Risk of death for hematological malignancies for residents close to an Italian petrochemical refinery: a population-based case-control study.
We investigated the risk of death for hematological malignancies (HMs) in the area surrounding an Italian petrochemical refinery, where atmospheric concentrations of benzene (known carcinogen) had not been adequately monitored in the past. We performed a population-based case-control study, using conditional logistic regression to estimate odds ratios (ORs) of HM death, with 95 % confidence intervals (CIs), and p trends, in relation to tertiles of time-weighted average residential proximity to the refinery. We identified 177 HM deaths and 349 sex- and age-matched controls from municipal files. Confounding factors were investigated from interviews with consenting relatives for 109 HM deaths and 178 matched controls. For males and females combined, risk of HM death was unrelated to residential proximity. For females, ORs of HM death by increasing tertiles of proximity were 1, 2.74 (95 % CI 1.48-5.09, significant) and 1.49 (95 % CI 0.76-2.92) (p trend 0.184). For the subgroup of persons who plausibly spent most of their time at home (long-term retired, homemakers or unemployed, 53 cases, 79 controls), the ORs of leukemia plus non-Hodgkin lymphoma death (38 cases, 56 controls) by increasing tertiles of proximity were 1, 3.44 (95 % CI 1.04-11.37, significant) and 3.25 (95 % CI 0.82-12.87) (p trend 0.083). No increased risk of HM death for males and females combined living close to the refinery was found. However, the findings for females and a subgroup plausibly spending most of their time at home suggest a relation between increased risk of HM death and residential proximity to the refinery.


Neuronal Ensembles Organize Activity to Generate Contextual Memory.
Contextual learning is a critical component of episodic memory and important for living in any environment. Context can be described as the attributes of a location that are not the location itself. This includes a variety of non-spatial information that can be derived from sensory systems (sounds, smells, lighting, etc.) and internal state. In this review, we first address the behavioral underpinnings of contextual memory and the development of context memory theory, with a particular focus on the contextual fear conditioning paradigm as a means of assessing contextual learning and the underlying processes contributing to it. We then present the various neural centers that play roles in contextual learning. We continue with a discussion of the current knowledge of the neural circuitry and physiological processes that underlie contextual representations in the Entorhinal cortex-Hippocampal (EC-HPC) circuit, as the most well studied contributor to contextual memory, focusing on the role of ensemble activity as a representation of context with a description of remapping, and pattern separation and completion in the processing of contextual information. We then discuss other critical regions involved in contextual memory formation and retrieval. We finally consider the engram assembly as an indicator of stored contextual memories and discuss its potential contribution to contextual memory.


Left ventricular assist devices as bridge to heart transplantation in congestive heart failure with pulmonary hypertension.
Severe pulmonary hypertension (PH) has been considered a significant contraindication to cardiac transplantation. Ongoing clinical experience, however, has shown that temporary support using left ventricular assist devices (LVADs) in these patients can result in significant reductions in PH. A comprehensive review of the available literature regarding the use of LVADs in heart failure patients with PH was conducted. The existing literature to date supports the use of LVADs in heart failure patients with PH and demonstrates that significant reductions in PH in these patients can be achieved. This subsequently allows for safe and effective cardiac transplantation in patients who were previously excluded from this modality. For heart failure patients with severe PH, the use of LVADs can provide significant benefits by significantly reducing PH and allowing subsequent staged transplantation.


An analytical system for rapid separation of tissue nucleotides at low pressures on conventional anion exchangers.
An analytical anion-exchange procedure has been developed for the rapid separation of acid-soluble nucleotides (the so-called "free" or tissue nucleotides). It permits assay at low pressures (275-415 kPa; 40-60 psi) in less than 1 h on 10-cm columns of Aminex resins (conventional styrene-type anion exchangers) with alkaline citrate solutions as the eluent. Separation variables have been investigated, to determine optimum conditions for the routine analysis of samples containing tissue nucleotides. Also described here is a simple solvent-extraction procedure for removing HCIO4 or CCI3CO2H quantitatively from cell extracts that contain acid-soluble nucleotides: they are removed from aqueous acid solutions with a water-insoluble amine dissolved in a water-immiscible solvent.


Genetic variation in Toll-like receptor signalling and the risk of inflammatory and immune diseases.
There has been growing interest in the role of host genetic factors in humans and susceptibility to infectious and inflammatory diseases. Genetic variation in Toll-like receptors (TLRs), key innate immune receptors or their signalling molecules, have been described. Variation in certain TLRs has been linked to disease susceptibility. This genetic variation can result in an altered immune response to pathogenic challenge as well as exorbitant immune activation and inflammation, and thus may influence the pathogenesis or outcome of disease. Examples include variants of TLR4 in sepsis, malaria, inflammatory bowel disease and atherosclerosis; variants in TLR2 in tuberculosis and asthma; a variant in Mal (a key signal for TLR2 and TLR4) in malaria, tuberculosis and systemic lupus erythematosus; and variants in the kinase IRAK4 in pyogenic infections. These associations provide us with a validation for the role of TLRs in human disease, and also suggest possible strategies to limit or boost TLR function in the effort to develop new therapies.


Toward Sustained Product Formation in the Liquid-Phase Hydrogenation of Mandelonitrile over a Pd/C Catalyst.
The liquid-phase hydrogenation of the aromatic cyanohydrin mandelonitrile (MN, C6H5CH(OH)CN) over a carbon-supported Pd catalyst to produce the primary amine phenethylamine (PEA, C6H5CH2CH2NH2) is investigated with respect to the transition from operation in single-batch mode to repeat-batch mode. While a single-batch reaction returns a complete mass balance, product analysis alongside mass balance measurements for a six-addition repeat-batch procedure shows an attenuation in the rate of product formation and an incomplete mass balance from the fourth addition onward. This scenario potentially hinders possible commercial operation of the phenethylamine synthesis process, so it is investigated further. With reference to a previously reported reaction scheme, the prospects of sustained catalytic performance are examined in terms of acid concentration, stirrer agitation rate, catalyst mass, and hydrogen availability. Gas-liquid mass transfer coefficient measurements indicate efficient gas → liquid transfer kinetics within the experimental constraints of the Henry's law limitation on hydrogen solubility in the process solvent (methanol). Deviations from the optimized product selectivity are attributed to mass transport constraints, specifically the H2(solv) → 2H(ads) transition, which is ultimately restrained by the availability of H2(solv). Finally, in an attempt to better understand the deactivation pathways, inelastic neutron scattering measurements on a comparable industrial-grade catalyst operated in an analogous reaction in fed-batch mode indicate the presence of an oligomeric overlayer postreaction. This overlayer is thought to be formed via oligomerization of hydroxyimine or imine species via specific pathways that are identified within a postulated global reaction scheme.


Determination of vertical dimension by hydraulic intraoral jack.
This paper describes the application of a hydraulic intraoral jig to the establishment of the vertical dimension of occlusion for full denture construction. The device enables the patient to establish an occlusal height which is most comfortable without the intervention or guidance of the dentist. Six patients for whom new dentures were to be constructed in the University of Otago School of Dentistry were invited to participate in the study. A conventional technique of denture construction was employed, but an additional stage was introduced after the jaw records had been taken and the casts mounted. Each patient was instructed in the use of the hydraulic jig and was asked to find a comfortable bite height in his own time. The results were compared with occlusal heights determined by conventional subjective methods. The former results proved to be more repeatable than those utilizing rest position and an average free-way space. The results are discussed and the implications outlined. Suggestions for further research using the hydraulic jig are made and the authors conclude that the hydraulic jig may be used to determine vertical dimension for full denture construction.


Unsupervised Simplification of Image Hierarchies via Evolution Analysis in Scale-Sets Framework.
Region-based hierarchical image representation is crucial in many computer vision applications. However, in practice, an image hierarchy is usually dense, and contains many less informative branches. It is expected that a hierarchy should be accurate and simplified, which is not only desirable for different applications, but also saves considerable computational load for the further analysis. To achieve this target, this paper proposes a novel approach for unsupervised simplification of region-based image hierarchies, which employs the global and local evolution analyses of a hierarchy. First, we introduce a global evolution analysis in the scale-sets framework, which provides clues for eliminating less informative branches. Moreover, a hybrid unsupervised simplification method is designed, utilizing the information from global and local evolution functions. A number of experiments on various images have shown that the proposed approach is effective and efficient in removing less informative nodes (averagely about 90% of the whole nodes), while preserving salient image details and retaining the accuracy.


AICRG, Part III: The influence of antibiotic use on the survival of a new implant design.
The American College of Surgeons guidelines suggest that complex oral surgery may benefit from prophylactic antibiotic coverage. The use of preoperative antibiotics, postoperative antibiotics, or both during implant placement is a widely accepted practice in the United States, whereas dentists in other countries rarely use antibiotics. The purpose of this study was to determine if antibiotic coverage at the time of implant placement improves the survival of the Ankylos implant. As part of a comprehensive, multicentered, multidisciplinary, prospective, independent, international clinical study, designed and coordinated in the United States by the Ankylos Implant Clinical Research Group (AICRG), the use of preoperative (several regimens) and postoperative antibiotics (yes/no) were carefully documented to assess their influence on improving survival. A total of 1500 Ankylos implants were placed and followed for a period of 3 to 5 years. The decision to use antibiotics and the regimen to be employed was made by the treating surgeon. Failure was defined as removal of the implant for any reason. All data were entered into a computerized database for analysis. The use of preoperative antibiotics produced no significant improvement (P = .21, Fisher's exact test) in survival compared with those placed without antibiotic coverage. There was no significant difference between the regimens defined as AHA-1990, AHA-1997, and Peterson's recommendations. The results of this study suggest that there was little or no advantage to providing antibiotic coverage when placing this implant. These findings also suggest that the use of antibiotics for implant placement may not be as beneficial as once believed. If validated by other studies, the elimination of this practice for routine implant placement would represent a small but significant step forward in the reduction of unnecessary antibiotic use.


Ghost marker detection and elimination in marker-based optical tracking systems for real-time tracking in stereotactic body radiotherapy.
To propose a simple model to explain the origin of ghost markers in marker-based optical tracking systems (OTS) and to develop retrospective strategies to detect and eliminate ghost markers. In marker-based OTS, ghost markers are virtual markers created due to the cross-talk between the two camera sensors, which can lead to system execution failure or inaccuracy in patient tracking. As a result, the users have to limit the number of markers and avoid certain marker configurations to reduce the chances of ghost markers. In this work, the authors propose retrospective strategies to detect and eliminate ghost markers. The two camera sensors were treated as mathematical points in space. The authors identified the coplanar within limit (CWL) condition as the necessary condition for ghost marker occurrence. A simple ghost marker detection method was proposed based on the model. Ghost marker elimination was achieved through pattern matching: a ghost marker-free reference set was matched with the optical marker set observed by the OTS; unmatched optical markers were eliminated as either ghost markers or misplaced markers. The pattern matching problem was formulated as a constraint satisfaction problem (using pairwise distances as constraints) and solved with an iterative backtracking algorithm. Wildcard markers were introduced to address missing or misplaced markers. An experiment was designed to measure the sensor positions and the limit for the CWL condition. The ghost marker detection and elimination algorithms were verified with samples collected from a five-marker jig and a nine-marker anthropomorphic phantom, rotated with the treatment couch from -60° to +60°. The accuracy of the pattern matching algorithm was further validated with marker patterns from 40 patients who underwent stereotactic body radiotherapy (SBRT). For this purpose, a synthetic optical marker pattern was created for each patient by introducing ghost markers, marker position uncertainties, and marker displacement. The sensor positions and the limit for the CWL condition were measured with excellent reproducibility (standard deviation ≤ 0.39 mm). The ghost marker detection algorithm had perfect detection accuracy for both the jig (1544 samples) and the anthropomorphic phantom (2045 samples). Pattern matching was successful for all samples from both phantoms as well as the 40 patient marker patterns. The authors proposed a simple model to explain the origin of ghost markers and identified the CWL condition as the necessary condition for ghost marker occurrence. The retrospective ghost marker detection and elimination algorithms guarantee complete ghost marker elimination while providing the users with maximum flexibility in selecting the number of markers and their configuration to meet their clinic needs.


Comparison Between the Fecal Bacterial Microbiota of Healthy and Diarrheic Captive Musk Deer.
Diarrhea constitutes one of the most common diseases affecting the survival of captive musk deer and is usually caused by an imbalance in intestinal microbiota. Currently, research regarding the structure and function of intestinal microbiota in diarrheic musk deer is lacking. Therefore, in the present study, high-throughput 16S-rRNA gene sequencing was used to analyze the intestinal microbiota in feces of healthy captive musk deer (HMD) (n = 8) and musk deer with mild (MMD) (n = 8), and severe (n = 5) (SMD) diarrhea to compare the difference in intestinal microbiota of musk deer under various physiological conditions. The results showed that the diversity of HMD fecal microbiota was significantly higher than that of the two diarrhea samples. β Diversity results indicated that there were extremely significant differences in bacterial communities between the HMD sample and the MMD and SMD samples. However, no significant difference was found between the two diarrhea samples. LefSe analysis showed that the degree of intestinal physiological dysfunction in musk deer was correlated with the types of major pathogens. The main pathogen in the MMD group is Escherichia-Shigella, whereas Fusobacterium is the main pathogen in the SMD group. PICRUSt functional profile prediction indicated that the intestinal microbiota disorder could also lead to changes in the abundance of genes in metabolic pathways of the immune system. Altogether, this study provides a theoretical basis for the exploration of treatments for diarrhea in captive musk deer, which is of considerable significance to the implementation of the musk deer release into the wild program.


Principles of nidotherapy in the treatment of persistent mental and personality disorders.
The principles of a psychological intervention for psychiatric disorders, nidotherapy, are described following its use in the treatment of patients with severe mental illness, most of whom also have personality disorders. Nidotherapy is the collaborative systematic assessment and modification of the environment to minimise the impact of any form of mental disorder on the individual or on society. It is particularly appropriate to consider for chronic and recurring disorders in which there is no prospect of short-term improvement. An analysis of the treatment suggests its main tenets are the development of a joint consensus (collateral collocation) of environmental change needed, formulation of targets, consequent monitoring and adjustments made to test the effectiveness of intervention, and a joint structure (arbitrage solving) to adjudicate when changes are considered feasible or impractical by one party and not the other. Case vignettes are used to describe the main features of the treatment. Although nidotherapy includes some of the elements of cognitive, occupational and family therapy, and even social work, it is different in that it focuses on changing the environment, not the person. It is therefore much more acceptable to those patients who have repeatedly challenged the justification of conventional therapy for their conditions. Nidotherapy deserves further enquiry as a useful addition to existing psychological treatments.


Gluon thermodynamics at intermediate coupling.
We calculate the thermodynamic functions of Yang-Mills theory to three-loop order using the hard-thermal-loop perturbation theory reorganization of finite temperature quantum field theory. We show that at three-loop order hard-thermal-loop perturbation theory is compatible with lattice results for the pressure, energy density, and entropy down to temperatures T approximately 2-3T{c}.


Health Equity and Antibiotic Prescribing in the United States: A Systematic Scoping Review.
We performed a scoping review of articles published from 1 January 2000 to 4 January 2022 to characterize inequities in antibiotic prescribing and use across healthcare settings in the United States to inform antibiotic stewardship interventions and research. We included 34 observational studies, 21 cross-sectional survey studies, 4 intervention studies, and 2 systematic reviews. Most studies (55 of 61 [90%]) described the outpatient setting, 3 articles were from dentistry, 2 were from long-term care, and 1 was from acute care. Differences in antibiotic prescribing were found by patient's race and ethnicity, sex, age, socioeconomic factors, geography, clinician's age and specialty, and healthcare setting, with an emphasis on outpatient settings. Few studies assessed stewardship interventions. Clinicians, antibiotic stewardship experts, and health systems should be aware that prescribing behavior varies according to both clinician- and patient-level markers. Prescribing differences likely represent structural inequities; however, no studies reported underlying drivers of inequities in antibiotic prescribing.


Ultradian pulsatility of plasma glucose and insulin secretion rate: circadian and sleep modulation.
Insulin release is a complex oscillatory process with rapid pulses (10 min) superimposed on slower circhoral oscillations (50-100 min). The exact mechanism of the circhoral oscillations, which are probably in part the consequence of a negative feedback loop linking glucose and insulin secretion rate, remains unclear. Stimulatory effects of sleep on insulin secretion are achieved by an enhancement of the oscillation amplitude which could be partly mediated by GH. The different patterns observed after acute or chronic shift of sleep suggest however an interaction between sleep influence and circadian rhythmicity, as described for numerous pituitary hormones. The intra-sleep awakenings have a modulatory effect on glucose levels but no systematic relationship exists between glucose or insulin secretion rate oscillations and the REM-NREM sleep cycles. Irrespective of the mechanisms involved, sleep or GH stimulatory effects result from a modulation of the oscillation amplitude rather than of their frequency which is probably an important feature of insulin efficacy.


Neural Correlates of Food Cue Exposure Intervention for Obesity: A Case-Series Approach.
People with overweight have stronger reactivity (e.g., subjective craving) to food cues than lean people, and this reactivity is positively associated with food intake. Cue reactivity is a learned response that can be reduced with food cue exposure therapy. It was hypothesized that participants after food cue exposure therapy would show reduced neural activity in brain regions related to food cue reactivity and increased neural activity in brain regions related to inhibitory-control as compared to participants receiving a control lifestyle intervention. Neural activity of 10 women with overweight (BMI ≥ 27 kg/m2) in response to individually tailored visually presented palatable high-caloric food stimuli was examined before vs. after a cue exposure intervention (n = 5) or a control lifestyle (n = 5) intervention. Data were analyzed case-by-case. Neural responses to food stimuli were reduced in food-cue-reactivity-related brain regions after the lifestyle intervention in most participants, and generally not after the cue exposure therapy. Moreover, cue exposure did not lead to increased activity in inhibitory-control-related brain regions. However, decreased neural activity after cue exposure was found in most participants in the lateral occipital complex (LOC), which suggests a decreased visual salience of high-caloric food stimuli. Receiving a cue exposure therapy did not lead to expected neural responses. As cue exposure relies on inhibitory learning mechanisms, differences in contexts (e.g., environments and food types) between the intervention setting and the scanning sessions may explain the general lack of effect of cue-exposure on neural activity.


Preoperative platelet-lymphocyte ratio is superior to neutrophil-lymphocyte ratio as a prognostic factor for soft-tissue sarcoma.
Inflammation can promote tumor growth, invasion, angiogenesis and even metastasis. Inflammatory markers have been identified as prognostic indicators in various malignances. This study compared the usefulness of platelet-lymphocyte ratio (PLR) with that of neutrophil-lymphocyte ratio (NLR) for predicting outcomes of patients who underwent radical resection for soft tissue sarcoma (STS). We included 222 STS patients in this retrospective study. Kaplan-Meier curves and multivariate Cox proportional models were used to calculate overall survival (OS) and disease free survival (DFS). In univariate analysis, elevated PLR and NLR were both significantly associated with decreased OS. In multivariate analysis, PLR (HR: 2.60; 95 % CI: 1.17-5.74, P = 0.019) but not NLR was still identified as independent predictors of outcome. Median OS was 62 and 76 months for the high PLR and low PLR groups, respectively. High PLR and NLR were both significantly associated with shorter DFS in univariate analysis, with median DFS of 18 and 57 months in the high PLR and low PLR groups. In multivariate analysis, elevated PLR (HR: 1.77; 95 % CI: 1.05-2.97, P = 0.032) was also related to decreased DFS. Our findings provide a new and valuable clue for diagnosing and monitoring STS. Prediction of disease progression is not only determined by the use of clinical or histopathological factors including tumor grade, tumor size, and tumor site but also by host-response factors such as performance status, weight loss, and systemic inflammatory response. They also significantly affect clinical outcomes. Thus, PLR can be used to enhance clinical prognostication. Furthermore, the PLR can be assessed from peripheral blood tests that are routinely available without any other complicated expenditure, thus providing lower cost and greater convenience for the prognostication. Elevated preoperative PLR as an independent prognostic factor is superior to NLR in predicting clinical outcome in patients with STS.


Identification and quantitative determination of fentanyl metabolites in patients by gas chromatography--mass spectrometry.
Although fentanyl has been used widely as a short-acting narcotic analgesic, its metabolism in humans has not been clarified. In this study, three fentanyl metabolites were identified in the urine of eight surgical patients receiving 0.3-0.5 mg of fentanyl intravenously. The metabolites 4-N-(N-propionylanilino)piperidine, 4-N-(N-hydroxypropionylanilino)piperidine and 1-(2-phenethyl)-4-N-(N-hydroxypropionylanilino)piperidine, and unchanged fentanyl were identified by GC-mass spectrometry in urine collected 6 h after administration. Fentanyl and its main metabolite, 4-N-(N-propionylanilino)piperidine, were determined quantitatively in the urine of five additional patients receiving 0.5 mg fentanyl intravenously. Urinary excretion of fentanyl and 4-N-(N-propionylanilino)-piperidine during the first 12 h after injection accounted for 0.3-4.0% and 26 to 55% of the dose, respectively.


Tissue factor-dependent activation of platelets by cells and microvesicles of SK-OS-10 human osteogenic sarcoma cell line.
Cultured SK-OS-10 cells (human osteogenic sarcoma metastatic to lung) shed microvesicles (dia. 300-1000 nm) that contained procoagulant and proaggregatory activities inhibitable by hirudin, by anti-tissue factor antibody and by phospholipase A2. These results show that SK-OS-10 cells belong to a group including U87MG human glioblastoma and HL-60 promyelocytic leukemia in which these activities are due to a thrombin-dependent mechanism arising from the presence of tissue factor on the surface of the tumor cells and their shed microvesicles.


Risk Factors for Wound Complications After Direct Anterior Approach Hip Arthroplasty.
Previous studies have suggested that wound complications may be higher after direct anterior approach (DAA) hip arthroplasty, but, specific risk factors have not been closely examined. We conducted a retrospective case-control study of 651 consecutive DAA hip arthroplasty surgeries performed by 2 surgeons over a 3-year period. Outcome measures included any postoperative wound problem (including prolonged drainage, wound dehiscence, wound necrosis, suture granuloma, and superficial infection) requiring additional intervention or reoperation. Univariate odds ratios (ORs) were calculated, and multivariate logistic regression analysis was performed to determine risk correlation. Receiver operator characteristic (ROC) curves were created to determine disease predictability. A total of 75 patients (11.5%) experienced wound complications requiring additional intervention, of which, 13 (1.9%) required reoperation. Multivariate regression analysis found that development of wound complications was significantly and independently associated with body mass index (BMI) 30-35 kg/m2 (OR 2.05; 95% confidence interval [CI] 1.08-3.88), BMI 35-40 kg/m2 (OR 3.40; 95% CI 1.42-8.26), BMI > 40 kg/m2 (OR 7.28; 95% CI 2.55-20.78), and diabetes mellitus (OR 2.97; 95% CI 1.46-6.07). Reoperation for wound complication was significantly associated with BMI > 40 kg/m2 (OR 5.68; 95% CI 1.17-27.48) and diabetes mellitus (OR 13.08; 95% CI 3.97-43.11). Optimal cutoff values for BMI were found through receiver operator characteristic curve analysis to be 28.0 kg/m2 for development of wound complications and 28.2 kg/m2 for reoperation for wound complications. Obesity and diabetes mellitus are significantly associated with postoperative wound-healing complications and the need for reoperation for these wound complications after DAA hip arthroplasty.


Endometrial stromal tumors: the new WHO classification.
Endometrial stromal tumors are rare uterine mesenchymal neoplasms that have intrigued pathologists for years, not only because they commonly pose diagnostic dilemmas, but also because the classification and pathogenesis of these tumors has been widely debated. The current World Health Organization recognizes 4 categories of endometrial stromal tumor: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS). uterine sarcoma. These categories are defined by the presence of distinct translocations as well as tumor morphology and prognosis. Specifically, the JAZF1-SUZ12 (formerly JAZF1-JJAZ1) fusion identifies a large proportion of ESN and LG-ESSs, whereas the YWHAE-FAM22 translocation identifies HG-ESSs. The latter tumors appear to have a prognosis intermediate between LG-ESS and UUS, which exhibits no specific translocation pattern. This review (1) presents the clinicopathologic features of endometrial stromal tumors; (2) discusses their immunophenotype; and (3) highlights the recent advances in molecular genetics which explain their pathogenesis and lend support for a new classification system.


Dementia severity and pattern of cognitive performance in vascular dementia.
We evaluated the influence of dementia severity on cognitive performance in two groups of individuals with vascular dementia (VaD). Performance on the Mini-Mental State Exam (MMSE) was used to determine dementia severity. Tests of executive function, psychomotor speed, memory, language, and visuospatial function were administered. As expected, individuals with severe VaD (MMSE < 18) performed significantly more poorly than individuals with mild VaD (MMSE > or = 18) on most tests. More important, deficits were evident for both groups in each cognitive domain when compared to normative data. These results indicate that multiple cognitive domains are affected even in mild cases of VaD. Clinicians should be aware that although the presence of "patchy" cognitive deficits may indicate stroke, general cognitive dysfunction may occur in mild cases of VaD.


Genetic heterogeneity in sporadic colorectal adenomas.
The majority of colorectal cancers develop from adenomatous polyps under the influence of factors that are still poorly understood. Tumourigenesis is generally considered a multistep process in which multiple genetic alterations occur, eventually reflected in abnormalities of the cellular DNA content. Macroscopical features such as tumour size and tumour architecture (tubular, tubulovillous, or villous) are correlated wit the chance of malignancy in the lesion. Grade of dysplasia can be considered an indicator for the level of progression of the adenoma towards invasive carcinoma. These characteristics were correlated with the presence or absence of K-ras mutations and the DNA ploidy in a prospective study performed on 46 large sporadic colorectal adenomas resected by endoscopy. DNA ploidy and K-ras mutations were analysed in two samples taken at distant sites in the adenomas. Aneuploidy was present in 12 adenomas (26 per cent) and K-ras mutations occurred in 26 (57 per cent). A highly significant correlation was found between aneuploidy and adenoma size, architecture, and grade of dysplasia. The presence of K-ras mutations was significantly correlated only with the size of the adenomas. The proportion of adenomas with aneuploidy and/or a K-ras mutation increased when two samples were analysed instead of one. This observation suggests that the prevalence of genetic mutations and of aneuploidy is probably underestimated, as generally only one sample is investigated. No correlation was observed between K-ras mutations and ploidy. This study demonstrates the presence of genetic heterogeneity in colorectal adenomas and supports the notion that K-ras mutation is an early event, while aneuploidy is a late event in the adenoma-carcinoma sequence.


IS THE EXTREMELY LOW HETEROZYGOSITY LEVEL IN YPONOMEUTA RORELLUS CAUSED BY BOTTLENECKS?
Among the common and widespread species of the small ermine moths (Yponomeuta) the almost complete absence of genetic variability from a sample of 75 protein loci is a striking feature of Y. rorellus. Congeners exhibit normal to high H levels. At least for soluble proteins, this variation estimate is a real one, not resulting from an inability of the zymogram technique to detect variation nor from a biased sample of loci. The most likely explanation for the dearth of variation observed is a bottleneck at the species' origin. Moreover, ongoing population-size fluctations in the historical past of Y. rorellus may have prevented the recovery of equilibrium H levels as a consequence of genetic drift in small populations.


Squamous metaplasia of the tracheal epithelium in children.
Thirty-seven (1-6%) tracheas from 2170 children showed squamous metaplasia. (Cases with tracheo-oesophageal fistula and congenital heart disease were excluded). The metaplasia extended into the bronchi in 15 cases. Features of pulmonary retention were present in seven cases. Respiratory infection, probably viral, seemed to be the most significant causative factor in 20 children, including those with cystic fibrosis. Tracheal instrumentation was a possible factor in 11 cases but oxygen therapy alone did not seem important. The metaplasia was almost certainly congenital in one child and probably in two others but no stillborn infants showed metaplasia. In many children the metaplasia seemed to be due to a combination of factors.


Psychological preparation for nasogastric feeding in children.
Psychological preparation of children undergoing enteral nutrition by nasogastric tube was evaluated in a prospective study of 48 children nursed at home. They were randomly allocated to receive either standard informal preparation or detailed psychological preparation and support. The children were divided into two groups according to age: group A comprised toddlers and younger children aged 2-6 years and group B comprised older children and adolescents aged 7-16 years. Detailed questionnaires were administered to all parents and older children by dietetic colleagues who were blinded to the type of preparation received by the children. The results emphasize that detailed psychological preparation of families takes time. Passage of a nasogastric tube was seen as very distressing to both parents and children. Having a nasogastric tube was perceived as a major problem by group A. There was no statistical difference in the effects of enteral nutrition between younger children who received routine preparation and those who received detailed preparation; however, parental assessment of their child's behaviour was the sole means of determining how the younger child felt and reacted. In group B, there were marked differences: scores suggested that those who received detailed preparation had been better prepared for enteral feeding in hospital and at home and that the passage of the nasogastric tube, although unpleasant, was less distressing to them (P < 0.05). Talking to a nurse and play therapist was seen by parents as essential (P < 0.05). The authors conclude that children should be prepared for painful procedures and followed up sensitively, according to their needs.


Examining the association between music lessons and intelligence.
Although links between music training and cognitive abilities are relatively well-established, unresolved issues include the generality of the association, the direction of causation, and whether the association is mediated by executive function. Musically trained and untrained 9- to 12-year olds were compared on a measure of IQ and five measures of executive function. IQ and executive function were correlated. The musically trained group had higher IQs than their untrained counterparts and the advantage extended across the IQ subtests. The association between music training and executive function was negligible. These results provide no support for the hypothesis that the association between music training and IQ is mediated by executive function. When considered jointly with the available literature, the findings suggest that children with higher IQs are more likely than their lower-IQ counterparts to take music lessons, and to perform well on a variety of tests of cognitive ability except for those measuring executive function.


Splanchnic release of neuropeptide Y during prolonged exercise with and without beta-adrenoceptor blockade in healthy man.
Plasma levels of neuropeptide Y- (NPY-) like immunoreactivity (Li) and catecholamines in the brachial artery, femoral vein and hepatic vein were monitored during physical exercise in a total of 19 healthy men to detect any local release from the leg and splanchnic region. In addition, propranolol (0.15 mg kg-1 i.v.) was given during exercise to determine whether beta-adrenoceptor blockade influenced the increase in plasma NPY-Li and catecholamines. Leg and splanchnic blood flows were measured using indicator dilution techniques and indocyanine green dye. Graded arm exercise was associated with elevations of arterial plasma NPY-Li (two-fold) and noradrenaline (12-fold) comparable to those previously found during leg exercise. During prolonged leg exercise a significant vasoconstriction and release of NPY-Li and noradrenaline was observed in the splanchnic region while no net exchange was found in the exercising leg where marked vasodilatation occurred. Administration of propranolol during exercise produced a clear-cut additional increase in plasma NPY-Li as well as in noradrenaline and adrenaline. It is concluded that splanchnic vasoconstriction during exercise is associated with a local release of both NPY-Li and noradrenaline. The additional elevation in plasma NPY-Li and catecholamines after propranolol during exercise is probably due to increased nerve activity and/or decreased disposal.


Tumoral calcinosis demonstrated on Tc-99m sestamibi scintigraphy.
A 61-year-old uremic male under hemodialysis underwent Tc-99m sestamibi scintigraphy due to suspicious secondary hyperparathyroidism. The images showed increased uptake in the right forearm, left shoulder, right knee and, to a lesser extent, in the left hip and the right thigh. Subsequent Tc-99m MDP bone scintigraphy and x-ray studies revealed intense extraosseous uptake and calcified masses in areas corresponding to those found in Tc-99m sestamibi scintigraphy, suggesting tumoral calcinoses. We demonstrate the rare case in which Tc-99m sestamibi was taken up by tumoral calcinoses.


Simvastatin and metformin inhibit cell growth in hepatitis C virus infected cells via mTOR increasing PTEN and autophagy.
Hepatitis C virus (HCV) infection has been related to increased risk of development of hepatocellular carcinoma (HCC) while metformin (M) and statins treatment seemed to protect against HCC development. In this work, we aim to identify the mechanisms by which metformin and simvastatin (S) could protect from liver cancer. Huh7.5 cells were infected with HCV particles and treated with M+S. Human primary hepatocytes were treated with M+S. Treatment with both drugs inhibited Huh7.5 cell growth and HCV infection. In non-infected cells S increased translational controlled tumor protein (TCTP) and phosphatase and tensin homolog (PTEN) proteins while M inhibited mammalian target of rapamycin (mTOR) and TCTP. Simvastatin and metformin co-administered down-regulated mTOR and TCTP, while PTEN was increased. In cells infected by HCV, mTOR, TCTP, p62 and light chain 3B II (LC3BII) were increased and PTEN was decreased. S+M treatment increased PTEN, p62 and LC3BII in Huh7.5 cells. In human primary hepatocytes, metformin treatment inhibited mTOR and PTEN, but up-regulated p62, LC3BII and Caspase 3. In conclusion, simvastatin and metformin inhibited cell growth and HCV infection in vitro. In human hepatocytes, metformin increased cell-death markers. These findings suggest that M+S treatment could be useful in therapeutic prevention of HCV-related hepatocellular carcinoma.


Clinical, motor, and biological correlates of depressive disorders after focal subcortical lesions.
The authors studied depression after focal subcortical lesions (SCLs) in 45 highly selected subjects. Secondary major depression (secondary MD) occurred in 20.0%, depressive disorder NOS (secondary DDNOS) in 4.4%, and secondary dysthymia in 0.0%. secondary MD after SCLs was associated with pallidal lesions (88.9%) and dystonia without geste antagonistique; subjects with secondary DDNOS had nigrotegmental lesions and parkinsonism. Depressive severity after SCLs correlated positively with severity of parkinsonism and dystonia. Pallidal lesions disrupting neurotransmitter systems and pallidothalamic and parietal input to the frontal lobe may lead to secondary MD, whereas nigrotegmental lesions may predispose to secondary MD forme fruste (secondary DDNOS) through disruption of mesocortical frontal or nigrostriatal dopamine tracts. Patients should be closely followed over several years for depression after such lesions, especially when accompanied by parkinsonism or dystonia without geste antagonistique.


Development of UK guidance on the management of erectile dysfunction resulting from radical radiotherapy and androgen deprivation therapy for prostate cancer.
To develop a management strategy (rehabilitation programme) for erectile dysfunction (ED) after radiotherapy (RT) or androgen deprivation therapy (ADT) for prostate cancer that is suitable for use in a UK NHS healthcare context. PubMed literature searches of ED management in this patient group together with a survey of 28 experts in the management of treatment-induced ED from across the UK were conducted. Data from 19 articles and completed questionnaires were collated. The findings discussed in this article confirm that RT/ADT for prostate cancer can significantly impair erectile function. While many men achieve erections through PDE5-I use, others need combined management incorporating exercise and lifestyle modifications, psychosexual counselling and other erectile aids. This article offers a comprehensive treatment algorithm to manage patients with ED associated with RT/ADT. Based on published research literature and survey analysis, recommendations are proposed for the standardisation of management strategies employed for ED after RT/ADT. In addition to implementing the algorithm, understanding the rationale for the type and timing of ED management strategies is crucial for clinicians, men and their partners.


Before the big time: early history of the Training School at Vineland, 1888 to 1949.
Leaders of the Training School at Vineland made major contributions to the field of mental retardation from 1890 to 1940. S. O. Garrison originated the cottage plan and emphasized education and self-support. E. R. Johnstone pioneered teacher training, published a journal, initiated social action programs, and established a research laboratory. H. H. Goddard standardized the Binet-Simon scales in the United States, validated heredity as a cause of mental retardation, and hosted the production of the first group intelligence tests. S. D. Porteus supplemented the Binet with measures of personality. E. A. Doll established that birth injury could cause mental retardation, investigated the educability of profoundly retarded individuals, produced the Vineland Social Maturity Scale, and fostered electroencephalographic research.


Sexual risk behavior, sexually transmitted infections, and HIV transmission risks in HIV-positive men who have sex with men (MSM) - approaches for medical prevention.
Rising incidence rates of HIV and STIs (sexually transmitted infections) among MSM (men who have sex with men) in Germany since 2001 call for new approaches in medical prevention. The present study addresses appropriate parameters to identify those HIV-positive MSM who are at high risk for transmitting HIV and STIs. Over a two-year period, 223 HIV-positive MSM attending the HIV outpatient clinic at the University Medical Center Essen (Germany) were systematically surveyed with respect to their sexual behavior, substance abuse, and psychological well-being in the preceding year. Data analyzed included laboratory and clinical data from the time of the initial HIV diagnosis until January 2014. In HIV-positive MSM, a history of substance abuse, promiscuity, younger age, and known STIs was associated with a greater incidence of unprotected sexual intercourse and STIs. Apart from a detectable viral load, additional HIV-specific parameters associated with an increased HIV transmission risk included untreated HIV infection, adherence problems, changes in antiretroviral treatment over the preceding twelve months, known multiresistant HIV infection, and a higher CD 4 nadir. Despite routine quarterly monitoring of viral loads - the result thereof was communicated to patients - only 60 % of individuals assessed their HIV transmission risk correctly. In HIV-positive MSM, patient history and routine laboratory tests allow for the establishment of patient profiles that suggest sexual behavior associated with a high risk of HIV and STI transmission, thus offering new approaches for medical prevention.


[Exploration on the Construction of Intensive Care Clinical Information Management System].
This study introduces the feasibility study experience of intensive care clinical information management system in order to provide reference for the construction of intensive care clinical information management system in other hospitals. Four kinds of mainstream intensive care clinical information management system software were used to evaluate the implementation effect of each software such as equipment integration, information integration and application function module, so as to explore the construction scheme of intensive care clinical information management system. The optimized construction scheme and comprehensive feasibility study report of intensive care clinical information management system were formed, which provided an objective basis for the final scheme design, demonstration, procurement and decision-making of the hospital. The trial and feasibility study of intensive care clinical information management system contribute to optimize the construction scheme.


Thermometry of bosonic mixtures in Optical Lattices via Demixing.
Motivated by recent experiments and theoretical investigations on binary mixtures, we investigate the miscible-immiscible transition at finite temperature by means of Quantum Monte Carlo. Based on the observation that the segregated phase is strongly affected by temperature, we propose to use the degree of demixing for thermometry of a binary bosonic mixture trapped in an optical lattice. We show that the proposed method is especially sensitive at low temperatures, of the order of the tunnelling amplitude, and therefore is particularly suitable in the regime where quantum magnetism is expected.


Interleukin genes and associations with colon and rectal cancer risk and overall survival.
Interleukins are a group of cytokines that contribute to growth and differentiation, cell migration, and inflammatory and anti-inflammatory responses by the immune system. In our study, we examined genetic variation in genes from various anti-inflammatory and proinflammatory interleukins to determine association with colon and rectal cancer risk and overall survival. Data from two population-based incident studies of colon cancer (1,555 cases and 1,956 controls) and rectal cancer (754 cases and 954 controls) were used. After controlling for multiple comparisons, single nucleotide polymorphisms (SNPs) from four genes, IL3, IL6R, IL8, IL15, were associated with increased colon cancer risk, and CXCR1 and CXCR2 were significantly associated with increased rectal cancer risk. Only SNPs from genes within the IL-8 pathway (IL8, CXCR1 and CXCR2) showed a significant association with both colon and rectal cancer risk. Several SNPs interacted significantly with IL8 and IFNG SNPs and with aspirin/non-steroidal anti-inflammatory drug (NSAID), cigarette smoking, estrogen use and BMI. For both colon and rectal cancer, increasing numbers of risk alleles were associated with increased hazard of death from cancer; the estimated hazard of death for colon cancer for the highest category of risk alleles was 1.74 (95% confidence interval [CI] 1.18-2.56) and 1.96 (95% CI 1.28-2.99) for rectal cancer. These data suggest that interleukin genes play a role in risk and overall survival for colon and rectal cancer.


Traction fibre: toward a "tensegral" model of the spindle.
Most current hypotheses of mitotic mechanisms are based on the "PAC-MAN" paradigm in which chromosome movement is generated and powered by disassembly of kinetochore microtubules (k-MTs) by the kinetochore. Recent experiments demonstrate that this model cannot explain force generation for anaphase chromosome movement [Pickett-Heaps et al., 1996: Protoplasma 192:1-10]. Another such experiment is described here: a UV-microbeam cut several kinetochore fibres (k-fibres) in newt epithelial cells at metaphase and the half-spindle immediately shortened: in several cells, the remaining intact spindle fibres bowed outwards as they came under increased compression. Thus, severing of k-MTs can lead to increased tension between chromosomes and poles. This observation cannot be explained by models in which force is produced by motor molecules at the kinetochore actively disassembling k-MTs. Rather, we argue that tensile forces act along the whole k-fibre, which, therefore, can be considered as a classic "traction fibre." We suggest that anaphase polewards force is generated by MTs interacting with the spindle matrix and when k-MTs are severed, polewards force continues to act on the remaining kMT-stub; spindle MTs act as rigid struts concurrently resisting and being controlled by these forces. We suggest that the principles of "cellular tensegrity" [Ingber, 1993: J. Cell Sci. 104:613-627] derived from the behaviour and organization of the interphase cell apply to the spindle. In an evolutionary context, this argument further suggests that the spindle might originally have evolved as the mechanism by which a single tensegral unit (cytoplast) is divided into two cytoplasts; use of the spindle for segregating chromosomes might represent a secondary, more recent development of this primary function. If valid, this concept has implications for the way the spindle functions and for the spindle's relationship to cytokinesis.


A Microbial Signature of Psychological Distress in Irritable Bowel Syndrome.
Irritable bowel syndrome (IBS) is associated with alterations along the brain-gut-microbiota axis. Previous studies have suggested a parallel segregation of microbial features and psychological burden in IBS. This study aimed at exploring the microbial correlates of psychological distress in patients with IBS. Forty-eight patients with IBS (Rome III criteria, M (SD) age = 42 (15) years, 35 female, 25 diarrhea-dominant, 5 constipation-dominant, and 18 alternating-type IBS) were assessed for psychological and clinical variables with validated questionnaires, fecal samples underwent microbial 16S rRNA analyses (regions V1-2). Microbial analyses comprised examination of alpha and beta diversity, correlational analyses of bacterial abundance and comparisons among subgroups defined by thresholds of psychological and IBS symptom variables, and machine learning to identify bacterial patterns corresponding with psychological distress. Thirty-one patients (65%) showed elevated psychological distress, 22 (31%) anxiety, and 10 depression (21%). Microbial beta diversity was significantly associated with distress and depression (q = .036 each, q values are p values false discovery rate-corrected for multiple testing). Depression was negatively associated with Lachnospiraceae abundance (Spearman's ρ = -0.58, q = .018). Patients exceeding thresholds of distress, anxiety, depression, and stress perception showed significantly higher abundances of Proteobacteria (q = .020-.036). Patients with anxiety were characterized by elevated Bacteroidaceae (q = .036). A signature of 148 unclassified species accounting for 3.9% of total bacterial abundance co-varied systematically with the presence of psychological distress. Psychological variables significantly segregated gut microbial features, underscoring the role of brain-gut-microbiota interaction in IBS. A microbial signature corresponding with psychological distress was identified. ClinicalTrials.gov identifier NCT02536131, retrospectively registered.


The Effect of Support Surfaces on the Incidence of Pressure Injuries in Critically Ill Patients: A Randomized Clinical Trial.
To analyze whether a viscoelastic mattress support surface can reduce the incidence of stage 2 pressure injuries compared to a standard hospital mattress with pyramidal overlay in critically ill patients. A randomized clinical trial with intention-to-treat analysis was carried out recruiting patients with Braden scale ≤14 on intensive care unit admission from April 2016 to April 2017. Patients were allocated into two groups: intervention group (viscoelastic mattress) and control group (standard mattress with pyramidal overlay). The level of significance adopted was 5%. A total of 62 patients were included in the study. There was a predominance of males (53%) and the mean age was 67.9 (SD 18.8) years. There were no differences in clinical or severity characteristics between the patients in the control group and the intervention group. Pressure injuries occurred in 35 patients, with a median time of 7 days (ITQ 4-10) from admission. The frequency of pressure injuries was higher in the control group (80.6%) compared to the intervention group (32.2%; p < 0.001). Viscoelastic support surfaces reduced the incidence of pressure injuries in moderate or higher risk critically ill patients when compared to pyramidal support surfaces.


HIV-1 Tat amino acid residues that influence Tat-TAR binding affinity: a scoping review.
HIV-1 remains a global health concern and to date, nearly 38 million people are living with HIV. The complexity of HIV-1 pathogenesis and its subsequent prevalence is influenced by several factors including the HIV-1 subtype. HIV-1 subtype variation extends to sequence variation in the amino acids of the HIV-1 viral proteins. Of particular interest is the transactivation of transcription (Tat) protein due to its key function in viral transcription. The Tat protein predominantly functions by binding to the transactivation response (TAR) RNA element to activate HIV-1 transcriptional elongation. Subtype-specific Tat protein sequence variation influences Tat-TAR binding affinity. Despite several studies investigating Tat-TAR binding, it is not clear which regions of the Tat protein and/or individual Tat amino acid residues may contribute to TAR binding affinity. We, therefore, conducted a scoping review on studies investigating Tat-TAR binding. We aimed to synthesize the published data to determine (1) the regions of the Tat protein that may be involved in TAR binding, (2) key Tat amino acids involved in TAR binding and (3) if Tat subtype-specific variation influences TAR binding. A total of thirteen studies met our inclusion criteria and the key findings were that (1) both N-terminal and C-terminal amino acids outside the basic domain (47-59) may be important in increasing Tat-TAR binding affinity, (2) substitution of the amino acids Lysine and Arginine (47-59) resulted in a reduction in binding affinity to TAR, and (3) none of the included studies have investigated Tat subtype-specific substitutions and therefore no commentary could be made regarding which subtype may have a higher Tat-TAR binding affinity. Future studies investigating Tat-TAR binding should therefore use full-length Tat proteins and compare subtype-specific variations. Studies of such a nature may help explain why we see differential pathogenesis and prevalence when comparing HIV-1 subtypes.


Value of computed tomography in the staging of testicular tumors.
To analyze the value of computed tomography (CT) for the exact staging of testicular tumors, 2 groups of 28 patients each were examined. All patients underwent retroperitoneal lymph node dissection in the course of their treatment. Pretherapeutic stages as determined by CT were compared to the histologically verified definite tumor stages. In 68% of the patients, the stage found by CT was correct but 3 (5%) false-positive and 13 false-negative results were obtained. Thus, almost 40% (13/33) of the patients with clinical stage I disease presumably would have had a progression if managed by a surveillance strategy. It can be concluded that this strategy should be restricted to certain centers with guaranteed long-term standardized patient observation and extremely high patient compliance.


An increased number of gamma/delta T-cells and gastric epithelial cell expression of the groEL stress-protein homologue in Helicobacter pylori-associated chronic gastritis of the antrum.
Numerous studies have shown that the presence of Helicobacter pylori in the stomach is linked to the development of chronic gastritis most commonly seen in the antrum. However, the pathogenic mechanisms are unclear. In 23 of 31 patients, examined due to symptoms from the upper gastrointestinal tract, H. pylori-associated chronic gastritis of the antrum was diagnosed histologically and by growth of H. pylori. Immunoperoxidase staining on gastric biopsy specimens from these patients showed an increased number of gamma/delta T-cells within the epithelium. Furthermore, the Mab ML30 (raised against the 65 kDa heat shock protein of mycobacteria) demonstrated positive staining in the gastric epithelial cells in all H. pylori-positive but not in H. pylori-negative biopsy specimens. H. pylori also reacted with ML30, as detected by immunoperoxidase staining as well as by immunoblotting. Intraepithelial gamma/delta T cells may play a role in host defense against invading H. pylori, and the bacteria may trigger an autoimmune response to stress proteins expressed by the gastric epithelial cells.


Response of restraint stress-selected lines of Japanese quail to heat stress and Escherichia coli challenge.
Japanese quail selected for divergent corticosterone response to restraint stress were evaluated for their susceptibility to heat stress and challenge with Escherichia coli. These quail lines are designated as high stress (HS), low stress (LS), and the random-bred control (CS) lines. Heat stress (35°C, 8 h/d) began at 24 d until the end of the study at 39 d. Birds were challenged with an aerosol spray containing 2 × 10(9) cfu of E. coli at 25 and 32 d. At 38 d, the surviving birds were necropsied and the intestinal tract was screened for both Salmonella and Campylobacter. Body weights of the CS birds were higher than both HS and LS at 17, 25, and 32 d. At 32 d, there was no difference in mortality between males and females and the CS line had higher mortality compared with the LS line with the HS line being intermediate. At 38 d, females of the CS line that were both heat stressed and challenged had a mortality incidence of 25%, which was significantly higher than male birds of the same line and treatment (5.3%). There was an increased incidence in Salmonella enterica serotype Agona isolation after heat stress, with the LS birds having less isolation than the HS birds. Mean corticosterone levels of male birds were not significantly affected by line, heat stress, or E. coli challenge; however, the LS line subjected to heat stress had one-third the level of the HS line, a difference identical to that seen in the original selection for response to restraint stress.


Quantifying the Effects of Halogen Bonding by Haloaromatic Donors on the Acceptor Pyrimidine.
The effects of intermolecular interactions by a series of haloaromatic halogen bond donors on the normal modes and chemical shifts of the acceptor pyrimidine are investigated by Raman and NMR spectroscopies and electronic structure computations. Halogen-bond interactions with pyrimidine's nitrogen atoms shift normal modes to higher energy and upfield shift 1 H and 13 C NMR peaks in adjacent nuclei. This perturbation of vibrational normal modes is reminiscent of the effects of hydrogen bonded networks of water, methanol, or silver on pyrimidine. The unexpected observation of vibrational red shifts and downfield 13 C NMR shifts in some complexes suggests that other intermolecular forces such as π interactions are competing with halogen bonding. Natural bond orbital analyses indicate a wide range of charge transfer is possible from pyrimidine to different haloaromatic donors and computed halogen bond binding energies can be larger than a typical hydrogen bond. These results emphasize the importance in strategic selection of substituents and electron withdrawing groups in developing supramolecular structures based on halogen bonding.


Monoclonal Antibody Use for Coronavirus Disease 2019 in Pediatric Patients: A Multicenter Retrospective Study.
Monoclonal antibodies for COVID-19 are authorized in high-risk patients aged ≥12 years, but evidence in pediatric patients is limited. In our cohort of 142 patients treated at seven pediatric hospitals between 12/1/20 and 7/31/21, 9% developed adverse events, 6% were admitted for COVID-19 within 30 days, and none received ventilatory support or died.


Fenestrations in regenerating skeletal muscle capillaries.
A new observation of fenestrae with diaphragms in the endothelial wall of regenerating skeletal muscle capillaries is described in seven-day-old wounds of the cremaster muscle of adult male guinea pigs. The fenestrations were 44 nm in diameter and contained diaphragms with a central dense structure. These findings suggest an additional route for physiological exchange mechanisms in wound capillaries.


Pulmonary embolism in patients in acute COVID-19, long-COVID and post-COVID syndrome.
COVID-19 is a disease caused by the SARS-CoV-2 virus, which, after entering a living organism, uses the ACE-2 protein as a receptor and several other proteins as cofactors of infection. Disease symptomatology is extensive, involving mostly predominant respiratory symptoms, as well as those of the nervous, gastrointestinal, circulatory and other systems. Incidence of COVID-19 also results in markedly different laboratory findings on the hemostatic system with the predominant feature of increased D-dimer levels. In the pathogenesis of thromboembolic complications in COVID-19, all elements of Virchow's triad are involved: endothelial damage, coagulation disorders and blood flow disorders. Coagulopathy increases with the severity of the clinical course of COVID-19. One of the causes of mortality associated with COVID-19 is pulmonary embolism. SARS-CoV-2 infection increases the risk of thromboembolic complications not only in the acute period of the disease. Also in the period of about a month after recovery, there is an increased risk of venous thrombosis and consequently, life-threatening pulmonary embolism. The classic biomarker of pulmonary embolism in the general population is D-dimers. Among imaging studies, the gold standard for diagnosing this disease is computed tomography of the pulmonary arteries (CTPA). Other useful diagnostic tests are ventilation-perfusion lung scintigraphy (VQ Scans) or echocardiography. Currently reviewed guidelines and recommendations recommend extens ive thromboprophylaxis in COVID-19 patients in both acute and chronic phases of the disease. Keywords: COVID-19, pulmonary embolism, laboratory and imaging diagnostics, thromboprophylaxis.


The haematology of clinically healthy, farmed juvenile Asian seabass (Lates calcarifer Bloch)-reference intervals, and indicators of subclinical disease.
This study establishes the blood reference intervals (RIs) for clinically healthy and farmed juvenile Asian seabass (Lates calcarifer), within 4-6 weeks after stocking into flow-through, marine aquaculture systems. The 90% percentile RIs (n = 156, mean bodyweight 41.8 g) are as follows: glucose (GLU) 2.4-11.3 mmol/L, haematocrit (Hct) 18.9%-39.2%, haemoglobin concentration (Hb) 56.0-85.0 g/L, total plasma protein (TPP) 56.0-77.0 g/L, total red blood cell (RBC) count 4.1-11.2 × 1012 /L, total white blood cell (WBC) count 5.3-69.9 × 109 /L, total lymphocytes 4.7-51.4 × 109 /L, monocytes 0.3-16.2 × 109 /L and heterophils count 0.6-8.4 × 109 /L. Pearson's method analysis showed weak but significantly positive correlations between fish bodyweight and Hct, Hb, TPP and total RBC count (p < 0.05). Histopathology of 42 of the 156 clinically healthy fish used to derive the RIs, with blood values within the 90% percentile range, did not exhibit any abnormal pathology. In contrast, histopathology from a different group of clinically healthy L. calcarifer (n = 72, mean bodyweight 31.3 g) with blood values falling outside of these established 90% percentile RIs showed that 25% of these fish had severe, chronic granulomatous enteritis, and 13% had severely depleted lipid stores in their liver. Point biserial correlation analysis of blood values from this second group of 72 fish showed that elevated total WBC, monocyte and heterophil counts and reduced Hct levels are significantly associated (p < 0.05) with the occurrence of severe, chronic granulomatous enteritis and depleted lipid stores in their liver. Reduced blood GLU and TPP levels in the second group of fish were significantly associated with fish that had depleted lipid stores in liver (p < 0.05), corroborating a period of malnutrition. This study is among the first to establish blood RIs for clinically healthy, farmed juvenile L. calcarifer and detection of subclinical diseases in fish to support early intervention.


A translational pharmacology approach to understanding the predictive value of abuse potential assessments.
Within the drug development industry the assessment of abuse potential for novel molecules involves the generation and review of data from multiple sources, ranging from in-vitro binding and functional assays through to in-vivo nonclinical models in mammals, as well as collection of information from studies in humans. This breadth of data aligns with current expectations from regulatory agencies in both the USA and Europe. To date, there have been a limited number of reviews on the predictive value of individual models within this sequence, but there has been no systematic review on how each of these models contributes to our overall understanding of abuse potential risk. To address this, we analyzed data from 100 small molecules to compare the predictive validity for drug scheduling status of a number of models that typically contribute to the abuse potential assessment package. These models range from the assessment of in-vitro binding and functional profiles at receptors or transporters typically associated with abuse through in-vivo models including locomotor activity, drug discrimination, and self-administration in rodents. Data from subjective report assessments in humans following acute dosing of compounds were also included. The predictive value of each model was then evaluated relative to the scheduling status of each drug in the USA. In recognition of the fact that drug scheduling can be influenced by factors other than the pharmacology of the drug, we also evaluated the predictive value of each assay for the outcome of the human subjective effects assessment. This approach provides an objective and statistical assessment of the predictive value of many of the models typically applied within the pharmaceutical industry to evaluate abuse potential risk. In addition, the impact of combining information from multiple models was examined. This analysis adds to our understanding of the predictive value of each model, allows us to critically evaluate the benefits and limitations of each model, and provides a method for identifying opportunities for improving our assessment and prediction of abuse liability risk in the future.


Synergistic Interactions of a Synthetic Lubricin-Mimetic with Fibronectin for Enhanced Wear Protection.
Lubricin (LUB), a major mucinous glycoprotein of mammalian synovial fluids, is believed to provide excellent lubrication to cartilage surfaces. Consequently, when joint disease or replacement leads to increased friction and surface damage in the joint, robust synthetic LUB alternatives that could be used therapeutically to improve lubrication and surface protection are needed. Here, we report the characterization of a lubricating multiblock bottlebrush polymer whose architecture was inspired by LUB, and we investigate the role of fibronectin (FN), a glycoprotein found in the superficial zone of cartilage, in mediating the tribological properties of the polymer upon shear between mica surfaces. Our surface forces apparatus (SFA) normal force measurements indicate that the lubricin-mimetic (mimLUB) could be kept anchored between mica surfaces, even under high contact pressures, when an intermediate layer of FN was present. Additional SFA friction measurements show that FN would also extend the wearless friction regime of the polymer up to pressures of 3.4 MPa while ensuring stable friction coefficients (μ ≈ 0.28). These results demonstrate synergistic interactions between mimLUB and FN in assisting the lubrication and wear protection of ideal (mica) substrates upon shear. Collectively, these findings suggest that our proposed mimLUB might be a promising alternative to LUB, as similar mechanisms could potentially facilitate the interaction between the polymer and cartilage surfaces in articular joints and prosthetic implants in vivo.


Location, number and morphology of parathyroid glands: results from a large anatomical series.
Surgical management of parathyroid gland disease may sometimes be difficult, due mainly to the surgeon's failure to successfully detect parathyroids in unusual locations. The records of 942 cadavers (574 men and 368 women) who underwent autopsy in the Department of Forensic Medicine in Athens during the period 1988-2009 were reviewed. In total, 3,796 parathyroid glands were resected and histologically verified. Parathyroid glands varied in number. In 47 cases (5 %), one supernumerary (fifth) parathyroid was found, while in 19 cases (2 %) three parathyroid glands found. Superior glands were larger than inferior ones. However, there was no significant difference between the genders with respect to gland size. In 324 (8.5 %) out of 3,796, the glands were detected in an ectopic location: 7 (0.2 %) in the thyroid parenchyma, 79 (2 %) in different sites in the neck and 238 (6.3 %) in the mediastinum, 152 (4.1 %) of which were found in the upper and 86 (2.2 %) in the lower mediastinum. Significant anatomical variations of normal parathyroid glands may exist regarding number and location-knowledge that is essential for their successful identification and surgical management.


Gamma-hydroxybutyrate increases tryptophan availability and potentiates serotonin turnover in rat brain.
Gamma-hydroxybutyrate (GHB) is both a therapeutic agent and a recreative drug. It has sedative, anxiolytic and euphoric effects. These effects are believed to be due to GHB-induced potentiation of cerebral GABAergic and dopaminergic activities, but the serotonergic system might also be involved. In this study, we examine the effects of pharmacological doses of GHB on the serotonergic activity in rat brain. Administration of 4.0 mmol/kg i.p. GHB to rats induces an accumulation of tryptophan and 5-HIAA (5-hydroxyindole acetic acid) in the frontal cortex, striatum and hippocampus without causing significant change in the tissue serotonin content. In the extracellular space, GHB induced a slight decrease in serotonin release. The tryptophan and 5-HIAA accumulation induced by GHB is mimicked by the GHB receptor agonist para-chlorophenyl-transhydroxycrotonate (NCS-356) and blocked by NCS-382 (6,7,8,9-tetrahydro-5-[H]-benzocycloheptene-5-ol-4-ylidene acetic acid) a selective GHB receptor antagonist. GHB induces the accumulation of either a derivative of or [3H]-tryptophan itself in the extracellular space, possibly by increasing tryptophan transport across the blood-brain barrier. The blood content of certain neutral amino-acids, including tryptophan, is also increased by peripheral GHB administration. Some of the effect of GHB could be reproduced by baclofen and reduced by the GABAB antagonist CGP 35348. Taken together, these results indicate that the GHB-induced stimulation of tissue serotonin turnover may be due to an increase in tryptophan transport to the brain and in its uptake by serotonergic cells. As the serotonergic system may be involved in the regulation of sleep, mood and anxiety, the stimulation of this system by high doses of GHB may be involved in certain neuropharmacological events induced by GHB administration.


Association of pulmonary function with cognitive performance in early, middle and late adulthood.
Pulmonary function has been associated with some measures of cognitive performance, mostly in late adulthood. This study investigated whether this association is present for a range of cognitive measures, at three stages of adulthood, and whether it remains after controlling for demographic, health and lifestyle factors. The relationship between forced expiratory volume at 1 s (FEV1), a measure of pulmonary function, and cognitive test performance was examined in three cohorts aged 20-24, 40-44 and 60-64. After controlling for demographic variables, smoking, physical activity, and respiratory disease, significant associations between FEV1 and cognitive test performance were evident in each age group for most cognitive measures. The association between FEV1 and measures of speed increased with age. FEV1 has a small but reliable positive association with cognitive test performance throughout adulthood, possibly reflecting a common physiological factor.


Chemical stimulation of the nucleus of the solitary tract and the resulting blood pressure response.
The cardiovascular effects of catecholamines and related substances after local application into the nucleus tractus solitarii (NTS) of the medulla oblongata of urethane anesthetized rats are summarized. The catecholamines in the nanomolar dose range appear to activate stereospecifically receptor sites in the NTS, resulting in a decrease in blood pressure. Bradycardia occurs after bilateral administration of higher doses. The type of catecholaminergic receptors involved is discussed on the basis of the effects of different catecholamine receptor stimulating agents and pharmacological blockade. Both alpha-methylnoradrenaline and alpha-methyladrenaline are active and it is concluded that they both may contribute to the antihypertensive action of alpha-methyldopa. It is probable that an alpha-type of receptor mediates these hypotensive effects in the NTS. The nature of this receptor needs further characterization.


Low Stromal Area and High Stromal Microvessel Density Predict Poor Prognosis in Pancreatic Cancer.
Excessive stroma is a unique property of cancer tissue of the pancreas. The aim of this study was to analyze the relationship of cancer stromal area (SA) and tumor microvessel density (MVD) with prognostic and clinicopathological findings. Pancreatic adenocarcinoma tissues obtained from 104 patients were subjected to cytokeratin 19 and CD31 double immunostaining to identify cancer cells and endothelial cells simultaneously. Stromal area and MVD were assessed in the same sections. Patients were divided into 2 groups for each analysis by the median value of the respective measure. Stromal area negatively correlated with MVD. The low SA group harbored more poorly differentiated carcinoma than the high SA group. Patients of the low SA group showed a higher incidence of hematogenous recurrence. As a consequence, patients in the low SA and the high MVD groups had poorer prognosis in terms of both disease-free survival and overall survival than their respective groups. Multivariate analysis showed that a low SA was an independent prognostic factor for disease-free and overall survival. Our data indicate that the stroma of pancreatic cancer may play an auxiliary role as a barrier to cancer cell invasion. The depletion of tumor stroma alone does not suppress pancreatic cancer progression.


Improving CD20 antibody therapy: obinutuzumab in lymphoproliferative disorders.
Soon after the anti-CD20 monoclonal antibody rituximab began to change the management of indolent and aggressive B cell lymphomas, development of alternative antibodies - including chemoimmunoconjugates - was undertaken. Among humanized and fully human CD20 antibodies, obinutuzumab has emerged as one antibody that seems to have lived up to the promise of improved efficacy based on in vitro and preclinical experiments. The data available, thus, far establish obinutuzumab's preferred role as the anti-CD20 antibody of choice in chronic lymphocytic leukemia and untreated follicular lymphoma, as well as an important addition to the treatment of rituximab-refractory indolent lymphomas. Additional trials in aggressive lymphoma are required to define the place of this new antibody in the management of patients with curable lymphoma subtypes. There are greater toxicities associated with this treatment, including increased infusion-related reactions and cytopenias, but these are manageable with standard supportive care measures.


Myocardial Bridges on Coronary Computed Tomography Angiography - Correlation With Intravascular Ultrasound and Fractional Flow Reserve.
Myocardial bridges (MB) are commonly seen on coronary CT angiography (CCTA) in asymptomatic individuals, but in patients with recurrent typical angina symptoms, yet no obstructive coronary artery disease (CAD), evaluation of their potential hemodynamic significance is clinically relevant. The aim of this study was to compare CCTA to invasive coronary angiography (ICA), including intravascular ultrasound (IVUS), to confirm MB morphology and estimate their functional significance in symptomatic patients.Methods and Results:We retrospectively identified 59 patients from our clinical databases between 2009 and 2014 in whom the suspicion for MB was raised by symptoms of recurrent typical angina in the absence of significant obstructive CAD on ICA. All patients underwent CCTA, ICA and IVUS. MB length and depth by CCTA agreed well with length (0.6±23.7 mm) and depth (CT coverage) as seen on IVUS. The product of CT length and depth (CT coverage), (MB muscle index (MMI)), ≥31 predicted an abnormal diastolic fractional flow reserve (dFFR) ≤0.76 with a sensitivity and specificity of 74% and 62% respectively (area under the curve=0.722). In patients with recurrent symptoms of typical angina yet no obstructive CAD, clinicians should consider dynamic ischemia from an MB in the differential diagnosis. The product of length and depth (i.e., MMI) by CCTA may provide some non-invasive insight into the hemodynamic significance of a myocardial bridge, as compared with invasive assessment with dFFR.


Staging laparotomy in non-Hodgkin's lymphoma.
In 57 patients with non-Hodgkin's lymphoma, a clinical, radiographic, scintigraphic and pathological correlative study showed the following results: (1) the inferior venacavagram, lymphangiogram and gallium-67 scan have a low sensitivity in detecting lymphoma: their accuracy is high when the findings are interpreted as abnormal (93%, 83% and 80% respectively), but low when they are interpreted as normal (47%, 67% and 58% respectively); (2) the clinical evaluation of spleen and liver is unreliable; (3) the incidence of lymphocytic lymphoma in the para-aortic-iliac nodes is high; (4) a pattern of involvement by contiguity and a predilection for the spleen were observed in lymphocytic lymphoma; (5) in lymphocytic lymphoma there is no liver involve without concomitant splenic involvement; (6) no definite pattern of spread could be seen in histiocytic lymphoma; (7) surgical staging changed the classification of the lymphoma in 56% of cases, 46% being reclassified to a more advanced stage; (8) surgical staging significantly improves the assessment of the stage of disease and therefore permits accurate treatment planning.


Production of singlet delta oxygen by atmospheric pollutants.
Singlet delta oxygen (1O2) was generated at atmospheric pressure using heterogeneous gas-phase photosensitization. Polycyclic aromatic hydrocarbons (PAH), known constituents of the atmosphere, were found to be efficient sensitizers in the production of singlet delta oxygen under simulated environmental conditions. A novel mechanism involving singlet delta oxygen is proposed in which PAH on particle surfaces are self-activated to form direct-acting mutagens.


Melatonin treatment during the incubation of sensitization attenuates methamphetamine-induced locomotor sensitization and MeCP2 expression.
Behavior sensitization is a long-lasting enhancement of locomotor activity after exposure to psychostimulants. Incubation of sensitization is a phenomenon of remarkable augmentation of locomotor response after withdrawal and reflects certain aspects of compulsive drug craving. However, the mechanisms underlying these phenomena remain elusive. Here we pay special attention to the incubation of sensitization and suppose that the intervention of this procedure will finally decrease the expression of sensitization. Melatonin is an endogenous hormone secreted mainly by the pineal gland. It is effective in treating sleep disorder, which turns out to be one of the major withdrawal symptoms of methamphetamine (MA) addiction. Furthermore, melatonin can also protect neuronal cells against MA-induced neurotoxicity. In the present experiment, we treated mice with low dose (10mg/kg) of melatonin for 14 consecutive days during the incubation of sensitization. We found that melatonin significantly attenuated the expression of sensitization. In contrast, the vehicle treated mice showed prominent enhancement of locomotor activity after incubation. MeCP2 expression was also elevated in the vehicle treated mice and melatonin attenuated its expression. Surprisingly, correlation analysis suggested significant correlation between MeCP2 expression in the nucleus accumbens (NAc) and locomotion in both saline control and vehicle treated mice, but not in melatonin treated ones. MA also induced MeCP2 over-expression in PC12 cells. However, melatonin failed to reduce MeCP2 expression in vitro. Our results suggest that melatonin treatment during the incubation of sensitization attenuates MA-induced expression of sensitization and decreases MeCP2 expression in vivo.


[The teaching of medical ethics in medical school].
Medical ethics constitutes some kind of core, which enables the physicians to decide in complicated clinical situations. This subject is taught during medical studies through only one semester. Number of teaching hours designed for this crucial in later physician's practice subject is insufficient. Additional problem in teaching process is inconsistence between the Law and the Code of Medical Ethics. As a result it causes alarmingly weak preparation of students to take practical decisions according to ethical and moral values of the Code of Medical Ethics. What is also important, in 2012 a medical studies schedule was changed, which in author's opinion had very negative effect on medical ethics teaching. In our opinion it is vital to increase number of teaching hours spent on medical ethics, create a model of gradual ethical knowledge transfer to students on every year of studies, which should be based on clinical subjects in master-student relations. Authors of this article discuss in a complex way problems of medical ethics teaching at medical studies supporting their thesis with author's survey carried out on large group of students of Medical University of Silesia in Katowice.


Seasonality of water chemistry, carbonate production, and biometric features of two species of Chara in a shallow clear water lake.
The objective of this study was to analyze the temporal variability of biometric features and the carbonate production of two charophytes: Chara polyacantha A. Braun and Chara rudis A. Braun against the background of the physical-chemical properties of water. The investigation was carried out in a small, mid-forest Lake Jasne (western Poland). It is a polymictic, mesotrophic, hardwater ecosystem dominated by charophyte vegetation. Each month, 10 individuals of each species were characterized in terms of morphometric features, fresh and dry weight, and the percentage of calcium carbonate. Additionally, physical-chemical parameters of the water were studied. The results of physical-chemical analyses indicated similar habitat conditions for both species. Despite smaller dry weight C. polyacantha was characterized by greater morphological variability and higher rates of growth and percentage share of calcium carbonate in dry mass than C. rudis. The percentage of calcium carbonates in dry mass did not differ significantly between the species and exceeded 60%, reaching the maximum (76% in C. polyacantha) in July and August. For both species, distinct correlations between the structure of biomass and morphological features were found. The obtained results show the great importance of charophyte vegetation in carbon cycling and functioning of lake ecosystems.


Prenatal ultrasound diagnosis of frontonasal dysplasia.
We report a case of prenatal ultrasound diagnosis of frontonasal dysplasia. This represents a very rare disorder involving the face (hypertelorism, median cleft lip, absence of the nasal tip) and often the central nervous system (CNS) (cranium bifidum occultum, ethmoidal cephalocele, agenesis of the corpus callosum). Although several of the typical anomalies are diagnosable by ultrasound in utero (hypertelorism, median cleft lip, anterior cephalocele), very few cases have been reported prenatally, the present being only the third. In the present case, hemimegalencephaly is first reported among the anomalies possibly associated with frontonasal dysplasia. The diagnosis was made at 22 weeks' gestation and was confirmed by necropsy following termination of pregnancy.


The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase.
The global activator GacA, a highly conserved response regulator in Gram-negative bacteria, is required for the production of exoenzymes and secondary metabolites in Pseudomonas spp. The gacA gene of Pseudomonas aeruginosa PAO1 was isolated and its role in cell-density-dependent gene expression was characterized. Mutational inactivation of gacA resulted in delayed and reduced formation of the cell-density signal N-butyryl-L-homoserine lactone (BHL), of the cognate transcriptional activator RhIR (VsmR), and of the transcriptional activator LasR, which is known to positively regulate RhIR expression. Amplification of gacA on a multicopy plasmid caused precocious and enhanced production of BHL, RhIR and LasR. In parallel, the gacA gene dosage markedly influenced the BHL/RhIR-dependent formation of the cytotoxic compounds pyocyanin and cyanide and the exoenzyme lipase. However, the concentrations of another known cell-density signal of P. aeruginosa, N-oxododecanoyl-L-homoserine lactone, did not always match BHL concentrations. A model accounting for these observations places GacA function upstream of LasR and RhIR in the complex, cell-density-dependent signal-transduction pathway regulating several exoproducts and virulence factors of P. aeruginosa via BHL.


Incidence of Listeria spp. in Breton live shellfish.
Live shellfish samples (120) were collected from nine littoral sites in Brittany (western France). They were screened for Listeria spp. and a count of faecal coliforms was carried out. Analysis of the results revealed Listeria spp. in 55% of samples, a much higher rate than the previous, infrequent, recorded data. Furthermore, the study demonstrated that the frequency of Listeria spp. in winter was more important than in summer (P < 0.001), and underlined a significant relationship between the occurrence of these bacteria and the concentration of faecal coliforms (P < 0.001). Finally, comparison of the official and Gen-Probe methods revealed the limits of the standardized technique in the search for L. monocytogenes in shellfish.


Perceptions, expectations, and reactions to cleft lip and palate surgery in native populations: a pilot study in rural India.
Many charitable organizations conduct overseas missions to correct cleft lip and palate where surgical care is unavailable. However, little is known about cultural and societal attitudes regarding the cleft deformity. A 15-item questionnaire was designed to elicit from parents general knowledge concerning cleft lip and palate, beliefs regarding its causation, and expectations of what surgery would accomplish. Shorter second and third questionnaires were administered after the screening process and after surgery. The initial phase of this project was undertaken in Deesa, a midsized rural town in India. Fifty-two families were selected randomly for the initial questionnaire. These interviews were conducted verbally, assisted by translators. Children in 25 of these 52 families subsequently underwent surgery. The results of the interviews indicated that 64% of parents did not limit their child's social interaction and were not ashamed to be seen in public. Twenty-six percent exercised some constraints, and 10% kept their children totally isolated, not permitting them to leave the house or attend school. Regarding causation, the vast majority (84%) ascribed the cleft to "God's will" and 10% to sins committed in past lives. Only one parent acknowledged the influence of genetics, although several had a positive family history. Environmental factors were not an issue. Most families expected their child's life to be better when the facial deformity was corrected. Marriage prospects were the main concern, more so for girls than boys. Educational opportunity was a second strong theme. A greater understanding of the beliefs and expectations in this region was gained by means of this study.


Health-promoting lifestyle and life satisfaction in full-time employed adults with congenital heart disease: grit as a mediator.
Enhancing life satisfaction is vital for adults with congenital heart disease (ACHD). Life satisfaction potentially correlates with a health-promoting lifestyle and grit. However, the mediating role of grit-a trait marked by perseverance and long-term goal-oriented passion-between a health-promoting lifestyle and life satisfaction in ACHD remains unverified. This study aimed to examine the relationships between health-promoting lifestyle, grit, and life satisfaction in full-time employed ACHD and to confirm the mediating role of grit. A total of 181 full-time employed ACHD aged 20-59 years with patient-reported New York Heart Association class I-IV were recruited from two medical centers in northern Taiwan. Participants completed questionnaires, including the short version of the Chinese Health-Promoting Lifestyle Profile scale, Grit-10 scale, and Satisfaction with Life Scale between February and December 2022. Data analysis employed the Hayes PROCESS macro. Health-promoting lifestyle, grit, and life satisfaction were discovered to be positively correlated. Overall grit score was a partial mediator between a health-promoting lifestyle and life satisfaction, accounting for 20% of the total variation. Of the grit domains, perseverance served as a partial mediator between a health-promoting lifestyle and life satisfaction, accounting for 32% of the total variation, whereas passion had a nonsignificant mediation effect. A health-promoting lifestyle boosts ACHD individuals' life satisfaction through grit, particularly perseverance. Integrating grit into such a lifestyle could benefit from comprehending support systems and influential factors aiding grit development for enhanced life satisfaction.


Biomimetic Sensing System for Tracing Pb2+ Distribution in Living Cells Based on the Metal-Peptide Supramolecular Assembly.
Metal-peptide interactions provide plentiful resource and design principles for developing functional biomaterials and smart sensors. Pb2+, as a borderline metal ion, has versatile coordination modes. The interference from competing metal ions and endogenous chelating species greatly challenges Pb2+ analysis, especially in complicated living biosystems. Herein, a biomimetic peptide-based fluorescent sensor GSSH-2TPE was developed, starting from the structure of a naturally occurring peptide glutathione. Lewis acid-base theory was employed to guide the molecular design and tune the affinity and selectivity of the targeting performance. The integration of peptide recognition and aggregation-induced emission effect provides desirable sensing features, including specific turn-on response to Pb2+ over 18 different metal ions, rapid binding, and signal output, as well as high sensitivity with a detection limit of 1.5 nM. Mechanism investigation demonstrated the balance between the chelating groups, and the molecular configuration of the sensor contributes to the high selectivity toward Pb2+ complexation. The ion-induced supramolecular assembly lights up the bright fluorescence. The ability to image Pb2+ in living cells was exhibited with minimal interference from endogenous biothiols, no background fluorescence, and good biocompatibility. With good cell permeability, GSSH-2TPE can monitor changes in Pb2+ levels and biodistribution and thus predict possible damage pathways. Such metal-peptide interaction-based sensing systems offer tailorable platforms for designing bioanalytical tools and show great potential for studying the cell biology of metal ions in living biosystems.


[A Case of Bilateral HER2-Positive Invasive Ductal Carcinoma with Complete Response on One Side with Trastuzumab Deruxtecan].
A 52-year-old female with stage Ⅳ, bilateral, HER2-positive, breast cancer as well as bilateral axillary lymph node(LN) metastasis and bilateral pulmonary metastasis was administered trastuzumab plus pertuzumab plus docetaxel as a standard chemotherapy. After this treatment the right breast cancer, right axillary LN metastasis, and bilateral pulmonary metastases contracted, while the left breast cancer and left axillary LN metastasis expanded. Trastuzumab emtansine was then administered, and the left axillary LN metastasis contracted, however, the left breast cancer expanded, resulting in marked breast engorgement. When trastuzumab deruxtecan(T-DXd)was administered, the left breast cancer contracted for the first time during the overall treatment process, and the signs of breast inflammation disappeared. Other lesions showed no recrudescence. T-DXd was administered seven times, and, at the stage of maximum contraction during the treatment period, a total left mastectomy and left axillary LN dissection were performed. Pathological examination then confirmed that tumor cells were no longer present in the left breast and left axillary LN. In this case T-DXd was highly effective for the local treatment of intractable, HER2-positive, breast cancer.


NEAR-EARTH ASTEROID LIGHTCURVE ANALYSIS AT THE CENTER FOR SOLAR SYSTEM STUDIES: 2019 JULY-SEPTEMBER.
Lightcurves for 28 near-Earth asteroids (NEAs) obtained at the Center for Solar System Studies (CS3) from 2019 July to September were analyzed for rotation period, peak-to-peak amplitude, and signs of satellites or tumbling. 2059 Baboquivari, (90403) 2003 YE45, and 2016 AU130 are candidates for membership within the very wide binary asteroids class. The 2019 data led to a seemingly unambiguous period of 4.7906 h for (441987) 2010 NY65, which overturned previous results that have now been updated.


Y1 receptors in the nucleus accumbens: ultrastructural localization and association with neuropeptide Y.
Neuropeptide Y (NPY) is present in aspiny neurons in the nucleus accumbens (NAc), which also contains moderate levels of ligand binding and mRNA for the Y1 receptor. To determine the potential functional sites for receptor activation, we examined the electron microscopic immunocytochemical localization of antipeptide antisera against the Y1 receptor in the rat NAc. We also combined immunogold and immunoperoxidase labeling to show that, in this region, Y1 receptors are present in certain somatodendritic and axonal profiles that contain NPY or that appose NPY containing neurons. The Y1-like immunoreactivity (Y1-LI) was seen occasionally along plasma membranes but was associated more commonly with smooth endoplasmic reticulum (SER) and tubulovesicular organelles in somata and dendrites of spiny and aspiny neurons. The mean density of immunoreactive dendrites and spines per unit volume was greater in the "motor-associated" core than in the shell of the NAc. Y1-LI was also seen in morphologically heterogenous axon terminals, including those forming asymmetric excitatory-type synapses, and in selective astrocytic processes near this type of junction. We conclude that Y1 receptors play a role in autoregulation of NPY-containing neurons but are also likely to be internalized along with endogenous NPY in NAc. Our results also implicate Y1 receptors in the NAc in post- and presynaptic effects of NPY and in glial functions involving excitatory neurotransmission. In addition, they suggest involvement of Y1 receptors in determining the output of a select population of neurons associated with motor control in the NAc core.