Using the Ratio of Urine Testosterone to Estrone-3-Glucuronide to Identify the Sex of Chinese Giant Salamanders (Andrias davidianus).
Minimally invasive sampling was used to determine the sex of Chinese giant salamanders (Andrias davidianus). Urine samples (n = 25) were collected from 6 adults in the breeding season and from 19 individuals (7 adults and 12 juveniles) in the non-breeding season. The hormone testosterone (T) and estrone-3-glucuronide (E1G) in urine were collected from Chinese giant salamanders (CGSs), and the hormone extracts were analyzed by enzyme immunoassays (EIA). The data demonstrated that the urine T concentration of the male CGSs was significantly higher than that of the females during the breeding season (p < 0.05) and even more pronounced during the non-breeding season (p < 0.01). The urine E1G concentration of the males was less pronounced than that of the females during the breeding season (p < 0.01) and significantly lower during the non-breeding season (p < 0.05). The urine T/E1G values of all the male salamanders were significantly higher than those of the females (p < 0.01) during both the breeding season and the non-breeding season. An interesting pattern was found in this study: the value of urine log10(T/E1G) of the male CGSs was higher than 1, whereas the value for the females was lower than 1, during both the breeding and non-breeding seasons, and in the adult and sub-adult age groups of CGSs. There were 25 salamanders in this study and the accuracy rate reached 100% by using a log10(T/E1G) value of 1. The results of the log10(T/E1G) value provide new insight into the future development of the sex identification of CGSs and also lay the foundation for accurate sex identification in the preparation for artificial release. This is the first study to show that the T/E1G ratio in urinary hormones is reliable for the sex identification of CGSs. Additionally, urinary hormone T/E1G measures are promising sex identification tools for amphibian or monomorphic species and for those whose secondary sex characteristics are visible only during the breeding season.


Evolution of Intra-arterial Therapy for Acute Ischemic Stroke in The Netherlands: MR CLEAN Pretrial Experience.
The Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) trial showed efficacy of intra-arterial (IA) treatment in acute ischemic stroke (AIS). We studied the evolution of IA treatment for AIS and its effects on clinical outcome and recanalization in The Netherlands in the pre-MR CLEAN era. Data on 517 patients with AIS treated with IA therapy were collected retrospectively from all intervention centers in The Netherlands from 2002 to the start of participation in the MR CLEAN trial. Clinical outcome was measured by means of the modified Rankin Scale score and recanalization with the Thrombolysis in Cerebral Infarction Scale. IA therapy was first used in patients with basilar artery occlusion. Over the years, there was a gradual increase in the number of anterior circulation strokes treated. There was a shift in applied therapies from primary IA therapy to combined intravenous and IA therapy and from IA thrombolysis to mechanical thrombectomy. Time from symptom onset to treatment decreased. Recanalization rates gradually increased. At the same time, there was a trend toward more favorable outcomes after 3 months and fewer deceased patients both at discharge and after 3 months. However, none of these changes reached statistical significance. The treatment approach used in the MR CLEAN trial was the result of an evolution of practise in the preceding years, with gradual improvement in technical and clinical outcomes.


Racial Discrimination of Adolescents With Special Healthcare Needs.
Examine racial discrimination of adolescents of color by type of special healthcare need (SHCN). Pooled cross-sectional data of youth over 10 years of age from 2018 to 2020 National Surveys of Children's Health were used (n = 48,220). Rates of discrimination by SHCN diagnoses within racial and ethnic groups were examined. Adolescents of color with SHCNs were almost twice as likely to experience racial discrimination as peers of color without SHCNs. Asian youth with SHCNs were over 3.5 times likely to experience racial discrimination as peers without. Youth with depression experienced highest rates of racial discrimination. Compared to peers without, Black youth with asthma or a genetic disorder, and Hispanic youth with autism or intellectual disabilities, experienced higher rates of racial discrimination. SHCN status heightens racial discrimination for adolescents of color. However, this risk was not uniform by racial or ethnic group for every SHCN type.


Physical association of uPAR with the alphaV integrin on the surface of human NK cells.
The urokinase-type plasminogen activator receptor (uPAR) serves as a receptor for urokinase plasminogen activator (uPA) and plays a role in invasion and migration of certain immune cells, including NK cells. Although uPAR is anchored to the plasma membrane via a glycosylphosphatidylinositol lipid moiety, we have previously shown that uPAR crosslinking results in MAP kinase signaling and increased integrin expression on the surface of the human NK cell line, YT. We report, herein, that the binding of uPA to uPAR also activates the MAP kinase signaling cascade. Furthermore, we show the physical association between uPAR and integrins on YT cells using cocapping and fluorescence microscopy. These results suggest that signaling initiated by either uPAR binding to uPA or by uPAR clustering may depend on the physical association of uPAR with integrins, a process that may be a prerequisite for NK cell accumulation within established tumor metastases during adoptive therapy.


Recreational boating as a potential stressor of coastal striped dolphins in the northwestern Mediterranean Sea.
Striped dolphin (Stenella coeruleoalba) is the most abundant cetacean species in the western Mediterranean Sea. Coastal populations are locally exposed to intense recreational boating, a growing activity over the last thirty years. Dedicated boat surveys carried out since 1988 (13,896 km of effort), enabled to map relative abundance for two periods, 1988-2003 and 2004-2019, which evidenced a significant decrease of habitat use in the inshore part of study area. Coastal traffic was surveyed from a shore lookout located in Cap d'Antibes (French Riviera) during 47 daily sessions from May 2017 to April 2018: traffic flow often exceeded one boat per minute in summer, with a majority of motorboats. Underwater recordings showed that inshore noise was about 10 dB higher than in the open sea, with much energy being propagated by fast boats, including in the medium to high frequency domain. Ambient noise data collected during spring 2020 lockdown evidenced a clear noise level decrease compared to normal situations. Although other stressors may not be neglected, this study suggested that intense motorboat traffic is a likely contributor to the observed striped dolphin partial habitat loss.


Influences of Linker and Nucleoside for the Helical Self-Assembly of Perylene Along DNA Templates.
Six different conjugates of perylene with 2'-deoxyuridine and with 2-amino-2'-deoxyadenosine were synthesized and applied for DNA-templated assembly in aqueous buffer solutions. They differ by the linkers ethynylene, phenylene, and phenylene-ethynylene between nucleoside and chromophore. The nucleosides were investigated as monomers in CHCl3 and dimethyl sulfoxide by optical spectroscopy. The properties of the four phenylene-linked conjugates are similar to that of perylene as reference because these linkers separate both aromatic parts. The ethynylene linker electronically couples the chromophore with the respective nucleoside and thus red shifts the absorbance. The DNA-templated assembly properties were elucidated by mixing the templates in aqueous buffer with the perylene-nucleoside conjugates from a dimethyl sulfoxide stock solution. Specific binding of the nucleosides was probed by comparing the results with dA20 and T20 as single-stranded DNA templates. Our studies reveal the structural parameters that are important for the DNA-templated assembly of perylenes. First, perylene-2'-deoxyuridine conjugates do not form DNA-templated helical assemblies, regardless of the choice of linker. Second, the ethynylene linker is crucial for successful DNA-templated chromophore assemblies of perylene-2-amino-2'-deoxyadenosine conjugates. Third, in contrast, the phenylene linker inhibits self-assembly along single-stranded DNA templates. In conclusion, the 2-amino-2'-deoxyadenosin in combination with the ethynylene linker provides the best structural feature for specific and helical DNA-templated assembly of perylenes. This result is important for the design of future DNA-based supramolecular architectures with chromophores, in particular DNA-based light-harvesting systems and DNA systems for emitting or sensing circularly polarized luminescence.


Decreased calcium and magnesium urinary excretion during prostaglandin synthesis inhibition in the rat.
The effect of endogenous renal prostaglandins on calcium and magnesium reabsorption was investigated. Renal tubular handling of calcium and magnesium was studied by clearance methods in anesthetized Sprague-Dawley and Brattleboro rats, either intact or thyroparathyroidectomized (ATPTX), before and during prostaglandin synthesis inhibition by meclofenamate, indomethacin, or piroxicam infusion. These three inhibitors had similar effects on calcium and magnesium excretion: A significant decrease in absolute and fractional excretions of both cations was observed in intact Sprague-Dawley rats, and in ATPTX rats of both strains, but not in intact Brattleboro rats. These results suggest an inhibitory effect of prostaglandins on vasopressin-, glucagon-, but not PTH-mediated calcium and magnesium reabsorption. This effect is likely to occur in the thick ascending limb of Henle, which is both a target site for these polypeptidic hormones, and a segment where the bulk of calcium and magnesium is reabsorbed.


The Psychometric Properties of the World Health Organization Quality of Life-Bref Questionnaire in College Students.
Background and purpose: Because there are conflicting perspectives on the factor structure of the World Health Organization Quality of Life-BREF (WHOQOL-BREF) Questionnaire among college students, we evaluated the psychometric properties of the instrument in a sample of US college students. Methods: We conducted secondary analysis of data collected from 1,138 undergraduate students from a large metropolitan university in the southeastern United States. Results: Confirmatory factor analysis did not support the original four-factor structure. Based on exploratory factor analysis, three factors were retained and rotated using Varimax rotation, which accounted for 96% of the item variance. Cronbach's alphas for the factors were: social/psychological health 0.84; physical health 0.81; and environment 0.77. Sexual minorities had significantly lower scores on all factors than those who identified as heterosexuals. Conclusions: In this sample of college students, the WHOQOL-BREF was three-dimensional, and a significant amount of the item variance was explained. Lower quality of life scores of nonWhites and sexual minority college students point to a critical need that should be addressed.


Triplet exciton dynamics of pure organics with halogen substitution boosted two photon absorption and room temperature phosphorescence: A theoretical perspective.
Organic room temperature phosphorescence (RTP) molecules have shown promising applications in organic light emitting diodes and vivo imaging. Thus, triplet exciton dynamics in solid phase should be revealed and the molecule should possess large two photon absorption (TPA) cross sections under near-infrared excitation. The effects of halogen substitution and intermolecular interaction on RTP and TPA properties are studied at molecular level for a series of derivatives. Surrounding environment in solid phase is considered by combined quantum mechanics and molecular mechanics method. Intermolecular interactions are evaluated by the independent gradient model and calculated through the molecular force field energy decomposition method. Minimum energy crossing point, Huang-Rhys factor and reorganization energy are discussed, triplet exciton dynamics are investigated by thermal vibration correlation function method. Results indicate that the largest TPA cross sections are found for molecule in water. The halogen substitution can enlarge the proportion of (π, π*) and facilitate the intersystem crossing process. Restricted intramolecular rotation motions of dihedral angle in low frequency regions are found for Br-Np-Cz-BF2 in solid phase. While enhanced vibrations of bond length and bond angle in high frequency regions are detected for I-Np-Cz-BF2. Effects of halogen substitution and intermolecular interaction on triplet exciton dynamics are highlighted.


Augmented Reality Supported Cervical Transpedicular Fixation on 3D-Printed Vertebrae Model: An Experimental Education Study.
To investigate the use of Augmented Reality (AR) technology as it contributes to spinal surgery education with the free-hand technique, and might reduce the error ratio. Ten candidates, with anatomy education but no surgical experience, applied 36 pedicle screws with C2-C3 posterior transpedicular fixation technique to nine vertebrae models produced via a three-dimensional (3D) printer. Using AR to apply pedicle screws to the experimental vertebrae model increased the safety screw ratio significantly. In comparison of Grade 0 screws to other grades: 6/18 screws (33.3%) in the free-hand technique Group (n=18), and 14/18 screws (77.8%) in the AR Group (n=18), were measured for screw insertion safety ratios. The difference was statistically significant (p=0.018). The resemblance between our results and the results of previous studies researching supportive systems indicates our 3D printed vertebra model might be a helpful educational material. AR increases the safety ratio of cervical pedicle screw fixation significantly. The parameters investigated and used for the production of vertebrae models in this study can be used for experimental material production for future studies to investigate pedicle screw positioning.


Some results on the multipartite Ramsey numbers m j (C 3,C m ,n 1 K 2,n 2 K 2,…,n i K 2).
The graph K j × t is a graph which is complete and multipartite which includes j partite sets and t vertices in each partite set. The multipartite Ramsey number (M-R-number) m j ( G 1 , G 2 , … , G n ) is the smallest integer t for the mentioned graphs G 1 , G 2 , … , G n , in a way which for each n-edge-coloring ( G 1 , G 2 , … , G n ) of the edges of K j × t , G i contains a monochromatic copy of G i for at least one i. The size of M-R-number m j ( n K 2 , C 7 ) for j ≥ 2 , n ≤ 6 , the M-R-number m j ( n K 2 , C 7 ) for j = 2 , 3 , 4 , n ≥ 2 , the M-R-number m j ( n K 2 , C 7 ) for each j ≥ 5 , n ≥ 2 , the M-R-number m j ( C 3 , C 3 , n 1 K 2 , n 2 K 2 , … , n i K 2 ) for j ≤ 6 , and i , n i ≥ 1 , and the size of M-R-number m j ( C 3 , C 3 , n K 2 ) for j ≥ 2 and n ≥ 1 have been calculated in various articles hitherto. We acquire some bounds of M-R-number m j ( C 3 , C 3 , n 1 K 2 , n 2 K 2 , … , n i K 2 ) in this essay in which i , j ≥ 2 , and n i ≥ 1 , also the size of M-R-number m 4 ( C 3 , C 4 , n K 2 ) for each n ≥ 1 is computed in this paper.


Evaluation of the retinal ganglion cell and choroidal thickness in young Turkish adults with hyperopic anisometropic amblyopia.
The purpose of this study is to compare the choroidal thickness (CT) and ganglion cell complex (GCC) thickness of the normal fellow eyes and the amblyopic eyes using enhanced depth imaging optical coherence tomography (EDI-OCT) in young Turkish adults with hyperopic anisometropic amblyopia. Patients with unilateral hyperopic anisometropic amblyopia were enrolled and underwent a full ophthalmological assessment, including best-corrected visual acuity, cycloplegic refraction, and axial length (AL) measurements. Cirrus EDI-OCT was used to obtain subfoveal CT, GCC thickness, retinal nerve fiber layer (RNFL), and central macular thickness (CMT) measurements. Comparison was performed between the amblyopic eyes and the normal fellow eyes. Forty-three hyperopic anisometropic amblyopic patients were enrolled in this study. Mean age of 23 female and 20 male patients was 24.8 ± 7.4 years. Mean AL was 21.9 ± 1.3 and 22.4 ± 0.9 mm in amblyopic and fellow eyes, respectively (P < 0.05). Mean subfoveal CT measurements were 325.4 ± 44.2 and 317.9 ± 42.7 µ in amblyopic and fellow eyes, respectively. There was no statistically significant difference between the groups (P > 0.05). Mean GCC thickness was 83.8 ± 3.6 µ in amblyopic eyes and 83.5 ± 3.9 µ in the fellow eyes. Statistically significant difference was not seen between the groups (P > 0.05). Mean RNFL and mean CMT measurements were also similar in two groups (P > 0.05). Subfoveal CT, CMT, RNFL, and GCC thickness measurements were not statistically significant between hyperopic anisometropic amblyopic eyes and normal fellow eyes.


Tetra-kis(1-allyl-1H-imidazole-κN)bis-(thio-cyanato-κN)manganese(II).
The structure of the title compound, [Mn(NCS)(2)(C(6)H(8)N(2))(4)], consists of isolated mol-ecules of [Mn(NCS)(2)(Aim)(4)] (Aim = 1-allyl-imidazole), which contain a compressed octa-hedral MnN(6) chromophore (site symmetry [Formula: see text]). The NCS(-) anions are trans and four N atoms from the Aim ligands define the equatorial plane. The mean Mn-N(Aim) and Mn-N(NCS) distances are 2.270 and 2.229 Å, respectively. Weak C-H⋯N inter-actions contribute to the crystal packing stability.


Later onset of apoptosis in the bulbourethral glands after castration compared to that in the seminal vesicles.
Androgens affect many different target organs within the male reproductive tract to stimulate their development and secretory cytodifferentiation, and to maintain structure and function in adulthood. Castration causes regression of these organs via apoptosis. However, not all organs of the reproductive tract are equally sensitive to androgen withdrawal. The effects of castration on the mouse seminal vesicles (SVs) and bulbourethral glands (BUGs) were compared in terms of protein and DNA contents, epithelial apoptosis, and proliferative response of epithelial cells to androgen. Castration induced similar, marked decreases in protein contents in the SV and BUG by 2 days after castration which reached a minimum at 16 days post castration. Both organs underwent a decrease in DNA content, but the kinetics of this decline differed. In the SV, DNA content was significantly decreased by 4 days whereas in the BUG this did not occur until 16 days post castration. By day 16 both organs had regressed to roughly the same degree. The apoptotic index in the epithelium reflected this difference in timing as well. Apoptotic index of the SV epithelium was highest on day 3 after castration and declined thereafter. On the other hand, the apoptotic index in the BUG didn't begin to increase until 7 days after castration and became maximal on day 12. Daily injections of testosterone propionate (TP) from day 8, 16, or 30 after castration all increased epithelial labelling index in the SVs to a similar degree. However, the TP-induced increase in the epithelial labelling index in the BUG beginning on day 8 after castration was considerably less than that in BUGs receiving TP treatment from day 16 or 30 after castration. Thus, the proliferative response of the epithelium depended upon prior apoptosis in the gland, with the timing being delayed in the BUG as compared with the SV. The present results indicate that castration induces epithelial apoptosis and reduction in glandular DNA content considerably later in the BUG than in the SV though reduction in protein content in the BUG fell simultaneously with that in the SV.


Can SARS-CoV-2 trigger new onset of autoimmune disease in adults? A case-based review.
Although it has been proposed that SARS-CoV-2 can cause autoimmunity by inducing a transient immunodeficiency of both innate and acquired immunity components in which the immune system fails to identify autoantigens adequately, the exact mechanism that causes this disease remains unknown. We aim to systematically review of existing case reports for evidence of new autoimmune diseases in adults caused by SARS-CoV-2 infection. PRISMA-P 2020 method was used to search for literature in "PubMed" databases using the string "COVID-19 AND autoimmune disease AND complication". We used JBI Critical Appraisal Checklist to assess the articles' quality. The literature search yielded 666 articles. 58 articles met our eligibility criteria. Based on our critical appraisal, we placed 35 articles in the good category and 23 articles in the medium category. Data was synthesized by grouping similar data into a table, including: gender, age, COVID-19 severity, types of autoimmune diseases, autoimmune profile and relevant findings, when autoimmune diseases are diagnosed, complications, and outcome to draw conclusions. The new onset of autoimmune disease in adult triggered by SARS-CoV-2 included Guillain-Barré syndrome and Miller Fisher syndrome, systemic lupus erythematosus, immune thrombocytopenia, autoimmune haemolytic anemia, latent autoimmune diabetes in adults, myositis, acute demyelinating encephalomyelitis, autoimmune encephalitis, central nervous system vasculitis, and autoimmune thyroid diseases. SARS-CoV-2 can trigger new onset of a variety of autoimmune diseases. Doctors who take care patients infected by COVID-19 must be aware of the complications of autoimmune diseases. Future cohort or cross-sectional studies on SARS-CoV-2-related autoimmune disease should be conducted.


Amino acid sequence of subunit V of bovine heart cytochrome oxidase, the heme alpha-containing subunit.
The complete amino acid sequence of the heme alpha-containing subunit V of bovine heart cytochrome oxidase was determined to be: H2N-Ser-His-Gly-Ser-His-Glu-Thr-Asp-Glu-Glu-Phe-Asp-Ala-Arg-Trp-Val-Thr-Tyr-Phe-Asn-Lys-Pro-Asp-Ile-Asp-Ala-Trp-Glu-Leu-Arg-Lys-Gly-Met-Asn-Thr-Leu-Val-Gly-Tyr-Asp-Leu-Val-Pro-Glu-Pro-Lys-Ile-Ile-Asp-Ala-Ala-Leu-Arg-Ala-Cys-Arg-Arg-Leu-Asn-Asp-Phe-Ala-Ser-Ala-Val-Arg-Ile-Leu-Glu-Val-Val-Lys-Asp-Lys-Ala-Gly-Pro-His-Lys-Glu-Ile-Tyr-Pro-Tyr-Val-Ile-Gln-Glu-Leu-Arg-Pro-Thr-Leu-Asn-Glu-Leu-Gly-Ile-Ser-Thr-Pro-Glu-Glu-Leu-Gly-Leu-Asp-Lys-Val-COOH. The subunit V is a single polypeptide which consists of 109 amino acid residues. The protein contains 48.6% hydrophobic residues and 34.0% hydrophilic residues and it is an acidic protein having a net charge of -3 at neutral pH. The molecular weight of subunit V was calculated to be 12,436 and that for the heme alpha-containing polypeptide was 13,295.


Practitioner Reflections on Sex Offender Treatment in Remote Communities.
We offer reflections on practitioner service provision for sex offenders when working in remote communities. The social ecological model framework is used to capture the influence on practitioner working at an individual, relationship, community, and societal level. The social construction and geographic conditions of sexual offending within remote communities present myriad challenges for professionals working in these isolative settings in which they are embedded. Challenges include being the sole expert in a community, unavoidable dual relationships, community anxieties, and restrictive guidelines and assessment measures. Despite the challenges presented to practitioners operating in remote communities, many opportunities are available for building local and international peer relationships, connecting with the community, individualized treatment for clients, and flexibility in the adaptation of best practice to fit the needs of remote communities while maintaining ethical integrity.


The efficiency of high-flow nasal cannula for adult patients with coronavirus disease 19 in Jeddah, Saudi Arabia.
Early use of a high-flow nasal cannula (HFNC) provides positive outcomes for preventing the risk of intubation. However, the efficiency and usage of HFNC in the case of coronavirus disease 2019 (COVID-19) among adult patients with multiple risk factors remain debatable and require more investigation. The aim of this study was to determine the efficiency of HFNC in preventing the possible risk of intubation. This study was an observational cross-sectional study that was conducted at a selected hospital in Jeddah, Saudi Arabia, from July 2020 to August 2021. The data were collected from patients' medical records through the hospital health information system. Adult COVID-19 patients who used HFNC were included, while those who used bilevel positive airway pressure or continuous positive airway pressure without any trials of HFNC and neonatal or pediatric patients were excluded. The exposure of HFNC setting which included variables such as percentages of the fraction of inspired oxygen and the duration of using HFNC were measured to find the relation with respiratory rate oxygenation (ROX) index as a measurement of patient outcome. The data were analyzed by using the online calculator socscistatistics. com for prevalence statistics, and correlation tests of significance. Prevalence statistics were presented in mean, median, frequencies, and percentages. Statistical tests were used to measure correlations of key variables. P < 0.05 of ANOVA and t-tests was considered statistically significant. A total of 159 adult COVID-19 patients using HFNC were included, and most of these patients were male. The median age was 64 years. Most of patients were reported to have hypertension and diabetes mellitus. The majority (94.34%) of patients were successfully weaned from HFNC and shows effective intervention with a mean of 7.53 of ROX score. Appropriate implementation of HFNC might be a successful intervention for preventing the risk of intubation. According to the success rate of HFNC, which was considered a positive outcome, there might be a promising intervention for HFNC to prevent the risk of intubation and decrease the mortality rate.


Clinical Significance of FANCD2 Gene Expression and its Association with Tumor Progression in Hepatocellular Carcinoma.
Fanconi anemia complementation group D2 (FANCD2) gene is vitally involved in DNA damage responses. We investigated the clinical significance of FANCD2 expression in hepatocellular carcinoma (HCC). FANCD2 mRNA expression of resected HCC tissues was assessed in two HCC cohorts; Our cases (n=111), and The Cancer Genome Atlas (TCGA; n=371). Gene set enrichment analysis (GSEA) was conducted using the TCGA dataset. Proliferation and invasion assays were performed using siRNAs, and the effect of inhibition of the mechanistic target of rapamycin (mTOR) pathway was evaluated. FANCD2 expression was up-regulated in tumor tissues. Cases with high FANCD2 expression had poorer prognoses in both cohorts, and were associated with larger tumor size and invasive phenotypes. FANCD2 knockdown attenuated proliferation and invasion of HCC cells. FANCD2 expression was suppressed by mTOR inhibition. GSEA supported these findings. Elevated FANCD2 expression in HCC could be a novel biomarker for poor prognosis with potential therapeutic relevance.


Oestrogen receptors and their relation to neural receptive tissue of the labia minora.
To assess the cellular distributions of oestrogen receptors alpha and beta (ER alpha and ER beta) and neuronal nitric oxide synthase (nNOS) in the labia minora, as knowledge about ER type and function may clarify the role of oestrogens in vaginal scar formation and improve outcomes in female genital surgery. Labial samples were taken from 10 girls (aged 2-9 years) who underwent surgery for labial fusion. The waste tissue strips obtained were used for immunohistochemical identification of ER alpha and ER beta, and nNOS in the labia minora. There was ER alpha nuclear staining in the stroma of the labia minora close to the clitoris, and basal and suprabasal in the epidermal cells membrane restricted to superficial sections of the labia minora. ER beta was found in the stroma of the labia minora closer to the clitoris and in superficial sections, in the basal epidermal cells membrane and apocrine glandular epithelial cells membrane. There was also ER beta cell membrane staining in the basal and suprabasal epithelial cells and fibroblasts in the lamina propria. Established ER presence allows the consideration of the introitus of the vagina as a target for oestrogen therapy in various clinical and surgical situations. Continuing elucidation of the immunohistochemistry of this external genital tissue might assist in the development of molecular tools to treat genital abnormalities. Details of this immunohistochemistry may also advance the understanding of the effects of sexual differentiation on the brain and other organ systems.


Impacts of social distancing, rapid antigen test and vaccination on the Omicron outbreak during large temperature variations in Hong Kong: A modelling study.
The impacts of non-pharmaceutical interventions (NPIs) and vaccine boosters on the transmission of the largest outbreak of COVID-19 (the fifth wave) in Hong Kong have not been reported. The outbreak, dominated by the Omicron BA.2 subvariant, began to spread substantially after the Spring Festival in February, 2022, when the temperature varied greatly (e.g. a cold surge event). Tightening social distancing measures did not succeed in containing the outbreak until later with the use of rapid antigen tests (RAT) and increased vaccination rates. Temperature has been previously found to have significant impact on the transmissibility. Understanding how the public health interventions influence the number of infections in this outbreak provide important insights on prevention and control of COVID-19 during different seasons. We developed a transmission model incorporating stratified immunity with vaccine-induced antibody responses and the daily changes in population mobility, vaccination and weather factors (i.e. temperature and relative humidity). We fitted the model to the daily reported cases detected by either PCR or RAT between 1 February and 31 March using Bayesian statistics, and quantified the effects of individual NPIs, vaccination and weather factors on transmission dynamics. Model predicted that, with the vaccine uptake, social distancing reduced the cumulative incidence (CI) from 58.2% to 44.5% on average. The use of RAT further reduced the CI to 39.0%. Without vaccine boosters in these two months, the CI increased to 49.1%. While public health interventions are important in reducing the total infections, the outbreak was temporarily driven by the cold surge. If the coldest two days (8.5 °C and 8.8 °C) in February were replaced by the average temperature in that month (15.2 °C), the CI would reduce from 39.0% to 28.2%. Preventing and preparing for the transmission of COVID-19 considering the change in temperature appears to be a cost-effective preventive strategy to lead people to return to normal life.


Potent benzimidazolone-based CGRP receptor antagonists.
The previously disclosed spirohydantoin-based CGRP receptor antagonists were optimized for potency through modification of the benzimidazolone substituents. Compounds were identified which had minimal shift in the cAMP functional assay containing 50% human serum. Blockade of CGRP-mediated vasodilation was observed with these compounds in a rhesus pharmacodynamic assay and the in vivo potency correlated with the in vitro activity in the serum-shifted functional assay.


Sticking to the recipe. Develop one program with basic guidelines for improving care, effectiveness without overwhelming providers, the IOM says.
The IOM's call for a national initiative to determine best medical practices has some wondering how such an effort would work. But most everyone agrees that providers and payers are overwhelmed by data about clinical effectiveness. "Once we get an innovation, let's study it right away so we can be sure every person who could benefit gets it, or if it doesn't work, let's do no harm," says WellPoint's Samuel Nussbaum, left.


Understanding Associations Between Race/Ethnicity, Experiences of Discrimination, and Psychotic-like Experiences in Middle Childhood.
The present study aimed to examine factors that may account for race/ethnicity differences in psychotic-like experiences (PLEs) in a middle childhood sample, including evidence for experiences of discrimination as a psychosocial mediator of these differences. In a sample of 9- to 10-year-olds (N = 10,839) from the Adolescent Brain Cognitive Development Study, we compared PLEs across racial/ethnic groups. We also examined whether experiences of discrimination indirectly linked racial/ethnic identity and PLEs and whether social support moderated this indirect association. Differences between racial/ethnic groups were found in the endorsement of PLEs, such that Black and Hispanic participants endorsed higher levels of PLEs compared with Asian, multiracial/multiethnic, and White participants. These differences were accounted for in part by experiences of discrimination, an indirect effect that was in turn attenuated by increased social support. This is the first study to suggest that the experience of discrimination may indirectly link the association between racial/ethnic differences and endorsement of PLEs using the Prodromal Questionnaire-Brief Child Version and additionally that social support may act as a moderator of this mediation. Results provide evidence that social inequities such as racial discrimination may contribute to increases in PLEs. These findings shed further light on the links between structural racism and mental health inequities for people in minoritized groups.


The uptake and release of [3-H]-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthlane (ADTN) by striatal nerve terminals.
A study has been made of the uptake and release of [G-3H]-2-amino 6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) by crude striatal synaptosomes of the rat. 2 Uptake was rapid, temperature-dependent and could be suppressed by a variety of metabolic inhibitors. 3 The Michaelis-Menten kinetincs indicated the presence of two distinct transport systems in the striatum which were of much higher capacity than those found in the cerebellum, which lacks dopaminergic innervation. 4 Uptake of [3-H]ADTN was strongly inhibited by dopamine and the two potent dopamine-uptake inhibitors, benztropine and nomifensine, but only weakly by imipramine and amphetamine (the latter in non-reserpine-treated animals). 5 Accumulated [3-H]ADTN could be released from striatal slices by elevated K+. A similar release was evoked upon the addition of the ionophore, A23187. 6 The most potent releaser of [3-H]ADTN was (+)-amphetamine. This effect occurred at concentrations inactive against ADTN uptake. The neuroleptic cis-flupenthixol produced an inhibition of the spontaneous release. 7 It is concluded that [3-H]ADTN is accumulated preferentially into areas of the rat brain rich in dopamine. The pharmacological specificity of the uptake suggests that it is a good substrate for the dopamine carrier. Following uptake, [3-H]-ADTN may be released by K+ and a calcium ioniphore, which raises the possibility that ADTN might act as a false transmitter.


Rasmussen's encephalitis: Early diagnostic criteria in children.
Rasmussen's encephalitis (RE) is a rare chronic inflammatory brain disorder resulting in progressive neurodegeneration in one cerebral hemisphere. The inflammatory process is accompanied by progressive loss of function of the affected hemisphere, associated with drug-resistant partial epilepsy. The diagnosis is based on a range of clinical, electroencephalographic, radiological and biochemical arguments, without any specific formal marker, which makes the diagnosis of the disease complex, especially in its initial phase. Seizures are refractory to anti-seizures medication (ASM) and to classical immunomodulatory treatments. These treatments are also ineffective to stop the degenerative process. Only surgical treatment with hemispherotomy (surgical disconnection of a cerebral hemisphere) allows definitive cessation of seizures but this leads to definitive motor and cognitive deficits. The etiology of RE is not known, but there is strong evidence for an immunopathogenic mechanism involving T-cell mediated immunity. The emergence of biotherapies targeting against various cytokines offers potential therapeutic perspectives. This disease is currently a real challenge in terms of: (i) early diagnosis, before the constitution of marked hemispheric atrophy and the appearance of neurological and cognitive consequences; (ii) recognition of incomplete form; (iii) therapeutic management due to advances in the field of targeted treatment of inflammation; (iv) surgery and recovery possibilities.


Maternal serum adiponectin and leptin levels and their gene expression, postpartum body mass index, and breastfeeding duration based on mode of delivery: A prospective study.
Adipokines are involved in inflammatory responses, associated with body mass index whose concentrations may change in response to inflammatory conditions, including surgery and delivery. We examined adiponectin and leptin levels and their gene expression at birth, body mass index, and breastfeeding duration at 24 months postpartum according to mode of delivery. In this study, 90 normal pregnant women were investigated. Blood samples were collected after delivery. Serum levels and gene expression of adiponectin and leptin were evaluated. Body mass index and breastfeeding duration were calculated at 24 months postpartum. Data were analyzed using SPSS-16 and p < 0.05 was considered as significant. Serum leptin level was significantly higher in vaginal delivery than in cesarean section (p = 0.033). No significant difference was found between two groups regarding adiponectin level and gene expression, while leptin gene expression was significantly higher in cesarean (p = 0.005). Postpartum body mass index did not differ between the two groups (p = 0.14). On the other hand, postpartum body mass index was significantly higher than the equivalent prepregnancy index in both groups (p < 0.001) and was associated with serum leptin and adiponectin in vaginal delivery (r = 0.46, p = 0.001, and r = -0.3, p = 0.04, respectively). The duration of breastfeeding was longer in vaginal delivery (p = 0.008). Cesarean section was associated with lower maternal leptin levels and shorter breast-feeding duration compared to vaginal delivery. Leptin gene expression was significantly higher in cesarean section than in vaginal delivery. Postpartum body mass index, adiponectin level, and gene expression did not differ between the two groups.


Cholinergic projections to the basolateral amygdala: a combined Evans Blue and acetylcholinesterase analysis.
The origins and acetylcholinesterase (AChE, EC 220.127.116.11) content of neurons projecting to the AChE-rich basolateral amygdala were studied by infusing Evans Blue (EB), a retrogradely transported fluorescent label, into that neural region and, following microscopic evaluation of labelled somata, staining the same tissue sections for AChE according to the pharmacohistochemical regimen. The following basal forebrain areas contained cells labelled with EB: the lateral preoptic area, ventral pallidum, nuclei of the diagonal band, medial septal nucleus, bed nucleus of the stria terminalis, and substantia innominata. The majority of the basal forebrain neurons projecting to the basolateral amygdala stained intensely for AChE, suggesting that they were cholinergic. In the brainstem, EB-labelled neurons staining intensely for AChE were found less frequently, but a few were observed in the nucleus tegmenti pendunculopontis, locus ceruleus, subcerulear region, and reticular formation. Cells accumulating EB after basolateral amygdala infusion but demonstrating no, weak, or moderate AChE activity were seen in the orbitofrontal, anterior cingulate, temporal, and insular cortices; the mediodorsal, paraventricular, and parataenial nuclei of the thalamus; the periventricular gray substance; the ventromedial mesencephalic tegmentum; the lateral and compact portions of the substantia nigra; the dorsal raphe; the dorsal tegmental nucleus; and the dorsal parabrachial nucleus. On the basis of staining intensity, intracellular organization of the AChE reaction product, and previous results in the literature, we conclude that the major cholinergic input to the basolateral amygdala derives from the basal forebrain.


STAT3 can be activated through paracrine signaling in breast epithelial cells.
Many cancers, including breast cancer, have been identified with increased levels of phosphorylated or the active form of Signal Transducers and Activators of Transcription 3 (STAT3) protein. However, whether the tumor microenvironment plays a role in this activation is still poorly understood. Conditioned media, which contains soluble factors from MDA-MB-231 and MDA-MB-468 breast cancer cells and breast cancer associated fibroblasts, was added to MCF-10A breast epithelial and MDA-MB-453 breast cancer cells. The stimulation of phosphorylated STAT3 (p-STAT3) levels by conditioned media was assayed by Western blot in the presence or absence of neutralized IL-6 antibody, or a JAK/STAT3 inhibitor, JSI-124. The stimulation of cell proliferation in MCF-10A cells by conditioned media in the presence or absence of JSI-124 was subjected to MTT analysis. IL-6, IL-10, and VEGF levels were determined by ELISA analysis. Our results demonstrated that conditioned media from cell lines with constitutively active STAT3 are sufficient to induce p-STAT3 levels in various recipients that do not possess elevated p-STAT3 levels. This signaling occurs through the JAK/STAT3 pathway, leading to STAT3 phosphorylation as early as 30 minutes and is persistent for at least 24 hours. ELISA analysis confirmed a correlation between elevated levels of IL-6 production and p-STAT3. Neutralization of the IL-6 ligand or gp130 was sufficient to block increased levels of p-STAT3 (Y705) in treated cells. Furthermore, soluble factors within the MDA-MB-231 conditioned media were also sufficient to stimulate an increase in IL-6 production from MCF-10A cells. These results demonstrate STAT3 phosphorylation in breast epithelial cells can be stimulated by paracrine signaling through soluble factors from both breast cancer cells and breast cancer associated fibroblasts with elevated STAT3 phosphorylation. The induction of STAT3 phosphorylation is through the IL-6/JAK pathway and appears to be associated with cell proliferation. Understanding how IL-6 and other soluble factors may lead to STAT3 activation via the tumor microenvironment will provide new therapeutic regimens for breast carcinomas and other cancers with elevated p-STAT3 levels.


Mutations in the acetolactate synthase (ALS) enzyme affect shattercane (Sorghum bicolor) response to ALS-inhibiting herbicides.
Shattercane [Sorghum bicolor (L.) Moench ssp. Arundinaceum (Desv.)] is a competitive weed in North America's corn, soybean, sorghum, and other agronomic crops. Control of shattercane with POST herbicides in corn became possible with the introduction of acetolactate synthase (ALS)-inhibiting herbicides in the 1980s, and their extensive use resulted in the evolution of ALS-inhibitors resistant shattercane. Shattercane seeds were collected from 16 south-eastern and south-central Nebraska fields that were treated with primisulfuron for three consecutive years. Three resistant plants were found in greenhouse evaluations of more than 30,000 plants. Results from a greenhouse bioassay conducted to assess the response of each shattercane biotype to ALS-inhibiting herbicides showed a differential response to ALS inhibitors within and between chemical classes. Biotype P8-30 was resistant or partially resistant to all ALS-inhibiting herbicides applied and displayed a unique amino acid sequence substitution (Trp574 to Leu) relative to the other two resistant biotypes, P2-205 and P9-102. Whole plant dose-response studies confirmed a 4- to the 12-fold level of primisulfuron resistance in three shattercane biotypes compared with the known primisulfuron-susceptible shattercane biotype. The ALS gene was sequenced using primers designed from the corn ALS sequence to identify mutations in the ALS gene that confer resistance. A total of seven nucleotide substitutions were detected in the three herbicide-resistant biotypes P2-205, P8-30, and P9-102. These biotypes are being crossed to adapted sorghum lines (grain, sweet, and forage) to broaden germplasm with resistance to ALS-inhibiting herbicides. The discovery of these mutants should accelerate the development of sorghum genotypes that tolerate ALS-based herbicides, which provide additional choices for sorghum farmers to control weeds, especially grasses, in their fields.


Use of cryopreserved umbilical cord with negative pressure wound therapy for complex diabetic ulcers with osteomyelitis.
The objective of this study was to evaluate the combined use of cryopreserved human umbilical cord (cUC) allograft and negative pressure wound therapy (NPWT) in treating complex diabetic foot ulcers (DFUs) with bone exposure and osteomyelitis. These types of wound are known to carry a high morbidity and mortality. A single-center, retrospective chart review was performed to assess the efficacy of the combined use of cUC with NPWT, by the same surgeon, to help promote the closure of complex DFUs presenting with biopsy-proven osteomyelitis. Change in wound size and volume, time to wound closure, and number of cUC applications were assessed. We identified of 14 wounds in 13 patients, with an average initial wound area of (mean±standard devaition) 33.2±21.7cm2 and wound volume of 52±26.2cm3. All achieved complete re-epithelialisation with an average time to closure of 24.0±10.9 weeks, using between 2-5 cUC applications. No adverse events were noted and none of the wounds required limb amputation during the a follow-up of 24 months for each patient. The results suggest that combined use of cUC and NPWT may be effective in improving the healing of complex DFUs that present with osteomyelitis. Prospective, randomised controlled trials are warranted to confirm this efficacy as well as its potential applications in other chronic wounds.


Cs-131 brachytherapy for patients with recurrent glioblastoma combined with bevacizumab avoids radiation necrosis while maintaining local control.
Re-irradiation of recurrent glioblastoma (GBM) may delay further recurrence but re-irradiation increases the risk of radionecrosis (RN). Salvage therapy should focus on balancing local control (LC) and toxicity. We report the results of using intraoperative Cesium-131 (Cs-131) brachytherapy for recurrent GBM in a population of patients who also received bevacizumab. Twenty patients with recurrent GBM underwent maximally safe neurosurgical resection with Cs-131 brachytherapy between 2010 and 2015. Eighty Gy was prescribed to 0.5 cm from the surface of the resection cavity. All patients previously received adjuvant radiotherapy and temozolomide, and received bevacizumab before or after salvage brachytherapy. Seven of 20 (35%) tumors were multiply recurrent and had been previously salvaged with external beam radiotherapy. Patients received MRI scans every 2 months monitored for recurrence, progression, and RN. Median tumor diameter was 4.65 cm (range, 1.2-6.3 cm). Median number of seeds pace was 41 (range, 20-74) with total seed activity 96.8U (range, 41.08-201.3U). At a median followup of 19 months, crude LC was 85% and median overall survival was 9 months (range, 5-26 months). There were two postoperative wound infections (10%), three seizures (15%), and 0% incidence of RN. Our study demonstrates that while LC and survival are similar to other studies of postoperative external beam radiotherapy, no RN occurred in any of these patients, including 7 multiply re-irradiated patients. Of interest, there were patients with multiple recurrences whose survival extended beyond 20 months. These findings suggest that the use of highly conformal Cs-131 brachytherapy is a promising treatment for patients with recurrent GBM with minimal risk of development of RN.


The influence of mild cataract on ISCEV standard electroretinogram recorded from mydriatic eyes.
To investigate the effect of mild cataract and its surgery on the ISCEV standard electroretinogram (ERG) by comparing pre- and postoperative ERGs elicited from fully dilated eyes. Twenty-two patients participated. Each eye had cataract of grade 2 according to Emery-Little classification. None had complications during and after phacoemulsification and intraocular lens implantation. According to the ISCEV standard, pre- and 1-week postoperative full-field ERGs, dark adapted (DA) 0.01, DA 3, DA 3 oscillatory potentials (OPs), DA 10, and light adapted (LA) 3, and LA 3 flicker, were elicited from fully dilated eyes using skin electrodes. Photopic negative response (PhNR) 1 amplitude was measured from the baseline to the trough before the i-wave in the LA 3 ERG waveform. Statistical analysis was performed using SigmaPlot version 11.0 (Systat Software, Inc., San Jose, CA, USA). Pre- and postoperative data were compared using a paired t-test. Non-normally distributed data were evaluated using the Wilcoxon signed rank test. The pre- and 1-week postoperative amplitudes in each component were as follows: DA 0.01: 48.4 ± 19.5 μV and 57.1 ± 20.0 μV (p = 0.002), a-wave of DA3: 51.5 ± 14.8 μV and 58.3 ± 17.3 μV (p = 0.003), b-wave of DA3: 88.3 ± 27.5 μV and 101.5 ± 29.7 μV (p = 0.003), DA 3 ΣOPs (sum of DA 3 OP1, OP2, and OP3 amplitude): 30.7 ± 16.3 μV and 37.1 ± 21.9 μV (p < 0.001), a-wave of DA 10: 65.5 ± 18.8 μV and 74.2 ± 19.5 μV (p < 0.001), b-wave of DA 10: 95.5 ± 29.6 μV and 111.1 ± 29.9 μV (p < 0.001), a-wave of LA 3: 7.2 ± 2.6 μV and 8.2 ± 2.2 μV (p = 0.025), b-wave of LA 3: 30.6 ± 12.9 μV and 35.3 ± 12.7 μV (p = 0.003), PhNR1: 5.8 ± 2.5 μV and 5.5 ± 2.6 μV (p = 0.562), and LA 3 flicker: 25.4 ± 8.9 μV and 27.8 ± 8.6 μV (p = 0.039), respectively. The implicit time of all the components did not reveal significant differences before and after surgery. Cataractous lens removal and intraocular lens implantation may influence ISCEV standard ERGs, even if the cataract is relatively mild.


Prevalence and Associated Risk Factors of Suicidal Ideation Among Brazilian Pregnant Women: A Population-Based Study.
Suicide is a leading cause of death during the perinatal period in high-income countries (HIC). There remains a lack of population-based studies about suicidal ideation (SI) during pregnancy among low and middle income countries (LMIC). Using the case of Brazil, we aim to estimate the prevalence of SI during pregnancy and its association with antenatal depression (AD) and sociodemographic factors in a LMIC. We used data from the Brazilian National Survey (PNS-2019), a population-based study, with a complex and probabilistic sampling method. Of the 27,136 women of reproductive age (15 to 49 years old) who participated in the PNS, a total of 769 women reported being pregnant at the time of the interview. All PNS participants answered the Patient Health Questionnaire-9 (PHQ-9) and a questionnaire with sociodemographic data. SI was defined as any answer to the PHQ-9 item 9 other than 0 (not at all). Logistic regression models were performed to obtain crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for the association between explanatory variables and SI during pregnancy. Among 769 women, 33 (3.9%, 95% CI: 3.0-5.1%) reported SI during pregnancy. In the adjusted analysis, higher odds of SI were associated with being 20 to 34 years old (aOR:0.24, 95% CI: 0.08-0.74) or 35 to 49 years old (aOR:0.15; 95% CI: 0.04-0.50), having 9 to 11 years of education (aOR 0.23, 95% CI: 0.61-0.86), acheiving the highest family income category (aOR:0.08, 95% CI: 0.01-0.58), not living in the South/Southeast regions of Brazil (aOR:5.52, 95% CI: 2.36-12.9), and having probable mild AD (aOR:10.5 95% CI: 2.3-47.9) or moderate AD (aOR:241.3, 95% CI: 58.4-996.7). In Brazil, SI affects almost 4% of pregnant women and is associated with sociodemographic vulnerability. Clinically, women with mild symptoms of depression may also experience SI during pregnancy. These findings are important for designing effective perinatal mental health interventions in LMICs.


Functional evidence of reversible ischemic injury immediately after the sympathetic storm associated with experimental brain death.
Acute brain death from increased intracranial pressure results in a transient increase in myocardial adenosine and lactate, which indicates that oxygen demand exceeds oxygen delivery during the sympathetic "storm". The aim of this study was to determine the functional significance of this period of ischemia. Brain death was inflicted on 40 Westran pigs (36.5-68.0 kg) by inflating a 21-ml subdural balloon over 3 minutes. In 38 animals, micromanometry and sonomicrometry were used to obtain left ventricular pressure-volume loops to determine the preload recruitable stroke work (PRSW) relationship. Data files were recorded before and at 15-minute intervals after beginning balloon inflation. Plasma troponin I was measured before and 60 minutes after beginning balloon inflation in the 38 instrumented and 2 non-instrumented animals. All animals experienced the classical sympathetic storm. The slope of the PRSW relationship decreased, and the volume-axis intercept shifted to the right 15 minutes after beginning balloon inflation (p < 0.0001). Progressive incremental recovery (leftward shift) occurred between subsequent time points (p < or = 0.0018). In the instrumented animals, the mean plasma troponin I level increased from 1.4 +/- 1.6 microg/liter to 2.8 +/- 2.3 microg/liter (p < 0.001). However, troponin I was not detected before or after induction of brain death in the plasma of either non-instrumented animal (p = 0.001). The sympathetic storm produced transient contractile dysfunction, consistent with ischemic injury. However, troponin I release reflected surgical instrumentation and not brain death.


The role of tonal onglides in German nuclear pitch accents.
A perception experiment with native German listeners provided evidence for the relevance of the tonal onglide in nuclear accents--the pitch movement leading towards the target on the accented syllable. Listeners were able to distinguish between two pragmatic meanings of a short phrase (given/non-contrastive and new/contrastive) using the tonal onglide as the sole acoustic cue. On the basis of these findings, we argue that the onglide merits a phonological status in an intonation model of German and should not be regarded as merely phonetic detail.


Colon cancer stem cells: implications for prevention and therapy.
The recent identification of colon cancer tumor-initiating cells adds further support to the cancer stem cell hypothesis. Ongoing basic and translational research efforts are aimed at gaining an increased understanding of the biology of these cells, as well as methods of targeting them. In addition, the relationship between colon carcinogenesis and inflammatory conditions, such as longstanding colitis and inherited syndromes, might be linked to the effect of the processes on stem cells in the colon. This review summarizes current literature on colon cancer stem cells and proposes strategies aimed at targeting these cells for colon cancer prevention and therapy.


Fact-finding survey of doctors at the departments of pediatrics and pediatric surgery on the transition of patients with childhood-onset chronic disease from pediatric to adult healthcare.
The number of adult patients with childhood-onset chronic diseases is increasing. However, the process of transitioning these patients from child- to adult-centered medical services faces many difficulties. Despite the key role that doctors in the pediatric field are considered to play in transition, few fact-finding surveys about transition have been conducted among these doctors. The aim of this study was to demonstrate the current status and challenges in the transition of patients with childhood-onset chronic diseases by a fact-finding survey of pediatricians and pediatric surgeons at a university hospital. A cross-sectional survey was performed using an anonymous self-administered questionnaire. Seventy-six doctors of pediatrics and pediatric surgery (excluding junior residents) in a university hospital were asked to answer an anonymous self-report questionnaire. A multidisciplinary research team selected items related to the transitional process. Sixty (79%) doctors participated, of whom 52 (87%) showed awareness of transition. No doctor answered that "Transition is conducted smoothly." Doctors with shorter pediatric department experience had lower awareness and poorer experience with transition. In contrast to pediatric surgeons, pediatricians explained "job-seeking activities" and "contraceptive methods" to the patient, and reported a higher patient age at which to initiate explanation of transition to the patient and his/her family. Among factors inhibiting transition, 39 (65%) respondents selected "The patient's family members do not desire transition" and 34 (57%) selected "Although a relevant adult healthcare department is available, it will not accept the patient." The medical providers most frequently considered to have responsibility for playing a central role in the transition process were "pediatrician/pediatric surgeon," "medical social worker," and "regional medical liaison office." To promote transition, pediatric and adult healthcare departments should share concerns about and cooperate in the establishment of more effective methods of transition, and provide multidisciplinary collaboration to support patients and their families.


Micropropagation and cytogenetic assessment of Zingiber species of Northeast India.
An improved micropropagation protocol was developed for Zingiber moran and Z. zerumbet, two wild species of the genus Zingiber, found in Northeast India. The effects of growth regulators, sugar concentrations, and nutrients were tested on the rate of shoot initiation and multiplication. An increase in proliferation and multiplication occurred in modified Murashige and Skoog (MS) medium supplemented with benzyladenine and kinetin. About 2 % sucrose and 0.7 % agar were found to be the optimum for shoot multiplication and regeneration. Naphthalene acetic acid at 0.5 mg/L produced the best rooting response for both the species. Regenerated plantlets were acclimatized successfully and cytogenetic stability was confirmed by RAPD profiling and ploidy checks.


Expression of c-ABL, c-KIT, and platelet-derived growth factor receptor-beta in ovarian serous carcinoma and normal ovarian surface epithelium.
Tyrosine kinases, such as c-KIT, c-ABL, and platelet-derived growth factor-beta (PDGFR-beta), are important regulators of cell growth. Highly potent and selective inhibitors of tyrosine kinases are being investigated as alternatives to standard chemotherapy. One such inhibitor, imatinib mesylate, is being used to treat gastrointestinal stromal tumors and chronic myelogenous leukemia. Ovarian carcinomas frequently develop resistance to conventional chemotherapeutic agents. Immunohistochemical expression of c-ABL, PDGFR-beta, and c-KIT was evaluated in ovarian carcinomas to determine whether treatment with imatinib mesylate might be feasible. The expression of c-ABL, c-KIT, and PDGFR-beta in tumors was evaluated by immunohistochemical analysis of 52 ovarian serous carcinomas, including 21 low-grade (well differentiated) and 31 high-grade (poorly differentiated) tumors. Fourteen normal ovaries were also evaluated. In normal ovarian surface epithelium, c-ABL was expressed universally. PDGFR-beta was expressed in the majority (93%) of samples of normal ovarian epithelium, whereas the c-KIT protein was undetectable in normal ovarian surface epithelium. Overall, c-ABL was expressed in 71% of serous carcinomas. c-ABL was expressed more frequently in the low-grade serous carcinomas (81%) compared with the high-grade serous carcinomas (65%). PDGFR-beta expression was observed in 81% of serous carcinomas overall and was observed more frequently in higher-grade tumors. c-KIT immunohistochemical staining was absent in low-grade tumors but was present in 26% of high-grade serous carcinomas. The majority of ovarian serous carcinomas express one or more of the kinases targeted by the tyrosine kinase inhibitor, imatinib mesylate, suggesting the potential usefulness of this drug in the treatment of ovarian carcinoma.


Lanthanide-Catalyzed Tandem Insertion of Secondary Amines with 2-Alkynylbenzonitriles: Synthesis of Aminoisoindoles.
A lanthanide-catalyzed intermolecular hydroamination of 2-alkynylbenzonitriles with secondary amines has been disclosed, providing a streamlined access to a range of aminoisoindoles in moderate to excellent yields. The salient features of this reaction include high bond-formation efficiency, mild reaction conditions, 100 % atomic efficiency and good functional group tolerance. This methodology has also been successfully applied to the construction of other nitrogen-containing compounds, such as 5 H-imidazo[2,1-a]isoindoles and isoquinolines. A plausible mechanism for the formation of aminoisoindoles involving initial N-H activation by a lanthanide complex followed by C≡N insertion into a Ln-N bond to form an amidinate lanthanide intermediate, which undergoes the cyclization is proposed.


Changes in plasma steroid and thyroid hormones and insulin during final maturation and spawning of the sea lamprey, Petromyzon marinus.
Circulating levels of plasma estradiol-17 beta, androgens, thyroxine, triiodothyronine, immunoreactive insulin, plasma fatty acids, and protein were measured at interval during the period of final gonadal maturation, prior to spawning of male and female sea lampreys. Plasma estradiol levels fluctuated significantly and generally covaried in males and females through time. In females, possibly in relation to environmental changes, mean plasma estradiol levels peaked four times during the final spawning period but decreased sharply at the time of ovulation. In males, mean plasma estradiol peaked seven times during the final prespawning period and, in contrast to females, peaked significantly at the time of final spermiation. Plasma androgens were extremely low and covaried in males and females through time. Like plasma steroid profiles, there were coordinated changes in plasma triiodothyronine and thyroxine levels in males and females through the prespawning season. There was a slight increase in plasma insulin during the terminal maturation of the lampreys. However, at ovulation, the insulin levels abruptly decreased in females, whereas in males they remained unchanged. Plasma protein and fatty acid levels gradually decreased until ovulation/spermiation. At ovulation plasma fatty acid levels increased.


A misinterpreted case of aorta prosthesis endocarditis: remember the phenomenon of microbubbles.
A 17-year-old male with a history of newly implanted mechanical valve at the aortic position, presented with fever, rigors, and painful cutaneous abscesses on his lower extremities and was suspected for infective endocarditis. Transthoracic echocardiography (TTE) showed a vegetation-like structure following the movement of the mechanical heart valve (MHV), which eventually proved to be a product of degassing microbubbles (MB).


Hypoxic preconditioning decreases nuclear factor κB activity via Disrupted in Schizophrenia-1.
Nuclear factor κB is a key mediator of inflammation during conditions of hypoxia. Here, we used models of hypoxic pre-conditioning as mechanism to decrease nuclear factor κB activity induced by hypoxia. Our initial studies suggested that Disrupted in Schizophrenia-1 may be induced by hypoxic pre-conditioning and possibly involved in the regulation of nuclear factor κB. In this study we used Disrupted in Schizophrenia-1 exogenous over-expression and knock-down to determine its effect on ataxia telangiectasia mutated--nuclear factor κB activation cascade. Our results demonstrated that hypoxic pre-conditioning significantly increased the expression of Disrupted in Schizophrenia-1 at mRNA and protein levels both in vitro and in vivo. Over-expression of Disrupted in Schizophrenia-1 significantly attenuated the hypoxia-mediated ataxia telangiectasia mutated phosphorylation and prevented its cytoplasm translocation where it functions to activate nuclear factor κB. We further determined that Disrupted in Schizophrenia-1 activated the protein phosphatase 2A, preventing the phosphorylation of ataxia telangiectasia mutated serine-1981, the main regulatory site of ataxia telangiectasia mutated activity. Cellular levels of Disrupted in Schizophrenia-1 protein significantly decreased nuclear factor κB activation profiles and pro-inflammatory gene expression. Taken together, these results demonstrate that hypoxic pre-conditioning decreases the activation of nuclear factor κB through the transcriptional induction of Disrupted in Schizophrenia-1.


[The comparative analysis of laparoscopic and minilaparotomic techniques in emergency abdominal surgery].
Owing the experience of 16 101 miniinvasive operations by acute diseases of the abdominal cavity, the authors pose that the introduction of polytechnological methods has certain perspectives. The combination of different methods with the use of modern technologies lead to better results.


Design, synthesis, and cytotoxic screening of novel azole derivatives on hepatocellular carcinoma (HepG2 Cells).
Novel azole derivatives 3-30 were designed, synthesized, and screened for their antitumor activity on HepG2 cell line. The cytotoxicity screening demonstrated that imidazolone 8 and triazoles 25 and 29 exhibited more potent cytotoxic activities by 1.21-, 4.75-, and 1.8-fold compared to Sorafenib (SOR). Furthermore, vascular endothelial growth factor receptor-2 (VEGFR-2) enzyme inhibition assay declared that compounds 25 and 29 had inhibitory activity at the nanomolar concentration. Moreover, the tested compounds exhibited good β-tubulin (TUB) polymerization inhibition percentages. In addition, DNA flow cytometry analysis over HepG2 cells indicated that triazoles 25 and 29 demonstrated arrest at G1 and G2/M phase of the cell cycle and induced apoptotic activity by increasing sub-G1 phase. Finally, mechanistic studies of the proapoptotic activities of compounds 8, 10, 11, 25, and 29 indicated that they induced upregulation of P53, Fas/Fas-ligand, and BAX/BCL-2 ratio expression that resulted in increasing the active caspase 3/7 percentages and trigger apoptosis.


The effect of particle size on hydrolysis reaction rates and rheological properties in cellulosic slurries.
The effect of varying initial particle sizes on enzymatic hydrolysis rates and rheological properties of sawdust slurries is investigated. Slurries with four particle size ranges (33 microm < x < or = 75 microm, 150 microm < x < or = 180 microm, 295 microm < x < or = 425 microm, and 590 microm < x < or = 850 microm) were subjected to enzymatic hydrolysis using an enzyme dosage of 15 filter paper units per gram of cellulose at 50 degrees C and 250 rpm in shaker flasks. At lower initial particle sizes, higher enzymatic reaction rates and conversions of cellulose to glucose were observed. After 72 h 50 and 55% more glucose was produced from the smallest size particles than the largest size ones, for initial solids concentration of 10 and 13% (w/w), respectively. The effect of initial particle size on viscosity over a range of shear was also investigated. For equivalent initial solids concentration, smaller particle sizes result in lower viscosities such that at a concentration of 10% (w/w), the viscosity decreased from 3000 cP for 150 microm < x < or = 180 microm particle size slurries to 61.4 cP for 33 microm < x < or = 75 microm particle size slurries. Results indicate particle size reduction may provide a means for reducing the long residence time required for the enzymatic hydrolysis step in the conversion of biomass to ethanol. Furthermore, the corresponding reduction in viscosity may allow for higher solids loading and reduced reactor sizes during large-scale processing.


Recent advances the investigation of proptosis.
Clincal assessment of the patient presenting with proptosis determines the investigations required to make the diagnosis.


[Technics and methods of intravital microangiography in the rat lung under conditions of shock].
Report on a method of opacifying the pulmonary terminal blood stream track in normal animals and those with experimentally induced tourniquet-shock. Based on own experiences from more than than 200 experimental animals (rats) material, technique, and method are described in detail, and some important errors are discussed that might arise and should be avoided.


Hyaluronan Works on the Right for Directional Gut Looping.
The cellular basis of left-right asymmetric organogenesis remains largely unknown, but signaling events on the left side were thought to be dominant. In this issue of Developmental Cell, however, Sivakumar et al. (2018) suggest that covalent modification of hyaluronan on the right side initiates directional looping of the developing midgut.


Medical Graduate's Basic Knowledge and Clinical Skills Assessment in Otorhinolaryngology Post Internship.
Exposure to otorhinolaryngology in India has been shadowed by an inadequate curriculum. Our study brings forth the lacunae in medical education setup related to ENT. We introspect why the subject is not a first choice for specialization. 100 medical graduates were assessed at the end of internship postings for: (1) subject knowledge, (2) basic and emergency procedures, (3) diagnosis and investigation of common and emergency conditions. 84% take ENT as a minor subject. Least awareness is seen regarding its relation with skull base, head and neck and plastic surgery. Very few knew about advanced surgeries and instruments in the field. Majority rejected ENT as a primary choice and its upgradation as major subject. Routine and emergency procedures based on ENT were not a matter of ease by majority of subjects. Post internship doctors lagged in doing basic clinical and diagnostic steps. Diagnosis of various pathologies was not a skill of majority of subjects under study. A lack of basic knowledge of important emergency conditions in ENT was noticed. Our study points at inadequate training in ENT and under estimation of its scope. The outcome raises a need to revise the curriculum and methodology to come at par with world standards, reflecting its true expanse and tremendous scope.


A comparison of the effects of cyclosporine (CsA) on hepatic microsomal drug metabolism in three different strains of rat.
1. Male albino Wistar (W), Sprague-Dawley (SD) and Fischer-344 (F344) rats, Rattus norvegicus, were dosed orally once daily with cyclosporine (CsA), 25 mg/kg/day, for 14 days. Control and treated rats were then sacrificed and selected assays were performed to measure differences in hepatic microsomal enzyme activity including: protein (PROT), cytochrome P-450 (CYT-P450) and cytochrome b5 (CYT-b5) levels, NADPH-cytochrome c reductase (CYT-c) activity, ethylmorphine N-demethylase (ETM) and aniline hydroxylase (ANL) activities. 2. Two-way analysis of variance (ANOVA) indicated that the effect of treatment alone showed significant strain-related differences in all parameters examined except CYT-b5 levels, while the effect of strain alone indicated significant differences in PROT, CYT-B5, CYT-c, and ANL. 3. The interaction component of the two-way ANOVA (treatment x strain) indicated strain-related differences in substrate metabolism only (ETM and ANL). 4. F344 rats were found to be significantly different from either Sprague-Dawley or Wistar rats in terms of the effect of CsA on ETM and ANL metabolism.


Validation of an analytical method for quality control of residual solvents (n-hexane and acetone) in D-002: new active ingredient from beeswax.
D-002 is a new natural product consisting of a mixture of aliphatic fatty alcohols, which shows antioxidant and anti-ulcer effects in experimental models. A new validated methodology for determining simultaneously residual n-hexane and acetone in D-002 using the headspace gas chromatography (HS/GC) is described. The very poor solubility of D-002 in most solvents did necessary sample preparations in solid state. Limit test conditions allowed a detection of residual n-hexane and acetone more sensitively than that recommended for such purposes in the general method of the European Pharmacopoeia. Validation assays, applied to both D-002 residual solvents, proved: suitable sensitivity; very high linearity (correlation coefficients > or =0.999, R.S.D. of slopes < or =0.8% and R.S.D. of response factors < or =5% and no biases) and accuracy (average recoveries between 94.7 and 100.1%); and precision was < or =2.1%. The method was found suitable for quality control and stability studies of this new product.


Orbital-dependent Electron-Hole Interaction in Graphene and Associated Multi-Layer Structures.
We develop an orbital-dependent potential to describe electron-hole interaction in materials with structural 2D character, i.e. quasi-2D materials. The modulated orbital-dependent potentials are also constructed with non-local screening, multi-layer screening, and finite gap due to the coupling with substrates. We apply the excitonic Hamiltonian in coordinate-space with developed effective electron-hole interacting potentials to compute excitons' binding strength at M (π band) and Γ (σ band) points in graphene and its associated multi-layer forms. The orbital-dependent potential provides a range-separated property for regulating both long- and short-range interactions. This accounts for the existence of the resonant π exciton in single- and bi-layer graphenes. The remarkable strong electron-hole interaction in σ orbitals plays a decisive role in the existence of σ exciton in graphene stack at room temperature. The interplay between gap-opening and screening from substrates shed a light on the weak dependence of σ exciton binding energy on the thickness of graphene stacks. Moreover, the analysis of non-hydrogenic exciton spectrum in quasi-2D systems clearly demonstrates the remarkable comparable contribution of orbital dependent potential with respect to non-local screening process. The understanding of orbital-dependent potential developed in this work is potentially applicable for a wide range of materials with low dimension.


"Eight-drugs-in-one-day" chemotherapy administered before and after radiotherapy to adult patients with malignant gliomas.
Thirty-one adult patients with malignant glioma (23 with glioblastoma multiforme, six with anaplastic astrocytoma, and two with brainstem glioma) were treated with up to ten cycles of "eight-drugs-in-one-day" chemotherapy (methylprednisolone 300 mg/m2, vincristine 1.5 mg/m2 [maximum of 2 mg/cycle], CCNU 75 mg/m2, procarbazine 75 mg/m2, hydroxyurea 3000 mg/m2, cisplatin 90 mg/m2, cytosine arabinoside 300 mg/m2, and imidazole carboxamide 150 mg/m2). Chemotherapy was planned as two cycles before and eight cycles after 60 Gy of involved brain irradiation. A total of 117 cycles of chemotherapy was administered. There was one treatment-related death. Myelosuppression was the most frequent toxic effect (leucopenia was less than 1000/mm3 in 9% of cycles and 1000-2500/mm3 in 25%; thrombocytopenia was less than 100,000/mm3 in 33% of cycles). Sixteen patients developed infections requiring treatment, two of which were life-threatening. Five patients suffered ototoxicity. Nausea and vomiting were observed in 35% of patients. A reversible rise in creatinine was observed in five patients. One patient developed a severe motor neuropathy, and three patients developed mild peripheral neuropathies. Three patients had episodes of atrial fibrillation. One new bundle branch block with supraventricular tachycardia was observed in a patient with pulmonary embolus. Five patients developed thrombophlebitis, three of whom had pulmonary emboli. Two patients suffered strokes in areas anatomically separate from their tumor. Eleven patients declined to continue therapy after receiving an average of three cycles. Two had complete, and five had partial responses. The median survival time was 47 weeks. The responses and survival times observed are comparable to less toxic treatment protocols for adults with malignant gliomas.


Interlaminar differences of spike activation threshold in the auditory cortex of the rat.
The neural circuits of the auditory cortex are a substrate for the dual purpose of representing and storing the auditory signal on one hand, and sending its relevant features to other cortical and subcortical areas on the other hand. The ability to process and transform the signal crucially depends on achievement of the neuronal spike threshold following spatiotemporal summation of the synaptic signals. We used patch-clamp recording in a thin slice preparation to compare neuronal responses to current injection of layer II/III and layer V neurons. We found that while the two classes of neurons do not differ in passive neuronal properties, layer II/III neurons possess a lower firing threshold relative to layer V neurons (-44.8 +/- 2.4 mV vs. -34.3 +/- 4.0 mV). We speculate that a lower spiking threshold in layer II/III neurons might favor local intracolumnar activation for representation and storage of the auditory information whereas a more positive spiking threshold for layer V neurons may prevent unnecessary cortical spread of a scarcely processed signal.


Recombination technologies for enhanced transgene stability in bioengineered insects.
Transposon-based vectors currently provide the most suitable gene transfer systems for insect germ-line transformation and are used for molecular improvement of the Sterile Insect Technique. However, the long time stability of genome-integrated transposon constructs depends on the absence of transposase activity that could remobilize the transposon-embedded transgenes. To achieve transgene stability transposon vectors are usually non-autonomous, lacking a functional transposase gene, and chosen so that endogenous or related transposon activities are not present in the host. Nevertheless, the non-autonomous transposon-embedded transgenes could become unstable by the unintended presence of a mobilizing transposase that may have been undetected or subsequently entered the host species by horizontal gene transfer. Since the field release of transgenic insects will present environmental concerns relating to large populations and high mobility, it will be important to ensure that transgene constructs are stably integrated for maintaining strain integrity and eliminating the possibility for unintentional transfer into the genome of another organism. Here we review efficient methods to delete or rearrange terminal repeat sequences of transposons necessary for their mobility, subsequent to their initial genomic integration. These procedures should prevent transposase-mediated remobilization of the transgenes, ensuring their genomic stability.


Comparison of modified supports on the base of glycoprotein interaction studies and of adsorption investigations.
The features of matrices, suitable for affinity chromatography, have been extensively investigated and got subject for several reviews. But these investigations show, that there is still a lack in adsorbent characterization and a demand of comparative investigations of adsorbents, based on different materials with a range of different surface functionalities. In this work the performance of self-prepared silica and cellulose-based adsorbents were compared with commercially available polymeric supports. A model system was chosen comprising the lectins concanavalin A (ConA) and wheat germ agglutinin (WGA), which were covalently attached to the support matrices, combining the selectivity of the lectin-sugar interaction with the chemical and mechanical properties of the support that influence the efficacy of the prepared adsorbent. The verification of the different supports provides information about tayloring carbohydrate specific lectin adsorbents. The characterization outlines the main features of the different adsorbents and takes into account the properties of the pure supports. It encompasses immobilization kinetics and isotherms as well as the description of the binding capacity of the adsorbents by depicting adsorption isotherms. The separation performances were also investigated in terms of glycoprotein purification factors and recoveries. Further, detailed information about binding of GOD to immobilized ConA are obtained.


Use of retrograde cold crystalloid cardioplegia in a patient with unexpected cold agglutination.
Undetected cold agglutinins were encountered in a patient undergoing coronary artery bypass grafting using antegrade cold blood cardioplegia. Macroemboli were infused into the coronary arterial tree. These were flushed out by the use of retrograde cold crystalloid cardioplegia. Activated cold agglutinins may be hazardous in cold blood cardioplegia.


Complement C1q binding affects spin-labeled heterosaccharides of rabbit antibodies in immune but not artificial immunoglobulin G aggregates.
IgG anti-hapten antibodies were purified from the sera of rabbits homozygous for allotypic determinants d11 and d12 in the constant region of the heavy chain. Correlative with this determinant is the absence (d11) or presence (d12) of an oligosaccharide chain just below the hinge region of the IgG molecule. Both d11 and d12 molecules contain a complex heterosaccharide chain located near the carboxyl terminus of the second constant region domain. The two populations of IgG antibodies were thus selectively labeled with the spin probe Tempamine in their second constant region domains by reductive amination primarily of terminal N-acetylneuraminic acid residues. Chemical and enzymatic cleavages showed about 80% of the attached spin labels were N-acetylneuraminic acid-associated. Analysis of probe adducts by ESR spectrometry showed the presence of slower and faster moving subcomponents. Formation of immune complexes by antigen induces slight but significant restrictions of spin label mobility for both d11 and d12 IgG molecules. This restriction is qualitatively different from that seen in glutaraldehyde-, carbodiimide-, or ethanol-induced aggregates of the same IgG antibodies. The addition of purified complement C1 subcomponent C1q to immune aggregates resulted in marked immobilization of spin labels, the rotational correlation time of which was 30-40 mu s for both d11 and d12 molecules (evaluated by saturation transfer spectroscopy). A similar spin probe immobilizing effect is not seen when C1q binds to chemically aggregated IgG antibodies (which also do not activate C1). A novel model is proposed in which C1q is hypothesized to juxtapose Fc moieties in a discrete fashion required for subsequent C1 activation processes mediated by immune complexes.


Pyrotinib plus capecitabine for trastuzumab-resistant, HER2-positive advanced breast cancer (PICTURE): a single-arm, multicenter phase 2 trial.
Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer and primary resistance to trastuzumab have a poor clinical outcome and lack good evidence to inform clinical decision. This study investigated the efficacy and safety of pyrotinib plus capecitabine in this population. This phase 2 trial was conducted at 16 sites in China. Patients received oral pyrotinib 400 mg once daily and capecitabine 1000 mg/m2 twice a day on days 1-14 of each 21-day cycle until disease progression or intolerable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS). Between June 2019 and September 2021, 100 patients were enrolled with a median age of 51 years (range, 24-69). All patients had been treated with trastuzumab and 21 (21.0%) patients had prior use of pertuzumab. As of August 31, 2022, the median follow-up duration was 20.1 months (range, 1.3-38.2). The median PFS was 11.8 months (95% confidence interval [CI], 8.4-15.1), which crossed the pre-specified efficacy boundary of 8.0 months. The objective response rate was 70.0% (70/100), with a median duration of response of 13.8 months (95% CI, 10.2-19.3). The disease control rate was 87.0% (87/100). The median overall survival was not reached. The most common grade ≥ 3 treatment-emergent adverse event was diarrhea (24 [24.0%]). No treatment-related deaths occurred. Pyrotinib plus capecitabine can be considered to be a treatment option in HER2-positive advanced breast cancer patients who have shown primary resistance to trastuzumab. Even in the era of modern anti-HER2 treatments, this clinical setting warrants more investigations to meet unmet needs. ClinicalTrials.gov, NCT04001621. Retrospectively registered on June 28, 2019.


Cancer after pre-eclampsia: follow up of the Jerusalem perinatal study cohort.
To compare the incidence of cancer among women with and without a history of pre-eclampsia. Cohort study. Jerusalem perinatal study of women who delivered in three large hospitals in West Jerusalem during 1964-76. 37 033 women. Age adjusted and multivariable adjusted hazard ratios for cancer incidence for the entire cohort and for women who were primiparous at study entry. Cancer developed in 91 women who had pre-eclampsia and 2204 who did not (hazard ratio 1.27, 95% confidence interval 1.03 to 1.57). The risk of site specific cancers was increased, particularly of the stomach, ovary epithelium, breast, and lung or larynx. The incidence of cancer of the stomach, breast, ovary, kidney, and lung or larynx was increased in primiparous women at study entry who had a history pre-eclampsia. A history of pre-eclampsia is associated with increases in overall risk of cancer and incidence at several sites. This may be explained by environmental and genetic factors common to the development of pre-eclampsia and cancer in this population.


Analgesic activity of substance P in rats: tolerance and cross-tolerance with enkephalin.
In rats, tolerance to the analgesic effect of intraventricular substance P (SP) develops quickly. In rats made tolerant to [D-Ala2, D-Leu5]enkephalin the analgesic efficacy of SP is reduced significantly. The latter result suggests some overlap in the sites of action of SP and [D-Ala2,D-Leu5] enkephalin. Since SP seems to lack any direct effect on opiate receptors of the brain, the present data suggest that the analgesic effect of SP is mediated by enkephalin release at supraspinal levels which are related to pain control.


Secondary school implementation of a healthy eating policy.
Healthy canteen policies regulating the sales of food and beverages are available across all the states and territories in Australia. The aim of this study was to assess the compliance with a newly updated healthy school canteen policy in New South Wales (NSW) among a sample of secondary schools. A cross-sectional study of secondary school canteen menus was undertaken in selected regions across NSW (September 2017-November 2017). Government and Catholic secondary schools with a canteen menu publicly available on school websites were eligible for inclusion. Menus were classified according to the NSW Healthy School Canteen Strategy using a Quick Menu Audit tool, previously validated in primary schools. Of 62 Catholic and 128 Government secondary schools located in the study region, 53 secondary schools (25 Catholic and 28 Government) were eligible to participate. The average percentage of "everyday" (healthy) items on secondary school menus was 54% (strategy criteria is >75%). Twenty-eight per cent of menus had no "sugary drinks" (should not be sold). None of the 53 menus assessed met all strategy criteria regarding the availability of foods and beverages. There was no statistically significant difference in meeting; (a) 75% minimum "everyday" items and (b) no "sugary drinks," by socio-economic region, remoteness, school enrolments or school type. If public health benefits of healthy eating policies are to be realised, secondary schools need to be supported to implement such policies. SO WHAT?: Future research assessing the impact of intervention strategies to support policy implementation in secondary schools is recommended.


Total arsenic concentrations in toenails quantified by two techniques provide a useful biomarker of chronic arsenic exposure in drinking water.
Accurate quantitation of any contaminant of interest is critical for exposure assessment and metabolism studies that support risk assessment. A preliminary step in an arsenic exposure assessment study in Nevada quantified total arsenic (TAs) concentrations in tissues as biomarkers of exposure. Participants in this study (n=95) were at least 45 years old, had lived in the area for more than 20 years, and were exposed to a wide range of arsenic concentrations in drinking water (3-2,100 ppb). Concentrations of TAs in blood, urine, and toenails determined by hydride generation-atomic fluorescence spectrometry (HG-AFS) ranged from below detection to 0.03, 0.76, and 12 ppm, respectively; TAs in blood rarely exceeded the limit of detection. For comparison, TAs in toenails determined by neutron activation analysis (NAA) ranged from below detection to 16 ppm. Significant (P<0.0001) positive regressions were seen between the TAs concentration in toenails and in drinking water (adjusted r(2)=0.3557 HG-AFS, adjusted r(2)=0.3922 NAA); TAs concentrations in urine were not described by drinking water As (adjusted r(2)=0.0170, P=0.1369). Analyses of TAs in toenails by HGAFS and NAA yielded highly concordant estimates (r=0.7977, P<0.0001). These results suggest that toenails are a better biomarker of chronic As exposure than urine in the current study, because the sequestration of As in toenails provides an integration of exposure over time that does not occur in urine.


Inhibition of muscle spindle afferent activity during masseter muscle fatigue in the rat.
The influence of muscle fatigue on the jaw-closing muscle spindle activity has been investigated by analyzing: (1) the field potentials evoked in the trigeminal motor nucleus (Vmot) by trigeminal mesencephalic nucleus (Vmes) stimulation, (2) the orthodromic and antidromic responses evoked in the Vmes by stimulation of the peripheral and central axons of the muscle proprioceptive afferents, and (3) the extracellular unitary discharge of masseter muscle spindles recorded in the Vmes. The masseter muscle was fatigued by prolonged tetanic masseter nerve electrical stimulation. Pre- and postsynaptic components of the potentials evoked in the Vmot showed a significant reduction in amplitude following muscle fatigue. Orthodromic and antidromic potentials recorded in the Vmes also showed a similar amplitude decrease. Furthermore, muscle fatigue caused a decrease of the discharge frequency of masseter muscle spindle afferents in most of the examined units. The inhibition of the potential amplitude and discharge frequency was strictly correlated with the extent of muscle fatigue and was mediated by the group III and IV afferent muscle fibers activated by fatigue. In fact, the inhibitory effect was abolished by capsaicin injection in the masseter muscle that provokes selective degeneration of small afferent muscle fibers containing neurokinins. We concluded that fatigue signals originating from the muscle and traveling through capsaicin-sensitive fibers are able to diminish the proprioceptive input by a central presynaptic influence. In the second part of the study, we examined the central projection of the masseter small afferents sensitive to capsaicin at the electron-microscopic level. Fiber degeneration was induced by injecting capsaicin into the masseter muscle. Degenerating terminals were found on the soma and stem process in Vmes and on the dendritic tree of neurons in Vmot. This suggests that small muscle afferents may influence the muscle spindle activity through direct synapses on somata in Vmes and on dendrites of neurons in Vmot.


Phosphatidylglyerol Lipid Binding at the Active Site of an Intramembrane Protease.
Transmembrane substrate cleavage by the small Escherichia coli rhomboid protease GlpG informs on mechanisms by which lipid interactions shape reaction coordinates of membrane-embedded enzymes. Here, I review and discuss new work on the molecular picture of protein-lipid interactions that might govern the formation of the substrate-enzyme complex in fluid lipid membranes. Negatively charged PG-type lipids are of particular interest, because they are a major component of bacterial membranes. Atomistic computer simulations indicate POPG and DOPG lipids bridge remote parts of GlpG and might pre-occupy the substrate-docking site. Inhibition of catalytic activity by PG lipids could arise from ligand-like lipid binding at the active site, which could delay or prevent substrate docking. Dynamic protein-lipid H-bond networks, water access to the active site, and fluctuations in the orientation of GlpG suggest that GlpG has lipid-coupled dynamics that could shape the energy landscape of transmembrane substrate docking.


Surgical correction of far advanced otosclerosis.
The patient with far advanced otosclerosis (a nonmeasurable bone-air gap) may appear superficially to be suffering from profound or total sensorineural impairment. Only by a careful history and examination can a proper diagnosis be made. Stapedectomy has produced satisfactory results in 46 per cent of these cases in our hands.


Proteomic analyses of somatic and zygotic embryos of Cyclamen persicum Mill. reveal new insights into seed and germination physiology.
In the horticulturally important ornamental species Cyclamen persicum Mill., somatic embryogenesis is an efficient vegetative propagation method and the development of artificial seeds is an ultimate aim. This study aims at a systematic comparison of the proteomes of zygotic embryos, somatic embryos grown in liquid medium containing 30 or 60 g l(-1) sucrose, germinating embryos of both types and endosperm in order to obtain novel insights into seed and germination physiology. Using high resolution two-dimensional isoelectric focussing/sodium dodecylsulfate polyacrylamide gel electrophoresis (2D IEF/SDS PAGE), 74% of the proteins expressed in zygotic embryos were found in similar abundance in somatic embryos grown in 60 g l(-1) sucrose. Somatic embryos grown in 30 g l(-1) sucrose accumulated fewer protein species than those grown in 60 g l(-1). Selected proteins were identified following mass spectrometry (nano-LC-MS/MS). Four enzymes involved in glycolysis (UDP-glucose pyrophosphorylase, fructose bisphosphate aldolase, triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase GAPDH) were specifically induced in somatic embryos. 11S globulin proteins identified by MS were present in high levels in somatic embryos, zygotic embryos and endosperm, whereas 7S globulins were detected mainly in endosperm and zygotic embryos. These are the first storage proteins identified in C. persicum. Xyloglucans are known to be another group of seed storage compounds in C. persicum. Interestingly, xyloglucan endotransglycosylases were found to be highly expressed in endosperm tissue. We discuss the physiological implications of these observations.


[Chronic otitis and hearing loss revealing a disseminated tuberculosis in a child].
Ear localization is sometimes the first symptom of tuberculosis. We report a case of a teen with a chronic otitis revealing a disseminated tuberculosis. The investigations showed ear, bones and pulmonary localisations. The outcome with treatment showed a persistent hearing loss. Middle ear tuberculosis should be suspected in patients with chronic otitis and risk factors of tuberculosis. A disseminated tuberculosis should be investigated and an early treatment is necessary to prevent hearing loss.


Effects of an agonist interleukin-2/Fc fusion protein, a mutant antagonist interleukin-15/Fc fusion protein, and sirolimus on cardiac allograft survival in non-human primates.
To tilt the immunologic balance toward tolerance and away from rejection, non-human primate recipients of cardiac allografts were treated with interleukin (IL)-2/Fc, mutant (m) antagonist type mIL-15/Fc, and sirolimus. Heterotopic heart transplants were performed on 8 fully mismatched cynomolgus macaques. An untreated control recipient rejected its graft by post-operative Day 6. The remaining 7 animals received oral or intramuscular immunosuppression with sirolimus. A recipient treated with sirolimus alone rejected at the end of 28 days of immunosuppression. The remaining 6 monkeys also received IL-2/Fc and mIL-15/Fc intramuscularly until 28 days after transplant. One animal received a second 28-day course of fusion protein starting at Day 50. In these 6 animals, sirolimus was continued for 28 days (n = 4) or until protein levels were low (n = 2). In the 4 monkeys treated with a 28-day course of sirolimus and fusion proteins, mean graft survival was 51.5 days (range, 28-76 days). The animal receiving a second course of fusion protein rejected its graft on Day 177, despite detectable levels of the fusion proteins and sirolimus. The central memory, effector memory, and naïve CD4(+) and CD8(+) T-cell populations in the peripheral blood did not change significantly during fusion protein administration. A 2.5-fold expansion in CD4(+)CD25(+) lymphocytes occurred in recipients treated with fusion proteins and sirolimus that was not observed in the recipient treated with sirolimus alone. Although IL-2/Fc, mIL-15/Fc, and sirolimus administered in this manner permitted modest prolongation of graft survival and expansion of CD4(+)CD25(+) T cells, tolerance was not achieved.