Characteristics and current clinical practices of opioid treatment programs in the United States.
Given rising rates of opioid use disorder (OUD) and related consequences, opioid treatment programs (OTPs) can play a pivotal role in the U.S. opioid crisis. There is a paucity of recent research to guide how best to leverage OTPs in the opioid response. We conducted a national survey of U.S. OTPs using a 46-question electronic survey instrument covering three domains: 1) OTP characteristics; 2) services offered; and 3) current clinical practices. Descriptive statistics and multivariable logistic regression examined variables in these domains. Among responding OTPs, 32.4% reported using all three medications for OUD treatment; 95.8% used methadone, 61.8% used buprenorphine, and 43.9% used naltrexone. The mean (SD) number of patients currently receiving methadone was 383 (20.4), buprenorphine 51 (7.0), extended-release naltrexone 6 (1.0). Viral hepatitis testing was provided by 60.9% of OTPs, 15.3% provided hepatitis B vaccination, 14.9% provided hepatitis A vaccination, and 12.6% provided medication treatment for hepatitis C virus infection. HIV testing was provided by 60.7% of OTPs, 9.5% provided pre-exposure prophylaxis, and 8.4% provided medication treatment for HIV. OTP characteristics associated with using all three forms of medications for OUD included: providing medication for alcohol use disorder (aOR = 5.24, 95% CI:2.99-9.16), providing telemedicine services (aOR = 3.82, 95% CI:2.14-6.84), and directly providing naloxone to patients (aOR = 2.57, 95% CI:1.53-4.29). Multiple barriers to providing buprenorphine and extended-release naltrexone were identified. Efforts are needed to increase availability of all medications approved to treat OUD in OTPs, integrate infectious disease-related services, and expand the reach of OTPs in the U.S.


A basic study on sonoporation with microbubbles exposed to pulsed ultrasound.
Sonoporation is an ultrasound technique that enables large molecules that normally do not penetrate the cell membrane to pass through it. Recent studies show that pulsed ultrasound in the presence of microbubbles increases the permeability of the cell membrane. However, the mechanism and basic properties of this sonoporation remain unclear. We thus investigated the mechanism of generation and frequency of occurrence of sonoporation, as well as the repair of a cell membrane damaged by microbubbles. The spatial relationship between microbubbles and cells was observed microscopically when cells were sonicated with pulsed ultrasound. Effects of microbubbles on the cells were observed with a high-speed camera, and the ratio of cell membrane damage and repair was examined using fluorescent microscopy. Damage to the cell membrane, caused mainly by mechanical effects of the expansion and contraction of microbubbles, significantly increased the permeability of the cell membrane. The frequency of cell membrane damage was closely associated with the presence of microbubbles and increased with increase in acoustic pressure. The ratio of repair of damaged cells was about 70% during 3 min after a single shot of pulsed ultrasound, indicating that repair of damaged cell membranes requires little time. We examined the frequency of occurrence of cell membrane damage and repair in sonoporation using pulsed ultrasound and microbubbles. Our results should prove useful for improving pulsed-ultrasound sonoporation.


The complementary role of sequential 99mTc-MDP and 67Ga-citrate scanning in the diagnosis and follow-up of neuroblastoma.
Fourteen children with histopathologically confirmed neuroblastoma underwent 38 studies using 99mTc-methylene-diphosphonate (MDP) and galliumcitrate Ga67 whole-body scintigraphy during various stages of the disease. Ten patients (71%) showed 99mTc-MDP accumulation in the primary tumoral site, whereas 11 patients (78.6%) showed 67Ga concentration. In 12 patients (86%), at least one of these two radiopharmaceuticals concentrated in the primary tumor. Nine patients had osseous or extraosseous metastases. All of these metastases (100%) were positive on 99mTc-MDP scintigraphy. No 67Ga-citrate uptake was demonstrable in osseous metastases; only one extraosseous lung metastasis concentrated this radiopharmaceutical. 67Ga-citrate was superior to 99mTc-MDP with regard to accurately demonstrating the extent of primary tumors. Only 99mTc-MDP indicated the relationship of the tumor to the kidneys and neighbouring osseous structures, providing early screening of kidney compression and possible damage caused by the tumor. From these results, we found these two methods to be complementary for the diagnosis and follow-up of neuroblastoma; their combined use resulted in high diagnostic accuracy and a considerable gain of information. We therefore recommend sequential 99mTc-MDP and 67Ga-citrate scans for the diagnosis and evaluation of the primary tumor; periodic 99mTc-MDP whole-body scans should be used in the follow-up of treatment, and for discovering disease exacerbations and metastases.


Muscarine reduces inwardly rectifying potassium conductance in rat nucleus accumbens neurones.
1. Intracellular recordings were made from neurones in the nucleus accumbens in slices from the rat brain maintained in vitro. 2. Muscarine (1-100 microM) depolarized 101 of 107 neurones; this was associated with an increase in the input resistance. The potential change reversed polarity with conditioning hyperpolarization and the reversal potential was linearly related to the logarithm of the extracellular potassium concentration. 3. The depolarization caused by muscarine was not changed by tetrodotoxin (1 microM) or by a solution that contained lower levels of calcium (0.24 instead of 2.4 mM), higher levels of magnesium (5 instead of 1.2 mM) and cobalt (2 mM). 4. Muscarine caused an inward current and a decrease in slope conductance when applied to neurones voltage clamped near their resting potential (-82 mV). The current caused by muscarine reversed polarity at the potassium equilibrium potential. The current-voltage relation of the neurones between -60 and -120 mV was well fitted by assuming a voltage-independent potassium conductance and an inward rectifier potassium conductance; muscarine reduced predominantly the inward rectifier conductance. 5. Phorbol-12,13-diacetate (3 microM) and 5-hydroxytryptamine mimicked the action of muscarine. The inward currents caused by muscarine or 5-hydroxytryptamine were occluded by the inward current evoked by the phorbol ester. 6. The depolarization caused by muscarine was competitively antagonized by pirenzepine; the dissociation constant of 11 nM suggested involvement of the M1 receptor. 7. It is concluded that muscarine acts at M1 receptors to reduce the membrane potassium conductance and that activation of protein kinase C may be an intermediate step.


An investigation on removal of ciprofloxacin and norfloxacin by phycoremediation with an emphasis on acute toxicity and biochemical composition.
Ciprofloxacin (CIP) and norfloxacin (NOR) belong to the class of emerging contaminants that are frequently detected in the aquatic environment as a binary mixture, responsible for the development of antibiotic-resistant genes and antibiotic-resistant bacteria. This study aims to investigate five different algal species Chlorella vulgaris (Cv), Chlorella pyrenoidosa (Cp), Scenedesmus obliquus (So), Tetradesmus sp (T) and Monoraphidium sp (M) for their tolerance and removal of binary mixture. The effects on biochemical composition in the algal species concerning the binary mixture and its removal efficiency are first reported in this study. The acute toxicity (96 h EC50) values are in the order of So > Cp > T > M > Cv, Chlorella vulgaris is the most sensitive algal species with 17.73 ± 0.24 mg/L and Scenedesmus obliquus is the least sensitive algal species with 39.19 ± 0.79 mg/L. The removal efficiency of the binary mixture was found to be in the order of So > Cp > T > M > Cv, Scenedesmus obliquus removed CIP (52.4%) and NOR (87.5%) with biodegradation as the major contributing removal mechanism. Furthermore, less toxic biotransformed products were detected in Scenedesmus obliquus and the biochemical characterization revealed that the growth-stimulating effect is higher with lipid (35%), carbohydrate (18%), and protein (33%) providing an advantage in the production of valuable biomass.


The use of heart rate variability for the early detection of treatable complications after aneurysmal subarachnoid hemorrhage.
High-grade aneurysmal subarachnoid hemorrhage patients are monitored in the ICU for up to 21 days, as they are at risk for complications such as vasospasm of cerebral arteries, cardiac arrhythmias and neurogenic stress cardiomyopathy. The diagnosis of these treatable complications is often delayed by the limitations of monitoring capabilities. We applied computational analysis to a cohort of 24 aneurysmal subarachnoid hemorrhage patients, to identify heart rate variability and ECG frequency profiles that may be potential biomarkers of severe vasospasm, reversible cardiomyopathy and death.


LKB1 in Intestinal Epithelial Cells Regulates Bile Acid Metabolism by Modulating FGF15/19 Production.
Liver kinase B1 (LKB1) is a master upstream protein kinase involved in nutrient sensing and glucose and lipid metabolism in many tissues; however, its metabolic role in intestinal epithelial cells (IEC) remains unclear. In this study, we investigated the regulatory role of LKB1 on bile acid (BA) homeostasis. We generated mice with IEC-specific deletion of LKB1 (LKB1ΔIEC) and analyzed the characteristics of IEC development and BA level. In vitro assays with small interfering RNA, liquid chromatography/mass spectrometry, metagenomics, and RNA-sequencing were used to elucidate the regulatory mechanisms underlying perturbed BA homeostasis. LKB1 deletion resulted in abnormal differentiation of secretory cell lineages. Unexpectedly, BA pool size increased substantially in LKB1ΔIEC mice. A significant reduction of the farnesoid X receptor (FXR) target genes, including fibroblast growth factor 15/19 (FGF15/19), known to inhibit BA synthesis, was found in the small intestine (SI) ileum of LKB1ΔIEC mice. We observed that LKB1 depletion reduced FGF15/19 protein level in human IECs in vitro. Additionally, a lower abundance of bile salt hydrolase-producing bacteria and elevated levels of FXR antagonist (ie, T-βMCA) were observed in the SI of LKB1ΔIEC mice. Moreover, LKB1ΔIEC mice showed impaired conversion of retinol to retinoic acids in the SI ileum. Subsequently, vitamin A treatment failed to induce FGF15 production. Thus, LKB1ΔIEC mice fed with a high-fat diet showed improved glucose tolerance and increased energy expenditure. LKB1 in IECs manages BA homeostasis by controlling FGF15/19 production.


A comprehensive method to prevent top-coal spontaneous combustion utilizing dry ice as a fire extinguishing medium: test apparatus development and field application.
There is a high potential for coal spontaneous combustion (CSC) above the roof beams of supports during the mining-stopped period. Early detection of temperature abnormal zones and corresponding measures are necessary to prevent CSC. In this work, a top-coal temperature measurement method was proposed, combining the coal surface temperature detection and the drilling temperature observation. Furthermore, an apparatus was developed that dramatically increases the rate of dry ice sublimation, resulting in the rapid release of cryogenic carbon dioxide gas. The device utilizes water from firefighting pipes in underground coal mines as a heat source for dry ice sublimation without electrical energy and has been applied and validated taking Silaogou Coal Mine in China as a field test site. Specifically, we found that during the stoppage period, the coal above the supports near the air inlet tunnel is more likely to appear hot spots; the carbon dioxide gas generated by the dry ice phase change device can quickly reduce the hot spots temperature, and the coal temperature does not rebound after the gas injection is stopped. Based on the above analysis, this work can effectively prevent the early top-coal spontaneous combustion during the stop mining period.


Definition of false-positive reactions in screening for hepatitis C virus antibodies.
The rate of false-positive hepatitis C virus enzyme immunoassay results was determined to be at least 10% among 1,814 reactive serum samples based on (i) negative results in an independent confirmation assay, (ii) negative PCR results, and (iii) no patients developing clinical or biochemical signs of hepatitis during a 1-year follow-up.


Excitation functions for fast-neutron induced reactions on zinc.
Cross sections of the 64Zn(n, p)64Cu, natZn(n, x)67Cu, 66Zn(n, 2n)65Zn and 70Zn(n, 2n)69mZn reactions have been measured by using the activation technique at 14.0 MeV neutron energy. The neutrons were produced via the 3H(d, n)4He reaction. The present experimental data illustrated satisfactory agreement with most of the previously reported experimental data. Experimental data are compared with evaluated nuclear data of the CENDL-3.2, ENDF/B-VIII.0, JENDL-5, BROND-3.1 and JEFF-3.3 libraries. Besides, these excitation functions were calculated by using theoretical model of the TALYS-1.96 code from thresholds up to 20 MeV. A group set of parameters was obtained which better reproduce the experimental data than the default parameters.


Gene expression analysis at the onset of aposporous apomixis in Paspalum notatum.
Apomixis is a route of asexual reproduction through seeds, that progresses in the absence of meiosis and fertilization to generate maternal clonal progenies. Gametophytic apomicts are usually polyploid and probably arose from sexual ancestors through a limited number of mutations in the female reproductive pathway. A differential display analysis was carried out on immature inflorescences of sexual and apomictic tetraploid genotypes of Paspalum notatum, in order to identify genes associated with the emergence of apospory. Analysis of approximately 10,000 transcripts led to the identification of 94 high-quality differentially expressed sequences. Assembling analysis, plus validation, rendered 65 candidate unigenes, organized as 14 contigs and 51 singletons. Thirty-four unigenes were isolated from apomictic plants and 31 from sexual ones. A total of 45 (69.2%) unigenes were functionally categorized. While several of the differentially expressed sequences appeared to be components of an extracellular receptor kinase (ERK) signal transduction cascade, others seemed to participate in a variety of central cellular processes like cell-cycle control, protein turnover, intercellular signalling, transposon activity, transcriptional regulation and endoplasmic reticulum-mediated biosynthesis. In silico mapping revealed that a particular group of five genes silenced in apomictic plants clustered in a rice genomic area syntenic with the region governing apospory in Paspalum notatum and Brachiaria brizantha. Two of these genes mapped within the set of apo-homologues in P. notatum. Four genes previously reported to be controlled by ploidy were identified among those expressed differentially between apomictic and sexual plants. In situ hybridization experiments were performed for selected clones.


When resources are scarce, consider growing your own.
Many health care facilities have difficulty finding and hiring properly trained perioperative nurses. Educators who are trying to alleviate this problem should consider setting up their own programs to educate new RNs and experienced nurses from other health care areas into the perioperative arena. This article provides basic information about setting up a perioperative nursing education program, including how to select the participants and preceptors and how to structure the program.


Synthesis, biological activities and pharmacokinetic properties of new fluorinated derivatives of selective PDE4D inhibitors.
A new series of selective PDE4D inhibitors has been designed and synthesized by replacing 3-methoxy group with 3-difluoromethoxy isoster moiety in our previously reported cathecolic structures. All compounds showed a good PDE4D3 inhibitory activity, most of them being inactive toward other PDE4 isoforms (PDE4A4, PDE4B2 and PDE4C2). Compound 3b, chosen among the synthesized compounds as the most promising in terms of inhibitory activity, selectivity and safety, showed an improved pharmacokinetic profile compared to its non fluorinated analogue. Spontaneous locomotor activity, assessed in an open field apparatus, showed that, differently from rolipram and diazepam, selective PDE4D inhibitors, such as compounds 3b, 5b and 7b, did not affect locomotion, whereas compound 1b showed a tendency to reduce the distance traveled and to prolong the immobility period, possibly due to a poor selectivity.


Pepper fruit as a model to study the metabolism of antioxidants, ROS and RNS.
Pepper (Capsicum annuum L.) is the second worldwide most consumed vegetable nowadays, with southern European countries being among the major producer areas. Pepper fruits contain high levels of vitamins A and C (ascorbate) and low calories what makes this produce greatly appropriate for human diet. In fact, fruits have enormous interest from the culinary and gastronomic points of view and can be used as raw, canned, condiment and food colorant, among others. Ripening of pepper fruits, an ethylene-independent process in this plant species, is somehow modulated by nitric oxide (NO), and the profile of several reactive nitrogen species (RNS) could be used as an index of this physiological stage. Regarding to the antioxidants' metabolism in fruits [1,2], it has been hypothesized that ascorbate plays an important role as a redox buffer during the ripening process. Furthermore, the interplay among enzymatic antioxidants protects pepper fruits against damage promoted by chilling conditions. The oxidative metabolism of peroxisomes seems to also participate in the regulation of the ripening process of fruits.


Retracted: Order Management and Completion Date Prediction of Manufacturing Job-Shop Based on Deep Learning.
[This retracts the article DOI: 10.1155/2022/3458116.].


SIRT1-dependent mitochondrial biogenesis supports therapeutic effects of 4-butyl-polyhydroxybenzophenone compounds against NAFLD.
The mitochondria have been identified as key targets in nonalcoholic fatty liver disease (NAFLD), one of the most prevalent chronic liver damage diseases globally. Meanwhile, the biological information analysis in this study revealed that SIRT1, PPARG, PPARA, and PPARGC1A (mitochondrial biogenesis-related proteins) were NAFLD therapeutic targets. Therefore, the design and synthesis of targeted drugs that promote mitochondrial biogenesis and improve mitochondrial function are particularly important for NAFLD treatment. Recently, we introduced butyls, hydroxyls, and halogens to benzophenone and synthesized a series of NAFLD-related 4-butylpolyhydroxybenzophenone compounds, aiming at investigating the hepatoprotective activity from the aspect of mitochondrial biogenesis. The structure-activity relationship demonstrated that hydroxyl and ketone groups were active groups interacting with mitochondrial biogenesis proteins (SIRT1 and PGC1α), and the activity was stronger when the o-hydroxyl group was present on the benzene ring. In contrast, the activity was little affected by the presence of the p-hydroxyl group, m-hydroxyl group, butyl group type, or halogen. In addition, in vitro studies confirmed that these compounds could directly bind to SIRT1 and PGC1α, markedly promote their interaction, significantly increase the expression of proteins and genes related to mitochondrial biogenesis (SIRT1, PGC1α, NRF1, TFAM, COX1, and ND6) and subsequently ameliorate mitochondria dysfunction, which was evidenced by the decreased ROS, upregulated ATP production, increased MMP, and enhanced mitochondrial number. According to the outcomes of our in vitro and in vivo experiments, 4-butyl-polyhydroxybenzophenone compounds could also effectively reduce the formation of lipid droplets and liver injury index (ALT, AST, LDH, AKP, γ-GT, and GDH) and improve the level of antioxidant enzymes (GSH and SOD). Particularly, the treatment of these compounds after a high-fat diet could significantly reduce body weight, decrease liver coefficient, attenuate liver damage, and ameliorate lipid accumulation in rat liver, demonstrating their therapeutic effects on NAFLD. Mechanistically, 4-butyl-polyhydroxybenzophenone compounds promoted mitochondrial biogenesis and eventually prevented NAFLD liver injury by activating the PGC1α signaling pathway in a SIRT1-dependent manner, which was strongly supported by SIRT1 inhibitor EX527.


The Theiler's murine encephalomyelitis virus (TMEV) model for multiple sclerosis shows a strong influence of the murine equivalents of HLA-A, B, and C.
Following intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV), susceptible mouse strains develop a chronic demyelinating disease characterized histologically by mononuclear cell-rich infiltrates in the central nervous system (CNS). An immune-mediated basis for this disease is strongly supported by previous studies demonstrating a correlation between clinical disease susceptibility, the presence of particular H-2 region genotypes, and the development of chronically elevated levels of TMEV-specific, MHC class II-restricted delayed-type hypersensitivity (DTH). The present study compared disease susceptibility in (B10.S X SJL)F1 and (B10.S(26R) X SJL)F1 mice which differ only at the D region of the H-2 complex. The data conclusively demonstrates a major influence for homozygosity of H-2s alleles at the H-2D region (the murine equivalent of the human class I HLA-A, B, and C genes) in determining disease susceptibility, as measured by either clinical or histopathological endpoints. In addition, disease susceptibility strongly correlated with the development of high levels of TMEV-specific DTH in the susceptible (B10.S X SJL)F1 strain. However, disease susceptibility did not appear to correlate with TMEV titers in the CNS, TMEV-specific humoral (ELISA and neutralizing) immune responses, or virus-specific splenic T cell proliferative responses. These findings lend additional support to our hypothesis that CNS myelin damage is mediated by a TMEV-specific DTH response. The possible role of class I-restricted responses in the demyelinating process is discussed and murine TMEV-induced demyelinating disease is compared with experimental allergic encephalomyelitis as relevant animal models for human multiple sclerosis.


The epidemiology of cattle abortion in Algeria.
In Algeria, the epidemiology of cattle abortions is not well understood. Therefore, the present study aims to estimate the prevalence of abortion in 75 Algerian cattle herds and correlate its possible association with brucellosis positivity and some managerial risk factors. The cattle abortion herd prevalence was 41.33% [95% CI 30.16-52.5%]. As for brucellosis, the serological evidence of brucellosis exposure was observed in 9 out of 75 herds accounting for 12% [95% CI 4.65-19.35] herd seroprevalence. The risk factor analysis using the univariable analysis followed by multivariable logistic regression did confirm that brucellosis positivity (OR = 5.19), mixed herd (OR = 2.5), contact with other herd (OR = 2.91), presence of dog in the herd (OR = 2.89), imported cattle (OR = 1.91), and farmers with less than 2 years' experience (OR = 2.69) as risk factors for abortion in Algerian cattle herds. Targeting these factors using a comprehensive control measure is needed to improve animal welfare and reduce economic losses associated with abortion in dairy cattle.


Enhanced expression of NLRP3 inflammasome-related inflammation in peripheral blood mononuclear cells in Sjögren's syndrome.
The aim of this study was to identify the association of NLRP3 inflammasome-induced inflammation with disease activity and damage in Sjögren's syndrome. A total of 33 female patients with Sjögren's syndrome and 34 sex- and age-matched, healthy controls were consecutively enrolled. The mRNA expression levels of NLRP3, ASC, caspase-1, interleukin-1β (IL-1β), and IL-18 in peripheral blood mononuclear cells (PBMCs) were measured, as well as serum IL-1β and IL-18 protein expression levels. Protein levels for mature IL-1β (p17) and caspase-1 (p20) were analyzed by western blotting. The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and Sjögren's Syndrome Disease Damage Index (SSDDI) were also evaluated. Patients with Sjögren's syndrome group showed higher expression of mRNA IL-1β and IL-1β at the protein level than controls (p<0.001 of both). Enhanced expression of mature IL-1β (p17) and caspase-1 (p20) proteins in Sjögren's syndrome were noted, compared to controls. The mRNA levels of caspase-1 and ASC were significantly increased in patients with Sjögren's syndrome compared to controls (p=0.001 and p=0.002, respectively). Based on the SSDDI scores, patients with damage (SSDDI≥1) had higher IL-1β mRNA expression compared to patients without damage (SSDDI=0) (p=0.034). SSDDI scores were closely related with IL-18 protein levels (r=0.357, p=0.041). The levels of IL-1β mRNA and IL-1β protein were correlated with the mRNA level of NLRP3 (r=0.597, p<0.001 and r=0.502, p=0.003, respectively). IL-1β mRNA expression was responsible for the presence of damage for Sjögren's syndrome (p=0.034). This study confirmed that NLRP3 inflammasome-mediated inflammation might be implicated in the pathogenesis of Sjögren's syndrome.


Preliminary validation study of the Spanish version of the satisfaction with life scale in persons with multiple sclerosis.
To assess Life Satisfaction, using the Satisfaction with Life Scale (SWLS), and to analyze its psychometric properties in Multiple Sclerosis (MS). Persons with MS (n = 84) recruited at the MS Centre of Catalonia (Spain) completed a battery of subjective assessments including the SWLS, the World Health Organization Quality of Life instrument and disability module (WHOQOL-BREF, WHOQOL-DIS) and the Hospital Anxiety Depression Scale-Depression (HADS-D); sociodemographic and disability status data were also gathered. Psychometric properties of the SWLS were investigated using standard psychometric methods. Internal consistency (Cronbach's alpha coefficient) was 0.84. A factor analysis using a principal components method showed a one factor structure accounting for 62.6% of the variance. Statistically significant correlations were confirmed between SWLS with WHOQOL-BREF, WHOQOL-DIS and HADS-D. SWLS scores were significantly different between a priori defined groups: probable depressed versus nondepressed and participants perceiving a mild versus severe impact of disability on their lives. To the best of our knowledge, this study is the first to report on the psychometrics properties of the SWLS in persons with MS. It might be a valuable tool to use in appraising persons with MS through the continuum of care. The Spanish version of the Satisfaction with Life Scale (SWLS) is a reliable and valid instrument in Multiple Sclerosis (MS). The SWLS is able to discriminate between participants with low or high scores on depressive symptoms or disability impact on life. SWLS might be useful through the continuum of care in persons with MS, including Rehabilitation Services.


A case-control study of the association between socio-demographic, lifestyle and medical history factors and multiple sclerosis.
The etiology of multiple sclerosis (MS) remains poorly understood. Socio-demographic characteristics may play important roles in its development. In a case-control study of MS, a total of 200 newly diagnosed MS patients and 202 frequency age- and sex-matched controls were studied. A direct and significant association was observed between cigarette smoking and the risk of MS. Higher education seemed to reduce the risk of MS. Contact with cats was inversely associated with MS, particularly in males, whereas contact with caged birds increased the risk significantly, especially in females. A strong family aggregation of MS was observed among cases. A past history of trauma and eye problems appeared to pose a high risk of MS. Cases had a significant family history of eye problems, mumps, measles, rubella, cancer and auto-immune diseases. If smoking and history of certain infectious diseases increase the risk of MS significantly, they could be modified and avoided, thereby reducing the likelihood of being afflicted by MS.


Acute immune thrombocytopenic purpura in an adolescent with 2009 novel H1N1 influenza A virus infection.
Although both leukopenia and thrombocytopenia are not uncommon hematological findings among patients with novel 2009 H1N1 influenza virus infection, immune thrombocytopenic purpura has rarely been shown to be associated with this novel influenza A infection. Here, we describe a previously healthy adolescent who presented with fever, influenza-like symptoms and acute onset of generalized petechiae and active oral mucosa bleeding on the third day of his illness. Severe leukopenia and thrombocytopenia were found. There was neither malignancy nor blast cells found by bone marrow aspiration. Real-time reverse transcriptase polymerase chain reaction was positive for novel 2009 H1N1 influenza infection. Novel influenza-associated atypical immune thrombocytopenic purpura was diagnosed. The patient recovered uneventfully after oseltamivir and methylprednisolone therapy.


Survival of multiply-resistant Klebsiella aerogenes and other gram-negative bacilli on finger-tips.
The survival of various Gram-negative bacilli was evaluated by inoculating the finger-tips of volunteers and determining the number of recoverable organisms in finger washings taken at increasing time intervals up to 60 min. Three epidemic gentamicin-resistant multiply-resistant strains of Klebsiella aerogenes (capsular types K2, K16 and K21) survived better than Pseudomonas aeruginosa, Escherichia coli or non-epidemic antibiotic sensitive klebsiellae of corresponding capsular type. The survival of the epidemic klebsiellae was not altered by curing them of their resistance plasmids. Transfer of their plasmids to E. coli K12 and to sensitive non-epidemic strains of K. aerogenes of corresponding capsular type did not enhance the relatively poor survival of the recipients. We conclude that the enhanced survival on skin of multiply-resistant klebsiellae is not plasmid mediated but may well contribute to the transmissability of these organisms during hospital outbreaks especially when compared with E. coli and Ps. aeruginosa.


The MMPI and chronic pain: the diagnosis of psychogenic pain.
This study investigates the capacity of the MMPI to discriminate among groups of patients with different types of pain. When multivariate analysis of variance is used, the standard set of MMPI scales discriminates between acute pain and chronic pain but not between chronic pain of two different etiologies (surgical-iatrogenic vs. unknown). The three scales that discriminate acute from chronic pain patients are those in the "neurotic triad," Hs, D, and Hy. The possibility that the unknown pain etiology group could be broken down into psychogenic pain and undetected somatogenic pathology subgroups was explored using cluster analysis. This procedure did not yield any group of patients who could be identified as having chronic pain of psychogenic origin. These results suggest that the MMPI is not a reliable tool for the differential diagnosis of chronic pain. It appears, however, that patterns of findings are partly contingent on population characteristics. Researchers should be cautious about generalizing to populations other than those from which samples are drawn.


Spherical carrier amplification strategy for electrochemical immunosensor based on polystyrene-gold nanorods @L-cysteine/MoS2 for determination of tacrolimus.
A novel sensitive electrochemical immunosensor has been designed for determination of tacrolimus (Tac) based on spherical carrier amplification strategy. In this work, a spherical signal carrier was prepared by conjugating gold nanorods (AuNRs) functionalized L-cysteine (AuNRs@L-Cys) onto polystyrene nanoparticles (PS) to form a nanostructure, greatly increasing the amount of loaded capture antibodies. The PS was a stable spherical functional polymer with large specific surface area and was labeled with AuNRs@L-Cys via coupling reagent to increase active groups, biocompatibility and conductivity. The capture antibodies could be attached on the PS- AuNRs@L-Cys via linkage reagent glutaraldehyde (GA). Furthermore, single-layer molybdenum disulfide (MoS2) fixed by chitosan were utilized to construct the base of this immunosensor, increasing the carrying capacity and stability of the electrode. After electrochemical reduction, the conductivity and electron transfer rate of MoS2 were obviously improved, which offered a platform for this immunosensor and further amplified the signal. Under the optimized conditions, the proposed immunosensor revealed a linear Tac-concentration behavior from 1.0 to 30 ng mL-1 with a detection limit of 0.17 ng mL-1 (S/N = 3). The immunoassay was successfully applied to the quantification of Tac in serum samples with acceptable precision. The results indicated that a potentially analytical platform may be used to recognize the concentration of other drugs.


Insertional biceps tendinopathy palliated successfully with intra-articular triamcinolone acetonide injection in a dog: A case report.
This report describes a dog diagnosed with insertional biceps tendinopathy that was palliated with intra-articular triamcinolone acetonide injections. The patient was a 6-year-old spayed female Chihuahua dog that had left thoracic limb lameness for 3 months before presentation. On physical examination, moderate pain was elicited by performing the biceps test and isolated full elbow extension on the left thoracic limb. Gait analysis showed asymmetrical peak vertical force and vertical impulse between thoracic limbs. Computed tomography (CT) revealed enthesophyte formation on the ulnar tuberosity of the left elbow joint. Ultrasonography showed a heterogeneous fibre pattern at the biceps tendon insertion site on the left elbow joint. These findings confirmed insertional biceps tendinopathy based on physical examination, CT and ultrasonography results. The dog received an intra-articular triamcinolone acetonide injection with hyaluronic acid in the left elbow joint. Clinical signs improved after the first injection, including a range of motion, pain and gait. A second injection was given in the same manner because of recurring mild lameness 3 months later. No clinical signs were observed during the follow-up period.


Characterization of hematogenous cellular constituents of the murine decidua: a surface marker study.
Decidual tissue, which includes typical (stromal type) decidual cells as well as infiltrating leukocytes, appears to play a local immunoregulatory role in the maintenance of pregnancy in nature. The present study evaluated the contribution of numerous leukocyte subsets characterized on the basis of morphology combined with cell surface markers to the development of murine decidua during syngeneic (CBA female X CBA male) and allogeneic (CBA female X C57BL/6 male) pregnancy. Collagenase dispersed decidua were subjected to total and differential counts and cell surface labeling for a radioautographic identification of various markers: S-IgM on B cells, Thy-1 on T cells, neither marker on null lymphocytes, Lyt- (1 or 2 or 1,2) antigens on T cell subsets, Mac-1 and I-A on macrophages, using 125I-labeled monoclonal antibodies or a sandwich labeling with 125I-protein A. The total cellularity of decidua basalis showed a biphasic rise in both pregnancies, with peaks on day 11 and days 15 and 16, but the allopregnant decidua showed a higher accumulation of all cell types indicating that an allogeneic conceptus causes an augmented deciduogenesis. The number of decidual cells, the most frequent cell class, rose to a peak on day 11 followed by a decline possibly due to cell death. The number of lymphocytes, the next frequent cell class, showed a parallel pattern initially, followed by a sharp secondary rise on day 16. This rise may be due to a withdrawal of progesterone, an antiinflammatory hormone. Null cells predominated amongst decidual lymphocytes (45-80%), as well as in the progestational endometrium (53%), indicating a hormonal control of their accumulation. The frequency of B cells was low (10-13%) and T cells (25-45%) comparable to that in the blood, with Lyt-1 only class being the most common T cell subset. Allopregnant decidua also showed a late rise in the total number of Lyt-2 only cells which may have a suppressor function. Macrophages, the next common leukocyte class, all expressed Mac-1. Their number rose to a plateau by day 12, but at a higher level in allopregnancy. I-A (needed for antigen presentation) was expressed by an increasing proportion (5-60%) of macrophages with advancing gestation. These findings provide a basis for further functional studies.


First case of endometrial cancer after yolk sac tumor in a patient with Li-Fraumeni syndrome.
Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disease with high penetrance caused by a germline variant of TP53 gene. We report the first case of endometrial cancer after yolk sac tumor with LFS. The presented female patient underwent right adnexectomy at age 23 because of a yolk sac tumor of the ovary. At the age of 27, the patient was diagnosed with endometrial adenocarcinoma, received cytoreductive surgery and chemotherapy. Given that her personal cancer history along with a strong family history of cancer, her father passing away from lung cancer at age 48 and her grandmother dying of ovarian cancer at age 50, the patient was referred for genetic counseling and testing. Genetic screening revealed a heterozygous pathogenic TP53 c.844C > T, p.( R282 W) with NM_000546.5 variant, a class 5 (C5) variant. This is the first reported case of a yolk sac tumor accompanied by subsequent endometrial cancer that is associated with LFS. We reported a first case of an endometrial cancer after yolk sac tumor patient with a tumor family history of harboring the germline TP53 pathogenic variation which expanded types of tumor that can be presented in patients with LFS. This case highlights the importance of genetic testing for patients with malignant tumors, as well as patients with a family history of malignant tumors. And our case highlights the necessity of screening for gynecologic tumor in LFS patients.


Anticonvulsant drug-induced osteomalacia: alterations in mineral metabolism and response to vitamin D3 administration.
Parameters of mineral metabolism were examined in 6 patients with moderately severe anticonvulsant drug-induced osteomalacia. Compared to 15 matched controls, the patients exhibited significantly reduced serum calcium, inorganic phosphate, and 25-hydroxyvitamin D concentration, elevated serum alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) concentration, reduced intestinal 47Ca absorption, reduced urinary calcium and increased urinary hydroxyproline excretion, and reduced forearm bone mass. Intestinal absorption of vitamin D3 was normal. Following 4 months of treatment with vitamin D3 (4000 units/day), serum 25-OHD concentration was increased to 3 times mean normal values and all parameters except serum iPTH, urinary calcium excretion, and forearm bone mass were returned to levels not significantly different from normal. Serum iPTH concentration was reduced by 39% (P less than 0.05); 24-h urinary calcium excretion rose by 98% (P less than 0.001), and forearm bone mass increased by 5.6% (P less than 0.05). It is concluded that moderate-dose vitamin D3 supplementation is effective in normalizing parameters of mineral metabolism in this disorder, despite evidence of resistance to the biologic effects of vitamin D.


Pneumatic dilatation in achalasia under endoscopic guidance: correlation pre- and postdilatation by radionuclide scintiscan.
Pneumatic dilation of the lower esophageal sphincter was accomplished by endoscopic visualization and positioning of a modified polyurethane dilator (90 F diameter) without fluoroscopy in 17 consecutive patients with advanced symptomatic achalasia. All patients were monitored for completeness of dilation by pre- and postdilation radionuclide scintiscan. Despite advanced megaesophagus, prior dilatations, or complicating disease, all patients showed prompt relief of symptoms.


Abnormal distortion of aortic corevalve bioprosthesis with suicide left ventricle, aortic insufficiency, and severe mitral regurgitation during transcatheter aortic valve replacement.
We present a patient with critical degenerative aortic stenosis, mitral annular and aortomitral continuity calcification, and senile sigmoid septal hypertrophy who underwent transcatheter aortic valve replacement using the CoreValve bioprosthesis. Immediately after predilation of the aortic valve (18-mm balloon), the patient developed severe hypotension and dynamic left ventricular outflow tract (LVOT) obstruction with systolic anterior motion of the anterior mitral leaflet, causing severe mitral regurgitation. After deployment of a 26-mm bioprosthesis, a transesophageal echocardiogram and left ventriculogram showed that the frame of the bioprosthesis appeared distorted and underexpanded. On the mitral side of the aorta (side of the aortomitral curtain between 12:00 and 3:00, echo short axis view), we found moderate periprosthetic aortic insufficiency with worse mitral regurgitation. The left ventricle was small and hyperdynamic (ejection fraction >85%). The patient soon developed complete heart block, atrial fibrillation, and ventricular tachycardia. She was resuscitated with aggressive intravenous fluids, vasopressors, and an emergently placed atrioventricular sequential pacemaker. We postdilated the 26-mm bioprosthesis with a 22-mm Z-Med balloon and subsequently with a 25-mm balloon. Each balloon was inflated to its nominal volume and pressure and conformed the nitinol frame of the valve to the net circular shape and expected diameter. However, as soon as each balloon was deflated, the surrounding aortic root anatomy visibly recoiled and the frame returned to its smaller diameter with a distorted shape. A second 26-mm CoreValve bioprosthesis was then deployed in a "valve-in-valve" configuration. Soon after, the patient's hemodynamics improved, her clinical condition stabilized, and she completely recovered. © 2016 Wiley Periodicals, Inc.


Personality characteristics of alcoholics dropping out of treatment.
Twenty seven male alcoholics were prospectively studied to find out the characteristics of those who drop out soon after discharge from the hospital. Seven persons, failed to make a single visit over a six-month period, and were termed 'dropouts'.On admission, after detoxification, all 27 patients were individually administered, the following tests:(1) Bhatia's Performance Test of Intelligence(2) Multiphasic Questionnaire(3) Internal-External Locus of Control Scale and(4) 16 P. F. Questionnaire (Form C).Dropouts did not differ from the completers on any of the socio-demographic or clinical variables. Two personality characteristics significantly differentiated the dropouts from the completers.


Nerve growth factor antagonizes the neurotoxic action of capsaicin on primary sensory neurones.
The protein nerve growth factor (NGF) is a naturally occurring trophic substance for sympathetic neurones and for at least those primary sensory neurones containing substance P (refs 4-6). Thus retrogradely transported NGF increased substance P and protein content in corresponding dorsal root ganglia. Moreover, anti-NGF antibodies administered to newborn rats decreased substance P and somatostatin levels in dorsal root ganglia and dorsal spinal cord, suggesting an important role for NGF in the postnatal development of peptidergic sensory neurones. These neurones appear to be selectively affected by the neurotoxin capsaicin (8-methyl-N-vanillyl-6-nonenamide). Treatment of newborn rats with capsaicin led to degeneration of primary sensory neurones containing substance P, somatostatin, vasoactive intestinal polypeptide and cholecystokinin. The mechanism by which capsaicin evokes its neurotoxic effect is unknown. We report here that in newborn rats concomitant administration of NGF partially antagonized the deleterious effect of capsaicin on substance P-containing neurones in dorsal root ganglia as assessed by morphological and biochemical criteria. We conclude that capsaicin destroys the perikarya of primary sensory peptidergic neurones by interfering with the action of NGF, probably by blocking its retrograde axonal transport.


Management of complications of extensor tendon injuries.
Treatment goals for the management of extensor tendon injuries include restoration of function, minimizing disability, and decreasing the risk of complications. These goals can be achieved with an accurate understanding of the zone-specific concerns for extensor tendon injuries, early referral to hand therapy, and active communication between hand surgeons and therapists. This article reviews extensor tendon injuries by zone, outlines optimal management strategies that help prevent complications, and describes the treatment of these complications.


Phytochemicals and biological activities of mutamba (Guazuma ulmifolia Lam.): A review.
Guazuma ulmifolia Lam. (Malvaceae), popularly known as mutamba and guácimo, is a tree found in the Latina America, especially in Brazil and Mexico. Mutamba tree has been used as traditional medicine to treat several pathological conditions, such as diarrhoea, coughs, and gastrointestinal and cardiovascular disorders. Phytochemical studies on this plant have resulted in the discovery of secondary metabolites that have shown bioactivities, including antimicrobial, antiprotozoal, antioxidant, and antidiarrheal activities, and cardioprotective effect. The traditional uses of G. ulmifolia have been experimentally proved by in vitro and in vivo studies, in which its bioactivities were associated to its phytochemical composition, mainly proanthocyanidins dimer B and trimer C (condensed tannins). The current review assesses and summarizes the progress about the phytochemical and healthy properties of G. ulmifolia published until 2019. This review intends to present the current knowledge and perspectives about G. ulmifolia and its potential use as food and therapeutic plant.


The extensor mechanism of the knee.
Disorders related to the knee extensor mechanism are common and rarely require imaging. Non specific anterior knee pain, fracture, dislocation, overuse tendinopathy and chronic patellofemoral instability are the commonest conditions encountered. Imaging is used in acute trauma, and for the assessment of cases of anterior knee pain resistant to conservative measures. The role of the radiograph is now largely restricted to cases of suspected fracture. Ultrasound is the optimum technique for suspected tendon and bursal pathology and MRI is widely used for the assessment of dysplasia and instability of the patellofemoral joint, including acute dislocation.


QR code technology in individual identification training provides an introduction in hands-on forensic DNA genotyping to medical students.
Forensic biology is a subject in the field of forensic science that stresses practical teaching and training in laboratory skills. Visualization of deoxyribonucleic acid (DNA) profiles is important in individual identification and is easily performed by well-trained examiners. Therefore, developing a novel training project for obtaining individual DNA profiles can improve the quality of teaching for medical students or trainees. DNA profiles based on quick response (QR) codes can also be applied to practical teaching and operation training for individual identification. A novel training project was developed through an experimental course in forensic biology. Blood samples and buccal swabs with oral epithelial cells, as used in the forensic DNA laboratory, were obtained from medical students at Fujian Medical University. DNA was isolated, and a number of short tandem repeat (STR) loci were used as genetic markers to generate DNA profiles. The students converted DNA profiles and individual information into a QR code. The QR code could then be scanned by a mobile phone for consulting and retrieval. Gene identity cards with QR codes were produced and provided to every student. The participation rate and passing rate of students who participated in the novel training project were calculated and compared with those of students in the traditional experimental course, and a chi-square test was carried out by SPSS 23.0 software to evaluate the teaching effectiveness. p < 0.05 indicated significant differences. In addition, a survey was conducted to investigate the likelihood of using of gene identity cards with QR codes in the future. A total of 54 of 91 medical students who studied forensic biology participated in the novel training project in 2021. Only 31 of 78 students who studied forensic biology participated in the traditional experimental course in 2020. The participation rate in the novel training project was 24% higher than that of the traditional experimental course. The participants in the novel training project showed better performance in forensic biological handling techniques. The passing rate of the students in the forensic biology course with the novel training project was approximately 17% higher than that of the students in the former course. The participation rates and passing rates of the two groups were significantly different (χ = 6.452, p = 0.008 and χ = 11.043, p = 0.001). In the novel training project, all participants made 54 gene identity cards with QR codes. Furthermore, in the DNA profiles of four African students who participated, we found two rare alleles that were not discovered in Asians. The survey showed that the use of gene identity cards with QR codes was accepted by most participants, and the likelihood of future utilization was 78%. We established a novel training project to promote the learning activities of medical students in experimental forensic biology courses. The participants showed great interest in using gene identity cards with QR codes to store general individual identity information and DNA profiles. They also examined the genetic population differences between different races based on DNA profiles. Hence, the novel training project could be useful for training workshops, forensic experimental courses, and medical big data research.


3H-Apomorphine interactions with dopamine receptors in calf brain.
3H-apomorphine binds to membranes from areas of the corpus striatum and limbic system of calf brain saturable and with a drug specificity indicating that it labels dopamine receptors. In terms of drug specificity, log-logit displacement curve slopes and number of binding sites, 3H-apomorphine interacts with receptors in a manner more like 3H-dopamine than 3H-haloperidol. These properties of 3H-apomorphine binding are those of an apparently "pure" agonist in contrast to the partial agonist effects of apomorphine upon the dopamine-sensitive adenylate cyclase.


Screen-based digital learning methods in radiation oncology and medical education.
The field of radiation oncology is rapidly advancing through technological and biomedical innovation backed by robust research evidence. In addition, cancer professionals are notoriously time-poor, meaning there is a need for high quality, accessible and tailored oncological education programs. Digital learning (DL) is well-placed to cater to these needs, as it provides teaching options that can be delivered flexibly and on-demand from anywhere in the world. The evidence for usage of these techniques in medical education has expanded rapidly in recent years. However, there remains many reservations in the oncological community to adopting and developing DL, largely due to a poor familiarity with the pedagogical evidence base. This article will review the application of the screen-based DL tools that are at educators' disposal. It will summarize best-practice in developing tailored, made-for-screen videos, gamification, and infographics. It also reviews data behind the following practical tips of 1) strategically combining text with graphics to decrease cognitive load, 2) engaging users through use of interactive elements in digital content, and 3) maximizing impact through thoughtful organization of animations/images. Overall, the digital space evolving is well placed to cater to the evolving educational needs of oncology learners. This review and its practical tips aim to inspire further development in this arena, production of high-yield educational products, use of engaging delivery methods and programs that are tailored to individual learning needs.


Smartphone application for emergency signal detection.
Currently, a number of studies focus on the study and design of new healthcare technologies to improve elderly health and quality of life. Taking advantage of the popularity, portability, and inherent technology of smartphones, we present an emergency application for smartphones, designated as knock-to-panic (KTP). This innovative and novel system enables users to simply hit their devices in order to send an alarm signal to an emergency service. This application is a complete and autonomous emergency system, and can provide an economic, reliable, and unobtrusive method for elderly monitoring or safety protection. Moreover, the simple and fast activation of KTP makes it a viable and potentially superior alternative to traditional ambient assisted living emergency calls. Furthermore, KTP can be further extended to the general population as well and not just be limited for elderly persons. The proposed method is a threshold-based algorithm and is designed to require a low battery power consumption. The evaluation of the performance of the algorithm in collected data indicates that both sensitivity and specificity are above 90%.


Novel biomarkers in the prognosis of patients with atherosclerotic coronary artery disease.
Biomarkers have a variety of clinical applications in multiple stages of diagnosis and therapy. Troponin T and brain natriuretic peptide are the best-known in the cardiovascular field, but experimental studies have identified new biomarkers with potential clinical value. In this article, novel biomarkers of kidney injury are investigated in the context of their relationship with atherosclerotic coronary disease. This review was carried out through a search in the PubMed database using as keywords each biomarker to be studied with the descriptor (DECS/MeSH) "Myocardial Infarction", and the keywords "coronary" and "cardiovascular", using the Boolean operator "AND". After the selection, 24 articles published between 2003 and 2017 were identified for the review. Eight biomarkers were investigated: neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor 23 (FGF23), tissue inhibitor of metalloproteinase-2 (TIMP-2), syndecan-1, interleukin-6 (IL-6), galectin-3, and the vascular cell adhesion molecules ICAM-1 and VCAM-1. Most identified articles were experimental studies, studies on human subjects having few participants. There are several promising biomarkers in the setting of coronary disease. The main evidence available in the literature suggests that elevated NGAL levels are associated with better prognosis after cardiac arrest and with comorbid kidney injury; elevated FGF23 is associated with coronary artery disease severity; TIMP-2 protects against coronary artery disease; increased expression of syndecan-1 is observed in myocardial infarction (MI) and protects against an exacerbated inflammatory response; IL-6 is associated with atherosclerotic disease and major cardiovascular outcomes; galectin-3 correlates with adverse clinical events post-MI; and elevated ICAM-1/VCAM-1 levels are associated with risk of coronary disease. Further studies are required to better investigate the role of each of these biomarkers in both stable coronary disease and acute coronary syndrome.


Operative strategy can reduce the incidence of major bile duct injury in laparoscopic cholecystectomy.
Major bile duct injury (BDI) rates remain in the range of 0.3 to 0.5 per cent for laparoscopic cholecystectomy (LC). The dominant surgical technique worldwide continues to be the "infundibular" technique of dissection that was popularized in the early 1990s. Proponents of the "critical view of safety" (CV) technique have suggested that most of these injuries are avoidable. The objective of our study was to determine whether routine use of the CV technique reduced the observed/expected single-institution rate of major BDI over a 5-year period in a teaching hospital. All patients (n = 3042) who underwent LC for any indication at one institution over a 60-month period were identified by database search. Major BDI was identified by Common Procedural Terminology codes indicating operative repair and confirmed by review of medical records. One patient sustained a transection-excision of the common duct requiring hepaticoduodenostomy. Based on published data, the observed BDI rate was one in nine to one in 15 of the expected rate. This represents an order-of-magnitude improvement in the safety of LC at a single institution where the majority of cases were performed by residents. We suggest that the "critical view" technique should be widely adopted.


Creating the Coupled Band Gaps in Piezoelectric Composite Plates by Interconnected Electric Impedance.
In this paper, we investigate the coupled band gaps created by the locking phenomenon between the electric and flexural waves in piezoelectric composite plates. To do that, the distributed piezoelectric materials should be interconnected via a 'global' electric network rather than the respective 'local' impedance. Once the uncoupled electric wave has the same wavelength and opposite group velocity as the uncoupled flexural wave, the desired coupled band gap emerges. The Wave Finite Element Method (WFEM) is used to investigate the evolution of the coupled band gap with respect to propagation direction and electric parameters. Further, the bandwidth and directionality of the coupled band gap are compared with the LR and Bragg gaps. An indicator termed ratio of single wave (RSW) is proposed to determine the effective band gap for a given deformation (electric, flexural, etc.). The features of the coupled band gap are validated by a forced response analysis. We show that the coupled band gap, despite directional, can be much wider than the LR gap with the same overall inductance. This might lead to an alternative to adaptively create band gaps.


An investigation of the actions of the calcium entry facilitator Bay K 8644 on the rat vas deferens.
The pre- and postsynaptic actions of the calcium entry facilitator Bay K 8644 were investigated in the rat isolated vas deferens. Bay K 8644 had no presynaptic effect on adrenergic neurotransmission in the epididymal portion. Bay K 8644 and alpha 1-adrenoceptor agonists potentiated, and the calcium entry blocker nifedipine abolished, the non-adrenergic contraction to a single stimulus in prostatic portions. Bay K 8644 sensitised the prostatic portion to, but did not increase the maximum height of, spontaneous direct contractions produced by alpha-agonists.


A warning on the use of synthetic DNA primers for initiation of reverse transcription on RNA templates: unexpected initiation at a mismatched nucleotide.
A synthetic 13-mer oligodeoxynucleotide designed to specifically initiate on lactic dehydrogenase (LDH) mRNA was shown to prime with high efficiency the synthesis of DNA complementary to the last 133 nucleotides of mitochondrial 16S ribosomal RNA on a mouse liver total poly(A)+ RNA template. One especially interesting feature of this reaction was that reverse transcriptase has been able to initiate at the 3' terminal C residue of the primer despite the fact that it was facing an A. This observation therefore establishes the ability of reverse transcriptase to initiate directly on a mismatched nucleotide.


Gingival crevicular fluid levels of aspartate amino transferase, sulfide ions and N-benzoyl-DL-arginine-2-naphthylamide in diabetic patients with chronic periodontitis.
The aim of this study is to analyze the correlations between plaque index (PlI), gingival index (GI), probable pocket depth (PPD), clinical attachment level (CAL), aspartate aminotransferase (AST), N-benzoyl-DL-arginine-2-naphthylamide (BANA) and sulfide ion activity (SIA) of diabetic patients with chronic periodontitis with regard to disease activity detected by AST levels. A total of 95 sites from eight diabetic patients with chronic periodontitis and 74 sites from eight systemically healthy patients with chronic periodontitis were enrolled in the study. The patients had no history of periodontal treatment or any antibiotic therapy during the last 6 months and were nonsmokers. All the sites selected for the study had a CAL of at least 2 mm. Gingival crevicular fluid volumes (GCFV) were measured in all sites. According to the result of AST analysis, 45 sites were AST positive and 50 were AST negative in the diabetic group and 36 sites were AST positive and 38 were AST negative in the control group. There was a significant correlation between BANA hydrolysis and PPD in both diabetic and control groups, but no correlation between PPD and AST levels. A significant correlation was observed between AST-positive sites and GI, but not between GI and BANA hydrolysis. In both groups, the correlation between SIA and BANA hydrolysis was significant, but no correlation was revealed between SIA and AST levels in either diabetic or control groups. The GCF metabolites had significant correlations with periodontally diseased sites in patients with chronic periodontitis, whether diabetic or systemically healthy, and may help to confirm clinical findings.


[Resection of a mediastinal parathyroid adenoma by video-assisted thoracoscopy radio-guided by a gamma probe. A case report].
We present a case of primary hyperparathyroidism in a 47 year old woman. The pre-operative 99mTc-sestaMIBI scan detected a single parathyroid adenoma located in the anterior or medium mediastinum. Surgery was carried out following 99mTc-sestaMIBI administration and using gamma probe radio-guided video-assisted thoracoscopy. The aim of this case report is to present this technique that allows adenoma resection with minimally invasive surgery. A reduction of surgical complications and an increase in the probability of surgical success could be obtained.


Shisa6 traps AMPA receptors at postsynaptic sites and prevents their desensitization during synaptic activity.
Trafficking and biophysical properties of AMPA receptors (AMPARs) in the brain depend on interactions with associated proteins. We identify Shisa6, a single transmembrane protein, as a stable and directly interacting bona fide AMPAR auxiliary subunit. Shisa6 is enriched at hippocampal postsynaptic membranes and co-localizes with AMPARs. The Shisa6 C-terminus harbours a PDZ domain ligand that binds to PSD-95, constraining mobility of AMPARs in the plasma membrane and confining them to postsynaptic densities. Shisa6 expressed in HEK293 cells alters GluA1- and GluA2-mediated currents by prolonging decay times and decreasing the extent of AMPAR desensitization, while slowing the rate of recovery from desensitization. Using gene deletion, we show that Shisa6 increases rise and decay times of hippocampal CA1 miniature excitatory postsynaptic currents (mEPSCs). Shisa6-containing AMPARs show prominent sustained currents, indicating protection from full desensitization. Accordingly, Shisa6 prevents synaptically trapped AMPARs from depression at high-frequency synaptic transmission.


Variability in radiation dose and image quality: A comparison across fluoroscopy-system vendors, generations of equipment and institutions.
To evaluate differences in radiation dose and image quality across institutions, fluoroscope vendors and generations of fluoroscopes for pediatric cardiac catheterization. Increased recognition of the potentially harmful effects of ionizing radiation has spurred technological advances in fluoroscopes, as well as increased focus on optimizing fluoroscope performance. There is currently little understanding of variability in the dose-image quality relationship across institutions, fluoroscope vendor and/or generation of equipment. We evaluated latest generation fluoroscopes from Phillips, Siemens, GE, and Toshiba, and an older generation Phillips fluoroscope (release date 2003) at three different institutions. Radiation dose was measured using an anthropomorphic dose-assessment phantom with effective dose in mSv estimated from Monte Carlo simulations. Image quality phantom images were scored on a 12-point scale by three blinded reviewers. Fluoroscope effective doses ranged from 0.04 to 0.14 mSv/1,000 pulses for fluoroscopy with associated composite image quality scores ranging from 8.0 ± 0.6 to 10.4 ± 1.3. For cineangiography, effective doses ranged from 0.17 to 0.57 mSv/1,000 frames with image quality scores ranging from 10.1 ± 0.3 to 11.1 ± 0.3. There was modest correlation between effective dose and image quality (r = 0.67, P = 0.006). The older generation fluoroscope delivered consistently higher doses than the newer generation systems (2.3- to 3.5-fold higher for fluoroscopy; 1.1- to 3.4-fold higher for cineangiography) without appreciable differences in image quality. Technological advances have markedly improved fluoroscope performance. Comparing latest generation systems across vendors and institutions, we found variability in the dose-IQ relationship and speculate that this reflects both equipment and institutional optimization practices.


Quality of life and its relation with sleep habits of children with epilepsy from Eastern India.
Epilepsy is one of the most common chronic disorders of the central nervous system. The quality of life of children with epilepsy is influenced by various factors including their sleep. To assess the quality of life and sleep habits among children with epilepsy and to determine the association of QOL and sleep habits, with sociodemographic and clinical variables. A cross-sectional study was carried out among 50 epileptic children aged 4-18 years, recruited using a convenient sampling technique from the IPDs and OPDs of the Paediatrics department of a tertiary care hospital in Eastern India. The data were collected using QOLCE-16 and CSHQ from parents of children with epilepsy. The collected data were analyzed using descriptive and inferential statistics such as ANOVA and Pearson correlation test. The overall mean score of QOL was 50.78 ± 17.98, with the cognitive domain having the highest mean score of 65.50 ± 27.79 and the social domain having the lowest mean score of 29.87 ± 22.81. The overall mean sleep score was found to be 56.98 ± 8.13. Daytime sleepiness, parasomnias, and bedtime resistance were found to be frequent sleep problems in children with epilepsy. There was a significant negative correlation between QOL and sleep disturbances in children with epilepsy (r = -0.65, P ≤ 0.001). The QOL of children with epilepsy should be improved to reduce the effect of sleep problems. Epilepsy children should be treated appropriately with due focus on medication compliance as it was found to be one of the determinants in improving their QOL.


Disturbance of microsomal detoxication mechanisms in liver by chlorophenol pesticides.
The pesticide pentachlorophenol known as an uncoupler of mitochondrial oxidative phosphorylation was shown to disturb liver microsomal detoxication functions by a selective inhibition of the terminal oxygenation enzyme P-450. At lower concentrations the flavin moiety of this enzyme chain is not inhibited but rather is stimulated, whereby a qualitative shift in detoxication of aromatic amines from C-oxygenation to N-oxygenation is obtained. The effects were due to the pentachlorophenol itself and not to a metabolite. Similar effects of varying strength were also obtained with other chlorophenol pesticides; 2,4,di-, 2,4,6,-tri and 2,3,4,6-tetrachlorophenol, di- and hexachlorophen, tri- and nonachloro-2-hydroxydiphenyl ethers. The relevance of these findings to the possible synergistic influence of chlorophenols on the carcinogenic effects of polyaromatic amines and hydrocarbons is discussed.


Bioremediation of Per- and Poly-Fluoroalkyl Substances (PFAS) by Synechocystis sp. PCC 6803: A Chassis for a Synthetic Biology Approach.
One of the main concerns in industrialized countries is represented by per- and poly-fluoroalkyl substances (PFAS), persistent contaminants hardly to be dealt with by conventional wastewater treatment processes. Phyco-remediation was proposed as a green alternative method to treat wastewater. Synechocystis sp. PCC6803 is a unicellular photosynthetic organism candidate for bioremediation approaches based on synthetic biology, as it is able to survive in a wide range of polluted waters. In this work, we assessed the possibility of applying Synechocystis in PFAS-enriched waters, which was never reported in the previous literature. Respirometry was applied to evaluate short-term toxicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), which did not affect growth up to 0.5 and 4 mg L-1, respectively. Continuous and batch systems were used to assess the long-term effects, and no toxicity was highlighted for both compounds at quite high concentration (1 mg L-1). A partial removal was observed for PFOS and PFOA, (88% and 37%, with removal rates of about 0.15 and 0.36 mg L-1 d-1, respectively). Measurements in fractionated biomass suggested a role for Synechocystis in the sequestration of PFAS: PFOS is mainly internalized in the cell, while PFOA is somehow transformed by still unknown pathways. A preliminary bioinformatic search gave hints on transporters and enzymes possibly involved in such sequestration/transformation processes, opening the route to metabolic engineering in the perspective application of this cyanobacterium as a new phyco-remediation tool, based on synthetic biology.


Prospective evaluation of a composite scoring system for mammographically detected cytologically assessed impalpable breast abnormalities.
The aim of all breast screening programmes is a reduction in deaths from the disease. It is hoped that this can be achieved with minimal intervention in the patient cohort who do not have cancer. In this study we have assessed the efficacy of a combination of mammographic and cytological scoring systems in the evaluation of 208 women with screen-detected non-palpable breast lesions. All mammograms were scored 1-5 and those with a score of 3 or more required needle localization. A cytology score of 1 to 5 was generated for each patient according to a similar system and an aggregate score for each patient was achieved by the addition of the mammographic and cytology score. Ninety-three of the 208 patients had malignancy--the positive predictive value for mammography alone in this series was 45%. All 58 patients who had an aggregate score of 8 or greater had cancer. The 60 patients who had an aggregate score of 4 had benign disease on excision biopsy. We suggest that a 'wait and repeat mammogram' approach is appropriate in patients with grade 3 mammography and benign (grade 1) cytology. Patients with an intermediate aggregate score of 5-7 should have an excision biopsy and those with an aggregate score of 8 could have definitive surgery rather than excision biopsy. Application of this aggregate scoring technique would enhance the delivery of more appropriate surgery to a majority of patients with screen-detected breast abnormalities.


Necker cube reversal reduced by two dimensional spatial perceptual cue.
The influence of conceptualization of a specific two-dimensional perceptual cue on the perception of the reversible Necker cube pattern was investigated. It was found that it reduced markedly the spontaneous reversal rate.


High pressure treatment as a tool for engineering of enzymatic reactions in cellulosic fibres.
Ultrahigh hydrostatic pressure (UHP) was applied to enhance the enzymatic hydrolysis of xylan in cellulosic fibers. The pretreatment improved xylan accessibility in the fiber cell wall and a 5-10-fold increase in the initial hydrolysis rate of xylan by xylanase was observed when Eucalyptus globulus kraft bleached pulp was pretreated at hydrostatic pressures of 300-400 MPa for 15-45 min. The rate and the extent of hydrolysis can be controlled by varying the pressure and the exposure time of UHP treatment prior to enzymatic hydrolysis. Sequential UHP pretreatment and hydrolysis by xylanase disaggregated the hydrated cellulose fibrils and led to the gelation of cell wall regions accessible to enzymatic attack. UHP could therefore become a tool for the engineering of enzymatic reactions within cellulosic fibers to obtain products with tailored properties.


Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis.
Kaposi's sarcoma herpesvirus (KSHV) is an angiogenesis-inducing oncovirus whose ability to usurp the oxygen-sensing machinery is central to its oncogenicity. By upregulating the hypoxia-inducible factors (HIFs), KSHV reprograms infected cells to a hypoxia-like state, triggering angiogenesis. Here we identify a link between KSHV replicative biology and oncogenicity by showing that KSHV's ability to regulate HIF2α levels and localization to the endoplasmic reticulum (ER) in normoxia enables translation of viral lytic mRNAs through the HIF2α-regulated eIF4E2 translation-initiation complex. This mechanism of translation in infected cells is critical for lytic protein synthesis and contributes to KSHV-induced PDGFRA activation and VEGF secretion. Thus, KSHV regulation of the oxygen-sensing machinery allows virally infected cells to initiate translation via the mTOR-dependent eIF4E1 or the HIF2α-dependent, mTOR-independent, eIF4E2. This "translation initiation plasticity" (TRIP) is an oncoviral strategy used to optimize viral protein expression that links molecular strategies of viral replication to angiogenicity and oncogenesis.


Synthesis and spectroscopic behavior of highly luminescent Eu(3+)-dibenzoylmethanate (DBM) complexes with sulfoxide ligands.
In this paper the synthesis, characterization and photoluminescent behavior of the [RE(DBM)3L2] complexes (RE=Gd and Eu) with a variety of sulfoxide ligands; L=benzyl sulfoxide (DBSO), methyl sulfoxide (DMSO), phenyl sulfoxide (DPSO) and p-tolyl sulfoxide (PTSO) have been investigated in solid state. The emission spectra of the Eu(3+)-beta-diketonate complexes show characteristics narrow bands arising from the 5D0-->7F(J) (J=0-4) transitions, which are split according to the selection rule for C(n), C(nv) or C(s) site symmetries. The experimental Judd-Ofelt intensity parameters (Omega2 and Omega4), radiative (A(rad)) and non-radiative (A(nrad)) decay rates, and R02 for the europium complexes have been determined and compared. The highest value of Omega2 (61.9x10(-20)cm2) was obtained to the complex with PTSO ligand, indicating that Eu3+ ion is in the highly polarizable chemical environment. The higher values of the experimental quantum yield (q) and emission quantum efficiency of the emitter 5D0 level (eta) for the Eu-complexes with DMSO, DBSO and PTSO sulfoxides suggest that these complexes are promising Light Conversion Molecular Devices (LCMDs). The lower value of quantum yield (q=1%), for the hydrated complex [Eu(DBM)3H2O], indicates that the luminescence quenching occurs via multiphonon relaxation by coupling with the OH-oscillators from water molecule coordinated to rare earth ion. The pure red emission of the Eu-complexes has been confirmed by (x, y) color coordinates.


Electrodiagnostic evaluation of auditory function.
This article considers the types of deafness in small animals and how electrodiagnostic testing can aid in evaluating auditory dysfunction.


Hepatic enzyme decline after pediatric blunt trauma: a tool for timing child abuse?
Previous research in adult patients with blunt hepatic injuries has suggested a pattern of serum hepatic transaminase concentration decline. Evaluating this decline after pediatric blunt hepatic trauma could establish parameters for estimating the time of inflicted injuries. Deviation from a consistent transaminase resolution pattern could indicate a developing complication. Retrospective review of pediatric patients with injuries including blunt liver trauma admitted to one of four urban level 1 trauma centers from 1990 to 2000. Cases were excluded for shock, death within 48 h, complications, or inability to determine injury time. Transaminase concentration decline was modeled by individual patients, by injury grade, and as a ratio with regard to injury time. One hundred and seventy-six patients met inclusion criteria. The rate of aspartate aminotransferase (AST) clearance changed significantly over time. Alanine aminotransferase (ALT) fell more slowly. Of the 118 patients who had multiple measurements of AST, for 112 (95%) the first concentration obtained was the highest. When ALT was greater than AST, the injury was older than 12h (97% specificity (95% CI, 95-99%), sensitivity 42% (95% CI, 33-50%)). Patients with enzymes that rose after 14 h post-injury were more likely to develop complications (RR=24, 95% CI 10-58). Hepatic transaminases rise rapidly after uncomplicated blunt liver injury, then fall predictably. Persistently stable or increasing concentrations may indicate complications. ALT>AST indicates subacute injury.


Myofascial trigger points alter the modular control during the execution of a reaching task: a pilot study.
Myofascial trigger points (TP) constitute a conundrum in research and clinical practice as their etiopathogenesis is debated. Several studies investigating one or few muscles have shown that both active and latent TP causes an increased muscle activity, however the influence of TP on modular motor control during a reaching task is still unclear. Electromyographic signals, recorded from the muscles of the shoulder girdle and upper arm during a reaching task, were decomposed with Non-Negative Matrix Factorization algorithm. The extracted matrices of motor modules and activation signals were used to label the muscles condition as dominant or non-dominant. The presence of latent and active TP was detected in each muscle with manual examination. Despite a similar muscle activity was observed, we found that muscles with active TP had increased weighting coefficients when labeled in the dominant condition. No influences were found when muscles were in the non-dominant condition. These findings suggest that TP altered the motor control without co-contraction patterns. As a preliminary evidence, the present results suggest that the increased weighting coefficients in presence of TPs are associated with an alteration of the modular motor control without affecting the dimensionality of motor modules for each individual and reciprocal inhibition.


Mesoscale modelling of polymer aggregate digestion.
We use mesoscale simulations to gain insight into the digestion of biopolymers by studying the break-up dynamics of polymer aggregates (boluses) bound by physical cross-links. We investigate aggregate evolution, establishing that the linking bead fraction and the interaction energy are the main parameters controlling stability with respect to diffusion. We show via a simplified model that chemical breakdown of the constituent molecules causes aggregates that would otherwise be stable to disperse. We further investigate breakdown of biopolymer aggregates in the presence of fluid flow. Shear flow in the absence of chemical breakdown induces three different regimes depending on the flow Weissenberg number ( W i ). i) At W i ≪ 1 , shear flow has a negligible effect on the aggregates. ii) At W i ∼ 1 , the aggregates behave approximately as solid bodies and move and rotate with the flow. iii) At W i ≫ 1 , the energy input due to shear overcomes the attractive cross-linking interactions and the boluses are broken up. Finally, we study bolus evolution under the combined action of shear flow and chemical breakdown, demonstrating a synergistic effect between the two at high reaction rates.


Efficient regioselective synthesis and potential antitumor evaluation of isoxazolo[5,4-b]pyridines and related annulated compounds.
The reaction of 5-amino-3-methylisoxazole with appropriate α,β-unsaturated ketones gave the corresponding isoxazolo[5,4-b]pyridines. Treatment of 1 with 2,6-dibenzylidenecyclohexanone or 2-benzylidenedimedone afforded the corresponding isoxazolo[5,4-b]quinoline derivatives. 4,6,8,9-Tetrahydroisoxazolo[5,4-b]quinolin-5-one derivative was also obtained by multicomponent condensation reaction of 1 with dimedone and benzaldehyde. Heterocyclic annulation of the isoxazolo[5,4-b]pyridine system was achieved via reaction of 1 with benzylidene derivatives of indandione, quinuclidone, pyrazolone, and oxazolone. A representative of some newly synthesized compounds was evaluated as antitumor agents.


Insight into geometric preferences in uranium(VI) mixed tris(imido) systems.
Uranium tris(imido) species have been synthesized using different imido groups in the axial and equatorial positions by treating [(MesPDIMe)U(THF)]2 (1-THF), which is a uranium(iv) dimer that is supported by MesPDIMe tetraanions, with mixed organoazide solutions. While the origin of the geometric preference isn't clear, both steric and electronic factors are likely at play.


pKa determination of histidine residues in α-conotoxin MII peptides by 1H NMR and constant pH molecular dynamics simulation.
α-Conotoxin MII (α-CTxMII) is a potent and selective peptide antagonist of neuronal nicotinic acetylcholine receptors (nAChR's). Studies have shown that His9 and His12 are significant determinants of toxin binding affinity for nAChR, while Glu11 may dictate differential toxin affinity between nAChR isoforms. The protonation state of these histidine residues and therefore the charge on the α-CTx may contribute to the observed differences in binding affinity and selectivity. In this study, we assess the pH dependence of the protonation state of His9 and His12 by (1)H NMR spectroscopy and constant pH molecular dynamics (CpHMD) in α-CTxMII, α-CTxMII[E11A], and the triple mutant, α-CTxMII[N5R:E11A:H12K]. The E11A mutation does not significantly perturb the pKa of His9 or His12, while N5R:E11A:H12K results in a significant decrease in the pKa value of His9. The pKa values predicted by CpHMD simulations are in good agreement with (1)H NMR spectroscopy, with a mean absolute deviation from experiment of 0.3 pKa units. These results support the use of CpHMD as an efficient and inexpensive predictive tool to determine pKa values and structural features of small peptides critical to their function.


[DNA-binding activity of bis-netropsins containing a cis-diaminoplatinum group between two netropsin fragments].
The binding to DNA of Pt-bis-Nt and its modified analogue (Pt*-bis-Nt), which differs from Pt-bis-Nt by the fact that the connecting chain between two netropsin fragments contains two additional glycine residues, has been studied. Elongating the chain in the bis-netropsin molecule increases the cytotoxicity and leads to a complete disappearance of the antiherpetic activity of bis-netropsin. A study of the binding of two bis-netropsins with the oligonucleotide duplex containing an AT cluster, which is present at the replication initiation site of herpes virus (OriS), revealed significant structural differences between complexes of bis-netropsins with this DNA oligomer. It was shown by CD spectroscopy that the binding of Pt-bis-Nt in the elongated conformation and in the form of a hair-pin with the parallel orientation of two bis-netropsin fragments makes a greater contribution than it is the case in the complex formation with Pt*-bis-Nt. At high binding rates, Pt*-bis-Nt binds to the AT cluster in OriS predominantly in the form of associates based on the antiparallel double-stranded pyrrolcarboxyamide motif. The interaction of Pt-bis-Nt and Pt*-bis-Nt with the single-stranded oligonucleotide (64 nt), which corresponds to the upper strand at the replication initiation site of herpes virus (OriS*), was also studied. Substantial differences in the binding of bis-netropsins with OriS* and thermostability of the resulting complexes were found by CD spectroscopy and by studying the melting of complexes of bis-netropsins with OriS*.


Impact of SARS-CoV-2 viral load and duration of symptoms before hospital admission on the mortality of hospitalized COVID-19 patients.
Assess the impact of viral load estimated by cycle threshold (Ct) of reverse transcription real time-polymerase chain reaction (rRT-PCR) and the days from symptoms onset on mortality in hospitalized patients with COVID19. Retrospective observational study of 782 patients with a positive rRT-PCR from a nasopharyngeal swab was performed within the first 24 h from admission. Demographic data, clinical manifestations and laboratory parameters were collected. Uni- and multivariate analyses were performed to identify factors associated with mortality at 60 days. Ct was divided into three groups and the mortality rate decreased from 27.3 to 20.7% and 9.8% for Ct values of ≤ 20, 21-25 and > 25, respectively (P = 0.0001). The multivariate analysis identified as predictors of mortality, a Ct value < 20 (OR 3.13, CI 95% 1.38-7.10), between 21-25 (OR 2.47, CI 95% 1.32-4.64) with respect to a Ct value > 25. Days from symptoms onset is a variable associated with mortality as well (DSOA) ≤ 6 (OR 1.86, CI 95% 1.00-3.46), among other factors. Patients requiring hospital admission within 6 DSOA with a Ct value ≤ 25 had the highest mortality rate (28%). The inclusion of Ct values and DSOA in the characterization of study populations could be a useful tool to evaluate the efficacy of antivirals.


A subset of cells in the nerve net of Hydra oligactis defined by a monoclonal antibody: its arrangement and development.
A monoclonal antibody, termed JD1, was generated that bound to a subset of the nerve cells in the hypostome and tentacles of Hydra oligactis. Using a whole-mount technique the spatial pattern of the subset of nerve cells and their processes could be clearly visualized using indirect immunofluorescence. The subset largely corresponds to the epidermal sensory cells. Using the same technique the development of the pattern during head regeneration and budding was examined. The appearance of the nerve cells coincides with the formation of both the tentacles and hypostome. When head regeneration does not occur, JD1+ cells do not appear suggesting the differentiation of JD1+ cells is an integral event in head formation dependent on antecedent patterning processes.


Safety and efficacy for robot-assisted versus open pancreaticoduodenectomy and distal pancreatectomy: A systematic review and meta-analysis.
This meta-analysis was conducted to compare the clinical safety and efficacy of robot-assisted pancreaticoduodenectomy (RAPD) or robot-assisted distal pancreatectomy (RADP) with open surgery. Multiple databases (PubMed, Medline, EMBASE and Cochrane Library) were searched to identify studies comparing the outcomes of RAPD and open pancreaticoduodenectomy (OPD) or RADP and open distal pancreatectomy (ODP) (up to December 31, 2017). Fixed and random effects models were applied according to different conditions. Fifteen non-randomized controlled trials (11 RAPD vs. OPD and 4 RADP vs. ODP) involving 3690 patients were included. Robot-assisted surgery had longer operative time (RAPD vs. OPD: P = 0.0005; RADP vs. ODP: P < 0.00001) but lesser blood loss than open surgery (RAPD vs. OPD: P = 0.0009; RADP vs. ODP: P = 0.0007). RAPD was associated with less wound infection, a lower positive margin rate, lower overall complications, and faster postoperative off-bed activity. There was no significant difference in the lymph node yield, the rate of pancreatic fistula, delayed gastric emptying, reoperation, length of hospital stay and mortality between the two groups. Compared with ODP, RADP was associated with less blood transfusion, fewer lymph nodes harvested, lower complications and shorter hospital stay. There was no significant difference between the two groups in the rate of spleen preservation, positive margin, pancreatic fistula, and mortality. Robot-assisted surgery is a safe and feasible alternative to OPD and ODP with regard to perioperative outcomes. However, due to the lack of high-quality randomized controlled trials, the evidence is still limited.


Integration of alkaline phosphatase in the intestinal brush border membrane.
Alkaline phosphatase has been solubilized from porcine intestinal mucosa by two different methods: treatment of the mucosa by Emulphogen BC 720 and papain hydrolysis of enterocyte brush border membrane vesicles. Two differnt enzyme forms have been obtained by these methods. The two enzyme forms ('detergent form' and 'papain form') have been purified to homogeneity by similar techniques and exhibit closely related molecular characteristics. However, the detergent form displays a hydrophobic behaviour and aggregates in media free of detergent. The two forms can be differentiated by their electrophoretic mobility on polyacrylamide gel in the absence of sodium dodecyl sulphate. By electrophoresis on polyacrylamide gel in the presence of sodium dodecyl sulphate, it has been shown that the detergent and papain forms of alkaline phophatase are dimers consisting of two apparently identical subunits whose molecular weights are 64 000 and 61 000, respectively. The difference between these molecular weights has been attributed to the existence of a hydrophobic region in the detergent form which is present on each subunit.


Genetic models of human and mouse dendritic cell development and function.
Dendritic cells (DCs) develop in the bone marrow from haematopoietic progenitors that have numerous shared characteristics between mice and humans. Human counterparts of mouse DC progenitors have been identified by their shared transcriptional signatures and developmental potential. New findings continue to revise models of DC ontogeny but it is well accepted that DCs can be divided into two main functional groups. Classical DCs include type 1 and type 2 subsets, which can detect different pathogens, produce specific cytokines and present antigens to polarize mainly naive CD8+ or CD4+ T cells, respectively. By contrast, the function of plasmacytoid DCs is largely innate and restricted to the detection of viral infections and the production of type I interferon. Here, we discuss genetic models of mouse DC development and function that have aided in correlating ontogeny with function, as well as how these findings can be translated to human DCs and their progenitors.


Contemporary interpretation of informed consent: autonomy and paternalism.
The Supreme Court's decision in the Montgomery case has questioned what is meant by 'informed consent'. Clinicians must establish who is a reasonable patient and exactly what they want to know. Obtaining informed consent requires a relationship to be built between patient and clinician and must respect patient autonomy.


Geometric modeling of functional trileaflet aortic valves: development and clinical applications.
The dimensions of the aortic valve components condition its ability to prevent blood from flowing back into the heart. While the theoretical parameters for best trileaflet valve performance have already been established, an effective approach to describe other less optimal, but functional models has been lacking. Our goal was to establish a method to determine by how much the dimensions of the aortic valve components can vary while still maintaining proper function. Measurements were made on silicone rubber casts of human aortic valves to document the range of dimensional variability encountered in normal adult valves. Analytical equations were written to describe a fully three-dimensional geometric model of a trileaflet valve in both the open and closed positions. A complete set of analytical, numerical and graphical tools was developed to explore a range of component dimensions within functional aortic valves. A list of geometric guidelines was established to ensure safe operation of the valve during the cardiac cycle, with practical safety margins. The geometry-based model presented here allows determining quickly if a certain set of valve component dimensions results in a functional valve. This is of great interest to designers of new prosthetic heart valve models, as well as to surgeons involved in valve-sparing surgery.


Sperm nuclear maturity and chromatin stability in subfertile patients: Density gradient centrifugation is fair but non-discriminative in selecting the right population.
Multiple technologies exploring chromatin structure anomalies have been applied during the last decade to evaluate fertility disorders and to increase the predictive value of sperm analysis for procreation in vivo and in vitro. Our aim was to implement sperm nuclear maturity and nuclear chromatin stability as a functional test for male infertility diagnosis and to compare it with a fertile group. As semen processing is an integral part of assisted reproductive technologies the impact of density gradient centrifugation in selecting sperm based on nuclear maturity and stability was also analyzed. Flow cytometry combined with fluorescent dyes exhibiting affinity for DNA was implemented. Both nuclear parameters correlated significantly with semen parameters. The control fertile group had significantly higher mean condensed population and a significantly lower hypocondensed and hypercondensed fractions as compared to the subfertile study group. Density gradient centrifugation succeeded in selecting the condensed population in both the control and study groups, while reducing the hypocondensed percentage. The hypercondensed population which was ten-fold higher in the study group remained unchanged after selection, in both the control and the study groups. Sperm nuclear maturity and chromatin stability appears to be homogenous in the fertile sperm donors and heterogeneous in subfertile patients. Sperm preparation for assisted reproduction should aim to minimize the risk of abnormal spermatozoa being used for fertilization.


Parkinson's disease: a conceptualization of neuropsychological deficits within an information-processing framework.
Parkinson's disease patients are frequently impaired in a variety of neuropsychological tasks involving memory, perceptual motor performance and cognitive flexibility. Although various theories have been forwarded to explain specific impairments, few attempts have been made to account for all the deficits within a single theoretical framework. Furthermore, the frequent occurrence of dementia, the adverse side effects of medication and the motor symptoms of the disease tend to interfere with neuropsychological performance. This has hindered the clear delineation of the neuropsychological profile of Parkinsonian patients. The present paper examines the evidence for intellectual deficits in non-demented Parkinson's disease patients. A number of problems inherent in cognitive research on Parkinson's disease are discussed. The contribution of dementia, motor symptom severity and medication in the expression of these intellectual impairments is examined. It is suggested that many of the neuropsychological deficits described in Parkinson's disease may result from a common underlying deficit in some aspect of information processing. Although it is not possible to pinpoint the precise mechanism(s) involved on the basis of the available evidence, several possibilities are suggested by cognitive and electrophysiological data.


Diversity, astaxanthin production, and genomic analysis of Rhodotorula paludigena SP9-15.
Astaxanthin is a carotenoid known for its powerful antioxidant properties. This study focused on isolating yeast strains capable of producing astaxanthin from flower and fruit samples collected in Thailand. Out of 115 isolates, 11 strains were identified that produced astaxanthin. Molecular identification techniques revealed that these isolates belonged to two species: Rhodotorula paludigena (5 isolates) and Rhodosporidiobolus ruineniae (6 isolates). Whole-genome analysis of one representative strain, R. paludigena SP9-15, identified putative candidate astaxanthin synthesis-associated genes, such as CrtE, CrtYB, CrtI, CrtS, CrtR, CrtW, CrtO, and CrtZ. High-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) confirmed astaxanthin production. Further optimization of astaxanthin production was carried out by investigating the effects of various factors on the growth rate and astaxanthin production. The optimal conditions were 40 g/L glucose as a carbon source, pH 7.5, and cultivation at 25 °C with 200 rpm for 3 days. Under these conditions, R. paludigena SP9-15 synthesized biomass of 11.771 ± 0.003 g/L, resulting in astaxanthin with a content of 0.558 ± 0.018 mg/g DCW (dry cell weight), an astaxanthin yield of 6.565 ± 0.238 mg/L, and astaxanthin productivity of 2.188 ± 0.069 g/L/day. These findings provide insights into astaxanthin production using red yeast strains from Thailand and highlight the potential of R. paludigena SP9-15 for further application.