of this study enhance our understanding about the genetic architecture of primary microcephaly in our local pedigrees and add to the allelic heterogeneity of 3 known MCPH genes. The data generated will help to develop specific strategies to reduce the high incidence rate of MCPH in Pakistani population.


The Gene Expression Barcode: leveraging public data repositories to begin cataloging the human and murine transcriptomes.
Various databases have harnessed the wealth of publicly available microarray data to address biological questions ranging from across-tissue differential expression to homologous gene expression. Despite their practical value, these databases rely on relative measures of expression and are unable to address the most fundamental question--which genes are expressed in a given cell type. The Gene Expression Barcode is the first database to provide reliable absolute measures of expression for most annotated genes for 131 human and 89 mouse tissue types, including diseased tissue. This is made possible by a novel algorithm that leverages information from the GEO and ArrayExpress public repositories to build statistical models that permit converting data from a single microarray into expressed/unexpressed calls for each gene. For selected platforms, users may upload data and obtain results in a matter of seconds. The raw data, curated annotation, and code used to create our resource are also available at http://rafalab.jhsph.edu/barcode.


The Tomato Sequencing Project, the first cornerstone of the International Solanaceae Project (SOL).
The genome of tomato (Solanum lycopersicum) is being sequenced by an international consortium of 10 countries (Korea, China, the United Kingdom, India, The Netherlands, France, Japan, Spain, Italy and the United States) as part of a larger initiative called the 'International Solanaceae Genome Project (SOL): Systems Approach to Diversity and Adaptation'. The goal of this grassroots initiative, launched in November 2003, is to establish a network of information, resources and scientists to ultimately tackle two of the most significant questions in plant biology and agriculture: (1) How can a common set of genes/proteins give rise to a wide range of morphologically and ecologically distinct organisms that occupy our planet? (2) How can a deeper understanding of the genetic basis of plant diversity be harnessed to better meet the needs of society in an environmentally friendly and sustainable manner? The Solanaceae and closely related species such as coffee, which are included in the scope of the SOL project, are ideally suited to address both of these questions. The first step of the SOL project is to use an ordered BAC approach to generate a high quality sequence for the euchromatic portions of the tomato as a reference for the Solanaceae. Due to the high level of macro and micro-synteny in the Solanaceae the BAC-by-BAC tomato sequence will form the framework for shotgun sequencing of other species. The starting point for sequencing the genome is BACs anchored to the genetic map by overgo hybridization and AFLP technology. The overgos are derived from approximately 1500 markers from the tomato high density F2-2000 genetic map (http://sgn.cornell.edu/). These seed BACs will be used as anchors from which to radiate the tiling path using BAC end sequence data. Annotation will be performed according to SOL project guidelines. All the information generated under the SOL umbrella will be made available in a comprehensive website. The information will be interlinked with the ultimate goal that the comparative biology of the Solanaceae-and beyond-achieves a context that will facilitate a systems biology approach.


Mindfulness and hemodynamics in asians: a literature review.
Mindfulness interventions have been increasingly incorporated into clinical settings. Evidence supporting mindfulness practices are predominantly established in Western populations. Neurophysiological evidence has not been established to support the effectiveness of mindfulness practice in Asian populations. Greater understanding of the neurophysiological mechanisms underlying mindfulness would enable hemodynamics as measured by fNIRS to be used to monitor mindfulness practice as an adjunct to psychotherapy with Asian clients. Research relating to fNIRS and hemodynamics for mindfulness in Asians was reviewed. The inclusion criteria for this review were recent publications in peer-reviewed journals from 2008 to 2018, with the search terms 'fNIRS', 'hemodynamics' and 'mindfulness', for studies in Asia. Databases included Medline, PubMed, PSYCINFO, Google Scholar and SCOPUS. Initial searches yielded 86 results. Five duplicated articles were removed, and remaining abstracts were screened; and assessed for eligibility against the structured performa. Three full text papers which fit the inclusion criteria were included in the current review. This review highlighted the paucity of rigorous empirically validated research for hemodynamics as measured with fNIRS for mindfulness practice in Asia.


Monoclonal antibodies specific to porin of Haemophilus influenzae type b: localization of their cognate epitopes and tests of their biological activities.
The major outer membrane protein of Haemophilus influenzae type b (Hib) is porin (Mr 38,000, 341 amino acids). To identify antigenic determinants on Hib porin that might be exposed at the bacterial cell surface, seven mouse monoclonal anti-Hib porin antibodies were generated. The monoclonal antibodies were tested for their binding to intact cells by flow cytometry; all but one bound to the cell surface. Digestions of Hib porin with cyanogen bromide, hydroxylamine or trypsin generated fragments, the identities of which were confirmed by microsequencing of the amino termini. Following electrophoresis and immunoblotting of the fragments, the specificities of the monoclonal antibodies for their cognate sequences were determined. The porin gene ompP2 was expressed in the baculovirus expression vector system; the recombinant porin was recognized by all of the monoclonal antibodies. Deletions were created by omega mutagenesis of ompP2, generating proteins truncated after amino acids 139, 174, 182, and 264. These deletion proteins were tested for reactivities with the monoclonal antibodies, thereby establishing the boundaries of three antigenic determinants that were recognized by the monoclonals: domain (i), amino acids 104-139; domain (ii) amino acids 162-174; and domain (iii), amino acids 267-341. The biological activities of monoclonal antibodies that were representative of these three classes were tested for their bactericidal activity in complement-mediated lysis of whole cells. The monoclonal antibodies were also tested for their immunoprotective properties in the infant rat model of bacteraemia. Although the monoclonal antibodies were surface-binding, they were neither bactericidal nor protective.


Relation of a postmortem renal index of hypertension to atherosclerosis and coronary artery size in young men and women. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group.
In a cooperative multicenter study, the Pathobiological Determinants of Atherosclerosis in Youth, we measured atherosclerosis of the aorta and right coronary artery (RCA) in 2403 black and white men and women 15 through 34 years of age who died of external causes and were autopsied in forensic laboratories. We measured the diameter of the opened, flattened, and fixed RCA and the diameter, intimal thickness, intimal cross-sectional area, medial thickness, and medial cross-sectional area of the pressure-perfused, fixed left anterior descending (LAD) coronary artery. Using the ratio of intimal thickness to outer diameter of the small renal arteries to predict mean arterial pressure during life, we classified the cases as normotensive (mean arterial pressure < 110 mm Hg) or hypertensive (mean arterial pressure > or = 110 mm Hg). The prevalence of hypertension by age, sex, and race corresponded closely with that measured in a survey of the living population. Hypertension had little or no effect on fatty streaks. Hypertension was associated with more extensive raised lesions in the abdominal aortas and RCAs of blacks > 20 years of age and in the RCAs of whites > 25 years of age. At all ages, women had less extensive raised lesions in the RCAs than did men, but the effect of hypertension on raised lesions was similar to that in men. Adjustment for serum lipoprotein cholesterol levels and smoking in a subset of cases yielded results similar to those obtained without adjustment. Hypertension was associated with larger diameters of the RCA and LAD coronary artery and with larger cross-sectional intimal and medial areas of the LAD coronary artery. Hypertension augments atherosclerosis in both men and women primarily by accelerating the conversion of fatty streaks to raised lesions beginning in the third decade of life, and the effect of hypertension increases with age.


Complications in simultaneous bilateral total knee arthroplasty, is it a safe procedure?
There is controversy regarding various aspects of simultaneous bilateral total knee replacement (SBTKR). We found disparity in the postoperative outcomes and complications associated with the procedure in the literature linked with the topic. To retrospectively analyze the need for blood transfusion after surgery and complications associated with total knee replacement according to the type of procedure (SBTKR or unilateral). Retrospective cohort analytical study. We included 251 patients with severe knee osteoarthritis that were divided into two groups. 124 (49%) who underwent SBTKR and 127 upon whom unilateral total knee replacement (UTKR) was performed. Demographic data, days of hospitalization, complications within the first 90 days after surgery (thromboembolic events, superficial and deep infection, stiffness, death); and percentages of patients transfused with blood products during hospitalization were evaluated. There were no statistical differences in the analysis of postoperative complications in the first 90 days after surgery. In the SBTKR group, 8 patients (6.5%) presented some thromboembolic complication during the postoperative period, while this event was observed in only 2 patients (1.5%) from the other group. The analysis showed a statistically significant drop in postoperative hemoglobin, on average that of 0.8 g/dl, in the SBTKR patient group compared to the UTKR group (95% CI 0.44-1.13; p < 0.001). A higher proportion of patients who required transfusion were observed in the SBTKR group (40%) (OR = 7.12; 95% CI 3.3-16; p < 0.001). We analyzed the cause of postoperative transfusion in the patients who required transfusion taking into account two parameters: hemoglobin less than 8 g/dl and the clinical needs of the patients (symptoms of hypotension, decay, difficulty to rehabilitate without pain, dyspnea). 59 patients received transfusion (50 in the SBTKR group and 9 in the other group). Of these, 19 patients (32.2%) did not meet any transfusion criteria. We consider SBTKR a safe procedure, which does not increase postoperative complications compared to UTKR. Although there is an increase in blood loss in SBTKR, it does not generate clinical symptoms of relevance. Level III.


The relationship between electrocardiographic changes and early mortality rate in acute myocardial infarction.
In 587 patients with acute myocardial infarction (AMI) and no previous MI, electrocardiographically estimated infarct size was related to three-month mortality. Mortality was found to be higher in patients with transmural MI (Q or R-wave changes in standard ECG) than in patients with subendocardial infarction (ST-T wave changes in standard ECG). In patients with anterior MI, precordial mapping with 24 chest electrodes was analyzed four days after arrival in hospital (n = 197). Neither the sum of R-waves, the sum of Q-waves, nor the number of Q-waves correlated significantly with early mortality, although there was a trend towards higher mortality among patients with more pronounced ECG changes. Finally, in patients with inferior AMI (n = 230), neither the sum of R-waves nor the sum of Q-waves in leads II, III and aVF on the fourth day influenced three-month mortality. However, when subtracting the sum of Q-waves from the sum of R-waves, there was a significant correlation between the estimated infarct size and the early mortality.


Massive ketonuria during sedation with propofol in a 12 year old girl with severe head trauma.
Severe ketonuria developed during sedation with propofol in a 12 year old girl with brain injury. Deep sedation with propofol (5.1 mg/kg/h) was required because of agitation and severe intracranial hypertension; as a part of our management protocol, glucose intake was restricted to 5 Kcal/h. After 18 hours of propofol infusion there was intense ketonuria (8+ by Ketostix) without any evidence of metabolic acidosis (pH, HCO3- and anion gap were within normal values). At this time, indirect calorimetry (Deltatrac) confirmed that energy expenditure was principally based on fat consumption (70% of energy expenditure). Lowering the propofol infusion rate and increasing glucose intake reduced fat consumption to 39% within 8 hours: at this time, Ketostix was negative for ketone bodies. This case illustrates a potential risk of ketonuria during prolonged sedation with propofol (a 10% solution of intralipid), particularly if glucose intake is restricted. Monitoring urinary ketone bodies is recommended under these circumstances.


Meeting highlights: genome informatics.
We bring you the highlights of the second Joint Cold Spring Harbor Laboratory and Wellcome Trust 'Genome Informatics' Conference, organized by Ewan Birney, Suzanna Lewis and Lincoln Stein. There were sessions on in silico data discovery, comparative genomics, annotation pipelines, functional genomics and integrative biology. The conference included a keynote address by Sydney Brenner, who was awarded the 2002 Nobel Prize in Physiology or Medicine (jointly with John Sulston and H. Robert Horvitz) a month later.


Different modes of APC/C activation control growth and neuron-glia interaction in the developing Drosophila eye.
The development of the nervous system requires tight control of cell division, fate specification and migration. The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that affects different steps of cell cycle progression, as well as having postmitotic functions in nervous system development. It can therefore link different developmental stages in one tissue. The two adaptor proteins, Fizzy/Cdc20 and Fizzy-related/Cdh1, confer APC/C substrate specificity. Here, we show that two distinct modes of APC/C function act during Drosophila eye development. Fizzy/Cdc20 controls the early growth of the eye disc anlage and the concomitant entry of glial cells onto the disc. In contrast, fzr/cdh1 acts during neuronal patterning and photoreceptor axon growth, and subsequently affects neuron-glia interaction. To further address the postmitotic role of Fzr/Cdh1 in controlling neuron-glia interaction, we identified a series of novel APC/C candidate substrates. Four of our candidate genes are required for fzr/cdh1-dependent neuron-glia interaction, including the dynein light chain Dlc90F Taken together, our data show how different modes of APC/C activation can couple early growth and neuron-glia interaction during eye disc development.


Accuracy of prostate weight estimation by digital rectal examination versus transrectal ultrasonography.
The ability to estimate prostate weight is useful. Two commonly used methods for estimating prostate weight are digital rectal examination (DRE) and transrectal ultrasonography (TRUS). We evaluated the relative accuracy of these weight estimates by comparing them to prostate weight following radical retropubic prostatectomy (RRP). Between 1989 and 2001 more than 36,000 community men participated in a large prostate cancer screening study. Of these men 2,238 underwent RRP. In this subset we examined the correlation between documented preoperative DRE and TRUS estimates of prostate weight with actual gland weight. DRE estimates of prostate weight by multiple examiners correlated poorly with RRP specimen weight (r = 0.2743). However, TRUS estimates correlated moderately well (r = 0.6493). TRUS provided more accurate estimates of prostate weight for smaller glands, although it generally underestimated gland weight compared to the weight of the surgical specimen. In a large, community based prostate cancer screening study prostate weight estimated by DRE was shown to correlate poorly with actual prostate weight. Compared with DRE, TRUS provides a better estimate of prostate weight. In addition, TRUS measurements were more accurate in smaller prostate glands.


[Antithrombin activity of methyl esters of arginine-containing peptides].
The capacity of methyl esters of arginine-containing substrates to inhibit the proteolytic activity of thrombin is studied. A relationship between the structure of peptides and their capacity to inhibit the thrombin-fibrinogen reaction is investigated. Parameters Ks, k2 and k3, which characterize individual stages of the protein process are calculated from experimentally obtained kcat, Km and I50 values. It is shown that the antithrombin activity of peptides becomes maximal only in the case when residues of hydrophobic amino acids would be simultaneously present both at the positions of P2 and P3 of oligopeptides.


Enantioselective synthesis of ibuprofen esters in AOT/isooctane microemulsions by Candida cylindracea lipase.
The enantioselective esterification of racemic ibuprofen, catalyzed by a Candida cylindracea lipase, was studied in a water-in-oil microemulsion (AOT/isooctane). By using n-propanol as the alcohol, an optimal W(0) ([H(2)O]/[AOT] ratio) of 12 was found for the synthesis of n-propyl-ibuprofenate at room temperature. The lipase showed high preference for the S(+)-enantiomer of ibuprofen, which was esterified to the corresponding S(+)-ibuprofen ester. The R(-)-ibuprofen remained unesterified in the microemulsion. The calculated enantioselectivity value (E) for S-ibuprofen ester was greater than 150 (conversion 0.32). The enzyme activities of n-alcohols with different chain lengths (3-12) were compared, and it appeared that short- (propanol and butanol) and long-chained (decanol and dodecanol) alcohols were better substrates than the intermediate ones (pentanol, hexanol, and octanol). However, unlike secondary and tertiary alcohols, all of the tested primary alcohols were substrates for the lipase. The reversible reaction (i.e., the hydrolysis of racemic ibuprofen ester in the microemulsion) was also carried out enantioselectively by the enzyme. Only the S form of the ester was hydrolyzed to the corresponding S-ibuprofen. The reaction yield was, however, only about 4% after 10 days of reaction. The corresponding yield for the esterification of ibuprofen was about 35% (10 days). The high enantioselectivity displayed by the lipase in the microemulsion system was seen neither in a similar esterification reaction in a pure organic solvent system (isooctane) nor in the hydrolysis reaction in an aqueous system (buffer). The E value for S-ibuprofen ester in the isooctane system was 3.0 (conversion 0.41), and only 1.3 for S-ibuprofen in the hydrolysis reaction (conversion 0.32). The differences in enantioselectivity for the lipase in various systems are likely due to interfacial phenomena. In the microemulsion system, the water in which the enzyme is dissolved is separated from the solvent by a layer of surfactant molecules, thus creating an interface with a relatively large area. Such interfaces are not present in the pure organic solvent systems (no surfactant) nor in aqueous systems.


Variable effects of parabrachial nucleus lesions on salt appetite in rats depending upon experimental paradigm and saline concentration.
Previous studies have demonstrated that bilateral lesions of the gustatory (medial) zone of the parabrachial nucleus (PBN) in the pons eliminate the salt (sodium chloride; NaCl) appetite induced in rats by treatment with the diuretic drug, furosemide. The present studies reexamined NaCl intake of rats with PBN lesions induced by ibotenic acid, using multiple models of salt appetite. The impairment of a conditioned taste aversion, an established consequence of PBN damage, was used as an initial screen with which to assess the effectiveness of the lesions. Rats with PBN lesions did not drink either 0.3 of a molar (M) solution of NaCl or 0.5 M NaCl in response to daily treatment with desoxycorticosterone acetate. These findings suggest that the excitatory stimulus of salt appetite mediated by mineralocorticoids is abolished by PBN lesions. In contrast, rats with PBN lesions drank some 0.5 M NaCl and more 0.3 M NaCl, in addition to water, in response to hypovolemia induced by subcutaneous injection of 30% polyethylene glycol solution. Those findings suggest that an excitatory stimulus of salt appetite, presumably mediated by Angiotensin II, is not abolished by PBN lesions. These and other observations indicate that lesions of the gustatory PBN in rats may or may not eliminate salt appetite, depending on which model is used and which concentration of NaCl solution is available.


Clinical evaluation of HTR polymer bone replacement grafts in human mandibular Class II molar furcations.
A biocompatible microporous composite of PMMA (poly-methyl-methacrylate), PHEMA (poly-hydroxyl-ethyl-methacrylate), and calcium hydroxide (HTR) or autogenous osseous coagulum (AOC) bone replacement grafts were evaluated in 15 pairs of mandibular molar Class II furcations in 9 patients. Following initial preparation, full thickness flaps were raised to gain access to the furcations; mechanical hand and ultrasonic root and defect debridement and chemical (tetracycline) root preparation were performed; paired furcations in each patient were randomly grafted with either HTR or AOC; and the host flaps replaced or slightly coronally positioned. Weekly, then monthly, deplaquing was performed until surgical re-entry at 6 to 12 months. Both treatments improved the clinical status of the treated furcations. Direct clinical measurements demonstrated essentially equivalent clinical results with both bone replacement graft materials related to most hard and soft tissue changes in the furcations. Differences in favor of HTR were found for horizontal residual furcation depth (2.4 mm vs. 3.9 mm), horizontal furcation fill (1.9 mm vs. 0.8 mm), and percent horizontal furcation fill (44.4% vs. 17.1%) (all P < or = 0.05 paired t test). These favorable results with HTR polymer are similar to several reports with other graft materials and with GTR barriers, and suggest that HTR polymer may be a useful therapeutic adjunct in the clinical management of grade II mandibular molar furcations.


Web services as applications' integration tool: QikProp case study.
Web services are a new technology that enables to integrate applications running on different platforms by using primarily XML to enable communication among different computers over the Internet. Large number of applications was designed as stand alone systems before the concept of Web services was introduced and it is a challenge to integrate them into larger computational networks. A generally applicable method of wrapping stand alone applications into Web services was developed and is described. To test the technology, it was applied to the QikProp for DOS (Windows). Although performance of the application did not change when it was delivered as a Web service, this form of deployment had offered several advantages like simplified and centralized maintenance, smaller number of licenses, and practically no training for the end user. Because by using the described approach almost any legacy application can be wrapped as a Web service, this form of delivery may be recommended as a global alternative to traditional deployment solutions.


Schoolgirls' experience and appraisal of menstrual absorbents in rural Uganda: a cross-sectional evaluation of reusable sanitary pads.
Governments, multinational organisations, and charities have commenced the distribution of sanitary products to address current deficits in girls' menstrual management. The few effectiveness studies conducted have focused on health and education outcomes but have failed to provide quantitative assessment of girls' preferences, experiences of absorbents, and comfort. Objectives of the study were, first, to quantitatively describe girls' experiences with, and ratings of reliability and acceptability of different menstrual absorbents. Second, to compare ratings of freely-provided reusable pads (AFRIpads) to other existing methods of menstrual management. Finally, to assess differences in self-reported freedom of activity during menses according to menstrual absorbent. Cross-sectional, secondary analysis of data from the final survey of a controlled trial of reusable sanitary padand puberty education provision was undertaken. Participants were 205 menstruating schoolgirls from eight schools in rural Uganda. 72 girls who reported using the intervention-provided reusable pads were compared to those using existing improvised methods (predominately new or old cloth). Schoolgirls using reusable pads provided significantly higher ratings of perceived absorbent reliability across activities, less difficulties changing absorbents, and less disgust with cleaning absorbents. There were no significant differences in reports of outside garment soiling (OR 1.00 95%CI 0.51-1.99), or odour (0.84 95%CI 0.40-1.74) during the last menstrual period. When girls were asked if menstruation caused them to miss daily activities there were no differences between those using reusable pads and those using other existing methods. However, when asked about activities avoided during menstruation, those using reusable pads participated less in physical sports, working in the field, fetching water, and cooking. Reusable pads were rated favourably. This translated into some benefits for self-reported involvement in daily activities, although reports of actual soiling and missing activities due to menstruation did not differ. More research is needed comparing the impact of menstrual absorbents on girls' daily activities, and validating outcome measures for menstrual management research.


[Glycopeptide obtained from k-casein and its effect on protein assimilation].
The products of restricted proteolysis of kappa-casein were separated by gel filtration. Intravenous injection of high- and low-molecular fractions substantially reduced the pentagastrin-stimulated acid secretion in the anesthetized rat stomach. Intermediate fractions had lesser physiological activity. One of the active fractions administered intraintestinally inhibited acid secretion and reduced the pentagastrin-stimulated secretion in rat weanling isolated stomach. All the active fractions inhibited the stimulated secretion in rats with a ligated vagus. It is concluded that the nervous system does not play a crucial role in the mechanism by which gastric acid secretion is inhibited by the products of restricted proteolysis of kappa-casein. Decreasing acid secretion in the stomach, glycopeptide provides for the conditions favouring the efficacy of protein utilization at an early age. It is suggested that the effect of glycopeptide obtained from kappa-casein on the process of assimilation is mediated via peptide hormones.


Inter-individual variability in current direction for common tDCS montages.
The direction of applied electric current relative to the cortical surface is a key determinant of transcranial direct current stimulation (tDCS) effects. Inter-individual differences in anatomy affect the consistency of current direction at a cortical target. However, the degree of this variability remains undetermined. Using current flow modelling (CFM), we quantified the inter-individual variability in tDCS current direction at a cortical target (left primary motor cortex, M1). Three montages targeting M1 using circular electrodes were compared: PA-tDCS directed current perpendicular to the central sulcus in a posterior-anterior direction relative to M1, ML-tDCS directed current parallel to the central sulcus in a medio-lateral direction, and conventional-tDCS applied electrodes over M1 and the contralateral forehead. In 50 healthy brain scans from the Human Connectome Project, we extracted current direction and intensity from the grey matter surface in the sulcal bank (M1BANK) and gyral crown (M1CROWN), and neighbouring primary somatosensory cortex (S1BANK and S1CROWN). Results confirmed substantial inter-individual variability in current direction (50%-150%) across all montages. Radial inward current produced by PA-tDCS was predominantly located in M1BANK, whereas for conventional-tDCS it was clustered in M1CROWN. The difference in radial inward current in functionally distinct subregions of M1 raises the testable hypothesis that PA-tDCS and conventional-tDCS modulate cortical excitability through different mechanisms. We show that electrode locations can be used to closely approximate current direction in M1 and precentral gyrus, providing a landmark-based method for tDCS application to address the hypothesis without the need for MRI. By contrast, ML-tDCS current was more tangentially orientated, which is associated with weaker somatic polarisation. Substantial inter-individual variability in current direction likely contributes to variable neuromodulation effects reported for these protocols, emphasising the need for individualised electrode montages, including the control of current direction.


The influence of RAMP1 overexpression on CGRP-induced osteogenic differentiation in MG-63 cells in vitro: an experimental study.
The aim of this study was to elucidate the influence of receptor activity modifying protein 1 (RAMP1) overexpression on the expression and distribution of calcitonin receptor-like receptor (CRLR) in MG-63 cells. Our research also focused on whether RAMP1 overexpression enhanced the promoting effect of exogenous CGRP on osteogenic differentiation in MG-63 cells. We first constructed a eukaryotic expression vector containing human RAMP1 and stably transfected it into MG-63 cells. Real-time PCR and Western blotting were used to determine the expression levels of RAMP1 and CRLR mRNA and protein, respectively. Immunofluorescence analysis was employed to compare the distribution of CRLR in transfected cells. After treatment with CGRP, the extent of osteogenic differentiation was evaluated by simultaneous monitoring of alkaline phosphatase activity, the expression patterns of osteoblastic markers and mineralisation staining. We found that RAMP1 was more highly expressed in the transfected group compared with the control groups (P < 0.01). The CRLR expression was significantly higher than that in the control groups (P < 0.05). In addition, after 7 days of CGRP treatment to induce osteogenic differentiation, the expression of collagen I mRNA was markedly increased in the transfected group (P < 0.05). The transfected group exhibited more granular precipitation in the cytoplasm with alkaline phosphatase staining after 7 and 14 days of differentiation. When stained with Alizarin Red, cells overexpressing RAMP1 were darker and formed many mineralised nodules with clear boundaries and calcium deposition typical of mineralised bone matrix structures at 28 days post-induction of differentiation. The CGRP-induced ALP activity in the RAMP1 overexpression group was significantly higher 3, 6 and 9 days after induction than that in the two control groups (P < 0.05). RAMP1 overexpression promotes CRLR expression, localisation on the cell membrane and enhanced CGRP-mediated differentiation of MG-63 cells. This study contributes to a better understanding of the molecular mechanisms governing CGRP-induced MG-63 differentiation.


High-density lipoprotein functionality, cardiovascular health, and patterns of alcohol consumption: new insights and future perspectives.
Cardiovascular diseases (CVD) pose a significant public health challenge, contributing to 422 million disability-adjusted life years in 2021. The role of high-density lipoproteins (HDL) and alcohol consumption, one of their major modifiable determinants, remains controversial. The objective of this review is to provide a comprehensive narrative overview of HDL functionality and its predictive value for CVD in relation to patterns of alcohol consumption. HDL phenotypes beyond HDL-cholesterol (HDL-c) such as distribution of HDL subspecies, HDL particle abundance, and reverse cholesterol transport capacity are promising indicators of atherosclerotic CVD risk. Low-to-moderate alcohol consumption seems to improve HDL functionality and reduce the incidence of CVD among primarily middle-aged men and postmenopausal women. Advancements in our understanding of HDL biogenesis, structure, and function hold promise for improving HDL-related measures and their predictive value for cardiovascular health. Low-to-moderate alcohol consumption appears to not only increase HDL-c concentration found in the HDL fraction of plasma but also enhance HDL functionality, providing insights into the underlying mechanisms linking alcohol exposure and cardiovascular health benefits. However, rigorous, well designed intervention trials of alcohol consumption on hard cardiovascular outcomes are needed to identify robust causal associations of HDL phenotypes and alcohol consumption with cardiovascular risk.


Triethyl-ammonium bis-(2-oxido-2,2-diphenyl-acetato-κO,O)anti-monate(III).
The coordination around the Sb atom in the title compound, (C(6)H(16)N)[Sb(C(14)H(10)O(3))(2)], is fourfold in a pseudo-trigonal-bipyramidal pattern in which one of the equatorial sites is occupied by the stereoactive lone pair of electrons. The four ligating atoms comprise the hydoxylate and carboxyl-ate O atoms from two independent benzilate ligands, each of which forms a five-membered chelating ring, spanning an axial and an equatorial site about the Sb atom. The hydroxy-late atoms occupy the two equatorial sites, and the carboxyl-ate atoms are in the pseudo-axial sites; the O-Sb-O angle is 147.72 (5)°. One carboxyl-ate group shows quite different bond lengths from those of the other group; one O atom is clearly the carbonyl atom and the other O atom the hydroxy-late atom. In the other ligand, there is less distinction in the C-O bonds. This is presumably related to the carbonyl O atom being the acceptor atom of a strong N-H⋯O hydrogen bond, which links the ammonium cation to the Sb complex anion.


Layer-by-layer hybrid chemical doping for high transmittance uniformity in graphene-polymer flexible transparent conductive nanocomposite.
A traditional transparent conducting film (TCF) such as indium tin oxide (ITO) exhibits poor mechanical flexibility and inconsistent transmittance throughout the UV-VIS-NIR spectrum. Recent TCFs like graphene films exhibit high sheet resistance (Rs) due to defect induced carrier scattering. Here we show a unique hybrid chemical doping method that results in high transmittance uniformity in a layered graphene-polymer nanocomposite with suppressed defect-induced carrier scattering. This layer-by-layer hybrid chemical doping results in low Rs (15 Ω/sq at >90% transmittance) and 3.6% transmittance uniformity (300-1000 nm) compared with graphene (17%), polymer (8%) and ITO (46%) films. The weak localization effect in our nanocomposite was reduced to 0.5%, compared with pristine (4.25%) and doped graphene films (1.2%). Furthermore, negligible Rs change (1.2 times compared to 12.6 × 103 times in ITO) and nearly unaltered transmittance spectra were observed up to 24 GPa of applied stress highlighting mechanical flexibility of the nanocomposite film.


A Protein Rotaxane Controls the Translocation of Proteins Across a ClyA Nanopore.
Rotaxanes, pseudorotaxanes, and catenanes are supramolecular complexes with potential use in nanomachinery, molecular computing, and single-molecule studies. Here we constructed a protein rotaxane in which a polypeptide thread is encircled by a Cytolysin A (ClyA) nanopore and capped by two protein stoppers. The rotaxane could be switched between two states. At low negative applied potentials (<-50 mV) one of the protein stoppers resided inside the nanopore indefinitely. Under this configuration the rotaxane prevents the diffusion of protein molecules across the lipid bilayer and provides a useful platform for single-molecule analysis. High negative applied potentials (-100 mV) dismantled the interlocked rotaxane system by the forceful translocation of the protein stopper, allowing new proteins to be trapped inside or transported across the nanopore. The observed voltage threshold for the translocation of the protein stopper through the nanopore related well to the biphasic voltage dependence of the residence time measured for the freely diffusing protein stopper. We propose a model in which molecules translocate through a nanopore when the average dwell time decreases with the applied potential.


Host cell transcriptome profile during wild-type and attenuated dengue virus infection.
Dengue viruses 1-4 (DENV1-4) rely heavily on the host cell machinery to complete their life cycle, while at the same time evade the host response that could restrict their replication efficiency. These requirements may account for much of the broad gene-level changes to the host transcriptome upon DENV infection. However, host gene function is also regulated through transcriptional start site (TSS) selection and post-transcriptional modification to the RNA that give rise to multiple gene isoforms. The roles these processes play in the host response to dengue infection have not been explored. In the present study, we utilized RNA sequencing (RNAseq) to identify novel transcript variations in response to infection with both a pathogenic strain of DENV1 and its attenuated derivative. RNAseq provides the information necessary to distinguish the various isoforms produced from a single gene and their splice variants. Our data indicate that there is an extensive amount of previously uncharacterized TSS and post-transcriptional modifications to host RNA over a wide range of pathways and host functions in response to DENV infection. Many of the differentially expressed genes identified in this study have previously been shown to be required for flavivirus propagation and/or interact with DENV gene products. We also show here that the human transcriptome response to an infection by wild-type DENV or its attenuated derivative differs significantly. This differential response to wild-type and attenuated DENV infection suggests that alternative processing events may be part of a previously uncharacterized innate immune response to viral infection that is in large part evaded by wild-type DENV.


Identification of an epigenetic profile classifier that is associated with survival in head and neck cancer.
Panels of prognostic biomarkers selected using candidate approaches often do not validate in independent populations, so additional strategies are needed to identify reliable classifiers. In this study, we used an array-based approach to measure DNA methylation and applied a novel method for grouping CpG dinucleotides according to well-characterized genomic sequence features. A hypermethylation profile among 13 CpG loci, characterized by polycomb group target genes, mammalian interspersed repeats, and transcription factor-binding sites (PcG/MIR/TFBS), was associated with reduced survival (HR, 3.98; P = 0.001) in patients with head and neck squamous cell carcinoma. This association was driven by CpGs associated with the TAP1 and ALDH3A1 genes, findings that were validated in an independent patient group (HR, 2.86; P = 0.04). Together, the data not only elucidate new potential targets for therapeutic intervention in head and neck cancer but also may aid in the identification of poor prognosis patients who may require more aggressive treatment regimens.


A narrow band-rejection filter based on block copolymers.
We demonstrate filtering characteristics of a polymer band-rejection filter (PBRF) with highly-ordered microphase-separated structure of block copolymers (BCPs). This PBRF is characterized by an Optical Density > 5 blocking at the center wavelength and narrow blocking full bandwidth of 8 nm. Moreover, the wavelength is easily tuned by blending two BCPs with different molecular-weight. A low frequency Raman shift of 200 cm(-1) are, in fact, detected with a sufficient resolution by using this filter in Raman spectroscopy.


Pharmacokinetic evaluation of a transdermal anastrozole-in-adhesive formulation.
Anastrozole is a well-established active pharmaceutical ingredient (API) used for the treatment of hormone-sensitive breast cancer (BC) in postmenopausal women. However, treatment with the only available oral formulation is often associated with concentration-dependent serious side effects such as hot flashes, fatigue, muscle and joint pain, nausea, diarrhea, headache, and others. In contrast, a sustained-release system for the local application of anastrozole should minimize these serious adverse drug reactions. Anastrozole-in-adhesive transdermal drug delivery systems (TDDS) were developed offering efficient loading, avoidance of inhomogeneity or crystallization of the drug, the desired controlled release kinetics, storage stability, easy handling, mechanical stability, and sufficient stickiness on the skin. In vitro continuous anastrozole release profiles were studied in Franz diffusion cells. In vivo, consecutive drug plasma kinetics from the final anastrozole transdermal system was tested in beagle dogs. For drug analysis, a specific validated liquid chromatography- mass spectrometry method using fragment ion detection was developed and validated. After efficient drug loading, a linear and sustained 65% drug release from the TDDS over 48 h was obtained. In vivo data showed a favorable anastrozole plasma concentration-time course, avoiding side effect-associated peak concentrations as obtained after oral administration but matching therapeutic plasma levels up to 72 h. These results provide the basis for establishing the transdermal application of anastrozole with improved pharmacokinetics and drug safety as novel therapeutic approach and promising option to treat human BC by decreasing the high burden of unwanted side effects.


A fair test of the fair innings?
Priority setting in health care under conventional rules of health economic evaluation is based upon the ethos of attempting to maximize post-treatment health gain given available health care resources. In his later years, Alan Williams advocated the "fair innings argument,'' which balances differences in whole lifetime experiences of health with differences in post-treatment outcomes when prioritizing people for health care. This article reports a study that presented respondents with a number of abstract health care decision contexts in an attempt to test the extent to which post-treatment health maximization, the fair innings argument, or, indeed other "decision rules,'' are evident in the respondents' answers. The results indicate that the most commonly observed decision rule differs substantially across health care contexts, and therefore imply that rather than pursue an overarching decision rule, it may be more appropriate to vary the rule according to the particular health care decision context under consideration.