Femoral bone density in young male adults with stress fractures.
Femoral bone mineral density (BMD) was measured by dualphoton absorptiometry in 41 young military recruits who had one or several stress fractures, during their physical training program. These fractures involved the following locations: Femur (neck: n = 10, diaphysis: n = 2), calcaneus (n = 10), tibia (n = 8), fibula (n = 3), metatarsus (n = 8). The stress fracture group generally had a lower bone density than that of a control group, consisting of 48 young military recruits matched for age, height and weight. However, the BMD was significantly lower (-10%) in patients with femoral and calcaneal locations, but it did not differ for other locations. To determine the possible effect of this intense physical activity on bone mineral mass, bone mass was measured again in 35 subjects from the control group at the end of their training. The BMD remained stable or increased in 28 subjects, but decreased significantly (greater than 2%) in 7 subjects, demonstrating the individual variability in the adaptation of bone to this stress. Our results suggest that lowered bone mass could be a factor that encourages the development of stress fractures (femoral and calcaneal) in young subjects submitted to intense physical activity to which they are not accustomed.


Sympathetic influence on cerebral blood flow and metabolism during exercise in humans.
This review focuses on the possibility that autonomic activity influences cerebral blood flow (CBF) and metabolism during exercise in humans. Apart from cerebral autoregulation, the arterial carbon dioxide tension, and neuronal activation, it may be that the autonomic nervous system influences CBF as evidenced by pharmacological manipulation of adrenergic and cholinergic receptors. Cholinergic blockade by glycopyrrolate blocks the exercise-induced increase in the transcranial Doppler determined mean flow velocity (MCA Vmean). Conversely, alpha-adrenergic activation increases that expression of cerebral perfusion and reduces the near-infrared determined cerebral oxygenation at rest, but not during exercise associated with an increased cerebral metabolic rate for oxygen (CMRO(2)), suggesting competition between CMRO(2) and sympathetic control of CBF. CMRO(2) does not change during even intense handgrip, but increases during cycling exercise. The increase in CMRO(2) is unaffected by beta-adrenergic blockade even though CBF is reduced suggesting that cerebral oxygenation becomes critical and a limited cerebral mitochondrial oxygen tension may induce fatigue. Also, sympathetic activity may drive cerebral non-oxidative carbohydrate uptake during exercise. Adrenaline appears to accelerate cerebral glycolysis through a beta2-adrenergic receptor mechanism since noradrenaline is without such an effect. In addition, the exercise-induced cerebral non-oxidative carbohydrate uptake is blocked by combined beta 1/2-adrenergic blockade, but not by beta1-adrenergic blockade. Furthermore, endurance training appears to lower the cerebral non-oxidative carbohydrate uptake and preserve cerebral oxygenation during submaximal exercise. This is possibly related to an attenuated catecholamine response. Finally, exercise promotes brain health as evidenced by increased release of brain-derived neurotrophic factor (BDNF) from the brain.


Clinical Utilization of Repeated Open Application Test Among American Contact Dermatitis Society Members.
The repeated open application test (ROAT) provides useful information regarding allergens in suspected cases of allergic contact dermatitis; however, standardized methodology has not been established. The aim of this study was to assess how ROAT is used in clinical and research settings. We distributed a survey regarding ROAT practice to the American Contact Dermatitis Society and conducted a literature review of ROAT utilization in research. A total of 67 American Contact Dermatitis Society members participated in the survey. Respondents most frequently recommend application of leave-on products twice daily (46.0%) and rinse-off products once daily (43.5%). The most commonly used anatomical sites include the forearm (38.7%) and antecubital fossa (32.3%). Most respondents continue ROAT for 1 (49.2%) or 2 weeks (31.7%). Literature review of 32 studies (26 leave-on, 6 rinse-off) revealed that application frequency is most common at twice daily for both leave-on (96.2%) and rinse-off (50.0%) products. The most common anatomical site is the forearm (62.5%), with an overall study duration of 3 to 4 weeks (65.6%). When comparing ROAT clinical and research practice, the majority trend was consistent for leave-on product application frequency and anatomical site, but not for rinse-off product application frequency, or overall duration. Further research is needed to determine best practice recommendations.


Comparison of early exercise treadmill test and oral dipyridamole thallium-201 tomography for the identification of jeopardized myocardium in patients receiving thrombolytic therapy for acute Q-wave myocardial infarction.
Thrombolytic therapy has become the treatment of choice for patients with acute myocardial infarction. Researchers are not yet able to identify patients with salvage of myocardium who are at risk for recurrent coronary events. Thus, a prospective trial was performed in 46 patients with myocardial infarction (28 anterior and 18 inferior) who received thrombolytic therapy to determine if early thallium tomography (4.7 days) using oral dipyridamole would identify more patients with residual ischemia than early symptom-limited exercise treadmill tests (5.5 days). There were no complications during the exercise treadmill tests or oral dipyridamole thallium tomography. Mean duration of exercise was 11 +/- 3 minutes and the peak heart rate was 126 beats/min. Thirteen patients had positive test results. After oral dipyridamole all patients had abnormal thallium uptake on the early images. Positive scans with partial "filling in" of the initial perfusion defects were evident in 34 patients. Angina developed in 13 patients and was easily reversed with intravenous aminophylline. Both symptom-limited exercise treadmill tests and thallium tomography using oral dipyridamole were safely performed early after myocardial infarction in patients receiving thrombolytic therapy. Thallium tomography identified more patients with residual ischemia than exercise treadmill tests (74 vs 28%). Further studies are required to determine whether the results of thallium tomography after oral dipyridamole can be used to optimize patient management and eliminate the need for coronary angiography in some patients.


A reevaluation of the functional organization and cytoarchitecture of the feline lateral posterior complex, with observations on adjoining cell groups.
The organization of the cat's lateral posterior complex was reevaluated and its cytoarchitecture described. Analysis of visual representations within the complex confirmed that the pulvinar, lateral zone (LPL), and interjacent zone (LPi) correspond to separate representations of the visual field and established that the zones exhibit heterogeneous connections as a result of retinotopic interconnections with extrastriate areas which represent varying amounts of the visual field. A common system of visual representation extending through layers with differing anatomical connections was identified within zone LPL. The concept of an "isorepresentation cord" was introduced to describe these variable correspondences between sensory representations and connectional relationships. Isorepresentation cords are conceived as holding in common representation of a common locus on a sensory surface without functioning as a unit with respect to connections. Visual representations within the lateral posterior complex consist of many such cords arranged in orderly array. Zone LPm (medial) was also delineated more accurately on the basis of its connections with the ectosylvian visual area. Analysis of termination patterns which occupy boundary regions adjacent to and between the principal zones further established the existence of a collection of cell groups which form a thin, irregular shell investing the principal zones. The identification of these additional cell groups and the recognition of connectional heterogeneity within the principal zones of the complex made it possible to identify and describe the subtle cytoarchitectural differences which characterize the subdivisions of the lateral posterior complex and their boundaries with adjoining nuclear groups. The present findings are discussed with respect to the functions of the lateral posterior complex in interconnecting cortical visual and visuomotor areas, and with respect to the conceptual issues raised by variable correspondences between sensory representations and connectional relationships within thalamus.


[Endocrine insufficiency in alcaptonuria? A case report and survey of the literature (author's transl)].
In a 49 years old patient with alcaptonuria we studied the question whether disturbances of the endocrine organs by deposition of products of homogenistic acid could be detected analogous to disturbances of connective tissue. The function of the hypothalamus and the pituitary gland were shown to be normal. The only defect of the endocrine organs was a hypergonadotropic hypogonadism with a serum testosterone of 5.4 and 9.4 mumol/l respectively (155 and 270 ng/dl rsp.) at elevated LH and FSH values. A sufficient stimulation of the testosterone in serum by chorionic gonadotropin (Primogonyl) could be demonstrated, thus supporting the diagnosis of a compensated insuffiency of the Leydig cells. This disorder might be a late endocrine defect due to the basic metabolic disturbance of the disease.


Low back pain and health-related quality of life in community-dwelling older adults.
Investigation of self-reported of low back pain (LBP) over the last month and associated health-related quality of life (HRQoL) in a sample of a community-dwelling population aged ≥65. Cross-sectional study including older adults selected randomly from population records. Data were collected within a sample stratified by age and sex. Physical and psychological healths were investigated using a standardized definition of LBP and the EuroQoL-5D for HRQoL. Analyses were first conducted on the entire sample (N = 3042) and subsequently considering the subsample who reported LBP and a paired sample drawn from the pool of LBP-free respondents. 889 (29 %) respondents reported LBP within the past month, present 'most days' or 'every day' in 52 % and limiting activities in the same proportion. Average pain score was 4.6 (SD 2.2; 0-10 scale). Age was associated with pain frequency and duration, with younger groups more often reporting pain 'some days' and 'dating back <3 months'. Results of regression analyses showed that individuals suffering from LBP had significantly more problems than LBP non-sufferers on all EQ-5D subscales, except self-care: pain/discomfort (OR 5.33; 95 % CI [4.19-6.79]), mobility (OR 2.66; 95 % CI [2.04-3.46]), usual activities (OR 1.92; 95 % CI [1.42-2.60]), anxiety/depression (OR 1.59; 95 % CI [1.23-2.04]) and self-care (OR 1.29; 95 % CI [0.84-1.98]). LBP appears to be a more permanent condition in the older groups. LBP may be a part of the definition of a subgroup of elderly at risk of becoming frail in relation with higher levels of functional limitations, psychological difficulties and social restrictions, hence globally impaired HRQoL.


A concept of consciousness.
The term "consciousness", so widely used in clinical settings, is considered extremely complex and practically undefinable. Historically, consciousness was ignored by the great classical philosophers, and was regarded as a basic condition of "being". This changed with Descartes and during the ensuing centuries. A simplified, reductionistic and easily definable concept of consciousness is proposed; consciousness is proposed to consist of three main components: vigilance, mental contents, and selective attention. These three components can be investigated with modern neuroscientific methods--vigilance being the most readily explorable function. The striking differences between sleep and coma are pointed out (along with some observations on sleep initiation). Special attention is paid to epileptic impairment of consciousness and, in particular, to the spike-wave absence which is thought to be due to a temporary suspension of the "working memory circuits" within the frontal lobe.


Anatomical approach to PCNL: concept of ideal puncture zone in a 3D perspective.
To describe a concept of ideal 'puncture zone' as against any single ideal 'puncture tract' for percutaneous nephro-lithotomy (PCNL) and present our results. Through this narrative, we aim to reduce the gaps in inter-understanding of an erstwhile description of ideal tract and real-life puncture making. The puncture zone principle was applied for our novel puncture making technique during PCNL. The largest imaginary cone that can fit into a respective calyx, with its tip in the pelvis defines the 'puncture zone' for that calyx. This concept allows fine-tuning of the ideal puncture tract based upon the desired corresponding manipulation zone and also shifts the focus of puncture making to infundibulum anatomy from the tip of calyx. The surgical technique and retrospective review of 136 cases done between 2015 and 2021 using this concept are presented. Primary outcome included stone-free rate, pseudo-aneurysm and blood transfusion at 3 months of follow-up. 33 cases had multiple (> 3) stones, 21 only calyceal/infundibular stones, eight partial staghorn and 12 were complete staghorn stones. Mean stone size was 29 ± 15 (Range: 5-53) mm. Complete clearance was achieved in 127 cases, four of which required two tracts. Blood transfusion was required in one case. No pseudo-aneurysms were encountered. The puncture zone concept has provided good results in our hands. It may help easier understanding of PCN puncture making and provides a background for reconciliation between description of an ideal tract and practical puncturing techniques used by different surgeons.


Genome-based breeding approaches in major vegetable crops.
Vegetable crops are major nutrient sources for humanity and have been well-cultivated since thousands of years of domestication. With the rapid development of next-generation sequencing and high-throughput genotyping technologies, the reference genome of more than 20 vegetables have been well-assembled and published. Resequencing approaches on large-scale germplasm resources have clarified the domestication and improvement of vegetable crops by human selection; its application on genetic mapping and quantitative trait locus analysis has led to the discovery of key genes and molecular markers linked to important traits in vegetables. Moreover, genome-based breeding has been utilized in many vegetable crops, including Solanaceae, Cucurbitaceae, Cruciferae, and other families, thereby promoting molecular breeding at a single-nucleotide level. Thus, genome-wide SNP markers have been widely used, and high-throughput genotyping techniques have become one of the most essential methods in vegetable breeding. With the popularization of gene editing technology research on vegetable crops, breeding efficiency can be rapidly increased, especially by combining the genomic and variomic information of vegetable crops. This review outlines the present genome-based breeding approaches used for major vegetable crops to provide insights into next-generation molecular breeding for the increasing global population.


Transcriptional networks regulating root vascular development.
Vascular development involves multiple processes, including the establishment of vascular stem cells (e.g. procambium/cambium cells), stem cell divisions, and cell specification. A number of key transcription factors regulating vascular development have been identified, and the molecular mechanisms underlying these regulators have been keenly investigated. These studies uncovered that transcriptional regulation and phytohormone signaling have central roles in proceeding vascular developmental processes. Recent research approaches contributed to identify key transcription factors and their downstream genes, which enhanced our understanding of vascular development. This review discusses some research approaches and emerging molecular mechanisms that mediate the activation of transcriptional networks regulating root vascular development.


Is maxillomandibular advancement an effective treatment for obstructive sleep apnea? Systematic literature review and meta-analysis.
To evaluate the effectiveness of maxillomandibular advancement surgery in the treatment of Obstructive Sleep Apnea by comparing the pre- and postoperative Apnea and Hypopnea Index, in addition to classifying the degree of evidence and risk of intervention bias. A systematic review of the literature was carried out in the PUBMED, LILACS, EMBASE, SCOPUS, WEB OF SCIENCE and COCHRANE platforms, including cohort studies with polysomnographic follow-up, without other associated pharyngeal or nasal surgical procedures. The risk of study bias was assessed using the Modified Delphi technique. Pre- and postoperative Apnea and Hypopnea Index data were plotted for meta-analysis, and the quality of evidence was assessed using the GRADE system. Of 1882 references, 32 articles were selected for full-text reading, of which four studies were included, totaling 83 adults with obstructive sleep apnea who underwent maxillomandibular advancement. The meta-analysis was in favor of the intervention (DM = -33.36, 95% CI -41.43 to -25.29, p < 0.00001), with a mean percentage reduction in the Apnea and Hypopnea Index of 79.5% after surgery, even though the level of evidence was classified as very low quality by the GRADE system. The meta-analysis was in favor of the intervention, characterizing maxillomandibular advancement surgery as an effective treatment for obstructive sleep apnea in adults.


A Deep Insight into Different Acidic Additives as Doping Agents for Enhancing Proton Conductivity on Polybenzimidazole Membranes.
The use of phosphoric acid doped polybenzimidazole (PBI) membranes for fuel cell applications has been extensively studied in the past decades. In this article, we present a systematic study of the physicochemical properties and proton conductivity of PBI membranes doped with the commonly used phosphoric acid at different concentrations (0.1, 1, and 14 M), and with other alternative acids such as phytic acid (0.075 M) and phosphotungstic acid (HPW, 0.1 M). The use of these three acids was reflected in the formation of channels in the polymeric network as observed by cross-section SEM images. The acid doping enhanced proton conductivity of PBI membranes and, after doping, these conducting materials maintained their mechanical properties and thermal stability for their application as proton exchange membrane fuel cells, capable of operating at intermediate or high temperatures. Under doping with similar acidic concentrations, membranes with phytic acid displayed a superior conducting behavior when compared to doping with phosphoric acid or phosphotungstic acid.


The autistic child's recognition of age- and sex-related characteristics of people.
Matched autistic, normal, and nonautistic retarded children were tested for their ability to choose schematic and photographed faces of a man, a woman, a girl, and a boy, to accompany videotaped sequences depicting a person of each class in (a) gestures, (b) vocalizations, and (c) "contexts" that might be considered typical for an individual of this age and sex. Although both autistic and control subjects were able to choose drawings of nonpersonal objects to correspond with videotaped cues, the autistic children were markedly impaired in selecting appropriate faces for the videotaped individuals. It is suggested that these results may reflect autistic children's relative disability in differentiating adults from children and males from females.


Nomogram predicting overall prognosis for invasive micropapillary carcinoma of the breast: a SEER-based population study.
The prognosis of invasive micropapillary carcinoma (IMPC) of the breast is determined by many clinicopathological factors. This study aims to identify prognostic factors and develop reliable nomogram to predict the overall survival (OS) in patients with IMPC. Log-rank test and Cox proportional hazards analysis were used to identify variables and construct a nomogram based on the training cohort. C-index and calibration curves were performed to evaluate the performance of the model in the training cohort and validation cohorts. We collected the patient data from the Surveillance, Epidemiology and End Results (SEER) database. This database holds data related to the cancer incidence from 18 population-based cancer registries in the USA. The SEER database was used to screen 754 eligible patients as the study cohort. The whole cohort was randomly divided into a training cohort (n=377) and a validation cohort (n=377). Age at diagnosis, hormone receptors, number of positive regional lymph nodes and clinical stage were independent prognostic factors for patients with IMPC. The calibration curves presented excellent consistency between the actual and nomogram-predict survival probabilities in the training and validation cohorts. The C-index values of the nomogram were 0.794 and 0.774 for OS in the training and validation cohorts, respectively. The novel nomogram provides new insights of the risk of each prognostic factor and can assist doctors in predicting the 1-year, 3-year and 5-year OS in patients with IMPC.


A retrospective comparison of functional renal failure in cirrhosis treated by conventional therapy or the peritoneo-venous shunt (LeVeen).
Between 1973 to 1976, 12 ascitic cirrhotic patients with a mean plasma creatinine (pCr) of 4.4 +/- 3.0 mg/dl) were treated conservatively. During the same period 11 cirrhotics with ascites (pCr 4.3 +/- 2.8 mg/dl) were treated with LeVeen peritoneal jugular shunt. In the medically treated group mean survival was 2.4 +/- 2.7 weeks after detection of pCr elevation greater than 2.3 mg/dl. The 11 surgical patients with pCr elevation above 2.3 mg/dl survived a mean of 21.8 +/- 34.5 weeks after surgery. Four patients survived more than six months. The LeVeen shunt also resulted in significant weight loss, reduction in blood urea nitrogen (BUN), elevation of serum sodium, and increase of renal clearance of sodium. In appropriately selected patients it reverses the hepato-renal syndrome.


Sporobolomyces inositophilus, a new species of ballistosporous yeast isolated from a dead leaf of Sasa sp. in Japan.
A new species of ballistosporous yeast, Sporobolomyces inositophilus was isolated from a dead leaf of Sasa sp. collected at a mountain in Japan. This yeast is assumed to have a close relationship to Sporobolomyces singularis since it produces bilaterally symmetrical ballistospores and pale-coloured colonies and resembles Sporobolomyces singularis in these respects. These two species differ from typical species of Sporobolomyces and seem to constitute a natural taxonomic group.


Hyperglycaemic memory affects the neurovascular unit of the retina in a diabetic mouse model.
The aim of this study was to evaluate damage to the neurovascular unit in a mouse model of hyperglycaemic memory. A streptozotocin-induced mouse model of diabetes (C57BL/6J background) received insulin-releasing pellets and pancreatic islet-cell transplantation. Damage to the neurovascular unit was studied by quantitative retinal morphometry for microvascular changes and microarray analysis, with subsequent functional annotation clustering, for changes of the retinal genome. Sustained microvascular damage was confirmed by persistent loss of pericytes in the retinal vasculature (PC/mm2): compared with healthy controls (1981 ± 404 PC/mm2), the pericyte coverage of the retinal vasculature was significantly reduced in diabetic mice (1571 ± 383 PC/mm2, p < 0.001) and transplanted mice (1606 ± 268 PC/mm2, p < 0.001). Genes meeting the criteria for hyperglycaemic memory were attributed to the cytoskeletal and nuclear cell compartments of the neurovascular unit. The most prominent regulated genes in the cytoskeletal compartment were Ddx51, Fgd4, Pdlim7, Utp23, Cep57, Csrp3, Eml5, Fhl3, Map1a, Mapk1ip1, Mnda, Neil2, Parp2, Myl12b, Dynll1, Stag3 and Sntg2, and in the nuclear compartment were Ddx51, Utp23, Mnda, Kmt2e, Nr6a1, Parp2, Cdk8, Srsf1 and Zfp326. We demonstrated that changes in gene expression and microvascular damage persist after euglycaemic re-entry, indicating memory. The datasets generated during and/or analysed during the current study are available in the GEO repository, GSE87433, www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=idmbysgctluxviv&acc=GSE87433 .


Should infectious disease modelling research be subject to ethics review?
Should research projects involving epidemiological modelling be subject to ethical scrutiny and peer review prior to publication? Mathematical modelling had considerable impacts during the COVID-19 pandemic, leading to social distancing and lockdowns. Imperial College conducted research leading to the website publication of a paper, Report 9, on non-pharmaceutical interventions (NPIs) and COVID-19 mortality demand dated 16th March 2020, arguing for a Government policy of non-pharmaceutical interventions (e.g. lockdowns, social distancing, mask wearing, working from home, furlough, school closures, reduced family interaction etc.) to counter COVID 19. Enquiries and Freedom of Information requests to the institution indicate that there was no formal ethical committee review of this specific research, nor was there any peer review prior to their online publication of Report 9. This paper considers the duties placed upon researchers, institutions and research funders under the UK 'Concordat to Support Research Integrity' (CSRI), across various bioethical domains, and whether ethical committee scrutiny should be required for this research.


Annot: a Django-based sample, reagent, and experiment metadata tracking system.
In biological experiments, comprehensive experimental metadata tracking - which comprises experiment, reagent, and protocol annotation with controlled vocabulary from established ontologies - remains a challenge, especially when the experiment involves multiple laboratory scientists who execute different steps of the protocol. Here we describe Annot, a novel web application designed to provide a flexible solution for this task. Annot enforces the use of controlled vocabulary for sample and reagent annotation while enabling robust investigation, study, and protocol tracking. The cornerstone of Annot's implementation is a json syntax-compatible file format, which can capture detailed metadata for all aspects of complex biological experiments. Data stored in this json file format can easily be ported into spreadsheet or data frame files that can be loaded into R ( https://www.r-project.org/ ) or Pandas, Python's data analysis library ( https://pandas.pydata.org/ ). Annot is implemented in Python3 and utilizes the Django web framework, Postgresql, Nginx, and Debian. It is deployed via Docker and supports all major browsers. Annot offers a robust solution to annotate samples, reagents, and experimental protocols for established assays where multiple laboratory scientists are involved. Further, it provides a framework to store and retrieve metadata for data analysis and integration, and therefore ensures that data generated in different experiments can be integrated and jointly analyzed. This type of solution to metadata tracking can enhance the utility of large-scale datasets, which we demonstrate here with a large-scale microenvironment microarray study.


Climate Changes in Central Asia as a Prerequisite and Trigger of Plague Microbe (Yersinia pestis) Speciation.
Two physical and climatic factors that were distant and recent prerequisites and a transformation trigger for a clone of the ancestral pseudotuberculous microbe Yersinia pseudotuberculosis O:1b (the causative agent of the Far East scarlet-like fever (FESLF)) into a population of the plague microbe derivative Y. pestis are considered. One remote prerequisite was the aridification of the Central Asian landscapes in the second half of the Cenozoic period and the formation of the Gobi Arid Zone. The arid conditions of Central Asia determined the formation of adaptive species-specific protective behavior in the Tarbagan marmot (Marmota sibirica) when installing the plug of a wintering hole, which later contributed to the massive infection of the animals with FESLF by the aberrant (traumatic, not alimentary) method during hibernation. A recent prerequisite and a real trigger of Y. pestis speciation was the onset of the last maximum (Sartan) ice age in Central Asia at the turn of the Pleistocene and Holocene, 22 000-15 000 years ago. Freezing of the cooling burrows of the Tarbagan marmot caused a behavioral shift in the larval population of the marmot flea Oropsylla silantiewi and the transition to the cold winter-spring months of the year from saprophagy in the nesting litter to hematophagy on the bodies of sleeping animals. Larval scarifications in the oral cavity of sleeping marmots have become the entrance gate for a unique traumatic FESLF infection. The constellation of climatic changes, the heterothermal (and, accordingly, heteroimmune) condition of the family groups of sleeping marmots, and the year-round propagation of marmot fleas in wintering burrows, combined with behavioral shifts in marmots and fleas caused by climatic changes, led to the formation of conditions in the parasitic system M. sibirica-O. silantiewi in which the transformation of the FESLF microbe into the causative agent of the plague occurred according to peripatric speciation. Thus, the climatic changes that happened at different times in the Cenozoic initially led to a shift in behavior of the Tarbagan marmot and, subsequently, to a shift in the behavior of the fleas parasitizing it. Ultimately, the change in the behavior of marmots and fleas caused the transition of the clone(s) of the FESLF causative agent into a new ecological niche and adaptive zone, as well as the transformation into a population(s) of the plague microbe.


The cytocidal effect of high energy shock waves on human prostatic tumour cell lines.
This report describes the effect of high energy shock waves (HESW) generated by a Siemens Lithostar on four human prostatic carcinoma cell lines in vitro. The effects of temperature, shock wave energy, cell density and the number of HESW were investigated. Pressure measurements were carried out in the focus of the lithotriptor and inside test tubes that were placed in the focus. Direct cell kill was inversely related to temperature, whereas a linear relationship was found with shock wave energy. Cell kill appeared to be independent of cell density. All four cell lines were sensitive to the treatment with HESW, but displayed a different dose-response pattern. In vitro treatment of PC-3 cells retarded their growth upon injection into nude mice. It is concluded that human prostatic tumour cells are killed by HESW. Therefore, HESW could be of potential value in tumour treatment.


Hormonal regulatory role of eyestalk factors on growth of heart in mud crab, Scylla serrata.
The present study was attempted to know the growth regulation of eyestalk factors on the growth of heart in Scylla serrata using eyestalk extractions and bilateral eyestalk ablations. The bilateral eyestalk ablation led to the maximum growth indices of the heart ((H) indices) to 0.162 and 0.158 in ablated male and female, respectively, in comparison to 0.153 and 0.167 in the control male and female and 0.147 and 0.157 in injected male and female, respectively. The data have shown that the heart of male crabs grows faster than female crabs. The study has also shown that bilateral eyestalk ablation resulted in a significant increase in the heart indices in males and has least effect on the growth of the female heart. The results presented strongly support a potential role of the eyestalk factors and molting hormone regulating the growth of the heart in S. serrata.


A missense mutation converts the Na+,K+-ATPase into an ion channel and causes therapy-resistant epilepsy.
The ion pump Na+,K+-ATPase is a critical determinant of neuronal excitability; however, its role in the etiology of diseases of the central nervous system (CNS) is largely unknown. We describe here the molecular phenotype of a Trp931Arg mutation of the Na+,K+-ATPase catalytic α1 subunit in an infant diagnosed with therapy-resistant lethal epilepsy. In addition to the pathological CNS phenotype, we also detected renal wasting of Mg2+. We found that membrane expression of the mutant α1 protein was low, and ion pumping activity was lost. Arginine insertion into membrane proteins can generate water-filled pores in the plasma membrane, and our molecular dynamic (MD) simulations of the principle states of Na+,K+-ATPase transport demonstrated massive water inflow into mutant α1 and destabilization of the ion-binding sites. MD simulations also indicated that a water pathway was created between the mutant arginine residue and the cytoplasm, and analysis of oocytes expressing mutant α1 detected a nonspecific cation current. Finally, neurons expressing mutant α1 were observed to be depolarized compared with neurons expressing wild-type protein, compatible with a lowered threshold for epileptic seizures. The results imply that Na+,K+-ATPase should be considered a neuronal locus minoris resistentia in diseases associated with epilepsy and with loss of plasma membrane integrity.


Understanding the phase contrast optics to restore artifact-free microscopy images for segmentation.
Phase contrast, a noninvasive microscopy imaging technique, is widely used to capture time-lapse images to monitor the behavior of transparent cells without staining or altering them. Due to the optical principle, phase contrast microscopy images contain artifacts such as the halo and shade-off that hinder image segmentation, a critical step in automated microscopy image analysis. Rather than treating phase contrast microscopy images as general natural images and applying generic image processing techniques on them, we propose to study the optical properties of the phase contrast microscope to model its image formation process. The phase contrast imaging system can be approximated by a linear imaging model. Based on this model and input image properties, we formulate a regularized quadratic cost function to restore artifact-free phase contrast images that directly correspond to the specimen's optical path length. With artifacts removed, high quality segmentation can be achieved by simply thresholding the restored images. The imaging model and restoration method are quantitatively evaluated on microscopy image sequences with thousands of cells captured over several days. We also demonstrate that accurate restoration lays the foundation for high performance in cell detection and tracking.


Positioning Therapies in the Management of Crohn's Disease.
In the past decade, several new therapies with different mechanisms of action have been approved for the management of moderate to severe Crohn's disease. However, there is limited guidance on optimal positioning of agents as first- or second-line therapies because of the absence of head-to-head trials. Furthermore, given the lack of comparative studies, treatment guidelines have provided limited insight. In this review, we discuss data on key treatment attributes, comparative efficacy and safety, factors predictive of response to each agent, and propose an algorithm for positioning therapies for the management of patients with low-risk and high-risk Crohn's disease.


Legal Aspects of Migraine in the Workplace.
This study explores legal aspects of migraine in the workplace. While the high prevalence of migraine is well-documented, its effects on the livelihoods of those living with the disease are less understood. Because migraine symptoms are often invisible, discussions concerning migraine in the workplace can be challenging. What are the rights of persons with migraine in the workplace? Time off may provide a brief respite, but it is not a long-term solution. Claiming disability for migraine has challenges, including barriers to doing so and required paperwork. How can persons with migraine remain employed and productive? How can persons with migraine receive accommodation from their employer or take time off to treat their condition? Many employers offer comprehensive benefit packages that allow for sick days, time off, mental health days, and accommodations that may give persons with migraine temporary reprieve. However, it may not be sufficient, particularly for those with chronic migraine. Further, not all employers offer comprehensive benefits. Employees with migraine may need to seek protection under the law. Our research closely examines the primary legal avenues that persons with migraine may pursue while living and working with migraine. In exploring the legal aspects of migraine, we couple our exploration with relevant case law. Through this lens, we conclude that migraine is becoming less stigmatized and more legitimized in the eyes of the court. It is the belief of the authors that at least some of the change in the attitude towards migraine is the result of strong patient advocacy and significant advances in research over the past several years.


Increased levels of 5-fluorouracil-induced DNA lesions in Bloom's syndrome.
In Bloom's syndrome (BS) the regulation of uracil-DNA glycosylase, an enzyme involved in the repair of DNA containing 5-FU, is altered. 5-FU induces higher levels of DNA fragmentation in BS cells than in non-BS cells. The increase in DNA fragmentation is connected to the cytotoxic mechanism where 5-FU is incorporated into DNA. When 5-FU induces DNA fragmentation by a mechanism not involving the incorporation of drug into DNA, the levels of DNA fragmentation in BS and non-BS cells remain similar.


[Surgical treatment of spine metastatic tumor].
To explore the value of surgical treatment on spine metastatic tumor. 31 cases of spine metastatic tumor with severe pain or/and neurological deficit were selected and treated with various operative methods. Except for 4 cases, all the patients survived from 3 months to 7 years (average 17.6 months). The patients had no complication during treatment. The symptoms and neurological functions recovered with various extent after operation. Surgical treatment should cautiously be adopted. When the spine metastatic tumor with severe pain and neurological deficit has no response to the conservative methods, the surgical treatment with decompression and internal fixation should be performed to improve the life quality for the patients.


Immediate active range of motion after modified 2-incision repair in acute distal biceps tendon rupture.
Different rehabilitation protocols have been used after repair of distal biceps ruptures. This study investigates the safety of immediate active range of motion protocol after modified 2-incision distal biceps tendon repair in acute ruptures. Case series; Level of evidence, 4. Twenty-one patients with a minimum follow-up of 2 years were participants in this study. After repair, the upper extremities were placed in a sling for 1 to 2 days and then immediate active range of motion was started. For the first 6 weeks, the elbow was allowed activities of daily living as tolerated by the patient with a 1-lb weight-lifting restriction. Elbow range of motion, isometric and dynamic flexion, and supination strengths were recorded and Disabilities of the Arm, Shoulder and Hand (DASH) scores were obtained. Mean follow-up extension was 0 degrees and mean follow-up flexion was 141 degrees on the operated side, with supination of 74 degrees and pronation of 75 degrees. The mean DASH score for 21 patients was 3.6 +/- 3.6 (range, 0-11.4). The mean follow-up isometric flexion strength was found to be 5% (P = .411), and the power (dynamic strength) of flexion was 12% greater on the operated side (P = .046). However, follow-up isometric supination strength was 9% less on the involved side than on the noninvolved side (P = .030), and the power of supination was 11% less on the operated side (P = .007). There were no tendon reruptures at follow-up, determined by physical examination. A modified 2-incision distal biceps repair allows a safe immediate active range of motion protocol with early return of nearly full range of motion and strength, without any clinically significant disability.


Preliminary observations on the experimental transmission of chronic wasting disease (CWD) from elk and white-tailed deer to fallow deer.
To determine the transmissibility of chronic wasting disease (CWD) to fallow deer (Dama dama) and to provide information about clinical course, lesions and suitability of currently used diagnostic procedures for detection of CWD in this species, 13 fawns were inoculated intracerebrally with CWD brain suspension from elk (n=6) or white-tailed deer (n=7). Three other fawns were kept as uninfected controls. Three CWD-inoculated deer were killed 7.6 months post-inoculation (mpi). None had abnormal prion protein (PrPd) in their tissues. One sick deer died at 24 mpi and one deer without clinical signs was killed at 26 mpi. Both animals had a small focal accumulation of PrPd in the midbrain. Between 29 and 37 mpi, three other deer became sick and were killed. All had shown gradual decrease in appetite and some loss of body weight. Microscopical lesions of spongiform encephalopathy were not observed, but PrPd was detected in tissues of the central nervous system (CNS) by immunohistochemistry, western blot and by two commercially available rapid diagnostic tests. This study demonstrates that intracerebrally inoculated fallow deer amplified CWD PrPd from white-tailed deer and elk in the absence of lesions of spongiform encephalopathy. Four years after CWD inoculation, the remaining five inoculated and two control deer are alive and apparently healthy.


An economic, sustainability, and energetic model of biodiesel production from microalgae.
A new process evaluation methodology of microalgae biodiesel has been developed. Based on four evaluation criteria, i.e. the net energy ratio (NER), biodiesel production costs, greenhouse gases (GHG) emission rate and water footprint, the model compares various technologies for each step of the process, from cultivation to oil upgrading. An innovative pathway (hybrid raceway/PBR cultivation system, belt filter press for dewatering, wet lipid extraction, oil hydrotreating and anaerobic digestion of residues) shows good results in comparison to a reference pathway (doubled NER, lower GHG emission rate and water footprint). The production costs are still unfavourable (between 1.94 and 3.35 €/L of biodiesel). The most influential parameters have been targeted through a global sensitivity analysis and classified: (i) lipid productivity, (ii) the cultivation step, and (iii) the downstream processes. The use of low-carbon energy sources is required to achieve significant reductions of the biodiesel GHG emission rate compared to petroleum diesel.


The relationship between overweight in adolescence and premature death in women.
The impact of adiposity in adolescence on death during adulthood is uncertain. To examine the relation between adiposity in adolescence and premature death in women. Prospective cohort study. United States. 102,400 women from the Nurses' Health Study II who were 24 to 44 years of age and free of cancer at baseline. Ninety percent were of non-Hispanic white ethnicity. In 1989, current weight and height and recalled weight at age 18 years were assessed by using validated questionnaires, and body mass index (BMI) was calculated. Hazard ratios for death and 95% CIs were adjusted for potential confounders, including cigarette smoking, alcohol use, and physical activity during adolescence. During 12 years of follow-up, 710 participants died. Compared with a BMI of 18.5 to 21.9 kg/m2 at age 18 years, the hazard ratio for premature death was 0.98 (95% CI, 0.78 to 1.23) for a BMI less than 18.5 kg/m2, 1.18 (CI, 0.97 to 1.43) for a BMI of 22.0 to 24.9 kg/m2, 1.66 (CI, 1.31 to 2.10) for a BMI of 25.0 to 29.9 kg/m2, and 2.79 (CI, 2.04 to 3.81) for a BMI of 30 kg/m2 or greater. Among participants who never smoked, a BMI of 22.0 to 24.9 kg/m2 at age 18 years was also associated with increased premature death (hazard ratio, 1.50 [CI, 1.16 to 1.94]). Associations between BMI at age 18 years and death could only partly be explained by adult BMI measured in 1989. Because of the observational study design, residual confounding by imperfectly measured or unknown confounders may still be present. Moderately higher adiposity at age 18 years is associated with increased premature death in younger and middle-aged U.S. women.


Reduction of severe acute respiratory syndrome coronavirus-2 infectivity by admissible concentration of ozone gas and water.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the global coronavirus disease 2019 (COVID-19) pandemic. Because complete elimination of SARS-CoV-2 appears difficult, decreasing the risk of transmission is important. Treatment with 0.1 and 0.05 ppm ozone gas for 10 and 20 hr, respectively, decreased SARS-CoV-2 infectivity by about 95%. The magnitude of the effect was dependent on humidity. Treatment with 1 and 2 mg/L ozone water for 10 s reduced SARS-CoV-2 infectivity by about 2 and 3 logs, respectively. Our results suggest that low-dose ozone, in the form of gas and water, is effective against SARS-CoV-2.


Pedicled partial thickness clavicular graft for oromandibular reconstruction.
To report our experience on pedicled partial-thickness clavicular graft (PPCG) for oromandibular reconstruction. PPCG was used for oromandibular reconstruction after tumor resection in 23 patients with early-stage gingival carcinoma but were eager for postoperative dental implant therapy for restoration of good occlusal function. PPCG was harvested during neck dissection. The sternocleidomastoid (SCM) myocutaneous flap was also harvested in 18 cases. Dental implants were placed in the clavicular graft of 19 cases, and the other 4 declined because of financial concerns. Postoperative viability of the flaps and the dental implants were assessed. All the clavicular grafts survived without necrosis and implant-supported dentures of 19 patients provided satisfactory occlusion and masticatory function. Complications, although low in occurrence, included partial skin pedicle loss, nonunion between the clavicular graft and the remaining inferior border of the mandible, and clavicular bone fracture. PPCG is a simple but reliable procedure for reconstruction of severe alveolar defects. Correct preoperative evaluation and precise surgical technique contribute to higher success rates and lower complication rates. It is a viable reconstructive option for early-stage gingival carcinoma requiring neck dissection without postoperative radiation therapy.


The burden of gout in acne keloidalis nuchae-Insights from a population-based study.
The risk of gout amid patients with acne keloidalis nuchae (AKN) has not been investigated in the past. To assess the risk of developing gout among patients with AKN relative to control subjects. A population-based retrospective study followed patients with AKN (n = 2677) and age-, sex-, and ethnicity-matched control subjects (n = 13 190). The incidence of new-onset gout was compared between the two groups. Hazard ratio (HR) for the risk of gout was obtained using a multivariate Cox regression model. The incidence rate of gout was 1.12 (95% CI, 0.68-1.76) and 0.48 (95% CI, 0.34-0.66) per 1000 person-years among patients with AKN and controls, respectively. The crude risk of developing gout was significantly higher in patients with AKN (HR, 2.27; 95% CI, 1.26-4.10; p = 0.007). After controlling for age, sex, and ethnicity, AKN emerged as an independent risk factor of gout (adjusted HR, 2.34; 95% CI, 1.29-4.22; p = 0.005). When adjusting for other confounders such as body mass index, diabetes mellitus, hypertension, and dyslipidemia, the risk of gout in AKN fell out of significance (adjusted HR, 1.39; 95% CI, 0.73-2.65; p = 0.311), CONCLUSION: Patients with AKN experience an increased risk of gout. The risk is not independent and is mainly mediated through the metabolic comorbidities typifying AKN. We recommend screening for gout in patients with suggestive complaints.


Encoding of acquired sound-sequence salience by auditory cortical offset responses.
Behaviorally relevant sounds are often composed of distinct acoustic units organized into specific temporal sequences. The meaning of such sound sequences can therefore be fully recognized only when they have terminated. However, the neural mechanisms underlying the perception of sound sequences remain unclear. Here, we use two-photon calcium imaging in the auditory cortex of behaving mice to test the hypothesis that neural responses to termination of sound sequences ("Off-responses") encode their acoustic history and behavioral salience. We find that auditory cortical Off-responses encode preceding sound sequences and that learning to associate a sound sequence with a reward induces enhancement of Off-responses relative to responses during the sound sequence ("On-responses"). Furthermore, learning enhances network-level discriminability of sound sequences by Off-responses. Last, learning-induced plasticity of Off-responses but not On-responses lasts to the next day. These findings identify auditory cortical Off-responses as a key neural signature of acquired sound-sequence salience.


[Antibiotic prophylaxis in cardiac surgery: practice patterns].
To assess the prescription patterns in French and foreign centres for antibiotic prophylaxis in cardiac surgery. Phone and written surveys concerned 64 French and 70 foreign centres. It focused on the first injection, the duration of treatment and the recommended agents. 87% of the French centres and 67% of the foreign centres answered the questionnaire. The first injection took place at anaesthesia induction in all French centres but during administration of premedication in 11% of foreign centres (p < 0.05). The duration of prophylaxis was restricted to the intraoperative period only in 20% and 15% of centres, respectively (ns), as specified by the recommendations. No French centres carried on the antibiotics more than 48 h versus 11% of foreign centres (p < 0.05). Cephalosporines of the second generation were prescribed in 84 and 49% of centres, respectively (p < 0.05). The combination of two antibiotics was less frequent in France than in foreign countries (5 versus 17%, p < 0.01). In absence of betalactamin allergy glycopeptides were not utilized in France versus 8% in foreign countries (p < 0.05). In case of allergy vancomycin was used in 66% of French and 42% of foreign centres. The French recommendations may have influenced favourably the antibiotic choice but the prophylaxis duration was too long in most of the non French European centres.


Characterization of the novel HLA-DPA1*02:26 allele by sequencing-based typing.
HLA-DPA1*02:26 differs from HLA-DPA1*02:01:01:02 by one nucleotide substitution in codon 186 in exon 4.


Engaging stemness improves cancer immunotherapy.
Intra-tumoral immune cells promote the stemness of cancer stem cells (CSCs) in the tumor microenvironment (TME). CSCs promote tumor progression, relapse, and resistance to immunotherapy. Cancer stemness induces the expression of neoantigens and neo-properties in CSCs, creating an opportunity for targeted immunotherapies. Isolation of stem-like T cells or retaining stemness in T clonotypes strategies produces exhaustion-resistance T cells with superior re-expansion capacity and long-lasting responses after adoptive cell therapies. Stem cells-derived NK cells may be the next generation of NK cell products for immunotherapy. Here, we have reviewed mechanisms by which stemness factors modulated the immunoediting of the TME and summarized the potentials of CSCs in the development of immunotherapy regimens, including CAR-T cells, CAR-NK cells, cancer vaccines, and monoclonal antibodies. We have discussed the natural or genetically engineered stem-like T cells and stem cell-derived NK cells with increased cytotoxicity to tumor cells. Finally, we have provided a perspective on approaches that may improve the therapeutic efficacy of these novel adoptive cell-based products in targeting immunosuppressive TME.


Dietary Supplementation with a Cocoa-Carob Blend Modulates Gut Microbiota and Prevents Intestinal Oxidative Stress and Barrier Dysfunction in Zucker Diabetic Rats.
We have recently developed a cocoa-carob blend (CCB) rich in polyphenols with antidiabetic properties. In this study, we investigated whether its benefits could be related to gut health and gut microbiota (GM) composition and the likely phenolic metabolites involved. Zucker diabetic fatty rats were fed on a standard or a CCB-rich diet for 12 weeks. Intestinal barrier structure and oxidative and inflammatory biomarkers were analyzed in colonic samples. GM composition and phenolic metabolites were evaluated from feces. The results show that CCB improved mucin and tight-junction proteins and counteracted gut oxidative stress and inflammation by regulating sirtuin-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) levels. CCB also modulated the composition of the GM, showing increases in Akkermansia and Bacteroides and decreases in Ruminococcus genera. Correlation analysis strengthened the associations between these genera and improved pathological variables in diabetic animals. Moreover, 12 phenolic metabolites were identified in CCB feces, being2,3-dihydroxybenzoic and 3,4,5-trihydroxybenzoic acids significantly associated with increased levels of Akkermansia and Oscillospira genera. Our findings support the potential use of CCB to prevent intestinal damage and dysbiosis in T2D, which would help to delay the progression of this pathology.


Pulmonary Embolism Presenting as an Anterior ST-elevation Myocardial Infarction: A Case Report.
While the electrocardiogram (ECG) for pulmonary embolism typically shows tachycardia or evidence of right heart strain, it can demonstrate ischemic changes similar to acute coronary syndrome. The patient in this case presented with syncope, chest pain, and an ECG showing an anterior acute myocardial infarction (AMI) without evidence of right heart strain. His cardiac catheterization showed no coronary artery occlusions, but some signs of pulmonary embolism (PE), which was confirmed on computed tomography angiography of the chest. This case demonstrates that PE should be high on the differential for AMI and describes an uncommonly encountered mimic for classic ST-elevation myocardial infarction ECG changes. Further diagnostics to confirm the diagnosis should be obtained when indicated.


Normative Data of Pulmonary Function Tests and Radiographic Measures of Chest Development in Children Without Spinal Deformity: Is a T1-T12 Height of 22 cm Adequate?
Retrospective case series. To develop normative data of pulmonary function tests (PFTs) and radiographic measures of chest development in normal children and to determine if the prior proposed T1-T12 height of 22 cm for spinal fusion in a growing child is adequate for pulmonary function based on normative PFT values at skeletal maturity. Shortening of the spine from T1-T12 is a concern with early thoracic fusion for spinal deformity, as it has a deleterious effect on the development of the pulmonary system. Children with mild asthma who had pulmonary function tests (PFTs) >90% and without chest or spinal deformity were identified. PFT data included absolute forced vital capacity (FVC), %-predicted FVC, absolute forced expiratory volume in one second (FEV1), %-predicted FEV1, and FEV1/FVC. Radiographic measurements performed on chest radiographs included T1-T12 height, coronal chest width (CCW), and space available for the lung (SAL) bilaterally. These data were analyzed for all patients and for patients with T1-T12 heights 22-24 cm. To assess the impact of T1-T12 shortening on PFTs at skeletal maturity, spirometric standards for healthy adult lifetime nonsmokers were used. Of 1,797 PFT studies, 149 children (average age 12.4 ± 3.0 years; girls, 97) were analyzed. For the entire cohort, PFT values were as follows: FVC 3.0 ± 0.9 L, %-predicted FVC 103.9% ± 10.6%, absolute FEV1 2.7 ± 0.9 L, %-predicted FEV1 106.9% ± 11.1%, and FEV1/FVC 90.7% ± 2.6%. The averages for T1-T12 height was 25.6 ± 3.8 cm, CCW 25.5 ± 3.4 cm, and SAL bilaterally 19.0 ± 3.5 cm. For the 21 patients (girls 11; average age 9.7 ± 1.4 years) with T1-T12 heights 22-24 cm, absolute FVC was 2.2 ± 0.3 L, %-predicted FVC was 104.0% ± 13.0%, absolute FEV1 was 2.0 ± 0.3 L, %-predicted FEV1 was 108.2% ± 15.0%, and FEV1/FVC was 91.0% ± 2.7%. If these kids with 22-24 cm T1-T12 heights maintained the same thoracic height, they were calculated to have %-predicted FVC of 44% (girl) and 42% (boy) and %-predicted FEV1 of 42% (girl) and 43% (boy) at skeletal maturity (15 years old). Percent-predicted FEV1 and FVC values for normal children with a T1-T12 height of 22 cm at skeletal maturity were <50%. Though this analysis does not take into consideration radial expansion of the chest or children with scoliosis (idiopathic, congenital, neuromuscular), these values are concerning and may not be adequate to guarantee that children with early-onset scoliosis who are fused with T1-T12 heights of 22 cm will have an asymptomatic pulmonary status in adulthood. Level IV.


Catalytic site studies on tuna (Thunnus albacares) pyloric caeca aminopeptidase.
Tuna pyloric caeca aminopeptidase (tAP) is a glycosylated zinc-metalloenzyme containing apparently two identical subunits. The enzyme is reversibly inhibited in a time-dependent manner by amastatin. Slow development of tAP inhibition by this inhibitor could be demonstrated. Dissociation of the complex of tAP with amastatin is also slow. Two molar equivalents of the inhibitor are bound by the enzyme suggesting the presence of one catalytic site in each subunit. Chemical modification of tAP with 1-cyclohexyl-3-(2-morpholinoethyl) carbonyl-metho-p-toluene sulfonate and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinone revealed the presence of essential acidic amino acid residues probably located at the active site. Compatible with the presence of arginine and tyrosine residues at the catalytic site of most metalloproteinases, tAP is reversibly inhibited by phenylglyoxal and inactivated by tetranitromethane in a time-dependent fashion. The rate of inhibition by these modifiers could be significantly decreased if the enzyme was previously treated with amastatin suggesting that the modified amino acid residues are located at the catalytic site. Diethylpyrocarbonate did not affect the activity of both native and zinc-depleted tAP suggesting that histidine is not involved in the zinc-ligand formation.


Melatonin alleviates circadian system disruption induced by chronic shifts of the light-dark cycle in Octodon degus.
Modern 24-h society lifestyle is associated with experiencing frequent shifts in the lighting conditions which can negatively impact human health. Here, we use the degus, a species exhibiting diurnal and nocturnal chronotypes, to: (a) assess the impact of chronic shifts of the light:dark (LD) cycle in the animal's physiology and behaviour and (b) test the therapeutic potential of melatonin in enhancing rhythmicity under these conditions. Degus were subjected to a "5d + 2d" LD-shifting schedule for 19 weeks. This protocol aims to mimic lighting conditions experienced by humans during shift work: LD cycle was weekly delayed by 8h during 5 "working" days (Morning, Afternoon and Night schedule); during weekends (2 days), animals were kept under Morning schedule. After 9 weeks, melatonin was provided daily for 6h in the drinking water. The "5d + 2d" shifting LD schedule led to a disruption in wheel-running activity (WRA) and body temperature (Tb) rhythms which manifested up to three separate periods in the circadian range. This chronodisruption was more evident in nocturnal than in diurnal degus, particularly during the Afternoon schedule when a phase misalignment between WRA and Tb rhythms appeared. Melatonin treatment and, to a lesser extent, water restriction enhanced the 24-h component, suggesting a potential role in ameliorating the disruptive effects of shift work.


Artesunate alleviates psoriasis-like dermatitis by reducing interleukin-23 expression in tumor necrosis factor-alpha-induced HaCaT cells.
Artesunate (ART), an antimalarial drug with a multifunctional immunomodulatory effect, reduces psoriasis disease. ART can alleviate psoriasis-like dermatitis in mice but has no effect on proinflammatory cytokines in the blood. Thus, we hypothesized that the skin might be the target tissue of ART during the treatment of psoriasis. The interleukin (IL)-23/IL-17 axis has a key role in the pathogenesis of psoriasis. However, whether and how ART manipulates the IL-23 signal during psoriasis is unknown. This study found that IL-23 is highly expressed in the epidermis of psoriasis lesions and positively correlated with histological neutrophil infiltration and clinical psoriasis area and severity index (PASI) scores. Furthermore, ART inhibits the migration and cell cycle, as well as tumor necrosis factor-alpha (TNF-α)-induced IL-23 expression in HaCaT cells in a dose-dependent manner, probably through interference with the nuclear factor kappa B (NF-κB) signalling pathway. Animal experiments in imiquimod (IMQ)-induced psoriasis-like mice model also suggested that ART dose-dependently reduces IL-23 in the epidermis and ameliorates neutrophil infiltration. These findings thus provide further molecular evidence supporting ART as a promising drug for psoriasis in clinic.


Regional and Rural-Urban Differences in the Use of Direct-acting Antiviral Agents for Hepatitis C Virus: The Veteran Birth Cohort.
Veterans with hepatitis C virus (HCV) infection may face geographic obstacles to obtaining treatment. We studied the influence of region and rural versus urban residence on receipt of direct-acting antiretroviral (DAA) medications for HCV. Veterans receiving care within Veterans Affairs Healthcare System born between 1945 and 1965. This is a observational study using national electronic health record data. Receipt of DAAs was defined as ≥1 filled prescription from January 1, 2014 to December 31, 2016. Region (South, Northeast, Midwest, and West) and residence (urban, rural-micropolitan, small rural towns, and isolated rural towns) variables were created using residential zone improvement plan codes and rural-urban commuting area (RUCA) codes. Multivariable models were adjusted for age, race, sex, severity of liver disease, comorbidities, and prior treatment experience. Among 166,353 eligible patients 64,854 received, DAAs. Variation by rural-urban residence depended on region. In unadjusted analyses, receipt varied by rural-urban designations within Midwest, and West regions (P<0.05) but did not vary within the South (P=0.12). Southern rural small town had the lowest incidence of DAA receipt (40.1%), whereas the incidence was 52.9% in Midwestern isolated rural towns. In adjusted logistic analyses, compared with southern urban residents (the largest single group), southern rural small town residents had the lowest odds ratio, 0.85 (95% confidence interval, 0.75-0.93), and Midwestern residents from isolated and small rural towns had the highest odds (odds ratio, both 1.27) to receive treatment. Substantial geographic variation exists in receipt of curative HCV treatment. Efforts are needed to provide more equitable access to DAAs.


Managing the curb - Public space and use of curbside cafes during the Coronavirus pandemic.
Urban streets, especially curbside spaces, are increasingly complex and often contested. The Coronavirus pandemic created a new demand for street space to enable physical distancing. The urgency of the pandemic and the fear of covid exposure suspended traditional community engagement opportunities, opposition from residents and business owners, and considerations over the privatization of public street space. This exploratory paper uses the case studies of Toronto and Chicago to trace the past and present regulations and programs affecting curbside parking spaces. Through these cases, this paper addresses larger questions that relate the historical conceptions around curbside parking use with those put forward in response to the pandemic. Given the popularity of pandemic-related curbside space programs and their potential to become long-term interventions, this paper also raises several questions around privatization, access and social equity that must be addressed in future iterations of programs affecting curbside space.


Macrophage-activating factor for cytotoxicity produced by a human T-cell hybridoma.
Human MAF-C (macrophage-activation factor for cytotoxicity)-producing hybridoma H2-E3-5 was prepared by somatic cell fusion of PHA-activated peripheral blood lymphocytes with emetine/actinomycin D-treated cloned human acute lymphatic leukemia cells (CEM). The following activities were assayed: (1) macrophage-migration-inhibitory factor (MIF), (2) macrophage-activation factor for glucose consumption (MAF-G), (3) macrophage-activation factor for O2-formation (MAF-O), and (4) macrophage-activation factor for cytotoxicity (MAF-C). After anion-exchange chromatography, MAF-C activity could be distinguished from MIF and MAF-O activities. It is shown that MAF-C is not the same as MAF-G from the culture supernatants of CEM 11, a parent cell line of H2-E3-5. Furthermore, MAF-C from H2-E3-5 culture supernatants activated differentiated macrophages but not monocytes.


Role of basic aminoalkyl chains in the lead optimization of Indoloquinoline alkaloids.
Indoloquinoline (IQ) is an important class of naturally occurring antimalarial alkaloids, mainly represented by cryptolepine, isocryptolepine, and neocryptolepine. The IQ structural framework consists of four isomeric ring systems differing via the linkage of indole with quinoline as [3,2-b], [3,2-c], [2,3-c], and [2,3-b]. Structurally, IQs are planar and thus they bind strongly to the DNA which largely contributes to their biological properties. The structural rigidity and associated nonspecific cellular toxicity is a key shortcoming of the IQ structural framework for preclinical development. Thus, the lead optimization efforts were aimed at improving the therapeutic window and ADME properties of IQs. The structural modifications mainly involved attaching the basic aminoalkyl chains that positively modulates the vital physicochemical and topological parameters, thereby improves biological activity. Our analysis has found that the aminoalkylation consistently improved the selectivity index and provided acceptable in-vivo antimalarial/anticancer activity. Herein, we critically review the role of aminoalkylation in deciphering the antimalarial and cytotoxic activity of IQs.


Inputs of anthropogenic nitrogen influence isotopic composition and trophic structure in SE Australian estuaries.
Urban development in coastal settings has increased the input of nitrogen into estuaries globally, in many cases changing the composition of estuarine ecosystems. By focussing on three adjacent estuaries with a gradient of anthropogenic N loadings, we used stable isotopes of N and C to test for changes due to increased anthropogenic N input on the structure of some key trophic linkages in estuaries. We found a consistent enrichment in δ(15)N corresponding to increased anthropogenic N at the three ecosystem levels studied: fine benthic organic matter, grazing invertebrate, and planktivorous fish. The degree of enrichment in δ(15)N between fine benthic organic matter and the grapsid crab Parasesarma erythrodactyla was identical across the three sites. The glassfish Ambassis jacksoniensis showed lower levels of enrichment compared to basal food sources at the higher N-loaded sites, suggesting a possible effect of anthropogenic N in decreasing food-chain length in these estuaries.


Endogenous alpha-synuclein is induced by valproic acid through histone deacetylase inhibition and participates in neuroprotection against glutamate-induced excitotoxicity.
Emerging evidence suggests that alpha-synuclein (alpha-syn), which is traditionally thought to have a pathophysiological role in neurodegenerative diseases, can have neuroprotective effects. This study aimed to investigate whether endogenous alpha-syn in neurons can be induced by valproic acid (VPA), a mood-stabilizer, anticonvulsant and histone deacetylase (HDAC) inhibitor, and if so, whether the alpha-syn induction is neuroprotective. VPA treatment of rat cerebellar granule cells caused a robust dose- and time-dependent increase in levels of alpha-syn protein and mRNA and in the intensity of alpha-syn immunostaining. Knockdown of VPA-induced alpha-syn overexpression with alpha-syn antisense oligonucleotides or siRNA completely blocked VPA-induced neuroprotection. alpha-Syn knockdown also exacerbated glutamate neurotoxicity, stimulated the expression of the proapoptotic gene ubiquitin-conjugating enzyme E2N, and downregulated the expression of the anti-apoptotic gene Bcl-2. Induction of alpha-syn by VPA was associated with inhibition of HDAC activity, resulting in hyperacetylation of histone H3 in the alpha-syn promoter and a marked increase in alpha-syn promoter activity. Moreover, VPA-induced alpha-syn induction and neuroprotection were mimicked by HDAC inhibitors sodium 4-phenylbutyrate and trichostatin A (TSA). alpha-syn was also induced by VPA in rat cerebral cortical neurons. Additionally, treatment of rats with VPA, sodium butyrate, or TSA markedly increased alpha-syn protein levels in the cortex and cerebellum. Together, our results demonstrate for the first time that VPA induces alpha-syn in neurons through inhibition of HDAC and that this alpha-syn induction is critically involved in neuroprotection against glutamate excitotoxicity. Clinically, VPA may represent a suitable treatment for excitotoxicity-related neurodegenerative diseases.


Factors affecting home-measured resting heart rate in the general population: the Ohasama study.
We recently demonstrated that a home-measured resting heart rate (HR) can predict cardiovascular disease mortality, and it is possible that the determinants of home HR are different from casual HR. Therefore, clarifying the determinants of home HR should be useful. Home HR was obtained using a self-monitored blood pressure (BP) measuring device. The impact of factors including home-measured BP and lifestyle on home HR was examined in 1275 members of the general Japanese population aged > or =40 years. Multivariate linear regression analysis demonstrated that younger age (beta = -0.08, P < or = .01), current smoking (beta = 3.22, P < or = .01), female gender (beta = 2.07, P < or = .01), and sedentary lifestyle (walking for < or =1 h/day) (beta = 2.43, P < or = .01) were determinants of elevated morning home HR. No significant association was observed between home HR and home systolic BP, whereas casual HR was significantly and positively associated with casual systolic BP. The difference between casual and home HR was also significantly and positively associated with the difference between casual and home systolic BP, suggesting that positive association between BP and HR obtained in clinic settings would be a reflection of the so-called white-coat effect. We observed that, with the exception of BP, most determinants of home HR were consistent with the determinants observed in previous studies using casual HR. These results suggest that reduction of home HR through modification of smoking habit or sedentary lifestyle may have a potential to decrease cardiovascular risk in addition to decreasing in these modifiable risk factor per se.


The Illinois Forest Preserve District Act of 1913 and the emergence of metropolitan park system planning in the USA.
In 1913, the Illinois Legislature enacted the Forest Preserve District Act. After adoption of the Act by voters in Cook County, the Chicago metropolitan area became among the first in the USA to establish a park system with an outer ring of nature preserves. This article chronicles the story of how the Cook County Forest Preserve District was established, its historical context and its influence on planning practice. It contends that although Chicago was not the originator of the idea of outer parks, it added significantly to development of the concept of comprehensive park system planning. The article contends that the paradigm of park management changed from conservation of the native landscape to multiple use management during the 20-year struggle to establish the district, and that passage of the Act was largely the result of the efforts of two individuals - Dwight Perkins and Jens Jensen.


Modulation of NMDA receptors by glycine--introduction to some basic aspects and recent developments.
Glycine is a co-agonist at NMDA receptors and it's presence is a prerequisite for channel activation by glutamate or NMDA. Physiological concentrations reduce one form of NMDA receptor-desensitization. Interactions between the glycineB site and other domains of the NMDA receptor are complex and include the glutamate, Mg2+ and polyamines sites. Glycine shows different affinities at various NMDA receptor subtypes probably via to allosteric interactions between NMDA2 subunits and the glycine recognition site on the NMDAR1 subunit. There is still some debate whether the glycineB site is saturated in vivo but it seems likely that this depends on regional differences in receptor subtype expression, local glycine or D-serine concentrations and the expression of specific glycine transporters. GlycineB antagonists and partial agonists have been reported to have good therapeutic indices as neuroprotective agents against focal ischaemia and trauma, anti-epileptics, anxiolytics, anti-psychotomimetics and in models of chronic pain. They clearly lack two potentially serious side effects classically associated with NMDA receptor blockade, namely neurodegenerative changes in the cingulate/retrosplenial cortex and psychotomimetic-like effects. This improved therapeutic profile may be partially due to the ability of full glycineB antagonists to reveal glycine-sensitive desensitization and possibly also via functional and/or regional NMDA receptor subtype selectivity.


The promise of organoids for unraveling the proteomic landscape of the developing human brain.
Cerebral organoids offer an opportunity to bioengineer experimental avatars of the developing human brain and have already begun garnering relevant insights into complex neurobiological processes and disease. Thus far, investigations into their heterogeneous cellular composition and developmental trajectories have been largely limited to transcriptional readouts. Recent advances in global proteomic technologies have enabled a new range of techniques to explore dynamic and non-overlapping spatiotemporal protein-level programs operational in these humanoid neural structures. Here we discuss these early protein-based studies and their potentially essential role for unraveling critical secreted paracrine signals, processes with poor proteogenomic correlations, or neurodevelopmental proteins requiring post-translational modification for biological activity. Integrating emerging proteomic tools with these faithful human-derived neurodevelopmental models could transform our understanding of complex neural cell phenotypes and neurobiological processes, not exclusively driven by transcriptional regulation. These insights, less accessible by exclusive RNA-based approaches, could reveal new knowledge into human brain development and guide improvements in neural regenerative medicine efforts.


Success of resin infiltration treatment on interproximal tooth surfaces in young adults-A practice-based follow-up study.
Arresting active initial caries lesions is part of the modern caries controlling system. Resin infiltration (RI) system has been found a promising method in arresting interproximal initial lesions. The aim was to investigate whether RI arrests progression of active caries lesions. Participants (n = 20) of the retrospective study were patients in the Dental Teaching Unit, City of Oulu, Finland, mean age 26 years (SD5.2). Indication for RI was radiographically diagnosed progressing (ICDAS 1-3) interproximal lesions (n = 54). RI treatments were performed in 2015-2017. Controls were initial lesions in the same bitewing radiographs without RI or other treatment (n = 24). For analyzes teeth were categorized as lower and upper premolars and molars. The change in lesions during the follow-up period was recorded surface wise as follows: deterioration / improvement from ICDAS score 3/improvement from ICDAS score 2/improvement per se/at follow-up, lesion was less diffuse/no change. The changes in each tooth surface were analyzed between RI intervention and control teeth by using Chi-square test. Proportions of successful and failed surfaces were given. The mean length of follow-up period was 17.4 m (SD7.2). Arresting of caries lesions (ICDAS scores 2 and 3) was distinctly better in RI group (63.0%) compared with the controls (29.1%). The situation progressed among 29.2% of the controls whereas the respective proportion among the intervention group was 14.8%. Progression of lesions was more distinct in all tooth groups in the control group. Outcome was successful despite the lesion depth. Resin infiltration seems effective in arresting progression of initial caries lesions with monitoring period of 1.5 years.


Synthesis and antiviral activity of a novel glycosyl sulfoxide against classical swine fever virus.
A novel compound-2″,3″,4″,6″-tetra-O-acetyl-β-d-galactopyranosyl-(1→4)-2',3',6'-tri-O-acetyl-1-thio-β-d-glucopyranosyl-(5-nitro-2-pyridyl) sulfoxide-designated GP6 was synthesized and assayed for cytotoxicity and in vitro antiviral properties against classical swine fever virus (CSFV) in this study. We showed that the examined compound effectively arrested CSFV growth in swine kidney cells (SK6) at a 50% inhibitory concentration (IC50) of 5 ± 0.12 μg/ml without significant toxicity for mammalian cells. Moreover, GP6 reduced the viral E2 and E(rns) glycoproteins expression in a dose-dependent manner. We have excluded the possibility that the inhibitor acts at the replication step of virus life cycle as assessed by monitoring of RNA level in cells and culture medium of SK6 cells after single round of infection as a function of GP6 treatment. Using recombinant E(rns) and E2 proteins of classical swine fever virus produced in baculovirus expression system we have demonstrated that GP6 did not influence glycoprotein production and maturation in insect cells. In contrast to mammalian glycosylation pathway, insect cells support only the ER-dependent early steps of this process. Therefore, we concluded that the late steps of glycosylation process are probably the main targets of GP6. Due to the observed antiviral effect accompanied by low cytotoxicity, this inhibitor represents potential candidate for the development of antiviral agents for anti-flavivirus therapy. Further experiments are needed for investigating whether this compound can be used as a safe antiviral agent against other viruses from unrelated groups.


Force Generation in the Coiling Tendrils of Passiflora caerulea.
Tendrils of climbing plants coil along their length, thus forming a striking helical spring and generating tensional forces. It is found that, for tendrils of the passion flower Passiflora caerulea, the generated force lies in the range of 6-140 mN, which is sufficient to lash the plant tightly to its substrate. Further, it is revealed that the generated force strongly correlates with the water status of the plant. Based on a combination of in situ force measurements with anatomical investigations and dehydration-rehydration experiments on both entire tendril segments and isolated lignified tissues, a two-phasic mechanism for spring formation is proposed. First, during the free coiling phase, the center of the tendril begins to lignify unilaterally. At this stage, both the generated tension and the stability of the form of the spring still depend on turgor pressure. The unilateral contraction of a bilayer as being the possible driving force for the tendril coiling motion is discussed. Second, in a stabilization phase, the entire center of the coiled tendril lignifies, stiffening the spring and securing its function irrespective of its hydration status.


Are we applying interventions with research evidence when targeting secondary complications of the stroke-affected upper limb.
This study aimed to survey occupational therapy practice with reference to the current evidence for management of secondary complications of the stroke-affected upper limb. A questionnaire was developed to identify the clinical practice of occupational therapists in managing the client's stroke-affected upper limb. Participants were recruited via an email to the national occupational therapy neurology listserve. Occupational therapists working in stroke rehabilitation were invited to complete the questionnaire online or to print off and return. Fifty-five occupational therapists completed the questionnaire. Results revealed that treatment techniques with little to no evidence were used frequently, including pillow cushion supports (98%), positional stretch (94%) and slings (61%). Alternatively, treatment techniques with significant supporting evidence were used at a lower frequency, such as electrical stimulation (39%). The results of the questionnaire highlight an inconsistent application of evidence within clinical practice and the consistent application of treatment techniques with poor supporting evidence. This result does not represent poor clinical practice. Rather, it highlights the need for the research literature to articulate the clinical reasoning underpinning clinicians' selection of treatment techniques and to determine the effectiveness of frequently used, but poorly supported treatment techniques.


CARD14 alterations in Tunisian patients with psoriasis and further characterization in European cohorts.
Rare highly penetrant gain-of-function mutations in caspase recruitment domain family, member 14 (CARD14) can lead to psoriasis, a chronic inflammatory disease of the skin and other organs. To investigate the contribution of rare CARD14 variants to psoriasis in the Tunisian population and to expand knowledge of CARD14 variants in the European population. CARD14 coding exons were resequenced in patients with psoriasis and controls from Tunisia and Europe, including 16 European cases with generalized pustular psoriasis (GPP). Novel variants were evaluated for their effect on nuclear factor (NF)-κB signalling. Rare variants in CARD14 were significantly enriched in Tunisian cases compared with controls. Three were collectively found in 5% of Tunisian cases, and all affected the N-terminal region of the protein harbouring its caspase recruitment domain or coiled-coil domain. These variants were c.349G>A (p.Gly117Ser), c.205C>T (p.Arg69Trp) and c.589G>A (p.Glu197Lys). c.589G>A (p.Glu197Lys) led to upregulation of NF-κB activity in a similar manner to that of previously described psoriasis-associated mutations. p.Arg69Trp led to sevenfold downregulation of NF-κB activity. One Tunisian case harboured a c.1356+5G>A splice alteration that is predicted to lead to loss of exon 9, which encodes part of the coiled-coil domain. No cases of GPP harboured an interleukin-36RN mutation, but one of 16 cases of GPP with a family history of psoriasis vulgaris harboured a c.1805C>T (p.Ser602Leu) mutation in CARD14. These observations provide further insights into the genetic basis of psoriasis in the Tunisian population and provide functional information on novel CARD14 variants seen in cases from Tunisia and other populations.


Why do worms need cholesterol?
Cholesterol is a structural component of animal membranes that influences fluidity, permeability and formation of lipid microdomains. It is also a precursor to signalling molecules, including mammalian steroid hormones and insect ecdysones. The nematode Caenorhabditis elegans requires too little cholesterol for it to have a major role in membrane structure. Instead, its most probable signalling functions are to control molting and induce a specialized non-feeding larval stage, although no cholesterol-derived signalling molecule has yet been identified for these or any other functions.


Video-assisted thoracoscopic lung biopsy in the diagnosis of interstitial lung disease: a prospective, multi-center study in 224 patients.
To evaluate whether the location and number of lung biopsies obtained by video-assisted thoracoscopy (VAT) influence the diagnosis of diffuse interstitial lung disease (ILD). To assess the applicability of an Ambulatory Surgery Program (ASP). Prospective, multicenter study of VAT lung biopsies due to suspected ILD from January 2007 to December 2009, including 224 patients from 13 Spanish centers (mean age 57.1 years; 52.6% females). Data were prospectively collected in every institution and sent to the coordination center for analysis. The most affected areas in high resolution chest CT were the lower lobes (55%). Bronchoscopy was performed in 84% and transbronchial biopsy in 49.1%. In 179 cases (79.9%), more than one biopsy was performed, with a diagnostic agreement of 97.2%. A definitive histopathologic diagnosis was obtained in 195 patients (87%). Idiopathic pulmonary fibrosis was the most frequent diagnosis (26%). There were no statistically significant factors that could predict a greater diagnostic yield (neither anatomical location nor number of biopsies). Seventy patients (31.3%) were included in an ASP. After discharge, there were complications in 12 patients (5.4%), similar between patients admitted postoperatively (9/154: 5.8%) and those included in an ASP (3/70: 4.3%). Anatomical location and number of lung biopsy specimens did not seem to influence the diagnosis. The patients included in an ASP had a complication rate comparable to that of the hospitalized, so this procedure can be included in a surgical outpatient program. Lung biopsy obtained by VAT is a powerful and safe tool for diagnosis of suspected ILD, resulting in a definitive diagnosis for the majority of patients with a low morbidity rate.


Identification of Metabolic Biomarkers Using Serial 18F-FDG PET/CT for Prediction of Recurrence in Advanced Epithelial Ovarian Cancer.
To evaluate the prognostic value of metabolic parameters derived from serial 18F fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with advanced epithelial ovarian cancer (EOC). Thirteen patients with advanced EOC who received surgical staging and adjuvant platinum-based combination chemotherapy were prospectively enrolled. 18F-FDG PET/CT was performed before and after the surgical staging, and after third cycle of chemotherapy. Tumor glucose metabolism at baseline and its change after operation and third cycle of chemotherapy such as changes of maximum standardized uptake values (ΔSUVmax) via 18F-FDG PET/CT were measured, and assessed regarding their ability to predict recurrence. Median duration of progression-free survival (PFS) was 25 months (range, 13-34), and although optimal debulking was performed in 10 patients, 5 (38.5%) patients experienced recurrence. Univariate analyses showed significant associations between recurrence and low ΔSUVmax after surgical staging, and low SUVmax change after third cycle of chemotherapy. Multivariate analysis identified low ΔSUVmax after third cycle of chemotherapy as an independent risk factor for recurrence (P=.047, hazard ratio (HR) 16.375, 95% CI 1.041-257.536). Kaplan-Meier survival curves showed that PFS significantly differed in groups categorized based on ΔSUVmax after chemotherapy (P=.001, log-rank test). 18F-FDG PET/CT allows for prediction of treatment response by the level of FDG uptake in terms of SUV at baseline and after chemotherapy. The metabolic response measured as ΔSUVmax after third cycle of chemotherapy appears to be promising predictor of recurrence in patients with advanced EOC.


A Hox Code Defines Spinocerebellar Neuron Subtype Regionalization.
Coordinated movement requires the integration of many sensory inputs including proprioception, the sense of relative body position and force associated with movement. Proprioceptive information is relayed to the cerebellum via spinocerebellar neurons, located in the spinal cord within a number of major neuronal columns or as various scattered populations. Despite the importance of proprioception to fluid movement, a molecular understanding of spinocerebellar relay interneurons is only beginning to be explored, with limited knowledge of molecular heterogeneity within and between columns. Using fluorescent reporter mice, neuronal tracing, and in situ hybridization, we identify widespread expression of Hox cluster genes within spinocerebellar neurons. We reveal a "Hox code" based on axial level and individual spinocerebellar column, which, at cervico-thoracic levels, is essential for subtype regionalization. Specifically, we show that Hoxc9 function is required in most, but not all, cells of the thoracic spinocerebellar column, Clarke's column, revealing heterogeneity reliant on Hox signatures.


Unitary acitvity of ventrolateral nucleus during placing movement and associated postural adjustment.
The activity of neurons in the ventrolateral nucleus of the thalamus (VL) was analyzed in the cat during placing movements of both the right and left forelimbs. The purpose was to determine if thalamic neuron discharge patterns could be related to movement and/or to postural changes. Placing tests were conducted on animals maintained in a standing position and partially restrained by a hammock. Each of the forelimbs rested on a flat surface containing a strain gauge which allowed the stance forces to be measured. Two mobile plates, one on the left and one on the right, were used to elicit a contact placing reaction. The response was composed of an isometric phase, during which the body weight was shifted from the stimulated limb to the opposite forelimb while the stimulated limb was gently pushed backwards, and a movement phase during which the stimulated paw actually accomplished the placing reaction. (1) About half the recorded neurons (47/86) in the VL region demonstrated a change in activity, generally an increase of discharge frequency, during placing of the right of left forelimb. (2) Almost all the reactive units (45/47) responded to contralateral placing. Two units changed their activity with ipsilateral placing only, whereas 18 units were active during placing of both forelimbs. The discharge pattern of cells activated during ipsilateral placing was considered as related to the isometric postural adjustment of the contralateral limbs. (3) Cells reactive during contralateral tests were located preferentially in the ventrolateral part of VL. Units reactive during ipsilateral tests (postural units) were also clustered in the ventrolateral half of VL which is the zone controlling limb musculature. Some of the 'postural units' were identified as receiving afferents from cerebellar nuclei and projecting to motor cortex. (4) Changes in discharge frequency were observed during either the isometric phase, the movement phase, or both. The same type of patterns were observed during contralateral and ipsilateral placing. About half of the cells responding during the contralateral placing movement did so throughout the entire duration of the movement, and were not specifically related to either the flexion or the extension phase of the placing. (5) The timing of the discharge of VL units with respect to the isometric phase and to the movement phase of the motor sequence varied from cell to cell. No topographic arrangement of neurons with the same pattern of discharge could be found within the nucleus.


Novel N-(4-Piperidinyl)benzamide antimalarials with mammalian protein farnesyltransferase inhibitory activity.
Protein farnesyltransferase of Plasmodium falciparum is a potential target in the treatment of malaria for which increased drug resistance is observed. The design, synthesis and evaluation of a series of N-(4-piperidinyl)benzamides is reported. The most potent compounds showed in vitro activity against the parasite at submicromolar concentrations.


Postoperative computed tomographic control of 38 patients with craniopharyngioma.
Computed tomography scanning was performed on 38 patients 1-12 years after surgery for craniopharyngioma. Recurrence of the tumor had appeared in nine patients. Thirteen patients had a residual tumor, and 16 were tumor-free after primary surgery. In addition, one patient became tumor-free after total removal of the recurrent tumor. After partial removal, the rate of recurrence was high and the quality of life was impaired.


Effect of self-efficacy and physical activity goal achievement on arthritis pain and quality of life in patients with rheumatoid arthritis.
To examine physical activity and achievement of physical activity goals in relation to self-reported pain and quality of life among patients with rheumatoid arthritis (RA). At baseline, 271 patients with RA were asked to specify a physical activity goal, and filled in questionnaires assessing physical activity, motivation, and self-efficacy for physical activity, arthritis pain, and quality of life. Six months later, patients indicated to what extent they had achieved their baseline physical activity goal and completed the same set of questionnaires. These data were used to construct multiple mediation models that placed physical activity and physical activity goal achievement as mediators between self-efficacy and motivation on one hand, and arthritis pain and quality of life on the other. A total of 106 patients with RA completed both questionnaires. Self-efficacy at baseline predicted subsequent level of physical activity and achievement of physical activity goals. Goal achievement had a direct effect upon quality of life outcomes. Bootstrapping confidence intervals revealed indirect effects of self-efficacy upon arthritis pain and quality of life through goal achievement, but not through physical activity. Higher levels of self-efficacy for physical activity increase the likelihood that patients will achieve their physical activity goals. Achievement of physical activity goals seems to be related to lower self-reported arthritis pain, and higher levels of quality of life. In practice, clinicians can foster self-efficacy and goal achievement by assisting patients in setting realistic and attainable exercise goals, developing action plans, and by providing feedback on goal progress.


Study finds risk of suicide higher for female nurses.
Female nurses have a higher risk of suicide compared with some other occupations, according to a new analysis.


Antibacterial Spiropyrimidinetriones with N-Linked Azole Substituents on a Benzisoxazole Scaffold Targeting DNA Gyrase.
Herein, we report spiropyrimidinetriones (SPTs) incorporating N-linked azole substituents on a benzisoxazole scaffold with improved Gram-positive antibacterial activity relative to previously described analogues. SPTs have an unusual spirocyclic architecture and represent a new antibacterial class of bacterial DNA gyrase and topoisomerase IV inhibitors. They are not cross-resistant to fluoroquinolones and other DNA gyrase/topoisomerase IV inhibitors used clinically. The activity of the SPTs was assessed for DNA gyrase inhibition, and the antibacterial activity across Gram-positive and Gram-negative pathogens with N-linked 1,2,4-triazoles substituted on the 5-position provides the most worthwhile profile. Directed nucleophilic and electrophilic chemistry was developed to vary this 5-position with carbon, nitrogen, or oxygen substituents and explore structure-activity relationships including those around a target binding model. Compounds with favorable pharmacokinetic parameters were identified, and two compounds demonstrated cidality in a mouse model of Staphylococcus aureus infection.


Lipid production by Yarrowia lipolytica growing on industrial glycerol in a single-stage continuous culture.
Yarrowia lipolytica LGAM S(7)1 presented remarkable growth on industrial glycerol used as sole carbon substrate. Nitrogen-limited flask cultures were accompanied by restricted synthesis of reserve lipid, whilst amounts of citric acid were produced extracellularly. On the contrary, high amounts of reserve lipid (up to 3.5 g/l, 43% w/w of lipids in dry biomass) were produced in highly aerated continuous cultures. Lipid production was favoured at low specific dilution rates whilst fat-free material yield increased over the whole range of D (h(-1)). The maximum volumetric productivity obtained was 0.12 g lipid/1 h. Storage lipid composition did not present remarkable changes in the specific dilution rates tested. Oleate and linoleate were the dominant cellular fatty acids.