Effect of glycemic control on the Diabetes Complications Severity Index score and development of complications in people with newly diagnosed type 2 diabetes.
The aim of the present study was to assess the longitudinal accumulation of diabetes-related complications and the effect of glycemic control on the Diabetes Complications Severity Index (DCSI) score in people with newly diagnosed type 2 diabetes (T2D). A retrospective cohort study was conducted using electronic health records from a large integrated healthcare system. People with newly diagnosed T2D were identified between 2005 and 2016 and stratified by initial HbA1c category (<7%, <8%, ≥8%). The DCSI scores were determined for each study year, and the cumulative incidence of diabetes-related complications was assessed. A Cox proportional hazard model was used to evaluate the effect of baseline HbA1c and worsening glycemic (HbA1c) control on longitudinal changes in DCSI scores. Of 32 174 people identified as having newly diagnosed T2D, 14 016 (44%), 21 657 (67%), and 9983 (31%) had an initial or baseline HbA1c <7%, <8%, and ≥8%, respectively. Ten years after diabetes diagnosis, retinopathy, chronic kidney disease, coronary heart disease, and neuropathy were diagnosed in 22%, 29%, 24%, and 36% of people. Baseline HbA1c did not affect the observed trend in longitudinal changes in DCSI scores throughout the 11-year period. For people in each of the initial HbA1c groups (<7%, <8%, ≥8%), worsening or persistently poor glycemic control was significantly associated with a 10%, 19%, or 16% increase in the risk of experiencing an increased DCSI score, respectively (all P < 0.01). Baseline glycemic control had no apparent effect on longitudinal changes in DCSI score. Worsening or persistently poor glycemic control was associated with an increased risk of an increase in the DCSI score.


Catalytic and peroxidase-like activity of carbon based-AuPd bimetallic nanocomposite produced using carbon dots as the reductant.
In this report, carbon-based AuPd bimetallic nanocomposite (AuPd/C NC) was synthesized using carbon dots (C-dots) as the reducing agent and stabilizer by a simple green sequential reduction strategy, without adding other agents. The as synthesized AuPd/C NC showed good catalytic activity and peroxidase-like property. The structure and morphology of these nanoparticles were clearly characterized by UV-Vis spectroscopy, X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). The AuPd/C NC catalyst exhibits noticeably higher catalytic activity than Pd and Au nanoparticles in catalysis reduction of 4-nitrophenol (4-NP). Moreover, based on the high peroxidase-like property of AuPd/C NC, a new colorimetric detection method for hydrogen peroxide (H2O2) has been designed using 3,3',5,5'-tetramethyl-benzidine (TMB) as the substrate, which provides a simple and sensitive means to detect H2O2 in wide linear range of 5 μM-500 μM and 500 μM-4 mM with low detection limit of 1.6 μM (S/N = 3). Therefore, the facile synthesis strategy for bimetallic nanoparticles by the mild reductant of carbon dot will provide some new thoughts for preparing of carbon-based metal nanomaterials and expand their application in catalysis and analytical chemistry areas.


Sharing Objective Measures of Adherence to a Vaginal Microbicide Promotes Candor About Actual Use and Bolsters Motivation to Prevent HIV.
Discrepancies between self-reported and actual adherence to biomedical HIV interventions is common and in clinical trials can compromise the integrity of findings. One solution is to monitor adherence biomarkers, but it is not well understood how to navigate biomarker feedback with participants. We surveyed 42 counselors and interviewed a subset of 22 to characterize their perspectives about communicating with participants about residual drug levels, an objective marker of adherence, within MTN-025/HOPE, a Phase 3b clinical trial of a vaginal ring to prevent HIV. When biomarkers indicated low drug levels that mismatched high adherence by self-report, counselors encountered barriers to acceptance and comprehension among participants. However, discrepancies between low self-report and higher drug levels generally stimulated candor. Women recollected times they had not used the product and disclosed problems that counselors thought might otherwise have remained forgotten or concealed. Navigating conversations toward HIV prevention was easier at mid-range drug levels and when women indicated motivation to prevent HIV. Ratings of residual drug level offered a somewhat objective measure of adherence and protection that counselors perceived as meaningful to participants and as a valuable catalyst for broaching conversation about HIV prevention. However, communication about drug levels required that counselors navigate emotional barriers, respond skillfully to questions about accuracy, and pivot conversations non-judgmentally away from numerical results and toward the priority of HIV prevention. Findings suggest a role for biomarker feedback in future clinical trials as well as other clinical contexts where biomarkers may be monitored, to motivate disclosure of actual adherence and movement toward HIV prevention.Clinical Trial Number NCT02858037.


New sharing arrangements meet hospitals' technical support needs.
Just within thid decade, a variety of multihospital arrangements have been developed that make clinical engineering services available to hospitals on a shared basis. This article summarizes available data to describe the diverse approaches and organizational structures into which these programs are evolving.


Cooperative nutrient accumulation sustains growth of mammalian cells.
The coordination of metabolic processes to allow increased nutrient uptake and utilization for macromolecular synthesis is central for cell growth. Although studies of bulk cell populations have revealed important metabolic and signaling requirements that impact cell growth on long time scales, whether the same regulation influences short-term cell growth remains an open question. Here we investigate cell growth by monitoring mass accumulation of mammalian cells while rapidly depleting particular nutrients. Within minutes following the depletion of glucose or glutamine, we observe a growth reduction that is larger than the mass accumulation rate of the nutrient. This indicates that if one particular nutrient is depleted, the cell rapidly adjusts the amount that other nutrients are accumulated, which is consistent with cooperative nutrient accumulation. Population measurements of nutrient sensing pathways involving mTOR, AKT, ERK, PKA, MST1, or AMPK, or pro-survival pathways involving autophagy suggest that they do not mediate this growth reduction. Furthermore, the protein synthesis rate does not change proportionally to the mass accumulation rate over these time scales, suggesting that intracellular metabolic pools buffer the growth response. Our findings demonstrate that cell growth can be regulated over much shorter time scales than previously appreciated.


Evaluation of factors influencing confidence and trust in the patient-physician relationship: a survey of patient in a hand clinic.
The purpose of this study was to identify the skills found most important to gain patient's trust from a patient's perspective. One hundred and twenty-two patients were surveyed prospectively using a questionnaire assessing professionalism, physical environment, verbal and non-verbal communication skills. Factors required to establish a trusting patient-surgeon relationship were ranked in order of importance before and after initial consultation with a surgeon in a hand surgery clinic model. No significant relationship was identified between gender, age, education or income, and answers provided by respondents. Technical ability, verbal communication skills and respect of patient's autonomy by the physician were found most important. The visit with the surgeon significantly affected the ranking of some of the skills deemed important. Patients view respect of autonomy and verbal communication skills as the most important attributes when developing trust and confidence in a surgeon, followed by technical proficiency.


The Drosophila trithorax protein is a coactivator required to prevent re-establishment of polycomb silencing.
Polycomb group (PcG) and Trithorax (TRX) complexes assemble at Polycomb response elements (PREs) and maintain respectively the repressed and active state of homeotic genes. Although PcG and TRX complexes are distinct, their binding to some PRE fragments in vitro depends on GAGA motifs. GAGA factor immunoprecipitates with both complexes. In presence of a PRE, TRX stimulates expression and prevents the return of repression at later stages. When TRX levels are reduced, repression is re-established in inappropriate regions of imaginal discs, suggesting that TRX insufficiency impairs the epigenetic memory of the active state. Targeting a GAL-TRX fusion shows that TRX is a coactivator that stimulates expression of an active gene but cannot initiate expression by itself. Targeting a histone acetylase to a PRE does not affect embryonic silencing but causes a loss of memory in imaginal discs, suggesting that deacetylation is required to establish the memory of the repressed state.


Identification of carrier status of Xp22.31 microdeletions associated with X-linked ichthyosis at the single-cell level using haplotype linkage analysis by karyomapping.
Currently, owing to the limitations of high-throughput sequencing depth and the allele dropout caused by the whole-genome amplification, detection of chromosomal variants in embryos with CNVs <5 Mb is unsatisfactory at the single-cell level using only conventional sequencing methods. Therefore, here we aimed to use a strategy of preimplantation genetic testing for monogenic (PGT-M) to compensate for the shortcomings of conventional sequencing methods. The purpose of this study is to report the effectiveness of haplotype linkage analysis by karyomapping for preimplantation diagnosis microdeletion diseases. Six couples carrying chromosomal microdeletions associated with X-linked ichthyosis were recruited, and all couples entered the PGT process. Multiple displacement amplification (MDA) method was used to amplify the whole-genome DNA of trophectoderm cells. Then karyomapping based on single nucleotide polymorphism (SNP) was used for haplotype linkage analysis to detect alleles carrying microdeletions, and CNVs of embryos were identified to determine euploid identity. Amniotic fluid tests were performed in the second trimester to verify the PGT-M results. All couples were tested for chromosomal microdeletions, with deletion fragments ranging in size from 1.60 to 1.73 Mb, and one partner in each couple did not carry the microdeletion. Three couples successfully underwent PGT-M assisted conception and obtained healthy live births. This study shows that haplotype linkage analysis by karyomapping could effectively detect the carrier status of embryos with microdeletions at the single-cell level. This approach may be applied to the preimplantation diagnosis of various chromosomal microvariation diseases.


Early bisphosphonate therapy post proximal femoral fracture fixation does not impact fracture healing: a systematic review and meta-analysis.
There is conjecture on the optimal timing to administer bisphosphonate therapy following operative fixation of low-trauma hip fractures. Factors include recommendations for early opportunistic commencement of osteoporosis treatment, and clinician concern regarding the effect of bisphosphonates on fracture healing. We performed a systematic review and meta-analysis to determine if early administration of bisphosphonate therapy within the first month post-operatively following proximal femur fracture fixation is associated with delay in fracture healing or rates of delayed or non-union. We included randomized controlled trials examining fracture healing and union rates in adults with proximal femoral fractures undergoing osteosynthesis fixation methods and administered bisphosphonates within 1 month of operation with a control group. Data were pooled in meta-analyses where possible. The Cochrane Risk of Bias Tool and the GRADE approach were used to assess validity. For the outcome of time to fracture union, meta-analysis of three studies (n = 233) found evidence for earlier average time to union for patients receiving early bisphosphonate intervention (MD = -1.06 weeks, 95% CI -2.01--0.12, I2 = 8%). There was no evidence from two included studies comprising 718 patients of any difference in rates of delayed union (RR 0.61, 95% CI 0.25-1.46). Meta-analyses did not demonstrate a difference in outcomes of mortality, function or pain. We provide low-level evidence that there is no reduction in time to healing or delay in bony union for patients receiving bisphosphonates within 1 month of proximal femur fixation.


Contribution of inter-muscular synchronization in the modulation of tremor intensity in Parkinson's disease.
Involuntary central oscillations at single and double tremor frequencies drive the peripheral neuromechanical system of muscles and joints to cause tremor in Parkinson's disease (PD). The central signal of double tremor frequency was found to correlate more directly to individual muscle EMGs (Timmermann et al. 2003). This study is aimed at investigating what central components of oscillation contribute to inter-muscular synchronization in a group of upper extremity muscles during tremor in PD patients. 11 idiopathic, tremor dominant PD subjects participated in this study. Joint kinematics during tremor in the upper extremity was recorded along with EMGs of six upper arm muscles using a novel experimental apparatus. The apparatus provided support for the upper extremity on a horizontal surface with reduced friction, so that resting tremor in the arm can be recorded with a MotionMonitor II system. In each subject, the frequencies of rhythmic firings in upper arm muscles were determined using spectral analysis. Paired and pool-averaged coherence analyses of EMGs for the group of muscles were performed to correlate the level of inter-muscular synchronization to tremor amplitudes at shoulder and elbow. The phase shift between synchronized antagonistic muscle pairs was calculated to aid coherence analysis in the muscle pool. Recorded EMG revealed that rhythmic firings were present in most recorded muscles, which were either synchronized to form phase-locked bursting cycles at a subject specific frequency, or unsynchronized with a random phase distribution. Paired coherence showed a stronger synchronization among a subset of recorded arm muscles at tremor frequency than that at double tremor frequency. Furthermore, the number of synchronized muscles in the arm was positively correlated to tremor amplitudes at elbow and shoulder. Pool-averaged coherence at tremor frequency also showed a better correlation with the amplitude of resting tremor than that of double tremor frequency, indicating that the neuromechanical coupling in peripheral neuromuscular system was stronger at tremor frequency. Both paired and pool-averaged coherences are more consistent indexes to correlate to tremor intensity in a group of upper extremity muscles of PD patients. The central drive at tremor frequency contributes mainly to synchronize peripheral muscles in the modulation of tremor intensity.


Swallowing dysfunction in patients hospitalised due to a COPD exacerbation.
Swallowing dysfunction is common in COPD patients with severe exacerbations but this kind of dysfunction is potentially correctable, at least in some patients. Further interventional studies on this topic are urgently needed. https://bit.ly/3mFKNq1.


Bacterial metabolic 'toxins': a new mechanism for lactose and food intolerance, and irritable bowel syndrome.
Lactose and food intolerance cause a wide range of gut and systemic symptoms, including gas, gut pain, diarrhoea or constipation, severe headaches, severe fatigue, loss of cognitive functions such as concentration, memory and reasoning, muscle and joint pain, heart palpitations, and a variety of allergies (Matthews and Campbell, 2000; Matthews et al., 2005; Waud et al., 2008). These can be explained by the production of toxic metabolites from gut bacteria, as a result of anaerobic digestion of carbohydrates and other foods, not absorbed in the small intestine. These metabolites include alcohols, diols such as butan 2,3 diol, ketones, acids, and aldehydes such as methylglyoxal (Campbell et al., 2005, 2009). These 'toxins' induce calcium signals in bacteria and affect their growth, thereby acting to modify the balance of microflora in the gut (Campbell et al., 2004, 2007a,b). These bacterial 'toxins' also affect signalling mechanisms in cells around the body, thereby explaining the wide range of symptoms in people with food intolerance. This new mechanism also explains the most common referral to gastroenterologists, irritable bowel syndrome (IBS), and the illness that afflicted Charles Darwin for 50 years (Campbell and Matthews, 2005a,b). We propose it will lead to a new understanding of the molecular mechanism of type 2 diabetes and some cancers.


Deep sequencing of phage display libraries to support antibody discovery.
The use of next generation sequencing (NGS) for the analysis of antibody sequences both in phage display libraries and during in vitro selection processes has become increasingly popular in the last few years. Here, our methods developed for DNA preparation, sequencing and data analysis are presented. A key parameter has also been to develop new software designed for high throughput antibody sequence analysis that is used in combination with publicly available tools. As an example of our methods, we provide data from the extensive analysis of five scFv libraries generated using different heavy chain CDR3 diversification strategies. The results not only confirm that the library designs were correct but also reveal differences in quality not easily identified by standard DNA sequencing approaches. The very large number of reads permits extensive sequence coverage after the selection process. Furthermore, as samples can be multiplexed, costs decrease and more information is gained per NGS run. Using examples of results obtained post phage display selections against two antigens, frequency and clustering analysis identified novel antibody fragments that were then shown to be specific for the target antigen. In summary, the methods described here demonstrate how NGS analysis enhances quality control of complex antibody libraries as well as facilitates the antibody discovery process.


Safety and efficacy of percutaneous coronary intervention versus coronary artery bypass graft in patients with STEMI and unprotected left main stem disease: A systematic review & meta-analysis.
Owing to its large area of supply, left main coronary artery disease (LMCAD) has the highest mortality rate among coronary artery lesions, resulting in debate about its optimal revascularization technique. This meta-analysis compares percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) for the treatment of LMCAD. MEDLINE, TRIP, and Cochrane Central databases were queried from their inception until 25 April 2021, to determine MACCE (major adverse cardiac and cardiovascular events), all-cause mortality, repeat revascularization, myocardial infarction (MI) and stroke rates post-revascularization for different follow-ups. 7 RCTs and 50 observational studies having 56,701 patients were included. A random-effects model was used with effect sizes calculated as odds ratios (odds ratio, OR). In the short term (1 year), PCI had significantly higher repeat revascularizations (OR = 3.58, 95% CI 2.47-5.20; p < 0.00001), but lower strokes (OR = 0.55, 95% CI 0.38-0.81; p = 0.002). In the intermediate term (2-5 years), PCI had significantly higher rates of repeat revascularizations (OR = 3.47, 95% CI 2.72-4.44; p < 0.00001) and MI (OR = 1.39, 95% CI 1.17-1.64; p = 0.0002), but significantly lower strokes (OR = 0.54, 95% CI 0.42-0.70; p < 0.0001). PCI also had significantly higher repeat revascularizations (OR = 2.58, 95% CI 1.89-3.52; p < 0.00001) in the long term (≥5 years), while in the very long term (≥10 years), PCI had significantly lower all-cause mortalities (OR = 0.77, 95% CI 0.61-0.96; p = 0.02). PCI was safer than CABG for patients with stroke for most follow-ups, while CABG was associated with lower repeat revascularizations. However, further research is required to determine PCI's safety over CABG for reducing post-surgery MI.


Development of a Novel Class of Self-Assembling dsRNA Cancer Therapeutics: A Proof-of-Concept Investigation.
Cancer has proven to be an extremely difficult challenge to treat. Several fundamental issues currently underlie cancer treatment, including differentiating self from nonself, functional coupling of the recognition and therapeutic components of various therapies, and the propensity of cancerous cells to develop resistance to common treatment modalities via evolutionary pressure. Given these limitations, there is an increasing need to develop an all-encompassing therapeutic that can uniquely target malignant cells, decouple recognition from treatment, and overcome evolutionarily driven cancer resistance. We describe herein a new class of programmable self-assembling double-stranded RNA (dsRNA)-based cancer therapeutics that uniquely targets aberrant genetic sequences and in a functionally decoupled manner, undergoes oncogenic RNA-activated displacement (ORAD), initiating a therapeutic cascade that induces apoptosis and immune activation. As a proof of concept, we show that RNA strands targeting the EWS/Fli1 fusion gene in Ewing sarcoma cells that are end blocked with phosphorothioate bonds and additionally sealed with a 2'-deoxyuridine (2'-U)-modified DNA protector can be used to induce specific and potent killing of cells containing the target oncogenic sequence but not wild type.


Norm Values of Muscular Strength Across the Life Span in a Healthy Swiss Population: The COmPLETE Study.
Grip strength is used to estimate whole-body strength for health surveillance purposes. Explosive strength is considered important, yet economic measures able to detect early deterioration of neuromuscular capabilities are lacking. Whether handgrip maximum rate of force development (GRFD) or whole-body strength tests are better predictors of lower body power than handgrip maximum strength (GFmax) and their trajectories throughout the life span are unknown. GRFD should be more closely related to lower body power than GFmax, and its trajectories over the life span should more closely follow that of lower body power. Cross-sectional. Level 2b. A total of 613 healthy participants aged 20 to 91 years were tested for countermovement jump peak power, GFmax, handgrip rate of force development, and midthigh pull peak force (MTP). Cubic splines and linear models were built for age trajectories, generalized additive models for quintile curves, and linear regression was used to assess predictive quality. Peak power (Pmax) declined linearly to 60% of young adult level, with GRFD, GFmax, and MTP remaining stable up to age 50 years and then declining more sharply to 52% to 71% of young adult levels. Trajectories were similar for male and female participants. GRFD (β = 0.17) and MTP (β = 0.08) were worse predictors of Pmax than GFmax (β = 0.24) in models adjusted for age, sex, lean body mass, and vigorous physical activity levels. GRFD was not superior to maximum strength in predicting lower body power. For health surveillance purposes, it therefore appears that GFmax tests are more economical and equally good predictors of lower body explosive strength at older age. The data provided can be used as norm values for healthy subjects. Incorporating countermovement jump testing for early detection of declines in explosive capabilities might be advised.


Synthesis of biocompatible nanocrystalline cellulose against folate receptors as a novel carrier for targeted delivery of doxorubicin.
We designed amine-functionalized nanocrystalline cellulose grafted folic acid/magnetic nanoparticles (AF-NCC/Fe3O4 NPs) against folate receptors for targeted delivery of doxorubicin (DOX). Toxicity is a major side effect of DOX, damaging vital organs such as the heart, kidney, and liver; for example, it causes dilated cardiomyopathy and hepatotoxicity. Accordingly, we aimed to reduce this adverse effect and increase the targeted delivery of DOX to the right point of cancer cells by using the unique features of cancer cells. The characterizations were approved in each step using Fourier transform infrared (FTIR), scanning electron microscope (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), energy dispersive X-ray (EDX), zeta potential, and dynamic light scattering (DLS) analysis techniques. Encapsulation efficacy of AF-NCC/Fe3O4 NPs was 99.6%; drug release investigations showed excellent stability in physiological conditions (pH ∼ 7.4) and a high release rate in the low pH condition of cancer environments (pH ∼ 5.0). The hemolysis assay and Masson's trichrome and hematoxylin and eosin (H&E) staining results showed that the nanocarrier was entirely biocompatible. In vitro cell viability study approved that the designed nanocarrier increased the therapeutic effects of DOX on Saos-2 cells. The cellular internalization results displayed a high percentage of uptake within 2 h. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was applied for the evaluation of tumor protein p53 (p53), p21, and Bcl-2-associated X protein (Bax). DOX exerted its effects through DNA damage and oxidative stress that led to p53 upregulation, and p53 inhibited cell cycle progression. This arrest initiated apoptosis and inhibited cell migration. In summary, encapsulating DOX in AF-NCC/Fe3O4 NPs dramatically decreases the toxic effects of this chemotherapeutic agent on vital organs, especially on the heart. This smart nanocarrier increases the delivery of DOX using acid folic on its surface and also enhances the DOX release in the acidic environment of cancer cells. DOX exerts its therapeutic effects by the initiation of apoptosis and inhibition of migration.


Chronic obstructive pulmonary disease and hospitalizations for pneumonia in a US cohort.
To better understand risk factors for pneumonia hospitalizations in people with impaired lung function. We analyzed longitudinal data from participants in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). We limited our analysis to 20,375 participants aged 45 and older at baseline. We stratified the sample based on prebronchodilator baseline lung function data, according to modified GOLD criteria, including a "restrictive" category (FEV(1)/FVC>70% and FVC<80%). We defined "pneumonia" as a hospitalization with a pneumonia discharge diagnosis (ICD-9 codes 480-486) within 36 months. We used Cox proportional hazard models to determine pneumonia risk associated with COPD stage, adjusting for age, sex, race, smoking status and comorbid disease (diabetes mellitus or cardiovascular disease at the baseline examination). Pneumonia hospitalization risk was associated with older age, male gender, comorbid conditions, smoking status, and level of lung function impairment. Overall, people with normal lung function had the lowest pneumonia hospitalization rate (1.5 per 1000 person-years) and those with GOLD stage 3 or 4 COPD had the highest rate (22.7 per 1000 person-years). After adjusting for other potential confounding factors, GOLD stages 3 or 4 and 2 COPD were associated with an increased risk of pneumonia (hazard ratio [HR] 5.65, 95% confidence interval [CI] 3.29, 9.67 and 2.25 (1.35, 3.75), respectively) relative to normal lung function. COPD severity (GOLD stage) is an important and independent predictor of pneumonia hospitalizations in this cohort.


Comparative assessment of a metabolically attenuated Mycoplasma gallisepticum mutant as a live vaccine for the prevention of avian respiratory mycoplasmosis.
In a previous study, signature sequence mutagenesis (SSM) was used to identify a mutant with a disruption of the gene encoding the metabolic factor, dihydrolipoamide dehydrogenase, and that mutant was designated Mg 7. The current study assessed the safety, immunogenicity and efficacy of Mg 7 in comparison to two commercially available vaccines (ts-11 and F) as well as a laboratory vaccine strain, GT5. Intratracheal vaccination of chickens with all four attenuated mutants induced varying levels of protection against intratracheal challenge with virulent Mycoplasma gallisepticum strain R(low). Mg 7 vaccinated chickens rapidly cleared the challenge strain, had lower histopathologic tracheal lesion scores when compared to unvaccinated chickens, and mounted a strong humoral anti-M. gallisepticum-specific IgG response. The IgG levels increased 2- to 3-fold upon R(low) challenge. Mg 7 induced a greater level of protection against intratracheal R(low) challenge than that observed with the other three attenuated strains, as evidenced by a lower recovery of R(low) from tracheas and lower histopathologic lesion scores in tracheas and air sacs. Based on these findings, Mg 7 appears to have good potential as a safe and effective vaccine for the prevention of avian mycoplasmosis.


Escherichia coli sacroiliitis: report of a case and review of the literature.
Pyogenic sacroiliitis is rare and usually occurs in patients with an underlying illness. Typically, the responsible organisms are Staphylococcus aureus or Streptococcus pneumoniae. We describe a healthy 17-year-old boy with bacterial sacroiliitis caused by Escherichia coli. This case illustrates the importance of considering this diagnosis in febrile patients with no obvious source of infection.


Hybrid Quantum Neural Network for Drug Response Prediction.
Cancer is one of the leading causes of death worldwide. It is caused by various genetic mutations, which makes every instance of the disease unique. Since chemotherapy can have extremely severe side effects, each patient requires a personalized treatment plan. Finding the dosages that maximize the beneficial effects of the drugs and minimize their adverse side effects is vital. Deep neural networks automate and improve drug selection. However, they require a lot of data to be trained on. Therefore, there is a need for machine-learning approaches that require less data. Hybrid quantum neural networks were shown to provide a potential advantage in problems where training data availability is limited. We propose a novel hybrid quantum neural network for drug response prediction based on a combination of convolutional, graph convolutional, and deep quantum neural layers of 8 qubits with 363 layers. We test our model on the reduced Genomics of Drug Sensitivity in Cancer dataset and show that the hybrid quantum model outperforms its classical analog by 15% in predicting IC50 drug effectiveness values. The proposed hybrid quantum machine learning model is a step towards deep quantum data-efficient algorithms with thousands of quantum gates for solving problems in personalized medicine, where data collection is a challenge.


Saponin from Platycodi radix inactivates PI3K/AKT signaling pathway to hinder colorectal cancer cell proliferation, invasion, and migration through miR-181c/d-5p/RBM47.
Colorectal cancer (CRC) is the third frequent cancer and second leading reason of cancer-related mortality all over the globe. Saponins from Platycodi radix (SPR) and microRNAs (miRNAs) have been reported to regulate CRC cell progression. Real-time quantitative polymerase chain reaction (RT-qPCR) detected miR-181c-5p, miR-181d-5p, and RBM47 expression level. Cell counting kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), colony formation, transwell, and wound healing assays validated that miR-181c-5p and miR-181d-5p promote CRC cell proliferation, migration and invasion and SPR exerts opposite effects. Cignal Finder Reporter Array and western blot proved that the activity of PI3K/AKT pathway was decreased by RBM47 overexpression. RNA pulldown, luciferase reporter, and RNA-binding protein immunoprecipitation (RIP) assays proved the interaction between miR-181c/d-5p and RBM47, and RBM47 and PTEN. Rescue experiments were carried out to validate that RBM47 reverses the influence of miR-181c/d-5p on the progression of CRC cells. The stability of PTEN was probed by real-time quantitative polymerase chain reaction in CRC cells treated with Actinomycin D (Act D). To be concluded, SPR inactivates PI3K/AKT signaling pathway to suppress CRC cell proliferation, invasion, and migration via miR-181c/d-5p/RBM47. Elucidating the mechanisms of SPR underlying CRC may offer novel insight into CRC treatment.


Which symptoms of depression and anxiety are most strongly associated with happiness? A network analysis of Indian and Kenyan adolescents.
Network analyses have been applied to understand the relationships between individual symptoms of depression and anxiety. However, little is known about which symptoms are most strongly associated with "positive" indicators of mental health, such as happiness. Furthermore, few studies have examined symptom networks in participants from low- and middle-income countries. To address these gaps, we applied network analyses in a sample of Indian adolescents (Study 1; n=1080) and replicated these analyses in a pre-registered study with Kenyan adolescents (Study 2; n=2176). Participants from both samples completed the same measures of depressive symptoms, anxiety symptoms, and happiness. Feeling sad and feeling like a failure had the strongest (negative) associations with happiness items. These two symptoms, as well as worrying and feeling nervous, had the strongest associations with other symptoms of depression and anxiety. Symptoms of depression and anxiety formed a single cluster, which was distinct from a cluster of happiness items. Main findings were consistent across the two samples, suggesting a cross-culturally robust pattern. We used cross-sectional data, and we administered scales assessing a limited subset of symptoms and happiness items. Our findings support the idea that some symptoms of depression and anxiety are more strongly associated with happiness. These findings contribute to a body of literature emphasizing the advantages of symptom-level analyses. We discuss how efforts to understand associations between individual symptoms and "positive" mental health indicators, like happiness, could have theoretical and practical implications for clinical psychological science.


Environmental boron contamination in waters of Hisarcik area in the Kutahya Province of Turkey.
Our aim was to determine boron levels in waters of rich boron mine areas in Turkey. There is a naturally occurring high level of boron in the ground waters of some parts of Turkey. Our study area is Hisarcik village in the Kutahya Province of Turkey which has a large number of boron mines. Boron occurs in combined form, usually borax (Na2B4O7 x 10H2O) and colemanite (Ca2B6O11 x 5H2O). Water samples were collected from many springs in order to determine boron concentrations and the amount of boron that is exposed to 88 samples from the drinking water (tap water), 37 from ground water and 257 from stream or pond water (surface water). Urine samples taken from 42 residents in this area were analyzed for boron and compared with its levels in drinking waters. The inductively coupled plasma/mass spectrometry (ICP/MS) method was used for the analysis of boron concentrations. Water boron contents at differing locations of this area ranged from 2.05 to 29.00 mg B/l. Mean value of boron was 10.20+/-4.08 mg B/l. Total urinary boron excretion was ranged from 0.04 to 50.70 mg B/l and mean value was 8.30+/-10.91 mg B/l. Current information on sources, occurrence, pollution potential and toxicity of environmental boron is discussed.


Progression of microstructural putamen alterations in a case of symptomatic recurrent seizures using diffusion tensor imaging.
Microstructural alterations of the putamen were recently reported in patients with partial and generalized epilepsy disorders. However, it is unknown whether these alterations pre-exist or are secondary to recurrent seizures. Here we investigated the progression of putamen fractional anisotropy (FA) alterations in a case of recurrent psychomotor seizures using longitudinal diffusion tensor imaging (DTI) shortly before (DTI-1) and after a psychomotor seizure (DTI-2). We obtained FA values of a hypothesis-guided putamen region-of-interest (ROI) and seven exploratory ROIs. FA values from both DTIs were compared with reference values from 19 controls. Relative to controls, the patient's putamen FA was increased at DTI-1 (13% left putamen, 7% right putamen), an effect that was exacerbated at DTI-2 (24% left putamen (p<0.05), 20% right putamen). In the exploratory ROIs we found FA reductions in the corticospinal tract, temporal lobe, and occipital lobe (p<0.05) relative to controls at DTI-1 and DTI-2. In contrast to the putamen, all exploratory ROIs showed no relevant FA change between DTI-1 and DTI-2. These results suggest that recurrent seizures may lead to progressive microstructural putamen alterations.


Stridor in the Newborn.
Stridor in the newborn period may result from numerous causes, both congenital and acquired. Its presentation is diverse, and understanding the subtleties of that diversity is the key to determining the likely cause of the stridor, as well as the urgency for specialist evaluation. This article presents a framework for evaluating the quality of stridor in the newborn, as well as a review of the characteristics of stridor associated with entities commonly encountered in the neonatal airway.


Regioselective Claisen-Schmidt Adduct of 2-Undecanone from Houttuynia cordata Thunb as Insecticide/Repellent against Solenopsis invicta and Repositioning Plant Fungicides against Colletotrichum fragariae.
The U.S. Department of Agriculture (USDA) has established research programs to fight the phytopathogen Colletotrichum fragariae and the invasive red imported fire ant, Solenopsis invicta. C. fragariae is known to cause anthracnose disease in fruits and vegetables, while S. invicta is known for its aggressive behavior and painful stings and for being the cause of significant damage to crops, as well as harm to humans and animals. Many plants have been studied for potential activity against C. fragariae and S. invicta. Among the studied plants, Houttuynia cordata Thunb has been shown to contain 2-undecanone, which h is known for its antifungal activity against Colletotrichum gloesporioides. Based on the mean amount of sand removed, 2-undecanone showed significant repellency at 62.5 µg/g, similar to DEET (N,N-diethyl-meta-toluamide), against S. invicta. The 2-Undecanone with an LC50 of 44.59 µg/g showed toxicity against S. invicta workers. However, neither H. cordata extract nor 2-undecanone had shown activity against C. fragariae despite their known activity against C. gloesporioides, which in turn motivates us in repositioning 2-undecanone as a selected candidate for a Claisen-Schmidt condensation that enables access to several analogs (2a-f). Among the prepared analogs, (E)-1-(3-methylbenzo[b]thiophen-2-yl)dodec-1-en-3-one (2b) and (E)-1-(5-bromothiophen-2-yl)dodec-1-en-3-one (2f) showed promising activity against C. fragariae, revealing a distinctive structural activity relationship (SAR). The generated analogs revealed a clear regioselectivity pattern through forming the C=C alkene bond at position C-1. These data open the window for further lead optimization and product development in the context of managing C. fragariae and S. invicta.


Plasma adipokines and glycaemic progression among African Americans: Findings from the Jackson Heart Study.
To evaluate the association between plasma biomarkers including leptin, adiponectin, adiponectin-to-leptin ratio and high-sensitivity C-reactive protein (hsCRP) with risk of glycaemic progression and incident dysglycaemia (pre-diabetes or diabetes) in a community-based sample of African American (AAs). We analysed data from 3223 participants without type 2 diabetes at baseline (2000-2004) who attended ≥1 follow-up visit. Poisson regression was used to generate risk ratios (RRs) for glycaemic progression and incident dysglycaemia. Over a median of 7 years, 46.4% developed glycaemic progression (n=1495). After adjusting for demographic and lifestyle variables, the RRs (95% CI) for glycaemic progression comparing highest (Q4) to lowest (Q1) quartiles were 1.30 (1.10-1.54), 0.74 (0.65-0.84), 0.70 (0.62-0.80) and 1.22 (1.07-1.38) for leptin, adiponectin, adiponectin-leptin ratio and hsCRP, respectively. Upon additional adjustment for BMI, the corresponding RRs (95% CIs) were 1.15 (0.94-1.42), 0.76 (0.67-0.86), 0.72 (0.62-0.84) and 1.14 (0.99-1.31) respectively. Among participants with normal glycaemia, the RRs (95% CIs) for incident pre-diabetes in Q4 vs Q1 were 1.37 (1.13-1.67), 0.73 (0.63-0.85), 0.70 (0.59-0.82) and 1.28 (1.10-1.48) for leptin, adiponectin, adiponectin-leptin ratio and hsCRP, respectively; equivalent RRs for incident diabetes were 5.15 (2.63-10.10), 0.36 (0.20-0.68), 0.21 (0.12-0.38) and 3.04 (1.70-5.44), respectively. In this large community-based cohort of AAs, our results suggest that high plasma leptin and hsCRP, as well as low adiponectin and adiponectin-to-leptin ratio, are associated with higher risks of glycaemic progression. The findings point to the potential utility of these biomarkers in predicting and preventing glycaemic progression in this high-risk population.


Diagnostic significance of hepatitis B viral antigens in patients with glomerulonephritis-associated hepatitis B virus infection.
Hepatitis B viral infection can lead to hepatitis B virus-associated glomerulonephritis, a clinically significant subtype of secondary nephritis. In the present study, we examined the presence of PreS1/S2 antigen in renal tissues by use of immunohistochemistry and investigated the use of PreS1/S2 and 2 HBV serum antigens, HBe-Ag and HBs-Ag, in the diagnosis. We assessed the presence of these 3 antigens in patients with confirmed hepatitis B virus-associated glomerulonephritis (n = 22) and patients without this disease (n = 19). Our results indicate that the combined use of PreS1/S2-Ag and serum HBe-Ag in the diagnosis of hepatitis B virus-associated glomerulonephritis had good positive predictive value (0.89), modest negative predictive value (0.77), and substantial agreement based on Cohen's kappa coefficient (κ = 0.660, P < 0.001). We suggest that our results be considered in the development of more definitive diagnostic criteria for hepatitis B virus-associated glomerulonephritis.


Phospholipid impregnation of abdominal rubber drains: resistance to bacterial adherence but no effect on drain-induced bacterial translocation.
In order to evaluate the effect of surface modification of biomaterials on bacterial adherence and bacterial translocation after intraperitoneal biomaterial implantation, phosphatidylcholine- or phosphatidylinositol-impregnated rubber drain pieces, which had been intraperitoneally implanted in the rat for 2 and 7 days, or unimplanted, were incubated in vitro with 3H-labelled Escherichia coli and Enterobacter cloacae. As compared with unimpregnated pieces, the adherence of bacteria significantly decreased to phosphatidylcholine- and phosphatidylinositol-impregnated rubber drain pieces that were either unimplanted or implanted for 2 days, but not for 7 days. The supplementation of albumin in the medium reduced the adherence of bacteria to the unimplanted, unimpregnated drain pieces, but did not further decrease adherence of bacteria to the unimplanted, phospholipid-impregnated brain pieces. Bacterial growth was inhibited after incubation in nutrient broth supplemented with phospholipids. The incidence of enteric bacterial translocation induced by intraperitoneal drain implantation did not differ between phospholipid-impregnated and unimpregnated drain pieces. Scanning electron microscopy revealed a large amount of biofilm and fibrous deposition on the surface of the implanted, phospholipid-impregnated rubber drain pieces. Thus, phospholipid impregnation of rubber drains reduces bacterial adherence and inhibits bacterial growth, without influencing the incidence of bacterial translocation.


50 years of psychological research on patients with COPD--road to ruin or highway to heaven?
To review the topic of behavioural research on patients with COPD over the past 50 years in order to help inform clinical management and future research on psychosocial aspects of COPD. Narrative literature review. Nine orientations in behavioural research on COPD patients are identified and concisely examined: psychoanalytic approach, psychosomatics, neuropsychology, quality of life, psychomaintenance, patient education, coping and illness cognitions, self-management, and collaborative care. These approaches form a historical sequence of psychosocial perspectives on COPD, of successively increasing utility in COPD research and care. In the past 50 years behavioural research on COPD patients has evolved considerably. Over time, a trend for the patient to become the central actor in the management of the illness is discernable. Evidence-based reviews indicate that self-management offers COPD patients effective options for managing their illness, leading to positive outcomes such as reduced frequency of hospitalization, greater exercise tolerance, and enhanced quality of life. Future research should focus on how self-management skills can be incorporated formally into medical care. In addition to offering suggestions on how clinicians may be instrumental in improving self-management behaviour in COPD patients, and thereby improve care outcomes, we highlight the importance of gaining insight into the perceptions of patients of their own situation, and incorporating a respect for patient perspectives into the philosophy of care.


Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation.
Severe acute respiratory syndrome coronavirus 2 cell entry depends on angiotensin-converting enzyme 2 and transmembrane serine protease 2 and is blocked in cell culture by camostat mesylate, a clinically proven protease inhibitor. Whether camostat mesylate is able to lower disease burden in coronavirus disease 2019 sepsis is currently unknown. Retrospective observational case series. Patient treated in ICU of University hospital Göttingen, Germany. Eleven critical ill coronavirus disease 2019 patients with organ failure were treated in ICU. Compassionate use of camostat mesylate (six patients, camostat group) or hydroxychloroquine (five patients, hydroxychloroquine group). Clinical courses were assessed by Sepsis-related Organ Failure Assessment score at days 1, 3, and 8. Further, viral load, oxygenation, and inflammatory markers were determined. Sepsis-related Organ Failure Assessment score was comparable between camostat and hydroxychloroquine groups upon ICU admission. During observation, the Sepsis-related Organ Failure Assessment score decreased in the camostat group but remained elevated in the hydroxychloroquine group. The decline in disease severity in camostat mesylate treated patients was paralleled by a decline in inflammatory markers and improvement of oxygenation. The severity of coronavirus disease 2019 decreased upon camostat mesylate treatment within a period of 8 days and a similar effect was not observed in patients receiving hydroxychloroquine. Camostat mesylate thus warrants further evaluation within randomized clinical trials.


Physical Performance and Risk of Postoperative Delirium in Older Adults Undergoing Aortic Valve Replacement.
Delirium is a major risk factor for poor recovery after surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). It is unclear whether preoperative physical performance tests improve delirium prediction. To examine whether physical performance tests can predict delirium after SAVR and TAVR, and adapt an existing delirium prediction rule for cardiac surgery, which includes Mini-Mental State Examination (MMSE), depression, prior stroke, and albumin level. Prospective cohort, 2014-2017. Single academic center. A total of 187 patients undergoing SAVR (n=77) or TAVR (n=110). The Short Physical Performance Battery (SPPB) score was calculated based on gait speed, balance, and chair stands (range: 0-12 points, lower scores indicate poor performance). Delirium was assessed using the Confusion Assessment Method. We fitted logistic regression to predict delirium using SPPB components and risk factors of delirium. Delirium occurred in 35.8% (50.7% in SAVR and 25.5% in TAVR). The risk of delirium increased for lower SPPB scores: 10-12 (28.2%), 7-9 (34.5%), 4-6 (37.5%) and 0-3 (44.1%) (p-for-trend=0.001). A model that included gait speed <0.46 meter/second (OR, 2.7; 95% CI, 1.2-6.4), chair stands time ≥11.2 seconds (OR, 3.5; 95% CI, 1.0-12.4), MMSE <24 points (OR, 2.9; 95% CI, 1.3-6.4), isolated SAVR (OR, 5.4; 95% CI, 2.1-13.8), and SAVR and coronary artery bypass grafting (OR, 15.8; 95% CI, 5.5-45.7) predicted delirium better than the existing prediction rule (C statistics: 0.71 vs 0.61; p=0.035). Assessing physical performance, in addition to cognitive function, can help identify high-risk patients for delirium after SAVR and TAVR.


Cholesterol ester transfer protein (CETP) Taq1B polymorphism influences the effect of a standardized cardiac rehabilitation program on lipid risk markers.
Cardiac rehabilitation programs (CR) are standard treatment for patients with coronary artery disease (CAD), yet a large variation in risk factor and lipoprotein changes exists. We investigated the role of three common genetic polymorphisms (CETP Taq1B, LIPC -514 and apo E) associated with alterations of lipoprotein metabolism, in patients before and after standardized CR. Three-hundred and seven patients were recruited for this study. DNA samples were collected and all three genotypes were determined for every patient. While the hepatic lipase LIPC promoter polymorphism and apo E genotype showed little or no correlation with response to CR, CETP Taq1B showed significant association with changes in plasma lipid and lipoproteins. The B1 homozygotes for CETP Taq1B genotype showed significant reduction in TC (-0.25+/-0.07, p < 0.01), LDL-C (-0.15+/-0.06, p < 0.050) and TG (-0.20+/-0.08, p < 0.05). B2 carriers showed no significant change in these parameters. HDL-C, exercise capacity and BMI improved independent of genotype. Individuals with the B1B1 genotype appear to respond well to CR, whereas B2 carriers exhibit marginal gains in lipoprotein risk factors. Although the B2 carriers had similar benefits in exercise capacity and weight reduction, long-term consequences of little or no change in lipoprotein risk factors require further investigation to establish appropriate management strategies.


Primary cutaneous B-cell lymphomas: part II. Therapy and future directions.
The choice of therapy for primary cutaneous B-cell lymphoma (PCBCL) relies on correct histopathologic classification and the exclusion of systemic disease. In part II of this continuing medical education article, we will review the available therapies for the different types of PCBCL. Primary cutaneous follicle center lymphoma (PCFCL) and primary cutaneous marginal zone lymphoma (PCMZL) are indolent tumors with an excellent prognosis. They are managed similarly with local therapy, such as radiotherapy or surgical excision, for isolated disease and observation for asymptomatic multifocal presentations. Relapses are common in both PCFCL and PCMZL, but overall survival remains excellent. Primary cutaneous diffuse large B-cell lymphoma (both leg type and other) has a much poorer prognosis than indolent PCBCL, and it often requires an aggressive approach with radiation therapy and/or multiagent chemotherapy. Investigational approaches hold promise for the treatment of these malignancies, particularly primary cutaneous diffuse large B-cell lymphoma.


SARS-CoV-2 and pregnancy outcomes under universal and non-universal testing in Sweden: register-based nationwide cohort study.
To assess associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pregnancy outcomes considering testing policy and test-positivity-to-delivery interval. Nationwide cohort study. Sweden. From the Pregnancy-Register we identified 88 593 singleton births, 11 March 2020-31 January 2021, linked to data on SARS-CoV-2-positivity from the Public Health Agency, and information on neonatal care admission from the Neonatal Quality Register. Adjusted odds ratios (aORs) were estimated stratified by testing-policy and test-positivity-to-delivery interval. Five-minute Apgar score, neonatal care admission, stillbirth and preterm birth. During pregnancy, SARS-CoV-2 test-positivity was 5.4% (794/14 665) under universal testing and 1.9% (1402/73 928) under non-universal testing. There were generally lower risks associated with SARS-CoV-2 under universal than non-universal testing. In women testing positive >10 days from delivery, generally no significant differences in risk were observed under either testing policy. Neonatal care admission was more common (15.3% versus 8.0%; aOR 2.24, 95% CI 1.62-3.11) in women testing positive ≤10 days before delivery under universal testing. There was no significant association with 5-minute Apgar score below 7 (1.0% versus 1.7%; aOR 0.64, 95% CI 0.24-1.72) or stillbirth (0.3% versus 0.4%; aOR 0.72, 95% CI 0.10-5.20). Compared with term births (2.1%), test-positivity was higher in medically indicated preterm birth (5.7%; aOR 2.70, 95% CI 1.60-4.58) but not significantly increased in spontaneous preterm birth (2.3%; aOR 1.12, 95% CI 0.62-2.02). Testing policy and timing of test-positivity impact associations between SARS-CoV-2-positivity and pregnancy outcomes. Under non-universal testing, women with complications near delivery are more likely to be tested than women without complications, thereby inflating any association with adverse pregnancy outcomes compared with findings under universal testing. Testing policy and time from SARS-CoV-2 infection to delivery influence the association with pregnancy outcomes.


Direct microRNA detection with universal tagged probe and time-resolved fluorescence technology.
microRNAs have emerged as the central player in gene expression regulation and have been considered as potent cancer biomarkers for early disease diagnosis. Direct microRNA detection without amplification and labeling is highly desired. Here we present a rapid, sensitive and selective microRNA detection method based on the base stacking hybridization coupling with time-resolved fluorescence technology. Other than planar microarrays, magnetic beads are used as reaction platforms. In this method, one universal tag is used to report all microRNA targets. Its specificity allows for discrimination between microRNAs differing by a single nucleotide, and between precursor and mature microRNAs. This method also provides a high sensitivity down to 20 fM. Moreover, the full protocol can be completed in about 3 h starting from total RNA.


A bioresponsive diselenide-functionalized hydrogel with cascade catalytic activities for enhanced local starvation- and hypoxia-activated melanoma therapy.
Glutathione (GSH) consumption-enhanced cancer therapies represent important potential cancer treatment strategies. Herein, we developed a new multifunctional diselenide-crosslinked hydrogel with glutathione peroxidase (GPx)-like catalytic activity for GSH depletion-enhanced glucose oxidase (GOx)-mediated tumor starvation and hypoxia-activated chemotherapy. By increasing acid and H2O2 during GOx-induced tumor starvation, the degradation of the multiresponsive scaffold could be promoted, which led to accelerated release of the loaded drugs. Meanwhile, the overproduced H2O2 led to accelerated intracellular GSH consumption under the cascade catalysis of small molecular selenides released from the degraded hydrogel, further enhancing the curative effect of in situ H2O2 and subsequent multimodal cancer treatment. Following the GOx-induced amplification of hypoxia, tirapazamine (TPZ) was transformed into the highly toxic benzotriazinyl radical (BTZ·), exhibiting enhanced antitumor activity. This GSH depletion-augmented cancer treatment strategy effectively boosted GOx-mediated tumor starvation and activated the hypoxia drug, leading to significantly enhanced local anticancer efficacy. STATEMENT OF SIGNIFICANCE: There has been a growing interest in depleting intracellular GSH as a potential strategy for improving ROS-based cancer therapy. Herein, a bioresponsive diselenide-functionalized dextran-based hydrogel with GPx-like catalytic activity was developed for GSH consumption-enhanced local starvation- and hypoxia-activated melanoma therapy. Results showed that the overproduced H2O2 led to accelerated intracellular GSH consumption under the cascade catalysis of small molecular selenides released from the degraded hydrogel, further enhancing the curative effect of in situ H2O2 and subsequent multimodal cancer treatment.


Accuracy of a simplified 3D-printed implant surgical guide.
The accuracy of 3D printing technology is essential for clinical applications. However, depending on the 3D printing method, machine, and environment, the accuracy varies even if the same computer-aided design (CAD) model is printed. The purpose of this in vitro study was to evaluate the differences between the CAD model and the printed parts with a simplified guide designed based on the implant guide and to compare the accuracy among 3 types of 3D printers. A maxilla and mandible implant guide made of complex anatomic structures is difficult to measure accurately. For accurate measurements, 16 simplified guides were designed based on the maxilla and mandible implant guide. The 16 simplified guides were fabricated by using the following 3 different 3D printer technologies: photopolymer jetting (PolyJet), stereolithography apparatus (SLA), and multijet printing (MJP). Each simplified guide was measured 4 times with digital calipers for 20 linear measurements. The measured simplified guides were compared with the CAD model, and the accuracy of the 3D printers was compared. The mean absolute difference and mean relative difference were calculated, and the Bland-Altman analysis was used to evaluate the limits of agreement between the CAD model and the printed parts. The Wilcoxon signed-rank test was performed to evaluate the significant differences among the 3D printers (α=.05). The mean absolute difference and the mean relative difference between the CAD model and the 3D-printed parts were 0.06 ±0.05 mm (0.46 ±0.51%) for PolyJet, 0.09 ±0.05 mm (0.66 ±0.62%) for SLA, and 0.31 ±0.33 mm (1.11 ±0.70%) for MJP. When the 3D printers were compared, significant differences were found between SLA and MJP (P=.006) and between PolyJet and MJP (P=.001). When the CAD models and the 3D-printed parts of the simplified implant guides were compared, significant accuracy differences were observed. The PolyJet and SLA 3D printers met the required accuracy for clinical applications in dentistry. The most suitable 3D printer, however, should be selected considering all factors.


Role of keratinocytes and immune cells in the anti-inflammatory effects of Tripterygium wilfordii Hook. f. in a murine model of psoriasis.
Tripterygium wilfordii Hook. f. (TwHf) belonging to the Celastraceae family is widely used for psoriasis treatment, especially in topical therapy in Chinese traditional medicine. In this study, we investigated the anti-psoriatic effects of topical administration of Tripterygium wilfordii Hook. f. root decoction (TwHf-RD), as well as its safety and potential mechanisms of action in vivo and in vitro. Psoriasis-like lesions were induced in mice using imiquimod (IMQ). The liver and kidney function and the pathological changes in the liver, kidney, and spleen were measured using ELISA and hematoxylin and eosin (H&E) staining after TwHf-RD treatment. H&E staining was used to determine the optimum concentration of TwHf-RD. The expression levels of ki67 and apoptosis related-factors in vivo and in vitro were measured by immunohistochemical staining, flow cytometry, and western blotting. Immunocyte differentiation and pro-inflammatory cytokine (IL-17A, IL-17F, IL-10, IL-22, IL-23, IFN-γ, and TNF-α) expression levels were determined by flow cytometry and RT-qPCR. TwHf-RD treatment attenuated skin inflammation, inhibited keratinocyte (KC) proliferation, increased the levels of apoptosis factors, and influenced the differentiation and inflammatory response of T lymphocytes and regulatory T cells in mice. In vitro experiments proved that Tripterygium wilfordii Hook. f. root extract (TwHf-RE) regulates the proliferation and apoptosis of PAM212 cells. TwHf-RD alleviates IMQ-induced psoriasis lesions by regulating the proliferation and apoptosis of KC and immune cells and by inhibiting immunocyte differentiation and pro-inflammatory cytokine expression.


Treatment of hypertension in individuals with the cardiometabolic syndrome: role of an angiotensin II receptor blocker, telmisartan.
Arterial hypertension is a global public health problem owing to its high prevalence and association with increased risk for cerebral, cardiac and renal events. Hypertension frequently clusters with other cardiometabolic risk factors, such as dysglycemia, low levels of high-density lipoprotein cholesterol and high triglyceride levels. These, along with other factors such as central obesity, increased inflammation, endothelial dysfunction and thrombosis, are components of the metabolic syndrome. All guidelines recommend that the first-line therapy in metabolic syndrome should be based on lifestyle modification, consisting of diet and moderate exercise for at least 30 min/day. Concerning drug treatment of hypertension associated with other cardiometabolic risk factors, many results of head-to-head studies have demonstrated a reduction in new-onset Type 2 diabetes in hypertensive patients treated with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, when compared with conventional antihypertensive therapy. The explanations of the different actions of both these drugs include several mechanisms related to pancreatic insulin release and insulin sensitivity improvement. Another mechanism by which the inhibition of the renin-angiotensin system may improve insulin sensitivity is through the partial peroxisome proliferator-activated receptor-gamma agonism of telmisartan. For that reason, telmisartan has been considered by some experts to be an antihypertensive agent that is particularly useful in the treatment of hypertension associated with cardiometabolic risk factors. The impact of the promising metabolic action exhibited by telmisartan on the outcome of hypertensive patients aggregating other cardiometabolic risk factors waits for adequately randomized and powered clinical trials.


Gab1 and Mapk Signaling Are Essential in the Hair Cycle and Hair Follicle Stem Cell Quiescence.
Gab1 is a scaffold protein that acts downstream of receptor tyrosine kinases. Here, we produced conditional Gab1 mutant mice (by K14- and Krox20-cre) and show that Gab1 mediates crucial signals in the control of both the hair cycle and the self-renewal of hair follicle stem cells. Remarkably, mutant hair follicles do not enter catagen, the destructive phase of the hair cycle. Instead, hair follicle stem cells lose quiescence and become exhausted, and thus no stem cell niches are established in the bulges. Moreover, conditional sustained activation of Mapk signaling by expression of a gain-of-function Mek1(DD) allele (by Krox20-cre) rescues hair cycle deficits and restores quiescence of the stem cells. Our data thus demonstrate an essential role of Gab1 downstream of receptor tyrosine kinases and upstream of Shp2 and Mapk in the regulation of the hair cycle and the self-renewal of hair follicle stem cells.


Corrigendum to "Role of Mitochondria in the Oxidative Stress Induced by Electromagnetic Fields: Focus on Reproductive Systems".
[This corrects the article DOI: 10.1155/2018/5076271.].


[Changes in heat capacity upon protein denaturation].
By the use of infrared spectroscopy it has been shown that the configurational heat capacity of hydrogen bonds represents the principal contribution into the denaturational change of heat capacity of proteins.


They really want to go back home, they hate it here: the importance of place in Canadian health professionals' views on the barriers facing Aboriginal patients accessing kidney transplants.
Aboriginal Canadian patients with end-stage kidney disease receive disproportionately fewer transplants than non-Aboriginal patients. The reasons for this are poorly understood and likely to be complex. This qualitative study employed thematic analysis of in-depth interviews with Canadian kidney health professionals (n=23) from programs across Canada to explore their perspective on this disparity. Individual-level factors were the most commonly reported barriers to Aboriginal patients accessing transplants-most notable of which was patients' remote living location. Understanding the role of 'place' as a barrier to accessing care and the lived experiences of Aboriginal patients emerged as key research priorities.


Primary inguinal hernia repair in The Netherlands.
To assess the operative methods used in Dutch surgical practice to repair the inguinal floor of the primary hernia. Survey by questionnaire. University department of Surgery, The Netherlands. All Dutch Surgeons. Answers to questions about the methods of repair used, specific surgical options, and materials. Comparison of training hospitals and district hospitals. Replies were received from 145/155 departments (94%), but from only 448/774 individual surgeons (58%). 192 (43%) used one method alone (Bassini 71, Shouldice 49, McVay 36, Griffith 24 and others 12) and 256 (57%) of surgeons used combinations of 11 different methods. Only 9 used a prosthetic mesh and 7 laparoscopic repair. The Shouldice method was significantly more popular in training hospitals compared with non-training hospitals (36%) (71/199) compared with (20%) (48/249) (p < 0.05). There were many modifications to accepted methods. Only 78% (94/121) of surgeons who said that they did a standard shouldice repair incised the transversalis fascia. 64% (287) of surgeons said that they modified their technique to suit individual patients. In the Netherlands there is no standard technique of inguinal hernia repair.


Analysis of the frequency of inheritance of transposed Ds elements in Arabidopsis after activation by a CaMV 35S promoter fusion to the Ac transposase gene.
The Ac/Ds transposon system of maize shows low activity in Arabidopsis. However, fusion of the CaMV 35S promoter to the transposase gene (35S::TPase) increases the abundance of the single Ac mRNA encoded by Ac and increases the frequency of Ds excision. In the experiments reported here it is examined whether this high excision frequency is associated with efficient re-insertion of the transposon. This was measured by using a Ds that carried a hygromycin resistance gene (HPT) and was inserted within a streptomycin resistance gene (SPT). Excision of Ds therefore gives rise to streptomycin resistance, while hygromycin resistance is associated with the presence of a transposed Ds or with retention of the element at its original location. Self-fertilisation of most individuals heterozygous for Ds and 35S::TPase produced many streptomycin-resistant (strep(r)) progeny, but in many of these families a small proportion of strep(r) seedlings were also resistant to hygromycin (hyg(r)). Nevertheless, 70% of families tested did give rise to at least one strep(r), hyg(r) seedling, and over 90% of these individuals carried a transposed Ds. In contrast, the Ac promoter fusion to the transposase gene (Ac::TPase) produced fewer strep(r)hyg(r) progeny, and only 53% of these carried a transposed Ds. However, a higher proportion of the strep(r) seedlings were also hyg(r) than after activation by 35S::TPase. We also examined the genotype of strep(r), hyg(r) seedlings and demonstrated that after activation by 35S::TPase many of these were homozygous for the transposed Ds, while this did not occur after activation by Ac::TPase. From these and other data we conclude that excisions driven by 35S::TPase usually occur prior to floral development, and that although a low proportion of strep(r) progeny plants inherit a transposed Ds, those that do can be efficiently selected with an antibiotic resistance gene contained within the element. Our data have important implications for transposon tagging strategies in transgenic plants and these are discussed.


Oscillation of the human ankle joint in response to applied sinusoidal torque on the foot.
1. Low-frequency (3-30 Hz) oscillatory rotation of the ankle joint in plantarflexion-dorsiflexion was generated with a torque motor. Torque, rotation about the ankle and electromyograms (e.m.g.s) for the gastrocnemius-soleus and the anterior tibial muscles were recorded.2. Fourier coefficients at each drive frequency were used to calculate the effective compliance (ratio of rotation and torque). The compliance has a sharp resonance when tonic, voluntary muscle activity is present.3. The resonant frequency of compliance is between 3 and 8 Hz. The location of the resonant frequency and the magnitude of the compliance at resonance depend upon both the degree of tonic muscle activity and the amplitude of the driving torque. The resonant frequency increases with increasing tonic activity.4. With tonic muscle activity, the compliance in the frequency range below resonance increases with increasing amplitudes of driving torque.5. The e.m.g., when evoked by the rhythmic stretch, lags the start of stretching by between 50 and 70 msec.6. When tonic muscle activity is present, the resonant frequency of the stretch reflex is between 5 and 6.5 Hz.7. Following the start of driven oscillation at frequencies near resonance, slowly increasing amplitudes of angular rotation (to a limit) are observed.8. Distortion (from the sinusoidal wave shape) of angular rotation is frequently observed with drive frequencies between 8 and 12 Hz during which there sometimes occur spontaneous recurrences of oscillation at the drive frequency. For the angular rotation, a significant portion of the power may be in subharmonic frequency components of the drive frequency when that frequency is between 8 and 12 Hz.9. Self-sustaining oscillation (clonus) near the resonant frequency of the compliance is sometimes observed after the modulation signal to the motor is turned off. This is most often seen when the gastrocnemius-soleus muscles are fatigued. Clonus may be evoked by driven oscillation at any frequency.10. The hypothesis that physiological tremor, which occurs between 8 and 12 Hz, is a consequence of stretch reflex servo properties seems to be at odds with the observations of resonance in the compliance and of self-generated clonus both occurring in the 5-8 Hz region.


Special Issue: Bioactive Compounds, Nutritional Quality, and Oxidative Stability of Edible Oils and By-Products of Their Extraction.
Edible oils (refined, virgin, and cold-pressed oils) are one of the most important components of the daily human diet and have a considerable influence on the proper functioning of our body [...].


Quantitative evaluation of vascular permeability in the gerbil brain after transient ischemia using Evans blue fluorescence.
Mongolian gerbils were used to evaluate brain edema during restoration of flow following bilateral carotid occlusion for 1 h. We have modified the method for fluorometric measurement of Evans blue to monitor vascular protein leakage (vasogenic edema). The extraction of extravasated Evans blue was performed by homogenizing the whole brain in 50% trichloroacetic acid. The supernatant was diluted fourfold with ethanol and the Evans blue fluorescence was measured. The tissue blank was negligible. Evans blue content of the plasma was similarly determined and the ratio of tissue to plasma Evans blue content was calculated. Furthermore, Evans blue fluorescence was used for microscopic investigation. It is suggested that Evans blue fluorescence can be applied for quantification of protein leakage with much more sensitivity and accuracy than the colorimetric absorbance method, as well as for tissue localization of protein leakage.


The genetic basis of Gilles de la Tourette Syndrome.
Gilles de la Tourette Syndrome (TS) is a neuropsychiatric disorder that is caused by a likely complex genetic basis, interacting with environmental factors. Just as multiple large scale collaborative projects for TS are starting out and the first ever genomewide association study for TS has been published, this review provides a synthetic overview of more than two decades of active research. Studies of the dopaminergic and serotonergic pathways, have yielded inconsistent results, although, for instance, the involvement of DRD2, MAO-A, and DAT1 has been supported by independent findings. The study of chromosomal aberrations in TS etiology has implicated multiple genes, with SLITRK1 being the most prominent example. Common underlying themes with other neurodevelopmental disorders are emerging and attention on neurexins, neuroligins, and genes from the histaminergic and glutamatergic pathways is increased. Propelled by the gradual availability of large scale TS cohorts, and novel methodologies for the study of both common and rare genetic variants, the new era of TS genetics holds the promise to identify novel targets for improved therapies.


Supporting The Mental Health Of Elite-Level Coaches Through Early Intervention.
Current evidence indicates that elite-level coaches encounter a range of performance, organizational, and personal stressors that may influence or compromise mental health. With exposure to these stressors, supports need to be established to protect and preserve the mental health of elite-level coaches. Given the paucity of evidence available, this article proposes a number of considerations that should be taken into account when developing a mental health and rehabilitation framework for high-performance coaches. We argue that early intervention should be positioned at the core of this framework, to address the onset of symptoms prior to the emergence of a mental disorder or mental health crisis. Mental health screening and monitoring of coaches, the psychological safety of high-performance environments, the mental health literacy of coaches, and the tailored pathways to support are discussed. Beyond these strategies, it is proposed that rehabilitation and reintegration should be addressed to assist coaches who are currently experiencing mental ill health or have left their role due to mental health reasons. Although further research is needed to implement evidence-based strategies, it is recommended that a future mental health framework should incorporate the perspectives of coaches to ensure it is consistent with their needs and experiences.


Satisfaction With Web-Based Healthcare Content in Cancer Survivors: A Cross-Sectional Survey.
Health-related web content is constantly increasing, and cancer survivors use it to manage their health and activities of daily living. However, the actual usage of and satisfaction with web contents among cancer survivors is unclear. Therefore, we conducted a web-based cross-sectional survey to understand the satisfaction with web content in those cancer survivors who use the Internet to cope with their anxiety/stress, sleeplessness, or cognitive difficulties. The survey questionnaire was e-mailed to 1.2 million voluntary registrants at a research company. Cancer survivors who accessed any content via the Internet and experienced anxiety/stress, sleeplessness, or cognitive difficulties were included in the study. Out of the 412 survivors who completed the survey, 357 experienced some degree of anxiety or stress, 258 experienced sleeplessness, and 161 experienced some cognitive difficulties, such as forgetfulness or lack of attention. They used web contents to record their health or (n = 205), relieve their anxiety or stress (n = 238), and devise activities of daily living (n = 232) during cancer therapy, including surgery, chemotherapy, and radiation. The web contents included "interactive contents" (users engage with the web content by responding to it in some form), "non-interactive contents" (information medium without any user engagement), "web-storage," or "scrolling." Multivariate logistic regression revealed greater satisfaction with "interactive contents" in cancer survivors. This reflects that the sharing of personal experiences as well as objective information should be considered to create satisfying and effective web contents.


Population pharmacokinetics of vactosertib, a new TGF-β receptor type Ι inhibitor, in patients with advanced solid tumors.
Vactosertib, a novel inhibitor of transforming growth factor-β type Ι receptor, is under development for the treatment of various cancers. The objective of this study was to characterize the population pharmacokinetics of vactosertib in patients with solid tumors. Vactosertib population pharmacokinetics was assessed by nonlinear mixed-effects modelling of plasma concentration-time data obtained from a first-in-human phase 1 trial conducted in patients with advanced solid tumors. The final population pharmacokinetic model was constructed by assessing the effect of covariates on pharmacokinetic parameters including demographic characteristics, laboratory values, hepatic and renal function, and concomitant medications. The robustness of the final model was evaluated using a bootstrap method as well as visual predictive check based on Monte Carlo simulations and goodness-of-fit plots. A total of 559 concentrations from 29 patients were available for pharmacokinetic analysis. A two-compartment linear model with first-order absorption and absorption lag time adequately described the population pharmacokinetics of vactosertib. The estimates of apparent clearance (CL/F) and volume of central compartment (Vc/F) were 31.9 L/h (inter-individual variability, 0.481) and 82.9 L (inter-individual variability, 0.534), respectively. The mixture model accounts for both typical absorption profile in the majority of patients and distinct profile in some patients with uncommon gastrointestinal conditions. Body mass index was significantly associated with Vc/F. The model developed in this study adequately describes the population pharmacokinetics of vactosertib in patients with advanced solid tumors. The pharmacokinetic characteristics assessed using the model would provide useful quantitative information to assist the future clinical development of vactosertib.


Human innate lymphoid cell precursors express CD48 that modulates ILC differentiation through 2B4 signaling.
Innate lymphoid cells (ILCs) develop from common lymphoid progenitors (CLPs), which further differentiate into the common ILC progenitor (CILP) that can give rise to both ILCs and natural killer (NK) cells. Murine ILC intermediates have recently been characterized, but the human counterparts and their developmental trajectories have not yet been identified, largely due to the lack of homologous surface receptors in both organisms. Here, we show that human CILPs (CD34+CD117+α4β7+Lin-) acquire CD48 and CD52, which define NK progenitors (NKPs) and ILC precursors (ILCPs). Two distinct NK cell subsets were generated in vitro from CD34+CD117+α4β7+Lin-CD48-CD52+ and CD34+CD117+α4β7+Lin-CD48+CD52+ NKPs, respectively. Independent of NKPs, ILCPs exist in the CD34+CD117+α4β7+Lin-CD48+CD52+ subset and give rise to ILC1s, ILC2s, and NCR+ ILC3s, whereas CD34+CD117+α4β7+Lin-CD48+CD52- ILCPs give rise to a distinct subset of ILC3s that have lymphoid tissue inducer (LTi)-like properties. In addition, CD48-expressing CD34+CD117+α4β7+Lin- precursors give rise to tissue-associated ILCs in vivo. We also observed that the interaction of 2B4 with CD48 induced differentiation of ILC2s, and together, these findings show that expression of CD48 by human ILCPs modulates ILC differentiation.


Taxonomically and functionally diverse microbial communities in deep crystalline rocks of the Fennoscandian shield.
Microbial life in the nutrient-limited and low-permeability continental crystalline crust is abundant but remains relatively unexplored. Using high-throughput sequencing to assess the 16S rRNA gene diversity, we found diverse bacterial and archaeal communities along a 2516-m-deep drill hole in continental crystalline crust in Outokumpu, Finland. These communities varied at different sampling depths in response to prevailing lithology and hydrogeochemistry. Further analysis by shotgun metagenomic sequencing revealed variable carbon and nutrient utilization strategies as well as specific functional and physiological adaptations uniquely associated with specific environmental conditions. Altogether, our results show that predominant geological and hydrogeochemical conditions, including the existence and connectivity of fracture systems and the low amounts of available energy, have a key role in controlling microbial ecology and evolution in the nutrient and energy-poor deep crustal biosphere.


Extensive aneurysm of the aortic arch and descending aorta. Extra-anatomical reconstruction and exclusion of the aneurysmal sac.
A new technique for repair of extensive aneurysm reaching from the ascending aorta to the diaphragm is presented. The operation consists of the reconstruction of the aortic arch and descending aorta and the exclusion of the aneurysmal sac in a single operation. Two successful cases are presented.


Feasibility of low contrast media volume in CT angiography of the aorta.
Using smaller volumes of contrast media (CM) in CT angiography (CTA) is desirable in terms of cost reduction and prevention of contrast-induced nephropathy (CIN). The purpose was to evaluate the feasibility of low CM volume in CTA of the aorta. 77 patients referred for CTA of the aorta were scanned using a standard MDCT protocol at 100 kV. A bolus of 50 ml CM (Iopromide 300 mg Iodine/ml) at a flow rate of 6 ml/s was applied (Iodine delivery rate IDR = 1.8 g/s; Iodine load 15 g) followed by a saline bolus of 40 ml at the same flow rate. Scan delay was determined by the test bolus method. Subjective image quality was assessed and contrast enhancement was measured at 10 anatomical levels of the aorta. Diagnostic quality images were obtained for all patients, reaching a mean overall contrast enhancement of 324 ± 28 HU. Mean attenuation was 350 ± 60 HU at the thoracic aorta and 315 ± 83 HU at the abdominal aorta. A straightforward low volume CM protocol proved to be technically feasible and led to CTA examinations reaching diagnostic image quality of the aorta at 100 kV. Based on these findings, the use of a relatively small CM bolus can be incorporated into routine clinical imaging.


Experimental mucormycosis in congenitally athymic (nude) mice.
Athymic nude (nu/nu) mice and their phenotypically normal (nu/+) littermates displayed a similar susceptibility to acute lethal infection with Absidia corymbifera. Although the clinical manifestations of acute infection were also similar in both groups, the nude mice tended to develop more extensive lesions and were less effective in eliminating viable A. corymbifera spores than their heterozygous littermates. The results suggested that thymus-dependent processes did not play an essential role in primary resistance to mucormycosis.


Tetracycline-regulated gene expression in the pathogen Ustilago maydis.
A powerful approach to explore gene function is the use of tetracycline-regulated expression. Here, we report the establishment of this titratable gene expression system for Ustilago maydis. Obstacles of premature polyadenylation of the native tetR gene, high basal activity of the tetracycline-responsive promoter, and toxicity of the viral activation domain were overcome by designing a synthetic tetR* gene according to context-dependent codon usage, removing cryptic enhancer elements from the promoter, and using an acidic minimal activation domain, respectively. We verified tetracycline-dependent dose-response using optimised components and applied a straightforward single-step promoter replacement cassette to regulate expression of pheromone response factor, a key transcription factor regulating mating. Pheromone response in liquid culture and mating on solid media was abolished in the presence of tetracycline and doxycycline. Thus, functionality of this versatile new tool for the plant pathogen was proven in a biological context.


Alteration in the inherent metallic and surface properties of nickel-titanium root canal instruments to enhance performance, durability and safety: a focused review.
The expanded use of nickel-titanium (NiTi) rotary instruments in root canal procedures has led to the development of a wide variety of shapes, designs and applications. Root canal anatomy has not changed, however, and the same challenges exist in both initial treatment and the revision of unacceptable treatment. These challenges include application with high levels of achievement and low to no levels of adverse effects, such as instrument fracture, root canal wall ledging, dentine wall perforation and so forth. To that end, many manufacturers have been seeking ways to alter the presently available and wide range of root canal instrument designs, with a focus on altering the surface of the alloy or altering the alloy microstructure with post-machining or post-twisting heat treatment. This focused review will address the impact that these modifications have had on instrument flexibility, resistance to cyclic fatigue and cutting efficiency.


Medical students' occupational exposures to potentially infectious agents.
To describe the epidemiology of occupational exposures sustained by third-year medical students at a state university medical school, and identify associated factors that may be modified to decrease exposure risk. The cohort consisted of all third-year students after completion of each third-year clerkship rotation. At the end of each clinical rotation (a total of six for each student during the year), questionnaires were distributed to the 119 students. Demographic information, type of exposure, rotation, circumstances, compliance with CDC universal precaution recommendations, and post-exposure prophylaxis (PEP) were assessed. Inferential statistics were used to describe the results. Of a total of 714 questionnaires, 644 (90.2%) were returned. Of the 644, there were 60 reports (9.3%) of one or more exposures to blood or body fluids. The incidence of exposure varied with clerkship: 23 on surgery, 18 on obstetrics-gynecology, eight on outpatient medicine, four on psychiatry, four on pediatrics, and three on internal medicine. Thirty-six (60%) were skin or mucous membrane exposures to blood, body fluid, or respiratory secretions, and 24 (40%) were percutaneous exposure by instrument. Ten (17%) of the exposures resulted in official incident reports and seven accepted PEP recommendations. Medical students are often exposed to body fluids during their initial clerkship year, primarily in their surgical rotations. Additional education on these rotations may be useful in reducing exposure risk.


Expression profiling of potato cultivars with contrasting tuberization at elevated temperature using microarray analysis.
Temperature is one of the most significant factors affecting potato yield. Night temperature beyond 18-22 °C drastically reduces tuber formation, constraining potato cultivation in tropics and subtropics. Identification of genes and pathways affected by high temperature is crucial for developing thermo tolerant cultivars for these regions. In the present study, two cultivars with contrasting tuberization behavior at night temperatures (24 °C) were selected for gene expression analysis using a customized microarray chip representing 39,031 potato genes. A total of 2500 genes were differentially expressed on 21 d and 4096 genes on 14 d after stress. Gene ontology and pathway analysis provided insights into the probable biological processes and pathways governing tuberization at elevated temperature. Pathway maps were constructed to graphically represent the gene expression patterns. Genes associated with photosynthesis, hormonal activity, sugar transporters and transcription factors were differentially expressed. The results are presented and discussed in terms of tuberization at high temperature. The effect of high temperature on expression of genes controlling tuberization was also analyzed. This study provided useful information on potato tuberization at elevated temperature and make available a framework for further investigations into heat stress in potato.


Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. Molecular basis for the synergy between interferon-gamma and lipopolysaccharide.
Macrophages can become activated to kill both tumor cells and a variety of microbes. Results here show that synthesis of nitric oxide (NO), a mediator of many macrophage cytotoxic functions, was greatly increased when cells of the mouse macrophage cell line RAW 264.7 were costimulated with bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), compared to LPS alone. This increase paralleled increases in cytotoxicity. Northern analysis showed that increased production of NO was preceded by markedly enhanced expression of mRNA for the inducible form of macrophage NO synthase (mac-NOS), which catalyzes the synthesis of NO. Cycloheximide inhibited the induction of mac-NOS mRNA by IFN-gamma and LPS, indicating that expression of this mRNA required de novo protein synthesis. Elevated expression of mac-NOS mRNA was not due to an increase in its stability. Rather, the combination of IFN-gamma and LPS induced a much higher rate of transcription of the mac-NOS gene than did stimulation with LPS alone. These results provide one explanation of why priming and triggering stimuli, such as IFN-gamma and LPS, respectively, synergistically activate macrophages and may be applicable to explaining how IFN-gamma augments NO-dependent microbicidal activity in macrophages as well.


Analysis of Degradation Kinetics and Migration Pattern of Chlorfenapyr in Celery (Apium graveliens L.) and Soil Under Greenhouse Conditions at Different Elevations.
The degradation kinetics and migration pattern of chlorfenapyr in celery and soil at Lhasa and Pengzhou were investigated. A simple, rapid analytical method for the quantification of chlorfenapyr in celery and soil was developed using gas chromatography-tandem mass spectrometer. The results indicated that the half-lives of chlorfenapyr in celeries and soils at Lhasa were 6.3 days and 12.8 days. While the half-lives of chlorfenapyr in celeries and soils at Pengzhou were 6.9 days and 20.4 days. The half-lives of chlorfenapyr in celeries and soils at Lhasa were shorter than that at Pengzhou, while the half-lives of chlorfenapyr in soils at Lhasa and Pengzhou were longer than that in celeries at Lhasa and Pengzhou. The final residues of chlorfenapyr in celeries at Lhasa and Pengzhou were 5.074 ± 0.144 mg/kg and 5.981 ± 0.234 mg/kg after 7 days of spraying, respectively. When chlofenapyr was sprayed to soils only, the average root concentration factor of chlorfenapyr were 3.57-4.02, while the average translocation factor of chlorfenapyr in leaves and stems were 0.28-0.38 and 0.20-0.25, respectively. Chlorfenapyr was easy to migrate from soil to the roots of celery, followed by leaves and stems. The limit value of chlorfenapyr in celery has not been specified in China's National MRL standard (GB 2763 in National food safety standard-maximum residue limits for pesticides in food. Standard, Beijing, 2021), this study was useful to draw up the limit values of chlorfenapyr residues in celery at different elevations.


Snail peptide expression pattern in the nervous system of the medicinal leech.
Distribution of neurons immunopositive to antibodies against the "command neuron peptides" (CNPs) encoded by the snail Helix Command-Specific 2 (HCS2) gene was investigated in the nervous system of medicinal leech Hirudo. Immunopositive neurons were found in the leech segmental ganglia, brain and tail ganglionic masses, and peripheral ganglia. The CNPs immunopositive fibers were observed in neuropils of all ganglia and in some nerves. The role of CNPs immunopositive cells in animal behavior and the putative functions of the CNPs neuropeptide family are discussed.


Management of the hematologic complications of hepatitis C therapy.
Consensus guidelines are in place for treating chronic hepatitis C virus infection. This article highlights some of the hematologic complications of hepatitis C therapy. Management options are presented.


Follow-up results of 415 patients after endoscopic sinus surgery.
Endoscopic sinus surgery (ESS) is a method used with success in the treatment of chronic inflammatory paranasal sinus diseases. Between February 1991 and June 1995 the Messerklinger technique for ESS was used in 415 patients who had been pre-operatively evaluated in detail according to the staging system used in our clinic. Average post-operative follow-up was 23 months. Our general success rate was found to be 86.3% upon evaluating the subjective improvements in the patients' symptoms in the post-operative period. The major and minor complication rates in our series were 0.24 and 20.24%, respectively.


Concentrations of organochlorines in sperm whales (Physeter macrocephalus) from Southern Australian waters.
Concentrations of DDTs, PCBs and HCHs were measured in sperm whales involved in two mass stranding events on the west coast of Tasmania, Australia in February 1998. DDTs and PCBs were present in all samples analysed, while only three contained HCHs. The relationships between organochlorines, sex, age and reproductive groups were marked by high variability. Differences in organochlorine concentrations were observed between animals from the two stranding sites and discussed in light of the ecology of this species. Concentrations of all pollutants were stratified throughout the vertical aspect of the blubber and possible reasons for and the implications of this are discussed. Concentrations of compounds were higher than those documented in this species in the Southern Hemisphere previously, although were relatively lower than those documented in the Northern Hemisphere. However, comparisons were confounded by spatial and temporal differences. Continued monitoring of marine mammals throughout this region in a co-coordinated, standardized manner is essential for establishing definite temporal and spatial variations in pollutant concentrations.


Effect of saturated and unsaturated fatty acid supplementation on bio-plastic production under submerged fermentation.
Polyhydroxyalkanoates (PHAs) are intracellular reserve material stored by gram-negative bacteria under nutrient-limited condition. PHAs are utilized in biodegradable plastics (bio-plastics) synthesis due to their similarity with conventional synthetic plastic. In the present study, the effect of addition of saturated and unsaturated fatty acids (palmitic acid, stearic acid, oleic acid and linoleic acid) on the production of PHAs by the soil bacterium Alcaligenes sp. NCIM 5085 was studied. Fatty acid supplementation in basal media produced saturated and unsaturated PHAs of medium and short chain length. Gas chromatography analysis of palmitic acid-supplemented media showed the presence of short chain length (scl) PHAs which could potentially serve as precursors for bio-plastic production. The scl PHA was subsequently characterized as PHB by NMR and FTIR. On the other hand, oleic acid and linoleic acid addition showed both saturated and unsaturated PHAs of different chain lengths. Palmitic acid showed maximum PHB content of 70.8 % at concentration of 15 g l-1 under shake flask cultivation. When shake flask cultivation was scaled up in a 7.5-l bioreactor (working volume 3 l), 7.6 g l-1 PHA was produced with a PHB yield (YP/X) and productivity of 75.89 % and 0.14 g l-1 h, respectively.


Reiter's disease: successful treatment of the skin manifestations with oral etretinate.
Cutaneous manifestations in a case of Reiter's disease were successfully treated by oral etretinate administration. The clinical and histopathological similarities between the skin lesions of Reiter's disease and those of pustular psoriasis, which is known to respond to aromatic retinoids, suggested this treatment.


Decline of oral functions in old-old adults and their relationship with age and sex: The SONIC study.
Many physical functions decline with aging, but it is not known whether oral functions vary according to sex or decline with aging, as it occurs with physical functions. The present study aimed to examine the association of sex, age, and elapsed years with occlusal force and tongue pressure using a generalized linear mixed-effect model (GLMM) over a 3-year period among old-old Japanese adults. Participants were community-dwelling older adults who participated in a survey (June 2014-March 2017) and a follow-up survey (July 2017-December 2019) after 3 years (n = 951: 70-year group, n = 466; 80-year group, n = 391; 90-year group, n = 94). Dental examinations including the number of teeth, occlusal force, and tongue pressure were conducted, and a GLMM was used to estimate the association of sex, age, and elapsed years with occlusal force and tongue pressure, adjusting for the number of teeth. The GLMM showed that occlusal force was significantly associated with sex (reference; male, non-standardized coefficient: B = -66.9 [female], p < 0.001), age (reference; 70-year group, B = -81.7 [80-year group], p < 0.001, B = -87.2 [90-year group], p < 0.001), and the number of teeth (B = 13.8, p < 0.001), but did not significantly decrease with elapsed years. Tongue pressure was significantly associated with sex (reference; male, B = -0.94 [female], p = 0.034) and age (reference; 70-year group, B = -1.78 [80-year group], p < 0.001, B = -5.47 [90-year group], p < 0.001). Tongue pressure decreased significantly with elapsed years (B = -0.82, p < 0.001). These findings suggest that tongue pressure significantly decreased over time, but occlusal force did not. Tongue-related muscles may be more susceptible to aging than masticatory muscles.