A Monoclonal Antibody to M-Phase Phosphoprotein 1/Kinesin-Like Protein KIF20B.
Kinesin-like protein KIF20B, originally named M-phase phosphoprotein 1 (MPP1), is a plus-end-directed kinesin-related protein that exhibits in vitro microtubule-binding and -bundling properties as well as microtubule-stimulated ATPase activity. It has been characterized as a slow molecular motor that moves toward the plus-end of microtubules. Human autoantibodies directed against KIF20B have been described in up to 25% of patients with idiopathic ataxia and less commonly in other neuropathies and autoinflammatory conditions. One of the limitations of research into the structure and function of KIF20B has been a reliable monoclonal antibody that can be used in a variety of applications. To establish a reference standard for anti-KIF20B immunoassays and facilitate studies on the role of KIF20B in developmental cell biology, we developed an IgG1 monoclonal antibody, 10C7, which reacts with the cognate KIF20B protein in Western immunoblots and in addressable laser bead immunoassays. In HEp2 cells, leptomeningeal pericytes, and transfected HEK293T cells, indirect immunofluorescence studies showed that reactivity was mainly localized to a proportion of interphase nuclei, but during metaphase, it was redistributed throughout the cytoplasm and perichromatin mass. Later in telophase/anaphase, KIF20B was localized to the stem body and midzone of the midbody. 10C7 also showed remarkable staining of a subset of cells in the cerebellum, ovary, and testis tissues. KIF20B was shown to have extensive coiled-coil domains. The monoclonal antibody, 10C7, will be of value to diagnostic laboratory scientists interested in having a reliable reference standard for anti-KIF20B immunoassays as well as cell, molecular, and developmental biology researchers.


Doppler flow measurement in coronary artery bypass grafts and early postoperative clinical outcome.
The present investigation attempts to correlate flow measurements made intraoperatively in coronary bypass grafts with clinical outcome. A total of 352 consecutive patients undergoing isolated coronary artery surgery underwent hemodynamic assessment of their bypass grafts (328 internal thoracic artery and 582 saphenous vein grafts) at the end of cardiopulmonary bypass (CPB) by using a 8 MHz pulsed Doppler ultrasound flowmeter. The total patient population was divided into three groups of distinct outcome (A: normal, 228 patients; B: complicated, 106 patients; C: poor, 18 patients) on the basis of a combination of the following parameters: difficult weaning from bypass, use of inotropic drugs, reduced left-ventricular stroke work index, myocardial infarction, intraaortic balloon counterpulsation, and death of cardiac origin. Univariate analysis has shown clinical outcome to be influenced by preoperative clinical condition and not by flow in bypass grafts (average flow per graft [ml/min] was 60 +/- 2 [mean +/- SEM] in group A, 58 +/- 3 in group B and 43 +/- 6 in group C: NS by analysis of variance). Multivariate analysis (Fisher linear discriminant analysis) selected only the two following factors leading to normal (group A) or adverse (groups B and C) outcome: unstable angina (p = 0.026) and duration of additional CPB after unclamping the aorta (p < 10(-5). To conclude, clinical outcome was not influenced by flow as measured in well-functioning bypass grafts by pulsed Doppler technique.


Mohs micrographic surgery for cutaneous lymphadenoma.
Cutaneous lymphadenoma clinically present as pink papules or plaques resembling a basal cell carcinoma on the head and neck of young adults. Surgical excision is the treatment for these benign tumors. Cutaneous lymphadenoma may occur in an anatomically sensitive area, where margin control and conservative excision are indicated. Although not previously described in the literature, Mohs micrographic surgery (MMS) is a treatment option for cutaneous lymphadenoma. We present a series of three individuals with cutaneous lymphadenoma treated with MMS.


Matrix metalloproteinase-2: the forgotten enzyme in aneurysm pathogenesis.
The pathogenesis of abdominal aortic aneurysm (AAAs) involves progressive cycles of proteolysis and inflammation, the product of proteolysis driving subsequent inflammation. Little is yet known about the initiating events. We review the specific literature examining the possibility that MMP-2 may be the initial catalyst. Histologically, elastolysis is one of the earliest observable events in aneurysm genesis. Matrix metalloproteinase-2 (MMP-2), as the dominant gelatinase differentially expressed in aneurysmal tissue and cells derived from aneurysms, would be a good candidate. We report the results of in vivo and in vitro experiments, which lend support to the importance of MMP-2 as an aneurysmal initiator.


[Effect of electroacupuncture intervention on spinal AMPA-receptor expression in rats with neuropathic pain].
To observe the effect of electroacupuncture (EA) intervention on changes of spinal a-amino-3- ydroxy-5-methylisoxazole-4-propionate acid (AMPA) receptor (GluR 1) expression in rats with chronic constrictive injury (CCI) pain, so as to explore its mechanisms underlying improvement of neuropathic pain. Sixty male SD rats were randomly divided into sham-operation, CCI model and EA groups (n=20). Neuropathic pain model was established by ligature of the right sciatic nerve. EA stimulation (2 Hz, 1-3 mA) was applied to "Weizhong" (BL 40) and "Huantiao" (GB 30) on the injured limb for 30 min, once a day for 7 days beginning from the 11th day on after CCI. The mechanical and thermal pain thresholds were measured before and after the CCI procedure (baseline) and after EA intervention. The AMPA receptor subunit GluR 1 protein and gene expression in L5-L 6 segments of the spinal cord was detected using Western blot (WB), immunohistochemistry and re- verse transcription (RT)-polymerase chain reaction (PCR), separately. As the results of mechanical and thermal pain thresholds in our past study, EA intervention could markedly raise CCl-reduced decreased pain threshold. Compared with the sham-operation group, the expression levels of spinal GluR 1 protein and mRNA in the model group were significantly increased (P<0.05, P<0.01). Following EA intervention, the expression levels of GluR 1 protein and mRNA were remarkably down-regulated in the EA group in comparison with those of the model group (all P<005). EA intervention can down-regulate CCI-induced increase of AMPA receptor GIuR 1 expression in the lumbar spinal cord in CCI rats, which may contribute to its effect in alleviating neuropathic pain.


Characterization of airborne particles during production of carbonaceous nanomaterials.
Despite the rapid growth in nanotechnology, very little is known about the unintended health or environmental effects of manufactured nanomaterials. The development of nanotechnology risk assessments and regulations requires quantitative information on the potential for exposure to nanomaterials. The objective of this research isto characterize airborne particle concentrations during the production of carbonaceous nanomaterials, such as fullerenes and carbon nanotubes, in a commercial nanotechnology facility. We measured fine particle mass concentrations (PM2.5), submicrometer size distributions, and photoionization potential, an indicator of the particles' carbonaceous content, at three locations inside the facility: inside the fume hood where nanomaterials were produced, just outside the fume hood, and in the background. The measurements were not selective for engineered nanomaterials and may have included both engineered nanomaterials and naturally occurring or incidental particles. Average PM2.5 and particle number concentrations were not significantly different inside the facility versus outdoors. However, large, short-term increases in PM2.5 and particle number concentrations were associated with physical handling of nanomaterials and other production activities. In many cases, an increase in the number of sub-100 nm particles accounted for the majority of the increase in total number concentrations. Photoionization results indicate that the particles suspended during nanomaterial handling inside the fume hood were carbonaceous and therefore likely to include engineered nanoparticles, whereas those suspended by other production activities taking place outside the fume hood were not. Based on the measurements in this study, the engineering controls at the facility appear to be effective at limiting exposure to nanomaterials.


What is the link between synaesthesia and sound symbolism?
Sound symbolism is a property of certain words which have a direct link between their phonological form and their semantic meaning. In certain instances, sound symbolism can allow non-native speakers to understand the meanings of etymologically unfamiliar foreign words, although the mechanisms driving this are not well understood. We examined whether sound symbolism might be mediated by the same types of cross-modal processes that typify synaesthetic experiences. Synaesthesia is an inherited condition in which sensory or cognitive stimuli (e.g., sounds, words) cause additional, unusual cross-modal percepts (e.g., sounds trigger colours, words trigger tastes). Synaesthesia may be an exaggeration of normal cross-modal processing, and if so, there may be a link between synaesthesia and the type of cross-modality inherent in sound symbolism. To test this we predicted that synaesthetes would have superior understanding of unfamiliar (sound symbolic) foreign words. In our study, 19 grapheme-colour synaesthetes and 57 non-synaesthete controls were presented with 400 adjectives from 10 unfamiliar languages and were asked to guess the meaning of each word in a two-alternative forced-choice task. Both groups showed superior understanding compared to chance levels, but synaesthetes significantly outperformed controls. This heightened ability suggests that sound symbolism may rely on the types of cross-modal integration that drive synaesthetes' unusual experiences. It also suggests that synaesthesia endows or co-occurs with heightened multi-modal skills, and that this can arise in domains unrelated to the specific form of synaesthesia.


Case studies in advanced monitoring: OptiVol.
Two cases of congestive heart failure with decompensation are presented. The OptiVol fluid index (Medtronic, Inc., Minneapolis, MN) provides an objective gauge of fluid status that can be difficult to obtain with routine clinical history or even with physical examination. The Cardiac Compass Report (Medtronic, Inc.) can identify a patient's ability to achieve euvolemia and the need for pharmacologic and nonpharmacologic interventions. Future studies will help define diagnostic and management algorithms using the OptiVol index, as well as in combination with other parameters in the Cardiac Compass Report, to facilitate proactive monitoring of patients with congestive heart failure.


Caffeine, CYP1A2 Genotype and Exercise Performance: A Systematic Review and Meta-analysis.
To summarise and meta-analyse existing evidence regarding the influence of CYP1A2 genotypes on the acute effects of caffeine for exercise performance, and to investigate the interaction between genotype, dosage, and timing of caffeine supplementation. Six databases were searched for studies determining the effect of caffeine (except mouth rinsing) on exercise performance between CYP1A2 genotypes. Three-level meta-analyses were performed using standardized mean differences (SMD; Hedge's g) to determine the effect of caffeine on exercise outcomes within and between CYP1A2 genotypes (AA, AC, CC). Meta-regressions were performed for dose, timing, and for the presence of reported conflict of interests (RCOI). A meta-analysis was also performed with baseline values to assess for imbalances between genotypes. Thirteen studies, totalling 119 outcomes and 440 participants were included (233 AA, 175 AC, 34 CC). Caffeine improved performance for AAs (SMD = 0.30, 95%CI: 0.21; 0.39, p < .0001) and ACs (SMD = 0.16, 95%CI: 0.06; 0.25, p = 0.022), but reduced for CCs (SMD = -0.22, 95%CI: -0.44; -0.01, p < .0001). Dose affected only CCs, with greater doses generating more positive SMDs (CC*dose estimate: +0.19/1 mg/kg BM, 95%CI: 0.04; 0.33, p = 0.01). Timing influenced only CCs, with better performance with later onset of exercise after supplementation (CC*timing estimate: +0.01 /minute, 95%CI: 0.00; 0.02, p = 0.02). RCOI only affected SMDs of CCs (CC*RCOI estimate: -0.57, 95%CI: -1.02; -0.12, p = 0.01). After excluding studies with RCOI, no influence of genotype was seen (all p ≥ 0.19). Small, non-significant differences were seen in placebo between genotypes (SMDs AAs vs. CCs: -0.13; AAs vs. ACs: -0.12; ACs vs. CCs: -0.05; all p ≥ 0.26). Caffeine improved performance for AAs and ACs, but worsened performance for CCs. Dose and timing moderated the efficacy of caffeine for CCs only. Caution is advised since baseline differences and studies with RCOI could have influenced these results.


In Yarrowia lipolytica mitochondria, the alternative NADH dehydrogenase interacts specifically with the cytochrome complexes of the classic respiratory pathway.
In Yarrowia lipolytica, mitochondria contain a branched respiratory chain constituted by the classic complexes I, II, III and IV, plus an alternative external NADH dehydrogenase (NDH2e) and an alternative oxidase (AOX). The alternative enzymes are peripheral, single-subunit oxido-reductases that do not pump protons. Thus, the oxidation of NADH via NDH2e-ubiquinone-AOX would not contribute to the proton-motive force. The futile oxidation of NADH may be prevented if either NDH2e or AOX bind to the classic complexes, channelling electrons. By oxymetry, it was observed that the electrons from complex I reached both cytochrome oxidase and AOX. In contrast, NDH2e-derived electrons were specifically channelled/directed to the cytochrome complexes. In addition, the presence of respiratory supercomplexes plus the interaction of NDH2e with these complexes was evaluated using blue native PAGE, clear native PAGE, in-gel activities, immunoblotting, mass spectrometry, and N-terminal sequencing. NDH2e (but not the redirected matrix NDH2i from a mutant strain, Deltanubm) was detected in association with the cytochromic pathway; this interaction seems to be strong, as it was not disrupted by laurylmaltoside. The association of NDH2e to complex IV was also suggested when both enzymes coeluted from an ion exchange chromatography column. In Y. lipolytica mitochondria the cytochrome complexes probably associate into supercomplexes; those were assigned as follows: I-III(2), I-IV, I-III(2)-IV(4), III(2)-IV, III(2)-IV(2), IV(2) and V(2). The molecular masses of all the complexes and putative supercomplexes detected in Y. lipolytica were estimated by comparison with the bovine mitochondrial complexes. To our knowledge, this is the first evidence of supercomplex formation in Y. lipolytica mitochondria and also, the first description of a specific association between an alternative NADH dehydrogenase and the classic cytochrome pathway.


The Trophic Life Cycle Stage of the Opportunistic Fungal Pathogen Pneumocystis murina Hinders the Ability of Dendritic Cells To Stimulate CD4+ T Cell Responses.
The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists of a trophic stage and an ascus-like cystic stage. Infection with the cyst stage induces proinflammatory immune responses, while trophic forms suppress the cytokine response to multiple pathogen-associated molecular patterns (PAMPs), including β-glucan. A targeted gene expression assay was used to evaluate the dendritic cell response following stimulation with trophic forms alone, with a normal mixture of trophic forms and cysts, or with β-glucan. We demonstrate that stimulation with trophic forms downregulated the expression of multiple genes normally associated with the response to infection, including genes encoding transcription factors. Trophic forms also suppressed the expression of genes related to antigen processing and presentation, including the gene encoding the major histocompatibility complex (MHC) class II transactivator, CIITA. Stimulation of dendritic cells with trophic forms, but not a mixture of trophic forms and cysts, reduced the expression of MHC class II and the costimulatory molecule CD40 on the surface of the cells. These defects in the expression of MHC class II and costimulatory molecules corresponded with a reduced capacity for trophic form-loaded dendritic cells to stimulate CD4+ T cell proliferation and polarization. These data are consistent with the delayed innate and adaptive responses previously observed in immunocompetent mice inoculated with trophic forms compared to responses in mice inoculated with a mixture of trophic forms and cysts. We propose that trophic forms broadly inhibit the ability of dendritic cells to fulfill their role as antigen-presenting cells.


An introduction of CO₂ conversion by dry reforming with methane and new route of low-temperature methanol synthesis.
Carbon dioxide is one of the highest contributors to the greenhouse effect, as well as a cheap and nontoxic building block for single carbon source chemistry. As such, CO₂ conversion is one of most important research areas in energy and environment sciences, as well as in catalysis technology. For chemical conversion of CO₂, natural gas (mainly CH₄) is a promising counterpart molecule to the CO₂-related reaction, due to its high availability and low price. More importantly, being able to convert CH₄ to useful fuels and molecules is advantageous, because it is also a kind of "greenhouse effect" gas, and can be an energy alternative to petroleum oil. In this Account, we discuss our development of efficient catalysts with precisely designed nanostructure for CO₂ reforming of CH₄ to produce syngas (mixture of CO and H₂), which can then be converted to many chemicals and energy products. This new production flow can establish a GTL (gas-to-liquid) industry, being currently pushed by the shale gas revolution. From the viewpoint of GTL industry, developing a catalyst for CO₂ reforming of CH₄ is a challenge, because they need a very high production rate to make the huge GTL methane reformer as small as possible. In addition, since both CO₂ and CH₄ give off carbon deposits that deactivate non-precious metallic catalysts very quickly, the total design of catalyst support and supported metallic nanoparticles is necessary. We present a simple but useful method to prepare bimodal catalyst support, where small pores are formed inside large ones during the self-organization of nanoparticles from solution. Large pores enhance the mass transfer rate, while small pores provide large surface areas to disperse active metallic nanoparticles. More importantly, building materials for small pores can also be used as promoters or cocatalysts to further enhance the total activity and stability. Produced syngas from methane reforming is generally catalytically converted in situ via one of two main routes. The first is to use Fischer-Tropsch synthesis (FTS), a process that catalytically converts syngas to hydrocarbons of varying molecular weights. The second is methanol synthesis. The latter has better atomic economy, since the oxygen atom in CO is included in the product and CO₂ can be blended into syngas as a reactant. However, production of methanol is very inefficient in this reaction: only 10-15% one-pass conversion typically at 5.0-10.0 MPa and 523-573 K, due to the severe thermodynamic limitations of this exothermal reaction (CO + 2H₂ = CH₃OH). In this Account, we propose and develop a new route of low-temperature methanol synthesis from CO₂-containing syngas only by adding alcohols, including methanol itself. These alcohols act as homogeneous cocatalysts and the solvent, realizing 70-100% one-pass conversion at only 5.0 MPa and 443 K. The key step is the reaction of the adsorbed formate species with alcohols to yield ester species at low temperatures, followed by the hydrogenation of ester by hydrogen atoms on metallic Cu. This changes the normal reaction path of conventional, high-temperature methanol synthesis from formate via methoxy to methanol.


Synthesis and in vivo antihyperglycemic activity of 5-(1H-pyrazol-3-yl)methyl-1H-tetrazoles.
A series of 5-[(5-aryl-1H-pyrazol-3-yl)methyl]-1H-tetrazoles 3a-h have been synthesized and evaluated for their in vivo antihyperglycemic activity. Some of the synthesized compounds have shown significant glucose lowering activity in male Sprague-Dawley rats in sucrose loaded model. These compounds were also evaluated for their peroxisome proliferator activated receptor gamma agonistic property, but none of them displayed any significant activity.


Expression of FOXC2, PinX1, Ki-67 and Cyclin D1 in cutaneous cell carcinoma.
We investigated the expression of FOXC2, PinX1, Ki-67 and Cyclin D1 in cutaneous cell carcinoma. We collected 30 cutaneous squamous cell carcinoma (SCC), 30 cutaneous basal cell carcinoma (BCC) and 30 normal skin tissues. The protein expression and gene expression of FOXC2, endogenous telomerase-inhibiting gene PinX1, Ki-67 and Cyclin D1 was measured by immunohistochemistry (IHC) and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. In SCC and BCC tissues, the positive rate of protein expression and mRNA level of PinX1 were both significantly lower than those in normal tissues. However, the positive rate of protein expression and mRNA level of FOXC2, Ki-67 and Cyclin D1 were significantly higher than those in normal tissues (p<0.05). There was no significant difference between SCC and BCC (p>0.05). In conclusion, FOXC2 may participate in the carcinogenesis process of SCC and BCC. It may also correlate with the expression PinX, Ki-67 and Cyclin D1. However, FOXC2 alone cannot be used as a diagnostic indicator of SCC.


Responders to antihypertensive treatment: how may they be identified?
The identification of responders to antihypertensive treatment is valuable as an aid to management, in determining the characteristics of a responder and as a measure of treatment efficacy. This paper discusses the various methods of identifying a responder and the factors influencing response, including the placebo factor and regression to the mean. Response is also discussed in terms of fall in systolic and diastolic pressure. Antihypertensive drugs that have a greater effect on systolic pressure rather than on diastolic pressure are identified, for example methyldopa; and drugs with more equal effects on systolic and diastolic pressure, such as verapamil, are also identified. If it is proven that isolated systolic hypertension requires active treatment it is important to identify those drugs with a greater effect on systolic pressure.


The effect of the pellet binder "Lignosol FG" on the chicken's disgestive system and general performance.
The use of the pellet binder "Lingnosol FG" in broiler diets at three levels plus a control group revealed differences in the consistency, quantity and color of the caecal contents between the treated and untreated groups. By week 4, post-mortem examinations revealed that birds receiving Lignosol FG had enlarged caeca and the caecal contents were dark brown, shiny, tenacious and gelatinous which continued to slaughter age (7 weeks). The use of the pellet binder had little effect on general performance although there was an indication that it had the effect of increasing feed consumption and body weights but with a slight increase in feed conversion (feed/gain).


Associations between women's empowerment, care seeking, and quality of malaria care for children: A cross-sectional analysis of demographic and health surveys in 16 sub-Saharan African countries.
Fever and malaria are highly prevalent among children under five across sub-Saharan Africa, but utilization and quality of care for febrile illness remain insufficient. Many studies examine socioeconomic and demographic determinants of care seeking; however, few assess how women's empowerment influences care seeking and quality. We examine associations of women's empowerment with: a) care utilization for children with fever and malaria and b) the quality of that care in 16 sub-Saharan African countries. This cross-sectional study used data from Demographic and Health Surveys conducted between 2010 and 2018. We constructed indices for economic, educational, sociocultural, and health-related empowerment and calculated the proportion of children with fever and malaria who sought care and received a range of recommended clinical actions. We used multivariable Poisson hurdle models to assess associations between empowerment, utilization, and number of components of quality care, controlling for socioeconomic and demographic factors. Our sample consisted of 25 871 febrile children, 4731 of whom had malaria diagnosed by rapid diagnostic test. Empowerment among mothers of children with fever was 0.50 (interquartile range, 0.38-0.63). In both the fever and malaria groups, over 30% of children were not taken for care. Among care seekers, febrile children received on average 0.47 (SD = 0.37) of components of quality care, and children with malaria received 0.38 (SD = 0.34). Multidimensional women's empowerment was significantly associated with care seeking and quality among febrile children, and with quality among children with malaria. Associations persisted after adjustment for socioeconomic and demographic characteristics. Results demonstrate substantial gaps in women's empowerment and poor utilization and quality of care for fever and malaria among children. Increased women's empowerment is associated with seeking care and, separately, obtaining high-quality care. To improve health outcomes, consideration of how empowering women can promote care seeking and extract quality from the health system is warranted.


Tumor-lymphatic interactions in an activated stromal microenvironment.
Metastasis to lymph nodes is a common feature of many human tumors and may facilitate dissemination to other parts of the body. Peritumoral lymphatics, which are located at the periphery of a primary tumor, appear to be anything but peripheral for metastasis, as recent studies have highlighted their critical role in disseminating tumor cells to local lymph nodes. The metastatic process, including lymphangiogenesis, is likely governed by a complex series of interactions among tumor cells, endothelial cells, and non-endothelial stromal components. Therefore, a detailed understanding of the biology of the tumor microenvironment, particularly as it pertains to peritumoral lymphatics near the tumor-stromal junction, may someday translate into clinical approaches that target metastasis at the invasive front.


Rehabilitation using single stage implants.
Implant related prosthesis has become an integral part of rehabilitation of edentulous areas. Single stage implant placement has become popular because of its ease of use and fairly predictable results. In this paper, we present a series of cases of single stage implants being used to rehabilitate different clinical situations. All the implants placed have been successfully restored and followed up for up to one year.


Determination of (pseudo)plastic flow properties of pharmaceutical semisolids using rheological AUC parameters.
The purpose of this study was to develop a simple and unique method of data reduction for pharmaceutical semisolids. Application and accuracy of different regression models for rate-controlled rotating cylinder and T-shaped spindle data was compared in a conventional analysis of variance. Methods employed to determine area under the flow curve (AUC) parameters included integration of fitting function, planimetration, and calculation of trapezoids. Complex rheological behavior such as structure breakdown at low rates of shear (D) and deflocculation of particle aggregates at high values for D is not sufficiently described by conventional fitting functions. Iterating the nonlinear power law function tau = tau 0 + k2. Dn0, however, gives the best fit of data for pharmaceutical samples, estimating a yield value, tau 0.1 calculated for D = 0.1 s-1 following double logarithmic transformation. Alternatively, rheological AUC parameters are determined for D: 0 < or = D < or = 98 s-1. Validating models, maximum deviation for different methods of determination is smaller than Srel of 5 consecutive planimetration experiments. In case of sufficient fit of experimental data, integration of a nonlinear power law function is acceptable. Convenient fitting parameters tau and n0 can be substituted by area parameters such as AT, Arel, or R for all liquids, and hydrophilic and lipophilic gels, as well as o/w and w/o emulsions being investigated. The new AUC method offers robust data reduction and universal pharmaceutical application for different Newtonian and (pseudo)plastic materials. The approach is, however, limited to instrumental conditions and the range of D.


Metoprolol-Associated Central Nervous System Complications.
Metoprolol is a common medication used by the elderly because it is affordable and has proven to decrease mortality in cardiovascular disease. Multiple studies have reported central nervous system (CNS) side effects associated with use of beta-blockers. The risk of beta-blocker CNS side effects is directly associated with the lipophilic property of the drug. We present the case of an 84-year-old male presented to the clinic complaining of increased confusion, fatigue, lightheadedness, nightmares, sleep disturbance, and gait problems for four weeks. The patient was evaluated for neurogenic and cardiogenic causes of his symptoms and both were ruled out. We believe that further review of his medical chart and medication reconciliation will lead us to the underlying cause of his symptoms. Despite being an effective treatment option, there are risks associated with beta-blocker therapy. The most common symptoms are psychiatric conditions, bizarre and vivid dreams, sleep disturbances, delirium, psychosis, and visual hallucinations. Elderly patients who are started on beta-blockers require close monitoring for any adverse neurological symptoms.


Portable laser spectrometer for airborne and ground-based remote sensing of geological CO2 emissions.
A 24 kg, suitcase sized, CW laser remote sensing spectrometer (LARSS) with a ~2 km range has been developed. It has demonstrated its flexibility in measuring both atmospheric CO2 from an airborne platform and terrestrial emission of CO2 from a remote mud volcano, Bledug Kuwu, Indonesia, from a ground-based sight. This system scans the CO2 absorption line with 20 discrete wavelengths, as opposed to the typical two-wavelength online offline instrument. This multi-wavelength approach offers an effective quality control, bias control, and confidence estimate of measured CO2 concentrations via spectral fitting. The simplicity, ruggedness, and flexibility in the design allow for easy transportation and use on different platforms with a quick setup in some of the most challenging climatic conditions. While more refinement is needed, the results represent a stepping stone towards widespread use of active one-sided gas remote sensing in the earth sciences.


Hypertension in children.
Hypertension is a common finding in children, and increases the risk for future cardiovascular events. This review focuses on recent advances in pediatric hypertension research including changes in hypertension guidelines, epidemiology, predictors of hypertension, blood pressure (BP) measurement, effects on target organs, and treatment of hypertension. Changes in the 2017 hypertension guidelines by the American Academy of Pediatrics (AAP) have resulted in increased prevalence of elevated BP and hypertension in the United States, and there is no international consensus on these changes. Despite rising pediatric overweight and obesity in China, hypertension prevalence is stable, suggesting multifactorial effects on childhood BP. Maternal diabetes and exposure to particulate matter are associated with higher childhood BP, and body size in infancy and early childhood is a determinant of adult high BP. Children with elevated BP have evidence of target organ damage with altered retinal vasculature and pulse wave velocity parameters compared to normotensive patients. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be the best antihypertensive medications for the pediatric population even for African-American patients. Research continues to illuminate contributors to pediatric hypertension and demonstrates opportunities for further study on the effects of hypertension and its management in children.


Exploring the Protein Sequence Space with Global Generative Models.
Recent advancements in specialized large-scale architectures for training images and language have profoundly impacted the field of computer vision and natural language processing (NLP). Language models, such as the recent ChatGPT and GPT-4, have demonstrated exceptional capabilities in processing, translating, and generating human language. These breakthroughs have also been reflected in protein research, leading to the rapid development of numerous new methods in a short time, with unprecedented performance. Several of these models have been developed with the goal of generating sequences in novel regions of the protein space. In this work, we provide an overview of the use of protein generative models, reviewing (1) language models for the design of novel artificial proteins, (2) works that use non-transformer architectures, and (3) applications in directed evolution approaches.


Kinetic behavior of light emission in cholesteric liquid crystal lasers: An experimental study.
Some dynamical aspects of fluorescence and lasing have been studied in a dye-doped cholesteric liquid crystal by measuring the response of the material to nanosecond optical pumping. It has been found that as the pumping energy is increased the fluorescence pulse duration decreases, reaching a minimum at the lasing threshold. Above the threshold the temporal profiles are irregular and consist of a set of narrow pulses whose measured duration is limited by the detector risetime (1 ns). The results are interpreted in terms of a recently proposed model [JETP, 118, 822 (2014)] that makes use of rate equations to account for the laser generation in cholesteric liquid crystals. The prediction of such equations for an experimental configuration appropriate for fluorescence lifetime measurements is analyzed.


Dermoscopy of naevi in patients with oculocutaneous albinism.
Oculocutaneous albinism (OCA) increases predisposition to skin malignancies. Nevertheless, the differential diagnosis between melanoma and naevi in patients with OCA is still challenging, because pigmentary lesions have rarely been described in this population. We aimed to describe the dermoscopic patterns of naevi in patients with OCA. We prospectively evaluated 83 naevi from 37 patients with OCA in a single centre in Brazil. Lesions were analysed by eye and by dermoscopy and were grouped by dermoscopic pattern. Eight main patterns were identified: homogeneous structureless pattern (n = 28; 33.7%), globular pattern (n = 27; 32.5%), reticular pattern (n = 8; 9.6%), peripheral reticular pattern with central hypopigmentation (n = 8; 9.6%), peripheral globules (n = 8; 9.6%), irregular brown globules with pink background (n = 2; 2.4%), reticular globular disorganized pattern (n = 1; 1.2%) and peripheral reticular globular with central hypopigmentation (n = 1; 1.2%). We found previously undescribed dermoscopic patterns in patients with OCA, in addition to confirming previously described patterns. These descriptions may help the understanding of pigmented naevi in patients with OCA.


Characterizing phosphoproteins and phosphoproteomes using mass spectrometry.
The reversible phosphorylation of proteins plays a major role in many vital cellular processes by modulating protein function and transmitting signals within cellular pathways and networks. Because phosphorylation is dynamic and the sites of modification cannot be predicted by an organism's genome, proteomic measurements are required to identify sites of and changes in the phosphorylation state of proteins. The low stoichiometry of phosphorylation sites that accompany the multifarious nature of protein phosphorylation in biological systems continues to challenge the dynamic range of present mass spectrometry (MS) technologies and proteomic measurements, despite the preponderance of research and analytical methods devoted to this area. This review addresses some of the strategies and limitations involving the use of MS to map and quantify changes in protein phosphorylation sites for samples that range from a single protein to an entire proteome, and presents several compelling reasons as to why comprehensive phosphorylation site analysis has proven to be so elusive without a hypothesis-driven experimental approach to elicit more meaningful and confident results.


Image Risk Assessment of the Thyroid Cancer Model Based on Discriminant Analysis and the Value of TAP and CEA Combined Detection.
The incidence rate of thyroid disease is increasing rapidly worldwide, and the number of thyroid patients is increasing. In this study, serum TAP (tumor abnormal protein) and CEA (carcinoembryonic antigen) were used to detect patients with thyroid nodules of class IV and above to explore the value of serum TAP combined detection of CEA in the risk assessment of thyroid cancer. In this paper, 400 patients with thyroid nodules above class IV diagnosed by physical examination in our hospital health management center from January 2019 to June 2021 were included in the study. Combined with the pathological test results, the patients were divided into risk groups. At the same time, different groups of serum TAP and CEA levels were detected by aggregation and electrochemiluminescence methods, and serum TAP and CEA levels were analyzed according to the pathological diagnostic indicators of CEA levels. The results showed that the levels of serum TAP and CEA in patients with thyroid cancer were significantly higher than those in patients with benign thyroid diseases, and the difference was statistically significant (P < 0.05). The sensitivity, specificity, and AUC under the ROC curve area of serum TAP were 85.25%, 85.06%, and 0.605, respectively. The sensitivity, specificity, and AUC under the ROC curve area of serum CEA were 89.85%, 88.00%, and 0.627, respectively. The sensitivity, specificity, and AUC under the ROC curve area of serum TAP combined with CEA were 96.84%, 96.79%, and 0.915, respectively. Therefore, the combined detection of serum TAP and CEA has a high early screening value in thyroid cancer.


Markers of Low-Iron Status Are Associated with Female Athlete Triad Risk Factors.
The Female Athlete Triad (Triad) is common in female athletes. The Triad is caused by low-energy availability (EA), which is often difficult to measure and has been postulated to be associated with low-iron status. Here, we explore whether markers of low-iron status may be associated with indicators of low EA including Triad risk factors. A total of 239 female National Collegiate Athletic Association Division I athletes completed preparticipation examinations that included Triad risk factors, medication/supplement use, diagnosis of anemia, and elected to complete dual-energy x-ray absorptiometry scan to measure bone mineral density. The association of markers of low iron (defined as self-report of iron supplementation and/or history of anemia) with each component of the Triad risk assessment score was assessed by stratifying low-iron status across different levels of Triad risk category. Differences across iron status groups were assessed using Fisher exact testing. Every component of the Triad risk assessment score excluding delayed menarche was associated with low-iron status. The proportion of women who reported low iron was 11.5% in the low-risk EA group compared with 50% in the moderate-risk and 66.7% in the high-risk EA groups (P = 0.02); respectively. These numbers were 11.6%, 25.0%, and 66.7% (P = 0.02) for body mass index; 9.7%, 16.7%, and 25.0% (P < 0.05) for oligomenorrhea; 10.3%, 45.5%, and 50.0% (P < 0.01) for bone mineral density; and 10.4%, 20.8%, and 30.8% (P = 0.03) for history of stress reaction or fracture. Lean/endurance athletes were more likely to have low-iron status than other athletes (15.5% vs 3.4%, P = 0.02). Markers for low-iron status were associated with Triad risk factors. Our study suggests that female athletes with a history of anemia or iron supplementation may require further screening for low EA.


[Prognosis of supratentorial parenchymal hemorrhages].
The prognostic value of a group of parameters recorded upon hospital admission was assessed in a series of 135 supratentorial hemorrhages. The patients were divided into 3 groups based on survival < 30 days, between 30 days and 1 year, or > 1 year. Patients in the group with the shortest survival period were older; had more Glasgow scale scores < or = 10 and more Canadian scale scores < or = 5; had more hematomas > or = 4 cm in diameter revealed in computerized tomography with frequent midline shift and frequent ventricular hemorrhagic invasion; had higher stress reaction (hyperglycemia, leukocytosis and heart arrhythmia). Cholesterinemia, however, was lower in the shortest survival group. A range of quality of life was observed in the group (44%) with survival longer than 1 year. The subgroup with motor independence (Rankin < 3) (19%) differed from those with less motor independence (Rankin > or = 3) in that they were younger, more often had mean scores > or = 5 on the Canadian scale and normal blood pressure levels. We conclude that prognostic value of the clinical evaluation scales used, along with age and size of hematoma, was good.


Achievement of hemodialysis discontinuation with lenalidomide and dexamethasone therapy in a refractory BJP-type multiple myeloma patient.
A 63-year-old man with Bence Jones-κ multiple myeloma (MM) presented with renal impairment. First, we administered a bortezomib-containing regimen which is considered to be the first choice among therapeutic approaches for MM patients with renal failure. However, his condition was refractory to bortezomib, and the renal dysfunction worsened (creatinine 12.55mg/dl) necessitating the initiation of hemodialysis. Subsequently, we administered an adjusted dose of lenalidomide and dexamethasone. Dialysis could be discontinued after 3 cycles of lenalidomide therapy. After 4 cycles, he achieved a stringent complete response (sCR) with the creatinine level at 1.85mg/dl. This case suggests lenalidomide to be an effective drug for patients with multiple myeloma and renal impairment refractory to treatment with bortezomib.


Differences and over-time changes in levels of prescription opioid analgesic dispensing from retail pharmacies in Canada, 2005-2010.
To examine qualitative and quantitative levels and trends of prescription opioid analgesics ("opioids") use and the potential impact of prescription monitoring programs (PMPs), in the 10 Canadian provinces, for 2005-2010. Opioid dispensing data from a representative sample of 2700 retail pharmacies were obtained. Individual opioid dispensing values were translated into defined daily doses per day/1000 population and categorized into "weak opioids" and "strong opioids" by standardized methods. Opioid prescription rates between provinces and over time, as well as the impact of PMPs, were examined using regression analyses techniques (i.e., Poisson, ANOVAs). Significant differences between provinces in the overall standardized rates of dispensing for total opioids, as well as for "weak opioids" and "strong opioids" categories, were found. The majority of provinces featured increases or curvilinear trends in the standardized amounts of opioids dispensed over time, mainly driven by increases in "strong opioids" use. In addition, significant inter-provincial differences in the levels of dispensing of individual opioids were found. Comparisons of changes in opioid dispensing between provinces with and without PMPs did not indicate significant differences. Opioid use featured significant quantitative and qualitative differences between provinces in Canada and showed an overall increasing trend mainly driven by changes in "strong opioids" in the study period. Reasons for the observed differences are not clear yet require systematic examination to allow evidence-based interventions in the interest of equitable pain treatment as well as the reduction of high levels of opioid-related morbidity and mortality in Canada.


Advances in chronic obstructive pulmonary disease.
COPD is one of the commonest causes of morbidity and mortality in the world and is increasing in prevalence. Current therapies are not very effective and no current treatment prevents the relentless progression of airflow limitation that characterizes this disease. Smoking cessation is the only strategy that reduces this decline in lung function and, although bupropion is the most effective aid to quitting, more effective treatments of nicotine addition are needed. The mainstay of treatment is bronchodilators for symptom relief and inhaled anticholinergics and beta2-agonists are useful by reducing hyperinflation of the lungs. A new once daily inhaled anticholinergic is the most effective bronchodilator, but long-acting inhaled beta2-agonsts are also useful. Theophylline is used as an additional bronchodilator in more severe patients and may have some anti-inflammatory action. By contrast, inhaled corticosteroids are poorly effective and do not reduce disease profession, although recent studies with combination inhalers (corticosteroid + long-acting beta2-agonist) have shown better effects. Long-term oxygen therapy is needed by patients with pulmonary hypertension and right heart failure. There is a pressing need to develop new classes of therapy, and several new drugs are currently in development, including inteleukin-8 antagonists, phosphodiesterase-4 inhibitors, protease inhibitors and antioxidants.


Vibration monitoring based on flexible multi-walled carbon nanotube/polydimethylsiloxane film sensor and the application on motion signal acquisition.
Flexible sensors at small scales have potential applications in many fields. Until now, the research on high-performance vibration sensors based on soft materials with high sensitivity and precision, fast response and high stability are still in its infancy. In this work, a flexible, wearable and high precision film sensor based on multi-walled carbon nanotube (MWCNT) was prepared via a vacuum filtration process and then encapsulated within polydimethylsiloxane (PDMS). The sensor exhibits an ultrahigh sensitivity with gauge factor of 214.3 at flexural strain of 0.4%. When used to monitor the vibration responses of a carbon-fiber beam induced by the base excitation and impact hammer, the time and frequency responses were comparable with the results obtained by the accelerometer, with difference less than 1\!%. In addition, when the MWCNT/PDMS thin film was employed as an electronic skin sensor attached on the human body to detect human activities, the high sensitivity and repeatability demonstrate a great potential application in monitoring human motion.


Direct and Selective 3-Amidation of Indoles Using Electrophilic N-[(Benzenesulfonyl)oxy]amides.
Selective C-H amidation of 1H-indoles at the C3 position is reported as a direct entry to biologically important 3-aminoindoles. This transformation is achieved using novel N-[(benzenesulfonyl)oxy]amides as electrophilic nitrogen agents in the presence of ZnCl2. Interestingly, analogous reactions in the absence of ZnCl2 resulted in the formation of indole aminal products.


Adult-onset Alexander disease with typical "tadpole" brainstem atrophy and unusual bilateral basal ganglia involvement: a case report and review of the literature.
Alexander disease (ALX) is a rare neurological disorder characterized by white matter degeneration and cytoplasmic inclusions in astrocytes called Rosenthal fibers, labeled by antibodies against glial fibrillary acidic protein (GFAP). Three subtypes are distinguished according to age at onset: infantile (under age 2), juvenile (age 2 to 12) and adult (over age 12). Following the identification of heterozygous mutations in GFAP that cause this disease, cases of adult-onset ALX have been increasingly reported. We present a 60-year-old Japanese man with an unremarkable past and no family history of ALX. After head trauma in a traffic accident at the age of 46, his character changed, and dementia and dysarthria developed, but he remained independent. Spastic paresis and dysphagia were observed at age 57 and 59, respectively, and worsened progressively. Neurological examination at the age of 60 revealed dementia, pseudobulbar palsy, left-side predominant spastic tetraparesis, axial rigidity, bradykinesia and gaze-evoked nystagmus. Brain MRI showed tadpole-like atrophy of the brainstem, caused by marked atrophy of the medulla oblongata, cervical spinal cord and midbrain tegmentum, with an intact pontine base. Analysis of the GFAP gene revealed a heterozygous missense mutation, c.827G>T, p.R276L, which was already shown to be pathogenic in a case of pathologically proven hereditary adult-onset ALX. The typical tadpole-like appearance of the brainstem is strongly suggestive of adult-onset ALX, and should lead to a genetic investigation of the GFAP gene. The unusual feature of this patient is the symmetrical involvement of the basal ganglia, which is rarely observed in the adult form of the disease. More patients must be examined to confirm, clinically and neuroradiologically, extrapyramidal involvement of the basal ganglia in adult-onset ALX.


Influence of follicular health on the steroidogenic and morphological characteristics of bovine granulosa cells in vitro.
In 24-h cultures, steroid production by cells from non-atretic follicles increased with increasing follicular diameter. Cells from atretic follicles, of all sizes, produced low amounts of oestradiol-17 beta, but very high amounts of progesterone, relative to cells from non-atretic follicles. Increasing the culture period to 72 h caused little change in daily progesterone and oestradiol-17 beta production by granulosa cells from atretic follicles. In contrast, in cells from non-atretic follicles, daily progesterone production increased and daily oestradiol-17 beta production decreased to the levels observed with cells from atretic follicles. Dibutyryl cyclic AMP (1.0 mM) significantly stimulated progesterone production by cells from atretic, but not from non-atretic, follicles. Testosterone (1 microgram/ml) had no effect on progesterone production by cells from atretic follicles, while oestradiol-17 beta, oestrone, testosterone, androstenedione and 5 alpha-dihydro-testosterone (0-1000 ng/ml) each significantly suppressed progesterone production by cells from non-atretic follicles in a dose-dependent manner. Morphometric analysis revealed few subcellular differences between cells from non-atretic and atretic follicles. Mean cell volume was significantly higher for cells from atretic compared to non-atretic follicles, but the mean volumes of the major subcellular components were not influenced by follicle health. The mean surface area of the plasma and nuclear membrane, and granular endoplasmic reticulum was also significantly higher in cells from atretic compared to non-atretic follicles.


Lifestyle Related Cancer Risk and Protective Behaviors Vary among a Convenient Sample of Physically Active, Young-to-Middle-Aged Adults 18-49.
It is an assumption that physically active adults lead an overall healthy lifestyle. To examine this assumption, we administered a cross-sectional, web-based survey to a sample of young-to-middle-aged US adults between 18 and 49 who self-reported participation in at least one recreational sporting event in the past month. Logistic regressions were conducted to examine demographic characteristics associated with cancer risk and protective behaviors. Gender was represented equally (N = 938), and the average age was 32 years (SD: 8.4). Most participants reported >three days of moderate- to high-intensity physical activity (79%), but not meeting fruit and vegetable consumption guidelines (78%). Many reported current tobacco use (32%), binge drinking at least once in the past 30 days (62%), and suboptimal sun protection use (67%). Participation in lifestyle-related cancer risk and protective behaviors varied based on age, sex, education, routine doctor visits, perceived overall health, health-information-seeking behavior (how participants obtained health information), or team-based sport participation in regression models. Future interventions should be tailored to address varied cancer risk profiles among even physically active adults to encourage multiple healthy behavior changes.


Linear growth in young people with restrictive eating disorders: "Inching" toward consensus.
While the assessment of acute medical stability in patients with eating disorders should never be minimized, careful attention toward other specific age-related consequences of malnutrition can improve psychological outcomes and reduce long-term, potentially irreversible medical complications, like linear growth impairment. While the impact of malnutrition on linear growth is widely recognized, emerging data highlight consensus in several key areas: the time from onset to time of diagnosis, age at illness onset, pubertal stage at illness onset, and adequacy of weight restoration to achieve catch-up growth. This review provides concrete and actionable steps to help providers identify and explore deviations in expected growth and development while prioritizing early and aggressive weight restoration to provide the best opportunity for catch-up linear growth in patients with eating disorders. The impact of restrictive eating disorders on growth and development cannot be overstated, particularly in pre- and peripubertal patients. While many consequences of malnutrition are reversible, the loss of genetic height potential may prove irreversible without early and aggressive weight restoration.


Ureaplasma spp. in male infertility and its relationship with semen quality and seminal plasma components.
We investigated the prevalence of Ureaplasma spp. in semen samples of infertile men in Shanghai, China and evaluated the correlation between the sperm parameters (seminal volume, sperm concentration, progressive motility and non-progressive) and the secretary function in these infectious populations. Semens were collected from 540 infertile men and 260 fertile control group in shanghai, China and subjected to standard bacterial and Ureaplasma spp. culture. Positive Ureaplasma spp. isolates were further tested by PCR to detect the biovars and serotypes of Ureaplasma spp. Sperm seminological variabilities were analyzed by Computer-Assisted Semen Analysis according to the fifth edition of World Health Organization (WHO) laboratory manual for the examination and processing of human semen. Seminal markers were measured by the automatic analyzer. The prevalence of Ureaplasma spp. in semen specimens was 39.6% (214/540) and 19.2% (50/260) in infertile and control group, respectively. Significant difference was observed between the two groups (P < 0.001). Among all clinical isolates from infertile men (n = 214), 59.3% (n = 127) was Ureaplasma parvum (UPA), 26.2% (n = 56) was Ureaplasma urealyticum (UUR), and 14.5% (n = 31) was mixed species. While those numbers in control group (n = 50) were 64.0% (n = 32), 20.0% (n = 10), 16.0% (n = 8), respectively. There was no significant difference between any two groups (P > 0.05). The progressive motility and the NAG activity of infertile men infected with UPA and mixed species were significantly lower than those of UUR infected subgroup (P < 0.05). The infection of Ureaplasma spp. plays an important pathogenic role in male infertility. UPA has higher pathogenicity on the progressive motility and the secretary function of epididymis than UUR.


[Primary malignant lymphoma of the brain].
Primary malignant lymphoma of the brain is a disease of unknown etiology, which is increasing in incidence and has an unfavorable prognosis. Despite the lack of specific changes on CT or MRI in most cases, these procedures may typically facilitate the diagnosis: a focal-enhancing mass with subependymal spread on CT or MRI and hyperattenuation on nonenhanced CT are the most reliable features in the diagnosis of primary malignant lymphoma of the brain. Peritumoral edema and mass effect are usually not prominent features. On unenhanced CT scans they usually appear homogeneously isodense to mildly hyperdense relative to the gray matter. On MRI these tumors are slightly hypointense on T1-weighted images and slightly hyperintense on PD- and T2-weighted images relative to the gray matter. On CT and MRI enhancement is usually homogeneous. Contrast-enhanced MRI, with its multiplanar capability, lack of bone-induced artifacts, and high-contrast resolution, is likely to reveal subependymal spread and meningeal involvement that have escaped detection by CT. Because there are no specific features on CT or MRI in most cases, patients who are suspected of having primary malignant lymphoma of the brain should immediately undergo biopsy and, if the diagnosis is confirmed, whole-brain radiation therapy. With early diagnosis and treatment, these patients benefit from radiation therapy.


Psychological Correlates of Excessive Healthy and Orthorexic Eating: Emotion Regulation, Attachment, and Anxious-Depressive-Stress Symptomatology.
Orthorexia nervosa, the pathological obsession with eating healthy, shares risks and significant comorbidity with other mental disorders. Based on a behavioral conceptualization of the overlap, emotion regulation, attachment style, and anxious-depressive-stress symptomatology are prominent but insufficiently researched endophenotypes for orthorexia nervosa. This study aimed at identifying ways in which difficulties in emotion regulation and attachment-related anxiety and avoidance become apparent in orthorexia nervosa and healthy orthorexia. Additionally, the moderating role of anxious, depressive, and stress symptoms was explored. A convenience sample of 399 adults (266 women) completed questionnaires to measure orthorexia nervosa and healthy orthorexia, difficulties in emotion regulation, partnership-related bond, and anxious-depressive-stress symptomatology. The healthy orthorexia subscale was negatively associated with lack of emotional awareness but no other subscale of difficulties in emotion regulation or attachment-related anxiety and avoidance. Orthorexia nervosa scores were positively linked to difficulties in emotion regulation as well as attachment-related anxiety and avoidance. Multiple linear regression indicated non-acceptance of emotional responses and impulse control difficulties to be the strongest predictors for orthorexia nervosa. Both subscales also mediated the effects of attachment style on orthorexia nervosa with anxious-depressive-stress symptomatology moderating some of these effects. Individuals with higher orthorexia nervosa tendencies showed difficulties in emotion regulation, a common feature also of affective and eating disorders. Improvement in understanding the psychological features of orthorexia nervosa can enable a better differentiation from other disorders, advances in the development of treatment approaches and treatment planning, and outlines directions for future research on mechanisms.


Candida tropicalis antifungal cross-resistance is related to different azole target (Erg11p) modifications.
Candida tropicalis ranks between third and fourth among Candida species most commonly isolated from clinical specimens. Invasive candidiasis and candidemia are treated with amphotericin B or echinocandins as first-line therapy, with extended-spectrum triazoles as acceptable alternatives. Candida tropicalis is usually susceptible to all antifungal agents, although several azole drug-resistant clinical isolates are being reported. However, C. tropicalis resistant to amphotericin B is uncommon, and only a few strains have reliably demonstrated a high level of resistance to this agent. The resistance mechanisms operating in C. tropicalis strains isolated from clinical samples showing resistance to azole drugs alone or with amphotericin B cross-resistance were elucidated. Antifungal drug resistance was related to mutations of the azole target (Erg11p) with or without alterations of the ergosterol biosynthesis pathway. The antifungal drug resistance shown in vitro correlated very well with the results obtained in vivo using the model host Galleria mellonella. Using this panel of strains, the G. mellonella model system was validated as a simple, nonmammalian minihost model that can be used to study in vitro-in vivo correlation of antifungals in C. tropicalis. The development in C. tropicalis of antifungal drug resistance with different mechanisms during antifungal treatment has potential clinical impact and deserves specific prospective studies.


PML silencing inhibits cell proliferation and induces DNA damage in cultured ovarian cancer cells.
The promyelocytic leukemia (PML) gene is a tumor suppressor gene. It was first identified in acute promyelocytic leukemia, in which it is fused to retinoic acid receptor α by the (15;17) chromosomal translocation. The function of the PML protein is frequently lost or aberrant in human solid tumors. In human ovarian carcinoma tissue, PML detected by immunohistochemistry was highly expressed. A PML-silencing vector, pSRG-shPml, was constructed and used to transfect human ovarian cancer cells. Cells were cultured and selected with puromycin for 10-15 days, and then the PML mRNA expression levels were detected by RT-qPCR and immunofluorescence. Proliferation and clone number of PML-depleted cells were detected using MTT assay and colony-forming assay. The protein expression associated with DNA damage and apoptosis was assessed in PML-depleted cells using western blot analysis and immunofluorescence. The results showed that PML was highly expressed in human ovarian tissue. The proliferation and colony formation of ovarian cancer cells were significantly inhibited after PML was depleted. Western blot analysis and immunofluorescence revealed that p-H2AX and cleaved caspase-3 expression significantly increased after PML silencing. PML was located in the nucleus, and it formed foci after X-ray irradiation. PML foci increased significantly with increasing irradiation doses.


The prevalence of stress and burnout in UK emergency ambulance service workers and its impact on their mental health and well-being.
To assess the prevalence of burnout among emergency ambulance service workers in one ambulance station; to determine if there are any variances based on socio-demographic information such as gender, clinical grade and length of service; to examine the distinctions between personal, work-related and patient-related burnout; to identify current workplace interventions to reduce stress and burnout that will improve mental health and well-being. Mixed methods - the Copenhagen Burnout Inventory (CBI) was utilised, measuring burnout across three domains (personal, work-related and patient-related) alongside collecting demographic information such as gender, role, full-time or part-time employment and length of service. A free-text space was available to provide opinions on causes of burnout and on how current practice can be improved; these were analysed via thematic analysis. Seventy-eight staff members completed the questionnaire. These were: 16 emergency care assistants, 15 technicians and 47 paramedics. Thirty-eight (48.7%) staff members experienced personal burnout, 42 (53.8%) experienced work-related burnout and 29 (37.1%) experienced patient-related burnout. It was found that those most at risk of burnout were full-time male employees with more than 10 years' experience and employed within a paramedic position. Six themes were identified through thematic analysis: unnecessary callouts, shift patterns, support options, management, sickness absence and job demands. Findings suggest that burnout is prevalent within the ambulance service environment and can result in long-term sickness absences and declining mental health. This requires further investigation into causation alongside consideration of preventative measures and interventions to improve ambulance service staff well-being while increasing staff resilience to prevent burnout. Support for managers in recognising symptoms of burnout is also imperative because providing them with the training to recognise a mental health issue, interpret it and promptly treat it can mean the difference between sickness absences, future PTSD, unwell staff presenting at work and staff feeling valued and supported by management. The introduction of mandatory counselling and well-being sessions was also recommended by participants to improve staff mental health and well-being and reduce instances of work-related burnout, while providing financial advantages to the ambulance service with a reduction in additional overtime and sickness payments.


Morbidity and Mortality Conference: Its Purpose Reclaimed and Grounded in Theory.
The morbidity and mortality conference (MMC) remains a central activity within the departments of our academic healthcare institutions. It is deeply rooted in the premise that we can learn from our mistakes, thereby improving the care we provide. Recent advances in our understanding of medical error and quality improvement have challenged the value of traditional models of MMC. As a result the purpose of MMC has become clouded and ill-defined: Is it an educational conference that promotes mastery of clinical acumen, or is it a venue to drive quality improvement by addressing systems-based issues in delivering care? Or can it serve both purposes? Review of the history of MMC, the literature, and critical application of education theory demonstrates the source of the confusion and the challenges in viewing it through the exclusive lens of either education or quality improvement. Application of experiential learning theory helps resolve this discord showing how the conference facilitates the development of clinical mastery while informing quality improvement programs about important and relevant systems-based issues. Building on this, we present a model for MMC involving five essential elements: case-based involving an adverse patient event, anonymity for participants, expert guided critical analysis, reframing understanding of the case presentation and related systems-based factors, and projection to practice change. This model builds on previously described models, is grounded in the literature, and helps clarify its role from both the educational and the quality improvement perspectives.


Uncovering genomic features and maternal origin of korean native chicken by whole genome sequencing.
The Korean Native Chicken (KNC) is an important endemic biological resource in Korea. While numerous studies have been conducted exploring this breed, none have used next-generation sequencing to identify its specific genomic features. We sequenced five strains of KNC and identified 10.9 million SNVs and 1.3 million InDels. Through the analysis, we found that the highly variable region common to all 5 strains had genes like PCHD15, CISD1, PIK3C2A, and NUCB2 that might be related to the phenotypic traits of the chicken such as auditory sense, growth rate and egg traits. In addition, we assembled unaligned reads that could not be mapped to the reference genome. By assembling the unaligned reads, we were able to present genomic sequences characteristic to the KNC. Based on this, we also identified genes related to the olfactory receptors and antigen that are common to all 5 strains. Finally, through the reconstructed mitochondrial genome sequences, we performed phylogenomic analysis and elucidated the maternal origin of the artificially restored KNC. Our results revealed that the KNC has multiple maternal origins which are in agreement with Korea's history of chicken breed imports. The results presented here provide a valuable basis for future research on genomic features of KNC and further understanding of KNC's origin.


Buprenorphine Alters Inflammatory and Oxidative Stress Molecular Markers in Arthritis.
Buprenorphine is recommended for use as an analgesic in animal models including in murine models of collagen-induced arthritis (CIA). However, the effect of buprenorphine on the expression of disease-associated biomarkers is not well defined. We examined the effect of buprenorphine administration on disease progression and the expression of inflammatory and oxidative stress markers, in a murine model of CIA. Buprenorphine administration altered the expression of cytokines, IFN-γ, IL-6, and MMP-3, and oxidative markers, for example, iNOS, superoxide dismutase (SOD1), and catalase (CAT), in the CIA mice. As buprenorphine is an analgesic, we further monitored the association of expression of these biomarkers with pain scores in a human cohort of early rheumatoid arthritis (RA). Serum MMP-3 levels and blood mRNA expression of antioxidants sod1 and cat correlated with pain scores in the RA cohort. We have demonstrated that administration of buprenorphine alters the expression of inflammatory and oxidative stress-related molecular markers in a murine model of CIA. This caveat needs to be considered in animal experiments using buprenorphine as an analgesic, as it can be a confounding factor in murine studies used for prediction of response to therapy. Furthermore, the antioxidant enzymes that showed an association with pain scores in the human cohort may be explored as biomarkers for pain in future studies.


Nature-inspired functional porous materials for low-concentration biomarker detection.
Nanostructuration is a promising tool for enhancing the performance of sensors based on electrochemical transduction. Nanostructured materials allow for increasing the surface area of the electrode and improving the limit of detection (LOD). In this regard, inverse opals possess ideal features to be used as substrates for developing sensors, thanks to their homogeneous, interconnected pore structure and the possibility to functionalize their surface. However, overcoming the insulating nature of conventional silica inverse opals fabricated via sol-gel processes is a key challenge for their application as electrode materials. In this work, colloidal assembly, atomic layer deposition and selective surface functionalization are combined to design conductive inverse opals as an electrode material for novel glucose sensing platforms. An insulating inverse opal scaffold is coated with uniform layers of conducting aluminum zinc oxide and platinum, and subsequently functionalized with glucose oxidase embedded in a polypyrrole layer. The final device can sense glucose at concentrations in the nanomolar range and is not affected by the presence of common interferents gluconolactone and pyruvate. This method may also be applied to different conductive materials and enzymes to generate a new class of highly efficient biosensors.


A glucokinase-like enzyme carries out glucose phosphorylation in capillaries of normal and spontaneously hyperglycemic rabbits.
We have studied glucose phosphorylation at increasing glucose concentrations (1, 5, 10, 25, 50, and 100 mmol/liter) in capillaries of the choroidocapillary lamina from the eye of normal female albino rabbits (n = 10; body wt 1800-2000 g; mean +/- SEM morning glycemia: 147.77 +/- 4.02 mg/dl) and from the eye of spontaneously hyperglycemic rabbits (n = 5, body wt 1800-2000 g, mean +/- SEM morning glycemia; 211.00 +/- 10.76 mg/dl). In the 3000g supernatant of capillary homogenates, the glucose phosphorylating activity (NADP reduction measured as optical density change at 366 nm at pH 7.5) increased progressively with the rise of glucose concentration (r = 0.36; P < 0.05), approaching the peak at high glucose level (25 mmol/liter), with values ranging from 5.32 +/- 0.46 (SEM) nmol/min/mg protein to 7.14 +/- 0.74 (+34.21%, P < 0.01). When measured at a more alkaline pH (8.2) the glucose phosphorylation was higher than at pH 7.5 and retained the responsiveness to increasing glucose concentrations. These kinetic characteristics differ from those seen in most tissues and are somewhat reminiscent of those shown by hepatic glucokinase. Indeed, by subtracting the activity at 1 mmol/liter glucose from that at higher glucose concentrations, we calculated the "glucokinase component" which together with the "hexokinase component" form the total glucose phosphorylating activity. Glucose phosphorylation in capillaries from spontaneously hyperglycemic rabbits was lower than normal (values: 3.66 +/- 0.31 vs 5.32 +/- 0.46 of the normal rabbits; -31.20%; P < 0.05). This could contribute to the hyperglycemia by reducing glucose utilization. However, in these animals the enzyme activity retained the responsivity to increasing glucose concentrations (r = 0.41, P < 0.05). Therefore, the actual capillary glucose phosphorylation in these animals would depend upon both the enzyme level (which is reduced) and the glucose concentration (which is increased). Due to the in vivo inhibition of the hexokinase component, the glucokinase component may be predominant in vivo, making the stimulating effects of hyperglycemia much more pronounced than it would appear from our data in vitro. This may lead to glucose overutilization. These kinetic characteristics of glucose phosphorylation in capillaries might be relevant to the mechanisms leading to diabetic microangiopathy.


Theophylline and Caffeine as Alternatives During an Aminophylline Shortage.
The latest aminophylline shortage has prompted a need for alternative reversal agents for pharmacological stress testing. Cardiac stress testing is common for diagnosis and prognosis in patients with coronary heart disease. Options for pharmacological stress test agents include adenosine, regadenoson, dipyridamole, and dobutamine, whereas aminophylline is the recommended reversal agent. Adenosine and dobutamine can be used as alternatives to regadenoson and dipyridamole to decrease or eliminate the use of aminophylline. Alternatives to aminophylline include theophylline and caffeine. It is important to efficiently identify alternatives during a drug shortage to maintain optimal patient outcomes.


Asymmetric genetic attributions for one's own prosocial versus antisocial behavior.
People tend to rate prosocial or positive behavior as more strongly influenced by the actor's genes than antisocial or negative behavior. The current study tested whether people would show a similar asymmetry when rating the role of genes in their own behavior, and if so, what variables might mediate this difference. Participants were prompted to think about an example of their own behavior from the past year that was either prosocial or antisocial. Those in the prosocial condition rated the role of genetics in causing the behavior as significantly greater than did those in the antisocial condition. A mediation analysis suggested that this asymmetry could be accounted for by a tendency to view prosocial behavior as more natural and more aligned with one's true self than antisocial behavior. These findings add to a growing body of evidence suggesting that people's reasoning about genetics may be influenced by evaluative judgments.


Crystalline Neutral Aluminum Selenide/Telluride: Isoelectronic Aluminum Analogues of Carbonyls.
Neutral aluminum chalcogenides (R-Al(L)═Ch; L = ligand, Ch = chalcogen), stabilized by a Lewis base ligand, represent isoelectronic counterparts to carbonyl compounds and have long been pursued for isolation. Herein, we present the synthesis of an aluminum selenide, [N]-Al(iPr2-bimy)═Se, and an aluminum telluride, [N]-Al(iPr2-bimy)═Te, under ambient conditions ([N] = 1,8-bis(3,5-di-tert-butylphenyl)-3,6-di-tert-butylcarbazolyl; iPr2-bimy = 1,3-diisoproplylbenzimidazole-2-ylidene). These compounds arise from the oxidation reaction of [N]-Al(iPr2-bimy) with Se and (nBu)3P═Te, respectively. One notable characteristic of the Al and Ch interaction is the presence of an Al-Ch σ bond, strengthened by the electrostatic attraction between the Al+ and Ch- centers as well as the donation of lone pairs from Ch into vacant orbitals at Al. This results in an Al-Ch multiple bond with an ambiphilic nature. Preliminary investigations into their reactivity unveil their remarkable propensity for facile (cyclo)addition reactions with diverse substrates, including PhCCH, PhCN, AdN3, MeI, PhSiH3, and C6F6, leading to the formation of unprecedented main group heterocycles and alumachalcogenides.


Optoelectronic functional materials based on alkylated-π molecules: self-assembled architectures and nonassembled liquids.
The engineering of single molecules into higher-order hierarchical assemblies is a current research focus in molecular materials chemistry. Molecules containing π-conjugated units are an important class of building blocks because their self-assembly is not only of fundamental interest, but also the key to fabricating functional systems for organic electronic and photovoltaic applications. Functionalizing the π-cores with "alkyl chains" is a common strategy in the molecular design that can give the system desirable properties, such as good solubility in organic solvents for solution processing. Moreover, the alkylated-π system can regulate the self-assembly behavior by fine-tuning the intermolecular forces. The optimally assembled structures can then exhibit advanced functions. However, while some general rules have been revealed, a comprehensive understanding of the function played by the attached alkyl chains is still lacking, and current methodology is system-specific in many cases. Better clarification of this issue requires contributions from carefully designed libraries of alkylated-π molecular systems in both self-assembly and nonassembly materialization strategies. Here, based on recent efforts toward this goal, we show the power of the alkyl chains in controlling the self-assembly of soft molecular materials and their resulting optoelectronic properties. The design of alkylated-C60 is selected from our recent research achievements, as the most attractive example of such alkylated-π systems. Some other closely related systems composed of alkyl chains and π-units are also reviewed to indicate the universality of the methodology. Finally, as a contrast to the self-assembled molecular materials, nonassembled, solvent-free, novel functional liquid materials are discussed. In doing so, a new journey toward the ultimate organic "soft" materials is introduced, based on alkylated-π molecular design.


Optimized templates for bottom-up growth of high-performance integrated biomolecular detectors.
Electrochemical deposition of metals represents an important approach in the bottom-up fabrication of nanostructures and microstructures. We have used this approach to generate high-performance chip-based biosensors using silicon as a platform for the generation of sensor arrays. Here, we explore the applicability of different materials to support the electrodeposition and identify the parameters that are essential for robust sensor growth. We show that inexpensive materials can be used as templates for electrodeposition, and demonstrate that these low-cost sensors exhibit clinically-relevant levels of sensitivity and specificity. In particular, we prove herein that the glass-based sensors successfully detect E. coli in urine, when present at the 100 cfu μL(-1) levels found typically in samples of patients with urinary tract infections.


New insights link low-virulent disc infections to the etiology of severe disc degeneration and Modic changes.
Within the last 5 years, international research collaborations including those of several research groups skilled in microbiology, immunology and pathophysiology, have identified a low-virulent intradiscal infection with the ability to provoke gradual and progressive disc degeneration, end-plate disruption, Modic changes and persistent clinical lower-back pain. Certain strains of the Propionibacterium acne bacterium seem able to invade, colonize and develop a protective biofilm inside the disc. The interaction of P. acne, disc tissues and mononuclear cells of the bone marrow are shown to trigger a relevant immunological response and an ensuing destructive inflammation of the disc and adjacent vertebrae. This process presents on MRI as Modic changes. Recent proof-of-concept data provide compelling evidence for this bacterial disc infection hypothesis.


Dense and Acidic Organelle-Targeted Visualization in Living Cells: Application of Viscosity-Responsive Fluorescence Utilizing Restricted Access to Minimum Energy Conical Intersection.
Cell-imaging methods with functional fluorescent probes are an indispensable technique to evaluate physical parameters in cellular microenvironments. In particular, molecular rotors, which take advantage of the twisted intramolecular charge transfer (TICT) process, have helped evaluate microviscosity. However, the involvement of charge-separated species in the fluorescence process potentially limits the quantitative evaluation of viscosity. Herein, we developed viscosity-responsive fluorescent probes for cell imaging that are not dependent on the TICT process. We synthesized AnP2-H and AnP2-OEG, both of which contain 9,10-di(piperazinyl)anthracene, based on 9,10-bis(N,N-dialkylamino)anthracene that adopts a nonflat geometry at minimum energy conical intersection. AnP2-H and AnP2-OEG exhibited enhanced fluorescence as the viscosity increased, with sensitivities comparable to those of conventional molecular rotors. In living cell systems, AnP2-OEG showed low cytotoxicity and, reflecting its viscosity-responsive property, allowed specific visualization of dense and acidic organelles such as lysosomes, secretory granules, and melanosomes under washout-free conditions. These results provide a new direction for developing functional fluorescent probes targeting dense organelles.


Fluctuation relations between hierarchical kinetically equivalent networks with Arrhenius-type transitions and their roles in systems and structural biology.
The legality of using simple kinetic schemes to determine the stochastic properties of a complex system depends on whether the fluctuations generated from hierarchical equivalent schemes are consistent with one another. To analyze this consistency, we perform lumping processes on the stochastic differential equations and the generalized fluctuation-dissipation theorem and apply them to networks with the frequently encountered Arrhenius-type transition rates. The explicit Langevin force derived from those networks enables us to calculate the state fluctuations caused by the intrinsic and extrinsic noises on the free energy surface and deduce their relations between kinetically equivalent networks. In addition to its applicability to wide classes of network related systems, such as those in structural and systems biology, the result sheds light on the fluctuation relations for general physical variables in Keizer's canonical theory.


Effect of repeated administration of PGF2alpha in the early post partum period on the prevalence of clinical endometritis and probability of pregnancy at first insemination in lactating dairy cows.
Two experiments were performed to determine the effects of repeated administration of PGF2alpha in the immediate post partum period on the prevalence of clinical endometritis at 22 and 58 days post partum, and the probability of pregnancy at first insemination, in post partum dairy cows. In Experiment 1, 228 cows on day 7 post partum were used. Cows in Group 1 (n = 114) were treated twice with PGF2alpha (25 mg, im) 8 h apart on days 7 and 14 post partum, and only once on days 22 and 35 post partum. Cows in Group 2 (n = 114) served as untreated controls. Vaginoscopy and transrectal palpation of the genital tract were done on days 22 and 58 post partum. Cows in both groups were inseminated at estrus after a voluntary waiting period of 100 days. Pregnancy was determined by transrectal palpation between 45 and 50 days after insemination. Repeated administration of PGF2alpha in the immediate post partum period did not reduce the prevalence of clinical endometritis on days 22 or 58 post partum (65 versus 62% on day 22 and 28.3 versus 35.2% on day 58 in Groups 1 and 2, respectively). There was no significant difference in the probability of pregnancy at first insemination between cows in both groups. In Experiment 2, 418 cows on day 7 post partum were used. Cows in Group 1 (n = 209) were treated twice with PGF2alpha (25 mg, im) 8h apart on days 7 and 14 post partum, and only once on days 22 and 35 post partum. Cows in Group 2 (n = 209) served as untreated controls. Cows in both groups were subjected to the Presynch and Ovsynch protocols on days 49 and 75 post partum, respectively. Pregnancy was determined by transrectal ultrasonography between days 29 and 32 after timed insemination. There was no significant difference in the probability of pregnancy at first insemination between cows in both groups. In conclusion, repeated administration of PGF2alpha to cows in this herd had no effect on the prevalence of clinical endometritis at 22 and 58 days post partum, and that there was no effect on the probability of pregnancy after insemination at estrus among cows with a voluntary waiting period of > 100 days, or at timed AI at 85 days in milk when Presynch was employed.


Toxicity of metals to a freshwater snail, Melanoides tuberculata.
Adult freshwater snails Melanoides tuberculata (Gastropod, Thiaridae) were exposed for a four-day period in laboratory conditions to a range of copper (Cu), cadmium (Cd), zinc (Zn), lead (Pb), nickel (Ni), iron (Fe), aluminium (Al), and manganese (Mn) concentrations. Mortality was assessed and median lethal times (LT₅₀) and concentrations (LC₅₀) were calculated. LT₅₀ and LC₅₀ increased with the decrease in mean exposure concentrations and times, respectively, for all metals. The LC(50) values for the 96-hour exposures to Cu, Cd, Zn, Pb, Ni, Fe, Al, and Mn were 0.14, 1.49, 3.90, 6.82, 8.46, 8.49, 68.23, and 45.59 mg L⁻¹, respectively. Cu was the most toxic metal to M. tuberculata, followed by Cd, Zn, Pb, Ni, Fe, Mn, and Al (Cu > Cd > Zn > Pb > Ni > Fe > Mn > Al). Metals bioconcentration in M. tuberculata increases with exposure to increasing concentrations and Cu has the highest accumulation (concentration factor) in the soft tissues. A comparison of LC₅₀ values for metals for this species with those for other freshwater gastropods reveals that M. tuberculata is equally sensitive to metals.


The examination of some vinyl acetate/olefin copolymers by pyrolysis gas chromatography mass spectrometry.
A study of the thermal degradation of some vinyl acetate/olefin copolymers reveals that side chain scissions at the backbone and scissions within the side chains themselves yield fragments which are apparently characteristic of the parent olefin.


Epidemiological factors affecting outpatient department service utilization and hospitalization in patients with diabetes: A time-series analysis from an Ethiopian hospital between 2018 and 2021.
The burden of diabetes-related deaths reached two million in 2019 globally. Accessibility to health care services and adherence to follow-up and therapy are key to improving outcomes for diabetic patients. We aimed to assess outpatient department (OPD) service utilization and diabetes-related hospitalizations over a period of 44 months. A retrospective cohort study was conducted on OPD visits and hospitalizations recorded between January 1, 2018, and August 31, 2021, at the St Luke Catholic Hospital (Ethiopia). All diabetic patients were included in the analysis. A linear regression model was used for univariate analysis of OPD visits and hospitalizations and their association with potential predictors. The autoregressive integrated moving average (ARIMA) method was applied to both the time series of OPD visits and hospitalizations. Potential predictors were sociodemographic factors, COVID-19 cases, mean monthly temperature and precipitations. In the time series analysis, OPD visits increased over time (P < 0.01) while hospitalizations were stable. The time series model was ARIMA (0,1,1) for OPD visits and ARIMA (0,0,0) for hospitalizations. There were 1685 diabetes OPD patients (F = 732, 43%). Females had an average of 16% fewer OPD accesses per month (P < 0.01) and a lower number of hospitalizations per month (P = 0.03). There were 801 patients missing follow-up (48%). The time between follow-up increased with age (P < 0.01). OPD visits decreased differently by geographic area as COVID-19 cases increased (P < 0.01). There were 57 fewer forecast OPD visits per month on average using COVID-19 cases as ARIMA regressor. The odds ratio (OR) of new diagnosis at hospitalization was lower in patients with type 2 diabetes (OR = 0.26, 95% CI = 0.14-0.49, P = 0.02). Despite an increase in OPD visits for diabetic patients over the study period, the number of losses at follow-up and diagnoses at hospitalization remains high. Female sex, older age, and COVID-19 were associated with impaired OPD service accessibility. Primary health care should be implemented to achieve better health coverage and improve diabetes management.


Obstructive sleep apnea in patients on conventional and short daily hemodialysis.
Obstructive sleep apnea (OSA) is common among patients on maintenance hemodialysis. However, the factors associated with the origin of OSA as well as the cardiovascular consequences in this population are not completely understood. We evaluated, by standard overnight polysomnography, 24-hour ambulatory blood pressure (BP) monitoring and echocardiography in 30 patients (14 males, age 34 +/- 11 years, BMI 23.2 +/- 5.2) - 15 on short daily hemodialysis (SDH) and 15 matched patients on conventional hemodialysis (CHD). The hemodialysis dose (standard Kt/V) was higher in patients on SDH than on CHD (p = 0.001). OSA (apnea-hypopnea index >5 events/h) was present in 13 patients (43%). Patients with OSA were predominantly males (77 vs. 44%), presented a higher BMI (25.5 +/- 6.2 vs. 21.5 +/- 3.6), a larger neck circumference (38 +/- 1 vs. 34 +/- 1 cm) and a lower Kt/V (2.6 +/- 0.3 vs. 2.2 +/- 0.1) than patients with no OSA (p < 0.05). Neck circumference and lower Kt/V were independently associated with OSA on multivariate analysis. No patient with Kt/V >2.5 (n = 10) presented OSA. On the other hand, hypertensive patients with OSA needed more BP control pills (p = 0.03). Despite similar BP control, patients with OSA presented a higher interventricular septum thickness (11.5 +/- 0.5 vs. 9.9 +/- 0.3 mm; p = 0.011). In conclusion, among patients on maintenance hemodialysis, the traditional risk factors for OSA are present and interact with hemodialysis efficiency. Among these patients, OSA is associated with difficult BP control and heart remodeling suggesting that OSA may contribute to poor cardiovascular outcome.


Use of E-beam radiation to eliminate Listeria monocytogenes from surface mould cheese.
Camembert and Brie soft cheese varieties were subjected to E-beam irradiation as a sanitation treatment. The effects of treatments on microbiota and selected physicochemical properties were also studied. The absorbed doses required to meet the food safety objective (FSO) according to EU and USDA criteria for Listeria monocytogenes were 1.27 and 2.59 kGy, respectively. The bacterial load, mainly lactic acid bacteria, was reduced by the treatment but injured cells were recovered during storage at 14°C. The radiation treatment gave rise to negligible changes in the pH and water activity at doses required to achieve microbial safety.


The effect of internalized stigmatization on care burden in adolescent psychiatric patients and their parents.
The purpose of this study was to determine the effect of internalized stigma perceived by adolescents with mental disorders and their families, on the burden of care on their families. The study was conducted in a descriptive and correlational desing with adolescents and their parents who applied to the child and adolescent psychiatry outpatient clinic between March 1 and June 1, 2022. A total 101 adolescents and 101 parents who met the sampling criteria and agreed to participate in the study. Only 1 parent per adolescent was included in the study. It was found that the mean age of the adolescents was 15.05 ± (1.80), 57.4% were female and 56.4% were secondary school graduates, and 26.7% of the adolescents, all of whom were unemployed, were diagnosed with a mood disorder, 50.5% had received outpatient treatment previously, and 22.8% had chronic diseases. It was found that the mean age of the parents who participated in the study was 45.53 ± (6.48), 77.1% were female and 28.7% were secondary school graduates. Also, 22.8% of the parents had a chronic disease, 28.7% had a chronic disease in their family and 32.7% had another family member in need of care, and 17.0% of the parents had received training on mental disorders previously. It was found that the parents' total means ZBI score was 42.74 ± (11.92). When the ZBI total scores were examined in terms of sociodemographic variables, no significant differences were found between the groups according to the variables. There was only a weak, positive and significant relationship between the age of the parents and in the present study, it was found that adolescents with mental disorders and their families experienced internalized stigmatization and this stigmatization increased the care burden on parents. Mental health and psychiatric nurses can facilitate this population's access to treatment by planning and implementing psychosocial interventions to reduce the internalized stigma of children and adolescents and their families.


Cutaneous malakoplakia. Report of a case.
A case of cutaneous malakoplakia in a 44-year-old women under immunosuppressive therapy after renal transplantation for nephrosclerosis is reported. A nodular lesion with inflammatory signs appeared on her right buttock. Histopathology showed a dermal infiltrate with histiocytes containing Michaelis-Gutmann bodies. Electron microscopy showed Michaelis-Gutmann bodies with concentric laminar structure ('target' appearance). Tissue culture revealed Escherichia coli growth. Lesions recurred on surrounding skin and left buttock after excision. Clofazimine treatment resulted in total remission.


Acoustic emission source localization in thin metallic plates: A single-sensor approach based on multimodal edge reflections.
This paper presents a new acoustic emission (AE) source localization for isotropic plates with reflecting boundaries. This approach that has no blind spot leverages multimodal edge reflections to identify AE sources with only a single sensor. The implementation of the proposed approach involves three main steps. First, the continuous wavelet transform (CWT) and the dispersion curves of the fundamental Lamb wave modes are utilized to estimate the distance between an AE source and a sensor. This step uses a modal acoustic emission approach. Then, an analytical model is proposed that uses the estimated distances to simulate the edge-reflected waves. Finally, the correlation between the experimental and the simulated waveforms is used to estimate the location of AE sources. Hsu-Nielsen pencil lead break (PLB) tests were performed on an aluminum plate to validate this algorithm and promising results were achieved. Based on these results, the paper reports the statistics of the localization errors.


Circ_0023984 Facilitates Esophageal Squamous Cell Carcinoma Progression by Regulating miR-433-3p/REV3L Axis.
It has been revealed that circular RNAs (circRNAs) play an important role in regulating the malignant phenotype of tumor cells, thus involving in the progression of malignancies. However, the role of circ_0023984 in esophageal squamous cell carcinoma (ESCC) remains largely unclear. The quantitative real-time polymerase chain reaction and Western blot assays were used to detect the expression of circ_0023984, microRNA (miR)-443-3p, and protein reversionless 3-like (REV3L). In vitro and in vivo assays were performed using cell counting kit-8, colony formation, transwell, wound healing, flow cytometry, and xenograft assays. The interaction miR-433-3p and circ_0023984 or REV3L was confirmed by dual-luciferase reporter, pull-down or RIP assays. Circ_0023984 was highly expressed in ESCC tissues and cells, knockdown of circ_0023984 suppressed cancer cell proliferation, migration, invasion, and promoted cell apoptosis in vitro. Mechanistic analysis confirmed that circ_0023984 functioned as a sponge for miR-433-3p to positively regulate the expression of REV3L that was verified to be a target of miR-433-3p. Circ_0023984 knockdown repressed the tumorigenesis of ESCC cells via targeting miR-433-3p. Additionally, miR-433-3p performed anti-proliferative, anti-migratory, and anti-invasive abilities in ESCC cells, which were reversed by REV3L overexpression. Pre-clinically, silencing of circ_0023984 suppresses the tumorigenesis and growth of xenografts in nude mice. Circ_0023984 exerted an oncogenic role in ESCC tumorigenesis and aggressiveness through promoting cell growth, migration, and invasion via miR-433-3p/REV3L axis.