Characterization of Sentinel Lymph Node Immune Signatures and Implications for Risk Stratification for Adjuvant Therapy in Melanoma.
Although sentinel lymph node (SLN) biopsy is a standard procedure used to identify patients at risk for melanoma recurrence, it fails to risk-stratify certain patients accurately. Because processes in SLNs regulate anti-tumor immune responses, the authors hypothesized that SLN gene expression may be used for risk stratification. The Nanostring nCounter PanCancer Immune Profiling Panel was used to quantify expression of 730 immune-related genes in 60 SLN specimens (31 positive [pSLNs], 29 negative [nSLNs]) from a retrospective melanoma cohort. A multivariate prediction model for recurrence-free survival (RFS) was created by applying stepwise variable selection to Cox regression models. Risk scores calculated on the basis of the model were used to stratify patients into low- and high-risk groups. The predictive power of the model was assessed using the Kaplan-Meier and log-rank tests. During a median follow-up period of 6.3 years, 20 patients (33.3%) experienced recurrence (pSLN, 45.2% [14/31] vs nSLN, 20.7% [6/29]; p = 0.0445). A fitted Cox regression model incorporating 12 genes accurately predicted RFS (C-index, 0.9919). Improved RFS was associated with increased expression of TIGIT (p = 0.0326), an immune checkpoint, and decreased expression of CXCL16 (p = 0.0273), a cytokine important in promoting dendritic and T cell interactions. Independent of SLN status, the model in this study was able to stratify patients into cohorts at high and low risk for recurrence (p < 0.001, log-rank). Expression profiles of the SLN gene are associated with melanoma recurrence and may be able to identify patients as high or low risk regardless of SLN status, potentially enhancing patient selection for adjuvant therapy.


Experimental infection of calves with Newcastle disease virus induces systemic and mucosal antibody responses.
Calves were infected intranasally and intratracheally with Newcastle disease virus (NDV), an avian paramyxovirus. Clinical signs, viral replication, and antibody production were evaluated. This study showed that NDV replicated in calves, as evidenced by development of NDV-specific humoral and mucosal antibody responses, but was attenuated in this unnatural host. These results suggest that NDV has the potential for development as a host-range-restricted, intranasal vaccine vector for cattle that lack preexisting immunity to NDV.


Mini medical record application: annual register for flu shot vaccinations.
This application is an Intranet-based system. A database has been established utilizing patient information on the basis of age, medical diagnosis and employment history. If a health care provider or support staff states that a patient is over 65 years of age or has been diagnosed with a chronic disease and this limits the patient's ability to fight off infection, the need for preventive care is activated. In this situation the preventive care is the administration of an annual flu shot. For anyone over 65 years of age or with a chronic illness, a bulk mail of reminder cards with the dates of availability of injection is generated and mailed. All health care workers are notified at work of vaccination sites that they can use. In addition, should a patient have an appointment with a provider and a preventive flu injection is indicated, a reminder appears on the registration form. This reminder indicates a flu shot is needed as well as other preventive intervention.


Effects of peripheral circular contours on dynamic spatial orientation.
The rod-and-frame effect (RFE) was investigated with the use of a frame that oscillated about an axis at its center at five different frequencies, ranging from .013 to .213 Hz. The resultant RFE shifted continuously with the roll motion of the frame, and it was significantly larger at the lowest frequency (.013 Hz) than under comparable static conditions. The dynamic RFE was lowest at the higher oscillation frequencies. Oscillatory roll vection--apparent self-motion--was reported by 3 of the 9 subjects when the frame was oscillating at its highest frequency (.213 Hz). The subjects yielded large increases in the RFE during the sessions with reports of vection. Surrounding the kinetic frame with a circular contour eliminated all reports of vection and significantly interacted with frequency to reduce the RFE--but only at low frequencies. The reduction amounted to 21.2% averaged over all 9 subjects at the three lowest frequencies. A surrounding contour, therefore, suppressed low-frequency kinetic visual orientation information that might otherwise have produced larger changes in apparent self-orientation and perceived vertical. Vection-sensitive subjects differed from nonvection subjects by exhibiting (1) a high-frequency fall-off in real-motion gain, (2) a high-frequency enhancement in illusory-motion gain, and (3) only a small and nonsignificant increase in illusory-movement phase lag with increases in frequency.


A combination of ion exchange and electrochemical reduction for nitrate removal from drinking water. Part II: electrochemical treatment of a spent regenerant solution.
The process of electrochemical treatment of a solution after strong basic anion exchanger regeneration was studied. The goal of the study was to reduce the nitrate content in the solution to allow its use in a closed loop. Diaphragmless, flow-through cells in a recirculation mode with and without a fluidizing bed of inert particles in the interelectrode space equipped with copper (Cu) cathodes and activated titanium anodes were used. The temperature was maintained at 20 degrees C. To assess the influence of recirculation of the regenerant solution on the quality of the treated water, the effect of the addition of copper ions to the solution, postelectrolysis cathode treatment, and enhanced mass transfer on the electrolysis results with respect to current efficiency and residual nitrate and nitrite concentration were investigated using an artificial solution. On the basis of the experimental results, a laboratory-scale unit for selective nitrate removal was designed and constructed that integrated ion exchange and electrochemical cell to one assembly. The process of recirculation of regenerant solution was tested using groundwater.


Autoradiographic distribution of [3H](+)-pentazocine and [3H]1,3-di-o-tolylguanidine (DTG) binding sites in guinea pig brain: a comparative study.
Binding studies suggested the selectivity of (+)-pentazocine for sigma receptors, and subsequent synthesis and testing of [3H](+)-pentazocine confirmed its high potency and selectivity for sigma sites. Newer data have demonstrated the selectivity of (+)-pentazocine for a subtype of the sigma receptor called sigma-1. Based on these findings, the distribution of [3H](+)-pentazocine binding sites in the guinea pig brain was examined using in vitro autoradiography. [3H](+)-Pentazocine binding was high in the cingulate cortex, dorsal diagonal band, periaqueductal gray, cerebellum and cranial nerve nuclei. It was relatively low in the nucleus accumbens, neocortical areas and caudate nucleus. A significant correlation was found between the binding of [3H](+)-pentazocine and [3H]1,3-di-o-tolylguanidine, a selective sigma ligand across brain regions. However, certain nuclei exhibited markedly different ratios of binding of the two ligands. Since DTG is not selective for the sigma subtypes, while (+)-pentazocine is selective for the sigma-1 type, the data are suggestive of relative differences in the distributions of sigma-1 and sigma-2 sites.


Production, purification and characterization of novel beta glucosidase from newly isolated Penicillium simplicissimum H-11 in submerged fermentation.
β-Glucosidase is an important component of the cellulase complex. It not only hydrolyzes cellobiose and short-chain cellooligosaccharides to glucose, but also removes the inhibitory effect of cellobiose on the β-1, 4-endoglucanase and exoglucanase, thereby increasing the overall rate of cellulose biodegradation. β-glucosidasefrom culture supernatant of a fungus Penicillium simplicissimum was purified to homogeneity, by using ammonium sulfate fraction, Sephadex G-100 chromatography, and its properties were studied. The molecular mass of the enzyme was about 126.0 kDa, as identified by 12% SDS-PAGE. The optimum pH and temperature were 4.4 ~ 5.2 and 60 °C, respectively. The enzyme was stable in pH 5.2 ~ 6.4 and under 40 °C. Metal profile of the enzyme showed that Mn(2+) enhances its activity, while Cu(2+), Co(2+)and Fe(3+) cause obvious inhibition. The K m and V max was 14.881 mg/ml and 0.364 mg ml/min against salicin as a Substrate. This enzyme had secondary protein structure as evidenced by FTIR spectrum.


A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma.
Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is an independent predictor of poor outcomes subsequent to surgical resection or liver transplantation (LT); however, MVI currently cannot be adequately determined preoperatively. Radiogenomic venous invasion (RVI) is a contrast-enhanced computed tomography (CECT) biomarker of MVI derived from a 91-gene HCC "venous invasion" gene expression signature. Preoperative CECTs of 157 HCC patients who underwent surgical resection (N = 72) or LT (N = 85) between 2000 and 2009 at three institutions were evaluated for the presence or absence of RVI. RVI was assessed for its ability to predict MVI and outcomes. Interobserver agreement for scoring RVI was substantial among five radiologists (κ = 0.705; P < 0.001). The diagnostic accuracy, sensitivity, and specificity of RVI in predicting MVI was 89%, 76%, and 94%, respectively. Positive RVI score was associated with lower overall survival (OS) than negative RVI score in the overall cohort (P < 0.001; 48 vs. >147 months), American Joint Committee on Cancer tumor-node-metastasis stage II (P < 0.001; 34 vs. >147 months), and in LT patients within Milan criteria (P < 0.001; 69 vs. >147 months). Positive RVI score also portended lower recurrence-free survival at 3 years versus negative RVI score (P = 0.001; 27% vs. 62%). RVI is a noninvasive radiogenomic biomarker that accurately predicts histological MVI in HCC surgical candidates. Its presence on preoperative CECT is associated with early disease recurrence and poor OS and may be useful for identifying patients less likely to derive a durable benefit from surgical treatment.


Synthesis and cytotoxicity of 3,4-diaryl-2(5H)-furanones.
A series of 3,4-diaryl-2(5H)-furanone derivatives were synthesized and evaluated for their cytotoxicity in a small panel of cancer cell lines. Four out of 10 compounds in this series, for example 3-(3,4,5-trimethoxyphenyl)-4-(4-methoxyphenyl)-, 3-(3,4,5-trimethoxyphenyl)-4-(3-hydroxy-4-methoxyphenyl)-, 3-(3,4,5-trimethoxyphenyl)-4-(3-amino-4-methoxyphenyl)-, and 3-(3,4,5-trimethoxyphenyl)-4-(2-naphthyl)-2(5H)-furanones, were found to have potent cytotoxic activities with ED50 values of less than 20 nM in most of the cell lines tested.


Transplant Outcomes From Deceased Donors Dying With Burns Injury, a Systematic Review.
The ever-expanding organ supply and demand gap necessitates alternate sources of organ donors. Initially thought to be a contraindication, organ procurement from nonsurvivable burns patients is possibly an additional organ donor source. We aimed to conduct a systematic review investigating the prevalence and outcomes of the use of burn victims as a source of organ donation for transplantation. Medline and EMBASE were searched between 1990 and 2020, using the following keywords: organ procurement, organ donation, organ transplantation, and burns. Studies were not excluded based on patient numbers and included both published abstracts/conference proceeding and journal articles. Studies were excluded if specific organs were not identified or if posttransplant outcomes were not recorded. Primary and secondary outcomes of interest were post-transplantation organ function and complications respectively. Six manuscripts met study inclusion criteria. Fourteen burns donors were identified, including both donation after circulatory death and donation after brain death pathways. The total body surface area of burn ranged from 4% to 90%. A total of 4 hearts, 2 lungs, 8 livers, 1 pancreas, and 24 kidneys were transplanted with varying duration of follow-up and outcomes. A very small number of studies have reported the posttransplant outcomes of organs derived from victims of burn injury, including very limited information regarding graft function in the short or long term. Hence, recommendations for the utilization of organs from victims of burn injury should remain guarded and subject to surveillance.


Patient Satisfaction with Orthopedic Telemedicine Health Visits During the COVID-19 Pandemic.
Background:Telemedicine usage in orthopedic surgery has seen a dramatic increase as a result of the severe acute respiratory syndrome coronavirus 2 pandemic. The purpose of this study was to examine patient perceptions with telemedicine at a large orthopedic practice.Materials and Methods:An anonymous online survey was distributed to all patients who received a telemedicine health visit at our institution for musculoskeletal complaints from March 17 to June 1, 2020. Responses were scored on a 5-point Likert scale (strongly disagree, disagree, neutral, agree, and strongly agree, 1-5) and analyzed by average score and percent reaching top box.Results:A majority of patients (76.5%) were satisfied with their visit, and only 19.2% did not want telemedicine as a future option. Patients who presented for follow-up visits (4.11 vs. 3.94, p = 0.0053; 48% vs. 41%, p = 0.02) and utilized video (4.21 vs. 3.88, p < 0.001; 51% vs. 39%, p < 0.001) were more satisfied. Average satisfaction between older (>65 years) and younger patients was similar (4.06 vs. 4.06, p = 0.97), however, younger patients were more likely to reach top box (42% vs. 51%, p < 0.001). Confidence that the physician came to the correct diagnosis (r = 0.78, p < 0.001) and receiving the same information and care as an in-office visit (r = 0.60, p < 0.001) demonstrated the strongest correlation with satisfaction and desire for future telemedicine visits, respectively. Interestingly, 31.1% of patients would have sought treatment elsewhere had telemedicine not been an option.Conclusions:Overall, satisfaction rates are high for orthopedic patients undergoing telemedicine visits. Patients are more confident in telemedicine when presenting for a follow-up visit and with the use of video.


Anxiety Presentations and Treatments in Populations With Kidney Disease.
Anxiety is common in patients with chronic kidney disease, but in its extreme expressions, anxiety can also be a complicating comorbid psychiatric illness. There is only a small literature base on anxiety disorders in patients with renal disease, and many of the studies are not sufficiently specific about which anxiety disorders are being studied. Larger epidemiological studies are required to delineate the incidence, prevalence, and outcomes associated with the varied anxiety disorders. In addition, the impact of the co-occurrence of anxiety with other chronic psychiatric or medical problems, needs further study. Anxiety is a clinical condition that warrants treatment, primarily due to its association with mortality in end-stage renal disease patients, and its negative impact on perceived quality of life. Therapeutic options for patients with anxiety and kidney disease include both pharmacologic and nonpharmacologic approaches. Current treatment strategies for anxiety specific to patients with renal disease are provided.


Increased B-type natriuretic peptide levels in early-onset versus late-onset preeclampsia.
We compared B-type natriuretic peptide (BNP) levels, clinical and laboratory findings in early-onset preeclampsia (EOP), late-onset preeclampsia (LOP) and healthy pregnant groups. We studied 40 healthy pregnant and 40 preeclamptic patients. Preeclamptics were divided in two groups, the EOP group (n=20) and LOP group (n=20), according to gestational age at the onset of disease. The distinction criterion for early- vs. late-onset was set as week 34 of gestation. The concentration of the BNP levels was measured by a sandwich fluorescence immunoassay. For statistical analysis of the clinical and laboratory findings non-parametric methods were applied. BNP levels were higher in EOP [61.35 (36.95-93.25) pg/mL] and LOP patients [32.4 (19.15-39.2) pg/mL] than in healthy pregnant women [10.05 (6.08-16.03) pg/mL] (both p<0.001). Furthermore, EOPs had significantly higher BNP levels as compared to LOP patients (p<0.001). A BNP cut-off <24.5 pg/mL had a negative-predictive value of 85.1% excluding preeclampsia. There was a significant inverse correlation between plasma BNP levels of EOP patients and sodium (p<0.05) and total protein concentrations (p<0.05). In the EOP group, a significant positive correlation was observed between plasma levels of BNP and hematocrit (p<0.05), serum potassium (p<0.05), urea (p<0.05) and 24-h proteinuria (p<0.05). BNP levels were significantly higher in EOP than in LOP patients. The cut-off value <24.5 pg/mL seems to be a powerful discriminative indicator excluding preeclampsia. The amount of proteinuria and total protein levels correlate with the elevation of the BNP levels. In EOP the extent of proteinuria is higher than in the LOP.


Cardiac output measurement by pulse dye densitometry: a comparison with the Fick's principle and thermodilution method.
To evaluate the agreement between cardiac output (CO) measurements obtained by a new dye dilution technique using pulse dye densitometry (PDD) and thermodilution (TD) and the direct Fick method (F). Prospective clinical study in a university hospital, cardiac surgery intensive care unit. Fifty-eight cardiac surgery patients after admission to the intensive care unit (six were excluded due to a low pulse signal quality using the PDD method). Mean CO was 5.3+/-1.8 l/min for PDD, 5.7+/-1.68 l/min for TD, and 6.16+/-1.66 l/min for F. There was a good correlation between PDD and TD ( r(2)=0.93) and between PDD and F ( r(2)=0.77). Bias and precision between PDD and TD were -0.39+/-0.5 l/min and -0.69+/-0.85 l/min between PDD and F. In general, PDD determined lower CO values than TD and F. Especially in patients with CO below 5 l/min PDD underestimated CO in comparison to TD and F (bias and precision: -0.51+/-0.40 l/min and -0.83+/-1.0 l/min). Comparison between PDD and TD showed good agreement for the normal to high CO range. However, agreement was poor in patients with low CO. In the latter patient group PDD showed relevant underestimation of CO compared to TD and F. Due to these limitations PDD cannot entirely replace the pulmonary artery catheter for CO determination.


Plasmodium falciparum in vitro schizont maturation tests in Mozambique are not improved by removing immune parasite carriers' plasma.
To study the effect of immune parasite carriers' plasma on Plasmodium falciparum schizont maturation, peripheral blood stages were incubated for 24-40 h in RPMI medium with either 5% carrier's plasma + 5% non-immune AB serum or 10% non-immune serum. The number of schizonts per 200 asexual P. falciparum was lower in non-immune serum than in the presence of carrier's plasma in 19 of 26 cases, due to increased frequency of schizont rupture when carrier's plasma was absent. It is concluded that, under these test conditions, the replacement of immune plasma by non-immune serum makes schizont maturation tests, which are based on the proportion of schizonts among asexual P. falciparum as a measure of growth, more difficult to interpret.


Whole genome sequencing and evolution analyses of Human metapneumovirus.
Human metapneumovirus (HMPV) is a major pathogen of acute respiratory tract infections (ARTIs) in children. Whole genome sequence analyses could help understand the evolution and transmission events of this virus. In this study, we sequenced HMPV whole genomes to improve the identification of molecular epidemiology in Beijing, China. Nasopharyngeal aspirates of hospitalized children aged < 14 years old with ARTIs were screened for HMPV infection using qPCR. Fourteen pairs of overlapping primers were used to amplify whole genome sequences of HMPV from positive samples with high viral loads. The epidemiology of HMPV was analysed and 27 HMPV whole genome sequences were obtained. Sequence identity and the positional entropy analyses showed that most regions of HMPV genome are conserved, whereas the G gene contained many variations. Phylogenetic analysis identified 25 HMPV sequences that belonged to a newly defined subtype A2b1; G gene sequences from 24 of these contained a 111-nucleotide duplication. HMPV is an important respiratory pathogen in paediatric patients. The new subtype A2b1 with a 111-nucleotide duplication has become predominate in Beijing, China.


Reversal of defunctioning stoma following rectal cancer surgery: are we getting better? A population-based single centre experience.
The aim was to assess factors influencing the timing of defunctioning stoma (DS) reversal following low anterior resection of rectum for cancer (LAR). All patients operated with LAR and a primary DS during a 9-year period were included. Reversal later than 120 days after LAR was considered as delayed. A DS not reversed within 2 years was considered as permanent. In the present study, median age at LAR was 67 years, 45% were females, median body mass index was 25, 87% had American Society of Anesthesiologists class I or II, 64% had pre-operative radiotherapy, and 3% had cancer stage IV. A total of 79% (92/116) underwent stoma reversal, whereof 25% (23/92) were reversed within 120 days. The most common health-related reasons for delayed stoma reversal were adjuvant chemotherapy in 38%, symptomatic anastomotic leakage in 16% and other post-operative adverse events in 13%. In 35% delayed stoma reversal was because of low priority within the healthcare system. A total of 18% (20/110) never had their DS reversed (n = 11) or had their DS converted to a permanent end colostomy (n = 9). Major risk factors for permanent stoma were stage IV cancer in 55%, and symptomatic anastomotic leakage in 30%. One fourth of the patients had their defunctioning stoma reversed within 120 days. The most common identifiable medical reasons for delayed stoma reversal were adjuvant chemotherapy and symptomatic anastomotic leakage, while in one out of three patients it was because of low priority by the healthcare provider.


The connections of the sensory organ of Bellonci with the brain in Isopoda (crustacea).
The peduncle linking the organ of Bellonci with the brain was examined in Sphaeroma serratum and Anilocra frontalis. This peduncle, in its extension to the brain, becomes a nerve-like tract with bundles of pedicles originating from the sensory cell bodies located in the organ of Bellonci. It ends at the level of the medulla interna in an alveolar region resulting from the swelling of the sensory pedicle terminations. At this level three types of connections have been observed. The first is characterized by afferent synapses to the brain with, in the sensory pedicle endings, structures similar to the presynaptic ribbons noted by some authors in photoreceptors of arthropods. The two other types include nerve fibres originating from the brain, one with small electron lucent vesicles, a second displaying larger vesicles with a core of medium density. These fibres form efferent synapses to the organ of Bellonci. The sensory differentiation of the organ of Bellonci in Isopoda is confirmed but its true role is not specified.


Employment Standards for Australian Urban Firefighters: Part 1: The Essential, Physically Demanding Tasks.
This communication is the first of four describing the development of defensible firefighter-selection tests. The purpose was to identify a subset of essential, physically demanding tasks performed by contemporary urban firefighters. From existing procedural documentation and job analyses, 11 fire-station visits and interviews with 106 firefighters, and one focus-group meeting, 31 physically demanding tasks were identified and incorporated into a workforce survey. Using this tool, firefighters rated the importance, perceived difficulty, typical task durations, and annual performance frequency of each task. Data from 989 respondents were analyzed, enabling a consolidation of these tasks into a subset of essential activities. These processes yielded a content-valid list of 15 essential, physically demanding tasks covering the full width of duties performed by urban firefighters from Australia's largest fire and rescue organization.


Observations on the reproductive performance of ewe lambs synchronised for oestrus.
Oestrus induction and synchronisation achieved by means of progesterone implants (Silestrus; Abbott) and one or two injections of 500 in FSH (Gestyl; Organon) at 15-day intervals was followed by natural service in 194 10-month-old ewe lambs, fed on pasture (Group A, of 101 animals) or pasture and concentrates (Group B, of 93 animals) used to study the influence of nutrition and of induction of a second synchronised oestrus on the percentage of oestrus manifestations, conception rate, number of lambings and of lambs born among the above animals.


Three other types of duodenal polyps: mucosal cysts, focal foveolar hyperplasia, and hyperplastic polyp originating from islands of gastric mucosa.
Seven cases are reported that initially presented on endoscopic examination as duodenal polyps originating from islands of gastric mucosa within the duodenal bulb. Microscopic examination revealed mucosal cysts (MC), focal foveolar hyperplasia (FFH), and hyperplastic polyp (HPP). These lesions must be added to the list of neoplastic and tumorlike lesions of the duodenum that may endoscopically present as polyps.


Beals smoothing revisited.
Beals smoothing is a multivariate transformation specially designed for species presence/absence community data containing noise and/or a lot of zeros. This transformation replaces the observed values of the target species by predictions of occurrence on the basis of its co-occurrences with the remaining species. In many applications, the transformed values are used as input for multivariate analyses. As Beals smoothing values provide a sense of "probability of occurrence", they have also been used for inference. However, this transformation can produce spurious results, and it must be used with caution. Here we study the statistical and ecological bases underlying the Beals smoothing function, and the factors that may affect the reliability of transformed values are explored using simulated data sets. Our simulations demonstrate that Beals predictions are unreliable for target species that are not related to the overall ecological structure. Furthermore, the presence of these "random" species may diminish the quality of Beals smoothing values for the remaining species. A statistical test is proposed to determine when observed values can be replaced with Beals smoothing predictions. Two real-data example applications are presented to illustrate the potentially false predictions of Beals smoothing and the necessary checking step performed by the new test.


[How to evaluate sudden cardiac death risk after myocardial infarction?].
Sudden cardiac death is the mode of death of more than half of coronary heart disease patients. Preventing sudden cardiac death involves prevention of ventricular arrhythmias occurrence as well as the treatment by an implantable cardioverter defibrillator. The evaluation of sudden cardiac death risk should consider the underlying cardiopathy, the associated coronary risk factors and all pharmacological treatment efficient to reduce ventricular remodeling and myocardial ischemia. Only significant low ejection fraction and positive ventricular testing in some cases are now considered are now considered by the current French recommendations for cardioverter defibrillator implantation in primary prevention. However, other noninvasive markers such as heart rate variability and T wave alternans are of interest in sudden cardiac death risk stratification after myocardial infarction.


Peripheral arterial thrombolytic therapy.
The management of the patient with an acute arterial occlusion or pulmonary embolus presents many challenges. Thrombolytic therapy offers a treatment option that was not available in the past. We now have several nonsurgical options for treating patients with both peripheral arterial and pulmonary arterial occlusions. There are choices as to the appropriate drug as well as the route, dose, and length of administration. The work underway is aimed at refining technique. Studies that are ongoing now focus on which drug and mode of delivery benefits certain groups of patients. Although each clinical situation is unique, the guidelines to be established through further investigations will aid clinicians in selecting the appropriate therapeutic modality.


A recurrent SHANK1 mutation implicated in autism spectrum disorder causes autistic-like core behaviors in mice via downregulation of mGluR1-IP3R1-calcium signaling.
The genetic etiology and underlying mechanism of autism spectrum disorder (ASD) remain elusive. SHANK family genes (SHANK1/2/3) are well known ASD-related genes. However, little is known about how SHANK missense mutations contribute to ASD. Here, we aimed to clarify the molecular mechanism of and the multilevel neuropathological features induced by Shank1 mutations in knock-in (KI) mice. In this study, by sequencing the SHANK1 gene in a cohort of 615 ASD patients and 503 controls, we identified an ASD-specific recurrent missense mutation, c.2621 G > A (p.R874H). This mutation demonstrated strong pathogenic potential in in vitro experiments, and we generated the corresponding Shank1 R882H-KI mice. Shank1 R882H-KI mice displayed core symptoms of ASD, namely, social disability and repetitive behaviors, without confounding comorbidities of abnormal motor function and heightened anxiety. Brain structural changes in the frontal cortex, hippocampus and cerebellar cortex were observed in Shank1 R882H-KI mice via structural magnetic resonance imaging. These key brain regions also showed severe and consistent downregulation of mGluR1-IP3R1-calcium signaling, which subsequently affected the release of intracellular calcium. Corresponding cellular structural and functional changes were present in Shank1 R882H-KI mice, including decreased spine size, reduced spine density, abnormal morphology of postsynaptic densities, and impaired hippocampal long-term potentiation and basal excitatory transmission. These findings demonstrate the causative role of SHANK1 in ASD and elucidate the underlying biological mechanism of core symptoms of ASD. We also provide a reliable model of ASD with core symptoms for future studies, such as biomarker identification and therapeutic intervention studies.


Halomonas salipaludis sp. nov., isolated from a saline-alkali wetland soil.
Strain WRN001T, a Gram-staining-negative, strictly aerobic, non-motile bacterium was isolated from the natural saline-alkali wetland soil of Binhai new district, Tianjin, China (38°46' N, 117°13' E). Cells of strain WRN001T were 0.3-0.5 µm in width and 1.5-2.5 µm in length, and the growth occurred optimally at 33-37 °C, pH 7.5-8.0, and in the presence of 8-10% (w/v) NaCl. Based on 16S rRNA gene sequence analysis, the isolate could be affiliated to the genus Halomonas, and the highest 16S rRNA gene sequence similarity of strain WRN001T to its closest relative Halomonas qiaohouensis DSM 26770 T was 97.5%. The size of the genome as presented here was 5,475,884 bp with a G + C content of 63.8 mol %. The major respiratory quinone of strainWRN001T was Q-9, and the dominant fatty acids were summed feature 8, summed feature 3, C10:0, C12:0, C12:0 3-OH, C16:0, and C17:0 cyclo. The major polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phophatidylcholine (PC), two phospholipids (PL), aminolipid (AL), and three unidentified lipids (L). These data combined with the low digital DDH values between strain WRN001T and the close relative, Halomonas alkalitolerans CGMCC 1.9129 T (42.2%) and based on comparisons with currently available genomes, the highest average nucleotide identity (ANIm) value was 91.4% to Halomonas alkalitolerans CGMCC 1.9129 T (GenBank accession No. GCA_001971685.1). Therefore, we propose a novel species in the genus Halomonas to accommodate this novel isolate: Halomonas salipaludis sp. nov. (type strain WRN001T = KCTC 52853 T = ACCC 19974 T).


The evolving role of the masseter-to-facial (V-VII) nerve transfer for rehabilitation of the paralyzed face.
In cases where the proximal stump of the facial nerve is unavailable for repair or interposition nerve grafting, and there are intact distal facial nerve branches and viable mimetic muscles, then the masseter-to-facial (V-VII) nerve transfer can provide an effective means of smile restoration. Positive attributes of the V-VII transfer include: limited donor site morbidity, anatomic consistency, a dense population of myelinated motor nerve fibers capable of producing strong motion, synergy with the facial nerve and potential for effective cerebral adaptation yielding an effortless smile. The technique can be utilized in isolation or combined with cross face nerve grafts to further enhance spontaneity and resting tone.


Analysis of cross-talk cancellation of bilateral bone conduction stimulation.
When presenting a stereo sound through bilateral stimulation by two bone conduction transducers (BTs), part of the sound at the left side leaks to the right side, and vice versa. The sound transmitted to the contralateral cochlea becomes cross-talk, which can affect space perception. The negative effects of the cross-talk can be mitigated by a cross-talk cancellation system (CCS). Here, a CCS is designed from individual bone conduction (BC) transfer functions using a fast deconvolution algorithm. The BC response functions (BCRFs) from the stimulation positions to the cochleae were obtained by measurements of BC evoked otoacoustic emissions (OAEs) of 10 participants. The BCRFs of the 10 participants showed that the interaural isolation was low. In 5 of the participants, a cross-talk cancellation experiment was carried out based on the individualized BCRFs. Simulations showed that the CCS gave a channel separation (CS) of more than 50 dB in the 1-3 kHz range with appropriately chosen parameter values. Moreover, a localization test showed that the BC localization accuracy improved using the CCS where a 2-4.5 kHz narrowband noise gave better localization performance than a broadband 0.4-10 kHz noise. The results indicate that using a CCS with bilateral BC stimulation can improve interaural separation and thereby improve spatial hearing by bilateral BC.


Ulcerative colitis with chronic liver disease, eosinophilia and auto-immune thyroid disease.
A patient with chronic mild ulcerative colitis is described. Her illness was characterized by fluctuating blood eosinophilia, chronic persistent hepatitis and hypersensitivity to sulphasalazine. She subsequently developed auto-immune thyroid disease. The inter-relationships of these various disorders are discussed.


Raman spectroscopy of follicular fluid and plasma with machine-learning algorithms for polycystic ovary syndrome screening.
Polycystic ovary syndrome (PCOS) is the main cause of anovulatory infertility and affects women throughout their lives. The specific diagnostic method is still under investigation. In the present study, we aimed to identify the metabolic tracks of the follicular fluid and plasma samples from women with PCOS by performing Raman spectroscopy with principal component analysis and spectral classification models. Follicular fluid and plasma samples obtained from 50 healthy (non-PCOS) and 50 PCOS women were collected and measured by Raman spectroscopy. Multivariate statistical methods and different machine-learning algorithms based on the Raman spectra were established to analyze the results. The principal component analysis of the Raman spectra showed differences in the follicular fluid between the non-PCOS and PCOS groups. The stacking classification models based on the k-nearest-neighbor, random forests and extreme gradient boosting algorithms yielded a higher accuracy of 89.32% by using follicular fluid than the accuracy of 74.78% obtained with plasma samples in classifying the spectra from the two groups. In this regard, PCOS may lead to the changes of metabolic profiles that can be detected by Raman spectroscopy. As a novel, rapid and affordable method, Raman spectroscopy combined with advanced machine-learning algorithms have potential to analyze and characterize patients with PCOS.


Rich Country, Poor People: the challenges of providing psychiatric services in the public and the private sectors in Papua New Guinea.
To describe some of the challenges in the provision of psychiatric services in Papua New Guinea. Many of the challenges faced when providing mental health care are not clinical in nature, but rather a combination of social, cultural, economic and infrastructural factors that hinder the adequate provision of, and access to, psychiatric services in Papua New Guinea.


Cross-face nerve transplant.
The two stage principle is one of the most important features of the procedure. It allows starting the operation at a very early stage (one to six months). The donor area in the periphery is very well supplied, therefore as many facial fascicles as necessary can be sacrificed on the healthy side. We have never noticed any functional disturbances. The nerves leading to the buccinator muscle and those which innervate the lateral pull of the mouth are especially suitable. This weakening of the strong pull of the mouth is of great value for symmetry but unfortunately relapse to the original state is common. The selection of the nerve fascicles on the healthy side must be executed in a deep layer below the muscles because all large branches are located here. The end of the sural grafts should positioned far back on the paralyzed side to enable easy anastomoses at the second stage. A face lift incision on the paralyzed side and tightening of the skin are of additional value and provide some support to the elongated muscles. The combination of cross-face nerve transplant with other substitutional methods in which muscles are used for reinnervation is very promising. In our experience physiotherapy is a very important measure. It should be started after the onset of the palsy and continued until restoration of the face is complete. It is usually applied three times a week with exponential current and at a strength of 20 to 60 milliamperes. Each group of muscles receives a 2 to 3 minutes dosage. It is helpful if the patient can use a stimulation apparatus at home daily for short treatments.


Spondylodiscitis associated with recurrent Serratia bacteremia due to a transjugular intrahepatic portosystemic shunt (TIPS): a case report.
We report a case of spondylodiscitis caused by multiresistant Serratia marcescens in a cirrhotic patient who had several Serratia bacteremias after the placement of a transjugular intrahepatic portosystemic shunt (TIPS) device. We concluded that an endovascular stent that can not be removed makes management of recurrent bacteremia difficult. Furthermore, back pain due to bacteremia is indicative of spondylodiscitis. Serratia marcescens can be an aggressive pathogen, causing spinal infection.


An x-ray study of the paracrystalline nature of bone apatite.
X-ray diffraction from oriented bone sections show that the crystalline apatite content of untreated mature cortical bovine bone has, in fact, a paracrystalline structure (i.e., no long range order). There is anisotropy in both lattice distortions and the sizes of the coherently diffracting domains. The paracrystalline mean distance fluctuations (g) were found to be 1.5 (+/- 0.1)% and 2.9 (+/- 0.2)% for the basal and prism planes respectively, the corresponding paracrystalline sizes being 220 (+/- 20) and 70 (+/- 10) A. The paracrystalline structure became more ordered above 600 degrees C, suggesting the association of hydroxyl and possibly carbonate and other ions with the paracrystalline structure. The paracrystalline model for bone apatite helps explain anomalies between X-ray and electron microscope measurements of crystal size and also more of the biological functions of the crystalline apatite.


Quality orthopaedic care in sudden-onset disasters: suggestions from Médecins Sans Frontières-France.
A huge change is needed in the conception and implementation of surgical care during sudden-onset disasters (SOD). The inadequate surgical response mounted by the majority of foreign medical teams (FMT) after Haiti's earthquake is a striking example of the need for a structured professional approach. Logistical capacity already exists to provide safe, timely, effective, efficient, equitable and ethical patient-centred care with minimum standards. However, knowledge, skills and training in the fields of general, orthopaedic and plastic surgery need further clarification. Surgical activity data and clinical examples from several Médecins Sans Frontières-France (MSF) projects are used here to describe the skill set and experience essential for surgeons working in SOD contexts.


A combined luciferase imaging and reverse transcription polymerase chain reaction assay for the study of Leishmania amastigote burden and correlated mouse tissue transcript fluctuations.
Laboratory mice display features of bona fide hosts for parasites such as Leishmania major and Leishmania donovani. Characterizing the amastigote population size fluctuations and the mouse transcript abundance accounting for these fluctuations demands the capacity to record in real time and integrate quantitative multiparametric datasets from the host tissues where these processes occur. To this end, two technologies, luciferase-expressing Leishmania imaging and a very sensitive quantitative analysis of both Leishmania and mouse transcripts, were combined. After the inoculation of either L. major or L. donovani, the amastigote population size fluctuations - increase, plateau and reduction - were monitored by bioluminescence. It allowed a limited number of mice to be selected for further analysis of both mouse and amastigote transcripts using the real-time quantitative polymerase chain reaction assay we set up. The illustrative examples displayed in the present analysis highlight a correlation between the transcriptional signatures displayed by mouse tissues with the amastigote burden fluctuations. We argue that these two combined technologies will have the potential to provide further insights on complex phenotypes driven by Leishmania developmental programs in the tissues of the mammal hosts.


The effects of warm water immersion on blood pressure, heart rate and heart rate variability in people with chronic fatigue syndrome.
Chronic fatigue syndrome (CFS) is a central sensitisation syndrome with abnormalities in autonomic regulation of blood pressure (BP), heart rate (HR) and heart rate variability (HRV). Prior to exploring the effects of hydrotherapy as a treatment for this population, changes in BP, HR and HRV during warm water immersion need to be established. The study aimed to determine the effects of warm water immersion on BP, HR and HRV in adults with CFS compared to matched-pair healthy adults. A quasi-experimental, single-blinded study design was used with nine CFS participants and nine matched controls. Participants' BP, HR and HRV were measured before, after 5 minutes and post warm water immersion at the depth of the fourth intercostal space, using the Ithlete® System and Dräger BP monitor. There was a significant difference between groups in HRV prior to immersion (control group: 73 [55-74] vs. chronic fatigue syndrome group: 63 [50-70]; p = 0.04). There was no difference in HRV post-immersion. A significant difference in HR after immersion was recorded with the control group having a lower HR than those with CFS (78 [60-86] vs. 86 [65-112]; p = 0.03). The low HRV present in the CFS group prior to immersion suggests autonomic dysregulation. Individuals with CFS may have reduced vagal nerve activation post-immersion. During immersion, HRV of the CFS participants improved similar to that of the healthy controls. Prior to immersion, differences were present in the HRV of the participants with CFS compared to healthy controls. These differences were no longer present post-immersion. Warm water immersion appears safe and may be beneficial in the management of individuals with CFS.


[Evaluation of inpatient adolescent psychiatric therapy--a comparison of the attitudes of adolescents and parents].
This paper reports methods and findings of a retrospective study on this subject. Remarkable contrasts regarding central aspects of adolescent psychiatric inpatient treatment offer an interesting variety of hypotheses and desire quantitative and qualitative amplifications of the study.


Pyridine hydroxamic acids are specific anti-HCV agents affecting HDAC6.
Recently we reported benzohydroxamic acids (BHAs) as potent and selective inhibitors of hepatitis C virus (HCV) replicon propagation. In this work 12 pyridine hydroxamic acids (PHAs) were synthesized and tested in full-genome replicon assay. It was found that PHAs possessed very similar anti-HCV properties compared to BHAs. Both classes of hydroxamic acids caused hyperacetylation of α-tubulin pointing to inhibition of histone deacetylase 6 (HDAC6) as part of their antiviral activity. The tested compounds did not inhibit the growth of poliovirus, displaying high selectivity against HCV.


5-Hydroxytryptamine agonistic action of methysergide and the absence of supersensitivity to 5-HT agonists in spinal flexor reflexes in rats.
The intravenous administration of L-5-hydroxytryptophan (5-HTP), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), p-chloroamphetamine (PCA), LSD and methysergide to acute spinal rats, transected at C1, stimulated the flexor reflexes induced by electrical stimulation applied to the skin of the toe. The enhancement produced by 5-HTP, 5-MeODMT and PCA, was not antagonized by the prior administration of a dose of LSD or methysergide, although the enhancement produced by 5-MeODMT, LSD and methysergide, but not that produced by 5-HTP and PCA, was antagonized by cyproheptadine. In rats treated with 5,6-dihydroxytryptamine (intracisternal administration, 2 weeks previously) supersensitivity was observed to the effects of 5-HTP, a precursor of 5-HT, while subsensitivity was observed for the effects of PCA, a releaser of 5-HT. However, no supersensitivity was observed for the effects of 5-MeODMT, LSD and methysergide. These results suggest that methysergide may have an agonistic action on the 5-HT receptors in spinal cord and that supersensitivity to 5-HTP in rats treated with 5,6-dihydroxytryptamine was due to the lack of uptake of 5-HT into terminals of descending 5-HT fibres or to the change in 5-HT receptors which were not sensitive to 5-MeODMT, LSD, methysergide or cyproheptadine.


Tumor-suppression function of transcription factor USF2 in prostate carcinogenesis.
Although the transcription factor USF2 has been implicated in the regulation of cellular growth and proliferation, it is unknown whether alterations in USF2 contribute to tumorigenesis and tumor development. We examined the role of USF2 in prostate tumorigenesis. Western blot analysis revealed markedly decreased USF2 levels in three androgen-independent prostate cancer cell lines, PC-3, DU145, and M12, as compared to nontumorigenic prostate epithelial cells or the androgen-dependent cell line, LNCaP. Ectopic expression of USF2 in PC-3 cells did not affect the cell proliferation rate of PC-3 cells on plastic surfaces. However, it dramatically decreased anchorage-independent growth of PC-3 cells in soft agar (90-98% inhibition) and the invasion capability (80% inhibition) of PC-3 cells in matrix gel assay. Importantly, expression of USF2 in PC-3 cells inhibited the tumorigenicity of PC-3 cells in an in vivo nude mice xenograft model (80-90% inhibition). These results suggest that USF2 has tumor-suppression function. Consistent with its function in tumor suppression, we found that the USF2 protein is present in normal prostate epithelial cells but absent in 18 of 42 (43%) human prostate cancer tissues (P = 0.015). To further examine the functional role of USF2 in vivo, we generated mice with genetic deletion of USF2 gene. We found that USF2-null mice displayed marked prostate hyperplasia at a young age, suggesting that USF2 is involved in the normal growth and differentiation of prostate. Together, these studies demonstrate that USF2 has tumor-suppressor function and plays a role in prostate carcinogenesis.


Geometric requirements and examples of important structures in the assembly of square building blocks.
The basic structures for linking squares into polyhedra and networks (reticulation) are enumerated, and corresponding examples are described in which crystals were synthesized by linking paddle wheel (square) units into metal-organic frameworks (MOFs)--named MOF-102 to MOF-112.


Improvement of water-solubility of biarylcarboxylic acid peroxisome proliferator-activated receptor (PPAR) δ-selective partial agonists by disruption of molecular planarity/symmetry.
To elucidate the molecular basis of peroxisome proliferator-activated receptor (PPAR) δ partial agonism, X-ray crystal structures of complexes of the PPARδ ligand-binding site with partial agonists are required. Unfortunately, reported PPARδ partial agonists, biphenylcarboxylic acids 1 and 2, possess insufficient aqueous solubility to allow such crystals to be obtained. To improve the aqueous solubility of 1 and 2, substituents were introduced at the 2-position of the biaryl moiety, focusing on disruption of molecular planarity and symmetry. All 2-substituted biphenyl analogs examined showed more potent PPARδ agonistic activity with greater aqueous solubility than 1 or 2. Among these biphenyls, 25 showed potent and selective PPARδ partial agonistic activity (EC(50): 5.7 nM), with adequate solubility in phosphate buffer (0.022 mg/mL). The 2-substituted pyridyl analog 27 showed weaker PPARδ partial agonistic activity (EC(50): 76 nM) with excellent solubility in phosphate buffer (2.7 mg/mL; at least 2700 times more soluble than 2). Our results indicate that two strategies to improve aqueous solubility, that is, introduction of substituent(s) to modify the dihedral angle and to disrupt molecular symmetry, may be generally applicable to bicyclic molecules. Combination of these approaches with the traditional approach of reducing the molecular hydrophobicity may be particularly effective.


The inhibitory effect of p75 neurotrophin receptor on growth of human hepatocellular carcinoma cells.
p75 neurotrophin receptor (p75NTR), a member of the TNF receptor superfamily, is a focus for study at present. Up to now, its role and functions in hepatocellular carcinoma were not fully elucidated. In this study, we investigated the expression of p75NTR in hepatocellular carcinoma and the impact of its alteration on tumor growth. We found that the expression of p75NTR was decreased significantly in 158 cases of hepatocellular carcinoma tissues as compared with their adjacent noncancerous counterparts, and its expression was also significantly decreased in various human hepatocellular carcinoma cell lines. Down-regulating p75NTR by specific siRNA promoted the growth of normal liver cell lines, whereas up-regulating p75NTR inhibited the growth of hepatocellular carcinoma cell lines in vitro and caused dramatic attenuation of tumor growth in vivo by induction of cell cycle arrest. Furthermore, we found that up-regulating p75NTR could down-regulate the expression of cyclin A, cyclin D1, cyclin E, cdk2, p-Rb and PCNA, but up-regulate the expression of Rb. Conversely, the results were inverse when p75NTR was down-regulated by specific siRNA. Therefore, we provided the evidence that p75NTR was a potential tumor suppressor and might be used as a therapeutic target for hepatocellular carcinoma.


Efficacy and safety of doxofylline compared to theophylline in chronic reversible asthma -- a double-blind randomized placebo-controlled multicentre clinical trial.
Experimental studies have shown that doxofylline is endowed with a remarkable bronchodilator activity with less extra-respiratory effects than theophylline. This trial was designed to compare the efficacy and safety of doxofylline, theophylline, and placebo in patients with chronic reversible bronchial asthma. Three hundred forty-six patients were randomly assigned to a 12-week oral treatment with either doxofylline 400 mg t.i.d. (high dose), doxofylline 200 mg t.i.d. (low dose), theophylline 250 mg t.i.d. (active control) or placebo. Pulmonary function tests (PFTs) were performed biweekly. Patients kept records of peak flow meter (PFM) measurements, asthma attack rate and beta-2-agonist use (albuterol). Changes in FEV1 2 hours after the administration of treatments versus baseline exhibited statistically significant differences between doxofylline 400 mg t.i.d. and placebo and between theophylline and placebo. Similar differences were monitored on the other variables (FVC, PFER, FEF(25-75%). Asthma attack rate and use of albuterol decreased remarkably with doxofylline 400 mg t.i.d. and theophylline. There were few statistically significant differences between doxofylline 200 mg t.i.d. and placebo. Significantly more patients had to interrupt treatment because of adverse events under theophylline than under doxofylline 400 mg t.i.d. (p=0.001). With doxofylline 400 mg t.i.d., the number of patients treated to spare one drop-out due to theophylline was 5. This study provides evidence that doxofylline 400 mg t.i.d. is an effective treatment for relieving airway obstruction and displays a better safety profile with respect to theophylline 250 mg t.i.d. with a favorable risk-to-benefit ratio.


Epidemiology of sexually transmitted viral hepatitis in human immunodeficiency virus-positive men who have sex with men in Asia.
Both human immunodeficiency virus (HIV) and viral hepatitis constitute major disease burden globally. As with other parts of the world, the HIV epidemic in Asia impacts mainly on men who have sex with men, one of the at-risk populations for sexually transmitted viral hepatitis. With the increasing availability of effective antiretroviral therapy, HIV-related mortality of people living with HIV has markedly reduced. Liver disease has become an important cause of mortality and morbidity in the HIV-infected population. With the improvement of socioeconomic conditions and availability of healthcare in Asian countries in recent years, the epidemiology of sexually transmitted viral hepatitis among HIV-positive men who have sex with men has also evolved. This review updates the epidemiology of different types of sexually transmitted viral hepatitis in this defined population in Asia.


Histologic features associated with lymph node metastasis in stage T1 and superficial T2 rectal adenocarcinomas in abdominoperineal resection specimens. Identifying a subset of patients for whom treatment with adjuvant therapy or completion abdominoperineal resection should be considered after local excision.
Local excision of rectal adenocarcinomas that are confined to the submucosa is an accepted method of surgical excision. Adjuvant therapy and possibly completion abdominoperineal resection (APR) may be appropriate if lymph node (LN) metastases are present. Identifying the patients at high risk of having LN metastases would assist in disease management. We retrospectively examined 73 APR resection specimens with T1 or superficial T2 adenocarcinomas. The leading edge of the tumor was evaluated for budding, microacinar structures, or isolated or small clusters of undifferentiated cells. The features were correlated with LN metastases. Eleven specimens had LN metastases. Extensive budding, microacinar structures, or undifferentiated cells, tumor grade 3, and small vessel vascular space invasion were associated with LN metastases. Limiting the comparison to grade 1 and 2 adenocarcinomas showed association of extensive budding, microtubular architecture, and undifferentiated cells along the advancing edge with LN-metastases. If these histologic features are extensively present, the patient may be a candidate for adjuvant therapy or completion APR. The morphologic features of the advancing edge are independent of the tumor grade of the neoplastic glands within the body of the tumor; they can be incorporated into the evaluation of overall tumor grade.


Involvement of Rho-Kinase/LIM Kinase/Cofilin Signaling Pathway in Corporal Fibrosis after Cavernous Nerve Injury in Male Rats.
The molecular mechanism of corporal fibrosis leading to erectile dysfunction (ED) following cavernous nerve (CN) injury is poorly understood. To determine whether the LIMK2/cofilin pathway, the downstream effectors of ROCK1, was involved in ED and corporal fibrosis following bilateral CN injury in male rats. Forty-eight 10-week-old male Sprague-Dawley rats were equally divided into three groups: sham surgery (S); bilateral CN crush injury (I); and bilateral CN resection (R). Within each groups, two subgroups were analyzed at 1 and 4 weeks postoperatively. Electrostimulation was performed to assess erectile function by the ratio of maximal intracavernous pressure to mean arterial pressure (ICP/MAP) and areas under the ICP curve to MAP (AUC/MAP). Penile tissue was processed for Masson's trichrome staining, Western blot (ROCK1, total LIMK2, phospho-LIMK2, total cofilin, phospho-cofilin), immunohistochemistry (alpha-SM actin [α-SMA]), and double immunofluorescent staining (ROCK1, phospho-LIMK2, vimentin). At each time point, both I and R groups showed a significantly lower percent of ICP/MAP and AUC, and decreased SM cell/collagen ratio and expression of α-SMA than S group. Densitometry revealed a significantly higher expression of ROCK1 in I and R groups compared with S group at all time points. The LIMK2 phosphorylation in I and R groups significantly increased at 1 week, but not at 4 weeks. The cofilin phosphorylation in R group significantly increased to that in S group starting at 1 week, while that in I group was increased significantly at 4 weeks. The double immunofluorescent staining noted that coexpression of vimentin with ROCK1 or phospho-LIMK2 in I and R groups was significantly increased mainly in the subtunical area at 1 week but not at 4 weeks. The ROCK1/LIMK2/cofilin pathway may be involved in ED related to corporal fibrosis, and it appears to be functional particularly in the early period after CN injury.


[Mechanic valve prosthesis and pregnancy: Is Phenprocoumon replaceable?].
We report the case of a 30-year-old pregnant patient with mechanical valve replacement in mitral and aortic position. She had discontinued Phenprocoumon-treatment in the 5+4 week of pregnancy by herself. Because of rheumatic fever she had undergone a mechanical aortic and mitral valve replacement 12 years ago. Due to a thrombosis of the mitral valve, an acute reoperation had to be done 5 years later. 2 years ago, a partially re-thrombosis of the mechanical mitral valve was treated by intravenous thrombolysis. These complications had been probably due to incomplicance. The patient had experienced 3 abortions before. The vaginal sonography determined an intact gestation. The laboratory test revealed an INR of 1.2. The transesophageal echocardiography showed a partially thrombosed mechanical mitral valve. The abdominal ultrasonography detected an embolic splenic infarction. These findings were consistent with partially thrombosed mechanical mitral valve with thromboembolic splenic infarction among incompetent oral anticoagulation. After initial heparinization with under twice daily control of the partial thromboplastin time the joint decision was made to restart Phenprocoumon (target INR 2.5 to 3.5, and additional ASS 100 mg /day). 9 days later the patient had a missed abortion. An uncomplicated curettage was performed under therapeutic i.v. heparinization. The use of coumarins in pregnancy carries a fetal risk. But it is the most secure anticoagulation after a mechanical valve replacement, especially in high-risk patients. Alternatives are heparins. They don't cross the placenta but are associated with a slightly elevated risk of thromboembolism.


Five-year clinical outcomes of rigid iris-fixated phakic intraocular lens in northern Chinese.
To investigate the 5-year clinic outcomes of rigid iris-fixated pIOL on the visual performance, complications and intraocular light scattering in northern Chinese. Thirty eyes implanted with iris-fixated phakic IOLs (pIOLs group) and 34 eyes with high myopia (myopia group) were involved in this study. At preoperatively, 6 months, 1, 3, and 5 years postoperatively, the uncorrected visual acuity (UCVA), best-spectacle corrected visual acuity (BSCVA), endothelial cell density (ECD), and intraocular pressure (IOP) were measured in pIOLs group. The objective scatter index (OSI), modulation transfer function cut off (MTF cut off), and Strehl ratio were measured by Optical Quality Analysis System and a pseudophakic dysphotopsia questionnaire (PDQ) was used to evaluate the subjects' satisfaction in pIOLs and myopia groups. At 5 years postoperatively, an UCVA of 20/20 or better was found in 43.33% of eyes in pIOLs group. At 6 months, 1, 3, and 5 years postoperatively, the mean ECD decrease were 1.29% ± 0.45%, 2.59% ± 1.30%, 6.67% ± 2.26%, and 10.80% ± 3.48%. The value of OSI in pIOLs group was significantly higher than that in myopia group (P < 0.001). The PDQ results showed that the subjects in myopia group complained less with intolerance of bright lights than those in pIOLs group. The values of Strehl ratio and MTF cut off in pIOLs group were significantly lower than that in myopia group (P < 0.001). Iris-fixated pIOL induce more intraocular light scattering. A significant decrease in ECD was observed at 5 years postoperatively. An annual evaluation of ECD is necessary for patients undergoing pIOL implantation.


One-Pot Biocatalytic Cascade Reduction of Cyclic Enimines for the Preparation of Diastereomerically Enriched N-Heterocycles.
Ene-reductases (EREDs) catalyze the reduction of electron-deficient C═C bonds. Herein, we report the first example of ERED-catalyzed net reduction of C═C bonds of enimines (α,β-unsaturated imines). Preliminary studies suggest their hydrolyzed ring-open ω-amino enones are the likely substrates for this step. When combined with imine reductase (IRED)-mediated C═N reduction, the result is an efficient telescoped sequence for the preparation of diastereomerically enriched 2-substituted saturated amine heterocycles.


The effect of ovarian cancer screening on sexual activity and functioning: results from the UK collaborative trial of ovarian cancer screening RCT.
To examine the impact of multimodal (MMS) and ultrasound (USS) screening on the sexual activity and functioning of 22 966 women in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) RCT. Fallowfield's Sexual Activity Questionnaire (FSAQ) was completed prior to randomisation, then annually in a random sample (RS) of women from MMS, USS and control groups. Any women in the study who required repeat screening due to unsatisfactory results formed an Events Sample (ES); they completed questionnaires following an event and annually thereafter. Over time in the RS (n=1339) there was no difference between the MMS and USS groups in sexual activity compared with controls. In the ES there were significant differences between the USS group (n=10 156) and the MMS group (n=12 810). The USS group had lower pleasure scores (mean difference=-0.14, P=0.046). For both groups women who had ⩾2 repeat screens, showed a decrease in mean pleasure scores compared with their annual scores (mean difference=-0.16, P=0.005). Similarly mean pleasure scores decreased following more intensive screens compared with annual screening (mean difference=-0.09, P=0.046). Ovarian cancer screening did not affect sexual activity and functioning unless a woman had abnormal results and underwent repeated or higher level screening.


Gut bacterial metabolites of indigestible polysaccharides in intestinal fermentation as mediators of public health.
The gut microbiome is regarded as an essential dynamic organ that functions in nourishment, epithelial development and innate immunity. One important benefit of the dietary polysaccharides to human health is due to its fermentability in gut. It is been known quite well that dietary fiber is able of impacting colon microbiota. Fermented products from these polysaccharides, especially short-chain fatty acids (SCFAs) are bioactive molecules with health benefits. It is proposed that the dietary polysaccharide-deriving SCFAs could be converted into glucose and /or directly signal intestinal receptors and therefore contribute the benefits via gut-brain neural circuits. In addition, fermented polysaccharides can facilitate the beneficial bacteria to generate bioactive molecules important for the normal maturation of the host immune system. Manipulation of the microbiota and metabolites from intestinal microbiota might be a promising new approach for the prevention or treatment diseases (Fig. 2, Ref. 30).


Early caffeine exposure: transient and long-term consequences on brain excitability.
The influence of pre- and postnatal caffeine treatment on brain excitability during development and adulthood is reviewed. Pre- and postnatal exposure to caffeine induces sex- and age-specific long-term neurochemical alterations in the brain and the behavior of rodents. Because adenosine neuromodulation is closely related to the regulation of brain excitability the increased expression in adenosine receptor system due to neonatal caffeine treatment should cause transient and permanent changes in seizure susceptibility. So far, findings have been focused on primarily developmental changes of the brain adenosine modulatory system and have demonstrated that the alterations are not restricted to a single brain region. Neurobehavioral changes and the anticonvulsant effect of early caffeine exposure are dependent on the caffeine dose, developmental stage of exposure and age of testing. Although outcomes of caffeine treatment are still a matter of debate, our review raise questions concerning the impact of early caffeine treatment on regulation of seizure susceptibility during development and adulthood.


Differential activation of NLRP3 inflammasome by Acinetobacter baumannii strains.
Acinetobacter baumannii is an emerging nosocomial, opportunistic pathogen with growing clinical significance globally. A. baumannii has an exceptional ability to rapidly develop drug resistance. It is frequently responsible for ventilator-associated pneumonia in clinical settings and inflammation resulting in severe sepsis. The inflammatory response is mediated by host pattern-recognition receptors and the inflammasomes. Inflammasome activation triggers inflammatory responses, including the secretion of the pro-inflammatory cytokines IL-1β and IL-18, the recruitment of innate immune effectors against A. baumannii infection, and the induction programmed cell death by pyroptosis. An important knowledge gap is how variation among clinical isolates affects the host's innate response and activation of the inflammasome during A. baumannii infection. In this study, we compared nine A. baumannii strains, including clinical locally-acquired isolates, in their ability to induce activation of the inflammasome and programmed cell death in primary macrophages, epithelial lung cell line and mice. We found a variation in survival outcomes of mice and bacterial dissemination in organs among three commercially available A. baumannii strains, likely due to the differences in virulence between strains. Interestingly, we found variability among A. baumannii strains in activation of the NLRP3 inflammasome, non-canonical Caspase-11 pathway, plasmatic secretion of the pro-inflammatory cytokine IL-1β and programmed cell death. Our study highlights the importance of utilising multiple bacterial strains and clinical isolates with different virulence to investigate the innate immune response to A. baumannii infection.


Ligand-independent activation of vascular endothelial growth factor receptor 1 by low-density lipoprotein.
Elevated serum low-density lipoprotein (LDL) is a risk factor for atherosclerotic disorders. However, prominent atherosclerosis, which has been observed in LDL receptor (LDLR)-knockout mice, has diminished the significance of LDLR as a cause of atherosclerosis, while elaborate studies have focused on the receptors for denatured LDL. Here we report that native LDL (nLDL) activates vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1) but not VEGFR2 through LDLR and is as potent as VEGF in macrophage migration. Binding and co-endocytosis of VEGFR1 and LDLR were enhanced by nLDL, which is concomitant with ubiquitination-mediated degradation of VEGFR1. We propose that LDLR-mediated use of VEGFR1 by nLDL could be a potential therapeutic target in atherosclerotic disorders.


Spacer stability and prostate position variability during radiotherapy for prostate cancer applying a hydrogel to protect the rectal wall.
The aim was to evaluate the spacer dimensions and prostate position variability during the course of radiotherapy for prostate cancer. CT scans were performed in a group of 15 patients (G1) after the 10 ml injection of a hydrogel spacer (SpaceOAR™) and 30 patients without a spacer (G2) before the beginning of treatment (CT1) and in the last treatment week, 10-12 weeks following spacer implantation (CT2). Spacer dimensions and displacements were determined and prostate displacements compared. Mean volume of the hydrogel increased slightly (17%; p<0.01), in 4 of 15 patients >2 cm(3). The average displacement of the hydrogel center of mass was 0.6mm (87%≤ 2.2mm), -0.6mm (100% ≤ 2.2mm) and 1.4mm (87% ≤ 4.3mm) in the x-, y- and z-axes (not significant). The average distance between prostate and anterior rectal wall before/at the end of radiotherapy was 1.6 cm/1.5 cm, 1.2 cm/1.3 cm and 1.0 cm/1.1cm at the level of the base, middle and apex (G1). Prostate position variations were similar comparing G1 and G2, but significant systematic posterior displacements were only found in G2. A stable distance between the prostate and anterior rectal wall results during the radiotherapy course after injection of the spacer before treatment planning. Larger posterior prostate displacements could be reduced.


Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer.
SIR-Spheres are radioactive yttrium90 microspheres (SIR-Spheres, Sirtex Medical Limited, Australia) used to selectively target high levels of ionising radiation to tumors within the liver. This trial was designed to measure any increased patient benefit by adding a single administration of SIR-Spheres to a regimen of regional hepatic artery chemotherapy (HAC) administered as a 12 day infusion of floxuridine and repeated at monthly intervals, vs. the same chemotherapy alone. A phase III randomised clinical trial entering 74 patients was undertaken on patients with bi-lobar non-resectable liver metastases from primary adenocarcinoma of the large bowel. Patient benefit criteria assessed in the trial were tumor response, time to disease progression in the liver, overall survival, quality of life, and treatment related toxicity. Tumor response was measured by serial changes in both cross-sectional tumor areas and total tumor volumes, provided any response lasted not less than three months as well as changes in serum carcino-embryonic antigen (CEA). The partial and complete response rate (PR + CR) was significantly greater for patients receiving SIR-Spheres when measured by tumor areas (44%) vs. 17.6%, P = 0.01) tumor volumes (50% vs. 24%, P = 0.03) and CEA (72% vs. 47%, P = 0.004). The median time to disease progression in the liver was significantly longer for patients receiving SIR-Spheres in comparison to patients receiving HAC alone when measured by either tumor areas (9.7 vs. 15.9 months, P = 0.001), tumor volumes (7.6 vs. 12.0 months, P = 0.04) or CEA (5.7 vs. 6.7 months, P = 0.06). The one, two, three and five-year survival for patients receiving SIR-Spheres was 72%, 39%, 17% and 3.5%, compared to 68%, 29%, 6.5% and 0% for HAC alone. Cox regression analysis suggests an improvement in survival for patients treated with SIR-Spheres who survive more than 15 months (P = 0.06). There was no increase in grade 3-4 treatment related toxicity and no loss of quality of life for patients receiving SIR-Spheres in comparison to patients receiving HAC alone. The combination of a single injection of SIR-Spheres plus HAC is substantially more effective in increasing tumor responses and progression free survival than the same regimen of HAC alone.


Health-related quality of life and clinical outcome after radiotherapy of patients with intracranial meningioma.
This retrospective, single-institutional study investigated long-term outcome, toxicity and health-related quality of life (HRQoL) in meningioma patients after radiotherapy. We analyzed the data of 119 patients who received radiotherapy at our department from 1997 to 2014 for intracranial WHO grade I-III meningioma. Fractionated stereotactic radiotherapy (FSRT), intensity modulated radiotherapy (IMRT) or radiosurgery radiation was applied. The EORTC QLQ-C30 and QLQ-BN20 questionnaires were completed for assessment of HRQoL. Overall survival (OS) for the entire study group was 89.6% at 5 years and 75.9% at 10 years. Local control (LC) at 5 and 10 years was 82.4% and 73.4%, respectively. Local recurrence was observed in 22 patients (18.5%). Higher grade acute and chronic toxicities were observed in seven patients (5.9%) and five patients (4.2%), respectively. Global health status was rated with a mean of 59.9 points (SD 22.3) on QLQ-C30. In conclusion, radiotherapy resulted in very good long-term survival and tumor control rates with low rates of severe toxicities but with a deterioration of long-term HRQoL.


Lemierre's syndrome with fourth nerve palsy.
Lemierre's syndrome is characterized by acute oropharyngeal infection with secondary internal jugular vein thrombophlebitis and subsequent metastatic infections. The anaerobe Fusobacterium necrophorum is the usual etiologic agent, although other microorganisms, including Streptococcus, Staphylococcus, Enterococcus, Bacteroides, and Lactobacilli, may be present alone or in combination with F. necrophorum. Common sites of metastatic infection include the lungs and joints. Thromboembolic complications, such as septic pulmonary embolism, persistent jugular vein occlusion, hepatic abscesses, and nephropathy, may occur. We report a case of Lemierre's syndrome in a 3-year-old Caucasian boy who subsequently presented with manifestations of a fourth (trochlear) nerve palsy.


Effectiveness of radiofrequency ablation for hepatocellular carcinomas larger than 3 cm in diameter.
Radiofrequency ablation is a safe and effective treatment for hepatocellular carcinomas 3.1 to 8.0 cm in diameter. Case series with prospective data collection. Tertiary referral center. Eighty-six patients with hepatocellular carcinoma treated with radiofrequency ablation from May 1, 2001, to December 31, 2002, were placed into categories of those with tumors 3 cm or smaller (group 1, n = 51) and those with tumors 3.1 to 8.0 cm (group 2, n = 35) in diameter. Radiofrequency ablation was performed with a single or cluster cool-tip electrode. The choice of treatment route was based on tumor size and position. Complication, treatment mortality, and complete ablation rates. Radiofrequency ablation was performed percutaneously in 26 patients in group 1 and 9 patients in group 2, with laparoscopy in 2 patients in group 1 and 1 patient in group 2, and with open operation in 23 patients in group 1 and 25 patients in group 2. The complication rates were 12% and 17% in group 1 and group 2, respectively (P =.48); treatment mortality rates were 0% and 3%, respectively (P =.41). Complete ablation rates after a single session of ablation assessed by means of computed tomography 1 month after treatment were 94% and 91% in group 1 and group 2, respectively (P =.68). Radiofrequency ablation is a safe and effective treatment for patients with hepatocellular carcinomas 3.1 to 8.0 cm in diameter.


Caffeine/sleep-deprivation interaction in mice produces complex memory effects.
Sleep deprivation negatively impacts memory, causing deficits in memory processes. Of interest is any agent that can offset such deficits. Mice were given varying doses of caffeine for 14 days and then deprived of sleep for 6 hours by the 'gentle handling' method. Memory was assessed using the Novel Object Recognition Test and Y maze alternation. The study was designed to ascertain the impact of varying doses of caffeine combined with total sleep-deprivation on spatial and non spatial memory in mice. Adult Swiss Webster mice of both sexes were assigned to six groups viz., vehicle (distilled water), or one of five selected doses of caffeine (10, 20, 40, 80 and 120 mg/kg) for 14 days via the oral route. Open field novel object recognition test and Y maze spatial working memory tests were carried out on day 14. Results were analysed using multi-factorial ANOVA followed by Tukey HSD test and expressed as mean ± S.E.M, with p values less than 0.05 were considered statistically significant. Novel object recognition tests (NOR) revealed that pre-training and pre-test sleep deprivation and caffeine combination impaired non spatial and spatial memory in male and female mice. The study shows the complex interactions with memory that may arise when total sleep deprivation is superimposed on caffeine administration.


[Sensitivity to chlorine-containing disinfectants of Salmonella typhi strains with transmissible drug resistance].
Sensitivity of 201 S. typhi strains to antibiotics and chlorine containing disinfectants was studied. The strains were isolated in the regions of the Left Bank Ukraine. Among the typhoid cultures the proportion of R+ strains was on the whole equal to 29.3 per cent. Chloramine resistant strains amounted to 21.8 per cent. Among chloramine resistant strains the number of the cultures carrying R plasmids was 3 times higher than that of the strains sensitive to disinfectant. Simultaneous transfer of the R plasmid and chloramine resistance to the recipient strain suggested that resistance of the S. typhi strains to chloramine was of plasmid nature.


Uncovering the composition of microbial community structure and metagenomics among three gut locations in pigs with distinct fatness.
Uncovering the phylogenetic composition of microbial community and the potential functional capacity of microbiome in different gut locations is of great importance to pig production. Here we performed a comparative analysis of gut microbiota and metagenomics among jejunum, ileum and cecum in pigs with distinct fatness. 16S rRNA gene sequencing revealed dramatic differences of microbial composition, diversity and species abundance between small intestine and cecum. Clostridium and SMB53 were enriched in the small intestine, while Prevotella, Treponema, Ruminococcus and Faecalibacterium showed a higher abundance in the cecum. Functional capacity analysis of gut microbiome revealed that the microbiome of small intestine plays important roles in the metabolism of small molecule nutrients, while the microbiome of cecum has the stronger ability to degrade xylan, pectin and cellulose. We identified tens of fatness associated-bacterial species including Escherichia spp. that showed a notable increase of relative abundance in all three gut locations of high fatness pigs. We further suggested that the potential pathogens, inflammation process, and microbial metabolism and nutrient sensing are involved in the high fatness of pigs. These results improve our knowledge about microbiota compositions in different gut locations, and give an insight into the effect of gut microbiota on porcine fatness.


Targeted clinical education for staff attitudes towards deliberate self-harm in borderline personality disorder: randomized controlled trial.
The aim of the present study was to assess the impact of attending targeted clinical education on borderline personality disorder on the attitudes of health clinicians towards working with deliberate self-harm behaviours commonly exhibited by patients diagnosed with this complex disorder. Comparisons of clinicians across service settings, occupational fields, and other demographic areas were also made. A purpose-designed demographic questionnaire and the Attitudes Towards Deliberate Self-Harm Questionnaire were used to collect the demographic information and assess the attitudes of 99 mental health and emergency medicine practitioners across two Australian health services and a New Zealand health service, both before and after education attendance. Statistically significant improvements in attitude ratings were found for both emergency medicine clinicians and mental health clinicians in working with deliberate self-harm behaviours in borderline personality disorder, following attendance at the education program with a medium affect size (t(32)=-3.45, p=0.002, d=0.43 and t(65)=-5.12, p=0.000, d=0.42, respectively). Clinicians across occupational areas of nursing, allied health, and medical fields demonstrated equivocal levels of improvement in their attitude ratings. Results are discussed in terms of the necessity of providing regular access to targeted clinical education for health professionals working with patients diagnosed with borderline personality disorder.


Amelioration of bromobenzene hepatotoxicity by Withania somnifera pretreatment: Role of mitochondrial oxidative stress.
The present study investigated the possible protective role of Withania somnifera (Linn.) Dunal (Solanaceae) root powder against bromobenzene-induced oxidative damage in rat liver mitochondria. Administration of bromobenzene (10 mmol/kg body weight) to rats resulted in increased levels of liver marker enzymes, lipid peroxidation, TNF-α, IL-1β and VEGF. There was also marked depletion in the levels of mitochondrial enzymes and antioxidant activity. Pre-treatment with W. somnifera significantly decreased the levels of liver marker enzymes, TNF-α, IL-1β, VEGF and ameliorated histopathological manifestations in bromobenzene-treated rats. The molecular docking analysis predicted that the pro-inflammatory mediator NF-κB showed significant interaction with selected various active components of W. somnifera (withaferin A, withanolide D and withanolide E). This study demonstrates a good protective effect of W. somnifera against bromobenzene-induced oxidative stress.


Piezo-phototronic effect enhanced UV photodetector based on CuI/ZnO double-shell grown on flexible copper microwire.
In this work, we present a facile, low-cost, and effective approach to fabricate the UV photodetector with a CuI/ZnO double-shell nanostructure which was grown on common copper microwire. The enhanced performances of Cu/CuI/ZnO core/double-shell microwire photodetector resulted from the formation of heterojunction. Benefiting from the piezo-phototronic effect, the presentation of piezocharges can lower the barrier height and facilitate the charge transport across heterojunction. The photosensing abilities of the Cu/CuI/ZnO core/double-shell microwire detector are investigated under different UV light densities and strain conditions. We demonstrate the I-V characteristic of the as-prepared core/double-shell device; it is quite sensitive to applied strain, which indicates that the piezo-phototronic effect plays an essential role in facilitating charge carrier transport across the CuI/ZnO heterojunction, then the performance of the device is further boosted under external strain.


Big knowledge visualization of the COVID-19 CIDO ontology evolution.
The extensive international research for medications and vaccines for the devastating COVID-19 pandemic requires a standard reference ontology. Among the current COVID-19 ontologies, the Coronavirus Infectious Disease Ontology (CIDO) is the largest one. Furthermore, it keeps growing very frequently. Researchers using CIDO as a reference ontology, need a quick update about the content added in a recent release to know how relevant the new concepts are to their research needs. Although CIDO is only a medium size ontology, it is still a large knowledge base posing a challenge for a user interested in obtaining the "big picture" of content changes between releases. Both a theoretical framework and a proper visualization are required to provide such a "big picture". The child-of-based layout of the weighted aggregate partial-area taxonomy summarization network (WAT) provides a "big picture" convenient visualization of the content of an ontology. In this paper we address the "big picture" of content changes between two releases of an ontology. We introduce a new DIFF framework named Diff Weighted Aggregate Taxonomy (DWAT) to display the differences between the WATs of two releases of an ontology. We use a layered approach which consists first of a DWAT of major subjects in CIDO, and then drill down a major subject of interest in the top-level DWAT to obtain a DWAT of secondary subjects and even further refined layers. A visualization of the Diff Weighted Aggregate Taxonomy is demonstrated on the CIDO ontology. The evolution of CIDO between 2020 and 2022 is demonstrated in two perspectives. Drilling down for a DWAT of secondary subject networks is also demonstrated. We illustrate how the DWAT of CIDO provides insight into its evolution. The new Diff Weighted Aggregate Taxonomy enables a layered approach to view the "big picture" of the changes in the content between two releases of an ontology.


[Spirituality--the French concept of secularity--Judaism and care].
Judaism is based on faith in one God who gives us life. The believer must follow a certain number of laws and rules to draw closer to God. Healthcare professionals are sometimes at a loss as to how to follow them and need assistance in implementing them in order to meet Jewish patients' needs in the best way they can.


[Implementation of RPNs in psychiatry and mental health].
Advanced practice nursing, a profession created in 2018, is expanding rapidly in France. In order for it to be operational, but also to facilitate its deployment and implementation, changes in the legislative and regulatory texts concerning all the mentions are still necessary. For advanced practice nurses with a diploma in psychiatry and mental health, the challenges in terms of training, implementation and prospects for autonomy are significant in view of the difficulties in this care sector.


[PCR identification of DNA of hosts of the taiga tick nymphs (Ixodes persulcatus: Ixodinae) in St. Petersburg and its suburbs].
PCR identification of host DNA in unfed females and males of taiga tick Ixodes persulcatus was performed. Amplification of each sample was done using primers species-specific by 12S rDNA mitochondrial gene. Four species of small mammals (Apodemus uralensis, Clethrionomys glareolus, Microtus arvalis, and Sorex araneus) and two passeriform bird species (Fringilla coelebs and Parus major) were analysed. For one third of tick samples, hosts of previous stages were established using this method. In five cases, feeding on more than one host species was detected.


Encephalitis due to a free-living amoeba (Balamuthia mandrillaris): case report with literature review.
Amebic infections can spread to the central nervous system with a lengthy but usually fatal course. A typical case is presented to raise awareness of this increasingly reported infectious process that may have a more favorable outcome if diagnosed in its early stages. A 38-year-old male presented with an ulcerating 10 x 8 cm mass on his thigh and smaller skin nodules. In less than 6 months seizures developed due to granulomatous lesions of the brain. Biopsies/excisions of the thigh lesion, a subcutaneous nodule, and a brain lesion were performed. He failed to respond to broad spectrum antibiotics and antineoplastic agents, and died within 6 weeks of the initial MRI scan of the brain. Rare amebic trophozoites were appreciated in the biopsy specimens on post-mortem review, and Balamuthia mandrillaris confirmed as the infecting agent on immunofluorescence studies. Granulomatous amebic encephalitis is a parasitic infection with a lengthy clinical course before rapid deterioration due to extensive brain lesions is noted. Either early treatment with antimicrobials or-in rare cases-excision of the brain lesion(s) may offer the chance of a cure.


CELPI: trial protocol for a randomised controlled trial of a Carer End of Life Planning Intervention in people dying with dementia.
Dementia is a leading cause of death in developed nations. Despite an often distressing and symptom laden end of life, there are systematic barriers to accessing palliative care in older people dying of dementia. Evidence exists that 70% of people living with severe dementia attend an emergency department (ED) in their last year of life. The aim of this trial is to test whether a Carer End of Life Planning Intervention (CELPI), co-designed by consumers, clinicians and content specialists, improves access to end of life care for older people with severe dementia, using an ED visit as a catalyst for recognising unmet needs and specialist palliative care referral where indicated. A randomised controlled trial (RCT) enrolling at six EDs across three states in Australia will be conducted, enrolling four hundred and forty dyads comprising a person with severe dementia aged ≥ 65 years, and their primary carer. Participants will be randomly allocated to CELPI or the control group. CELPI incorporates a structured carer needs assessment and referral to specialist palliative care services where indicated by patient symptom burden and needs assessment. The primary outcome measure is death of the person with dementia in the carer-nominated preferred location. Secondary outcomes include carer reported quality of life of the person dying of dementia, hospital bed day occupancy in the last 12 months of life, and carer stress. An economic evaluation from the perspective of a health funder will be conducted. CELPI seeks to support carers and provide optimal end of life care for the person dying of dementia. This trial will provide high level evidence as to the clinical and cost effectiveness of this intervention. ACTRN12622000611729 registered 22/04/2022.


Disparity-constrained stereo endoscopic image super-resolution.
With the increasing usage of stereo cameras in computer-assisted surgery techniques, surgeons can benefit from better 3D context of the surgical site in minimally invasive operations. However, since stereo cameras are placed together at the confined endoscope tip, the size of lens and sensors is limited, resulting in low resolution of stereo endoscopic images. How to effectively exploit and utilize stereo information in stereo endoscopic super-resolution (SR) becomes a challenging problem. In this work, we propose a disparity-constrained stereo super-resolution network (DCSSRnet) to reconstruct images using a stereo image pair. In particular, a disparity constraint mechanism is incorporated into the generation of SR images in the deep neural network framework with effective feature extractors and atrous parallax attention modules. Extensive experiments were conducted to evaluate the performance of proposed DCSSRnet on the da Vinci dataset and Medtronic dataset. The results on endoscopic image datasets demonstrate that the proposed approach produces a more effective improvement over current SR methods on both quantitative measurements. The ablation studies further verify the effectiveness of the components of the proposed framework. The proposed DCSSRnet provides a promising solution on enhancing the spatial resolution of stereo endoscopic image pairs. Specifically, the disparity consistency of the stereo image pair provides informative supervision for image reconstruction. The proposed model can serve as a tool for improving the quality of stereo endoscopic images of endoscopic surgery systems.


Prognosis of Crohn's disease with onset in childhood or adolescence.
A long-term follow-up study of 522 patients (1955-1974) with onset of Crohn's disease under age 21 was conducted. Follow-up information was obtained for 513 (98.4%) of the patients. The mean follow-up for the entire series was 7.7 years with a greater than five-year follow-up for 67% of patients. Nearly 60% of the patients were ages 16--20 at onset of disease. Operation had been performed for 69% of the patients and 13 (2.4%) had died. Among the survivors 67% considered themselves to be in suboptimal health. Although clinical features and complications varied considerably with anatomic disease location, colonic disease generally caused more disability than small intestine location of disease. Age at onset did not correlate with clinical severity except for presence of growth retardation. Thus, this long-term follow-up study demonstrated the chronic nature of Crohn's disease with onset under age 21. It also emphasized that the disease more commonly affected adolescents than children, that operation was required in about two thirds of the patients, and that, while mortality was low, morbidity from the disease continued for many years.


Saethre-Chotzen syndrome with familial translocation at chromosome 7p22.
Chromosome analysis of a male infant and his mother with Saethre-Chotzen syndrome demonstrated an apparently balanced translocation, t(2;7)(p23;p22). This association lends support to localization of the gene for Saethre-Chotzen syndrome to the 7p2 region and supports further involvement of gene(s) in the 7p22 region.


Total knee arthroplasty in ochronosis.
Alkaptonuria is disorder of tyrosine metabolism due to deficiency of homogentisic oxidase characterized by excretion of homogentisic acid in urine, deposition of oxidized homogensitate pigments in connective tissues and articular cartilages (ochronosis). The result is dark pigmentation and weakening of the tissues resulting in chronic inflammation and osteoarthritis. Management of alkaptonuric ochronic osteoarthritis is usually symptomatic and replacements have comparable outcomes to osteoarthritis in patients without ochronosis. I report a case of a patient with ochronosis of knee treated with total knee replacement and report operative pearls for surgery in this rare disorder.


Spontaneous and serial rupture of both Achilles tendons associated with secondary hyperparathyroidism in a patient receiving long-term hemodialysis.
The spontaneous and serial rupture of the bilateral Achilles tendons without history of significant trauma is an uncommon complication in long-term hemodialysis (HD) patients. The majority of these patients have additional predisposing factors, such as previous use of fluoroquinolone antibiotics or corticosteroids. In general, this condition is associated with a coexisting systemic disease, including chronic kidney disease (CKD), secondary hyperparathyroidism, systemic lupus erythematosus (SLE), and diabetes mellitus (DM). Here, we report a 46-year-old man who had been undergoing regular HD for 11 years. He developed a spontaneous and consecutive rupture of both Achilles tendons. Based on previous reports of tendon ruptures in uremic patients and on the patient's lack of corticosteroid or fluoroquinolone use, we believe that secondary hyperparathyroidism was the predisposing factor in this patient. The mechanism seems to be related to a high parathyroid hormone (PTH) level, which results in osteolytic bone resorption at the tendon insertion site. Treatment and prevention of such tendon ruptures include early surgical repair and control of secondary hyperparathyroidism, by use of vitamin D analogs, and total parathyroidectomy, with or without autotransplantation of a parathyroid gland.


Sequence analysis of feline immunoglobulin mRNAs and the development of a felinized monoclonal antibody specific to feline panleukopenia virus.
In response to immunization, B-cells generate a repertoire of antigen-specific antibodies. Antibody-based immunotherapies hold great promise for treating a variety of diseases in humans. Application of antibody-based immunotherapy in cats is limited by the lack of species-specific complete sequences for mRNAs encoding rearranged heavy and light chain immunoglobulins in B cells. To address this barrier, we isolated mRNAs from feline peripheral blood mononuclear cells (PBMCs), and used available immunoglobulin sequences and 5' and 3' RACE to clone and sequence heavy and light chain immunoglobulin mRNAs. We recovered mRNA from PBMCs from two cats, cloned and sequenced the variable and constant domains of the feline heavy chains of IgG1a (IGHG1a), IgG2 (IGHG2), and IgA (IGHA), and the light chains (lambda and kappa). Using these sequences, we prepared two bicistronic vectors for mammalian expression of a representative feline heavy (IGHG1a) together with a light (lambda or kappa) chain. Here we report novel feline Ig sequences, a technique to express antigen-specific felinized monoclonal antibodies, and the initial characterization of a functional felinized monoclonal antibody against feline panleukopenia virus.


Alternate "Drug" Delivery Utilizing β-Lactam Cores: Syntheses and Biological Evaluation of β-Lactams Bearing Isocyanate Precursors.
The synthesis of a small set of β-lactams containing isocyanate precursors is described. The release of the isocyanate precursor in model hydrolysis experiments was substantiated by trapping experiments, thus confirming that β-lactams can be designed that are capable of releasing alternatively reactive species. Preliminary biological assessments are also briefly discussed.