Mechanism of intermediate filament recognition by plakin repeat domains revealed by envoplakin targeting of vimentin.
Plakin proteins form critical connections between cell junctions and the cytoskeleton; their disruption within epithelial and cardiac muscle cells cause skin-blistering diseases and cardiomyopathies. Envoplakin has a single plakin repeat domain (PRD) which recognizes intermediate filaments through an unresolved mechanism. Herein we report the crystal structure of envoplakin's complete PRD fold, revealing binding determinants within its electropositive binding groove. Four of its five internal repeats recognize negatively charged patches within vimentin via five basic determinants that are identified by nuclear magnetic resonance spectroscopy. Mutations of the Lys1901 or Arg1914 binding determinants delocalize heterodimeric envoplakin from intracellular vimentin and keratin filaments in cultured cells. Recognition of vimentin is abolished when its residues Asp112 or Asp119 are mutated. The latter slot intermediate filament rods into basic PRD domain grooves through electrosteric complementarity in a widely applicable mechanism. Together this reveals how plakin family members form dynamic linkages with cytoskeletal frameworks.


Using the StomaphyX(TM) endoplicator to treat a gastric bypass complication.
As the number of bariatric operations performed increases, the number of patients requiring reoperation for failed weight loss is expected to proportionately increase. Natural orifice surgery is an alternative approach to revisional gastric bypass surgery when postoperative complications, such as dilatation of the gastrojejunostomy, gastrogastric fistula, and gastric pouch, dilation occur. The present article reports on the safe and successful use of an endoscopic tissue plicating device in a patient found to have a dilated gastric pouch and a gastrogastric fistula 12 years after an open, nondivided RYGB. The procedure was performed without complications and resulted in a reduced pouch size to approximately 30cc to 50cc and redirection of the flow of gastric contents through her gastrojejunostomy. The patient's early satiety returned and, 1 year postoperatively, she had incurred a 45-pound weight loss. The morbidity and mortality of revision gastric bypass was avoided while the patient's goal of moderate weight loss was achieved. Tissue plicating devices offer an alternative for repair of some postbariatric complications. With the rapid advances in endoluminal technology and increasing experience with natural orifice surgery, the ability to successfully address surgical problems through less invasive means will continue to improve.


Greatly improved catalytic activity and direct electron transfer rate of cytochrome C due to the confinement effect in a layered self-assembly structure.
The greatly improved catalytic and electrochemical properties of cytochrome C (cyt C) in a confined environment have been achieved by assembling cyt C within sulfonated graphene (G-SO(3)H) nanosheets.


Temporospatial nano-heterogeneity of self-assembly of extracellular polymeric substances on microplastics and water environmental implications.
Environmental behavior and ecotoxicity of microplastics (MPs) are significantly influenced by the omnipresent self-assembly of microbial extracellular polymeric substances (EPS) on them. However, mechanisms of EPS self-assembly onto MPs at nanoscale resolution and effects of aging are unclear. For the first time, temporospatial nano-heterogeneity of self-assembly of EPS onto fresh and one-year aged polypropylene (PP) MPs were investigated by atomic-force-microscopy-infrared-spectroscopy (AFM-IR). Natural aging caused high degree nanoscale fragmentation of MPs physically and chemically. Self-assembly of EPS on MPs was aging-dependent. Polysaccharides were assembled on MP surface faster than proteins. Initially, regardless of the fresh or aged MPs, polysaccharides and proteins, with the former being predominant, were successively and separately assembled to different nanospaces because of their competition for binding sites. More and more proteins and polysaccharides were superimposed on each other with assembly time due to intermolecular forces. The nanochemical textural analysis showed that the nano-heterogeneity of EPS assembly to MPs was clearly correlated with the aging-induced nanochemical and nanomechanical heterogeneity of MP surface. The spontaneous self-assembly of EPS with temporospatial nano-heterogeneity on MPs have multiple impacts on behavior, ecotoxicity and fate of MPs and their associated pollutants as well as other key ecological processes in aquatic environment.


Lactobacillus plantarum culture supernatants improve intestinal tissue exposed to deoxynivalenol.
In the present study, histological, morphometrical and ultrastructural analysis were performed to investigate intestinal mucosa changes in piglets exposed to deoxynivalenol alone or associated with two strains of Lactobacillus plantarum and the respective culture supernatants. Jejunal explants were incubated for 4h in culture medium with a) only culture medium (DMEM, control group), b) deoxynivalenol (DON, 10μM), c) heat-inactivated Lactobacillus plantarum strain1 - LP1 (1.1×108 CFU/ml) plus DON, d) heat-inactivated Lactobacillus plantarum strain2-LP2 (2.0×109 CFU/ml) plus DON, e) heat-inactivated Lactobacillus plantarum strain1 culture supernatant (CS1) plus DON, and f) heat-inactivated Lactobacillus plantarum strain1 culture supernatant (CS1) plus DON. Explants exposed to DON and DON plus LP1 and LP2 showed a significant increase in histological changes (mainly villi atrophy and apical necrosis) and a significant decrease in villi height when compared to unexposed explants. However, explants treated with CS1+DON and CS2+DON remained similar to the control group both in histological and morphometrical aspects. DON also induced a significant decrease in goblet cell density compared to control whereas CS1+DON treatment induced an increase in the number of goblet cells in comparison to DON explants. In addition, ultrastructural assessment showed control, CS1+DON and CS2+DON explants with well delineated finger shape villi, meanwhile DON-treated, LP1+DON and LP2+DON explants showed a severe villi atrophy with leukocytes exudation on the intestinal surface. Taken together, our results indicate that the culture supernatant treatment reduced the toxic effects induced by DON on intestinal tissue and may contribute as an alternative strategy to reduce mycotoxin toxicity.


Contributions of trace elements to the sea by small uncontaminated rivers: Effects of a water reservoir and a wastewater treatment plant.
Trace element contributions from small rivers to estuaries is an issue barely addressed in the literature. In this work, freshwater flowing into the Ria of Cedeira (NW Iberian Peninsula) was studied during a hydrological year through the input from three rivers, one considered uncontaminated (the Das-Mestas River), a second affected by urban treated wastewater discharges (the Condomiñas River), and the third containing a water reservoir for urban supply (the Forcadas River). With the objective of assessing the possible influence of human pressure, the annual yields for selected trace elements (Al, Fe, As, Cd, Co, Cr, Cu, Mn, Mo, Ni and Pb) were estimated and compared by normalizing by basin surface. Both dissolved and particulate transported elements were considered. After the data treatment and analysis it can be highlighted that: (i) the Das Mestas River is suitable to be included between the short European pristine baseline of small rivers, at least regarding the transported trace elements; (ii) natural enrichments were identified associated to the lithology of the basin in the Das-Mestas River (i.e. As) and in the Condomiñas River (i.e. Co, Cr and Ni); this fact highlights the importance of considering the local background for a proper assessment; (iii) the impoundment in the Forcadas River is related with a general decrease, even depletion, of the particulate and dissolved transported trace elements, except Mn; (iv) the discharge of sewage to the Condomiñas River is increasing the inputs to the ria of some trace elements in the particulate phase (i.e. Al, Cu and Pb). Both observed human-induced changes can be regarded as typical disturbances of trace element contributions from small rivers to estuaries.


Two successful pregnancies obtained following oocyte vitrification and embryo re-vitrification.
Recent clinical reports not only show that cryopreserved embryos can be successfully used for human fertility treatment, but also that cryopreserved oocytes may be used successfully as an adjunct to human assisted reproductive technologies. Vitrification is known to establish a glass-like solid state during the cooling process. The high concentration of cryoprotectants and an extremely rapid rate of cooling are responsible for the formation of the solid state, and also prevent formation of intracellular ice crystals. Hence, in theory, vitrification should minimize cryo-injuries, and therefore has great promise for oocyte and embryo cryopreservation. This article describes two pregnancies from vitrified-warmed blastocysts obtained after intracytoplasmic sperm injection fertilization of vitrified-warmed oocytes. Vitrification was employed to cryopreserve the oocytes and the subsequent blastocysts. The results present the intriguing implication that vitrification may serve as an efficient method for clinical oocyte cryopreservation and embryo re-cryopreservation.


Soil characterization by energy dispersive X-ray fluorescence: sampling strategy for in situ analysis.
This work describes a sampling strategy that will allow the use of portable EDXRF (energy dispersive X-ray fluorescence) instruments for "in situ" soil analysis. The methodology covers a general approach to planning field investigations for any type of environmental studies and it was applied for a soil characterization study in the zone of Campana, Argentina, by evaluating data coming from an EDXRF spectrometer with a radioisotope excitation source. Simulating non-treated sampled as "in situ" samples and a soil characterization for Campana area was intended. "In situ" EDXRF methodology is a powerful analytical modality with the advantage of providing data immediately, allowing a fast general screening of the soil composition.


Estimating a breakpoint in the pattern of spread of COVID-19 in South Korea.
Amid the global coronavirus disease 2019 (COVID-19) crisis, South Korea has been lauded for successfully preventing the spread of this infectious disease, which may be due to the aggressive implementation of preventive policies. This study was performed to evaluate the pattern of spread of COVID-19 in South Korea considering the potential impact of policy interventions on transmission rates. A SIR (susceptible-infected-removed) model with a breakpoint that allows a change in transmission rate at an unknown point was established. Estimated trajectories of COVID-19 from SIR models with and without a breakpoint were compared. The proposed model with a break fitted the actual series of infection cases much better than the classic model. The estimated breakpoint was March 7, 2020 and the transmission rate dropped by 0.23 after the breakpoint. A counterfactual study based on our estimate indicated that the number of infected could have reached 2 500 000 compared to the peak of 8000 in the observed series. It is critical to consider a change in the transmission rate to evaluate the trajectory of spread of COVID-19 in South Korea. Our estimation and counterfactual experiments indicate that public health interventions may play a role in determining the pattern of spread of infectious diseases.


PSMA theragnostics for metastatic castration resistant prostate cancer.
There has been tremendous growth in the development of theragnostics for personalized cancer diagnosis and treatment over the past two decades. In prostate cancer, the new generation of prostate specific membrane antigen (PSMA) small molecular inhibitor-based imaging agents achieve extraordinary tumor to background ratios and allow their therapeutic counterparts to deliver effective tumor doses while minimizing normal tissue toxicity. The PSMA targeted small molecule positron emission tomography (PET) agents 18F-DCFPyL (2-(3-{1-carboxy-5-((6-(18)F-fluoro-pyridine-3-carbonyl)-amino)-pentyl}-ureido)-pentanedioic acid) and Gallium-68 (68Ga)-PSMA-11 have been approved by the United States Food and Drug Administration (FDA) for newly diagnosed high risk prostate cancer patients and for patients with biochemical recurrence. More recently, the Phase III VISION trial showed that Lutetium-177 (177Lu)-PSMA-617 treatment increases progression-free survival and overall survival in patients with heavily pre-treated advanced PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). Here, we review the PSMA targeted theragnostic pairs under clinical investigation for detection and treatment of metastatic prostate cancer.


The collaborative transplant study registry.
The Collaborative Transplant Study (CTS) was initiated in 1982. Over the last 30 years, it has collected information on over half a million kidney, liver, heart, lung, and pancreas transplant procedures. Participation is voluntary and the study has strictly scientific objectives. Analyses of the CTS database serve as an international reference source in the field of solid organ transplantation.


Biogenesis of cytochrome c oxidase--in vitro approaches to study cofactor insertion into a bacterial subunit I.
Biogenesis of cytochrome c oxidase is a complex process involving more than 30 known accessory proteins in yeast for the regulation of transcription and translation, membrane insertion and protein processing, cofactor insertion, and subunit assembly. Here, we focus on the process of cofactor insertion into subunit I of cytochrome c oxidase using the soil bacterium Paracoccus denitrificans as a model organism. The use of bacterial systems facilitates biogenesis studies, as the number of required assembly factors is reduced to a minimum. Both, co- and posttranslational cofactor insertion scenarios are discussed, and several approaches to shed light on this aspect of biogenesis are presented. CtaG, the Paracoccus homolog of yeast Cox11 which is involved in copper delivery to the Cu(B) center, has been purified and characterized spectroscopically. A previously unreported signal at 358 nm allows monitoring copper transfer from copper-loaded CtaG to an acceptor. Both CtaG and apo-subunit I were purified after expression in Escherichia coli to develop an in vitro copper transfer system, probing the posttranslational insertion hypothesis. To mimic a potential cotranslational insertion process, cell-free expression systems using E. coli and P. denitrificans extracts have been established. Expression of subunit I in the presence of the detergent Brij-35 produces high amounts of "solubilized" subunit I which can be purified in good yield. With this system it may be feasible to trap and purify assembly intermediates after adding free cofactors, purified assembly proteins, or P. denitrificans membranes.


A humanized monoclonal antibody produced in transgenic plants for immunoprotection of the vagina against genital herpes.
The ability to produce monoclonal antibodies (Mabs) in plants offers the opportunity for the development of an inexpensive method of mucosal immunoprotection against sexually transmitted diseases. To investigate the suitability of plant-expressed Mabs for vaginal preventive applications, we compared a humanized anti-herpes simplex virus 2 (HSV-2) Mab expressed in mammalian cell culture with the same antibody expressed in soybean. We found these Mabs to be similar in their stability in human semen and cervical mucus over 24 h, their ability to diffuse in human cervical mucus, and their efficacy for prevention of vaginal HSV-2 infection in the mouse.


Bilateral intraparotid and extraparotid Warthin's tumours.
Warthin's tumour is a benign adenoma in the parotid gland, but extraparotid and synchronous bilateral Warthin's tumours may occur. In this report, we describe a patient with simultaneous bilateral involvement of the parotid glands and neck by multiple Warthin's tumours, an occurrence not previously described.


Retrospective study of the incidence of sarcoidosis-like reaction in patients treated with immunotherapy.
To assess the frequency of radiographically evident drug-induced sarcoidosis-like reaction (DISR) in patients treated with anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) therapy, anti-programmed cell death protein 1 (PD-1) therapy, or a combination of both in a single centre. The images and medical records of 457 patients with metastatic melanoma or head and neck cancer treated with either anti-CTLA-4 therapy, anti-PD-1 therapy, or a combination of both at University of California medical centre were reviewed retrospectively and the incidence of radiological manifestations of DISR was assessed among these treatment groups. Radiological manifestations of DISR were found in 19/457 patients (4.1%). The mean interval from the initiation of immunotherapy to development of DISR was 5.5 months (range 2.3-13.5 months). Mean interval from radiological detection of DISR to imaging evidence of resolution was 5.8 months (range 1.6-18.3 months). Three patients out of 81 (3.7%), 11/297 (3.7%), and 5/79 (6.3%) developed sarcoidosis-like reaction after treatment with anti-CTLA-4 antibody, anti-PD-1 antibody, and a combination of both, respectively. Most patients with DISR were asymptomatic and did not require systemic therapy. Most patients did not demonstrate concomitant increased maximum standardised uptake value (SUVmax) in other organs on their integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT). In the present retrospective study of patients treated with immune checkpoint inhibitors (ICIs), DISR occurred in approximately 3.7% of patients treated with either anti-CTLA-4 or anti-PD-1 antibody and 6.3% of patients treated with a combination of both.


Incidence and Treatment Outcomes of Post Traumatic BPPV in Traumatic Brain Injury Patients.
The aim of this study is to assess the incidence of post traumatic BPPV and evaluate its treatment outcomes in mild and moderate traumatic head injury patients. The study population consisted of 128 patients (89 male:39 female) who were admitted with head and neck injury (Motor Vehicle Accident, Blow to the head, Fall from Height, Whiplash injury) as inpatients in Department of Neurosurgery in Tertiary care hospital in Kerala during a 2 month period from 1st April 2014 to 31st May 2014. The age range was 10-70 years and mean 39.8 with standard deviation 15.5. All cases were evaluated and serially followed up to a period of 6 months in Department of Otorhinolaryngology. In our study, the number of patients with mild injuries (Glasgow coma scale 13-15) were 108 and moderate injury (Glasgow coma scale 9-12) were 20. We found out that post traumatic BPPV was found to be 17% of the traumatic brain injury patients. All patients were treated with particle re-positioning maneuvers and were followed up for a period of 6 months. Recurrence were reported in 9 (40.9%) patients. In these patients re positioning maneuvers were repeated.


Anticipated regret in shared decision-making: a randomized experimental study.
Explicit consideration of anticipated regret is not part of the standard shared decision-making protocols. This pilot study aimed to compare decisions about a hypothetical surgery for breast cancer and examined whether regret is a consideration in treatment decisions. In this randomized experimental study, 184 healthy female volunteers were randomized to receive a standard decision aid (control) or one with information on post-surgical regret (experimental). The main outcome measures were the proportion of subjects choosing lumpectomy vs. mastectomy and the proportion reporting that regret played a role in the decision made. We hypothesized that a greater proportion of the experimental group (regret-incorporated decision aid) would make a surgical treatment preference that favored the less regret-inducing option and that they would be more likely to consider regret in their decision-making process as compared to the control group. A significantly greater proportion of the experimental group subjects reported regret played a role in their decision-making process compared to the control counterparts (78 vs. 65 %; p = 0.039). Recipients of the regret-incorporated experimental decision aid had a threefold increased odds of choosing the less regret-inducing surgery (OR = 2.97; 95 % CI = 1.25, 7.09; p value = 0.014). In this hypothetical context, the incorporation of regret in a decision aid for preference-sensitive surgery impacted decision-making. This finding suggests that keying in on anticipated regret may be an important element of shared decision-making strategies. Our results make a strong argument for applying this design and pursuing further research in a surgical patient population. Clinicaltrials.gov, NCT02563808.


Essential and toxic trace element concentrations in different commercial veal cuts in Spain.
The aim of this study was to evaluate essential and toxic element concentration of ten commercially available veal cuts, together with diaphragm, cardiac muscle and liver tissue from 10 animals of "Galician Supreme Veal". Essential trace elements (Co, Cr, Cu, Fe, Mn, Mo, Ni, Se and Zn) and toxic elements (As, Cd, Hg and Pb) were determined by ICP-MS. Essential trace element concentrations ranged from 0.002-55.64mg/kg between muscles. Toxic element concentrations were very low, and high numbers of samples showed unquantifiable residues of Cd and Pb. Veal cuts including muscles with a high proportion of oxidative slow-twitch fibers (diaphragm and cardiac muscle) showed significantly higher essential trace element concentrations, the lower concentrations being found in veal cuts including glycolytic fast-twitch fibers (eye round). Our results suggest that essential and toxic trace element concentration could be used as a new meat quality parameter, or to add further value to certain products (i.e. livestock reared on extensive systems with high physical activity).


Mental health status, including depression and quality of life among members of an elderly club in suburban Bangkok.
Evolution of medical technologies extent human life expectancy. The United Nations found Thai elderly population were increased rapidly compared with other developing countries. Global estimations of the burden of disease show that mental illness plays a prominent role. Elderly club is one of the several ways to promote social interaction, gain self esteem, slow progression of physical and mental disabilities in old age people. However, the activities which certainly proper for each elderly group remains unclear because various demographic data background of elderly in each area. To determine the mental health status, including depression and quality of life among members of the Thammasat hospital elderly club which covers elderly members in northen Bangkok, Pathumthani and Ayutthaya province. A cross-sectional descriptive study was conducted. Seventy members were sampled for interview from 207 members. The assessment tools were Thai Mental Health Indicator (TMHI-54), Thai Geriatric Depression Scale (TGDS), Stress self assessment questionnaire, and World Health Organization Quality of Life-Brief-Thai Version (WHOQOL-BREF-THAI). The majority of the sample was females (78.6%). The age ranged from 60 to 84 years old (mean 70.24). The prevalences of psychological problems were; poor mental health (12.90%), depression (5.7%) and stress (15.2%). The sample reported poorer quality of life on 3 sub-domains of WHOQOL; physical (2.9%), psychological (1.4%) and social relationship (4.30%) domains. The level of depression, reported by those who had not enough income, was significantly higher than those who had enough income (p = 0.022). Quality of life (physical and social relationship domain) among those aged younger than 70 years, was better than that among those aged 70 or older (p = 0.024 and p = 0.023 respectively). Quality of life (psychological domain) among those who had not enough income, was significantly poorer than those with enough income (p = 0.020). Quality of life in term of social relationship was better among those living in urban areas (p = 0.037) or having better education (p = 0.014). Regular or irregular club's activity attending was not related with mental status and quality of life. The majority of the sample had equal or better mental health status and quality of life compared with the general population. The prevalence of depression was slightly lower than other Thai studies.


Restricted mean survival time versus conventional effect summary for treatment decision-making: A mixed-methods study.
Treatment effect is typically summarized in terms of relative risk reduction or number needed to treat ("conventional effect summary"). Restricted mean survival time (RMST) summarizes treatment effect in terms of a gain or loss in event-free days. Older adults' preference between the two effect summary measures has not been studied. We conducted a mixed methods study using a quantitative survey and qualitative semi-structured interviews. For the survey, we enrolled 102 residents with hypertension at five senior housing facilities (mean age 81.3 years, 82 female, 95 white race). We randomly assigned respondents to either RMST-based (n = 49) or conventional decision aid (n = 53) about the benefits and harms of intensive versus standard blood pressure-lowering strategies and compared decision conflict scale (DCS) responses (range: 0 [no conflict] to 100 [maximum conflict]; <25 is associated with implementing decisions). We used a purposive sample of 23 survey respondents stratified by both their random assignment and DCS from the survey. Inductive qualitative thematic analysis explored complementary perspectives on preferred ways of summarizing treatment effects. The mean (standard deviation) total DCS was 22.0 (14.3) for the conventional decision aid group and 16.7 (14.1) for the RMST-based decision aid group (p = 0.06), but the proportion of participants with a DCS <25 was higher in the RMST-based group (26 [49.1%] vs 34 [69.4%]; p = 0.04). Qualitative interviews suggested that, regardless of effect summary measure, older individuals' preference depended on their ability to clearly comprehend quantitative information, clarity of presentation in the visual aid, and inclusion of desired information. When choosing a blood pressure-lowering strategy, older adults' perceived uncertainty may be reduced with a time-based effect summary, although our study was underpowered to detect a statistically significant difference. Given highly variable individual preferences, it may be useful to present both conventional and RMST-based information in decision aids.


Non-invasive visualization of amyloid-beta deposits in Alzheimer amyloidosis mice using magnetic resonance imaging and fluorescence molecular tomography.
Abnormal cerebral accumulation of amyloid-beta peptide (Aβ) is a major hallmark of Alzheimer's disease. Non-invasive monitoring of Aβ deposits enables assessing the disease burden in patients and animal models mimicking aspects of the human disease as well as evaluating the efficacy of Aβ-modulating therapies. Previous in vivo assessments of plaque load have been predominantly based on macroscopic fluorescence reflectance imaging (FRI) and confocal or two-photon microscopy using Aβ-specific imaging agents. However, the former method lacks depth resolution, whereas the latter is restricted by the limited field of view preventing a full coverage of the large brain region. Here, we utilized a fluorescence molecular tomography (FMT)-magnetic resonance imaging (MRI) pipeline with the curcumin derivative fluorescent probe CRANAD-2 to achieve full 3D brain coverage for detecting Aβ accumulation in the arcAβ mouse model of cerebral amyloidosis. A homebuilt FMT system was used for data acquisition, whereas a customized software platform enabled the integration of MRI-derived anatomical information as prior information for FMT image reconstruction. The results obtained from the FMT-MRI study were compared to those from conventional planar FRI recorded under similar physiological conditions, yielding comparable time courses of the fluorescence intensity following intravenous injection of CRANAD-2 in a region-of-interest comprising the brain. In conclusion, we have demonstrated the feasibility of visualizing Aβ deposition in 3D using a multimodal FMT-MRI strategy. This hybrid imaging method provides complementary anatomical, physiological and molecular information, thereby enabling the detailed characterization of the disease status in arcAβ mouse models, which can also facilitate monitoring the efficacy of putative treatments targeting Aβ.


The impact of metrical structure on performance stability in bimanual 1:3 tapping.
Participants performed a three-beat (strong-weak-weak) finger-tapping pattern with one hand while synchronizing taps of the other hand with either the strong tap (metrically congruous rhythm) or one of the weak taps (metrically incongruous rhythms). We tested the hypothesis that performance would be less stable during the production of the incongruous rhythms. The tapping sequences were performed at two different tempi (Experiment 1) and under two different cognitive descriptions of the task (Experiment 2). Metrically incongruous rhythms showed greater force differentiation between strong and weak taps, increases in the variability of the timing within and between hands, and frequent breakdowns of the between-hand coordination. Tempo variations and the different cognitive descriptions of the task did not influence performance. We suggest that the difficulty in producing incongruous rhythms arises from interference between the required incongruous metric pattern and a spontaneously available pattern in which the potential boundary-markers of the metric units systematically coincide.


Bisphenol A exposure modulates reproductive and endocrine system, mitochondrial function and cellular senescence in female adult rats: A hallmarks of polycystic ovarian syndrome phenotype.
Bisphenol A (BPA) mimics estrogen and consequently suspected to be detrimental to female reproductive system. Biomonitoring confirms the BPA burden in body leading to a complex condition called polycystic ovarian syndrome (PCOS) which is frequently attributed to female infertility. Due to unclear precise molecular pathomechanisms of BPA in PCOS, we intend to examine the molecular mechanisms of the reproductive, endocrine, mitochondrial features, and cellular senescence in BPA-treated rats. We analyzed vaginal smears and ovarian follicles using microscope, assessed sex hormones by ELISA, analyzed BPA target gene expression by semi-quantitative RT-PCR, assessed senescence induction by β-galactosidase staining and immunofluorescence in BPA-treated rats. Our data showed hormonal imbalance, impaired folliculogenesis, abnormal expression patterns of target genes, CDKN2A overexpression and enhanced ROS levels in BPA-treated rats. This study provides insights on the effects of BPA exposure on ovulatory, hormonal, mitochondrial dysfunction, and senescence that benefit in better understanding of PCOS induced by BPA.


Using clinical patient characteristics to predict treatment outcome of cognitive behavior therapies for individuals with medically unexplained symptoms: A systematic review and meta-analysis.
For individuals with medically unexplained symptoms (MUS), cognitive behavioral therapy (CBT) is the best-evaluated treatment. This systematic review and meta-analyses identify clinical patient characteristics associated with the treatment outcome of CBT for MUS. A systematic literature search (PubMed, PsycInfo, Web of Science) resulted in 53 eligible studies; of these 32 studies could be included in meta-analyses. Pooled correlation coefficients between predictors and treatment outcome were calculated with a random-effects model. Moderator analyses were conducted to examine differences between subgroups of MUS and different levels of methodological study quality. Meta-analyses demonstrated that individuals with higher symptom intensity (r = 0.38; p < 0.001), lower physical functioning (r = -0.29; p < 0.001), lower emotional and social functioning (r = -0.37; p < 0.001), more potential symptom-related incentives (r = -0.15; p = 0.001), or longer symptom duration (r = 0.10; p = 0.033) at the beginning of treatment reported less change of symptom severity until the end of therapy or higher end-of-treatment symptom severity. The pooled effect sizes did not differ between certain subgroups of MUS or between different levels of methodological quality. Our findings indicated that clinical characteristics of MUS patients are associated with treatment outcome of CBT. We discuss how the results can be used to optimize and personalize future treatments for MUS.


[Natural killer and cytotoxic T lymphocyte-mediated cytotoxicity enhanced by genetic overexpression of MHC class I chain-related protein A in oral squamous cell carcinoma: an experimental study in vivo].
To investigate the effect on natural killer (NK) and cytotoxic T lymphocyte (CTL)-mediated cytotoxicity by genetic overexpression of MHC class I chain-related protein A (MICA) in oral squamous cell carcinoma (OSCC). The OSCC cells by genetic overexpression of MICA were detected to identify the biological features including cell growth curve, cell cycle distribution, plate clone forming rate and tumorigenicity in nude mice. The expression of natural killer group 2, member D (NKG2D) receptor and the cytotoxicity to target tumor cells of NK92 and CTL cells, which co-cultured with the transfected OSCC cells or the non-transfected or blank vector-transfected controls, were measured by flow cytometry and lactate dehydrogenase (LDH) release assay. There was no difference in biological features before and after MICA gene transfection to OSCC cells. Flow cytometry and LDH release assay showed that MICA-overexpressed OSCC cells enhanced the cytotoxicity to target tumor cells and up-regulated the expression of NKG2D on NK92 and CTL (P<0.05). MICA may be considered as a promising immunotherapy target of OSCC.


Pulsed dose rate (PDR) brachytherapy as salvage treatment of locally advanced or recurrent gynecologic cancer.
Pulsed dose rate (PDR) brachytherapy is a new treatment option permitting dose distribution optimization in interstitial implants. It possesses the advantage of equipment simplification and radiation protection to the staff, compared to the manually afterloading technique. This study presents the first clinical results from The Finsen Center with PDR-brachytherapy in patients with locally advanced or recurrent gynecologic cancer. Between June 1993 and August 1996, 34 patients with gynecologic malignancies (22 pelvic recurrences, 12 primary locally advanced) have been treated with external irradiation, four-field box technique, to 46 Gy/23 fractions, 5 F/week and 192Ir-interstitial PDR-brachytherapy in pulses of 0.6 Gy, one pulse per hour to a total of 30 Gy. The Martinez Universal Perineal Interstitial Template applicator was used for all implantations. The overall complete response rate was 74%. At median 14 months follow-up (range 3-40) 15 patients were alive with no evidence of disease. Seven of 14 patients with a second recurrence or progressive disease were still alive. The overall 1- and 2-year survival was 71% and 63%, respectively. There was no difference in survival probability when stratifying the patients by primary diagnosis (recurrent vs. primary advanced), relapse locations (central vs. central + pelvic wall mass) or treatment volume. Seventeen chronic grade III complications were observed in 10 patients. Large treatment volumes significantly correlated to severe gastrointestinal complications. Fifteen of 17 chronic grade III complications were observed in patients treated for recurrent disease. PDR-brachytherapy in combination with external irradiation is an effective treatment option for patients with locally advanced or recurrent gynecologic cancer, although substantial toxicity is observed in patients with large treatment volumes and recurrent disease.


Impact of Dietary Quality on Genital Oncogenic Human Papillomavirus Infection in Women.
Most cervical cancers are directly linked to oncogenic or high-risk human papillomavirus (HR-HPV) infection. This study evaluates associations between diet quality and genital HPV infection in women. This study included 10 543 women from the 2003-2016 National Health and Nutrition Examination Survey. The outcome was the genital HPV infection status (HPV-negative, low-risk [LR] HPV, and HR-HPV). Dietary quality was evaluated using the Healthy Eating Index (HEI), in which a higher score indicates a better diet quality. Women who did not consume total fruits (15.8%), whole fruits (27.5%), or green vegetables and beans (43%) had a significantly higher risk of HR-HPV infection than women who complied with the Dietary Guidelines for Americans (HR-HPV odds ratio = 1.76, 1.63, and 1.48 for a HEI score of 0 vs 5, respectively) after adjusting confounding factors. Similar results of these food components on LR-HPV infection were found. In addition, intake of whole grains and dairy was inversely associated with LR-HPV infection. This study showed that women who did not eat fruits, dark-green vegetables, and beans had a higher risk of genital HR-HPV infection. Intake of these food components is suggested for women to prevent HPV carcinogenesis.


The Nagar syndrome (acrofacial dysostosis): evidence for autosomal dominant inheritance.
A 10-year-old girl with the Nagar acrofacial dysostosis syndrome and normal intelligence is presented. Severe conductive hearing loss remains the major handicap. It is suggested that her syndrome is due to a dominant gene mutation.


Effect of desipramine on propranolol-induced diminution of noradrenaline release by nerve stimulation.
In atria from rats killed 1 h after either chronic parenteral (daily subcutaneous injections of 5 mg/kg/day for 15 days) or prolonged oral administration of (-)-propranolol (1 mg/ml ad libitum during 15 days) there was a 50% decrease in the overflow of [3H]noradrenaline ([3H]NA) elicited by cardioaccelerans nerve stimulation at 2 Hz, as previously reported for the in vitro exposure of guinea pig atria to propranolol. The chronotropic responses to nerve stimulation and to isoprenaline were also significantly reduced. On the other hand, 40 h after the last injection of propranolol, the overflow of [3H]NA induced by stimulation was still reduced to 50% of the control values, whereas no blockage to nerve stimulation or to isoprenaline was observed. Neither the basal output of [3H]NA nor the tissue levels of the endogenous transmitter were modified by any of the treatment schedules applied. In a separate set of experiments performed in isolated guinea pig atria stimulated at 4 Hz during 1 min, the in vitro exposure to 0.5 microM desipramine prevented the 30% decrease in the overflow of [3H]NA caused by 0.1 microM (-)-propranolol. Desipramine, by itself, did not modify the overflow of the transmitter. It is concluded that propranolol, both in vitro and after chronic in vivo treatments, reduces the overflow of [3H]NA in response to nerve stimulation. The fact that the in vitro effect of the beta-blocker is antagonized by desipramine suggests that propranolol may have to be taken up by the nerve terminals in order to exert its presynaptic inhibition on the release of noradrenaline.


The X-Linked Intellectual Disability Gene Zdhhc9 Is Essential for Dendrite Outgrowth and Inhibitory Synapse Formation.
Palmitoylation is a reversible post-translational lipid modification that facilitates vesicular transport and subcellular localization of modified proteins. This process is catalyzed by ZDHHC enzymes that are implicated in several neurological and neurodevelopmental disorders. Loss-of-function mutations in ZDHHC9 have been identified in patients with X-linked intellectual disability (XLID) and associated with increased epilepsy risk. Loss of Zdhhc9 function in hippocampal cultures leads to shorter dendritic arbors and fewer inhibitory synapses, altering the ratio of excitatory-to-inhibitory inputs formed onto Zdhhc9-deficient cells. While Zdhhc9 promotes dendrite outgrowth through the palmitoylation of the GTPase Ras, it promotes inhibitory synapse formation through the palmitoylation of another GTPase, TC10. Zdhhc9 knockout mice exhibit seizure-like activity together with increased frequency and amplitude of both spontaneous and miniature excitatory and inhibitory postsynaptic currents. These findings present a plausible mechanism for how the loss of ZDHHC9 function may contribute to XLID and epilepsy.


Scedosporium prolificans sclerokeratitis 10 years after pterygium excision with adjunctive mitomycin C.
Scedosporium prolificans is an unusual infection, especially following pterygium surgery. A 63-year-old man who developed an uncomfortable, red right eye 10 years after pterygium surgery with adjunctive mitomycin C is described. To the best of the authors' knowledge, this is the first reported case of S. prolificans sclerokeratitis following pterygium surgery with adjunctive mitomycin C.


Data to model risks for recolonizing wolves in Scandinavia through the integration of territory presence and human-driven mortalities.
This dataset article describes the data and sources used to model risks for the recolonizing wolf (Canis lupus) in Sweden and Norway in the article "Integrated spatially-explicit models predict pervasive risks to recolonizing wolves in Scandinavia from human-driven mortality" (Recio et al., 2018). Presences on wolf territories were used to model the potential distribution of the species. Presences of human-driven mortalities including traffic collisions, culling (protective/defensive, and licensed hunting), and illegal killing (i.e. poaching) were used to model predictions on the distribution of these mortalities. Sources for the independent variables used for the models are also described.


Anisotropy of the sea surface height wavenumber spectrum from altimeter observations.
In this paper, the zonal and meridional sea surface height (SSH) wavenumber spectra are systematically calculated using along-track and gridded altimeter products, and the slopes of the SSH wavenumber spectra over the mesoscale band, which is defined by the characteristic length scale of mesoscale signals, are estimated. The results show that the homogeneous spectral slopes calculated from the along-track and gridded altimeter datasets have a similar spatial pattern, but the spectral slopes from gridded altimeter data are generally steeper than that from the along-track data with an averaged difference of 1.5. Significant differences are found between the zonal and meridional spectra, which suggest that SSH wavenumber spectra are indeed anisotropic. Furthermore, the anisotropy exhibits strong regional contrast: in the equatorial region, the zonal spectrum is steeper than its corresponding meridional spectrum, while in the eastward-flowing high EKE regions the meridional spectrum is steeper than its zonal counterpart. The anisotropy of SSH wavenumber spectral slopes implies that EKE distributes anisotropically in different directions, and this distribution is closely associated with the generation and nonlinear evolution of mesoscale movements.


A radiation hybrid map of 18 growth factor, growth factor receptor, hormone receptor, or neurotransmitter receptor genes on the distal region of the long arm of chromosome 5.
The distal portion of the long arm of human chromosome 5 contains an impressive number of genes encoding growth factors, growth factor receptors, and hormone/neurotransmitter receptors. The order of and relative distance between 18 of these genes was determined by radiation hybrid mapping. There is only a single gap in a contiguous radiation map from 5q22-5q35. For this set of radiation hybrids, one map unit (centiray) corresponds to 20-50 kb of DNA. Close physical proximity for several pairs of loci was predicted by the map. Two sets of these were found to be contained in single YAC clones. The physical map produced by radiation hybrid mapping should prove useful in efforts to identify four disease genes that have been assigned to distal 5q by linkage studies.


Pernio and early SARS-CoV-2 variants: natural history of a prospective cohort and the role of interferon.
Cases of new-onset pernio and recurrences in our cohort align tightly with trends in mean 7-day COVID-19 positivity in Wisconsin and mean temperature in Madison, Wisconsin by month.


Effects of tea saponin on growth and development, nutritional indicators, and hormone titers in diamondback moths feeding on different host plant species.
The diamondback moth (DBM) is an important worldwide pest. This insect has been studied for several decades; however, its control remains problematic. Numerous chemical insecticides have become ineffective and chemical residues constitute an important problem. In the present study, we determined the mortality of 3rd instar DBM larvae feeding on three different host plant species and exposed to various concentrations of tea saponin (TS). In addition, we evaluated growth and development parameters, nutritional indicators, and juvenile hormone (JH) and molting hormone (MH) titers in 2nd instar larvae exposed to LC20 and LC50 doses of TS. We found that treatment of DBM larvae with LC20 and LC50 doses of TS led to lower growth rates, decreased feed consumption, reduced frass production, lower pupal weights, reduced percentage pupation, slower adult emergence percentages, and diminished fecundity, but prolonged durations of the larval and pupal periods. The efficiency of conversion of ingested and digested food increased, but the approximate digestibility did not differ significantly between treatments and controls. JH and MH titers were higher after TS treatment; these increases varied according to the host species and TS concentration. Our results indicate that TS represents a potential new alternative insecticide based on its natural origin, low cost, and minimum environmental impact.


The first transformation method for the thermo-acidophilic archaeon Thermoplasma acidophilum.
A transformation method yielding up to 10(4) transformants per μg circular DNA was developed for Thermoplasma acidophilum. The method is based on a natural DNA uptake process in which T. acidophilum cells keep their integrity and turn competent at pH 3.5 and 58°C. Shuttle vector maintenance could not be detected, since the used Nov(R) gyraseB gene integrated into its chromosomal counterpart by homologous recombination.


Travel time to health facilities in Papua New Guinea: Implications for coverage and equity in child vaccinations.
With infant and child mortality rates that are among the highest in the Pacific region, and basic vaccination coverage rates that are 39% among children 12-23 months, increased coverage of vaccines is a high priority investment for Papua New Guinea (PNG). Using recently gathered household survey data for PNG, this paper contributes to the evidence-base for enhancing investments in frontline facilities by examining the implications of travel time to health facilities for basic vaccination coverage among children in PNG. We find that vaccination coverage rates among children 12-23 months old in PNG are decreasing in distance to healthcare facilities; and this holds whether the outcome is receipt of basic vaccinations (BCG; 3 dose pentavalent; OPV3; Measles), or basic vaccinations-plus (basic vaccinations + Hepatitis B + PCV3). We also find that travel time to health facilities lowers vaccination rates among children 12-23 months old in poor households to a greater extent than for children from richer households. Thus, enhanced geographical access to and resourcing of frontline facilities is likely to expand not only immunization coverage, lower mortality and increase aggregate economic gains, but also improve the distribution of immunization coverage in PNG across socioeconomic groups.


Suramin and minocycline treatment of experimental African trypanososmiasis at an early stage of parasite brain invasion.
The effect of treatment on relapses of Trypanosoma brucei (T. b.) brucei infections in mice in relation to passage of the parasites across the blood-brain barrier (BBB) as visualized by immunohistochemistry was studied. Three daily intraperitoneal injections of 20mg/kg suramin starting at 15 days post-infection (p.i.), when trypanosomes had begun to traverse the BBB, were curative, but not when starting at 21 days p.i. when parasite brain invasion was more pronounced. Relapses occurred in all mice after one or two daily injections of suramin starting at 15 days p.i., but they were delayed when treatment was supplemented with minocycline, which impedes penetration of T. b. brucei into the brain. This study supports the notion that suramin may be effective even when minor parasite neuroinvasion has appeared in African trypanosomiasis and it shows that minocyline can affect relapses of the disease.


Bilateral acetabular fractures treated with delayed total hip arthroplasty.
Acetabular fractures after seizures are uncommon, and fewer than 30 cases are described in the literature. We present a patient with bilateral acetabular fractures after a seizure, with bilateral quadrilateral plate destruction and protrusio deformity. The patient underwent delayed staggered bilateral total hip arthroplasty 3 months after initial injury, with use of the femoral head as autograft for the protrusio deformities.


CAD-associated reader error in CT colonography.
Computed tomographic colonographic interpretation with computer-aided detection (CAD) may be superior to unaided viewing, although polyp characteristics may influence accuracy. Reader error due to polyp characteristics was evaluated in a multiple-case, multiple-reader trial of computed tomographic colonography with CAD. Two experts retrospectively reviewed 52 positive cases (74 polyps) and categorized them as hard, moderate, or easy to detect. Each case was evaluated without and with CAD. Features that may influence a reader's ability to detect a polyp or to accept or reject a CAD mark were tabulated. The association between polyp characteristics and detection rates in the trial was assessed. The difference in detection rates (CAD vs unassisted) was calculated, and regression analysis was performed. Of 64 polyps found by CAD, experts categorized 20 as hard, 28 as moderate, and 16 as easy to detect. Reader characterization errors predominated (47.3%) over other errors. Factors associated with lower detection rates included small size, flat morphology, and resemblance to a thickened fold. CAD was superior for polyps resembling lipomas compared to those that did not resemble lipomas (average increase in detection rate with CAD, 12.8% vs 5.5%; P < .05). Polyp characteristic may impair computed tomographic colonographic interpretation augmented by CAD. Readers can avoid errors of measurement by evaluating diminutive polyp candidates with sample measurements. Caution should be taken when evaluating focally thick folds and when using visual impression to dismiss a polyp candidate as a lipoma when it is submerged in densely tagged fluid.


Measurement of temperament and character in mood disorders: a model of fundamental states as personality types.
Personality assessment may allow reliable measurement of risk of mood disorders. A group of adults (804) representative of the general population were assessed by questionnaire. Personality types were measured by the Temperament and Character Inventory (TCI). Specific TCI configurations define personality types that can be described as hyperthymic, cyclothymic, irritable, and depressive. Each type had a unique profile of emotions, suicide attempts, and hospitalization. TCI traits are associated with mood disorders. Different ways of measuring Kraepelinean subtypes may disagree. Whether differences in personality cause psychopathology, or vice versa, remains uncertain. Personality profiles help in assessing suicidality and planning treatment.


Clinical physics, applicator choice, technique, and equipment for electron intraoperative radiation therapy.
IORT has been a widely used modality since the 1980s. The initial euphoria experienced at the beginning, however, has subsided, with the result that most centers still practicing IORT are academic institutions. The reason for the reduction in IORT performed at community hospitals is partly related to the method of treatment--namely, transporting the patient from the OR to the radiation therapy department. The advent of mobile linear accelerators, which require little or no shielding and can therefore be used in most OR rooms, is likely to reiginite interest in this modality. There are currently six new centers in the United States that practice IORT with a mobile linear accelerator and more than that in Europe.


Pattern of psychiatric morbidity and alcohol dependence in patients with alcoholic liver disease.
Fifty-six male patients with alcoholic liver disease were evaluated for the presence and severity of alcohol dependence and psychiatric illness using a severity of alcohol dependence questionnaire and research diagnostic criteria, respectively. Forty-three (76.7%) patients were found to be dependent; 26 (46.4%) moderately, and 17 (30.3%) severely. Patients with alcoholic hepatitis were significantly (P less than 0.05) more often found to be dependent than patients with alcoholic cirrhosis. Psychiatric morbidity was observed in 42 (75%) of the patients with alcoholic liver disease and 15 (26.7%) of the nonalcoholic cirrhotics. The difference was highly significant (P less than 0.01). The commonest disorders in patients with alcoholic liver disease were neuroses (33.0%), followed by affective disorders (26.8%). It was, however, not possible to ascertain whether psychiatric disorders antedated alcoholism or were secondary to it. Detection of moderate to severe dependence on alcohol and psychiatric morbidity in about three-fourths of the patients with alcoholic liver disease warrants an increased awareness and a multidisciplinary approach for the management of these patients.


Human interaction in the NICU and its association with outcomes on the Brief Infant-Toddler Social and Emotional Assessment (BITSEA).
Extremely preterm infants represent one of the highest risk categories for impairments in social competence. Few studies have explored the impact of the neonatal intensive care unit (NICU) environment on social development. However, none have specifically analyzed the effects of the care structure the infant receives during hospitalization on later social competence indicators. To identify associations between the care structures received by extremely preterm infants in the NICU and scores on the Brief Infant-Toddler Social and Emotional Assessment (BITSEA) post-discharge. 50 extremely preterm infants (mean gestational age: 25 weeks during hospitalization; mean chronological age during follow-up assessment: 2 years, 4 months). A secondary analysis of BITSEA data was performed exploring its relation to care structure data we extracted from electronic medical records (i.e., how much time infants were engaged in human interaction during their first thirty days of hospitalization and what types of interaction they were exposed to). Extremely preterm infants spend a considerable amount of time alone during hospitalization (80%) with nursing care comprising the majority of human interaction. Infants who experienced greater human interaction scored significantly higher on the Social Competence (p = 0.01) and lower on the Dysregulation (p = 0.03) BITSEA subscales. Human interaction and isolation in the NICU is associated with social competence and dysregulation outcomes in extremely preterm infants. Further research is needed to understand how various NICU care structures including centralized nursing teams, parental skin-to-skin care, and early therapy may synergistically play a positive role in developing social competence.


An efficient, green and sustainable potassium hydroxide activated magnetic corn cob biochar for imidacloprid removal.
The extensive use of imidacloprid (IMI) has led to its being frequently detected in natural water, also caused the potential damage to the ecosystem. Development of efficient, green and sustainable technique is demanded to eliminate this problem. A novel biochar (KMCBC) derived from agriculture waste of corn cob was first time co-modified by potassium hydroxide (KOH), ferric chloride (FeCl3) and zinc chloride (ZnCl2), which showed the greater adsorption amount (410 mg g-1 at 298 K) for imidacloprid (IMI). Pseudo-second-order kinetic and Langmuir isotherm models fitted well with the experimental data, together with the physicochemical characterization analysis, demonstrating that the adsorption process of IMI by KMCBC might be mainly controlled by micropore filling, π-π electron donor-acceptor and functional groups interactions (H-bonding and complexation). Additionally, the thermodynamics parameters suggested that IMI adsorption in this study was a spontaneous, endothermic and randomly increasing process. Besides, KMCBC owned the easy separation performance and promising environmental safety, also exhibited a high selective adsorption capacity regardless of solution pH (its optimum adsorption performance for IMI was obtained at pH = 5), inorganic ions strength and humic acid (HA) concentrations. The regenerated KMCBC (synergistic ultrasound/ethanol) could sustainably and efficiently adsorb IMI in the reuse cycles. Therefore, this study provided an efficient, green and sustainable adsorbent of KMCBC for IMI removal.


Clinical and radiological evidence of the recurrence of reversible pegvisomant-related lipohypertrophy at the new site of injection in two women with acromegaly: a case series.
Pegvisomant-related lipohypertrophy may revert when changing the site of injection, but the lipohypertrophy may recur at the new site of injection. The strength of evidence, however, is weak and comes from information obtained from physical examination only. We studied two Caucasian women with acromegaly, aged 51 and 71 years, with pegvisomant-related lipohypertrophy. Our two patients were evaluated at baseline, when the site of pegvisomant injection was the periumbilical abdominal region, and then four months after switching the injection site from the abdomen to both thighs. Both physical examination and radiological studies (magnetic resonance imaging and dual energy X-ray absorptiometry) demonstrated that the abdominal lipohypertrophy progressively reverted in both patients after switching the site of injection to the thighs. However, lipohypertrophy reappeared at the new site of injection. The radiological outcome confirmed the reversibility of pegvisomant-related lipohypertrophy and strengthened the body of evidence on this issue. In clinical practice, physical examination of the injection site or sites leads to an early detection of lipohypertrophy during pegvisomant treatment. Radiological procedures may be of help to confirm subcutaneous fat changes and for a precise monitoring of fat redistribution. Patients should get appropriate information about lipohypertrophy before starting pegvisomant treatment since the rotation of the site of injection may prevent lipohypertrophy.


[Current situation of electronic medical records in ophthalmological departments in Germany].
Electronic medical records are required in ophthalmology clinics to be integrated into digital care networks and efficient clinical registry databases. To assess the prevalence and methods of electronic medical recordkeeping in inpatient ophthalmological care in Germany. An online questionnaire was sent to all German university eye hospitals and ophthalmology departments in June 2021. It included 13 open and closed option questions concerning current practices of digital recordkeeping, including the structure of data storage and the recording of billing-relevant codes in the departments. A total of 44 (44%) out of 100 clinics responded. Patient documentation was completely digital in 15 (34%) clinics and partly digital and paper-based in the remaining 29 (66%). A total of 16 different constellations of documentation programs were specified. The most frequently used programs were Orbis (27%) (Dedalus HealthCare, Bonn, Germany), FIDUS (18%) (Arztservice Wente, Darmstadt, Germany), and SAP/i.s.h.med (16%) (SAP Deutschland, Walldorf, Germany; Cerner Deutschland, Berlin, Germany) and 3 clinics indicated primary use of paper records. Structured documentation of findings was performed in 61% of the departments, while 23% used a semistructured manner and 15% used a nonstructured format. Electronic documents are stored as DICOM (Digital Imaging and Communications in Medicine) documents 20% of the clinics and as PDF (Portable Document Format) files in 34% of the clinics while 23% store scanned printouts. Methods of medical record keeping in German eye clinics are heterogeneous, with paper-based documentation continuing to play an important role. This, as well as the high number of different electronic medical record software pose important challenges in terms of interoperability and secondary use of clinical data.


Porous amorphous powder form phase-selective organogelator for rapid recovery of leaked aromatics and spilled oils.
Phase-selective organogelators (PSOGs) have drawn wide attention due to their potential applications in recovery of leaked aromatics and spilled oils. However, powder form PSOGs with fast gelling abilities and broad applicabilities are still limited. Herein, we developed three D-gluconic acetal-based gelators with different alkyl chains, all of which show excellent gel properties for hydrocarbon solvents. The spectroscopic and X-ray results revealed that the gel formation was the synergy of hydrogen bonding, π-π stacking and van der Waals forces. Surprisingly, the powder form gelator A with a cis double bond in the alkyl chain could instantly and selectively gel aromatic hydrocarbons, and also rapidly solidify crude oils with widely ranging viscosities from seawater at room temperature within minutes. Further research revealed that A powder exhibited porous amorphous morphology because the cis double bonds broke the crystalline chain-chain interdigitation between the assemblies. Therefore, the fast dispersion and recombination of fibers under the action of oil molecules lead to the fast room temperature gel process. Overall, a non-toxic and low-cost powder form PSOG with rapid room temperature phase selective gelation ability for a wide range of oils makes it promising for the emergency treatment of oil spill and aromatics leakage.


Nonselective currents and channels in plasma membranes of protoplasts from coats of developing seeds of bean.
In developing bean (Phaseolus vulgaris) seeds, phloem-imported nutrients move in the symplast from sieve elements to the ground parenchyma cells where they are transported across the plasma membrane into the seed apoplast. To study the mechanisms underlying this transport, channel currents in ground parenchyma protoplasts were characterized using patch clamp. A fast-activating outward current was found in all protoplasts, whereas a slowly activating outward current was observed in approximately 25% of protoplasts. The two currents had low selectivity for univalent cations, but the slow current was more selective for K(+) over Cl(-) (P(K):P(Cl) = 3.6-4.2) than the fast current (P(K):P(Cl) = 1.8-2.5) and also displayed Ca(2+) selectivity. The slow current was blocked by Ba(2+), whereas both currents were blocked by Gd(3+) and La(3+). Efflux of K(+) from seed coat halves was inhibited 25% by Gd(3+) and La(3+) but was stimulated by Ba(2+) and Cs(+), suggesting that only the fast current may be a component in the pathway for K(+) release. An "instantaneous" inward current observed in all protoplasts exhibited similar pharmacology and permeability for univalent cations to the fast outward current. In outside-out patches, two classes of depolarization-activated cation-selective channels were observed: one slowly activating of low conductance (determined from nonstationary noise to be 2.4 pS) and another with conductances 10-fold higher. Both channels occurred at high density. The higher conductance channel in 10 mM KCl had P(K):P(Cl) = 2.8. Such nonselective channels in the seed coat ground parenchyma cell could function to allow some of the efflux of phloem-imported univalent ions into the seed apoplast.


[Effects of CD147 on the production of matrix metalloproteinase-9 by fibroblasts and the invasion of melanoma cells].
To investigate a possible role of CD147 in the production of matrix metalloproteinase-9 (MMP-9) by fibroblasts and the invasion of melanoma cells. We cocultured CD147-expression melanoma cells with fibroblasts and examined the MMP-9 expression of fibroblasts by zymography and the invasion of melanoma cells by transwell invasion assay. MMP-9 expression was enhanced in conditioned media, while cocultured with melanoma cells in a dose-dependent manner, and CD147 antibody inhibited the production of MMP-9 in the fibroblasts. When fibroblasts were cultured at the bottom of the lower compartment of transwell invasion model, the number of melanoma cells that invaded significantly increased. Addition of anti-CD147 antibody to the upper compartment transwell invasion model resulted in the significant inhibition of the melanoma cell invasion in reconstituted basement membrane. CD147 expressed in melanoma cells plays an important role in the melanoma cell invasion by stimulating the production of MMP-9 by fibroblasts.


De novo KCNA6 variants with attenuated KV 1.6 channel deactivation in patients with epilepsy.
Mutations in the genes encoding neuronal ion channels are a common cause of Mendelian neurological diseases. We sought to identify novel de novo sequence variants in cases with early infantile epileptic phenotypes and neurodevelopmental anomalies. Following clinical diagnosis, we performed whole exome sequencing of the index cases and their parents. Identified channel variants were expressed in Xenopus oocytes and their functional properties assessed using two-electrode voltage clamp. We identified novel de novo variants in KCNA6 in four unrelated individuals variably affected with neurodevelopmental disorders and seizures with onset in the first year of life. Three of the four identified mutations affect the pore-lining S6 α-helix of KV 1.6. A prominent finding of functional characterization in Xenopus oocytes was that the channel variants showed only minor effects on channel activation but slowed channel closure and shifted the voltage dependence of deactivation in a hyperpolarizing direction. Channels with a mutation affecting the S6 helix display dominant effects on channel deactivation when co-expressed with wild-type KV 1.6 or KV 1.1 subunits. This is the first report of de novo nonsynonymous variants in KCNA6 associated with neurological or any clinical features. Channel variants showed a consistent effect on channel deactivation, slowing the rate of channel closure following normal activation. This specific gain-of-function feature is likely to underlie the neurological phenotype in our patients. Our data highlight KCNA6 as a novel channelopathy gene associated with early infantile epileptic phenotypes and neurodevelopmental anomalies.


A simple method for atraumatic control of small vessels.
The use of a surgical clip to maintain tension on an elastic band provides gentle temporary occlusion without special instruments or equipment.


Characterization of Gut Microbiota in Prenatal Cold Stress Offspring Rats by 16S rRNA Sequencing.
Our previous study showed a reduction of anxiety-like behavior in offspring rats suffered from prenatal cold stress; whether this was related to changes in the offspring gut microbiota is unclear. To obtain the evidence for the role of the gut microbiota in prenatal cold stress offspring, 16S rRNA sequencing technology was used. Male and female offspring rat feces were collected from a room temperature group and a prenatal cold stress group (n ≥ 8) for microbial DNA extraction, followed by 16S rRNA sequencing. The results indicated that prenatal cold stress could change the offspring's gut microbiota composition. Prenatal cold stress significantly upregulates Lactobacillus, Lactobacillus_gasseri, Bacteroides, and Bacteroides-acidifaciens in female offspring, whereas prenatal cold stress significantly reduced Lachnospiraceae and Prevotellaceae in male offspring. These data showed the characterization of gut microbiota in prenatal cold stress offspring rats, and these data suggest that microbiological intervention in the future can potentially prevent the negative effects caused by cold stress to animals.


Selective preconcentration of chemical warfare agent degradation products using a zirconia preconcentration column.
Zirconia (ZrO(2)) has strong Lewis acid sites which have an affinity for the strongly electronegative phosphonate group of organo-phosphates. To investigate whether this affinity can be used for selective preconcentration, the retention of methyl, ethyl, and propylphosphonic acid (MPA, EPA and PPA) and inorganic anion matrix components on ZrO(2) was investigated. Only organo-phosphates and sulfate exhibited retention on zirconia. After preconcentration, the retained species were eluted from ZrO(2) by 0.75 mM Na(2)CO(3), and separated by a Dionex Ionpac AS11 anion-exchange column (250 mm x 2 mm I.D.) and a Hypercarb RPLC column (50 mm x 4.6 mm I.D., 3 microm) in series followed by suppressed conductivity detection. Calibration curve showed a linear response for MPA, EPA and PPA in the range of 0.01 microM to 1 microM (R(2)>0.9989). Detection limits after preconcentration of a 10 mL sample were 0.16, 0.19 and 0.16 microg/L for MPA, EPA, and PPA, respectively.


Site of action of a ribosomal RNA methylase responsible for resistance to erythromycin and other antibiotics.
The enzyme which confers resistance to erythromycin in the producing organism Streptomyces erythraeus dimethylates a single adenine residue in Bacillus stearothermophilus 23 S rRNA. This corresponds to residue Ade 2058 in Escherichia coli 23 S RNA. The methylase responsible for resistance to macrolides, lincomycin, and streptogramin B-related antibiotics in Staphylococcus aureus also acts at this site.


Immunomodulatory effects of temperature and pH of water in an Indian freshwater sponge.
Eunapius carteri, a freshwater sponge of India, inhabits the ponds and lakes and experiences variations of temperature and pH of water throughout the year. Sponges bear evolutionary and ecological importance with limited information on their immunological attribute and adaptational resilience in a changing environment. This paper reports temperature and pH specific responses of immune related parameters in sponge maintained in the experimental conditions of laboratory. Innate immunological parameters like phagocytosis and generation of cytotoxic molecules like superoxide anion, nitric oxide and phenoloxidase activity were estimated in E. carteri at different environmentally realistic water temperatures (10, 20, 30 and 40°C) and pH (6.4, 7.4 and 8.4). Phagocytosis and cytotoxicity are established as important immune parameters of invertebrates. Calalase, an antioxidant enzyme and phosphatases are involved in pathogen destruction and are considered as components of innate immunity. Activities of catalase, acid and alkaline phosphatases were estimated in E. carteri at different thermal regimes and pH. Modulation of phagocytic and cytotoxic responses and the activities of catalase and phosphatases at different water temperatures and pH indicated temperature and pH specific immunological status of E. carteri. Present investigation deals with the effects of selected hydrological parameters on the fundamental immune related parameters in sponge indicating its adaptational plasticity. Immunological resilience of this species in the face of variation of water temperature and pH is thought to be a special adaptive feature of sponge, a reported "living fossil".


A Survey of Acupuncture-Providing Registered Massage Therapists in Ontario, Canada: Motivation, Training, and Practice Characteristics.
An increasing number of licensed massage therapists in several countries are providing acupuncture to their clients, but little is known about this practice. To characterize the motivations, training backgrounds, practice patterns, and clinical experiences of licensed massage therapists who perform acupuncture. The study used a cross-sectional, online survey design involving acupuncture-providing registered massage therapists (RMTs) in the province of Ontario, Canada, where acupuncture is explicitly permitted within the massage therapy profession's scope. Analysis involved descriptive statistics and thematic content analysis of qualitative findings. The survey response rate was 33.7% (n=212), representing 25.5% of all Ontario RMTs rostered to practice acupuncture. Participant demographics mirrored the RMT profession as a whole, except that providers were, on average, several years older than other RMTs. Most respondents (72.7%) had completed over 200 hours of training in acupuncture; most training included clean needle technique (96.8%), clinical supervision (93.5%), traditional Chinese medicine content (83.4%), and a final examination (96.8%). Respondents typically used acupuncture in about one-third of their sessions (mean 32.3%, SD 5.0) with an average of 10.5 weekly clients (SD 14.3). Acupuncture-providing RMTs had been initially motivated by acupuncture's potential effectiveness for musculoskel-etal conditions (97.2%), a wish to attract more clients (61.3%), and physical fatigue from delivering manual therapies (48.3%). Most reported being more likely to achieve excellent clinical results (84.9%), experience greater professional satisfaction (79.9%), and attract or retain clients (64.8%) since using acupuncture. A minority also reported earning a higher income (34.6%) and experiencing more adverse events in practice (21.5%). Qualitative responses added explanatory nuance to numeric results. This study of the use of acupuncture by Ontario's licensed massage therapists represents a first scholarly account of an emerging global trend that holds promise in enhancing clinical care, professional stability, and provider longevity. Additional research is needed to investigate the practice's use in other jurisdictions, and to establish international standards for safe and effective practice.


Combined Radiological and Endoscopic Evaluation of Sino Nasal Anatomical Variations in Patients of Chronic Rhinosinusitis: A North Indian Study.
To determine the prevalence of anatomical variations of nasal cavity and paranasal sinuses of patients with chronic rhinosinusitis (CRS) on CT scan imaging. To correlate the Anatomical variations with the extent of CRS. 100 patients attending the ENT outpatient department with clinically diagnosed CRS were selected for study based on inclusion and exclusion criteria. Patients were subjected to CT scan and diagnostic nasal endoscopy. The correlation of anatomical variation with severity of CRS based on radiological score and endoscopic score was observed. Deviated nasal septum was the most common anatomical variation observed in 71% cases. Followed by Agger nasi (68%), concha bullosa (55%), Onodi cell (25%), Haller cell (14%), frontal sinus hypoplasia (2%) and uncinate bulla (1%) respectively. Statistically significant relationship of radiological score with left side Bullous Concha Bullosa and highly statistically significant relationship with Haller Cell was observed. While statistically significant relationship between Deviated Nasal Septum on left side with endoscopic score was also observed. Correlation of anatomical variation with CRS concludes on the note that some variations cause impaired sinus drainage and ventilation leading to recurrent sinusitis. Also, incidence of these variations was comparable to other studies done in asymptomatic population therefore, simply detection of a solitary anatomical variant itself does not determine predisposition to disease or the pathogenesis of the CRS and that we should have a critical look out for these anatomical variations from point of view of surgical management.


Building and revising adaptive capacity sharing for technical incident response: A case of resilience engineering.
We report an organization's method for recruiting additional, specialized human resources during anomaly handling. The method has been tailored to encourage sharing adaptive capacity across organizational units. As predicted by Woods' theory, this case shows that sharing adaptive capacity allows graceful extensibility that is particularly useful when a system is challenged by frequent but unpredictably severe events. We propose that (1) the ability to borrow adaptive capacity from other units is a hallmark of resilient systems and (2) the deliberate adjustment adaptive capacity sharing is a feature of some forms of resilience engineering. Some features of this domain that may lead to discovery of resilience and promote resilience engineering in other settings, notably hospital emergency rooms.


Ovarian sex cord tumor with annular tubules: case report and review of the literature
To report a case of ovarian sex cord tumor with annular tubules (SCTAT) and conduct a literature review on diagnosis, treatment and prognosis of this condition. Case report of a woman with a final diagnosis of advanced SCTAT seen at the National Cancer Institute in Bogota (Colombia) who received surgical treatment and chemotherapy with a satisfactory course after 6 months. A literature search was conducted in the Medline via PubMed, LILACS and Scielo databases, including case reports and series of women diagnosed with SCTAT published since 1990, not using age ranges. Information about diagnosis, treatment and reported prognosis was retrieved. A narrative summary of the findings was prepared. Fourteen publications with 26 patients were included. Mean age at diagnosis was 22.5 years. The main symptoms were menstruation abnormalities and pelvic pain. Computed tomography (CT) was the imaging technology most frequently used. Surgical treatment was used in all cases, together with chemotherapy in 29 %; 2 patients received radiotherapy. Recurrence occurred in 20 % of cases. Mortality was 12.5 %, with all deaths occurring within the first year. There is a paucity of information about the diagnostic utility of imaging, tumor markers and histochemical studies, as well as prognosis of this disease condition. Surgery is the treatment of choice, taking into consideration the patient's wishes regarding fertility, as well as the stage of the tumor. Further studies are needed to provide more detailed information about this condition.


Efficacy of Utilizing Both 3-Dimensional Multimodal Fusion Image and Intra-Arterial Indocyanine Green Videoangiography in Cerebral Arteriovenous Malformation Surgery.
An understanding of the complex morphology of an arteriovenous malformation (AVM) is important for successful resection. We have previously reported the utility of intra-arterial indocyanine green (ICG) videoangiography for this purpose, but that method cannot detect the angioarchitecture covered by brain tissue. 3-dimensional (3D) multimodal fusion imaging is reportedly useful for this same purpose, but cannot always visualize the exact angioarchitecture due to poor source images and processing techniques. This study examined the results of utilizing both techniques in patients with AVMs. Both techniques were applied in 12 patients with AVMs. Both images were compared with surgical views and evaluated by surgeons. Although evaluations for identifying superficial feeders by ICG videoangiography were high in all cases, the more complicated the AVM, the lower the evaluation by 3D multimodal fusion imaging. Conversely, evaluation of the estimated range of the nidus was high in all cases by 3D multimodal fusion imaging, but low in all but one case by ICG videoangiography. Nidus flow reduction was recognized by Flow 800 analysis obtained after ICG videoangiography. These results showed that utilizing both techniques together was more useful than each modality alone in AVM surgery. This was particularly effective in identifying superficial feeders and estimating the range of the nidus. This technique is expected to offer an optimal tool for AVM surgery.


Brain volume regulation in response to hypo-osmolality and its correction.
Hyponatremia exerts most of its clinical effects on the brain. An acute onset (usually in <24 hours) of hyponatremia causes severe, and sometimes fatal, cerebral edema. Given time, the brain adapts to hyponatremia, permitting survival despite extraordinarily low serum sodium concentrations. Adaptation to severe hyponatremia is critically dependent on the loss of organic osmolytes from brain cells. These intracellular, osmotically active solutes contribute substantially to the osmolality of cell water and do not adversely affect cell functions when their concentration changes. The adaptation that permits survival in patients with severe, chronic (>48 hours' duration) hyponatremia also makes the brain vulnerable to injury (osmotic demyelination) if the electrolyte disturbance is corrected too rapidly. The reuptake of organic osmolytes after correction of hyponatremia is slower than the loss of organic osmolytes during the adaptation to hyponatremia. Areas of the brain that remain most depleted of organic osmolytes are the most severely injured by rapid correction. The brain's reuptake of myoinositol, one of the most abundant osmolytes, occurs much more rapidly in a uremic environment, and patients with uremia are less susceptible to osmotic demyelination. In an experimental model of chronic hyponatremia, exogenous administration of myoinositol speeds the brain's reuptake of the osmolyte and reduces osmotic demyelination and mortality caused by rapid correction.


Histochemical assessment of nuclear protein content and enzyme activity in confluent nonarrested and low-serum arrested WI-38 fibroblasts at mid and late population doubling levels.
Cultures of WI-38 fibroblasts maintained in low-serum medium have little mitotic activity. Such arrested cultures can serve as a useful adjunct to the normal-serum proliferating fibroblast model system of senescence since the reduced cycling activity more accurately reflects in vivo conditions. Normal-serum plateau phase cultures and 17-day low-serum arrested plateau phase cultures were examined at both mid and late population doubling levels (PDL). Acidic, basic and total nuclear protein contents were determined by staining with toluidine blue O, alkaline fast green and acid fast green, respectively. Succinate dehydrogenase and glucose-6-phosphate dehydrogenase were localized with the nitroblue tetrazolium staining reaction. Quantification of individual cell staining was done on a Vickers M85 microdensitometer. Low-serum arrested cells at both mid and late PDL showed a significant increase in acidic protein staining and a decrease in basic protein staining when compared with normal-serum nonarrested cells. Enzyme activities in arrested cells were lower than nonarrested cells at mid PDL but equivalent to nonarrested cells at late PDL. This study demonstrates that the use of selected quantitative histochemical staining in combination with cytophotometry can be employed to differentiate arrested from nonarrested fibroblast populations as well as mid PDL from late PDL cultures.


Evaluation of potential ecological risk, possible sources and controlling factors of heavy metals in surface sediment of Caohai Wetland, China.
Caohai, a plateau wetland in Southwest China, is a national nature reserve providing protection for a variety of threatened and endangered species of migrant birds (e.g., the black-necked crane Grus nigricollis). It has been experiencing the increasing environmental problems with heavy metals due to anthropogenic activities. However, the contamination of heavy metals in different habitats is unclear. Surface sediment samples from these habitats were thus collected to analyze the distribution characteristics, potential risk and possible sources for heavy metals (Cd, Hg, Pb, Zn, Ni, Cr, Cu, Be, and V). The results showed that all of Cd, Hg, Pb, Zn, Cr, and Ni concentrations exceeded the background values, and these elements (except Cr and Ni) presented comparatively high levels in habitat adjacent to urban in comparison with the other habitats. Based on the regression analysis, we found that metals with higher EFs (Cd, Hg, Pb, and Zn) were mainly controlled by anthropogenic loadings, while metals with lower EFs (Cr, Ni, Be, and V) were mainly associated with sediment properties (pH or NOM). In addition, the results from geo-accumulation index, Hakanson potential ecological risk assessment, and risk assessment code showed that Cd and Hg posed a medium to high environmental risk to the ecosystem, and the other heavy metals posed no or low risk. Therefore, to protect this wetland ecosystem and to supply a well habitat for migratory birds, greater efforts aimed at reducing anthropogenic discharges and remediating sediment contaminated with heavy metals should be pursued.


[New advances in atopic dermatitis].
Atopic Dermatitis (AD) is one of the most frequent chronic skin diseases. AD is characterized by a complex, heterogeneous pathogenesis. In this review, we highlight some selected aspects of the pathophysiology of AD, which have gained much attention during recent years. These aspects profoundly changed our view of the pathogenesis of AD and will have impact on its management.


Increased sensitivity of lymphocytes from atopic individuals to histamine-induced suppression.
Histamine depressed lymphocyte reactivity to phytohemagglutinin and, to a lesser degree, concanavalin A, when administered simultaneously with mitogen to lymphocyte cultures. Addition of histamine at later times to the cultures appeared to have a slightly enhancing effect on the lymphocyte response. Stimulation of lymphocytes with pokeweed mitogen was in some cases enhanced, even by high concentrations of histamine. Lymphocytes from atopic individuals were more sensitive to the inhibitory effect of histamine than lymphocytes from nonatopic individuals. The sensitivity appeared age-dependent, but within each age group histamine evoked significantly more suppression on lymphocytes from atopic than from nonatopic individuals. The possibility that the altered reactivity of lymphocytes to histamine, which appears to be associated with atopic allergy, is of pathogenic importance, is discussed, and a hypothesis for the development of atopic disease is proposed.


The regulation of AMPA receptor-binding sites.
A wide variety of mechanisms have been identified that can regulate the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-receptor complex. Modulation has been shown to occur at the nucleic acid level via RNA editing and alternative splicing. At the posttranslational level, processes such as phosphorylation, glycosylation, chemical modification of reactive groups on the receptor proteins, interaction with a putative receptor-associated modulatory protein, and changes in the lipid environment have been reported to regulate receptor binding and function. In this review, we discuss general aspects of the cell biology, pharmacology, and function of AMPA receptors. In particular, we focus on some factors shown to modulate agonist binding and discuss possible molecular mechanisms underlying the regulation observed.


Treatment of type 2 diabetes: a structured management plan.
The prevalence of type 2 diabetes is rising dramatically - largely due to the greater consumption of calorie-rich food combined with increasingly sedentary lifestyles - and this is set to double by 2030. Adequate management of the disease is vital to reduce the incidence of severe and life-threatening complications that arise as a consequence of diabetes. Current guidelines for the management of blood glucose levels have set target glycosylated haemoglobin (HbA(1c)) levels to <7.5%, a figure that many people do not achieve with current treatment strategies, highlighting a need for a simple, effective approach to diabetes treatment to improve glycaemic control. Recently, an algorithm for the initiation and adjustment of therapy in type 2 diabetes has been put forward in a consensus statement, which offers a structured approach to disease management. A step-wise plan for type 2 diabetes treatment, from the point of initial diagnosis to the initiation and adjustment of insulin therapy, aims to achieve glycaemic control and reduce the massive healthcare, economic and social consequences of the disease.


Patch tracheoplasty in body tissue engineering using collagenous connective tissue membranes (biosheets).
Collagenous connective tissue membranes (biosheets) are useful for engineering cardiovascular tissue in tissue engineering. The aim was to evaluate the use of biosheets as a potential tracheal substitute material in vivo in a rabbit model. Group 1: Rectangular-shaped Gore-Tex (4×7mm) was implanted into a 3×6mm defect created in the midventral portion of the cervical trachea. Group 2: Rectangular-shaped dermis was implanted into a tracheotomy of similar size. Group 3: Biosheets were prepared by embedding silicone moulds in dorsal subcutaneous pouches in rabbits for 1month. Rectangular-shaped biosheets were implanted into a tracheotomy of similar size in an autologous fashion. All groups (each containing 10 animals) were sacrificed 4weeks after implantation. All materials maintained airway structure for up to 4weeks after implantation. Regenerative cartilage in implanted Biosheets in group 3 was confirmed by histological analysis. Tracheal epithelial regeneration occurred in the internal lumen of group 3. There were significant differences in the amounts of collagen type II and glycosaminoglycan between group 3 and group 1 or 2. We confirm that cartilage can self-regenerate onto an airway patch using Biosheets.


p52 signaling promotes cellular senescence.
Nuclear factor-κB is a multi-subunit transcription factor that plays a central role in cellular senescence. We previously reported that an increase in the p52 subunit is seen in senescent cells and aged tissue. In the current work, we examined the mechanism by which p52 is activated and whether the increase in p52 promotes senescence. Using both primary mouse embryonic fibroblasts (MEFs) and WI-38 human lung fibroblasts, we examined cells after serial passage and following prolonged culture. An increase in p52 was found in the nucleus relative to pre-senescent cells. The increase in p52 protein was not reflected by an increase in NFKB2 mRNA or by an increase in the abundance of upstream activating kinases, IKKα and NIK. To examine whether p52 promotes senescence, we over-expressed mature p52 in primary MEFs. Significantly more senescence was seen compared to control, a finding not seen with p52 mutated at critical DNA binding residues. In addition, blocking p52 nuclear translocation with the peptide inhibitor, SN52, decreased β-galactosidase (β-gal) formation. Subsequent filtration studies demonstrated that proteins in conditioned media (CM) were necessary for the increase in p52 and mass spectrometry identified S100A4 and cyclophilin A (CYPA) as potential factors in CM necessary for induction of p52. The requirement of these proteins in CM for induction of p52 was confirmed using depletion and supplementation studies. In addition, we found that activation of STAT3 signaling was required for the increase in p52. Finally, genome wide ChIP-sequencing analysis confirmed that there is an increase in p52 chromatin enrichment with senescence and identified several downstream factors whose expression is regulated by increased p52 binding. These results demonstrate that p52 nuclear translocation is increased in senescent cells by factors in conditioned media and that mature p52 induces cellular senescence. The data are consistent with the prior observation that p52 is elevated in aged tissue and support the hypothesis that p52 contributes to organismal aging.


Talus osteochondral bruises and defects: diagnosis and differentiation.
Acute bone bruises of the talus after ankle injury need to be managed differently from osteochondral defects. Bone bruises have a benign course, but there may be persistent edema. A bone bruise should not delay rehabilitation unless symptoms persist or significant edema is close to the subchondral plate. Osteochondral defects have a less predictable prognosis, and rehabilitation should aim at promoting healing of the subchondral fracture. A period of nonweight bearing reduces the cyclical pressure load through the fissure and promotes healing. Surgery should be reserved for chronic symptomatic lesions or for those patients undergoing lateral ligament reconstruction.


Identification of arsenobetaine as a major arsenic compound in muscle of two demersal sharks, shortnose dogfish Squalus brevirostris and starspotted shark Mustelus manazo.
The major water-soluble arsenic compound was isolated from the muscle of shortnose dogfish Squalus brevirostris and of starspotted shark Mustelus manazo, both of which are demersal sharks. The isolated compound was identified to be arsenobetaine by its chromatographic and spectrometric analyses.


Digital epidemiology and infodemiology of hand-foot-mouth disease (HFMD) in Italy. Disease trend assessment via Google and Wikipedia.
The study aimed to evaluate the epidemiological trend of hand, foot and mouth disease (HFMD) in Italy using data on Internet search volume. A cross-sectional study design was used. Data on Internet searches were obtained from Google Trends (GT) and Wikipedia. We used the following Italian search term: "Malattia mano-piede-bocca" (Hand-foot-mouth disease, in English). A monthly time-frame was extracted, partly overlapping, from July 2015 to December 2022. GT and Wikipedia were overlapped to perform a linear regression and correlation analyses. Statistical analyses were performed using the Spearman's rank correlation coefficient (rho). A linear regression analysis was performed considering Wikipedia and GT. Search peaks for both Wikipedia and GT occurred in the months November-December during the autumn-winter season and in June during the spring-summer season, except for the period from June 2020 to June 2021, probably due to the restrictions of the COVID19 pandemic. A temporal correlation was observed between GT and Wikipedia search trends. This is the first study in Italy that attempts to clarify the epidemiology of HFMD. Google search and Wikipedia can be valuable for public health surveillance; however, to date, digital epidemiology cannot replace the traditional surveillance system.


Complete reaction mechanisms of mercury oxidation on halogenated activated carbon.
The reaction mechanisms of mercury (Hg) adsorption and oxidation on halogenated activated carbon (AC) have been completely studied for the first time using density functional theory (DFT) method. Two different halogenated AC models, namely X-AC and X-AC-X (X=Cl, Br, I), were adopted. The results revealed that HgX is found to be stable-state on the AC edge since its further desorption from the AC as HgX, or further oxidation to HgX2, are energetically unfavorable. Remarkably, the halide type does not significantly affect the Hg adsorption energy but it strongly affects the activation energy barrier of HgX formation, which obviously increases in the order HgI<HgBr<HgCl. This trend coincides with the experimental observations which reported the efficiency of halogen impregnated AC for Hg elimination significantly decreases as I-AC>Br-AC>Cl-AC. Thus, the study of the complete reaction mechanism is essential because the adsorption energy can not be used as a guideline for the rational material design in the halide impregnated AC systems. The activation energy is an important descriptor for the predictions of sorbent reactivity to the Hg oxidation process.


Thoracoscopic Radial Diaphragm Plication.
In appropriately selected patients diaphragm plication improves quality of life by alleviating dyspnea and allowing patients to return to their routine activities. Many plication techniques exist, but the optimal surgical approach remains unclear. We report our experience with a minimally invasive radial diaphragm plication technique. It offers 2 distinct advantages: (1) suture placement avoids the phrenic nerve fibers, allowing for potential nerve recovery, and (2) the interrupted radial sutures improve the distribution of tension along the flaccid muscle and may achieve a more durable repair.