Hormonal regulation of thyroidal protein phosphokinase activities. II. Differential sensitivity of type I and type II cAMP-dependent enzymes to the treatment of rats with thyroxine.
Two cAMP-dependent protein kinase activities can be separated from rat thyroid cytosol. Their elution properties during the gel chromatography, as well as their sedimentation coefficients after sucrose-gradient ultracentrifugation and their capacity to dissociate in the presence of histones, suggest they are like the Type I and Type II protein kinases described in many other tissues. The sensitivity of the two types of kinases to thyroxine treatment is different. The activity of Type I is not changed during the first 5 days of treatment. Thereafter, it decreased by about 50% and is maintained at that level for up to one month. The activity of the Type II enzyme decreased rapidly by about 30-40% already on the second day of treatment, and after 10 days it reached 50% of the initial level. This differential reactivity of the two types of enzymes to the thyroxine treatment leads to profound modifications in their relative activities between the second and the fifth day of treatment. The significance of these results and the possible role of the two types of kinases in the control of different steps of iodine metabolism have been discussed.


[Integration of behaviorism in the technics and methods of psychologic action].
Behaviourism is described as the study, the analysis and modifications of behaviours interacting with the milieu: a unit of methods and applications is noted and a theoretical body of behaviour changes is emphasized. In the clinic, the objective attitude and statement that psychopathology is the science of abnormal behaviours and not the science of mental states, contrast behaviourism with other methods such as psychoanalysis. In therapy and revalidation, behaviourism is one of the individual or group psychological reeducation method.


Perioperative Chemotherapy versus Adjuvant Chemotherapy in Patients with Resectable Gastric Cancer: A Systematic Review with meta-analysis.
The study aimed to investigate the prognosis and safety of perioperative chemotherapy (PC) compared with adjuvant chemotherapy (AC). We systematically searched and assessed studies in PubMed, Embase, and the Cochrane Library from inception to 1st September 2022. Eighteen studies were eligible for the analysis, including 4686 patients in total. Our study found that patients with resectable gastric cancer undergoing PC had favorable prognosis on OS (HR 0.77; 95% CI 0.69 to 0.87) and DFS (HR 0.76; 95% CI 0.69 to 0.84) than those who undergoing AC. Addition of neoadjuvant chemotherapy (NAC) to AC provided higher R0 resection rate but did not increase the risk of postoperative complication rate and most of the adverse event rates. Our study demonstrated that PC shows better OS and DFS in Asians with resectable gastric cancer compared with AC. PC should be preferred because of its favorable prognosis and similar safety.


Explaining the perspective of people living with HIV on health-promoting behaviours based on Pender's model: A directed content analysis.
Health-promoting behaviours are an important challenge in people living with HIV (PLHIV). Knowing PLHIV's perspective can be helpful for more effective health-promoting behaviour planning. Therefore, the present study aims to explain PLHIV's perspective on health-promoting behaviours based on Pender's health-promotion model. A qualitative study with a directed content analysis approach. Altogether, 17 PLHIV referring to the Behavioural Diseases Consultation and Control Center in Tehran, Iran and were selected through purposive sampling. The data were collected through semi-structured individual interviews and the results were analysed through directed content analysis based on Pender's model. Data management was done by MAXQDA V10. Data analysis led to the extraction of 396 codes in 35 subcategories and 15 main categories in 6 constructs of Pender's model, including the perceived benefits (health assurance and optimal disease control), perceived barriers (insufficient knowledge and awareness, lack of motivation, adverse outcomes of the disease and socioeconomic status), perceived self-efficacy (endeavouring to have a healthy lifestyle, responsibility for one's health and that of others), activity-related affect (positive and negative feelings), the interpersonal influences (family, friends and relatives and social media) and situational influences (the resources available to the community and community's culture). In this study, the contribution of PLHIV was used and their perspectives were surveyed. The findings of this study can help policymakers and planners formulate health policies to select the most appropriate strategies and approaches to promoting effective healthy behaviours among PLHIV.


Faecal microflora and beta-glucuronidase expression are altered in an irinotecan-induced diarrhea model in rats.
Chemotherapy-induced diarrhea (CID) is a well recognized side effect of cancer treatment. However, the pathophysiology behind this debilitating side effect remains unclear. Irinotecan causes cholinergic and delayed onset diarrhea in patients, in which beta-glucuronidase produced by gut bacteria is thought to be involved. Diarrhea occurred, as expected, following irinotecan treatment. beta-glucuronidase expression increased in the jejunum and colon. Faecal flora changed quantitatively after treatment also, with increases in E. coli, Staphylococcus spp. and Clostridium spp. (all beta-glucuronidase producing) and decreases in Lactobacillus spp., Bifidobacterium spp. (both beneficial bacteria), and Bacteroides spp. (beta-glucuronidase producing, major component of intestinal flora). Rats were treated with 200 mg/kg irinotecan and killed at various time points up to 72 h. Rats were monitored for diarrhea. Sections were stained for beta-glucuronidase expression, and faecal DNA was analysed using real time PCR. Irinotecan-induced diarrhea may be caused by an increase in beta-glucuronidase producing bacteria. However, the increase in bacteria may also be caused by irinotecan, further exaggerating the toxicity of the drug and emphasising the need for these specific bacteria to be therapeutically targeted for successful treatment regimens to be accomplished.


Optimizing Pharmacist Team-Integration for ICU Patient Management: Rationale, Study Design, and Methods for a Multicentered Exploration of Pharmacist-to-Patient Ratio.
The workload of healthcare professionals including physicians and nurses in the ICU has an established relationship to patient outcomes, including mortality, length of stay, and other quality indicators; however, the relationship of critical care pharmacist workload to outcomes has not been rigorously evaluated and determined. The objective of our study is to characterize the relationship of critical care pharmacist workload in the ICU as it relates to patient-centered outcomes of critically ill patients. Optimizing Pharmacist Team-Integration for ICU patient Management is a multicenter, observational cohort study with a target enrollment of 20,000 critically ill patients. Participating critical care pharmacists will enroll patients managed in the ICU. Data collection will consist of two observational phases: prospective and retrospective. During the prospective phase, critical care pharmacists will record daily workload data (e.g., census, number of rounding teams). During the retrospective phase, patient demographics, severity of illness, medication regimen complexity, and outcomes will be recorded. The primary outcome is mortality. Multiple methods will be used to explore the primary outcome including multilevel multiple logistic regression with stepwise variable selection to exclude nonsignificant covariates from the final model, supervised and unsupervised machine learning techniques, and Bayesian analysis. Our protocol describes the processes and methods for an observational study in the ICU. This study seeks to determine the relationship between pharmacist workload, as measured by pharmacist-to-patient ratio and the pharmacist clinical burden index, and patient-centered outcomes, including mortality and length of stay.


Demonstration of specific cell-mediated anti-tumor immunity in lung cancer to autologous tissue extracts.
Cell-mediated immunity (CMI) of lung cancer patients to autologous tumor antigens was assessed by mixed lymphocyte tumor interactions (MLTI) as measured in a microculture (200 microliter) lymphocyte proliferation (LP) assay. Positive lymphoproleferative responses were observed with cryopreserved intact mitomycin-C-treated autologous tumor cells (8/12 or 67% patients reactive) and with hypotonic membrane extracts (HMP) of tumor cells (28/40 or 70%). Good correlation was found between reactivity to tumor cells and extracts in parallel testing. In contrast, HMP of autologous normal lung tissue elicited very little LP reactivity, with only one patient giving a weak response by the SI criterion and low level of n cpm. Upon repeat testing, many patients gave reproducibly positive LP responses to tumor HMP. Patients at all clinical stages of disease and with different histologic tumor types had a similar proportion of HMP reactivity. Most reactive patients responded to a broad range of protein concentrations of tumor HMP, and LP responses were frequently elicited with 1 microgram or less of HMP. Thus, HMP appear to afford a convenient source of reactive tumor antigen for assessing anti-tumor immunity.


Vidatox 30 CH has tumor activating effect in hepatocellular carcinoma.
Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate the risk of interaction with cancer therapy or worse they omit conventional therapy thus reducing the possibility of cancer remission. Herein we analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths. We found out that Vidatox increases HCC proliferation and invasion whereas it does not seem to interact with sorafenib, the orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma. Our results suggest that the concentration of Vidatox used in the present study has not anti-neoplastic effects and care must be taken in hiring Vidatox in patients with HCC.


Determination of red blood cell superoxide dismutase and glutathione peroxidase in newborns in relation to neonatal hemolysis.
Superoxide dismutase and glutathione peroxidase activities have been determined in newborns. Their mean values are approximately the same as in normal adults. In some cases a low content of superoxide dismutase and/or a high (superoxide dismutase/glutathione peroxidase) ratio are associated with hematological symptoms. In addition, a low superoxide dismutase activity is associated with hyperbilirubinemia and is present in two of the three cases showing maximal acetylphenylhdrazine-induced hemoloysis.


The permeability coefficient of the wall of a villous membrane.
The equations hitherto used to correct the permeability coefficient for the unstirred layer influence are valid only for flat membranes. Therefore, appropriate equations for membranes with a villous surface (e.g., small intestine) have been derived. They take into account the non-linear concentration gradient in the intervillous part of the unstirred layer. Quantitative information about the geometry of the villous surface and the unstirred layer thickness are needed to calculate the permeability coefficient of the membrane wall (e.g., intestinal epithelium). The concentration of highly permeable substances drops sharply already in the upper part of intervillous space, so that the tips of the villi function as effective absorbing area. The intervillous concentration gradient of a substance with a low permeability coefficient is so small, that such a substance is absorbed by the total surface area of the villous membrane. The effective absorbing area of substances with intermediate permeability coefficient lies between the described limits.


Role of KRAS and BRAF gene mutations in mucinous ovarian carcinoma.
The goals of this study were to perform a comprehensive assessment of the prevalence of KRAS oncogene mutations in invasive epithelial ovarian carcinomas of various histologic subtypes, and for any subgroup(s) in which KRAS mutation was found to be common, to address the hypothesis that those tumors without KRAS mutation had sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene. A total of 104 primary, invasive epithelial ovarian carcinomas from a 10-year period at this institution were selected for study based on histologic classification. The histologic cell type was serous in 21 cases, endometrioid in 30 cases, clear cell in 31 cases, and mucinous in 22 cases. Additional clinical and pathological information was abstracted from patient records, and pathology review was performed for all cases. Direct sequence analysis of exon 2 of the KRAS gene, containing codon 12, was performed using DNA isolated from all tumor specimens. Sequence analyses of exons 11 and 15 of the BRAF gene were performed for the 22 cases of mucinous ovarian carcinoma. Activating KRAS mutations were more common in mucinous tumors (50%) than in all other histologic types combined (5%; P < 10(-7)). Mutation of KRAS was more common in stage I tumors than in advanced stage tumors (P = 0.0004). Of the 11 mucinous tumors with KRAS mutations, 6 were of Mullerian (endocervical) type and 5 were of gastrointestinal type. No mucinous tumor was found to harbor a BRAF mutation. These data indicate that KRAS oncogene mutations exist in several histologic types of invasive epithelial ovarian carcinoma, especially stage I tumors, but are common only in tumors of mucinous histology. Mutations are equally prevalent in mucinous ovarian cancers of Müllerian and gastrointestinal types. In contrast to other solid tumor types frequently affected by KRAS mutation, mucinous ovarian cancers without a KRAS mutation have not sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene.


The preliminary results of proton and carbon ion therapy for chordoma and chondrosarcoma of the skull base and cervical spine.
To evaluate the short-term outcomes in terms of tumor control and toxicity of patients with skull base or cervical spine chordoma and chondrosarcoma treated with intensity-modulated proton or carbon-ion radiation therapy. Between 6/2014 and 7/2018, a total of 91 patients were treated in our Center. The median age was 38 (range, 4-70) years. Forty-six (50.5%) patients were treated definitively for their conditions as initial diagnosis, 45 (49.5%) patients had recurrent tumors including 14 had prior radiotherapy. The median gross tumor volume was 37.0 (range, 1.6-231.7) cc. Eight patients received proton therapy alone, 28 patients received combined proton and carbon ion therapy, 55 patients received carbon-ion therapy alone. With a median follow-up time of 28 (range, 8-59) months, the 2-year local control (LC), progression free (PFS) and overall survival (OS) rates was 86.2, 76.8, and 87.2%, respectively. Those rates for patients received definitive proton or carbon-ion therapy were 86.7, 82.8, and 93.8%, respectively. On multivariate analyses, tumor volume of > 60 cc was the only significant factor for predicting PFS (p = 0.045), while re-irradiation (p = 0.012) and tumor volume (> vs < 60 cc) (p = 0.005) were significant prognosticators for OS. Grade 1-2 late toxicities were observed in 11 patients, and one patient developed Grade 3 acute mucositis. Larger tumor volume and re-irradiation were related to inferior survival for this group of patients. Further follow-up is needed for long-term efficacy and safety.


A Novel Neutral and Mesophilic β-Glucosidase from Coral Microorganisms for Efficient Preparation of Gentiooligosaccharides.
β-glucosidases can produce gentiooligosaccharides that are lucrative and promising for the prebiotic and alternative food industries. However, the commercial production of gentiooligosaccharides using β-glucosidase is challenging, as this process is limited by the need for high thermal energy and increasing demand for the enzyme. Here, a putative β-glucosidase gene, selected from the coral microbial metagenome, was expressed in Escherichia coli. Reverse hydrolysis of glucose by Blg163 at pH 7.0 and 40 °C achieved a gentiooligosaccharide yield of 43.02 ± 3.20 g·L-1 at a conversion rate of 5.38 ± 0.40%. Transglycosylation of mixed substrates, glucose and cellobiose, by Blg163 consumed 21.6 U/0.5 g glucose/g cellobiose, achieving a gentiooligosaccharide yield of 70.34 ± 2.20 g·L-1 at a conversion rate of 15.63%, which is close to the highest yield reported in previous findings. Blg163-mediated synthesis of gentiooligosaccharides is the mildest reaction and the lowest β-glucosidase consumption reported to date.


Biologicals in the treatment of chronic rhinosinusitis with nasal polyps – position of the Polish Society of Otorhinolaryngologists –Head and Neck Surgeons and the Polish Society of Allergology experts
Chronic rhinosinusitis with nasal polyps (CRSwNP) has a significant impact on the well-being and social functions of the patient. The generalized inflammatory process with the formation of nasal polyps and excess eosinophils in the mucosa of the paranasal sinuses is called type 2 inflammation, which is mediated by Th2 lymphocytes – cells of the immune system responsible for chronic inflammatory processes. Today, we also know the key pro-inflammatory mediators against which new drugs have been developed, the so-called biological drugs, are produced in cell lines. In this document, we present currently available biologicals approved for the treatment of patients with T2-related chronic rhinosinusitis.


Medical diagnoses and growth of children residing in Russian orphanages.
Survey the health of young children residing in Russian orphanages. Retrospective chart review of all 193 'healthy' young children (105M:88F, age range 2-72 months) residing in orphanages in Murmansk, Russia. Mothers of these institutionalized children had complex histories including chronic health problems (38%), use of tobacco (41%), alcohol (39%) and illicit drugs (7%). Frequent diagnoses of the children included rickets (21%), foetal alcohol syndrome (10%), anemia (6%), developmental delay (11% mild, 25% moderate, 28% severe), behavioural problems (60%) and 'perinatal encephalopathy' (46%<1 year of age). At orphanage entry, growth delays were common (underweight 34%, short stature 25%, microcephaly 34%). During orphanage residence, height z scores further decreased (p=0.01), but head circumference improved (p<0.0001, paired t-tests). Head circumferences increased significantly in 62% of microcephalic children. Smaller children (z score<-2) at entry exhibited more rapid growth (z score/month) for weight (+0.24 vs. -0.12, p=0.04), height (+0.81 vs. -0.65, p=0.0001), and head circumference (+1.02 vs. -0.10, p=0.0004). Growth correlated with child developmental status. Young institutionalized children in Murmansk have complex medical status, social histories and frequent growth and developmental delays. Anthropometric measurements-particularly head circumference-improved during orphanage residence in children who entered with more severe growth delays.


Low oxygen atmosphere facilitates proliferation and maintains undifferentiated state of umbilical cord mesenchymal stem cells in an hypoxia inducible factor-dependent manner.
As we approach the era of mesenchymal stem cell (MSC) application in the medical clinic, the standarization of their culture conditions are of the particular importance. We re-evaluated the influences of oxygens concentration on proliferation, stemness and differentiation of human umbilical cord Wharton Jelly-derived MSCs (WJ-MSCs). Primary cultures growing in 21% oxygen were either transferred into 5% O2 or continued to grow under standard 21% oxygen conditions. Cell expansion was estimated by WST1/enzyme-linked immunosorbent assay or cell counting. After 2 or 4 weeks of culture, cell phenotypes were evaluated using microscopic, immunocytochemical, fluorescence-activated cell-sorting and molecular methods. Genes and proteins typical of mesenchymal cells, committed neural cells or more primitive stem/progenitors (Oct4A, Nanog, Rex1, Sox2) and hypoxia inducible factor (HIF)-1α-3α were evaluated. Lowering O2 concentration from 21% to the physiologically relevant 5% level substantially affected cell characteristics, with induction of stemness-related-transcription-factor and stimulation of cell proliferative capacity, with increased colony-forming unit fibroblasts (CFU-F) centers exerting OCT4A, NANOG and HIF-1α and HIF-2α immunoreactivity. Moreover, the spontaneous and time-dependent ability of WJ-MSCs to differentiate into neural lineage under 21% O2 culture was blocked in the reduced oxygen condition. Importantly, treatment with trichostatin A (TSA, a histone deacetylase inhibitor) suppressed HIF-1α and HIF-2α expression, in addition to blockading the cellular effects of reduced oxygen concentration. A physiologically relevant microenvironment of 5% O2 rejuvenates WJ-MSC culture toward less-differentiated, more primitive and faster-growing phenotypes with involvement of HIF-1α and HIF-2α-mediated and TSA-sensitive chromatin modification mechanisms. These observations add to the understanding of MSC responses to defined culture conditions, which is the most critical issue for adult stem cells translational applications.


In Vitro Fermentation Patterns and Methane Output of Perennial Ryegrass Differing in Water-Soluble Carbohydrate and Nitrogen Concentrations.
The objective of this study was to determine the effect of perennial ryegrass (PRG) forages differing in their concentration of water-soluble carbohydrates (WSC) and crude protein (CP), and collected in spring and autumn, on in vitro rumen fermentation variables, nitrogen (N) metabolism indicators and methane (CH4) output, using a batch culture system. Two contrasting PRG pastures, sampled both in autumn and spring, were used: high (HS) and low (LS) sugar pastures with WSC concentrations of 322 and 343 g/kg for HS (autumn and spring), and 224 and 293 g/kg for LS in autumn and spring, respectively. Duplicates were incubated for 24 h with rumen inocula in three different days (blocks). Headspace gas pressure was measured at 2, 3, 4, 5, 6, 8, 10, 12, 18, and 24 h, and CH4 concentration was determined. The supernatants were analysed for individual volatile fatty acids (VFA) concentrations, and NH3-N. The solid residue was analysed for total N and neutral detergent insoluble N. Another set of duplicates was incubated for 4 h for VFA and NH3-N determination. The HS produced more gas (218 vs. 204 mL/g OM), tended to increase total VFA production (52.0 mM vs. 49.5 mM at 24 h), reduced the acetate:propionate ratio (2.52 vs. 3.20 at 4 h and 2.85 vs. 3.19 at 24 h) and CH4 production relative to total gas production (15.6 vs. 16.8 mL/100 mL) and, improved N use efficiency (22.1 vs. 20.9). The contrasting chemical composition modified in vitro rumen fermentation tending to increase total VFA production, reduce the acetate:propionate ratio and CH4 concentration, and improve N use efficiency through lower rumen NH3-N.


Correlated duplications and losses in the evolution of palmitoylation writer and eraser families.
Protein post-translational modifications (PTMs) change protein properties. Each PTM type is associated with domain families that apply the modification (writers), remove the modification (erasers) and bind to the modified sites (readers) together called toolkit domains. The evolutionary origin and diversification remains largely understudied, except for tyrosine phosphorylation. Protein palmitoylation entails the addition of a palmitoyl fatty acid to a cysteine residue. This PTM functions as a membrane anchor and is involved in a range of cellular processes. One writer family and two erasers families are known for protein palmitoylation. In this work we unravel the evolutionary history of these writer and eraser families. We constructed a high-quality profile hidden Markov model (HMM) of each family, searched for protein family members in fully sequenced genomes and subsequently constructed phylogenetic distributions of the families. We constructed Maximum Likelihood phylogenetic trees and using gene tree rearrangement and tree reconciliation inferred their evolutionary histories in terms of duplication and loss events. We identified lineages where the families expanded or contracted and found that the evolutionary histories of the families are correlated. The results show that the erasers were invented first, before the origin of the eukaryotes. The writers first arose in the eukaryotic ancestor. The writers and erasers show co-expansions in several eukaryotic ancestral lineages. These expansions often seem to be followed by contractions in some or all of the lineages further in evolution. A general pattern of correlated evolution appears between writer and eraser domains. These co-evolution patterns could be used in new methods for interaction prediction based on phylogenies.


Microbial isotopic fractionation of perchlorate chlorine.
Perchlorate contamination can be microbially respired to innocuous chloride and thus can be treated effectively. However, monitoring a bioremediative strategy is often difficult due to the complexities of environmental samples. Here we demonstrate that microbial respiration of perchlorate results in a significant fractionation ( approximately -15 per thousand ) of the chlorine stable isotope composition of perchlorate. This can be used to quantify the extent of biotic degradation and to separate biotic from abiotic attenuation of this contaminant.


Cranio-cerebral erosion (growing fracture of the skull in children). Part I. Pathology.
Seventeen cases of cranio-cerebral erosion were subjected to detailed histopathological study in order to get a better insight into the pathogenesis of this lesion. It was found that the bone and brain at the site and edge of the defect show not only evidence of damage at the time of initial injury, but also of "active" progressive damage months and years later. The possible causes for continuing damage to the brain and bone are discussed.


ACLY: A biomarker of recurrence in breast cancer.
ACLY is a cytoplasmic metabolic enzyme involved in lipid synthesis. It also affects proliferation and metastasis of breast cancer. However, the correlation of ACLY expression with breast cancer recurrence is unclear. The Oncomine and TCGA databases were used to investigate the mRNA expression of ACLY in breast cancer. Immunohistochemistry (IHC) was used to evaluate ACLY expression level in tumor tissues and normal tissues from 127 breast cancer patients. Next, the prognostic role of ACLY was explored by analyzing the clinicopathological features and prognosis during follow-up. The role of ACLY in breast cancer cells drug resistance was further detected by CCK-8 assays and quantitative real-time polymerase chain reaction (qRT-PCR). ACLY mRNA and protein expression was significantly increased in the breast cancer tissues compared to normal tissues. Clinically, high ACLY levels were associated with ER status, PR status, tumor size, TNM stage, and lymph node invasion. Upregulated ACLY predicted worse tumor relapse-free survival (RFS) of breast cancer patients in univariate analyses and in multivariate models. In subgroup analysis, patients with high ACLY expression showed worse RFS in the TNM III or ER positive subgroups. Moreover, ACLY over-expression induced the resistance of breast cancer cells to docetaxel and promoted the expression of multi-drug resistant protein ABCB1/ABCG2. Our study highlights the possibility of ACLY as a potential and independent biomarker for the recurrence prediction in breast cancer patients. It may be related to ACLY promoting drug resistance in breast cancer cells.


A survey of inner city youth and their parents about participation in sports.
Several studies have explored motivating factors for sports participation for youth, but limited data is available regarding factors motivating inner-city children to participate in sports. A consecutive sample of parents (n=100 parents) and children (n=138 children) attending a health fair in an inner-city community were surveyed regarding motivating factors for enrolling in a team sport (or enrolling their child in a team sport). Parents and children indicated the importance of 10 factors (1=not very important to 4=very important) on separate but similar written surveys. "Developing healthy habits" and "Becoming physically fit and healthy" received the highest mean rankings from both parents and children. "Helping my child gain or lose weight" received one of the lowest rankings from parents. To encourage sports participation by inner-city children, health care professionals and others should emphasize identified motivational factors for children and their parents.


PAX8: a sensitive and specific marker to identify cancer cells of ovarian origin for patients prior to neoadjuvant chemotherapy.
Neoadjuvant chemotherapy followed by cytoreduction surgery has been used where an accurate cytologic or pathologic diagnosis is usually required before the initiation of neoadjuvant chemotherapy. However, it is difficult to make definitive diagnosis of presence of cancer cells, particularly gynecologic versus non-gynecologic origin, from those ascites specimens due to the absence of specific biomarkers of gynecologic cancers. In the present study, we evaluated if, in addition to the routine morphologic diagnosis, the biomarker PAX8 could be useful in recognition of ovarian epithelial cancer cells prior to the neoadjuvant chemotherapy. Two hundred and two cytology specimens including 120 pretreatment ovarian cancer samples, 60 benign controls, and 22 malignant non-gynecologic cases were studied. All cytology slides were morphologically reviewed in a blinded fashion without knowing corresponding pathology diagnosis, if present. A total of 168 cytology specimens with a cell block were stained with PAX8 and Calretinin. These included patients with potential for ovarian cancer neoadjuvant chemotherapy (n=96), metastatic cancers (n=22), and benign controls (n=50). Among the 96 ascitic samples prior to neoadjuvant chemotherapy, 76 (79%) showing morphologic features consistent with cancers of ovarian primary were all PAX+/Calretinin-. The remaining 20 (21%) cases were positive for adenocarcinoma, but morphologically unable to be further classified. Among the 22 metastatic cancers into the pelvis, one case with PAX8+/Calretinin- represented a renal cell carcinoma and the remaining 21 PAX8-/Calretinin- metastatic cancers were either breast metastasis (n=4) and the metastasis from gastrointestinal tract (n=17). Among the 50 benign control pelvic washing cases, 5 PAX8+/Calretinin-cases represented endosalpingiosis (n=4) and endometriosis (n=1), 25 PAX8-/Calretinin+cases showed reactive mesothelial cells, and the remaining 20 specimens with PAX8-/Calretinin- phenotype typically contained inflammatory or blood cells without noticeable diagnostic epithelia. PAX8 identifies all Müllerian derived benign or malignant epithelia. When combining with Calretinin, PAX8 is a sensitive marker to diagnose the carcinomas of ovarian origin, which will be ideal to be used for those patients with a possible advanced ovarian cancer prior to receiving neoadjuvant chemotherapy.


Correlations of serum cystatin C level and gene polymorphism with vascular cognitive impairment after acute cerebral infarction.
The aim of this study was to explore the possible correlations of serum cystatin C level and cystatin C gene (CST3) polymorphism with vascular cognitive impairment in patients who had acute cerebral infarction. A total of 152 patients with acute cerebral infarction were recruited in this case-control study. Patients were divided into vascular cognitive impairment (VCI) group (n = 71) and cognitive impairment no dementia (CIND) group (n = 81). The serum concentrations of cystatin C were measured with immunoturbidimetric assay while the gene polymorphisms of CST3 were determined by technique polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In the VCI group, serum cystatin C level was significantly higher than that in the control group. The frequency of the B allele was found to be higher in the VCI group as compared with that of the CIND group (18.5% vs 7.7%, p = 0.006). In logistic regression analysis, significant associations of VCI with high serum cystatin C level (OR 3.837 (1.176-12.520), p = 0.026) and CST3 B allele (OR 2.038 (1.048-3.963), p = 0.036) were also found. A high cystatin C level and CST3 B allele confer risks for VCI after acute cerebral infarction. It is probable that measurement of the serum cystatin C level and detection of CST3 gene polymorphism would aid in the early diagnosis of VCI, but further studies are warranted.


Relationship between presence of vasoconstrictor activity in cerebrospinal fluid and time after subarachnoid haemorrhage from rupture of cerebral arterial aneurysms.
The relationship between clinical condition and vasoconstrictor factors in cerebrospinal fluid was studied in 19 patients for up to six weeks after subarachnoid haemorrhage. Vasoconstrictor activity was assayed biologically. Sixteen of 19 patients improved as vasoconstrictor activity declined; this pattern was not significantly influenced by surgery. Serial angiography was performed on three patients and a qualitative relationship was shown between arterial dilatation, clinical improvement, and reduced pharmacological activity.


Surgical management of penile carcinoma in situ: results from an international collaborative study and review of the literature.
To evaluate recurrence after penile-sparing surgery (PSS) in the management of carcinoma in situ (CIS) of the penis in a large multicentre cohort of patients. We identified consecutive patients from five major academic centres, treated between June 1986 and November 2014, who underwent PSS for pathologically proven penile CIS. The primary outcome was local recurrence-free survival (RFS), which was estimated using the Kaplan-Meier method. A total of 205 patients were identified. Treatment methods included circumcision, glansectomy, wide local excision, laser therapy and total glans resurfacing. Over a median (interquartile range [IQR]) follow-up of 40 (26-65.6) months, there were 48 local recurrences, with 45.8% occurring in the first year and 81.3% occurring by year 5. The majority of recurrences were observed in the laser group (58.3%). The median (IQR) time to local recurrence was 15.9 (5.66-26.14) months. The 1- 2- and 5-year RFS rates were 88.4, 85.6 and 75%, respectively, and the median (IQR) RFS time was 106.5 (80.2-132.2) months. Among patients with penile CIS selected for surgical management, durable responses at intermediate- to long-term follow-up were noted. For those with glandular CIS, glans resurfacing offered the best outcomes.


Cornerstones to shape modeling for the 21st century: introducing the AKA-Glucose project.
In this paper, we have reflected on the historical development during the twentieth century of several major cornerstones on which the edifice of mathematical modeling in nutrition and the health sciences was built. When we consider the scope and magnitude of problems in nutrition and the health sciences that have been addressed and solved by mathematical modeling, we as a group can justifiably feel a certain amount of satisfaction. But we should not be complacent. So much more remains to be done. The increasing pace of developments in biology (e.g., the human genome project) places a whole new range of challenges before us. We can also reflect on the mathematical basis of modeling and consider that we enter the twenty-first century with a solid foundation on which to build bigger and better models. At the same time, we have at our disposal computers of immense power. At the start of the twentieth century, no one could have foreseen where we are today. In our lifetimes, computers have been developed from lumbering behemoths with the calculating ability of an abacus to the present day machines with calculating capabilitie that we are only beginning to appreciate. There is general consensus that developments in the field of computing will continue far into the twenty-first century. Therefore, w can confidently assert that developments in modeling will not be greatly limited by our present mathematical foundation or by the capabilities of computers. In this paper, we have mainly dwelt on three cornerstones: the model development environment model dissemination and database technologies data exchange and post-fitting analysis. We have focused on SAAM, WinSAAM, and AKA-Glucose as illustrating these cornerstones, while acknowledging that there are many other modeling programs that also represent them. However, a building usually has four cornerstones. If one cornerstone is missing, then there may be a structural weakness in the entire building. We contend that, at the start of the twenty-first century, the edifice of modeling is missing the important fourth cornerstone: a modeling community. As modelers, we should cease to bowl alone. Now is the time to make a new beginning, to give modeling some formality, structure, and direction. We should form a community of modelers as we move into the 21st century.


A new species of Fauveliopsidae (Annelida) from the North Sea.
A new species of the genus Laubieriopsis Petersen, 2000 is described based on 28 specimens collected in the north-east part of the North Sea. It is characterized by fixed number of chaetigers (22), paired genital papillae, bidentate neurochaeta of chaetigers 1-4, the absence of acicular chaetae on chaetigers 5-21 and, on the last chaetiger, one acicular and three capillary chaetae enlarged and directed backward. The present study brings the number of known species of Laubieriopsis to five and the number of Northeast Atlantic species of this genus to two.


A cross-sectional study on nutrient intake and -status in inflammatory bowel disease patients.
Inflammatory bowel disease (IBD) can be associated with nutritional problems. The aim of this study was to investigate diet and nutritional status of IBD patients. A total of 78 participants (35 men and 43 women aged 18-74 years) were included in this cross-sectional study. The majority (80 %) of the participant received infliximab treatment. Participants filled out disease related questionnaires and 31 participants also a 3-day food record. Body composition was measured and blood samples analysed in order to estimate nutritional status. The majority (87 %) claimed that diet affects digestive tract symptoms and 72 % had changed diet accordingly. The most common foods restricted were dairy products (60 %), processed meat (55 %), soft drinks (46 %), alcohol (45 %) and fast food (44 %). Body mass index was mostly in the overweight range but 46 % of the participants had been diagnosed with some nutritional deficiency since IBD diagnosis (most common was iron deficiency: 39 %). Patients who restricted meat products had lower ferritin values (48 ± 39 vs. 95 ± 74 μg/L, P = 0.011). Intake of vitamin D and calcium were not adequate (65 % below recommeded intake for both) and 60 % had poor vitamin D status. IBD patients often change their dietary intake in order to affect digestive tract symptoms. Many patients have a history of nutrient deficiency. Restriction of dairy and meat consumption is common and is negatively associated with intake or status of micronutrients like calcium and iron. Dietary advice by a dietitian and use of potentially helpful dietary supplements is indicated.


Kaempferol inhibits Entamoeba histolytica growth by altering cytoskeletal functions.
The flavonoid kaempferol obtained from Helianthemum glomeratum, an endemic Mexican medicinal herb used to treat gastrointestinal disorders, has been shown to inhibit growth of Entamoeba histolytica trophozoites in vitro; however, the mechanisms associated with this activity have not been documented. Several works reported that kaempferol affects cytoskeleton in mammalian cells. In order to gain insights into the action mechanisms involved in the anti-amoebic effect of kaempferol, here we evaluated the effect of this compound on the pathogenic events driven by the cytoskeleton during E. histolytica infection. We also carried out a two dimensional gel-based proteomic analysis to evidence modulated proteins that could explain the phenotypical changes observed in trophozoites. Our results showed that kaempferol produces a dose-dependent effect on trophozoites growth and viability with optimal concentration being 27.7 μM. Kaempferol also decreased adhesion, it increased migration and phagocytic activity, but it did not affect erythrocyte binding nor cytolytic capacity of E. histolytica. Congruently, proteomic analysis revealed that the cytoskeleton proteins actin, myosin II heavy chain and cortexillin II were up-regulated in response to kaempferol treatment. In conclusion, kaempferol anti-amoebic effects were associated with deregulation of proteins related with cytoskeleton, which altered invasion mechanisms.


Testing Experimental Therapies in a Guinea Pig Model for Hemorrhagic Fever.
Hemorrhagic fever viruses are among the deadliest pathogens known to humans, and often, licensed medical countermeasures are unavailable to prevent or treat infections. Guinea pigs are a commonly used animal for the preclinical development of any experimental candidates, typically to confirm data generated in mice and as a way to validate and support further testing in nonhuman primates. In this chapter, we use Sudan virus (SUDV), a lethal filovirus closely related to Ebola virus, as an example of the steps required for generating a guinea pig-adapted isolate that is used to test a monoclonal antibody-based therapy against viral hemorrhagic fevers.


Detergent induced lysis of erythrocytes in kwashiorkor.
The effect of the non-ionic detergent Nonidet P40 on lysis of erythrocytes in children suffering from kwashiorkor was studied. The concentration of the detergent causing 50% haemolysis was significantly reduced in these patients. Detergent haemolysis was more sensitive than osmotic fragility (which was reduced). The abnormality was only slight in marasmic children.


Sexual auras: predominance of epileptic activity within the mesial temporal lobe.
The occurrence of sexual auras (SAs), defined as erotic feelings accompanied by sexual arousal and orgasm, was investigated in 244 consecutive patients with medically refractory focal epilepsy. All patients were evaluated with prolonged video/EEG monitoring, high-resolution MRI, and the Wada test. One female and two male patients with hippocampal sclerosis and /or atrophy experienced SAs. In accordance with the findings on interictal and ictal EEGs, the epileptogenic zone could be localized to the speech-dominant mesial temporal lobe in one case and to the non-speech-dominant mesial temporal lobe in two cases. All patients were treated by selective amygdalohippocampectomy. Our results indicate that: (1) SAs occur in men and women, (2) SAs occur predominantly in seizures originating from the nondominant temporal lobe (but may also be associated with seizure onset in the dominant hemisphere), and (3) SAs point toward a seizure onset in mesial temporal structures.


Relationship between phthalates exposures and hyperuricemia in U.S. general population, a multi-cycle study of NHANES 2007-2016.
Phthalates exposure might cause kidney damage and a potential risk for hyperuricemia. However, direct evidence on phthalates and hyperuricemia is somewhat limited. To examine associations between 10 phthalates metabolites and hyperuricemia in a large-scale representative of the U.S. A cross-sectional study of 6865 participants aged over 20 from NHANES 2007-2016 was performed. All participants had complete data on ten phthalate metabolites (MECPP, MnBP, MEHHP, MEOHP, MiBP, cx-MiNP, MCOP, MCPP, MEP, MBzP), hyperuricemia, and covariates. We used multivariable logistics regression, restricted cubic splines (RCS) model, and Bayesian kernel machine regression (BKMR) models to assess single, nonlinear, and mixed relationships between phthalate metabolites and hyperuricemia. As a complement, we also assessed the relationship between phthalate metabolites and serum uric acid (SUA) levels. The multivariable logistics regression showed that MECPP, MEOHP, MEHHP, MBzP, and MiBP were generally positively associated with hyperuricemia (PFDR < 0.05), especially in MiBP (Q3 (OR (95 %): 1.31 (1.02, 1.68)) and Q4 (OR (95 %): 1.68 (1.27, 2.24)), compared to Q1). All ten phthalate metabolites had a linear dose-response relationship with hyperuricemia in the RCS model (P for non-linear >0.05). BKMR showed that mixed phthalate metabolites were associated with a higher risk of hyperuricemia, with MBzP contributing the most (groupPIP = 0.999, condPIP = 1.000). We observed the consistent results between phthalate metabolites and SUA levels in three statistical models. The relationship between phthalate metabolites and hyperuricemia remained in the sensitivity analysis. The present study suggests that exposure to phthalates, individually or jointly, might increase the risk of hyperuricemia. Since hyperuricemia influences on the quality of life, more explorations are needed to confirm these findings.


A Miniature Fabry-Pérot Fiber Interference Sensor Based on Polyvinyl Chloride Membrane for Acoustic Pressure Sensing in Mid-High-Frequency Band.
In this paper, a Fabry-Pérot interference fiber sensor was fabricated by using a Polyvinyl chloride membrane (20 μm in thickness) attached at the end of a ferrule with an inner diameter of 1.1 mm. In consideration of the vibration response of the membrane, the feature of the first-order natural frequency of membrane was analyzed by COMSOL Multiphysics. The acoustic sensing performance of the Fabry-Pérot fiber interference sensor was studied in air. The results reveal that the sensor possessed good acoustic pressure sensitivity, in the order of 33.26 mV/Pa. In addition, the noise-limited minimum detectable pressure level was determined to be 58.9 μPa/Hz1/2 and the pressure-induced deflection obtained was 105 nm/Pa at the frequency of 1 kHz. The response of the sensor was approximately consistent with the reference sensor from 1 to 7 kHz. All these results support that the fabricated Fabry-Pérot fiber interference sensor may be applied for ultra-sensitive pressure sensing applications.


[In vitro spermatogenesis… new horizon to restore fertility?].
The survival of the young boy after cancer has considerably progressed in recent years due to the efficiency of chemo/radiotherapy against the tumor cells. However, this treatment causes adverse effects on healthy tissues, including fertility. Freezing testicular tissue before highly gonadotoxic treatment is a prerequisite for preserving fertility in prepubertal boys that do not produce sperm yet. But which strategy proposes to restore fertility from frozen-thawed testicular tissue? One potential solution would be to consider an in vitro maturation of spermatogonial stem cells. In this article we trace the chronological development of in vitro spermatogenesis that resulted in mouse sperm production in vitro and give an overview of new challenges for the future.


Gluteal Augmentation with Hyaluronic Acid Filler: A Retrospective Analysis Using the BODY-Q Scale.
Minimally invasive techniques, such as filler injection, are now available for posterior body contouring. However, limited data on the outcome of gluteal augmentation with hyaluronic acid (HA) are available in the literature. We performed a retrospective analysis of 43 patients with Body Mass Index ≤ 30, and low-grade ptosis or no ptosis who underwent gluteal augmentation with HA at our clinics. Treatment response was evaluated with a patient-reported assessment scale (BODY-Q) at baseline, and after 6 months. Patients were satisfied with treatment as observed by a statistically significant increase in mean BODY-Q scores at 6 months (8.14 ± 2.19 vs. 14.40 ± 2.38, p < 0.0001). Such increase was more pronounced in patients who were treated with a higher number of vials (8-12 vials vs. 14-20 vials). No serious complications were observed during or after treatment. Gluteal augmentation with hyaluronic fillers is a safe, minimally invasive procedure with good aesthetic results. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Crystal structure of the N-terminal domain of human SIRT7 reveals a three-helical domain architecture.
Human SIRT7 is an NAD(+) dependent deacetylase, which belongs to sirtuin family of proteins. SIRT7, like other sirtuins has conserved catalytic domain and is flanked by N- and C-terminal domains reported to play vital functional roles. Here, we report the crystal structure of the N-terminal domain of human SIRT7 (SIRT7(NTD) ) at 2.3 Å resolution as MBP-SIRT7(NTD) fusion protein. SIRT7(NTD) adopts three-helical domain architecture and comparative structural analyses suggest similarities to some DNA binding motifs and transcription regulators. We also report here the importance of N- and C-terminal domains in soluble expression of SIRT7. Proteins 2016; 84:1558-1563. © 2016 Wiley Periodicals, Inc.


Clinical and genetic analysis of essential hypertension with CYB gene m.15024G>A mutation.
To explore the role of mitochondrial CYB 15024G>A mutation in the development of essential hypertension. Mitochondrial genome sequences of hypertensive patients were obtained from previous studies. Clinical and genetic data of a hypertensive patient with mitochondrial CYB 15024G>A mutation and its pedigree were analyzed. Lymphocytes derived from patient and family members were transformed into immortalized lymphoblastoid cell lines, and the levels of adenosine triphosphate (ATP), mitochondrial membrane potential and intracellular reactive oxygen species (ROS) were detected. The penetrance of this essential hypertension family was 42.9%, and the age of onset was 46-68 years old. Mitochondrial genome sequencing results showed that all maternal members carried a highly conserved mitochondrial CYB 15024G>A mutation. This mutation could affect the free energy of mitochondrial CYB for secondary and tertiary structure and protein folding, thereby changing its structural stability and the structure of the electron transfer function area around the mutation site. Compared with the control, the cell line carrying the mitochondrial CYB 15024G>A mutation showed significantly decreased levels of mitochondrial CYB, ATP and mitochondrial membrane potential, and increased levels of ROS (P<0.01). Mitochondrial CYB 15024G>A mutation may affect the structure of respiratory chain subunits and mitochondrial function, leading to cell dysfunction, which suggests that the mutation may play a synergistic role in essential hypertension.


Validation of translated Obstetric Quality of Recovery (ObsQoR-10A) score after nonelective cesarean delivery (CD) in an Arabic-speaking population.
The ObsQoR-11 is a validated scale that assesses recovery after cesarean delivery (CD). This observational study aimed to evaluate the psychometric properties of its Arabic version. The original ObsQoR-11 was translated into an Arabic version (ObsQoR-10A). All participants completed the ObsQoR-10A at 24 h and 48 h postoperatively after CD. Validity, reliability, responsiveness, and feasibility were assessed. The ObsQoR-10A correlated with Global Health Numerical Rating Scale (NRS) at 24 h (R = 0.68, 95% CI: 0.56-0.80, P < 0.001) and at 48 h (R = 0.66, 95% CI: 0.54-0.78, P < 0.001) and differentiated between good and poor recovery (median scores at 24 h 88 vs. 71, P < 0.001; at 48 h 95.5 vs. 70, P < 0.001). ObsQoR-10A correlated with hospital length of stay at 24 h (R = -0.21, 95% CI: -0.40 to -0.02, P = 0.03) and at 48 h (R = -0.21, 95% CI: -0.40 to -0.03, P = 0.02); gestational age at 24 h (R = 0.22, 95% CI: 0.03-0.40, P = 0.02); change in hemoglobin at 24 h (R = -0.30, 95% CI: 0.51 to -0.10, P < 0.01); and total opioids at 48 h (R = -0.45, 95% CI: -0.62 to -0.27, P < 0.001). There was a significant difference between 24 h and 48 h postoperative ObsQoR-10A scores (median difference: -18; P < 0.001 which shows responsiveness). Other key measures included a Cronbach's alpha of 0.87, split-half 0.75, and intra-class correlation >0.62 with no floor or ceiling effects. Median (IQR) completion time was 3 (3-5) and 3 (2.5-3.5) minutes at 24 h and 48 h. ObsQoR-10A is a valid, reliable, responsive, and a clinically feasible tool in an Arabic-speaking obstetric population.


Allergic reaction to abciximab with atypical manifestations.
Abciximab (ReoPro, Eli Lilly and Company, Indianapolis, Indiana) is an intravenous agent that had been approved for treatment of acute coronary syndrome undergoing coronary interventions. It is a chimeric monoclonal antibody fragment that binds to the glycoprotein IIb/IIIa receptor with a potential for the development of an immune response to variable portions within the antigen binding site following its administration. We describe a 58-year-old man who developed sudden headache, short of breath, choking and restlessness after receiving Abciximab for coronary intervention. Discontinuation of abciximab and administration of intravenous fluids, steroid and antihistamines led to improvement of his symptoms gradually.


Are Mobile Applications in Laryngology Designed for All Patients?
Mobile applications (apps) are multiplying in laryngology, with little standardization of content, functionality, or accessibility. The purpose of this study is to evaluate the quality, functionality, health literacy, readability, accessibility, and inclusivity of laryngology mobile applications. Of the 3230 apps identified from the Apple and Google Play stores, 28 patient-facing apps met inclusion criteria. Apps were evaluated using validated scales assessing quality and functionality: the Mobile App Rating Scale (MARS) and the Institute for Healthcare Informatics App Functionality Scale. The Clear Communication Index (CDC) Institute of Medicine Strategies for Creating Health Literate Mobile Applications, and Patient Education Materials Assessment Tool (PEMAT) were used to evaluate apps health literacy level. Readability was assessed using established readability formulas. Apps were evaluated for language, accessibility features, and representation of a diverse population. Twenty-six apps (92%) had adequate quality (MARS score > 3). The mean PEMAT score was 89% for actionability and 86% for understandability. On average, apps utilized 25/33 health literate strategies. Twenty-two apps (79%) did not pass the CDC index threshold of 90% for health literacy. Twenty-four app descriptions (86%) were above an 8th grade reading level. Only 4 apps (14%) showed diverse representation, 3 (11%) had non-English language functions, and 2 (7%) offered subtitles. Inter-rater reliability for MARS was adequate (CA-ICC = 0.715). While most apps scored well in quality and functionality, many laryngology apps did not meet standards for health literacy. Most apps were written at a reading level above the national average, lacked accessibility features, and did not represent diverse populations. Laryngoscope, 133:1540-1549, 2023.


A semiquantitative morphologic assessment of chlordecone-potentiated chloroform hepatotoxicity.
A semiquantitative morphologic procedure has been applied to chlordecone potentiation of CHCl3-induced liver injury in male Sprague-Dawley rats. The distance of the injured area from the terminal hepatic venule (THV) to the portal area was measured and the damaged cells were classified by type. The results were plotted graphically, along with elevations in plasma enzyme activities (GPT and OCT), to depict the pattern of damage. Chlordecone pretreatment enhanced the severity of the CHCl3-induced cellular changes and increased the number of cells affected. Dosages of 5 mg/kg of chlordecone did not potentiate CHCl3 toxicity, but higher dosages (10-50 mg/kg) enhanced the toxic response in a dose-dependent manner.


Anisotropic chitosan/tunicate cellulose nanocrystals hydrogel with tunable interference color and acid-responsiveness.
A robust chitosan/tunicate cellulose nanocrystals (TCNCs) anisotropic hydrogel with bright interference colors was fabricated via combining the prestretching orientation method and chemically-physically dual cross-linking. The oriented regenerated chitosan nanofibrous network enabled the TCNCs alignment by covalent interaction and hydrogen bonding. The stretching alignment endows the chitosan/TCNCs hydrogel with enhanced tensile strength, from 0.63 MPa (draw ratio 1.0) to 2.06 MPa (draw ratio 3.5). Moreover, the orientation of chitosan nanofibers led to birefringence appearance, which could be regulated with the TCNCs introduction or draw ratios. The hydrogel swelled completely in 2 min in pH = 3 solution and the interference color disappeared. The oriented chitosan/TCNCs hydrogels showed distinct color change under acid stimulation, which could be quantitatively measured or directly observed under crossed polarizers. This work demonstrated a strategy for fabricating the interference color regulatable hydrogels with acid-response property for sensors and environmental monitoring.


Antibiotic resistance mechanisms in Acinetobacter spp. strains isolated from patients in a paediatric hospital in Mexico.
The aim of this study was to identify Acinetobacter spp. strains from paediatric patients, to determine their genetic relationship, to detect antibiotic resistance genes and to evaluate the role of efflux pumps in antibiotic resistance. A total of 54 non-duplicate, non-consecutive Acinetobacter spp. isolates were collected from paediatric patients. Their genetic relationship, antibiotic resistance profile, efflux pump activity, antibiotic resistance genes and plasmid profile were determined. The isolates were identified as 24 Acinetobacter haemolyticus, 24 Acinetobacter calcoaceticus-baumannii (Acb) complex and 1 strain each of Acinetobacter junii, Acinetobacter radioresistens, Acinetobacter indicus, Acinetobacter lwoffii, Acinetobacter ursingii and Acinetobacter venetianus. The 24 A. haemolyticus were considered genetically unrelated. One strain was resistant to carbapenems, two to cephalosporins, two to ciprofloxacin and sixteen to aminoglycosides. The antibiotic resistance genes blaOXA-214 (29%), blaOXA-215 (4%), blaOXA-264 (8%), blaOXA-265 (29%), blaNDM-1 (4%), aac(6')-Ig (38%) and the novel variants blaOXA-575 (13%), blaTEM-229 (75%), aac(6')-Iga (4%), aac(6')-Igb (13%) and aac(6')-Igc (42%) were detected. Among 24 Acb complex, 5 were multidrug-resistant, carbapenem-resistant strains carrying blaOXA-51 and blaOXA-23; they were genetically related and had the same plasmid profile. Other species were susceptible. In some strains of A. haemolyticus and Acb complex, the role of RND efflux pumps was evidenced by a decrease in the MICs for cefotaxime, amikacin and ciprofloxacin in the presence of an efflux pump inhibitor. This study identified isolates of A. haemolyticus carrying new β-lactamase variants and shows for the first time the contribution of efflux pumps to antibiotic resistance in this species.


The identification of ketamine and its metabolites in biologic fluids by gas-chromatography-mass spectrometry.
A simple gas chromatography-mass spectrometric method for the identification of ketamine and its metabolites in urine, blood, serum, and plasma has been developed in order to investigate a coma due to overdose of the drug.


Body Image Disturbance and Obsessive-Compulsive Disorder Symptoms Improve After Orthognathic Surgery.
Although body image disturbance (BID), anxiety, depression, and obsessive-compulsive disorder (OCD) are the most common comorbid psychological conditions among patients presenting for orthognathic surgery (OS), little is known about whether psychological symptoms relate to facial deformity or how symptoms change after OS. To fill these knowledge gaps, this study investigated preoperative and postoperative psychological symptoms and preoperative baseline facial deformity in patients who underwent OS. This study included 49 patients who underwent OS by a single surgeon between 2011 and 2018. The patients completed validated psychological tests to assess symptoms of anxiety (Beck Anxiety Inventory), depression (Patient Health Questionnaire-9), BID (BID Questionnaire, BIDQ), and OCD (Florida Obsessive-Compulsive Inventory). In addition, we measured severity of preoperative facial deformity with the Facial Aesthetic Index (FAI). We compared preoperative and postoperative symptoms using univariate nonparametric Wilcoxon signed rank tests. We tested associations between the 4 types of preoperative psychological symptoms and baseline Facial Aesthetic Index category using Spearman's rank correlations. Postoperatively, both BIDQ scores (median 2 to 1.2, P < .001) and Florida Obsessive-Compulsive Inventory scores (median number of OCD symptoms 1 to 0, P < .001) decreased, whereas anxiety and depression symptoms showed no change (P > .45). Preoperative BIDQ was significantly associated with the severity of the facial deformity (ρ = 0.32, P = .025; median BIDQ: mild FAI = 1.0, severe FAI = 2.1). Our results show that patients with more severe facial deformity have a higher BID preoperatively and that both BID and OCD improve after OS. Interestingly, anxiety and depression symptoms did not change after OS.


Cigarette smoke condensate affects the retinoid pathway in human amnion.
The preterm premature rupture of membranes (PPROM) is a frequent pathology responsible of more than 30% of preterm births. Tobacco smoking is one of the most frequently described risk factors identified and contributes to the pre term weakening of fetal membranes. As previously demonstrated, all-trans retinoic acid (atRA) regulates several genes involved in the extracellular matrix dynamics, an essential actor in fetal membrane ruptures. We hypothesized that cigarette smoke may affect this pathway in human amnion. Amnion was obtained from full-term fetal membranes collected from non-smoking women after cesarean births and used either as explants or for the isolation of derived epithelial cells. The pro-healing and transcriptomic effects of atRA were studied by a scratch assay experiment and quantitative RT-PCR, respectively, after treatment with dimethyl sulfoxyde (DMSO), atRA, DMSO + cigarette smoke condensate (CSC), or atRA + CSC. Our results show a strong alteration of the retinoid pathway after CSC treatment on amnion-derived epithelial cells and explants. We first demonstrated that CSC inhibits the activity of the RARE reporter gene in amnion-derived epithelial cells. Then, atRA's effects on both the transcription of its target genes and wound healing were demonstrated to be inhibited or at least decreased by the CSC in human amnion epithelial cells. Here, we demonstrated that CSC altered the retinoid signal, already known to have roles in fetal membrane physiopathology. These results highlight a potential negative action of maternal smoking on the retinoid pathway in human amnion and more generally on pregnancy.


The density of GABAB binding sites in the substantia nigra is greater in rat pups than in adults.
Baclofen-displaced [3H]GABA (gamma-aminobutyric acid) binding to GABAB sites was assayed in brain regions obtained from adult and 14- to 17-day-old rats. The substantia nigra of rat pups exhibited a 3- to 5-fold higher density (Bmax) of GABAB binding sites than the nigra of adult rats. In contrast, the density of GABAB sites was lower in hippocampal and cerebellar tissue from pups, both approximately two-thirds the density in corresponding adult structures. This anatomically selective overproduction of GABAB receptors in immature substantia nigra is consistent with the increased anticonvulsant efficacy of the GABAB agonist baclofen observed in rat pups.


Impact of Surgical Margins on Overall Survival after Gastrectomy for Gastric Cancer: A Validation of Japanese Gastric Cancer Association Guidelines on a Western Series.
No consensus exists on the resection extent needed to ensure oncological safety in gastrectomy for gastric adenocarcinoma (GAC). This study aims to assess the impact of margin adequacy according to Japanese Gastric Cancer Association (JGCA) guidelines on overall survival (OS). Patients who underwent surgery for stage I-III GAC at our institution between 2010 and 2017 were included. Margin adequacy according to JGCA, National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO) guidelines was assessed, and their predictive value on OS was evaluated with Harrell's C-index. Patients were analyzed according to their margins' adherence to JGCA guidelines, and a propensity score matching (PSM) was run. Indication to either total gastrectomy (TG) or distal gastrectomy (DG) according to each guideline was also assessed. A total of 279 patients were included, of whom 220 (79%) underwent DG. Adequate margins according to JGCA were obtained in 209 patients (75%). On multivariate analysis, JGCA margin adequacy was independently associated with OS, together with American Society of Anesthesiologist class, neoadjuvant chemotherapy, lymphadenectomy extent, R0 resection, and postoperative N stage. After PSM, patients with JGCA adequate margins showed better OS, recurrence-free survival (RFS), and local RFS than patients with JGCA inadequate margins. For 220 DG, JGCA guidelines would have recommended TG in 25 patients (11%), NCCN in 30 (14%), and ESMO in 90 (41%) (p < 0.001). Adequacy of surgical resection margins to JGCA guidelines leads to improved survival outcomes and allows for a more organ-preserving approach than Western guidelines.


Double-blind controlled trial of venlafaxine for treatment of adults with attention deficit/hyperactivity disorder.
Attention deficit/hyperactivity disorder (ADHD) is one of the most common mental disorders beginning in childhood that may continue to adulthood. The purpose of this study was to evaluate the possible therapeutic effect of venlafaxine in adults with ADHD. In a double-blind setting, drug-naïve adults with a diagnosis of ADHD based on DSM-IV-TR criteria were randomly selected to receive either venlafaxine (up to 225 mg/day) or a placebo for 6 weeks. The Conners Adult ADHD Rating Scale self-report screening version was administered before and during the treatment at 2-week intervals to measure the therapeutic effects. The mean age (SD) of patients was 30.5 (8.1) years. Eleven out of 20 patients receiving venlafaxine and 13 out of 21 patients receiving the placebo were male. The two groups were not significantly different in terms of age, educational level, weight, or blood pressure. Significant decrease was observed in both subscales (inattentive, hyperactive/impulsive), total ADHD symptoms score, and ADHD index in both the venlafaxine and the placebo groups. Seventy-five percent of treatment group versus 20% of placebo group met treatment response criteria when defined as a 25% drop in total ADHD score (p = 0.001). No serious adverse effects were reported during the trial. In this double-blind trial, the symptoms of adult ADHD decreased after a 6-week trial of either venlafaxine or a placebo with no significant difference. However, a significant treatment response defined as a 25% drop in ADHD index (measured by a self-report scale) was achieved by venlafaxine. The interpretation of these results is limited by the short duration of follow-up in this study.


Evaluation of nitric oxide (NO) and nitric oxide synthases (NOS) in the amniotic fluid in an experimental gastroschisis rat model.
Intestinal damage due to gastroschisis (G), an anomaly found with increasing incidence by pediatric surgeons, is intimately associated with endogenous nitric oxide (NO) production and NO synthase (NOS) expression. Aim of the study was to evaluate NO production and NOS isoforms in the intestine and amniotic fluid (AF) using a rat model of gastroschisis. A gastroschisis rat model was surgically created at 18.5 days of gestation (term=22 days). 3 groups of 12 fetuses each were studied: control (C), sham (S) and (G). Morphometric data of body weight (BW), intestinal weight (IW) and the IW/BW ratio were evaluated and compared. Indirect quantification of NO (nitrite and nitrate - NOx) was analyzed by chemiluminescence, and the expression of the 3 isoforms was analyzed by Western blotting. Group G showed an increase in IW and IW/BW compared with groups C and S. IW: G=0.27 ± 0.06, C=0.20 ± 0.02, S=0.20 ± 0.02 (p<0.01); IW/BW: G=4.11 ± 0.57, C=5.21 ± 1.04, S=5.18 ± 1.23 (p<0.05). NO in the G group was lower in the intestine and higher in AF, as opposed to C and S, where it had increased in the intestine and decreased in AF. Intestinal NOx: G=0.85 ± 0.28, C=1.86 ± 0.82, S=1.80 ± 0.69 (p<0.05); NOx in AF: G=161.87 ± 52.11, C=6.99 ± 5.45, S=48.73 ± 13.183 (p<0.001). The intestinal inflammation in gastroschisis promotes the release of nitric oxide to the environment (AF). Perhaps NO in the AF may be an inflammatory marker for G.


Heteroarylation of azine N-oxides.
Azine N-oxides undergo highly regioselective metalation with TMPZnCl·LiCl under mild conditions. A palladium-catalyzed Negishi cross-coupling reaction of the resulting organozinc species with heteroaromatic bromides provides heterobiaryls specifically oxidized at one nitrogen position in up to 95% yield.


Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apotosis.
Semaglutide, a glucagon-like peptide-1 (GLP-1) analogue with an extended half-life of approximately 1 week has being come into clinic trial to treat parkingson's disease but little is known about its effect to prevent against Alzheimer's disease (AD). The goal of the present study was to explore the potential mechanisms of semaglutide to protect against AD. We treated SH-SY5Y cell line with Aβ25-35 as an AD model. Further, SH-SY5Y cells damaged by Aβ25-35 were treated by semaglutide. Autophagy-related proteins and apoptosis-related proteins were measured to explore molecular mechanisms for semaglutide to protect against Aβ25-35. Semaglutide enhanced autophagy by increasing the expression of LC3II, Atg7, Beclin-1 and P62 which were inhibited by Aβ25-35. Further we showed that semaglutide inhibited apoptosis by inhibiting the expression of Bax induced by Aβ25-35 and increasing the expression of Bcl2 inhibited by Aβ25-35. Our results provide a clue for the hypothesis that autophagy enhancement and apoptosis inhibition may be involved in the effect of semaglutide to protect against Aβ 25-35.


The moyamoya phenomenon with accompanying intracranial aneurysm.
Three cases illustrating the moyamoya phenomenon and an aneurysm in the periphery of the lateral ventricle in angiograms are reported. The mechanism of occurrence of an aneurysm in the moyamoya phenomenon is discussed.


Labor induction with randomized comparison of cervical, oral and intravaginal misoprostol.
This study attempts to evaluate the safety and effectiveness of 50μgm intracervical misoprostol in comparison with intravaginal and sublingual for the induction of labor at term pregnant women. This study is designed as a parallel clinical trial study. Three hundred and fifteen term pregnancies requiring induction of labor were treated with the maximum used misoprostol intracervical, sublingual, and vaginal doses. Participants were randomly allocated into three groups of 105. The dose was repeated every 4 h until adequate uterine contraction and Bishop Score were achieved. The duration of induction to births, time to the active phase, the rate of births, and the need for caesarean section were compared in three groups. Additionally, labor course and side effects were recorded and analyzed. Data were analyzed using SPSS software. A significance level of p < 0.05 was considered for statistical analyses. Labor was successfully induced in all cases most (63%) of which required a single dose of misoprostol. Ninety-three (93.0%, p < 0.05) cervical participants proceeded to vaginal births. This figure was also the same in the vaginal and sublingual group of 83 cases (83.0%). The other 41 cases received caesarean section with more indications of failure to progress and meconium-stained liquor. The results indicated that 278 (92.7%) births were achieved in less than 10 h. Time from start of medication to the active phase of labor and childbirth was 3.01 ± 0.86 and 6.1 ± 1.3 h in the Cervical group, 4.2 ± 0.66 and 8.4 ± 0.92 h in the sublingual group, and 5.06 ± 1.1 and 9.2 ± 1.5 h in the vaginal group respectively (p < 0.001). The Caesarean rate was lower in the cervical group than in the two other groups (p = 0.05). No significant differences were observed between the study groups in terms of Apgar score and meconium-stained amniotic fluid. Furthermore, no maternal and neonatal complications were observed. In addition to the sublingual and intravaginal routes of administration, intracervical misoprostol at a single dose of 50μgm appears to be an effective method for induction of labor in women with an unfavorable cervix. Like all medical interventions, a discussion of the risks, benefits, and alternatives to induction of labor with this medication in each woman should be undertaken before treatment. This clinical study was approved by the Iranian Registry of Clinical Trials with IRCT ID: IRCT20190415043278N1 . Registration date was on May 13, 2019 and May 27, 2019 respectively ( http://www.irct.ir ).


Cynanchum komarovii extract for the treatment of rheumatoid arthritis by acting on synovial cells in vitro and in vivo.
Cynanchum komarovii (CK), the northwest Chinese region's common medicinal herb, was traditionally utilized to treat arthritis, toothache, bald sores and cholecystitis. Various forms of arthritis can be treated with CK, based on "Medicinal Plants of Chinese Desert Areas". However, the exact mechanism of action in rheumatoid arthritis (RA) is uncertain. To evaluate the in vitro and in vivo effects of CK extracts on RA and to preliminarily investigate its anti-RA mechanism of action. The main components of CK extract were analyzed by HPLC method. The effects of CK on the proliferation and apoptosis of human rheumatoid arthritis fibroblast-like synoviocytes (HFLS-RA) cells and the expression of apoptosis-related proteins in HFLS-RA cells were evaluated by CCK8 assay, flow cytometry and WB assay. To verify the anti-RA effect of CK extracts in vivo, a collagen-induced arthritis (CIA) rat model was established. The rats were divided into six groups: normal group, model group, CK high-dose group (1000 mg/kg, CK-H), CK medium-dose group (500 mg/kg, CK-M), CK low-dose group (250 mg/kg, CK-L) and methotrexate-positive drug group (MTX); the drug was administered continuously for 28 days. Body weight changes, joint swelling, arthritis index, bone density, ankle lesions, immune organ index, splenic lesions and inflammatory factor expression were used to evaluate the in vivo anti-RA activity of the extract. The findings of in vitro experiments showed that 10% CK-containing serum decreased the expression level of Bcl-2, increased the expression levels of Bax and Cleaved Caspase-3 in synovial cells, and prevented TNF-α induced aberrant proliferation and apoptotic antagonism in HFLS-RA cells. According to in vivo studies, CK extract at doses above 250 mg/kg was effective in controlling the levels of inflammatory factors, lowering the arthritis index, and improving foot swelling in CIA rats. When administered at doses up to 1000 mg/kg, CK extract significantly improved synovial lesions, increased bone density, and decreased abnormally elevated immune organ index in CIA rats. CK has significant anti-RA activity, and its anti-RA mechanism of action may be related to the regulation of the expression levels of apoptosis related proteins and the promotion of apoptosis in synovial cells.


The effect of age, pairing, copulation, and 2-Br-alpha-ergocryptine in the male Mongolian gerbil on the prolactin cells in the anterior pituitary identified by immunocytochemical and Herlant's tetrachrome methods.
Near-adjacent, midsagittal sections of pituitaries of infantile and adult male Mongolian gerbils in several experimental groups (bachelor, paired, tartaric acid-injected, postcopulatory gerbil, and postcopulatory animal injected with 2-bromo-alpha-ergocryptine [CB-154]), were stained by a modification of Herlant's tetrachrome and by the peroxidase-labeled antibody method for prolactin. Cell counts of erythrosinophils and cells immunoreactive for prolactin were made. Sequential staining procedures and thin adjacent sections were used to correlate the staining results. Erythrosinophils were very rare in the infant pituitaries; they increased (P less than .01) in numbers in bachelor pituitaries, remained at the same level (P greater than .05) in paired animals, increased (P less than .01) in the postcopulatory gerbils that were injected with tartaric acid, and increased much less (P less than .05) in postcopulatory males that were injected with CB-154. Prolactin cells were present in modest numbers in infant pituitaries; they increased (P less than .01); in bachelors and reached their highest number in paired animals (P less than .001); they remained unchanged (P greater than .05) in tartaric acid-injected postcopulatory animals but declined (P less than .001) in CB-154-injected, postcopulatory animals. The number of prolactin cells was always significantly greater (P less than .001) than the number of erythrosinophils. Correlative studies revealed the erythrosinophils, some of the light blue cells, and some of the chromophobes gave positive immunocytochemical reactions for prolactin. Apparently, CB-154 inhibited the erythrosinophils and the immunoreactive prolactin cells in the postcopulatory male gerbil, as indicated by a reduction in the number, size, and staining intensity of the cells.


Epigenetic therapy of leukemia: An update.
Carcinogenesis is classically thought to result from genetic alterations in DNA sequence such as deletions, mutations, or chromosomal translocations. These in turn may lead to the activation of oncogenes, inactivation of tumor suppressor genes or formation of chimeric oncoproteins. Epigenetics, in contrast, refers to a number of biochemical modifications of chromatin, either to DNA directly or to its associated protein complexes that affect gene expression without altering the primary sequence of DNA [Robertson KD, Wolffe AP. DNA methylation in health and disease. Nat Rev Genet 2000;1:11-9; Jones PA, Baylin SB. The epigenomics of cancer. Cell. 2007;128:683-92]. A fundamental difference between genetic and epigenetic alterations is the irreversible nature of genetic lesions whereas epigenetic ones are potentially reversible, allowing for therapeutic intervention. In the last decade, it has become apparent that epigenetic changes play an important role in cancer, particularly in leukemia. Significant advances have been made in the elucidation of these processes as well as in translating this knowledge to the clinic, as in the development of new prognostic biomarkers or targeted therapies. In this review, we will focus on recent advances in epigenetic therapy in leukemia.


Edoxaban versus Warfarin in Patients with Atrial Fibrillation at the Extremes of Body Weight: An Analysis from the ENGAGE AF-TIMI 48 Trial.
The effects of anticoagulants at extremes of body weight (BW) are not well described. The aim of this study was to analyze the pharmacokinetics/pharmacodynamics and clinical outcomes in patients randomized to warfarin, higher dose edoxaban (HDER), and lower dose edoxaban (LDER) regimens at extremes of BW in ENGAGE AF-TIMI 48. We analyzed three BW groups: low BW (LBW: <5th percentile, ≤55 kg, N = 1,082), middle BW (MBW: 45th-55th percentile, 79.8-84 kg, N = 2,153), and high BW (HBW: >95th percentile, ≥120 kg, N = 1,093). In the warfarin arm, LBW patients had higher rates of stroke/systemic embolism (SSE: 6.5 vs. 4.7 in MBW vs. 1.6% in HBW, P trend < 0.001), major bleeding (MB: 9.3 vs. 7.7 vs. 6.5%, P trend = 0.08), and worse net clinical outcome of systemic embolic event, MB, or death (31.5 vs. 19.1 vs. 16.0%, P trend < 0.0001). The time-in-therapeutic range with warfarin was lowest in LBW patients (63.0 vs. 69.3 vs. 70.1% patients, P trend < 0.001). The pharmacokinetic/pharmacodynamic profile of edoxaban was consistent across BW groups. The risk of SSE was similar between HDER and warfarin for each of the three weight groups (P int = 0.52, P int-trend = 0.86). MB was reduced by LDER versus warfarin (P int = 0.061, P int-trend = 0.023), especially in LBW patients. Net clinical outcomes were improved by HDER versus warfarin (P int = 0.087, P int-trend = 0.027), especially in LBW patients. Patients with LBW in ENGAGE AF-TIMI 48 had in general a more fragile clinical status and poorer international normalized ratio control. The pharmacokinetic/pharmacodynamic profile of edoxaban was consistent across extremes of BW, resulting in similar efficacy compared with warfarin, while major or clinically relevant non-MB and net outcomes were most favorable with edoxaban as compared to warfarin in LBW patients.


EndothelinA-endothelinB receptor cross-talk in rat basilar artery in situ.
The rationale for the therapeutic use of dual as opposed to selective endothelin (ET) receptor antagonists stems in part from cross-talk between the ET(A) and ET(B) receptors. However, whether ET(A)-ET(B) receptor cross-talk is present in the cerebral vasculature is difficult to discern since findings of cross-talk contrast even among the few reports available. Thus, this study tested whether ET(A)-ET(B) receptor cross-talk is present in the rat basilar artery. In an in situ cranial window, 0.1 μM sarafotoxin S6c, an ET(B) receptor agonist, relaxed basilar artery basal tone by 54%. ET-1 (3 nM) in the absence and presence of 10 μM BQ123, an ET(A) receptor agonist, induced 13% contraction and 15% relaxation, respectively. In contrast, the 3-nM ET-1 plateau contraction was relaxed by only ∼50% by 3-10 μM BQ123 and 10 μM BQ610, ET(A) receptor antagonists. N(ω)-nitro-L: -arginine, an NO synthase inhibitor, did not enhance contraction to 3 nM ET-1, suggesting that the partial relaxation of the ET-1 plateau contraction did not involve unmasked endothelial ET(B) receptor-mediated relaxation. The ∼50% ET-1 contraction that remained following ET(A) receptor antagonist was relaxed by 3-10 μM BQ788, consistent with an ET(B) receptor-mediated component of contraction. However, 10 μM BQ788 in the absence of prior ET(A) receptor antagonist did not cause relaxation. Subsequent BQ123 addition in the presence of BQ788 completely relaxed the ET-1 contraction. PD145065 (1 μM), an ET(A/B) receptor antagonist, completely relaxed 3-nM ET-1 contracted vessels in both the absence and presence of BQ123. These findings suggest that the inability of ET(A) receptor antagonist to completely relax the ET-1 plateau contraction in rat basilar artery is due to ET(A)-ET(B) receptor cross-talk.


Vismodegib: a guide to its use in locally advanced or metastatic basal cell carcinoma.
Vismodegib is the first Hedgehog pathway inhibitor to be approved in the USA, where it is indicated for the treatment of adults with metastatic basal cell carcinoma (BCC), or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. In an ongoing, noncomparative, phase II trial, oral vismodegib was effective in and had an acceptable tolerability profile in the treatment of patients with locally advanced or metastatic BCC.


Evaluation of the vestibular evoked myogenic potential during parabolic flight in humans.
The purpose of this study was to investigate how gravity affects the vestibular evoked myogenic potential (VEMP). Eight healthy subjects (seven men, one woman; age range 19-45 years) participated in experiments in which three different gravity levels [microgravity (MG), normal gravity (NG), and hypergravity (HG)] were imposed during a parabolic flight procedure. The VEMP was evoked in response to an intense mono-aural click while the subjects kept the sternocleidomastoid (SCM) muscle contracted bilaterally. Background electromyographic activity of the SCM during the test was corrected. The p13-n23 amplitude was significantly greater under MG than under NG or HG. There was no difference in p13 latency between the three gravity levels. Possible mechanisms related to this phenomenon are discussed.


Autologous buccal mucosa vulvovaginoplasty for high urogenital sinus.
Feminizing genitoplasty for mid to high urogenital sinus confluence is challenging surgery, especially in the postpubertal patient. We report a surgical alternative for a complex postpubertal case with scarce perineal tissue. An autologous buccal mucosa vulvovaginoplasty was performed in a postpubertal patient with adrenogenital syndrome, permitting vaginal lengthening, creation of labia minora and minimal urethral dissection. This surgical approach avoided female hypospadias, as seen with the total urogenital sinus mobilization repair, and the risks of extensive urethral dissection, seen with the vaginal pull-through procedure, but yet solved the dilemma of mucosal coverage for the vulva and anterior vaginal wall. Buccal mucosa is a natural replacement for the female vulvar and vaginal glabrous skin, and is an excellent adjunct or alternative in challenging reconstructions.


In vitro interaction of posaconazole and caspofungin against clinical isolates of Candida glabrata.
Combinations of caspofungin and posaconazole were evaluated by fractional inhibitory concentration index against 119 Candida glabrata isolates. Synergy was seen in 18% of all isolates and in 4% of fluconazole-resistant isolates at 48 h without evidence of antagonism. This antifungal combination may have utility against this organism.


Treatment of Dry Eye from Laser-Assisted In Situ Keratomileusis With Recombinant Human Nerve Growth Factor (Cenegermin).
To describe 2 patients with neurotrophic keratitis after laser-assisted in situ keratomileusis surgery who were treated with recombinant human nerve growth factor (cenegermin) and the treatment course. Case series. After an 8 week course of cenegermin, there was an improvement in visual acuity, corneal sensitivity, and ocular surface staining. However, these effects were short lived, and the disease regressed at subsequent follow-up visits. Although recombinant human nerve growth factor seems to be effective in short term for neurotrophic keratitis secondary to laser-assisted in situ keratomileusis surgery, alternative dosing for patients with this patient population should be considered to achieve long-lasting resolution.


Parathyroid hormone and calcitonin levels in vitamin D deficient rickets.
In six infants aged between 5 and 8 months with vitamin D deficient rickets, we have studied blood levels of calcium (Ca), phosphorus (P), alkaline phosphatase, immunoreactive parathyroid hormone (PTH) and calcitonin (CT), as well as urinary excretion of Ca, P, hydroxyproline and cyclic AMP, both under basal conditions and during a 4h infusion of 20 mg/kg 10% Ca gluconate in normal saline. Under basal conditions all the infants had high alkaline phosphatase (range: 470--770 U.I./1); PTH (range: 620--1200 pg Eq/ml) and CT (range: 440--750 pg/ml) but two infants had hypocalcaemia and four had normocalcaemia and hypophosphataemia. The urinary Ca excretion was low whereas the urinary P, hydroxyproline and cyclic AMP excretions were high. During Ca infusion the total serum Ca and CT levels increased, while alkaline phosphatase and PTH fell. After the end of the infusion, CT levels fell perceptibly; phosphaturia, hydroxyprolinuria and cyclic AMP decreased on the day of the infusion.


Detection of melanin influence on skin samples based on Raman spectroscopy and optical coherence tomography dual-modal approach.
Melanoma is responsible for more than half of the deaths related to skin cancer in the last few decades. A dual-modality optical biopsy system with Raman spectroscopy and optical coherence tomography approach was built with the goal of achieving noninvasive skin measurement. To mimic melanoma and evaluate the effect of melanin on skin, models have been created by dissolving synthetic melanin in dimethyl sulfoxide and adding it to fresh skin samples. Compared to the untreated samples, morphological images showed that the imaging depth on melanin-treated skin has been increased from 250 μm to 350 μm due to the optical clearing effect of the DMSO solvent, and Raman analysis revealed that relative spectral intensities of melanin-treated samples were lower in the amide-I and CH2 -deformation bands, and higher in the CH2 -twist and C-C stretch bands. Using machine learning for skin type classification, an accuracy of 89% is achieved.


CX3C-chemokine receptor 1 modulates cognitive dysfunction induced by sleep deprivation.
Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS's response to SD. Middle-aged wild-type (WT) C57BL/6 and CX3CR1-/- mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes. CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1-/- S group, the CX3CR1-/- SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted. These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.


Variability in the distribution of callosal projection neurons in the adult rat parietal cortex.
Previous reports have shown that the barrel field area of the parietal cortex of the adult rat contains relatively few callosal projection neurons, even though callosal projection neurons are abundant in this cortical region in the neonatal rat. Furthermore, it has been shown that many of the callosal neurons which seem to disappear as the animal matures do not die, but project to ipsilateral cortical areas. These findings rely on the ability of retrograde transport techniques which utilize injections of horseradish peroxidase (HRP) or of fluorescent dyes into one hemisphere. We now show that several technical modifications of the HRP technique yield a wider distribution of HRP-containing neurons in the contralateral barrel field area of the adult rat than previously reported. These include implants of HRP pellets into transected axons of the corpus callosum, the addition of DMSO and nonidet P40 to Sigma VI HRP, wheat germ agglutinin HRP and the use of tetramethyl benzidine as the chromogen in the reaction procedure. Our findings have implications for transport studies in general and for the development of the cortical barrel field in particular.


Performance of rapid on-site evaluation of touch imprints of lung tissue biopsies for the diagnosis of pulmonary cryptococcosis in patients without HIV infection.
The diagnosis of pulmonary cryptococcosis depends on serum testing, histopathology and mycological culture; there are few studies on touch imprints of lung tissue biopsies for the diagnosis of pulmonary cryptococcosis in patients without HIV infection. The purpose of the current study was to investigate the accuracy and timeliness of on-site touch imprint cytology in the diagnosis of pulmonary cryptococcosis during CT-guided percutaneous lung biopsy. We retrospectively analysed the diagnosis and treatment of 56 patients with final proof of pulmonary cryptococcosis through histopathology and culture or surgical resection from September 2015 to February 2021. Diagnostic methods and treatment and the turnaround time for diagnosis were analysed. The sensitivity of rapid on-site evaluation was 89.3%, and the sensitivity of serology, histopathology and mycological culture was 53.6%, 91.1% and 61.5%, respectively, compared with the final diagnosis. The average turnaround time to diagnose pulmonary cryptococcosis by on-site touch imprint cytology was 8.3 ± 0.9 min, which was significantly faster than serum testing, histopathology and mycological culture. On-site touch imprint cytology showed good sensitivity and timeliness in the diagnosis of pulmonary cryptococcosis. In addition, it contributed to the triage of biopsies based on the preliminary diagnosis. On-site touch imprint cytology should be applied and promoted in the diagnosis of pulmonary cryptococcosis during biopsy.


Skull base tumours part I: imaging technique, anatomy and anterior skull base tumours.
Advances in cross-sectional imaging, surgical technique and adjuvant treatment have largely contributed to ameliorate the prognosis, lessen the morbidity and mortality of patients with skull base tumours and to the growing medical investment in the management of these patients. Because clinical assessment of the skull base is limited, cross-sectional imaging became indispensable in the diagnosis, treatment planning and follow-up of patients with suspected skull base pathology and the radiologist is increasingly responsible for the fate of these patients. This review will focus on the advances in imaging technique; contribution to patient's management and on the imaging features of the most common tumours affecting the anterior skull base. Emphasis is given to a systematic approach to skull base pathology based upon an anatomic division taking into account the major tissue constituents in each skull base compartment. The most relevant information that should be conveyed to surgeons and radiation oncologists involved in patient's management will be discussed.


War injuries to the thoracic esophagus.
Presentation of our experience in the treatment of war injuries to the thoracic esophagus at the Split University Hospital, Croatia, during the 1991-1995 wars in Croatia and Bosnia-Herzegovina. Retrospective analysis of clinical and surgical data on patients with war injuries to the esophagus. Of 2494 treated injured persons, 5 patients (0.2%) had injuries to the esophagus. We performed temporary double-exclusion of the esophagus in all our patients, followed by gastric interposition after partial esophagegtomy in three patients and simple suturing with pericardial protection of the esophagus in one patient. One of our patients died after double-exclusion due to septic complications in spite of antimicrobial chemoprophylaxis regularly performed in all injured persons. Final surgical outcome and mortality rate (20%) in our patients were quite satisfactory. Prompt transportation, appropriate diagnostic methods and an adequate surgical treatment can markedly reduce mortality and complications rate in war injuries to the thoracic esophagus.


Validation of a clinical assessment tool for cicatrising conjunctivitis.
This study was designed to validate a semi-quantitative clinical assessment tool for cicatrising conjunctivitis (CC). Fifty-five patients (109 eyes) with mucous membrane pemphigoid (MMP) and 31 patients (61 eyes) with Stevens-Johnson syndrome (SJS) were included. Three methods were used for validation: (1) comparison of inter- and intra-observer reproducibility for the components selected for the initial version of the tool, (2) quantitative measurement of the scarring component with a fornix depth measurer, compared with qualitative Tauber grading methodology, (3) the final version of the tool was compared with the published Sotozono SJS grading system. Main outcome measures included: inter- and intra-observer reproducibility, calculation of composite measures of scarring and morbidity, component redundancy, and correlation with other grading systems. Inter- and intra-observer agreement was moderate-to-excellent for graded components of conjunctival hyperaemia, upper and lower symblepharon, upper and lower fornix depth, corneal vascularisation, and corneal opacity. There was poor-to-good agreement for limitation of motility which was rejected from inclusion in the final tool. Composite scores for scarring components and morbidity components showed good-to-excellent agreement and distribution of ocular disease severity. Analysis of the composite components showed no redundancy - all components contributed independently. Comparison with both Tauber and Sotozono grading methodologies showed good concordance. This study has developed the first validated assessment tool applicable to causes of CC. The tool is concise and discriminates patients with varying disease severity. It measures both disease activity and severity and is suitable for clinical and research applications.


Reactive airways dysfunction syndrome (RADS) due to chlorine gas exposure.
Reactive Airways Dysfunction Syndrome (RADS) has been described following exposure to various irritant gases. We describe a case of RADS occurring following exposure to chlorine gas and which has persisted at 6 years follow-up.