Fermented nondigestible fraction from common bean (Phaseolus vulgaris L.) cultivar Negro 8025 modulates HT-29 cell behavior.
The aim of the study was to evaluate the effect of a fermented nondigestible fraction (FNDF) of cooked bean (Phaseolus vulgaris L.) cultivar Negro 8025 on human colon adenocarcinoma HT-29 cell survival. Negro 8025 was chosen for in vitro fermentation based on comparison of chemical composition with 2 other cultivars: Azufrado Higuera and Pinto Durango. Negro 8025 had 58% total dietary fiber, 27% resistant starch, and 20 mg of (+)-catechin equivalents per gram of sample. Short-chain fatty acids (SCFAs) production and pH of the medium were measured after fermentation as indicators of colon protection through induced arrest on cell culture and apoptosis. Butyrate and pH of FNDF of Negro 8025 were higher than the control fermented raffinose extract. The FNDF inhibited HT-29 cell survival in a time- and concentration-dependent manner. The lethal concentration 50 (LC(50)) was 13.63% FNDF (equivalent to 7.36, 0.33, and 3.31 mmol of acetic, propionic, and butyric acids, respectively). DNA fragmentation, an apoptosis indicator, was detected by the TdT-mediated dUTP nick end labeling method in cells treated with the LC(50)-FNDF and a synthetic mixture of SCFAs mimicking LC(50)-FNDF. Our results suggest that common bean is a reliable source of fermentable substrates in colon, producing compounds with potential chemoprotective effect on HT-29 colon adenocarcinoma cells, so it may present an effective alternative to mitigate colon cancer development.


Behavioural pharmacology and its contribution to the molecular basis of memory consolidation.
Recent findings have significantly advanced our understanding the mechanisms of memory formation. Most of these advances stemmed from behavioural pharmacology research involving, particularly, the localized infusion of drugs with specific molecular actions into specific brain regions. This approach has revealed brain structures involved in different memory types and the main neurotransmitter systems and sequence of metabolic cascades that participate in memory consolidation. Biochemical studies and, in several cases, studies of genetically manipulated animals, in which receptors or enzymes affected by the various drugs were absent or overexpressed, have complemented the pharmacological research. Although most studies have concentrated on the involvement of the hippocampus, many have also investigated the entorhinal cortex, other regions of the cortex, and the amygdala. Behavioural pharmacology has been of crucial importance in establishing the major neurohumoral and hormonal systems involved in the modulation of memory formation. These systems act on specific steps of memory formation in the hippocampus and in the entorhinal, parietal, and cingulate cortex. A specialized system mediated by the basolateral amygdaloid nucleus, and involving several neuromodulatory systems, is activated by emotional arousal and serves to regulate memory formation in other brain regions. The core mechanisms involved in the formation of explicit (declarative) memory are in many respects similar to those of long-term potentiation (LTP), particularly in the hippocampus. However, there are also important differences between memory formation and LTP. Memory formation involves numerous modulatory influences, the co-participation of various brain regions other than the hippocampus, and some properties that are specific to memory and absent in LTP (i.e. flexibility of response). We discuss the implications of these similarities and differences for understanding the neural bases of memory.


Spatiotemporal Distribution of the Environmental Microbiota in Food Processing Plants as Impacted by Cleaning and Sanitizing Procedures: the Case of Slaughterhouses and Gaseous Ozone.
Microbial complexity and contamination levels in food processing plants heavily impact the final product fate and are mainly controlled by proper environmental cleaning and sanitizing. Among the emerging disinfection technologies, ozonation is considered an effective strategy to improve the ordinary cleaning and sanitizing of slaughterhouses. However, its effects on contamination levels and environmental microbiota still need to be understood. For this purpose, we monitored the changes in microbiota composition in different slaughterhouse environments during the phases of cleaning/sanitizing and ozonation at 40, 20, or 4 ppm. Overall, the meat processing plant microbiota differed significantly between secondary processing rooms and deboning rooms, with a greater presence of psychrotrophic taxa in secondary processing rooms because of their lower temperatures. Cleaning/sanitizing procedures significantly reduced the contamination levels and in parallel increased the number of detectable operational taxonomic units (OTUs), by removing the masking effect of the most abundant human/animal-derived OTUs, which belonged to the phylum Firmicutes Subsequently, ozonation at 40 or 20 ppm effectively decreased the remaining viable bacterial populations. However, we could observe selective ozone-mediated inactivation of psychrotrophic bacteria only in the secondary processing rooms. There, the Brochothrix and Pseudomonas abundances and their viable counts were significantly affected by 40 or 20 ppm of ozone, while more ubiquitous genera like Staphylococcus showed a remarkable resistance to the same treatments. This study showed the effectiveness of highly concentrated gaseous ozone as an adjunct sanitizing method that can minimize cross-contamination and so extend the meat shelf life.IMPORTANCE Our in situ survey demonstrates that RNA-based sequencing of 16S rRNA amplicons is a reliable approach to qualitatively probe, at high taxonomic resolution, the changes triggered by new and existing cleaning/sanitizing strategies in the environmental microbiota in human-built environments. This approach could soon represent a fast tool to clearly define which routine sanitizing interventions are more suitable for a specific food processing environment, thus limiting the costs of special cleaning interventions and potential product loss.


Survey of characteristics of exposure to mainstream cigarette smoke using discarded cigarette butts from Korean smokers.
Evaluating the characteristics of exposure to mainstream cigarette smoke is an essential field in tobacco research because of the large risk burden among smokers. Detailed evaluation of the complex factors pertaining to the exposure of smokers to mainstream cigarette smoke was attempted by analysis of discarded cigarette butts. A total of 5475 samples of discarded cigarette butts was collected to investigate the exposure characteristics in relation to Korean smokers. The basic physico-chemical characteristics of cigarettes, including the filter length, filter type, menthol addition, and nicotine and tar content, were determined and the manufacturer and cigarette size were identified. The tobacco-burned percentage (TBP)) and tar staining were used as physical markers, and actual human exposure to cigarette smoke was determined using the part filter method. Multiple linear regression analyses and generalized ordinal logistic regression analysis were conducted to identify the relationship between the socio-demographic factors and the physico-chemical characteristics of the cigarettes themselves and the exposure characteristics. Significant associations were observed between the TBP and age group, occupational group, manufacturer, tar staining, ISO tar content, and filter length. Increased odds of smoking with a heavier tar stain among Korean smokers were associated with blue collar workers vs. other workers, manufacturer B vs. other manufacturers, recess filter vs. other filter types, ISO tar content, and TBP. Finally, significant associations between the log-transformed human-smoked tar and nicotine yields and occupational group, the TBP, tar staining, and physico-chemical properties of cigarettes were found and were used to propose models for predicting the actual exposure to tar and nicotine. The proposed models account for 60-61% and 47-49% of the variance of human exposure to tar and nicotine, respectively. This analysis of discarded cigarette butts revealed that various factors, including socio-demographic factors such as age group and occupational group, as well as the physico-chemical properties of cigarette products such as the filter type and length, cigarette size, ISO tar and nicotine content, and mentholation, affect the characteristics of exposure of Korean smokers to mainstream cigarette smoke.


A Novel Splicesite Mutation in the EDAR Gene Causes Severe Autosomal Recessive Hypohydrotic (Anhidrotic) Ectodermal Dysplasia in an Iranian Family.
Hypohidrotic ectodermal dysplasia (HED) is a rare congenital disorder arising from deficient development of ectoderm-derived structures including skin, nails, glands and teeth. The phenotype of HED is associated with mutation in EDA, EDAR, EDARADD and NEMO genes, all of them disruptingNF-κB signaling cascade necessary for initiation, formation and differentiation in the embryo and adult. Here we describe a novel acceptor splice site mutation c.730-2 A>G(IVS 8-2 A>G) in EDAR gene in homozygous form in all affected members of a family,and in heterozygous form in carriers. Bioinformatics analysis showed that this mutation can create a new broken splicing site and lead to aberrant splicing.


Risk Factors for Postural and Functional Balance Impairment in Patients with Chronic Obstructive Pulmonary Disease.
Reduced balance function has been observed during balance challenging conditions in the chronic obstructive pulmonary disease (COPD) population and is associated with an increased risk of falls. This study aimed to examine postural balance during quiet standing with eyes open and functional balance in a heterogeneous group of COPD and non-COPD (control) subjects, and to identify risk factors underlying balance impairment using a large panel of methods. In COPD and control subjects, who were mostly overweight and sedentary, postural and functional balance were assessed using center-of-pressure displacement in anterior-posterior (AP) and medio-lateral (ML) directions, and the Berg Balance Scale (BBS), respectively. COPD showed 23% greater AP sway velocity (p = 0.049). The presence of oxygen therapy, fat mass, reduced neurocognitive function, and the presence of (pre)diabetes explained 71% of the variation in postural balance in COPD. Transcutaneous oxygen saturation, a history of exacerbation, and gait speed explained 83% of the variation in functional balance in COPD. Neurocognitive dysfunction was the main risk factor for postural balance impairment in the control group. This suggests that specific phenotypes of COPD patients can be identified based on their type of balance impairment.


Conceptual combination: extension and intension. Commentary on Aerts, Gabora, and Sozzo.
Aerts et al. provide a valuable model to capture the interactive nature of conceptual combination in conjunctions and disjunctions. The commentary provides a brief review of the interpretation of these interactions that has been offered in the literature, and argues for a closer link between the more traditional account in terms of concept intensions, and the parameters that emerge from the fitting of the Quantum Probability model.


Mutual interdependence of MSI1 (CAC3) and YAK1 in Saccharomyces cerevisiae.
The MSI1 (CAC3) gene of Saccharomyces cerevisiae has been implicated in diverse cellular functions, including suppression of the RAS/cAMP/protein kinase A signaling pathway, chromatin assembly and transcriptional co-repression. Seeking to identify the molecular mechanisms by which Msi1p carries out these distinct activities, a novel genetic interaction was uncovered with YAK1, which encodes a kinase that antagonizes the RAS/cAMP pathway. MSI1 was capable of efficiently suppressing the heat shock sensitivity caused by deletion of yak1. Surprisingly, the YAK1 gene is required for Msi1p to associate with Cac1p in the yeast two-hybrid system. A new activity of Msi1p was identified: the ability to activate transcription of a reporter gene when tethered near the promoter, but only in the absence of fermentable carbon sources. This transcriptional activation function was diminished substantially by the loss of YAK1. Furthermore, MSI1 influences YAK1 function; over-expression of YAK1 decreased the growth rate, but only in the presence of a functional MSI1 gene. Finally, it is shown that YAK1 antagonizes nuclear accumulation of Msi1p in non-fermenting cells. Taken together, these data demonstrate a novel interaction between Msi1p and Yak1p in which each protein influences the activity of the other.


[Coronary heart disease and dyslipdemia - dosing recommendations at beginning and end of treatment].
Secondary prevention in patients with coronary heart disease includes treatment with platelet inhibitors, beta-blockers, ACE inhibitors or AT (1)-blockers, and statins. Initiation of therapy generally does not require a slow gradual dose increase. In treatment naive patients with acute coronary syndromes, administration of a loading dose of aspirin and/or clopidogrel is recommended. To reduce flushing, nicotinic acid should be initiated at low stepwise increasing dosages. beta-blocker therapy should not be stopped acutely in coronary heart disease patients. If beta-blocker therapy has to be terminated, blood pressure should be monitored closely and, if necessary controlled with other medication. Termination of statin therapy in the acute phase after strokes or acute coronary syndromes is associated with increased cardiovascular events and should therefore be avoided.


New Features of Electrocardiogram in a Case Report of Arrhythmogenic Right Ventricular Cardiomyopathy: A Care-Compliant Article.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a crucial health problem. With sudden death often being the first presentation, early diagnosis for ARVC is essential. Up to date, electrocardiogram (ECG) is a widely used diagnostic method without invasive harms. To diagnose and treat ARVC as well as possible, we should clearly elucidate its pathophysiological alterations. A 66-year-old farmer presented to the Emergency Department with continuous palpitation, chest tightness, profuse sweating, and nausea with no obvious predisposing causes. An ECG indicated ventricular tachycardia (VT). The patient experienced a sudden drop in blood pressure and acute confusion. After an immediate electrical conversion, his consciousness was gradually restored, and symptoms relieved. The patient was then transferred to the Department of Cardiology to receive ECG, echocardiography, coronary angiogram, biochemical assays, endocardiac tracing, and radiofrequency ablation. In the end, he was diagnosed with ARVC, evidenced by bilateral ventricle dilation and epsilon waves in leads V1-V3. Appropriate therapies were provided for this patient including pharmacological intervention and radiofrequency ablation. Although the diagnosis of ARVC is not difficult, this patient's ECG manifested several interesting features and should be further investigated: T wave inversions were found extensively in the anterior and inferior leads, revealing the involvement of bilateral ventricles; VTs with different morphologies and cycle lengths were found, and some VTs manifested the feature of irregularly irregular rhythm, reminding us to carefully differentiate some special VTs from atrial fibrillation (AF); and epsilon waves gradually appeared in leads V1-V3 and avR since the onset of ARVC. Most importantly, the epsilon waves behind QRS complex appeared in both sinus rhythm and ventricular premature beats/VT originating from cardiac apex, whereas the epsilon waves prior to QRS complex occurred in VT originating from right ventricular outflow tract (RVOT). The features of T wave inversion and epsilon wave in ECGs and the appearance of VTs with different morphologies can reflect the progression of ARVC. The position relationship between epsilon wave and QRS complex in VT depends on ventricular activation sequence, that is, the localization of epsilon wave depends on where VT is originating from.


Potential for a hazardous geospheric response to projected future climate changes.
Periods of exceptional climate change in Earth history are associated with a dynamic response from the geosphere, involving enhanced levels of potentially hazardous geological and geomorphological activity. The response is expressed through the adjustment, modulation or triggering of a broad range of surface and crustal phenomena, including volcanic and seismic activity, submarine and subaerial landslides, tsunamis and landslide 'splash' waves, glacial outburst and rock-dam failure floods, debris flows and gas-hydrate destabilization. In relation to anthropogenic climate change, modelling studies and projection of current trends point towards increased risk in relation to a spectrum of geological and geomorphological hazards in a warmer world, while observations suggest that the ongoing rise in global average temperatures may already be eliciting a hazardous response from the geosphere. Here, the potential influences of anthropogenic warming are reviewed in relation to an array of geological and geomorphological hazards across a range of environmental settings. A programme of focused research is advocated in order to: (i) understand better those mechanisms by which contemporary climate change may drive hazardous geological and geomorphological activity; (ii) delineate those parts of the world that are most susceptible; and (iii) provide a more robust appreciation of potential impacts for society and infrastructure.


Magnitude and breadth of a nonprotective neutralizing antibody response in an efficacy trial of a candidate HIV-1 gp120 vaccine.
A candidate vaccine consisting of human immunodeficiency virus type 1 (HIV-1) subunit gp120 protein was found previously to be nonprotective in an efficacy trial (Vax004) despite strong antibody responses against the vaccine antigens. Here we assessed the magnitude and breadth of neutralizing antibody responses in Vax004. Neutralizing antibodies were measured against highly sensitive (tier 1) and moderately sensitive (tier 2) strains of HIV-1 subtype B in 2 independent assays. Vaccine recipients were stratified by sex, race, and high versus low behavioral risk of HIV-1 acquisition. Most vaccine recipients mounted potent neutralizing antibody responses against HIV-1(MN) and other tier 1 viruses. Occasional weak neutralizing activity was detected against tier 2 viruses. The response against tier 1 and tier 2 viruses was significantly stronger in women than in men. Race and behavioral risk of HIV-1 acquisition had no significant effect on the response. Prior vaccination had little effect on the neutralizing antibody response that arose after infection. Weak overall neutralizing antibody responses against tier 2 viruses is consistent with a lack of protection in this trial. The magnitude and breadth of neutralization reported here should be useful for identifying improved vaccines.


[The effect of ultrasound in biology].
The article deals with the basic definitions and characteristics of ultrasound. The primary effects of ultrasound such as heat production, microstreaming, cavitation, chemical effects and biologic effects of ultrasound such as teratogeny and mutagenesis of the stronger doses without any clear evidence of deleterious effects, are described.


Understanding the Psychological Well-Being of International Arrivals in a Purpose-Designed Australian COVID-19 Quarantine Facility.
Equivocal evidence suggests that mandatory supervised quarantine can negatively affect psychological well-being in some settings. It was unclear if COVID-19 supervised quarantine was associated with psychological distress in Australia. The sociodemographic characteristics associated with distress and the lived experiences of quarantine are also poorly understood. Therefore, this study aimed to evaluate the mental well-being of international arrivals undergoing supervised COVID quarantine in a purpose designed facility in the Northern Territory, Australia. We conducted a concurrent triangulation mixed-methods study comprising of an observational cross-sectional survey (n = 117) and individual qualitative interviews (n = 26). The results revealed that several factors were associated with distress, including significantly higher levels of depression for those who smoked, drank alcohol, had pre-existing mental health conditions and had no social networks in quarantine. Levels of psychological distress were also related to waiting time for re-entry (the time between applying to repatriate and returning to Australia) and flight origin. Qualitative data showed that despite quarantine being viewed as necessary, unclear communication and a perception of lack of control were affecting emotional well-being. This information is useful to inform the further development of models to identify those at most risk and support psychological well-being in quarantine settings.


Rational design of non-resistant targeted cancer therapies.
Drug resistance is one of the major problems in targeted cancer therapy. A major cause of resistance is changes in the amino acids that form the drug-target binding site. Despite of the numerous efforts made to individually understand and overcome these mutations, there is a lack of comprehensive analysis of the mutational landscape that can prospectively estimate drug-resistance mutations. Here we describe and computationally validate a framework that combines the cancer-specific likelihood with the resistance impact to enable the detection of single point mutations with the highest chance to be responsible of resistance to a particular targeted cancer therapy. Moreover, for these treatment-threatening mutations, the model proposes alternative therapies overcoming the resistance. We exemplified the applicability of the model using EGFR-gefitinib treatment for Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Cancer (LSCC) and the ERK2-VTX11e treatment for melanoma and colorectal cancer. Our model correctly identified the phenotype known resistance mutations, including the classic EGFR-T790M and the ERK2-P58L/S/T mutations. Moreover, the model predicted new previously undescribed mutations as potentially responsible of drug resistance. Finally, we provided a map of the predicted sensitivity of alternative ERK2 and EGFR inhibitors, with a particular highlight of two molecules with a low predicted resistance impact.


Endothelial atypical cannabinoid receptor: do we have enough evidence?
Cannabinoids and their synthetic analogues affect a broad range of physiological functions, including cardiovascular variables. Although direct evidence is still missing, the relaxation of a vast range of vascular beds induced by cannabinoids is believed to involve a still unidentified non-CB1 , non-CB2 Gi/o protein-coupled receptor located on endothelial cells, the so called endothelial cannabinoid receptor (eCB receptor). Evidence for the presence of an eCB receptor comes mainly from vascular relaxation studies, which commonly employ pertussis toxin as an indicator for GPCR-mediated signalling. In addition, a pharmacological approach is widely used to attribute the relaxation to eCB receptors. Recent findings have indicated a number of GPCR-independent targets for both agonists and antagonists of the presumed eCB receptor, warranting further investigations and cautious interpretation of the vascular relaxation studies. This review will provide a brief historical overview on the proposed novel eCB receptor, drawing attention to the discrepancies between the studies on the pharmacological profile of the eCB receptor and highlighting the Gi/o protein-independent actions of the eCB receptor inhibitors widely used as selective compounds. As the eCB receptor represents an attractive pharmacological target for a number of cardiovascular abnormalities, defining its molecular identity and the extent of its regulation of vascular function will have important implications for drug discovery. This review highlights the need to re-evaluate this subject in a thoughtful and rigorous fashion. More studies are needed to differentiate Gi/o protein-dependent endothelial cannabinoid signalling from that involving the classical CB1 and CB2 receptors as well as its relevance for pathophysiological conditions.


Red Clover (Trifolium pratense) and Zigzag Clover (T. medium) - A Picture of Genomic Similarities and Differences.
The genus clover (Trifolium sp.) is one of the most economically important genera in the Fabaceae family. More than 10 species are grown as manure plants or forage legumes. Red clover's (T. pratense) genome size is one of the smallest in the Trifolium genus, while many clovers with potential breeding value have much larger genomes. Zigzag clover (T. medium) is closely related to the sequenced red clover; however, its genome is approximately 7.5x larger. Currently, almost nothing is known about the architecture of this large genome and differences between these two clover species. We sequenced the T. medium genome (2n = 8x = 64) with ∼23× coverage and managed to partially assemble 492.7 Mbp of its genomic sequence. A thorough comparison between red clover and zigzag clover sequencing reads resulted in the successful validation of 7 T. pratense- and 45 T. medium-specific repetitive elements. The newly discovered repeats led to the set-up of the first partial T. medium karyotype. Newly discovered red clover and zigzag clover tandem repeats were summarized. The structure of centromere-specific satellite repeat resembling that of T. repens was inferred in T. pratense. Two repeats, TrM300 and TrM378, showed a specific localization into centromeres of a half of all zigzag clover chromosomes; TrM300 on eight chromosomes and TrM378 on 24 chromosomes. A comparison with the red clover draft sequence was also used to mine more than 105,000 simple sequence repeats (SSRs) and 1,170,000 single nucleotide variants (SNVs). The presented data obtained from the sequencing of zigzag clover represent the first glimpse on the genomic sequence of this species. Centromeric repeats indicated its allopolyploid origin and naturally occurring homogenization of the centromeric repeat motif was somehow prevented. Using various repeats, highly uniform 64 chromosomes were separated into eight types of chromosomes. Zigzag clover genome underwent substantial chromosome rearrangements and cannot be counted as a true octoploid. The resulting data, especially the large number of predicted SSRs and SNVs, may have great potential for further research of the legume family and for rapid advancements in clover breeding.


Turning tapes into text: issues surrounding the transcription of interviews.
Transcription of interview data is a common practice in qualitative health research. However, there has been little discussion of the techniques of transcription and the issues inherent in the use of transcription as a strategy for managing qualitative data in nursing publications. The process of transcription may disclose or obscure certain information. Researchers need to question practices of transcription that have been taken for granted and make transparent the processes used to preserve the integrity of data. This paperfirst examines research reported in nursing and allied health journals employing interviews for data collection and the attention given to the transcription phase. It then deals with issues of concern regarding the transcription of interviews, and offers suggestions for promoting validity.


Medical malpractice as reflected by the forensic evaluation of 4450 autopsies.
A multicentre retrospective analysis of 4450 autopsies carried out due to suspicion of medical malpractice in 17 German institutes of forensic medicine from 1990 to 2000 was performed for the German Federal Ministry of Health. During the time period analysed an increase of cases could be mentioned. The main results of the study are: in the cooperating institutes the total number of autopsies due to suspected medical malpractice ranged from 1.4 to 20%. In more than 40% of the cases preliminary proceedings were started because the manner of death was certified as non-natural or not clarified. Hospital doctors were more affected by medical malpractice claims than doctors in private practice. However, the number of confirmed cases of medical malpractice was higher for doctors in private practice than for hospital doctors. Although surgery is still at the top of the disciplines involved in medical malpractice claims the number of confirmed surgical cases was below the average. Mistakes in care were confirmed to be above the average. Medico-legal autopsies are still a very sufficient method to evaluate cases of medical malpractice: 2863 cases could already be clarified by autopsy. Up to now there is no systematic registration of medical malpractice charges in Germany. A systematic registration should be initiated to build up and/or improve error reporting systems and, thus, to improve patient safety. Compared to other sources of medical malpractice claims (arbitration committees of the medical chambers, reference material of health and insurance companies, files of civil courts) the data of the present multicentre study are in so far unique as only lethal cases were evaluated and a complete autopsy report was available as basis of an expert opinion in alleged medical malpractice cases.


[Steroid-induced osteoporosis: pathogenesis and therapeutic consequences].
Many chronic inflammatory diseases require treatment with steroids, however, a remarkable proportion of steroid-treated patients suffer from osteoporosis as major complication after longterm treatment. Steroid-induced osteoporosis represents one of the most important secondary causes of osteoporosis. The pathogenesis is complex, there exists evidence that steroids cause a reduction of circulating testosterone and estrogen concentration and adversely affect calcium balance. The most important mechanism is a decrease in osteoblastic activity. As a consequence loss of bone mineral density and increased risk of fracture develop. In spite of better understanding of the causal relationships preventive strategies were infrequently applied. If we care for patients with steroid therapy we have both to consider the problem of steroid-induced osteoporosis and to focus on strategies to evaluate patients at risk. The dosage of the steroid, life style factors (such as lack of exercise, alcohol consumption and smoking), menopausal status, low bone mineral density at baseline and previous osteoporotic fractures predispose for the manifestation of steroid-induced osteoporosis. Therapeutic decisions depend on risk factors of the individual patient. Supplementation of calcium and vitamin D is usually appropriate, and postmenopausal women should be offered hormone replacement therapy. The prescription of bisphosphonates is strongly recommended to patients at elevated risk.


[Bacterial coinfection in the critically-ill COVID-19 patient: incidence, impact and need for antimicrobial therapy].
To assess the frequency of bacterial coinfection upon ICU admission in SARS-CoV-2 pneumonia patients, its microbiology, and impact on prognosis.The secondary objective was to identify risk factors for coinfection on admission. Retrospective study, including patients with SARS-CoV-2 pneumonia admitted to the ICU.We defined bacterial coinfection by respiratory symptoms, radiological data, positive and clinically significant microbiological results in samples obtained in the first 48 h of admission and/or a determination of procalcitonin ≥ 0.5 ng/mL in the first 48 h.We evaluated demographic variables, comorbidities, SARS-CoV-2 infection data, severity scores, treatments received, need for respiratory support and outcomes (ICU and hospital mortality). A total of 182 patients were analyzed, 62 (34.1%) with bacterial coinfection.The most frequent microbiology was S. pneumoniae and M. pneumoniae. 96.1% of the patients received antibiotic therapy on admission, 98.9% corticosteroids, 27.5% tocilizumab, and 7.7% remdesivir.85.7% required invasive mechanical ventilation.The SOFA score (OR: 1.315, 95% CI1.116-1.548) and the delay in ICU admission (OR: 0.899, 95% CI 0.831-0.972) were related to the risk of coinfection. Bacterial coinfection increases the risk of death in hospital (OR 2.283; 95% CI 1.011.5.151; p=0.047). Bacterial coinfection is common in COVID patients admitted to the ICU and increases the risk of death. It is not possible to identify with certainty, at the time of admission, which patients do not benefit from antibiotic treatment.


Genital tract infections, bacterial vaginosis, HIV, and reproductive health issues among Lima-based clandestine female sex workers.
Sociodemographic and behavioral characteristics of 212 Peruvian female sex workers (FSWs) were analyzed. The association between genital tract infections (GTIs) and risk factors by multivariate analysis was evaluated. Eighty-eight percent of FSWs were diagnosed with at least one GTI (HSV-2 80.1%, BV 44.8%, candidiasis 9.9%, syphilis seropositivity 9.4%, Trichomonas vaginalis 2.4%, HIV seropositivity 2.4%). Reported condom use with clients was nearly universal (98.3%), but infrequent with husband/regular partners (7.3%). In multivariate analysis BV was negatively associated with more consistent condom use (PRR = 0.63, 95% CI, 0.42-0.96). Many had not visited a Sexually Transmitted Infection (STI) clinic or been tested for HIV in the past year (40.6%, 47.1%, resp.). Nonclient contraceptive use was low (57%) and induced abortion was common (68%). High GTI burden and abortions suggest that a services-access gap persists among marginalized FSWs. Continued health outreach programs and integrating family planning and reproductive health services into existing STI clinic services are recommended.


Lymphatic lipid transport: sewer or subway?
The lymphatics began receiving attention in the scientific community as early as 1622, when Gasparo Aselli noted the appearance of milky-white vessels in the mesentery of a well-fed dog. Since this time, the lymphatic system has been historically regarded as the sewer of the vasculature, passively draining fluid and proteins from the interstitial spaces (along with lipid from the gut) into the blood. Recent reports, however, suggest that the lymphatic role in lipid transport is an active and intricate process, and that when lymphatic function is compromised, there are systemic consequences to lipid metabolism and transport. This review highlights these recent findings, and suggests future directions for understanding the interplay between lymphatic and lipid biology in health and disease.


Genetic Compatibility Underlies Benefits of Mate Choice in an External Fertilizer.
Mate choice is a common feature of sexually reproducing species. In sessile or sedentary external fertilizers, however, direct interactions between reproductive partners are minimal, and instead mate recognition and choice must occur at the level of gametes. It is common for some sperm and egg combinations to have higher fertilization success than others, but it remains unclear whether differences in fertilization reflect gamete-level mate choice (GMC) for paternal quality or parental compatibility. Here, we examine the mechanisms underlying GMC in an externally fertilizing ascidian. A manipulative mate-choice assay confirmed that offspring viability was greater in clutches where we allowed GMC than in clutches where we precluded GMC. A complementary quantitative genetic experiment then revealed that paternal quality effects were generally weaker than parental compatibility effects, particularly for the trait combination underlying the benefits of GMC. Overall, our data suggest that gametes that are more compatible at fertilization produce more viable offspring than gametes that are less compatible at fertilization. Therefore, although the regalia we typically associate with sexual selection are absent in external fertilizers, mechanisms that allow females to bias fertilization in favor of some males over others produce significant fitness benefits in organisms reproducing via the ancestral strategy.


Monocyte to Lymphocyte Ratio, Neutrophil to Lymphocyte Ratio, and Red Cell Distribution Width are the Associates with Gouty Arthritis.
Neutrophils, monocytes, and macrophages activations are associated with a gout attack. Monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), red cell distribution width (RDW), and mean platelet volume (MPV) are well-known inflammation markers. In this study, we aimed to investigate whether they could be a predictive marker to the gout attack. A hundred and ten gout patients (male/female, 86/24) and 90 (male/female, 64/26) age-, gender-, and body mass index-matched volunteer controls were included in the study. Blood samples were obtained in the intercritical and attack period of the patients. Hemogram, serum uric acid (SUA), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) values were studied. In the attack period NLR (p < 0.001), PLR (p < 0.05), MLR (p < 0.001), RDW (p < 0.05), MPV (p < 0.05), ESR (p < 0.001), CRP (p < 0.001) and SUA (p < 0.001) values were significantly higher than intercritical period values. According to the results of regression analysis; There was an independent strong relationship between the gout attack and SUA, (Beta [β] = 0.352, p < 0.001), ESR (β = 0.329, p < 0.001), CRP (β = 0.286, p < 0.001), MLR (β = 0.126, p < 0.001), RDW (β = 0.100, p = 0.003) and NLR (β = 0.082, p = 0.014). MLR, RDW, and NLR may be a strong predictive marker for a gout attack. MPV and PLR values in the gout attack may be associated with systemic inflammation.


Coordination- and Redox-Noninnocent Behavior of Ambiphilic Ligands Containing Antimony.
Stimulated by applications in catalysis, the chemistry of ambiphilic ligands featuring both donor and acceptor functionalities has experienced substantial growth in the past several years. The unique opportunities in catalysis offered by ambiphilic ligands stem from the ability of their acceptor functionalities to play key roles via metal-ligand cooperation or modulation of the reactivity of the metal center. Ligands featuring group 13 centers, most notably boranes, as their acceptor functionalities have undoubtedly spearheaded these developments, with remarkable results having been achieved in catalytic hydrogenation and hydrosilylation. Motivated by these developments as well as by our fundamental interest in the chemistry of heavy group 15 elements, we became fascinated by the possibility of employing antimony centers as Lewis acids within ambiphilic ligands. The chemistry of antimony-based ligands, most often encountered as trivalent stibines, has historically been considered to mirror that of their lighter phosphorus-based congeners. There is growing evidence, however, that antimony-based ligands may display unique coordination behavior and reactivity. Additionally, despite the diverse Lewis acid and redox chemistry that antimony exhibits, there have been only limited efforts to explore this chemistry within the coordination sphere of a transition metal. By incorporation of antimony into the framework of polydentate ligands in order to enforce the main group metal-transition metal interaction, the effect of redox and coordination events at the antimony center on the structure, electronics, and reactivity of the metal complex may be investigated. This Account describes our group's continuing efforts to probe the coordination behavior, reactivity, and application of ambiphilic ligands incorporating antimony centers. Structural and theoretical studies have established that both Sb(III) and Sb(V) centers in polydentate ligands may act as Z-type ligands toward late transition metals. Although coordinated to a metal, the antimony centers in these complexes retain residual Lewis acidity, as evidenced by their ability to participate in anion binding. Anion binding events at the antimony center have been shown by structural, spectroscopic, and theoretical studies to perturb the antimony-transition metal interaction and in some cases to trigger reactivity at the metal center. Coordinated Sb(III) centers in polydentate ligands have also been found to readily undergo two-electron oxidation, generating strongly Lewis acidic Sb(V) centers in the coordination sphere of the metal. Theoretical studies suggest that oxidation of the coordinated antimony center induces an umpolung of the antimony-metal bond, resulting in depletion of electron density at the metal center. In addition to elucidating the fundamental coordination and redox chemistry of antimony-containing ambiphilic ligands, our work has demonstrated that these unusual behaviors show promise for use in a variety of applications. The ability of coordinated antimony centers to bind anions has been exploited for sensing applications, in which anion coordination at antimony leads to a colorimetric response via a change in the geometry about the metal center. In addition, the capacity of antimony Lewis acids to modulate the electron density of coordinated metals has proved to be key in facilitating photochemical activation of M-X bonds as well as antimony-centered redox-controlled catalysis.


Reminder-dependent alterations in long-term declarative memory expression.
The reminder of a previously-learned memory can render that memory vulnerable to disruption or change in expression. Such memory alterations have been viewed as supportive of the framework of memory reconsolidation. However, alternative interpretations and inconsistencies in the replication of fundamental findings have raised questions particularly in the domain of human declarative memory. Here we present a series of related experiments, all of which involve the learning of a declarative memory, followed 1-2 days later by memory reminder. Post-reminder learning of interfering material did result in modulation of subsequent recall at test, but the precise manifestation of that interference effect differed across experiments. With post-reminder performance of a visuospatial task, a quantitative impairment in test recall performance was observed within a visual list-learning paradigm, but not in a foreign vocabulary learning paradigm. These results support the existence of reminder-induced memory processes that can lead to the alteration of subsequent memory performance by interfering tasks. However, it remains unclear whether these effects are reflective of modulation or impairment of the putative memory reconsolidation process.


Little Earth Experiment: An instrument to model planetary cores.
In this paper, we present a new experimental facility, Little Earth Experiment, designed to study the hydrodynamics of liquid planetary cores. The main novelty of this apparatus is that a transparent electrically conducting electrolyte is subject to extremely high magnetic fields (up to 10 T) to produce electromagnetic effects comparable to those produced by moderate magnetic fields in planetary cores. This technique makes it possible to visualise for the first time the coupling between the principal forces in a convection-driven dynamo by means of Particle Image Velocimetry (PIV) in a geometry relevant to planets. We first present the technology that enables us to generate these forces and implement PIV in a high magnetic field environment. We then show that the magnetic field drastically changes the structure of convective plumes in a configuration relevant to the tangent cylinder region of the Earth's core.


Four-year clinical performance of a lithia disilicate-based core ceramic for posterior fixed partial dentures.
The objective of this research was to test the hypothesis that 3-unit fixed partial dentures (FPDs) made from a moderately high-strength core ceramic will adequately resist fracture in posterior regions if fabricated with a minimal connector size of 4 mm. Thirty ceramic FPD core frameworks were prepared using a hot-pressing technique and a lithia disilicate-based core ceramic. The maximum occlusal force was measured for each patient prior to tooth preparation. Connector heights and widths were measured for each FPD. Patients were recalled annually after cementation for 4 years and evaluated using 11 clinical criteria. All FPDs were examined by 2 independent clinicians, and rankings for each criterion were made from 1 to 4 (4 = excellent; 1 = unacceptable). The fracture rate was approximately 3% per year, and the proportion of good overall ratings in the nonfractured FPDs was reduced by more than 6% per year, where a good overall rating was defined to be a rank of 3 or 4 in all 11 criteria. There was little evidence that the use of either resin-reinforced glass-ionomer cement (Protec CEM) or dual-cure resin cement (Variolink II) made any difference in terms of fracture rate or overall rating (P= .30, .63, .97, and .71 for the 4 years, respectively). From a fracture resistance perspective, 4 of the 30 ceramic FPDs fractured within the 4-year evaluation period, representing an 86.7% success rate. Another FPD was replaced because of a caries lesion on 1 abutment tooth away from the margin. One FPD fracture was associated with the subject having the greatest occlusal force (1,031 N). The other 2 fractures were associated with FPDs that exhibited connector heights of less than 3 mm. All criteria were ranked good to excellent during the 4-year period for the remaining FPDs. Fractured FPDs were associated with a connector height of less than 4 mm; thus, the hypothesis was accepted.


Quantitative echocardiographic assessment of regional wall motion and left ventricular asynchrony with color kinesis in cardiac surgery patients.
Conventional echocardiographic interpretation of regional wall motion abnormalities is subjective and experience dependent. Delayed contraction in the ejection phase (tardokinesis) and regional systolic asynchrony, sensitive markers of myocardial ischemia, cannot be accurately assessed visually. We used color kinesis (CK), a technique that evaluates spatiotemporal patterns of endocardial motion, to objectively detect regional wall motion abnormalities in patients undergoing coronary bypass surgery, and we compared it with conventional assessment of grayscale images by less experienced reviewers; we used expert grading as the gold standard for comparisons. Quantitative CK analysis agreed more closely with expert grading than less experienced reviewers (kappa coefficients, 0.74 versus 0.52 and 0.5). Global tardokinesis, identified in 9 of 26 patients (2 with normal fractional area change), was associated with an increased index of systolic asynchrony. Regional tardokinesis was identified in 48 of 150 segments: 27 segments had a normal magnitude of wall motion, 18 were hypokinetic, and 3 were severely hypokinetic/akinetic. Mildly hypokinetic segments showed delayed systolic motion, whereas residual motion of severely hypokinetic/akinetic segments occurred in early systole, reflecting passive effects produced by adjacent myocardial contraction. Quantitative CK may be a useful supplement to visual assessment, particularly for less experienced readers. By diagnosing tardokinesis, common among cardiac surgical patients even with normal standard ejection phase indices, quantitative CK may improve the intraoperative detection of regional ischemic changes. Quantitative color kinesis allows for objective and sensitive intraoperative echocardiographic assessment of abnormal spatial and temporal patterns of regional ventricular wall motion, with potentially important implications for improving myocardial ischemia detection in patients undergoing cardiac surgery.


Dynamic ultrametricity in spin glasses.
We investigate the dynamics of spin glasses from the "rheological" point of view, in which aging is suppressed by the action of small, nonconservative forces. The different features can be expressed in terms of the scaling of relaxation times with the magnitude of the driving force, which plays the role of the critical parameter. Stated in these terms, ultrametricity loses much of its mystery and can be checked rather easily. This approach also seems a natural starting point to investigate what would be the real-space structures underlying the hierarchy of time scales. We study in detail the appearance of this many-scale behavior in a mean-field model, in which dynamic ultrametricity is clearly present. A similar analysis is performed on numerical results obtained for a three-dimensional spin glass: In that case, our results are compatible with either that dynamic ultrametricity is absent or that it develops so slowly that even in experimental time-windows it is still hardly observable.


Underconnectivity between voice-selective cortex and reward circuitry in children with autism.
Individuals with autism spectrum disorders (ASDs) often show insensitivity to the human voice, a deficit that is thought to play a key role in communication deficits in this population. The social motivation theory of ASD predicts that impaired function of reward and emotional systems impedes children with ASD from actively engaging with speech. Here we explore this theory by investigating distributed brain systems underlying human voice perception in children with ASD. Using resting-state functional MRI data acquired from 20 children with ASD and 19 age- and intelligence quotient-matched typically developing children, we examined intrinsic functional connectivity of voice-selective bilateral posterior superior temporal sulcus (pSTS). Children with ASD showed a striking pattern of underconnectivity between left-hemisphere pSTS and distributed nodes of the dopaminergic reward pathway, including bilateral ventral tegmental areas and nucleus accumbens, left-hemisphere insula, orbitofrontal cortex, and ventromedial prefrontal cortex. Children with ASD also showed underconnectivity between right-hemisphere pSTS, a region known for processing speech prosody, and the orbitofrontal cortex and amygdala, brain regions critical for emotion-related associative learning. The degree of underconnectivity between voice-selective cortex and reward pathways predicted symptom severity for communication deficits in children with ASD. Our results suggest that weak connectivity of voice-selective cortex and brain structures involved in reward and emotion may impair the ability of children with ASD to experience speech as a pleasurable stimulus, thereby impacting language and social skill development in this population. Our study provides support for the social motivation theory of ASD.


Vasculature of the equine and canine iris.
Methyl methacrylic casts were prepared and tissue was freshly collected for histologic examination to compare the vascular supply and the structure of the vessels of the iris in the adult horse with those of the dog. In the horse, ciliary blood vessels divided in the iris and formed a complete major arterial circle of the iris. In the dog, the ciliary blood vessels divided in the ciliary body and, by means of recurrent branches, formed a complete arterial circle. From this circle, radial arteries extended toward the pupillary margin. The radial vessels in the horse were nearly straight and joined to form a prominent minor arterial circle of the iris at the level of the sphincter pupillae muscle. Radial blood vessels in the horse did not appear to be controlled by the sphincter muscles. Venous blood of the iris of the horse was carried to the ophthalmic vessels via 4 prominent vortex veins. Drainage from the iris of the dog was by way of 4 to 6 circular collecting veins in the ciliary region. From this site, blood passed either via the ciliary veins or via small vortex veins to the dorsal and ventral external ophthalmic and then to the ophthalmic plexus.


Induction of specific chromosomal aberrations by adenovirus type 12 in human embryonic kidney cells.
Nonrandom chromosomal breaks in chromosomes 1 and 17 were provoked in human embryonic kidney cells 24 hr after infection with adenovirus type 12. These chromosomal changes disappeared in persistently infected cultures. Neutralization of the virus with type-specific antiviral serum prior to infection prevented the occurrence of chromosomal aberrations. No viral deoxyribonucleic acid (DNA) synthesis, as determined by autoradiography, was seen in metaphases containing adenovirus type 12-induced chromosomal aberrations. Ultraviolet irradiation of the virus reduced chromosomal aberrations linearly. This reduction in aberrations was fourfold slower than the inactivation of viral infectivity. At 24 hr after infection of cells with purified (3)H-labeled adenovirus type 12, the isotope was found to be associated with the nuclei. The uptake of isotope was reduced ninefold when the labeled virus was neutralized with type-specific antiviral serum. This difference is considered to account for neutralization of labeled virions. In metaphases infected with labeled viruses, most of the clustered grains were seen only on one arm of the chromatid, even after 72 hr. Isochromatid labeling was found, however, in a small percentage of chromosomes, and increased with time after infection. This increase was threefold between 24 and 72 hr after infection, whereas the mean grain counts decreased twofold during the same period. This has been tentatively interpreted to mean that most of the viral DNA molecules or parts thereof are merely attached to cellular chromatin, but a small fraction of them becomes gradually integrated as time proceeds. Certain chromosomal sites appeared to be preferentially labeled when chromosome 2 was used as a model for evaluation.


Expression of a cell surface glycoprotein (p180) related to cell-substratum adhesion during differentiation of mouse myeloid leukemia cells.
Mouse myeloid leukemia M1 cells were induced to differentiate in vitro into macrophages and granulocytes by various inducers including ascitic fluid. Differentiated M1 cells induced with ascitic fluid expressed a differentiation-associated cell surface glycoprotein with a molecular weight of 180,000 (p180), which can be labeled by lactoperoxidase-catalyzed radioiodination or metabolic labeling with L-[14C]fucose. p180 was also induced by treatment with conditioned medium of hamster embryo cells, dexamethasone, dibutyryl cyclic adenosine 3':5'-monophosphate, and prostaglandin E1. Ascitic fluid, conditioned medium of hamster embryo cells, and dexamethasone induced all the differentiation-associated properties tested, whereas dibutyryl cyclic adenosine 3':5'-monophosphate and prostaglandin E1 induced lysozyme activity and adhesiveness to the substratum but not phagocytosis, locomotive activity, Fc receptors, or morphological changes. The adherent cells induced by dibutyryl cyclic adenosine 3':5'-monophosphate produced a large amount of p180, while the floating cells produced very little, but no difference was detected in the lysozyme activities of the two cell types. These results suggest that p180 is associated with cell-substratum adhesion of differentiated M1 cells.


Glucokinase is the likely mediator of glucosensing in both glucose-excited and glucose-inhibited central neurons.
Specialized neurons utilize glucose as a signaling molecule to alter their firing rate. Glucose-excited (GE) neurons increase and glucose-inhibited (GI) neurons reduce activity as ambient glucose levels rise. Glucose-induced changes in the ATP-to-ADP ratio in GE neurons modulate the activity of the ATP-sensitive K(+) channel, which determines the rate of cell firing. The GI glucosensing mechanism is unknown. We postulated that glucokinase (GK), a high-Michaelis constant (K(m)) hexokinase expressed in brain areas containing populations of GE and GI neurons, is the controlling step in glucosensing. Double-label in situ hybridization demonstrated neuron-specific GK mRNA expression in locus ceruleus norepinephrine and in hypothalamic neuropeptide Y, pro-opiomelanocortin, and gamma-aminobutyric acid neurons, but it did not demonstrate this expression in orexin neurons. GK mRNA was also found in the area postrema/nucleus tractus solitarius region by RT-PCR. Intracarotid glucose infusions stimulated c-fos expression in the same areas that expressed GK. At 2.5 mmol/l glucose, fura-2 Ca(2+) imaging of dissociated ventromedial hypothalamic nucleus neurons demonstrated GE neurons whose intracellular Ca(2+) oscillations were inhibited and GI neurons whose Ca(2+) oscillations were stimulated by four selective GK inhibitors. Finally, GK expression was increased in rats with impaired central glucosensing (posthypoglycemia and diet-induced obesity) but was unaffected by a 48-h fast. These data suggest a critical role for GK as a regulator of glucosensing in both GE and GI neurons in the brain.


PTEN degradation after ischemic stroke: a double-edged sword.
Tumor suppressor phosphatase and tensin homolog (PTEN) is highly expressed in neurons and PTEN inhibition has been reported to be neuroprotective against ischemic stroke in experimental models. On the other hand, PTEN deletion has been shown to lead to cognitive impairment. In the current study, we examined the expression and functions of PTEN in an ischemic stroke rodent model. We found rapid S-nitrosylation and degradation of PTEN after cerebral ischemia/reperfusion injury. PTEN degradation leads to activation of Akt. PTEN partial deletion or PTEN inhibition increased the expression of GABAA receptor (GABAAR) γ2 subunit and enhanced GABAA receptor current. After cerebral ischemia, increased expression of GABAAR γ2 subunit was observed in the ischemia region and the penumbra area. We also observed PTEN loss in astrocytes after cerebral ischemia. Astrocytic PTEN partial knockout increased astrocyte activation and exacerbated ischemic damage. We speculated that ischemic stroke induced neuronal PTEN degradation, hence enhanced GABAA receptor-medicated neuronal activity inhibition which could attenuate excitotoxicity and provide neuroprotection during the acute phase after stroke, while inhibiting long-term functional recovery and contributing to vascular cognitive impairment after stroke. On the other hand, ischemic stroke induced astrocytic PTEN loss and enhanced ischemic damage and astrogliosis. Taken together, our study indicates that ischemic stroke induces rapid PTEN degradation in both neurons and astrocytes which play both protective and detrimental action in a spatiotemporal- and cell-type-dependent manner. Our study provides critical insight for targeting PTEN signaling pathway for stroke treatment.


Visual inspection with acetic acid as a feasible screening test for cervical neoplasia in Iran.
The aim of this study was to estimate the sensitivity and specificity of visual inspection of the uterine cervix with acetic acid (VIA) as a screening test for cervical carcinoma and its precursors. One thousand and two hundred eligible women were screened by VIA and Papanicolaou smear. Those positive on one or both of these screening tests (n = 308) or those who had clinically suspicious lesions, even if the tests were negative [25% of remainders (n = 290)], were referred for colposcopy. Three hundred and fifty five of 598 women at colposcopy underwent biopsies or endocervical curettage. Those with cervical intraepithelial neoplasia I (CIN I) or worse lesions, diagnosed by histology, were considered true positive. VIA was positive in 191 women (16.1%). In 175 true-positive cases, VIA detected 130 cases, yielding a sensitivity of 74.3% and a specificity of 94%. By considering atypical squamous cell of undetermined significance or worse lesions on Papanicolaou smear as referring threshold for colposcopy, the sensitivity and specificity of cytology were 72 and 90.2%, respectively. In conclusion, the sensitivity and specificity of VIA is high and comparable with that of cytology. Hence, VIA can be undertaken as a feasible method of screening in cervical cancer in countries where access to cytopathology is limited.


Is the loose anagen hair syndrome a keratin disorder? A clinical and molecular study.
To report the clinical features of the loose anagen hair syndrome and to test the hypothesis that the typical gap between the hair and the inner root sheath may result from hereditary defects in the inner root sheath or the apposed companion layer. Case series. A pediatric dermatology unit (referral center). A consecutive sample of 17 children (13 girls). For 9 of them and their first-degree relatives, molecular analyses were performed in the K6HF gene with 50 appropriate controls. Minoxidil therapy (5% lotion) in 11 patients for 1 to 12 months. Clinical and follow-up features and determination of mutations in the K6HF gene. Most patients had easily pluckable hair with no sign of scalp inflammation or scarring. Ten patients seldom cut their hair, and 4 had unmanageable hair. One patient had hypodontia. Two patients had an additional clinical phenotype of diffuse partial woolly hair. The family history was positive for loose anagen hair syndrome in 5 patients. Marked improvement was noted after treatment with 5% minoxidil lotion in 7 of the 11 patients treated. Polymerase chain reaction analysis of the gene segments encoding the alpha-helical 1A and 2B subdomains of K6hf, the type II cytokeratin exclusively expressed in the companion layer, was performed in 9 families. In 3 of these 9 families, a heterozygous glutamic acid and lysine mutation, E337K, was identified in the L2 linker region of K6HF. Diffuse partial woolly hair can be associated with loose anagen hair syndrome. A keratin mutation, E337K in K6HF, was possibly causative in 3 of the 9 families studied. Another keratin, and possibly the type I partner of K6hf, could be responsible for loose anagen hair syndrome in other patients, or the gene involved may be a minor gene.


Smoking during pregnancy is associated with a decreased incidence of obstetric anal sphincter injuries in nulliparous women.
Smoking is a modifiable lifestyle factor that has been shown to be associated with adverse perinatal outcomes and to have adverse health and dose-dependent connective tissue effects. The objective of this study was to examine whether smoking during pregnancy was associated with the incidence of obstetric anal sphincter injuries (OASIS) among six birthweight groups in singleton vaginal deliveries, considering nulliparous and multiparous women separately between 1997 and 2007 in Finland. A retrospective population-based register study. Populations included women with spontaneous singleton vaginal deliveries, consisting of all 213,059 nulliparous and all 288,391 multiparous women. Incidence of OASIS (n = 2,787) between smoking status groups was adjusted using logistic regression analyses. Of the nulliparous women, 13.1% were smokers, 3.6% had given up smoking during the first trimester of their pregnancy and 81.1% were non-smokers. Among these groups 0.7%, 0.9% and 1.1%, respectively suffered OASIS (p≤0.001). Nulliparous women who smoked had a 28% (95% CI 16-38%, p≤0.001) lower risk of OASIS compared to non-smokers, when adjusting for background variables. In multiparous women, the overall frequencies of OASIS were much lower (0.0-0.2%). A similar inverse relationship between OASIS rates and smoking was significant in pooled univariate analysis of multiparous women, but multivariate analysis revealed statistically insignificant results between non-smokers and smokers. Nulliparous women who were smokers had a 28% lower incidence of OASIS. However, smoking during pregnancy cannot be recommended since it has shown to be associated with other adverse pregnancy outcomes and adverse health effects. The observed association warrants clinical repetition studies and, if confirmed, also in vitro studies focusing on connective tissue properties at a molecular and cellular level.


HCV NS3 protease enhances liver fibrosis via binding to and activating TGF-β type I receptor.
Viruses sometimes mimic host proteins and hijack the host cell machinery. Hepatitis C virus (HCV) causes liver fibrosis, a process largely mediated by the overexpression of transforming growth factor (TGF)-β and collagen, although the precise underlying mechanism is unknown. Here, we report that HCV non-structural protein 3 (NS3) protease affects the antigenicity and bioactivity of TGF-β2 in (CAGA)9-Luc CCL64 cells and in human hepatic cell lines via binding to TGF-β type I receptor (TβRI). Tumor necrosis factor (TNF)-α facilitates this mechanism by increasing the colocalization of TβRI with NS3 protease on the surface of HCV-infected cells. An anti-NS3 antibody against computationally predicted binding sites for TβRI blocked the TGF-β mimetic activities of NS3 in vitro and attenuated liver fibrosis in HCV-infected chimeric mice. These data suggest that HCV NS3 protease mimics TGF-β2 and functions, at least in part, via directly binding to and activating TβRI, thereby enhancing liver fibrosis.


Eye movements in patients with neurodegenerative disorders.
The neural pathways and brain regions involved in eye movements during ocular fixation and gaze control include the cerebrum, brainstem and cerebellum, and abnormal eye movements can indicate the presence of neurodegeneration. In some patients, oculomotor signs are key to making a diagnosis. Careful clinical examination of eye movements in patients with neurodegenerative disorders is, therefore, an invaluable adjunct to neurological and cognitive assessments. Eye movement recordings in the laboratory are generally not necessary for diagnostic purposes, but can be a useful addition to the clinical examination. Laboratory recordings of eye movements can provide valuable information about disease severity, progression or regression in neurodegenerative disease, and hold particular promise for objective evaluation of the efficacy of putative neuroprotective and neurorestorative therapies. For example, aspects of saccade performance can be tested to probe both motor and cognitive aspects of oculomotor behaviour. This Review describes the oculomotor features of the major age-related movement disorders, including Parkinson disease, Huntington disease, dementia and other neurodegenerative disorders. Findings in presymptomatic individuals and changes associated with disease progression are discussed.


Primary carcinoid tumor of the kidney with estrogen and progesterone receptor expression.
Primary carcinoid tumors are uncommon neoplasms in the kidney. The current study presents a case of primary carcinoid tumor of the kidney in a 49-year-old female who suffered from painless gross hematuria for half a month. Left hydronephrosis, a horseshoe kidney and a space-occupying lesion of the left ureter were found by abdominal computed tomography scans and ultrasonic testing. Surgery was performed and an oval tumor was found under the left ureter; the tumor and left kidney were excised completely. The neoplasm was composed of solid nests of cells, trabeculae, adenoid structures and anastomosing cords in a loose and myxoid background. The tumor cells, which were consistent in volume, exhibited centrally oval nuclei with inconspicuous nucleoli, and eosinophilic finely granular cytoplasm. Upon immunohistochemical staining, the neoplastic cells were positive for AE1/AE3, vimentin, synaptophysin, chromogranin A, estrogen receptor and progesterone receptor, while being negative for epithelial membrane antigen, inhibin A, cluster of differentiation (CD)99, S-100 and CD10. Based on the histological characteristics, a diagnosis of primary carcinoid tumor of the left kidney was formed. The patient did not receive further treatment. The total follow-up period was 18 months after the surgery and repeated imaging examinations every 6 months revealed no recurrence.


Isolation of a slowly adhering cell fraction containing stem cells from murine skeletal muscle by the preplate technique.
This protocol details a procedure, known as the modified preplate technique, which is currently used in our laboratory to isolate muscle cells on the basis of selective adhesion to collagen-coated tissue culture plates. By employing this technique to murine skeletal muscle, we have been able to isolate a rapidly adhering cell (RAC) fraction within the earlier stages of the process, whereas a slowly adhering cell (SAC) fraction containing muscle-derived stem cells is obtained from the later stages of the process. This protocol outlines the methods and materials needed to isolate RAC and SAC populations from murine skeletal muscle. The procedure involves mechanical and enzymatic digestion of skeletal muscle tissue with collagenase XI, dispase and trypsin followed by plating the resultant muscle slurry on collagen type I-coated flasks where the cells adhere at different rates. The entire preplate technique requires 5 d to obtain the final preplate SAC population. Two to three additional days are usually required before this population is properly established. We also detail additional methodologies designed to further enrich the resultant cell population by continuing the modified preplating process on the SAC population. This process is known as replating and requires further time.


The Effect of Prenatal Alcohol Exposure on Fetal Growth and Cardiovascular Parameters in a Baboon Model of Pregnancy.
Prenatal alcohol exposure often results in an array of fetal developmental abnormalities termed fetal alcohol spectrum disorders (FASDs). Despite the high prevalence of FASDs, the pathophysiology of fetal damage by alcohol remains poorly understood. One of the major obstacles in studying fetal development in response to alcohol exposure is the inability to standardize the amount, pattern of alcohol consumption, and peak blood alcohol levels in pregnant mothers. In the present study, we used Doppler ultrasonography to assess fetal growth and cardiovascular parameters in response to alcohol exposure in pregnant baboons. Baboons were subjected to gastric alcohol infusion 3 times during the second trimester equivalent to human pregnancy, with maternal blood alcohol levels reaching 80 mg/dL within 30 to 60 minutes following alcohol infusion. The control group received a drink that was isocaloric to the alcohol-containing one. Doppler ultrasonography was used for longitudinal assessment of fetal biometric parameters and fetal cardiovascular indices. Fetal abdominal and head circumferences, but not femur length, were significantly decreased in alcohol-exposed fetuses near term. Peak systolic velocity of anterior and middle cerebral arteries decreased during episodes of alcohol intoxication, but there was no difference in Doppler indices between groups near term. Acute alcohol intoxication affected fetal cerebral blood flow independent of changes in the fetal cardiac output. Unlike fetal growth parameters, changes in vascular indices did not persist over gestation. In summary, alcohol effects on fetal growth and on fetal vascular function have different time courses.


Porcine brachial artery tortuosity for in vivo evaluation of neuroendovascular devices.
We report a novel model of arterial tortuosity in the porcine brachial artery for testing of endovascular devices in the flexed forelimb position. This provides an ideal vascular territory for an in vivo assessment of guidewires, microcatheters, and endovascular implants because it closely mimics the challenging curvature at the carotid siphon.


Demonstration of a vertical pin Ge-on-Si photo-detector on a wet-etched Si recess.
In this paper, we demonstrate a vertical pin Ge-on-Si photo-detector on a wet-etched Si recess on a SOI wafer. A 120 nm-deep Si recess is etched on the SOI wafer with a 340 nm-thick top Si layer by the TMAH solution. The measured results show that the responsivity is more than 0.60 A/W for TE polarization and is more than 0.65 A/W for TM polarization at 1550 nm wavelength. Compared to the photo-detector without the Si recess, the responsivities for both TE and TM polarizations are improved by ~10%. A low dark current of 170 nA is achieved at a bias voltage of -1 V. And, the 3 dB-bandwidth at a bias voltage of -3 V is 21.5 GHz. This approach can be used to improve the coupling and absorption for high responsivity of photo-detector while maintain its high speed on a thick SOI platform based on the simulation results.


Nontransitivity of sperm precedence in Drosophila.
Sperm competition is an important component of fitness in Drosophila, but we still do not have a clear understanding of the unit of selection that is relevant to sperm competition. Here we demonstrate that sperm competitive ability is not a property of the sperm haplotype, but rather of the diploid male's genotype. Then we test whether the relative sperm competitive ability of males can be ranked on a linear array or whether competitive ability instead depends on particular pairwise contests among males. Sperm precedence of six chromosome-extracted lines was tested against three different visible marker lines (cn bw, bwD, and Cy), and the rank order of the six lines differed markedly among the mutant lines. Population genetic theory has shown that departures from transitivity of sperm precedence may be important to the maintenance of polymorphism for genes that influence sperm competitive ability. The nontransitivity seen in sperm precedence should theoretically increase the opportunity for polymorphism in genes that influence this phenotype.


The related adaptors, adaptor in lymphocytes of unknown function X and Rlk/Itk-binding protein, have nonredundant functions in lymphocytes.
Adaptors play a critical role in regulating signaling pathways that control lymphocyte development and activation. Adaptor in lymphocytes of unknown function X (ALX) and Rlk/Itk-binding protein (RIBP) are adaptors related by structure and sequence, coexpressed in T cells. Mice deficient for each adaptor demonstrated that ALX and RIBP, respectively, negatively and positively regulate T cell activation in response to TCR/CD28 stimulation. However, these results did not preclude that they may function redundantly in other cell populations, or in response to other stimuli. Therefore, to understand the relationship between these related adaptors, ALX/RIBP-deficient mice were generated. We demonstrate that although ALX and RIBP are expressed throughout T cell development, T cell development occurs normally in these mice. Using the H-Y TCR transgenic model, positive and negative selection were found to proceed unimpeded in the absence of ALX and RIBP. We demonstrate that RIBP is also expressed in B cells; however, RIBP- and ALX/RIBP-deficient mice had normal B cell development, and responded equivalently to wild type in response to IgM, CD40, B cell-activating factor/B lymphocyte stimulator, CpG, and LPS. Interestingly, T cells deficient in both ALX and RIBP behaved similarly to those deficient in ALX alone during T cell activation in response to TCR/CD28, exhibiting increased IL-2 production, CD25 expression, and proliferation, thus showing that ALX deficiency masked the effect of RIBP deficiency. ALX/RIBP-deficient T cells did not have any alterations in either activation-induced cell death or Th1/2 polarization. Therefore, we did not find any functional redundancy or synergy during lymphocyte development, selection, activation, or survival in ALX/RIBP-deficient mice, demonstrating that these molecules function independently.


[Multidimensional geriatric assessment as clinical approach to the multimorbid patient in acute care].
The multidimensional geriatric assessment is an interdisciplinary diagnostic process, taking into account several health dimensions. The resulting know-ledge is used to establish a treatment plan. The multidimensional geriatric assessment has shown its efficacy in the acute care treatment of multidimensionally ill and polymorbid patients in acute geriatric structures. The multidimensional geriatric assessment plays a central role in questions regarding the allocation of resources and is becoming more important because of the demographic development and the rapidly changing framework in our health system. It ensures that older patients don't slip through the net in a more fragmented clinical medicine. Growing evidence allows using this assessment approach in polymorbid patients being treated in specialised fields as traumatology, cardiology, oncology and nephrology.


[Expression of P27kip1 in renal cell carcinoma and its clinical significance].
To investigate the expression of cyclin-dependent kinase inhibitor p27kip1 in renal cell carcinoma and its clinical significance. The expressions of p27kip1 mRNA and protein were evaluated using reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry with tissue chip technique in renal cell carcinoma (RCC) tissues, adjacent tissues and 786-0 cell line. The relationship between the expression of p27kip1 and the tumor size, the clinical stage, pathological type and stage were evaluated, and the results by the 3 methods were analyzed to evaluate the relationship between the mRNA and protein of p27kip1. The expression of p27kip1 protein (detected by immunohistochemistry and Western blotting) in RCC tissue was significantly lower than that in the adjacent normal tissues (P<0.05). The expression of p27kip1 mRNA (by RT-PCR) showed no significant difference between the two groups. p27kip1 protein expression was found to be inversely correlated to the tumor grade and clinical stage (P<0.05). Western blotting and immunohistochemistry showed a high coincidence rate in the detection of P27kip1 protein expression in RCC samples (P<0.001, K=0.828). p27kip1 mRNA expression shows no difference between RCC and normal tissues, while the protein expression is significantly lower in the cancer tissues, suggesting a regulatory mechanism of p27kip1 expression at the transcriptional level. Low expression of p27kip1 protein may promote the development and progression of RCC. p27kip1 protein may serve as a diagnostic and prognostic marker of RCC.


Considerations and guidance to control the rebound in COVID-19 cases.
Induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, the COVID-19 pandemic has caused a serious crisis for healthcare systems worldwide. COVID-19 vaccine coverage has increased in many countries, but the COVID-19 epidemic has rapidly expanded, with a daily increase of 30,390 COVID-19 cases and 9,761 deaths since August 12, 2021. This article provides a brief overview of growing concerns about a rebound of the COVID-19 pandemic caused by the Delta variant and public health epidemic control measures that have recently been relaxed. As of August 13, 2021, 465,679 cases of COVID-19 due to the Delta variant of SARS-CoV-2 have been detected in over 120 countries. Epidemic control measures were relaxed in some areas, such as allowing large gatherings and improper criteria for ending self-isolation. Even in China, where the epidemic was tightly controlled with strict non-pharmaceutical interventions (NPIs), new COVID-19 cases, and asymptomatic cases in particular, spiked in the first 13 days of August. More importantly, most of those cases were local, while most of the cases accounting for the previous increase were imported. Therefore, relaxed epidemic control measures and asymptomatic infections possibly caused by the Delta variant of SARS-CoV-2 may increase the risk of virus transmission. Accordingly, suggestions for COVID-19 containment, such as encouraging vaccination of the general population, using Internet of Things technology (loT) to reduce the possibility of contact with the asymptomatic infected, and enhancing disease surveillance, have been offered here.


Antisense gene therapy of brain cancer with an artificial virus gene delivery system.
Therapeutic genes are delivered to the nuclear compartment of cancer cells following intravenous administration with a non-immunogenic "artificial virus" gene delivery system that uses receptor-specific monoclonal antibodies (MAb) to navigate the biological barriers between the blood and the nucleus of the cancer cell. Mice implanted with intracranial U87 human glial brain tumors are treated with a nonviral expression plasmid encoding antisense mRNA against the human epidermal growth factor receptor gene (EGFR). The plasmid DNA is packaged within the interior of polyethylene glycol-modified (PEGylated) immunoliposomes, and delivered to the brain tumor with MAbs that target the mouse transferrin receptor (TRFR) and the human insulin receptor (INSR). The mouse TRFR MAb enables transport across the tumor vasculature, which is of mouse brain origin, and the INSR MAb causes transport across the plasma membrane and the nuclear membrane of the human brain cancer cell. The lifespan of the mice treated weekly with an intravenous administration of the EGFR antisense gene therapy packaged within the artificial virus is increased 100% relative to mice treated either with a luciferase gene or with saline.


Babesia odocoilei infection in a Saskatchewan elk (Cervus elaphus canadensis) herd.
An 8-year-old female elk (Cervus elaphus canadensis) cow, presented for chronic severe weight loss and unthriftiness, was diagnosed with Babesia odocoilei infection based on blood smear evaluation, polymerase chain reaction (PCR), and DNA sequence analysis. Subsequently, velvet antler from a male that died acutely on the same farm was also PCR positive for Babesia spp. Both animals originated from a game ranch of Saskatchewan-bred and -raised animals with no known history of tick exposure, but with a history of numerous sudden deaths of unknown etiology. The presence of B. odocoilei in Canada might be a result of a recent introduction that could have deleterious effects on local wild ungulates or may represent discovery of a previously unrecognized endemic disease in local wildlife.


Task-oriented kindergarten behavior pays off in later childhood.
: Research has traditionally neglected child-learning skills as important when entering kindergarten. In this article, we consider a novel dimension of school readiness by examining prospective associations between early classroom engagement skills, reflecting self-regulation and the ability to remain on task, and later academic adjustment in emerging adolescence. : Kindergarten teachers rated classroom engagement skills of 960 children from the Québec Longitudinal Study of Child Development. Outcomes measured at 10-years-old children include a direct assessment of achievement in mathematics and fourth-grade teacher ratings of academic achievement, teacher-child conflict, inattention, victimization, proactive and indirect aggression, and antisocial behavior in the classroom. : Multiple regression analyses revealed that kindergarten classroom engagement skills were associated with better fourth-grade math test scores and teacher-rated academic success. Early classroom engagement also predicted less teacher-child conflict, inattention, victimization by peers, proactive and indirect aggression, and antisocial behavior in fourth grade. : Easily measurable, context-based assessments of task orientation and focus represent robust components of children's readiness to learn at school entry.


Multicentre evaluation of the Thrombotest International Sensitivity Index used with a steel ball coagulometer.
To compare the International Sensitivity Index (ISI) of the Thrombotest reagent used with a steel ball coagulometer (KC) to the ISI of the same reagent used with the manual (tilt tube) technique. The study was carried out by eight laboratories using their own KC instrument and method of testing. All laboratories used the same batch of Thrombotest to determine the clotting times of fresh blood samples from 20 local healthy volunteers and 60 patients on long term oral anticoagulant therapy. KC clotting times were plotted against manual clotting times on double logarithmic scales. Orthogonal regression lines were calculated to assess the ISI. In two laboratories the ISI of the KC method was lower than that of the manual method; these differences, however, were 2% or less. In the other laboratories no clinically important differences were observed between ISI values obtained. However, the clotting times determined with the KC methods were shorter than the manual values. The ISI of Thrombotest determined with the KC methods was very similar to the manual value. Therefore, use of the ISI value supplied by the manufacturer without adjustment is justified. The mean normal prothrombin time, however, must be determined locally.


Primer for nutritionists: Managing the side effects of antidepressants.
Depression is a chronic disease affecting a significant portion of the U.S. Due to the popularity of ADs most nutrition professionals working in the outpatient setting will encounter patients taking one of these medications. Nutritionist can assist patients in managing the short and long term side effects of ADs and, taking into account other nutritional issues, improve overall wellbeing of the patient. The objective of this paper is to identify what side effects nutritionists can help manage, provide the information necessary to help nutritionists feel comfortable assisting with that management, and, as a result, play a valuable role in the team that is vested in the health and wellbeing of the patient.


Sustainability of fisheries through marine reserves: a robust modeling analysis.
Among the many factors that contribute to overexploitation of marine fisheries, the role played by uncertainty is important. This uncertainty includes both the scientific uncertainties related to the resource dynamics or assessments and the uncontrollability of catches. Some recent works advocate for the use of marine reserves as a central element of future stock management. In the present paper, we study the influence of protected areas upon fisheries sustainability through a simple dynamic model integrating non-stochastic harvesting uncertainty and a constraint of safe minimum biomass level. Using the mathematical concept of invariance kernel in a robust and worst-case context, we examine through a formal modeling analysis how marine reserves might guarantee viable fisheries. We also show how sustainability requirement is not necessarily conflicting with optimization of catches. Numerical simulations are provided to illustrate the main findings.


Oral matrix metalloproteinase inhibition and arterial remodeling after balloon dilation: an intravascular ultrasound study in the pig.
Inhibition of matrix metalloproteinase (MMP) activity after balloon angioplasty by intraperitoneal injection of batimastat reduces late lumen loss by inhibition of constrictive remodeling. In the present study, we investigated whether the oral MMP inhibitor marimastat inhibits constrictive remodeling in favor of neutral or expansive remodeling. In 26 pigs, balloon dilation was performed in 101 peripheral arteries. Pigs were treated with marimastat or served as controls and were euthanized 42 days after intervention. Intravascular ultrasound was performed at all time points. Vessel area (VA) loss was assessed by calculating the change in VA at termination relative to after intervention. Arteries were divided in 3 categories: expansive remodeling (VA loss < -5%), neutral (-5% <or= VA loss <or= +5%), and constrictive remodeling (VA loss > +5%). In the marimastat group, a significant reduction (53%) of late lumen loss was observed that was fully explained by impaired constrictive remodeling. In the marimastat group, the prevalence of constrictive remodeling was reduced (38% versus 75% in the control group) in favor of not only neutral but also expansive remodeling (21% and 42% versus 4% and 21% in the control group, respectively, P:<0.01). In contrast to the control group, acute luminal gain in the marimastat group did not correlate with late VA loss. Irrespective of the acute luminal gain by balloon dilation, the oral MMP inhibitor marimastat inhibited constrictive arterial remodeling in favor of both neutral and expansive remodeling.


Structure of the iSH2 domain of human phosphatidylinositol 3-kinase p85β subunit reveals conformational plasticity in the interhelical turn region.
Phosphatidylinositol 3-kinase (PI3K) proteins actively trigger signaling pathways leading to cell growth, proliferation and survival. These proteins have multiple isoforms and consist of a catalytic p110 subunit and a regulatory p85 subunit. The iSH2 domain of the p85β isoform has been implicated in the binding of nonstructural protein 1 (NS1) of influenza A viruses. Here, the crystal structure of human p85β iSH2 determined to 3.3 Å resolution is reported. The structure reveals that this domain mainly consists of a coiled-coil motif. Comparison with the published structure of the bovine p85β iSH2 domain bound to the influenza A virus nonstructural protein 1 indicates that little or no structural change occurs upon complex formation. By comparing this human p85β iSH2 structure with the bovine p85β iSH2 domain, which shares 99% sequence identity, and by comparing the multiple conformations observed within the asymmetric unit of the bovine iSH2 structure, it was found that this coiled-coil domain exhibits a certain degree of conformational variability or `plasticity' in the interhelical turn region. It is speculated that this plasticity of p85β iSH2 may play a role in regulating its functional and molecular-recognition properties.


Manipulating objects with internal degrees of freedom: evidence for model-based control.
There is substantial evidence that humans possess an accurate and adaptable internal model of the dynamics of their arm that is utilized by the nervous system for controlling arm movements. However, it is not known if such model-based strategies are used for controlling dynamical systems outside the body. The need to predict events in the external world is not restricted to the execution of reaching movements or to the handling of rigid tools. Model-based control may also be critical for performing functional tasks with non-rigid objects such as stabilizing a cup of coffee. The present study investigated the strategies used by humans to control simple mass-spring objects. Subjects made straight line reaching movements to a target while interacting with a robotic manipulandum that simulated the dynamics of a one-dimensional mass on a spring. After learning, neither hand nor object kinematics returned to those of free reaching, suggesting that this task was not learned as a perturbation of free reaching. Although there are control strategies (such as slowing the movement of the hand) that would require little or no knowledge of object dynamics, subjects did not adopt these strategies. Instead, they tailored their motor commands to the particular object being manipulated. When object parameters were unexpectedly altered in a way that required no changes in kinematics to successfully complete the task, subjects nonetheless exhibited substantial kinematic deviations. These deviations were consistent with those predicted by a model of the arm-plus-object system driven by a low-impedance controller that incorporated an explicit inverse model of arm-plus-object dynamics. The observed behavior could not be reproduced by a controller that relied on modulating hand impedance alone with no inverse model. These results were therefore consistent with the hypothesis that subjects learn to control the kinematics of manipulated objects by forming an internal model that specified the forces to be exerted by the hand on the object to induce the desired motion of that object.


Distinctive responses in the medial amygdala to same-species and different-species pheromones.
Chemosignals related to reproductive and social status (pheromones) carry messages between opposite-sex and same-sex individuals in many species. Each individual must distinguish signals relevant to its own social behavior with conspecifics from signals used by other (heterospecific) species relevant to their social behavior. In male hamsters, the medial amygdala responded in a categorically different way to conspecific stimuli (socially relevant) and heterospecific stimuli (not socially relevant but serving similar purposes for other species), and may play an important role in this decision. Immediate-early gene responses to conspecific chemosignals and heterospecific chemosignals were characteristically different. The categorical responses, generated by chemosensory input from the vomeronasal organ and (probably) GABA inhibition within the amygdala, were not apparent at more peripheral sensory levels. This is the first evidence for an important role of the amygdala, a limbic structure known to be involved in social and emotional behavior, in discrimination of species specificity in chemosignals.


[Albumin mRNA from rat liver cells. Analysis of immunoadsorption of individual polyribosomes].
The analysis of albumin polyribosomes immunoadsorption is carried out using "sandwich" immunoadsorbents prepared on the basis of two aminobenzylcelluloses: commercial (paraaminobenzylcellulose) and synthesised (methaaminobenzyloxymethylcellulose). A method is worked out which is good for the estimation of the adaptibility of different aminobenzylcellulose preparations as an insoluble basis for the immunoadsorbent. Major properties of the "sandwich" sorbent (the accessible capacity and specificity) and the percent of isolated individual polyribosomes are found to be interrelated and determined by conditions of the immunoadsorption reaction. The increase of polyribosomes and sorbent concentrations and their ratio in the incubation medium results in the increase of the sorbent accessible capacity and the decrease in the inspecific adsorption but at the same time the percent of adsorbed polyribosomes decrease too. The "excess" of adsorbent with respect to polyribosomes, participating in the binding reaction, is necessary for the quantitative isolation of individual polyribosomes.


[Evaluation of the cost of maintenance therapy (6 months) with 150 mg ranitidine vs 20 mg omeprazole vs 20 mg omeprazole every other day in duodenal ulcer].
Prevention of ulcer relapse and of its complications is a problem which remains to be solved. Our study involved 250 patients, with healed duodenal ulcer. We evaluated efficacy and costs of three different maintenance therapies: ranitidine 150 mg/day, omeprazole 20 mg/day every other day and omeprazole 20 mg/day. Six months later, we found the incidence of relapse to be 24.4% (32/131) in the once-a-day ranitidine group, 19.7% (13/66) in the day every-other-day omeprazole group, and 3.8% (2/53) in the once-a-day omeprazole group. Further, we evaluated costs relative to relapsing patients, and total costs for each treatment group. From these data, we conclude that personalized maintenance therapy with omeprazole is the most cost-effective: a dosage of 20 mg/day is extremely effective in maintaining remission, and is therefore most indicated in patients at risk; omeprazole 20 mg/day every-other-day affords better compliance, lower costs and fewer relapses with respect to standard H2-antagonist dosages.


Surgical hyperparathyroidism in calcium stone formers. A retrospective study of 20 cases.
Urinary lithiasis, hypercalciuria and hyperparathyroidism are strictly related diseases, and the urologist diagnoses primary hyperparathyroidism (PHP) in the majority of cases. Herein we retrospectively analyze our experience of 20 cases of surgically proved PHP, operated on in the last 4 years. Hypercalcemia was the keystone for the diagnosis of all our cases PTH radioimmunoassay on selectivity sampled blood revealed a fundamental tool in the management of patients with suspicious or certain hyperparathyroidism. It confirmed the diagnosis in all the cases and gave the preoperative localization of parathyroid adenomas in 70% of the cases. Besides, it made it possible to discriminate between parathyroid adenomas and diffuse hyperplasia preoperatively, so offering a considerable aid to the surgeon in deciding between the conservative and liberal approach to parathyroid surgery. At follow-up, 3 out of 14 cases revealed renal hypercalciuria, which could have been the cause of hyperparathyroidism, as proposed by Reiss and associates previously. The relationship between hypercalciuria and hyperparathyroidism and the problem of a new classification of parathyroid hyperfunction are discussed.