Factors Influencing Hearing Aid Adoption in Patients With Hearing Loss in Korea.
The purpose of this study was two-fold: 1) to identify differences in the characteristics of adopters and non-adopters of hearing aids (HAs); and 2) to investigate factors influencing the purchase of HA. This study was conducted among 1,464 subjects (818 male and 646 female) with hearing loss. A national face-to-face survey was performed from August 2019 to October 2020 by otologists or HA experts. The questionnaire consisted of three domains: demographic, audiological, and HA-related domains. Multivariate logistic regression analysis was performed after adjusting for degree of hearing loss. The mean age of the participants was 70.4 ± 12.2 years. Of the 1,464 respondents, 1,190 (81.3%) had already purchased HA. We identified educational level, household income, hearing loss period, place of HA purchase, and government HA assistance program status as factors influencing HA adoption. Among these factors, third party reimbursement was the most important factor affecting HA purchase intent. The main reasons for not adopting HA were feeling that their hearing was adequate, inability to afford HA, and perceptions that HA are uncomfortable. Various factors are involved in the purchase of HA, but disabled registration status and third party reimbursement were identified as the most critical factors. In the future, the government should take a more active role in increasing the distribution of HA to patients with hearing loss.


Research gaps identified in Iran's health technology assessment reports.
Identifying gaps in the evidence is a useful byproduct of conducting a health technology assessment (HTA). This study aims to identify research gaps in Iran's HTA reports. We reviewed the HTA reports published between 2014 and 2016. Then, we developed two separate questionnaires for principal investigators (PIs) and independent HTA researchers. The questionnaire for independent HTA researchers consisted of four main parts. However, the PIs' questionnaire consisted of two main parts. We also conducted a literature search in the PubMed database in November 2017 to find frameworks for prioritizing research gaps. We also conducted a semi-structured interview with the head of the Iran's HTA Office at that time and sought feedback based on his expert opinion about questionnaires, the priority-setting tool and our process for extracting research gaps. A total of 11 HTA reports published between 2014 and 2016 by Iran's HTA Office were selected for the study. Of these 11 reports, 5 involved technologies related to medical equipment, while 6 involved medical and surgical interventions. Assessing the outcomes of technology use in various indications and updating HTAs when new evidence arises; evaluating the viewpoints of patients, clinicians and key technology users; conducting post-marketing evaluations of technology; comparing the impact of the technology in question to other treatments for the same condition; and requesting long-term clinical and cost-effectiveness data for technologies with limited follow-up periods were identified as the main gaps by independent HTA researchers and PIs. The research gaps identified from Iran's HTAs could be utilized by research funding agencies.


Correlates of verbal and physical aggression among patrons of licensed venues in Australia.
The current study aimed to examine the association between patron demographics and substance use, and experiences of verbal and physical aggressive incidents within the last 3 months among patrons of night-time entertainment precincts (NEP) in Australia. Patron interviews (n = 4216) were conducted around licensed venues in the NEPs of five Australian cities. Seven correlates of verbal and physical aggressive incidents were examined: gender, age, occupation, blood alcohol concentration, pre-drinking, energy drink use and illicit drug use in the current session. A total of 7.5% and 8.2% of respondents reported involvement in a verbally and physically aggressive incident in the past 3 months, respectively. Multivariate logistic regression models indicated men and people <25 years old were significantly more likely to report both verbal and physical aggressive incidents. A significant occupation effect showed lower levels of both verbal and physical aggression in managers/professionals compared with non-office workers. The likelihood of being involved in a verbally aggressive incident significantly increased with energy drink consumption, while the likelihood of being involved in a physically aggressive incident significantly increased with blood alcohol concentration, energy drink consumption and illicit drug use. This study highlights the different correlates of verbal and physical aggression within NEPs, suggesting they should be viewed as distinct types of violence, rather than points on a continuum. Major modifiable correlates with verbal and physical aggression included intoxication, energy drink consumption, and illicit drug use, suggesting the need for further interventions and policy development to address these key issues. [Hyder S, Coomber K, Pennay A, Droste N, Curtis A, Mayshak R, Lam T, Gilmore W, Chikritzhs T, Miller PG. Correlates of verbal and physical aggression among patrons of licensed venues in Australia. Drug Alcohol Rev 2018;37:6-13].


Decoupling of nucleotide- and microtubule-binding sites in a kinesin mutant.
Molecular motors require ATP to move along microtubules or actin filaments. To understand how molecular motors function, it is crucial to know how binding of the motor to its filamentous track stimulates the hydrolysis of ATP by the motor, enabling it to move along the filament. A mechanism for the enhanced ATP hydrolysis has not been elucidated, but it is generally accepted that conformational changes in the motor proteins occur when they bind to microtubules or actin filaments, facilitating the release of ADP. Here we report that a mutation in the motor domain of the microtubule motor proteins Kar3 and Ncd uncouples nucleotide- and microtubule-binding by the proteins, preventing activation of the motor ATPase by microtubules. Unlike the wild-type motors, the mutants bind tightly to both ADP and microtubules, indicating that interactions between the nucleotide- and microtubule-binding sites are blocked. The region of the motor that includes the mutated amino acid could transmit or undergo a conformational change required to convert the motor ATPase into a microtubule-stimulated state.


Porcine fetuses with pulmonary hypoplasia resulting from experimental swine influenza virus infection.
Porcine fetuses between 51 and 57 days of gestation were inoculated intraallantoically with swine influenza virus and examined 3, 7, 13, 28 and 58 days after inoculation. At 3 and 7 days, severe epithelial necrosis was seen in most bronchial buds and there was moderate epithelial necrosis in more fully differentiated major bronchi. As a result of the epithelial injury, bronchial buds did not develop further and the surrounding mesoderm failed to differentiate. By 28 days, the lungs of inoculated fetuses were about one-half the size of the normal control lungs. Microscopically, the lungs of the inoculated fetuses were composed of major bronchi surrounded by multiple islands of cartilage, medium to large arteries and a few small, incompletely developed lobules. Influenza virus was isolated most consistently and in greatest quantity from the lung, trachea and chorion of inoculated fetuses. Influenza viral antigen was shown in the epithelium of bronchial buds, bronchi and the trachea by direct fluorescent antibody staining. Hemagglutination inhibiting antibodies to influenza virus were first found in the serum of an inoculated fetus at 13 days and in the sera of all inoculated fetuses at 28 and 58 days.


Er:YAG lasers versus ultrasonic and hand instruments in periodontal therapy: clinical parameters, intracrevicular micro-organism and leukocyte counts.
The aim of this study was to compare the clinical parameters and crevicular cell population, particularly leukocyte counts, changes after initial periodontal therapy with different instruments by a chairside laboratory technique, in severe periodontitis patients. Although scaling and root planing (SRP) with hand curettes or ultrasonic scalers may alter the subgingival microbial composition and improve clinical parameters, it is known that this effect decreases as the pocket depth (PD) increases. Thirty systemically healthy subjects with severe chronic periodontitis were randomly assigned to three groups (n=10), and were treated either with hand curettes, ultrasonic scalers, or Er:YAG laser alone. Clinical measurements were made before and 90 days after treatment. A total of four subgingival plaque samples were collected from pockets with a PD 4-6 and ≥7 mm and were analyzed with a phase-contrast microscopy for microorganism proportions and leukocyte counts at baseline and 7 and 90 days after treatment. From day 0 to day 90, clinical parameters were significantly improved in all groups (p<0.01), but there were no significant differences among groups. Laboratory assessments revealed significant differences in all groups between baseline, day 7, and day 90. However, considering changes from day 7 to day 90, hand curettes were the most successful for maintaining the levels of micro-organisms and leukocytes. Although Er:YAG lasers are promising in treating periodontitis, the results of this study favor finishing SRP with hand curettes. Moreover, as there is a similar tendency between micro-organism and leukocyte count changes, leukocyte counts may be used as chairside marker to evaluate the efficacy of SRP.


An innovative framework for psychosocial assessment in complex mental capacity evaluations.
This study describes an innovative tool developed by the Regional Capacity Assessment Team (RCAT) to assess unique psychosocial factors related to capacity evaluations. Capacity is a socio-legal construct entailing the ability to understand choices, appreciate consequences and follow through (or direct a surrogate) with chosen options. RCAT's targeted psychosocial assessment includes medico-legal factors, social history and supports, coping skills, religious/cultural factors and risk of abuse. RCAT completes the psychosocial assessment to determine whether a full capacity assessment is required (referral disposition) and to determine the impact of an adult's social functioning on their decision-making capacity (capacity determination). RCAT's psychosocial assessment protocol was developed after a comprehensive literature review of capacity assessment and incorporates recommended practices in geriatric social work and psychology. This study will synthesise the pertinent literature, discuss cultural interviewing processes significant to capacity, caregiver assessment and describe the tool itself. Suggestions for future research and appropriate implementation of this tool are provided.


A new model of nerve injury in the rat reveals a role of Regulator of G protein Signaling 4 in tactile hypersensitivity.
Tactile hypersensitivity is one of the most debilitating symptoms of neuropathic pain syndromes. Clinical studies have suggested that its presence at early postoperative stages may predict chronic (neuropathic) pain after surgery. Currently available animal models are typically associated with consistent tactile hypersensitivity and are therefore limited to distinguish between mechanisms that underlie tactile hypersensitivity as opposed to mechanisms that protect against it. In this study we have modified the rat model of spared nerve injury, restricting the surgical lesion to a single peripheral branch of the sciatic nerve. This modification reduced the prevalence of tactile hypersensitivity from nearly 100% to approximately 50%. With this model, we here also demonstrated that the Regulator of G protein Signaling 4 (RGS4) was specifically up-regulated in the lumbar dorsal root ganglia and dorsal horn of rats developing tactile hypersensitivity. Intrathecal delivery of the RGS4 inhibitor CCG63802 was found to reverse tactile hypersensitivity for a 1h period. Moreover, tactile hypersensitivity after modified spared nerve injury was most frequently persistent for at least four weeks and associated with higher reactivity of glial cells in the lumbar dorsal horn. Based on these data we suggest that this new animal model of nerve injury represents an asset in understanding divergent neuropathic pain outcomes, so far unravelling a role of RGS4 in tactile hypersensitivity. Whether this model also holds promise in the study of the transition from acute to chronic pain will have to be seen in future investigations.


Inter- and intraobserver assessment of periacetabular osteodensitometry after cemented and uncemented total hip arthroplasty using computed tomography.
This study was initiated to evaluate the reproducibility of a novel method for measuring the periacetabular bone density after insertion of cemented and uncemented acetabular cups using CT in vivo. CT scans were obtained from 20 patients after cemented polyethylene cup implantation (ZCA, Zimmer, USA) and 20 patients after uncemented titanium alloy cup fixation (Cerafit, Ceraver, France). A manual segmentation of cancellous and cortical pelvic bone ventral, dorsal and cranial to the cup was undertaken. Values are given in Hounsfield units. Inter- and intraobserver studies were conducted using a special analysis software tool. To define the reproducibility of the method, all measurements were evaluated according to Bland and Altman. For both cemented and uncemented acetabular cups, reproducibility of bone density measurement for cortical and cancellous bone cranial, ventral and dorsal to the cup was high. There was no significant difference between the intraobsever study (two repeated measurements) and the interobserver study (two investigators), indicating the reproducibility of the method independent of the investigator. In conclusion, the periacetabular bone density measurement as conducted in this CT study is a new reproducible method for in vivo evaluation of cortical and cancellous pelvic bone after cemented and uncemented acetabular cup implantation. In vivo CT measurements will allow a thorough assessment of periacetabular stress-shielding phenomena.


Measuring and reflecting depth of anesthesia using wavelet and power spectral density.
This paper evaluates depth of anesthesia (DoA) monitoring using a new index. The proposed method preconditions raw EEG data using an adaptive threshold technique to remove spikes and low-frequency noise. We also propose an adaptive window length technique to adjust the length of the sliding window. The information pertinent to DoA is then extracted to develop a feature function using discrete wavelet transform and power spectral density. The evaluation demonstrates that the new index reflects the patient's transition from consciousness to unconsciousness with the induction of anesthesia in real time.


Measurement of peripheral tissue thickness by ultrasound during the perioperative period.
We have studied changes in peripheral tissue thickness with a novel hand-held ultrasound device during the perioperative course of 60 healthy surgical patients in three different intraoperative body positions. The nil-by-mouth period led to a significant decrease in forehead tissue thickness. Standardized infusion therapy with Ringer's solution at a rate of 8 ml kg-1 h-1 resulted in a gradual increase in tissue thickness, which was significantly different from preoperative baseline values after 90 min. Packed cell volume decreased significantly after the start of infusion and remained low over the rest of the observation time. Different body positions did not influence changes in tissue thickness. We conclude that changes in perioperative tissue thickness in healthy patients can be detected easily by ultrasound, independent of body position. This method may prove useful for the non-invasive assessment of fluid balance state.


Leishmaniasis and phlebotomine sand flies in Oman Sultanate.
There are few data on leishmaniases and sandflies in Oman Sultanate. We carried out an eco-epidemiological study in 1998 in the two main mountains of the country, the Sharqiyah and the Dhofar. This study allowed us to isolate and identify three Leishmania strains from patients exhibiting cutaneous leishmaniasis. The typing carried out by isoenzymatic study and by molecular biology were congruent: two strains of Leishmania donovani zymodeme (Z) MON-31 isolated in the Sharqiyah and one L. tropica ZROM102 (ZMON-39 variant for 4 isoenzymes) from the Dhofar. No strain was isolated from canids. The study of sandflies identified 14 species distributed in the genera Phlebotomus, Sergentomyia and Grassomyia: Ph. papatasi, Ph. bergeroti, Ph. duboscqi, Ph. alexandri, Ph. saevus, Ph. sergenti, Se. fallax, Se. baghdadis, Se. cincta, Se. christophersi, Se. clydei, Se. tiberiadis, Se. africana, and Gr. dreyfussi. In Sharqiyah, the only candidate for the transmission of L. donovani was Ph. alexandri, but the low densities observed of this species do not argue in favor of any role. In Dhofar, Ph. sergenti is the most important proven vector of L. tropica, but Ph. saevus, a locally much more abundant species, constitutes a good candidate for transmission.


Inhibition of promoter activity by methylation: possible involvement of protein mediators.
To study the relationship between DNA methylation and promoter activity we have methylated in vitro the promoters of the mouse metallothionein I gene and the herpes simplex virus thymidine kinase gene. We have transiently transfected these promoters fused to the human growth hormone in their methylated or unmethylated state into mouse L or F9 cells. Promoters methylated by methylase (M.) Hpa II and M.Hha I caused inhibition of reporter gene expression in L cells but not in F9 cells, while methylation of all CpGs by M.Sss I caused inhibition in both cell lines. Repression of promoter activity by M.Hpa II and M.Hha I methylation, but not by M.Sss I methylation, could be alleviated by cotransfection with an excess of untranscribable DNA methylated with M.Sss I. The methylated sites in nuclei isolated from the transfected L cells, but not F9 cells, were found to be protected from Msp I digestion. Taken together these results suggest that a factor present in L cells and missing in F9 cells mediates the methylation-directed inhibition of promoter activity. The ability of methylated DNA to overcome the inhibition seems to reflect competition for the mediator factor. Interestingly, treatment with Zn2+ ions brought about activation of the methylated promoter of the metallothionein gene. Similarly, butyrate could override the repression of the thymidine kinase methylated promoter. These activations were not accompanied by demethylation of the promoter or displacement of the mediator factor.


Prolonged survival and effective palliation in patients with squamous cell carcinoma of the esophagus following endoscopic laser therapy.
Endoscopic laser therapy provides effective symptomatic palliation for patients with squamous cell carcinoma of the esophagus. To investigate whether this treatment also prolongs survival, a retrospective case-control study was performed. Ten patients with squamous cell carcinoma of the esophagus, diagnosed between 1983 and 1985, were treated with the neodymium: yttrium aluminum garnet laser (Cooper Lasersonics, Model 8000, Santa Clara, CA). Twenty patients with the same diagnosis observed between 1979 and 1984 served as age-matched controls. There was no significant difference in sex, race, location of the cancer, prior treatment, or dysphagia scores for the two groups. Laser therapy produced a significant improvement in the mean dysphagia score. Life table analysis demonstrated a median survival of 17.5 months for the patients treated with endoscopic laser therapy compared with 5.7 months for the control subjects (P less than 0.05). One-year survival after laser treatment was 75%, compared with 20% in the control group (P less than 0.05). These results suggest that endoscopic laser therapy is effective for prolonging survival and improving the quality of life in patients with squamous cell carcinoma of the esophagus.


Development of a cell-based nonradioactive glucose uptake assay system for SGLT1 and SGLT2.
Sodium-dependent glucose cotransporters (SGLT1 and SGLT2), which have a key role in the absorption of glucose in the kidney and/or gastrointestinal tract, have been proposed as a novel therapeutic strategy for diabetes and cardiomyopathy. Here we developed a simple cell-based, nonradioactive method for functional screening of SGLT1 and SGLT2 inhibitors. Stable cell lines expressing human SGLT1 and SGLT2 were established by transfecting HEK293 cells with vectors (pCMV6-Neo) having full-length human SGLT1 and SGLT2 and selecting the positive clones following neomycin treatment. We confirmed the gene expression of SGLT1 and SGLT2 by reverse transcription polymerase chain reaction (RT-PCR) and immunoblotting. Furthermore, to analyze the function of SGLTs, we incubated stable cell lines with 2-deoxyglucose or fluorescent d-glucose analog (2-NBDG) and performed glucose uptake assay. A significant (P<0.001) increase in glucose uptake was observed in both cell lines. The increased glucose uptake in both cell lines was completely inhibited when treated with nonspecific SGLT1/SGLT2 inhibitors and phlorizin (100μM), but not when treated with nonspecific sodium-independent facilitative glucose transporter (GLUT) inhibitors (100μM). Taken together, our data suggest that cell-based methods developed for screening SGLT1/SGLT2 inhibitors are phlorizin sensitive and specific for respective glucose transporters. This assay provides a simple and rapid method for identifying novel and selective SGLT inhibitors.


Sleep Quality of Call Handlers Employed in International Call Centers in National Capital Region of Delhi, India.
Call center sector in India is a relatively new and fast growing industry driving employment and growth in modern India today. Most international call centers in National Capital Region (NCR) of Delhi operate at odd work hours corresponding to a time suitable fortheir international customers. The sleep quality of call handlers employed in these call centers is in jeopardy owing to their altered sleep schedule. To assess the sleep quality and determine its independent predictors among call handlers employed in international call centers in NCR of Delhi. A cross-sectional questionnaire-based study was conducted on 375 call handlers aged 18-39 years employed in international call centers in NCR of Delhi. Sleep quality was assessed using Athens Insomnia scale along with a pre-tested, structured questionnaire. The mean age of respondents was 24.6 (SD 2.4) years. 78% of participants were male. 83.5% of respondents were unmarried. 44.3% of call handlers were cigarette smokers. Physical ailments were reported by 37% call handlers. 77.6% of call handlers had somesuspicion of insomnia or suspected insomnia; the rest had no sleep problem. Smoking, poor social support, heavy workload, lack of relaxation facility at office, and prolonged travel time to office were independent predictors of sleep quality (p<0.05). Call handlers have to compromise upon their sleep owing to the contemporary work settings in call centers. Safeguarding their health becomes an occupational health challenge to public health specialists.


Risk assessment of soil heavy metal contamination at the census tract level in the city of Santa Ana, CA: implications for health and environmental justice.
(1) Background: exposure to heavy metals is associated with adverse health effects and disproportionately impacts low-income communities and communities of color. We carried out a community-based participatory research study to examine the distribution of heavy metal concentrations in the soil and social vulnerabilities to soil heavy metal exposures across Census tracts in Santa Ana, CA. (2) Methods: soil samples (n = 1528) of eight heavy metals including lead (Pb), arsenic (As), manganese (Mn), chromium (Cr), nickel (Ni), copper (Cu), cadmium (Cd), and zinc (Zn) were collected in 2018 across Santa Ana, CA, at a high spatial resolution and analyzed using XRF analysis. Metal concentrations were mapped out and American Community Survey data was utilized to assess metals throughout Census tracts in terms of social and economic variables. Risk assessment was conducted to evaluate carcinogenic and non-carcinogenic risk. (3) Results: concentrations of soil metals varied according to landuse type and socioeconomic factors. Census tracts where the median household income was under $50 000 had 390%, 92.9%, 56.6%, and 54.3% higher Pb, Zn, Cd, and As concentrations compared to high-income counterparts. All Census tracts in Santa Ana showed hazard index >1, implying the potential for non-carcinogenic health effects, and nearly all Census tracts showed a cancer risk above 10-4, implying a greater than acceptable risk. Risk was predominantly driven by childhood exposure. (4) Conclusions: findings inform initiatives related to environmental justice and highlight subpopulations at elevated risk of heavy metal exposure, in turn underscoring the need for community-driven recommendations for policies and other actions to remediate soil contamination and protect the health of residents.


Gray matter volumes of early sensory regions are associated with individual differences in sensory processing.
Sensory processing (i.e., the manner in which the nervous system receives, modulates, integrates, and organizes sensory stimuli) is critical when humans are deciding how to react to environmental demands. Although behavioral studies have shown that there are stable individual differences in sensory processing, the neural substrates that implement such differences remain unknown. To investigate this issue, structural magnetic resonance imaging scans were acquired from 51 healthy adults and individual differences in sensory processing were assessed using the Sensory Profile questionnaire (Brown et al.: Am J Occup Ther 55 (2001) 75-82). There were positive relationships between the Sensory Profile modality-specific subscales and gray matter volumes in the primary or secondary sensory areas for the visual, auditory, touch, and taste/smell modalities. Thus, the present results suggest that individual differences in sensory processing are implemented by the early sensory regions. Hum Brain Mapp 38:6206-6217, 2017. © 2017 Wiley Periodicals, Inc.


Facilitators and Barriers to Dementia Assessment and Diagnosis: Perspectives From Dementia Experts Within a Global Health Context.
Dementia poses one of the greatest global health challenges, affecting 50 million people worldwide. With 10 million new cases each year, dementia is a growing burden, particularly in low- and middle-income countries (LMIC). This study aimed to identify the facilitators and barriers to providing quality dementia assessment and care in LMICs from a global health perspective. A qualitative semi-structured interview study with 20 dementia expert healthcare providers from 19 countries. To be included, providers had to: practice dementia assessment or care in LMICs where the population over age 60 is projected to more than double by 2050 and be recognized as a leading dementia expert in the region based on position, research publications, and/or policy leadership. Interviews were analyzed by a multidisciplinary team of researchers using thematic analysis. Barriers to dementia assessment and care included stigma about dementia, poor patient engagement in and access to healthcare, inadequate linguistic and cultural validation, limited dementia capable workforce, competing healthcare system priorities, and insufficient health financing. Facilitators included the rise in dementia awareness campaigns, dementia training for general practitioners, availability of family support and family caregivers, and national and international collaborations including coordinated policy efforts and involvement in international research initiatives. Findings from this study provide insights for prioritizing dementia assessment and care capacity-building in LMICs as a global health priority and for tailored public health approaches to strengthen dementia assessment and care at the individual, community, national, and multi-national levels.


Eucalypts face increasing climate stress.
Global climate change is already impacting species and ecosystems across the planet. Trees, although long-lived, are sensitive to changes in climate, including climate extremes. Shifts in tree species' distributions will influence biodiversity and ecosystem function at scales ranging from local to landscape; dry and hot regions will be especially vulnerable. The Australian continent has been especially susceptible to climate change with extreme heat waves, droughts, and flooding in recent years, and this climate trajectory is expected to continue. We sought to understand how climate change may impact Australian ecosystems by modeling distributional changes in eucalypt species, which dominate or codominate most forested ecosystems across Australia. We modeled a representative sample of Eucalyptus and Corymbia species (n = 108, or 14% of all species) using newly available Representative Concentration Pathway (RCP) scenarios developed for the 5th Assessment Report of the IPCC, and bioclimatic and substrate predictor variables. We compared current, 2025, 2055, and 2085 distributions. Overall, Eucalyptus and Corymbia species in the central desert and open woodland regions will be the most affected, losing 20% of their climate space under the mid-range climate scenario and twice that under the extreme scenario. The least affected species, in eastern Australia, are likely to lose 10% of their climate space under the mid-range climate scenario and twice that under the extreme scenario. Range shifts will be lateral as well as polewards, and these east-west transitions will be more significant, reflecting the strong influence of precipitation rather than temperature changes in subtropical and midlatitudes. These net losses, and the direction of shifts and contractions in range, suggest that many species in the eastern and southern seaboards will be pushed toward the continental limit and that large tracts of currently treed landscapes, especially in the continental interior, will change dramatically in terms of species composition and ecosystem structure.


MoTe2 van der Waals homojunction p-n diode with low resistance metal contacts.
Although many studies have focused on transition metal dichalcogenide heterojunction p-n diodes, homojunction p-n diodes still require more extensive study. We present a van der Waals p-MoTe2/n-MoTe2 homojunction p-n diode with low resistance metal contacts. Such two-dimensional homojunction devices with low contact resistance can be used in various applications in the electronics industry. The device structure consists of stacked nanoflakes of p-MoTe2 and n-MoTe2. In this investigation, we implement a deep ultraviolet light-driven doping technique in a N2 gas environment to modulate the carrier concentration in a multilayered p-MoTe2 flake, which is consequently inverted to n-MoTe2. The deep ultraviolet light-driven doping provides environmental stability in the treated devices. We use ohmic metal contacts for the homojunction p-n diode and achieve excellent gate-dependent rectifying behavior with a rectification ratio of up to 104. Contrary to heterojunctions, the ideality factor is found to be 1.05 for the zero gate bias, indicative of good interface quality at the p-MoTe2/n-MoTe2 junction, owing to low charge trapping sites at the homojunction interface. In addition, low-temperature measurements are performed to determine the barrier height for different gate biases. This study contributes to research on van der Waals homojunction p-n diodes, which show much potential for nanoelectronic and optoelectronic devices.


Insulin kinetics, models, and delivery schedules.
Several insulin models are examined as to their responses to various insulin inputs and glucose utilization and production control. It is shown that the action of insulin on glucose utilization correlates best with model compartments having a 30--50-min delay compared with plasma, whereas glucose production control is rapid. It is further shown that whereas the predicted plasma insulin response curves are nearly the same for various models, the responses at possible sites of action (e.g., receptors or slowly exchanging tissues) can differ considerably for the different models. By determining the parameter values for the glucose-insulin system in a patient through isotope kinetics studies, it is possible to use the patient's model either as a direct algorithm for insulin delivery or as a tool for studying glucose control under various conditions and thus aid in the design of appropriate algorithms or schedules for insulin delivery.


How therapists respond to "uneven" alliances in couple and family therapy: A conversation-analytic study.
This article examines how family and couple therapists respond to uneven alliances with their clients at the micro-level of therapeutic exchanges in the context of Interpersonal Process Recall (IPR) interviews. We operationalize uneven alliance with the interactional concept of asymmetry of affiliation. To this end, first, using conversation analysis (CA), we identify episodes of asymmetry of affiliation in the moment-by-moment conversation between the therapist and the client in therapy consultation. Second, applying CA to the IPR interview data, we examine how therapists orient to the episodes of the session in which the asymmetry of affiliation was identified. The findings demonstrate therapists' two key practices of orienting to the episodes of asymmetry of affiliation: (1) therapists' exclusive identification with one participant by typically invoking gender roles and (2) therapists' investigation of their agency in the emergence of asymmetry.


[Prognostic value of myocardial injury in patients with COVID-19].
Objective: To analyze the prognostic value of myocardial injury in patients with COVID-19. Method: Confirmed cases of COVID-19 patients admitted from January 31st to February 5th at isolation ward of Renmin Hospital of Wuhan University were divided into non-survival group and survival group according to the clinical outcomes 5 weeks after admission. Data including demographics, comorbidities, vital signs, laboratory results were obtained. Cardiac injury was defined as serum concentration of high sensitivity cardiac troponin I (hs-cTnI) above 0.04 μg/L. Univariate and multivariate Cox regression were used to analyze the prognostic value of myocardial injury in patients with COVID-19. Kaplan-Meier analysis was used to plotted survival curve and analyze the impact of myocardial injury on the survival outcome of COVID-19 patients. Results: A total of 202 patients were included, the age was 63 (51, 70) years old, 88 (43.6%) of them were male, 85 (42.1%) of them had comorbidities, 125 (61.9%) of them were severely to critically ill. Till March 11, 33 patients died, all of them were critically ill patients. The age, proportion of males, comorbidities, respire rate, serum levels of hs-cTnI and incidence of heart failure in the non-survival group were significantly higher than those in the survival group (all P<0.05). The hospitalization time of non-survival group was significantly shorter than that of survival group (6(4, 9) vs. 32(23, 36), P<0.001). Myocardial injury was an important prognostic factor of COVID-19 (HR=5.382, 95%CI 2.404-12.05, P<0.001). Kaplan-Meier survival analysis showed that the presence of myocardial injury was significantly associated with the reduced survival rate among COVID-19 patients (P<0.001). Conclusion: Myocardial injury is an important prognostic factor of COVID-19, COVID-19 patients with myocardial injury face a significantly higher risk of death.


Statistical analysis of Clewell et al. PBPK model of trichloroethylene kinetics.
A physiologically based pharmacokinetic model for trichloroethylene (TCE) in rodents and humans was calibrated with published toxicokinetic data sets. A Bayesian statistical framework was used to combine previous information about the model parameters with the data likelihood, to yield posterior parameter distributions. The use of the hierarchical statistical model yielded estimates of both variability between experimental groups and uncertainty in TCE toxicokinetics. After adjustment of the model by Markov chain Monte Carlo sampling, estimates of variability for the animal or human metabolic parameters ranged from a factor of 1.5-2 (geometric standard deviation [GSD]). Uncertainty was of the same order as variability for animals and higher than variability for humans. The model was used to make posterior predictions for several measures of cancer risk. These predictions were affected by both uncertainties and variability and exhibited GSDs ranging from 2 to 6 in mice and rats and from 2 to 10 for humans.


Can tactile stimuli be subitised? An unresolved controversy within the literature on numerosity judgments.
There is a growing interest in the question whether the phenomenon of subitising (fast and accurate detection of fewer than 4-5 stimuli presented simultaneously), widely thought to affect numerosity judgments in vision, can also affect the processing of tactile stimuli. In a recent study, in which multiple tactile stimuli were simultaneously presented across the body surface, Gallace et al (2006 Perception 35 247-266) concluded that tactile stimuli cannot be subitised. By contrast, Riggs et al (2006 Psychological Science 17 271 275), who presented tactile stimuli to participants' fingertips, came to precisely the opposite conclusion, arguing instead that subitising does occur in touch. Here, we re-analyse the data from both studies using more powerful statistical procedures. We show that Riggs et al's error data do not offer strong support for the subitising account and, what is more, Gallace et al's data are not entirely compatible with a linear model account of numerosity judgments in humans either. We then report an experiment in which we compare numerosity judgments for stimuli presented on the fingertips with those for stimuli presented on the rest of the body surface. The results show no major differences between the fingers and the rest of the body, and an absence of subitising in either condition. On the basis of these observations, we discuss whether the purported existence of subitisation in touch reflects a genuine cognitive phenomenon, or whether, instead, it may reflect a bias in the interpretation of the particular psychometric functions that happen to have been chosen by researchers to fit their data.


Energy Balance After Sodium-Glucose Cotransporter 2 Inhibition.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors cause substantially less weight loss than expected from the energy excreted via glycosuria. Our aim was to analyze this phenomenon quantitatively. Eighty-six patients with type 2 diabetes (HbA1c 7.8 ± 0.8% [62 ± 9 mmol/mol], estimated glomerular filtration rate [eGFR] 89 ± 19 mL ⋅ min(-1) ⋅ 1.73 m(-2)) received empagliflozin (25 mg/day) for 90 weeks with frequent (n = 11) assessments of body weight, eGFR, and fasting plasma glucose (FPG). Time-dependent glucose filtration was calculated as the product of eGFR and FPG; time-dependent glycosuria was estimated from previous direct measurements. The relation of calorie-to-weight changes was estimated using a mathematical model of human energy metabolism that simulates the time course of weight change for a given change in calorie balance and calculates the corresponding energy intake changes. At week 90, weight loss averaged -3.2 ± 4.2 kg (corresponding to a median calorie deficit of 51 kcal/day [interquartile range (IQR) 112]). However, the observed calorie loss through glycosuria (206 kcal/day [IQR 90]) was predicted to result in a weight loss of -11.3 ± 3.1 kg, assuming no compensatory changes in energy intake. Thus, patients lost only 29 ± 41% of the weight loss predicted by their glycosuria; the model indicated that this difference was accounted for by a 13% (IQR 12) increase in calorie intake (269 kcal/day [IQR 258]) coupled with a 2% (IQR 5) increase in daily energy expenditure (due to diet-induced thermogenesis). This increased calorie intake was inversely related to baseline BMI (partial r = -0.34, P < 0.01) and positively to baseline eGFR (partial r = 0.29, P < 0.01). Chronic glycosuria elicits an adaptive increase in energy intake. Combining SGLT2 inhibition with caloric restriction is expected to be associated with major weight loss.


Clinically significant changes in pain along the Pain Intensity Numerical Rating Scale in patients with chronic low back pain.
Low back pain (LBP) is the most common cause of chronic pain. Numerous clinical scales are available for evaluating pain, but their objective criteria in the management of LBP patients remain unclear. This study aimed to determine an objective cutoff value for a change in the Pain Intensity Numerical Rating Scale (ΔPI-NRS) three months after LBP treatment. Its utility was compared with changes in six commonly used clinical scales in LBP patients: Pain Disability Assessment Scale (PDAS), Pain Self-Efficacy Questionnaire (PSEC), Pain Catastrophizing Scale (PCS), Athens Insomnia Scale (AIS), EuroQoL 5 Dimension (EQ5D), and Locomo 25. We included 161 LBP patients treated in two representative pain management centers. Patients were partitioned into two groups based on patient's global impression of change (PGIC) three months after treatment: satisfied (PGIC = 1, 2) and unsatisfied (3-7). Multivariate logistic regression analysis was performed to explore relevant scales in distinguishing the two groups. We found ΔPI-NRS to be most closely associated with PGIC status regardless of pre-treatment pain intensity, followed by ΔEQ5D, ΔPDAS, ΔPSEC, and ΔPCS. The ΔPI-NRS cutoff value for distinguishing the PGIC status was determined by ROC analysis to be 1.3-1.8 depending on pre-treatment PI-NRS, which was rounded up to ΔPI-NRS = 2 for general use. Spearman's correlation coefficient revealed close relationships between ΔPI-NRS and the six other clinical scales. Therefore, we determined cutoff values of these scales in distinguishing the status of ΔPI-NRS≥2 vs. ΔPI-NRS<2 to be as follows: ΔPDAS, 6.71; ΔPSEC, 6.48; ΔPCS, 6.48; ΔAIS, 1.91; ΔEQ5D, 0.08; and ΔLocomo 25, 9.31. These can be used as definitive indicator of therapeutic outcome in the management of chronic LBP patients.


Hydration of Biodentine, Theracal LC, and a prototype tricalcium silicate-based dentin replacement material after pulp capping in entire tooth cultures.
The calcium-releasing ability of pulp-capping materials induces pulp tissue regeneration. Tricalcium silicate-based materials produce calcium hydroxide as a by-product of hydration. Assessment of hydration and calcium ion leaching is usually performed on samples that have been aged in physiological solution for a predetermined period of time. The hydration and activity of the materials in vivo may not be similar to those displayed in vitro because of insufficient fluid available in contact with dentin. The aim of this research was the assessment of hydration of Biodentine, Theracal LC, and a prototype radiopacified tricalcium silicate-based material after pulp capping and to compare it with direct hydration in an aqueous solution. The extent of hydration of Biodentine, Theracal LC, and a prototype radiopacified tricalcium silicate-based material with a similar composition to Biodentine but not incorporating the additives was assessed by scanning electron microscopy and energy dispersive spectroscopy of polished specimens after being allowed to hydrate in Hank's balanced salt solution for 14 days. The extent of hydration was compared with material hydration when used as direct pulp capping materials by using a tooth culture model. Material activity was also assessed by x-ray diffraction analysis to investigate the deposition of calcium hydroxide by the materials, and calcium ion leaching in Hank's balanced salt solution was assessed by ion chromatography. Biodentine and the prototype tricalcium silicate cement hydrated and reaction by-products were deposited in the cement matrix both after pulp capping and when incubated in an aqueous solution. Calcium hydroxide was formed, and calcium ions were leached in solution. Theracal LC hydration was incomplete because of the limited moisture diffusion within the material. Thus, no calcium hydroxide was produced, and a lower calcium ion leaching was recorded. Theracal LC had a heterogeneous structure with large unhydrated particles because not enough moisture was present to allow hydration to proceed. Biodentine composition was shown to be optimized, and the environmental conditions did not affect material microstructure. Biodentine exhibited formation of calcium hydroxide and calcium ion leaching, which are beneficial to the dental pulp.


Pantoea agglomerans: a mysterious bacterium of evil and good. Part II--Deleterious effects: Dust-borne endotoxins and allergens--focus on grain dust, other agricultural dusts and wood dust.
Pantoea agglomerans, a Gram-negative bacterium developing in a variety of plants as epiphyte or endophyte is particularly common in grain and grain dust, and has been identified by an interdisciplinary group from Lublin, eastern Poland, as a causative agent of work-related diseases associated with exposure to grain dust and other agricultural dusts. The concentration of P. agglomerans in grain as well as in the settled grain and flour dust was found to be high, ranging from 10(4)-10(8) CFU/g, while in the air polluted with grain or flour dust it ranged from 10(3)-10(5) CFU/m(3) and formed 73.2-96% of the total airborne Gram-negative bacteria. The concentration of P. agglomerans was also relatively high in the air of the facilities processing herbs and other plant materials, while it was lower in animal farms and in wood processing facilities. Pantoea agglomerans produces a biologically-potent endotoxin (cell wall lipopolysaccharide, LPS). The significant part of this endotoxin occurs in dusts in the form of virus-sized globular nanoparticles measuring 10-50 nm that could be described as the 'endotoxin super-macromolecules'. A highly significant relationship was found (R=0.804, P=0.000927) between the concentration of the viable P. agglomerans in the air of various agricultural and wood industry settings and the concentration of bacterial endotoxin in the air, as assessed by the Limulus test. Although this result may be interfered by the presence of endotoxin produced by other Gram-negative species, it unequivocally suggests the primary role of the P. agglomerans endotoxin as an adverse agent in the agricultural working environment, causing toxic pneumonitis (ODTS). Numerous experiments by the inhalation exposure of animals to various extracts of P. agglomerans strains isolated from grain dust, including endotoxin isolated with trichloroacetic acid (LPS-TCA), endotoxin nanoparticles isolated in sucrose gradient (VECN), and mixture of proteins and endotoxin obtained by extraction of bacterial mass in saline (CA-S), showed the ability of these extracts to evoke inflammatory and fibrotic changes in the lungs, to stimulate alveolar macrophages to produce superoxide anion (O2(-)), interleukin-1 (IL-1) and chemotactic factors for other macrophages and neutrophils, and to increase the pulmonary concentrations of toll-like receptors and chemokines. The most potent properties showed the CA-S which may be attributed to the allergenic properties of P. agglomerans proteins enhanced by the presence of the autologous endotoxin. The results of these experiments are in accord with the clinical studies which revealed a high reactivity of the agricultural and grain industry workers to allergenic extracts of P. agglomerans, and the presence in these populations of hypersensitivity pneumonitis and asthma cases caused by this bacterium. P. agglomerans has been also identified as a potential causative agent of allergic dermatitis in farmers and of allergic pulmonary disorders in cattle. In conclusion, similar to the cotton industry, also in the grain industry and in agriculture, Pantoea agglomerans should be regarded as one of the major causative agents of work-related diseases, caused by the adverse effects of protein allergens and endotoxin produced by this bacterium.


The Mechano-Ubiquitinome of Articular Cartilage: Differential Ubiquitination and Activation of a Group of ER-Associated DUBs and ER Stress Regulators.
Understanding how connective tissue cells respond to mechanical stimulation is important to human health and disease processes in musculoskeletal diseases. Injury to articular cartilage is a key risk factor in predisposition to tissue damage and degenerative osteoarthritis. Recently, we have discovered that mechanical injury to connective tissues including murine and porcine articular cartilage causes a significant increase in lysine-63 polyubiquitination. Here, we identified the ubiquitin signature that is unique to injured articular cartilage tissue upon mechanical injury (the "mechano-ubiquitinome"). A total of 463 ubiquitinated peptides were identified, with an enrichment of ubiquitinated peptides of proteins involved in protein processing in the endoplasmic reticulum (ER), also known as the ER-associated degradation response, including YOD1, BRCC3, ATXN3, and USP5 as well as the ER stress regulators, RAD23B, VCP/p97, and Ubiquilin 1. Enrichment of these proteins suggested an injury-induced ER stress response and, for instance, ER stress markers DDIT3/CHOP and BIP/GRP78 were upregulated following cartilage injury on the protein and gene expression levels. Similar ER stress induction was also observed in response to tail fin injury in zebrafish larvae, suggesting a generic response to tissue injury. Furthermore, a rapid increase in global DUB activity following injury and significant activity in human osteoarthritic cartilage was observed using DUB-specific activity probes. Combined, these results implicate the involvement of ubiquitination events and activation of a set of DUBs and ER stress regulators in cellular responses to cartilage tissue injury and in osteoarthritic cartilage tissues. This link through the ER-associated degradation pathway makes this protein set attractive for further investigation in in vivo models of tissue injury and for targeting in osteoarthritis and related musculoskeletal diseases.


Identification of a gene module associated with BMD through the integration of network analysis and genome-wide association data.
Bone mineral density (BMD) is influenced by a complex network of gene interactions; therefore, elucidating the relationships between genes and how those genes, in turn, influence BMD is critical for developing a comprehensive understanding of osteoporosis. To investigate the role of transcriptional networks in the regulation of BMD, we performed a weighted gene coexpression network analysis (WGCNA) using microarray expression data on monocytes from young individuals with low or high BMD. WGCNA groups genes into modules based on patterns of gene coexpression. and our analysis identified 11 gene modules. We observed that the overall expression of one module (referred to as module 9) was significantly higher in the low-BMD group (p = .03). Module 9 was highly enriched for genes belonging to the immune system-related gene ontology (GO) category "response to virus" (p = 7.6 × 10(-11)). Using publically available genome-wide association study data, we independently validated the importance of module 9 by demonstrating that highly connected module 9 hubs were more likely, relative to less highly connected genes, to be genetically associated with BMD. This study highlights the advantages of systems-level analyses to uncover coexpression modules associated with bone mass and suggests that particular monocyte expression patterns may mediate differences in BMD.


Onychomycosis--epidemiology, diagnosis and management.
Onychomycosis is a fungal infection of nails caused by dermatophytes, yeasts or nondermatophyte molds and represents about 30% of mycotic cutaneous infections. Increasingly onychomycosis is being viewed as more than a mere cosmetic problem. In spite of improved personal hygiene and living environment, onychomycosis continues to spread and persist. The prevalence rate of onychomycosis is determined by age, predisposing factor, social class, occupation, climate, living environment and frequency of travel. Onychomycosis in immunocompromised patients can pose a more serious health problem. Dermatophytes are the most frequently implicated causative agents in onychomycosis. Previously regarded as contaminants, yeasts are now increasingly recognised as pathogens in fingernail infections, as are some moulds. Clinical diagnosis of onychomycosis is based on the patients' history; a physical examination, microscopy and culture of nail specimens. The treatment of onychomycosis has been attempted throughout the ages, but only in the last two decades have safe, effective systemic treatments been available for this chronic superficial fungal disease. Oral Griseofulvin and Ketoconazole; once the agents of choice for the treatment of onychomycosis, have been superseded by newer systemic compounds that have a higher cure and lower relapse rates, cause fewer side effects and are suitable for short-term dosing.


Updated Polychlorinated Biphenyl Mass Budget for Lake Michigan.
This study revisits and updates the Lake Michigan Mass Balance Project (LMMBP) for polychlorinated biphenyls (PCBs) that was conducted in 1994-1995. This work uses recent concentrations of PCBs in tributary and open lake water, air, and sediment to calculate an updated mass budget. Five of the 11 LMMBP tributaries were revisited in 2015. In these five tributaries, the geometric mean concentrations of ∑PCBs (sum of 85 congeners) ranged from 1.52 to 22.4 ng L-1. The highest concentrations of PCBs were generally found in the Lower Fox River and in the Indiana Harbor and Ship Canal. The input flows of ∑PCBs from wet deposition, dry deposition, tributary loading, and air to water exchange, and the output flows due to sediment burial, volatilization from water to air, and transport to Lake Huron and through the Chicago Diversion were calculated, as well as flows related to the internal processes of settling, resuspension, and sediment-water diffusion. The net transfer of ∑PCBs is 1240 ± 531 kg yr-1 out of the lake. This net transfer is 46% lower than that estimated in 1994-1995. PCB concentrations in most matrices in the lake are decreasing, which drove the decline of all the individual input and output flows. Atmospheric deposition has become negligible, while volatilization from the water surface is still a major route of loss, releasing PCBs from the lake into the air. Large masses of PCBs remain in the water column and surface sediments and are likely to contribute to the future efflux of PCBs from the lake to the air.


Initial testing of a pixelated silicon detector prototype in proton therapy.
As technology continues to develop, external beam radiation therapy is being employed, with increased conformity, to treat smaller targets. As this occurs, the dosimetry methods and tools employed to quantify these fields for treatment also have to evolve to provide increased spatial resolution. The team at the University of Wollongong has developed a pixelated silicon detector prototype known as the dose magnifying glass (DMG) for real-time small-field metrology. This device has been tested in photon fields and IMRT. The purpose of this work was to conduct the initial performance tests with proton radiation, using beam energies and modulations typically associated with proton radiosurgery. Depth dose and lateral beam profiles were measured and compared with those collected using a PTW parallel-plate ionization chamber, a PTW proton-specific dosimetry diode, EBT3 Gafchromic film, and Monte Carlo simulations. Measurements of the depth dose profile yielded good agreement when compared with Monte Carlo, diode and ionization chamber. Bragg peak location was measured accurately by the DMG by scanning along the depth dose profile, and the relative response of the DMG at the center of modulation was within 2.5% of that for the PTW dosimetry diode for all energy and modulation combinations tested. Real-time beam profile measurements of a 5 mm 127 MeV proton beam also yielded FWHM and FW90 within ±1 channel (0.1 mm) of the Monte Carlo and EBT3 film data across all depths tested. The DMG tested here proved to be a useful device at measuring depth dose profiles in proton therapy with a stable response across the entire proton spread-out Bragg peak. In addition, the linear array of small sensitive volumes allowed for accurate point and high spatial resolution one-dimensional profile measurements of small radiation fields in real time to be completed with minimal impact from partial volume averaging.


Effect of odor stimulations on physical activity: A systematic review.
Fewer and fewer people are reaching physical activity recommendations. Therefore, it seems important to make the practice of physical activity more enjoyable to increase the participation rate. Several environmental factors have been studied to see their impact on sports practice, and some studies investigated the effect of odors. This systematic review aims to provide a thorough view of the literature on the effect of different odors on physical activity. The search strategy consisted of using index terms and keywords in MEDLINE, EMBASE, EBM Reviews - Cochrane Central Register of Controlled Trials, CINAHL, SPORTDiscus, and Web of Science search engine. Data from 19 studies that included 458 participants revealed that the odors had different results on strength, cardiovascular, precision, and postural balance tasks depending on the odors' exposition. Among results, an important distinction was made between pleasant and unpleasant odors. Therefore, pleasant odors had better results on physical activity by improving participants' feeling. Even though this review clarified evidence about the effect of odors on physical activity, better methodological consistency is needed across studies such as the odor administration method to produce more meaningful results.


Modulating mTOR Signaling as a Promising Therapeutic Strategy for Atherosclerosis.
For more than a decade, atherosclerosis has been one of the leading causes of death in developed countries. The issue of treatment and prevention of the disease is especially acute. Despite the huge amount of basic and clinical research, a significant number of gaps remain in our understanding of the pathogenesis of atherosclerosis, and only their closure will bring us closer to understanding the causes of the disease at the cellular and molecular levels and, accordingly, to the development of an effective treatment. One of the seemingly well-studied elements of atherogenesis is the mTOR signaling pathway. However, more and more new details are still being clarified. Therapeutic strategies associated with rapamycin have worked well in a number of different diseases, and there is every reason to believe that targeting components of the mTOR pathway may pay off in atherosclerosis as well.


A Systematic Scoping Review of the Prevalence, Etiological, Psychological, and Interpersonal Factors Associated with BDSM.
BDSM (bondage, discipline, dominance, submission, and sadomasochism) encompasses a diverse set of sexual interests. Research interests in BDSM have been historically underpinned by examining potential mental health issues, unhealthy fixations on specific sexual behaviors, and/or the presence of childhood trauma, as is predicted by psychopathological and psychoanalytic models. The objective of this scoping review was to provide an overview of the current landscape of BDSM research, including incidence rates, evidence for psychopathological, psychoanalytical, biological, and social etiological factors, demographics of BDSM practitioners, and the psychological correlates of those with BDSM interests. After the literature search and screening process, 60 articles were included. BDSM related fantasies were found to be common (40-70%) in both males and females, while about 20% reported engaging in BDSM. Results show little support for psychopathologic or psychoanalytic models. In the selected samples studied, BDSM practitioners appear to be white, well educated, young, and do not show higher rates of mental health or relationship problems. Research supports BDSM being used as a broadening of sexual interests and behaviors instead of a fixation on a specific interest. Future empirical research should focus on non-pathological models of BDSM, discrimination of BDSM practitioners, interpersonal relationships, and biological factors.


Usefulness of Kelly clamp crushing technique during hepatic resection.
Recently, there are various kinds of parenchymal transection methods. The aim of this study is to evaluate the usefulness of the Kelly clamp crushing technique compared to ultrasonic dissector during hepatic resection. Comparisons between 10 ultrasonic dissector group and 10 Kelly clamp crushing technique group were performed by using nine items (transaction time, right lobe volume, perioperative transfusion, total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), hospital stay, postoperative morbidity, in-hospital mortality). The mean transection time in the Kelly clamp crushing technique group was 27+/-15.5 mins (range 15-60) and was 48+/-7.1 mins (range 35-60) in the ultrasonic dissector group (p<0.05), and no patients received transfusion in both groups. Since the Kelly clamp crushing technique shortens operative time and there is no significant difference in blood loss and in results of liver function tests compared to using the ultrasonic dissector, we propose that the Kelly clamp crushing technique should be considered as a standard method of liver resection.


Biological energy sources: the surface energy and the physical chemistry of water. Examples from studies on muscle contraction.
The physical chemistry of water at nanometre dimensions was used to explain the conformational changes and water breaking properties of the glucose transporter protein (GLUTI) in human erythrocytes more than ten years ago. The energy for this hidden work arises from cycles of evaporation and condensation of water within the cells but was several times larger than resting metabolism. Physical chemical principles can quantify the hidden work done and demonstrate that a significant source of energy is available, which is free of the metabolic energy derived from the hydrolysis of ATP. Therefore, a more widespread biological use of this "free" energy source was probable and a working hypothesis, which applied this energy to supplement the work derived from ATP hydrolysis in muscle, was proposed. The scheme gives a complete explanation for the unexpected and novel findings in skeletal muscle reported from Italy. The problem of using two energy sources and the novel properties of water at nanometer dimensions as they would apply in muscle are briefly discussed but they merit further interdisciplinary studies.


Bioinks and Bioprinting Strategies for Skeletal Muscle Tissue Engineering.
Skeletal muscles play important roles in critical body functions and their injury or disease can lead to limitation of mobility and loss of independence. Current treatments result in variable functional recovery, while reconstructive surgery, as the gold-standard approach, is limited due to donor shortage, donor-site morbidity, and limited functional recovery. Skeletal muscle tissue engineering (SMTE) has generated enthusiasm as an alternative solution for treatment of injured tissue and serves as a functional disease model. Recently, bioprinting has emerged as a promising tool for recapitulating the complex and highly organized architecture of skeletal muscles at clinically relevant sizes. Here, skeletal muscle physiology, muscle regeneration following injury, and current treatments following muscle loss are discussed, and then bioprinting strategies implemented for SMTE are critically reviewed. Subsequently, recent advancements that have led to improvement of bioprinting strategies to construct large muscle structures, boost myogenesis in vitro and in vivo, and enhance tissue integration are discussed. Bioinks for muscle bioprinting, as an essential part of any bioprinting strategy, are discussed, and their benefits, limitations, and areas to be improved are highlighted. Finally, the directions the field should expand to make bioprinting strategies more translational and overcome the clinical unmet needs are discussed.


Alginate-Based Hydrogel Beads as a Biocompatible and Efficient Adsorbent for Dye Removal from Aqueous Solutions.
In this study, sodium alginate was employed as a starting material for preparing two kinds of biocompatible adsorbents, including calcium alginate hydrogel beads and magnetic hydrogel beads. Fourier transform infrared spectroscopy, X-ray diffraction pattern, and scanning electron microscopy/energy-dispersive X-ray techniques were used to characterize the prepared adsorbents. The performance of the prepared adsorbents for the removal of methyl violet from aqueous solution was studied in detail. Both kinetics and equilibrium aspects of methyl violet adsorption were investigated, and the obtained equilibrium and kinetics data were described with various adsorption models. The effects of initial dye concentration, adsorbent dosage, and temperature on adsorption performance were investigated. Thermodynamic parameters of adsorption were obtained as well.


Tubulointerstitial nephritis and uveitis syndrome in children: report of three cases.
Tubulointerstitial nephritis and uveitis syndrome is a rare and probably underdiagnosed condition. Renal and ocular manifestations may not occur simultaneously, making the diagnosis more difficult. Nephritis may be asymptomatic; therefore, renal function evaluation is essential for diagnosis. Urinary β2-microglobulin levels may be particularly useful. Uveitis, mostly anterior, nongranulomatous and bilateral, occurs usually after the onset of nephritis. Treatment includes corticosteroids and, eventually, other immunosuppressant agents. Renal disease is usually benign and resolves spontaneously or after treatment with systemic corticosteroids. Uveitis, however, may be chronic or recurrent. The authors described the cases of three pediatric patients diagnosed with tubulointerstitial nephritis and uveitis syndrome. The goal of this paper was to warn the medical community over the need to screen patients with uveitis for renal disease.


An Image-Analysis-Based Method for the Prediction of Recombinant Protein Fiber Tensile Strength.
Silk fibers derived from the cocoon of silk moths and the wide range of silks produced by spiders exhibit an array of features, such as extraordinary tensile strength, elasticity, and adhesive properties. The functional features and mechanical properties can be derived from the structural composition and organization of the silk fibers. Artificial recombinant protein fibers based on engineered spider silk proteins have been successfully made previously and represent a promising way towards the large-scale production of fibers with predesigned features. However, for the production and use of protein fibers, there is a need for reliable objective quality control procedures that could be automated and that do not destroy the fibers in the process. Furthermore, there is still a lack of understanding the specifics of how the structural composition and organization relate to the ultimate function of silk-like fibers. In this study, we develop a new method for the categorization of protein fibers that enabled a highly accurate prediction of fiber tensile strength. Based on the use of a common light microscope equipped with polarizers together with image analysis for the precise determination of fiber morphology and optical properties, this represents an easy-to-use, objective non-destructive quality control process for protein fiber manufacturing and provides further insights into the link between the supramolecular organization and mechanical functionality of protein fibers.


Vascular gene therapy: a reality of the 21st century.
Current therapies for the treatment of atherosclerotic vascular disease are aimed at either disrupting or bypassing flow-limiting lesions. Preventative strategies are necessary to decrease the burden of disease but are limited by genetic predispositions to certain diseases and the body's innate response to injury. Gene therapy, defined as the purposeful therapeutic overexpression or attenuation of a gene product, has enormous potential benefits in vascular disease prevention and treatment strategies. This article reviews the scientific considerations involved in the development of gene therapy strategies and outlines some of the gene products that are currently being used. These interventional genetic approaches will be reviewed in the context of specific vascular disease processes, including atherosclerosis, restenosis, and thrombosis. Gene therapy will serve an enhancing and adjuvant role to evolving surgical therapies.


KATAMARI1/MURUS3 Is a novel golgi membrane protein that is required for endomembrane organization in Arabidopsis.
In plant cells, unlike animal and yeast cells, endomembrane dynamics appear to depend more on actin filaments than on microtubules. However, the molecular mechanisms of endomembrane-actin filament interactions are unknown. In this study, we isolated and characterized an Arabidopsis thaliana mutant, katamari1 (kam1), which has a defect in the organization of endomembranes and actin filaments. The kam1 plants form abnormally large aggregates that consist of endoplasmic reticulum with actin filaments in the perinuclear region within the cells and are defective in normal cell elongation. Map-based cloning revealed that the KAM1 gene is allelic to the MUR3 gene. We demonstrate that the KAM1/MUR3 protein is a type II membrane protein composed of a short cytosolic N-terminal domain and a transmembrane domain followed by a large lumenal domain and is localized specifically on Golgi membranes. We further show that actin filaments interact with Golgi stacks via KAM1/MUR3 to maintain the proper organization of endomembranes. Our results provide functional evidence that KAM1/MUR3 is a novel component of the Golgi-mediated organization of actin functioning in proper endomembrane organization and cell elongation.


Giant cell tumour of talar body.
Giant cell tumour (osteoclastoma) of talar bone is a rare entity and is seen more commonly in the third decade of life. We report this disease entity in a 17-years-old girl. The patient presented with painful swelling of the left ankle with an osteolytic lesion in the talus on conventional radiographs. Intralesional curettage and autologous bone grafting was performed following which patient's pain and swelling disappeared. Complete range of movement at the ankle joint was regained with minimal restriction at the subtalar joint. There is no evidence of relapse at six months follow up.


[Acute pancreatitis and pregnancy. A recent case report].
The authors report a case of acute pancreatitis occurring at the end of pregnancy. Pancreatitis and pregnancy in association with one another is a very serious condition. Research of the literature shows that the maternal mortality is 37% and the perinatal mortality 37.9%. These results mean that it is very important to make the diagnosis as early as possible and to work out the treatment to be given after the Caesarean operation so as to minimise the ill effects for the mother and the infant. The diagnosis is made by ultrasound of the abdomen and the levels of the amylase in the blood. It is possible to work out a correct management for these patients. The first priority is to deliver the fetus as soon as possible after the 34th week of amenorrhoea. The treatment should be multi-disciplinary and at the Caesarean there should be present an obstetrician, a surgeon who specialises in bowel conditions, a gastroenterologist and a neonatologist.


Science and Serendipity: Finding Coca-Cola in China.
Four years of wide-ranging anthropological research yielded a surprising discovery: the Coca-Cola Company, working through an industry-funded scientific nonprofit, had quietly reshaped China's obesity science and policy to align with Coke's position that exercise, not food and drink, is what matters-a view few experts accept. Hoping to get the results to the key audiences, the author submitted a capstone article to a series of high-impact medical journals that was repeatedly rejected. Eventually the article was published in a top journal, but not as "scientific research." This prompted reflection on the differences between the methods of anthropology and medical science. Anthropological research is distinguished by methodological openness, serendipity, narrative sense-making, and personalism. It is personalistic in that the body is a research tool, and a solo researcher at the center acts as data clearinghouse and marshals regional expertise to show how things make cultural sense. Using the Coke-in-China research, this article illustrates how this systematic yet self-consciously subjective approach was effective in breaching the walls of industry science and uncovering the social ties and institutional mechanisms that allowed corporate schemes to remain hidden while gaining such power. The author encourages readers in medicine and public health to think about the complex, human process by which they reach their own conclusions. A better understanding of how each science is human in its own way might open up space for greater dialogue and even more collaborative knowledge-making at the crossroads of anthropology and the health sciences.


Exiguobacterium sp. A1b/GX59 isolated from a patient with community-acquired pneumonia and bacteremia: genomic characterization and literature review.
Bacterial species belonging to the genus Exiguobacterium are facultative anaerobic, non-spore-forming, Gram-positive bacilli, and rarely associated with human infections. Herein, we reported the first case of community-acquired pneumonia (CAP) and bacteremia due to Exiguobacterium spp. in China. An adult male with severe CAP was hospitalized. The pathogen was isolated from his bloodstream and broncho-alveolar lavage fluid. The correct identification of the micro-organism was achieved using 16S rRNA sequencing, and its antibiotic susceptibility test was performed by microdilution method. The Whole Genome Sequencing (WGS) was used to characterize its genetic features and to elucidate its potential pathogenic mechanisms. Furthermore, its genome sequence was also compared with those of 3 publicly-available Exiguobacterium strains. A PubMed search was performed for further understanding the features of Exiguobacterium infections. Phylogenetic analysis of the 16S rRNA gene sequence showed that the strain GX59 was most closely related to Exiguobacterium AT1b (99.7%). The genome of GX59 was 2,727,929 bp in size, harbouring 2855 putative protein-coding genes, 5 rRNA operons, 37 tRNA genes and 1 tmRNA. The multiple genome comparison of 4 Exiguobacterium strains demonstrated that Exiguobacterium contained 37 genes of secretion systems, including sec, tat, FEA, Type IV Pili and competence-related DNA transformation transporter (Com). Virulence factors of the micro-organism included tlyC, NprR, MCP, Dam, which might play a critical role in causing lethal infection. The study highlighted the potential pathogenicity of the genus Exiguobacterium for its unique genes encoding various virulence factors and those associated with antibiotic resistance, therefore, its clinical significance should be valued.


Cognitive-behavioral psychotherapy for children and adolescents with posttraumatic stress disorder after a single-incident stressor.
To test the efficacy of a group-administered cognitive-behavioral psychotherapy (CBT) protocol for pediatric posttraumatic stress disorder (PTSD) after a single-incident stressor. After a school-wide selection-to-treatment procedure conducted in two elementary and two junior high schools, children and adolescents with DSM-IV PTSD by structured interview were entered into an 18-week, group-administered CBT protocol using a single case across time and setting experimental design. Assessments of PTSD, anxiety, depression, trait anger, locus of control, and disruptive behavior were conducted at baseline, posttreatment, and at 6-month follow-up. Experimental control across time (staggered start date) and setting (school and age) was demonstrated. Fourteen of 17 subjects completed treatment. Of these, 8 (57%) no longer met DSM-IV criteria for PTSD immediately after treatment; 12 (86%) of 14 were free of PTSD at 6-month follow-up. On intent-to-treat analyses, treatment produced a robust beneficial effect posttreatment on the Clinician-Administered PTSD Scale-Child and Adolescent Version, with additional improvement accruing at follow-up (p < .001). Improvements of a similar magnitude were seen for depression (p < .001), anxiety (p < .001), and anger (p < .005). Locus of control remained external from pre- to posttreatment but became strongly internal at follow-up (p < .001). More clinical trials are required to confirm that CBT is a safe, acceptable, and effective treatment for PTSD in children and adolescents.


Comprehensive Study of Si-Based Compounds in Selected Plants (Pisum sativum L., Medicago sativa L., Triticum aestivum L.).
This review describes the role of silicon (Si) in plants. Methods of silicon determination and speciation are also reported. The mechanisms of Si uptake by plants, silicon fractions in the soil, and the participation of flora and fauna in the Si cycle in terrestrial ecosystems have been overviewed. Plants of Fabaceae (especially Pisum sativum L. and Medicago sativa L.) and Poaceae (particularly Triticum aestivum L.) families with different Si accumulation capabilities were taken into consideration to describe the role of Si in the alleviation of the negative effects of biotic and abiotic stresses. The article focuses on sample preparation, which includes extraction methods and analytical techniques. The methods of isolation and the characterization of the Si-based biologically active compounds from plants have been overviewed. The antimicrobial properties and cytotoxic effects of known bioactive compounds obtained from pea, alfalfa, and wheat were also described.


Long-term management of IPF with pirfenidone - a clinical case study with 5 years follow-up.
Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic interstitial lung disease that is associated with a median survival of 2-5 years from initial diagnosis. To date, the search for an effective treatment has involved numerous clinical trials of investigational agents but without significant success. Nevertheless, research over the past 10 years has provided us with a wealth of information on its histopathology, diagnostic work-up, and a greater understanding of its pathophysiology. Specifically, IPF is no longer thought to be a predominantly pro-inflammatory disorder. Rather, the fibrosis in IPF is increasingly understood to be the result of a fibroproliferative and aberrant wound healing cascade. The development of therapeutic targets has therefore shifted in accordance with this paradigm change. Emerging clinical data from recently published and ongoing trials investigating new potential pharmacological agents should be considered in the routine clinical management of these patients. Based upon encouraging results from randomised-controlled trials showing a positive effect in slowing decline in pulmonary function and reducing disease progression, pirfenidone was approved in 2011 as the first treatment in patients with IPF. This case study describes the clinical course of a patient enrolled into the Phase III and open-label extension studies of pirfenidone.


Structure-Guided Mutations in the Terminal Organelle Protein MG491 Cause Major Motility and Morphologic Alterations on Mycoplasma genitalium.
The emergent human pathogen Mycoplasma genitalium, with one of the smallest genomes among cells capable of growing in axenic cultures, presents a flask-shaped morphology due to a protrusion of the cell membrane, known as the terminal organelle, that is involved in cell adhesion and motility and is an important virulence factor of this microorganism. The terminal organelle is supported by a cytoskeleton complex of about 300 nm in length that includes three substructures: the terminal button, the rod and the wheel complex. The crystal structure of the MG491 protein, a proposed component of the wheel complex, has been determined at ~3 Å resolution. MG491 subunits are composed of a 60-residue N-terminus, a central three-helix-bundle spanning about 150 residues and a C-terminal region that appears to be quite flexible and contains the region that interacts with MG200, another key protein of the terminal organelle. The MG491 molecule is a tetramer presenting a unique organization as a dimer of asymmetric pairs of subunits. The asymmetric arrangement results in two very different intersubunit interfaces between the central three-helix-bundle domains, which correlates with the formation of only ~50% of the intersubunit disulfide bridges of the single cysteine residue found in MG491 (Cys87). Moreover, M. genitalium cells with a point mutation in the MG491 gene causing the change of Cys87 to Ser present a drastic reduction in motility (as determined by microcinematography) and important alterations in morphology (as determined by electron microscopy), while preserving normal levels of the terminal organelle proteins. Other variants of MG491, designed also according to the structural information, altered significantly the motility and/or the cell morphology. Together, these results indicate that MG491 plays a key role in the functioning, organization and stabilization of the terminal organelle.


Release parameters at the foul line and the official result in javelin throwing.
Range in javelin throwing is determined by the release parameters and aerodynamic factors. The current study was designed to investigate the effects of release speed, release angle and uncorrected angle of attack measured at the foul line on the official javelin throwing result. The data were collected in international competitions for 26 elite male and 15 elite female javelin throwers (total 248 throws). Multiple regression models were constructed to predict the range of throw for a) individual throwers, b) a group of throwers using the mean value for each thrower in the analysis, and c) all individual throws registered for each gender separately. The data collection was carried out using a computerised photocell gate that consists of two invisible infrared walls two metres apart, perpendicular to the throwing direction. Release speed was found to have the highest correlation with the official throwing result. The three release parameters accounted for 56% of the variance in the official result for the male and 51% for the female throwers. For individual male and female throwers, the variance explained by the model was between 46 and 87%. Among the individual male throwers an increase of 1 m.s-1 in the release speed from 29 to 30 m.s-1 was calculated to increase the official result between 2.12 to 6.14 m while among the female throwers the effect of increase from 24 to 25 m.s-1 in the release speed was from 2.25 to 3.68 m. The study emphasises the importance of investigating javelin throwing biomechanics on an individual thrower basis.


Home-fortification with iron and zinc sprinkles or iron sprinkles alone successfully treats anemia in infants and young children.
Although iron deficiency is the most common single-nutrient deficiency in infants and children, other deficiencies may develop concurrently, including zinc deficiency. In previous studies, we used home-fortification with "Sprinkles," single-serve sachets containing microencapsulated ferrous fumarate added to weaning foods, to successfully treat anemia. This mode of micronutrient delivery is amenable to the delivery of other micronutrients. However, the relative efficacy of multiple micronutrient supplements for the treatment of anemia requires evaluation due to possible nutrient interactions. Thus, we evaluated the relative efficacy of Sprinkles formulated with iron and zinc in anemic infants, compared with Sprinkles formulated with iron alone. We studied 304 anemic infants (mean age 10.3 +/- 2.5 mo; hemoglobin 87.4 +/- 8.4 g/L) in rural Ghana. A combined supplementation group (FeZn) received daily Sprinkles containing 80 mg iron and 10 mg zinc; a comparison group (Fe) received Sprinkles (80 mg iron) without zinc for 2 mo. The rate of recovery from anemia was higher in the Fe group compared with the FeZn group (74.8 vs. 62.9%; P = 0.048). The plasma zinc concentration decreased significantly in both groups (P < 0.05). A significant decline in the height for age Z-score was observed in the FeZn group (P = 0.0011), but there was no change in the Fe group. These results suggest that in a controlled setting, home-fortification using micronutrient Sprinkles with iron, or iron and zinc, was very successful in treating anemia; however, this intervention alone was insufficient to improve zinc status or promote catch-up growth in this stunted and wasted population.


Valuing Equal Protection in Aviation Security Screening.
The growing number of anti-terrorism policies has elevated public concerns about discrimination. Within the context of airport security screening, the current study examines how American travelers value the principle of equal protection by quantifying the "equity premium" that they are willing to sacrifice to avoid screening procedures that result in differential treatments. In addition, we applied the notion of procedural justice to explore the effect of alternative selective screening procedures on the value of equal protection. Two-hundred and twenty-two respondents were randomly assigned to one of three selective screening procedures: (1) randomly, (2) using behavioral indicators, or (3) based on demographic characteristics. They were asked to choose between airlines using either an equal or a discriminatory screening procedure. While the former requires all passengers to be screened in the same manner, the latter mandates all passengers undergo a quick primary screening and, in addition, some passengers are selected for a secondary screening based on a predetermined selection criterion. Equity premiums were quantified in terms of monetary cost, wait time, convenience, and safety compromise. Results show that equity premiums varied greatly across respondents, with many indicating little willingness to sacrifice to avoid inequitable screening, and a smaller minority willing to sacrifice anything to avoid the discriminatory screening. The selective screening manipulation was effective in that equity premiums were greater under selection by demographic characteristics compared to the other two procedures.


Maturation of cognitive control: delineating response inhibition and interference suppression.
Cognitive control is integral to the ability to attend to a relevant task whilst suppressing distracting information or inhibiting prepotent responses. The current study examined the development of these two subprocesses by examining electrophysiological indices elicited during each process. Thirteen 18 year-old adults and thirteen children aged 8-11 years (mean=9.77 years) completed a hybrid Go/Nogo flanker task while continuous EEG data were recorded. The N2 topography for both response inhibition and interference suppression changed with increasing age. The neural activation associated with response inhibition became increasingly frontally distributed with age, and showed decreases of both amplitude and peak latency from childhood to adulthood, possibly due to reduced cognitive demands and myelination respectively occurring during this period. Interestingly, a significant N2 effect was apparent in adults, but not observed in children during trials requiring interference suppression. This could be due to more diffuse activation in children, which would require smaller levels of activation over a larger region of the brain than is reported in adults. Overall, these results provide evidence of distinct maturational processes occurring throughout late childhood and adolescence, highlighting the separability of response inhibition and interference suppression.


Murine intestinal intraepithelial lymphocytes I. Relationship of a novel Thy-1-,Lyt-1-,Lyt-2+, granulated subpopulation to natural killer cells and mast cells.
Highly purified populations of intraepithelial lymphocytes (IEL) were obtained from the murine small intestine. We found that 84% of IEL expressed Lyt-2 and that 45-55% possessed the unique phenotype, Thy-1-,Lyt-1-,Lyt-2+. Sixty percent of IEL had granules in their cytoplasm and thus resembled the large granulated lymphocytes associated with natural killer (NK) activity. However, less than 15% of IEL had NK activity in a 6-h assay. This activity resided in a subpopulation of Lyt-2- lymphocytes, leaving a large population of Thy-1-,Lyt-1-,Lyt-2+ granulated cells (45-55% of IEL) with unknown function. Sensitive radioenzymic assays for histamine showed that IEL from healthy CBA mice do not contain this amine. IgE-binding assays revealed that IEL, unlike mast cells, do not carry high-affinity receptors for IgE. Thus, only a small percentage of granulated IEL (less than 15%) possess NK activity, whereas 45-55% of IEL have granules, lack typical characteristics of mast cells, express the unique antigenic phenotype, Thy-1-,Lyt-1-,Lyt-2+ and have unknown function.


A prospective study of acute, unintentional, pediatric superwarfarin ingestions managed without decontamination.
We determine the incidence of clinically important bleeding in children with superwarfarin rodenticide ingestions not treated with gastrointestinal decontamination or prophylactic vitamin K. We prospectively studied patients younger than 6 years of age who reported to our poison center with acute unintentional superwarfarin ingestions. Patients who received gastrointestinal decontamination or prophylactic vitamin K were excluded. Forty-eight- to 96-hour prothrombin time or international normalized ratio (INR) blood tests were recommended, and telephone contact was attempted at least 3 days after ingestion. A total of 595 consecutive patients were enrolled during the 16-month study period. Fifty patients were excluded: 8 who were known to have ingested 1 pellet or less; 25 who received activated charcoal; 15 who were treated with induced emesis; and 2 who received prophylactic vitamin K. The resulting study group contained 545 patients. Eighty-two patients were lost to follow-up. Follow-up was obtained for 463 patients, including 222 by telephone contact alone, 62 by 48- to 96-hour INR, and 179 by both methods. None of the patients had clinically important coagulopathy. Two patients had an INR of 1.5 or greater (1.5 and 1.8) without symptoms. Single nosebleeds were reported in another 2 patients with normal 48-hour INRs. Another child had a small amount of blood crusted in the nose with no other symptoms and no laboratory work available. One child with a normal 48-hour INR had blood-streaked stools that were thought to be caused by an anal fissure. Children with acute unintentional superwarfarin ingestions of less than 1 box may be managed without gastric decontamination or prophylactic vitamin K. Laboratory testing for coagulopathy should be reserved for cases involving clinically evident bleeding abnormalities.


Sera from Breakthrough Infections with SARS-CoV-2 BA.5 or BF.7 Showed Lower Neutralization Activity against XBB.1.5 and CH.1.1.
From December 2022 to January 2023, SARS-CoV-2 infections caused by BA.5 and BF.7 subvariants of B.1.1.529 (Omicron) spread in China. It is urgently needed to evaluate the protective immune responses in the infected individuals against the current circulating variants to predict the future potential infection waves, such as the BQ.1.1, XBB.1.5, and CH1.1 variants. In this study, we constructed a panel of pseudotyped viruses for SARS-CoV-2 for the past and current circulating variants, including D614G, Delta, BA.1, BA.5, BF.7, BQ.1.1, XBB.1.5 and CH.1.1. We investigated the neutralization sensitivity of these pseudotyped viruses to sera from individuals who had BA.5 or BF.7 breakthrough infections in the infection wave of last December in China. The mean neutralization ID50 against infected variants BA.5 and BF.7 are 533 and 444, respectively. The highest neutralizing antibody level was observed when tested against the D614G strain, with the ID50 of 742, which is about 1.52-folds higher than that against the BA.5/BF.7 variant. The ID50 for BA.1, Delta and BQ.1.1 pseudotyped viruses were about 2-3 folds lower when compared to BA.5/BF.7. The neutralization activities of these serum samples against XBB.1.5 and CH.1.1 decreased 7.39-folds and 15.25-folds when compared to that against BA.5/BF.7. The immune escape capacity of these two variants might predict new infection waves in future when the neutralizing antibody levels decrease furtherly.


A long-term double-blind comparative study on proquazone (Biarison) and ibuprofen in rheumatoid arthritis.
The efficacy and tolerance of proquazone, 900 mg, and ibuprofen, 1200 mg, were compared in a randomized, double-blind clinical trial of 6 months' duration, with 44 patients, 21 on proquazone and 23 on ibuprofen. Comparison of proquazone-treated patients with patients treated with iburofen showed a significantly better improvement , as is demonstrated by the significant differences in the Lansbury Index, in nocturnal pain, final assessment of therapeutic effect, and number of interruptions due to lack of efficacy. All differences were in favour of proquazone, proving its therapeutic superiority over ibuprofen. The side effects in the proquazone group were mainly gastrointestinal, and 2 patients broke off treatment prematurely due to diarrhoea (in one patient, lack of efficacy was a contributory cause). A third patient discontinued because of moderate nausea and dizziness. In the ibuprofen group, 4 patients discontinued because of side effects (skin eruptions, dizziness, epigastric discomfort, and one thrombocytopenia) in addition to lack of efficacy. Proquazone seems to be an effective and well tolerated anti-inflammatory analgesic.


Effects of temperature and ethanol on agonist and antagonist binding to rat heart muscarinic receptors in the absence and presence of GTP.
The effect of temperature on the binding of four agonists and three antagonists to rat heart muscarinic receptors was studied in the absence and presence of GTP. The binding of agonists to two states (or classes) of receptors, in the absence of GTP, led to enthalpy and entropy changes that decreased sharply above 25 degrees C, suggesting that agonists induced 'isomerization' reactions (large conformational changes and/or receptor-effector association). Both temperature increase and ethanol decreased hydrophobic interactions, thereby hindering binding and/or agonist-induced 'isomerization' reactions. Addition of GTP to the incubation medium also appeared to reverse (or prevent) 'isomerization' reactions. For agonist binding to the low-affinity state, in the presence of GTP, and for antagonist binding, the thermodynamic parameters observed could be readily explained by simple receptor-ligand associations; large entropy increases and small enthalpy increases, provoked by hydrophobic and ionic interactions, were partly neutralized by entropy and enthalpy decreases, due to hydrogen bonds and van der Waals interactions. The muscarinic antagonists used (atropine, n-methylscopolamine and dexetimide), being more hydrophobic molecules than the agonists tested (carbamylcholine, oxotremorine and pilocarpine), induced larger entropy changes or more negative enthalpy changes.


Specific binding of single-stranded telomeric DNA by Cdc13p of Saccharomyces cerevisiae.
Cdc13p is a single strand telomere-binding protein of Saccharomyces cerevisiae; its telomere-binding region is within amino acids 451-693, Cdc13(451-693)p. In this study, we used purified Cdc13p and Cdc13(451-693)p to characterize their telomere binding activity. We found that the binding specificity of single-stranded TG(1-3) DNA by these two proteins is similar. However, the affinity of Cdc13(451-693)p to DNA was slightly lower than that of Cdc13p. The binding of telomeric DNA by these two proteins was disrupted at NaCl concentrations higher than 0.3 m, indicating that electrostatic interaction contributed significantly to the binding process. Because both proteins bound to strand TG(1-3) DNA positioned at the 3' end, the 5' end, or in the middle of the oligonucleotide substrates, our results indicated that the location of TG(1-3) in single-stranded DNA does not appear to be important for Cdc13p binding. Moreover, using DNase I footprint analysis, the structure of the telomeric DNA complexes of Cdc13p and Cdc13(451-693)p was analyzed. The DNase I footprints of these two proteins to three different telomeric DNA substrates were virtually identical, indicating that the telomere contact region of Cdc13p is within Cdc13(451-693)p. Together, the binding properties of Cdc13p and its binding domain support the theory that the specific binding of Cdc13p to telomeres is an important feature of telomeres that regulate telomerase access and/or differentiate natural telomeres from broken ends.


Quantification of HIV DNA in the brain by PCR: differences between fresh frozen and formalin fixed tissue.
HIV-1 DNA extracted from frozen and formalin fixed brain tissue can be detected using PCR. This work has been extended by amplifying, using semiquantitative PCR, HIV DNA extracted from frontal lobe tissue of 16 patients with AIDS (eight positive and eight negative for p24 antigen). DNA was amplified using HIV-1 pol gene digoxigenin labelled primers and detected by chemiluminescence and densitometry. Cloned standards were amplified in parallel for quantification. HIV DNA levels detected in frozen tissue showed a correlation with p24 positivity and the severity of the histological diagnosis. This correlation was less clear in the formalin fixed material.