Synthesis of a new class of fused cyclotetraphosphazene ring systems.
Octachlorocyclotetraphosphazene (1) was reacted with butylamines [n-butyl, i-butyl, sec-butyl, and t-butyl] in a 1:0.8 mol ratio in THF to obtain cyclotetraphosphazenes bearing a P-NH group, N4P4Cl7(NHR) [R = n-butyl (2a), i-butyl (2b), sec-butyl (2c), t-butyl (2d)](2a-d). The cyclotetraphosphazene derivatives 2a, 2b, and 2c were treated with sodium hydride giving rise to a new type of cyclophosphazene compounds (P8N8 ring) consisting of three fused tetramer rings (3a-c). Whereas reaction of sodium hydride with the t-butylaminocyclophosphazene derivative (2d) gave a P-O-P bridged compound (4) presumably as a result of hydrolysis reaction associated with moisture in the solvent. It is likely that the 16-membered cyclooctaphosphazene derivatives (3a-c) are formed by a proton abstraction/chloride ion elimination, intramolecular nucleophilic attack, ring opening and intermolecular condensation processes, respectively.


Treating breast cancer with cell-based approaches: an overview.
Breast cancer is the most common malignancy in women. Despite there being considerable progress in the treatment of this disease, metastatic dissemination is still considered an incurable condition at the present time, causing 500,000 deaths worldwide every year. Although most of the research efforts have been focused on pharmacological approaches, over the last three decades, the use of bone marrow and peripheral blood-derived cell therapy approaches have been attempted and developed. Areas covered: This review will briefly address cell therapy for breast cancer, including autologous stem cell transplantations for overcoming the myelosuppressive effects of high-dose chemotherapy, allogeneic stem cell transplants and adoptive immunotherapy using bone-marrow derived T-cells. Expert opinion: The treatment of breast cancer using bone marrow or peripheral-blood derived cells has evolved from a supportive care approach to allow dose escalation of conventional chemotherapy to a therapeutic strategy aimed at eliciting immune cell mediated anticancer immunity. This latter principle has led to the development of adoptive immunotherapies, either with 'natural' or genetically engineered effectors, which are being intensively investigated for their great potential against several solid tumors, including breast cancer.


Research on the magneto-optic current sensor for high-current pulses.
A new magneto-optic current sensor with a dual-orthogonal configuration is proposed and demonstrated, which can resolve the problem which value of high-current pulses is ambiguous from the Faraday rotation in the conventional magneto-optic current sensor. In this dual-orthogonal configuration, the transmission axis of the polarizer makes two given angles, which are 0 degrees and 45 degrees , with the orientation of the s-polarized lights of two polarizing cube beam splitters. If the intrinsic linear birefringence of the sensing element is one-fourth less than the Faraday rotation generated from the high-current pulse, the measurement current influenced by it can be ignored and four outputs of the magneto-optic current sensor are in quadrature. The value of the current pulse can be calculated by an arctangent data reduction method, which can avoid the insensitive zone of the sine function, where the measurement current has a reduced accuracy. A measurement of the high-current pulse (up to 720 kA) of an electric gun, with good theoretical accuracy ( approximately 3%) and in agreement well with that of the calibrated Rogowski coil, is launched.


Voice characteristics of amateur female tenors are comparable with those of male tenors.
In order to explore the suitability of adding female voices to the tenor sections of amateur choirs, six male and six female tenors were screened for voice characteristics. Audio signals and signals from an electroglottograph were analyzed by means of VoceVista computer software. All subjects produced closed quotients of 60% or higher in singing with a loud chest voice. There was more variance between the individuals than between groups of male and female singers. Long-time average spectra showed a general trend in the presence of a high-intensity peak between 4 and 5 kHz. The results revealed no significant differences in the most important voice characteristics between female and male tenor voices.


[Advances in the ecological risk management of pollution point sources of toxicants in aquatic environment].
Progress in this field in developed countries and China was reviewed and the prospects were also presented in this paper. Based on the water quality standards and discharge standards, the chemical-specific approach in common use could not effectively control complex discharges containing toxic organics. Therefore, applying this traditional approach only was not a valuable measure. Toxicity-based approach could be used at the same time to supply the gap for the control of complex discharges containing toxic organics effectively based on the requirements of ecological risk management. Toxicity identification evaluation (TIE) for identifying the key toxicants causing the effluent ecotoxicity was a core of the ecological risk management of point sources of toxics. The prospects were also described for the development of TIE methodology and the application of toxicity-based approach to the ecological risk management of point sources of toxicants in aquatic environment in China.


Personality Disorders in Elderly Inpatients With Major Depression.
We studied 154 patients with major depression, with and without personality disorder (PD), consecutively admitted to a geriatric unit and compared their characteristics and responses to acute inpatient treatment. Thirty-seven patients (24%) met DSM-III-R criteria for PD. PD not otherwise specified and dependent PD were the most frequent PD diagnoses, whereas dramatic cluster PDs were rare. Patients with PD were significantly more likely to have had 1) recurrent depression, 2) an earlier age at first episode, and 3) a concurrent anxiety disorder. There was a higher proportion of patients with PD to have 1) never married, 2) separated or divorced, or 3) attempted suicide. During inpatient stays of similar lengths, both groups received similar treatment and improved to a similar and significant extent.


Ultrasound imaging techniques in density separation of polyolefin waste.
Ultrasound imaging techniques are investigated using a multi-element sensor array for purposes of monitoring and measurement ofpolyolefin waste particles inside the black ferrous liquid ofa magnetic density separator (MDS). A medical ultrasound imaging system with real-time capability was adapted first to assess the potential of imaging technology inside the MDS. An image processing routine was developed to determine the depth distribution of the detected particles as they are carried by the flow in the MDS channel. This real-time information is vital for optimizing the splitter position, which directly influences quality and recovery of the MDS polyolefin products. Despite successes in the laboratory, the medical technology proved unsatisfactory for continuous high-quality image forming in the industrial set-up as it requires regular operator intervention. Therefore, research has been initiated into alternative imaging methods, which are also being investigated in other fields such as non-destructive testing and geophysics. The influence of different ultrasound datasets and related image-forming techniques were investigated, for which dedicated algorithms were implemented in Matlab. The main advantages and disadvantages of the different techniques are addressed. It is concluded that the alternative imaging methods may be more robust and deliver higher image quality compared to the commercial medical imager. In particular, sizing of polyolefin particles may improve significantly if the method takes into account the correct ultrasound velocities of both the ferrous liquid and the immersed polyolefin particles.


Corrigendum: Examining the intersection of cognitive and physical function measures: Results from the brain networks and mobility (B-NET) study.
[This corrects the article DOI: 10.3389/fnagi.2023.1090641.].


GLOBAL OPIOID EPIDEMIC: DOOMED TO FAIL WITHOUT GENETICALLY BASED PRECISION ADDICTION MEDICINE (PAM™): LESSONS LEARNED FROM AMERICA.
It is a reality that globally opioid deaths have soared for men and women of all social, economic status and age from heroin and fentanyl overdoses. Specifically, in the United States, deaths from narcotic overdoses have reached alarming metrics since 2010. In fact, the Fentanyl rise is driven by drug dealers who sell it as heroin or who use it to lace cocaine or to make illegal counterfeit prescription opioids. The President's Commission on the crisis has linked the death toll as equivalent to "September 11th every three weeks." In fact, The U.S. Centre for Disease Control (CDC) released data showing that opioid-related overdoses were up 15% in the first three quarters of 2016 compared to 2015. Various governmental organizations including NIDA, are actively seeking solutions. However, we argue that unless the scientific community embraces genetic addiction risk coupled with potential precision or personalized medicine to induce "dopamine homeostasis" it will fail. We now have evidence that a ten-gene and eleven single nucleotide polymorphism (SNP) panel predicts Addiction Severity Index (ASI) for both alcohol and drugs of abuse (e.g., Opioids). In a large multi-addiction centre study involving seven diverse treatment programs, the genetic addiction risk score (GARS™) was shown to have a predictive relationship with ASI-MV derived alcohol (≥ seven alleles), and other drugs (≥ 4 alleles) severity risk scores. In a number of neuroimaging studies, we also display that in both animal (bench) and abstinent Chinese severe heroin-dependent patients (bedside), BOLD dopamine activation across the brain reward circuitry revealed increases in resting state functional connectivity as well volume connectivity. It is also known that published nutrigenomic (coupling gene polymorphisms with altered KB220z) studies reveal improved clinical outcomes related to obesity.


Chronic Social Stress Time-Dependently Affects Neuropathic Pain-Related Cold Allodynia and Leads to Altered Expression of Spinal Biochemical Mediators.
Clinical data have shown that chronic exposure to stress may be accompanied by an enhancement of inflammation-related pain sensitivity. In this context, little is however known on the impact of stress on neuropathic pain. In the present study we addressed this issue by combining the chronic constriction injury (CCI) model with an ongoing social stress (OSS) paradigm. Cold plate and von Frey tests were performed in 48 rats divided into four groups: OSS exposed to OSS, CCI subjected to chronic nerve constriction, OSS+CCI with a combination of neuropathy and stress and CON, a control group lacking any manipulation. While we did not observe any stress-related differences in mechanical sensitivity throughout the observation period, CCI rats were more sensitive to cold stimulation than OSS+CCI in the initial phase of neuropathy. A switch was observed at a later stage, leading to a hypersensitivity of the OSS+CCI compared to the CCI rats. At this time point we investigated the spinal mRNA expression of neuron and glia related molecules potentially involved in neuropathic pain and stress. The combination of psychosocial stress and neuropathic pain seemed to enhance glial cell activation, pro-inflammatory cytokine and neurotrophic factor mRNA levels, rather than glutamatergic transmission. Our data show that long lasting social stress may lead to time-dependent alteration of neuropathy-related cold pain sensitivity while mechanically-induced pain remains unchanged.


Extracorporeal membrane oxygenation in the pre and post lung transplant period.
Evolution in technology has resulted in rapid increase in utilization of extracorporeal membrane oxygenation (ECMO) as a bridge to recovery and/or transplantation. Although there is limited evidence for the use of ECMO, recent improvements in ECMO technology, personnel training, ambulatory practices on ECMO and lung protective strategies have resulted in improved outcomes in patients bridged to lung transplantation. This review provides an insight into the current outcomes and best practices for utilization of ECMO in the pre- and post-lung transplantation period.


Neuro-otologic evaluation of the patient with acute, severe head injuries: correlations among physical findings, auditory evoked responses, and computerized tomography.
Long-term clinical neurologic and otologic sequelae of traumatic head injury are well recognized. In this article, we describe the relationship among neurophysiologic, neuro-otologic, and neuroradiologic findings in a series of fifty patients with acute, severe head injury. Seventy percent of the patients had one or more otologic abnormalities, of which hemotympanum was most common. Outcome of computerized tomography (CT), auditory brainstem response (ABR), and otologic examination findings were not mutually dependent. For example, otologic disease was found in 50% of the patients with normal ABR. All but one patient in the series showed brain damage by CT; yet only 14% of the series had evidence of temporal bone fracture and, unexpectedly, one third of this group yielded normal otologic findings and a normal ABR. We conclude that combined application of otologic examination, CT scanning, and auditory evoked response assessment provides complementary information on structural and functional neuro-otologic status in persons with acute, severe head injury.


Nursing Home Registered Nurses' and Licensed Practical Nurses' Knowledge of Causes of Falls.
Reducing falls in nursing homes requires a knowledgeable nursing workforce. To test knowledge, 8 validated vignettes representing multifactorial fall causes were administered to 47 nurses from 3 nursing homes. Although licensed practical nurses scored higher than registered nurses in individual categories of falls, when we computed the average score of all 8 categories between groups of registered nurses and licensed practical nurses, registered nurses scored higher (F = 4.106; P < .05) in identifying 8 causal reasons for older adults to fall.


The disparity change score: a new methodology to examine health disparities in New Mexico.
One overarching goal of Healthy People 2010 is to eliminate health disparities. Reducing disparities improves the overall health status of a population but is a lengthy process. The disparity change score (DCS) is a method for tracking health disparities over time. Rates, rate ratios, and DCSs were calculated to track disparities during two time periods by sex, race/ethnicity, education, and income for key health indicators. Time periods were 10 years apart for all death indicators; length between time periods varied for other indicators depending on data collection systems. Sex-, race/ethnicity-, education-, and income-based disparities and disparity changes for New Mexico were identified. In general, males, American Indians, and those with the lowest income and education experienced the greatest health disparities. Five disparities that are worsening were identified for targeted interventions, mainly for males (firearm-related death and suicide) and American Indians (diabetes death and influenza/pneumonia death), but also for white non-Hispanics (drug-related death). Examining disparities at one point in time discounts disparity change over time. The DCS can help identify large disparities that are worsening and toward which resources for targeted interventions can be redirected. New Mexico should consider interventions for the five key disparities identified in this study.


Laparoscopic resection of chronic sigmoid diverticulitis with fistula.
A growing number of operations for sigmoid diverticulitis are being done laparoscopically. There is a paucity of data on the outcome of laparoscopy for sigmoid diverticulitis complicated by colonic fistula. The aim of this study was to compare the results of laparoscopic resection of sigmoid diverticulitis with and without colonic fistula. A retrospective review was conducted of all patients who underwent laparoscopic resection of sigmoid diverticulitis complicated by fistula at a single tertiary care institution over a 7-year period. Comparison was made with a group of patients who underwent resection for diverticulitis without fistula during the same study period. Forty-two patients were analyzed (group 1: diverticular fistula, group 2: no fistula). The median age was similar (49 vs. 50 years, P = .68). A chronic abscess was present in 24% of patients in group 1 and 10% in group 2 (P = .40). Fistula types were colovesical (71%), colovaginal (19%), and colocutaneous (10%). Operation types were sigmoidectomy (57% vs. 81%) and anterior resection (43% vs. 19%) in groups 1 and 2, respectively (P = .18). Ureteral catheters were used more frequently in group 1 (67% vs. 33% [P = .06]). No difference was noted in operative time, blood loss, conversion rate, length of stay, overall complications, wound infection rate, readmission rate, reoperation rate, and mortality. All patients healed without fistula recurrence. Patients with sigmoid diverticulitis with fistula can be successfully treated with laparoscopic excision, with similar outcomes for patients without fistula.


The perception of family function by adolescents with epilepsy in a rural nigerian community.
The family plays a significant role in epilepsy management in sub-Saharan Africa and how this role is perceived by persons with epilepsy could influence epilepsy outcomes. The objective of the study was to assess perception of family function by adolescents with epilepsy (AWE). The sociodemographic and epilepsy characteristics of AWE in a rural Nigerian community were assessed and the Family APGAR tool was used in assessing their perception of satisfaction with family functioning. Adolescents (n = 1708) constituted 26% of the community's population and 18 (10.5/1000) had epilepsy. The AWE age range was 11-19 years (mean 16.7 ± 2.6 years) with a male preponderance (15, 83.3%). The family was the only source of care. Family dysfunction (Family APGAR Score <7) was indicated by 15 (83.3%) of the AWE. The strongest perception of family function was in adaptability while the weakest was with growth. The indication of family dysfunction was significant (P<0.05) in the older (age 14-19 years) AWE when compared with the younger AWE (11-13 years) in the study. Most of the AWE indicated living in a dysfunctional family setting. The study highlights the need to address the role of the family in the provision of comprehensive epilepsy care.


Presence of interferon in acute- and convalescent-phase sera of humans with influenza or influenza-like illness of undetermined etiology.
Interferon (IFN;titer, greater than 10 units) was present in the acute-phase sera of 30 of 40 subjects with culture and/or serologically documented, naturally acquired influenza A/Brazil/78 (H1N1) and in the acute-phase sera of five of 27 subjects with an influenza-like illness of undetermined etiology. No statistical correlation existed between the quantity of IFN in acute-phase serum and the course of the clinical illness. Antiviral activity in all of nine acute-phase sera and three of four sera obtained on the fifth to seventh days of illness was neutralized to greater than 50% by antibody to virus-induced human leukocyte IFN (HuIFN-alpha). In contrast, none of five sera collected between 21 and 23 days after the onset of illness contained IFN sensitive to neutralization by antibody to HuIFN-alpha. Resistance of IFN in convalescent-phase sera to neutralization by antibody to HuIFN-alpha suggests that multiple IFN species may evolve during viral infections.


An integrated and multi-purpose microscope for the characterization of atomically thin optoelectronic devices.
Optoelectronic devices based on graphene and other two-dimensional (2D) materials, such as transition metal dichalcogenides (TMDs), are the focus of wide research interest. They can be the key to improving bandwidths in telecommunications, capacity in data storage, and new features in consumer electronics, safety devices, and medical equipment. The characterization of these emerging atomically thin materials and devices strongly relies on a set of measurements involving both optical and electronic instrumentation ranging from scanning photocurrent mapping to Raman and photoluminescence (PL) spectroscopy. Furthermore, proof-of-concept devices are usually fabricated from micro-meter size flakes, requiring microscopy techniques to characterize them. Current state-of-the-art commercial instruments offer the ability to characterize individual properties of these materials with no option for the in situ characterization of a wide enough range of complementary optical and electrical properties. Presently, the requirement to switch atomically thin materials from one system to another often radically affects the properties of these uniquely sensitive materials through atmospheric contamination. Here, we present an integrated, multi-purpose instrument dedicated to the optical and electrical characterization of devices based on 2D materials which is able to perform low frequency electrical measurements, scanning photocurrent mapping, and Raman, absorption, and PL spectroscopy in one single setup with full control over the polarization and wavelength of light. We characterize this apparatus by performing multiple measurements on graphene, transition metal dichalcogenides (TMDs), and Si. The performance and resolution of each individual measurement technique is found to be equivalent to that of commercially available instruments. Contrary to nowadays' commercial systems, a significant advantage of the developed instrument is that for the first time the integration of a wide range of complementary optoelectronic and spectroscopy characterization techniques is demonstrated in a single compact unit. Our design offers a versatile solution to face the challenges imposed by the advent of atomically thin materials in optoelectronic devices.


Comparison of IIF, ELISA and IgG avidity tests for the detection of anti-Toxoplasma antibodies in single serum sample from pregnant women.
A valid estimate of test efficiency is needed to choose adequate screening and detecting strategies in diagnosis of acute toxoplasmosis. Therefore, in the present study we evaluated the efficiency of diagnostic laboratory methods to detect anti-toxoplasma antibodies in single serum samples of pregnant women by indirect immunofluorescence test (IIF), enzyme-linked immunosorbent assay (ELISA) and IgG avidity tests in north-western Iran. In an analytical-descriptive study, during March 2010 to April 2013, 391 pregnant women aged 21 to 35 years who were referred by gynaecologists or infectious disease specialists for anti-toxoplasma antibody evaluation were studied. A peripheral blood sample was collected from individuals and serum was prepared immediately for anti-toxoplasma antibody evaluation by IIF, ELISA and IgG avidity tests. ELISA and IgG avidity tests were used as gold standard. Evaluation of anti-toxoplasma antibodies by IIF revealed that 280 cases (71.61%) were seropositive and 111 (28.38%) seronegative, while evaluation by ELISA revealed that 267 cases (68.28%) were seropositive and 124 (31.70%) seronegative; 65 (16.62%) were IgM positive by both IIF and ELISA tests. There were 45 (69.23%) and 7 (10.76%) IgM positive suspected cases respectively in IIF and ELISA confirmed by the IgG avidity test for recent toxoplasmosis. This study highlights how to manage and evaluate pregnant women who are suspected to be infected with toxoplasmosis by using diagnostic tests, especially in a single serum sample indication.


Chronicles of a reductase: Biochemistry, genetics and physio-pathological role of GSNOR.
S-nitrosylation is a major redox posttranslational modification involved in cell signaling. The steady state concentration of S-nitrosylated proteins depends on the balance between the relative ability to generate nitric oxide (NO) via NO synthase and to reduce nitrosothiols by denitrosylases. Numerous works have been published in last decades regarding the role of NO and S-nitrosylation in the regulation of protein structure and function, and in driving cellular activities in vertebrates. Notwithstanding an increasing number of observations indicates that impairment of denitrosylation equally affects cellular homeostasis, there is still no report providing comprehensive knowledge on the impact that denitrosylation has on maintaining correct physiological processes and organ activities. Among denitrosylases, S-nitrosoglutathione reductase (GSNOR) represents the prototype enzyme to disclose how denitrosylation plays a crucial role in tuning NO-bioactivity and how much it deeply impacts on cell homeostasis and human patho-physiology. In this review we attempt to illustrate the history of GSNOR discovery and provide the evidence so far reported in support of GSNOR implications in development and human disease.


The Impact of CB1 Receptor on Nuclear Receptors in Skeletal Muscle Cells.
Cannabinoids are abundant signaling compounds; their influence predominantly arises via engagement with the principal two G-protein-coupled cannabinoid receptors, CB1 and CB2. One suggested theory is that cannabinoids regulate a variety of physiological processes within the cells of skeletal muscle. Earlier publications have indicated that expression of CB1 receptor mRNA and protein has been recognized within myotubes and tissues of skeletal muscle from both murines and humans, thus representing a potentially significant pathway which plays a role in the control of skeletal muscular activities. The part played by CB1 receptor activation or inhibition with respect to these functions and relevant to targets in the periphery, especially skeletal muscle, is not fully delineated. Thus, the aim of the current research was to explore the influence of CB1 receptor stimulation and inhibition on downstream signaling of the nuclear receptor, NR4A, which regulates the immediate impacts of arachidonyl-2'-chloroethylamide (ACEA) and/or rimonabant in the cells of skeletal muscle. Murine L6 skeletal muscle cells were used in order to clarify additional possible molecular signaling pathways which contribute to alterations in the CB1 receptor. Skeletal muscle cells have often been used; it is well-documented that they express cannabinoid receptors. Quantitative real-time probe-based polymerase chain reaction (qRT-PCR) assays are deployed in order to assess the gene expression characteristics of CB1 receptor signaling. In the current work, it is demonstrated that skeletal muscle cells exhibit functional expression of CB1 receptors. This can be deduced from the qRT-PCR assays; triggering CB1 receptors amplifies both NR4A1 and NR4A3 mRNA gene expression. The impact of ACEA is inhibited by the selective CB1 receptor antagonist, rimonabant. The present research demonstrated that 10 nM of ACEA notably amplified mRNA gene expression of NR4A1 and NR4A3; this effect was suppressed by the addition of 100 nM rimonabant. Furthermore, the CB1 receptor antagonist led to the downregulation of mRNA gene expression of NR4A1, NR4A2 and NR4A3. In conclusion, in skeletal muscle, CB1 receptors were recognized to be important moderators of NR4A1 and NR4A3 mRNA gene expression; these actions may have possible clinical benefits. Thus, in skeletal muscle cells, a possible physiological expression of CB1 receptors was identified. It is as yet unknown whether these CB1 receptors contribute to pathways underlying skeletal muscle biological function and disease processes. Further research is required to fully delineate their role(s).


Treatment of congenital liver cysts. A surgical technique tailored through a 35-year experience.
The most important aims of the treatment of CLC are long-term relief of symptoms and elimination of cysts. Treatment of choice is yet debated. Data of patients treated for CLC during a 35-years experience were retrospectively analyzed. Variables analyzed were: age, sex, hepatic cyst location, cyst diameter, symptoms, surgical procedure, short and long-term outcomes. We examined 49 consecutive patients treated for CLC (mean follow-up, 76 months). The study was divided into two periods: 1975-1999 and 2000-2010. Procedures performed in the first period were needle aspiration and sclerotherapy (n= 6), hepatic resections (9), cystojejunostomy (4), open unroofing (10), and laparoscopic unroofing (8). Omentopexy within the residual cystic cavity was associated with seven open and two laparoscopic unroofing cases. Rates of morbidity and recurrence were 23.5% and 44.1%, respectively. One patient died in the peri-operative period. Procedures performed in the second period were open unroofing (9), laparoscopic unroofing (5), and hepatic resection (1). Omentopexy was associated with all open procedures and two laparoscopic procedures. Overall morbidity in this group was 16.6%, and recurrence occurred in one patient (6.7%). Cyst unroofing and omentopexy is a safe and highly effective procedure for the treatment of CLC. Laparoscopy is confirmed as the procedure of choice except for cases in which the cysts are in the posterior right liver, where a wide mobilization of the liver is necessary.


Marfan's syndrome: a refractive challenge for optometrists.
We present an interesting case of a child with Marfan's syndrome with ectopia lentis, who was followed for five years. The changes in refractive and visual findings of this child during this period are discussed. The importance of careful oculo-visual examination and possible management options in such children are highlighted.


Rikkunshito for Preventing Chemotherapy-Induced Nausea and Vomiting in Lung Cancer Patients: Results from 2 Prospective, Randomized Phase 2 Trials.
The herbal medicine rikkunshito has the potential to improve chemotherapy-induced nausea and vomiting (CINV) by stimulating ghrelin secretion. We aimed to evaluate the efficacy and safety of rikkunshito in preventing CINV for patients with lung cancer. Two separate prospective, randomized, phase II parallel design studies were conducted in patients with lung cancer. Fifty-eight and sixty-two patients scheduled to receive highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC), respectively, were randomized 1:1 to receive either standard antiemetic therapy in accordance with international guidelines (S group) or standard antiemetic therapy plus oral rikkunshito (R group). The primary endpoint was overall complete response (CR)-that is, no emesis and rescue medication in the first 120 h post-chemotherapy. Secondary endpoints included CR in the acute (0-24 h) and delayed (>24-120 h) phases and safety. Fifty-seven patients (S group, 28; R group, 29) receiving HEC and sixty-two patients (S group, 30; R group, 32) receiving MEC with comparable characteristics were evaluated. The CR rates were similar across the S and R groups for the HEC study in the overall (67.9% vs. 62.1%), acute (96.4% vs. 89.6%), and delayed (67.9% vs. 62.1%) phases, respectively, and for the MEC study in the overall (83.3% vs. 84.4%), acute (100% vs. 100%), and delayed (83.3% vs. 84.4%) phases, respectively. No severe adverse events were observed. Although rikkunshito was well tolerated, it did not demonstrate an additional preventative effect against CINV in lung cancer patients receiving HEC or MEC. Clinical Trial Registry Information: This study is registered with the University Hospital Medical Information Network (UMIN) Clinical Trial Registry, identification numbers UMIN 000014239 and UMIN 000014240.


Cognitive and functional status predictors of delirium and delirium severity after coronary artery bypass graft surgery: an interim analysis of the Neuropsychiatric Outcomes After Heart Surgery study.
Cognitive and functional impairment increase risk for post-coronary artery bypass graft (CABG) surgery delirium (PCD), but how much impairment is necessary to increase PCD risk remains unclear. The Neuropsychiatric Outcomes After Heart Surgery (NOAHS) study is a prospective, observational cohort study of participants undergoing elective CABG surgery. Pre-operative cognitive and functional status based on Clinical Dementia Rating (CDR) scale and neuropsychological battery are assessed. We defined mild cognitive impairment (MCI) based on either (1) CDR global score 0.5 (CDR-MCI) or (2) performance 1.5 SD below population means on any cognitive domain on neurocognitive battery (MCI-NC). Delirium was assessed daily post-operative day 2 through discharge using the confusion assessment method (CAM) and delirium index (DI). We investigate whether MCI - either definition - predicts delirium or delirium severity. So far we have assessed 102 participants (mean age 65.1 ± 9; male: 75%) for PCD. Twenty six participants (25%) have MCI-CDR; 38 (62% of those completing neurocognitive testing) met MCI-NC criteria. Fourteen participants (14%) developed PCD. After adjusting for age, sex, comorbidity, and education, MCI-CDR, MMSE, and Lawton IADL score predicted PCD on logistic regression (OR: 5.6, 0.6, and 1.5, respectively); MCI-NC did not (OR [95% CI]: 11.8 [0.9, 151.4]). Using similarly adjusted linear regression, MCI-CDR, MCI-NC, CDR sum of boxes, MMSE, and Lawton IADL score predicted delirium severity (adjusted R(2): 0.26, 0.13, 0.21, 0.18, and 0.32, respectively). MCI predicts post-operative delirium and delirium severity, but MCI definition alters these relationships. Cognitive and functional impairment independently predict post-operative delirium and delirium severity.


Observed and Normative Discount Functions in Addiction and other Diseases.
The aim of this paper is to find a suitable discount function able to describe the progression of a certain addiction or disease under treatment as a discounting process. In effect, a certain indicator related to a disease decays over time in a manner which is mathematically similar to the way in which discounting has been modeled. We analyze the discount functions observed in experiments which study addictive and other problematic behaviors as well as some alternative hyperbola-like discount functions in order to fit the patience exhibited by the subject after receiving the treatment. Additionally, it has been experimentally found that people with addiction display high rates of discount (impatience) and preference reversals (dynamic inconsistency). This excessive discounting must be correctly modeled by a suitable discount function, otherwise, it can become a trans-disease process underlying addiction and other disorders. The (generalized) exponentiated hyperbolic discount function is proposed to describe the progression of a disease with respect to the treatment, since it maintains the property of inconsistency by exhibiting a decreasing discount rate after an initial period in which the opposite occurs.


Multifunctional Octamethyltetrasila[2.2]cyclophanes: Conformational Variations, Circularly Polarized Luminescence, and Organic Electroluminescence.
Both symmetrical and unsymmetrical cyclophanes containing disilane units, tetrasila[2.2]cyclophanes 1-9, were synthesized. The syn and anti conformations and the kinetics of inversion between two anti-isomers were investigated by X-ray diffraction and variable-temperature NMR analysis, respectively. The flipping motion of two aromatic rings was affected by the bulkiness of the aromatic moiety (1 vs 6), the phase (solid vs solution), and the inclusion by host molecules (1 vs 1⊂[Ag2L]2+). The photophysical, electrochemical, and structural properties of the compounds were thoroughly investigated. Unsymmetrical tetrasila[2.2]cyclophanes 5-8 displayed blue-green emission arising from intramolecular charge transfer. Compound 6 emitted a brilliant green light in the solid state under 365 nm irradiation and showed a higher fluorescence quantum yield in the solid state (Φ = 0.49) than in solution (Φ = 0.05). We also obtained planar chiral tetrasila[2.2]cyclophane 9, which showed interesting chiroptical properties, such as a circularly polarized luminescence (CPL) with a dissymmetry factor of |glum| = ca. 2 × 10-3 at 500 nm. Moreover, an organic green light-emitting diode that showed a maximum external quantum efficiency (ηext) of ca. 0.4% was fabricated by doping 4,4'-bis(2,2'-diphenylvinyl)-1,1'-biphenyl with 6.


Probe-based confocal laser endomicroscopy imaging of endobronchial hamartomas.
Probe-based confocal laser endomicroscopy (pCLE) is a new technique that can microscopically image the airways in vivo during ordinary flexible bronchoscope procedures. pCLE can visualize the basement membrane of the bronchial epithelium, allowing the study of the different changes in benign or malignant/premalignant bronchial lesions. We present 2 cases of pathology-proven endobronchial hamartoma diagnosed by biopsy which show characteristic images under pCLE examination. The tumor was removed in both cases by rigid bronchoscopy using a diathermy loop and a cryoprobe.


WIP1, a homeostatic regulator of the DNA damage response, is targeted by HIPK2 for phosphorylation and degradation.
WIP1 (wild-type p53-induced phosphatase 1) functions as a homeostatic regulator of the ataxia telangiectasia mutated (ATM)-mediated signaling pathway in response to ionizing radiation (IR). Here we identify homeodomain-interacting protein kinase 2 (HIPK2) as a protein kinase that targets WIP1 for phosphorylation and proteasomal degradation. In unstressed cells, WIP1 is constitutively phosphorylated by HIPK2 and maintained at a low level by proteasomal degradation. In response to IR, ATM-dependent AMPKα2-mediated HIPK2 phosphorylation promotes inhibition of WIP1 phosphorylation through dissociation of WIP1 from HIPK2, followed by stabilization of WIP1 for termination of the ATM-mediated double-strand break (DSB) signaling cascade. Notably, HIPK2 depletion impairs IR-induced γ-H2AX foci formation, cell-cycle checkpoint activation, and DNA repair signaling, and the survival rate of hipk2+/- mice upon γ-irradiation is markedly reduced compared to wild-type mice. Taken together, HIPK2 plays a critical role in the initiation of DSB repair signaling by controlling WIP1 levels in response to IR.


A study of the mechanism of lymphokine production and release.
The release of lymphokine, a "lymph node activating factor" is not accompanied by changes in the functions of lymphocytes bound on cell membrane, such as the capacity for E rosette formation, PHA responsiveness and induction of the transplantation reaction. Neither is it accompanied by nucleolar transformation which would suggest the changes in nucleolar RNA synthesis and protein synthesis. However, in mixed lymphocyte cultures from which the lymph node activating factor is released, the number of naked lymphocytes increases markedly.


Biodiversity of bacterial ecosystems in traditional Egyptian Domiati cheese.
Bacterial biodiversity occurring in traditional Egyptian soft Domiati cheese was studied by PCR-temporal temperature gel electrophoresis (TTGE) and PCR-denaturing gradient gel electrophoresis (DGGE). Bands were identified using a reference species database (J.-C. Ogier et al., Appl. Environ. Microbiol. 70:5628-5643, 2004); de novo bands having nonidentified migration patterns were identified by DNA sequencing. Results reveal a novel bacterial profile and extensive bacterial biodiversity in Domiati cheeses, as reflected by the numerous bands present in TTGE and DGGE patterns. The dominant lactic acid bacteria (LAB) identified were as follows: Leuconostoc mesenteroides, Lactococcus garvieae, Aerococcus viridans, Lactobacillus versmoldensis, Pediococcus inopinatus, and Lactococcus lactis. Frequent non-LAB species included numerous coagulase-negative staphylococci, Vibrio spp., Kocuria rhizophila, Kocuria kristinae, Kocuria halotolerans, Arthrobacter spp./Brachybacterium tyrofermentans. This is the first time that the majority of these species has been identified in Domiati cheese. Nearly all the dominant and frequent bacterial species are salt tolerant, and several correspond to known marine bacteria. As Domiati cheese contains 5.4 to 9.5% NaCl, we suggest that these bacteria are likely to have an important role in the ripening process. This first systematic study of the microbial composition of Domiati cheeses reveals great biodiversity and evokes a role for marine bacteria in determining cheese type.


Topographical distribution of the astrocytic lamellae in the hypothalamus.
The distribution of astrocytic lamellae in hamster hypothalamus was studied by electron microscopy. The astrocytic lamellae (AL) are laminar expansions of the larger astrocyte processes devoided of cell organelles. In this paper, we describe the stratified structures of astrocytic lamellae which are found according to the following patterns: surrounding neuronal somata or delimiting one soma from the other, somata from blood vessels or from neuropile. In addition, layers of astrocytic lamellae are found surrounding nervous processes, blood vessels and forming a part of the subpial layer, as well as delineating the synaptic endings. Therefore, the astrocytic lamellae form a network through the hypothalamic components. The functional significance of these structures is discussed in relation to the physiologic studies on astrocytic membranes, as a basis for the understanding of their role in neuron metabolism.


Cdc42 and ARP2/3-independent regulation of filopodia by an integral membrane lipid-phosphatase-related protein.
Filopodia are dynamic cell surface protrusions that are required for proper cellular development and function. We report that the integral membrane protein lipid-phosphatase-related protein 1 (LPR1) localizes to and promotes the formation of actin-rich, dynamic filopodia, both along the cell periphery and the dorsal cell surface. Regulation of filopodia by LPR1 was not mediated by cdc42 or Rif, and is independent of the Arp2/3 complex. We found that LPR1 can induce filopodia formation in the absence of the Ena/Vasp family of proteins, suggesting that these molecules are not essential for the development of the protrusions. Mutagenesis experiments identified residues and regions of LPR1 that are important for the induction of filopodia. RNA interference experiments in an ovarian epithelial cancer cell line demonstrated a role for LPR1 in the maintenance of filopodia-like membrane protrusions. These observations, and our finding that LPR1 is a not an active lipid phosphatase, suggest that LPR1 may be a novel integral membrane protein link between the actin core and the surrounding lipid layer of a nascent filopodium.


Molecular Ion Desorption from LiF(110) Surfaces by Positron Annihilation.
We have studied the desorption of positive ions from a LiF(110) crystal surface using positron and electron irradiation at 500 eV to examine the interaction between positrons and ionic crystals. Only monatomic ions, such as H^{+}, Li^{+}, and F^{+}, are detected under electron irradiation. However, positron irradiation leads to the significant desorption of ionic molecules, specifically, FH^{+} and F_{2}^{+}. Molecular ion yields are more sensitive to temperature than atomic ion yields. Based on the findings, we propose a desorption model in which positronic compounds are initially produced at the surface and subsequently desorbed as molecular ions via Auger decay following positron annihilation.


Prevalence of ischaemic heart disease, arterial hypertension and intermittent claudication, and distribution of risk factors among middle-aged men in Moscow and Berlin.
The initial examinations of prospective epidemiological studies of the same kind performed in random samples of 50-54 years old men from Moscow and Berlin showed the following prevalence rates (each first figure for Moscow, second for Berlin): ischaemic heart disease 14.4/13.6%, arterial hypertension 18.0/19.0%, intermittent claudication 6.9/3.4%, cigarette smoking 46.5/51.4%, overweight 22.9/21.9%, impaired glucose tolerance 36.6/42.5%. Hypercholesterolaemia (24.6/8.1%) was not comparable because different determination methods were used. In both population samples almost a half of IHD and 1/3-1/2 of hypertension cases were newly detected only by the study examinations. More than 80% of the 50-54 years old men showed the presence of one or more risk factors. The following significant relationships between disease groups and risk factors were found: for IHD, with hypertension, impaired glucose tolerance, and hypercholesterolaemia (Moscow only); for hypertension, with overweight, impaired glucose tolerance, and hypercholesterolaemia (Moscow only); for intermittent claudication, with cigarette smoking, impaired glucose tolerance, and hypercholesterolaemia (Moscow only). These comparative studies demonstrate the benefit and need of further common research and efforts for prevention and control of cardiovascular diseases.


The effect of electrical current on healing skin incision. An experimental study.
The effect of electrostimulation on healing of a 6 cm long incision on the dorsum of rats was investigated. Postoperative stimulation was given with direct current (DC) to ten rats, and with alternating current (AC) to ten. Non-stimulated controls were used for each group. The words were biomechanically and biochemically tested three days after the final stimulation. Both DC and AC stimulation caused significant increase of the collagen content around the incision line compared with controls, but the collagen increase did not affect the tensile strength or the energy absorption. Electrostimulation of short duration is concluded to have a minor but significant enhancing effect on the formation of collagen in clean surgical wounds, but no effect on mechanical wound strength in the early postoperative period.


Estimating parameters for probabilistic linkage of privacy-preserved datasets.
Probabilistic record linkage is a process used to bring together person-based records from within the same dataset (de-duplication) or from disparate datasets using pairwise comparisons and matching probabilities. The linkage strategy and associated match probabilities are often estimated through investigations into data quality and manual inspection. However, as privacy-preserved datasets comprise encrypted data, such methods are not possible. In this paper, we present a method for estimating the probabilities and threshold values for probabilistic privacy-preserved record linkage using Bloom filters. Our method was tested through a simulation study using synthetic data, followed by an application using real-world administrative data. Synthetic datasets were generated with error rates from zero to 20% error. Our method was used to estimate parameters (probabilities and thresholds) for de-duplication linkages. Linkage quality was determined by F-measure. Each dataset was privacy-preserved using separate Bloom filters for each field. Match probabilities were estimated using the expectation-maximisation (EM) algorithm on the privacy-preserved data. Threshold cut-off values were determined by an extension to the EM algorithm allowing linkage quality to be estimated for each possible threshold. De-duplication linkages of each privacy-preserved dataset were performed using both estimated and calculated probabilities. Linkage quality using the F-measure at the estimated threshold values was also compared to the highest F-measure. Three large administrative datasets were used to demonstrate the applicability of the probability and threshold estimation technique on real-world data. Linkage of the synthetic datasets using the estimated probabilities produced an F-measure that was comparable to the F-measure using calculated probabilities, even with up to 20% error. Linkage of the administrative datasets using estimated probabilities produced an F-measure that was higher than the F-measure using calculated probabilities. Further, the threshold estimation yielded results for F-measure that were only slightly below the highest possible for those probabilities. The method appears highly accurate across a spectrum of datasets with varying degrees of error. As there are few alternatives for parameter estimation, the approach is a major step towards providing a complete operational approach for probabilistic linkage of privacy-preserved datasets.


Stroke at high altitude: Indian experience.
Stroke is a common medical emergency. There is limited knowledge about stroke at high altitude. We present the clinical profile of 30 cases of stroke at high altitude seen at our center between November 1998 to July 2000. A detailed neurological and systemic examination was carried out. Cases were investigated with blood counts, lipid profile, cardiac evaluation, and CT scan/MRI. Coagulation parameters were studied in some cases. Strokes formed 13.7/1000 of hospital admissions from high altitude area, compared to 1.05/1000 in nonhigh altitude area. All our cases from high altitude area were males (serving soldiers of armed forces). Their mean high altitude stay was 10.2 months, and they were all located at heights greater than 4270 m. Age ranged from 22 to 48 years (mean 33.4 yr). Except for smoking (in four cases), they had no preexisting risk factors. Twenty-two cases were of ischemic stroke, 2 of intracerebral hemorrhage, 4 of TIA/RIND (transient ischemic attack/reversible ischemic neurological deficit), and 2 had cerebral venous thrombosis. Out of 30 cases, 28 were of "stroke in young" (<45 yr) and were compared with cases in the same age group from nonhigh altitude areas. Polycythemia with Hb ranging from 16.2 to 22 g.dL(-1) was seen in 21 of these 28 cases (75%). Protein C and S deficiency was found in 1 case in each group. CT scan showed massive infarcts involving at least 50% of one cerebral hemisphere in 12 cases. Multiple infarcts were seen in one case. Long-term stay at high altitude is associated with higher risk of stroke. Although all types of stroke were seen, ischemic stroke was the commonest. Massive infarcts were common. Polycythemia was an important risk factor.


Prophylaxis and treatment of HIV-1 infection in pregnancy: Swedish Recommendations 2007.
Prophylaxis and treatment with antiretroviral drugs, a consequent low viral load, and the use of elective Caesarean section, are factors that radically decrease the risk of HIV transmission from mother to child during pregnancy and delivery. The availability of new antiretroviral drugs, updated general treatment guidelines and increasing knowledge of the importance of drug resistance, have necessitated recurrent revisions of the recommendations for 'Prophylaxis and treatment of HIV-1 infection in pregnancy'. For these reasons, The Swedish Reference Group for Antiviral Therapy (RAV) has, at an expert meeting on May 4, 2007, once more updated the treatment recommendations of 1999, 2002 and 2005, which were defined in cooperation with the Swedish Medical Products Agency (Läkemedelsverket). This new text takes the recently updated general HIV treatment recommendations into account. Furthermore, the very low risk of HIV transmission when the mother is treated with combination antiretroviral therapy, has undetectable levels of viraemia and no obstetric risk factors, has been considered in the recommendations concerning the mode of delivery. Finally, the recommendations for monitoring of infants born to HIV-infected mothers have been modified. The recommendations are evidence graded in accordance with the Oxford Centre for Evidence Based Medicine, 2001 (see http://www.cebm.net/levels_of_evidence.asp#levels).


Aneuploidies level in sperm nuclei in patients with infertility.
Male infertility is a relevant social and medical problem. Male infertility is mostly caused by genetic disorders. The purpose of the study was to analyze the correlation of chromosome aberrations, as well as DNA fragmentation and various manifestations of spermatogenesis disorder. Sperm samples of 58 males with infertility and 23 conditionally healthy males were studied. All patients diagnosed with asthenozoospermia, teratozoospermia, oligoasthenozoospermia and oligoteratozoospermia underwent subsequent analysis of sperm DNA fragmentation. Sperm DNA fragmentation was examined with sperm chromatin dispersion test (sperm chromatin dispersion, Spermprocessor, India) with an Axioscope 40 fluorescent microscope. Fluorescence in situ hybridization with fluorescent probes (Vysis Multi Vysion PGT, Abbot Molecular) was used to study chromosome abnormalities in sperm nuclei with regard to X and Y chromosomes, as well as to chromosomes 18 and 21. It was found that the development of pathospermia was characterized by genetic discontinuity, which manifests as DNA fragmentation and disjunction of chromosomes in meiosis with spermatogenesis. It was also found that the prevailing type of pathospermia in men with infertility was oligozoospermia. In addition, this group also had the highest rate of numerical chromosome abnormalities. This was caused by the degeneration of spermatozoids with aneuploidies in chromosomes.


[Haptoglobin (HPA)-subtypes in Swiss populations].
A subtyping of the haptoglobins of thirteen small Swiss populations, who live in mountainous regions of the Alps, and four larger Swiss populations has been undertaken. The impact of population and sample size on allele frequencies is discussed.


The Use of Neodymium-Doped Yttrium Aluminum Garnet Laser for Treatment of Hypertrophic Port-Wine Stain.
Port-wine stains (also called nevus flammeus) are congenital malformations of the capillaries and postcapillary venules. They occur in 0.1-2% of newborns without sex predilection. Although PWS lesions are flat early in life, with age, they become hypertrophic and darker. Pulsed dye laser therapy is the standard of care for treating these lesions, although other laser wavelengths have been utilized with varying degrees of success. We present the case of a gentleman with a hypertrophic PWS who had an excellent response to Nd:YAG laser treatment. The increased tissue penetration of longer laser wavelengths may be of benefit to patients with hypertrophic PWS, and further research into this concept is warranted.


[Dramatic alteration in optic nerve head topography after filtering surgery in an adult patient with traumatic glaucoma].
We treated an adult patient with traumatic glaucoma who exhibited dramatic elasticity in the topography of the optic nerve head, as shown in a Heidelberg Retina Tomograph (HRT) examination after filtering surgery. A 41-year-old man came to us with a right eye injury following an external blow. At the first examination, visual acuity was 0.4 (1.2) and intraocular pressure (IOP) was 11 mmHg in both eyes. Cells in the anterior chamber and angle dialysis were noted in all quadrants of the right eye, but there was no hyphema. Two weeks later, the patient returned to our hospital with pain in the right eye and a headache. Visual acuity in the right eye had decreased to 0.06 (0.1) and IOP was 50mmHg. A cilioconjunctival injection and corneal edema were observed. The patient was treated with medications, but IOP was uncontrollable and the optic disc cupping in the right eye was enlarged. Further, values for Cup Disc Area Ratio (C/D; 0.553) and Cup Volume (CV; 0.548) in the right eye were larger than those of the left (0.287 and 0.168, respectively) in an HRT examination. We performed a non-penetrating trabeculectomy 5 weeks after the injury. Two weeks after surgery, IOP was lowered to 7 mmHg, and C/D 0.122) and CV (0.062) were improved. Six months after the procedure, C/D (0.304) and CV (0.202) were nearly the same as those of the left eye (0.292 and 0.144). Although the duration of high IOP was short, high elasticity in the optic disc morphology of this adult case was shown quantitatively in an HRT examination.


Scanning electron microscopy of piliated Neisseria gonorrhoeae processed with hexamethyldisilazane.
Piliated Neisseria gonorrhoeae are virulent and attach readily to some human mucosal cells. The study of interactions between piliated Neisseria gonorrhoeae and surface structures of eukaryotic cells in tissue culture requires consistent high resolution imaging in scanning electron microscopy (SEM). The combination of the fixatives glutaraldehyde, osmium, tannic acid, and uranyl acetate improves preservation of pili and other delicate structures. Following the critical point drying (CPD) process, pili bundles remained intact, but charging produced image distortion in most of the specimens. The use of hexamethyldisilazane (HMDS) with air drying substantially reduced charging and image distortion. Less contrast and greater resolution of pili bundles and surface structures of bacteria or tissue culture cells were obtained at magnifications of 10,000 or higher. As an alternative to CPD, HMDS processing of cell culture monolayers was simple and was more efficient when a large number of samples was processed.


Mediastinal cystic lymphangioma in a patient with situs inversus totalis.
We present a case of cystic lymphangioma of the mediastinum complicated with situs inversus totalis. The 70-year-old man underwent thoracoscopic resection of a mediastinal cystic tumor, which was diagnosed as cystic lymphangioma. Cystic lymphangiomas are congenital cystic abnormalities of the lymphatic system. The head and neck area is often involved while the mediastinum is rarely affected. The rarity of this case is further attributed to the coexistence of situs inversus totalis.


Faecalibacterium prausnitzii and a Prebiotic Protect Intestinal Health in a Mouse Model of Antibiotic and Clostridium difficile Exposure.
Clostridium difficile (CD) infection (CDI) increases patient morbidity, mortality and healthcare costs. Antibiotic treatment induces gut dysbiosis and is both a major risk factor for CD colonization and treatment of CDI. Probiotics have been trialed to support commensal gut microbiota and reduce CDI. This study investigated commensal microbe Faecalibacterium prausnitzii (FP) and a prebiotic, both known to yield butyrate and be anti-inflammatory and immunomodulatory, on CD colonization and gut integrity in mice. Mice were randomly grouped and supplemented daily with FP, prebiotic, FP + prebiotic, FP/prebiotic supernatant, or saline throughout the entire study. Following treatment with clindamycin for 3 days, mice were exposed to CD. Feces were collected at baseline, the day after antibiotic, and 1, 3, and 5 days after CD exposure and cultured for bacterial overgrowth and CD colonization. On days 1 and 5 after CD exposure, mice were randomly euthanized, and proximal colon was dissected for histological analysis and preparation of RNA for analysis of proinflammatory and anti-inflammatory cytokines. Although all mice exhibited bacterial overgrowth and CD colonization, bacterial burden resolved quicker in the FP + prebiotic group. This was associated with induction and resolution of innate immune responses, anion exchanger, and tight junction protein preservation in proximal colon. CD toxin virulence potential was questionable as expression of CD toxin B receptor was depleted in the FP + prebiotic group. Supplementation with anti-inflammatory butyrate-supporting commensal bacteria and prebiotic may support innate immune responses and minimize bacterial burden and negative effects during antibiotic and CD exposure.


Recovery of spontaneous breathing following neuromuscular blockade with atracurium.
Atracurium 0.3 mg kg-1 was given to two groups of patients to compare the recovery of spontaneous breathing with that of peripheral neuromuscular function. Anaesthesia was maintained in one group (n = 6) with an infusion of etomidate (mean flow rate 24 micrograms kg-1 min-1) and in the other group (n = 5) with 0.5% halothane. From the time of discontinuing ventilation, about 5 min after the reappearance of the tetanic response, spontaneous breathing returned in an average time of 135 s (range 18-300) in the patients given etomidate and in 68 s (range 0-123) in the patients who received halothane (ns). The duration of action of atracurium was not significantly prolonged by halothane, probably because of the low concentration used. Adequate recovery of respiratory muscle function occurred within 30 min of administration of atracurium at a time when there was less than 25% recovery of the tetanic response of the adductor pollicis muscle. It was concluded that recovery of the muscles of respiration from neuromuscular blockade by atracurium occurred more rapidly than recovery of the muscles of the hand, but an adequate tidal volume in the absence of other clinical signs should not be regarded as a reliable indicator of complete return of neuromuscular function.


Evaluating the performance of genomic prediction accounting for effects of single nucleotide polymorphism markers in reproductive traits of Japanese Black cattle.
We examined the prediction accuracies of genomic best linear unbiased prediction (GBLUP), various weighted GBLUP according to the degrees of marker effects (WGBLUP) and machine learning (ML) methods, and compared them with traditional BLUP for age at first calving (AFC), calving difficulty (CD), and gestation length in Japanese Black cattle. For WGBLUP, firstly, BayesC and FarmCPU were used to estimate marker effects. Then, we constructed three weighted genomic relationship matrices from information of estimated marker effects in the first step: absolute value of the estimated marker-effect WGBLUP, estimated marker-variance WGBLUP, and genomic-feature WGBLUP. For ML, we applied Gaussian kernel, random forest, extreme gradient boost, and support vector regression. We collected a total of 2583 animals having both phenotypic records and genotypes with 30,105 markers and 16,406 pedigree records. For AFC, prediction accuracies of WGBLUP methods using FarmCPU exceeded BLUP by 25.7%-39.5%. For CD, estimated marker-variance WGBLUP using BayesC achieved the highest prediction accuracy. Among ML methods, extreme gradient boost, support vector regression, and Gaussian kernel increased prediction accuracies by 28.4%, 19.0%, and 36.4% for AFC, CD, and gestation length compared with BLUP, respectively. Thus, prediction performance could be improved using suitable WGBLUP and ML methods according to target reproductive traits for the population used.


Ribotyping differentiates relapse from reinfection in the treatment failures of Escherichia coli urinary tract infections in children.
Analysis of restriction fragment-length polymorphism of ribosomal DNA regions (ribotypes) was used as an epidemiologic tool to compare 25 pre- and posttreatment strains obtained from 12 patients treated with either cefpodoxime proxetil or amoxicillin-clavulanic acid. Ribotyping is a promising method to differentiate relapse from reinfection in the treatment failures of Escherichia coli urinary tract infections.


Hepatitis B and asymptomatic malaria coinfection in Sub-Saharan African immigrants: epidemiological and clinical features of HBV infection.
Here, we conducted an epidemiological study of hepatitis B virus (HBV) mono-infected and asymptomatic malaria/HBV coinfected immigrants and further discussed the possibility of malaria disease modifying the clinical presentation of HBV infection. A total of 195 African immigrants were examined for HBV infection or coinfection with HBV and asymptomatic malaria. HBV infection was diagnosed using serological tests and confirmed by PCR; furthermore, we performed a pan-Plasmodium-specific-nucleic-acid-sequence-based-amplification (NASBA) assay to detect asymptomatic malaria infection. The stage/grade of the liver disease was determined using echotomography and elastometry. PCR-NASBA results confirmed that 62 of 195 subjects (31.8%) were positive for Plasmodium infection, whereas 41 of 195 subjects (21%) tested positive for HBV chronic hepatitis (HBV-DNA positive). Among the HBV-positive subjects, 26 (63.4%) of them were mono-infected patients (Group A), whereas 15 (36.6%) patients had HBV chronic hepatitis and asymptomatic malaria coinfections (Group B). The HBV-DNA median levels were 1.4×105IU/mL in HBV-mono-infected patients and 2.0×105IU/mL in coinfected patients. Echotomography and hepatic elastometry presented similar findings for both groups of patients. Coinfected patients seem to present with the same clinical symptoms of the liver disease as HBV mono-infected patients.


A systematic review and combined analysis of therapeutic drug monitoring studies for long-acting risperidone.
This systematic review of therapeutic drug monitoring (TDM) identifies three long-acting injectable (LAI) risperidone formulations. Areas covered: Limited data is available on two formulations (RBP-7000 and in Situ Microparticle), but 20 TDM articles on the microsphere formulation were found. Risperidone TDM includes the serum concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, used for calculating: 1) the risperidone/9-hydroxyrisperidone (R/9-OH-R) ratio (a measure of CYP2D6; values >1 are indicative of a CYP2D6 poor metabolizer) and 2) the total risperidone concentration-to-dose (C/D) ratio (a measure of risperidone clearance with a normal value around 7 in oral risperidone). The weighted mean R/9-OH-R ratio was 0.48 (approximately twice that of oral risperidone TDM) in a combined analysis from 329 patients in 6 risperidone LAI studies without major confounders. The total C/D ratios from 297 patients in 6 risperidone LAI studies ranged from 7.4 to 9.7 ng/ml/mg/day with a weighted mean of 8.8 ng/ml/mg/day. Expert commentary: Clinicians using TDM for risperidone LAI microsphere formulation need to: 1) consider steady state to be reached ≥ 6 weeks after the first injection, 2) pay attention to a) co-medications with inducers/inhibitors, b) severe inflammations/infections, and c) hepatic/renal impairment, and 3) use Castberg's recommendation to calculate risperidone dosing.


Neonatal sepsis and its associated factors among neonates admitted to the neonatal intensive care unit in Wachemo University Comprehensive Specialized Hospital, Southern Ethiopia, 2022.
Neonatal sepsis is a major public health problem worldwide. It is one of the leading causes of neonatal mortality and morbidity worldwide. The neonatal mortality rate is higher in developing countries, where the extent and causes of neonatal sepsis are not yet known. Neonatal sepsis is a leading cause of neonatal mortality in Ethiopia. As a result, this study aimed to assess the proportion and identify maternal and neonatal risk factors for neonatal sepsis among neonates admitted to the neonatal intensive care unit. An institutional-based cross-sectional study was conducted from May 2022 to July 2022 at the Wachemo University Comprehensive Specialized Teaching Hospital, Neonatal Intensive Care Unit, southern Ethiopia. A total of 205 neonates with indexed mothers participated in the study. Using a consecutive sampling technique, a structured, pretested questionnaire was used to collect data from the study subjects. Data were entered into EpiData Manager version 3.1 for Windows and then exported to SPSS version 22 for further data cleaning and analysis. Descriptive analyses were performed by using frequency, percentage, and summary statistics to describe the key variables. A multivariate regression model was used to identify factors associated with neonatal sepsis. Finally, statistical significance was declared at a p-value of less than 0.05, and an adjusted odds ratio (AOR) with a 95% confidence level was used to declare the variable's association with the outcome variable. The overall prevalence rate of neonatal sepsis was 39.5% (95% CI: 33.7-45.9). Multivariable analysis was performed by taking a variable that is statistically significant in bivariate logistic regression as a candidate variable. Multivariable model analysis showed that unmarried status AOR = 18.37 (95% CI: 1.56-216.14), maternal fever during delivery AOR = 4.74 (95% CI: 1.63-13.8), and premature rupture of membrane AOR = 7.53 (95% CI: 2.19-25.6) were variables that increased the odds of developing neonatal sepsis. The study's findings indicate that neonatal sepsis is highly prevalent. Unmarried maternal status, maternal fever during delivery, and premature rupture of the membrane were predictors of neonatal sepsis. Therefore, providing training for health workers and close monitoring and evaluation during obstetric and neonatal care are crucial to halt the occurrence of neonatal sepsis.


Contribution of initial median-nerve somatosensory evoked potentials and brainstem auditory evoked potentials to prediction of clinical outcome in cerebrovascular critical care patients: a statistical evaluation.
In a prospective study of 200 patients with cerebrovascular disease (48 intracerebral hemorrhages, [ICH]; 64 subarachnoid hemorrhages, [SAH]; 48 supratentorial and 40 infratentorial ischemic strokes), we assessed the individual and combined prognostic value of median-nerve somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) within 72 hours of admission. Clinical outcome was graded in three ranked categories according to a modified Glasgow Outcome Scale. Likewise, the initial SEP and BAEP findings were graded in a three-class score. In all groups, the SEP were significantly correlated with outcome (P < 0.01). Likewise, after partialling out the prognostic effect of SEP, the contingency between BAEP and outcome was statistically significant, except in ICH (P = 0.07). The contingencies of SEP and outcome in ICH and supratentorial infarcts were higher than the corresponding partial contingencies for BAEP, while the latter were higher in infratentorial infarction and SAH. Therefore, in all disease groups except for SAH, the multiple contingency coefficients ranging from 0.67 to 0.75 were statistically significant and greater than either simple or partial contingencies alone. The results of the two evoked potential modalities combined permit statistically significant superior prognostication in most cerebrovascular diseases when compared to those of either of the modalities alone.


Challenges in the humanized mouse model for cancer: A commentary.
The complexity of the tumor microenvironment has been a challenge for understanding the mechanisms of therapy resistance. The development of improved animal models that closely mimic human disease is key for understanding and treating diseases. Recently, a new humanized mouse model has been developed that enables the study of human immune cells in tumor host-cell interactions. In this commentary we highlight the critical aspects of mast cells in immune therapy resistance. These mast cells release cytokines that downmodulate HLA class I on the malignant cells making them inaccessible the cytotoxic activity of T cells.


A case of endometrial carcinoma arising in a 36-year-old woman with uterine atypical polypoid adenomyoma (APA).
Atypical polypoid adenomyomas are tumors of low malignant potential. We present a case of endometrial carcinoma arising in a 36-year-old woman with atypical polypoid adenomyoma. The diagnosis and treatment of such a tumor is discussed through an English literature review.


The correlation of clinical and chromosomal alterations of benign meningiomas and their recurrences.
Meningiomas (MGs) are the frequent benign intracranial tumors. Their complete removal does not always guarantee relapse-free survival. Recurrence-associated chromosomal anomalies in MGs haves been proposed as prognostic factors in addition to the World Health Organisation (WHO) grading, tumor size and resection rate. The aim of this study was to evaluate the frequency of deletions on chromosomes in sporadic MGs and to correlate them with the clinical findings and tumor behaviour. Along with survival, the tumor recurrence was the main endpoint. Chromosomal loss of heterozygosity (LOH) was studied. 46 benign MGs were subjected to the analysis, complete tumor resection was intended and no early mortalities were observed. Incomplete removal was related to parasagittal location and psammomatous hisptopathology (p<0.01). Chromosomal alterations were present in 82.6% of cases; LOH at 22q (67.4%) and 1p (34.8%) were the most frequent and associated with male sex (p=0.04). Molecular findings were not specific for any of the histopathologic grade. Tumor recurrence (14 of 46) correlated with tumor size (≥35mm), LOH at 1p, 14q, coexistence of LOH at 1p/14q, 10q/14q, 'complex karyotype' status (≥2 LOHs excluding 22q), patient age (younger <35), and Simpson grading of resection rate (≥3 of worse prognosis). The last 3 variables were independent significant prognostic factors in multivariate analysis and of the same importance in recurrence prediction (Receiver Operating Characteristic curves comparison p>0.05). Among the cases of recurrence, tumor progression was observed in 3 of 14. In 2 cases, LOH on 1p and/or coexistence of LOH 1p/14q correlated with anaplastic transformation.


Covalent Allosteric Inactivation of Protein Tyrosine Phosphatase 1B (PTP1B) by an Inhibitor-Electrophile Conjugate.
Protein tyrosine phosphatase 1B (PTP1B) is a validated drug target, but it has proven difficult to develop medicinally useful, reversible inhibitors of this enzyme. Here we explored covalent strategies for the inactivation of PTP1B using a conjugate composed of an active site-directed 5-aryl-1,2,5-thiadiazolidin-3-one 1,1-dioxide inhibitor connected via a short linker to an electrophilic α-bromoacetamide moiety. Inhibitor-electrophile conjugate 5a caused time-dependent loss of PTP1B activity consistent with a covalent inactivation mechanism. The inactivation occurred with a second-order rate constant of (1.7 ± 0.3) × 102 M-1 min-1. Mass spectrometric analysis of the inactivated enzyme indicated that the primary site of modification was C121, a residue distant from the active site. Previous work provided evidence that covalent modification of the allosteric residue C121 can cause inactivation of PTP1B [Hansen, S. K., Cancilla, M. T., Shiau, T. P., Kung, J., Chen, T., and Erlanson, D. A. (2005) Biochemistry 44, 7704-7712]. Overall, our results are consistent with an unusual enzyme inactivation process in which noncovalent binding of the inhibitor-electrophile conjugate to the active site of PTP1B protects the nucleophilic catalytic C215 residue from covalent modification, thus allowing inactivation of the enzyme via selective modification of allosteric residue C121.


Hairy cell leukemia-variant treated with 2-chlorodeoxyadenosine--a report of three cases.
Three patients with B-prolymphocytic variant of HCL (HCL-V) were treated with a chlorinated purine analogue, 2-chlorodeoxyadenosine, at a daily dosage of 0.12 mg/kg in 2-hour intravenous infusion for 5 consecutive days. Partial remission was achieved in only 1 patient, who relapsed after 6 months. Two other patients did not respond to the treatment. HCL-V is a distinct clinicopathological entity which seems to be resistant to various therapeutic modalities. However, further observations are necessary in order to establish the efficacy of 2-CdA in the treatment of HCL-V.


Tip-cell migration controls stalk-cell intercalation during Drosophila tracheal tube elongation.
Branching morphogenesis remodels epithelial tissues into tubular networks. This process is crucial to many organs, from the insect trachea to the vertebrate vasculature. Although Drosophila tracheal development has been well characterized morphologically and genetically, very little is known about the forces involved during morphogenesis. The repertoire of cell behaviors underlying tracheal primary branch remodeling is limited to cell migration, cell-shape changes, and stalk-cell intercalation (SCI), a process in which cells insert in between cells previously in contact with each other. Here, we identify the major forces that contribute to tracheal primary branch remodeling by using genetic and microsurgery experiments. As the tip cells migrate, they elongate the branches and create a tensile stress. This tensile stress triggers SCI, which, in turn, allows the branches to further elongate. The mechanism that we describe contrasts with "convergent extension by cell intercalation" acting during Drosophila germ band extension (GBE), where cell intercalation is the cause of epithelium elongation. Surprisingly, in tracheal branches, one or two leading cells produce enough mechanical power to intercalate many lagging cells. This may apply to other tubular networks.


High-Intensity Interval Training as a Tool for Counteracting Dyslipidemia in Women.
Sedentary overweight or obese adult (age<60 years) women, allocated in type 2 diabetes mellitus (T2DM, n=13), dyslipidemia alone (DYS, n=12), dyslipidemia associated with hyperglycaemia (DYSHG, N=12), or healthy control (CON, n=10) groups, had their lipid, glucose, blood pressure, endurance performance, and anthropometry variables assessed before and after 16 weeks of a thrice-weekly high-intensity interval training (HIIT) program. Triglycerides reduced significantly (P<0.05) in all groups, and high-density lipoprotein increased (P<0.01) in T2DM, DYS and DYSHG; however, low-density lipoprotein reduced (P<0.05) only in DYSHG, and total cholesterol reduced (P<0.01) only in DYS and DYSHG. Fasting glucose reduced (P<0.05) significantly in T2DM, DYS and DYSHG, but with higher decreases in T2DM and DYSHG. Blood pressure, endurance performance and body composition improved (P<0.05) in all groups. The HIIT program was effective for restoring lipid profile of DYS and DYSHG, and fasting glucose of DYSHG to levels similar to those of CON, with a weekly time commitment 25% to 56% lower than the minimum recommended in current exercise guidelines. These findings suggest that HIIT may be a time-efficient intervention for counteracting dyslipidemia.


Assessment of partial sequencing of the 65-kilodalton heat shock protein gene (hsp65) for routine identification of Mycobacterium species isolated from clinical sources.
We assessed the ability of an in-house database, consisting of 111 hsp65 sequences from putative and valid Mycobacterium species or described groups, to identify 689 mycobacterial clinical isolates from 35 species or groups. A preliminary assessment indicated that hsp65 sequencing confirmed the identification of 79.4% of the isolates from the 32 species examined, including all Mycobacterium tuberculosis complex isolates, all isolates from 13 other species, and 95.6% of all M. avium-M. intracellulare complex isolates. Identification discrepancies were most frequently encountered with isolates submitted as M. chelonae, M. fortuitum, M. gordonae, M. scrofulaceum, and M. terrae. Reexamination of isolates with discrepant identifications confirmed that hsp65 identifications were correct in a further 40 isolates. This brought the overall agreement between hsp65 sequencing and the other identification methods to 85.2%. The remaining 102 isolates had sequence matches below our acceptance criterion, had nondifferential sequence matches between two or more species, were identified by 16S rRNA sequencing as a putative taxonomic group not contained in our database, or were identified by hsp65 and 16S rRNA gene sequencing as a species not in our biochemical test database or had conflicting identifications. Therefore, to incorporate the unconfirmed isolates it was necessary to create 29 additional entries in our hsp65 identification database: 18 associated with valid species, 7 indicating unique sequences not associated with valid or putative species or groups, and 4 associated with unique, but currently described taxonomic groups. Confidence in the hsp65 sequence identification of a clinical isolate is best when sequence matches of 100% occur, but our data indicate that correct identifications can be confidently made when unambiguous matches exceeding 97% occur, but are dependent on the completeness of the database. Our study indicates that for hsp65 sequencing to be an effective means for identifying mycobacteria a comprehensive database must be constructed. hsp65 sequencing has the advantage of being more rapid and less expensive than biochemical test panels, uses a single set of reagents to identify both rapid- and slow-growing mycobacteria, and can provide a more definitive identification.


Inability to predict mammary tumorigenesis in strain A mice from presence of mammary tumor virus or antigen in the milk.
Strain A females were milked and their milk was tested for mammary tumor virus (MTV) by the hyperplastic alveolar nodule test and for MTV antigen by microimmunodiffusion. An attempt was made to correlate these results with later occurrence of mammary tumors in the females. There was not full agreement between the results of the test for the presence of the MTV and those of the test for MTV antigen, and from these results it was impossible to predict accurately whether a specific female would later develop a tumor. It is concluded that, in this strain, factors other than the MTV can be the determinant in whether the individual female will develop a tumor.


The roles of chronological age and time perspective in memory positivity.
The observation that older adults show enhanced cognition for emotionally positive information has been labeled the positivity effect (Reed, Chan, & Mikels, 2014). According to the Socioemotional Selectivity Theory (SST, Carstensen, 1991), a prominent lifespan development theory, cognition is strongly influenced by motivational goals, and these goals are impacted by subjective time perspective. Although the positivity effect is most commonly observed in older adults, as age usually co-varies with time perspective, the SST posits that time perspective, not age, is the key explanatory factor of positivity. We examined the effects of these predictors on positivity in an episodic memory task in younger and older adults and found that age, not time perspective, was a key predictor of memory positivity. Our results add to the growing literature that challenge the notion that time perspective is the driving force behind age-related differences in emotional processing and functioning.


Radiation dose to the human body from intravenously administered 75Se-sodium selenite.
The dose of radiation to the human body and some of its organs after intravenous administration of 75Se-sodium selenite for diagnostic purposes has been calculated on the basis of followup of 26 patients for as long as 517 days with measurements of: 1. The retention of 75Se in the whole body. 2. The retention of 75Se in the blood, liver, kidneys, ovaries, testicles, and hair. 3. The excretion of 75Se in urine and feces. Whole-body counting and profile scanning were done on the patients and samples of blood from different organs, urine, and feces were measured for radioactivity. The dose of radiation received was calculated for an average patient of 70 kg. These doses were found to be slightly higher than previously reported on a smaller number of patients and with a shorter follow-up. They were slightly lower than those from 75Se-methionine to the whole body but higher to the liver and kidneys. The margin of error in this investigation was estimated to be about 20% for the whole-body dose and probably higher for different organs, mostly due to the poorly known rate of retention of selenite in different organs.


The effect of state and local flavored cigar sales restrictions, on retail sales of large cigars, cigarillos and little cigars in Massachusetts, California, Illinois, and New York.
In 2009, the Family Smoking Prevention and Tobacco Control Act prohibited flavored cigarettes but allowed for flavored cigars. Since, there has been a 34% increase in youth cigar use and widened racial disparities. State and local jurisdictions have increasingly enacted flavored tobacco product sales restrictions. As more jurisdictions consider implementing flavor restrictions, it is important to understand their effect on tobacco markets that have high flavor proliferation, including the cigar market. This study uses data from Truth Initiative's flavor policy database and NielsenIQ retailer scanner for California, Illinois, Massachusetts, and New York. We use a three-way fixed-effect model to assess the impact of the percentage of the population covered by a flavored cigar sales restriction on per capita unit sales of cigars. We find that population coverage by cigar sales restrictions was significantly associated with decreases in per capita cigar sales. More specifically, a 25% increase in the percentage of the population covered by a flavored cigar sales restriction was associated with a decrease in per capita all cigar sales of 15-19%, 4-10% for large cigars, 17-21% for cigarillos, and 2-41% for little cigars. Flavored cigar sales restrictions are an effective policy to reduce per capita cigar sales. The Food and Drug Administration's proposed product standards would increase population covered by a flavored cigar sales restriction to 100%, leading to potential significant reductions in cigar sales, especially little cigar, and cigarillo sales. This may also substantially reduce youth cigar use and racial disparities in cigar use. In April 2022, the US Food and Drug Administration published a proposed rule to prohibit characterizing flavors in all cigars and menthol cigarettes. Besides this proposed rule, there has been little federal action to date to reduce sales of flavored cigars. However, as of March 31, 2022, Massachusetts and 333 localities across 10 states have enacted policies that restrict the sale of flavored cigars and other tobacco products. We find that population coverage by cigar sales restrictions is significantly associated with decreases in per capita cigar sales.


Autoantibodies to Synaptic Receptors and Neuronal Cell Surface Proteins in Autoimmune Diseases of the Central Nervous System.
Investigations in the last 10 years have revealed a new category of neurological diseases mediated by antibodies against cell surface and synaptic proteins. There are currently 16 such diseases all characterized by autoantibodies against neuronal proteins involved in synaptic signaling and plasticity. In clinical practice these findings have changed the diagnostic and treatment approach to potentially lethal, but now treatable, neurological and psychiatric syndromes previously considered idiopathic or not even suspected to be immune-mediated. Studies show that patients' antibodies can impair the surface dynamics of the target receptors eliminating them from synapses (e.g., NMDA receptor), block the function of the antigens without changing their synaptic density (e.g., GABAb receptor), interfere with synaptic protein-protein interactions (LGI1, Caspr2), alter synapse formation (e.g., neurexin-3α), or by unclear mechanisms associate to a new form of tauopathy (IgLON5). Here we first trace the process of discovery of these diseases, describing the triggers and symptoms related to each autoantigen, and then review in detail the structural and functional alterations caused by the autoantibodies with special emphasis in those (NMDA receptor, amphiphysin) that have been modeled in animals.


Occurrence of resveratrol and piceid in American and European hop cones.
The recent discovery in hops of trans-resveratrol and its glucoside, trans-piceid, both famous in wine for their potential role in the "French paradox", opens new doors to understanding hop health benefits. In the present work, trans-resveratrol and trans-piceid were quantified by HPLC-APCI-MS/MS in 40 American and European hop cone samples from harvests of 2004, 2005, and 2006. Their content varies greatly, in the range 0.5-12 mg/kg. All German varieties revealed low amounts of stilbenes. The highest concentrations were found in Cascade (2004) and Willamette (2004 and 2006), two American low-alpha-acid varieties. Yet, probably because trans-resveratrol is a phytoalexin, a strong influence of harvest year was also observed.


PEDOT-embellished Ti3C2Tx nanosheet supported Pt-Pd bimetallic nanoparticles as efficient and stable methanol oxidation electrocatalysts.
Exploiting high-efficiency and durable electrocatalysts toward the methanol oxidation reaction (MOR) is crucial for the advancement of direct methanol fuel cells (DMFCs). Herein, we demonstrate the loading of platinum-palladium bimetallic nanoparticles (Pt-Pd NPs) onto poly(3,4-ethylenedioxythiophene) (PEDOT)-embellished titanium carbide (Ti3C2Tx) nanosheets as the electrocatalyst (Ti3C2Tx/PEDOT/Pt-Pd) via a facile and rapid chemical reduction-assisted one-pot hydrothermal process. The structural and morphological analyses of Ti3C2Tx/PEDOT/Pt-Pd indicate that the three-dimensional (3D) hybrid structure formed between PEDOT and Ti3C2Tx provides a sizable active surface and more active sites, which enhances the homogeneous dispersion of the Pt-Pd NPs and facilitates mass transfer. The Schottky junctions formed between PEDOT and Pt-Pd NPs contribute to charge transfer. The electronic effects and synergistic interactions between the support and catalyst favor the electrocatalytic activity of the catalyst. The electrochemical test results reveal that the Ti3C2Tx/PEDOT/Pt-Pd catalyst has prominent electrocatalytic capability for the MOR. Compared with Ti3C2Tx/Pt-Pd and commercial Pt/C catalysts, the Ti3C2Tx/PEDOT/Pt-Pd catalyst has a larger electrochemical activity surface area (ECSA = 122 m2 g-1) and higher mass activity (MA = 1445.4 mA mg-1), as well as better CO tolerance and more reliable long-term durability (a peak current density retention of 71% after 5200 s).


[Value of radiological methods in the diagnosis of biliary diseases].
The modern cross-sectional radiological methods of ultrasound, computed tomography, and magnetic resonance imaging provide manifold possibilities for the diagnosis of inflammatory and tumorous diseases of the gallbladder and the bile ducts as well as stone-related diseases. The invasive methods for direct imaging of the bile ducts, such as endoscopic retrograde cholangiopancreatography, are mainly used within therapeutic concepts. According to the literature, ultrasound and magnetic resonance imaging show a sensitivity of up to 100% in the diagnosis of intra- and extrahepatic cholestasis, but concerning the diagnosis of the cause of cholestasis these methods are limited. Therefore, additional MRI sequences or computed tomography are necessary. Computed tomography is particularly efficient for the diagnosis of the biliary system and adjacent anatomical and pathological structures within the pre- and postoperative period.


Evaluating the Social Media Performance of Hospitals in Spain: A Longitudinal and Comparative Study.
Social media is changing the way in which citizens and health professionals communicate. Previous studies have assessed the use of Health 2.0 by hospitals, showing clear evidence of growth in recent years. In order to understand if this happens in Spain, it is necessary to assess the performance of health care institutions on the Internet social media using quantitative indicators. The study aimed to analyze how hospitals in Spain perform on the Internet and social media networks by determining quantitative indicators in 3 different dimensions: presence, use, and impact and assess these indicators on the 3 most commonly used social media - Facebook, Twitter, YouTube. Further, we aimed to find out if there was a difference between private and public hospitals in their use of the aforementioned social networks. The evolution of presence, use, and impact metrics is studied over the period 2011- 2015. The population studied accounts for all the hospitals listed in the National Hospitals Catalog (NHC). The percentage of hospitals having Facebook, Twitter, and YouTube profiles has been used to show the presence and evolution of hospitals on social media during this time. Usage was assessed by analyzing the content published on each social network. Impact evaluation was measured by analyzing the trend of subscribers for each social network. Statistical analysis was performed using a lognormal transformation and also using a nonparametric distribution, with the aim of comparing t student and Wilcoxon independence tests for the observed variables. From the 787 hospitals identified, 69.9% (550/787) had an institutional webpage and 34.2% (269/787) had at least one profile in one of the social networks (Facebook, Twitter, and YouTube) in December 2015. Hospitals' Internet presence has increased by more than 450.0% (787/172) and social media presence has increased ten times since 2011. Twitter is the preferred social network for public hospitals, whereas private hospitals showed better performance on Facebook and YouTube. The two-sided Wilcoxon test and t student test at a CI of 95% show that the use of Twitter distribution is higher (P<.001) for private and public hospitals in Spain, whereas other variables show a nonsignificant different distribution. The Internet presence of Spanish hospitals is high; however, their presence on the 3 main social networks is still not as high compared to that of hospitals in the United States and Western Europe. Public hospitals are found to be more active on Twitter, whereas private hospitals show better performance on Facebook and YouTube. This study suggests that hospitals, both public and private, should devote more effort to and be more aware of social media, with a clear strategy as to how they can foment new relationships with patients and citizens.


[Pain caused by breeding: definition, judgment, pathogenesis].
Special terms of the "German Animal Protection Law (section 11b)"and the "European Agreement for Protection of Domestic Animals" particularly "torture-breeding, genetic characteristics, well-being, soundness, pains, injuries and specific use" are commented. Examples of torture-breedings are discussed: Dog (Merle-faktor, brachycephalie, atrichosis), cat (Mans-factor, W-gene, folded-ears), birds (tuffs, ear-drops, tailesness, hypertrophy of bill-warts, abnormal position of tarsal-joints, hypertrophy of imposing behavior).


Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials.
The aim of this study was to examine whether albumin reduced mortality when employed for the resuscitation of adult patients with severe sepsis and septic shock compared with crystalloid by meta-analysis. We searched for and gathered data from MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials and Web of Science databases. Studies were eligible if they compared the effects of albumin versus crystalloid therapy on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Disagreements were resolved by discussion with other two reviewers until a consensus was achieved. Data including mortality, sample size of the patients with severe sepsis, sample size of the patients with septic shock and resuscitation endpoints were extracted. Data were analyzed by the methods recommended by the Cochrane Collaboration Review Manager 4.2 software. A total of 5,534 records were identified through the initial search. Five studies compared albumin with crystalloid. In total, 3,658 severe sepsis and 2,180 septic shock patients were included in the meta-analysis. The heterogeneity was determined to be non-significant (P = 0.86, I(2) = 0%). Compared with crystalloid, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin (odds ratio (OR) 0.88; 95% CI, 0.76 to 1.01; P = 0.08). However, the use of albumin for resuscitation significantly decreased 90-day mortality in septic shock patients (OR 0.81; 95% CI, 0.67 to 0.97; P = 0.03). Compared with saline, the use of albumin for resuscitation slightly improved outcome in severe sepsis patients (OR 0.81; 95% CI, 0.64 to 1.08; P = 0.09). In this meta-analysis, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin compared with crystalloid and saline. Moreover, the 90-day mortality of patients with septic shock decreased significantly.


The Effect of Pranayama Applied to Hemodialysis Patients on Fatigue: A Randomized Controlled Trial.
The present study was conducted to examine the effects of Pranayama applied to hemodialysis patients on fatigue. The study was completed with 91 patients, including Pranayama (n = 30), Relaxation (n = 30), and Control groups (n = 31). The patients in the Pranayama group applied the interventions 15 to 20 minutes every day, once a day, for a total of 3 months, and the patients in the relaxation practice group applied the interventions 15 to 20 minutes every day, once a day, for a total of 3 months. Before the study commenced, permission was obtained from health care institutions, the ethics committee, and the patients. The data were collected with a Questionnaire, Piper Fatigue Scale (PFS), visual analog scale, and Vital Findings Form. Piper Fatigue Scale consists of 4 subdimensions, the total score obtained from the scale varies between 0 and 10, and as the score increases, the level of fatigue also increases. It was found that the patients in the Pranayama Group had decreased PFS total and subdimension mean scores after the procedure (P < .05); however, no significant changes were detected in the PFS total and subdimension mean scores of the patients in the Relaxation and Control groups (P > .05). Although the decrease in the daily fatigue severity of the patients in the Pranayama group was at a statistically significant level (P < .05), no statistically significant changes were detected in the fatigue severity of the patients in the Relaxation and Control groups (P > .05). It was also found that the blood pressure values of the patients in the Pranayama and Relaxation groups decreased (P < .05). It was found in the present study that Pranayama reduced the fatigue levels of hemodialysis patients. In this respect, it is recommended to teach and apply Pranayama techniques to patients with the support of nurses.