A new species of the odorous frog genus Odorrana (Amphibia, Anura, Ranidae) from southwestern China.
The genus Odorrana is widely distributed in the mountains of East and Southeastern Asia. An increasing number of new species in the genus have been recognized especially in the last decade. Phylogenetic studies of the O. schmackeri species complex with wide distributional range also revealed several cryptic species. Here, we describe a new species in the species complex from Guizhou Province of China. Phylogenetic analyses based on mitochondrial DNA indicated the new species as a monophyly clustered into the Odorrana clade and sister to O. schmackeri, and nuclear DNA also indicated it as an independent lineage separated from its related species. Morphologically, the new species can be distinguished from its congeners based on a combination of the following characters: (1) having smaller body size in males (snout-vent length (SVL) <43.3 mm); (2) head longer than wide; (3) dorsolateral folds absent; (4) tympanum of males large and distinct, tympanum diameter twice as long as width of distal phalanx of finger III; (5) two metacarpal tubercles; (6) relative finger lengths: II < I < IV < III; (7) tibiotarsal articulation reaching to the level between eye to nostril when leg stretched forward; (8) disks on digits with circum-marginal grooves; (9) toes fully webbed to disks; (10) the first subarticular tubercle on fingers weak; (11) having white pectoral spinules, paired subgular vocal sacs located at corners of throat, light yellow nuptial pad on the first finger in males.


Racial/Ethnic Disparities in Very Preterm Birth and Preterm Birth Before and During the COVID-19 Pandemic.
The coronavirus disease 2019 (COVID-19) pandemic may exacerbate existing racial/ethnic inequities in preterm birth. To assess whether racial/ethnic disparities in very preterm birth (VPTB) and preterm birth (PTB) increased during the first wave of the COVID-19 pandemic in New York City. This cross-sectional study included 8026 Black, Latina, and White women who gave birth during the study period. A difference-in-differences (DID) analysis of Black vs White disparities in VPTB or PTB in a pandemic cohort was compared with a prepandemic cohort by using electronic medical records obtained from 2 hospitals in New York City. Women who delivered from March 28 to July 31, 2020, were considered the pandemic cohort, and women who delivered from March 28 to July 31, 2019, were considered the prepandemic cohort. Reverse transcription-polymerase chain reaction tests for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were performed using samples obtained via nasopharyngeal swab at the time of admission. Clinical estimates of gestational age were used to calculate VPTB (<32 weeks) and PTB (<37 weeks). Log binomial regression was performed to estimate Black vs White risk differences, pandemic cohort vs prepandemic cohort risk difference, and an interaction term representing the DID estimator. Covariate-adjusted models included age, insurance, prepregnancy body mass index, and parity. Of 3834 women in the pandemic cohort, 492 (12.8%) self-identified as Black, 678 (17.7%) as Latina, 2012 (52.5%) as White, 408 (10.6%) as Asian, and 244 (6.4%) as other or unspecified race/ethnicity, with approximately half the women 25 to 34 years of age. The prepandemic cohort comprised 4192 women with similar sociodemographic characteristics. In the prepandemic cohort, VPTB risk was 4.4% (20 of 451) and PTB risk was 14.4% (65 of 451) among Black infants compared with 0.8% (17 of 2188) VPTB risk and 7.1% (156 of 2188) PTB risk among White infants. In the pandemic cohort, VPTB risk was 4.3% (21 of 491) and PTB risk was 13.2% (65 of 491) among Black infants compared with 0.5% (10 of 1994) VPTB risk and 7.0% (240 of 1994) PTB risk among White infants. The DID estimators indicated that no increase in Black vs White disparities were found (DID estimator for VPTB, 0.1 additional cases per 100 [95% CI, -2.5 to 2.8]; DID estimator for PTB, 1.1 fewer case per 100 [95% CI, -5.8 to 3.6]). The results were comparable in covariate-adjusted models when limiting the population to women who tested negative for SARS-CoV-2. No change was detected in Latina vs White PTB disparities during the pandemic. In this cross-sectional study of women who gave birth in New York City during the COVID-19 pandemic, no evidence was found for increased racial/ethnic disparities in PTB, among women who tested positive or tested negative for SARS-CoV-2.


Enhancing oral health for better mental health: Exploring the views of mental health professionals.
The association between oral health, self-esteem and quality of life is well established yet there is limited research on the impact of addressing the poor oral health of people living with mental health disorders. Greater consideration is warranted on how enhancing oral health in the course of mental healthcare might reduce the burden of a person's ill health. The role of mental health professionals is important in this regard yet uncertainty persists about the role these providers can and should play in promoting oral health care for people with mental health disorders. This qualitative study explored the issue of oral health and mental health with community based mental health professionals in Perth, Western Australia. It examined their views on the oral health status and experiences of their clients, and the different and alternative ways to improve access to care, knowledge and preventative regimens. Findings indicated participants' ambivalence, reluctance and lack of training in raising oral health issues, despite its acknowledged importance, indicating a siloed approach to care. Findings offer an opportunity to reflect on whether a more integrated approach to oral health care for people with mental health disorders would improve health outcomes.


Effects of the renin inhibitor N-[N-(3-(4-amino-1-piperidinyl-carbonyl)-2(R)-benzylpropionyl)-L- histid inyl] -(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6(2-pyridyl)-hexane-2-amide acetate in anesthetized rhesus monkeys.
The renin inhibitory effect of the non-peptide renin inhibitor S 2864 (N-[N-(3-(4-Amino-1-piperidinyl-carbonyl)-2(R)-benzylpropionyl)-L- histidinyl]-(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6(2-pyridyl)-hexane-2- amide acetate, CAS 135683-92-0) was characterized in vitro and in vivo in primates. In vitro, S 2864 inhibited the activity of purified human plasma renin with an IC50 of 3.8 x 10(-10) mol/l and did not affect related human aspartyl proteases like human cathepsin E, cathepsin D or pepsin. In vivo, in anesthetized sodium depleted rhesus monkeys S 2864 decreased mean arterial blood pressure after intraduodenal (i.d.) administration of 2 mg/kg significantly by 27% from 94 +/- 8 to 62 +/- 6 mmHg for 90 min. Heart rate was not changed. Cumulative intravenous (i.v.) administration of S 2864 or remikiren in doses of 1, 10 and 30 micrograms/kg significantly decreased systemic blood pressure, dP/dtmax and cardiac output while heart rate was not changed. Plasma angiotensin II (ANG II) levels as well as renin activity were dose dependently reduced after 10, 30 and 60 min. It is concluded that S 2864 is an effective specific inhibitor of human renin eliciting marked blood pressure lowering activities in primates.


Aspects of prewetting at nonplanar surfaces.
We employ Monte Carlo simulations in the grand canonical ensemble (GCEMC) to investigate the impact of nonplanarity of a solid substrate on the locus of the prewetting phase transition. The substrate is modelled as a periodic sequence of furrows of depth D and periodicity sx in the x direction; the furrows are infinitely long in the y direction. Our results indicate that a necessary prerequisite for a prewetting transition is the formation of a(n approximately) planar interface between molecularly thin films and an adjacent (bulk) gas. Thus, in general the prewetting transition is shifted to larger chemical potentials because the formation of a planar film-gas interface is more difficult next to a nonplanar compared with a planar solid surface. However, this shift turns out to be nonmonotonic depending on D on account of subtle packing effects manifested in the deviation of the local density Deltarho(x,Deltaz;D) at the nonplanar solid surface from that at a planar substrate. If D becomes sufficiently large prewetting as a discontinuous phase transition is suppressed because inside the furrow a highly ordered film forms that prevents a planar film-gas interface from forming.


Abnormal Muscularization of Intra-acinar Pulmonary Arteries in Two Cases Presenting as Sudden Infant Death.
Abnormal muscularization of acinar arteries is the hallmark of persistent pulmonary hypertension of newborn (PPHN), an uncommon disease with high rate of morbidity and mortality. PPHN presents with signs of respiratory distress immediately following birth. We herein report 2 cases presenting as a witnessed sudden unexpected death in the late neonatal period, preceded by respiratory deterioration and in whom the presence of abnormal muscularization of the acinar pulmonary arteries was reminiscent of PPHN. The significance of this report is twofold: to increase the awareness among pediatricians and pathologists of this feature that can present in some cases of Sudden Unexpected Death in Infancy/Sudden Infant Death Syndrome, and to highlight the importance of performing a thorough autopsy in order to identify the abnormality.


Tryptamines and Mental Health: Activating the 5-HT Receptor for Therapeutic Potential.
Tryptamines, a class of 3-aminoethyl-indoles that activate the serotonin receptor, show potential for novel mental health treatments. The FDA has granted "breakthrough therapy designation" to psilocybin and MDMA for treatment-resistant depression, major depressive disorder, and post-traumatic stress disorder, sparking global research efforts. Various clinical trials are currently investigating the therapeutic value of psilocybin for several mental health disorders. Results thus far indicate significant improvements in patient-reported outcomes via reductions in experiential avoidance. These advancements highlight a promising future for tryptamines in mental health therapy.


Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2.
Vertebrate female reproduction is limited by the oocyte stockpiles acquired during embryonic development. These are gradually depleted over the organism's lifetime through the process of apoptosis. The timer that triggers this cell death is yet to be identified. We used the Xenopus egg/oocyte system to examine the hypothesis that nutrient stores can regulate oocyte viability. We show that pentose-phosphate-pathway generation of NADPH is critical for oocyte survival and that the target of this regulation is caspase-2, previously shown to be required for oocyte death in mice. Pentose-phosphate-pathway-mediated inhibition of cell death was due to the inhibitory phosphorylation of caspase-2 by calcium/calmodulin-dependent protein kinase II (CaMKII). These data suggest that exhaustion of oocyte nutrients, resulting in an inability to generate NADPH, may contribute to ooctye apoptosis. These data also provide unexpected links between oocyte metabolism, CaMKII, and caspase-2.


Comparison between x-ray diffraction and quantitative surface calorimetry based on infrared thermography to evaluate strain-induced crystallinity in natural rubber.
The crystallinity of stretched crystallizable rubbers is classically evaluated using x-ray diffraction (XRD). As crystallization is a strongly exothermal phenomenon, quantitative surface calorimetry from infrared thermography offers an interesting alternative to XRD for determining the crystallinity. In this paper, the two measurement techniques have been used for evaluating the strain-induced crystallinity of the same unfilled natural rubber. This study provides the first comparison between the two techniques. The results obtained highlight the very satisfactory agreement between the two measurements, which opens a simple way for evaluating the strain-induced crystallinity from temperature measurements.


Metabolic, cardiovascular, and acid-base status after hepatic artery or portal vein reperfusion during orthotopic liver transplantation.
During liver transplantation, reperfusion traditionally is performed through the portal vein. After anecdotal observations that patients who underwent reperfusion first through the hepatic artery were more hemodynamically stable, we performed an exploratory, prospective, observational, nonrandomized study to compare cardiovascular stability, acid-base status, and metabolic gas exchange between patients who underwent reperfusion through either the portal vein or hepatic artery. We studied 20 patients undergoing liver transplantation (10 patients, reperfusion first through the portal vein; 10 patients, reperfusion first through the hepatic artery). Cardiovascular and acid-base parameters were compared at times before and after anastomosis of each vessel, and epinephrine use was recorded. Oxygen consumption (VO2) and carbon dioxide elimination (VCO2) were measured continuously by using an indirect calorimeter. Alanine aminotransferase (ALT) concentrations 24 hours after transplantation were compared as an index of reperfusion injury. Cardiovascular changes (mean arterial pressure, cardiac output) were similar for both groups, but more epinephrine was administered to the portal-vein group (P =.014). There was a greater increase in PaCO2 after portal reperfusion (median portal vein, 1.01 kPa; hepatic artery, 0.29 kPa; P =.015) and a trend toward more severe acidemia. VO2 increased more rapidly in the portal-vein group (P =.005), but overall changes in VO2 during the study period were similar. There were no differences in VCO2 between the groups or ALT concentrations 24 hours posttransplantation. These observational data suggest that hepatic arterial reperfusion may be associated with reduced epinephrine requirements and a slower rate of acid release, which could be advantageous in unstable patients. VO2 increases more slowly after hepatic artery reperfusion, which could indicate slower reoxygenation of the graft. Further studies of the relative merits of each technique are warranted.


Sensorimotor Cortical Neuroplasticity in the Early Stage of Bell's Palsy.
Neuroplasticity is a common phenomenon in the human brain following nerve injury. It is defined as the brain's ability to reorganize by creating new neural pathways in order to adapt to change. Here, we use task-related and resting-state fMRI to investigate neuroplasticity in the primary sensory (S1) and motor cortex (M1) in patients with acute Bell's palsy (BP). We found that the period directly following the onset of BP (less than 14 days) is associated with significant decreases in regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF), and intrinsic connectivity contrast (ICC) values in the contralateral S1/M1 and in ReHo and ICC values in the ipsilateral S1/M1, compared to healthy controls. The regions with decreased ReHo, fALFF, and ICC values were in both the face and hand region of S1/M1 as indicated by resting-state fMRI but not task-related fMRI. Our results suggest that the early stages of BP are associated with functional neuroplasticity in both the face and hand regions of S1/M1 and that resting-state functional fMRI may be a sensitive tool to detect these early stages of plasticity in patient populations.


Clinical Reliability of Adjustable Femoral Cortical Suspensory Fixation in Anterior Cruciate Ligament Reconstruction and Correlation of Clinical Outcomes With Demographic and Perioperative Factors.
Background and objective The primary goal of anterior cruciate ligament reconstruction (ACLR) is to protect the initial graft fixation against heavy loads encountered during the rehabilitation phase. The purpose of this study was to evaluate the functional outcomes (Lysholm score) and laxity [anterior tibial translation (ATT), anterior drawer test, Lachman test, and pivot shift test] of ACLR with adjustable-loop femoral cortical suspensory fixation (CSF) and tibial interferences crew fixation. Methods This study included 100 patients who underwent primary ACL reconstruction using quadruple hamstring grafts secured with TightRope® (Arthrex Inc, Naples, FL) femoral fixation and an interference screw on the tibial end. Six patients were excluded from the final analysis (four lost to follow-up, one suffered re-injury, and one had septic arthritis). The remaining 94 patients were evaluated for laxity and functional outcomes preoperatively, as well as at one, six, and 12 months postoperatively. Regression analysis was performed to determine the association between outcomes and 11 independent variables. This was designed as a prospective cohort study (level of evidence: II). Results The mean age of the participants was 28.46 ± 7.01 years. The median preoperative Lysholm knee score of 49 (mean ± SD: 48.2 ± 5.42) improved to 93 (92.7 ± 2.1) at six months and 98 (97.6 ± 2.1) at the one-year follow-up. The improvement was found to be statistically significant (p<0.01). The median ATT was 10 mm preoperatively, which decreased to 2 mm at one month, remained the same at six months, and rose to 3 mm at the one-year follow-up. ATT was found significantly reduced at one month postoperatively (p<.001) and did not show any significant further changes at subsequent follow-ups (p>0.05). Multiple linear regression revealed that one-year postoperative ATT (Rolimeter, Aircast Europa, Stephanskirchen, Germany) was independent of all demographic and perioperative variables tested. Conclusion Quadrupled hamstring graft ACLR with adjustable-loop fixation showed excellent subjective and objective outcomes with no residual laxity or failure of graft over mid-term follow-up. Postoperative laxity was not correlated with graft and tunnel dimensions.


Atraumatic dental treatment among Finnish elderly persons.
There is an increase in elderly dentate adults who will retain more of their natural teeth, and thus the demand for restorative dental services among them will be high. In Finland, systematic dental care for old people has not been organized. Health centres have mainly targeted the development of dental care for children, adolescents and young adults. With this background, atraumatic restorative treatment (ART) was seen as a complementary procedure in oral health services for the elderly. It was tested in 1997-1999 in Helsinki among 119 old people (mean age 72.5 years) living in their homes and receiving community-based support services. Patients were satisfied with having dental examination and oral health education at home. The ART fillings (n=33) were provided for 21 persons and depuration for 56. After 1 year, 25 fillings (58%) could be evaluated: 68% of the fillings were assessed as being good, 11% as having a slight marginal detect and 16% as having unacceptable marginal defect, and one filling was totally lost. In conclusion, ART is an appropriate approach in dental care for the elderly. However, more testing should be completed to find out how the screening could be organized to make the dental home visits more cost-effective and less time consuming.


MMTF-An efficient file format for the transmission, visualization, and analysis of macromolecular structures.
Recent advances in experimental techniques have led to a rapid growth in complexity, size, and number of macromolecular structures that are made available through the Protein Data Bank. This creates a challenge for macromolecular visualization and analysis. Macromolecular structure files, such as PDB or PDBx/mmCIF files can be slow to transfer, parse, and hard to incorporate into third-party software tools. Here, we present a new binary and compressed data representation, the MacroMolecular Transmission Format, MMTF, as well as software implementations in several languages that have been developed around it, which address these issues. We describe the new format and its APIs and demonstrate that it is several times faster to parse, and about a quarter of the file size of the current standard format, PDBx/mmCIF. As a consequence of the new data representation, it is now possible to visualize structures with millions of atoms in a web browser, keep the whole PDB archive in memory or parse it within few minutes on average computers, which opens up a new way of thinking how to design and implement efficient algorithms in structural bioinformatics. The PDB archive is available in MMTF file format through web services and data that are updated on a weekly basis.


Multifocal electroretinographic evaluation of long-term hydroxychloroquine users.
To observe the long-term effects of hydroxychloroquine sulfate on retinal electrical activity by multifocal electroretinography (mfERG) and to evaluate the regional variation of retinal dysfunction in subjects with hydroxychloroquine retinopathy. Multifocal ERG with 103-hexagon stimulation was performed on 19 patients (36 eyes) treated with hydroxychloroquine for systemic lupus erythematosus, rheumatoid arthritis, or localized atypical scleroderma. Visual acuity testing, Amsler grid testing, and Ishihara color vision testing were also performed. In 2 of the patients, hydroxychloroquine was discontinued due to concerns about toxicity. Both of these patients had additional mfERG performed after discontinuation of medication. Twelve patients (19 eyes) had a normal response density in one or both eyes, including 6 patients (12 eyes) with a low lifetime dose (< or =438 g) of hydroxychloroquine who had normal response densities in both eyes. Eleven patients (17 eyes) had abnormal response densities in one or both eyes, and 2 of these patients (4 eyes) had significant attenuation of response densities in almost the whole tested field; 4 patients had a normal mfERG result for one eye but had a slight decrease of response densities for the other eye. There were 4 patterns of abnormal mfERG amplitude change observed: (1) paracentral loss, (2) foveal loss, (3) peripheral loss, and (4) generalized loss. Implicit times were abnormal for pericentral responses in 3 patients. The results of color vision and Amsler grid testing were normal, except for one patient with a generalized loss pattern. In 2 subjects in whom hydroxychloroquine toxicity was suspected, response densities improved after termination of hydroxychloroquine. Long-term hydroxychloroquine use may be associated with mfERG abnormalities. The mfERG appears to detect retinal physiological change earlier than visual acuity testing, color vision testing, or Amsler grid testing can. The greatest value of the mfERG is in differentiating a retinal cause and, hence, providing important evidence for hydroxychloroquine toxicity, for whatever visual field loss is apparent on perimetry.


Metabolic disorders in children and adolescents with type 2 diabetes mellitus.
Type 2 diabetes mellitus (T2DM) in children and adolescents is increasing in incidence worldwide. It is the leading type of newly diagnosed diabetes in Taiwan among school children. T2DM is associated with metabolic syndrome in adults, so we tried to find out if these metabolic disorders are present in children. From 1989 to 2003, 22 children and adolescents were diagnosed with T2DM in our hospital. Their ages ranged from 8.8 to 17.0 (11.7+/-2.3) years; 6 of them were boys. We compared their clinical characteristics with those of 42 healthy and 237 obese children and adolescents. Physical examination was performed and plasma glucose and serum cholesterol, triglycerides, uric acid, creatinine, HDL-cholesterol, and insulin levels were measured and LDL-cholesterol was calculated. Demographic and laboratory data were compared among the T2DM, obese and control groups. The female: male ratio among the patients was 2.7: 1; 18% were overweight and 68% obese, and 64% had acanthosis nigricans. There were no significant differences between the T2DM and obese groups in terms of biochemistry profiles except for the higher plasma glucose in the T2DM group. Children with T2DM had higher levels of cholesterol and triglycerides but lower levels of HDL-cholesterol compared with healthy children. Among obese children without T2DM, the levels of glucose, triglycerides, uric acid, insulin, HOMA-IR were higher than in the healthy group, and HDL-cholesterol levels were lower. Children with T2DM or obesity should be evaluated for metabolic disorders.


Discriminating symptoms in schizophrenia. A report from the international pilot study of schizophrenia.
Schizophrenia is recognized by the presence of one or more clinical syndromes, but there is disagreement as to how far the boundaries of the concept should be extended. During the course of a World Health Organization study, using the Present State Examination and a computerized classification program, a nuclear schizophrenic syndrome was nearly always (95.1%) associated with a diagnosis of schizophrenic or paranoid psychosis. The only substantial exception was that 13 out of 79 patients diagnosed as manic were said to show the nuclear syndrome. The computer classification was concordant with a clinical diagnosis of schizophrenic or paranoid psychosis, manic psychosis, or depressive disorder, in 90% of cases. If appropriate precautions are taken, many of the sources of noncomparability in epidemiological, therapeutic, and prognostic studies can be brought under control.


Dendritic cells modulate lung response to Pseudomonas aeruginosa in a murine model of sepsis-induced immune dysfunction.
Host infection by pathogens triggers an innate immune response leading to a systemic inflammatory response, often followed by an immune dysfunction which can favor the emergence of secondary infections. Dendritic cells (DCs) link innate and adaptive immunity and may be centrally involved in the regulation of sepsis-induced immune dysfunction. We assessed the contribution of DCs to lung defense in a murine model of sublethal polymicrobial sepsis (cecal ligature and puncture, CLP). In this model, bone marrow-derived DCs (BMDCs) retained an immature phenotype, associated with decreased capacity of IL-12p70 release and impaired priming of T cell lymphocytes. Eight days after CLP surgery, we induced a secondary pulmonary infection through intratracheal instillation of 5 x 10(6) CFUs of Pseudomonas aeruginosa. Whereas all sham-operated mice survived, 80% of post-CLP mice died after secondary pneumonia. Post-CLP mice exhibited marked lung damage with early recruitment of neutrophils, cytokine imbalance with decreased IL-12p70 production, and increased IL-10 release, but no defective bacterial lung clearance, while systemic bacterial dissemination was almost constant. Concomitant intrapulmonary administration of exogenous BMDCs into post-CLP mice challenged with P. aeruginosa dramatically improved survival. BMDCs did not improve bacterial lung clearance, but delayed neutrophil recruitment, strongly attenuated the early peak of TNF-alpha and restored an adequate Il-12p70/IL-10 balance in post-CLP mice. Thus, adoptive transfer of BMDCs reversed sepsis-induced immune dysfunction in a relevant model of secondary P. aeruginosa pneumonia. Unexpectedly, the mechanism of action of BMDCs did not involve enhanced antibacterial activity, but occurred by dampening the pulmonary inflammatory response.


PetBERT: automated ICD-11 syndromic disease coding for outbreak detection in first opinion veterinary electronic health records.
Effective public health surveillance requires consistent monitoring of disease signals such that researchers and decision-makers can react dynamically to changes in disease occurrence. However, whilst surveillance initiatives exist in production animal veterinary medicine, comparable frameworks for companion animals are lacking. First-opinion veterinary electronic health records (EHRs) have the potential to reveal disease signals and often represent the initial reporting of clinical syndromes in animals presenting for medical attention, highlighting their possible significance in early disease detection. Yet despite their availability, there are limitations surrounding their free text-based nature, inhibiting the ability for national-level mortality and morbidity statistics to occur. This paper presents PetBERT, a large language model trained on over 500 million words from 5.1 million EHRs across the UK. PetBERT-ICD is the additional training of PetBERT as a multi-label classifier for the automated coding of veterinary clinical EHRs with the International Classification of Disease 11 framework, achieving F1 scores exceeding 83% across 20 disease codings with minimal annotations. PetBERT-ICD effectively identifies disease outbreaks, outperforming current clinician-assigned point-of-care labelling strategies up to 3 weeks earlier. The potential for PetBERT-ICD to enhance disease surveillance in veterinary medicine represents a promising avenue for advancing animal health and improving public health outcomes.


A young man with oligoarthritis: what is his cardiovascular risk?
Gout is the commonest cause of inflammatory arthritis among young men. A case of acute gout in a 39-year-old man is described. As part of his assessment, his cardiovascular risk factors were evaluated. He was found to have elevated body mass index, central obesity, hypertension, a family history of cardiovascular disease, and hypercholesterolemia. This case highlights the association between gout, hyperuricaemia and elevated cardiovascular risk. In young male patients, acute presentation with gout in primary care may provide the first opportunity for assessment of cardiovascular risk factors and primary prevention of ischaemic heart disease.


A profile of hospital union election activity, 1985--1994 NLRB rulemaking and results in right-to-work states.
The authors present union election results in non-governmental, short-term hospitals for the 10-year period 1985--1994. The authors include profiles for the periods before (1985--1989) and after (1990--1994) the National Labor Relations Board (NLRB) rulemaking. When comparing the period data, they found that the impact of rulemaking was a reduction in mean bargaining unit size, an increase in the absolute number of elections in hospitals, and an increase in the percentage of union wins. Their examination of hospital union election results in right-to-work (RTW) versus non-RTW states revealed that unions did not aggressively try to organize workers in non-RTW states and, when they did, they were not very successful. When the authors examined only initial recognition elections during the periods before and after rulemaking, as well as the whole 10 years, regression analysis identified three variables significantly related to union wins: the 1989 NLRB rule change, bargaining unit size, and employee participation rates.


Conformation and ion-binding of oligonucleotides.
The effective charge and the conformation of oligonucleotides may influence their pharmaceutical properties. Therefore, a method based on the convective diffusion process was used to measure both the diffusion coefficient and the effective charge number of four oligonucleotides with different chain lengths. Determinations were carried out at physiological ionic strength and at two temperatures, 20 and 40 degrees C. The results indicate that the longer oligonucleotides, i.e. number of nucleotides in the molecule from 15 to 30, are strongly ion-paired (75-80%) and the shorter oligonucleotide (seven nucleotides) is only ca. 50% ion-paired. The extent of ion-binding was not dependent on temperature. The conformation of the oligonucleotides appeared to be fairly compact in 0.15 M NaCl solution. The compact conformation and strong ion-pairing may influence the pharmacokinetics of oligonucleotides, possibly facilitating distribution into tissues.


Thermodynamics of water octamer in a uniform electric field.
We study the water octamer in a uniform electric field using the all-exchanges parallel tempering Monte Carlo method in the canonical ensemble. The heat capacity, quenched energy configurations, and the order parameter Q(4) are employed to understand the phase changes observed as a function of temperature and the strength of the applied electric field. At a low field strength of 0.1 V A(-1) a solidlike to liquidlike "melting" transition is detected. The corresponding heat capacity peak appears around 206 K, where Q(4) shows a significant change of slope. For E> or =0.5 V A(-1) such features are absent. However, at E=0.5 V A(-1) we find a solidlike to solidlike transition between cubic and extended structures around T approximately 25 K.


Farmers' preferences for automatic lameness-detection systems in dairy cattle.
As lameness is a major health problem in dairy herds, a lot of attention goes to the development of automated lameness-detection systems. Few systems have made it to the market, as most are currently still in development. To get these systems ready for practice, developers need to define which system characteristics are important for the farmers as end users. In this study, farmers' preferences for the different characteristics of proposed lameness-detection systems were investigated. In addition, the influence of sociodemographic and farm characteristics on farmers' preferences was assessed. The third aim was to find out if preferences change after the farmer receives extra information on lameness and its consequences. Therefore, a discrete choice experiment was designed with 3 alternative lameness-detection systems: a system attached to the cow, a walkover system, and a camera system. Each system was defined by 4 characteristics: the percentage missed lame cows, the percentage false alarms, the system cost, and the ability to indicate which leg is lame. The choice experiment was embedded in an online survey. After answering general questions and choosing their preferred option in 4 choice sets, extra information on lameness was provided. Consecutively, farmers were shown a second block of 4 choice sets. Results from 135 responses showed that farmers' preferences were influenced by the 4 system characteristics. The importance a farmer attaches to lameness, the interval between calving and first insemination, and the presence of an estrus-detection system contributed significantly to the value a farmer attaches to lameness-detection systems. Farmers who already use an estrus detection system were more willing to use automatic detection systems instead of visual lameness detection. Similarly, farmers who achieve shorter intervals between calving and first insemination and farmers who find lameness highly important had a higher tendency to choose for automatic lameness detection. A sensor attached to the cow was preferred, followed by a walkover system and a camera system. In general, visual lameness detection was preferred over automatic detection systems, but this preference changed after informing farmers about the consequences of lameness. To conclude, the system cost and performance were important features, but dairy farmers should be sensitized on the consequences of lameness and its effect on farm profitability.


[The effect of cyclosporine A in steroid-dependent nephrotic syndrome in children].
The aim of study was the analysis of cyclosporine A (CyA) treatment efficacy in children with steroid-dependent nephrotic syndrome (NS). The examined group consisted of 21 children (F--8, M--16) at the mean age 12.1 +/- 4.6 years with the relapses NS in the course of minimal change nephrotic syndrome (MCSN) in 9 (43%) and focal segmental glomerulosclerosis (FSGS) in 12 (57%) cases. All children were administrated CyA (Sandimun Neoral f. Novartis Pharma AG), together with prednisone (Encorton f. Polfa Pabianice) (0.2 - 0.5 mg/kg b.w./24 h) and ACE inhibitor (Enap f. Krka). The concentration of cyclospornine A in serum was measured by monoclonal antibody fluorescence polarization immunoassay. Serum concentration of creatinine, uric acid, albumin, cholesterol and creatinine clearance (Schwartz method) and proteinuria was analysed: A - before treatment, B--in 3rd day, C--in 3rd month, D--in 6th month, E--in 12th month of CyA treatment and F--after 3-6 months after finishing treatment. Blood pressure was measured by ABPM in examination A, D, E, and F. During administration of CyA the urinary protein excretion decreased successively and in 12th month of treatment was 4.5 +/- 3.9 mg/kg bw/24 h. The serum creatinine concentration increased by 33.9%, and uric acid by 52.8% in comparison to the initial level. Mean systolic blood pressure (RRs) in ambulatory blood pressure monitoring (ABPM) during 24 hours was 120.5 +/- 9.2 mmHg before treatment and increased by about 6% after 12 months of treatment. Respectively diastolic blood pressure (RRr) was 66.7 +/- 4.3 mmHg and increased to 71.0 +/- 2.5 mmHg at the end of 12 h month. The nocturnal fall of RRs before treatment was 14.2 +/- 2.8%, and RRr 14.9 +/- 2.1%. During treatment nocturnal fall of both RRs and RRr decreased to 9.2 +/- 2.7% for RRs and 9.8 +/- 2.7% for RRr after 6 months of treatment. After 12 months of treatment and in remission the nocturnal fall of blood pressure was still below 10%. CyA is an effective drug in children with relapses of steroid-dependent in the course of MCSN and FSGS. Side effects after CyA treatment, under the control of its concentration in serum and parameters of renal function are occasional and transient. Cyclosporine A disturbs the 24 hours rhythm of arterial blood pressure.


The effectiveness of individual placement and support for people with mental illness new on social benefits: a study protocol.
In Switzerland, people with a severe mental illness and unable to work receive disability benefits ('IV-pension'). Once they are granted these benefits, the chances to regain competitive employment are usually small. However, previous studies have shown that individual placement and support (IPS) supports a successful reintegration into competitive employment. This study focuses on the integration of newly appointed IV-pensioners, who have received an IV-pension for less than a year. The present pilot project ZHEPP (Zürcher Eingliederungs-Pilot Projekt; engl.: Zurich integration pilot project) is a randomized controlled trial (RCT). The 250 participants will be randomized to either the intervention or the control group. The intervention group receives support of a job coach according to the approach of IPS. Participants in the control group do not receive IPS support. Participation takes a total of two years for each participant. Each group is interviewed every six months (T0-T4). A two-factor analysis of variance will be conducted with the two factors group (intervention versus control group) and outcome (employment yes/no). The main criterion of the two-factor analysis will be the number of competitive employment contracts in each group. This study will focus on the impact of IPS on new IV-pensioners and aims to identify predictors for a successful integration. Furthermore, we will examine the effect of IPS on stigma variables and recovery orientation. ISRCTN54951166.


Antifungal Imidazole-Decorated Cationic Amphiphiles with Markedly Low Hemolytic Activity.
Herein we report that an imidazole-decorated cationic amphiphile derived from the pseudo-disaccharide nebramine has potent antifungal activity against strains of Candida glabrata pathogens. In combination with the natural bis-benzylisoquinoline alkaloid tetrandrine the reported antifungal cationic amphiphile demonstrated synergistic antifungal activity against Candida albicans pathogens. This unique membrane disruptor caused no detectible mammalian red blood cell hemolysis at concentrations up to more than two orders of magnitude greater than its minimal inhibitory concentrations against the tested C. glabrata strains. We provide evidence that potency against C. glabrata may be associated with differences between the drug efflux pumps of C. albicans and C. glabrata. Imidazole decorated-cationic amphiphiles show promise for the development of less toxic membrane-disrupting antifungal drugs and drug combinations.


Revealing local, enhanced optical field characteristics of Au nanoparticle arrays with 10 nm gap using scattering-type scanning near-field optical microscopy.
Anomalous optical properties displayed by plasmonic structures are commonly attributed to the enhanced, local field within their corrugations. Though theoretical calculations of such field enhancements abound, experimental observations are relatively few, because only few optical microscopic techniques have enough spatial resolution. We used scattering-type scanning near-field optical microscopy to resolve local optical characteristics of a gold nanoparticle array with 10 nm gap between adjacent particles. Subnanometer-resolution measurement of the optical field intensity was achieved by use of etched silicon atomic force microscopy probe tip. The result shows that, with a p-polarized excitation scheme, the induced field is enhanced and the phase undergoes a large change in the gap region. The spatially-resolved signals are attributed to the electromagnetic interaction within an array of vertical dipoles. We show that scattering-type near-field optical microscopy is well-suited to the investigation of field enhancements in plasmon-enhanced sensing and spectroscopy array structures.


Evaluation of a programme for 'Rapid Assessment of Febrile Travelers' (RAFT): a clinic-based quality improvement initiative.
Fever in the returned traveller is a potential medical emergency warranting prompt attention to exclude life-threatening illnesses. However, prolonged evaluation in the emergency department (ED) may not be required for all patients. As a quality improvement initiative, we implemented an algorithm for rapid assessment of febrile travelers (RAFT) in an ambulatory setting. Criteria for RAFT referral include: presentation to the ED, reported fever and travel to the tropics or subtropics within the past year. Exclusion criteria include Plasmodium falciparum malaria, and fulfilment of admission criteria such as unstable vital signs or significant laboratory derangements. We performed a time series analysis preimplementation and postimplementation, with primary outcome of wait time to tropical medicine consultation. Secondary outcomes included number of ED visits averted for repeat malaria testing, and algorithm adherence. From February 2014 to December 2015, 154 patients were seen in the RAFT clinic: 68 men and 86 women. Median age was 36 years (range 16-78 years). Mean time to RAFT clinic assessment was 1.2±0.07 days (range 0-4 days) postimplementation, compared to 5.4±1.8 days (range 0-26 days) prior to implementation (p<0.0001). The RAFT clinic averted 132 repeat malaria screens in the ED over the study period (average 6 per month). Common diagnoses were: traveller's diarrhoea (n=27, 17.5%), dengue (n=12, 8%), viral upper respiratory tract infection (n=11, 7%), chikungunya (n=10, 6.5%), laboratory-confirmed influenza (n=8, 5%) and lobar pneumonia (n=8, 5%). In addition to provision of more timely care to ambulatory febrile returned travellers, we reduced ED bed-usage by providing an alternate setting for follow-up malaria screening, and treatment of infectious diseases manageable in an outpatient setting, but requiring specific therapy.


From endosymbionts to host communities: factors determining the reproductive success of arthropod vectors.
Elucidating the factors determining reproductive success has challenged scientists since Darwin, but the exact pathways that shape the evolution of life history traits by connecting extrinsic (e.g., landscape structure) and intrinsic (e.g., female's age and endosymbionts) factors and reproductive success have rarely been studied. Here we collected female fleas from wild rodents in plots differing in their densities and proportions of the most dominant rodent species. We then combined path analysis and model selection approaches to explore the network of effects, ranging from micro to macroscales, determining the reproductive success of these fleas. Our results suggest that female reproductive success is directly and positively associated with their infection by Mycoplasma bacteria and their own body mass, and with the rodent species size and total density. In addition, we found evidence for indirect effects of rodent sex and rodent community diversity on female reproductive success. These results highlight the importance of exploring interrelated factors across organization scales while studying the reproductive success of wild organisms, and they have implications for the control of vector-borne diseases.


Advances in the neurorehabilitation of severe disorder of consciousness.
The paper describes the evolution of knowledge concerning severe brain injury which determines the Vegetative State/Unresponsive Wakefulness Syndrome. The term Vegetative State was proposed by Jennet and Plum in 1972. Later on, the Intensive Care Units progresses increased the survival of these patients and, contemporary, decreased their characteristic conditions of cachexia and severe dystonia. In 1994, the disease was conceived as a disconnection syndrome of the hemispheres from the brainstem, mainly due to a temporary or permanent deficit of the functions of the white matter. From 2005 on, the psychophysiological parameters relative to an emotional consciousness, albeit submerged, were described. Since then, it has been recognized that the brain of these patients was not only to be considered living but also working. The latest studies that have greatly improved the knowledge of the physiopathology of this particular state of consciousness. These new insights have led to the formation of a European Union Task Force, which has proposed in 2009 to change the name from a Vegetative State to Unresponsive Wakefulness Syndrome, outlining the character of syndrome and not that of state, as forms of even late recovery in consciousness levels have been observed and described.


PREVALENCE OF LYMPHATIC FILARIASIS, MALARIA AND SOIL TRANSMITTED HELMINTHIASIS IN A COMMUNITY OF BARDIYA DISTRICT, WESTERN NEPAL.
Lymphatic filariasis (LF), malaria and soil transmitted helminthiasis (STH) cause major health problems in Nepal, but in spite of this very few stud- ies have been carried out on these parasitic infections in Nepal. A cross sectional survey of all three categories of parasitic infections was carried out in Deuda- kala Village of Bardiya District, western Nepal. A total of 510 individuals aged 5 years and above were examined from finger prick blood for circulating filarial antigen (CFA), malaria antigen using a rapid diagnostic test (RDT), and malaria DNA using a PCR-based assay. In addition, 317 individuals were examined for soil-transmitted helminth (STH) eggs by the Kato-Katz technique. Prevalence of LF, malaria (antigen) and STH infection was 25.1%, 0.6% and 18.3%, respectively. PCR analysis did not detect any additional malaria cases. The prevalence of LF and STH infections differ significantly among different age groups and ethnic communities. The high prevalence of LF in the community studied indicates an immediate need for implementing a mass drug administration program for its control in this particular geographical area of Nepal.


Role of androgens in normal and pathological ovarian function.
Androgens mediate their actions via the androgen receptor (AR), a member of the nuclear receptor superfamily. AR-mediated androgen action is essential in male reproductive development and function; however, only in the last decade has the suspected but unproven role for AR-mediated actions in female reproduction been firmly established. Deciphering the specific roles and precise pathways by which AR-mediated actions regulate ovarian function has been hindered by confusion on how to interpret results from pharmacological studies using androgens that can be converted into oestrogens, which exert actions via the oestrogen receptors. The generation and analysis of global and cell-specific female Ar knockout mouse models have deduced a role for AR-mediated actions in regulating ovarian function, maintaining female fertility, and have begun to unravel the mechanisms by which AR-mediated androgen actions regulate follicle health, development and ovulation. Furthermore, observational findings from human studies and animal models provide substantial evidence to support a role for AR-mediated effects not only in normal ovarian function but also in the development of the frequent ovarian pathological disorder, polycystic ovarian syndrome (PCOS). This review focuses on combining the findings from observational studies in humans, pharmacological studies and animal models to reveal the roles of AR-mediated actions in normal and pathological ovarian function. Together these findings will enable us to begin understanding the important roles of AR actions in the regulation of female fertility and ovarian ageing, as well as providing insights into the role of AR actions in the androgen-associated reproductive disorder PCOS.


High Elongation and Transparent Nacre-Inspired PVA/MMT Nanocomposites.
Currently, high strength nacre-inspired PVA/MMT (polyvinyl alcohol/montmorillonite) nanocomposites with high MMT nanofiller content (50-70 wt%) have been constructed successfully. However, this seriously sacrifices the elongation and reduces the corresponding transparency. In this paper, high elongation and transparent PVA/MMT nanocomposites with high MMT content are prepared by the evaporation-induced assembly with the introduction of the micro-crosslinking. Results demonstrate that the micro-crosslinking can inhibit the formation of rod-shaped arrays, and contribute to a more ordered layered microstructure, where an elongation of 76.2% in 47.8 wt% MMT content nanocomposites is gained, nearly 19 times of that of non-crosslinked nanocomposites (ultimate strain is 4.1%). This provides a potential approach for compromise between high strength and excellent elongation at the same MMT content. Moreover, disappearance of rod-shaped arrays and resultant ordered layered microstructure make eventual films more transparent.


Fusion assessment in standalone lateral lumbar interbody fusion: 3D-printed titanium versus polyetheretherketone (PEEK) cages.
Compare fusion at two independent timepoints (early and late) between 3D-printed titanium (Ti) and polyetheretherketone (PEEK) cages in patients undergoing standalone lateral lumbar interbody fusion (SA-LLIF). We hypothesized that 3D-printed Ti cages show higher fusion rates at an early timepoint compared to PEEK. A retrospective study of patients undergoing SA-LLIF with 3D-printed Ti cages and PEEK cages between 11/2016 and 01/2020 at a single academic institution was done. Fusion was assessed for each treated level using multiplanar reconstructed computed tomography (CT) scans. Presence of fully bridged interbody trabecular bone or continuous bone centered in the cage was considered as fusion. In total, 91 patients (136 levels) were included in the final analysis, 49 patients (72 levels) in the early group and 42 patients (64 levels) in the late group. CT scans were performed on average 8.2±1.8 months postoperatively for the early group and 18.9±7.7 months for the late group. In the early group, fusion was significantly higher for 3D-printed Ti cages compared to PEEK cages (95.8% versus 62.5%; P=0.002), whereas in the late group no significant difference was seen (94.7% versus 80.0%; P=0.258). In SA-LLIF, porous 3D-printed Ti cages showed significantly higher fusion rates at an early timepoint compared to PEEK. However, the difference in fusion rates between 3D-printed Ti cages and PEEK cages was found not to be significantly different at a later timepoint in another patient group. This might support the assumption that 3D-printed Ti cages with a porous architecture are more osteoconductive compared to PEEK and tend to fuse earlier.


Usefulness of artificial intelligence in gastric neoplasms.
Recently, studies in many medical fields have reported that image analysis based on artificial intelligence (AI) can be used to analyze structures or features that are difficult to identify with human eyes. To diagnose early gastric cancer, related efforts such as narrow-band imaging technology are on-going. However, diagnosis is often difficult. Therefore, a diagnostic method based on AI for endoscopic imaging was developed and its effectiveness was confirmed in many studies. The gastric cancer diagnostic program based on AI showed relatively high diagnostic accuracy and could differentially diagnose non-neoplastic lesions including benign gastric ulcers and dysplasia. An AI system has also been developed that helps to predict the invasion depth of gastric cancer through endoscopic images and observe the stomach during endoscopy without blind spots. Therefore, if AI is used in the field of endoscopy, it is expected to aid in the diagnosis of gastric neoplasms and determine the application of endoscopic therapy by predicting the invasion depth.


Insight into the mechanism of fast movement of myosin from Chara corallina.
Chara myosin, two-headed plant myosin belonging to class XI, slides F-actin at maximally 60 microm s(-1). To elucidate the mechanism of this fast sliding, we extensively investigated its mechanochemical properties. The maximum actin activated ATPase activity, Vmax, was 21.3 s(-1) head(-1) in a solution, but when myosin was immobilized on the surface, its activity was 57.6 s(-1) head(-1) at 2 mg ml(-1) of F-actin. The sliding velocity and the actin activated ATPase activity were greatly inhibited by ADP, suggesting that ADP dissociation was the rate limiting step. With the extensive assay of motility by varying the surface density, the duty ratio of Chara myosin was found to be 0.49-0.44 from velocity measurements and 0.34 from the landing rate analysis. At the surface density of 10 molecules microm(-2), Chara myosin exhibited pivot movement under physiological conditions. Based on the results obtained, we will discuss the sliding mechanism of Chara myosin according to the working stroke model in terms of its physiological aspects. aspects.


The lungworm, Halocercus spp. (Nematoda: Pseudaliidae) in cetaceans from California.
Three cetaceans from Monterey Bay, California (USA), were infected with lung nematodes. A beaked whale calf, Mesoplodon sp. was infected with adult Halocercus sp. This represents a new host record for this nematode. The lungs of a northern right whale dolphin calf, Lissodelphis borealis, contained an unidentified nematode similar in size to Halocercus sp. The presence of Phyllobothrium delphini-type cestode larvae in its blubber is evidence that the calf was feeding on invertebrates. A pregnant harbor porpoise, Phocoena phocoena was infected with the lung nematode H. invaginatus, but the fetus was uninfected. We found no direct evidence of a transplacental mode of transmission for Halocercus sp.


Assessment of copper bioavailability and toxicity in vineyard runoff waters by DPASV and algal bioassay.
The aim of this study was to assess the toxicity of runoff waters in an agricultural multipollution context through an in-depth assessment of copper bioavailability and toxicity. Runoff waters were screened for major ions, metals and diuron. The potential environmental impact of these runoff waters was evaluated using the conventional 72-h growth inhibition test with the green alga Pseudokirchneriella subcapitata. The results suggested that the toxicity detected in the calcareous vineyard field was due to the presence of diuron, whereas the non-calcareous runoff waters were non-toxic. Chemical speciation modelling by MINEQL revealed that most of the copper present in the non-toxic natural runoff waters was complexed by organic matter. These samples were spiked with copper, and then the toxicity and the electrochemically bioavailable copper fraction were measured. Differential pulse anodic stripping voltammetry (DPASV) was used to detect labile complexes and free copper. This combined approach highlighted the presence of some labile copper complexes in samples reaching the EC10-these could have contributed to the copper toxicity.


Developmental, gender, and ethnic group differences in moods and ambulatory blood pressure in adolescents.
Adolescence is characterized by profound changes in physical, psychological, and social functioning thought to be accompanied by intense and varying moods. Within a psychophysiological framework, this study examined the prevalence of 12 self-reported mood states of adolescents; investigated associations between specific mood states and ambulatory blood pressure readings; and explored effects of interactions among moods, gender, ethnic group, and maturation on ambulatory blood pressures. The sample included 371 African American, European American, and Hispanic American adolescents 11 to 16 years old. Systolic (SBP) and diastolic (DBP) blood pressures were measured every 30 min with an ambulatory monitor and were synchronized with electronic activity monitoring and moods self-recorded during waking hours in a checklist diary. Moods differed significantly by gender, ethnic group, and maturation. Controlling for height, maturation, gender, ethnic group, mother's education, position, location, activity, other moods, and interactions of moods with other variables in a multilevel, random coefficients regression model, both positive and negative mood states were associated with higher levels of SBP and DBP; being relaxed or bored, or having a feeling of accomplishing things were associated with lower SBP and DBP. There were significant interaction effects of moods with physical maturity, gender, and ethnic group on ambulatory SBP and DBP. Further study of the modifying effects of gender, ethnic group, and stage of development on reports of moods, and their associations with cardiovascular responses is recommended.


Intracarotid Cancer Cell Injection to Produce Mouse Models of Brain Metastasis.
Metastasis, the spread and growth of malignant cells at secondary sites within a patient's body, accounts for > 90% of cancer-related mortality. Recently, impressive advances in novel therapies have dramatically prolonged survival and improved quality of life for many cancer patients. Sadly, incidence of brain metastatic recurrences is fast rising, and all current therapies are merely palliative. Hence, good experimental animal models are urgently needed to facilitate in-depth studies of the disease biology and to assess novel therapeutic regimens for preclinical evaluation. However, the standard in vivo metastasis assay via tail vein injection of cancer cells produces predominantly lung metastatic lesions; animals usually succumb to the lung tumor burden before any meaningful outgrowth of brain metastasis. Intracardiac injection of tumor cells produces metastatic lesions to multiple organ sites including the brain; however, the variability of tumor growth produced with this model is large, dampening its utility in evaluating therapeutic efficacy. To generate reliable and consistent animal models for brain metastasis study, here we describe a procedure for producing experimental brain metastasis in the house mouse (Mus musculus) via intracarotid injection of tumor cells. This approach allows one to produce large number of brain metastasis-bearing mice with similar growth and mortality characteristics, thus facilitating research efforts to study basic biological mechanisms and to assess novel therapeutic agents.


Spirotetramat reduces fitness of the spotted-wing Drosophila, Drosophila suzukii.
With climate change, the spotted-wing Drosophila (SWD, Drosophila suzukii) invades a great number of fruit production regions worldwide. A plethora of insecticides are being applied for management of this pest. As expected, SWD develops resistance against some potent insecticides or is rather insensitive to some others. Therefore, there is an urgent need to identify and characterize alternative insecticides to control SWD populations. Here, we have studied the effects of the orally applied inhibitor of the fatty acid synthesis pathway spirotetramat on SWD fitness with respect to fecundity and surface barrier function at different stages. In our experiments, we applied spirotetramat mixed with baker's yeast and showed that females and males were not repelled by effective concentrations of this insecticide. We found that spirotetramat, by trend, lowers egg numbers laid by fed females. These eggs rapidly desiccate, and only a few larvae hatch. Spirotetramat is lethal to larvae and reduces survival of adult flies under low-humidity conditions. Taken together, based on our data, we propose to use yeast supplemented with spirotetramat and additional SWD-specific attractants in traps in non-crop areas in order to eradicate SWD populations before they infest crop production sites.


[Adverse effects of ulcer drugs before and after release of cimetidine, ranitidine and sucralfate for over-the-counter sale].
During the period from the first marketing of cimetidine in 1977 and until 31 March 1990, the Danish Committee on Adverse Drug Reactions received 494 reports concerning a total of 612 suspected adverse reactions to peptic ulcer drugs (ATC group A02B). Out of these, adverse reactions to H2-receptor antagonists constituted 90%. The investigation confirms the fact that safe drugs are concerned which only rarely cause serious adverse reactions. During the first year after cimetidine, ranitidine and sucralfate became available over-the-counter (27 March 1989-31 March 1990), only one report about side effects caused by cimetidine sold over-the-counter was received. This corresponds to what might be anticipated from the usage figures, if availability over-the-counter does not result in particular adverse reaction problems. Decrease in the number of reports, alterations in the pattern of adverse reactions and under-reporting of known adverse reactions render employment of data from voluntary reports difficult.


Pterostilbene attenuates acute kidney injury in septic mice.
Acute kidney injury (AKI) is a severe complication of sepsis with a high mortality and morbidity. Pterostilbene (Pte) has been suggested to confer anti-apoptotic and anti-inflammatory effects. In the current study, the effects of Pte on AKI were evaluated in septic mice. Cecal ligation and puncture surgery was performed to induce sepsis. The results suggested that Pte administration significantly decreased the levels of serum urea nitrogen and creatinine, and improved the survival rate of septic mice. Additionally, the renal injury induced by sepsis was attenuated by pterostilbene treatment. Notably, pterostilbene reduced Bcl-2-associated X protein expression, and levels of interleukin-1β and tumor necrosis factor-α, and upregulated B-cell lymphoma 2 expression. The results indicate that pterostilbene may serve as a potential therapeutic candidate for the treatment of AKI induced by sepsis.


[Bilateral nephrectomy as a life saving procedure in a young woman with recurrent bacteremic shock].
On the basis of the recurrent bacteremic shock in young woman with bilateral reflux nephropathy and recurrent urinary tract infections (UTI) from early childhood we present diagnostic and therapeutic problems of complicated UTI. Negative results of localization diagnosis of UTI and clinical suspicious on renal microabscesses as a cause of recurrence bacteremic shock were the reason of bilateral nephrectomy--as a life saving procedure--and initiation of CAPD programme.


A longitudinal evaluation on 3-year change of anxiety and depression, and their risk factors among parents of childhood and adolescence patients with resectable osteosarcoma: A cohort study.
Psychological disorders often occur among parents of children with cancer. The current study aimed to explore the longitudinal change of anxiety and depression and their related factors among parents of childhood and adolescence patients with osteosarcoma. A total of 56 childhood and adolescence patients with osteosarcoma who underwent tumor resection and corresponding 104 parents were enrolled. Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and HADS-Depression (HADS-D) of parents were evaluated at baseline (the day of patients' hospital discharge), 0.5 year, 1 year, 2 years, and 3 years. From baseline to the 3rd year, HADS-A (from 8.3 ± 3.1 to 9.4 ± 3.1. P < .001), HADS-D score (from 7.7 ± 3.2 to 8.8 ± 2.9, P = .001), anxiety rate (from 45.2% to 60.6%, P = .038), depression rate (from 38.5% to 57.7%, P = .002) were elevated; meanwhile, anxiety severity (P = .001) and depression severity (P = .001) were also increased. Furthermore, multivariate logistic regression analysis presented that the role of mother, divorced/widowed marital status, declined family annual income, elevated Enneking stage, and amputation were independently correlated with elevated risk of parents' baseline anxiety or depression (all P < .05). Additionally, declined family annual income, elevated Enneking stage, and amputation were independently correlated with increased risk of parents' 3-year anxiety or depression (all P < .05). Anxiety and depression deteriorate with time in parents of childhood and adolescence patients with osteosarcoma, which are affected by parental role, marital status, family annual income, surgery type, and Enneking stage.


Competitive sorption of pyrene, phenanthrene, and naphthalene on multiwalled carbon nanotubes.
Knowledge of toxic chemical sorption by carbon nanotubes (CNTs) is critical for environmental application of CNTs as superior sorbents and for environmental risk assessment of both CNTs and toxic chemicals. Single-solute sorption results were reported in the literature, however, they cannot be used for predicting pollutant sorption by CNTs in wastewater and natural water systems where multiple organic contaminants are present. In this study, competitive sorption of pyrene, phenanthrene, and naphthalene on a multiwalled CNT material was investigated. All isotherms in single-, bi-, and tri-solute systems were fitted well by the Dubinin-Ashtakhov (DA) model. The isotherm of a given primary solute changed from being significantly nonlinear to nearly linear when competitors were added. The observed competitive sorption depended on the relative equilibrium concentrations of both primary and cosolutes. Significant competition was observed at relatively low concentrations of primary solute and high concentrations of competitors, while competition was much weaker in the case of relatively high concentrations of primary solute and low competitor concentrations. When the relative concentration of primary solute (Ce/Cs) approached 1, competition by other solutes seemed to disappear. Sorption and competition of three polycyclic aromatic hydrocarbons (PAHs) on CNTs could not be explained with either pore-filling or partition-adsorption mechanisms. A Polanyi-based surface adsorption mechanism was proposed to interpret the observed sorption and competition.


The refractive state of the eye in Icelandic horses with the Silver mutation.
The syndrome Multiple Congenital Ocular Anomalies (MCOA) is a congenital eye disorder in horses. Both the MCOA syndrome and the Silver coat colour in horses are caused by the same missense mutation in the premelanosome protein (PMEL) gene. Horses homozygous for the Silver mutation (TT) are affected by multiple ocular defects causing visual impairment or blindness. Horses heterozygous for the Silver mutation (CT) have less severe clinical signs, usually cysts arising from the ciliary body iris or retina temporally. It is still unknown if the vision is impaired in horses heterozygous for the Silver mutation. A recent study reported that Comtois horses carrying the Silver mutation had significantly deeper anterior chambers of the eye compared to wild-type horses. This could potentially cause refractive errors. The purpose of the present study was to investigate if Icelandic horses with the Silver mutation have refractive errors compared to wild-type horses. One hundred and fifty-two Icelandic horses were included in the study, 71 CT horses and five TT horses. All horses were genotyped for the missense mutation in PMEL. Each CT and TT horse was matched by a wild-type (CC) horse of the same age ± 1 year. Skiascopy and a brief ophthalmic examination were performed in all horses. Association between refraction and age, eye, genotype and sex was tested by linear mixed-effect model analysis. TT horses with controls were not included in the statistical analyses as they were too few. The interaction between age and genotype had a significant impact on the refractive state (P = 0.0001). CT horses older than 16 years were on average more myopic than wild-type horses of the same age. No difference in the refractive state could be observed between genotypes (CT and CC) in horses younger than 16 years. TT horses were myopic (-2 D or more) in one or both eyes regardless of age. Our results indicate that an elderly Icelandic horse (older than 16 years) carrying the Silver mutation is more likely to be myopic than a wild-type horse of the same age.


In vivo stress granule misprocessing evidenced in a FUS knock-in ALS mouse model.
Many RNA-binding proteins, including TDP-43, FUS, and TIA1, are stress granule components, dysfunction of which causes amyotrophic lateral sclerosis (ALS). However, whether a mutant RNA-binding protein disrupts stress granule processing in vivo in pathogenesis is unknown. Here we establish a FUS ALS mutation, p.R521C, knock-in mouse model that carries impaired motor ability and late-onset motor neuron loss. In disease-susceptible neurons, stress induces mislocalization of mutant FUS into stress granules and upregulation of ubiquitin, two hallmarks of disease pathology. Additionally, stress aggravates motor performance decline in the mutant mouse. By using two-photon imaging in TIA1-EGFP transduced animals, we document more intensely TIA1-EGFP-positive granules formed hours but cleared weeks after stress challenge in neurons in the mutant cortex. Moreover, neurons with severe granule misprocessing die days after stress challenge. Therefore, we argue that stress granule misprocessing is pathogenic in ALS, and the model we provide here is sound for further disease mechanistic study.


Many levels of control of V gene rearrangement frequency.
V, D, and J gene segments rearrange at very different frequencies. As with most biological systems, there are multiple levels of control of V gene recombination frequency, and here we review some of the work from our laboratory that addresses these various control mechanisms. One of the important factors that affect non-random V gene rearrangement frequency is the natural heterogeneity in recombination signal sequences (RSSs). Not only does variation in the heptamer and nonamer affect rearrangement, but variation in the spacer can also dramatically affect recombination. However, there are clearly other factors which control V gene rearrangement, as revealed by the fact that genes with identical RSSs can rearrange at different frequencies in vivo. Some of these other influences most likely affect the earliest stages of control--the change from an inaccessible state to an accessible state. Transcription factors can play a role in inducing these changes. Rearrangement of many VkappaI genes can be induced in a non-lymphoid cell line after ectopic expression of E2A, while neighboring VkappaII and VkappaIII genes do not rearrange, demonstrating that at least one level of control of induction of accessibility occurs at the level of the individual gene. Also, changes in chromatin structure can affect accessibility and might influence individual V gene rearrangement frequency.


Differentiation of small hyperechoic renal cell carcinoma from angiomyolipoma: computer-aided tissue echo quantification.
To assess the value of computer-aided tissue echo quantification in differentiating small hyperechoic renal cell carcinomas from angiomyolipomas, we studied ultrasonographic images of 15 renal cell carcinomas and 20 angiomyolipomas. After digitizing the images, we measured the absolute gray scale values of the renal cortex, central echo complex, and mass. The relative gray scale value (%) of the mass was calculated by setting the gray scale value of the cortex as 0% and the central echo complex as 100%. The relative gray scale value of renal cell carcinomas was in the range of 12 to 73% (mean, 28%), whereas that of angiomyolipomas was 30 to 204% (mean, 130%). The differentiation between small hyperechoic renal cell carcinomas and angiomyolipomas can be facilitated by computer-aided tissue echo quantification.


Improving the quality of EHR recording in primary care: a data quality feedback tool.
Electronic health record (EHR) data are used to exchange information among health care providers. For this purpose, the quality of the data is essential. We developed a data quality feedback tool that evaluates differences in EHR data quality among practices and software packages as part of a larger intervention. The tool was applied in 92 practices in the Netherlands using different software packages. Practices received data quality feedback in 2010 and 2012. We observed large differences in the quality of recording. For example, the percentage of episodes of care that had a meaningful diagnostic code ranged from 30% to 100%. Differences were highly related to the software package. A year after the first measurement, the quality of recording had improved significantly and differences decreased, with 67% of the physicians indicating that they had actively changed their recording habits based on the results of the first measurement. About 80% found the feedback helpful in pinpointing recording problems. One of the software vendors made changes in functionality as a result of the feedback. Our EHR data quality feedback tool is capable of highlighting differences among practices and software packages. As such, it also stimulates improvements. As substantial variability in recording is related to the software package, our study strengthens the evidence that data quality can be improved substantially by standardizing the functionalities of EHR software packages.


K-ion and Na-ion storage performances of Co3O4-Fe2O3 nanoparticle-decorated super P carbon black prepared by a ball milling process.
The hybridisation of Co3O4 and Fe2O3 nanoparticles dispersed in a super P carbon matrix is proposed as a favourable approach to improve the electrochemical performance (reversible capacity, cycling stability and rate capability) of the metal oxide electrodes in metal-ion batteries. Hybrid Co3O4-Fe2O3/C is prepared by a simple, cheap and easily scalable molten salt method combined with ball-milling and used in sodium-ion and potassium-ion batteries for the first time. The electrode exhibits excellent cycling stability and superior rate capability in sodium-ion cells with a capacity recovery of 440 mA h g-1 (93% retention) after 180 long-term cycles at 50-1000 mA g-1 and back to 50 mA g-1. In contrast, Co3O4-Fe2O3, Co3O4 and Fe2O3 electrodes display unsatisfactory electrochemical performance. The hybrid Co3O4-Fe2O3/C is also reactive with potassium and capable of delivering a reversible capacity of 220 mA h g-1 at 50 mA g-1 which is comparable with the most reported anode materials for potassium-ion batteries. The obtained results broaden the range of transition metal oxide-based hybrids as potential anodes for K-ion and Na-ion batteries, and suggest that further studies of these materials with potassium and sodium are worthwhile.


Predicting survival in glioblastoma with multimodal neuroimaging and machine learning.
Glioblastoma (GBM) is the most common and aggressive malignant glioma, with an overall median survival of less than two years. The ability to predict survival before treatment in GBM patients would lead to improved disease management, clinical trial enrollment, and patient care. GBM patients (N = 133, mean age 60.8 years, median survival 14.1 months, 57.9% male) were retrospectively recruited from the neurosurgery brain tumor service at Washington University Medical Center. All patients completed structural neuroimaging and resting state functional MRI (RS-fMRI) before surgery. Demographics, measures of cortical thickness (CT), and resting state functional network connectivity (FC) were used to train a deep neural network to classify patients based on survival (< 1y, 1-2y, >2y). Permutation feature importance identified the strongest predictors of survival based on the trained models. The models achieved a combined cross-validation and hold out accuracy of 90.6% in classifying survival (< 1y, 1-2y, >2y). The strongest demographic predictors were age at diagnosis and sex. The strongest CT predictors of survival included the superior temporal sulcus, parahippocampal gyrus, pericalcarine, pars triangularis, and middle temporal regions. The strongest FC features primarily involved dorsal and inferior somatomotor, visual, and cingulo-opercular networks. We demonstrate that machine learning can accurately classify survival in GBM patients based on multimodal neuroimaging before any surgical or medical intervention. These results were achieved without information regarding presentation symptoms, treatments, postsurgical outcomes, or tumor genomic information. Our results suggest GBMs have a global effect on the brain's structural and functional organization, which is predictive of survival.


[Nutritional physiology of whey and whey components].
Deriving from positive effects of whey drinking cures in antiquity, the Middle Ages and modern time, a review is given on nutritional significance of whey. The proteins are essential components of whey and belong to the proteins with highest biological value because of their amino acid composition. Besides, they show fundamental functional properties, which enable a varied application in foods, dietetic foods and beverages in form of different whey products (powder, protein concentrates and isolates). Whey proteins have found considerable usage in infant's nutrition as whey predominant formulas as well as whey protein hydrolysates in case of cow's milk protein intolerances. A recent field of research are biological active peptide sequences which become effective during digestion and are of importance for secretion of entero hormones as well as for immune enhancing effects. They may contribute to assess the biological value of whey proteins under enlarged points of view and to develop new application forms and areas. It is pointed to further fields of application (e.g. adipositas, gout, kidney insufficiency). Concerning the quantitatively most dominant lactose in whey, it is dealt with its importance for the healthy development of infants (adaptation to the increased lactose content of mother's milk) as well as with lactose intolerance and galactosaemia. In case of mineral salts of whey it is emphasized the high nutrient density of calcium (prophylaxis for osteoporosis), the beneficial Ca:P and Na:K proportions (antihypertensive in case of the last one), the promotion of absorption of mineral salts by lactose, and the high content of iodine. The whey is rich in B-vitamins, which contribute essentially for their satisfaction or requirement in case of a corresponding consumption. To be emphasized is the vitamin B12 in milk and whey, which is the sole source of this indispensable nutrient for blood-formation and cell division in lacto-ovo-vegetarian nutrition. In conclusion, a summarizing dietetics valuation of whey is performed.


Fibromuscular Dysplasia of the Coronary Arteries: A Case Report and Review of the Literature.
Fibromuscular dysplasia is a nonatherosclerotic and non-inflammatory vascular disease with primary lesion of renal and internal carotid arteries. We present a neonatal case of fibromuscular dysplasia who died on the second day of life. The newborn suffered from fibromuscular dysplasia of the coronary arteries and a congenital heart defect. The interesting feature of this case was the formation of aneurysms of the coronary arteries with pulmonary atresia. This case demonstrates a casuistically rare form of association between fibromuscular dysplasia of the coronary arteries and pulmonary artery atresia.


Changes in Sales of Vaping Products and Cigarettes Associated with the New York State Flavored Vaping Product Sales Restriction.
New York (NY) implemented a statewide restriction on the retail sale of flavored vaping products to reduce availability of vaping products having youth-appealing flavors in 2020. We assessed the intended effects of the NY law on sales of flavored vaping products and explored whether policy implementation had unintended effects on consumer behavior by evaluating policy-associated changes in sales of combusted cigarettes, which could serve as more harmful substitute products for NY consumers of flavored vaping products. We analyzed custom product-level weekly retail tobacco sales scanner data for NY and a comparison state (California [CA]) for convenience stores and other outlets for June 2018 through June 2021. We categorized flavor descriptors for vaping products as flavored or tobacco/unflavored and categorized cigarettes as menthol or nonmenthol. We used a difference-in-difference model to assess the effect of the sales restriction on unit sales of flavored and unflavored vaping products and menthol and nonmenthol cigarettes in NY compared with CA. Following NY policy implementation, flavored and total vaping product sales decreased in NY relative to CA. Unflavored vaping product sales increased in NY, while menthol cigarette sales did not change significantly relative to CA sales. The NY flavored vaping product policy was associated with fewer sales of flavored and total vaping products. The increase in sales of unflavored vaping products did not suggest complete substitution, and sales data suggest that consumers did not turn to cigarettes after flavored vaping products became unavailable. This study provides evidence that NY's flavored vaping product policy is associated with reduced flavored vaping product access and sales. Our analyses of potential unintended consequences indicate that some consumers switched from flavored to unflavored vaping products, but that cigarette sales did not change concurrent with the policy which means that decreased availability of flavored vaping products did not result in vapers switching to cigarettes. NY's policy had its intended effect with limited unintended consequences.


PDCD1 and CTLA4 polymorphisms affect the susceptibility to, and clinical features of, chronic immune thrombocytopenia.
Programmed death-1 (PD-1, PDCD1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4, CTLA4) play central roles in immune checkpoint pathways. Single nucleotide polymorphisms (SNPs) of PDCD1 and CTLA4 have been reported to be associated with susceptibility to some autoimmune diseases. However, the potential association between SNPs in these immune checkpoint genes and risk of chronic immune thrombocytopenia (cITP) remain controversial and obscure. The aims of this study were to clarify the influence of PDCD1 and CTLA4 SNPs on the risk of developing cITP and its clinical features. We obtained genomic DNA from 119 patients with cITP and 223 healthy controls; their genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Patients with cITP had a significantly higher frequency of the PDCD1 +7209 TT genotype compared with healthy controls. The CTLA4 -1577 GG genotype and CT60 GG genotype showed higher frequencies of platelet count <5 × 109 /l at diagnosis, minimum platelet count <5 × 109 /l, and bleeding symptoms. Moreover, the PDCD1 -606 AA genotype and +63379 TT genotype were significantly associated with a lower number of patients who achieved a complete response to prednisolone treatment. Our results suggest that the immune checkpoint polymorphisms may affect the susceptibility to the clinical features of cITP, and treatment response of the affected patients.


Efficacy of medium-chain triglyceride oil massage on growth in preterm infants: a randomized controlled trial: A CONSORT-compliant article.
Medium-chain triglyceride (MCT) oil consists of 8-12 carbons with higher absorption and provides better calories than long-chain triglyceride oil. This study was to explore the effect of MCT oil massage on growth in preterm infants. A prospective, single-blind, randomized (two treatments and one control) study was conducted. Preterm infants weighing between 1500 and 2000 g were recruited and randomly assigned to three groups: the MCT oil massage, massage alone and no massage groups. The standardized massage intervention consisted of two 5-min phases, including tactile and kinesthetic stimulation, which were given three times a day for 7 consecutive days. Premature infants in the oil massage group received massage with 10 mL/kg/day of MCT oil divided equally into three applications. Weight, length and head circumference were measured in the three groups at birth and on study days 1 to 7. Forty-eight neonates were evaluated with 16 in each of three groups. The linear mixed effect model was adjusted for other factors, and results showed that weight gain on the 4th day in the oil massage group was greater than that in the no massage group (P < .05). From the 5th to 7th day, weight gain in the oil massage group was greater than that in the other two groups (P < .05). Regarding head circumference and height, this study found that the MCT oil massage group did not have better results than the other two groups. No adverse events were noted in the massage groups. The results indicate that preterm infant daily massage with MCT oil is an effective intervention for weight gain that should be recognized as part of low-birth-weight infant developmental care. clinicaltrials.gov identifier NCT04281563, Registered on 24 February 2020.


Comparative studies on the interaction of benzo[a]pyrene with cells derived from poikilothermic and homeothermic vertebrates. I. Metabolism of benzo[a]pyrene.
The metabolism of benzo[a]pyrene (BP) to water-soluble derivatives was measured in cell cultures derived from poikilothermic and homeothermic vertebrates. Tritiated BP was added to the cultures and, after 24 hours of incubation, the medium was extracted with chloroform:methanol:water. The amount of BP metabolized per cell (relative efficiency of metabolism) was calculated from the 3H-BP equivalents in the aqueous phase of the extraction mixture. Many poikilothermic vertebrate cell cultures, including those derived from fish, toad, lizard, and turtle, were able to metabolize BP. In some instances, metabolism was as efficient as in rodent cell cultures. Cell multiplication was inhibited by BP, only in those cultures in which the metabolism of BP was highly efficient. Conversely, cytotoxicity was not observed in cell cultures with little or no ability to metabolize the carcinogen.


[Pneumorrhachis, spondylitis and meningitis secondary to emphysematous cystitis. Report of one case].
We report a 57-year-old woman who presented with low back pain, fever and impairment of consciousness. The patient was admitted to the intensive care unit in Glasgow 8, with neck stiffness, peritoneal irritation, leukocytosis, hyperglycemia requiring insulin and a urine test suspecting an infection. Brain CT was unremarkable, while CT of the abdomen and pelvis evidenced emphysematous cystitis, retropneumoperitoneum and pneumorrhachis. Blood, urine and cerebrospinal fluid cultures were positive to Escherichia coli. She was treated with ceftriaxone, ciprofloxacin and amikacin during one month followed by ciprofloxacin until completing 100 days. The air in the spinal canal and bladder decreased. However she suffered several infectious complications such as multiple paravertebral, epidural and psoas abscesses, L5-S1 spondylitis and a L3 fracture. As an inflammatory complication she developed a bulbar infarction and tetraparesis. She had a good clinical response with medical treatment, partial improvement of the paresis and reduction of epidural abscesses.


Ascites in cirrhosis: a review of management and complications.
Ascites is the most common manifestation in cirrhotic patients, and is associated with a reduced survival rate. Management of ascites is primarily focused on sodium restriction and diuretic treatment to which most patients respond appropriately. For the small group of patients who do not respond sufficiently, interventions such as large volume paracentesis and transjugular intrahepatic portosystemic shunt placement should be considered. Most important in the management of cirrhotic patients with ascites is prevention of complications. Spontaneous bacterial peritonitis and hepatorenal syndrome are severe complications with a poor prognosis when not detected and treated in an early stage. In all hospitalised patients with ascites, an infection of the ascitic fluid should be ruled out. For those patients at risk of developing spontaneous bacterial peritonitis, in particular patients after a first episode and patients with gastrointestinal bleeding, antibiotic prophylaxis should be given. To prevent the hepatorenal syndrome, substitution with albumin is essential, both in patients who experience an episode of spontaneous bacterial peritonitis and in patients treated with large volume paracentesis. For those patients unresponsive to standard treatment regimens, liver transplantation may be the only suitable treatment option.


Metastatic clival chordoma: a case report of multiple extraneural metastases following resection and proton beam radiotherapy in a 5-year old boy.
The authors report the case of a 5-year-old boy in whom extraneural metastases developed 5 years after he underwent an occipitocervical fusion and transoral approach to treat a clival chordoma without local recurrence. Following primary resection, the patient's postoperative course was complicated by recurrent meningitis secondary to CSF leak, which responded to antibiotics, and communicating hydrocephalus, for which a ventriculoperitoneal shunt was placed. The patient then underwent postoperative proton beam radiotherapy. Five years following his initial presentation, surveillance imaging revealed a new asymptomatic lung mass for which the patient underwent thoracotomy and resection of the mass. Histological examination of the lung mass revealed findings consistent with a de-differentiated chordoma, confirming extraneural metastasis from the original tumor without evidence of local recurrence. Chest wall and scalp metastases subsequently developed, and the patient was started on an adjuvant chemotherapy regimen that included imatinib and rapamycin followed by subsequent nivolumab and an EZH2 inhibitor for recurrent, disseminated disease. Despite this patient's remote and distant metastases, primary gross-total resection for chordoma remains a critical treatment objective, followed by proton beam radiotherapy. This case illustrates the importance of interval posttreatment imaging and the emerging potential to treat chordoma with molecularly targeted therapies.


Extracellular Vesicles as Biomarkers of Systemic Lupus Erythematosus.
Systemic lupus erythematosus is an autoimmune disease that predominantly affects women and typically manifests in multiple organs. The damage caused by this disorder is characterized by a chronic inflammatory state. Extracellular vesicles (EVs), including microvesicles (also known as microparticles), apoptotic bodies, and exosomes, are recognized vehicles of intercellular communication, carrying autoantigens, cytokines, and surface receptors. Therefore, the evidence of EVs and their cargo as biomarkers of autoimmune disease is rapidly expanding. This review will focus on biogenesis of extracellular vesicles, their pathophysiological roles, and their potential as biomarkers and therapeutics in inflammatory disease, especially in systemic lupus erythematosus.


Use of a new type of radiochromic film, a new parallel-plate micro-chamber, MOSFETs, and TLD 800 microcubes in the dosimetry of small beams.
The dosimetry of the fields usually employed in radiosurgery requires the use of small detectors to measure Total Scatter Factor (Sc,p), Tissue Maximum Ratio (TMR), Percentage Depth Dose (PDD), and Off Axis Ratio (OAR). In this paper new dosimeters are investigated: a new type of radiochromic film, a micro parallel-plate chamber (filled with both air and tetramethylsilane, TMS), MOSFETs, and TLD-800 microcubes. Their behavior has been compared with the response of radiographic film and with the values obtained with BEAM Monte Carlo simulation. The experimental data confirm that dosimetry with radiochromic films and TLDs gives consistent results for all beam diameters. The parallel-plate micro chamber underestimates the Sc,p for the smallest field diameters (4.4 mm and 6.7 mm); MOSFETs show an over-estimation for the Sc,p of the 4.4 mm, 6.7 mm, and 10.5 mm field diameters. BEAM Monte Carlo simulation employing a parallel beam and a standard 6 MV x-ray spectrum has been used to obtain a correction factor as a function of the field size for both the parallel-plate micro chamber and MOSFETs. High accuracy measurements of PDD and TMR have been made in a water phantom both with radiochromic film and with the micro parallel-plate chamber and have been compared with the data computed by BEAM Monte Carlo simulation. The latter dosimeter is preferred because of the quicker and simpler use and because it gives immediate readout. Measurements of OAR made with radiochromic films and with radiographic films give differences in the 80%-20% penumbra width within 0.6 mm for field diameters ranging from 4.4 mm to 19 mm.


The viscoelasticity of self-assembled proteoglycan combs.
Particle tracking microrheology with a fast digital camera allowed the slow and intermediate time regimes (10(-4)-10(1) s) of the linear viscoelasticity of giant aggrecan proteoglycans to be mapped. Combined with diffusing wave spectroscopy experiments this enabled us to probe the linear viscoelasticity of aggrecan over seven orders of magnitude in time (10(-6)-10(1) s) [Palmer et al., Biophys. J., 1999, 76, 1063; Papagiannopoulos et al., Biomacromolecules, 2007, 7, 2162]. When the comb side-groups self-assemble on the hyaluronic acid backbones they cause a dramatic increase in the relaxation time of the solutions and consequently the viscosity of the sample, but leave the elasticity of the solutions relatively unchanged. The experiments illustrate the modular nature of aggrecan's viscosity and clearly demonstrate the role of this molecule in vivo in cartilaginous composites, where it dissipates energy. Both one- and two-particle tracking microrheology were used to investigate the length-scale dependent viscoelasticity of the comb superstructures [Lui et al., Phys. Rev. Lett., 2006, 96, 118104] and the errors inherent in the two techniques were quantified [Savin and Doyle, Biophys. J., 2005, 88, 623; Waigh, Rep. Prog. Phys., 2005, 68, 685]. The behaviour of the viscoelasticity is compared with the predictions of dynamic scaling theory, indicating a significant contribution of the side-chain dynamics to the reptative motion of both the aggrecan aggregate and the monomers. The results have important implications for a molecular understanding of tissue function and pathology in osteoarthritis.


Current challenges for cancer vaccine adjuvant development.
Although much progress has been made in the last decade(s) toward development of effective cancer vaccines, there are still important obstacles to therapeutic successes. New generations of cancer vaccines will benefit from a combination adjuvant approach that targets multiple branches of the immune response. Herein we describe how combinatorial adjuvant strategies can help overcome important obstacles to cancer vaccine development, including antigen immunogenicity and tumor immune suppression. Tumor antigens may be both tolerogenic and may utilize active mechanisms to suppress host immunity, including downregulation of MHC molecules to evade recognition and upregulation of immune inhibitory receptors, to subvert an effective immune response. The current cancer vaccine literature was surveyed to identify advancements in the understanding of the biological mechanisms underlying poor antigen immunogenicity and tumor immune evasion, as well as adjuvant strategies designed to overcome them. Poor immunogenicity of tumor antigens and tumor immune evasion mechanisms make the design of cancer vaccines challenging. Growing understanding of the tumor microenvironment and associated immune responses indicate the importance of augmenting not only the effector response, but also overcoming the endogenous regulatory response and tumor evasion mechanisms. Therefore, new vaccines will benefit from multi-adjuvanted approaches that simultaneously stimulate immunity while preventing inhibition.


A new species and phylogenetic insights in Hesiospina (Annelida, Hesionidae).
Hesionids are a very speciose group of polychaetes. In the deep sea, they occur in different environments such as hydrothermal vents, cold seeps, abyssal depths or whale falls. In the present study, a new species of Hesionidae, Hesiospina legendrei sp. nov. has been identified based on morphological and molecular (16S and COI genes) data from hydrothermal vents located in Juan de Fuca Ridge (NE Pacific Ocean). This new species is characterized by trapezoid prostomium; proboscis with high number of distal papillae (20-27), a pair of sac-like structures inserted ventro-laterally in proboscis; notopodia lobe reduced with multiple, slender aciculae on segments 1-5; and neuropodia developed with single, simple chaeta, and numerous, heterogomph falcigers, with 1-2 inferiormost having elongated hood. Hesiospina legendrei sp. nov. is the third described species in the genus. Sequences from the two previously described Hesiospina species are included in the molecular analyses, and although the genes used in this study are not sufficient to resolve the relationships on genus level, the result raises questions about the cosmopolitan aspect of H. vestimentifera.