Association of serum KL-6 levels on COVID-19 severity: A cross-sectional study design with purposive sampling.
The main target of SARS-CoV2 is the alveolar type II (AT2) cells of the lung. SARS-CoV2 evades the innate immune system resulting in the release of proinflammatory cytokines (IL-1β, IL-6, TNF-α) which causes AT2 cell damage. Krebs von den Lungen (KL-6) is a specific biomarker of AT2 cell damage. KL-6 is produced in AT2 cells that are injured/regenerated. Research that discusses the role of KL-6 in COVID-19 is still being debated and not much has been done in Indonesia. This study was an analytical study with a prospective design on 75 COVID-19 patients who were treated. Subjects were divided into two large groups according to their degree of severity, 57 subjects with severe degrees and 18 subjects with non-severe degrees. The serum KL-6 levels were measured on days 0 and 6. Data were analyzed using paired t-test and independent t-test for data were normally distributed and Wilcoxon test and Mann Whitney test for data that were not normally distributed. In this study, the mean serum KL-6 for day 0 in the severe group was higher than the non-severe group with values of 45.70 U/mL and 44.85 U/mL. On day 6, the mean serum KL-6 in the severe group was lower than that in the non-severe group with values of 41.3 U/mL and 41.95 U/mL. Serum KL-6 in the severe group experienced an even greater decrease than the non-severe group. There was no significant association between serum KL-6 values on 0 days in the severity of COVID-19.


An extended posterior approach to the hip and pelvis for complex acetabular reconstruction that preserves the gluteal muscles and their neurovascular supply.
We investigated the detailed anatomy of the gluteus maximus, gluteus medius and gluteus minimus and their neurovascular supply in 22 hips in 11 embalmed adult Caucasian human cadavers. This led to the development of a surgical technique for an extended posterior approach to the hip and pelvis that exposes the supra-acetabular ilium and preserves the glutei during revision hip surgery. Proximal to distal mobilisation of the gluteus medius from the posterior gluteal line permits exposure and mobilisation of the superior gluteal neurovascular bundle between the sciatic notch and the entrance to the gluteus medius, enabling a wider exposure of the supra-acetabular ilium. This technique was subsequently used in nine patients undergoing revision total hip replacement involving the reconstruction of nine Paprosky 3B acetabular defects, five of which had pelvic discontinuity. Intra-operative electromyography showed that the innervation of the gluteal muscles was not affected by surgery. Clinical follow-up demonstrated good hip abduction function in all patients. These results were compared with those of a matched cohort treated through a Kocher-Langenbeck approach. Our modified approach maximises the exposure of the ilium above the sciatic notch while protecting the gluteal muscles and their neurovascular bundle.


Neurophysiological and clinical aspects of glucocorticoids and memory: a review.
Neuropsychologists are increasingly involved in the assessment and treatment of individuals with glucocorticoid (GC) dysfunction. This review examines the clinical and neurophysiological changes associated with alterations in GC levels, with specific emphasis on changes in hippocampal plasticity and memory impairments. Hypothalamic-pituitary-adrenal (HPA) axis regulation of GC production and GC effects at hippocampal receptors are examined. GC-related changes in memory and hippocampal plasticity are considered in a wide array of populations, including animals, healthy adults, patients receiving exogenous GC treatments, and patients with neuropsychiatric disorders resulting in GC dysregulation. Hypotheses regarding GC-related memory changes are considered, with emphasis on hippocampal neurotoxicity and changes in excitatory amino acids, glucose metabolism and neurotrophic factors. These hypotheses are examined, with special attention given to inconsistencies and contradictions within this body of research. Finally, implications for neuropsychological evaluation and future research are presented.


FungiPAD: A Free Web Tool for Compound Property Evaluation and Fungicide-Likeness Analysis.
The increasing prevalence of fungal diseases, continual development of resistance, and stringent environmental regulations have revealed an urgent need to develop more selective, safer, resistance-breaking, and cost-effective fungicides. However, most new fungicidal lead compounds fail in their late stages of development as a result of poor solubility or permeability, meaning that they have suboptimal physicochemical properties. Hence, the exploration of advanced technologies for compound "fungicide-likeness" assessment might overcome these obstacles and bring more chemical entities to market. FungiPAD ( http://chemyang.ccnu.edu.cn/ccb/database/FungiPAD/ ) is a free platform employed to predict physicochemical properties, bioavailability, and fungicide-likeness swiftly and powerfully using comprehensive approaches, such as physicochemical radars and qualitative and quantitative analyses. This platform contains data for over 16 000 physicochemical descriptors and the results of 2200 qualitative and 1100 quantitative analyses of marketed fungicides and provides comprehensive fungicide-likeness analysis for different compounds. The user-friendly interface facilitates interpretation and manipulation by non-computational scientists in support of fungicide discovery.


[Diagnostic significance of pancreatic serum-enzyme patterns after stimulation with secretin in chronic pancreatitis (author's transl)].
The pancreatic serum evocation test with secretin has regained importance now that it is possible to determine immunoreactive trypsin and pancreatic isoamylase. After secretin stimulation there was a significant abnormal increase in serum trypsin (p less than 0.01) in 34 patients with proven chronic pancreatitis associated with mild to moderate dysfunction (groups I-II), no rise if there was marked insufficiency (group III). Patients with steatorrhoea and obstruction in the region of the head of the pancreas formed a special group because, contrary to other patients in groups III, they had marked serum enzyme rise after secretin. In 24 control subjects with a normal pancreas there was no significant change in basal pancreatic serum enzyme levels with secretin stimulation. Trypsin and amylase reaction patterns differed during secretin stimulation, with a rise in the amylase occurring at the expense of pancreas isoamylase.


The development of familial hypertrophic cardiomyopathy: from mutation to bedside.
Hypertrophic cardiomyopathy (HCM) is a familial disorder characterized by left ventricular hypertrophy in the absence of other cardiac or systemic disease likely to cause this hypertrophy. HCM is considered a disease of the sarcomere as most causal mutations are identified in genes encoding sarcomeric proteins, although several other disorders have also been linked to the HCM phenotype. The clinical course of HCM is characterized by a large inter- and intrafamilial variability, ranging from severe symptomatic HCM to asymptomatic individuals. The general picture emerges that the underlying pathophysiology of HCM is complex and still scarcely clarified. Recent findings indicated that both functional and morphological (macroscopic and microscopic) changes of the HCM muscle are present before the occurrence of HCM phenotype. This review aims to provide an overview of the myocardial alterations that occur during the gradual process of wall thickening in HCM on a myofilament level, as well as the structural and functional abnormalities that can be observed in genetically affected individuals prior to the development of HCM with state of the art imaging techniques, such as tissue Doppler echocardiography and cardiovascular magnetic resonance imaging. Additionally, present and future therapeutic options will be briefly discussed.


Multi-detector computed tomography in coronary artery bypass graft assessment: a meta-analysis.
Multi-detector computed tomography (MDCT) has become an alternative to coronary angiography in diagnosis of graft occlusion and stenosis after coronary artery bypass. A literature search was performed for studies comparing angiography to 8-slice, 16-slice, and 64-slice MDCT in the assessment of coronary grafts. In assessing occlusion, 14 studies produced pooled sensitivity of 97.6%, specificity of 98.5%, diagnostic odds ratio of 934.2, area under the curve of 0.996, and Q* of 0.977. Ninety-six percent of all grafts were visualized for occlusion assessment. Beta blockers, symptomatic status, and postoperative period did not significantly affect diagnostic performance. Stenosis assessment produced sensitivity of 88.7% and specificity of 97.4%. Eighty-eight percent of patent grafts could be assessed for stenosis. The diagnostic accuracy of MDCT approaches angiography for diagnosing graft occlusion and stenosis in patients with venous and arterial coronary bypass grafts. Our findings show that cardiac surgeons will need to interpret MDCT images of both native and grafted vessels soon in preparation for primary or re-do coronary bypass grafting procedures.


A morphological mutant of Paracoccidioides brasiliensis strain IVIC Pb9. Isolation and wall characterization.
A morphological mutant of Paracoccidioides brasiliensis strain IVIC Pb9 was isolated after treatment of the yeast-like (Y) form with nitrosoguanidine. Colonies of the mutant grown at room temperature did not show the whitish cotton-like morphology typical of the mycelial form of the parental strain. Y-cells were much smaller than those produced by the parent and grew forming chains of different sizes. The main chemical difference in the wall of the Y-form was the replacement of the alpha-I,3-glucan, typical of the parental strain, by an amorphous I,3-mannan in the mutant.


Biotransformation of hop-derived monoterpene alcohols by lager yeast and their contribution to the flavor of hopped beer.
It is well-known that various beers contain many flavor compounds derived from barley malts, hops, yeast fermentation, and other raw materials. Among these flavor compounds, terpenoids are mainly derived from hops. Linalool, one of the monoterpene alcohols, has been found in various beers and been regarded as an important factor for a hop-derived beer flavor. We focus on contributions of other monoterpene alcohols (geraniol, beta-citronellol, nerol, and alpha-terpineol) to hopped beer flavor. Several researchers have reported that monoterpene alcohols are biotransformed by yeast and that geraniol is mainly transformed to beta-citronellol during the first 2-4 days in model fermentation. In this study, we investigated the biotransformation of monoterpene alcohols during fermentation of hopped beer by using various hop cultivars. As a result, geraniol drastically decreased during the first 3 days. beta-Citronellol was almost absent in wort and gently increased during the total fermentation period. The concentrations of geraniol and beta-citronellol in finished beer increased, depending on the initial concentration of geraniol in the wort. The continuous increase of beta-citronellol did not correspond to the fast decrease of geraniol. This increase of beta-citronellol might be partly explained by an occurrence of glycosidically bound flavor precursor and a glucoside hydrolase activity secreted from lager yeast. In addition, we examined flavor characteristics of monoterpene alcohols and found that there was an additive effect among linalool, geraniol, and beta-citronellol and that only 5 microg/L of geraniol and beta-citronellol were enough for this effect. Therefore, it is suggested that not only linalool but also geraniol and beta-citronellol might contribute to hopped beer flavor at lower levels, at which OAVs of these compounds become below 1.0.


Endocrine actions of interferon-tau in ruminants.
The ovine conceptus releases interferon-tau (IFNT), which prevents upregulation of the endometrial estrogen receptor (ESR1) and, consequently, oxytocin receptor (OXTR), thereby disrupting pulsatile release of prostaglandin F2alpha (PGF) in response to oxytocin. IFNT, through paracrine action on the endometrium, protects the corpus luteum (CL) during maternal recognition of pregnancy. Pregnancy also induces IFN stimulated genes (ISGs) in peripheral blood mononuclear cells (PBMCs), which is interpreted to reflect a "prompted" antiviral and immune cell response peripherally in ruminants. IFNT was recently demonstrated to be released from the uterus in amounts of 200 microg (2 x 10(7) U)/24 h via the uterine vein and to induce ISGs in the CL during maternal recognition of pregnancy. Delivery of recombinant ovine (ro) IFNT into the uterine vein in a location that is upstream of the utero-ovarian plexus from Day 10 to 17 maintained serum progesterone concentrations and extended normal 16-17 d estrous cycles to beyond 32 d. It is concluded from these studies that IFNT is released into the uterine vein and initiates a peripheral antiviral response to protect pregnancy from maternal viral infection. It also may have endocrine action through inducing luteal resistance to PGF and longer-term survival of the CL and maintenance of pregnancy.


Prenatal diagnosis of thanatophoric dysplasia at 24 weeks.
We report making the prenatal diagnosis of thanatophoric dysplasia at 24 weeks gestation. The ultrasound examination showed short limbs. By in utero radiological study, we could see the typical changes of this skeletal dysplasia. Radiological and histological studies confirmed the aborted fetus to be affected with thanatophoric dysplasia.


Career Adaptability: An Innovative Measurement to Aid Professional Development of New Graduate Nurses.
This cross-sectional quantitative study explored career adaptability and career intentions in newly licensed nurses working in acute care hospitals throughout North Carolina. Data were analyzed from 277 registered nurses completing an online study instrument. Findings demonstrate a relationship between levels of career adaptability and career intentions, offering career adaptability as a new measurement to explore newly licensed nurses' desire to pursue career and educational change and expand transition programs to include developing career trajectories within organizations.


Longitudinal Postoperative Course of Pain and Dysfunction Following Total Knee Arthroplasty.
Although the majority of patients undergoing total knee arthroplasty (TKA) report substantial improvement in pain and function, a significant subset experience persistent postsurgical pain and dysfunction. Better understanding of the longitudinal postoperative course is needed, including the association between patient status following physical rehabilitation at 6-weeks post-TKA, to 6-months outcomes. This study aims to described the postoperative course of TKA and examine variables associated with change in pain and functioning between 6-weeks and 6-months post-TKA. In this longitudinal study of 223 participants, assessments of analgesic intake, depression, anxiety, pain catastrophizing, dysfunction, resting and range of motion pain, and pain sensitivity were completed at 6-weeks post-TKA. Analgesic intake, pain ratings, and dysfunction data were also collected at 6-months post-TKA. Pain and dysfunction ratings were divided into none-mild and moderate-severe categories. Between 6-weeks and 6-months post-TKA, 75% of the sample stayed in the same pain category, 20% improved, and 5% worsened. In terms of functional changes between 6 weeks and 6 months, 65% of the sample stayed in the same functional category, whereas 31% improved and 5% worsened. These findings demonstrate that the majority of patients' pain and functioning remains stable between 6 weeks and 6 months post-TKA. However, a notable subset continues to improve or worsen in pain and functioning and the current study identifies variables associated with these changes.


Hypoxia in CNS Pathologies: Emerging Role of miRNA-Based Neurotherapeutics and Yoga Based Alternative Therapies.
Cellular respiration is a vital process for the existence of life. Any condition that results in deprivation of oxygen (also termed as hypoxia) may eventually lead to deleterious effects on the functioning of tissues. Brain being the highest consumer of oxygen is prone to increased risk of hypoxia-induced neurological insults. This in turn has been associated with many diseases of central nervous system (CNS) such as stroke, Alzheimer's, encephalopathy etc. Although several studies have investigated the pathophysiological mechanisms underlying ischemic/hypoxic CNS diseases, the knowledge about protective therapeutic strategies to ameliorate the affected neuronal cells is meager. This has augmented the need to improve our understanding of the hypoxic and ischemic events occurring in the brain and identify novel and alternate treatment modalities for such insults. MicroRNA (miRNAs), small non-coding RNA molecules, have recently emerged as potential neuroprotective agents as well as targets, under hypoxic conditions. These 18-22 nucleotide long RNA molecules are profusely present in brain and other organs and function as gene regulators by cleaving and silencing the gene expression. In brain, these are known to be involved in neuronal differentiation and plasticity. Therefore, targeting miRNA expression represents a novel therapeutic approach to intercede against hypoxic and ischemic brain injury. In the first part of this review, we will discuss the neurophysiological changes caused as a result of hypoxia, followed by the contribution of hypoxia in the neurodegenerative diseases. Secondly, we will provide recent updates and insights into the roles of miRNA in the regulation of genes in oxygen and glucose deprived brain in association with circadian rhythms and how these can be targeted as neuroprotective agents for CNS injuries. Finally, we will emphasize on alternate breathing or yogic interventions to overcome the hypoxia associated anomalies that could ultimately lead to improvement in cerebral perfusion.


B-Cell Lymphoma Presenting with Extensive Cutaneous Involvement.
Cutaneous lymphomas tend to be of T-cell origin, less commonly of B-cell origin. We report a 68-year-old male patient suffering from extensive cutaneous nodules which were found to be B-cell large cell lymphoma in nature. Our case is a good example to unexpected cutaneous involvement of diffuse large cell lymphomas. It may be debated whether it is a primary cutaneous lymphoma or cutaneous involvement of a systemic lymphoma. The case differs from other primary cutaneous lymphomas in the clinical course and in the pathologic and immunohistochemical features. Systemic B-cell lymphomas may also involve the skin. We think that our case demands attention because systemic B-cell lymphomas with such a great skin involvement is not reported in the literature before.


Critical and strong-coupling phases in one- and two-bath spin-boson models.
For phase transitions in dissipative quantum impurity models, the existence of a quantum-to-classical correspondence has been discussed extensively. We introduce a variational matrix product state approach involving an optimized boson basis, rendering possible high-accuracy numerical studies across the entire phase diagram. For the sub-Ohmic spin-boson model with a power-law bath spectrum ∝ω(s), we confirm classical mean-field behavior for s<1/2, correcting earlier numerical renormalization-group results. We also provide the first results for an XY-symmetric model of a spin coupled to two competing bosonic baths, where we find a rich phase diagram, including both critical and strong-coupling phases for s<1, different from that of classical spin chains. This illustrates that symmetries are decisive for whether or not a quantum-to-classical correspondence exists.


Antigen-specific polyclonal cytotoxic T lymphocytes induced by fusions of dendritic cells and tumor cells.
The aim of cancer vaccines is induction of tumor-specific cytotoxic T lymphocytes (CTLs) that can reduce the tumor mass. Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Thus, DCs-based vaccination represents a potentially powerful strategy for induction of antigen-specific CTLs. Fusions of DCs and whole tumor cells represent an alternative approach to deliver, process, and subsequently present a broad spectrum of antigens, including those known and unidentified, in the context of costimulatory molecules. Once DCs/tumor fusions have been infused back into patient, they migrate to secondary lymphoid organs, where the generation of antigen-specific polyclonal CTL responses occurs. We will discuss perspectives for future development of DCs/tumor fusions for CTL induction.


Progressive Support for Activities of Daily Living for Persons Living With Dementia.
Dementia is accompanied by increasing need for support in activities of daily living (ADLs). This brief report/literature review summarizes the practices to care for early stage, middle stage, and late stage ADL needs (dressing, toileting, and eating/nutrition), and examines commonalities across ADL needs and the extent to which practices are reflected in guidelines and/or evidence. A review of the grey and peer-reviewed literature, using some but not all procedures of a systematic review. Key terms were identified for ADLs overall and for each of the 3 ADLs, and a search was conducted using these words in combination with (a) dementia, Alzheimer's disease, and similar terms, and (b) practices, interventions, guidelines, recommendations, and similar terms. Searches were conducted using databases of peer-reviewed literature as well as the Grey Literature Reports and Google search engine. Sources were included if they provided evidence or recommendations on interventions to address ADL functioning for dressing, toileting, and feeding for persons living with dementia. As cognitive and functional impairment increases, the number of care practices and themes that embody care practices increases. The majority of practices are evidence-based, and most evidence is incorporated into guidelines. Virtually all practices reflect person-centered care principles. Five recommendations summarize the evidence and recommendations related to providing support to persons living with dementia in relation to dressing, toileting, and eating/nutrition.


Preparation of a CeO2 ball-core structure and its application in quantum dot sensitized solar cells.
A pomegranate-like nanosphere structure of CeO2 was prepared by a simple one-step hydrothermal method, and the novel CeO2 structure was printed on a TiO2 film to form a scattering layer, which constituted the composite structure of a photoanode in a thin film optoelectronic device. Then ZnCuInSe quantum dots, a ZnS passivation layer and a CuS counter electrode were prepared, and these parts were assembled into quantum dot-sensitized solar cells. By changing the thickness of the scattering layer film in the photoanode, the quantum dots were adsorbed on TiO2 more effectively. By using the special ball-core structure, light was scattered so that the photoanode used the light many times, which effectively increased the efficiency of photoelectron production. After electrochemical testing of the device, it was found that the photoconversion efficiencies of the TiO2 transparent layer and the CeO2 scattering layer composite photoanode were greater than that of a single TiO2 photoanode without a scattering layer. The results showed that when the thickness of the scattered layer was 10 ± 1 μm, the highest photoelectric conversion efficiency (PCE) was obtained, which was 20% higher than that seen with TiO2 alone.


[Clinical application of full age spectrum formula based on serum creatinine in patients with chronic kidney disease].
To compare the estimated glomerular filtration rates (eGFR) by five formulas based on serum creatinine (SCr), and to explore the diagnostic efficacy of full age spectrum (FAS) equation based on SCr for renal insufficiency in patients with chronic kidney disease (CKD). 2 219 patients with CKD admitted to department of nephrology of Guangdong Provincial Second People's Hospital from December 2015 to January 2018 were enrolled. According to the diagnostic criteria of kidney disease outcomes quality initiative (K/DOQI), patients were divided into CKD 1-5 stages. In all patients, Tc-GFR was measured by clearance rate of 99mTc-diethylene triaminepen taacetic acid (99mTc-DTPA) within 1 month, and SCr was determined. The eGFR was calculated by Cockcrofi-Gault (C-G) formula bases on SCr, Chinese modified modification of diet in renal disease (cMDRD) equation, Chronic Kidney Disease Epidemiology Collaboration Group (CKD-EPI) equation, measure and calculation (MC) equation and FAS equation, respectively, and body surface area (BSA) was used for correction of eGFR. The differences of Tc-GFR and eGFR calculated by different formulas were compared, and the correlations between eGFR calculated by different formulas and Tc-GFR were analyzed by Spearman correlation analysis. Tc-GFR was used as a reference standard to evaluate the bias, precision and accuracy of eGFR formulas, and the receiver operating characteristics (ROC) curve of each eGFR formula was plotted to evaluate its diagnostic efficacy for renal insufficiency in patients with CKD. According to the inclusion and exclusion criteria, 382 patients with CKD were enrolled in the final analysis. There were 31, 69, 92, 75 and 115 patients with CKD 1-5 stages, respectively. In all patients, the differences between Tc-GFR and eGFR calculated by different formulas were statistically significant, and eGFR was positively correlated with Tc-GFR. The best correlation coefficient was between eGFR of cMDRD formula and Tc-GFR (r = 0.883, P = 0.000), and the lowest was of MC formula (r = 0.848, P = 0.000). The best correlation between the eGFR calculated by FAS formula and the Tc-GFR was in CKD 2 stage (r = 0.538, P = 0.000), and the lowest correlation was found in CKD 5 stage (r = 0.229, P = 0.014). Compared with Tc-GFR (the reference equation), the FAS formula showed the smallest bias [the difference between Tc-GFR and eGFR = 8.64, 95% confidence interval (95%CI) = 7.04-10.19], and the best accuracy [the percentage of eGFR falling into the range of Tc-GFR ±30% (P30) = 42.67%, 95%CI = 37.69-47.65]; CKD-EPI equation showed the best precision (QR of the difference between Tc-GFR and eGFR = 17.43, 95%CI = 15.33-21.28). ROC curve analysis showed that the area under the curve (AUC) of cMDRD formula was the largest (0.944), and the specificity was the highest (87.23%); the sensitivity of CKD-EPI formula was the highest (94.00%); and the AUC of MC formula was the smallest (0.918). The AUC of FAS formula was 0.940 (95%CI = 0.917-0.964, P = 0.000), it was higher than that of MC formula, but there was no significant difference between FAS formula and other formulas. When the cut-off value of eGFR calculated by FAS formula was 32.62 mL×min-1×1.73 m-2, the sensitivity, specificity, positive predictive value, negative predictive value was 93.00%, 81.56%, 83.64%, 11.54%, respectively. Compared with C-G formula, cMDRD formula, CKD-EPI formula and MC formula, FAS formula showed smaller bias and higher accuracy, and had higher specificity and sensitivity in the diagnosis of renal insufficiency in patients with CKD, which could be applied to the determination of GFR in early stage of CKD. Chinese Clinical Trial Registry, ChiCTR1800017727.


Functional identification of the cDNA coding for a wheat endo-1,4-beta-D-xylanase inhibitor.
Using expressed sequence tag data, we obtained a full-length cDNA encoding a wheat protein inhibitor of xylanases (XIP-I). The 822 bp open reading frame encoded a protein of 274 amino acids with a molecular mass of 30.2 kDa, in excellent agreement with the native protein. Expression in Escherichia coli confirmed that the cDNA encoded a functional endo-1,4-beta-D-xylanase inhibitor. Its deduced amino acid sequence exhibited highest similarity to sequences classified as class III chitinases, but the inhibitor did not exhibit chitinase activity. This is the first full-length cDNA sequence that encodes a novel class of protein which inhibits the activity of endo-1,4-beta-D-xylanases.


A case of pancreatic intraepithelial neoplasia-3 with autoimmune pancreatitis.
We report a case of pancreatic intraepithelial neoplasia-3 (PanIN-3) with autoimmune pancreatitis (AIP). The patient, a 75-year-old man, had been diagnosed to have AIP with stenosis of the main pancreatic duct. After six years, computed tomography demonstrated dilatation of the main pancreatic duct in the mid-pancreas. Although we could not confirm the presence of any pancreatic tumor on the basis of imaging modalities alone, cytological examination of the pancreatic juice obtained by endoscopic retrograde pancreatography revealed atypical cells. Therefore, we performed pancreatoduodenectomy and obtained a pathologic diagnosis of PanIN-3 with AIP. The present case is informative in the context of pancreatic carcinogenesis in AIP.


Psychological controversies in gastroparesis: A systematic review.
To systematically review literature addressing three key psychologically-oriented controversies associated with gastroparesis. A comprehensive search of PubMed, CINAHL, and PsycINFO databases was performed to identify literature addressing the relationship between gastroparesis and psychological factors. Two researchers independently screened all references. Inclusion criteria were: an adult sample of gastroparesis patients, a quantitative methodology, and at least one of the following: (1) evaluation of the prevalence of psychopathology; (2) an outcome measure of anxiety, depression, or quality of life; and (3) evidence of a psychological intervention. Case studies, review articles, and publications in languages other than English were excluded from the current review. Prevalence of psychopathology was evaluated by three studies (n = 378), which found that combined anxiety/depression was present in 24% of the gastroparesis cohort, severe anxiety in 12.4%, depression in 21.8%-23%, and somatization in 50%. Level of anxiety and depression was included as an outcome measure in six studies (n = 1408), and while limited research made it difficult to determine the level of anxiety and depression in the cohort, a clear positive relationship with gastroparesis symptom severity was evident. Quality of life was included as an outcome measure in 11 studies (n = 2076), with gastroparesis patients reporting lower quality of life than population norms, and a negative relationship between quality of life and symptom severity. One study assessed the use of a psychological intervention for gastroparesis patients (n = 120) and found that depression and gastric function were improved in patients who received psychological intervention, however the study had considerable methodological limitations. Gastroparesis is associated with significant psychological distress and poor quality of life. Recommendations for future studies and the development of psychological interventions are provided.


Traditional health beliefs and practices among lower class black Americans.
The medical belief system of lower class black Americans reflects their social, political and economic marginality in the larger society. A moderate life-style is regarded as the basis for good health with special emphasis on protecting one's body from cold, keeping it clean inside and out and maintaining a proper diet. Illnesses and other life events are classified as "natural" or "unnatural." Natural illnesses result from the effects of cold, dirt and improper diet on the body causing changes in the blood. A number of beliefs about blood and its functions have important clinical implications for the treatment of hypertension and venereal disease and for family planning. Natural illnesses also result from divine punishment and serve as an instrument of social control. Unnatural illnesses are the result of witchcraft and reflect conflict in the social network. It is believed that physicians do not understand and cannot effectively treat such illnesses, but a variety of traditional healers offer help to the victims. Physicians must elicit such beliefs if they are to interact effectively and sensitively with black patients. Social change is required, however, to eliminate the feelings of powerlessness at the root of many of the health problems of poor black Americans.


Cancer Stem Cell Markers for Urinary Carcinoma.
Cancer stem cell (CSC) refers to cancer cells with stem cell properties, that is, they have the ability of "self-renewal" and "differentiation." Cancer stem cells exist in cancer cells and are the "culprit" of cancer recurrence and metastasis. It is difficult to be found because of its small amount, and it is difficult for anticancer drugs to produce effects on it. At present, the isolation and identification of cancer stem cells from many solid tumors are still quite difficult, mainly due to the lack of specific molecular markers of cancer stem cells. In this review, cancer stem cell surface markers and functional markers in urinary system were summarized. These markers can provide molecular targets for cancer therapy.


Soft-Computing-Based Estimation of a Static Load for an Overhead Crane.
Payload weight detection plays an important role in condition monitoring and automation of cranes. Crane cells and scales are commonly used in industrial practice; however, when their installation to the hoisting equipment is not possible or costly, an alternative solution is to derive information about the load weight indirectly from other sensors. In this paper, a static payload weight is estimated based on the local strain of a crane's girder and the current position of the trolley. Soft-computing-based techniques are used to derive a nonlinear input-output relationship between the measured signals and the estimated payload mass. Data-driven identification is performed using a novel variant of genetic programming named grammar-guided genetic programming with sparse regression, multi-gene genetic programming, and subtractive fuzzy clustering method combined with the least squares algorithm on experimental data obtained from a laboratory overhead crane. A comparative analysis of the methods showed that multi-gene genetic programming and grammar-guided genetic programming with sparse regression performed similarly in terms of accuracy and both performed better than subtractive fuzzy clustering. The novel approach was able to find a more parsimonious model with its direct implantation having a lower execution time.


[Lope de Vegas comedy "Los locos de Valencia" a view of a 16th century psychiatric institution].
With the comedy "Los locos de Valencia" (The Insane of Valencia) Lope de Vega left us valuable evidence of the nursing of the insane in the 16th century. After a summarizing presentation of the intricate plot of the play the manifold details about admission, general treatment of the mentally ill as well as the habits in the oldest psychiatric institution of the world are communicated and analysed by means of citations form comedy. Furthermore, an attempt is being made to demonstrate the nosolgic understanding of the Humanist and non-physician Lope de Vega for the psychiatric conditions and way of living from the same source.


[Thrombocytopenia in hepatitis-B-antigenemia (author's transl)].
Determination of hepatitis-B-antigen and thrombocytes in 1488 cases of liver diseases, 173 of whom had been treated with immunsuppressive drugs. There was no significant relation between hepatitis-B-antigenemia and thrombocyte-count, nor could an influence of the immunsuppressive therapy be evaluated. The thrombocyte-count was correlated with high significance only to the degree of the liver injury.


Wedge reversion antisymmetry and 41 types of physical quantities in arbitrary dimensions.
It is shown that there are 41 types of multivectors representing physical quantities in non-relativistic physics in arbitrary dimensions within the formalism of Clifford algebra. The classification is based on the action of three symmetry operations on a general multivector: spatial inversion, 1, time-reversal, 1', and a third that is introduced here, namely wedge reversion, 1†. It is shown that the traits of `axiality' and `chirality' are not good bases for extending the classification of multivectors into arbitrary dimensions, and that introducing 1† would allow for such a classification. Since physical properties are typically expressed as tensors, and tensors can be expressed as multivectors, this classification also indirectly classifies tensors. Examples of these multivector types from non-relativistic physics are presented.


Regulatory cross-talk determines the cellular levels of 53BP1 protein, a critical factor in DNA repair.
DNA double strand breaks (DSBs) severely disrupt DNA integrity. 53BP1 plays critical roles in determining DSB repair. Whereas the recruitment of 53BP1 to the DSB site is key for its function, recent evidence suggests that 53BP1's abundance also plays an important role in DSB repair because recruitment to damage sites will be influenced by protein availability. Initial evidence has pointed to three proteins, the ubiquitin-conjugating enzyme UbcH7, the cysteine protease cathepsin L (CTSL), and the nuclear structure protein lamin A/C, that may impact 53BP1 levels, but the roles of each protein and any interplay between them were unclear. Here we report that UbcH7-dependent degradation plays a major role in controlling 53BP1 levels both under normal growth conditions and during DNA damage. CTSL influenced 53BP1 degradation during DNA damage while having little effect under normal growth conditions. Interestingly, both the protein and the mRNA levels of CTSL were reduced in UbcH7-depleted cells. Lamin A/C interacted with 53BP1 under normal conditions. DNA damage disrupted the lamin A/C-53BP1 interaction, which preceded the degradation of 53BP1 in soluble, but not chromatin-enriched, cellular fractions. Inhibition of 53BP1 degradation by a proteasome inhibitor or by UbcH7 depletion restored the 53BP1-lamin A/C interaction. Depletion of lamin A/C, but not CTSL, caused a similar enhancement in cell sensitivity to DNA damage as UbcH7 depletion. These data suggest that multiple pathways collectively fine-tune the cellular levels of 53BP1 protein to ensure proper DSB repair and cell survival.


Mixed Method Study to Investigate Models of Australian Integrative Oncology.
This study explored the models of services and experiences of coordinators and directors engaged in providing complementary and alternative medicine (CAM) or integrative medicine (IM) in oncology centers throughout Australia. Fourteen leaders of IM programs from ten systematically selected Australian oncology centers were interviewed. Participants described their center's service model. Interview transcripts were thematically analyzed to identify underlying themes. Results were merged using the matrix technique for triangulation. Ten oncology centers were reviewed. IM was perceived in the context of supportive care and wellness. IM program types provided included the following: body-mind programs (56%); body-energy programs (23%), and body programs (21%). All programs were outpatient focused, generally did not require a doctors' referral, were freely accessible to cancer patients and carers at no or minimal cost, were centralized by coordinators, and involved volunteers, nurses, allied health practitioners, third parties, and patients in their treatment planning. Interaction between medical and CAM/IM teams was limited and tended to be informal. The underlying structure comprised four main themes: cultural context, human components, systematic components, and resource availability. Human components and resources were considered important in influencing cultural context and systematic components in the IM structure. Australian integrative oncology models are based on the concept of wellness and individualized care, focused on patient empowerment and engagement. IM models are generally independent of conventional medical care. Building relationships and trust between stakeholders and open collaboration with conventional medical care will be important to integrate IM into the hospital system. Systemic changes to deliver patient centered care in the provision of IM healthcare will facilitate the incorporation of CAM and IM into cancer services in hospital settings.


Conversion of naive T cells to a memory-like phenotype in lymphopenic hosts is not related to a homeostatic mechanism that fills the peripheral naive T cell pool.
To examine directly whether a limited number of naive T cells transferred to lymphopenic hosts can truly fill the peripheral naive T cell pool, we compared the expansion and phenotype of naive T cells transferred to three different hosts, namely recombination-activating gene-deficient mice, CD3epsilon-deficient mice, and irradiated normal mice. In all three recipients, the absolute number of recovered cells was much smaller than in normal mice. In addition, transferred naive T cells acquired a memory-like phenotype that remained stable with time. Finally, injected cells were rapidly replaced by host thymic migrants in irradiated normal mice. Only continuous output of naive T cells by the thymus can generate a full compartment of truly naive T cells. Thus, conversion of naive T cells to a memory-like phenotype in lymphopenic hosts is not related to a homeostatic mechanism that fills the peripheral naive T cell pool.


Protection, Prevention or Punishment? A Cross-Jurisdictional Analysis of Regulatory Immediate Action against Medical Practitioners.
Medical regulators protect the public from unsafe, unwell, or unscrupulous medical practitioners. To facilitate a swift response to serious allegations, many regulators are equipped with far-reaching emergency powers to immediately suspend, or impose conditions on, medical practitioners' registration before facts are proven. Failing to take urgent action may expose the public to ongoing avoidable harm and may erode public trust in the profession. Equally, imposing immediate action in response to allegations that are not subsequently proven can precipitously and irreparably injure a practitioner's career and emotional wellbeing. This is the second of two articles published in the Journal of Law and Medicine that explores the emerging jurisprudence in relation to these emergency regulatory powers. This article compares the approaches to immediate action in seven countries, providing insights for policy-makers and decision-makers into how modern regulatory frameworks attempt to balance the inherent tensions between the profession, the public and the State.


The contribution of mortality statistics to the study of multiple sclerosis in Australia.
Mortality statistics provided a valuable source of support for data obtained from prevalence surveys of multiple sclerosis in Australia. Firstly, multiple sclerosis mortality data for the decade 1971-80 in the States of Australia confirmed the relationship between increasing disease frequency and increasing south latitude shown by State and regional point prevalence surveys based on the national census day 30 June 1981. Secondly, a comparison with mortality data from the decade 1950-59 showed that in most States there had been a substantial fall in multiple sclerosis mortality in the more recent decade and this was clearly an important contributing factor to the rise in prevalence noted between the morbidity surveys of 1961 and 1981. Thirdly, multiple sclerosis mortality in the UK-born migrant population dying in Australia was found to be similar to that of the Australian-born population and very much lower than that found in the UK. This observation corroborated evidence from the 1981 morbidity surveys and suggested that migration from the UK to Australia may lower the risk of developing multiple sclerosis either through a reduction in disease incidence or the operation of environmental factors curbing disease expression.


Subarachnoid hemorrhage due to septic embolic infarction in infective endocarditis.
During antibiotic therapy, a 56-year-old man with a Streptococcus bovis endocarditis developed an infarction of the right middle cerebral artery (MCA). Thirty hours after stroke onset, cranial computed tomography controls demonstrated a secondary subarachnoid hemorrhage, marked in the cistern of the right MCA. The latent period, cerebrospinal fluid analysis, angiographic and pathologic findings favor the assumption of a pyogenic arterial wall necrosis of the MCA due to a septic embolus. This pathomechanism of intracranial hemorrhage in infective endocarditis should be distinguished from a rupture of a mycotic aneurysm.


Improved Transistor Performance by Modulating Molecular Packing with Donor and Acceptor Moieties.
The joint of the donor and acceptor moieties allows a facile and effective strategy to develop novel organic conjugated materials. However, few pieces of work report the understanding of the donor-acceptor interactions at the molecular level. Herein, we developed three small molecules containing one acceptor motif with different amounts of the donor unit. By combining theoretical calculations and energy level characterization, the lowest unoccupied molecular orbital (LUMO) levels of the three molecules were proven to be almost identical. The molecular packing modes were evaluated from crystal structure prediction. Owing to the donor-acceptor interactions, the packing mode can be tuned from a 1D slipped stacking to a 2D brick layer. The 2D molecular packing and charge transport channel endowed the materials a higher electron mobility of 3.29 cm2 V-1 s-1 in the single-crystal field-effect transistors after such modulation.


Phytoplasma SAP11 alters 3-isobutyl-2-methoxypyrazine biosynthesis in Nicotiana benthamiana by suppressing NbOMT1.
Phytoplasmas are bacterial phytopathogens that release virulence effectors into sieve cells and act systemically to affect the physiological and morphological state of host plants to promote successful pathogenesis. We show here that transgenic Nicotiana benthamiana lines expressing the secreted effector SAP11 from Candidatus Phytoplasma mali exhibit an altered aroma phenotype. This phenomenon is correlated with defects in the development of glandular trichomes and the biosynthesis of 3-isobutyl-2-methoxypyrazine (IBMP). IBMP is a volatile organic compound (VOC) synthesized by an O-methyltransferase, via a methylation step, from a non-volatile precursor, 3-isobutyl-2-hydroxypyrazine (IBHP). Based on comparative and functional genomics analyses, NbOMT1, which encodes an O-methyltransferase, was found to be highly suppressed in SAP11-transgenic plants. We further silenced NbOMT1 through virus-induced gene silencing and demonstrated that this enzyme influenced the accumulation of IBMP in N. benthamiana In vitro biochemical analyses also showed that NbOMT1 can catalyse IBHP O-methylation in the presence of S-adenosyl-L-methionine. Our study suggests that the phytoplasma effector SAP11 has the ability to modulate host VOC emissions. In addition, we also demonstrated that SAP11 destabilized TCP transcription factors and suppressed jasmonic acid responses in N. benthamiana These findings provide valuable insights into understanding how phytoplasma effectors influence plant volatiles.


Physiotherapy after thumb extensor tendon repair in Verdan zone III. Case study.
Finger tendon injuries represent very common consequences of hand injuries and, if not properly treated, can lead to substantial hand function impairment and interfere with activities of daily living. This article presents the results of rehabilitation of a female patient after thumb extensor tendon injury in Verdan's zone III. Based on standard diagnostic work-up (assessment of the active range of motion), we calculated the degree of functional hand function impairment according to Swanson's method. The diagnostic procedures also comprised measurements of dynamometric grip strength and precise grasp. The examinations were performed on four occasions, the first one during the first visit, and the last one a month after completion of the rehabilitation treatment in our Centre. Test results were used to design the treatment programme, which included among others the author's modification of Kleinert's dynamic reverse thumb splinting, peg-board exercises, physical therapy, individual therapy and home-based exercises. 1. The modified dynamic splint of our design fulfilled its task as both a preventive and therapeutic measure. 2. The dynamic splinting programme administered enabled early initiation of post-operative rehabilitation, which led to a very high degree of recovery of thumb and hand function. 3. The functional recovery outcomes achieved by our patient indicate the advisability of routine incorporation of full dynamic splinting in post-operative rehabilitation programmes of patients with thumb extensor tendon injuries.


Structure--function studies of the recombinant protein bioemulsifier AlnA.
Acinetobacter radioresistens KA53 produces an extracellular bioemulsifier, referred to as alasan. The surface active component of alasan is a 35.77 kDa protein AlnA. Although AlnA and the Escherichia coli outer membrane protein A (OmpA) have a high amino acid sequence homology, E. coli OmpA has no emulsifying activity. Comparison of the amino acid sequences of AlnA and E. coli OmpA revealed four hydrophobic regions in AlnA that were absent in E. coli OmpA. Deletions and substitutions (with the homologous OmpA sequence) were constructed in each of the four hydrophobic regions of AlnA by site-directed polymerase chain reaction (PCR) mutagenesis, using the overlap PCR method. Analysis of the emulsifying activities of the mutated AlnA molecules demonstrated that all four hydrophobic regions were necessary for emulsifying activity. However, most of the inactive mutated proteins still adhered avidly to hexadecane. These findings indicate that in addition to binding to hydrocarbons, the protein emulsifier must form a specific structure on the surface of the hydrocarbon that prevents coalescence of oil droplets. This is the first structure-function study of a protein bioemulsifer.


Insomnia in primary care: Considerations for screening, assessment, and management.
Insomnia, including insomnia disorder, is a common but often overlooked complaint in primary care settings. It is a risk factor for various medical and psychiatric diagnoses and is associated with substantial health care costs. While cognitive behavioral therapy for insomnia (CBT-I) is the first-line treatment for insomnia disorder, access to CBT-I is limited. This article provides a pragmatic approach to screening, assessment, and treatment of insomnia in the primary care setting, promoting a population health approach. The authors review the role of CBT-I, treatment of comorbid conditions, and pharmacologic recommendations in working with primary care patients with insomnia. In addition, the authors highlight the potential utility of technology in improving access to insomnia care.


Differentiating the functional role of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha (EPAS-1) by the use of RNA interference: erythropoietin is a HIF-2alpha target gene in Hep3B and Kelly cells.
Activation of the hypoxia-inducible factor alpha-subunits, HIF-1alpha and HIF-2alpha, seems to be subject to similar regulatory mechanisms, and transgene approaches suggested partial functional redundancy. Here, we used RNA interference to determine the contribution of HIF-1alpha vs. HIF-2alpha to the hypoxic gene induction. Surprisingly, most genes tested were responsive only to the HIF-1alpha siRNA, showing no effect by HIF-2alpha knock-down. The same was found for the activation of reporter genes driven by hypoxia-responsive elements (HREs) from the erythropoietin (EPO), vascular endothelial growth factor, or phosphoglycerate kinase gene. Interestingly, EPO was the only gene investigated that showed responsiveness only to HIF-2alpha knock-down, as observed in Hep3B and Kelly cells. In contrast to the EPO-HRE reporter, the complete EPO enhancer displayed dependency on HIF-2alpha regulation, indicating that additional cis-acting elements confer HIF-2alpha specificity within this region. In 786-0 cells lacking HIF-1alpha protein, the identified HIF-1alpha target genes were regulated by HIF-2alpha. Overexpression of the HIFalpha subunits in different cell lines also led to a loss of target gene specificity. In conclusion, we found a remarkably restricted target gene specificity of the HIFalpha subunits, which can be overcome in cells with perturbations in the pVHL/HIF system and under forced expression.


Key Word Signing Usage of Adults With Intellectual Disabilities: Influence of Communication Partners' Sign Usage and Responsivity.
In services for adults with intellectual disabilities, various staff members may have different key word signing (KWS) skills and conversational style. Little is known about how these clients use KWS with different staff members. Therefore, we observed staff-client conversations and examined how clients' KWS usage was shaped by staff members' KWS usage and conversational style. Three 10-min dyadic conversations between an adult with moderate or severe intellectual disabilities (N = 15) and three familiar staff members were filmed and transcribed. The KWS usage and conversational responsivity in the transcriptions was analyzed at group (using generalized estimating equations), subgroup, and individual levels. Clients appeared to produce significantly more KWS as partners imitated more signs and as partners were more responsive. There was a negative interaction between these two factors. Subgroup analyses showed that spontaneity of clients' KWS usage was a continuum. Findings suggest that staff can encourage clients' KWS usage by imitating manual signs but that clients' response efficiency should also be taken into account.


Molecular simulations of mesoscopic bilayer phases.
Dissipative particle dynamics simulations are used to study the self-assembly of lipids into bilayers. With a simple mesoscopic lipid-water model, we observe the formation of the liquid crystalline phase L(alpha) and gel phases in which the tails are interdigitated L(betaI) or noninterdigitated L(beta). For double-tail lipids experiments show all three phases, while for single-tail lipids only L(beta) and L(alpha) are observed. We show that at sufficiently high head-head repulsion the L(betaI) is stable for single-tail lipids. This suggests that it might be possible to induce an L(beta)-->L(betaI) transition by adding chaotropic salts.


Combination of bubble liposomes and high-intensity focused ultrasound (HIFU) enhanced antitumor effect by tumor ablation.
Ultrasound (US) is used in the clinical setting not only for diagnosis but also for therapy. As a therapeutic US technique, high-intensity focused ultrasound (HIFU) can be applied to treat cancer in a clinical setting. Microbubbles increased temperature and improved the low therapeutic efficiency under HIFU; however, microbubbles have room for improvement in size, stability, and targeting ability. To solve these issues, we reported that "Bubble liposomes" (BLs) containing the US imaging gas (perfluoropropane gas) liposomes were suitable for ultrasound imaging and gene delivery. In this study, we examined whether BLs and HIFU could enhance the ablation area of the tumor and the antitumor effect. First, we histologically analyzed the tumor after BLs and HIFU. The ablation area of the treatment of BLs and HIFU was broader than that of HIFU alone. Next, we monitored the temperature of the tumor, and examined the antitumor effect. The temperature increase with BLs and HIFU treatment was faster and higher than that with HIFU alone. Moreover, treatment with BLs and HIFU enhanced the antitumor effect, which was better than with HIFU alone. Thus, the combination of BLs and HIFU could be efficacious for cancer therapy.


DI-ICR-FT-MS-based high-throughput deep metabotyping: a case study of the Caenorhabditis elegans-Pseudomonas aeruginosa infection model.
In metabolomics there is an ever-growing need for faster and more comprehensive analysis methods to cope with the increasing size of biological studies. Direct-infusion ion-cyclotron-resonance Fourier-transform spectrometry (DI-ICR-FT-MS) is used in non-targeted metabolomics to obtain high-resolution snapshots of the metabolic state of a system. We applied this technology to a Caenorhabditis elegans-Pseudomonas aeruginosa infection model and optimized times needed for cultivation and mass-spectrometric analysis. Our results reveal that DI-ICR-FT-MS is a promising tool for high-throughput in-depth non-targeted metabolomics. We performed whole-worm metabolomics and recovered markers of the induced metabolic changes in C. elegans brought about by interaction with pathogens. In this investigation, we reveal complex metabolic phenotypes enabling clustering based upon challenge. Specifically, we observed a marked decrease in amino-acid metabolism with infection by P. aeruginosa and a marked increase in sugar metabolism with infection by Salmonella enterica. We were also able to discriminate between infection with a virulent wild-type Pseudomonas and with an attenuated mutant, making it possible to use this method in larger genetic screens to identify host and pathogen effectors affecting the metabolic phenotype of infection.


The Portable Warrior Test of Tactical Agility: A Novel Functional Assessment That Discriminates Service Members Diagnosed With Concussion From Controls.
Return-to-duty (RTD) readiness assessment for service members (SM) following concussion requires complex clinical considerations. The Portable Warrior Test of Tactical Agility (POWAR-TOTAL) is a functional assessment which improves on previous laboratory-based RTD assessments. Sixty-four SM diagnosed with concussion and 60 healthy control (HC) SM participated in this study. Group differences were analyzed to validate the POWAR-TOTAL. The High-level Mobility Assessment Test (HiMAT) was used to examine concurrent construct validity. An exploratory logistic regression analysis examined predictive validity. The groups were demographically well-matched except for educational level. POWAR-TOTAL measures were statistically significantly different between the groups with moderate to large effect sizes. Concussed participants were less likely to be able to complete all trials of the POWAR-TOTAL. Motor scores correlated highly with HiMAT scores. POWAR-TOTAL motor task performance and membership in the control group was significantly associated with self-reported physical readiness to deploy. The POWAR-TOTAL is a clinically feasible, military relevant assessment that is sensitive to differences between concussed and HC SM. This analysis supports the discriminant and construct validity of the POWAR-TOTAL, and may be useful for medical providers evaluating RTD readiness for SM who have sustained a concussion.


Modification of American Joint Committee on cancer prognostic groups for renal cell carcinoma.
To compare the predictive value of the current AJCC stage grouping for renal cell carcinoma (RCC) to our modifications. A total of 2120 patients with RCC from Fudan University Shanghai Cancer Center (FUSCC) database and 74 506 counterparts from SEER database were included. Cox regression was used to calculate the relative impacts between prognostic groups. The predictive accuracy of overall survival (OS) was assessed using the concordance index (C-index), which was compared by likelihood ratio test. In FUSCC cohort, the 5-year-OS rate for T3N0M0 patients was higher than T1-3N1M0 (72.7% vs 38.1%). The 5-year-OS rate for T4N0M0 was 36.2%, which was close to T1-3N1M0 but not to T4N1M0 (0%) and TanyNanyM1 (12.6%). The elements of AJCC groups were regrouped according to the ranks of hazard ratios. The modified stages II (T3N0M0), III (T1-3N1M0, T4N0M0), and IV (T4N1M0, TanyNanyM1) exhibited greater survival stratification than AJCC groups. The modifications were validated in SEER cohort and yielded similar survival outcomes. The predictive accuracy of OS in modified prognostic groups was significantly higher than AJCC groups in stages II-IV subgroups in both FUSCC (C-index: 0.801 vs 0.779, P < 0.001) and SEER cohort (C-index: 0.770 vs 0.764, P < 0.001). The modified AJCC prognostic groups for RCC provided significantly improved survival prediction compared with the 8th AJCC edition. A precise risk stratification of modified stages II-IV disease provides an important basis for risk-equivalent treatment recommendation.


The administration of oseltamivir results in reduced effector and memory CD8+ T cell responses to influenza and affects protective immunity.
The clinical benefits of oseltamivir (Tamiflu) are well established, but the effects of antiviral treatment on the immune response are poorly understood. By use of flow cytometric analyses and the mouse model, we thoroughly investigated the impact of such a treatment on the immune response and the generation of protective immunity to influenza. We demonstrated that influenza-specific CD8(+) effector T cell recruitment was reduced up to 81% in the lungs of mice treated with oseltamivir (5 or 50 mg/kg twice daily; EC50 49 nM in vitro) compared to saline controls, but cell generation was unaffected in draining lymph nodes. Importantly, we showed that oseltamivir administration significantly decreased the pools of tissue-resident and circulating effector memory (93.7%) and central memory CD8(+) T cells (45%) compared to saline controls. During heterologous secondary infection, a decreased memory CD8(+) T cell pool combined with reduced generation of secondary influenza-specific effectors in the lymph nodes resulted in 10-fold decreased CD8(+) T cell recall responses, which increased mouse morbidity and delayed viral clearance. Furthermore, antiviral administration led to a significant 5.7-fold decreased production of functional anti-influenza antibodies. Thus, our study demonstrates that antiviral treatment affects the development of the adaptive immune response and protective immunity against influenza.


Selenoproteins and their impact on human health through diverse physiological pathways.
In the last few decades, the importance of selenium in human health has been the subject of numerous studies. It is believed that the physiological effects of selenium occur mainly through the function of selenoproteins, which incorporate selenium in the form of one or more selenocysteine residues. Recent advances in understanding the complex regulation of selenoprotein synthesis and functional characterization of several members of the selenoprotein family have contributed to an improved comprehension of the role(s) of selenium in human health and the great diversity of physiological pathways influenced by this trace element.


Raman thermometry measurements of free evaporation from liquid water droplets.
Recent theoretical and experimental studies of evaporation have suggested that on average, molecules in the higher-energy tail of the Boltzmann distribution are more readily transferred into the vapor during evaporation. To test these conclusions, the evaporative cooling rates of a droplet train of liquid water injected into vacuum have been studied via Raman thermometry. The resulting cooling rates are fit to an evaporative cooling model based on Knudsen's maximum rate of evaporation, in which we explicitly account for surface cooling. We have determined that the value of the evaporation coefficient (gamma(e)) of liquid water is 0.62 +/- 0.09, confirming that a rate-limiting barrier impedes the evaporation rate. Such insight will facilitate the formulation of a microscopic mechanism for the evaporation of liquid water.


A Zwitterionic Ligand-Based Cationic Metal-Organic Framework for Rapidly Selective Dye Capture and Highly Efficient Cr2 O72- Removal.
A cationic metal-organic framework (MOF), [Cu2 L(H2 O)2 ]⋅(NO3 )2 ⋅5.5 H2 O (1) has been successfully synthesized from a zwitterionic ligand 1,1'-bis(3,5-dicarboxyphenyl)-4,4'-bipyridinium chlorine ([H4 L]Cl2 ). The framework of compound 1 contains classical {Cu2 (O2 C)4 } paddlewheels, and possesses typical nbo-type topology and two types of channels with sizes of 5.0 and 15.54 Å. Benefitting from the 3D cationic framework and high pore volume, compound 1 shows interesting selective adsorption ability for anionic dyes. Such material can be successfully employed in a chromatographic column to efficiently separate mixed dyes of Fluorescein Sodium and Methylene Blue. In addition, compound 1 exhibits excellent Cr2 O72- removal capacity with maximum adsorption amount of 222.5 mg g-1 , which ranks among the higher Cr2 O72- adsorption amounts of MOF materials ever reported, based on ion-exchange. The strategy to construct cationic MOFs based on zwitterionic ligands will promote the development of functional porous materials for the capture and removal of anionic pollutant species from contaminated liquid.


Laser-induced currents along molecular wire junctions.
The treatment of the previous paper is extended to molecular wires. Specifically, the effect of electron-vibrational interactions on the electronic transport induced by femtosecond omega+2omega laser fields along unbiased molecular nanojunctions is investigated. For this, the photoinduced vibronic dynamics of trans-polyacetylene oligomers coupled to macroscopic metallic leads is followed in a mean-field mixed quantum-classical approximation. A reduced description of the dynamics is obtained by introducing projective lead-molecule couplings and deriving an effective Schrodinger equation satisfied by the orbitals in the molecular region. Two possible rectification mechanisms are identified and investigated. The first one relies on near-resonance photon-absorption and is shown to be fragile to the ultrafast electronic decoherence processes introduced by the wire's vibrations. The second one employs the dynamic Stark effect and is demonstrated to be highly efficient and robust to electron-vibrational interactions.


Insulin-like growth factors and thecal-granulosa-cell function.
Insulin-like growth factors (IGFs) belong to a family of low mol. wt, single chain polypeptides inducing growth promotion and insulin-like metabolism effects and regulating both cell replication and differentiation. Recent studies in laboratory animals suggest that IGFs play an important role as intraovarian regulators in several mammalian species. The purpose of this article was to review current concepts of interactions between the IGFs and the thecal-granulosa-cell function. To provide a basic understanding of these interactions, we have first analysed data concerning biosynthesis, biochemical structure, pharmacokinetics, degradation, binding proteins and receptors for IGFs. Then we have discussed the specific interactions between IGFs and theca-granulosa-cell regulation, and analysed the significance of the relationship to the pathophysiology of some endocrine and reproductive disorders, including hyperandrogenism and female infertility.


The double peak-to-peak analysis for determining EMG onset of muscle contraction.
Identification of the onset of muscle contraction with EMG signal amplitude double of the baseline value (DP-P) has been recently reported for determining the temporal parameters of muscular activity. Due to its convenience, it is suitable for clinical application. However, there is a lack of report on the reliability and comparability of this method to other established methods. Therefore, this study examined the test-retest reliability of the DP-P method and compared it with an established method that used the mean + 3 standard deviations (mean + 3 s.d.) over the baseline value for muscles of the knee. The onset of contraction of vastus medialis obliquus (VMO) and vastus lateralis (VL) of eleven able-bodied volunteers performing isometric knee extension at 50%, 75% and 100% of MVC in 30-minute and 7-day intervals were analyzed with both the DP-P and mean + 3 s.d. methods. The ICC for within-day measurements of DP-P method ranged from 0.64 to 0.86 and that for between-day measurements ranged from 0.63-0.81. The ICC values were higher with submaximal than maximal contractions. There was a consistent delay of about 3 ms in EMG onset detection with the DP-P as compared to the mean + 3 s.d method. The DP-P method is a reliable method for muscle onset determination but the absolute onset time of muscle contraction obtained from this method should not be directly compared with other methods such as the mean + 3 s.d.


Factors predicting death, survival and functional outcome in a prospective study of early rheumatoid disease over fifteen years.
Sixty-four survivors from a prospective study of early rheumatoid disease were assessed again at a mean of 15.2 years from presentation and their status compared with 29 patients who had died. Eleven of the dead and only two of the survivors had been treated with steroids. There was a small increase in mortality due to the disease itself but only one death was directly caused by it. As might be expected, those who died were older. In the first year of disease, they had lower haemoglobin levels, a lower body mass, higher sedimentation rates and higher levels of blood urea. One-fifth at entry to the study and two-fifths by the time of death, had poor functional capacity. Of 64 survivors, six had poor functional capacity at entry and nine after 15 years. Discriminant analysis was performed to identify the most powerful combination of early features predicting a poor functional outcome. A combination including early erosive change, seropositivity, poor grip strength and cervical subluxation predicted the outcome correctly in 73% of survivors. Almost 60% of survivors remained with or improved to normal function at 15 years suggesting that morbidity is not as bad as has been suggested in the past.


Trypanosoma cruzi vaccine candidate antigens Tc24 and TSA-1 recall memory immune response associated with HLA-A and -B supertypes in Chagasic chronic patients from Mexico.
Trypanosoma cruzi antigens TSA-1 and Tc24 have shown promise as vaccine candidates in animal studies. We evaluated here the recall immune response these antigens induce in Chagasic patients, as a first step to test their immunogenicity in humans. We evaluated the in vitro cellular immune response after stimulation with recombinant TSA-1 (rTSA-1) or recombinant Tc24 (rTc24) in mononuclear cells of asymptomatic Chagasic chronic patients (n = 20) compared to healthy volunteers (n = 19) from Yucatan, Mexico. Proliferation assays, intracellular cytokine staining, cytometric bead arrays, and memory T cell immunophenotyping were performed by flow cytometry. Peripheral blood mononuclear cells (PBMC) from Chagasic patients showed significant proliferation after stimulation with rTc24 and presented a phenotype of T effector memory cells (CD45RA-CCR7-). These cells also produced IFN-γ and, to a lesser extent IL10, after stimulation with rTSA-1 and rTc24 proteins. Overall, both antigens recalled a broad immune response in some Chagasic patients, confirming that their immune system had been primed against these antigens during natural infection. Analysis of HLA-A and HLA-B allele diversity by PCR-sequencing indicated that HLA-A03 and HLA-B07 were the most frequent supertypes in this Mexican population. Also, there was a significant difference in the frequency of HLA-A01 and HLA-A02 supertypes between Chagasic patients and controls, while the other alleles were evenly distributed. Some aspects of the immune response, such as antigen-induced IFN-γ production by CD4+ and CD8+ T cells and CD8+ proliferation, showed significant association with specific HLA-A supertypes, depending on the antigen considered. In conclusion, our results confirm the ability of both TSA-1 and Tc24 recombinant proteins to recall an immune response induced by the native antigens during natural infection in at least some patients. Our data support the further development of these antigens as therapeutic vaccine against Chagas disease.


Spatial periodicity induced by a chemical wave train.
An all-chemical analog of clock-wave-front model for somitogenesis is proposed. The spatial periodicity can be obtained by arresting the homogeneous oscillations in a typical two-component reaction-diffusion system in the Hopf region by interacting with a chemical wave front. The patterns can be controlled by tuning the wave speed of the front.


The impact of pay-for-performance on quality of care for minority patients.
To determine whether racial disparities in process quality and outcomes of care change under hospital pay-for-performance. Retrospective cohort study comparing the change in racial disparities in process quality and outcomes of care between 2004 and 2008 in hospitals participating in the Premier Hospital Quality Incentive Demonstration versus control hospitals. Using patient-level Hospital Quality Alliance (HQA) data, we identified 226,096 patients in Premier hospitals, which were subject to pay-for-performance (P4P) contracts and 1,607,575 patients at control hospitals who had process of care measured during hospitalization for acute myocardial infarction (AMI), congestive heart failure (CHF), or pneumonia. We additionally identified 123,241 Medicare patients in Premier hospitals and 995,107 in controls who were hospitalized for AMI, CHF, pneumonia, or coronary artery bypass graft (CABG) surgery. We then compared HQA process quality indicators for AMI, CHF, and pneumonia between P4P and control hospitals, as well as risk-adjusted mortality rates for AMI, CHF, pneumonia, and CABG. Black patients initially had lower performance on process quality indicators in both Premier and non-Premier hospitals. The racial gap decreased over time in both groups; the reduction in the gap in Premier hospitals was greater than the gap reduction in non-Premier hospitals for AMI patients. During the study period, mortality generally decreased for blacks relative to whites for AMI, CHF, and pneumonia in both Premier and non-Premier hospitals, with the relative reduction for blacks greatest in Premier hospitals for CHF. Our results show no evidence of a deleterious impact of P4P in the Premier HQID on racial disparities in process quality or outcomes.


Accuracy of examination of the long head of the biceps tendon in the clinical setting: A systematic review.
To determine the diagnostic validity of high-resolution ultrasound and orthopaedic special tests in diagnosing long head of the biceps tendon pathologies in patients with shoulder pain. Systematic review with meta-analysis tools. MEDLINE, CINAHL and EMBASE. Included studies had to report on the diagnostic validity of orthopaedic special tests or high-resolution ultrasound (HRUS) compared with a reference standard for diagnosing long head of the biceps tendon target conditions (superior labrum anterior and posterior lesions, long head of the biceps tendon tendinopathy, dislocation, effusion or rupture). Risk of bias was assessed using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) tool. Of the 30 included studies, 8 focused on high-resolution ultrasound and 22 on orthopaedic special tests. High-resolution ultrasound proved highly specific for the diagnosis of long head of the biceps tendon pathologies. Pooled positive (LR+) and negative (LR-) likelihood ratios were 38.00 and 0.24 for dislocation, respectively, and 35.50 and 0.30 for complete rupture, respectively. The accuracy of orthopaedic special tests varied greatly across studies. The only test of value was Yergason's ma-noeuvre in confirming proximal long head of the biceps tendon pathologies except superior labrum anterior and posterior lesion (high specificity): the summary LR+ and LR- were 2.56 and 0.70, respectively. High-resolution ultrasound is reliable to confirm suspected long head of the biceps tendon pathologies. There is insufficient evidence to recommend individual orthopaedic special tests.


Preparation and evaluation of two microbiological media from shrimp heads and hulls.
Two peptones were extracted from raw shrimp waste after autolytic digestion. Digests were derived from shrimp heads and shrimp hulls, both of which are by-products of the shrimp processing industry. Digests were evaluated for suitability in supporting growth of microorganisms by measuring the total cell mass produced by five genera of bacteria and five genera of fungi in broths formulated from the peptones. Comparison was made to five commercially available medium preparations and a catfish peptone. A 0.5% solution of the lyophilized shrimp head digest, heated at 121 C for 15 min, resulted in a cloudy suspension. However, the digest supported excellent growth of fungi and good growth of bacteria. A heated 0.5% solution of the hull digest was clear and supported good growth of both bacteria and fungi.


Development and pilot testing of survey items to assess the culture of value and efficiency in hospitals and medical offices.
Given rising costs and changing payment models, healthcare organisations are increasingly focused on value and efficiency. The goal of our study was to develop survey items to assess clinician and staff perspectives about the extent to which the organisational culture in hospitals and medical offices supports value and efficiency. Development began with a literature review and interviews with experts and clinicians and staff from hospitals and medical offices. We identified key areas of value and efficiency culture, drafted survey items and conducted cognitive testing. Using purposive sampling to select sites, the 36-item surveys were pilot tested in 47 hospitals and 96 medical offices. Psychometric analysis was conducted on data from 3951 hospital respondents (42% response) and 1458 medical office respondents (63% response). Factor loadings, multilevel confirmatory factor analysis model fit and reliability estimates were acceptable for the 13 items grouped into 4 composite measures: Empowerment to Improve Efficiency (3 items), Efficiency and Waste Reduction (3 items), Patient Centeredness and Efficiency (3 items) and Management Support for Improving Efficiency and Reducing Waste (4 items). All composite measures were significantly intercorrelated and related to the four Overall Ratings of Healthcare Quality, indicating adequate conceptual convergence among the measures. Eight items assessing Experiences With Activities to Improve Efficiency were also included. We developed psychometrically sound survey items measuring value and efficiency culture. When added to the Agency for Healthcare Research and Quality Surveys on Patient Safety Culture, the item sets extend those surveys by assessing additional dimensions of organisational culture that affect care delivery. Healthcare organisations can use these item sets to assess how well their organisational culture supports value and efficiency and identify areas for improvement.


Morphological and anatomical variations among Phlebotomus (Phlebotomus) papatasi sensu lato (Diptera: Psychodidae).
Phlebotomus (Phlebotomus) papatasi (Scopoli) collected in human dwellings from an agricultural villages Chaura, located in Gaya district, Bihar, India, showed morphological and anatomical variations. Male sand flies of this species exhibited variations in the genital structures, while females showed differences in the spermathecae and antenna segment three (A3). When the mitochondrial DNA of both male and female P. (P.) papatasi sensu lato population subjected to DNA barcoding, both the sexes of P. (P.) papatasi variants were found to be associated. The differences in the morphometric characteristics clearly constitutes preliminary evidence for infraspecific variation in P. (P.) papatasi s.1. population in India.


Coronary artery bypass surgery in women.
Coronary bypass surgery is performed more frequently in men than in women. A selection bias in favor of men may exist in currently utilized evaluation precesses for patients with both chest pain syndromes and documented coronary artery disease. Surgery should be considered in women with significant left main coronary artery stenosis, "left main equivalent" coronary disease, severe three-vessel coronary disease with/without left ventricular dysfunction, two-vessel coronary disease (including a proximal left anterior descending artery stenosis), and unstable angina pectoris with decreased left ventricular function. Women and men undergoing coronary bypass surgery seem to benefit from internal mammary artery grafts used alone or in combination with saphenous vein grafts. Surgical mortality, incomplete revascularization, early and late graft occlusion, and recurrent angina are more prevalent in women who undergo surgery. However, long-term mortality following surgery is similar in men and women.


Probiotics: properties, examples, and specific applications.
Probiotics are beneficial components of the microbiota that have been used for centuries because of the health benefits they confer to the host. Only recently, however, has the contribution of probiotics to modulation of immunological, respiratory, and gastrointestinal functions started to be fully appreciated and scientifically evaluated. Probiotics such as Escherichia coli Nissle 1917 and lactic acid bacteria are currently used to, or have been evaluated for use to, prevent or treat a range of intestinal maladies including inflammatory bowel disease, constipation, and colon cancer. Engineering these natural probiotics to produce immunomodulatory molecules may help to further increase the benefit to the host. In this article, we will discuss some of the mechanisms of action of probiotics as well as advances in the rational design of probiotics.


A method of water-bloom prevention using underwater pulsed streamer discharge.
Water-bloom (also named as cyanobacterial bloom) is becoming a very serious pollution problem all over the world. In this paper, a new method for the prevention of water blooms using underwater streamer discharges is reported. Blumlein pulse forming network (B-PFN) and magnetic pulse compression circuit (MPC) were employed to apply high voltage pulses to water with cyanobacterial cells. The experimental results confirmed that the cyanobacterial cells sank to the bottom of the water bodies after applying underwater streamer discharges. Transmission electron microscope (TEM) observations showed that the discharge collapsed the gas vesicles (GVs)-the intercellular structure of water-bloom forming cyanobaterial cells-and did not affect the other part of contents of the cells. Cynabacterial cells lost buoyancy and sank to the bottom of the water bodies. Because of lower temperature and without enough sunlight at the bottom of the water bodies, the cells can be prevented from proliferation too quickly.


Resistance of 7,12-dimethylbenz[a]anthracene-deoxyadenosine adducts in DNA to hydrolysis by snake venom phosphodiesterase.
In enzymatic hydrolyses of 7,12-dimethylbenz[a]anthracene (DMBA)-modified DNA isolated from fetal mouse cell cultures, a low concentration of venom phosphodiesterase was sufficient for complete release of DMBA-deoxyguanosine adducts. However, efficient release of DMBA-deoxyadenosine adducts required much higher levels of phosphodiesterase. If these adducts exhibit similarly differential susceptibilities to exonucleases involved in DNA metabolism or repair, each adduct could result in significantly different biological effects in vivo.


The spatial structure of cone-opponent receptive fields in macaque retina.
The receptive field structure of long (L) to middle (M) wavelength (L/M) cone-opponent ganglion cells of the parafoveal macaque retina was investigated using drifting gratings. Gratings were luminance, chromatic or selective for the L- or M-cones. Based on these spatial tuning curves, receptive field profiles for the individual cones were derived. Receptive field profiles were coarse compared to single cones, and often could not be described by a simple Gaussian, having shallower flanks. There was a continuum of spatial properties, which blurred any systematic distinction between Type I and Type II receptive fields. Opponent center-surround organization within a single cone was rare. Usually, responses to all four grating types could be described based on the cone receptive field profiles. An exception was a few cells that showed irregularities of amplitude and phase at high spatial frequencies for one or other of the cone isolating conditions. The data are related to standard models of M/L opponent receptive fields and implications for central processing are considered.


An exploration of childhood victimization and family-of-origin characteristics of sexual offenders against children.
A comparison of the childhood victimization experiences and family-of-origin characteristics of 33 sexual offenders against children, 66 violent offenders, and 25 nonviolent offenders participating in assessment or treatment at a forensic division of a Canadian psychiatric hospital was undertaken using a semistructured interview designed specifically for this study. Overall, 31.5% of the sample reported contact sexual abuse (i.e., oral, vaginal, or anal) by age 14. Sexual offenders against children reported significantly more sexual abuse than both violent and nonviolent offenders and were more likely to have been sexually propositioned and exposed to. Sexual offenders against children were also more likely to report physical discipline as the primary type of discipline in the home. Analyses of the variables concerning characteristics of parents, siblings, and significant others also indicated significant differences between groups. Implications of these findings on the intergenerational hypothesis are discussed as well as their relevance for treatment.


Rhodium-Catalyzed Regioselective N2 -Alkylation of Benzotriazoles with Diazo Compounds/Enynones via a Nonclassical Pathway.
A novel rhodium-catalyzed highly selective N2 -alkylation of benzotriazoles with diazo compounds/enynones is achieved, providing N2 -alkylated benzotriazoles in good to excellent yields and with excellent N2 selectivities. Importantly, different to traditional carbene insertion into X-H (X=N, O etc) bonds, DFT calculations disclose that this selective N2 -alkylation probably proceeds through a formal 1,3- rather than 1,2-H shift to give the final products.


A pneumocyte-macrophage paracrine lipid axis drives the lung toward fibrosis.
Lipid-laden macrophages, or "foam cells," are observed in the lungs of patients with fibrotic lung disease, but their contribution to disease pathogenesis remains unexplored. Here, we demonstrate that fibrosis induced by bleomycin, silica dust, or thoracic radiation promotes early and sustained accumulation of foam cells in the lung. In the bleomycin model, we show that foam cells arise from neighboring alveolar epithelial type II cells, which respond to injury by dumping lipids into the distal airspaces of the lungs. We demonstrate that oxidized phospholipids accumulate within alveolar macrophages (AMs) after bleomycin injury and that murine and human AMs treated with oxidized phosphatidylcholine (oxPc) become polarized along an M2 phenotype and display enhanced production of transforming growth factor-β1. The direct instillation of oxPc into the mouse lung induces foam cell formation and triggers a severe fibrotic reaction. Further, we show that reducing pulmonary lipid clearance by targeted deletion of the lipid efflux transporter ATP-binding cassette subfamily G member 1 increases foam cell formation and worsens lung fibrosis after bleomycin. Conversely, we found that treatment with granulocyte-macrophage colony-stimulating factor attenuates fibrotic responses, at least in part through its ability to decrease AM lipid accumulation. In summary, this work describes a novel mechanism leading to foam cell formation in the mouse lung and suggests that strategies aimed at blocking foam cell formation might be effective for treating fibrotic lung disorders.


Functional Outcomes of Tibia Fractures Treated With Intramedullary Interlocking Nails by Suprapatellar Approach: A Prospective Study.
Background Tibia fractures are the most common lower extremity fractures. The subcutaneous anatomy of this long bone predisposes it to high fracture frequency in a high-energy trauma. The tibia is a major weight-bearing, long tubular bone that is axially and rotationally unstable when fractured, which ideally necessitates its surgical fixation in adults. Tibia fractures can be treated with a variety of choice of implants and surgical approaches. This study aims to assess the clinical and functional outcomes of a tibia fracture treated with intramedullary interlocking nails by a suprapatellar approach. Methodology A total of 32 patients were selected from patients admitted at Shri B. M. Patil Medical College and Research Centre with tibia fractures between January 2021 and May 2022. All the patients were treated with closed reduction and internal fixation with intramedullary interlocking nails by suprapatellar approach with a semi-extended knee position. All patients were followed up clinically and radiologically at regular intervals of six weeks, three months, six months, and one year. All functional outcomes were assessed based on modified Lysholm knee scores. Results A total of 31 patients showed union at the fracture site. One patient had nonunion and implant failure at the distal locking site, and two patients had persistent anterior knee pain at the end of one year. Functional outcome assessment based on modified Lysholm scores had excellent results, with a mean score of 95. Patients were followed up for a mean of 11.5 months. The mean time of union was observed as 12.5 months. Conclusions Suprapatellar tibia nailing is an effective alternative approach with ease of reduction and decreased intraoperative fluoroscopy time. The entry is in line with the medullary cavity preventing malreduction of proximal and distal tibia fractures. The additional proximal locking option also increases the stability of implant fixation.


Programming for survival: a meeting system that survives 8 years later.
Effective and useful interventions often deteriorate when researchers withdraw their direct supervision. We tested the survival of an intervention designed to produce effective weekly meetings in a student housing cooperative without direct researcher supervision. Chairperson performance, proposals completed per hour, and ratings of chairperson performance all increased when resident staff used a training manual, prompting checklist, and performance reviews. Eight years of follow-up revealed continuing high levels of meeting effectiveness. This study demonstrates a methodology for the direct observation and experimental analysis of intervention survival.


Targeting the Retinoid X Receptor Pathway Prevents and Ameliorates Murine Chronic Graft-Versus-Host Disease.
Most allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients receive peripheral blood stem cell grafts resulting in a 30%-70% incidence of chronic graft-versus-host disease (cGVHD), a major cause of mortality and morbidity in long-term survivors. While systemic steroids remain the standard of care for first-line therapy, patients may require long-term administration, and those with steroid-resistant or refractory cGVHD have a worse prognosis. Although durable and deep responses with second-line therapies can be achieved in some patients, there remains an urgent need for new therapies. In this study, we evaluated the efficacy of IRX4204, a novel agonist that activates RXRs and is in clinical trials for cancer treatment to prevent and treat cGVHD in two complementary murine models. In a major histocompatibility complex mismatched, non-sclerodermatous multiorgan system model with bronchiolitis obliterans, IRX4204 prevented and reversed cGVHD including associated pulmonary dysfunction with restoration of germinal center T-follicular helper: T-follicular regulatory cell balance. In a minor histocompatibility antigen disparate sclerodermatous model, IRX4204 treatment significantly prevented and ameliorated skin cGVHD by reducing Th1 and Th17 differentiation due to anti-inflammatory properties. Together, these results indicate that IRX4204 is a promising therapeutic option to treat cGVHD with bronchiolitis obliterans or sclerodermatous manifestations.


Clinical safety of chemotherapy for elderly cancer patients complicated with hypertension.
To access the safety of chemotherapy for elderly cancer patients complicated with hypertension. Elderly cancer patients who were complicated with hypertension and treated by chemotherapy were recruited. All patients were treated by chemotherapy after an intervention on hypertension by psychotherapy, exercise guidance, salt regulation and nutrition support, therapy on hypertension, as well as prevention on hypertension associated complications. In 68 eligible patients, two suspended chemotherapy because of adverse reactions and 4 because of disease progression. The remaining 62 patients completed chemotherapy smoothly based on good hypertension control. With effective control of blood pressure, chemotherapy for elderly cancer patients complicated with hypertension is generally safe.


Diagnostic validation of three test methods for detection of cyprinid herpesvirus 3 (CyHV-3).
Cyprinid herpesvirus 3 (CyHV-3) is the aetiological agent of koi herpesvirus disease in koi and common carp. The disease is notifiable to the World Organisation for Animal Health. Three tests-quantitative polymerase chain reaction (qPCR), conventional PCR (cPCR) and virus isolation by cell culture (VI)-were validated to assess their fitness as diagnostic tools for detection of CyHV-3. Test performance metrics of diagnostic accuracy were sensitivity (DSe) and specificity (DSp). Repeatability and reproducibility were measured to assess diagnostic precision. Estimates of test accuracy, in the absence of a gold standard reference test, were generated using latent class models. Test samples originated from wild common carp naturally exposed to CyHV-3 or domesticated koi either virus free or experimentally infected with the virus. Three laboratories in Canada participated in the precision study. Moderate to high repeatability (81 to 99%) and reproducibility (72 to 97%) were observed for the qPCR and cPCR tests. The lack of agreement observed between some of the PCR test pair results was attributed to cross-contamination of samples with CyHV-3 nucleic acid. Accuracy estimates for the PCR tests were 99% for DSe and 93% for DSp. Poor precision was observed for the VI test (4 to 95%). Accuracy estimates for VI/qPCR were 90% for DSe and 88% for DSp. Collectively, the results show that the CyHV-3 qPCR test is a suitable tool for surveillance, presumptive diagnosis and certification of individuals or populations as CyHV-3 free.


Reduction of Tryptophan Hydroxylase Expression in the Brain of Medaka Fish After Repeated Heat Stress.
Serotonin (i.e., 5-hydroxytryptamine [5-HT]) plays a key role in stress responses in vertebrates. In mammals and teleosts, tryptophan hydroxylase (Tph), a rate-limiting enzyme in the biosynthesis of 5-HT, includes two paralogs: Tph 1 and Tph 2. The response of the Tphs to stress has been reported in mammals, but less is known about the responses of these enzymes to stress in fish. In the present study, we examined whether heat stress affects the mRNA expression of these Tphs in the brain of medaka fish (Oryzias latipes). We also determined the concentration of 5-HT in the brain, the mRNA expression of heat shock protein 90 alpha (Hsp90α) in the liver, plasma cortisol concentration, and blood glucose concentration in medaka. Whole-body exposure to repeated heat stress significantly decreased the mRNA expression of Tph1 and Tph2 in male and female medaka, whereas single heat stress did not affect the expression of either of the mRNAs. The 5-HT concentration also decreased significantly after repeated heat stress sessions in both sexes, but did not decrease after a single heat stress session. After single and repeated heat stress sessions, Hsp90α mRNA expression increased in both sexes; however, increments in the concentrations of plasma cortisol and blood glucose occurred in male, but not in female, medaka. These results suggest that both types of Tphs are involved in reducing 5-HT in the brain and are reliable indicators of chronic stress response in both sexes. However, stress responses in plasma cortisol and blood glucose concentrations differ between male and female medaka.


Distinct role of adiposity and insulin resistance in glucose intolerance: studies in ventromedial hypothalamic-lesioned obese rats.
It remains unclear whether adiposity plays an important role in glucose intolerance independently of insulin resistance. We investigated whether adiposity and insulin resistance had distinct roles in glucose intolerance in rats. We examined glucose tolerance and insulin resistance using ventromedial hypothalamic (VMH)-lesioned rats in the dynamic and the static phases of obesity (2 and 14 weeks after lesioning, respectively). Rats were fed either normal chow or a fructose-enriched diet (60% of total calories). The intravenous glucose tolerance test (IVGTT) was performed by bolus injection of glucose solution (1 g/kg) and blood sampling after 0, 5 10, 30, and 60 minutes. Insulin resistance was evaluated from the steady-state plasma glucose (SSPG) value during continuous infusion of glucose, insulin, and somatostatin. SSPG was not increased in VMH-lesioned rats in the dynamic phase of obesity, but increased markedly in the static phase. The area under the glucose curve (glucose AUC) during IVGTT was increased in VMH-lesioned rats in the static phase, but not in the dynamic phase, when compared with their sham-operated counterparts. A fructose-enriched diet for 2 or 14 weeks increased SSPG values to a similar extent in both sham-operated and VMH-lesioned rats without inducing excess adiposity, but glucose intolerance was only developed in the obese rats. The plasma leptin level, an excellent indicator of adiposity, was significantly related to the glucose AUC independently of the insulin level. Insulin resistance or increased adiposity alone is not sufficient to impair glucose tolerance, but increased adiposity plays an important role in the development of glucose intolerance in an insulin-resistant state.