Use of emergency medical services by patients with decompensated obstructive lung disease.
Little information is available about the risk of relapse when patients with decompensated obstructive lung disease are treated in an emergency department for dyspnea. The purpose of our study was to determine if the risk of relapse was related to the severity and type of airway obstruction or to the time and duration of treatment. Over a period of 29 months, 496 patients with decompensated chronic obstructive pulmonary disease (COPD), asthma, or both were seen in the ED of the Albuquerque Veterans Administration Medical Center. Of 868 visits in which patients were treated and released, 244 (28.1%) were followed by a relapse within 14 days. Those who relapsed had a slightly higher one-second forced expiratory volume at baseline than those who did not (50.1 +/- 22.2% versus 45.5 +/- 20.6% predicted, P = .054). For 94 patients (group 1), asthma was the exclusive clinical diagnosis, and all available pulmonary function tests showed a bronchodilator response. For 268 patients (group 2), COPD was the exclusive diagnosis, and all tests showed no bronchodilator response. One hundred thirty-four patients (group 3) were either diagnosed as having both disorders or had varying bronchodilator response on sequential testing. The risk of relapse for group 3 patients (35.6%) was higher than for those in groups 2 (23.1%, P less than .001) or 1 (19.7%, P = .001). The frequency of relapse was higher for nighttime than daytime visits (36.1% versus 24.5%, P = .006) and for weekend than weekday visits (33.6% versus 26.6%, P = .049). Prognosis did not vary with the season or duration of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Dexter: a device for the assessment of microsurgical instrumentation and instruction of trainees.
We present an easily constructed devise, which allows the testing and comparison of microsurgical apparatus, providing a numerical result for statistical analysis. It also enables the trainee microsurgeon to practise basic microsurgical skills in a safe environment. Construction and uses are discussed.


Serum cholesterol binding reserve percentage in diabetes mellitus.
Serum cholesterol binding reserve percentage (SCBR%) in patients with diabetes mellitus (22.17 +/- 13.40%) was significantly lower than in controls (40.93 +/- 8.69%) (p less than 0.001). SCBR% of controls did not vary with age (age range 20-80 years). SCBR% declined significantly with increasing duration of diabetes. It also decreased with macrovascular complications and was lowest in multiple/fatal complications further corroborating the value of SCBR% as a risk indicator of atherogenesis. The relationship of SCBR% with treatment was very striking. All adequately controlled patients had a significantly higher SCBR% than those who were poorly controlled regardless of treatment modality and those adequately controlled on insulin had the highest SCBR%, which was close to that of normal controls.


Mechanism of recovery from acute virus infection. III. Subclass of T lymphocytes mediating clearance of lymphocytic choriomeningitis virus from the spleens of mice.
Spleen T lymphocytes from mice undergoing acute infection with lymphocytic choriomeningitis virus (LCM virus) were negatively selected by treatment with anti-Lyt or anti-L3T4 antibodies and complement. The subsets thus obtained were tested for their potential to lyse LCM virus-infected target cells in vitro and to confer on infected syngeneic recipients the ability to eliminate virus rapidly from their spleens. Both capacities were found to be associated with Lyt-1-2+, L3T4- cells. Previous studies had shown that LCM virus-specific cytotoxicity in vitro as well as reduction of replication of LCM virus in the adoptively immunized mouse requires compatibility at K and/or D of the major histocompatibility complex, and we conclude that clearance of LCM virus from the mouse's spleen is mediated by the subset of T lymphocytes that is functionally characterized as cytotoxic/suppressive.


Nonsteroidal anti-inflammatory drugs and cognitive function: do they have a beneficial or deleterious effect?
Studies suggest that high dose NSAID use may be associated with a reversible impairment of cognition in the elderly. Prolonged NSAID use, on the other hand, may prevent the decline in cognition associated with aging. However, it has yet to be to be definitively determined whether this protection arises from an anti-inflammatory effect that modifies pathways involved in Alzheimer's dementia, or is mediated by a platelet effect that decreases the risk of cerebrovascular disease. Further large-scale, randomised, controlled trials using NSAIDs are needed before patients can be advised that the known risks of NSAIDs are outweighed by their potential long term benefits on cognition. While clinicians await the results of such studies, they should continue to be alert to the possibility of acute CNS adverse effects in their elderly patients who are receiving NSAIDs and to prescribe the minimum dose that is necessary to control pain and inflammation.


A critical assessment of stillbirths at a tertiary care hospital.
Globally in 2015, 2.6 million stillbirths occurred with estimated stillbirth rate (SBR) of 18.4/1000 births. India is the world capital of stillbirth accounting for 22.6% of world's stillbirths. The objective of the study is to study the demographic profile of women experiencing stillbirth, to understand the risk factors for stillbirth in low resource settings, and to find the etiology of stillbirth so as to facilitate designing of a stillbirth prevention strategy. This was a cross-sectional observational study done at a tertiary care hospital of Delhi from June 2017 to December 2019. All babies delivered after 20 weeks of gestation showing no sign of life after birth were considered stillborn. Prestructured proforma was filled for each case and data were analyzed. A total of 50,461 births took place during the study period, out of which 1824 were stillborn, making SBR of 36.15/1000 births of our institution. Most of the women belonged to age group 21-25 years and more than 50% of women were illiterate. Twenty-nine percent of women were completely unbooked, 48% were referred from other centers and 23% were registered at our hospital. Placental causes accounted for 22%, hypertension for 23%, and labor complications for 9% of cases while in 22% cases, cause could not be found. Stillbirth remains a neglected issue. A significant proportion of stillbirths are preventable by adequate antenatal care. Notification of stillbirths will give us the exact figures and realization of the seriousness of the problem which will help us work towards the solutions.


Subdermal Nd-YAG laser for axillary hyperhidrosis.
Axillary hyperhidrosis is a common but difficult-to-treat condition with major social, labor, and emotional consequences. The aim of this study is to present the Nd-YAG laser as a safe and effective option for the treatment of axillary hyperhidrosis. From January 2002 to April 2007, 17 patients (15 women and 2 men) with axillary hyperhidrosis were treated using a subdermal 1,064-nm Nd-YAG laser. The results were evaluated by the patients as well as by the physician. The objective evaluation was realized by Minor's iodine starch test combined with planimetry. Histology was performed in axillary skin after the laser treatment. The subdermal laser-assisted axillary hyperhidrosis treatment using a 1,064-nm Nd-YAG laser resulted in significant clinical improvement. The treatment of axillary hyperhidrosis using the 1,064-nm Nd-YAG laser has the advantage of a minor invasive procedure without leaving large scars and causing temporary impairment. The laser proved to be effective and safe. Although the laser treatment has shown promising results in this pilot trial, further studies are necessary for final conclusions. The authors have indicated no significant interest with commercial supporters.


Early experience with the femtosecond laser for cataract surgery.
To describe the intraoperative complications and to evaluate the learning curve with femtosecond laser cataract surgery. Prospective, consecutive cohort study. The first 200 eyes undergoing femtosecond laser cataract surgery and refractive lens exchange in a single center. The initial 200 eyes undergoing cataract surgery between April 2011 and June 2011 by 6 surgeons were included in the study. The cases underwent anterior capsulotomy, lens fragmentation, and corneal incisions with the femtosecond laser. The procedure was completed by phacoemulsification and insertion of an intraocular lens. Data were collected about patient demographics, preoperative investigations and intraoperative complications. The cases were divided into 4 groups-group 1 included the first 50 cases, group 2 included cases 51 through 100, group 3 included cases 101 through 150, and group 4 included cases 151 through 200-and were analyzed. Intraoperative complication rates. The mean age of patients included was 69.2±9.8 years. Of the 200 eyes, 74.5% underwent a complete procedure of laser capsulotomy, lens fragmentation, and corneal incisions. Five eyes had suction breaks during the laser procedure that led to the remainder of the laser procedure being aborted. Twenty-one (10.5%) eyes showed the presence of small anterior capsular tags. The number of eyes with free-floating capsulotomies was 35 (17.5%). The other complications during the study were anterior radial tears (n = 8; 4%), posterior capsular ruptures (n = 7; 3.5%), and dropped nucleus (n = 4; 2%). A significant difference was noted among the sequential groups with respect to the number of docking attempts (P<0.001), miosis after the laser procedure (P<0.001), and free-floating capsulotomies (P<0.001), suggesting an improving learning curve. The surgeons with prior experience with femtosecond lasers had fewer complications in the first 100 cases (P<0.001). No difference in complications was observed after the initial 100 cases. In this case series, there was a clear learning curve associated with the use of femtosecond lasers for cataract surgery. Adjustment to surgical technique and prior experience with a femtosecond laser seemed to flatten the learning curve.


Beyond "sex prediction": Estimating and interpreting multivariate sex differences and similarities in the brain.
Previous studies have shown that machine-learning (ML) algorithms can "predict" sex based on brain anatomical/ functional features. The high classification accuracy achieved by ML algorithms is often interpreted as revealing large differences between the brains of males and females and as confirming the existence of "male/female brains". However, classification and estimation are different concepts, and using classification metrics as surrogate estimates of between-group differences may result in major statistical and interpretative distortions. The present study avoids these distortions and provides a novel and detailed assessment of multivariate sex differences in gray matter volume (GMVOL) that does not rely on classification metrics. Moreover, appropriate regression methods were used to identify the brain areas that contribute the most to these multivariate differences, and clustering techniques and analyses of similarities (ANOSIM) were employed to empirically assess whether they assemble into two sex-typical profiles. Results revealed that multivariate sex differences in GMVOL: (1) are "large" if not adjusted for total intracranial volume (TIV) variation, but "small" when controlling for this variable; (2) differ in size between individuals and also depends on the ML algorithm used for their calculation (3) do not stem from two sex-typical profiles, and so describing them in terms of "male/female brains" is misleading.


Fibroblast growth factor 21 and its relation to metabolic parameters in women with polycystic ovary syndrome.
The aim of this study was to compare the serum levels of fibroblast growth factor 21 (FGF-21) between patients with polycystic ovary syndrome (PCOS) and control subjects and to assess the possible relation with the hormonal and metabolic parameters. A total of 91 patients with PCOS and 53 age- and body mass index (BMI)-matched healthy controls were included in the study. We evaluated anthropometric, hormonal and metabolic parameters in all the cases. Serum FGF-21 and high sensitive C-reactive protein (hsCRP) levels were measured by ELISA. Mean fasting glucose and insulin, homeostasis model assessment insulin resistance index (HOMA-IR), triglyceride, total cholesterol, low density lipoprotein cholesterol, total testosterone, dehydroepiandrosterone sulfate (DHEAS) levels were significantly higher in PCOS patients. Serum FGF-21 levels were similar in PCOS (236.8 ± 171.2 pg/ml) and the control (224.6 ± 128.9 pg/ml) group (p = 0.654). FGF-21 level had no correlation with BMI, waist circumference, HOMA-IR, hsCRP and lipid parameters. However there was a significant negative correlation between FGF-21 and DHEAS levels (r = - 0.309, p = 0.003). FGF-21 levels were similar in women with PCOS compared with those of age- and BMI- matched controls.


Magnetoencephalography in the study of epilepsy.
A brief review is given about the basic principles of magnetoencephalography (MEG), a noninvasive brain research method in which weak magnetic fields are detected outside the human head with SQUID (Superconducting Quantum Interference Device) magnetometers. The active brain areas, producing the signal, are modelled by current dipoles, which are assumed to be situated in a spherically symmetric volume conductor. The locations of these "equivalent dipoles" can be found, in the optimal case, with a precision of a few millimeters. The new multichannel magnetometers allow measurements of spontaneous brain activity without EEG-triggered averaging. The 3-dimensional locations of superficial epileptogenic foci can be determined with respect to external landmarks on the skull and to known generator areas of evoked responses in the brain. Examples are given about MEG recordings of epileptic patients.


Effectiveness of terrestrial protected areas for conservation of lake fish communities.
Freshwater protected areas are rare even though freshwater ecosystems are among the most imperiled in the world. Conservation actions within terrestrial protected areas (TPAs) such as development or resource extraction regulations may spill over to benefit freshwater ecosystems within their boundaries. Using data from 175 lakes across Ontario, Canada, we compared common indicators of fish-assemblage status (i.e., species richness, Shannon diversity index, catch per unit effort, and normalized-length size spectrum slopes) to evaluate whether TPAs benefit lake fish assemblages. Nearest neighbor cluster analysis was used to generate pairs of lakes: inside versus outside, inside versus bordering, and bordering versus outside TPAs based on lake characteristics. The diversity and abundance indicators did not differ significantly across comparisons, but normalized-length size spectrum slopes (NLSS) were significantly steeper in lakes outside parks. The latter indicated assemblage differences (greater abundances of small-bodied species) and less-efficient energy transfer through the trophic levels of assemblages outside parks. Although not significantly different, pollution- and turbidity-tolerant species were more abundant outside parks, whereas 3 of the 4 pollution-intolerant species were more abundant within parks. Twenty-one percent of the difference in slopes was related to higher total dissolved solids concentrations and angling pressure. Our results support the hypothesis that TPAs benefit lake fish assemblages and suggest that NLSS slopes are informative indicators for aquatic protected area evaluations because they represent compositional and functional aspects of communities.


Comparison of attitudes towards five end-of-life care interventions (active pain control, withdrawal of futile life-sustaining treatment, passive euthanasia, active euthanasia and physician-assisted suicide): a multicentred cross-sectional survey of Korean patients with cancer, their family caregivers, physicians and the general Korean population.
This study determined attitudes of four groups-Korean patients with cancer, their family caregivers, physicians and the general Korean population-towards five critical end-of-life (EOL) interventions-active pain control, withdrawal of futile life-sustaining treatment (LST), passive euthanasia, active euthanasia and physician-assisted suicide. We enrolled 1001 patients with cancer and 1006 caregivers from 12 large hospitals in Korea, 1241 members of the general population and 928 physicians from each of the 12 hospitals and the Korean Medical Association. We analysed the associations of demographic factors, attitudes towards death and the important components of a 'good death' with critical interventions at EoL care. All participant groups strongly favoured active pain control and withdrawal of futile LST but differed in attitudes towards the other four EoL interventions. Physicians (98.9%) favoured passive euthanasia more than the other three groups. Lower proportions of the four groups favoured active euthanasia or PAS. Multiple logistic regression showed that education (adjusted OR (aOR) 1.77, 95% CI 1.33 to 2.36), caregiver role (aOR 1.67, 95% CI 1.34 to 2.08) and considering death as the ending of life (aOR 1.66, 95% CI 1.05 to 1.61) were associated with preference for active pain control. Attitudes towards death, including belief in being remembered (aOR 2.03, 95% CI 1.48 to 2.79) and feeling 'life was meaningful' (aOR 2.56, 95% CI 1.58 to 4.15) were both strong correlates of withdrawal of LST with the level of monthly income (aOR 2.56, 95% CI 1.58 to 4.15). Believing 'freedom from pain' negatively predicted preference for passive euthanasia (aOR 0.69, 95% CI 0.55 to 0.85). In addition, 'not being a burden to the family' was positively related to preferences for active euthanasia (aOR 1.62, 95% CI 1.39 to 1.90) and PAS (aOR 1.61, 95% CI 1.37 to 1.89). Groups differed in their attitudes towards the five EoL interventions, and those attitudes were significantly associated with various attitudes towards death.


Exploration of respiratory chain of Nocardia asteroides: purification of succinate quinone oxidoreductase.
Nocardia asteroides is a pathogenic bacterium that causes severe pulmonary infections and plays a vital role in HIV development. Its electron transport chain containing cytochromes as electron carriers is still undiscovered. Information regarding cytochromes is important during drug synthesis based on cytochrome inhibitions. In this study we explored the electron transport of N. asteroides. Spectroscopic analysis of cytoplasm and membranes isolated from N. asteroides indicates the presence of soluble cytochrome-c, complex-II and the modified a(1)c(1) complex as the terminal oxidase. The molecular weight of the respiratory complex-II isolated and purified from the given bacterium was 103 kDa and was composed of three subunits, of 14, 26 and 63 kDa. Complex-II showed symmetrical α-absorption peaks at 561 nm in the reduced state. Spectral analysis revealed the presence of only one heme b molecule (14-kDa subunit) in complex-II, which was confirmed by heme staining. Heme b content was found to be 9.5 nmol/mg in complex-II. The electron transport chain of N. asteroides showed the presence of soluble cytochrome-c, cytochrome-a(1)c(1) and cytochrome-b.


Outcomes and risk factors for failure after trabeculectomy in Taiwanese patients: medical chart reviews from 2006 to 2017.
To determine long-term outcomes and risk factors for failure after mitomycin C (MMC)-augmented initial trabeculectomy (IT) in Taiwanese patients. We reviewed medical records of patients with glaucoma undergoing IT during December 2006-December 2016. We defined complete success as an intraocular pressure (IOP) of >5 or ≤21 mm Hg or IOP reduction of ≥20% from baseline without supplemental medications and qualified success as the aforementioned IOP levels with or without supplemental medications. Kaplan-Meier survival and Cox proportional analyses evaluated success rates and risk factors for failure, respectively. We enrolled 190 patients (237 eyes; mean age: 54.0±15.3 years; mean postoperative follow-up period: 68.4±35.1 months). Mean IOP and glaucoma medications decreased from 22.2±10.8 to 14.4±5.2 mm Hg (p<0.001) and 3.0±0.7 to 1.8±1.2 (p=0.015), respectively, at the last visit. Cumulative qualified success rates were 93.9%, 93.0%, 86.5% and 67.1% at the 1, 2, 5 and 10 years follow-up, respectively; however, only 7.7% of the eyes reached complete success at the last visit. Eyes with poor preoperative visual acuity were associated with low qualified success rates (HR=1.689, p=0.027); patients aged >70 years had higher complete success rates than did those aged ≤70 years. Five cases (2.11%) exhibited bleb-associated complications. Despite satisfactory long-term success rates, most eyes needed medication for IOP control, supporting the notion of predisposed scarring vitality in patients of Chinese ethnicity following MMC-augmented trabeculectomy.


Zika virus degrades the ω-3 fatty acid transporter Mfsd2a in brain microvascular endothelial cells and impairs lipid homeostasis.
Zika virus (ZIKV) infection during pregnancy increases the risk of postnatal microcephaly. Neurovascular function provides a homeostatic environment for proper brain development. The major facilitator superfamily domain-containing protein 2 (Mfsd2a) is selectively expressed in human brain microvascular endothelial cells (hBMECs) and is the major transporter mediating the brain uptake of docosahexaenoic acid (DHA). We have discovered a pivotal role for Mfsd2a in the pathogenesis of ZIKV. ZIKV disrupted Mfsd2a both in cultured primary hBMECs and in the neonatal mouse brain. ZIKV envelope (E) protein specifically interacted with Mfsd2a and promoted Mfsd2a polyubiquitination for proteasome-dependent degradation. Infection with ZIKV or ectopic expression of ZIKV E impaired Mfsd2a-mediated DHA uptake. Lipidomic analysis revealed obvious differences in DHA-containing lipids after ZIKV infection. Supplementation with DHA rescued ZIKV-caused growth restriction and microcephaly. Our findings suggest endothelial Mfsd2a as an important pathogenic mediator and supplementation with DHA as a potential therapeutic option for ZIKV infection.


Interaction of hydrocortisone and illness severity on head growth in cohort of ELBW infants.
Extremely low birth weight (ELBW) infants comprise a fragile population at risk for neurodevelopmental disabilities (NDD). Systemic steroids were previously associated with NDD, but more recent studies suggest hydrocortisone (HCT) may improve survival without increasing NDD. However, the effects of HCT on head growth adjusted for illness severity during NICU hospitalization are unknown. Thus, we hypothesize that HCT will protect head growth, accounting for illness severity using a modified neonatal Sequential Organ Failure Assessment (M-nSOFA) score. We conducted a retrospective study that included infants born at 23-29 weeks gestational age (GA) and < 1000 g. Our study included 73 infants, 41% of whom received HCT. We found negative correlations between growth parameters and age, similar between HCT and control patients. HCT-exposed infants had lower GA but similar normalized birth weights; HCT-exposed infants also had higher illness severity and longer lengths of hospital stay. We found an interaction between HCT exposure and illness severity on head growth, such that infants exposed to HCT had better head growth compared to those not exposed to HCT when adjusted for illness severity. These findings emphasize the importance of considering patient illness severity and suggest that HCT use may offer additional benefits not previously considered. This is the first study to assess the relationship between head growth and illness severity in extremely preterm infants with extremely low birth weights during their initial NICU hospitalization. Infants exposed to hydrocortisone (HCT) were overall more ill than those not exposed, yet HCT exposed infants had better preserved head growth relative to illness severity. Better understanding of the effects of HCT exposure on this vulnerable population will help guide more informed decisions on the relative risks and benefits for HCT use.


Granular cell tumor presenting in the scrotum of a pediatric patient: a case report and review of the literature.
Granular cell tumors are neoplasms of Schwann cell origin. They typically arise in the head and neck of adults, with the tongue being the most common location; granular cell tumors of male genitalia are exceedingly rare. We identified only eight prior cases of scrotal granular cell tumor in the literature, and only one was in a child. Herein, we report a second case of childhood scrotal granular cell tumor and provide a review of the most relevant literature. A fifteen-year-old hispanic boy was referred to our hospital's pediatric surgery service for a painless and firm scrotal mass. Clinical impression was that of an epidermal inclusion cyst. There was no evidence of associated medical problems from the clinical history and physical examination. Surgical enucleation of the lesion demonstrated a solid nodule with morphological and immunohistochemical features consistent with a benign granular cell tumor. This is the second case reported of a scrotal granular cell tumor in a child. Although genital granular cell tumors are rare, and most are benign, careful clinical examination, complete surgical excision, expert histologic evaluation, and a close follow-up are recommended for accurate diagnosis and to rule out eventual malignancy.


Isolation of Vascular Wall Mesenchymal Stem Cells from the Thoracic Aorta of Adult Göttingen Minipigs: A New Protocol for the Simultaneous Endothelial Cell Collection.
Two main classes of perivascular multipotent populations have been described: the microvascular pericytes and the vascular wall mesenchymal stem cells (VW-MSCs). VW-MSCs are isolated from large vessels in many species and they participate in vascular remodeling together with other cellular components such as endothelial cells. Considering that the Göttingen Minipigs are widely used in Europe as a translational model in the field of cardiovascular diseases, the aim of the present research was to isolate VW-MSCs from the adult aorta of Göttingen Minipigs while preserving and also collecting endothelial cells. The results obtained in the present research demonstrated that this new protocol allows us to obtain a pure population of VW-MSCs and endothelial cells. VW-MSCs from Göttingen Minipigs responded fully to the MSC minima international criteria, being positive to CD105, CD90, and CD44 and negative to CD45 and CD34. Moreover, VW-MSCs presented a differentiative potential towards osteogenic, chondrogenic, and adipogenic lineages. Overall, the present protocol, preserving the viability and phenotypic features of the two isolated populations, opens future possibilities of using minipig VW-MSCs and endothelial cells in in vitro vascular remodeling studies.


Increased nitric oxide release by transient peripheral noxious inputs to the spinal cord of rats: an in vivo voltammetric approach.
Using in vivo voltammetric detection of nitric oxide (NO) a previous study demonstrated an increased NO release at the lumbar dorsal horn level of the spinal cord by peripheral inflammatory processes in decerebrated-spinalized rats. This study concerns the effects of acute peripheral stimulations. Gentle non-noxious or isolated nociceptive stimulation did not modify the oxidation current due to NO. However, transient transcutaneous repetitive electrical stimulation of the hindpaw at mild to high intensities (1, 3, and 6 mA) provoked increases in the voltammograms, which were prolonged after stimulation ceased. These effects were absent in animals pretreated with the N-methyl-D-aspartate channel blocker MK-801. The data provide novel direct evidence that NO participates, at least during repetitive stimulation, in the transmission of noxious afferent messages in the dorsal horn of the spinal cord.


A series of parapharyngeal glial heterotopia mimicking lymphatic malformation.
Otolaryngologists will most frequently encounter extra-cranial glial tissue within the nasal cavity, where it is known as a 'nasal glioma', and may communicate with the dura. However, glial tissue can also present extra-nasally in the form of a neck mass with no intracranial connection. In these rare cases, they can present soon after birth as an enlarging neck mass, causing compressive symptoms with airway obstruction and feeding difficulties. In this way, it is often initially misdiagnosed as a more common lesion such as a lymphatic malformation, teratoma, branchial anomaly or vascular malformation. As with many congenital head and neck masses, offering the most the appropriate management relies heavily on radiological imaging and, where possible, histopathology from a diagnostic biopsy. Once the diagnosis of extra-nasal glial heterotopia has been confirmed, the gold standard management is complete surgical excision. We review three cases of extra-nasal glial heterotopia presenting to our institution over an eleven year period as a large neck mass, which mimicked other congenital neck lumps, and discuss them in the context of those in the literature. We highlight how their clinical and radiological features can easily be confused with lymphatic malformations, and the potential implications of misdiagnosis. Raising awareness of this diagnostic confusion will highlight the need for management of these cases within an appropriate paediatric multidisciplinary setting.


Co-transplantation of pancreatic islets and microvascular fragments effectively restores normoglycemia in diabetic mice.
Insufficient revascularization of pancreatic islets is one of the major obstacles impairing the success of islet transplantation. To overcome this problem, we introduce in the present study a straightforward strategy to accelerate the engraftment of isolated islets. For this purpose, we co-transplanted 250 islets and 20,000 adipose tissue-derived microvascular fragments (MVF) from donor mice under the kidney capsule as well as 500 or 1000 islets with 40,000 MVF into the subcutaneous space of diabetic mice. We found that the co-transplantation of islets and MVF markedly accelerates the restoration of normoglycemia in diabetic recipients compared with the transplantation of islets alone. In fact, the transplantation of 250 islets with 20,000 MVF under the kidney capsule reversed diabetes in 88% of mice and the subcutaneous transplantation of 500 or 1000 islets with 40,000 MVF restored normoglycemia in 100% of mice. Moreover, diabetic mice receiving islets and MVF exhibited plasma insulin levels similar to nondiabetic control animals. Additional immunohistochemical analyses of the grafts revealed a significantly higher number of islet cells and microvessels in the co-transplantation groups. These findings demonstrate that the co-transplantation of islets and MVF is a promising strategy to improve the success rates of islet transplantation, which could be easily implemented into future clinical practice.


Residents' assessment of mentoring received on lecture performance in a teaching and learning curriculum program.
This study evaluated residents' assessment of the mentorship received and how it impacted lecture performance as part of a teaching and learning curriculum (TLC) program. An anonymous survey was emailed to residents completing the Virginia Commonwealth University (VCU) School of Pharmacy's TLC during 2018-2019 and 2019-2020. The survey collected information about: the type of mentorship received, residents' self-perceived lecture performance, and residents' desire to be involved in academia post-residency. Data were summarized using descriptive statistics. Fisher's exact tests investigated the association between residents' self-perceived lecture enhancement due to mentorship and: mentors' involvement, residents' confidence in understanding the lecture topic, mentors' affiliation with VCU, and semester when the lecture occurred. Responses to open-ended questions were analyzed using thematic analysis. Forty-two of 86 residents (48.8%) completed the survey. Residents who were part of the TLC but did not deliver a lecture (n = 7) or taught practitioners instead of students (n = 2) were excluded, resulting in 33 participants. The majority of residents (87.9%) agreed or strongly agreed that mentorship enhanced their lecture. Mentors' level of involvement was significantly associated with residents' perception that the mentorship they received enhanced their lecture (P < .008). Residents' confidence in understanding the lecture topic, mentor affiliation, and semester when the lecture occurred were not associated with residents' self-perceived lecture enhancement due to mentorship. Active mentorship was associated with better self-perceived lecture performance. The best criteria for lecture mentorship should be established in the future to help prepare residents to give lectures.


An inhibitory innervation at the gastroduodenal junction in anesthetized dogs.
Our aim was to investigate the existence of an inhibitory innervation at the gastroduodenal junction (GDJ) in the whole animal. Motility induced by vagal stimulation was monitored with strain force transducers on the gastric antrum, pylorus and duodenum. The experiments were carried out in two phases: the control phase following vagotomy (TV), and the treated phase where atropine sulfate (1 mg/Kg) was injected intravenously (TV+A). After TV, antral, pyloric and duodenal contractile activity was significantly increased (P less than 0.01) during the period of vagal stimulation. After (TV+A), spontaneous activity in the antrum and duodenum was abolished and vagal stimulation did not increase motility in these organs. Spontaneous pyloric activity present after atropine administration was inhibited by stimulation, and a concomitant relaxation of the pylorus was also demonstrated. Following the termination of the stimulus, a significant increase in contractions was noted on the pylorus. These experiments demonstrate the existence of an atropine-resistant inhibitory innervation at the GDJ in the anesthetized dog.


Quantitative evaluation of pontine atrophy using computer tomography.
Pontine volume was measured and evaluated by computer tomography (CT) in 37 healthy adults and in 29 adult autopsied brains which did not have chronic neurologic diseases. The pons was cut serially into 5 mm slices in the autopsied brains. In the CT examinations both 5 mm and 2 mm slices were studied. Pontine areas in horizontal planes were measured using an image analyzer, then pontine volume was calculated by accumulation of the mean value of the areas and cranio-caudal length. Pontine volume was approximately 19 cm3 and pontine atrophy could be defined as less than 12 cm3 (i.e. the mean - 2 SD) in both methods, which heretofore have not been reported.


Relationship between particulate matter exposure and female breast cancer incidence and mortality: a systematic review and meta-analysis.
The associations of PM with the risk and prognosis of breast cancer have not been determined. This systematic review aimed to provide an updated understanding of the relationship between PM exposure level and breast cancer incidence and mortality. Articles from Web of Science and PubMed databases were methodically inspected until March 8, 2020. In final, 15 studies were kept for analysis, which provided necessary information to estimate the impact of PM on breast cancer risk and prognosis. These studies were combined for quantitative analyses to evaluate the effect of per 10 μg /m3 increment exposure of PM2.5 (< 2.5 μm in aerodynamic diameter) and PM10 (< 10 μm in aerodynamic diameter) using random-effects model. PM2.5 exposure was associated with increased breast cancer mortality (relative risk [RR] = 1.09; 95% confidence interval [CI]: 1.02, 1.16; PQ-test = 0.158). No association of PM2.5 (1.02; 0.97, 1.18; 0.308) and PM10 (1.03; 0.98, 1.09; 0.009) with the increase incidence of breast cancer was observed. Stratified analysis suggested that PM2.5 was associated with the increase mortality of breast cancer (1.10; 1.03, 1.17; 0.529) in subgroup of developed country. PM10 was associated with breast cancer incidence based on studies published after 2017 (1.08; 1.00, 1.15; 0.157) and European studies (1.15; 1.06, 1.25; 0.502). Our study indicated that PM2.5 exposure was related to breast cancer mortality. Further researches in this field are needed to validate the conclusion.


Measurement of intradiscal pressure after lumbar discectomy.
Early physiotherapeutic exercises after lumbar discectomy have been shown to be helpful for pain control and in reducing the delay until the return to work. Many strategies exclude sitting body positions during the first weeks, because raised intradiscal pressure and an increased motion range in the lower lumbar disc levels have been found in unoperated individuals when seated. To evaluate whether these results can be extrapolated to the situation of an operated patient, we examined the feasibility of an intracranial pressure sensor for measuring intradiscal pressure after lumbar discectomy. An otherwise healthy patient underwent lumbar discectomy for a right-sided lumbar disc herniation at the level L4/5. Before surgery he had agreed voluntarily to the implantation of a pressure sensor and the manufacturer had provided data on the safe use of the sensor in the disc space. Intraoperatively the sensor was positioned in the disc space from the right side. Measurements were performed by means of individual readings by three different examiners at different time points. Before removal of the sensor its correct position was demonstrated by X-ray and computed tomography. The patient tolerated surgery very well, recovery and wound healing were un-eventful, and symptoms improved. The pressure monitoring system showed reproducible results without any signs of technical problems. The intradiscal pressure values were about ten times lower than the values known from unoperated individuals (lying: up to 130 mmHg, sitting: up to 50 mmHg, standing: up to 450 mmHg. 100 mmHg=0.013332 MPa). We present an easy to perform and technically safe technique for the measurement of intradiscal pressure after lumbar discectomy using an intracranial sensor. To assess the impact of intradiscal pressure on recovery after lumbar microdiscectomy a study with a larger cohort of patients and with long-term follow-up will be needed.


A perfect replacement for the mercury sphygmomanometer: the case of the hybrid blood pressure monitor.
This study validated a hybrid mercury-free device as a replacement of the mercury sphygmomanometer for professional use, and also as a standard for future validations. A validation study was performed according to the European Society of Hypertension International Protocol 2010 (ESH-IP) in 33 subjects using simultaneous blood pressure (BP) measurements. A total of six BP measurements were taken per participant simultaneously by a supervisor (S; hybrid auscultatory device Nissei DM3000) and two observers (A and B; mercury sphygmomanometers). ESH-IP analysis (99 BP readings): mean device-observer systolic/diastolic BP difference 0.2±2.0/0.1±2.0 mm Hg; systolic BP differences ≤5/10/15 mm Hg in 97/99/99 readings, respectively (diastolic 98/99/99). All 33 subjects had 2 of 3 BP differences ≤5 mm Hg and none without a difference ≤5 mm Hg. Further analysis (198 BP readings): mean differences S-A 0.1±2.4/0.2±2.4 mm Hg (systolic/diastolic), S-B 0.3±2.1/0.2±2.2, A-B 0.2±2.4/0.0±2.3; differences ≤2 mm Hg S-A in 88/84% (systolic/diastolic), S-B 87/85%, A-B 87/86% and ≤4 mm Hg S-A 95/96%, S-B 95/96%, A-B 95/98%. In conclusion, a hybrid mercury-free auscultatory BP monitor comfortably passed the ESH-IP 2010 requirements and has the same level of accuracy as the mercury sphygmomanometer. This device appears to be a reliable alternative to the mercury sphygmomanometer for professional use and also as a standard for future validations.


Educating genetic counselors in Australia: developing an international perspective.
The demand for genetic counseling services is increasing worldwide. This paper highlights the Australian experience of genetic counselor education and the history of the profession. The relevance of local factors, including the health care system, the education system and the small population in the evolution of the 1-year training programs are considered as an alternative model for emerging programs. The development of the education and training processes compared to that of other countries namely the United States of America (USA), the United Kingdom (UK) and Canada is discussed. The importance of international collaborations between the programs, to facilitate academic discussion and possible curriculum innovations, and to maintain professional understanding between genetic counselors is emphasized. Core genetic counseling competencies have been published for the UK and USA and an Australian set is proposed. In conclusion future directions are considered, including international issues around genetic counseling certification, reciprocity, and the potential for an Australian role in training genetic counselors in South East Asia.


Multiple human papillomavirus genes affect the adeno-associated virus life cycle.
The risk of cervical cancer, one of the most prevalent cancers in the world, is determined by two viruses. Human papillomavirus (HPV) is the main risk factor for developing cervical cancer. However, although little known, it is well substantiated that the human Parvovirus adeno-associated virus type 2 (AAV), and its encoded Rep78 protein, interacts with HPV and lowers the risk of cervical cancer. HPV also contributes to AAV inhibition by serving as a helper virus for AAV and stimulating higher AAV replication levels. Here we surveyed four HPV-16 early genes, E1, E2, E6 and E7, for their ability to increase/decrease the basal level of AAV replication in stratifying squamous epithelium (the epithelial raft culture system). It was found that the HPV-16 E1, E2 and E6 genes were able to help/enhance AAV-2 replication in epithelial raft cultures. Under these conditions, with all the HPV genes being expressed from the AAV p5 promoter, E1 appeared to have the strongest enhancing effect on AAV DNA replication (Southern blot), RNA expression (RT-PCR), protein expression (Western blot) and AAV virion production (2 plate-Southern blot). Further study of E1 mutants showed that the carboxy-half of E1, the putative helicase/ATPase domain, was the main contributor of helper activity. These data are important for understanding the HPV-AAV interaction and its effect on modifying cervical cancer risk. These data also suggest the possibility that the identified HPV helper genes may be useful in the generation of recombinant (r)AAV virions for gene therapy, as rAAV is increasing in popularity for such purposes.


The effectiveness of flumazenil in reversing the sedation and amnesia produced by intravenous midazolam.
In this double-blind study 31 outpatients undergoing third molar extraction were randomly assigned to one of two groups. All patients were sedated with intravenous midazolam (IV) by titration method. The flumazenil group (n = 20) received an average of 0.8 +/- 0.17 mg of flumazenil IV. The placebo patients (n = 11) each received 10 mL of normal saline. By both observer and patient alertness ratings, patients receiving flumazenil appeared significantly more alert than placebo patients at 5, 15, 30, and 60 minutes following reversal. After reversal the flumazenil group had significantly higher scores than the placebo group at all intervals through 60 minutes. All the patients receiving flumazenil were able to walk without assistance at 5 minutes, compared with only one patient in the placebo group, and more patients in the flumazenil group recognized the picture card shown to them at 5, 15, 30, and 60 minutes postreversal. Flumazenil is effective in terminating the amnestic properties of midazolam, but this appears to occur to a lesser extent than the reversal of its sedative properties.


[Curative effects of FTQ combined with cisplatin in treatment of advanced gastric cancer: a multicenter study].
To determine the clinical toxicities and antitumor effects of a chemotherapy regimen of FTQ, a compound preparation of tegafur, the drug prototype of 5-furacil (5-FU), gimeracil (CDHP), a decomposition inhibitor of 5-FU, oteracil potassium, phosphorylation inhibitor of 5-FU, and combined with cisplatin in patients with inoperable locally or metastatic advanced gastric cancer. 119 patients with inoperable locally or metastatic advanced gastric cancer admitted in 10 hospitals in China were divided into 2 groups: FTQ group (n = 59), undergoing a 3-week regime, i.e. oral use of 80 mg x m(-2) x d(-1) for 14 d and then discontinuance for 1 week and intravenous drip cisplatin 75 mg/m2 on days 1-3; and control group (n = 60) undergoing a 3-week regimen including oral use of tegafur 800 mg x m(-2) x d(-1) tid for 14 d and then discontinuance for 1 week and intravenous drip of cisplatin 75 mg/m2 on days 1-3. The curative was evaluated after at least after 2 regimens. There were 102 patients in the per-protocol population. The overall response rate of the FTQ group was 28. 3% (15/53), significantly higher than that of the control group (4.1%, 2/49, P = 0.004). The clinical improvement of the FTQ group was 50.9%, significantly higher than that of the control group (24.5%, P = 0.006). The main toxicities occurred in bone marrow and the digestive tract. The leucopenia and thrombocytopenia rates of the FTQ group were 47.45% and 32.22% respectively, both similar to those of the control group. There were no differences in the incidence rate of digestive canal side reaction between these 2 groups . The regimen of FTQ combined with cisplatin is generally well-tolerated and has substantial antitumor activity.


Detection of immunoglobulin indexes by immunoturbidimetry: patients with chronic hepatitis B.
The objective of this study was to explore the clinical effect of immunoglobulin test in patients with chronic hepatitis B. Fifty patients with chronic hepatitis B, 50 patients with liver failure and 50 patients with cirrhosis were selected from the Third People's Hospital of Baoji as experimental groups, and 50 healthy people as the control group. The immunoglobulin M (IgM), IgG and IgA levels in serum of the patients were tested by immunoturbidimetry before and after targeted treatment. Before treatment, the level of Ig in patients with hepatitis B, liver failure and cirrhosis were significantly higher than those in normal people; the level of Ig in patients with hepatitis B were significantly lower than those in patients with liver failure and cirrhosis, and the level of Ig in patients in different groups increased significantly as the disease developed. After treatment, the level of Ig in patients in different groups decreased significantly; patients in the experimental group who had good treatment result had significant decrease of Ig level, while patients in the experimental group who had aggravated disease condition had significant increase of Ig level. Detection of serum Ig level in patients with chronic hepatitis B can effectively help determine the condition of patients before and after treatment, so as to formulate appropriate treatment plan.


Utilising pneuRIP device in determining the adequacy of respiratory support when weaning high-flow nasal cannula in paediatric patients with acute respiratory distress: A pilot study.
Recognition of paediatric respiratory distress and timely intervention is critical, especially during the weaning phase of support in paediatric acute respiratory failure, as weaning too aggressively can lead to further setbacks in a patient's recovery. We aimed to determine if pulmonary function measurements obtained with the pneuRIP device, a noninvasive pulmonary function testing device that provides measurements of labored breathing index (LBI), phase angle and %rib cage (%RC) contribution to breathing, will provide predictive values to assess the adequacy of respiratory support while weaning from HFNC. We reviewed patients ages 0-18 years admitted to the PICU for respiratory distress due to respiratory infections receiving HFNC. Patients with history of chronic lung disease and chronic neuromuscular disease with baseline habnormal breathing patterns were excluded. Phase angle, LBI and %RC were obtained every hour and with every wean of HFNC. Nine patients were enroled. Mean LBI range remained 1.27-1.68 when LBI was plotted as a function of the HFNC flow rate. Mean values of %RC contribution to breathing ranged 43.65-57.12 as a function of the HFNC flow rate. No significant deviations existed in either %RC (P = 0.16) or LBI (P = 0.16) during the weaning of HFNC. Mean phase angle for all subjects was 41.48°-74.12° for the duration of wean and showed significant deviation from baseline during the weaning process (p = 0.001). Measurements of LBI and %RC on the pneuRIP device effectively demonstrated tolerance of weaning HFNC during the recovery phase of acute respiratory failure from a respiratory infection.


IGF-II induces CREB phosphorylation and cell survival in human lung cancer cells.
We have previously shown that lung tumors arising in MMTV-IGF-II transgenic mice displayed elevated levels of phosphorylated cAMP response element binding protein (CREB). To investigate the role that insulin-like growth factor II (IGF-II) and CREB play in human lung tumorigenesis, A549 and NCI-H358 cells were examined. In these cell lines, IGF-II administration enhances human tumor cell survival and CREB phosphorylation. Further, the effects of IGF-II on cell survival and CREB phosphorylation appeared to be mediated, at least in part, by activation of the Erk pathways, as inhibition of these signaling pathways reduced tumor cell survival and CREB phosphorylation. Specifically, Erk5 appeared as the predominant mediator of CREB phosporylation. To further verify the importance of CREB in human lung tumorigenesis, A549 and NCI-H358 cells were stably transfected with a vector containing a dominant negative CREB construct (KCREB). KCREB transfection significantly inhibited the soft agar growth of both human tumor cell lines. In contrast, overexpression of wild-type CREB in the normal human bronchial epithelial cell line, HBE135, enhanced soft agar growth. Therefore, our results indicate that CREB and its associated proteins play a significant role in lung adenocarcinoma and IGF-II induces CREB phosphorylation, at least in part, via the Erk5 signaling pathway.


A new and simple method to measure maximal aortic valve pressure gradients by Doppler echocardiography.
Most echocardiographic laboratories now use continuous-wave Doppler to measure transvalvular pressure gradients in patients with valvular aortic stenosis (AS). In many cases, particularly in the elderly, this technique can be difficult and time-consuming, and there is no immediate means of verifying the accuracy of the results. In the present study, a new and simple method is proposed to calculate maximal aortic valve gradients from the pulsed-wave Doppler tracing recorded in the left ventricular outflow tract. The method consists of calculating maximal aortic flow velocity and thus the maximal gradient by extrapolating to their point of intersection the initial accelerating velocity and the terminal decelerating velocity recorded on the pulsed Doppler tracing. In 20 patients with varying degrees of AS, there was an excellent correlation (r = 0.96, p less than 0.001) between the results obtained by this method and those obtained by continuous-wave Doppler. In 10 patients who had cardiac catheterization, the results also correlated well with the maximal gradient (r = 0.93, p less than 0.001) measured at cardiac catheterization. Because the method is simple, it should become an integral part of the Doppler examination in patients with AS. Its main advantages will be to serve as an independent confirmation of the results obtained by continuous-wave Doppler and to reduce in many patients the duration of the examination.


Development of second malignancies in rats after cure of acute leukemia L 5222 by single doses of 2-chloroethylnitrosoureas.
After cure of rat leukemia L 5222 in 79 BD IX rats by single doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea (Hydroxyethyl-CNU) a total of 9 rats (11%) developed secondary malignomas.


Scanning tunneling microscopy of the enzymes of muscle glycogenolysis.
Scanning tunneling microscopy (STM) has been used to examine the structures of the skeletal muscle enzymes phosphorylase and phosphorylase kinase. The interaction of these two proteins represents the last step in the process of signal transduction which results in muscle glycogen being converted into metabolic energy for use in muscle contraction. Phosphorylase b has a molecular weight of 97,000 and the dimer is seen by STM to have dimensions of 11 X 5.7 nm. Phosphorylase b has a tendency to form linear arrays of dimers on the graphite surface used as the support for STM imaging. Phosphorylase kinase is imaged as a butterfly-like object with lateral dimensions of 36 X 27 nm. The molecular thicknesses given by scanning tunneling microscopy for these two non-conducting molecules is significantly less than expected. The height measurement in STM is dependent not only on the surface topology of the object being imaged, but also on the electronic work function of the object compared to that of the graphite surface on which it lies. In addition to the individual proteins, a complex between phosphorylase and phosphorylase kinase has been observed by scanning tunneling microscopy.


Human plasma accelerates immortalization of B lymphocytes by Epstein-Barr virus.
Serum and plasma contain species-specific factors that modulate cell population growth and function, and that are required for proliferation of most cell cultures. Foetal calf serum (FCS) is the most common source of these growth factors. We studied the effect of human plasma (HP) on the immortalization process of B lymphocytes by Epstein-Barr virus (EBV) was studied. The effect of HP as compared to FCS was done through assessment of cell proliferation. It was found that HP (autologous and non-autologous plasma) is more effective than FCS in generating lymphoblastoid cell lines, regardless of EBV status of the donors: 65% of HP-supplemented cultures developed into lymphoblastoid cell lines by 7-14 culture days, as compared to 16% of cultures with FCS. In addition, 6% of HP-supplemented cultures did not achieve becoming lymphoblastoid cell lines by day 35 in comparison to 94% of cultures with FCS. The higher proliferative effect of HP was not altered by heat inactivation or filtration. HP maintained its proliferative activity at 4 degrees C over 8 months, thus indicating that HP contains a stable growth factor(s), which accelerates B-lymphocyte immortalization. The results support other studies that recommend the use of autologous plasma for tissue culture, mainly in the case of autologous transplantation. Furthermore, the use of HP allows preparation of lymphoblastoid cell lines from a small amount of peripheral blood in a shorter period of time and with a higher rate of success.


Kidney-lung connections in acute and chronic diseases: current perspectives.
Lung and kidney functions are intimately related in both health and disease. The regulation of acid-base equilibrium, modification of partial pressure of carbon dioxide and bicarbonate concentration, and the control of blood pressure and fluid homeostasis all closely depend on renal and pulmonary activities. These interactions begin in fetal age and are often responsible for the genesis and progression of diseases. In gestational age, urine is a fundamental component of the amniotic fluid, acting on pulmonary maturation and growth. Moreover, in the first trimester of pregnancy, kidney is the main source of proline, contributing to collagen synthesis and lung parenchyma maturation. Pathologically speaking, the kidneys could become damaged by mediators of inflammation or immuno-mediated factors related to a primary lung pathology or, on the contrary, it could be the renal disease that determines a consecutive pulmonary damage. Furthermore, non immunological mechanisms are frequently involved in renal and pulmonary diseases, as observed in chronic pathologies such as sleep apnea syndrome, pulmonary hypertension, progressive renal disease and hemodialysis. Kidney damage has also been related to mechanical ventilation. The aim of this review is to describe pulmonary-renal interactions and their related pathologies, underscoring the need for a close collaboration between intensivists, pneumologists and nephrologists.


Prevalence and risk factors associated with malnutrition among adolescents in rural Tanzania.
To determine the prevalence and risk factors associated with malnutrition among adolescents in a rural Tanzanian community. Cross-sectional survey of 1226 randomly selected adolescents from the Dodoma Health and Demographic Surveillance System (HDSS) in the Chamwino district in the Dodoma region. Anthropometric measurements for weight and height were collected. Height-for-age-z-scores (HAZs) and body mass index (BMI)-for-age-z-scores (BAZs) were computed. Descriptive estimates were documented in graphs and tables, and weighted linear regression models were used to examine predictors of malnutrition. Stunting prevalence was 18%, and thinness prevalence was 14%. Overweight and obesity affected 5.23% of participants. Girls had higher HAZs (β: 0.46, 95% CI 0.33, 0.59, P < 0.0001) and BAZs (β: 0.20, 95% CI 0.05, 0.35, P = 0.0098) than boys. Age was inversely associated with HAZs (β: -0.13, 95% CI -0.17, -0.08, P < 0.0001) and BAZs (β: -0.05, 95% CI -0.10, -0.004, P = 0.0327). Wealth score (β: 0.10, 95% CI 0.04, 0.16, P = 0.0009) and dietary diversity score (β: 0.04, 95% CI 0.01, 0.07, P = 0.0080) were positively associated with HAZs and BAZs. Out-of-school adolescents had higher HAZs (β: -0.49, 95% CI -0.75, -0.23, P = 0.0003) and BAZs (β: -0.68, 95% CI -0.99, -0.37, P < 0.0001) than adolescents who attended school. There are substantial variations of HAZs and BAZs across gender, age, education and wealth, with an emerging burden of overweight and obesity among adolescents in this rural population. Interventions are urgently required to curb both ends of the malnutrition spectrum.


Public perceptions of the use of gloves by healthcare workers and comparison with perceptions of student nurses.
There is evidence that non-sterile clinical gloves (NSCG) are over-used by healthcare workers (HCWs) and are associated with cross-contamination. This study aimed to determine attitudes of student nurses and members of the public to the use of NSCG. Third-year student nurses completed a questionnaire indicating tasks for which they would wear NSCG and influences on their decision. Correlations between tasks were identified using exploratory factor analysis. An online survey of the public was conducted using snowball sampling method. Sixty-seven students completed the questionnaire; they indicated use of NSCG for low-risk tasks and reported their own judgement as the main influence on their decision to wear them. Correlated tasks included 'perceived to be risky' or 'definitive indication for gloves/no gloves' and 'related to personal hygiene'. A total of 142 respondents completed the public survey. They reported being uncomfortable with HCW wearing gloves for some personal tasks, e.g. assisting to toilet and dressing, but 94% preferred their use for washing 'private parts'; 29% had observed inappropriate glove use by HCWs during recent contact with healthcare. Student nurses reported using NSCG routinely for tasks for which they are neither required nor recommended. The public observe inappropriate glove use and are uncomfortable with their use for some personal tasks.


Dynamical allosterism in the mechanism of action of DNA mismatch repair protein MutS.
The multidomain protein Thermus aquaticus MutS and its prokaryotic and eukaryotic homologs recognize DNA replication errors and initiate mismatch repair. MutS actions are fueled by ATP binding and hydrolysis, which modulate its interactions with DNA and other proteins in the mismatch-repair pathway. The DNA binding and ATPase activities are allosterically coupled over a distance of ∼70 Å, and the molecular mechanism of coupling has not been clarified. To address this problem, all-atom molecular dynamics simulations of ∼150 ns including explicit solvent were performed on two key complexes--ATP-bound and ATP-free MutS⋅DNA(+T bulge). We used principal component analysis in fluctuation space to assess ATP ligand-induced changes in MutS structure and dynamics. The molecular dynamics-calculated ensembles of thermally accessible structures showed markedly small differences between the two complexes. However, analysis of the covariance of dynamical fluctuations revealed a number of potentially significant interresidue and interdomain couplings. Moreover, principal component analysis revealed clusters of correlated atomic fluctuations linking the DNA and nucleotide binding sites, especially in the ATP-bound MutS⋅DNA(+T) complex. These results support the idea that allosterism between the nucleotide and DNA binding sites in MutS can occur via ligand-induced changes in motion, i.e., dynamical allosterism.


Medication errors in pediatric inpatients: a study based on a national mandatory reporting system.
The aim was to describe medication errors (MEs) in hospitalized children reported to the national mandatory reporting and learning system, the Danish Patient Safety Database (DPSD). MEs were extracted from DPSD from the 5-year period of 2010-2014. We included reports from public hospitals on patients aged 0-17 years and categorized by reporters as medication-related. Reports from psychiatric wards and outpatient clinics were excluded. A ME was defined as any medication-related error occurring in the medication process whether harmful or not. MEs were categorized as harmful if they resulted in actual harm or interventions to prevent harm. MEs were further categorized according to occurrence in the medication process, type of error, and the medicines involved. A total of 2071 MEs including 487 harmful MEs were identified. Most MEs occurred during prescribing (40.8%), followed by dispensing (38.7%). Harmful MEs occurred mainly during dispensing (40.3%). Dosing errors were the most reported type of error, 47.7% of all MEs and 45.4% of harmful MEs. Antibiotics and analgesics were the most frequently reported medication classes. Common medicines associated with MEs included morphine, paracetamol, and gentamicin. MEs caused no harm (74.9%), mild (11.7%), moderate (10.5%), or severe harm (1.3%), but none were lethal. MEs in hospitalized children occur in all medication processes and mainly involve dosing errors. Strategies should be developed to prevent MEs as these still threaten medication safety in pediatric inpatients. What is known: • Hospitalized children are more likely to experience medication errors than adults. • Voluntary national and local reporting and learning systems have previously been used to describe the nature and types of medication errors. What is new: • Medication errors in hospitalized children occur in all steps of the medication process, most frequently involving dosing errors and most commonly involving morphine, paracetamol, and gentamicin. • Of the medication errors, 1.3% cause severe harm, but no fatal errors were reported.


Unicentric Castleman's disease imitating metastatic melanoma: A case report.
This case report shows a unique case of Castleman's disease in the context of histopathological diagnosis of cutaneous melanoma where clinical and radiological features of Castleman's disease were masked by presumptive diagnosis of metastatic melanoma. The disease is part of a group of lymphoproliferative disorders with characteristic histopathological features that can occur in any lymph node in the body, characterised by slow growing painless masses which are asymptomatic until mass effect occurs. This case highlights the need for caution when considering management of lymphadenopathy with clinically/radiologically suspicious nodes. A 65 year old man with metastatic melanoma of the left elbow presented for axillary sentinel node mapping and was found to have a hypoechoic enlarged node on ultrasound. This was further investigated and found to be a lymphoproliferative growth pathognomonic for Castlemans disease. Whilst clinically detected lymphadenopathy in the draining node basin of a primary cutaneous melanoma is highly suspicious for nodal metastasis, it is sometimes not possible to confirm or exclude this diagnosis without complete histological examination of the node. Multidisciplinary input from the surgeon, histopathologist and radiologist is a key step in confirming diagnosis. Alternative diagnoses must be considered in the context of lymphadenopathy, even in the context of malignant melanoma.


Association Between Facility and Clinician Characteristics and Family Planning Services Provided During U.S. Outpatient Care Visits.
Recent guidelines from the Centers for Disease Control and Prevention emphasize the importance of access to comprehensive family planning services and recommend patient-centered contraceptive counseling be incorporated into routine primary care visits for reproductive-age individuals. This study aims to describe family planning service provision in outpatient care settings and assess differences by facility and clinician characteristics. Using National Ambulatory Medical Care Survey data, a nationally representative survey of outpatient care visits, we assessed family planning service provision by facility location, facility type, physician specialty, types of clinicians seen, and whether the patient was seen by their primary care provider. We used random intercept logistic regression with robust standard errors, adjusting for patient characteristics, and state and year fixed effects. The analytic sample included 53,489 patient visits with reproductive-age (15-49 years) individuals between 2011 and 2019. Family planning services were provided at 8% of total sampled visits and were more likely to be provided in urban compared with rural areas (adjusted odds ratio, 1.45; p = .02) and at community health centers compared with private physician practices (adjusted odds ratio, 1.74; p = .00). Family planning services were also more likely to be provided when the patient saw a physician assistant or nurse compared with only a physician. After controlling for observed covariates, measures of between-clinician heterogeneity indicate wide variation in which clinicians provided family planning services. Family planning services were more likely to be provided in urban areas, at community health centers, and when patients received team-based care. The wide variation between clinicians suggests a need to better incorporate family planning services into primary care and other outpatient settings to meet patient needs and preferences.


Evaluation of "gastric" emptying time in the J pouch compared with a standard esophagojejunal anastomosis.
Gastric emptying times and symptoms were recorded in 18 patients after total gastrectomy and either a 15-cm J-pouch (n = 10) or a standard esophagojejunal anastomosis (n = 8). A solid test meal labeled with 99mTc was used to compare the emptying times. The postoperative symptoms and nutritional status were also assessed. The J-pouch resulted in a prolonged period of food retention in the upper jejunum (p < 0.02) compared to that with a standard esophagojejunal anastomosis. The patients with a J-pouch had fewer episodes of postprandial pain (p < 0.03) or vomiting (< 0.04). They also had fewer dietary restrictions (p < 0.04) and better nutritional status.


Clinical trials--a brave new partnership: a new doctor-patient working relationship in research.
An outline of the development of a "brave new partnership" in clinical trials is provided in this specific personal account. This paper was one of several delivered in November 2007 by colleagues deemed to have contributed to the distinguished career of Professor Michael Baum, at a Festschrift convened to honour him. This account describes this strange, new doctor-patient relationship in the research process that we developed, both in our dialogues and in the work of the Consumers' Advisory Group for Clinical Trials (CAG-CT) that we jointly founded. This work formed but one facet of his outstanding contribution to society and academe, in the fields of medicine, ethics and science.


Revealing the prognostic and clinicopathological significance of systemic immune-inflammation index in patients with different stage prostate cancer: A systematic review and meta-analysis.
A novel inflammatory marker called the systemic immune-inflammation index (SII) was applied to predict the prognosis of different cancers. However, the role of SII in prostate cancer (PCa) remains unclear. This systematic review aims to explore the prognostic role of SII in different stage PCa. We comprehensively searched three public databases: PubMed, EMBASE, and the Cochrane Library. The hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were extracted to evaluate the association between SII and the prognosis and clinicopathological characteristics in different stage PCa patients. Ten studies and 7,986 patients were enrolled in our meta-analysis, 1,442 patients were diagnosed with metastatic-castration resistant prostate cancer (mCRPC), and 6544 patients were diagnosed with non-metastatic prostate cancer (nmPCa). According to the pooled results, we found that a high SII was associated with worse overall survival (OS) in mCRPC patients (HR = 1.94, 95% CI: 1.26-3.01, p = 0.003), and a high SII was associated with biochemical recurrence-free survival (BFS) in nmPCa patients (HR = 1.85, 95% CI: 1.06-3.24, p = 0.031). But there was no significant association observed between SII and progression-free survival (PFS) in mCRPC patients (HR = 1.90, 95% CI: 0.87-4.14, p = 0.107). And we found that the high SII was associated with advanced tumor stage of PCa (OR = 2.19, 95% CI: 1.11-4.33, p = 0.024), presence of lymph node involvement (OR = 2.72, 95% CI: 1.96-3.76, p < 0.001) and Gleason score (OR = 1.27, 95% CI: 1.13-1.44, p < 0.001). High SII was associated with bad OS in mCRPC patients, and associated with bad BFS and some adverse pathological features in nmPCa patients. We think SII can be a prognostic predictor for PCa patients. The application of SII will advance the diagnosis and treatment of different stage prostate cancer.


Key active site residues in the inhibition of acetylcholinesterases by soman.
Molecular modeling (GEMM 7.3) and molecular mechanics calculations (YETI V 5.3) using the X-ray coordinates for acetylcholinesterase (AChE) from Torpedo californica indicate electrostatic stabilization by the active site, Glu-199, of the developing positive charge on the incipient carbonium ion in the dealkylation in the adducts of AChE with PSCR and PSCS diastereomers of 2-(3,3-dimethylbutyl) methylphosphonofluoridate (soman). His-440 is indispensable as a general acid catalyst of C-O bond breaking in the dealkylation reaction and that of bond breaking to the Ser gamma-O in reactivation. This demand for catalysis seems to be satisfied for the reactivation of enzyme from the PSCS diastereomer of soman, but not from the P(S)C(R) diastereomer.


Effect of an injectable microencapsulated Vitamin B12 on serum and liver Vitamin B12 concentrations in calves.
To evaluate the efficacy of a long-acting injectable microencapsulated formulation of Vitamin B12 in dairy calves. Fifty calves, average liveweight 110kg, were randomly allocated to 5 groups of 10 animals and injected subcutaneously in the anterior neck with 0.12, 0.18, 0.24 and 0.3 mg Vitamin B12/kg liveweight using a formulation of microencapsulated Vitamin B12 in a lactide: glycolide copolymer. The untreated calves were injected with the same vehicle, without Vitamin B12. Subsequent changes in serum and liver Vitamin B12 concentrations were followed for 244 days. The microencapsulated Vitamin B12 significantly increased, then maintained serum and liver Vitamin B12 concentrations higher than those of untreated controls for at least 110 days. Injection of the microencapsulated Vitamin B12 at dose rates of 0.12 to 0.24 mg/kg liveweight will increase and maintain the Vitamin B12 status of calves for at least 110 days.


Comparison of Southern blot analysis with isotopic and nonisotopic in situ hybridization for the detection of human papillomavirus sequences in invasive carcinoma of the uterine cervix.
To compare the efficiency of hybridization methods for the detection of HPV genome, 22 cases of invasive squamous cell carcinoma of the uterine cervix were analyzed by Southern blot analysis and in situ hybridization carried out with 35S- and biotin-labeled probes. These cases contained from less than one to as many as 50 copies per cell of HPV 16 and 18 types. To increase the sensitivity of biotinylated probes, a silver enhancement procedure of the peroxidase reaction product was applied. Results showed that in situ hybridization performed with isotopic probes is as sensitive as Southern blot analysis and is more sensitive than that performed with biotin-labeled probe. However, the application of the silver enhancement procedure increases the percentage of HPV-positive cases from 27 to 50%.


A novel method for protein secondary structure prediction using dual-layer SVM and profiles.
A high-performance method was developed for protein secondary structure prediction based on the dual-layer support vector machine (SVM) and position-specific scoring matrices (PSSMs). SVM is a new machine learning technology that has been successfully applied in solving problems in the field of bioinformatics. The SVM's performance is usually better than that of traditional machine learning approaches. The performance was further improved by combining PSSM profiles with the SVM analysis. The PSSMs were generated from PSI-BLAST profiles, which contain important evolution information. The final prediction results were generated from the second SVM layer output. On the CB513 data set, the three-state overall per-residue accuracy, Q3, reached 75.2%, while segment overlap (SOV) accuracy increased to 80.0%. On the CB396 data set, the Q3 of our method reached 74.0% and the SOV reached 78.1%. A web server utilizing the method has been constructed and is available at http://www.bioinfo.tsinghua.edu.cn/pmsvm.


Advanced Modeling to Predict Pneumonia in Combat Trauma Patients.
Tools to assist clinicians in predicting pneumonia could lead to a significant decline in morbidity. Therefore, we sought to develop a model in combat trauma patients for identifying those at highest risk of pneumonia. This was a retrospective study of 73 primarily blast-injured casualties with combat extremity wounds. Binary classification models for pneumonia prediction were developed with measurements of injury severity from the Abbreviated Injury Scale (AIS), transfusion blood products received before arrival at Walter Reed National Military Medical Center (WRNMMC), and serum protein levels. Predictive models were generated with leave-one-out-cross-validation using the variable selection method of backward elimination (BE) and the machine learning algorithms of random forests (RF) and logistic regression (LR). BE was attempted with two predictor sets: (1) all variables and (2) serum proteins alone. Incidence of pneumonia was 12% (n = 9). Different variable sets were produced by BE when considering all variables and just serum proteins alone. BE selected the variables ISS, AIS chest, and cryoprecipitate within the first 24 h following injury for the first predictor set 1 and FGF-basic, IL-2R, and IL-6 for predictor set 2. Using both variable sets, a RF was generated with AUCs of 0.95 and 0.87-both higher than LR algorithms. Advanced modeling allowed for the identification of clinical and biomarker data predictive of pneumonia in a cohort of predominantly blast-injured combat trauma patients. The generalizability of the models developed here will require an external validation dataset.


Reoperative aortic root and transverse arch procedures: a comparison with contemporaneous primary operations.
Long-term survival and risk factors affecting outcome after reoperative root/ascending aorta and transverse arch procedures have not been clearly described. Two hundred patients (138 male patients; age, 60 +/- 15 years) underwent reoperative root/ascending aorta (n = 100) or transverse arch (n = 100) procedures at our institution from January 1998 to December 2004 and were compared with 480 consecutive contemporaneous patients with primary procedures (323 male patients; age, 62 +/- 16 years; 335 proximal aorta and 145 transverse arch procedures). Reoperative proximal aorta procedures had a higher hospital mortality (7%) than primary root/ascending aorta procedures (3%), but there was a less dramatic difference in operative mortality after primary and reoperative arch procedures (9% vs 10%). Separate multivariable analyses of root/ascending aorta procedures and arch procedures revealed chronic obstructive pulmonary disease and age to be significant risk factors for death after either procedure. In addition, an ejection fraction of less than 30% posed a significant risk for proximal aortic surgery, and diabetes and nonelective operations predicted poorer outcome after arch operations. For survivors of root/ascending aorta operations, there was no significant difference in long-term outcome between reoperations and primary procedures, with both restoring longevity to expected levels for an age- and sex-matched normal population. Patients undergoing arch operations, however, continued to have a poorer long-term outlook than their normal peers. In this series, reoperations in the transverse arch carry the same risk as primary arch procedures, but a higher operative mortality is seen with reoperative than with primary root/ascending aorta procedures. The long-term outlook is better for patients undergoing root/ascending operations than for patients undergoing aortic arch operations, with no difference in the longevity of patients undergoing primary procedures versus reoperations.


Erythrocyte sodium-lithium countertransport, adenosine triphosphatase activity and sodium-potassium fluxes in insulin-dependent diabetes.
Increased erythrocyte sodium-lithium countertransport activity has been implicated in the pathogenesis of diabetic nephropathy. However, its relationship to other cation membrane transport systems in incipient nephropathy is not yet clear. The present study was thus performed to: (1) explore associations between sodium-lithium countertransport and changes in the activity of other cation transport pathways and (2) to compare the sodium transport activities with clinical characteristics of insulin-dependent diabetic patients with and without evidence of incipient diabetic nephropathy. We measured erythrocyte sodium-lithium countertransport, passive sodium/potassium flux (at 1 degree C), adenine nucleotide content in intact erythrocytes and sodium/potassium-, magnesium- and calcium-dependent ATPase activity in erythrocyte membrane preparations from 34 insulin-dependent diabetic patients without microalbuminuria, 8 diabetic patients with microalbuminuria, and 8 age-matched healthy control subjects. Sodium-lithium countertransport was elevated in diabetic patients with normo- and microalbuminuria compared with control subjects [268 +/- 99 and 299(277-465), respectively, vs. 166 +/- 65 mumol/(1 cells x h)] and was positively correlated (r = 0.36, P < 0.05) with the albumin excretion rate. However, the activity of erythrocyte membrane ATPases was significantly decreased compared with control subjects. The ATP and ADP content was found to be significantly higher (P < 0.001) in erythrocytes from diabetic patients compared with control subjects (1,196 +/- 276 vs. 833 +/- 253 mumol/l cells and 353 +/- 97 vs. 255 +/- 64 mumol/l cells, respectively). The extent of erythrocyte potassium leakage correlated with hemoglobin A1c (r = 0.39, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Bidirectional regulation of calcium release-activated calcium (CRAC) channel by SARAF.
Store-operated calcium entry (SOCE) through the Ca2+ release-activated Ca2+ (CRAC) channel is a central mechanism by which cells generate Ca2+ signals and mediate Ca2+-dependent gene expression. The molecular basis for CRAC channel regulation by the SOCE-associated regulatory factor (SARAF) remained insufficiently understood. Here we found that following ER Ca2+ depletion, SARAF facilitates a conformational change in the ER Ca2+ sensor STIM1 that relieves an activation constraint enforced by the STIM1 inactivation domain (ID; aa 475-483) and promotes initial activation of STIM1, its translocation to ER-plasma membrane junctions, and coupling to Orai1 channels. Following intracellular Ca2+ rise, cooperation between SARAF and the STIM1 ID controls CRAC channel slow Ca2+-dependent inactivation. We further show that in T lymphocytes, SARAF is required for proper T cell receptor evoked transcription. Taking all these data together, we uncover a dual regulatory role for SARAF during both activation and inactivation of CRAC channels and show that SARAF fine-tunes intracellular Ca2+ responses and downstream gene expression in cells.


Stay Connected and Up To Date: GI Meetings and Seminars and the Coronavirus Disease 2019 Pandemic.
The novel coronavirus disease 2019 has become an unprecedented global health and societal problem. The rapid spreading of this pandemic, together with the absence of effective treatments or vaccines, has led governments around the world to take drastic actions, including limiting the free movement of citizens, establishing maximum capacities and enforcing social distancing measures, among others. Consequently, major medical congresses, meetings, conferences, and workshops have been either cancelled or delayed. This situation has forced rapid changes in how the medical and scientific communities interact, and they now mainly meet using online technology. While political leaders have closed the borders of their countries as a logical public health measure, we have witnessed medical societies, clinicians, and scientists breaking other barriers and creating a new reality of global technological collaboration unlike anything seen before. An immense variety of webinars, online conferences, podcasts, courses, and many other forms of uploaded content can be seen from the comfort of one's own workplace or home at any time, and this has exponentially increased our reach; however, this great number of possibilities can be overwhelming, and it is more important than ever to separate wheat from chaff when deciding what online event to attend. The purpose of this article is to describe the impact of coronavirus disease 2019 on congresses and meetings, to examine how GI physicians feel about the emerging trend of online initiatives and to offer suggestions on how to balance web-based meetings and daily work.


Inhibition of a lymphocyte membrane enzyme by delta9-tetrahydrocannabinol in vitro.
Delta-9-tetrahydrocannabinol (delta9-THC) inhibited the activity of lysolecithin acyl transferase, a membrane-bound lymphocyte enzyme, at concentrations above 1.3 muM. Stimulation of acyl transferase activity by concanavalin A, an early response in lymphocyte activation, was entirely abolished in the presence of delta9-THC.


[Serum levels of soluble intercellular molecule 1 (sICAM-1) in endometriosis].
To investigate the serum levels of ICAM-1 and its relationship to the extent of the disease. Serum sICAM-1 levels of 21 women with endometriosis were measured with a specific enzyme-linked immunosorbent assay, and 21 women without endometriosis were selected as control. Serum sICAM-1 levels were compared between endometriotic and non-endometriotic women, and among patients at different stages of endometriosis. Significantly higher serum sICAM-1 levels were observed in women with endometriosis [(0.30 +/- 0.07) microgram/ml] than in those without endometriosis [(0.18 +/- 0.05) microgram/ml] (P < 0.01); in women with stage I approximately II of endometriosis, the serum sICAM-1 levels were (0.24 +/- 0.06) microgram/ml, while in those with stage III approximately IV of endometriosis, the serum sICAM-1 level was (0.32 +/- 0.06) microgram/ml, the difference is of statistically significant.No differences of serum sICAM-1 level was found between proliferative and secretary phase in women with and without endometriosis. Significantly elevated serum sICAM-1 levels in women with endometriosis, especially in those with advanced stages of the disease suggests the molecule might be of value in pathogenesis of endometriosis.


Encoding a qubit in a trapped-ion mechanical oscillator.
The stable operation of quantum computers will rely on error correction, in which single quantum bits of information are stored redundantly in the Hilbert space of a larger system. Such encoded qubits are commonly based on arrays of many physical qubits, but can also be realized using a single higher-dimensional quantum system, such as a harmonic oscillator1-3. In such a system, a powerful encoding has been devised based on periodically spaced superpositions of position eigenstates4-6. Various proposals have been made for realizing approximations to such states, but these have thus far remained out of reach7-11. Here we demonstrate such an encoded qubit using a superposition of displaced squeezed states of the harmonic motion of a single trapped 40Ca+ ion, controlling and measuring the mechanical oscillator through coupling to an ancillary internal-state qubit12. We prepare and reconstruct logical states with an average squared fidelity of 87.3 ± 0.7 per cent. Also, we demonstrate a universal logical single-qubit gate set, which we analyse using process tomography. For Pauli gates we reach process fidelities of about 97 per cent, whereas for continuous rotations we use gate teleportation and achieve fidelities of approximately 89 per cent. This control method opens a route for exploring continuous variable error correction as well as hybrid quantum information schemes using both discrete and continuous variables13. The code states also have direct applications in quantum sensing, allowing simultaneous measurement of small displacements in both position and momentum14,15.


The influence of parathyroidectomy on restless legs syndrome in patients with renal hyperparathyroidism.
Restless legs syndrome (RLS) is a common and poorly understood movement disorder that leads to unpleasant leg sensations. Although RLS can be idiopathic, secondary etiologies such as iron deficiency and renal failure are common. The aim of this prospective cohort study was to evaluate whether RLS is a common feature in patients undergoing parathyroidectomy for renal hyperparathyroidism (rHPT) and if RLS-related symptoms can be influenced by surgery. After providing written consent, patients who underwent a parathyroidectomy for rHPT between January and November 2011 answered a validated RLS-screening-questionnaire (RLSSQ). If this was suggestive for RLS a confirming questionnaire (IRLS) was also completed on the day before surgery, on the fifth postoperative day, and again during follow-up (minimum 12 months). Perioperative parathyroid hormone and calcium levels, as well as the scores of the questionnaires were analyzed. Twenty-one patients (14 men, 7 women) with a mean age of 47.8 ± 3.2 years underwent total parathyroidectomy with bilateral cervical thymectomy and parathyroid autotransplantation for rHPT. The mean score of the RLSSQ of all 21 patients prior to operation was 6.1 ± 0.5. In 10 of 21 patients (47.6 %) the results of the RLSSQ were suggestive for RLS with a mean score of 8.0 ± 0.3. The consecutive scores of the IRLS in these latter patients significantly dropped from 26.6 ± 1.4 to 19.0 ± 2.2 between the preoperative and postoperative settings (p < 0.05). After a mean follow-up of 17.3 ± 3.7 months the mean scores of the RLSSQ and the IRLS were 6.1 ± 0.6 and 16.3 ± 1.8. rHPT may play a major role in the severity of RLS-associated symptoms in patients with renal failure. Consequently, parathyroidectomy may prove to be a valuable tool to reduce RLS-associated morbidity in affected patients. However, larger prospective trials are required to confirm the possible relation between RLS and rHPT seen in the present study


Halorubrum rubrum sp. nov., an extremely halophilic archaeon from a Chinese salt lake.
Two halophilic archaeal strains, YC87(T) and YCA11, were isolated from Yuncheng salt lake in Shanxi, China. Cells of the two strains were observed to be pleomorphic rod-shaped, stained Gram-negative and produced red-pigmented colonies. Strain YC87(T) was able to grow at 20-50 °C (optimum 37 °C), at 1.4-4.8 M NaCl (optimum 2.1 M NaCl), at 0.05-1.0 M MgCl2 (optimum 0.3 M MgCl2) and at pH 6.0-9.0 (optimum pH 7.0) while strain YCA11 was able to grow at 20-50 °C (optimum 37 °C), at 2.1-4.8 M NaCl (optimum 3.1 M NaCl), at 0.01-0.7 M MgCl2 (optimum 0.1 M MgCl2) and at pH 6.0-9.0 (optimum pH 7.5). The cells of both isolates were observed to lyse in distilled water. The minimum NaCl concentrations that prevented cell lysis were determined to be 8 % (w/v) for strain YC87(T) and 12 % (w/v) for strain YCA11. The major polar lipids of the two strains were identified as phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate and one major glycolipid chromatographically identical to sulfated mannosyl glucosyl diether; another major glycolipid and trace amounts of several unidentified lipids were also detected. The 16S rRNA gene sequences of the two strains were 99.8 % identical, showing 93.2-98.2 % similarity to members of the genus Halorubrum of the family Halobacteriaceae. The rpoB' gene similarity between strains YC87(T) and YCA11 was 99.3 % and showed 87.5-95.2 % similarity to the closest relative members of the genus Halorubrum. The DNA G+C content of strains YC87(T) and YCA11 were determined to be 64.9 and 64.5 mol%, respectively. The DNA-DNA hybridization value between strain YC20(T) and strain YC77 was 87 % and the two strains showed low DNA-DNA relatedness with Halorubrum cibi JCM 15757(T) and Halorubrum aquaticum CGMCC 1.6377(T), the most related members of the genus Halorubrum. The phenotypic, chemotaxonomic and phylogenetic properties suggest that strains YC87(T) and YCA11 represent a novel species of the genus Halorubrum, for which the name Halorubrum rubrum sp. nov. is proposed. The type strain is YC87(T) (=CGMCC 1.12124(T) = JCM 18365(T)).


Method validation for the determination of ochratoxin A in green and soluble coffee by immunoaffinity column cleanup and liquid chromatography.
A method was validated for the determination of ochratoxin A (OTA) in soluble and green coffee. Performance parameters evaluated included selectivity, accuracy, intermediate precision, linearity, limit of detection, limit of quantitation, and ruggedness. The method was found to be selective for OTA in both matrices tested. Recovery rates from soluble coffee samples ranged from 73.5 to 91.2%, and from green coffee samples from 68.7 to 84.5%. The intermediate precision (RSDr) was between 9.1 and 9.4% for soluble coffee and between 14.3 and 15.5% for green coffee analysis. The linearity of the standard calibration curve (r(2)) was <0.999 for OTA levels of 1.0-20.0 μg/kg in coffee samples. The limit of detection was determined to be 0.01 ng of OTA on column, while the limit of quantitation was found to be 0.03 ng on column. The limit of quantitation is equivalent to 0.6 μg/kg in soluble coffee samples and 0.3 μg/kg in green coffee samples. The results of the ruggedness trial showed two factors are critical for soluble coffee analysis: the extraction method, and the flow rate of the mobile phase. For green coffee analysis two critical factors detected were the extraction method and the storage temperature of the immunoaffinity column.Five samples of soluble coffee and 42 of green coffee were analysed using the validated method. All soluble coffee samples contained OTA at levels that ranged from 8.4 to 13.9 μg/kg. Six of the 42 green coffee samples analysed (14.3%) contained OTA at levels ranging from 0.9 to 19.4 μg/kg. The validated method can be used to monitor OTA levels in Colombian coffee for export or for local consumption.


IL-36 receptor is expressed by human blood and intestinal T lymphocytes and is dose-dependently activated via IL-36β and induces CD4+ lymphocyte proliferation.
We show that IL-36R is expressed by T (CD4+ and CD8+) and B (CD19+) lymphocytes in human blood and also by CD4+ T lymphocytes in the intestinal lamina propria. IL-36R protein was mostly stored in the cytoplasm of CD4 lymphocytes and B cells, during steady state conditions and the greatest expression of IL-36R mRNA was measured in CD4+ (T helper) lymphocytes. IL-36 β, which functions via IL-36R induced rapid and significant (P<0.05) proliferation of CD4+ lymphocytes, within 48h. IL-36R expression was also maintained on the surface of circulating CD4+ lymphocytes which enter the intestinal lamina propria. In conclusion our study is the first to show that (1) all human blood lymphocytes express IL-36R; (2) IL-36R expression is maintained by circulating CD4+ lymphocytes which enter the intestinal lamina propria and (3) IL-36R/IL-36 β induces rapid CD4 lymphocyte proliferation. The possible significance of these results in the context of human disease is discussed.


Blocking connexin43 hemichannels prevents TGF-β2 upregulation and epithelial-mesenchymal transition in retinal pigment epithelial cells.
Epithelial-mesenchymal transition (EMT) occurs when polarised epithelial cells change to a mesenchymal phenotype. EMT plays a role in several chronic conditions, including ocular diseases with retinal pigment epithelium (RPE) EMT associated with retinal diseases such as diabetic retinopathy (DR). Here, EMT results in breakdown of the blood-retinal barrier (BRB) leading to sub-retinal fluid deposition and retinal detachment. Previous studies have shown that blocking connexin43 (Cx43) hemichannels can protect against RPE BRB breakdown, but the underlying mechanism is unknown. To determine whether open Cx43 hemichannels may enable EMT of RPE cells and thus result in BRB breakdown, ARPE-19 cells were either challenged with high glucose plus the inflammatory cytokines IL-1β and TNF-α (HG + Cyt) to simulate DR or treated with the Cx43 hemichannel blocker tonabersat alongside the HG + Cyt challenge. HG + Cyt induced a morphological change in RPE cells to a fibroblastic phenotype with a corresponding decrease in epithelial zonular occludens-1 and an increase in the fibroblastic marker α-SMA. The HG + Cyt challenge also induced loss of transepithelial electrical resistance while increasing dye passage between RPE cells. All of these changes were significantly reduced with tonabersat treatment, which also prevented HG + Cyt-induced transforming growth factor-β2 (TGF-β2) release. In conclusion, Cx43 hemichannel block with tonabersat attenuated both TGF-β2 release and RPE EMT under disease-mimicking conditions, offering the potential to ameliorate the progression of EMT-associated retinal diseases.


Biomarkers Guided Treatment Strategies in Adult Patients with Asthma: Ready for the Clinical Field?
Asthma is a chronic inflammatory airways disorder mainly characterized by heterogeneity. In the more severe forms, a discordance often exists between symptoms and inflammation. Difficulty in managing asthma derives partly from the multiple phenotypes existing and our inability to recognize them. The use of non-invasive, with main representative the fraction of exhaled nitric oxide, or semi-invasive techniques such as induced sputum are effective tools that can help us to guide asthma treatment. In the latest years, several serum biomarkers related to asthmatic inflammation have been used for the better recognition of asthma sub-phenotypes to achieve optimization of therapy and disease outcome. In patients with mild-moderate asthma, as well as patients with more severe asthma, the use of blood eosinophils revealed an acceptable accuracy for the prediction of airway eosinophilia indicating that in future studies may facilitate both individualized treatment and management of asthma. None of the above techniques have been incorporated in clinical practice although sputum eosinophils can be used in patients with severe asthma particularly in specialized centers with great experience. Of great interest are blood eosinophils since current data support their role either as tool for treatment selections or/and as a biomarker of airway eosinophilia.


Interaction of smoking and metabolic syndrome on cardiovascular risk in a Chinese cohort.
The high prevalence of smoking and metabolic syndrome (MS) and increased incidence of cardiovascular disease (CVD) in China indicates that there may be an interaction between smoking and MS on cardiovascular risk. Therefore, we aimed to examine the independent and combined effects of smoking and MS on risk of CVD in a Chinese cohort. We analyzed data from a population-based prospective cohort of 3598 participants aged 35-74 years from Jiangsu China who were free of diabetes and CVD at enrollment and were followed for cardiovascular events (including myocardial infarction, ischemic stroke, hemorrhagic stroke, and cardiovascular mortality) until 31 August 2008. During 8 years (median 6.3 years) of follow-up, 82 participants developed CVD. After adjusting for age, sex, body mass index, alcohol consumption, family history of cardiovascular disease and MS, smoking significantly increased cardiovascular risk in a dose-response manner. After further adjustment for smoking status, the hazard ratio of CVD for participants with MS was 2.49 (95% confidence interval 1.59-3.90) compared with those without the syndrome. There was a statistically significant additive interaction between current smoking and MS on cardiovascular risk. The risk of CVD for current smokers with MS was 1.81 times as high as the sum of risks in participants with a single condition alone. Both cigarette smoking and MS are strong risk factors of CVD in the Chinese population. Moreover, this study further demonstrates an additive interaction of current smoking and MS on cardiovascular risk.