Parent Involvement in Maternal, Infant, and Early Childhood Home Visiting Programs: an Integrative Review.
Despite the evidence and investment in evidence-based federally funded maternal, infant, and early childhood home visiting, substantial challenges persist with parent involvement: enrolling, engaging, and retaining participants. We present an integrative review and synthesis of recent evidence regarding the influence of multi-level factors on parent involvement in evidence-based home visiting programs. We conducted a search for original research studies published from January 2007 to March 2018 using PubMed, Embase, Cochrane, and CINAHL databases. Twenty-two studies met criteria for inclusion. Parent and family characteristics were the most commonly studied influencing factor; however, consistent evidence for its role in involvement was scarce. Attributes of the home visitor and quality of the relationship between home visitor and participant were found to promote parent involvement. Staff turnover was found to be a barrier to parent involvement. A limited number of influencing factors have been adequately investigated, and those that have reveal inconsistent findings regarding factors that promote parent involvement in home visiting. Future research should move beyond the study of parent- and family-level characteristics and focus on program- and home visitor-level characteristics which, although still limited, have demonstrated some consistent association with parent involvement. Neighborhood characteristics have not been well studied and warrant future research.


High-content hydrogen water-induced downregulation of miR-136 alleviates non-alcoholic fatty liver disease by regulating Nrf2 via targeting MEG3.
This study was aimed to investigate the potential regulatory mechanism of high-content hydrogen water (HHW) in non-alcoholic fatty liver disease (NAFLD). A high-fat diet (HFD)-induced NAFLD mice model and cellular model were prepared. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total cholesterol (TCH) and triglycerides (TG) were measured. The expression levels of representative five microRNA (miRNAs) (miR-103, miR-488, miR-136, miR-505 and miR-148a) in liver tissues were determined by quantitative real-time PCR (qRT-PCR). The target of miR-136 was validated by RNA immunoprecipitation (RIP) and pull-down assay. MiR-136, MEG3 and nuclear factor erythroid 2-related factor 2 (Nrf2) expression levels following cell treatment were detected in hepatocytes using qRT-PCR and Western blotting. Moreover, cell viability and TG content were conducted. MiR-136 was downregulated, MEG3 as well as Nrf2 was upregulated and serum lipid level was reduced in NAFLD mice model after HHW treatment, which exerted the same effect in cellular model. RIP and RNA pull-down assay confirmed that MEG2 was a downstream target of miR-136. What's more, HHW ameliorated lipid accumulation by regulating miR-136/MEG3/Nrf2 axis in vitro and in vivo. Hence, HHW alleviated NAFLD by downregulation of miR-136 through mediating Nrf2 via targeting MEG3.


Synthesis of hyacinthacine B3 and purported hyacinthacine B7.
The synthesis of hyacinthacines B(3) and B(7) has confirmed the structure of the former alkaloid and shown that the structure of the latter is incorrect.


An Undergraduate Laboratory Series Using C. elegans That Prepares Students for Independent Inquiry.
Undergraduate neuroscience laboratories provide valuable opportunities for students to learn about neurobiological systems through active learning. Caenorhabditis elegans (C. elegans) is a valuable model for teaching students how to use a reductionist approach to neuroscientific inquiry. This series of lab modules trains students to utilize foundational laboratory techniques such as worm handling and maintenance, fluorescence imaging, behavioral assays, and Western blot. Upon completing this series of laboratory exercises, students are well prepared to engage in independent research projects using these research techniques. As supported by student survey results, this series of C. elegans laboratory exercises leads to the development of essential research skills, which students may be able to apply to a wide range of future scientific endeavors.


Effectiveness of acetic acid and formaldehyde for preventing protein degradation in the rumen.
Six rumen cannulated steers were in a replicated 3 X 3 Latin square arrangement to investigate degradability in the rumen of dry matter and crude protein from soybean meal that was untreated or treated with either 8% acetic acid or .3% formaldehyde. Polyester bags containing the soybean meals were suspended in the rumen of each steer and removed after 1, 2, 4, 8, 12, 16, and 24 h to calculate degradation rates. Soybean meals remaining in the polyester bags after 12 h of rumen exposure were collected and referred to as residues. Postruminal digestion was stimulated by incubating 200 mg of soybean meal residues with pepsin and pancreatin. Formaldehyde treatment of soybean meal was more effective than acetic acid treatment in preventing ruminal degradation of dry matter and crude protein under these experimental conditions. However, soybean meal treated with acetic acid and remaining in polyester bags after 12 h of ruminal exposure released a larger quantity of alpha-amino nitrogen during in vitro incubation with pepsin and pancreatin than did residue of soybean meal treated with formaldehyde. Acetic acid may prove to be an effective agent for increasing the supply of absorbable dietary amino acids.


Impact of the Mk VI SkinSuit on skin microbiota of terrestrial volunteers and an International Space Station-bound astronaut.
Microgravity induces physiological deconditioning due to the absence of gravity loading, resulting in bone mineral density loss, atrophy of lower limb skeletal and postural muscles, and lengthening of the spine. SkinSuit is a lightweight compression suit designed to provide head-to-foot (axial) loading to counteract spinal elongation during spaceflight. As synthetic garments may impact negatively on the skin microbiome, we used 16S ribosomal RNA (rRNA) gene amplicon procedures to define bacterial skin communities at sebaceous and moist body sites of five healthy male volunteers undergoing SkinSuit evaluation. Each volunteer displayed a diverse, distinct bacterial population at each skin site. Short (8 h) periods of dry hyper-buoyancy flotation wearing either gym kit or SkinSuit elicited changes in the composition of the skin microbiota at the genus level but had little or no impact on community structure at the phylum level or the richness and diversity of the bacterial population. We also determined the composition of the skin microbiota of an astronaut during pre-flight training, during an 8-day visit to the International Space Station involving two 6-7 h periods of SkinSuit wear, and for 1 month after return. Changes in composition of bacterial skin communities at five body sites were strongly linked to changes in geographical location. A distinct ISS bacterial microbiota signature was found which reversed to a pre-flight profile on return. No changes in microbiome complexity or diversity were noted, with little evidence for colonisation by potentially pathogenic bacteria; we conclude that short periods of SkinSuit wear induce changes to the composition of the skin microbiota but these are unlikely to compromise the healthy skin microbiome.


Risk factors for nonfatal self-harm and suicide among adolescents: two nested case-control studies conducted in the UK Clinical Practice Research Datalink.
The characteristics of adolescents who die by suicide have hitherto been examined in uncontrolled study designs, thereby precluding examination of risk factors. The degree to which antecedents of nonfatal self-harm and suicide at young age differ remains unknown. We delineated two nested case-control studies of patients aged 10-19 years using the Clinical Practice Research Datalink with interlinked hospital and national mortality records. Cases were adolescents who between 1st January 2003 and 31st December 2018 had died from suicide (N = 324) - study 1; experienced their first self-harm episode (N = 56,008) - study 2. In both studies, cases were matched on sex, age and practice-level deprivation quintile to 25 controls. By fitting conditional logistic regression, we examined how risks varied according to psychiatric diagnoses, prescribed psychotropic medication, patterns of clinical contact and area-level deprivation. Suicides occurred more often among boys (66%), but self-harm was more common in girls (68%). Most individuals who self-harmed or died from suicide presented to their GP at least once in the preceding year (85% and 75% respectively). Only a third of cases had one of the examined diagnostic categories recorded. Depression was most strongly associated with elevated risks for both outcomes (self-harm: OR 7.9; 95% CI 7.8-8.2; suicide: OR 7.4; 95% CI 5.5-9.9). Except for autism spectrum disorder, all other diagnostic categories were linked with similar risk elevations for self-harm as for suicide. Whilst self-harm risk rose incrementally with increasing levels of area-level deprivation, suicide risks did not. We observed few marked differences in risk factor profiles for nonfatal self-harm versus suicide. As most adolescents who had harmed themselves or died by suicide were known to services in the preceding year, their underlying pathology may not be adequately identified and treated. Our findings highlight the need for a multiagency approach to treatment and prevention.


Discrete emotion effects on lexical decision response times.
Our knowledge about affective processes, especially concerning effects on cognitive demands like word processing, is increasing steadily. Several studies consistently document valence and arousal effects, and although there is some debate on possible interactions and different notions of valence, broad agreement on a two dimensional model of affective space has been achieved. Alternative models like the discrete emotion theory have received little interest in word recognition research so far. Using backward elimination and multiple regression analyses, we show that five discrete emotions (i.e., happiness, disgust, fear, anger and sadness) explain as much variance as two published dimensional models assuming continuous or categorical valence, with the variables happiness, disgust and fear significantly contributing to this account. Moreover, these effects even persist in an experiment with discrete emotion conditions when the stimuli are controlled for emotional valence and arousal levels. We interpret this result as evidence for discrete emotion effects in visual word recognition that cannot be explained by the two dimensional affective space account.


DNA-enhanced peroxidase activity of a DNA-aptamer-hemin complex.
In vitro selection (SELEX) previously identified short single-stranded DNAs that specifically bound N-methylmesoporphyrin IX (NMM), a stable transition-state analogue for porphyrin-metallation reactions. Interestingly, iron(III)-protoporphyrin (hemin) was a good competitive inhibitor for the DNA-catalyzed metallation reaction, and appeared to bind strongly to the NMM-binding DNA aptamers. We investigated the peroxidase activity of the aptamer-hemin complexes to see if the DNA component of the complex, like the apoenzymes in protein peroxidases, could enhance the low intrinsic peroxidatic activity of hemin. Two porphyrin-binding DNA aptamers bound hemin with submicromolar affinity. The aptamer-hemin complexes had significantly higher peroxidase activity than hemin alone, under physiological conditions. The Vobs of the PS2.M-hemin complex was 250 times greater than that of hemin alone, and significantly superior to a previously reported hemin-catalytic-antibody complex. Preliminary spectroscopic evidence suggests the coordination of the hemin iron in the complex changes, such that the complex more closely resembles horseradish peroxidase and other heme proteins rather than hemin. A new class of catalytic activity for nucleic acids is reported. The aptamer-hemin complexes described are novel DNA enzymes and their study will help elucidate the structural and functional requirements of peroxidase enzymes in general and the ways that a nucleic acid 'apoenzyme' might work to enhance the intrinsic peroxidatic ability of hemin. These aptamer-hemin complexes could be regarded as prototypes for redox-catalyzing ribozymes in a primordial 'RNA world'.


SOAPdenovo2: an empirically improved memory-efficient short-read de novo assembler.
There is a rapidly increasing amount of de novo genome assembly using next-generation sequencing (NGS) short reads; however, several big challenges remain to be overcome in order for this to be efficient and accurate. SOAPdenovo has been successfully applied to assemble many published genomes, but it still needs improvement in continuity, accuracy and coverage, especially in repeat regions. To overcome these challenges, we have developed its successor, SOAPdenovo2, which has the advantage of a new algorithm design that reduces memory consumption in graph construction, resolves more repeat regions in contig assembly, increases coverage and length in scaffold construction, improves gap closing, and optimizes for large genome. Benchmark using the Assemblathon1 and GAGE datasets showed that SOAPdenovo2 greatly surpasses its predecessor SOAPdenovo and is competitive to other assemblers on both assembly length and accuracy. We also provide an updated assembly version of the 2008 Asian (YH) genome using SOAPdenovo2. Here, the contig and scaffold N50 of the YH genome were ~20.9 kbp and ~22 Mbp, respectively, which is 3-fold and 50-fold longer than the first published version. The genome coverage increased from 81.16% to 93.91%, and memory consumption was ~2/3 lower during the point of largest memory consumption.


Anxiety, depression and quality of life of cancer patients undergoing radiation therapy: a cross-sectional study in a community hospital outpatient centre.
The purpose of the present study is to determine the impact of illness characteristics and psychopathological comorbidity on the quality of life (QoL) of radio-oncological patients in health-related and individual dimensions. Sixty-three of 93 eligible patients (40 women and 23 men) were included in the study during their radiation therapy visit to an outpatient centre annexed to a community hospital in Southern Bavaria, Germany. In a semi-structured interview, we elicited individually relevant life domains rated by the patients according to the 'Schedule for the Evaluation of Individual Quality of Life - Direct Weighting'. In addition, the participants completed the 'European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire Core 30' and the 'Hospital Anxiety and Depression Scale'. We also assessed the demand for psychotherapy and utilization of psycho-oncological services. In total, 9.5% of the examined patients suffer from clinically relevant anxiety and/or depression [total Hospital Anxiety and Depression Scale (HADS) score >19]. There was a weak positive correlation between Karnofsky's Performance Status and QoL. Anxiety and depression were significantly correlated with impaired QoL, especially with impaired individual QoL. There was no association between psychopathological comorbidity and the requirement for psycho-oncological support. Conversely, patients who report difficulties in accepting help had a significantly lower QoL. Psychopathological comorbidity has a considerable influence on QoL of patients undergoing radiotherapy. Measuring the individual QoL appears as an adapted needs assessment and helps the psychotherapist in focusing on the patient's problems and desires. Furthermore, the patient's QoL is a main target in providing or planning mental health care in non-university oncological services.


Promoter opening (melting) and transcription initiation by RNA polymerase I requires neither nucleotide beta,gamma hydrolysis nor protein phosphorylation.
With some bacterial RNA polymerases and in eukaryotic RNA polymerase II, DNA melting during initiation requires the coupling of energy derived from beta,gamma hydrolysis of ATP. A detailed analysis of this possible requirement for eukaryotic RNA polymerase I reveals no such requirement. However, in some cases, beta,gamma non-hydrolyzable derivatives (beta,gamma imido or methylene) of nucleotide substrates have been found to significantly inhibit transcription initiation because of their inefficient use as the first nucleotide of the transcript. In addition, the results presented here show that protein kinase activity is not required as an integral part of transcription initiation by RNA polymerase I. Prior phosphorylation of proteins participating in the process is not ruled out.


Cortical Regions Activated by Spectrally Degraded Speech in Adults With Single Sided Deafness or Bilateral Normal Hearing.
Those with profound sensorineural hearing loss from single sided deafness (SSD) generally experience greater cognitive effort and fatigue in adverse sound environments. We studied cases with right ear, SSD compared to normal hearing (NH) individuals. SSD cases were significantly less correct in naming last words in spectrally degraded 8- and 16-band vocoded sentences, despite high semantic predictability. Group differences were not significant for less intelligible 4-band sentences, irrespective of predictability. SSD also had diminished BOLD percent signal changes to these same sentences in left hemisphere (LH) cortical regions of early auditory, association auditory, inferior frontal, premotor, inferior parietal, dorsolateral prefrontal, posterior cingulate, temporal-parietal-occipital junction, and posterior opercular. Cortical regions with lower amplitude responses in SSD than NH were mostly components of a LH language network, previously noted as concerned with speech recognition. Recorded BOLD signal magnitudes were averages from all vertices within predefined parcels from these cortex regions. Parcels from different regions in SSD showed significantly larger signal magnitudes to sentences of greater intelligibility (e.g., 8- or 16- vs. 4-band) in all except early auditory and posterior cingulate cortex. Significantly lower response magnitudes occurred in SSD than NH in regions prior studies found responsible for phonetics and phonology of speech, cognitive extraction of meaning, controlled retrieval of word meaning, and semantics. The findings suggested reduced activation of a LH fronto-temporo-parietal network in SSD contributed to difficulty processing speech for word meaning and sentence semantics. Effortful listening experienced by SSD might reflect diminished activation to degraded speech in the affected LH language network parcels. SSD showed no compensatory activity in matched right hemisphere parcels.


Local Rheology Relation with Variable Yield Stress Ratio across Dry, Wet, Dense, and Dilute Granular Flows.
Dry, wet, dense, and dilute granular flows have been previously considered fundamentally different and thus described by distinct, and in many cases incompatible, rheologies. We carry out extensive simulations of granular flows, including wet and dry conditions, various geometries and driving mechanisms (boundary driven, fluid driven, and gravity driven), many of which are not captured by standard rheology models. For all simulated conditions, except for fluid-driven and gravity-driven flows close to the flow threshold, we find that the Mohr-Coulomb friction coefficient μ scales with the square root of the local Péclet number Pe provided that the particle diameter exceeds the particle mean free path. With decreasing Pe and granular temperature gradient M, this general scaling breaks down, leading to a yield condition with a variable yield stress ratio characterized by M.


Tumor evolution and progression in multifocal and paired non-invasive/invasive urothelial carcinoma.
Although multifocal tumors and non-invasive/invasive components are commonly encountered in surgical pathology, their genetic relationship is often poorly characterized. We used next-generation sequencing (NGS) to characterize somatic alterations in a patient with five spatially distinct, high-grade papillary urothelial carcinomas (UCs), with one tumor harboring an underlying invasive component. NGS of 409 cancer-related genes was performed on DNA isolated from formalin-fixed paraffin-embedded (FFPE) blocks representing each papillary tumor (n = 5), the invasive component of one tumor, and matched normal tissue. We identified nine unique non-synonymous somatic mutations across the six UC samples, including five present in each carcinoma sample, consistent with clonal origin and limited intertumoral heterogeneity. Copy number and loss of heterogeneity (LOH) profiles were similar in all six carcinomas; however, the invasive carcinoma component uniquely showed focal CDKN2A loss and chromosome 9 LOH and did not harbor gains of chromosomes 5p or X that were present in the other tumor samples. Phylogenetic analysis supported the invasive component arising from a shared progenitor prior to the outgrowth of cells in the non-invasive tumors. Results were extended to three additional cases of upper tract UC with paired non-invasive/invasive components, which identified driving alterations exclusive to both non-invasive and invasive components. Lastly, we performed targeted RNA sequencing (RNAseq) using a custom bladder cancer panel, which confirmed gene expression signature differences between paired non-invasive/invasive components. The results and approaches presented here may be useful in understanding the clonal relationships in multifocal cancers or paired non-invasive/invasive components from routine FFPE specimens.


Predictors of remission from PTSD symptoms after sexual and non-sexual trauma in the community: A mediated survival-analytic approach.
Epidemiological data on the chronicity of posttraumatic stress disorder (PTSD) symptoms in relation to trauma type and underlying pathways are rare. The current study explored how PTSD symptoms change over time across different trauma types and examined mediators of their persistence. A trauma-exposed community sample, whereof approximately one quarter met diagnostic criteria for PTSD, provided retrospective data on the duration of PTSD symptoms. Those who remitted and those who had not at the time of assessment were compared regarding worst trauma, symptom severity, comorbidity, demographic and treatment-seeking variables. Time to remission was estimated using Cox proportional hazard models including candidate predictors of remission. A mediated survival analysis was used to explore indirect pathways that explain trauma-specific differences in remission times. Both the full sample and PTSD subgroup were analyzed separately. Overall, lower socio-economic status, lifetime and childhood sexual trauma, symptom severity, comorbid depression and past treatment were associated with non- and longer remissions. PTSD avoidance symptoms and comorbid depression were found to mediate longer remission times after lifetime or childhood sexual trauma. Our findings provide insight into the mechanisms and complicating factors of remission from PTSD symptoms after trauma, which might have important implications for therapeutic interventions.


Cardiac muscle mechanics from Doca- and aging spontaneously hypertensive rats.
Contractile properties of isolated papillary muscles from three age groups of spontaeously hypertensive rats (SHRs) were compared to those from age-matched Wistar-Kyoto rats (WKYs) to assess whether there were differences between the strains preceding and during the course of the hypertension. In all three age groups (7, 12, and 50 wk), the mechanical refractory periods (MRP) were longer and aftercontractions more prominent after paired pulse stimulation in preparations from SHRs than from age-matched WKYs. Other isometric twitch properties of SHR papillary muscles at Lmax were not different from WKYs, with the exception of a shorter half-relaxation time in the youngest SHR group. Although hypertension and cardiac hypertrophy increased in SHRs with age, aging had similar influences on most cardiac contractile properties in both strains. None of the isometric properties of papillary muscles from rats made hypertensive by Doca treatment were different from those in normotensive control preparations. This suggests that differences seen between SHRs and WKYs probably represent genetic differences between these strains and are not directly caused by the hypertension.


A flexible Bayesian model for studying gene-environment interaction.
An important follow-up step after genetic markers are found to be associated with a disease outcome is a more detailed analysis investigating how the implicated gene or chromosomal region and an established environment risk factor interact to influence the disease risk. The standard approach to this study of gene-environment interaction considers one genetic marker at a time and therefore could misrepresent and underestimate the genetic contribution to the joint effect when one or more functional loci, some of which might not be genotyped, exist in the region and interact with the environment risk factor in a complex way. We develop a more global approach based on a Bayesian model that uses a latent genetic profile variable to capture all of the genetic variation in the entire targeted region and allows the environment effect to vary across different genetic profile categories. We also propose a resampling-based test derived from the developed Bayesian model for the detection of gene-environment interaction. Using data collected in the Environment and Genetics in Lung Cancer Etiology (EAGLE) study, we apply the Bayesian model to evaluate the joint effect of smoking intensity and genetic variants in the 15q25.1 region, which contains a cluster of nicotinic acetylcholine receptor genes and has been shown to be associated with both lung cancer and smoking behavior. We find evidence for gene-environment interaction (P-value = 0.016), with the smoking effect appearing to be stronger in subjects with a genetic profile associated with a higher lung cancer risk; the conventional test of gene-environment interaction based on the single-marker approach is far from significant.


Association of COVID-19 Versus COVID-19 Vaccination With Kidney Function and Disease Activity in Primary Glomerular Disease: A Report of the Cure Glomerulonephropathy Study.
Patients with glomerular disease (GN) may be at increased risk of severe COVID-19, yet concerns over vaccines causing disease relapse may lead to vaccine hesitancy. We examined the associations of COVID-19 with longitudinal kidney function and proteinuria and compared these with similar associations with COVID-19 vaccination. Observational cohort study from July 1, 2021, to January 1, 2023. A prospective observational study network of 71 centers from North America and Europe (CureGN) with children and adults with primary minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy. COVID-19 and COVID-19 vaccination. Repeated measure of estimated glomerular filtration rate (eGFR); recurrent time-to-event outcome of GN disease worsening as defined by doubling of the urinary protein-creatinine ratio (UPCR) to at least 1.5g/g or increase in dipstick urine protein by 2 ordinal levels to 3+(300mg/dL) or above. Interrupted time series analysis for eGFR. Prognostic matched sequential stratification recurrent event analysis for GN disease worsening. Among 2,055 participants, 722 (35%) reported COVID-19 infection; of these, 92 (13%) were hospitalized, and 3 died (<1%). The eGFR slope before COVID-19 infection was-1.40mL/min/1.73m2 (± 0.29 SD); within 6 months after COVID-19 infection, the eGFR slope was-4.26mL/min/1.73m2 (± 3.02 SD), which was not significantly different (P=0.34). COVID-19 was associated with increased risk of worsening GN disease activity (HR, 1.35 [95% CI, 1.01-1.80]). Vaccination was not associated with a change in eGFR (-1.34mL/min/1.73m2±0.15 SD vs-2.16mL/min/1.73m2±1.74 SD; P=0.6) or subsequent GN disease worsening (HR 1.02 [95% CI, 0.79-1.33]) in this cohort. Infrequent or short follow-up. Among patients with primary GN, COVID-19 infection was severe for 1 in 8 cases and was associated with subsequent worsening of GN disease activity, as defined by proteinuria. By contrast, vaccination against COVID-19 was not associated with change in disease activity or kidney function decline. These results support COVID-19 vaccination for patients with GN. In this cohort study of 2,055 patients with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy, COVID-19 resulted in hospitalization or death for 1 in 8 cases and was associated with a 35% increase in risk for worsening proteinuria. By contrast, vaccination did not appear to adversely affect kidney function or proteinuria. Our data support vaccination for COVID-19 in patients with glomerular disease.


Self-assembly in poly(dimethylsiloxane)-poly(ethylene oxide) block copolymer template directed synthesis of Linde type A zeolite.
We describe the hydrothermal synthesis of zeolite Linde type A (LTA) submicrometer particles using a water-soluble amphiphilic block copolymer of poly(dimethylsiloxane)-b-poly(ethylene oxide) as a template. The formation and growth of the intermediate aggregates in the presence of the diblock copolymer have been monitored by small-angle X-ray scattering (SAXS) above the critical micellar concentration at a constant temperature of 45 °C. The early stage of the growth process was characterized by the incorporation of the zeolite LTA components into the surface of the block copolymer micellar aggregates with the formation of primary units of 4.8 nm with a core-shell morphology. During this period, restricted to an initial time of 1-3 h, the core-shell structure of the particles does not show significant changes, while a subsequent aggregation process among these primary units takes place. A shape transition of the SAXS profile at the late stage of the synthesis has been connected with an aggregation process among primary units that leads to the formation of large clusters with fractal characteristics. The formation of large supramolecular assemblies was finally verified by scanning electron microscopy, which evidenced the presence of submicrometer aggregates with size ranging between 100 and 300 nm, while X-ray diffraction confirmed the presence of crystalline zeolite LTA. The main finding of our results gives novel insight into the mechanism of formation of organic-inorganic mesoporous materials based on the use of a soft interacting nanotemplate as well as stimulates the investigation of alternative protocols for the synthesis of novel hybrid materials with new characteristics and properties.


Treatment of blocked elbow flexion in congenital radioulnar synostosis with radial head excision: a case series.
Congenital radioulnar synostosis (CRUS) causes a spectrum of presentations, most commonly a restriction of forearm rotation. Because most of these children are not treated operatively, many are not followed clinically after the diagnosis has been made. This report describes that a subset of the Cleary and Omer type IV synostoses (anterior dislocation of the radial head) can present with a progressive block to elbow flexion that worsens with growth. The location of this synostosis allows the physis of the radial head to grow untethered. The enlarged radial head can impinge upon the capitellum, blocking elbow flexion and snapping on the annular ligament. We propose excision of the radial head as a method of treating the anteriorly dislocated radial head in type IV synostoses. We evaluated 4 patients with Cleary and Omer type IV synostoses who presented with an anteriorly dislocated radial head impinging on elbow flexion with snapping of the annular ligament. Each patient was treated with excision of the radial head. In 4 patients excision of the radial head was performed through a lateral Kocher approach. At follow-up, all patients showed relief from their pain and mechanical symptoms, with return of baseline range of motion. One complication which occurred was transient radial nerve neuropraxia. Although surgery is rarely needed for CRUS, excision of the radial head may be indicated if progressive loss of elbow flexion occurs secondary to impingement of the anteriorly dislocated radial head with the distal humerus in patients with type IV synostosis. We report that excision of the radial head can successfully treat this condition. Patients with type IV CRUS should be educated about the potential for loss of elbow flexion and/or followed until skeletal maturity to evaluate for this potential condition. Case series consistent with level IV evidence; therapeutic study.


Interaction of leisure-time physical activity with body mass index on the risk of obesity-related cancers: A pooled study.
Physical activity (PA) has been associated with a lower risk of some obesity-related cancers, but the combined association and interaction of PA and body weight on obesity-related cancer risk is less clear. We examined the association of leisure-time PA (high/low) and its combination with body mass index (BMI, <25 [low]/≥25 [high] kg/m2 ) on obesity-related cancer risk in 570 021 individuals, aged 43 years on average at baseline, in five Scandinavian cohorts. We used Cox regression to calculate hazard ratios of obesity-related cancers (n = 19 074) and assessed multiplicative and additive interactions between PA and BMI on risk. High leisure-time PA, recorded in 19% of the individuals, was associated with a 7% (95% confidence interval [CI] 4%-10%) lower risk of any obesity-related cancer compared to low PA, with similar associations amongst individuals with a low and a high BMI (6% [1%-11%] and 7% [2%-11%]). High PA was also associated with decreased risks of renal cell (11% [9%-31%]) and colon cancer (9% [2%-16%]). When high PA and low BMI were combined, the relative risk reduction for all obesity-related cancers was 24% (95% CI 20%-28%); endometrial cancer, 47% (35%-57%); renal cell cancer, 39% (27%-51%); colon cancer, 27% (19%-35%); multiple myeloma, 23% (2%-40%) and pancreatic cancer, 21% (4%-35%), compared to low PA-high BMI. There were no additive or multiplicative interactions between PA and BMI on risk. The result of our study suggests a reduced risk of obesity-related cancer by leisure-time PA in both normal weight and overweight individuals, which further decreased for PA and normal weight combined.


Insular volume abnormalities associated with different transition probabilities to psychosis.
Although individuals vulnerable to psychosis show brain volumetric abnormalities, structural alterations underlying different probabilities for later transition are unknown. The present study addresses this issue by means of voxel-based morphometry (VBM). We investigated grey matter volume (GMV) abnormalities by comparing four neuroleptic-free groups: individuals with first episode of psychosis (FEP) and with at-risk mental state (ARMS), with either long-term (ARMS-LT) or short-term ARMS (ARMS-ST), compared to the healthy control (HC) group. Using three-dimensional (3D) magnetic resonance imaging (MRI), we examined 16 FEP, 31 ARMS, clinically followed up for on average 3 months (ARMS-ST, n=18) and 4.5 years (ARMS-LT, n=13), and 19 HC. The ARMS-ST group showed less GMV in the right and left insula compared to the ARMS-LT (Cohen's d 1.67) and FEP groups (Cohen's d 1.81) respectively. These GMV differences were correlated positively with global functioning in the whole ARMS group. Insular alterations were associated with negative symptomatology in the whole ARMS group, and also with hallucinations in the ARMS-ST and ARMS-LT subgroups. We found a significant effect of previous antipsychotic medication use on GMV abnormalities in the FEP group. GMV abnormalities in subjects at high clinical risk for psychosis are associated with negative and positive psychotic symptoms, and global functioning. Alterations in the right insula are associated with a higher risk for transition to psychosis, and thus may be related to different transition probabilities.


Treatment of uncomplicated gonorrhoea in women. Comparison of rosoxacin and spectinomycin.
A comparative study of the new antibacterial agent, rosoxacin, a quinoline derivative, with spectinomycin was made in women with uncomplicated cervical, urethral, pharyngeal, and rectal gonorrhoea. Rosoxacin was given in three oral regimens: 200 mg in a single dose, 300 mg in a single dose, and 300 mg in two doses of 150 mg four hours apart. All culture results 72 hours after administration were negative for Neisseria gonorrhoeae in all 81 women compared with 107 of 109 who received 2 g spectinomycin intramuscularly. Thirty-five of the women successfully treated with rosoxacin harboured penicillinase-producing strains of N gonorrhoeae (PPNG) and 46 non-penicillinase-producing (non-PPNG) strains. Fifty of the women treated with spectinomycin had PPNG strains and 59 non-PPNG strains. Mild self-limiting side effects, principally dizziness, occurred in varying frequency with rosoxacin, but these were difficult to evaluate owing to the characteristics of the patient population and the conditions under which the study was conducted.


[An outbreak of neonatal meningitis caused by enterovirus].
Six newborn infants affected by acute aseptic neonatal meningitis were attended during the months of June and July 1987. Fever, good general physical appearance and no associate focal symptomatology was the onset in five cases, whereas one of them had apnea spells. An increase in total cell count was present in CSF with polymorphonuclears predominance in two cases, being lymphocites more prevalent in the others. Enterovirus were demonstrated as a cause in three of them. After describing clinical facts and evolution, some epidemiological aspects are commented.


Graves' disease and diabetes mellitus associated with acute suppurative thyroiditis: a case report.
Acute suppurative thyroiditis (AST) is a rare disorder. The rarity of AST is a result of the resistance of the thyroid gland to local infection. Thyroid function tests are usually normal in AST. In a review of the literature from 1966 to 1995, only three cases of AST associated with thyrotoxicosis have been convincingly demonstrated. The thyrotoxicosis in these cases was caused by diffuse inflammation of the thyroid gland and to the disruption of follicles with the release of pre-formed thyroid hormone into the circulation. Thus, the thyrotoxicosis in these cases was transient. With successful therapy, nearly all patients showed complete recovery of thyroid function within two to three months. The patient in the case here was a diabetic woman with Graves' disease in whom thyrotoxicosis occurred after Klebsiella pneumoniae thyroiditis, with relapse nine months after discharge. Thus, the patient's thyrotoxicosis might not have been caused simply from thyroid tissue destruction by AST, but also as a result of enhancing autoimmune activity. No previous case has ever been reported in the English literature. In diabetics, the impairment of chemotaxis and phagocytosis has been noted. Therefore, diabetes mellitus (DM) might have been the precipitating factor for this patient's acquiring this unusual infection. Thyrotoxicosis and AST will increase insulin requirements and thus aggravate diabetes. In addition, poor control of blood sugar will enhance the severity of AST.


[Efficacy of computed tomography coronary angiography in cardiovascular surgery].
The clinical efficacy of multi-slice computed tomography (MSCT) in aortic lesions has improved in leaps and bounds. Using 64-slice MSCT with ECG-gating, it is possible to obtain scans that simultaneously achieve ultra-high-speed scanning, wide area scanning, and high-resolution data acquisition, thereby facilitating the routinization of isotropic data acquisition and a reduction in cardiac motion artifacts. Computed tomography coronary angiography (CTCA) using 64-slice MSCT is very useful for the preoperative and postoperative assessment of coronary arteries.


Healthcare Worker Attendance During the Early Stages of the COVID-19 Pandemic: A Longitudinal Analysis of Daily Fingerprint-Verified Data from All Public-Sector Secondary and Tertiary Care Facilities in Bangladesh.
The COVID-19 pandemic has overwhelmed hospitals in several areas in high-income countries. An effective response to this pandemic requires healthcare workers (HCWs) to be present at work, particularly in low- and middle-income countries (LMICs) where they are already in critically low supply. To inform whether and to what degree policymakers in Bangladesh, and LMICs more broadly, should expect a drop in HCW attendance as COVID-19 continues to spread, this study aims to determine how HCW attendance has changed during the early stages of the COVID-19 pandemic in Bangladesh. This study analyzed daily fingerprint-verified attendance data from all 527 public-sector secondary and tertiary care facilities in Bangladesh to describe HCW attendance from January 26, 2019 to March 22, 2020, by cadre, hospital type, and geographic division. We then regressed HCW attendance onto fixed effects for day-of-week, month, and hospital, as well as indicators for each of three pandemic periods: a China-focused period (January 11, 2020 [first confirmed COVID-19 death in China] until January 29, 2020), international-spread period (January 30, 2020 [World Health Organization declared a global emergency] until March 6, 2020), and local-spread period (March 7, 2020 [first confirmed COVID-19 case in Bangladesh] until the end of the study period). On average between January 26, 2019 and March 22, 2020, 34.1% of doctors, 64.6% of nurses, and 70.6% of other healthcare staff were present for their scheduled shift. Attendance rate increased with time in 2019 among all cadres. Attendance level of nurses dropped by 2.5% points (95% CI; -3.2% to -1.8%) and 3.5% points (95% CI; -4.5% to -2.5%) during the international-spread and the local-spread periods of the COVID-19 pandemic, relative to the China-focused period. Similarly, the attendance level of other healthcare staff declined by 0.3% points (95% CI; -0.8% to 0.2%) and 2.3% points (95% CI; -3.0% to -1.6%) during the international-spread and local-spread periods, respectively. Among doctors, however, the international-spread and local-spread periods were associated with a statistically significant increase in attendance by 3.7% points (95% CI; 2.5% to 4.8%) and 4.9% points (95% CI; 3.5% to 6.4%), respectively. The reduction in attendance levels across all HCWs during the local-spread period was much greater at large hospitals, where the majority of COVID-19 testing and treatment took place, than that at small hospitals. After a year of significant improvements, attendance levels among nurses and other healthcare staff (who form the majority of the healthcare workforce in Bangladesh) have declined during the early stages of the COVID-19 pandemic. This finding may portend an even greater decrease in attendance if COVID-19 continues to spread in Bangladesh. Policymakers in Bangladesh and similar LMICs should undertake major efforts to achieve high attendance levels among HCWs, particularly nurses, such as by providing sufficient personal protective equipment as well as monetary and non-monetary incentives.


The Potential Role of Catheter-Based Renal Sympathetic Denervation in Chronic and End-Stage Kidney Disease.
Sympathetic activation is a hallmark of chronic and end-stage renal disease and adversely affects cardiovascular prognosis. Hypertension is present in the vast majority of these patients and plays a key role in the progressive deterioration of renal function and the high rate of cardiovascular events in this patient cohort. Augmentation of renin release, tubular sodium reabsorption, and renal vascular resistance are direct consequences of efferent renal sympathetic nerve stimulation and the major components of neural regulation of renal function. Renal afferent nerve activity directly influences sympathetic outflow to the kidneys and other highly innervated organs involved in blood pressure control via hypothalamic integration. Renal denervation of the kidney has been shown to reduce blood pressure in many experimental models of hypertension. Targeting the renal nerves directly may therefore be specifically useful in patients with chronic and end-stage renal disease. In this review, we will discuss the potential role of catheter-based renal denervation in patients with impaired kidney function and also reflect on the potential impact on other cardiovascular conditions commonly associated with chronic kidney disease such as heart failure and arrhythmias.


Thickness-Prediction Method Involving Tow Redistribution for the Dome of Composite Hydrogen Storage Vessels.
Traditional thickness-prediction methods underestimate the actual dome thickness at polar openings, leading to the inaccurate prediction of the load-bearing capacity of composite hydrogen storage vessels. A method of thickness prediction for the dome section of composite hydrogen storage vessels was proposed, which involved fiber slippage and tow redistribution. This method considered the blocking effect of the port on sliding fiber tows and introduced the thickness correlation to predict the dome thickness at polar openings. The arc length corresponding to the parallel circle radius was calculated, and then, the actual radius values corresponding to the bandwidth were obtained by the interpolation method. The predicted thickness values were compared with the actual measured thickness. The maximum relative error of the predicted thickness was 4.19%, and the mean absolute percentage error was 2.04%. The results show that the present method had a higher prediction accuracy. Eventually, this prediction method was used to perform progressive damage analysis on vessels. By comparing with the results of the cubic spline function method, the analysis results of the present method approached the actual case. This showed that the present method improved the accuracy of the design.


The accumulation of Man(6)GlcNAc(2)-PP-dolichol in the Saccharomyces cerevisiae Deltaalg9 mutant reveals a regulatory role for the Alg3p alpha1,3-Man middle-arm addition in downstream oligosaccharide-lipid and glycoprotein glycan processing.
N-Glycans in nearly all eukaryotes are derived by transfer of a precursor Glc(3)Man(9)GlcNAc(2) from dolichol (Dol) to consensus Asn residues in nascent proteins in the endoplasmic reticulum. The Saccharomyces cerevisiae alg (asparagine-linked glycosylation) mutants fail to synthesize oligosaccharide-lipid properly, and the alg9 mutant, accumulates Man(6)GlcNAc(2)-PP-Dol. High-field (1)H NMR and methylation analyses of Man(6)GlcNAc(2) released with peptide-N-glycosidase F from invertase secreted by Deltaalg9 yeast showed its structure to be Manalpha1,2Manalpha1,2Manalpha1, 3(Manalpha1,3Manalpha1,6)-Manbeta1,4GlcNAcbeta1, 4GlcNAcalpha/beta, confirming the addition of the alpha1,3-linked Man to Man(5)GlcNAc(2)-PP-Dol prior to the addition of the final upper-arm alpha1,6-linked Man. This Man(6)GlcNAc(2) is the endoglycosidase H-sensitive product of the Alg3p step. The Deltaalg9 Hex(7-10)GlcNAc(2) elongation intermediates were released from invertase and similarly analyzed. When compared with alg3 sec18 and wild-type core mannans, Deltaalg9 N-glycans reveal a regulatory role for the Alg3p-dependent alpha1,3-linked Man in subsequent oligosaccharide-lipid and glycoprotein glycan maturation. The presence of this Man appears to provide structural information potentiating the downstream action of the endoplasmic reticulum glucosyltransferases Alg6p, Alg8p and Alg10p, glucosidases Gls1p and Gls2p, and the Golgi Och1p outerchain alpha1,6-Man branch-initiating mannosyltransferase.


Physical Exercise with Music Reduces Gray and White Matter Loss in the Frontal Cortex of Elderly People: The Mihama-Kiho Scan Project.
Findings from previous studies suggest that physical exercise combined with cognitive training produces more positive effects on cognitive function in elderly people than physical exercise alone. However, the brain plasticity associated with these proposed benefits of combined therapy has not yet been investigated in elderly subjects. We hypothesized that the dual task group would experience greater benefits than the physical exercise alone and non-exercise control groups with regard to both cognitive function and brain plasticity. This study investigated the effect of physical exercise with musical accompaniment on structural brain changes in healthy elderly people. Fifty-one participants performed physical exercise (once a week for an hour with professional trainers) with musical accompaniment (ExM), 61 participants performed the same exercise without music (Ex), and 32 participants made up the non-exercise group (Cont). After the 1-year intervention, visuospatial functioning of the ExM but not the Ex group was significantly better than that of the Cont group. Voxel-based morphometry analyses revealed that the ExM group showed greater right superior frontal gyrus volume and preserved volumes of the right anterior cingulate gyrus, left superior temporal gyrus, and insula. These results indicate that compared with exercise alone, physical exercise with music induces greater positive effects on cognitive function and leads to subtle neuroanatomical changes in the brains of elderly people. Therefore, physical exercise with music may be a beneficial intervention to delay age-related cognitive decline.


Probing Additive Loading in the Lamellar Phase of a Nonionic Surfactant: Gibbs Ensemble Monte Carlo Simulations Using the SDK Force Field.
Understanding solute uptake into soft microstructured materials, such as bilayers and worm-like and spherical micelles, is of interest in the pharmaceutical, agricultural, and personal care industries. To obtain molecular-level insight on the effects of solutes loading into a lamellar phase, we utilize the Shinoda-Devane-Klein (SDK) coarse-grained force field in conjunction with configurational-bias Monte Carlo simulations in the osmotic Gibbs ensemble. The lamellar phase is comprised of a bilayer formed by triethylene glycol mono- n-decyl ether (C10E3) surfactants surrounded by water with a 50:50 surfactant/water weight ratio. We study both the unary adsorption isotherm and the effects on bilayer structure and stability caused by n-nonane, 1-hexanol, and ethyl butyrate at several different reduced reservoir pressures. The nonpolar n-nonane molecules load near the center of the bilayer. In contrast, the polar 1-hexanol and ethyl butyrate molecules both load with their polar bead close to the surfactant head groups. Near the center of the bilayer, none of the solute molecules exhibits a significant orientational preference. Solute molecules adsorbed near the polar groups of the surfactant chains show a preference for orientations perpendicular to the interface, and this alignment with the long axis of the surfactant molecules is most pronounced for 1-hexanol. Loading of n-nonane leads to an increase of the bilayer thickness, but does not affect the surface area per surfactant. Loading of polar additives leads to both lateral and transverse swelling. The reduced Henry's law constants of adsorption (expressed as a molar ratio of additive to surfactant per reduced pressure) are 0.23, 1.4, and 14 for n-nonane, 1-hexanol, and ethyl butyrate, respectively, and it appears that the SDK force field significantly overestimates the ethyl butyrate-surfactant interactions.


[Peace-time gunshot wounds in children].
The authors have analyzed specific features of the clinical course, diagnosis and treatment of gunshot wounds in 34 children. The surgical treatment of gunshot wounds in peace-time is considered to be sparing and complex.


Effects of alkyl chain length, solvent and tandem Claisen rearrangement on two-dimensional structures of noncyclic isobutenyl compounds: scanning tunnelling microscopic study.
A series of isobutenyl compounds possessing various alkyl chain lengths (C(n)-1) with a carbon number of n = 14-21 were synthesized and their two-dimensional (2D) structures were systematically studied using scanning tunnelling microscopy (STM) at a highly oriented pyrolytic graphite (HOPG)/solvent interface. Two kinds of solvent, such as 1-phenyloctane (PO) and 1-phenylnonane (PN), were selected to examine the 2D structures by changing the alkyl chain length of the isobutenyl compounds. At the HOPG/PO interface, C(n)-1 molecules with shorter alkyl chains (n = 14-17) showed the same zig-zag shaped 2D structure regardless of the alkyl chain length, whereas an odd-even effect was recognized in C(n)-1 compounds with longer alkyl chains (n = 18-21) displaying the wavy and tripod structures, alternately. This odd-even effect was also observed at the HOPG/PN interface rather more distinctly. These results suggest that there is a specific alkyl chain length range that shows the odd-even effect in the present 2D system. After a tandem Claisen rearrangement (TCR), the 2D structures of all the C(n)-2 compounds formed were converged into the same linear structure, i.e. the odd-even effect was cancelled by the conformational limitation induced by the TCR.


Chromosome 17p deletions and p53 mutations in renal cell carcinoma.
Studies of the role of tumor suppressor genes in human renal cell carcinoma from our laboratory have suggested the presence of a disease gene(s) on the short arm of chromosome 3. Little is known about the role other tumor suppressor genes may play in this malignancy. Abnormalities of chromosome 17p and, in particular of p53, are common in many human malignancies. In order to evaluate the role of this region in renal cell carcinoma, we performed restriction fragment length polymorphism analyses of chromosome 17 with probes localized to the p53 region. Fourteen of 29 (48%) evaluable cell lines showed loss of heterozygosity at this locus. Northern blot analysis did not detect a p53 transcript in 4 of 27 cell lines tested. In addition, we screened cell lines for p53 mutations using a polymerase chain reaction-single strand conformation polymorphism technique. Cell lines positive for mutations by this technique were then sequenced. Mutations were detected in 11 of 33 (33%) cell lines, including 8 derived from primary tumors and 3 derived from metastatic foci. Six of 9 (67%) patients with loss of heterozygosity demonstrated a mutation in the remaining allele, while only 1 of 8 (13%) without loss of heterozygosity had a mutation. Three of 3 (100%) cell lines derived from metastases had the same mutation as their matched primary cell line. Loss or mutation of p53 did not correlate either with loss of chromosome 3p or with histological subtype. These results suggest that, while the primary disease gene for kidney cancer appears to be on chromosome 3, abnormalities of p53 are common and may be involved in the progression of this malignancy.


Reverse engineering sparse gene regulatory networks using cubature kalman filter and compressed sensing.
This paper proposes a novel algorithm for inferring gene regulatory networks which makes use of cubature Kalman filter (CKF) and Kalman filter (KF) techniques in conjunction with compressed sensing methods. The gene network is described using a state-space model. A nonlinear model for the evolution of gene expression is considered, while the gene expression data is assumed to follow a linear Gaussian model. The hidden states are estimated using CKF. The system parameters are modeled as a Gauss-Markov process and are estimated using compressed sensing-based KF. These parameters provide insight into the regulatory relations among the genes. The Cramér-Rao lower bound of the parameter estimates is calculated for the system model and used as a benchmark to assess the estimation accuracy. The proposed algorithm is evaluated rigorously using synthetic data in different scenarios which include different number of genes and varying number of sample points. In addition, the algorithm is tested on the DREAM4 in silico data sets as well as the in vivo data sets from IRMA network. The proposed algorithm shows superior performance in terms of accuracy, robustness, and scalability.


Prevalence and Progression of Incidental Terminal Ileitis on Non-diagnostic Colonoscopy: A Systematic Review and Meta-analysis.
Incidentally diagnosed terminal ileitis [IDTI] has been reported among asymptomatic persons undergoing non-diagnostic colonoscopy. The purpose of our study was to determine the prevalence and long-term outcomes of asymptomatic terminal ileitis. We performed a systematic review using three biomedical databases [Medline, Embase, and Web of Science] and relevant scientific meeting abstracts. We identified observational studies that reported the prevalence of IDTI in adults undergoing screening or polyp surveillance colonoscopy and/or the long-term outcomes of such lesions. A random-effects meta-analysis was conducted to determine the pooled prevalence rate of IDTI. The progression of IDTI to overt Crohn's disease [CD] was also described. Of 2388 eligible studies, 1784 were screened after excluding duplicates, 84 were reviewed in full text, and 14 studies were eligible for inclusion. Seven studies reported the prevalence of IDTI in 44 398 persons undergoing non-diagnostic colonoscopy, six studies reported follow-up data, and one study reported both types of data. The pooled prevalence rate of IDTI was 1.6% (95% confidence interval [CI] 0.1-21.8%) with significant heterogeneity [I2 = 99.7]. Among patients who had undergone non-diagnostic colonoscopy and had follow-up data [range 13-84 months reported in five studies], progression to overt CD was rare. IDTI is not uncommon on non-diagnostic colonoscopies. Based on limited data, the rate of its progression to overt CD seems low, and watchful waiting is likely a reasonable strategy. Further long-term follow-up studies are needed to inform the natural history of incidental terminal ileitis, factors that predict progression to CD, and therapeutic implications.


A DFT investigation of surface-enhanced Raman scattering of adenine and 2'-deoxyadenosine 5'-monophosphate on Ag20 nanoclusters.
We present a detailed analysis of the surface-enhanced Raman scattering (SERS) of adenine and 2'-deoxyadenosine 5'-monophosphate (dAMP) adsorbed on an Ag(20) cluster by using density functional theory. Calculated Raman spectra show that spectral features of all complexes depend greatly on adsorption sites of adenine and dAMP. The complexes consisting of adenine adsorbed on the Ag(20) cluster through N3 reproduce the measured SERS spectra in silver colloids, and thus demonstrated that adenine interacts with the silver surface via N3. We also investigate the SERS spectrum of adenine at the junction between two Ag(20) clusters and demonstrate that adenine can bind to the clusters through N3 and the external amino group, while dAMP can be adsorbed on the cluster in an end-on orientation with the ribose and phosphate groups near to or away from the silver cluster. In contrast to the adenine-Ag(20) complexes, the dAMP-Ag(20) complexes produce new and strong bands in the low- or high-wavenumber region of the Raman spectra, due to vibrations of the ribose and phosphate groups. Furthermore, the spectrum of dAMP bound to the Ag(20) cluster via N7 approaches the experimental SERS spectra on silver colloids.


Variation in joint shape of osteoarthritic knees.
To investigate the role of joint shape in knee osteoarthritis (OA) by determining which aspects of bone shape are different in OA knees compared with control knees. Using a statistical shape model, we compared radiographs showing the shape of OA knees with radiographs showing the shape of control knees in a population of 609 women (1,218 knees) extracted from the Rotterdam Study. Furthermore, we used magnetic resonance imaging to compare the shape of knees with cartilage defects with the shape of knees without cartilage defects. Three statistical shape modes, referring to 3 distinct aspects of the shape of the knee, were significantly associated with the presence of radiographic OA (modes 2, 4, and 15). Mode 2 reflected the width of the femoral and tibial bones, which was increased in patients with OA. Knees with cartilage defects also had wider femoral and tibial bones compared with knees without cartilage defects. Mode 4 reflected the variation in flexion of the knee during radiography. OA knees were more extended compared with control knees. Mode 15 showed that patients with OA had an elevated lateral tibial plateau, which was associated with pain. In women, knees with OA were wider, more extended during radiography, and had an elevated lateral tibial plateau. These results show that the shape of the knee is involved in OA, which might lead to novel imaging biomarkers to monitor or predict knee OA.


Prevalence of comorbid substance use in major depressive disorder in community and clinical settings, 1990-2019: Systematic review and meta-analysis.
Comorbidity between Substance Use Disorders (SUDs) and major depression is highly prevalent. This systematic review and meta-analysis aimed to estimate the prevalence of SUDs in subjects diagnosed with a major depressive disorder (MDD) in community, inpatient and outpatient settings. A comprehensive literature search of Medline, EMBASE, PsycINFO and CINAHL databases was conducted from 1990 to 2019. Prevalence of co-morbid SUDs and MDD were extracted and odds ratios (ORs) were calculated using random effects meta-analysis. There were 48 articles identified by electronic searches with a total sample size of 348,550 subjects that yielded 14 unique epidemiological studies, 2 national case registry studies, 7 large cohort studies and 20 clinical studies using in- or out-patients. The prevalence of any SUD in individuals with MDD was 0.250. Maximum prevalence was found with alcohol use disorder (0.208), followed by illicit drug use disorder (0.118) and cannabis use disorder (0.117). Meta-analysis showed the pooled variance of any AUD in men with MDD was 36%, which was significantly higher than that for females with MDD (19%, OR 2.628 95% CI 2.502, 2.760). Few studies were published over the last decade so current prevalence rates of SUD in MDD are needed. Meta-analysis revealed that SUDs in MDD are highly prevalent and rates have not changed over time. The persistently high prevalence suggests there is an urgent need for more informative studies to help develop better prevention and treatment options for reducing prevalence of SUDs in persons with major depression and co-morbid disorders.


NF-kappa B decoy suppresses cytokine expression and thermal hyperalgesia in a rat neuropathic pain model.
Pro-inflammatory cytokines have been shown to be involved in the genesis, persistence, and severity of neuropathic pain following nerve injury. The transcription factor, nuclear factor-kappa B (NF-kappaB), plays a pivotal role in regulating pro-inflammatory cytokine gene expression. To elucidate the role of NF-kappaB in the pathogenesis of neuropathic pain, using a gene-based approach of NF-kappaB decoy, we tested whether the activated NF-kappaB affected pain behavior via the expression of inflammatory mediators. Single endoneurial injections of NF-kappaB decoy, at the site of nerve lesion, significantly alleviated thermal hyperalgesia for up to 2 weeks and suppressed the expression of mRNA of the inflammatory cytokines, iNOS, and adhesion molecules at the site of nerve injury. This finding suggests that a perineural inflammatory cascade, that involves NF-kappaB, is involved in the pathogenesis of neuropathic pain.


Informing Rift Valley Fever preparedness by mapping seasonally varying environmental suitability.
Rift Valley Fever (RVF) poses a threat to human and animal health throughout much of Africa and the Middle East and has been recognized as a global health security priority and a key preparedness target. We combined RVF occurrence data from a systematic literature review with animal notification data from an online database. Using boosted regression trees, we made monthly environmental suitability predictions from January 1995 to December 2016 at a 5 × 5-km resolution throughout regions of Africa, Europe, and the Middle East. We calculated the average number of months per year suitable for transmission, the mean suitability for each calendar month, and the "spillover potential," a measure incorporating suitability with human and livestock populations. Several countries where cases have not yet been reported are suitable for RVF. Areas across the region of interest are suitable for transmission at different times of the year, and some areas are suitable for multiple seasons each year. Spillover potential results show areas within countries where high populations of humans and livestock are at risk for much of the year. The widespread environmental suitability of RVF highlights the need for increased preparedness, even in countries that have not previously experienced cases. These maps can aid in prioritizing long-term RVF preparedness activities and determining optimal times for recurring preparedness activities. Given an outbreak, our results can highlight areas often at risk for subsequent transmission that month, enabling decision-makers to target responses effectively.


Sub-nanometer Co3O4 clusters anchored on TiO2(B) nano-sheets: Pt replaceable Co-catalysts for H2 evolution.
Cobalt-based heterogeneous cocatalysts are important substitutions of noble metal cocatalysts in many important commercial chemical processes, but their efficiency is extremely low on a per metal atom basis, because only the atoms located at surface active-sites participate in the chemical reaction. Thus, cocatalysts with small cluster dispersions are highly desirable to maximize the amount of active-sites and enhance the per atom efficiency. Here, we report the synthesis of sub-nanometer Co3O4 clusters which are anchored to 2D ultrathin TiO2(B) nanosheets, as a cocatalyst for H2 evolution reaction (HER). It was found that the conduction type of Co3O4 clusters turns from P-type to N-type, and the heterojunction band structure between TiO2(B) and Co3O4 clusters changes from type II to type I, when the cluster size is reduced from nanometer scale to the sub-nanometer scale. With a suitable energy band matching between TiO2(B) and sub-nanometer Co3O4 clusters, the electrons generated in TiO2(B) during the photocatalytic process reduce the Co ions into metallic Co atoms, which produce excellent photocatalytic stability and extremely high HER efficiency comparable to that of the noble Pt cocatalyst.


Did you rule out neurosyphilis?
Neurosyphilis, formerly a frequent cause of dementia, is now a rare condition in developed countries. However, syphilis remains common in many developing countries, where adequate diagnosis and treatment of early syphilis may be lacking, increasing the chances of neurosyphilis and prevalence of syphilitic dementia. To present cases of syphilitic dementia seen in a cognitive and behavioral neurology unit in Brazil, emphasizing their first symptoms and the challenges they posed in diagnosis. At our unit of the Hospital das Clínicas of the University of São Paulo, all patients are submitted to blood treponemal tests. When the test is positive, a lumbar puncture is performed. We retrospectivelly reviewed all cases of neurosyphilis seen in our unit from January 1991 to November 2009. Nine cases of neurosyphilis (0.77% of the 1160 cases in our files) were identified over the period. Patients with neurosyphilis were all men, had a mean age of 47.8 (±13.0) years (median of 43 years), and presented with various neuropsychiatric syndromes and elusive diagnoses. The median time from onset of symptoms to diagnosis was 24 months and only one patient made a full recovery after treatment. Neurosyphilis is not frequent but remains present, causing several types of neuropsychiatric syndromes. As it is very simple to rule out neurosyphilis by performing a blood treponemal test, this test should be performed in all patients with neuropsychiatric symptoms, particularly in regions of the world where syphilis is still a commonly occurring disease.


Impact of a Focused Online Teaching Module on Airway Intervention: Can an Online Teaching Module Enable Knowledge Acquisition and Increased Confidence in Airway Management?
Teaching procedural skills via digital platforms is challenging. There is a paucity of literature on the feasibility of implementing an online asynchronous web-based learning (WBL) module for endotracheal intubation in Emergency Medicine. Learners completed a pre-test questionnaire prior to reviewing the module to assess their current knowledge. After completion of the online module, another assessment on airway management competency was completed. The purpose of our pilot study was to determine the feasibility of implementing an online airway module and investigate knowledge acquisition among learners who completed it. Additionally, we compared the relationship between pre-module confidence and knowledge between various training levels of those who completed the module. The study was IRB exempt. We conducted a quasi-experimental pre- and post-test study, where learners took a multiple-choice question-based test before watching content module, and after completion of modules, they went on to complete post-test questions. All responses were collected using Google survey and the data were collected over a period of 6 months. We performed descriptive statistics for the pre- and post-module. Frequency distribution was used for data summarization and chi-square test was used to assess the difference between variables. We received 366 responses in the pre-test module and 105 in post-test module. Responses were summarized into 5 broad categories which assessed knowledge about airway technique, anatomical landmarks, formulas for selecting blade size, tube size, depth of tube, and case-based scenarios. All questions showed a higher percentage of correct answers in the post-assessment compared to the pre-assessment. The results demonstrated that this WBL airway module resulted in significant knowledge acquisition, as well as increased confidence when approaching airway management. The study demonstrated that a WBL airway module is a feasible method of asynchronous education for healthcare providers in all levels of training.


Subjective memory complaints associated with depression and cognitive impairment in the elderly: A systematic review.
The aging process can be accompanied by a slight decline in cognitive functioning, and subjective memory complaints (SMC) appear to be common in the elderly population. To determine whether SMC is associated with cognitive loss or depression and can predict dementia. A systematic review of the literature was conducted. Articles were selected on the following databases, LILACS, SCOPUS, SCiELO, PubMed and Web of Science from August to October 2013. Article selection was based on inclusion and exclusion criteria. Studies published between 2010 and 2013, written in English, Spanish or Portuguese, involving populations 65 years or older, were included. Reviews were excluded. After the selection, a summary of the 20 articles retrieved was carried out. Of the total articles retrieved, fifteen were cross-sectional studies and five were longitudinal studies. Most of the cross-sectional studies associated SMC with depression, objective cognitive impairment and anxiety. The emergence of dementia in people with SMC was evidenced in longitudinal studies. Albeit less frequently, SMC were also associated with reduced quality of life, impairment in Activities of Daily Living (ADL), emergence of neuropsychiatric symptoms, lower hippocampal volume, amygdala volume reduction, increased activation of the left temporal, bilateral thalamus, caudate and posterior cingulate, and with the occurrence of ApoE ε4. SMC may be associated with changes in mood and/or cognition, and its occurrence appears to increase the likelihood of dementia. In order to further our understanding of the topic, future studies should consider the recruitment of representative samples with control groups and longitudinal designs.


Pain Management Throughout Pediatric Laparoscopic Appendectomy: A Systematic Review.
Opioid-related fatalities are a leading cause of accidental death in the United States. Appendicitis is a common cause of abdominal pain in children and adolescents. The management of pain throughout the laparoscopic appendectomy (LA) in the pediatric population is a critical concern. This study aimed to evaluate trends in analgesic use and patient satisfaction following LA, with a focus on reducing the reliance on opioids for pain management. From 2003 to 2023, 18258 articles were filtered for all types of analgesic use with LA. The publications were screened using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and 19 studies were included for analysis and review. The study included peer-reviewed experimental and observational studies involving individuals under 18 years. Pain management strategies varied across studies, involving a combination of analgesics, nerve blocks, and wound infiltrations. Analgesics such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids were administered before and after surgery. Some studies implemented patient-controlled analgesia (PCA) pumps. Other studies explored non-pharmacological interventions like magnetic acupuncture. The results showed a reduction in the need for postoperative analgesics in patients treated with LA, particularly when using non-opioid medications and novel analgesic techniques. Pediatric patients who received gabapentin reported lower opioid use, shorter hospital stays, and high satisfaction rates. However, the reliance on opioids remained significant in some cases, particularly among patients with peritonitis who required more morphine. Pain management in pediatric patients is multifaceted, involving preoperative and postoperative analgesics, nerve blocks, and PCA pumps. Efforts to improve pain management following pediatric LA while reducing opioid reliance are essential in the context of the ongoing opioid epidemic. The findings from this study highlight the potential benefits of non-opioid analgesics, nerve blocks, and alternative methods for managing postoperative pain in <18 appendectomy patients. Further research and standardization of pain management protocols are needed to ensure optimal patient outcomes and minimize the risk of opioid-related complications.


Scintigraphic diagnosis of thyroid cancer. Correlation of thyroid scintigraphy and histopathology.
Scintigraphy is part of the routine examination of thyroid disease, yet there are few published reports on its utility and pitfalls. Out of 2025 consecutive thyroid examinations after excluding 230 cases of proven thyroid malignancies, 403 patients who underwent surgery were studied for histopathologic correlation. There were 232 with cold nodules, 143 with multinodular goiters (MNG) and 28 with uniformly increased uptake suggestive of toxic goiter. Malignancy was reported in 72 of the 232 cold nodules (31%). In solitary nodules, the examination was useful in selecting cases for surgery and, in cold lesions, for planning of surgery. In the majority of patients with MNG or thyrotoxicosis who were operated on, scintigraphy provided no additional information. MNG requires scintigraphy only in selected cases where there is strong suspicion of malignancy. Contrary to reports in the literature, papillary carcinoma was found to be associated with MNG in our patients.


Effect of aldose reductase inhibitors on naphthalene cataract formation in the rat.
Naphthalene feeding can result in cataract formation in rats and rabbits due to specific metabolites of naphthalene. The concomitant administration of the aldose reductase inhibitor Al1576 to naphthalene-fed rats was proven to prevent cataract formation. To determine whether this effect was directly linked to the ability of Al1576 to inhibit enzyme aldose reductase, a variety of structurally diverse aldose reductase inhibitors, including the carboxylic acids tolrestat, Ponalrestat, and FK366, and the spirohydantoins, sorbinil and Al1576, were investigated for their ability to inhibit naphthalene-induced cataracts. Brown Norway rats, administered naphthalene by gavage, were fed normal rat chow containing these aldose reductase inhibitors at levels known to inhibit sugar cataract formation. The lens changes in these rats were monitored over a 90-day period by portable slit-lamp microscopy and histologic study. Al1576 showed a dose-dependent reduction in naphthalene-induced cataract formation, with no naphthalene-associated deposits seen in toluidine blue-stained lens sections. Sorbinil also reduced lens changes, whereas tolrestat, Ponalrestat, and FK366 had no effect. These results suggest that inhibition of naphthalene-induced cataract formation by structurally diverse aldose reductase inhibitors was not linked to the inhibition of aldose reductase.


Usefulness of recombinant human TSH aided radioiodine doses administered in patients with differentiated thyroid carcinoma.
The published studies confirming the safety and efficacy of rhTSH for diagnostic purposes have led to an increased interest in its use for preparation for radioiodine (RI) dose administration in patients with recurrent or persistent differentiated thyroid carcinoma (DTC). In order to establish the efficacy of RI therapy after rhTSH, we have reviewed 39 rhTSH-aided radioiodine treatment in a series of 28 DTC patients. Patients were divided into two groups: GI (n=17), with previous thyroid bed uptake and undetectable thyroglobulin (Tg) levels under levothyroxine treatment and GII (n=11), with proven metastatic local or distant disease. Median follow-up after the first rhTSH-aided radioiodine treatment was 32 +/- 13 months (range 8 to 54 months). Sixteen patients (94%) in GI were rendered disease free and one patient was shown to have persistent disease. In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, in four in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels were undetectable after rhTSH. In the follow-up, two patients with lateral neck uptake were rendered disease free, four patients died (three due to thyroid cancer) and five out of the remaining patients have persistent disease. In conclusion, rhTSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94%) patients (GI). rhTSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rhTSH is a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing the quality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patients only with stimulated Tg levels.


Regulation of chemerin chemoattractant and antibacterial activity by human cysteine cathepsins.
Chemerin, a ligand for the G-protein coupled receptor chemokine-like receptor 1, requires C-terminal proteolytic processing to unleash its chemoattractant activity. Proteolytically processed chemerin selectively attracts specific subsets of immunoregulatory APCs, including chemokine-like receptor 1-positive immature plasmacytoid dendritic cells (pDC). Chemerin is predicted to belong to the structural cathelicidin/cystatin family of proteins composed of antibacterial polypeptide cathelicidins and inhibitors of cysteine proteinases (cystatins). We therefore hypothesized that chemerin may interact directly with cysteine proteases, and that it might also function as an antibacterial agent. In this article, we show that chemerin does not inhibit human cysteine proteases, but rather is a new substrate for cathepsin (cat) K and L. cat K- and L-cleaved chemerin triggered robust migration of human blood-derived pDC ex vivo. Furthermore, cat K- and L-truncated chemerin also displayed antibacterial activity against Enterobacteriaceae. Cathepsins may therefore contribute to host defense by activating chemerin to directly inhibit bacterial growth and to recruit pDC to sites of infection.


The multiple sclerosis relapse experience: patient-reported outcomes from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry.
Among patients with relapsing-remitting multiple sclerosis, relapses are associated with increased disability and decreased quality of life. Relapses are commonly treated with corticosteroids or left untreated. We aimed to better understand patient perceptions of the adequacy of corticosteroids in resolving relapse symptoms. We examined self-reported data from 4482 participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry regarding evaluation, treatment, and recovery from relapses. Pearson's chi-square test was used to analyze categorical variables, while logistic regression was used to assess factors associated with patients' perceptions. Forty percent (1775/4482) of respondents were simply observed for disease worsening, whereas 25% (1133/4482) were treated with intravenous methylprednisolone (IVMP) and 20% (923/4482) with oral corticosteroids; additional treatments included adrenocorticotropic hormone, plasmapheresis, intravenous immunoglobulin, and others. Among patients who responded to questions about their most recent relapse, 32% (363/1123) of IVMP-treated and 34% (301/895) of oral corticosteroid-treated patients indicated their symptoms were worse one month after treatment than pre-relapse, as did 39% (612/1574) of observation-only patients; 30% (335/1122) of IVMP-treated patients indicated their treatment made relapse symptoms worse (13% [145/1122]) or had no effect (17% [190/1122]), as did 38% (340/894) of oral corticosteroid-treated patients (worse, 13% [116/894]; no effect, 25% [224/894]) and 76% (1162/1514) of observation-only patients (worse, 17% [264/1514]; no change, 59% [898/1514]). Overall, patients with relapsing multiple sclerosis who receive treatment report better outcomes than those who are simply observed. However, a sizeable percentage of patients feel that their symptoms following corticosteroid treatment are worse than pre-relapse symptoms and that treatment had no effect or worsened symptoms. Patient perceptions of relapse treatment deserve more attention, and more effective treatment options are needed.


Nitrogenase synthesis in Klebsiella pneumoniae: comparison of ammonium and oxygen regulation.
Rates of nitrogenase synthesis by Klebsiella pneumoniae were measured by pulse-labelling organisms with a mixture of 14C-labelled amino acids followed by sodium dodecyl sulphate gel electrophoresis and autoradiography. Populations from an NH4+-repressed, SO42--limited chemostat (0.46 mg dry wt ml-1), when released from NH4+ repression, simultaneously synthesized detectable quantities of the three nitrogenase polypeptides 45 min before acetylene-reducing activity was observed. Exposure of populations synthesizing nitrogenase to air or NH4+ (200 microgram N ml-1) repressed synthesis of both component proteins simultaneously, the rate initially decreasing by half in 11 to 12 min; in the presence of NH4+ a second slower phase with an approximate half-life of 30 min was observed. With 5% O2 in N2 the half-lives for the decreases in the rates of synthesis were 30 min for the Fe protein and 33 min for the Mo-Fe protein. Oxygen also repressed nitrogenase in a glutamine synthetase constitutive derivative of K. pneumoniae (strain SK24) which escapes NH4+ repression. Regulation of nitrogenase by O2 may therefore be independent of glutamine synthetase.


Protective Effects on 60Co-γ Radiation Damage of Pine Cone Polyphenols from Pinus koraiensis-Loaded Chitosan Microspheres In Vivo.
A novel chitosan microsphere for encapsulating pine cone polyphenols (PP) from P. koraiensis was successfully prepared using an emulsion crosslinking technique. The characteristics of pine polyphenol-loaded microspheres (PPM) were determined using scanning electron microscopy (SEM) and a laser particle size detector. It was found that PPMs were spherical in shape with uniform particle size distribution patterns. The drug content and encapsulation rate of the microspheres were 7.47% and 73.6%, respectively, at a Ch/GA mass ratio of 0.7. The animal experiments showed that PPM had a stronger radiation protective effect than PP. PPM significantly increased the immune organ indices, the quantity of marrow DNA, the superoxide dismutase (SOD) activity, the splenocyte proliferation index, and the phagocytosis activity of monocytes. PPM also decreased the numbers of micronuclei in bone marrow cells and malondialdehyde (MDA) levels in plasma in mice exposed to 60Co γ-irradiation. In addition, gender differences in biological responses to exposure to radiation were observed.


Polyvinyl alcohol cryogel based vessel mimicking material for modelling the progression of atherosclerosis.
The stiffness of Polyvinyl-alcohol cryogel can be adjusted through application of consecutive freeze-thaw cycles. This material has potential applications in the production of tissue mimicking phantoms in diagnostic ultrasound. The aim of this study was to use PVA-c to produce a range of geometrically and acoustically identical vessel phantoms modelling stages of atherosclerosis which could be verified through mechanical testing, thus allowing for more precision in quantitative in-vitro flow analysis of atherosclerosis. A series of anatomically realistic walled renal artery flow phantoms were constructed using PVA-c. In order to ensure precise modelling of atherosclerosis, a modified procedure of ISO27:2017 was used to compare the mechanical properties of PVA-c. Results were compared for the standard "dumbbell" test object and a modified vessel test object. The geometric accuracy and reproducibility of the vessel models were tested before and after implantation in flow phantoms. No significant difference was found between the mechanical properties of the dumbbell test samples and the vessels for any number of freeze thaw cycles, with a correlation coefficient of R2 = 0.9767 across the dataset, indicating that a direct comparison between the mechanical properties of the dumbbell test samples and the phantom vessels was established. The geometric reproducibility showed that before and after implantation there was no significant difference between individual vessel geometries (p = 0.337 & p = 0.176 respectively). Polyvinyl-alcohol cryogel is a useful material for the production of arterial flow phantoms. Care should be taken when using this material to ensure its mechanical properties have been correctly characterised. The guidelines of ISO37:2017 potentially provide the best procedure to ensure this.


CIITA-driven MHC-II positive tumor cells: preventive vaccines and superior generators of antitumor CD4+ T lymphocytes for immunotherapy.
In our study, we have investigated whether tumors of distinct histological origin can be rejected if expressing CIITA-driven MHC class II molecules. Moreover, we assessed whether antitumor lymphocytes generated by this approach could be used as an immunotherapeutic tool for established cancers. Stable CIITA-transfectants of C51colon adenocarcinoma, RENCA renal adenocarcinoma, WEHI-164 sarcoma as well as TS/A mammary adenocarcinoma were generated. Tumor cells transfectants were injected in vivo, and their growth kinetics and recipient's immune response were analyzed. Tumor rejection and/or retardation of growth was found for the first 3 CIITA-transfected tumor cell lines and confirmed for TS/A-CIITA. Animals rejecting CIITA-transfected tumors acquired specific immunological memory as demonstrated by resistance to challenge with parental tumors. Adoptive cell transfer experiments demonstrated that tumor immunity correlates with the efficient priming of CD4(+) T helper cells and the consequent activation of CD8(+) T lymphocytes. T cells from TS/A-vaccinated mice were used in an adoptive immunotherapy model of established tumors. The results showed the cure at early stages and significantly prolonged survival at later stages of tumor progression. Importantly, CD4(+) T cells were clearly superior to CD8(+) T cells in antitumor protective function. Interestingly, the protective phenotype was associated to both a Th1 and Th2 polarization of the immune effectors. These results establish the general application of our tumor vaccine model and disclose the additional application of this strategy for producing better lymphocyte effectors for adoptive antitumor immunotherapy.


Reliable outcomes and survivorship of unicompartmental knee arthroplasty for isolated compartment osteonecrosis.
Primary (or spontaneous) and secondary osteonecrosis of the knee can lead to severe joint degeneration, for which either total or unicompartmental arthroplasty may be considered. However, there are limited studies analyzing outcomes of unicompartmental knee arthroplasties (UKAs) for osteonecrosis involving an isolated compartment of the knee. The aims of this study were to analyze outcomes of UKAs for osteonecrosis with specific focus on 1) survivorship free of any revision or reoperation, 2) risk factors for failure, 3) clinical outcomes, and 4) complications. A total of 45 patients underwent 46 UKAs for knee osteonecrosis between 2002 and 2014 at our institution (The Mayo Clinic, Rochester, Minnesota). Twenty patients (44%) were female; the mean age of the patients was 66 years, and mean body mass index (BMI) was 31 kg/m2. Of the 46 UKAs, 44 (96%) were medial UKAs, and 35 (76%) were fixed-bearing design. Mean mechanical axis postoperatively was 1.5° varus (0° to 5° varus); 41 UKAs (89%) were performed for primary osteonecrosis. Mean follow-up was five years (2 to 12). Survivorship free of any revision in the cohort was 89% (95% CI 77 to 99) and 76% (95% CI 53 to 99) at five and ten years, respectively. In patients undergoing UKA for primary osteonecrosis survivorship free of any revision was 93% (95% CI 83 to 100)at both five and ten years. Secondary osteonecrosis was a significant risk factor for poorer survivorship free of any revision or reoperation (hazard ratio 7.7, p = 0.03). Three medial UKAs (6.5%) were converted to total knee arthroplasties (TKAs): two for lateral compartment degeneration and one for development of lateral osteonecrosis. No implants were revised for loosening, fracture, or wear. Knee Society scores improved from a mean of 60 (44 to 72) preoperatively to a mean of 94 postoperatively (82 to 100) (p < 0.001). There were no surgical complications. When done for primary osteonecrosis of the knee, UKA resulted in reliable clinical improvement, minimal complications, and durable estimated implant survivorship free of revision at ten years. UKA done for secondary osteonecrosis was substantially less durable at mid-term follow-up. Progression of knee degeneration, rather than implant failure or loosening, was most common indication for conversion to TKA. Cite this article: Bone Joint J 2018;100-B:450-4.


Cerebral preconditioning and ischaemic tolerance.
Adaptation is one of physiology's fundamental tenets, operating not only at the level of species, as Darwin proposed, but also at the level of tissues, cells, molecules and, perhaps, genes. During recent years, stroke neurobiologists have advanced a considerable body of evidence supporting the hypothesis that, with experimental coaxing, the mammalian brain can adapt to injurious insults such as cerebral ischaemia to promote cell survival in the face of subsequent injury. Establishing this protective phenotype in response to stress depends on a coordinated response at the genomic, molecular, cellular and tissue levels. Here, I summarize our current understanding of how 'preconditioning' stimuli trigger a cerebroprotective state known as cerebral 'ischaemic tolerance'.


Highly rapid and diverse sex chromosome evolution in the Odorrana frog species complex.
Sex chromosomes in poikilothermal vertebrates are characterized by rapid and diverse evolution at the species or population level. Our previous study revealed that the Taiwanese frog Odorrana swinhoana (2n = 26) has a unique system of multiple sex chromosomes created by three sequential translocations among chromosomes 1, 3, and 7. To reveal the evolutionary history of sex chromosomes in the Odorrana species complex, we first identified the original, homomorphic sex chromosomes, prior to the occurrence of translocations, in the ancestral-type population of O. swinhoana. Then, we extended the investigation to a closely related Japanese species, Odorrana utsunomiyaorum, which is distributed on two small islands. We used a high-throughput nuclear genomic approach to analyze single-nucleotide polymorphisms and identify the sex-linked markers. Those isolated from the O. swinhoana ancestral-type population were found to be aligned to chromosome 1 and showed male heterogamety. In contrast, almost all the sex-linked markers isolated from O. utsunomiyaorum were heterozygous in females and homozygous in males and were aligned to chromosome 9. Morphologically, we confirmed chromosome 9 to be heteromorphic in females, showing a ZZ-ZW sex determination system, in which the W chromosomes were heterochromatinized in a stripe pattern along the chromosome axis. These results indicated that after divergence of the two species, the ancestral homomorphic sex chromosome 1 underwent highly rapid and diverse evolution, i.e., sequential translocations with two autosomes in O. swinhoana, and turnover to chromosome 9 in O. utsunomiyaorum, with a transition from XY to ZW heterogamety and change to heteromorphy.


Potential regulatory factors in the pathogenesis of ankylosing spondylitis.
Ankylosing spondylitis (AS) is a chronic rheumatic disease that mainly affects the spinal joints (vertebrae). Spondylitis means inflammation of the spine, and ankylosing spondylitis means that bones tend to fuse. The AS causes the vertebrae to swell in the spine. Therefore, based on protein interaction network analysis, we conducted in-depth research on the molecular mechanism of key regulatory factors in the AS disease process. We carried out a differential analysis of the expression of miRNAs in disease samples and miRNAs in normal samples. Protein network interaction analysis is performed according to a group of target genes regulated by significant differentially expressed miRNAs and clustered into an interaction module. In addition, enrichment analysis of functions and pathways was performed on these modular genes. Based on the predictive analysis of multidimensional regulators, we identified a range of regulatory factors that have potential regulatory effects on AS, such as endogenous genes and transcription factors. We obtained 20 differentially expressed miRNAs and 7082 target genes and clustered into 11 modules. Enrichment results showed that these modular genes are mainly involved in the functions and pathways of protein polyubiquitination, neutrophil activation involved in immune response, and Wnt signaling pathway. We revealed ten transcription factors (MYC, NFKB1, and TP53). After network connectivity analysis, we obtained 12 internal drive genes (UBE2D1, CCNF, and NEDD4). These core genes are thought to be potential regulators of AS. MYC is also considered to be a core factor that inhibits SART3 phosphorylation and plays a vital role in the immunological pathogenesis of AS. The combination of the above analysis results can provide a new idea for biologists and medical scientists to study the immune pathogenesis of AS and can provide a valuable reference for subsequent treatment options.


Dry powder inhaler formulation of lipid-polymer hybrid nanoparticles via electrostatically-driven nanoparticle assembly onto microscale carrier particles.
Lipid-polymer hybrid nanoparticles have emerged as promising nanoscale carriers of therapeutics as they combine the attractive characteristics of liposomes and polymers. Herein we develop dry powder inhaler (DPI) formulation of hybrid nanoparticles composed of poly(lactic-co-glycolic acid) and soybean lecithin as the polymer and lipid constituents, respectively. The hybrid nanoparticles are transformed into inhalable microscale nanocomposite structures by a novel technique based on electrostatically-driven adsorption of nanoparticles onto polysaccharide carrier particles, which eliminates the drawbacks of conventional techniques based on controlled drying (e.g. nanoparticle-specific formulation, low yield). First, we engineer polysaccharide carrier particles made up of chitosan cross-linked with tripolyphosphate and dextran sulphate to exhibit the desired aerosolization characteristics and physical robustness. Second, we investigate the effects of nanoparticle to carrier mass ratio and salt inclusion on the adsorption efficiency, in terms of the nanoparticle loading and yield, from which the optimal formulation is determined. Desorption of the nanoparticles from the carrier particles in phosphate buffer saline is also examined. Lastly, we characterize aerosolization efficiency of the nanocomposite product in vitro, where the emitted dose and respirable fraction are found to be comparable to the values of conventional DPI formulations.