A New Method for Measuring Glenoid Version on Standard Magnetic Resonance Imaging.
The most effective method and modality for measuring glenoid version for different shoulder conditions is uncertain. Computed tomography (CT) imaging exposes the patient to radiation, and standard magnetic resonance imaging (MRI) does not consistently image the entire scapula. This study investigates the reliability of a new method for assessing glenoid version using routine shoulder MRI. MRI images of 20 patients undergoing arthroscopy for shoulder instability were independently assessed by 3 clinicians for osseous and chondrolabral glenoid version. To assess glenoid version, a line was drawn from medial corner of the glenoid body to midpoint of the glenoid face. A line perpendicular to this was the reference against which to measure glenoid version. Measurements were repeated after 3 months to assess intra- and interobserver reliability. Reliability was determined using intraclass correlation coefficients (ICCs). Interclass correlation coefficients showed at least good reliability for most estimates of intraobserver reliability (ICC ≥ .66) and excellent reliability for most estimates of interobserver reliability (ICC ≥ .84), with the exception of some inferior glenoid measurements where ICC was poor (ICC ≤.41). We propose that this new method of measuring glenoid on standard axial MRI can be used as a simple, practical, and reliable method in shoulder instability patients, which will reduce the requirement for CT in this group.


Role of Low-Level Light Therapy (LLLT) in Androgenetic Alopecia.
Androgenetic alopecia (AGA) is the commonest type of alopecia affecting over half of men and women. Only two drugs have been approved so far (minoxidil and finasteride), and hair transplant is the other treatment alternative. Low-level laser therapy (LLLT) has been claimed to be a new safe devise-based modality for stimulating hair growth in men and women in AGA. Searches of PubMed and Google Scholar were carried out using keywords alopecia, hair loss, and LLLT. Fifteen studies were found to be strongly relevant and were analyzed. Studies have shown that LLLT stimulated hair growth in both men and women. Studies with largest randomized controlled trials demonstrated statistically significant hair regrowth by terminal hair count in both males and females. One study also showed that LLLT and minoxidil had similar efficacy in hair growth and that combination therapy was even more effective. LLLT represents a non-invasive, safe, and potentially effective treatment option for patients with AGA who do not respond or are not tolerant to standard treatment of AGA. Moreover, combining LLLT with topical minoxidil solution and oral finasteride may act synergistic to enhance hair regrowth. However, the level of evidence of the studies is still low and hence more controlled large studies are needed.


Evaluation of solitary thyroid nodules.
The yield of malignancy when evaluating solitary thyroid nodules can be significantly increased by following a stepwise approach. The gold standard is fine needle aspiration. A thorough history and physical, thyroid scintigraphy, as well as exogenous suppression therapy, aid clinicians to efficiently evaluate the abundance of solitary thyroid nodules and isolate those which are likely to be neoplastic.


Assessment of visual function in MS patients: comparative study of some diagnostic tests.
Optic pathways are frequently involved in Multiple Sclerosis (MS). However, in some cases the involvement is asymptomatic or gives rise to only slight visual disturbances without alterations of visual acuity or of clinically evident visual field defects. In these cases several diagnostic tests permit an objective evaluation of the visual dysfunction. The aim of this study is to compare the value of contrast sensitivity test (CST), pattern reversal visual evoked potential (VEP), ophthalmoscopy, Goldmann perimetry in 45 MS patients with normal visual acuity. Examination of contrast sensitivity was carried out with a simple two-alternative forced choice test estimating the spatial frequency of 4 cycles/degree. The VEP was performed with a pattern reversal checkerboard at a spatial frequency of 1 and 2 cycles/degree. Fundus examination was abnormal in 12 patients; visual field defects were detected in 16 patients. 32 patients (71.1%) had abnormal CST in one or both eyes. VEP for the 30' checks was abnormal in 32 cases (71.1%) and that for the 15' checks in 36 cases (80.0%). All but 4 patients (91.2%) had one or more abnormal tests. All patients with abnormal perimetry and/or fundus examination had also CST and/or VEP altered. It is apparent that CST and VEP reveal a significant proportion of abnormalities in the visual system that have not been revealed by routine neuroophthalmological examination.


Towards open information management in health care.
The utilization of information technology as tool in health care is increasing. The main benefits stem from the fact that information in electronic form can be transferred to different locations rapidly and from the possibility to automate certain information management tasks. The current technological approach for this automation relies on structured, formally coded representation of information. We discuss the limitations of the current technological approach and present a viewpoint, grounded on previous research and the authors' own experiences, on how to progress. We present that a bottleneck in the automation of the management of constantly evolving clinical information is caused by the fact that the current technological approach requires the formal coding of information to be static in nature. This inherently hinders the expandability of the information case space to be managed. We present a new paradigm entitled open information management targeting unlimited case spaces. We also present a conceptual example from clinical medicine demonstrating open information management principles and mechanisms.


Complex modulation of cation channels in the tonoplast and plasma membrane of Saccharomyces cerevisiae: single-channel studies.
Detailed patch-clamp studies have been made of ion channels in the plasma membrane and tonoplast of the yeast Saccharomyces cerevisiae. The predominant tonoplast channel is a high-conductance cation-selective inward rectifier (passing ions easily into the cytoplasm from the vacuole), with its open probability (Po) peaking at about -80 mV (cytoplasm negative) and falling to near zero at +80 mV. It has a maximal slope conductance of approximately 150 pS in 100 mmol l-1 KCl, and conducts Na+, K+ and Ca2+. Elevated cytoplasmic Ca2+ concentration, alkaline pH and reducing agents can activate the channel, its likely physiological function being to adjust cytoplasmic Ca2+ concentration from the vacuolar reservoir. The predominant plasma-membrane channel is a strongly outward rectifying K+ channel (passing K+ easily out of the cytoplasm to the extracellular medium), which is activated by positive-going membrane voltages as well as by elevated cytoplasmic Ca2+ concentration and alkaline pH. Interaction between membrane voltage and [Ca2+]cyt is complex and defines three parallel closed states for the channel: a Ca(2+)-independent brief closure (I), a calcium-inhibited long closure (G) and, at large positive voltages, a calcium-induced brief blockade (B). This channel is likely to function in steady-state turgor regulation and in charge balancing during proton-coupled substrate uptake.


The association between relative deprivation and self-rated health, depressive symptoms, and smoking behavior in Taiwan.
Relative deprivation has been hypothesized as one explanation for the association between income inequality and health. However, few studies have examined the effect of relative deprivation on psychosocial and behavioral outcomes. Using a cross-sectional data from the National Survey on Knowledge, Attitude, and Practice of Health Promotion in Taiwan, this study examined the relationship between relative deprivation and physical health (self-rated health), psychosocial health (depressive symptoms), and behavioral health (smoking) among working-age Taiwanese men and women. We found that higher relative deprivation (measured by the Yitzhaki Index) is significantly associated with a higher prevalence of poor self-rated health, depressive symptoms, and current smoking in both genders. After controlling for demographic variables and absolute income, the prevalence ratios (PRs) of reporting poor health for each 10,000 NT-dollars higher in the Yitzhaki Index are between 1.25 and 1.57, depending on the reference groups. The PRs were between 1.33 and 1.77 for depressive symptoms, and between 1.04 and 1.46 for smoking. Additionally, the depressive symptoms attenuated the association between relative deprivation and self-rated health. The results were consistent with various definitions of reference groups. In conclusion, this study suggests that the psychosocial process of relative deprivation is a crucial mechanism linking income inequality to health. Narrowing the income gap between rich and poor may protect the physical and mental well-being of the population and reduce the prevalence of smoking.


The exception proves the rule? Dual targeting of nuclear-encoded proteins into endosymbiotic organelles.
Plant cells harbor two types of endosymbiotic organelle: mitochondria and chloroplasts. As a consequence of endosymbiotic gene transfer, the majority of their proteins are encoded in the nucleus and post-translationally 're'-imported into the respective target organelle. The corresponding transport signals are usually selective for a single organelle, but several proteins are transported into both the mitochondria and chloroplasts. To estimate the number of proteins with such dual targeting properties in Arabidopsis, we classified the proteins encoded by nuclear genes of endosymbiotic origin according to the respective targeting specificity of their N-terminal transport signals as predicted by the TargetP software package. Selected examples of the resulting protein classes were subsequently analyzed by transient transformation assays as well as by in organello protein transport experiments. It was found that most proteins with high prediction values for both organelles show dual targeting with both experimental approaches. Unexpectedly, however, dual targeting was even found among those proteins that are predicted to be localized solely in one of the two endosymbiotic organelles. In total, among the 16 candidate proteins analyzed, we identified 10 proteins with dual targeting properties. This unexpectedly high proportion suggests that such transport properties are much more abundant than anticipated.


Differential effects of ATP-MgCl2 on portal and hepatic arterial blood flow after hemorrhage and resuscitation.
Although ATP-MgCl2 administration after hemorrhage and resuscitation restores the decreased hepatic blood flow, it is not known whether this is due to the increase in portal blood flow or hepatic arterial blood flow. To study this, rats underwent a midline laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal shed blood volume was returned in the form of Ringer lactate (RL). The animals were resuscitated with four times the volume of the shed blood with RL, during and after which ATP-MgCl2 (50 mumol/kg body wt) or an equal volume of normal saline was infused intravenously over 95 min. Cardiac output and organ blood flow were determined by 85Sr-labeled microspheres at 90 min after the completion of resuscitation. The results indicate that portal blood flow and total hepatic blood flow decreased significantly after hemorrhage and resuscitation. ATP-MgCl2 treatment, however, restored these parameters to sham values. In contrast, hepatic arterial blood flow did not change significantly after either hemorrhage and resuscitation or ATP-MgCl2 infusion. Moreover, the depressed cardiac output was normalized and coronary blood flow was higher than shams after ATP-MgCl2 treatment. Unlike small intestinal blood flow, blood flows to the stomach, spleen, pancreas, mesentery, and cecum were not markedly affected with ATP-MgCl2 infusion. Thus the restoration of hepatic blood flow with ATP-MgCl2 treatment under such conditions is due to the increased portal blood flow, i.e., solely due to the increased small intestinal blood flow.


Reductive dechlorination of TCE by chemical model systems in comparison to dehalogenating bacteria: insights from dual element isotope analysis (13C/12C, 37Cl/35Cl).
Chloroethenes like trichloroethene (TCE) are prevalent environmental contaminants, which may be degraded through reductive dechlorination. Chemical models such as cobalamine (vitamin B12) and its simplified analogue cobaloxime have served to mimic microbial reductive dechlorination. To test whether in vitro and in vivo mechanisms agree, we combined carbon and chlorine isotope measurements of TCE. Degradation-associated enrichment factors ε(carbon) and ε(chlorine) (i.e., molecular-average isotope effects) were -12.2‰ ± 0.5‰ and -3.6‰ ± 0.1‰ with Geobacter lovleyi strain SZ; -9.1‰ ± 0.6‰ and -2.7‰ ± 0.6‰ with Desulfitobacterium hafniense Y51; -16.1‰ ± 0.9‰ and -4.0‰ ± 0.2‰ with the enzymatic cofactor cobalamin; -21.3‰ ± 0.5‰ and -3.5‰ ± 0.1‰ with cobaloxime. Dual element isotope slopes m = Δδ(13)C/ Δδ(37)Cl ≈ ε(carbon)/ε(chlorine) of TCE showed strong agreement between biotransformations (3.4 to 3.8) and cobalamin (3.9), but differed markedly for cobaloxime (6.1). These results (i) suggest a similar biodegradation mechanism despite different microbial strains, (ii) indicate that transformation with isolated cobalamin resembles in vivo transformation and (iii) suggest a different mechanism with cobaloxime. This model reactant should therefore be used with caution. Our results demonstrate the power of two-dimensional isotope analyses to characterize and distinguish between reaction mechanisms in whole cell experiments and in vitro model systems.


A novel vertebrate system for the examination and direct comparison of the relative biological effectiveness for different radiation qualities and sources.
The recent rapid increase of hadron therapy applications requires the development of high performance, reliable in vivo models for preclinical research on the biological effects of high linear energy transfer (LET) particle radiation. The aim of this paper was to test the relative biological effectiveness (RBE) of the zebrafish embryo system at two neutron facilities. Series of viable zebrafish embryos at 24-hour post-fertilization (hpf) were exposed to single fraction, whole-body, photon and neutron (reactor fission neutrons (<En = 1 MeV>) and (p (18 MeV)+Be, <En> = 3.5 MeV) fast neutron) irradiation. The survival and morphologic abnormalities of each embryo were assessed at 24-hour intervals from the point of fertilization up to 192 hpf and then compared to conventional 6 MV photon beam irradiation results. The higher energy of the fast neutron beams represents lower RBE (ref. source LINAC 6 MV photon). The lethality rate in the zebrafish embryo model was 10 times higher for 1 MeV fission neutrons and 2.5 times greater for p (18 MeV)+Be cyclotron generated fast neutron beam when compared to photon irradiation results. Dose-dependent organ perturbations (shortening of the body length, spine curvature, microcephaly, micro-ophthalmia, pericardial edema and inhibition of yolk sac resorption) and microscopic (marked cellular changes in eyes, brain, liver, muscle and the gastrointestinal system) changes scale together with the dose response. The zebrafish embryo system is a powerful and versatile model for assessing the effect of ionizing radiation with different LET values on viability, organ and tissue development.


Palladium nanoparticles decorated on amine functionalized graphene nanosheets as excellent nanocatalyst for the hydrogenation of nitrophenols to aminophenol counterparts.
We reported the improved catalytic property of Pd (0) nanoparticles decorated on amine-functionalized graphene nanosheets (Pd/GNS-NH2) for the hydrogenation of nitrophenol derivatives in the presence of NaBH4 at moderate conditions. Pd/GNS-NH2 nanocatalyst was synthesized by the deposition-reduction method. Sundry techniques such as ICP-OES, P-XRD, XPS, TEM, HR-TEM and EDX have been applied to explain the structure and morphology of the Pd/GNS-NH2 nanocatalyst. The results show that the Pd (0) nanoparticles are perfectly dispersed on the surface of the GNS-NH2 support material (dmean = 1.38-2.63 nm). The catalytic activity of the Pd/GNS-NH2 nanocatalyst was tested in the hydrogenation of nitrophenol derivatives in water in the presence of NaBH4 as reductant and the excellent activity of nanocatalyst have been detected against 2-nitrophenol, 4-nitrophenol, 2,4-dinitrophenol and 2,4,6-trinitrophenol derivatives with 116.8, 65.9, 42.8 and 11.4 min-1 initial TOF values, respectively. Another important point is that the nanocatalyst has very high reusability performance (at 5th reuse between 71.5 and 91.5%) for the hydrogenation of nitrophenols. Finally, catalytic studies have been carried out at various temperatures to calculate the Ea, ΔH≠ and ΔS≠.


Characteristics of medication errors with parenteral cytotoxic drugs.
Errors involving cytotoxic drugs have the potential of being fatal and should therefore be prevented. The objective of this article is to identify the characteristics of medication errors involving parenteral cytotoxic drugs in Sweden. A total of 60 cases reported to the national error reporting systems from 1996 to 2008 were reviewed. Classification was made to identify cytotoxic drugs involved, type of error, where the error occurred, error detection mechanism, and consequences for the patient. The most commonly involved cytotoxic drugs were fluorouracil, carboplatin, cytarabine and doxorubicin. The platinum-containing drugs often caused serious consequences for the patients. The most common error type were too high doses (45%) followed by wrong drug (30%). Twenty-five of the medication errors (42%) occurred when doctors were prescribing. All of the preparations were delivered to the patient causing temporary or life-threatening harm. Another 25 of the medication errors (42%) started with preparation at the pharmacies. The remaining 10 medication errors (16%) were due to errors during preparation by nurses (5/60) and administration by nurses to the wrong patient (5/60). It is of utmost importance to minimise the potential for errors in the prescribing stage. The identification of drugs and patients should also be improved.


Role of H₂O₂ in pea seed germination.
The imbibition of pea seeds with hydrogen peroxide H₂O₂ increased the germination as well as the seedling growth, producing an invigoration of the seeds. We propose that H₂O₂ could acts as signaling molecule in the beginning of seed germination involving specific changes at proteomic, transcriptomic and hormonal levels. These findings have practical implication in the context of seed priming technologies to invigorate low vigour seeds.


Taxable or tax-exempt? When taxable financing is the better way.
This article has tried to demonstrate that (depending on loan terms and repayment provisions) a lower interest rate may not automatically guarantee a lower financing cost. And the flexibility of loan provisions (and conversely the restrictions placed on hospital management) must be carefully considered to ensure that the hospital can readily adapt to basic changes in the delivery systems and payment mechanisms of health care. This article has used both tax-exempt and taxable financings . Hospitals should undertake a thorough evaluation of all financing aspects and alternatives before commitments are made that may have far-reaching consequences on future hospital operations and hospital viability. There is a place both for tax-exempt and taxable financing--each institution must carefully evaluate which best meets its particular needs.


Protease-activated receptor-4 (PAR 4): a role as inhibitor of visceral pain and hypersensitivity.
Protease-activated receptor-4 (PAR(4)) belongs to the family of receptors activated by the proteolytic cleavage of their extracellular N-terminal domain and the subsequent binding of the newly released N-terminus. While largely expressed in the colon, the role of PAR(4) in gut functions has not been defined. We have investigated the effects of PAR(4) agonist on colonic sensations and sensory neuron signalling, and its role in visceral pain. We observed that a single administration of the PAR(4) agonist peptide (AYPGKF-NH(2)), but not the control peptide (YAPGKF-NH(2)) into the colon lumen of mice significantly reduced the visceromotor response to colorectal distension at different pressures of distension. Further, intracolonic administration of the PAR(4) agonist, but not the control peptide, was able to significantly inhibit PAR(2) agonist- and transcient receptor potential vanilloid-4 (TRPV4) agonist-induced allodynia and hyperalgesia in response to colorectal distension. Protease-activated receptor-4 was detected in sensory neurons projecting from the colon, and isolated from the dorsal root ganglia, where it co-expressed with PAR(2) and TRPV4. In total sensory neurons, PAR(4) agonist exposure inhibited free intracellular calcium mobilization induced by the pro-nociceptive agonists of PAR(2) and TRPV4. Finally, PAR(4)-deficient mice experienced increased pain behaviour in response to intracolonic administration of mustard oil, compared with wild-type littermates. These results show that PAR(4) agonists modulate colonic nociceptive response, inhibit colonic hypersensitivity and primary afferent responses to pro-nociceptive mediators. Endogenous activation of PAR(4) also plays a major role in controlling visceral pain. These results identify PAR(4) as a previously unknown modulator of visceral nociception.


Chronological View of Peak and Diphasic Dyskinesia, Wearing Off and Freezing of Gait in Parkinson's Disease.
Dyskinesia, wearing off (WO) and freezing of gait (FOG) are troublesome complications degrading quality of life in the course of Parkinson's disease (PD). This study evaluated the gross chronological trend of 4 motor complications - peak dose dyskinesia (PDSK), diphasic dyskinesia (DDSK), WO and FOG in a large PD population with stratification by age at disease onset according to the PD duration. The motor complications of 1212 Korean PD patients were analyzed using Kaplan-Meier curves and Cox proportional hazards models. PDSK and WO appeared first as motor complications and showed accelerated development around the 5 year-PD-duration, while DDSK showed a rather constant development over time and FOG developed around the 10 year-disease duration at an accelerated rate (p < 0.001). A younger age at PD onset predicted an earlier appearance of PDSK, DDSK and WO (p < 0.001), while an older age at onset (≥60 years) was a predictor for FOG (p = 0.014). Motor complications developed with a distinguishing inclination over the PD duration. This study provides insight into the chronological trend of motor complications in PD at a glance.


Association between psychosocial factors and co-morbid cigarette smoking and alcohol use in a population experiencing homelessness.
The prevalence of combustible cigarette smoking in populations experiencing homelessness in the United States is five times that of the general population. The psychosocial well-being of persons who smoke and experience homelessness is poorer if such persons also use alcohol heavily. The PTQ2 study was a randomized clinical trial among persons experiencing homelessness who were also current smokers and heavy alcohol consumers. Secondary data analysis of the PTQ2 baseline data was conducted to examine associations among psychosocial variables (anxiety, depression, hopelessness, social network size), heaviness of smoking (cigarettes/day) and alcohol consumption (drinking days/month), and duration and frequency of homelessness. Among the 420 participants, the majority were male (75%), black (70%) and non-Hispanic (94%) with a mean age of 46.6 years (SD = 11.6). Bivariate analyses show that heaviness of smoking was positively correlated with social network size (r = 0.16, p = .001). Heaviness of drinking was positively correlated with the MINI anxiety score (r = 0.13, p = .009) and marijuana use (median total number of drinks in past 30 days among those who used marijuana in past 30 days vs. did not use: 50 vs. 24, p < .0001), and associated with frequency of homelessness (median total number of drinks in past 30 days among those experiencing homelessness once vs. >1 time: 30 vs. 44, p = .022). The findings highlight the psychosocial factors that warrant consideration when addressing heavy smoking and alcohol consumption in persons experiencing homelessness.


Hemoperitoneum after percutaneous liver biopsy. Video-laparoscopic management.
Percutaneous liver biopsy is a safe procedure, with a low rate of major complications. Among these massive hemoperitoneum is the most life threatening, and its management sometimes leads to an emergency invasive surgical approach. The following case highlights the possible role of laparoscopy in diagnosis and treatment of this condition. In this patient a significant intraperitoneal bleeding developed from a liver lesion 48 hours after needle-biopsy. Video-laparoscopic exploration evidenced a grade III laceration of the right lobe, successfully managed with coagulation and apposition of an absorbable haemostatic gauze. Peritoneal toilette and multiple drains completed the procedure. No surgical complications developed and the patient was discharged on 5th post-operative day. Minimally invasive surgery has been, in this case, an adequate alternative for the treatment of this bleeding complication of liver biopsy, offering advantages in terms of low morbidity, quick recovery and satisfying cosmetic results. Laparoscopy is gaining a prominent role in penetrating liver trauma, whenever conservative or angiographic management fails, and should be considered as the first surgical attempt especially in patients with stable hemodynamics despite active intraperitoneal bleeding.


Opsonization of Cryptococcus neoformans by a family of isotype-switch variant antibodies specific for the capsular polysaccharide.
A family of immunoglobulin isotype-switch variants was isolated by sib selection from a murine hybridoma which produced an immunoglobulin G subclass 1 (IgG1) antibody specific for the capsular polysaccharide of Cryptococcus neoformans. Antibodies of the IgG1, IgG2a, and IgG2b isotypes had similar serotype specificity patterns in double immunodiffusion assays which used polysaccharides of the four cryptococcal serotypes as antigens. A quantitative difference in the ability of the isotypes to form a precipitate with the polysaccharide was observed in a double immunodiffusion assay and confirmed in a quantitative precipitin assay. The relative precipitating activity of the antibodies was IgG2a greater than IgG1 much greater than IgG2b. Analysis by enzyme-linked immunosorbent assay of the reactivity of the three isotypes with cryptococcal polysaccharide showed identical titers and slopes, suggesting that the variable region of the class-switch antibodies was unaltered. This system allowed us to examine the effect of the Fc portion of the antibody on opsonization of encapsulated cryptococci. Yeast cells were precoated with antibodies of each isotype and incubated with murine macrophages or cultured human monocytes. Antibodies of all three isotypes exhibited a dose-dependent opsonization for phagocytosis by both human and murine phagocytes. The relative opsonic activity of the antibodies was IgG2a greater than IgG1 greater than IgG2b.


No evaluative conditioning effects with briefly presented stimuli.
Evaluative conditioning (EC) changes the preference towards a formerly neutral stimulus (conditioned stimulus; CS), by pairing it with a valent stimulus (unconditioned stimulus; US), in the direction of the valence of the US. When the CS is presented suboptimally (i.e., too briefly to be consciously perceived), contingency awareness between CS and US can be ruled out. Hence, EC effects with suboptimally presented CSs would support theories claiming that contingency awareness is not necessary for EC effects to occur. Recent studies reported the absence of EC with briefly presented CSs when both CS and US were presented in the visual modality, even though the CSs were identified at above-chance levels. Challenging this finding, Heycke et al. (R Soc Open Sci 4(9):160935, 2017) found some evidence for an EC effect with briefly presented visual stimuli in a cross-modal paradigm with auditory USs, but that study did not assess CS visibility. The present study realized a close replication of this study, while deviated from it using different stimuli, introducing a brief practice phase, and adding a CS visibility check. Overall EC for briefly presented stimuli was absent, and results from the visibility check show that an EC effect with briefly presented CSs was only found, when the CSs were identified at above-chance levels.


Lack of evidence for a causal relationship between hypoxic-ischemic encephalopathy and subdural hemorrhage in fetal life, infancy, and early childhood.
It has been asserted that hypoxic-ischemic encephalopathy (HIE) with cerebral swelling in the absence of marked trauma may be responsible for subural hemorrhage in the young. As this may have considerable implications in determining both the mechanism of death and the degree of force required to cause injury in certain cases of inflicted head injury in infancy, clarification is required. A retrospective study of 82 fetuses, infants, and toddlers with proven HIE and no trauma was undertaken from forensic institutes in Australia, the United Kingdom, Germany, Denmark, and the United States. The age range was 35 weeks gestation to 3 years, with a male to female ratio of 2:1. All cases had histologically confirmed HIE. Causes of the hypoxic episodes were temporarily resuscitated sudden infant death syndrome with delayed death (N = 30), drowning (N = 12), accidental asphyxia (N = 10), intrauterine/delivery asphyxia (N = 8), congenital disease (N = 6), aspiration of food/gastric contents (N = 4), inflicted asphyxia (N = 3), epilepsy (N = 1), dehydration (N = 1), drug toxicity (N = 1), complications of prematurity (N = 1), and complications of anesthesia (N = 1). The initiating event was not determined in 4 instances. In no case was there macroscopic evidence of subdural hemorrhage. In this study no support could be given to the hypothesis that HIE in the young in the absence of trauma causes subdural hemorrhage.


[Postoperative rehabilitation in patients with hip fractures].
The purpose of the present study was to determine the variables associated with the length of hospital stay and to evaluate the ability to reach prefracture ADL-status after operation on patients with proximal fractures of femur. One hundred patients with cervical and trochanteric fracture were operated with internal fixation and endoprosthesis during a two year period. The type of surgical procedure selection was made by the surgeons own decision as part of treatment routine. The data were collected using a structured interview, participating observation and content analysis. The follow-up period was six months. The mean hospitalization time was 31.5 days, when seven patients with extremely long hospitalization, due to waiting for a long term care, were excluded. Stepwise regression analysis was used to determine variables associated with a longer hospital stay. Variables that related to poor prognosis were age, sex of patient, operation delay, weightbearing, medication, dizziness, status post paralysis and circumstances of dwelling. A significant difference was found between internal fixation and endoprosthesis at patient with cervical fracture of femur regarding to the length of hospital stay and ability to reach prefracture ADL-status in two weeks after operation. Results of this study showed, that the objective, to discharge patients in two or three weeks, was not achieved. This study also showed, that all patients did not regain the prefracture ADL-status during a follow-up period. It is important to assure the effectiveness of treatment after discharge from hospital in primary care and to prevent proximal fractures of femur in the elderly.


Lifestyle weight-loss intervention may attenuate methylation aging: the CENTRAL MRI randomized controlled trial.
DNA methylation age (mAge), a methylation biomarker for the aging process, might serve as a more accurate predictor of morbidity and aging status than chronological age. We evaluated the role of multiple factors, including fat deposition, cardiometabolic risk factors and lifestyle weight-loss intervention, on the deviation of mAge from chronological age (mAge deviation) or 18-month change in mAge (∆mAge). In this sub-study of the CENTRAL magnetic resonance imaging weight-loss trial, we evaluated mAge by a validated 240-CpG-based prediction formula at baseline and after 18-month intervention of either low fat (LF) or mediterranean/low carbohydrate (MED/LC) diets. Among 120 CENTRAL participants with abdominal obesity or dyslipidemia, mAge (mean ± SD: 60.3 ± 7.5 years) was higher than the chronological age (48.6 ± 9.3 years) but strongly correlated (r = 0.93; p = 3.1 × 10-53). Participants in the lowest tertile of mAge deviation from their chronological age had significantly lower waist-circumference, visceral adipose tissue, intrahepatic fat (IHF) content, fasting-glucose and HOMA-IR, as compared with participants in the highest sex-specific residual tertile (p < 0.05 for all). IHF% remained associated with greater mAge deviation after further adjustments (β = 0.23; p = 0.02). After 18-month weight-loss lifestyle intervention, mAge remained significantly correlated with chronological age (r = 0.94, p = 1.5 × 10-55). mAging occurred, with no difference between lifestyle intervention groups (∆ = 0.9 ± 1.9 years in MED/LC vs. ∆ = 1.3 ± 1.9 years in LF; p = 0.2); however, we observed a mAging attenuation in successful weight losers (> 5% weight loss) vs. weight-loss failures ( ∆ = 0.6 years vs. ∆ = 1.1 years; p = 0.04), and in participants who completed the trial with healthy liver fat content (< 5% IHF) vs. participants with fatty liver (∆ = 0.6 years vs. ∆ = 1.8 years; p = 0.003). Overall, 18 months of weight-loss lifestyle intervention attenuated the mAging of the men, mainly the older, by 7.1 months than the expected (p < 0.05). Lifestyle weight-loss intervention may attenuate mAging. Deviation of mAge from chronological age might be related to body fat distribution and glycemic control and could indicate biological age, health status and the risk for premature cardiometabolic diseases. ClinicalTrials.gov NCT01530724. Registered 10 February 2012, https://clinicaltrials.gov/ct2/show/study/NCT01530724 .


Mutations in the gene encoding thyroid transcription factor-1 (TTF-1) are not a frequent cause of congenital hypothyroidism (CH) with thyroid dysgenesis.
Permanent congenital hypothyroidism (CH) has an incidence of 1/3000-4000 newborns and is among the most frequent cause of mental retardation and neurological alterations in children. In 80% to 85% of cases CH is associated with thyroid dysgenesis. A group of 61 patients with CH (22 with agenesis, 18 with ectopy, 1 with hypoplasia, and 20 cases with CH without thyroid enlargement but not further characterized) and 30 normal subjects were examined for the presence of mutations in the gene encoding the thyroid transcription factor 1 (TTF-1). The coding-region of the TTF-1 gene was analyzed in all cases by the single stranded conformational polymorphism (SSCP) and no mutations were detected. Direct sequencing also carried out in patients with thyroid agenesis confirmed the absence of mutations or polymorphisms in the TTF-1 gene. The absence of mutations in the TTF-1 gene in our samples indicates that the mutations in the TTF-1 gene are not a frequent cause of CH.


[Pharmacology in the twentieth century: the science of drugs through the analysis of Goodman and Gilman's textbook].
This article analyzes the presentation of pharmacology as a science in the textbook by Louis Goodman and Alfred Gilman, updated and reprinted many times between 1941 and 2006. In the first editions, pharmacology was characterized as the science of drugs and related to other areas of knowledge; the history of drug development, the role of this science in its social context and its relationship with industry were stressed. In the following editions, these aspects were minimized, almost disappearing in the 11th (2006). The treatment of historical aspects may contribute to understanding the development of pharmacology, as well as the material on relationships with industry and society is important when reflecting on the criteria for using drugs.


Case 291: Amyloid-associated Cystic Lung Disease and Coexistent Mucosa-associated Lymphoid Tissue Lymphoma.
History A 46-year-old woman with known mixed connective tissue disease with clinical features of scleroderma and polymyositis and who was not on specific medications was referred to our institution to assess for interstitial lung disease due to her predisposing condition. She was a nonsmoker, had no respiratory symptoms, and enjoyed good exercise tolerance. She did not have any cutaneous lesions or renal disease. There was no family history of pulmonary or systemic disease. Her routine blood test results revealed a white blood cell count of 4.6 × 109/L (normal range, [4.4-10.1] × 109/L), a hemoglobin level of 7.76 mmol/L (normal range, 7.26-9.18 mmol/L), a platelet count of 189 × 109/L (normal range, [170-380] × 109/L), a bilirubin level of 8 mmol/L (normal range, <19 mmol/L), and a creatinine level of 63 mmol/L (normal range, 45-82 mmol/L), all within normal limits. Lung function tests at presentation yielded normal results, with a diffusing capacity for carbon monoxide of 95% and a forced vital capacity of 2.29 (98% predicted value). However, this patient had an elevated serum globulin level of 47 g/L (normal range, 26-32 g/L) and an erythrocyte sedimentation rate of 36 mm/h (normal range, 0-20 mm/h), while C-reactive protein level was normal at less than 0.35 mg/dL. She was seropositive for antinuclear (titer >1/720), anti-Ro, anti-La, and anti-extractable nuclear antigen antibodies. Chest radiography and CT were performed at presentation and 14-year follow-up. PET/CT was performed at 7- and 13-year follow-up. Throughout this 14-year follow-up period, she remained completely free of respiratory symptoms and continued to go for a brisk walk every day. At 14-year follow-up, there was no substantial change in serum laboratory values, but a lung function test revealed her diffusing capacity for carbon monoxide had decreased to 52%, while her forced vital capacity remained good at 95%; these findings were suggestive of interval development of restrictive lung function.


Regulation of cell volume and diffusion of intracellular water in salivary acinar cells.
The regulation of acinar cell volume and the properties of intracellular water were investigated in perfused rat mandibular salivary glands by proton nuclear magnetic resonance (NMR) spectroscopy. Using an inversion-recovery pulse sequence, and an extracellular relaxation reagent (10 mM Gd-DTPA) to suppress the proton NMR signal from extracellular water, acinar cell volume (intracellular water content) in unstimulated glands was shown to depend upon Cl- uptake by basolateral Na+-K+-2Cl- cotransport. Muscarinic and beta-adrenoceptor stimulation induced shrinkage and swelling respectively. In pulsed-field-gradient NMR experiments, the diffusion coefficient of intracellular water was found to be more than an order of magnitude smaller than that of extracellular water. Using this intrinsic difference in diffusivity between the two compartments, cell volume regulation was investigated in intact, perfused glands in the absence of relaxation reagents. Using both NMR techniques, acinar cells in perfused glands were observed to behave like simple osmometers in response to anisosmotic media, and did not show the volume regulatory responses described in dissociated acinar cells.


[Injuries and damage caused by excessive stress in classical ballet].
Typical injuries of highly professional classical ballet dancers were evaluated in 108 members of German opera companies. We demonstrated the predominance of overuse-syndromes to acute injuries related to the excessive training-extends. Disorders of the feet, particularly tendinitis followed by low-back pain, chondromalacia patellae, jumpers knee, shin splints and muscle strains are most frequent. Considerable time often elapsed before diagnosing was made because complaints were ignored by dancers. Our inquiry includes range of motion of the spine and the extremities, serial x-rays and a systematic review of ballet-related injuries, training-programs and techniques.


Development and evaluation of digitally processed Z-contrast imaging: a technological advance in medical imaging.
For the first time in the field of medical imaging, harmonious use of Z-contrast imaging and digital image processing was developed as an analytical imaging tool and demonstrated in studying human and rabbit spermatozoa. The biological information generated is unique to the science of medical imaging. The versatility of its applications is wide as this advance in imaging technology can be applied to any area of medicine involving tissue analysis. Tissue analysis plays a vital role in both medical research and diagnostic patient care. Imaging in the Z-contrast mode of the scanning-transmission electron microscope affords biologists the capability to image tissue in its natural state such that heavy metal fixatives and stains are not used. The digitally processed Z-contrast image is not only devoid of artifacts caused by fluctuating mass-density, topography variations, and the addition of heavy metal contrast agents but also offers a biological blueprint of the atomic weight distribution in the tissue. The varying gray level intensities assigned to each pixel in the resulting image are specific to the average atomic weight differences inherent in the tissue. The advent of complementary Z-contrast imaging and digital image processing and their concomitant research possibilities offers areas of medical care and medical research an invaluable imaging tool.


Transgenic animal models that might be useful in identifying unsuspected oncogenic factors in tumour cell substrates.
The use of alternative short term models for the assessment of pharmaceutical carcinogenicity potential is expanding and evolving. Several mouse models of accelerated carcinogenesis have gained user confidence and are being applied to product development decision-making. These models have been highlighted as part of a consortium effort organized under ILSI to further evaluate their strengths and limitations compared to the standard two-years, two species cancer bioassay. Examples of trends that are developing in our understanding of applicability of these models to chemical carcinogenesis have been presented but a more comprehensive review of all the currently available data has been avoided. Such a review would be soon outdated as the anticipated data from the ILSI consortium studies will soon become available and greatly further impact our present appreciation of the capabilities of these models. As strengths and limitations of those models are being elucidated, mechanistic understanding of the models is expanding. In addition to those reviewed briefly in this paper, numerous other transgenic models with micro-injected oncogenes and disrupted tumour suppressor genes have demonstrated enhanced propensity for developing cancer. Critical experiments can be designed to test, conceptually, for the ability of any of these models to detect tumorigenic potential for a given dose of adventitious agent, or residual DNA sequence. The choice of model and of DNA sequence or adventitious agent to begin this evaluation must be carefully considered. From such data, risk may be better identified or prioritized, but such approaches may not be practical as general routine screens of finished vaccine product with unknown residual DNA sequence or adventitious agents.


Electrophoresis of proteins and protein-protein complexes in native polyacrylamide gels using a horizontal gel apparatus.
Electrophoresis of proteins and protein-protein complexes in polyacrylamide gels under native conditions using a horizontal gel apparatus is described. The advantage of this system is that it permits the detection of both negatively and positively charged proteins as well as protein-protein complexes in the same gel. During electrophoresis, a continuous gel sandwiched between two glass plates is placed horizontally on the platform and submerged in a reservoir buffer. The sample wells are made along the center of the gel, allowing positively and negatively charged proteins to migrate toward the cathode and anode, respectively. Several proteins with varying molecular weights and isoelectric point (pI) values and pairs of proteins capable of forming protein-protein complexes were chosen as model systems to illustrate the methodology. The effects of several parameters on the performance of the gel system including protein molecular weight, pI, and gel concentration were also examined and the results obtained by this method are comparable to those obtained by the vertical system. Following electrophoresis, both negatively and positively charged proteins as well as protein-protein complexes can be transferred by electroblotting onto polyvinylidene difluoride membranes for further analyses.


UTP inhibits Na+ absorption in wild-type and DeltaF508 CFTR-expressing human bronchial epithelia.
Ca2+-mediated agonists, including UTP, are being developed for therapeutic use in cystic fibrosis (CF) based on their ability to modulate alternative Cl- conductances. As CF is also characterized by hyperabsorption of Na+, we determined the effect of mucosal UTP on transepithelial Na+ transport in primary cultures of human bronchial epithelia (HBE). In symmetrical NaCl, UTP induced an initial increase in short-circuit current (Isc) followed by a sustained inhibition. To differentiate between effects on Na+ absorption and Cl- secretion, Isc was measured in the absence of mucosal and serosal Cl- (INa). Again, mucosal UTP induced an initial increase and then a sustained decrease that reduced amiloride-sensitive INa by 73%. The Ca2+-dependent agonists histamine, bradykinin, serosal UTP, and thapsigargin similarly induced sustained inhibition (62-84%) of INa. Mucosal UTP induced similar sustained inhibition (half-maximal inhibitory concentration 296 nM) of INa in primary cultures of human CF airway homozygous for the DeltaF508 mutation. BAPTA-AM blunted UTP-dependent inhibition of INa, but inhibitors of protein kinase C (PKC) and phospholipase A2 had no effect. Indeed, direct activation of PKC by phorbol 12-myristate 13-acetate failed to inhibit Na+ absorption. Apyrase, a tri- and diphosphatase, did not reverse inhibitory effects of UTP on INa, suggesting a long-term inhibitory effect of UTP that is independent of receptor occupancy. After establishment of a mucosa-to-serosa K+ concentration gradient and permeabilization of the mucosal membrane with nystatin, mucosal UTP induced an initial increase in K+ current followed by a sustained inhibition. We conclude that increasing cellular Ca2+ induces a long-term inhibition of transepithelial Na+ transport across normal and CF HBE at least partly due to downregulation of a basolateral membrane K+ conductance. Thus UTP may have a dual therapeutic effect in CF airway: 1) stimulation of a Cl- secretory response and 2) inhibition of Na+ transport.


The Enteric Nervous System and Its Emerging Role as a Therapeutic Target.
The gastrointestinal (GI) tract is innervated by the enteric nervous system (ENS), an extensive neuronal network that traverses along its walls. Due to local reflex circuits, the ENS is capable of functioning with and without input from the central nervous system. The functions of the ENS range from the propulsion of food to nutrient handling, blood flow regulation, and immunological defense. Records of it first being studied emerged in the early 19th century when the submucosal and myenteric plexuses were discovered. This was followed by extensive research and further delineation of its development, anatomy, and function during the next two centuries. The morbidity and mortality associated with the underdevelopment, infection, or inflammation of the ENS highlight its importance and the need for us to completely understand its normal function. This review will provide a general overview of the ENS to date and connect specific GI diseases including short bowel syndrome with neuronal pathophysiology and current therapies. Exciting opportunities in which the ENS could be used as a therapeutic target for common GI diseases will also be highlighted, as the further unlocking of such mechanisms could open the door to more therapy-related advances and ultimately change our treatment approach.


Reliability and Validity of Commercially Available Wearable Devices for Measuring Steps, Energy Expenditure, and Heart Rate: Systematic Review.
Consumer-wearable activity trackers are small electronic devices that record fitness and health-related measures. The purpose of this systematic review was to examine the validity and reliability of commercial wearables in measuring step count, heart rate, and energy expenditure. We identified devices to be included in the review. Database searches were conducted in PubMed, Embase, and SPORTDiscus, and only articles published in the English language up to May 2019 were considered. Studies were excluded if they did not identify the device used and if they did not examine the validity or reliability of the device. Studies involving the general population and all special populations were included. We operationalized validity as criterion validity (as compared with other measures) and construct validity (degree to which the device is measuring what it claims). Reliability measures focused on intradevice and interdevice reliability. We included 158 publications examining nine different commercial wearable device brands. Fitbit was by far the most studied brand. In laboratory-based settings, Fitbit, Apple Watch, and Samsung appeared to measure steps accurately. Heart rate measurement was more variable, with Apple Watch and Garmin being the most accurate and Fitbit tending toward underestimation. For energy expenditure, no brand was accurate. We also examined validity between devices within a specific brand. Commercial wearable devices are accurate for measuring steps and heart rate in laboratory-based settings, but this varies by the manufacturer and device type. Devices are constantly being upgraded and redesigned to new models, suggesting the need for more current reviews and research.


Aurora-A expression is independently associated with chromosomal instability in colorectal cancer.
AURKA (the official symbol for Aurora-A, STK15, or BTAK) regulates the function of centrosomes, spindles, and kinetochores for proper mitotic progression. AURKA overexpression is observed in various cancers including colon cancer, and a link between AURKA and chromosomal instability (CIN) has been proposed. However, no study has comprehensively examined AURKA expression in relation to CIN or prognosis using a large number of tumors. Using 517 colorectal cancers in two prospective cohort studies, we detected AURKA overexpression (by immunohistochemistry) in 98 tumors (19%). We assessed other molecular events including loss of heterozygosity (LOH) in 2p, 5q, 17q, and 18q, the CpG island methylation phenotype (CIMP), and microsatellite instability (MSI). Prognostic significance of AURKA was evaluated by Cox regression and Kaplan-Meier method. In both univariate and multivariate logistic regressions, AURKA overexpression was significantly associated with CIN (defined as the presence of LOH in any of the chromosomal segments; multivariate odds ratio, 2.97; 95% confidence interval, 1.40-6.29; P = .0045). In multivariate analysis, AURKA was associated with cyclin D1 expression (P = .010) and inversely with PIK3CA mutation (P=.014), fatty acid synthase expression (P=.028), and family history of colorectal cancer (P = .050), but not with sex, age, body mass index, tumor location, stage, CIMP, MSI, KRAS, BRAF, BMI, LINE-1 hypomethylation, p53, p21, beta-catenin, or cyclooxygenase 2. AURKA was not significantly associated with clinical outcome or survival. In conclusion, AURKA overexpression is independently associated with CIN in colorectal cancer, supporting a potential role of Aurora kinase-A in colorectal carcinogenesis through genomic instability (rather than epigenomic instability).


An integrated inundation model for highly developed urban areas.
A numerical model is developed in this study with various components for simulating the complex flow phenomena in urban drainage basins. The model integrates the HEC-1 model, a 1-D dynamic channel-flow model, a 2-D non-inertia overland-flow model and the SWMM model to reflect the hydraulic processes in areas with different characteristics. The inundation of underground infrastructure during flood is also considered in the model. The typhoon Nari event in 2001, which resulted in severe flood in downtown Taipei, is simulated by the model. The result is compared with the survey records of flooded areas, which reveals the storage effect of underground infrastrucures is significant to the simulation results of highly developed urban areas.


Gut dysbiosis in Huntington's disease: associations among gut microbiota, cognitive performance and clinical outcomes.
Huntington's disease is characterized by a triad of motor, cognitive and psychiatric impairments, as well as unintended weight loss. Although much of the research has focused on cognitive, motor and psychiatric symptoms, the extent of peripheral pathology and the relationship between these factors, and the core symptoms of Huntington's disease, are relatively unknown. Gut microbiota are key modulators of communication between the brain and gut, and alterations in microbiota composition (dysbiosis) can negatively affect cognition, behaviour and affective function, and may be implicated in disease progression. Furthermore, gut dysbiosis was recently reported in Huntington's disease transgenic mice. Our main objective was to characterize the gut microbiome in people with Huntington's disease and determine whether the composition of gut microbiota are significantly related to clinical indicators of disease progression. We compared 42 Huntington's disease gene expansion carriers, including 19 people who were diagnosed with Huntington's disease (Total Functional Capacity > 6) and 23 in the premanifest stage, with 36 age- and gender-matched healthy controls. Participants were characterized clinically using a battery of cognitive tests and using results from 16S V3 to V4 rRNA sequencing of faecal samples to characterize the gut microbiome. For gut microbiome measures, we found significant differences in the microbial communities (beta diversity) based on unweighted UniFrac distance (P = 0.001), as well as significantly lower alpha diversity (species richness and evenness) between our combined Huntington's disease gene expansion carrier group and healthy controls (P = 0.001). We also found major shifts in the microbial community structure at Phylum and Family levels, and identified functional pathways and enzymes affected in our Huntington's disease gene expansion carrier group. Within the Huntington's disease gene expansion carrier group, we also discovered associations among gut bacteria, cognitive performance and clinical outcomes. Overall, our findings suggest an altered gut microbiome in Huntington's disease gene expansion carriers. These results highlight the importance of gut biomarkers and raise interesting questions regarding the role of the gut in Huntington's disease, and whether it may be a potential target for future therapeutic intervention.


Similar regulation of human inducible nitric-oxide synthase expression by different isoforms of the RNA-binding protein AUF1.
The ARE/poly-(U) binding factor 1 (AUF1), a protein family consisting of four isoforms, is believed to mediate mRNA degradation by binding to AU-rich elements (ARE). However, evidence exists that individual AUF1 isoforms may stabilize ARE-containing mRNAs. The 3'-untranslated region of the human inducible nitric-oxide synthase (iNOS) contains five AREs, which promote RNA degradation. We have recently shown that the RNA-binding protein KSRP is critically involved in the decay of the iNOS mRNA. In this study we examined the effects of the individual AUF1 isoforms on iNOS expression. Overexpression of each AUF1 isoform reduces iNOS expression on mRNA and protein levels to the same extent by modulation of mRNA stability. Accordingly, knockdown of all or individual AUF1 isoforms by an RNA interference approach enhances iNOS expression. The AUF1 effect on iNOS expression is dependent on the iNOS 3'-untranslated region sequence, as demonstrated in transfection experiments with a reporter mRNA. Binding studies showed that all AUF1 isoforms interact with the same AU-rich region in the iNOS-3'-untranslated region. Cytokine stimulation altered intracellular AUF1 binding activities. These data demonstrate that AUF1 is an important factor that promotes iNOS mRNA degradation. Furthermore, all individual AUF1 isoforms act in a similar manner.


The antigen-binding fragment of human gamma immunoglobulin prevents amyloid β-peptide folding into β-sheet to form oligomers.
The amyloid beta-peptide (Aβ) plays a leading role in Alzheimer's disease (AD) physiopathology. Even though monomeric forms of Aβ are harmless to cells, Aβ can aggregate into β-sheet oligomers and fibrils, which are both neurotoxic. Therefore, one of the main therapeutic approaches to cure or delay AD onset and progression is targeting Aβ aggregation. In the present study, we show that a pool of human gamma immunoglobulins (IgG) protected cortical neurons from the challenge with Aβ oligomers, as assayed by MTT reduction, caspase-3 activation and cytoskeleton integrity. In addition, we report the inhibitory effect of IgG on Aβ aggregation, as shown by Thioflavin T assay, size exclusion chromatography and atomic force microscopy. Similar results were obtained with Palivizumab, a human anti-sincitial virus antibody. In order to dissect the important domains, we cleaved the pool of human IgG with papain to obtain Fab and Fc fragments. Using these cleaved fragments, we functionally identified Fab as the immunoglobulin fragment inhibiting Aβ aggregation, a result that was further confirmed by an in silico structural model. Interestingly, bioinformatic tools show a highly conserved structure able to bind amyloid in the Fab region. Overall, our data strongly support the inhibitory effect of human IgG on Aβ aggregation and its neuroprotective role.


Ectothermy and endothermy: evolutionary perspectives of thermoprotection by HSPs.
Living organisms respond to heat exposure by selectively expressing heat shock proteins (HSPs). Accumulation of HSPs confers thermotolerance in cell cultures and in ectotherms and is an important component of the heat shock response. This response, however, has not been directly examined in relation to different ;thermal states', namely ectothermy vs endothermy. By using avian development as a model system for transition from ectothermy to endothermy, we show that, in contrast to the ectothermic state, in the endothermic state the organism is more resistant to heat but relies less on HSPs as a first-line thermoprotective mechanism. Moreover, intraspecific, real-time, in vivo measurements in genetically diverse fowl strains relate improvement of thermoresistance in endotherms to improved body temperature (Tb) regulation, with a concomitant delay in the expression of HSPs. The time course of this delay and the Tb at which it occurs imply that the ontogenetic and evolutionary pathways leading to improved thermoresistance may have followed two, apparently non-related, parallel routes--cellular and peripheral (non-cellular). In search of other cellular components that differentially participate in the heat shock response, we revealed a significant expression of fatty acid synthase (FAS) in heat-exposed endotherms but not in ectotherms.


Treatment patterns and outcomes among patients with high-intermediate/high-risk diffuse large B-cell lymphoma in the USA.
Objective Clinical trials have demonstrated improved outcomes for patients with diffuse large B-cell lymphoma (DLBCL) treated with regimens containing rituximab, but variations in real-world treatment patterns and outcomes have not been studied. The objective of this study was to characterize real-world treatment patterns and outcomes in higher risk DLBCL patients. Methods Patients with an International Prognostic Index score (IPI) ≥3 who received initial rituximab-based therapy from 2005 to 2012 were identified via electronic medical record data from the International Oncology Network. Initial therapy, rates of complete response (CR), post-CR treatments, and outcomes were evaluated. Results Among 257 eligible patients, 75% achieved a CR: 77% (158/206) of patients receiving R-CHOP compared to 71% (36/51) of patients receiving initial therapies other than R-CHOP. Post-CR, 78% of the 158 patients receiving R-CHOP underwent active surveillance; 13% received maintenance rituximab-based treatment; and 6% received radiation therapy. Relapse rates among patients receiving maintenance rituximab, active surveillance, and radiation therapy were 28% (6/21), 19% (24/124), and 0%, (0/10), respectively (P = 0.08). Discussion This study found that active surveillance continues to be the most commonly utilized treatment regimen among DLBCL patients with an IPI score ≥3 achieving a CR on first-line R-CHOP. Other approaches aimed at increasing the time to relapse are being utilized as well, but the clinical benefit of these modalities is unclear. Conclusion Results of this study are consistent with the results from clinical trials and suggest the need for further evaluation of maintenance therapy options for patients at higher risk of relapse.


Biochemical and metabolic mechanisms by which dietary whey protein may combat obesity and Type 2 diabetes.
Consumption of milk and dairy products has been associated with reduced risk of metabolic disorders and cardiovascular disease. Milk contains two primary sources of protein, casein (80%) and whey (20%). Recently, the beneficial physiological effects of whey protein on the control of food intake and glucose metabolism have been reported. Studies have shown an insulinotropic and glucose-lowering properties of whey protein in healthy and Type 2 diabetes subjects. Whey protein seems to induce these effects via bioactive peptides and amino acids generated during its gastrointestinal digestion. These amino acids and peptides stimulate the release of several gut hormones, such as cholecystokinin, peptide YY and the incretins gastric inhibitory peptide and glucagon-like peptide 1 that potentiate insulin secretion from β-cells and are associated with regulation of food intake. The bioactive peptides generated from whey protein may also serve as endogenous inhibitors of dipeptidyl peptidase-4 (DPP-4) in the proximal gut, preventing incretin degradation. Indeed, recently, DPP-4 inhibitors were identified in whey protein hydrolysates. This review will focus on the emerging properties of whey protein and its potential clinical application for obesity and Type 2 diabetes.


Learning Brain Functional Networks With Latent Temporal Dependency for MCI Identification.
Resting-state functional magnetic resonance imaging (rs-fMRI) has become a popular non-invasive way of diagnosing neurological disorders or their early stages by probing functional connectivity between different brain regions of interest (ROIs) across subjects. In the past decades, researchers have proposed many methods to estimate brain functional networks (BFNs) based on blood-oxygen-level-dependent (BOLD) signals captured by rs-fMRI. However, most of the existing methods estimate BFNs under the assumption that signals are independently sampled, which ignores the temporal dependency and sequential order of different time points (or volumes). To address this problem, in this paper, we first propose a novel BFN estimation model by introducing a latent variable to control the sequence of volumes for encoding the temporal dependency and sequential information of signals into the estimated BFNs. Then, we develop an efficient learning algorithm to solve the proposed model by the alternating optimization scheme. To verify the effectiveness of the proposed method, the estimated BFNs are used to identify subjects with mild cognitive impairment (MCIs) from normal controls (NCs). Experimental results show that our method outperforms the baseline methods in the terms of classification performance.


Thyroidectomy blocks stress-induced prolactin rise in rats: role of the central serotonergic system.
Thyroidectomized (TX) adult Wistar male rats and their sham-operated controls were submitted to immobilization stress during forty minutes. Thyroidectomy partially blocks stress-induced prolactin (PRL) secretion. Previous administration of MK 212, a serotonin agonist, reverts this picture. The effect of MK 212 is specifically due to its interaction with 5HT2 receptors, since the injection of LY 53857, a selective blocker of these receptors, 30 min before MK 212, prevents the effect of this serotonin agonist. LY 53857, injected alone, yields a partial blockade of PRL secretion during stress in sham-operated rats. TX rats receiving LY 53857 or saline have comparable low values of plasma PRL during stress. It is suggested that thyroidectomy disrupts the functional integrity of the central serotonergic pathways involved in the stress-induced PRL rise.


The mediating role of psychological capital in the relationship between job stress and professional identity in Chinese medical interns.
Adaption to clinical work during the internship can induce several stressors among medical students, especially in the context of the coronavirus disease 2019 (COVID-19) pandemic. Particularly, job stress could be linked to the development of psychological traits and the formation of the professional identity of medical interns. This study aimed to explore the relationship between job stress, psychological capital, and professional identity through a mediation analysis of Chinese medical interns. A descriptive cross-sectional study was conducted in 30 hospitals and clinics in China from June 2021 to March 2022. A total of 665 medical interns filled out questionnaires related to demographic questions, psychological capital, job stress, and professional identity. Data analysis was executed using the IBM SPSS version 22.0 software and its add-in PROCESS Windows version 4.0. The findings indicated a statistically significant mediating effect of psychological capital between job stress and professional identity. Job stress and job stress combined with psychological capital accounted for 5.3% and 37.9%, respectively, of the variance in professional identity. The bootstrapping method corroborated the significance of the indirect effect of job stress through psychological capital (95% bootstrap CI = -4.7921, -2.4345). The current findings underscore the need for increased attention on improving the psychological capital of medical interns.


Excitatory but not inhibitory synaptic transmission is reduced in lethargic (Cacnb4(lh)) and tottering (Cacna1atg) mouse thalami.
Excitatory but not inhibitory synaptic transmission is reduced in lethargic (Cacnb4(lh)) and tottering (Cacna1atg) mouse thalami. Recent studies of the homozygous tottering (Cacna1atg) and lethargic mouse (Cacnb4(lh)) models of absence seizures have identified mutations in the genes encoding the alpha1A and beta4 subunits, respectively, of voltage-gated Ca2+ channels (VGCCs). beta subunits normally regulate Ca2+ currents via a direct interaction with alpha1 (pore-forming) subunits of VGCCs, and VGCCs are known to play a significant role in controlling the release of transmitter from presynaptic nerve terminals in the CNS. Because the gene mutation in Cacnb4(lh) homozygotes results in loss of the beta4 subunit's binding site for alpha1 subunits, we hypothesized that synaptic transmission would be altered in the CNS of Cacnb4(lh) homozygotes. We tested this hypothesis by using whole cell recordings of single cells in an in vitro slice preparation to investigate synaptic transmission in one of the critical neuronal populations that generate seizure activity in this strain, the somatosensory thalamus. The primary finding reported here is the observation of a significant decrease in glutamatergic synaptic transmission mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA receptors in somatosensory thalamic neurons of Cacnb4(lh) homozygotes compared with matched, nonepileptic mice. In contrast, there was no significant decrease in GABAergic transmission in Cacnb4(lh) homozygotes nor was there any difference in effects mediated by presynaptic GABAB receptors. We found a similar decrease in glutamatergic but not GABAergic responses in Cacna1atg homozygotes, suggesting that the independent mutations in the two strains each affected P/Q channel function by causing defective neurotransmitter release specific to glutamatergic synapses in the somatosensory thalamus. This may be an important factor underlying the generation of seizures in these models.


Delay of cataract development in the Shumiya cataract rat by the administration of drinking water containing high concentration of magnesium ion.
We discovered that the cataract development in the Shumiya cataract rat (SCR) can be prevented by the administration of deep-sea drinking water (DDW). A standard diet based on the American Institute of Nutrition guidelines (AIN-76) and DDW containing a high mineral concentration such as low, medium and high Mg2+ content (50, 200 and 1000 mg of Mg2+/l, respectively) were used in this study. SCRs were freely fed with combinations of the standard diet and purified water or DDW during 5-15 weeks of age. The opacities of SCR lenses were documented by anterior eye segment analysis system EAS-1000. The onset of opacification of cataractous SCR lenses administered a combination of standard diet and purified water started at 11 weeks of age, and mature cataracts had formed at 13 weeks of age. However, the supplementation of Mg2+ by administration with medium DDW showed the greatest effect of delay of cataract onset in SCR. In addition, even cataractous SCR lenses at 14 weeks of age showed differences in opacity level. The opacification and Ca2+ of the lenses in cataractous SCR administered medium DDW were lower than those administered purified water. In conclusion, the present study demonstrates that administration of DDW potently delays cataract development in SCR, and this may be caused by inhibiting the increase in Ca2+ levels in the lens.


GLYX-13 Ameliorates Schizophrenia-Like Phenotype Induced by MK-801 in Mice: Role of Hippocampal NR2B and DISC1.
Background: Evidence supports that the hypofunction of N-methyl-D-aspartate receptor (NMDAR) and downregulation of disrupted-in-schizophrenia 1 (DISC1) contribute to the pathophysiology of schizophrenia. N-Methyl D-aspartate receptor subtype 2B (NR2B)-containing NMDAR are associated with cognitive dysfunction in schizophrenia. GLYX-13 is an NMDAR glycine-site functional partial agonist and cognitive enhancer that does not induce psychotomimetic side effects. However, it remains unclear whether NR2B plays a critical role in the GLYX-13-induced alleviation of schizophrenia-like behaviors in mice. Methods: The effect of GLYX-13 was tested by observing changes in locomotor activity, novel object recognition ability, and prepulse inhibition (PPI) induced by dizocilpine (known as MK-801) in mice. Lentivirus-mediated NR2B knockdown in the hippocampus was assessed to confirm the role of NR2B in GLYX-13 pathophysiology, using Western blots and immunohistochemistry. Results: The systemic administration of GLYX-13 (0.5 and 1 mg/kg, i.p.) ameliorates MK-801 (0.5 mg/kg, i.p.)-induced hyperlocomotion, deficits in memory, and PPI in mice. Additionally, GLYX-13 normalized the MK-801-induced alterations in signaling molecules, including NR2B and DISC1 in the hippocampus. Furthermore, we found that NR2B knockdown produced memory and PPI deficits without any changes in locomotor activity. Notably, DISC1 levels significantly decreased by NR2B knockdown. However, the effective dose of GLYX-13 did not alleviate the memory and PPI dysfunctions or downregulation of DISC1 induced by NR2B knockdown. Conclusion: Our results suggest GLYX-13 as a candidate for schizophrenia treatment, and NR2B and DISC1 in the hippocampus may account for the molecular mechanisms of GLYX-13.


Enzalutamide and analytical interferences in digoxin assays.
Objective: We report two cases of elevated digoxin plasma levels in patients receiving enzalutamide. Cases reported: The first patient, an 84-year-old male treated with enzalutamide, was hospitalized due to deterioration in his general state. Atrial fibrillation was discovered and treatment with digoxin was initiated. Supratherapeutic digoxin concentrations (4 µg/L and 3.5 µg/L 3 days later) led to treatment being stopped despite the lack of clinical or biological signs of overdose. The second patient, an 84-year-old male treated with digoxin and enzalutamide, was hospitalized for the same reasons. Digoxin concentration upon admission was 2.8 μg/L. Despite stopping treatment, digoxin blood levels were observed to have increased on D3 and D7 following admission (3 and 3.6 μg/L, respectively). However, no clinical or biological findings indicated an overdose. Blood samples were sent to the Pharmacology and Toxicology Laboratory for analysis. Methods: The second patient's digoxin plasma level was determined using the chemiluminescent microparticle immunoassay (CMIA®, Abbott, Illinois) method. Enzalutamide levels were determined using HPLC-UV/DAD method. An interference study was performed using different assay methods by adding enzalutamide to control plasma at various concentrations from a Xtandi® (40mg) capsule. Results: Plasma concentration of digoxin at D7 for patient 2 was identical in both laboratories (3.5 vs. 3.6 µg/L). Enzalutamide was found in the patient's plasma (12,5 mg/L). Adding 4, 10, 20, and 40 mg/L of enzalutamide to the untreated plasma showed that the plasma concentration of digoxin was positive (from 0.35 to 3.69 µg/L) using the CMIA method. Conclusions: Our results highlight the analytical interferences of enzalutamide with digoxin assays using the CMIA method.


How to recognize adolescents at risk for HIV infection.
HIV infection is a growing problem for primary care physicians in that the coming of adolescents to clinics for primary care may not clearly demark members of a high-risk group. Therefore, clinicians need to be familiar with the risk categories and question the patients as to high-risk activities in order to determine their risk for HIV infection. Adolescents may be at a higher risk for HIV, but may not bear manifestations of infection with HIV infection until later. Therefore, it would behoove clinicians to establish the serologic status of adolescents at risk in a timely fashion in order to offer counseling and manage the protean manifestations of HIV-related disease that may occur. Counseling must also emphasize the importance of curtailing the high-risk activity so as to curb the spread of the infection.


Calcium-Rich Biochar Stimulates Salt Resistance in Pearl Millet (Pennisetum glaucum L.) Plants by Improving Soil Quality and Enhancing the Antioxidant Defense.
Shrimp waste is rich in organic compounds and essential plant nutrients, e.g., calcium (Ca), and converting these wastes to organic fertilizer is important for environmental preservation and to achieve sustainable agricultural management. In the current study, Ca-rich biochar was prepared from shrimp wastes (SWB) by pyrolysis at 300 °C. We hypothesized that the Ca-rich biochar will help in solving the problem of plant growth in saline soil by reducing sodium (Na) uptake and mitigating oxidative stress. The current study aimed to investigate the effect of SWB on the quality of saline sandy soil and the mechanism of salt resistance in pearl millet (Pennisetum glaucum L.). Pearl millet plants were planted in saline sandy soil (10 dS m-1) in wooden boxes (1.3 × 0.8 m size and 0.4 m height), and 5 doses (0, 1.0, 1.5, 2.0, and 2.5% (w/w)) of SWB were added. SWB application increased the soil quality and nutrient uptake by pearl millet plants. The highest rate of SWB increased the soil microbial biomass carbon and the activity of dehydrogenase enzyme by 43 and 47% compared to the control soil. SWB application reduced the uptake of sodium (Na+) and chloride (Cl-) and increased the K/Na ratio in the leaf tissues. SWB addition significantly increased the activity of antioxidant enzymes, e.g., ascorbate peroxidase (APX), polyphenol oxidase (PPO), and pyrogallol peroxidases (PPX). The application of 2.5% SWB to the saline soil increased the soluble carbohydrates and proline in plant leaves by 75 and 60%, respectively, and reduced the malondialdehyde (MDA) by 32% compared to the control. SWB enhanced the antioxidant defense and mitigated oxidative stress by improving the synthesis of osmoprotectants, e.g., soluble carbohydrates and proline. Sandy saline soils in arid and semiarid areas suffer greatly from low organic matter contents, which reduces the soil quality and increases the risk of salt during plant growth. The high organic matter and calcium content (30%) in the shrimp waste-derived biochar improved the quality of the saline sandy soil, reduced the uptake of toxic salts, and increased the quality of the forage material. The addition of recycled shrimp waste to saline low-fertility soils improves soil productivity and is safe for soil health.


[Association of AIRE gene polymorphisms with susceptibility to rheumatoid arthritis among ethnic Han Chinese from Shaanxi].
To assess the association of AIRE gene polymorphisms with rheumatoid arthritis (RA) among ethnic Han Chinese from Shaan'xi Province. Genomic DNA was prepared from 384 individuals with RA and 576 healthy controls. Four tag single nucleotide polymorphisms (SNP) in the AIRE gene (rs2075876, rs760426, rs1800520, and rs878081) were genotyped with a SNaPshot method. The genotypic and allelic frequencies were evaluated using a Chi square test. Genotyping data was corrected by Logistic regression for age and gender. The linkage disequilibrium (LD) block structure was examined using Hapview 4.2 software. All 4 SNPs have conformed to Hardy-Weinberg equilibrium (P > 0.05). Two SNPs were significantly associated with RA, which included G allele of rs2075876 (OR=1.41, 95% CI: 1.17-1.71, P=3.7 × 10(-4)); Dominant model (OR=1.79, 95% CI: 1.21-2.63, P=0.002), Recessive model (OR=1.48, 95% CI: 1.14-1.93, P=0.003). rs760426 A risk allele (OR=1.26, 95% CI: 1.04-1.52, P=0.01); Recessive model (OR=1.33, 95% CI: 1.02-1.73, P=0.03). In addition, rs878081 and rs1800520 SNPs were not allele and genotyped polymorphisms were significantly associated with RA susceptibility. The rs2075876 and rs760426 loci of the AIRE gene are associated with increased risk for rheumatoid arthritis among ethnic Han Chinese from ShaanXi.


Targeting gastrointestinal stromal tumors: the role of regorafenib.
Gastrointestinal stromal tumor (GIST) is a devastating disease in the metastatic setting, but its natural history has been dramatically altered by the development of small molecule tyrosine kinase inhibitors, most notably imatinib. Although patients with advanced GIST live much longer today than they did in the past, imatinib-refractory disease remains a tremendous problem. For disease that is refractory to imatinib and sunitinib, regorafenib is an excellent option. In this review, we discuss the biology and clinical work establishing regorafenib as the standard of care for advanced GIST refractory to both imatinib and sunitinib.


Cancer stem cells in lung cancer: Evidence and controversies.
The cancer stem cell (CSC) model is based on a myriad of experimental and clinical observations suggesting that the malignant phenotype is sustained by a subset of cells characterized by the capacity for self-renewal, differentiation and innate resistance to chemotherapy and radiation. CSC may be responsible for disease recurrence after definitive therapy and may therefore be functionally synonymous with minimal residual disease. Similar to other solid tumours, several putative surface markers for lung CSC have been identified, including CD133 and CD44. In addition, expression and/or activity of the cytoplasmic enzyme aldehyde dehydrogenase ALDH and capacity of cells to exclude membrane permeable dyes (known as the 'side population') correlate with stem-like function in vitro and in vivo. Embryonic stem cell pathways such as Hedgehog, Notch and WNT may also be active in lung cancers stem cells and therefore may be therapeutically targetable for maintenance therapy in patients achieving a complete response to surgery, radiotherapy or chemotherapy. This paper will review the evidence regarding the existence and function of lung CSC in the context of the experimental and clinical evidence and discuss some ongoing controversies regarding this model.


Genetically marked Rhizobium identifiable as inoculum strain in nodules of soybean plants grown in fields populated with Rhizobium japonicum.
The fate of an inoculum strain of Rhizobium japonicum was studied using a genetically marked strain I-11O subline carrying resistance markers for azide, rifampin, and streptomycin (I-110 ARS). At the time of planting into a field populated with R. japonicum, seeds of soybean cultivars Kent and Peking were inoculated with varying cell densities of strain I-110 ARS. At various times during the growing season, surface-sterilized root nodules were examined for the presence of the inoculum strain by plating onto selective media. The recovery of the inoculum strain was unambiguous, varying, in the case of Kent cultivar, from about 5% with plants (sampled at 51 days) that had been inoculated with 3 X 10(8) cells per cm of row to about 20% with plants (sampled at 90 days) that had been inoculated with 3 X 10(9) cells per cm. The symbiotically incompatible interaction of Peking and strain 110 in Rhizobium-populated field soil was confirmed by the finding that at 60 days after planting, only one nodule in 360 sampled contained strain I-110 ARS. The use of genetically marked Rhizobium bacteria was found to provide for precise identification of the inoculum strain in nodules of field-grown soybeans.


Laron syndrome abnormalities: spinal stenosis, os odontoideum, degenerative changes of the atlanto-odontoid joint, and small oropharynx.
Patients with Laron syndrome have an inborn growth hormone resistance. We investigated abnormalities in the upper airways and cervical spine in patients with Laron syndrome. We prospectively examined 11 patients (one child aged 9 years and 10 adults aged 36-68 years), 10 of whom underwent MR imaging of the spine or head; nine, radiography of the cervical spine; and four, CT of C1-C2. The width of the spinal canal was evaluated visually and quantitatively and compared with reference values. The smallest diameter of the oropharynx and the thickness of the palate were measured and compared with reference values. Nine age-matched female patients referred for MR imaging for unrelated reasons served as control subjects. Cervical spinal stenosis was present in seven of the adult patients, within a confidence interval of 95%. Anomaly of the dens compatible with os odontoideum was present in three patients, causing focal myelomalacia in two. The atlanto-odontoid joint showed osteoarthritic changes in six of the adult patients. The mediolateral diameter of the oropharynx was significantly smaller in the patients with Laron syndrome than in the control subjects (P <.005). There was no difference in the thickness of the soft palate. Patients with Laron syndrome develop significant narrowing of the cervical spinal canal and early degenerative changes of the atlanto-odontoid joint. Laron syndrome is associated with os odontoideum causing myelomalacia. The dimensions of the oropharynx are small. Patients may be prone to neurologic morbidity and sleep disturbances. Routine MR imaging of the cervical spine is recommended in these patients.


Genetic profiles of transcriptomic clusters of childhood asthma determine specific severe subtype.
Previous studies have defined transcriptomic subtypes of adult asthma using samples of induced sputum and bronchial epithelium; however, those procedures are not readily applicable in the clinic, especially for childhood asthma. We aim to dissect the transcriptomic clusters of childhood asthma using highly variably expressed genes of peripheral blood mononuclear cells (PBMC) among patients. Gene expression of PBMC from 133 asthmatic children and 11 healthy controls was measured with Illumina microarrays. We applied the k-means clustering algorithm of 2048 genes to assign asthmatic children into clusters. Genes with differential expression between asthma clusters and healthy controls were used to investigate whether they could identify severe asthma of children and adults. We identified 3 asthma clusters with distinct inflammatory profiles in peripheral blood. Cluster 1 had the highest eosinophil count. Cluster 2 showed lower counts of both eosinophils and neutrophils. Cluster 3 had the highest neutrophil count and the poorest treatment control. Compared with other patients, Cluster 3 exhibited a unique gene expression pattern which was associated with changes in the glucocorticoid signalling and activation of the T helper 1/T helper 17 (TH 1/TH 17) immune pathways. In the validation studies, an 84-gene signature could identify severe asthma in children on leucocytes, as well as severe asthma in adults on CD8+ T cells. Gene expression profiling of PBMC is useful for the identification of TH 1/TH 17-mediated asthma with poor treatment control. PBMC and CD8+ T cells could be important targets for the investigation and identification of severe asthma.


The impact of COVID-19 pandemic on the diagnosis and management of inborn errors of metabolism: A global perspective.
Quantitative estimates for the global impact of COVID-19 on the diagnosis and management of patients with inborn errors of metabolism (IEM) are lacking. We collected relevant data from 16 specialized medical centers treating IEM patients in Europe, Asia and Africa. The median decline of reported IEM related services in March 1st-May 31st 2020 compared to the same period in 2019 were as high as 60-80% with a profound impact on patient management and care for this vulnerable patient group. More representative data along with outcome data and guidelines for managing IEM disorders under such extraordinary circumstances are needed.


miR-142-3p down-regulation contributes to thyroid follicular tumorigenesis by targeting ASH1L and MLL1.
A previous micro-RNA expression profile of thyroid follicular adenomas identified miR-142 precursor among the miRNAs downregulated in the neoplastic tissues compared to normal thyroid gland. The aim of this work has been to assess the expression of miR-142-3p in a large panel of follicular thyroid adenomas and carcinomas and evaluate its effect on thyroid cell proliferation and target expression. The expression of miR-142-3p was analyzed by qRT-PCR in thyroid follicular adenomas and carcinomas, compared to normal thyroids. MiR-142-3p expression was restored in WRO cells and the effects on cell proliferation and target expression were evaluated. Here we show that miR-142-3p is downregulated in FTAs, FTCs, and FVPTCs. MiR-142-3p was demonstrated to reduce the proliferation rate of WRO and FTC133 cells, supporting its tumor suppressor role in thyroid cancerogenesis. Moreover, this microRNA was able to downregulate the expression of ASH1L and MLL1, by direct and indirect mechanisms, respectively. Consistently, an inverse correlation between miR-142-3p expression and ASH1L and MLL1 proteins was found in thyroid follicular adenomas and carcinomas. ASH1L and MLL1, which belong to the Trithorax group (TrxG) proteins and are major regulators of Homeobox gene expression, maintain active target gene transcription by histone 3 lysine 4 methylation. Interestingly, we found that FTCs and FTC cell lines express tumor specific, shorter forms of the two proteins. The capability of miR-142-3p to modulate the levels of these tumor-associated forms and to reactivate thyroid-specific Hox gene expression, likely contributes to its tumor suppressive function. These data demonstrate that miR-142-3p downregulation has a role in thyroid tumorigenesis, by regulating ASH1L and MLL1.


Willingness to date across race: differences among gay and heterosexual men and women.
Willingness to date members of other races was examined among 200 men with same-sex dating preference (n = 100) and opposite-sex dating preference (n = 100), and 200 women with same-sex dating preference (n = 100) and opposite-sex dating preference (n = 100) who were randomly selected from an Internet dating web site. Overall, results indicated a greater willingness among gay participants than heterosexual participants to date people of other races. A 2 (Sex) x 2 (Sexual Orientation) analysis of variance showed an interaction, with lesbian women more willing to date other races than gay men, while among heterosexual participants men were more willing than women to date other races. The role of mate selection theory, and the importance of the status afforded various races in U.S. society, were applied to interpret people's willingness to date other races.


Effect of body mass index on surgical times of lumbar laminoplasty and lower limb arthroplasties.
Obesity is an important factor affecting incidence and development of musculoskeletal degenerative changes. In addition, obese patients are considered less favorable surgical candidates for decompression surgery in degenerative lumbar spinal canal stenosis and lower limb arthroplasty. The purpose was to assess disease characteristics of lumbar spinal canal stenosis as well as lower limb osteoarthritis, and to investigate surgical times based on body mass index (BMI) in lumbar decompressive surgery and lower limb arthroplasties. A total of 1161 patients with a diagnosis of lumbar canal stenosis (LCS), hip osteoarthritis (HOA) and knee osteoarthritis (KOA) were enrolled. The present investigation was conducted as a retrospective study using routinely collected data. All patients underwent primary decompressive surgery (laminoplasty: LAM) or lower limb arthroplasty (total hip arthroplasty: THA and total knee arthroplasty: TKA). All of the patients were divided into 3 groups based on BMI (kg/m2) (Group A: ≤ 24.9; Group B: 25-29.9; Group C: ≥ 30) within each disease category. To assess disease characteristics, age, gender, and BMI were evaluated for each disease category. Moreover, surgical times for LAM, THA and TKA were also assessed based on BMI classification. A total of 269, 470, and 422 patients were allocated to the HOA category, the KOA category, and the LCS category, respectively. The KOA category included the oldest patients and largest BMI, compared to the HOA and the LCS categories. Regarding gender difference, LCS was more common in males than in females, while opposite phenomenon was observed in the HOA and the KOA categories. The heaviest group (Group C) was significantly younger than Groups A or B in TKA and LAM. Surgical time was significantly longer in patients with overweight or obese patients than in those with normal weight in TKA and LAM, while BMI didn't affect the time in THA. Disease characteristics of the KOA category and the LCS category were notably affected by BMI, and surgical times in TKA and LAM were significantly longer for overweight or obese patients, whereas THA was less affected by BMI concerning disease characteristics and surgical time.


Early childhood caries and dental plaque among 1-3-year-olds in Tehran, Iran.
The association between plaque and caries in older children and adults has been poor, however, some studies show that there may be a relationship in younger children. The aim was to study the relationships between dental caries and dental plaque among 12-36-month-olds in Tehran, Iran. A cross-sectional study among a stratified random sample of 504 children aged one to three years from 18 public health centres in Tehran. Mothers were interviewed about their child's date and order of birth, gender, primary caregiver, the mother's age and the educational level of both parents. Dental examination was carried out according to the WHO criteria. Early childhood caries (ECC) was defined as the presence of any dmf teeth. Dental plaque was visually inspected on the labial surfaces of upper central incisors. Data analysis included Chi-square test, t -test, anova and logistic regression modelling. The prevalence of ECC ranged from 3 to 33% depending on age group, with a mean dt of 1.1 for 26- to 36-month-olds. No gender-differences existed in ECC prevalence and mean dt. Dental plaque was visible on at least one index tooth for 65-75% of the children. Presence of ECC was related to the presence of dental plaque (OR = 1.5; 95% CI 1.0-2.3) when controlling for background factors by means of logistic regression. The high occurrence of visible plaque and rather high ECC prevalence call for improvement in oral health promotion programs of the children.


The Flight of Icarus: A Preliminary Study of the Emotional Correlates of Hubris in Gerontological Nurses during the SARS-CoV-2 Pandemic.
Persons in leadership positions are more likely to manifest hubristic symptomatology, the longer the person exercises power and the greater the power they exercise. No data exists for healthcare staff, such as nurses and more specifically for gerontological nurses who exercise power on their colleagues as well as older persons. This study aims to examine whether there are emotional correlates of gerontological nurses' experienced hubris when serving in a leadership position, and to investigate possible gender differences during SARS-CoV-2 pandemic, a little investigated period regarding its emotional aspects on healthcare professionals. Gerontological nurses in leadership positions completed Job Affect Scale, Emotional Labour Scale, Emotion Regulation Questionnaire, Generalized Immediacy Scale, General Index of Job Satisfaction, Maslach Burnout Inventory, Wong-Law Emotional Intelligence Scale, State-Anxiety-Inventory, Perceived Cohesion Scale, and a 5-point Likert scale measuring hubristic attributes. No statistically significant differences were found between male and female nurses regarding the abovementioned classic administered emotional scales and hubris. The analyses yielded only a negative correlation between negative affect and hubris. This research provides for the first time data regarding gerontological nurses in leadership positions, suggesting that various negative and positive emotional variables do no directly relate to hubristic symptoms for this group of healthcare professionals. As hubristic behaviors and their dangerous consequences are found not to be related to abovementioned emotional variables, researchers and hospital managers should consider and focus on other indices in their attempt to prevent such phenomena.


[Lateralization of emotional functions].
Recordings of the P300 waves in left and right hemispheres in response to neutral and emotionally significant words corroborate the rightfulness of the principle stating that any psychic function, for instance emotion, is organized and controlled by means of a close and complementary collaboration of both hemispheres. A predominance of a hemisphere manifests itself in organizing a certain stage of the integral emotional function.


Tennis injury data from The Championships, Wimbledon, from 2003 to 2012.
The primary aims of this retrospective study were to describe the burden of injury presenting to the medical team and the changes in injury profile over 10 years (2003-2012) at The Championships, Wimbledon. Secondary aims included description of gender difference in rates, distribution and pathology of injuries. Retrospective observational cohort of player injury presentations over 10 years (2003-2012) at The Championships, Wimbledon. The overall rate of presentation of injury for all players over the 10-year period was 20.7 per 1000 sets played. Injury rates were lower for male players (17.7 injuries per 1000 sets played) than female players (23.4 injuries per 1000 sets played). There was variability in the numbers of injuries reported by men and women players over the 10-year period. The rates of presentation of injury at this Grand Slam tennis tournament varied between male and female players, and between years. More robust systems of data collection are required in professional tennis to enable more sophisticated injury data analysis between sexes, years and different playing surfaces.