Corneal Cellular and Neuroinflammatory Changes After SARS-CoV-2 Infection.
The purpose of this study was to evaluate corneal cellular and ultrastructural changes and to quantify the neuroinflammatory process in patients after mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Thirty patients after SARS-CoV-2 infection and 41 age-matched controls were examined. All subjects underwent in vivo confocal microscopy of the corneal cell layers and subbasal nerve fibers with the Heidelberg Retina Tomograph II. Semiautomated analysis of basal epithelial, anterior and posterior stromal keratocyte, and endothelial cell density was performed. Dendritic cell (DC) density and area were also calculated, and subbasal nerve plexus morphology was analyzed. The posterior stromal keratocyte density was significantly lower in patients after SARS-CoV-2 infection ( P = 0.0006). DC density in the central cornea was significantly higher in patients after SARS-CoV-2 infection ( P = 0.0004). There was a significant difference in the DC area between the 2 groups ( P < 0.0001). Significantly altered subbasal nerve fiber morphology was detected in patients after SARS-CoV-2 infection compared with healthy volunteers ( P < 0.05). Corneal cellular and ultrastructural changes demonstrated in this study suggest neuroinflammatory consequences of COVID-19 in the cornea in the absence of ophthalmoscopic alterations.


Neural correlates and predictors of speech and language development in infants at elevated likelihood for autism: a systematic review.
Autism spectrum disorder (ASD) is an increasingly prevalent and heterogeneous neurodevelopmental condition, characterized by social communicative differences, and a combination of repetitive behaviors, focused interests, and sensory sensitivities. Early speech and language delays are characteristic of young autistic children and are one of the first concerns reported by parents; often before their child's second birthday. Elucidating the neural mechanisms underlying these delays has the potential to improve early detection and intervention efforts. To fill this gap, this systematic review aimed to synthesize evidence on early neurobiological correlates and predictors of speech and language development across different neuroimaging modalities in infants with and without a family history of autism [at an elevated (EL infants) and low likelihood (LL infants) for developing autism, respectively]. A comprehensive, systematic review identified 24 peer-reviewed articles published between 2012 and 2023, utilizing structural magnetic resonance imaging (MRI; n = 2), functional MRI (fMRI; n = 4), functional near-infrared spectroscopy (fNIRS; n = 4), and electroencephalography (EEG; n = 14). Three main themes in results emerged: compared to LL infants, EL infants exhibited (1) atypical language-related neural lateralization; (2) alterations in structural and functional connectivity; and (3) mixed profiles of neural sensitivity to speech and non-speech stimuli, with some differences detected as early as 6 weeks of age. These findings suggest that neuroimaging techniques may be sensitive to early indicators of speech and language delays well before overt behavioral delays emerge. Future research should aim to harmonize experimental paradigms both within and across neuroimaging modalities and additionally address the feasibility, acceptability, and scalability of implementing such methodologies in non-academic, community-based settings.


Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation.
Colon cancer is one of the leading causes of cancer-related death worldwide, and the therapeutic application of 5-fluorouracil (5-FU) is limited due to its nonspecificity, low bioavailability, and overdose. The present study is an attempt to improve the chemotherapeutic efficacy of 5-FU in colon cancers. Therefore, we have prepared 5-FU-loaded hyaluronic acid (HA)-conjugated silica nanoparticles (SiNPs) to target to colon cancer cells. In this study, we have showed the specific binding and intracellular accumulation of targeted nanoparticles based on HA surface modifications in colon carcinoma cells. The particles had spherical shapes with sizes of approximately 130 nm. HA-conjugated nanoparticles showed a sustained release pattern for 5-FU and continuously released for 120 hours. We have further investigated the cytotoxicity potential of targeted and nontargeted nanoparticles in colo-205 cancer cells. IC50 value of 5-FU/hyaluronic acid-conjugated silica nanoparticles (HSNP) was 0.65 µg/mL compared with ~2.8 µg/mL for 5-FU/SNP after 24 hours of incubation. The result clearly showed that HA-conjugated NP was more effective in inducing apoptosis in cancer cells than nontargeted NP. The 5-FU/HSNP showed ~45% of cell apoptosis (early and late apoptosis stage) compared with only 20% for 5-FU/silica nanoparticles (SNP)-treated group. The HA-conjugated nanoparticles provide the possibility of efficient drug transport into tumors that could effectively reduce the side effects in the normal tissues. 5-FU/HSNP was highly efficient in suppressing the tumor growth in xenograft tumor model. The proportion of Ki67 in 5-FU/HSNP-treated group was significantly lower than that of either free drug or nontargeted SiNPs. Altogether, we have showed that conjugation of HA to SiNPs could result in enhanced uptake of 5-FU through CD44-mediated endocytosis uptake and could result in significant antitumor efficacy. Thus, 5-FU/HSNP could be a promising drug delivery system for colon cancer therapy.


Increasing the Compressive Strength of Helicoidal Laminates after Low-Velocity Impact upon Mixing with 0° Orientation Plies and Its Analysis.
The helicoidal laminate is a kind of nature inspired fiber reinforced polymer, and the ply orientation affects their mechanical properties for engineering structural applications. A variety of helicoidal laminates with uniform and non-linear pitch angles mixed with additional 0° plies are fabricated to investigate the impact resistance through low-velocity impact and after-impact compression tests. Additionally, helicoidal laminates with constant pitch angles, quasi-isotropic laminate, and cross-ply laminates are also fabricated for a comparative study. The impact characteristics and the compressive strength are analyzed in view of the impact model, shear stress distribution, and fracture toughness. The results suggest that 10° or 20° are the better basic pitch angles before mixing 0° orientation plies. The 0° orientation plies may affect the contact stiffness, bending stiffness, damage extent, and compressive modulus. The compressive strength reaches the highest in tests on two samples with different percentages of 0° orientation plies and ply setups. Bending stiffness also dominates the impact response. The analysis on the laminate parameters provides ideas to improve the residual strength of helicoidal laminate.


[The functional importance of the intestinal immune system. A review. 1. Orthology (author's transl)].
The functional importance of the intestinal immune system will be shown in the following report. The secretory immune system, the pool of T-lymphocytes, the K-(killer-) and NK-(natural killer-) cells, the accessory cell-system (macrophages, mast cells, granulocytes), the so-called homing and the intestinal antigenabsorption will be described and discussed.


Cognitive Investments in Academic Success: The Role of Need for Cognition at University.
Previous research has shown that Need for Cognition (NFC), the individual tendency to engage in and enjoy cognitive endeavors, contributes to academic performance. Most studies on NFC and related constructs have thereby focused on grades to capture tertiary academic success. This study aimed at a more comprehensive approach on NFC's meaning to success in university. We examined not only performance but also rather affective indicators of success. The current sample consisted of 396 students of different subjects with a mean age of 24 years (139 male). All participants took part in an online survey that assessed NFC together with school performance and further personality variables via self-report. Success in university was comprehensively operationalized including performance, satisfaction with one's studies, and thoughts about quitting/changing one's major as indicators. The value of NFC in predicting tertiary academic success was examined with correlation analyses and path analysis. NFC significantly correlated with all success variables with the highest correlation for study satisfaction. Path analysis confirmed the importance of NFC for study satisfaction showing that NFC had a significant direct effect on study satisfaction and via this variable also a significant indirect effect on termination thoughts. This study clearly indicates that NFC broadly contributes to the mastery of academic requirements and that it is worthwhile to intensify research on NFC in the context of tertiary education.


A new model for the evolution of carnivory in the bladderwort plant (utricularia): adaptive changes in cytochrome C oxidase (COX) provide respiratory power.
The evolution of carnivorous plants has been modeled as a selective tradeoff between photosynthetic costs and benefits in nutrient-poor habitats. Although possibly applicable for pitfall and flypaper trappers, more variables may be required for active trapping systems. Bladderwort (utricularia) suction traps react to prey stimuli with an extremely rapid release of elastic instability. Trap setting requires considerable energy to engage an active ion transport process whereby water is pumped out through the thin bladder walls to create negative internal pressure. Accordingly, empirical estimates have shown that respiratory rates in bladders are far greater than in leafy structures. Cytochrome C oxidase (COX) is a multi-subunit enzyme that catalyzes the respiratory reduction of oxygen to water and couples this reaction to translocation of protons, generating a transmembrane electrochemical gradient that is used for the synthesis of adenosine triphosphate (ATP). We have previously demonstrated that two contiguous cysteine residues in helix 3 of COX subunit I (COX I) have evolved under positive Darwinian selection. This motif, absent in approximately 99.9 % of databased COX I proteins from eukaryotes, Archaea, and Bacteria, lies directly at the docking point of COX I helix 3 and cytochrome C. Modeling of bovine COX I suggests the possibility that a vicinal disulfide bridge at this position could cause premature helix termination. The helix 3-4 loop makes crucial contacts with the active site of COX, and we postulate that the C-C motif might cause a conformational change that decouples (or partly decouples) electron transport from proton pumping. Such decoupling would permit bladderworts to optimize power output (which equals energy times rate) during times of need, albeit with a 20 % reduction in overall energy efficiency of the respiratory chain. A new model for the evolution of bladderwort carnivory is proposed that includes respiration as an additional tradeoff parameter.


The effects of analgesic treatment and chest physiotherapy on the complications of the patients with rib fractures that arise from blunt chest trauma.
This prospective study aims to investigate the effect of chest physiotherapy and analgesic therapy on the possible complications of isolated rib fractures attributable to blunt thoracic trauma, such as hemothorax and pneumothorax. Patients who presented to Çanakkale Onsekiz Mart University School of Medicine Hospital's Emergency Department and Thoracic Surgery outpatient clinics within the first 24 hours of the post-traumatic period and did not have additional intrathoracic complications at presentation with blunt thoracic trauma and who were diagnosed with isolated rib fractures were enrolled in this prospective research study. The groups were designated as the patients who would receive analgesic treatment only (Group A) and the patients who would receive chest physiotherapy and analgesic treatment together (Group B). Patients who had first and second rib fractures or three or more rib fractures and who did not have additional organ injury were hospitalized in the Thoracic Surgery clinics; patients who had other organ trauma were hospitalized in related clinics. Patients were reassessed on their seventh and 30th post-traumatic days with physical examination and radiologic studies. The mean age of the 114 patients were 56.3±16.4 (22-87). There were 37 (32.5%) women and 77 (67.5%) men. Each group included 57 patients. The most common form of trauma was the same-level falls (31.6%). The mean number of rib fractures of all participants was 2.6±0.7 (1-10); the median number was 1.5. Fifty-two (45.6%) patients were hospitalized. The mean length of stay was 4.0±1.1 days. At the end of their treatment and follow-up periods, pleural effusion was found in 28 patients (24.6%) out of 114 enrolled at the side of trauma. Group B had a higher number of patients with pleural effusion (43.9%) than group A (5.3%). We performed tube thoracostomy in four patients, all of which were in group B (p<0.05). As a result of this study, chest physiotherapy maneuvers have increased the incidence of late hemothorax in patients with three or more isolated rib fractures. Also, minimal hemothoraces (<300 ml) may spontaneously regress, and no additional surgical treatment are required if the proper follow-up procedures are performed. It is advisable to hospitalize the blunt thoracic trauma patients who have three or more rib fractures and who are planned to undergo chest physiotherapy and or are prone to develop additional complications because of possible risks.


Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype.
Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis from putative bCSC and reverse engineering of transcription control networks, we identified two networks associated with this phenotype. One controlled by SNAI2, TWIST1, BNC2, PRRX1 and TBX5 drives a mesenchymal or CSC-like phenotype. The second network is controlled by the SCML4, ZNF831, SP140 and IKZF3 transcription factors which correspond to immune response modulators. Immune response network expression is correlated with pathological response to chemotherapy, and in the Basal subtype is related to better recurrence-free survival. In patient-derived xenografts, the expression of these networks in patient tumours is predictive of engraftment success. Our findings point out a potential molecular mechanism underlying the balance between immune surveillance and EMT activation in breast cancer. This molecular mechanism may be useful to the development of new target therapies.


Hepatitis B virus surface protein-induced hPIAS1 transcription requires TAL1, E47, MYOG, NFI, and MAPK signal pathways.
The protein inhibitor of activated STAT1 (PIAS1) plays important roles in regulating virus-induced chronic hepatitis, but the interaction between hepatitis B virus (HBV) and hPIAS1 is not clear. Our aim was to verify if HBV encoding proteins enhance the transcription of hPIAS1 and which cis-elements and transcription factors were involved in the mechanism. In order to do, so a series of molecular biological methods, along with functional and histological studies, were performed. We found that the HBV surface protein (HBs) enhanced hPIAS1 transcription through the activities of TAL1, E47, myogenin (MYOG), and NFI, dependent on the activation of p38MAPK and ERK signaling pathways in vitro, which might contribute to the ineffectiveness of treatment in CHB patients. Furthermore, liver samples from patients with high HBsAg levels and HBV DNA displayed increased hPIAS1 expression and high levels of TAL1, E47, MYOG, and NFI, compared to those patients with low HBsAg levels and HBV DNA, and healthy controls. These findings suggest that the HBs protein-induced hPIAS1 transcription requires TAL1, E47, MYOG, NFI, and MAPK signal pathways. It provides new potential targets for antiviral therapeutic strategies for controlling HBV-associated diseases.


Clinical diabetic nephropathy in a tropical African population.
Diabetic nephropathy is the single most important disorder leading to renal failure in adults in the Western countries and it is among the first three major causes of end stage renal disease in Nigeria. The aim of this study is to show the features of clinical diabetic nephropathy in the Olabisi Onabanjo University Teaching Hospital, Ogun State, Nigeria. The study group consists of 342 consecutive diabetic patients with persistent proteinuria (positive albustix) and diabetic retinopathy, seen from January 2000 to June 2001 in the Ogun State University Teaching Hospital, Sagamu. Clinical and laboratory parameters were recorded. Students' t-test and Spearman correlation coefficient were used in analysis. The frequency of occurrence of clinical diabetic nephropathy is 28.4% with majority already symptomatic despite normal biochemistry. Mean ages of type 1 and type 2 are 26+/-7.9 years and 53.4+/-6.3 years respectively with a sex ratio of 1.2:1. Mean duration of disease is 6.5+/-3.6 years and 9.4+/-4.1 years respectively. Two hundred and seventy-one (79.2%) patients were hypertensive. Nephrotic syndrome is not a common presentation. Diabetic nephropathy is a significant problem in this environment.


Development and application of an indirect enzyme-linked immunosorbent assay based on recombinant capsid protein for the detection of mink circovirus infection.
Mink circovirus (MiCV) is a newly discovered pathogen associated with mink diarrhea. The prevalence and economic importance of this virus remain poorly understood, and no specific serological assay has been developed for the diagnosis of MiCV infection. In this study, a recombinant capsid protein antigen expressed in Escherichia coli was utilized to establish an indirect enzyme-linked immunosorbent assay (iELISA). Results revealed that the assay had no cross-reactivity with other related pathogens, and the respective sensitivity and specificity of the proposed iELISA were 92.31% and 91.67% compared with those obtained of Western blot on 138 serum samples from minks. The correlation coefficient between iELISA and Western blot was 0.838 (p > 0.05). iELISA was applied to detect MiCV antibodies in 683 clinical serum samples from different farms from the major mink industry province in China, and 21 of 24 farms with 163 of 683 (23.87%) individuals were tested positive for MiCV antibodies. The positive rates of each of the 21 flocks ranged from 2.33% to 73.68%. These results indicated that iELISA was a sensitive and specific method suitable for the large-scale detection of MiCV infections in mink. This study provided an effective method for the serological diagnosis and positive rate investigation of MiCV infection.


Donor splice mutation in the 11beta-hydroxylase (CypllB1) gene resulting in sex reversal: a case report and review of the literature.
Mutations in the gene encoding 110-hydroxylase (CYPI]BJ) are the second most common cause of congenital adrenal hyperplasia (CAH), a disorder characterized by adrenal insufficiency and virilization of female external genitalia. We describe a new case of 1113-hydroxylase CAH caused by donor splice site mutation in the CYPllB1 gene. A 46,XX patient of Pakistani descent was identified with severe virilization soon after birth. The karyotype was negative for SRY. Pelvic ultrasound showed normal uterus and cervix. Periniogram revealed a 3-cm long urogenital sinus, ACTH stimulation test showed normal 17-hydroxyprogesterone, low cortisol, elevated 11-deoxycortisol and deoxycorticosterone (DOC) levels, consistent with 11beta-hydroxylase deficiency. Glucocorticoid treatment was started on the basis of a low baseline cortisol and severely virilized external genitalia. The patient did not develop salt wasting and/or hypertension. Analysis of the CYPllBlgene revealed homozygosity for a codon 318+1G--C substitution at the 5'-splice donor site of intron 5 resulting in a missense mutation. The parents of the patients are consanguineous and are heterozygous for the same mutation. In a previous reported case a donor splice mutation was identified for the first time at the same position codon 318 of the CYPIIB1 gene. We present this case in detail along with a literature review of 11beta-hydroxylase deficiency CAH.


Nutrient dynamics at the sediment-water interface in a Mediterranean lagoon (Thau, France): influence of biodeposition by shellfish farming activities.
The Thau Lagoon, a French Mediterranean shallow lagoon, is a site where extensive shellfish farming occurs. The aim of the present work is to evaluate the role of this activity on nutrient exchange at the sediment-water interface in relation to organic matter (OM) sedimentation and degradation. Two stations inside (C5) and outside (C4) of the shellfish farming areas were sampled at three seasons. Porewater chemistry surveys and calculated diffusive fluxes were used to evaluate the trophic status of the Thau lagoon. Quantitative (Particulate Organic Carbon) as well as qualitative OM (Hydrogen Index, Carbohydrates) analyses were performed on sediments to assess OM characteristics. Results emphasized that surficial sediments at C5 are always more enriched in OM. Porewater nutrient concentrations are 10-20 times higher at C5 than at C4. In June 2003, the porewater profiles exhibit a sharp gradient at the bottom waters, indicating a hypereutrophic status, leading to an anoxic crisis.


Frequency and diagnostic outcome of bilateral recall at screening mammography.
Our study was performed to determine the frequency of recall for bilateral breast lesions at screening mammography and compare its outcome with respect to unilateral recall. We included 329 132 screening mammograms (34 889 initial screens and 294 243 subsequent screens) from a Dutch screening mammography program between January 2013 and January 2018. During a 2-year follow-up, we collected radiological data, pathology reports and surgical reports of all recalled women. At bilateral recall, the lesion with the highest Breast Imaging Reporting and Data System score was used as the index lesion when comparing screening mammography characteristics at bilateral vs unilateral recall. A total of 9806 women were recalled at screening (recall rate, 3.0%). Bilateral recall comprised 2.8% (271/9806) of all recalls. Biopsy was more frequently performed after bilateral recall than unilateral recall (54.6% [148/271] vs 44.1% [4201/9535], P < .001), yielding a lower positive predictive value (PPV) of biopsy after bilateral recall (42.6% vs 51.7%, P = .029). The PPV of recall was comparable for both groups (23.2% [63/271] vs 22.8% [2173/9535], P = .85). Invasive cancers after bilateral recall were larger than those diagnosed after unilateral recall (P = .02), but histological subtype, histologic grading, receptor status and proportions of lymph node positive cancers were comparable. Bilateral recall infrequently occurs at screening mammography. Biopsy is more frequently performed following bilateral recall, but the PPV of recall is similar for unilateral and bilateral recall. Invasive cancers of both groups show comparable pathological features except of a larger tumor size after bilateral recall.


Programmed electrical stimulation-guided encircling cryoablation concomitant to surgical ventricular reconstruction for primary prevention of ventricular arrhythmias.
Surgical ventricular reconstruction (SVR) is an effective treatment to improve left ventricular (LV) function in patients with ischaemic heart failure and an LV anterior-apical aneurysm. Ventricular arrhythmia (VA) is an important cause for morbidity and mortality in these patients. Therefore, encircling cryoablation targeting the VA substrate may be required. Programmed electrical stimulation (PES) can identify patients at risk for VA. The objective of this study was to evaluate the incidence and type of VA during long-term follow-up after PES-guided encircling cryoablation concomitant to SVR for primary prevention of VA. Thirty-eight patients without spontaneous VA referred for SVR who underwent preoperative PES were included (PES group); 27 (71%) patients inducible for aneurysm-related VA received cryoablation. A historical cohort of 39 patients without spontaneous VA, preoperative PES and antiarrhythmic surgery served as the control group. Patients were discharged with an implantable cardioverter defibrillator (ICD). During 74 ± 35 months of follow-up, no arrhythmic deaths occurred. Five-year survival for the total study population was 78%. Twenty-eight (36%) patients experienced ≥1 VA. There were no differences in the number and type of ICD therapies between groups: shocks, P = 0.699 and antitachypacing, P = 0.403. Five-year VA-free survival was 61% for the PES group and 65% for the control group (hazard ratio 1.67, P = 0.290). The majority of the patients referred for SVR without previously documented VA was inducible for aneurysm-related VA. During the follow-up, more than one-third of the patients experienced sustained VA and 25% received appropriate ICD therapy. No difference in VA occurrence or ICD therapy was observed between groups.


GlaR (YugA)-a novel RpiR-family transcription activator of the Leloir pathway of galactose utilization in Lactococcus lactis IL1403.
Bacteria can utilize diverse sugars as carbon and energy source, but the regulatory mechanisms directing the choice of the preferred substrate are often poorly understood. Here, we analyzed the role of the YugA protein (now designated GlaR-Galactose-lactose operon Regulatory protein) of the RpiR family as a transcriptional activator of galactose (gal genes) and lactose (lac genes) utilization genes in Lactococcus lactis IL1403. In this bacterium, gal genes forming the Leloir operon are combined with lac genes in a single so-called gal-lac operon. The first gene of this operon is the lacS gene encoding galactose permease. The glaR gene encoding GlaR lies directly upstream of the gal-lac gene cluster and is transcribed in the same direction. This genetic layout and the presence of glaR homologues in the closest neighborhood to the Leloir or gal-lac operons are highly conserved only among Lactococcus species. Deletion of glaR disabled galactose utilization and abrogated or decreased expression of the gal-lac genes. The GlaR-dependent regulation of the gal-lac operon depends on its specific binding to a DNA region upstream of the lacS gene activating lacS expression and increasing the expression of the operon genes localized downstream. Notably, expression of lacS-downstream genes, namely galMKTE, thgA and lacZ, is partially independent of the GlaR-driven activation likely due to the presence of additional promoters. The glaR transcription itself is not subject to catabolite control protein A (CcpA) carbon catabolite repression (CRR) and is induced by galactose. Up to date, no similar mechanism has been reported in other lactic acid bacteria species. These results reveal a novel regulatory protein and shed new light on the regulation of carbohydrate catabolism in L. lactis IL1403, and by similarity, probably also in other lactococci.


Two distinct CXC chemokine receptors (CXCR3 and CXCR4) from the big-belly seahorse Hippocampus abdominalis: Molecular perspectives and immune defensive role upon pathogenic stress.
CXC chemokine receptor 3 (CXCR3) and 4 (CXCR4) are members of the seven transmembrane G protein coupled receptor family, involved in pivotal physiological functions. In this study, seahorse CXCR3 and CXCR4 (designated as HaCXCR3 and HaCXCR4) cDNA sequences were identified from the transcriptome library and subsequently molecularly characterized. HaCXCR3 and HaCXCR4 encoded 363 and 373 amino acid long polypeptides, respectively. The HaCXCR3 and HaCXCR4 deduced proteins have typical structural features of chemokine receptors, including seven transmembrane domains and a G protein coupled receptors family 1 profile with characteristic DRY motifs. Amino acid sequence comparison and phylogenetic analysis of these two CXC chemokine receptors revealed a close relationship to their corresponding teleost counterparts. Quantitative real time PCR analysis revealed that HaCXCR3 and HaCXCR4 were ubiquitously expressed in all the tested tissues, with highest expression levels in blood cells. The seahorse blood cells and kidney HaCXCR3 and HaCXCR4 mRNA expressions were differently modulated when challenged with Edwardsiella tarda, Streptococcus iniae, lipopolysaccharide, and polyinosinic:polycytidylic acid, confirming their involvement in post immune responses.


Socket-shield Technique: A Systematic (Scoping) Review of Case Series and Case Reports.
The present study is aimed to evaluate the effectiveness of the socket-shield technique (SST) and immediate implant placement (IIP) as the treatment of choice for the stabilization of soft and hard tissues at the extraction site and correlate with patient-related and implant-related factors. An electronic search was performed on Cochrane, EBSCO host, Medline/PubMed, Scopus, Wiley Library, Google website search, and Web of Science databases from January 2010 to September 2021. The search terms used were "socket-shield technique," "modified SST," "root membrane technique," "pontic shield technique," and "immediate implant." Case report and case series, both retrospective and prospective in nature, where SST procedures were done with IIP after tooth extraction were considered for the study. However, clinical trials on animals and studies with less than 3-month follow-up after implant placement were not considered for the study. The studies were collected, analyzed, and tabulated for further analysis to evaluate the aim and objectives of the study. Preliminary search identified through databases resulted in 350 articles, which on further screening led to exclusion of 299 articles based on the selection criteria. Therefore, 51 articles were considered for the final analysis which comprised 11 case studies and 40 case reports. With a wide age-group, the maxillary anterior region was the site of choice for the SST with IIP when compared to the posterior region. Better adaptability, maintenance of ridge contour, and good success rate followed by limited complications were observed among case series and reports. SST was successful in providing stability, esthetics, with lesser marginal bone loss and higher pink esthetic scores. However, well-designed prospective case series are few in number; thereby insufficient data on its reliability and longtime stability limit its application. SST provides a promising result and better esthetic outcome with minimal requirement of soft tissue grafts, thereby increasing its popularity and its application. However, further studies with a larger sample size and effective clinical research designs with a follow-up period are a requirement to establish the procedure and its reliability.


Development of Lipid Polymer Hybrid Drug Delivery Systems Prepared by Hot-Melt Extrusion.
This study sought to develop polymer-lipid hybrid solid dispersions containing the poorly soluble drug lopinavir (LPV) by hot-melt extrusion (HME). Hence, the lipid and polymeric adjuvants were selected based on miscibility and compatibility studies. Film casting was used to assess the miscibility, whereas thermal, spectroscopic, and chromatographic analyses were employed to evaluate drug-excipient compatibility. Extrudates were obtained and characterized by physicochemical tests, including in vitro LPV dissolution. Preformulation studies led to select the most appropriate materials, i.e., the polymers PVPVA and Soluplus®, the plasticizers polyethylene glycol 400 and Kolliphor® HS15, phosphatidylcholine, and sodium taurodeoxycholate. HME processing did not result in LPV degradation and significantly increased entrapment efficiency (93.8% ± 2.8 for Soluplus® extrudate against 19.8% ± 0.5 of the respective physical mixture). LPV dissolution was also increased from the extrudates compared to the corresponding physical mixtures (p < 0.05). The dissolution improvement was considerably greater for the Soluplus®-based formulation (24.3 and 2.8-fold higher than pure LPV and PVPVA-based extrudate after 120 min, respectively), which can be attributed to the more pronounced effects of HME processing on the average size and LPV solid-state properties in the Soluplus® extrudates. Transmission electron microscopy and chemical microanalysis suggested that the polymer-lipid interactions in Soluplus®-based formulation depended on thermal processing.


Cell preparation in immune response by immune ribonucleic acid. II. Independence of T lymphocytes in immune response against T-independent antigens.
The immune response of congenitally athymic (nude) mice induced by immune ribonucleic acid (iRNA) to lipopolysaccharides of Escherichia coli 0-55 (LPS) was studied. The thymus-independent nature of the immune response of mice to LPS was confirmed and nude mice responded to LPS in a manner similar to normal mice. An iRNA preparation extracted from the spleen of nude mice immunized with LPS could induce the proliferation of rosette-forming cells (RFC) in nude mice. iRNA preparations were insensitive to treatment with deoxyribonuclease and pronase, but were inactivated by ribonuclease treatment. The active fraction of the iRNA preparation had sedimentation values in a sucrose density gradient between 7 and 16 S and comprised only a small fraction of the total RNA present in the spleen cells, thereby indicating that the active moiety was one or more species of RNA. The anamnestic response was induced by treatment with iRNA made from the spleen of nude mice immunized with LPS. An increase in the number of rosette-forming cells (RFC), plaque forming cells (PFC) and formation of humoral antibody to LPS was seen after injection with a small amount of LPS 4 weeks after iRNA treatment.


Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy.
Changes in adaptive immune cells after chemotherapy in adult acute myeloid leukemia (AML) may have implications for the success of immunotherapy. This study was designed to determine the functional capacity of the immune system in adult patients with AML who have completed chemotherapy and are potential candidates for immunotherapy. We used the response to seasonal influenza vaccination as a surrogate for the robustness of the immune system in 10 AML patients in a complete remission post-chemotherapy and performed genetic, phenotypic, and functional characterization of adaptive immune cell subsets. Only 2 patients generated protective titers in response to vaccination, and a majority of patients had abnormal frequencies of transitional and memory B-cells. B-cell receptor sequencing showed a B-cell repertoire with little evidence of somatic hypermutation in most patients. Conversely, frequencies of T-cell populations were similar to those seen in healthy controls, and cytotoxic T-cells demonstrated antigen-specific activity after vaccination. Effector T-cells had increased PD-1 expression in AML patients least removed from chemotherapy. Our results suggest that while some aspects of cellular immunity recover quickly, humoral immunity is incompletely reconstituted in the year following intensive cytotoxic chemotherapy for AML. The observed B-cell abnormalities may explain the poor response to vaccination often seen in AML patients after chemotherapy. Furthermore, the uncoupled recovery of B-cell and T-cell immunity and increased PD-1 expression shortly after chemotherapy might have implications for the success of several modalities of immunotherapy.


Expression of a tumor-associated antigen, RCAS1, in canine mammary tumors.
Receptor-binding cancer antigen expressed on SiSo cells (RCAS1), one of novel cancer cell-surface antigens, is strongly expressed in invasive cancers. RCAS1 inhibits the in vitro growth of lymphocytes such as T cells and natural killer (NK) cells, and induces apoptotic cell death. We investigated the expression of RCAS1 in canine mammary tumor cell lines and tumor cells by immunohistochemistry, and also in situ deoxyribonucleic acid (DNA) fragmentation in tumor-infiltrating lymphocytes (TILs) by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. All canine mammary tumor cell lines expressed RCAS1 at both the messenger ribonucleic acid (mRNA) and protein level. Immunohistochemically, RCAS1 was negative in 100% of normal mammary glands, but was expressed in 100% of malignant tumors examined. In most malignant mammary tumors, RCAS1 was localized in the cytoplasm with no polarity of expression. In benign mammary tumors, it was detected on the luminal surface of the tumor cell. RCAS1 expression or localization was significantly correlated with malignancy. In situ DNA fragmentation of CD3-positive TILs was observed in RCAS1-expressing tumors. RCAS1-expressing tumors, indicating a possible induction of apoptotic cell death in TILs through RCAS1 expression. These observations suggest that RCAS1 probably plays an important role in tumor progression and escape from immune surveillance in canine mammary tumors.


Effect of Hand Intensive Training on Upper Limb Function of Stroke Patients with Hemiplegia.
To analyze the effect of hand intensive training on upper limb function of stroke patients with hemiplegia. 110 stroke patients were randomly divided into two groups: the reference group and the observation group. 55 patients in the reference group were treated with routine rehabilitation treatment, including routine joint activity training, bed training, exercise therapy, and ADL ability training; 55 cases in the observation group received intensive hand training on the basis of routine rehabilitation treatment, including inducing the patient's five finger extension, forcibly pulling the fingers and wrist joints, and suddenly opening his fist after clenching his fist. The treatment period of the two groups was 5 weeks. In the comparison results of Fugl-Meyer (FMA), the exercise effect of the observation group with increased hand intensive training was significantly better than that of the control group with stroke hemiplegia treated with conventional methods. The difference was statistically significant, t < 10.000, P < 0.05; In the comparative analysis of upper limb function test (UEFT), the effect of the observation group was significantly higher than that of the reference group treated with routine rehabilitation nursing (all P < 0.05); In the comprehensive comparison of exercise ability results, the observation group was higher than the reference group in the flexibility, fineness, and fineness of activity behavior after treatment. Strengthening hand intensive training can further improve the upper limb motor function of stroke patients with hemiplegia, reduce the severity of hemiplegia, and improve the recovery effect of stroke patients. It is worthy of clinical promotion and application.


Radionuclide study of functional resolution of unilateral renal vein thrombosis.
The diagnosis of unilateral renal vein thrombosis was established in a 50-year-old woman. A functional evaluation, by means of Tc-99m DTPA, was performed almost immediately, and at intervals up to nearly eight months later. Functional return of the involved kidney could be documented by plotting the ratio of affected kidney/total kidney activity. Conservative therapy was accompanied by a return of function of the kidney to 45% of total renal activity.


Comparing the Repair of Veneered Zirconia Crowns with Ceramic or Composite Resin: An in Vitro Study.
Current techniques for repairing porcelain-chipped restorations have several limitations. With advances in CAD/CAM technology, the combination of resin cements and high-strength ceramic materials might offer new options for repairing the chipping of veneering ceramic. The purpose of this study is to compare the load-to-failure of veneered zirconia crowns repaired by different materials. Veneered zirconia crowns were made on aluminum dies (n = 10/group). Feldspathic porcelain (Vita VM9, Vident) was applied to the zirconia coping (Vita In-Ceram YZ, Vident) in a cylindrical shape (Ø 10.5 mm, height 7.5 mm). A bevel cut on the porcelain veneer (45 degree, 3 mm width) was made at one side of each crown to simulate porcelain chipping. The crowns were then divided into four different groups according to the repair materials: 1. Conventional resin composite (A; Tetric EvoCeram, Ivoclar Vivadent); 2. Flowable resin composite (B; G-aenial Universal Flo, GC america); 3. CAD/CAM milled feldspathic ceramic (C; Vita Trilux Forte, Vident); 4. CAD/CAM milled lithium disilicate glass-ceramic (D; IPS e.max CAD, Ivoclar Vivadent). Resin cement (Multilink Automix, Ivoclar Vivadent) was used to cement the CAD/CAM ceramic materials to the beveled crowns. Each crown underwent 5000 cycles of thermocycling. The strength test was performed on an Instron universal testing machine by loading force on the center of repaired part to record load-to-failure. Data were analyzed by ANOVA and Tukey HSD post-hoc tests (α = 0.05). Mean loads-to-failure (in Newton +/- SD) of repaired veneered zirconia crowns were: Gr. A: 660.0 ± 200.5; Gr. B: 681.7 ± 175.9; Gr. C: 1236.0 ± 188.8; Gr. D: 1536.3 ± 286.1. Catastrophic failure was the most dominant failure mode in every group. Few specimens exhibited cohesive failure. Only one specimen in group D had adhesive failure. Within the limitation of the study, veneered zirconia crowns repaired with CAD/CAM ceramic materials have significantly higher load-to-failure than veneered crowns repaired with resin composite (p ≤ 0.05). Traditionally, porcelain-chipped restorations are often repaired with resin composite and bonding technique. Repairing chipped porcelain with CAD/CAM ceramics fitting the fractured parts can be alternative option with potential advantages. More well-designed studies are necessary to justify this novel repair technique.


ARMS-PCR for detection of BRAF V600E hotspot mutation in comparison with Real-Time PCR-based techniques.
BRAF mutation testing is one of the best examples how modern genetic testing may help to effectively use targeted therapies in cancer patients. Since many different genetic techniques are employed to assess BRAF mutation status with no available comparison of their sensitivity and usefulness for different types of samples, we decided to evaluate our own PCR-based assay employing the amplification refractory mutation system (ARMS-PCR) to detect the most common hotspot mutation c. T1799A (p. V600E) by comparing it with two qPCR based assays: a commercially available test with hybridizing probes (TIB MOLBIOL) and high resolution melting (HRM). Positive results were verified with Sanger sequencing. DNA from two cancer cell lines with known mutation status and from tissue samples from melanoma and gastric cancer was used. ARMS-PCR was the most sensitive method with the level of detection of the mutant allele at 2%. Similar sensitivity was observed for the qPCR-based commercial test employing hybridizing probes; however, this test cannot exclude negative results from poor or low quality samples. Another qPCR-based method, HRM, had lower sensitivity with the detection level of approximately 20%. An additional drawback of HRM methodology was the inability to distinguish between wild type and mutant homozygotes in a straightforward assay, probably due to the character of this particular mutation (T\>A). Sanger sequencing had the sensitivity of the detection of mutant allele similar to HRM, approx. 20%. In conclusion, simple ARMS-PCR may be considered the method of choice for rapid, cost-effective screening for BRAF p. V600E mutation.


A Simple and Effective Transplantation Device for Zebrafish Embryos.
Classical embryological manipulations, such as removing cells and transplanting cells within or between embryos, are powerful techniques to study complex developmental processes. Zebrafish embryos are ideally suited for these manipulations since they are easily accessible, relatively large in size, and transparent. However, previously developed devices for cell removal and transplantation are cumbersome to use or expensive to purchase. In contrast, the transplantation device presented here is economical, easy to assemble, and simple to use. In this protocol, we first introduce the handling of the transplantation device as well as its assembly from commercially and widely available parts. We then present three applications for its use: generation of ectopic clones to study signal dispersal from localized sources, extirpation of cells to produce size-reduced embryos, and germline transplantation to generate maternal-zygotic mutants. Finally, we show that the tool can also be used for embryological manipulations in other species such as the Japanese rice fish medaka.


Epigallocatechin gallate inhibits the growth of MDA-MB-231 breast cancer cells via inactivation of the β-catenin signaling pathway.
Epigallocatechin gallate (EGCG), a major constituent of green tea, has potential as a treatment for a variety of diseases, including cancer. EGCG induces apoptosis and inhibits tumorigenesis through multiple signaling pathways in breast cancer cells. β-catenin signaling modulators could be useful in the prevention and therapy of breast cancer. However, the precise anticancer effect of EGCG through the β-catenin signaling pathway in breast cancer is unclear. The present study investigated the association between β-catenin expression and clinicopathological factors of breast cancer patients, and the effect of EGCG on β-catenin expression in breast cancer cells. β-catenin expression was analyzed according to the clinicopathological factors of 74 patients with breast cancer. All patients were females diagnosed with invasive ductal carcinoma. Western blot analysis revealed that β-catenin was expressed at higher levels in breast cancer tissue than in normal tissue. β-catenin expression was associated with lymph node metastasis (P=0.04), tumor-node-metastasis stage (P=0.03) and estrogen receptor status (P<0.01). EGCG decreased MDA-MB-231 cell viability and significantly downregulated the expression of β-catenin, phosphorylated Akt and cyclin D1. Remarkably, additive effects of LY294002 and wortmannin, two phosphatidylinositol-3 kinase inhibitors, were observed. The present results suggest that EGCG inhibits the growth of MDA-MB-231 cells through the inactivation of the β-catenin signaling pathway. Based on these promising results, EGCG may be a potential treatment for triple negative breast cancer patients.


Obstetric antiphospholipid syndrome: still a challenge.
Obstetric complications such as fetal death, premature delivery, preeclampsia and recurrent abortions (since chromosomal or anatomic defects have been excluded) are characteristic manifestations of antiphospholipid syndrome (APS). They can occur in patients with known APS with previous arterial or venous events in any tissue or organ, or be its first and only manifestation. Pregnancy in a patient with APS is considered high risk and the full prenatal clinical follow-up must be carried with this in mind, eliminating or minimizing concomitant thrombotic risk factors.


Potentiation of triamcinolone-induced cleft palate in mice by maternal high dietary fat.
This study investigated whether the current range in dietary fat levels, which has arisen partly in response to some major health concerns, would affect frequency of congenital anomalies if continued into the period of early pregnancy. The effect of 5.6%, or 48% of calories from fat in the maternal diet, was tested on pregnant strain CD-1 mice injected with triamcinolone in doses of 0.01 mg, 0.02 mg, 0.04 mg, or 0.06 mg per day on days 11 through 14 of gestation. Frequency of cleft palate increased with increasing doses of triamcinolone, with clefts of the palate being rare at the two lower doses. No clefts appeared without triamcinolone on either diet. In combination with triamcinolone treatment, 226 fetuses exposed to a maternal low fat diet had normal palates and 86 had cleft palates. With exposure to high fat, 186 fetuses had normal palates and 101 had cleft palates, which was a significant increase in clefting (p < 0.05). Also, the latter group showed a greater degree of retardation in palate development (p < 0.05). Thus both a greater frequency and a more severe form of clefting support the conclusion that high dietary fat potentiated the cleft palate-producing effects of triamcinolone in mice.


COVID-19 and frequent use of hand sanitizers; human health and environmental hazards by exposure pathways.
Till date no medication or vaccine is available to cope with the COVID-19 infection and infection rate is increasing drastically across the globe. Only preventive measures and healthy life style with efficient immune system have been suggested by WHO to fight and stay safe from COVID-19. WHO recommended alcohol based hand sanitizers for frequent hand hygiene, which are mainly made up from ethanol, isopropyl alcohols, hydrogen peroxides in different combinations. These preparations may become toxic to human health and environment when misused. These chemicals have known toxic and hazardous impact on environment when released by evaporation. In early five months of 2020, American Association of Poison Control Center reported 9504 alcoholic hand sanitizer exposure cases in children under the age of 12 years and recognized that even a small amount of alcohol can cause alcohol poisoning in children that is responsible for confusion, vomiting and drowsiness, and in severe cases, respiratory arrest and death. Furthermore, frequent usage of said hand sanitizers has reported increased chance of antimicrobial resistance and chance of other viral diseases. Current review is designed with main objective to highlight the toxic and serious health risks to human health and environment by frequent using hand hygiene products with alcohols based formulations.


Miracidium of Allocreadium fasciatusi Kakaji 1969 (Trematoda: Allocreadiidae).
The miracidium of Allocreadium fasciatusi has 18 epidermal cells arranged in 3 tiers according to the formula 6,8,4. In the posterior part of the miracidium there is a fully formed redia while the anterior part contains 2 fluid-filled refractile sacs which appear to store the waste material released by the redia. The 2 excretory pores of the miracidium are middorsal and midventeral rather than lateral.


Endomysial fibrosis, rather than overall connective tissue content, is the main determinant of conduction disturbances in human atrial fibrillation.
Although in persistent atrial fibrillation (AF) a complex AF substrate characterized by a high incidence of conduction block has been reported, relatively little is known about AF complexity in paroxysmal AF (pAF). Also, the relative contribution of various aspects of structural alterations to conduction disturbances is not clear. In particular, the contribution of endomysial fibrosis to conduction disturbances during progression of AF has not been studied yet. During cardiac surgery, epicardial high-density mapping was performed in patients with acutely induced (aAF, n = 11), pAF (n = 12), and longstanding persistent AF (persAF, n = 9) on the right atrial (RA) wall, the posterior left atrial wall (pLA) and the LA appendage (LAA). In RA appendages, overall and endomysial (myocyte-to-myocyte distances) fibrosis and connexin 43 (Cx43) distribution were quantified. Unipolar AF electrogram analysis showed a more complex pattern with a larger number of narrower waves, more breakthroughs and a higher fractionation index (FI) in persAF compared with aAF and pAF, with no differences between aAF and pAF. The FI was consistently higher at the pLA compared with the RA. Structurally, Cx43 lateralization increased with AF progression (aAF = 7.5 ± 8.9%, pAF = 24.7 ± 11.1%, persAF = 35.1 ± 11.4%, P < 0.001). Endomysial but not overall fibrosis correlated with AF complexity (r = 0.57, P = 0.001; r = 0.23, P = 0.20; respectively). Atrial fibrillation complexity is highly variable in patients with pAF, but not significantly higher than in patients with acutely induced AF, while in patients with persistent AF complexity is higher. Among the structural alterations studied, endomysial fibrosis, but not overall fibrosis, is the strongest determinant of AF complexity.


Pulmonary rehabilitation for acute exacerbations of COPD: A systematic review.
This systematic review summarized the evidence on the effects (benefits and harms) of pulmonary rehabilitation for individuals with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). We included randomized controlled trials comparing pulmonary rehabilitation to either active interventions or usual care regardless of setting. In March 2022, we searched MEDLINE, Scopus, CENTRAL, CINAHL and Web of Sciences, and trial registries. Record screening, data extraction and risk of bias assessment were undertaken by two reviewers. We assessed the certainty of the evidence using the GRADE approach. This systematic review included 18 studies (n = 1465), involving a combination of mixed settings (8 studies), inpatient settings (8 studies), and outpatient settings (2 studies). The studies were at high risk of performance, detection, and reporting biases. Compared to usual care, pulmonary rehabilitation probably improves AECOPD-related hospital readmissions (relative risk 0.56, 95% CI 0.36 to 0.86; moderate certainty evidence) and cardiovascular submaximal capacity (standardized mean difference 0.73, 95% CI 0.48 to 0.99; moderate certainty evidence). Low certainty evidence suggests that pulmonary rehabilitation may be beneficial on re-exacerbations, dyspnoea, and impact of disease. The evidence regarding the effects of pulmonary rehabilitation on health-related quality of life and mortality is very uncertain (very low certainty evidence). Our results indicate that pulmonary rehabilitation may be an effective treatment option for individuals with AECOPD, irrespective of setting. Our certainty in this evidence base was limited due to small studies, heterogeneous rehabilitation programs, numerous methodological weaknesses, and a poor reporting of findings that were inconsistent with each other. Trialists should adhere to the latest reporting standards to strengthen this body of evidence. The study protocol was registered in Open Science Framework (https://osf.io/amgbz/).


Improved thermal stability of Langmuir-Blodgett films through an intermolecular hydrogen bond and metal complex.
Langmuir-Blodgett (LB) films of N-octadecanoyl-L-alanine and its silver and zinc complexes have been investigated by variable-temperature Fourier transform infrared transmission spectroscopy. The thermal stability of LB films is improved through an intermolecular hydrogen bond and metal complex. The intermolecular hydrogen-bonding interaction between hydrophilic head groups in the same monolayers and the metal complex between one head group and another in the neighboring monolayers considerably increase the interaction between the corresponding hydrophobic alkyl chains. It is shown that the transformation of the triclinic subcell packing of the molecules in the LB films prior to and after the silver complex into hexagonal packing occurs before the phase transition accompanied with a change in molecular orientation. The phase transition behavior of the LB films is varied from a small temperature interval to large one depending on the hydrogen bond and metal complex.


Turning low-molecular-weight drugs into prolonged acting prodrugs by reversible pegylation: a study with gentamicin.
Pegylation is a powerful technology to prolong the action of proteins in vivo, but it is impractical for low-molecular-weight (LMW) drugs, which are usually inactivated upon such modification. Here, we have applied a recently developed strategy of reversible pegylation to gentamicin, a LMW antibiotic. Variable length polyethyleneglycol (PEG-SH) chains were covalently linked to gentamicin using two heterobifunctional agents, each containing a spontaneously hydrolyzable bond. The inactive derivatives regained full antibacterial potency upon incubation under physiological conditions in vitro, and following systemic administration to rats, they released native active gentamicin with half-lives 7- to 15-fold greater than those of systemically administered nonderivatized gentamicin. In conclusion, reversibly pegylated prodrug derivatives of gentamicin were found to be capable of releasing gentamicin for prolonged periods in vivo. Most importantly, the major drawback of conventional pegylation, namely, the loss of pharmacological potency following irreversible derivatization, has been overcome.


The haemostatic effects of the Chinese herbal drug Yunnan Bai Yao: a pilot study.
The effects of Yunnan Bai Yao on the bleeding time in rats and the blood clotting time in rabbits and man were studied. The medicinal preparation markedly shortened both the bleeding and clotting times; the decreases were significantly more intense than those inconsistently produced by starch or by starch with calcium. These preliminary findings suggest that the action of Yunnan Bai Yao appears not to be due to its pH (5.2) or to vasoconstriction, but other factors such as its calcium content or the physical effect of its particle size cannot yet be excluded.


Jugular venous catheter-associated thrombosis and fatal pulmonary embolism: A case report.
Central venous catheters related thrombosis (CRT) insertion has been shown to increase the risk of venous thromboembolism, particularly pulmonary embolism (PE). Nevertheless, deaths cased due to PE have been rarely reported. A central venous catheter was introduced through the right jugular vein during the operation due to severe septic shock from a 57-year-old male patient. Two days after surgery, the hemodynamics was stable. On the 7th day, and low molecular weight heparin calcium (4100 units, once a day) was added for anticoagulation to prevent venous thromboembolism. On the 15th day, during the process of central venous catheter removal, the patient suddenly lost consciousness, suffered cardiac arrest, and received emergency cardiopulmonary resuscitation. Jugular venous catheter-associated thrombosis and fatal PE. An acute bedside ultrasound showed a thrombus drifting with the blood stream in the right jugular vein. The lower section of the xiphoid process by echocardiography showed decreased systolic amplitude of the right atrium and right ventricle, widened and fixed inferior vena cava, and no variation with respiration. Para-sternal left ventricular long axis section showed that the right ventricular outflow tract was significantly extended, and the contraction amplitude of the anterior and posterior walls of the left ventricle decreased. Left ventricular short axis section indicated a right ventricle enlargement and ventricular septum deviation of left ventricle, showing "D" sign. Apical 4-chamber view showed that the right ventricular ratio increased and the contractile capacity decreased. One and a half million units of urokinase were immediately given trough intravenous drip. Twenty minutes after thrombolysis, the patient's autonomic heart rhythm was recovered, but continued to suffer from hypotension and coma, followed by multiple organ failure, and died 50 hours later. Recent clinical practice guidelines recommend against the routine use of any anticoagulant thromboprophylaxis in patients with central venous catheters, but for patients at particularly high risk for CRT, consideration can be given to using higher doses of anticoagulant as prophylaxis, although there are virtually no data to support this approach.


[The role of body fat rate in the evaluation of obstructive sleep apnea].
Objective: To investigate the role of body fat ratio in the evaluation of obstructive sleep apnea(OSA). Methods: A retrospective analysis was made on 174 cases (between November, 2017 and April, 2018 showed that) of sleep monitoring in the Department of Otorhinolaryngology in Peking University Third Hospital. The data included the gender, age, body fat rate, body mass index (BMI), neck circumference, and apnea-hypopnea index (AHI). The above data were analyzed by non parametric correlation analysis, receiver operating characterristic (ROC) curve analysis and multiple factor Logistic regression analysis to study the relationship between the gender,age,body fat rate,BMI,neck circumference and other indexes of the patients with AHI. Results: Nonparametric correlation analysis showed that the correlation from strong to weak to AHI among women was BMI (r=0.621, P<0.001),body fat rate (r=0.602, P<0.001), age (r=0.570, P<0.001), neck circumference (r=0.402, P=0.014), respectively. BMI (r=0.599, P<0.001), neck circumference (r=0.493, P<0.001), body fat rate (r=0.318, P<0.001), and age (r=0.256, P=0.003) among men. ROC curve analysis showed that the strong to weak index (area under curve,AUC) of the AHI>15/h among women was the body fat rate (AUC=0.884, P=0.001), BMI(AUC=0.810, P=0.008), neck circumference (AUC=0.759, P=0.027), age (AUC=0.750, P=0.033), and the male was BMI (AUC=0.765,P<0.001), neck circumference (AUC=0.720, P<0.001), age (AUC=0.634, P=0.008), and body fat rate (AUC=0.632, P=0.010), respectively. Multifactor Logistic regression analysis showed that the body fat rate (OR=1.704,95%CI=1.012-2.870) in women was an independent risk factor for AHI greater than 15/h; the age of male (OR=1. 044, 95%CI=1.005-1.085) and BMI (OR=1.285, 95%CI=1.056-1.562) were independent risk factors for AHI greater than 15/h. Conclusion: Body fat rate can be used as a new indicator for predicting the severity of OSA,especially in adult female population. In adult female moderate to severe OSA patients (AHI>15/h), compared with BMI,neck circumference and age,the body fat rate has the greatest correlation with AHI. Compared with BMI,neck circumference and age,the body fat rate has a decisive role in predicting moderate to severe OSA (AHI>15/h).


Fenretinide-induced apoptosis of human head and neck squamous carcinoma cell lines.
Squamous cell carcinoma of the head and neck (HNSCC) has a high incidence of recurrence and associated second primary malignancy. The retinoid 13-cis-retinoic acid has been shown to be effective as both a chemopreventive and chemotherapeutic agent for HNSCC, but often with treatment-limiting toxicity. The synthetic retinoid fenretinide (N-(4-hydroxyphenyl)retinamide) (HPR) has significant antiproliferative activity against a number of animal and human malignancies and has been used in clinical trials as a chemopreventive agent in patients with breast and prostate cancer and oral leukoplakia. HPR has been shown to have a toxicity profile lower than that for other retinoids used in clinical trials. The aim of this study was to investigate the effect of HPR on the growth of HNSCC cell lines in vitro. Four HNSCC cell lines (JHU-011-SCC, JHU-020-SCC, JHU-022-SCC, and FaDu) were treated with a range of concentrations of HPR for various times. After HPR exposure, cell viability was determined by tetrazolium dye (MTT) colorimetric assay, comparing cell survival with that of untreated control cells. HPR-induced apoptosis was determined by flow-cytometric deoxyribonucleic acid cell-cycle analysis, ultrastructural analysis with electron microscopy, and deoxyribonucleic acid fragmentation detected by gel electrophoresis. HPR caused significant growth inhibition in three of the four HNSCC cell lines in a dose- and time-dependent fashion. In two cell lines (JHU-011-SCC, JHU-020-SCC) a significant antiproliferative effect was achieved between 1 and 2.5 micromol/L HPR after 72 hours of treatment. By deoxyribonucleic acid cell-cycle analysis, electron microscopy, and gel electrophoresis, HPR was shown to induce apoptosis in the JHU-011-SCC and JHU-020-SCC cell lines, but not in the FaDu cell line, which was insensitive to the growth inhibitory effect of HPR. This study has demonstrated that HPR reduces cell viability in HNSCC cells in vitro at clinically relevant doses, with the growth inhibition occurring through the induction of apoptosis.


Identification of Key microRNAs and Genes in Infantile Hemangiomas.
Infantile hemangiomas (IHs) are the most frequent vascular tumors that occur during infancy. Microribonucleic acids (miRNAs) have been demonstrated as critical regulators of gene expression in various diseases. However, the function of miRNAs in IH still remains largely unknown. In the present study, we performed a miRNA microarray analysis of IH and identified 68 differentially expressed miRNAs (DEMs). In addition, miRNA-gene networks and protein-protein interactions were constructed, and the hub miRNAs and genes of IH were screened out. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used for biological analysis of DEMs and differentially expressed genes (DEGs). The pathway enrichment analysis of DEMs revealed several tumor-related pathways, including proteoglycans in cancer, signaling pathway regulating pluripotency of stem cells and TGF-beta signaling pathway. DEGs were mainly enriched in biological processes, including intracellular signal transduction, cell adhesion, and cell death. KEGG pathway analysis indicated that DEGs were enriched in tumorigenesis- and angiogenesis-related pathways such as proteoglycans in cancer, MAPK signaling pathway and Rap1 signaling pathway. Collectively, this study first established a comprehensive miRNA-gene network in IH, which should provide novel insights into IH pathogenesis and be beneficial to the understanding of neovascularization-related disorders.


A Nurse's Perspective on Visual Rehabilitation of Outpatients With Low Vision in China.
The purposes of the study were to analyze patient use and satisfaction with low vision aids (LVAs) at the Wenzhou Medical University Low Vision and Rehabilitation Center and to assess the promotion of visual rehabilitation services as a new responsibility for nurses in China. Records of 178 patients with low vision (LV) from the Low Vision and Rehabilitation Center examined between October 2015 and October 2016 included basic patient information (e.g., age, diagnosis, visual acuity, educational level) and use of LVAs (patients' own aids, daily duration of LVA use, or refusal to use aids). Sixty percent owned LVAs. Of these, 66% were obtained from a hospital, 26% were obtained from commercial stores, and others were obtained from government or gifts. Patients reported that use of LVAs was reduced because of visual fatigue (39%), inconvenience (22%), and lack of benefit (12%). Reasons for the 40% who had never used visual rehabilitation were nonreferral by doctors (76%), refusal because of inconvenience, discomfort and cosmetics (20%), or a preference for other treatments (4%). Greater awareness of LV rehabilitation by nurses, ophthalmologists, patients, and the public is necessary. Additional government support for LV rehabilitation is also required.


The anatomical and physiological properties of the visual cortex argue against cognitive penetration.
We are consciously aware of visual objects together with the minute details that characterize each object. Those details are perceived instantaneously and in parallel. V1 is the only visual area with spatial resolution and topographical exactitude matching perceptual abilities. For cognition to penetrate perception, it needs to affect V1 image representation. That is unlikely because of the detailed parallel V1 organization and the nature of top-down connections, which can influence only large parts of the visual field.


Use of Psychotropic Medications in Breastfeeding Women.
Breastfeeding women who are prescribed with psychotropic medications on a regular basis are often concerned, regarding the possible implications of such treatment on the breastfed infant. A mother's well-being has a direct influence on the well-being of the baby. However, the notorious reputation of psychotropic medications may lead to suboptimal prescribing by the physician and poor adherence by the mother. A PubMed search (from 1976 through February 2017) was conducted for commonly used psychotropic drug classes, as well as individual medications commonly prescribed in these classes, along with the MeSH terms "breastfeeding"/"lactation". In each case, we chose studies that describe the pharmacokinetics of passage into breast milk and/or adverse effects in breastfed infants. No large-scale controlled studies regarding the safety of psychotropic medications in breastfeeding mothers were reported. Based on case reports and small studies, most psychotropic medications produce low milk levels and low plasma levels in the infant, while serious adverse effects in the breastfed infant are rarely reported. Safety data for some psychotropic medications are still unavailable. According to the data available in the literature to date, most psychotropic medications are expected to produce low levels in breast milk with no clinical importance. Nevertheless, an individual risk-benefit assessment of a proposed treatment should always be performed, as inter-individual differences may have a substantial effect on the breastfeeding infant's response to the treatment. Further studies and additional objective data are needed to consolidate and improve our current knowledge of psychopharmacotherapy in breastfeeding women. Birth Defects Research 109:957-997, 2017. © 2017 Wiley Periodicals, Inc.


Spontaneous Crenosoma vulpis infection in 10 dogs: laboratory, radiographic and endoscopic findings.
Crenosoma (C.) vulpis infection was diagnosed in 10 dogs aged between 0.5 and 12 years (median 4 years) during a 4-year period. The predominant clinical sign in all dogs was coughing which lasted from 1 day to > 4 months. Hematological abnormalities included eosinophilia in 5/9 dogs, basophilia in 3/9 dogs, and mild monocytosis in 6/9 dogs. Thoracic radiographs (n = 9) were normal in 1 dog, showed a mild bronchial or interstitial pattern in 4 dogs, and moderate to marked changes (bronchial-interstitial to alveolar) in 4 dogs. Endoscopic findings (n = 9) varied from mild erythematous bronchitis (n = 3) to marked bronchitis with accumulation of large amounts of mucus (n = 2), irregular nodular mucosal surface (n = 2), accumulation of pus (n = 1), and bronchial hemorrhage (n = 1). Adult worms were observed in 2 dogs. Bronchial lavage cytology revealed inflammation with predominance of eosinophils in 7/10 dogs, eosinophils and neutrophils in 2/10 dogs, and neutrophils in 1/10 dogs. C. vulpis larvae were identified in the BAL of 5/10 dogs. Fecal examinations with the Baermann technique was the most sensitive method and positive in all 10 dogs. C. vulpis infection has to be considered in the differential diagnosis in dogs of all ages presenting with acute or chronic cough.


The use of respiratory pathogen panel nasal polymerase chain reaction testing in predicting cutaneous enteroviral infections in the pediatric population.
To characterize the relationship between the presence of enteroviral skin infection, defined as a positive skin polymerase chain reaction (PCR) test, and the nasopharyngeal (NP) respiratory pathogen panel (RPP) PCR test which includes enterovirus/rhinovirus as an analyte. A retrospective chart review was performed on 543 subjects, age 18 years or younger, who had enterovirus (EV) skin swabs performed at an academic medical center in New York City between September 2014 and November 2019. Those patients with positive EV skin PCR were considered to have an enteroviral skin infection, and those with a negative EV skin PCR were considered not to have an enteroviral skin infection. Of those 543 children who had EV skin PCR, 170 also had an NP swab RPP performed. These NP swab RPP results were characterized as positive or negative, and if positive, it was noted if the patient was positive or negative for enterovirus/rhinovirus. The positive predictive value (PPV), negative predictive value (NPV), specificity, and sensitivity of a NP swab RPP for enteroviral skin infection were then calculated. An enterovirus/rhinovirus NP swab RPP had a NPV of 95%, PPV of 43%, sensitivity of 90%, and specificity of 62% for cutaneous enterovirus infection. The enteroviral skin PCR test is an assay that was validated at this institution. In clinically suspicious cases of EV, a positive NP swab RPP for enterovirus/rhinovirus is a sensitive test. A negative test is highly predictive of not having EV on the skin. Although further data are needed, given that NP swab RPP is readily available, these data may suggest that an NP swab RPP, when appropriately utilized, can support or exclude a clinical diagnosis of cutaneous enterovirus in the pediatric population.


Comparison of the urinary protein patterns of athletes by 2D-gel electrophoresis and mass spectrometry-a pilot study.
Urinary proteins and exercise-induced proteinuria have been the subject of much research. Proteinuria has been studied in depth after different running and cycling intensities and durations and the different mechanisms of glomerular filtration and tubular dysfunction have been elucidated. The present study was carried out to compare urinary protein profiles of athletes in different sport categories (endurance sport, team sport, strength sport). Doping-control urine samples obtained from in-competition testing and specimens derived from a control group were analysed by means of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and significantly deviating protein spots were enzymatically hydrolysed and identified by nanoflow liquid chromatography-orbitrap mass spectrometry. Endurance sport samples demonstrated a significant increase of mainly medium-sized urinary proteins such as transferrin, zinc alpha-2-glycoprotein and prostaglandin H2 D-isomerase (30-80 kDa) in 2D-PAGE experiments. Proteinuria was evident in all samples after protein concentration measurements (protein/creatinine > 15 mg/mmol). Alterations were also observed in strength sport samples, which showed an increase of low molecular weight proteins or protein fragments (<30 kDa, e.g., transthyretin, CD 59 antigen or an N-terminal transferrin fragment). In contrast, the concentration measurements did not imply proteinuria but total protein excretion was in a normal range. The study provides a first overview on 2D maps of the urinary proteome after different types of exercise. Future studies may lead to the establishment of urinary protein maps that are typical for a certain type of sport or even an individual athlete. These maps may complement the blood passport of athletes in doping control.


Uncommon neurodegenerative causes of dementia.
A group of neurodegenerative diseases is outlined that affect cortical and subcortical areas of the brain. These diseases give rise to atypical forms of dementia and, unlike Alzheimer's disease (AD), are often associated with neurological symptoms. Clinical symptoms reflect the localization of the degenerative process rather than the nature of the underlying histopathology. Degeneration of the frontal and anterior temporal lobe presents initially with behavioral alterations, but later in the course, impairment of cognition and activities of daily living develops. Posterior cortical atrophy affects the parietal and occipital association cortices and causes complex visual disturbances. In corticobasal degeneration (CBD) the focus of pathology includes the frontoparietal cortex and several subcortical nuclei, causing symmetrical rigidity, bradykinesia, myoclonus and dystonia. Progressive supranuclear palsy (PSP) involves the frontal, temporal and parietal cortex as well as parts of the brain stem. Clinical features include a hypokinetic rigid syndrome with nuchal dystonia and vertical gaze palsy. Huntington's disease is a prototypical autosomal dominant disorder that affects the extrapyramidal system and causes choreatic movements in combination with personality changes and cognitive deterioration. Amyotrophic lateral sclerosis (ALS) with dementia is a neurodegeneration of the frontotemporal cortex and of the anterior horn of the spinal cord. Behavioral change similar to frontotemporal dementia (FTD) is paralleled or followed by the classic features of motor neuron disease.


Synthesis of decadeoxyribonucleotides containing N6-methyladenine, N4-methylcytosine, and 5-methylcytosine: recognition and cleavage by restriction endonucleases (nucleosides and nucleotides part 74).
The naturally-occurring modified bases, N6-methyladenine, N4-methylcytosine, and 5-methylcytosine were chemically introduced in place of the adenine or cytosine in the decadeoxyribonucleotides containing recognition sequences of Bgl II, Sau 3AI, Mbo I and Mfl I. The modified oligomers bind to the enzymes but the rates of cleavage by the enzymes are variable.


High-Resolution Network with Dynamic Convolution and Coordinate Attention for Classification of Chest X-ray Images.
The development of automatic chest X-ray (CXR) disease classification algorithms is significant for diagnosing thoracic diseases. Owing to the characteristics of lesions in CXR images, including high similarity in appearance of the disease, varied sizes, and different occurrence locations, most existing convolutional neural network-based methods have insufficient feature extraction for thoracic lesions and struggle to adapt to changes in lesion size and location. To address these issues, this study proposes a high-resolution classification network with dynamic convolution and coordinate attention (HRCC-Net). In the method, this study suggests a parallel multi-resolution network in which a high-resolution branch acquires essential detailed features of the lesion and multi-resolution feature swapping and fusion to obtain multiple receptive fields to extract complicated disease features adequately. Furthermore, this study proposes dynamic convolution to enhance the network's ability to represent multi-scale information to accommodate lesions of diverse scales. In addition, this study introduces a coordinate attention mechanism, which enables automatic focus on pathologically relevant regions and capturing the variations in lesion location. The proposed method is evaluated on ChestX-ray14 and CheXpert datasets. The average AUC (area under ROC curve) values reach 0.845 and 0.913, respectively, indicating this method's advantages compared with the currently available methods. Meanwhile, with its specificity and sensitivity to measure the performance of medical diagnostic systems, the network can improve diagnostic efficiency while reducing the rate of misdiagnosis. The proposed algorithm has great potential for thoracic disease diagnosis and treatment.


Distribution and bioavailability of ceria nanoparticles in an aquatic ecosystem model.
Along with the increasing utilization of engineered nanoparticles, there is a growing concern for the potential environmental and health effects of exposure to these newly designed materials. Understanding the behavior of nanoparticles in the environment is a basic need. The present study aims to investigate the distribution and fate of ceria nanoparticles in an aquatic system model which consists of sediments, water, hornworts, fish and snails, using a radiotracer technique. Concentrations of ceria in the samples at regular time intervals were measured. Ceria nanoparticles were readily removed from the water column and partitioned between different organisms. Both snail and fish have fast absorption and clearance abilities. Hornwort has the highest bioaccumulation factors. At the end of the experiment, sediments accumulated most of the nanoparticles with a recovery of 75.7 ± 27.3% of total ceria nanoparticles, suggesting that sediments are major sinks of ceria nanoparticles.


Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights.
Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra- or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular-targeted therapies, targeted radionuclide therapies and epigenetic modification-based therapies. These topics are trending headlines and their combination with cell-based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced.


[Tuberculosis of the bones and joints].
The incidence of tuberculosis has increased over the last several years. Bones and joints tuberculosis makes 20% of all extrapulmonary locations of tuberculosis. In Poland this form of tuberculosis is underdiagnosed. We present three cases with tuberculosis of bones, joints and lung to remind the basic principles of diagnosis and treatment.


Radial Increment of Beech (Fagus sylvatica L.) Is under a Strong Impact of Climate in the Continental Biogeographical Region of Croatia.
European beech (Fagus sylvatica L.) is an important component of forests in the alpine and continental biogeographical regions of Croatia. This study aimed to (1) analyze the long-term response of beech to climate, (2) identify potentially critical climatic conditions that could negatively affect the radial increment (RI) and vitality of beech, and (3) evaluate differences in the response of beech between the two biogeographical regions in Croatia. We used the 16 × 16 km Croatian ICP Forests Level 1 network. On a total of 25 plots, we cored between 5 and 24 trees for dendrochronological analysis. Tree-ring widths (TRW) were measured and standardized using cubic spline. TRW chronologies for the two regions were calculated and correlated to the temperature and precipitation data and Standardized Precipitation and Evapotranspiration Index (SPEI) using bootstrapped correlations. Continental region precipitation from April to August and alpine region precipitation from June to August were significantly important for RI. Temperature was less important for RI than precipitation in both regions, but the importance of the negative impact of above-average temperatures in the continental region and the positive impact of above-average precipitation in the alpine region has increased over the last two decades. A comparison with the 3-month SPEI confirmed the significant influence of high temperatures and the lack of precipitation in August on the RI of beech trees in both regions.


Closed reduction for traumatic posterior dislocation of the shoulder using the 'lever principle': two case reports and a review of the literature.
Traumatic posterior dislocation of the shoulder is frequently missed because of its rarity and the absence of characteristic symptoms. Several signs should be emphasised: an overlap of the humeral head and glenoid rim in a true anteroposterior view and the light-bulb sign in the anteroposterior view. To make an accurate and early diagnosis, use of multidirectional radiographs combined with computed tomography is recommended. Closed reduction was successfully performed under general anaesthesia using the DePalma method with slight modification--the lever principle--by pushing the medial side of the upper arm laterally to adduct the shoulder as far as possible. The dynamics of the lever principle make it a safer and more effective method of achieving a closed reduction of a posterior dislocation of the shoulder than the conventional method of solely pushing the humeral head anteriorly, especially in patients with locking of the glenohumeral joint and impression fractures.


Evaluation of an instrument to measure nurses' familiarity with emergency preparedness.
The events of September 11, 2001, and the 2005 devastation of Hurricane Katrina have emphasized the importance of educating all nurses in emergency preparedness and bioterrorism. Further evaluation (secondary data analysis) of the Emergency Preparedness Information Questionnaire (EPIQ) was conducted, to assess nurses familiarity with emergency preparedness. This study confirmed that the EPIQ, as revised, has sound psychometric characteristics (construct validity and internal reliability) as a tool to measure nurses' self-reported level of familiarity with emergency preparedness. Additional studies using the revised EPIQ should provide data to assist civilian and military nurse educators and to facilitate the development of competency-based, relevant, emergency preparedness curricula.


Rhodium(I)-Catalyzed Carboacylation/Aromatization Cascade Initiated by Regioselective C-C Activation of Benzocyclobutenones.
Described here is the first example of a rhodium-catalyzed carboacylation/aromatization cascade of a C=O bond by C-C activation. In this transformation, a reactive rhodaindanone complex is regioselectively generated and adds across a C=O bond with subsequent elimination, thus providing a unique strategy to access a multisubstituted benzofuran scaffold. A diverse range of benzofuran analogues were obtained in good yields. Mechanistic studies show a tricyclic lactone was a viable intermediate. Application of this methodology to the total synthesis of C13-deOH-viniferifuran and C13-deOH-diptoindonesin G was achieved.


Poststroke Depressive Symptoms Are Associated With Increased Oxidative Deoxyribonucleic Acid Damage.
Poststroke depression is independently associated with poor health outcomes, such as increased mortality, disability, anxiety, and lower quality of life. Identifying the potential biomarkers and detailed mechanisms of poststroke depression may improve the effectiveness of therapeutic intervention. In this cross-sectional study, the authors recruited patients with subacute ischemic stroke who were consecutively admitted for neurorehabilitation. Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9), with a cutoff based on a summed-items score of 10. Polysomnography and laboratory tests for oxidative stress and inflammation were arranged. In total, 139 patients (97 men [69.8%] and 42 women [30.2%]; mean age: 63.2 years [±13.4]) with recent ischemic stroke were recruited and divided into two groups based on their depressive symptoms. Body mass index (BMI), the Barthel Index, percentage of antidepressant usage, and percentage of rapid eye movement (REM) sleep differed significantly between the two groups. The PHQ-9 score was significantly correlated with the levels of total antioxidant capacity, C-reactive protein, and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Urinary 8-OHdG, a marker of oxidative stress to DNA, remained significantly and positively correlated with PHQ-9 scores after adjusting for BMI, sleep-onset latency, Barthel Index, mean oxyhemoglobin saturation, age, antidepressant usage, and percentage of REM sleep by using multivariate linear regression. Depressive symptoms were related to increased oxidative DNA damage in patients with subacute ischemic stroke. Urinary 8-OHdG may serve as a potential biomarker for poststroke depression. Further longitudinal studies are needed to elucidate the causal relationship between poststroke depression and elevated oxidative stress level.


Stretch-induced calcium release in smooth muscle.
Smooth muscle cells undergo substantial increases in length, passively stretching during increases in intraluminal pressure in vessels and hollow organs. Active contractile responses to counteract increased transmural pressure were first described almost a century ago (Bayliss, 1902) and several mechanisms have been advanced to explain this phenomenon. We report here that elongation of smooth muscle cells results in ryanodine receptor-mediated Ca(2+) release in individual myocytes. Mechanical elongation of isolated, single urinary bladder myocytes to approximately 120% of slack length (DeltaL = 20) evoked Ca(2+) release from intracellular stores in the form of single Ca(2+) sparks and propagated Ca(2+) waves. Ca(2+) release was not due to calcium-induced calcium release, as release was observed in Ca(2+)-free extracellular solution and when free Ca(2+) ions in the cytosol were strongly buffered to prevent increases in [Ca(2+)](i). Stretch-induced calcium release (SICR) was not affected by inhibition of InsP(3)R-mediated Ca(2+) release, but was completely blocked by ryanodine. Release occurred in the absence of previously reported stretch-activated currents; however, SICR evoked calcium-activated chloride currents in the form of transient inward currents, suggesting a regulatory mechanism for the generation of spontaneous currents in smooth muscle. SICR was also observed in individual myocytes during stretch of intact urinary bladder smooth muscle segments. Thus, longitudinal stretch of smooth muscle cells induces Ca(2+) release through gating of RYR. SICR may be an important component of the physiological response to increases in luminal pressure in smooth muscle tissues.


Exosomes Derived from IDO1-Overexpressing Rat Bone Marrow Mesenchymal Stem Cells Promote Immunotolerance of Cardiac Allografts.
The immunosuppressive activity of mesenchymal stem cells (MSCs) has been exploited to induce tolerance after organ transplantation. The indoleamine 2,3-dioxygenase (IDO) may have beneficial effects in the immunoregulatory properties of MSCs. It was recently revealed that exosomes derived from MSCs play important roles in mediating the biological functions of MSCs. This study aimed to explore the roles of exosomes derived from MSCs in the induction of immune tolerance. Dendritic cells (DCs) and T-cells were cultured with exosomes derived from rat bone marrow MSCs (BMSCs) overexpressing IDO1 or controls. For the in-vivo study, rats received heart transplants and were treated with exosomes from IDO-BMSCs and heart function was evaluated. Flow cytometry was used to detect expression of cell surface markers. Cytokine levels were detected in culture supernatants or serum samples. Protein and microRNA expressions in exosomes were investigated by chips. Exosomes from IDO-BMSCs cultured with DCs and T-cells (1) downregulated CD40, CD86, CD80, MHC-II, CD45RA, CD45RA+CD45RB, OX62, and upregulated CD274 expression, (2) increased the number of regulatory T-cells (Tregs) and decreased the number of CD8+ T-cells, and (3) decreased the levels of pro-inflammatory cytokines, but increased the levels of anti-inflammatory cytokines compared with the other groups. Transplanted rats, which were injected with exosomes from IDO-BMSCs, had reduced allograft-targeting immune responses and improved cardiac allograft function. Exosomes secreted by IDO-BMSCs exhibited significant upregulations of the immunoregulatory protein FHL-1, miR-540-3p, and a downregulation of miR-338-5p. Exosomes derived from IDO-BMSCs can be used to promote immunotolerance and prolong the survival of cardiac allografts.


Arthroscopic evaluation of intra-articular haemangiomatous lesions: a technical note.
We are describing an arthroscopy tip, which is helpful in suspected/diagnosed cases of intra-articular haemangioma of the knee. Intra-articular haemangiomas of the knee are a rare but known condition. Arthroscopy or MRI can be used for diagnosis. Arthroscopy was performed in a case of haemangioma diagnosed on MRI performed for anterior knee pain. Appearances of the haemangioma were entirely different when hydrostatic pressures inside the knee joint were different. The picture with bright strawberry coloured haemangioma was seen when lowered hydrostatic pressure in the knee allowed the haemangioma to fill up, defining its full extent. The appearance of the same haemangioma changed to a pale appearance when we allowed hydrostatic pressure to build up inside the knee. We recommend that when dealing with intra-articular haemangiomas of the knee, arthroscopy should be performed under low hydrostatic pressure for better and complete visualisation of the haemangioma, which will prevent incomplete treatment.


A serious cause of panic attack.
We report on a case of a patient with atrial fibrillation in the setting of Wolff-Parkinson-White syndrome. The patient underwent synchronized electrical cardioversion, typically considered safe and effective, which resulted in a dangerous complication for the patient (degeneration into ventricular fibrillation). Discussion of common rhythm disturbances in WPW and management strategies are reviewed.


Epigenetic alterations as biomarkers in pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) prognosis remains very poor and has only marginally improved during the last decades. Epigenetic alterations have been the focus of many recent studies and offer valuable options for PDAC detection, prognosis and treatment. DNA methylation, histone modifications and microRNA (miR) level changes can be used as biomarkers. These alterations occur early in carcinogenesis and may be specific for PDAC. Additionally, epigenetic alterations can be analyzed from cell-free DNA, free-circulating nucleosomes or shed tumor cells in blood. High-throughput methods are available for miR and DNA methylation level detection. In particular, multiple promising miR level changes have been discovered. No single epigenetic biomarker that offers a sufficient specificity has been discovered yet, but patterns containing multiple independent biomarkers exist.


[New challenges and earlier approved methods in the laboratory diagnosis of prostate cancer].
Prostate cancer is usually a disease of elderly men, however, over 40 years of age the tumor can appear at any times. PSA is a protein molecule synthesized by prostate cells. Measurement of serum PSA has revolutionized the diagnosis and treatment of prostate cancer. However, PSA is not sufficiently specific for the detection of prostate cancer, since serum PSA might also be elevated in benign prostate diseases, as well as following physical stimulation of the gland (digital rectal examination, biopsy, catheterization, or even ejaculation). To increase the specificity of PSA, different derivative parameters have been developed i.e. PSA density (ratio of PSA to prostate volume), PSA velocity (change of PSA over a time period) or age-specific reference ranges. 65-95% of circulating PSA is bound to different proteins, while the rest of PSA circulates in a non-bound form (free PSA, fPSA). In addition to fPSA, the prostate health index [phi; (-2)proPSA/fPSA×√PSA] is increasingly used to differentiate between carcinoma-induced and non-carcinoma-induced increase in PSA. PCA3 is a non-coding messenger RNA, which is 60-70-fold overexpressed by cancer cells in the prostate. Measurement of urine PCA3 appears to be more sensitive than %tPSA, and is independent of prostate volume, age or tPSA. The author reviews laboratory biomarkers related to prostate cancer, used either in the routine clinical practice, or in research. Laboratory biomarkers seem to be useful tools to reduce the incidence of advanced stage, or metastatic prostate cancer, and the cancer-related death rate. A promising perspective for the future is the detection of circulating prostate cancer cells and the profiling of microRNAs, especially on the field of tumor prognosis.


Our-component model for counseling clients with traumatic childhood abuse.
To treat the effects of traumatic childhood abuse effectively, we propose a model which incorporates information from neurophysiological, psychoeducational, cognitive, and social work literature. The four components of the model reflect the broad range of explanations for pathology posed by researchers and also support the breadth of interventions available for use with survivors of childhood abuse. The model relies on individualized assessment and treatment related to the physiological response to abuse, faulty learning, cognitive and psychological problems, and social effects of abuse. This model contributes to the literature by providing a comprehensive framework complementary to many theoretical orientations, is useful across the helping disciplines, and appropriate in multidisciplinary settings.


Differential disease symptoms and full-length genome sequence analysis for three strains of Tobacco etch virus.
Tobacco etch virus (TEV) strains HAT, Mex21, and N have been the focus of numerous studies to dissect a host resistance mechanism in Capsicum spp. Little is known, however, about their general pathogenicity and genomic sequence data are not available on the TEV strains Mex21 and N. Four Nicotiana spp. were evaluated after inoculation with each TEV strain. Nicotiana tabacum 'Kentucky 14' and N. clevelandii plants expressed varied systemic symptoms dependent on the TEV strain; however, disease severity increased from HAT (mild mosaic symptoms) to Mex21 (more severe mosaic symptoms with stunting) to N (severe chlorosis and stunting). Nicotiana tabacum 'Samsun' plants developed relatively milder symptoms and N. glutinosa plants remained symptomless, although they were systemically infected. The genome of each TEV strain was sequenced and shown to consist of 9,495 nucleotides and a polyprotein of 3,054 amino acids. Comparison of their nucleotide sequences relative to the original HAT sequence (GenBank Accession No. M11458) revealed 95, 92, and 92 % identity for HAT-AU (from Auburn University), Mex21, and N, respectively. HAT-AU had 91 % sequence identity with Mex21 and N, while Mex21 and N were more closely related with 98 % nucleotide sequence identity. Similarly, the amino acid sequence identities for the full-length polyprotein ranged from 95 % for HAT-AU when compared with N to a high of 98 % identity between Mex21 and N.