Exploring the Pain in Patellofemoral Pain: A Systematic Review and Meta-Analysis Examining Signs of Central Sensitization.
Patellofemoral pain (PFP) has high recurrence rates and minimal long-term treatment success. Central sensitization refers to dysfunctional pain modulation that occurs when nociceptive neurons become hyperresponsive. Researchers in this area of PFP have been increasingly productive in the past decade. To determine whether evidence supports manifestations of central sensitization in individuals with PFP. We searched MeSH terms for quantitative sensory testing (QST) pressure pain thresholds (PPTs), conditioned pain modulation (CPM), temporal summation, sensitization, hyperalgesia, and anterior knee pain or PFP in PubMed, SPORTDiscus, CINAHL, Academic Search Complete, and EBSCOhost. Peer-reviewed studies that were written in English and published between 2005 and 2020 and investigated QST or pain mapping in a sample with PFP were included in this review. The initial search yielded 140 articles. After duplicates were removed, 78 abstracts were reviewed. The full text of 21 studies was examined, and we included 15 studies in our evaluation: 6 in the meta-analysis, 4 in the systematic review, and 5 in both the meta-analysis and systematic review. A random-effects meta-analysis was conducted for 4 QST variables (local PPTs, remote PPTs, CPM, temporal summation). Strong evidence supported lower local and remote PPTs, impaired CPM, and facilitated temporal summation in individuals with PFP compared with pain-free individuals. Evidence for heat and cold pain thresholds was conflicting. Pain mapping demonstrated expanding pain patterns associated with long duration of PFP symptoms. Signs of central sensitization were present in individuals with PFP, indicating altered pain modulation. The etiologic and treatment models of PFP should reflect the current body of evidence regarding central sensitization. Signs of central sensitization should be monitored clinically, and treatments with central effects should be considered as part of a multimodal plan of care.


Mechanism of contraction rhythm homeostasis for hyperthermal sarcomeric oscillations of neonatal cardiomyocytes.
The heart rhythm is maintained by oscillatory changes in [Ca2+]. However, it has been suggested that the rapid drop in blood pressure that occurs with a slow decrease in [Ca2+] preceding early diastolic filling is related to the mechanism of rapid sarcomere lengthening associated with spontaneous tension oscillation at constant intermediate [Ca2+]. Here, we analyzed a new type of oscillation called hyperthermal sarcomeric oscillation. Sarcomeres in rat neonatal cardiomyocytes that were warmed at 38-42 °C oscillated at both slow (~ 1.4 Hz), Ca2+-dependent frequencies and fast (~ 7 Hz), Ca2+-independent frequencies. Our high-precision experimental observations revealed that the fast sarcomeric oscillation had high and low peak-to-peak amplitude at low and high [Ca2+], respectively; nevertheless, the oscillation period remained constant. Our numerical simulations suggest that the regular and fast rthythm is maintained by the unchanged cooperative binding behavior of myosin molecules during slow oscillatory changes in [Ca2+].


First record and five new species of Xylographellini (Coleoptera: Ciidae) from China, with online DNA barcode library of the family.
We report the first record of the beetle tribe Xylographellini (Ciidae) from the continental Palaearctic Region, represented by five new species discovered in Yunnan and Sichuan provinces, China: Scolytocis danae sp. nov., Syncosmetus euryale sp. nov., Sync. medusa sp. nov., Sync. perseus sp. nov. and Sync. stheno sp. nov. Illustrations and identification keys are provided for these new species, and in order to facilitate further research of Ciidae we present an open-access DNA barcode library (dx.doi.org/10.5883/DS-SYNCOSM) containing 114 records (of 44 species in 14 genera), 15 of which belong to the newly described species. A phylogenetic analysis based on the barcode fragment of the cytochrome oxidase I gene did not recover much tree structure within Ciidae, however both Xylographus Mellié and Syncosmetus Sharp were recovered as clades, with a single Scolytocis Blair being the sister to the latter.


Allergenic components of bald-faced hornet (V. maculata) venom.
Bald-faced hornet (V. maculata) venom collected by electrical stimulation was fractionated using molecular exclusion gel-filtration and ion-exchange chromatography. Four fractions were selected for in-depth analysis. These were analyzed for phospholipase, hyaluronidase and protease enzyme activities, antigenicity as measured by reaction with anti-hornet venom rabbit serum, and allergenic activity, as determined by RAST reaction with sera from hornet-sensitive patients. The results of these studies suggest that the fractions containing phospholipase, hyaluronidase and protease possess allergenic activity. In addition, there appear to be other allergenic components in hornet venom. Allergic patients differ in their reactivity to the various allergenic components in hornet venom and may have IgE antibodies to one or more of these components.


High rate of detection of subtelomeric aberration by using combined MLPA and subtelomeric FISH approach in patients with moderate to severe mental retardation.
(1) To evaluate the prevalence of subtelomeric deletion in moderate to severe mental retardation population, (2) to assess the feasibility and cost-effectiveness of combined methodology in routine workup of this sub-population. Twenty unrelated patients using strict selection criteria were recruited for the study from the Clinical Genetic Service. Patients were initially screened by Multiplex Ligation-dependent Probe Amplification (MLPA) for subtelomeric imbalance followed by FISH analysis for anatomical integrity. This is then followed by parental subtelomeric FISH analysis. Three subtelomeric deletions were identified. They were Deletion 1p36, Deletion 1q44 and Deletion 10q26; these were previously unidentified by conventional technique. The prevalence of subtelomeric deletion in our cohort of moderate to severe mental retardation patients is consistent with published findings of around 10%. The figure is on the higher side if more stringent criteria is used. The combination of strict clinical criteria, MLPA and selective subtelomeric FISH was shown to be feasible and cost-effective.


The in vivo anti-leukemia activity of N-(1-Pyrenlyl) maleimide in a bioluminescent mouse model.
In a search for anticancer drugs by screening for inhibitors of telomerase, we have identified several small-molecule inhibitors that selectively inhibit telomerase in a cell-free system. Among these inhibitors, N-(1-pyrenyl) maleimide (NPM) induced apoptosis and displayed the greatest differential cytotoxicity against acute T cell leukemia-derived Jurkat cells cultured in vitro. In this work, the in vivo anti-leukemia activity of NPM was investigated using a bioluminescent mouse model. The luciferase-expressing Jurkat cells (Jurkat-Luc) were mixed with matrigel and injected subcutaneously into the nude mice. Drug treatment was commenced on day 7 after tumor implantation. The growth of xenografted tumors was significantly inhibited in the mice treated with NPM, which is comparable to the inhibitory effect of a classical anti-leukemia drug, cyclophosphamide. Combined treatment with NPM and cyclophosphamide further enhanced the growth inhibition of xenografted Jurkat-Luc cells. Immunohistochemistry staining with cleaved caspase 3 (cl-caspase 3) indicated a very heavy staining of cl-caspase 3 only in the tumor implants excised from the NPM-treated mice. We conclude that NPM induced apoptosis and inhibited the growth of xenografted Jurkat-Luc cells in nude mice, demonstrating that NPM displays anti-leukemia activity in vivo.


Correlated three-dimensional light and electron microscopy reveals transformation of mitochondria during apoptosis.
In addition to their role in cellular bioenergetics, mitochondria also initiate common forms of programmed cell death (apoptosis) through the release of proteins such as cytochrome c from the intermembrane and intracristal spaces. The release of these proteins is studied in populations of cells by western blotting mitochondrial and cytoplasmic fractions of cellular extracts, and in single cells by fluorescence microscopy using fluorescent indicators and fusion proteins. However, studying the changes in ultrastructure associated with release of proteins requires the higher resolution provided by transmission electron microscopy. Here, we have used fluorescence microscopy to characterize the state of apoptosis in HeLa cells treated with etoposide followed by electron microscopy and three-dimensional electron microscope tomography of the identical cells to study the sequence of structural changes. We have identified a remodelling of the inner mitochondrial membrane into many separate vesicular matrix compartments that accompanies release of proteins; however, this remodelling is not required for efficient release of cytochrome c. Swelling occurs only late in apoptosis after release of cytochrome c and loss of the mitochondrial membrane potential.


Biodegradation of cyanide in cassava wastewater using a novel thermodynamically-stable immobilized rhodanese.
Extracellular rhodanese obtained from Aureobasidium pullulans was employed in both free and immobilized forms for the biodegradation of cyanide present in cassava processing mill effluent (CPME). Crosslinking with glutaraldehyde (at an optimum concentration of 5% v/v) before entrapment in alginate beads resulted in the highest immobilization yield of 94.5% and reduced enzyme leakage of 1.8%. Rhodanese immobilized by cross-linking before entrapment (cbe) retained about 46% of its initial activity after eight cycles of catalysis compared to the entrapment in alginate alone (eaa) which lost more than 79% after the fifth catalytic cycle. A cross-examination of thermodynamic (ΔGd*, ΔSd*, ΔHd*) kinetic (kd, t1/2, D and z-values) parameters at 30-70 °C showed that cbe displayed a higher resistance to thermal inactivation when compared to the free enzyme (fe) and (eaa). The efficiency of cyanide biodegradation from the CPME by the fe, eaa and cbe were 55, 62, and 74% respectively after 6 h. Rhodanese immobilized via cbe had a higher resistance to thermal denaturation over other enzyme forms. Hence, this makes cbe adaptable for large-scale detoxification of cyanide from CPME.


[Vascular Calcification - Pathological Mechanism and Clinical Application - . The effect of phosphate binders on vascular calcification].
Vascular calcification is the abnormality in chronic kidney disease-mineral bone disorder (CKD-MBD) that directly affects the prognosis in relation with cardiovascular diseases. Phosphate binders (PB) are widely used to prevent hyperphosphatemia that can lead to vascular calcification. Two types of PB are available ; calcium (Ca) -based PB and non-Ca-based PB. Non-Ca-based PB has been shown to retard the progression of vascular calcification, while there is a great concern that Ca overload can promote calcification. Moreover, the newer non-Ca-based PBs have been developed including iron and magnesium. We must pay attention to select proper types of PB with costs, pill burdens and specific circumstances observed in Japan.


Expression of YKL-40 and MIP-1a proteins in exudates and transudates: biomarkers for differential diagnosis of pleural effusions? A pilot study.
YKL-40 is an extracellular matrix glycoprotein with a significant role in tissue inflammation and remodeling. MIP-1a has chemotactic and pro-inflammatory properties, and is induced by YKL-40 in several lung disorders. The aim of this study was to determine the levels of YKL-40 and MIP-1a in blood serum and pleural fluids of various pulmonary diseases, and to evaluate their potential role as differential diagnosis biomarkers. We recruited 60 patients (age: 62.5 ± 20.6 years) with pleural effusions: 49 exudates and 11 transudates (T). Exudates were further classified based on the underlying disease: ten with tuberculosis (TB), 13 with lung cancer (LCa), 15 with metastatic cancer (MCa) of non-lung origin and 11 with parapneumonic (PN) effusions. YKL-40 and MIP-1a levels were measured by ELISA. Pleural YKL-40 levels (ng/ml) were similar among all patient groups (TB: 399 ± 36, LCa: 401 ± 112, MCa: 416 ± 34, PN: 401 ± 50, T: 399 ± 42, p = 0.92). On the contrary, YKL-40 was significantly lower in the serum of TB patients (TB: 58 ± 22, LCa: 212 ± 106, MCa: 254 ± 140, PN: 265 ± 140, T: 229 ± 123, p < 0.001). Pleural MIP-1a protein levels (ng/ml) were statistically lower only in patients with LCa (TB: 25.0 ± 20.2, LCa: 7.3 ± 6.0, MCa: 16.1 ± 14.9, PN: 25.4 ± 27.9, T: 18.5 ± 7.9, p = 0.012), a finding also observed in serum MIP-1a levels (TB: 17.1 ± 7.6, LCa: 9.4 ± 7.0, MCa: 28.7 ± 28.7, PN: 33.3 ± 24.0, T: 22.9 ± 8.7, p = 0.003). Our data suggest that both YKL-40 and MIP-1a, particularly in serum, could prove useful for the differentiation of pleural effusions in clinical practice, especially of TB or LCa origin. However, large-scale studies are needed to validate these findings.


Participation of encephalitogen in incomplete Freund's adjuvant in the induction of experimental allergic encephalomyelitis in Hartley guinea pigs.
The addition of complete Freund's adjuvant (CFA) to encephalitogen is required for the induction of experimental allergic encephalomyelitis (EAE). On the other hand, administration of encephalitogen in incomplete Freund's adjuvant (IFA) protects the animal from the development of EAE. It is shown in this work that injection of homologous central nervous system (CNS) tissue or myelin basic protein (BP) in IFA, before challenge with CNS tissue in CFA, accelerated the onset of the disease in Hartley guinea pigs. It also appeared to protect the animals, however, because 22% of the group did not develop EAE at all, and in those which did, the disease was not as lethal as in controls. To produce this accelerated form of EAE with encephalitogen in IFA required (1) a time interval shorter than 9 days between the first injection and challenge and (2) that the first injection and the challenge be done in the same site, which could be hind or front foot pads but not the nuchal area. The results indicated that 'priming' by encephalitogen in IFA occurred when this two-step induction procedure was used. The experimental conditions may have bypassed suppressive mechanisms.


Feto-maternal correlation of PTX3, sFlt-1 and PlGF in physiological and pre-eclamptic pregnancies.
PTX3, sFlt-1 and PlGF levels in maternal blood are altered in some obstetric diseases, such as preeclampsia (PE). Nonetheless, only few data on their expression in the fetal compartment have been reported so far. An observational study was performed by prospectively collecting maternal and fetal serum samples in 51 singleton pregnancies divided into two groups: 22 PE women and 29 healthy controls. The relationships between maternal and fetal marker serum levels were evaluated by Spearman correlation. A feto-maternal correlation was neither identified for PTX3 in either PE or control groups (1.1 versus 3.8 ng/ml, p = 0.17 and 0.9 versus 1.3 ng/ml, p = 0.30, respectively), nor for sFlt-1 and PlGF in healthy pregnancies (158.2 versus 3326.0 pg/ml, p = 0.28 and 11.0 versus 230.9 pg/ml, p = 0.51). In contrast, PE patients showed a significant positive feto-maternal correlation for both sFlt-1 and PlGF (324.1 versus 10 825.0 pg/ml and 7.8 versus 31.6 pg/ml, respectively, p = 0.02 for both markers). According to our results, an independent fetal production of the analyzed soluble angiogenic markers can be hypothesized in pregnancies complicated by PE.


Aberration induction by mitomycin C in early primary spermatocytes of mice.
MC is well known to induce dominant lethal mutations in mouse spermatocytes. Tests were done to determine whether chromosomal aberrations could be identified in spermatocytes as being responsible for the dominant lethal effects. Male mice were treated with single doses of MC during DNA synthesis preceding meiosis and during early prophase of meiosis. Simultaneous labeling was performed to identify cells that were in S-phase during the time of treatment. Diakineses-metaphases I were analyzed for the occurrence of univalents, gaps, fragments and rearrangements. The frequencies of cells with aberrations increased with dose and time after treatment. Maximal values were obtained after 12 days, indicating that MC was most effective in cells undergoing DNA replication. 95% of these cells were labeled. The majority of aberrant cells contained one or more fragments. These cells will lead to dominant lethality of the zygotes after fertilization. Cells with rearrangements occurred 11 and 12 days after treatment. These cells can develop into sperm carrying a reciprocal translocation which would then give rise to semi-sterile progeny after fertilization. Further investigations are needed to study the transmission of rearrangements observed in primary spermatocytes.


Nitrogen isotope differences between atmospheric nitrate and corresponding nitrogen oxides: A new constraint using oxygen isotopes.
Tracking of reactive nitrogen (N) sources is important for the effective mitigation of N emissions. By combining the N and oxygen (O) isotopes of atmospheric NO3-, stable isotope mixing models were recently applied to evaluate the relative contributions of major NOx sources. However, it has long been unresolved how to accurately constrain the δ15N differences between NO3- and corresponding NOx (ε(NO2→NO3-) values). Here, we first incorporated the HC oxidation (NO2 → NO3-) pathway by using Δ17O values to evaluate the ε(NO2→NO3-) values, performed on NO3- in PM2.5 collected during the day and at night from January 4-13, 2015 at an urban site in Beijing. We found that the Δ17O-based ε values (ε17O-based(NO2→NO3-)) (15.6 ± 7.4‰) differed distinctly from δ18O-based ε values (ε18O-based(NO2→NO3-)) (33.0 ± 9.5‰) so did not properly incorporate the isotopic effects of the HC oxidation (NO2 → NO3-) pathway. Based on the ε(NO2→NO3-) values, δ15N values of NOx from coal combustion (CC), vehicle exhausts (VE), biomass burning (BB), and the microbial N cycle (MC), as well as NO3- in PM2.5, we further quantified the source contributions by using Stable Isotope Analysis in R (the SIAR model). We found that the respective fractional contributions of CC-NOx and MC-NOx were underestimated by 64% and were overestimated by 216% by using ε18O-based(NO2→NO3-) values. We concluded that the new ε17O-based(NO2→NO3-) values reduced uncertainties in contribution analysis and the evaluation method for atmospheric NO3- sources.


[Suicides in Germany: results from the official cause of death statistics].
The cause of death statistics is an elementary basis for determining important indicators such as death rates, years of life lost, and avoidable deaths as well as their changes over time. The results are used in epidemiological and medical research and provide important recommendations for prevention programs and for health policy in general.This article first gives an overview of the history, legal basis, and methodology of the cause of death statistics in Germany. This is followed by the presentation of the data on suicides in Germany with a focus on the year 2019. These data are mapped based on the characteristics of age, gender, region, and method of suicide. Comparisons with older data available since 1980 are made. The outlook gives an overview of the further development of the cause of death statistics, the reasons for current weaknesses in the data collection process, and possible solutions.


Renal dysplasia associated with ureteral ectopia and ipsilateral seminal vesicle cyst.
The simultaneous presence of renal aplasia/dysplasia, ureteral ectopia and seminal vesicle cyst represents an exceptionally rare malformation. The literature is reviewed here and a new case of such malformation, concerning a 45-year-old man affected by recurrent epididymitis, is reported.


Effects of clinical and metabolic variables and hormones on the expression of immune protein biomarkers in the endometrium of women with polycystic ovary syndrome and normal-cycling controls.
Women with polycystic ovary syndrome (PCOS) are at an elevated risk of endometrial cancer, which may be associated with the continuous proliferative state caused by the interaction between hormones and metabolic factors. To investigate the impact of hormones and metabolic factors in the proliferation and death of endometrium during the proliferative phase. Cross-sectional study with 11 women with PCOS and eight normal-cycling non-PCOS controls at the Federal University of the State of Rio de Janeiro from February 2011 to June 2019. Clinical, biochemical, and hormonal data were collected to analyze their influence on the expression of biomarkers related to the endometrial tissue breakdown. Hysteroscopy and endometrial biopsies were conducted, and the endometrial samples underwent immunohistochemistry for markers of apoptosis B-cell lymphoma 2 (BCL2), cleaved caspase-3 (CASP3), fas cell surface death receptor (FAS), FAS ligand (FASLG), BCL2 associated X (BAX), marker of proliferation Ki-67 (MKI67), and cell death using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL). CASP3 and TUNEL expressions were lower in both stroma and endometrium gland of PCOS women than in controls. MKI67 and homeostasis indexes (BCL2/BAX; FASLG/FAS) in the endometrium of the PCOS group were significantly higher. Body mass index (BMI) values were positively correlated with the expression of MKI67 and MKI67/TUNEL ratio in the endometrial stroma compartment. Fasting insulin levels were positively correlated with the expression of BCL2, and DHEA-S levels were negatively correlated with the expression of CASP3 of women with PCOS. BMI, insulin, and DHEA-S influence the endometrial homeostasis breakdown in PCOS in the endometrium stroma.


Post-marketing safety of antineoplasic monoclonal antibodies: rituximab and trastuzumab.
The aim of this study was to analyse the suspected adverse reactions associated with rituximab or trastuzumab reported to the Spanish Pharmacovigilance System. From this national database, we selected the spontaneous reports registered between 1 January 1999 and 1 June 2006 and analysed both age and gender of the patient, the dose prescribed, the severity of the report, the evolution, the latency and recovery periods of the adverse reaction, the reporting odds ratio (ROR) and the presence of other suspected drugs. From 49 927 records registered in the period of analysis, 69 were associated with rituximab and 23 with trastuzumab. White cell disorders (n = 18), hypotension (n = 7), dyspnoea (n = 6) and pneumonitis (n = 4) were the most common adverse reactions associated with rituximab. The mean latency period of white cell disorders was 20.9 +/- 7.8 days, except in two cases where it was clearly longer (87 +/- 13 days). Hypotension and dyspnoea appeared immediately or a few days after the administration of the drug, and rapidly resolved. Pneumonitis seems to be a delayed adverse reaction, which required on average, 3 months to develop. Cardiac failure was the adverse reaction more frequently associated with trastuzumab (n = 7). In five of the seven cases of cardiac failure reported patients had been taking other suspected medications. Our results are consistent with the safety profile of rituximab and trastuzumab observed in large randomised clinical trials.


Utilization of Colistin Versus β-Lactam and β-Lactamase Inhibitor Agents in Relation to Acute Kidney Injury in Patients with Severe Gram-Negative Infections.
Colistin is used to treat severe antibiotic-resistant Gram-negative infections (GNIs). With the rise of antibiotic resistance, colistin has been used increasingly as a 'last-line' therapy for multidrug-resistant GNIs. We evaluated the incidence of acute kidney injury (AKI) and mortality among patients receiving colistin or one of the new β-lactam/β-lactamase inhibitors (βL + βLI) (ceftazidime/avibactam, ceftolozane/tazobactam, or meropenem/vaborbactam). This retrospective cohort study used data from the Premier Healthcare Database. The cohort included propensity score-matched adults with an inpatient stay between January 2016 and December 2018. Patients given both colistin and BL + BLI as treatment for ≥ 72 h were excluded. AKI was defined as acute renal failure or dialysis during hospitalization with antibiotic administration. Propensity score matching was used to control for selection bias and confounding. Logistic regression evaluated associations between treatment, AKI, and in-hospital mortality. The total number of patients in the matched cohorts were 256 in each. Overall, 23.8% and 13.3% of patients receiving colistin or new βL + βLI agents, respectively, experienced AKI during hospitalization (p = 0.002); odds of AKI for colistin were 3.0 (95% CI 1.71, 5.21). Following propensity score-matching, patients without baseline renal disease experienced AKI during hospitalization to a higher degree in the colistin group compared to the βL + βLI group (17.1% vs. 6.8%); colistin use was associated with 3.7 times higher odds (95% CI 1.84, 7.42) of AKI compared to βL + βLI agents. The odds of mortality in patients on colistin developing AKI were more than three times that of patients receiving a BL + BLI agent who developed AKI. Among patients receiving colistin, incident AKI was associated with 6.1 times higher odds (95% CI 2.53, 14.71) of mortality. Patients receiving colistin for GNIs had significantly higher odds of AKI and mortality than those receiving βL + βLI.


[Tangier-disease (author's transl)].
Tangier disease is a rare autosomal recessive lipid transport disease characterized by the absence of the usual high density lipoproteins from plasma and cholesteryl ester storage in many organs. 25 cases of Tangier disease have been described so long. The predominant clinical symptoms include tonsilar hypertrophy, splenomegaly and peripheral neuropathy. The cholesteryl ester storage is limited to macrophages, Schwann's cells and intestinal smooth muscle cells. Hypocholest erolemia (less than 80mg/dl), hypertriglyceridemia (greater than 200 mg/dl), and the absence of high density lipoproteins in agarose electrophoresis are the major plasma abnormalities. The protein moiety of normal high density lipoprotein consists of apoprotein A-I and apoprotein A-II. In Tangier disease, serum concentrations of these apoproteins are reduced to less than 1% and 5-10%, respectively. Theories concerning the pathogenesis of Tangier disease are only incomplete and unproved up to now; however, a structural abnormality of apoprotein A-I causing an inability to bind to lipid or other proteins (apoprotein A-II) is consistent with several of the recent biochemical findings. The imbalance of cellular cholesterol metabolism caused by the absence of high density lipoproteins as well as the presumed role of these lipoproteins in cholesterol removal from cells are discussed in this article.


Detection of delamination of steel-polymer sandwich composites using acoustic emission and development of a forming limit diagram considering delamination.
The formability of steel-polymer sandwich composites was investigated using a new forming limit diagram (FLD) while considering delamination and fracture. The acoustic emission (AE) technique was used to observe delamination during the forming process. Several tests, including tensile and lap shear tests, were performed to identify the AE features of delamination. In addition, finite element simulations were carried out using the cohesive zone model to predict the delamination of steel-polymer sandwich composites. An FLD of the sandwich composite was also constructed using the finite element model. Finally, the effect of interfacial adhesion on the formability of sandwich composites was investigated, from which the optimal condition for interfacial adhesion (in terms of ensuring the formability of the sandwich composite) was obtained.


Metastatic behavior and tumorigenicity of a human melanoma cell line (MM-RU) after injection into nude mice.
The ability of the human amelanotic melanoma cell line MM-RU to produce experimental metastases and to grow tumors at subcutaneous inoculation sites in 4-week-old nude mice was examined. After i.v. inoculation of 10(6) cells, all injected mice (n = 21) developed consistent numbers of metastatic pulmonary colonies within 32 days. The coefficients of variation for the number of colonies were between 17%-23% in three independent experiments. Survival time after i.v. inoculation was 63 +/- 7 days (mean +/- SD) (n = 20). Within 20 days, subcutaneous inoculation of 5 x 10(6) cells resulted in tumor growths of 13 +/- 3 mm (mean +/- SD) at the inoculation sites in all nude mice (n = 12). The MM-RU cell line seems to be a simple, fast vehicle for testing the effect of melanoma growth modulators on experimental pulmonary metastases as well as on subcutaneously growing melanoma.


Ethylmalonic encephalopathy: Clinical course and therapy response in an uncommon mild case with a severe ETHE1 mutation.
Ethylmalonic encephalopathy (EE) is a rare metabolic disorder caused by dysfunction of ETHE1 protein, a mitochondrial dioxygenase involved in hydrogen sulfide (H2S) detoxification. EE is usually a fatal disease with a severe clinical course mainly associated with developmental delay and regression, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhoea. Treatment includes antioxidants, antibiotics that lower H2S levels and antispastic medications, which are not curative. The mutations causing absence of the ETHE1 protein, as is the case for the described patient, usually entail a severe fatal phenotype. Although there are rare reported cases with mild clinical findings, the mechanism leading to these milder cases is also unclear. Here, we describe an 11-year-old boy with an ETHE1 gene mutation who has no neurocognitive impairment but chronic diarrhoea, which is controlled by oral medical treatment, and progressive spastic paraparesis that responded to Achilles tendon lengthening.


Novel antineoplastic agents with efficacy against multidrug resistant tumor cells.
A novel series of pentafluorobenzenesulfonamides has been shown to inhibit the growth of a variety of human tumor cell lines. Among the cell types against which these agents were evaluated were the multidrug resistant (MDR) cell lines MCF-7/ADR and P388/ADR. The cytotoxic activity of members of this series of compounds was not affected by the multidrug resistant pump in MCF-7/ADR or P388/ADR cells.


Pan masala habits and risk of oral precancer: A cross-sectional survey in 0.45 million people of North India.
This cross-sectional community based study was conducted to estimate the prevalence of consumption habits for non tobacco pan masala (ASU) and the risk of developing oral precancer in North India. This study was conducted in the old town of Lucknow city in the state of Uttar Pradesh in India. Subjects residing for more than 6 months and aged 15 years or above, were enrolled in the study after their informed consent. A two page survey tool was used to collect the data. A three times more matched sample of non users was randomly obtained from this data to analyze and compare the final results. 0.45 million subjects were surveyed. Majority of tobacco users were in the age group of 20-35 years among males and 35-39 years among females. Consumption of non tobacco pan masala among males as well as females was most common in 15-19 years of age group. Prevalence of oral precancer (leukoplakia, submucous fibrosis, erythroplakia, lichen planus, smokers palate and verrucous hyperplasia) was 3.17% in non tobacco pan masala users and 12.22% in tobacco users. The odds of developing oral precancer in non tobacco pan masala users was 20.71 (18.79-22.82) and in tobacco users was 88.07 (84.02-92.31) at 95% confidence interval against non users of both. The odds of developing oral precancer even with consumption of pan masala is high, even when it is consumed without tobacco. It is hence recommended to discourage this habit.


Diagnosis of Genus Helicobacter through a hemi-nested PCR assay of 16S rRNA.
The present study aimed to establish a genus-specific PCR-based assay to detect helicobacters using 16S rRNA gene as the target template. We designed the hemi-nested primers based on sequences of 16S rRNA gene of 34 types of Helicobacter species. The inclusivity, sensitivity, and specificity of the PCR assay using these primers were examined in three different models, comprising feces simulated samples, BLAB/c mice infection model and clinic patients samples. The detection sensitivity of Helicobacter pylori, Helicobacter hepaticus and Helicobacter bilis strains from feces simulated samples was all 102 CFU/ml. We successfully detected H. hepaticus and H. bilis in the liver, cecum and feces of experimentally infected mice. H. pylori was successfully detected in the feces samples from 3 patients infected with H. pylori while not in the feces samples from 3 healthy human. However, the C97/C05-C97/C98 PCR assay detected H. pylori in the 2 positive samples. Due to the PCR assay's excellent inclusivity, high sensitivity and specificity it may be used to detect the presence of Helicobacters.


Effects of dietary trans-fat on biliary and fecal steroid excretion and serum lipoproteins in rats.
Rats were fed cholesterol-free or cholesterol-enriched diets containing olive oil or partially hydrogenated corn oil at the 10% level for ca. 30 days (c-18:1, 77.0% in the former diet and c-18:1,24.7% and t-18:1,42.5% in the latter). The linoleic acid content of these fat diets was made equivalent (1.7 energy %). After feeding cholesterol-free diets, trans fat compared to cis fat showed (a) no untoward effects on growth parameters, (b) a reduction of serum cholesterol levels without influencing concentrations of serum apolipoproteins A-1, B and E, (c) no effects on the bile flow and the concentration of biliary cholesterol and bile acids, (d) an increasing trend of fecal excretion of neutral and acidic steroids, both in terms of mg/day and mg/g feces, and (e) rather equivocal change in the composition of fecal, but not biliary steroids. Similar response patterns were also observed when cholesterol-enriched diets were fed except for a decrease in serum apo B and an ineffectiveness to increase fecal acidic steroids. Together with the results obtained from experiments simultaneously performed with safflower oil and completely hydrogenated corn oil, it seems that the steroid metabolism can be specifically modified by the geometry of dietary fats.


Identifying persistent, mobile and toxic (PMT) organic compounds detected in shale gas wastewater.
Shale gas exploitation is a water-intensive process, generating flowback and produced water (FPW) with complex chemical compositions. Reuse, disposal and treatment of FPW are of increasing concern, because of the potential risk of FPW contamination to the surrounding aquatic environment and drinking water sources when emitted. Among numerous organic substances present in FPW, of particular concern are those that are persistent, mobile and toxic (PMT) and very persistent and very mobile (vPvM). PMT and vPvM substances have the greatest potential to spread in groundwater and are the hardest to remediate. This study presents the outcome of a literature review to identify organic compounds that were previously detected in FPW. The 162 target compounds identified from this review were assessed to see if they can be considered PMT/vPvM substances based on their substance properties. Our results indicated that most FPW substances are "not PMT", accounting for 108 (66.7 %) compouds. In total 22 FPW substances can be considered PMT/vPvM or very likely to meet this criteria if more data were available. Examples of PMT substances in FPW include anthracene, 1,4-dioxane and 1,4-dichlorobenzene. PMT/vPvM compounds identified in FPW should be prioritized for risk management measures and monitoring in order to protect regional water resources.


Prednisone for patients with recurrent implantation failure: study protocol for a double-blind, multicenter, randomized, placebo-controlled trial.
Recurrent implantation failure (RIF) brings great challenges to clinicians and causes deep frustration to patients. Previous data has suggested that prednisone may play a promising role in the establishment of pregnancy and help improve the pregnancy outcome in women with RIF. But there is insufficient evidence from randomized clinical trials that had adequate power to determine if prednisone can enhance live births as the primary outcome. This trial is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial (1:1 ratio of prednisone versus placebo). Infertile patients with RIF who intend to undergo frozen-thawed embryo transfer (FET) after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) or pre-implantation genetic testing for aneuploidy (PGT-A) will be enrolled and randomly assigned to two parallel groups. Participants will be given the treatment of prednisone or placebo from the start of endometrial preparation till the end of the first trimester of pregnancy if pregnant. The primary outcome is live birth rate. The results of this study will provide evidence for the effect of prednisone on pregnancy outcomes in patients with RIF. Chinese Clinical Trial Registry, ChiCTR1800018783 . Registered on 9 October 2018.


Evaluation of the accuracy of colposcopy in detecting high-grade squamous intraepithelial lesion and cervical cancer.
The primary aim of this study was to evaluate the diagnostic accuracy of colposcopy in identifying high-grade squamous intraepithelial lesion or worse (HSIL+) and the characteristic performance of colposcopic images with various severity levels of cervical lesions. The medical records from 1828 women who underwent colposcopy at Affiliated Hospital of Tongji University from February 2016 to March 2019 were reviewed. Human papilloma virus (HPV) GenoArray test kit (HybriBio Ltd) and Thinprep cytologic test (TCT, Hologic, USA) were used to perform HPV genotyping and cytology. All colposcopic images were collected from the standard-of-care colposcope (Leisegang 3ML LED) and evaluated based on the 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) Colposcopy Standards. The linear by linear association, Pearson χ2 test, χ2 test, Kappa test, McNemar test and risk test were used to perform statistical analyses. The consistency between colposcopy and biopsy pathology was 59.35% with the moderate strength of kappa coefficient of 0.464. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of colposcopy and cytology for HSIL+ were 56.29%, 93.82%, 77.47%, 85.04% and 37.13%, 98.49%, 90.29%, 80.58%, respectively. The colposcopic features of HSIL+ were as follows: (1) thick or bulgy acetowhite epithelium with sharp border; (2) completely nonstained of Lugol's iodine; (3) type III/IV/V of gland openings; (4) punctation or atypical vessels. The data and findings herein provide the resource for evaluating the diagnostic value of colposcopy, and suggested that the accuracy of colposcopy is required to be further improved.


Prominent mitochondrial pathology in a case of refractory dermatomyositis: coincidence or concause?
Mitochondrial alterations are a common finding in muscle biopsy of sporadic inclusion body myositis (s-IBM) and polymyositis with mitochondrial pathology (PM-Mito). Both disorders generally have poor treatment response. Nevertheless, mitochondrial myopathology has been rarely reported in dermatomyositis (DM) outside areas of perifascicular atrophy and a relationship with therapeutic outcome is not established. We report on clinical, immunological, radiological, and myopathological findings of a case of severe, treatment-refractory anti-Mi-2-positive DM. A 77-year-old woman developed anti-Mi-2 DM with severe diffuse muscle weakness associated with abundant mitochondrial abnormalities at muscle biopsy, beside the typical features of inflammatory myopathy. The patient was poorly responsive to multiple-line therapies and finally anti-JAK (anti-Janus activated kinase) was administered, leading to partial clinical improvement. Given the usual satisfactory treatment response and favorable outcome of anti-Mi-2 DM, we suppose that mitochondrial dysfunction on muscle biopsy could represent a marker of disease severity in DM, predicting a worse response to treatment and a poor clinical outcome. JAK-inhibitors could represent a good treatment option in refractory anti-Mi-2 DM with mitochondrial abnormalities.


To target Tau pathologies, we must embrace and reconstruct their complexities.
The accumulation of hyperphosphorylated fibrillar Tau aggregates in the brain is one of the defining hallmarks of Tauopathy diseases, including Alzheimer's disease. However, the primary events or molecules responsible for initiation of the pathological Tau aggregation and spreading remain unknown. The discovery of heparin as an effective inducer of Tau aggregation in vitro was instrumental to enabling different lines of research into the role of Tau aggregation in the pathogenesis of Tauopathies. However, recent proteomics and cryogenic electron microscopy (cryo-EM) studies have revealed that heparin-induced Tau fibrils generated in vitro do not reproduce the biochemical and ultrastructural properties of disease-associated brain-derived Tau fibrils. These observations demand that we reassess our current approaches for investigating the mechanisms underpinning Tau aggregation and pathology formation. Our review article presents an up-to-date survey and analyses of 1) the evolution of our understanding of the interactions between Tau and heparin, 2) the various structural and mechanistic models of the heparin-induced Tau aggregation, 3) the similarities and differences between brain-derived and heparin-induced Tau fibrils; and 4) emerging concepts on the biochemical and structural determinants underpinning Tau pathological heterogeneity in Tauopathies. Our analyses identify specific knowledge gaps and call for 1) embracing the complexities of Tau pathologies; 2) reassessment of current approaches to investigate, model and reproduce pathological Tau aggregation as it occurs in the brain; 3) more research towards a better understanding of the naturally-occurring cofactor molecules that are associated with Tau brain pathology initiation and propagation; and 4) developing improved approaches for in vitro production of the Tau aggregates and fibrils that recapitulate and/or amplify the biochemical and structural complexity and diversity of pathological Tau in Tauopathies. This will result in better and more relevant tools, assays, and mechanistic models, which could significantly improve translational research and the development of drugs and antibodies that have higher chances for success in the clinic.


Pattern Electroretinogram in Ocular Hypertension, Glaucoma Suspect and Early Manifest Glaucoma Eyes: A Systematic Review and Meta-analysis.
To provide standardized confidence limits of the transient pattern electroretinogram (tPERG) P50 and N95 and steady state pattern electroretinogram (ssPERG) amplitudes in normal controls as compared to ocular hypertension (OHT), glaucoma suspect (GS), or early manifest glaucoma (EMG) eyes. The identification of standardized confidence limits in the context of pattern electroretinogram (PERG) might overcome the high intrinsic variability of the measure, and it might lead to a more intuitive understanding of the results as well as to an easier comparison of data from multiple tests, sites, and operators. The study protocol was prospectively registered on the International Prospective Register of Systematic Reviews (ID: CRD42022370032). A literature search was conducted on PubMed, Web of Science, and Scopus. Studies comparing PERG raw data in normal control eyes as compared to OHT, GS, or EMG were included. The risk of bias was assessed using the National Institute for Health and Clinical Excellence quality assessment tool. The main outcome was the P50, N95, and ssPERG amplitude difference between the control and the study groups' eyes. The standardized mean difference was calculated as a measure of the effect size for the primary outcome. A subanalysis was conducted based on the type of electrodes adopted for the PERG measurements (invasive vs. noninvasive). Of the 4580 eligible papers, only 23 were included (1754 eyes). Statistically significant amplitude differences were found in the P50, N95, and ssPERG amplitudes between normal controls and OHT, GS, and EMG eyes. The highest standardized mean difference values were observed in the ssPERG amplitude in all 3 sets of comparison. The subanalysis did not reveal any statistically significant differences between invasive and noninvasive recording strategies. The use of standardized values as the main outcome measures in the context of the PERG data analysis is a valid approach, normalizing several confounding factors which have affected the clinical utility of PERG both for individual patients and in clinical trials. Steady state PERG apparently better discriminates diseased eyes compared to tPERG. The adoption of skin-active electrodes is able to adequately discriminate between healthy and diseased statuses. Proprietary or commercial disclosure may be found after the references.


The prevalence of the academic learning difficulties: An observation tool.
This study seeks to develop an effective observation tool to determine the prevalence of various academic learning difficulties among school students at the primary level in Sana'a City, Yemen. A measure comprising of 34 items has been processed by the EFA and CFA for contriving ALD's psychometric properties. The study sample comprised 714 students between 6 - 14 years of age. The study's findings revealed that the observation tool under development could measure the prevalence of various academic learning difficulties to a great extent with accuracy. The learning difficulties were classified under five categories based on observation scores. The observed raw scores were standardised after taking the standard deviation from the sample's mean value into consideration. The study's findings suggested that the gender and grade of the subjects affected academic learning difficulties significantly. A brief discussion of the educational implications of these findings has also been presented.


[The value of combined detection of HbA2 and HbF for the screening of thalassemia among individuals of childbearing ages].
To assess the application value of combined detection of HbA2 and HbF for the screening of thalassemia among a population of childbearing age in Quanzhou, Fujian, and determine the optimal cut-off values for the region. Capillary hemoglobin electrophoresis and genetic testing for α and β globin gene mutations were simultaneously carried out on 11 428 patients with suspected thalassemia. Statistical methods were used to analyze the distribution of various types of thalassemia and compare the performance of HbA2 and HbF measurement for the screening of various types of thalassemia. The optimal cut-off values for HbA2 and HbF were determined with the ROC curves. 4591 patients with α, β, and αβ compound thalassemia were identified by genetic testing. The most common genotypes for α and β thalassemia included --SEA/αα and β654/βN, β41-42/βN, and β17/βN. The ROC curves were drawn to compare the performance of HbA2 screening for α-, β-, αβ-compound, static α-, mild α-, and intermediate α-thalassemia, and the maximum area under the curves was 0.674, 0.984, 0.936, 0.499, 0.731, 0.956, and the optimal cut-off values for HbA2 were 2.45%, 3.25%, 3.65%, 2.95%, 2.55%, 1.75%, respectively. HbA2 is an efficient indicator for identifying intermediate types of α-, β-, and αβ compound thalassemia. The combination of HbA2 and HbF measurement can effectively detect carriers for β-thalassemia mutations.


Hormone replacement therapy for postmenopausal osteoporosis.
The role of HRT for the prevention of osteoporosis has been clarified by the recent results of the WHI. There is consistent and favorable data from RCTs supporting the efficacy of HRT on the surrogate outcome of bone density at both cortical and trabecular sites, including a dose-response relationship. Both observational and RCT data provide support that HRT has a positive impact on the reduction of vertebral and hip fractures. The unfavorable risk/benefit profile of HRT, however, strongly limits its use for prevention of osteoporosis, given that there are other medications that have demonstrated fracture efficacy.


Integrating criminal justice, community healthcare, and support services for adults with severe mental disorders.
Persons with severe mental disorders are overrepresented in our nation's jails and prisons. Factors including cooccurring substance use disorders, homelessness, and lack of access to community services have contributed to this problem, as have gaps between criminal justice, healthcare, and community support systems. In order to address these issues, Project Link was developed by the University of Rochester Department of Psychiatry in collaboration with five local community agencies. Project Link is designed to prevent involvement of individuals with severe mental illness from entering the criminal justice system. While many models of diversion programs exist, they are all dependent on access to appropriate community-based services. This paper will describe the steps that Project Link has taken towards integrating criminal justice, healthcare, and community support services for individuals with severe mental disorders involved in the criminal justice system.


Apoptosis of lymphocytes in mice administered lipopolysaccharide from Leptospira interrogans.
We report that administration of leptospiral lipopolysaccharide (LPS) in mice results in massive surface marker changes in the lymphocytes of the spleen. It appears that many of these changes relate to the large number of cells undergoing apoptosis. It is also shown that tumor necrosis factor-alpha (TNF-alpha) induces similar effects and is produced in large quantities after injection of leptospiral LPS. It is likely that cytokines such as TNF-alpha are involved in apoptosis.


Regional assessments of supraspinatus muscle stiffness in normal adults using shear wave elastography.
To provide normal references for regional shear wave elastography assessments of supraspinatus muscle in a population. Shear wave elastography images of supraspinatus muscles were evaluated on 100 shoulders of 50 normal adults in a fixed position with 30° shoulder abduction both at rest and contraction. Shear wave velocity values and activity values of intramuscular tendon, anterior superficial, anterior deep, posterior superficial, posterior deep, and central subregions were measured. The possible differences in hand dominance, sexes, stratified age groups, and internal muscular-component subregions were discussed. The results showed that shear wave velocity values at rest and activity values differed significantly among supraspinatus muscular-component subregions. Shear wave velocity values at rest were normally highest in posterior deep and lowest in central subregions, whereas activity values were highest in central subregions. The results also showed evaluation of the intramuscular tendon using shear wave elastography to be practicable. The differences in shear wave velocity values at rest between the dominant and nondominant sides were not significant in each subregion, while the values at rest of the majority of subregions were significantly greater in males than in females. Stratified by age groups of 10 years, the shear wave velocity values at rest of some subregions tended to increase with age, with uncorrelations possibly related to insufficient sample sizes and different intensities of limb activities. This study suggested that regional assessments of supraspinatus stiffness using shear wave elastography are feasible, with further research supporting that it can provide information on the surgery, training, and rehabilitation of rotator cuff tears.


Daily rhythm of glutathione peroxidase activity, lipid peroxidation and glutathione levels in tissues of pinealectomized rats.
Melatonin is a component of the antioxidant defense system since it has radical scavenging and antioxidant activities. In the present study, we aimed to investigate the endogenous rhythm of antioxidant enzyme glutathione peroxidase (GSH-Px) activity, oxidized glutathione (GSSG) and lipid peroxidation levels in tissues of pinealectomized rats (PINX). Rats were sacrificed by decapitation at 4 h intervals. GSH-Px activity, GSSG and lipid peroxidation levels showed a daily rhythm both in controls and in PINX rats. GSH-Px and GSSG exhibited the peak levels after the peak time of melatonin which was determined previously by other groups. Lipid peroxidation levels increased progressively during the night and started to decline before the GSH-Px peak time. These findings suggest that endogenous melatonin is involved in the night time increase of GSH-Px activity and GSSG levels and modulates the daily rhythm pattern of GSH-Px. In conclusion, pinealectomy which eliminates the melatonin rhythm has a supressor effect on GSH-Px activity levels.


Pulmonary hypertension in chronic hypersensitivity pneumonitis.
The purpose of this study was to evaluate the prevalence and outcomes of pulmonary hypertension in chronic hypersensitivity pneumonitis and to examine the relationship between pulmonary function tests and pulmonary hypertension. We conducted a retrospective review of 120 patients with hypersensitivity pneumonitis seen at two centers for pulmonary diseases over a 5-year interval and identified patients with chronic hypersensitivity pneumonitis for whom both pulmonary function tests and Doppler echocardiography data were available. Chronic hypersensitivity pneumonitis was identified in 83 patients and Doppler echocardiography data were available for 73 of them. Pulmonary hypertension (sPAP ≥ 50 mmHg) was detected in 14 patients (19%), and was associated with a greater risk of death (median survival = 23 months vs. 98 months; P=0.003). Patients with pulmonary hypertension were older and had a significantly decreased PaO(2). There was a weak correlation between pulmonary function parameters and the underlying sPAP, with significance for FVC, FEV(1), and PaO(2) and inversely with PaCO(2). Using Doppler echocardiography for evaluation, pulmonary hypertension seems to be common in patients with chronic hypersensitivity pneumonitis, significantly impacts survival, and correlates with FVC, FEV(1), and PaO(2) and inversely with PaCO(2).


CT features of lung scar cancer.
To explore the CT features of lung scar cancer (LSC). CT images of 41 LSCs and 66 non-LSCs were retrospectively compared in terms of location, size, shape, border, speculation, lobulation, pleural indentation, surrounding ground-glass opacification (sGGO), vessel convergence, vacuolation, calcification and satellite opacification. Thirty-eight LSCs were histopathologically identified as adenocarcinoma. The LSCs and non-LSCs were located 8.73±8.65 and 12.55±10.67 mm from the pleura, respectively. The mean lesion sizes (3-D ratios) in the initial LSC, pre-surgical LSC and non-LSC images were 24.28±6.29 (0.33±0.65), 32.23±8.14 (0.60±0.18) and 23.24±3.73 (0.35±0.61) mm, respectively. The initial and pre-surgical LSC images showed significant differences in speculation and sGGO (P<0.05). Significant differences were also noted in vacuolation, vessel convergence and sGGO between the pre-surgical LSC and the non-LSC images (P<0.05) and in vacuolation between the initial LSC and the non-LSC images (P<0.05). Despite similar CT features of LSCs and non-LSCs, the early detection and diagnosis of LSCs is possible by studying scar-tissue changes such as enlargement and sGGO associated with well-defined lesion borders in follow-up CT images.


Changes in the surface charge properties of isolated cardiac sarcolemmal vesicles measured by light scattering. I. Characteristics of rat and canine preparations.
The cation-binding characteristics of isolated sarcolemmal vesicles from rat and canine cardiac muscle cells were investigated. To help elucidate the molecular properties involved in these interactions the cation-induced aggregation behavior of rat and canine cardiac sarcolemmal vesicles, sonicated unilamellar vesicles (SUVs) made from sarcolemmal lipid extracts, and SUVs generated from combinations of synthetic lipids similar to those found in the sarcolemmal membrane, as well as mitochondrial and sarcoplasmic reticulum enriched membrane fractions were examined. Our results indicate that cations, such as Ca2+, to indeed bind to the sarcolemmal membrane surface. They also suggest that two (or more) interacting sites are involved in the Ca2+-induced aggregation of the isolated sarcolemmal vesicles, and that sarcolemmal lipid components could be the primary binding sites. The modulating (secondary) sites on the other hand may be protein or carbohydrate in nature, or require specific lipid organizational properties. Finally, the results indicate that the interactions of cations, such as Ca2+, with the sarcolemmal surface are species specific, with the sarcolemmal membranes of both rat and canine preparations having different physico-chemical properties.


The growing incidence of type 1 diabetes in children: the 17-year French experience in Aquitaine.
While the incidence of type 1 diabetes in children has increased in various parts of the world, in France, no actual figures have been available since 1997. The aim of this study was to determine whether or not the pattern of increase in the incidence of type 1 diabetes in children aged less than 15 years varies with age at onset in Aquitaine (France) over a 17-year period. From 1988 to 1997, all newly diagnosed cases of type 1 diabetes were confirmed by registration into the French Registry of Incidence of Diabetes. Subsequently, all cases registered from 1998 to 2004 were collected within paediatric centres in Aquitaine as part of their hospital-based prospective records. In the overall population, the age- and gender-adjusted incidence rate increased from 8.86 per 100,000 per year (95% CI: 6.27-11.45) in 1988 to 13.47 per 100,000 per year (95% CI: 10.29-16.65) in 2004, indicating an annual increase in incidence of 3.34% (95% CI: 3.33-3.34). Median age at diabetes onset for cases in the first registration period (1988-1996) was significantly higher than that in the second registration period (1997-2004): 10.04 years (range: 6.64-12.53) versus 8.83 years (range: 5.48-11.73), respectively (P=0.01). The annual increase in incidence rate was highest in the youngest children and varied significantly with age (0-4 years: 7.59%; 5-9 years: 4.06%; 10-14 years: 1.28%). These results indicate a doubling of the incidence of type 1 diabetes in children every 30 years in Aquitaine, with an even steeper increase among younger children, thus underscoring the need for appropriate adaptation of the system of healthcare provision.


TALK score: Development and validation of a prognostic model for predicting larynx preservation outcome.
To develop and validate a simple prognostic tool that would help predict larynx preservation outcome. A retrospective review of 3 prospective studies. We reviewed consecutive chemotherapy/radiation protocols for patients (n = 170) with advanced, resectable, squamous cell, larynx, or pharynx cancer treated at Memorial Sloan-Kettering Cancer Center from 1988 to 1995 with larynx preservation intent. The outcome was successful larynx preservation. Model validation used data from U. S. Department of Veterans Affairs larynx preservation study. The developed model added one point for each poor prognostic covariate present (show in parentheses) and was given the acronym TALK: T stage (T4), albumin (<4 g/dL), maximum alcohol/liquor use (≥6 drinks/day or heavy drinking), and Karnofsky performance status (<80%). The 3-year larynx preservation rates by TALK score were 65% (0), 41% (1-2), and 6% (3-4), P < .0001; on validation, the TALK 3-4 group was particularly well demarcated. The TALK score is an easily applied and valid tool that should assist treatment selection.


Neural activation, cognitive control, and attention deficit hyperactivity disorder: Evaluating three competing etiological models.
Cognitive control impairments are observed across several psychiatric conditions, highlighting their role as a transdiagnostic marker. Individuals with attention deficit hyperactivity disorder (ADHD) have difficulties with inhibition, working memory, processing speed, and attention regulation. These cognitive control impairments may either mediate or moderate the association between neurobiological vulnerabilities and phenotypic presentation in neurodevelopmental disorders. Alternately, neurocognitive vulnerabilities in ADHD may be additive, akin to a multiple deficit model. We tested the mediation, moderation, and additive models using neurocognitive data in youth with ADHD. 7-11 year-old children diagnosed with ADHD (n = 75) and control children (n = 29) completed EEG recordings and neuropsychological testing (full scale IQ; cognitive control). Caregivers provided ADHD symptom ratings. Correlations and linear regression analyses were completed to examine the associations among cortical functioning (aperiodic slope), cognitive control, and ADHD symptoms. We found support for an additive model wherein vulnerabilities in aperiodic slope, event-related potentials, and cognitive control each explained unique variance in ADHD symptoms. There was some evidence that cognitive control moderates the effect of atypical cortical development on ADHD symptoms. There was no support for the mediation model. The etiology of ADHD symptoms is multifaceted and involves multiple "hits" across neurological and cognitive-behavioral factors.


Positive solutions of fractional integral equations by the technique of measure of noncompactness.
In the present study, we work on the problem of the existence of positive solutions of fractional integral equations by means of measures of noncompactness in association with Darbo's fixed point theorem. To achieve the goal, we first establish new fixed point theorems using a new contractive condition of the measure of noncompactness in Banach spaces. By doing this we generalize Darbo's fixed point theorem along with some recent results of (Aghajani et al. (J. Comput. Appl. Math. 260:67-77, 2014)), (Aghajani et al. (Bull. Belg. Math. Soc. Simon Stevin 20(2):345-358, 2013)), (Arab (Mediterr. J. Math. 13(2):759-773, 2016)), (Banaś et al. (Dyn. Syst. Appl. 18:251-264, 2009)), and (Samadi et al. (Abstr. Appl. Anal. 2014:852324, 2014)). We also derive corresponding coupled fixed point results. Finally, we give an illustrative example to verify the effectiveness and applicability of our results.


Improving protein template recognition by using small-angle x-ray scattering profiles.
Small-angle x-ray scattering (SAXS) is able to extract low-resolution protein shape information without requiring a specific crystal formation. However, it has found little use in atomic-level protein structure determination due to the uncertainty of residue-level structural assignment. We developed a new algorithm, SAXSTER, to couple the raw SAXS data with protein-fold-recognition algorithms and thus improve template-based protein-structure predictions. We designed nine different matching scoring functions of template and experimental SAXS profiles. The logarithm of the integrated correlation score showed the best template recognition ability and had the highest correlation with the true template modeling (TM)-score of the target structures. We tested the method in large-scale protein-fold-recognition experiments and achieved significant improvements in prioritizing the best template structures. When SAXSTER was applied to the proteins of asymmetric SAXS profile distributions, the average TM-score of the top-ranking templates increased by 18% after homologous templates were excluded, which corresponds to a p-value < 10(-9) in Student's t-test. These data demonstrate a promising use of SAXS data to facilitate computational protein structure modeling, which is expected to work most efficiently for proteins of irregular global shape and/or multiple-domain protein complexes.


Mortality in relation to oral contraceptive use and cigarette smoking.
As part of the Oxford Family Planning Association study, we compared mortality in relation to oral contraceptive use and smoking to highlight the differences between them from the perspective of public health. The study consisted of 17032 women, aged 25-39 years at entry, recruited between May 1, 1968, and July 31, 1974, who had used oral contraceptives, a diaphragm, or an intrauterine device. We assessed mortality from follow-up data recorded until Dec 31, 2000. The analysis is based on woman-years of observation. We analysed 889 deaths. Women who had ever used oral contraceptives had increased mortality from cervical cancer (rate ratio 7.2, 95% CI 1.1-303), and decreased mortality from other uterine (0.2, 0.0-0.8) and ovarian cancers (0.4, 0.2-0.7). Oral contraceptives had some adverse effect on deaths from ischaemic heart disease in women who smoked 15 or more cigarettes per day. For all causes of mortality, the rate ratio for death in women who ever used oral contraceptives was 0.89 (95% CI 0.77-1.02). By contrast, this rate ratio was 1.24 (1.03-1.49) in those who smoked one to 14 cigarettes per day, and 2.14 (1.81-2.53) in those who smoked 15 or more cigarettes per day. There was no harmful effect of oral contraceptive use on overall mortality. By contrast, death from all causes was more than twice as high in smokers of 15 or more cigarettes a day as in non-smokers. The harmful effect was already apparent in women aged 35-44 years.


Therapeutic drug monitoring in veterinary medicine.
This article presents some of the more important principles and concepts of therapeutic drug monitoring and when it might be an appropriate diagnostic procedure in veterinary medicine.


Bidimensional Analyses of the Intra- and Extracellular Proteomes of Steroid Producer Mycobacteria.
The importance of the pathogenic mycobacteria has mainly focused the omic analyses on different aspects of their clinical significance. However, those industrially relevant mycobacteria have received less attention, even though the steroid market sales in 2021 were estimated in $56.45 billion.The extracellular proteome, due to its relevance in the sterol processing and uptake, and the intracellular proteome, because of its role in steroids bioconversion, are the core of the present chapter. Both, monodimensional gels, as preparatory analysis, and bidimensional gels as proteome analysis are described. As a proof of concept, the protein extraction methods for both sub-proteomes of Mycobacterium are described. Thus, procedures and relevant key points of these proteome analyses are fully detailed.


Resolution of migraine by transcatheter patent foramen ovale closure with Premere Occlusion System in a preliminary series of patients with previous cerebral ischemia.
Transcatheter closure of PFO with nitinol devices may be problematic in young patients with migraine due the risk of late erosions. Alternative devices with less amount of metal as the last generation devices may be preferable in such cases. We present the results of transcatheter closure of PFO with the last generation Premere Occlusion System device in a preliminary series of young adults with migraine and previous cerebral ischemia. During a 12-month period (January 31, 2006 to December 31, 2006) 26 patients (18 female and 8 male, mean age 40 +/- 3.7 years) with previous stroke and severe disabling migraine were referred to our center for transcatheter closure of PFO. Migraine disability assessment score (MIDAS) was used to assess MHA incidence and severity. Patients were selected for Premere occlusion system (absence of atrial septal aneurysm and length >15 mm) on the basis of presence/absence of right and left bulging atrial septal aneurysm and length of PFO channel (<15 mm or >15 mm) on transesophageal echocardiography. Transesophageal echocardiography and transcranial Doppler were performed at 1 month, transthoracic echocardiography and cerebral magnetic resonance imaging at 6 and 12 months. Cardiologic and neurological visit was scheduled at 1, 6, and 12 months with MIDAS questionnaire administration. Ten patients (2 males, mean age 32 +/- 7.6 years, mean MIDAS score 38.9 +/- 5.8) underwent transcatheter PFO closure with the Premere occlusion system. Mean fossa ovalis diameters by ICE measurement was 20.6 +/- 3.1 mm. Thus, two 20-mm and eight 25-mm Premere devices were implanted. The procedure was successful in all of the patients with no perioperative and in-hospital complications. After a mean follow-up of 10.9 +/- 5.8 months, all patients were free from migraine symptoms (mean MIDAS score 2.9 +/- 1.9) with PFO complete closure in all patients on transesophageal and transcranial Doppler ultrasound. While waiting for larger studies evaluating the impact of new generation devices in curing PFO-related migraine, this preliminary anecdotal series suggests that the Premere occlusion system may be an effective and safe device for young patients with previous cerebral ischemia and migraine at least in the midterm period.


Radiation necrosis of the scalp: a complication of cranial irradiation and methotrexate.
A case of childhood leukemia with a severe skin reaction following a course of medium-dose cranial irradiation and intrathecal methotrexate is presented. Necrosis of the scalp of partial to full thickness resulted. The authors believe potentiation of the radiation reaction by methotrexate was the probable cause.


Comparison of outcome of higher versus lower transvalvular gradients in patients with severe aortic stenosis and low (<40%) left ventricular ejection fraction.
Left ventricular systolic dysfunction in patients with severe aortic stenosis (AS) is associated with poor outcome. This analysis was designed primarily to describe the clinical course of a large series of consecutive patients with severe AS and low ejection fraction (EF) (<40%) who, because of high surgical risk, were referred for transcatheter aortic valve implantation consideration. A cohort of 270 patients with severe AS and low EF (<40%) who were referred to participate in a clinical trial of transcatheter aortic valve implantation was studied. Clinical, hemodynamic, and periprocedural complications and follow-up mortality data were collected and compared between patients with low mean transvalvular gradients (≤40 mm Hg, n = 170 [63%]) and high transvalvular gradients (>40 mm Hg, n = 100 [37%]). Patients with low gradients were younger (mean age 79.8 ± 9.1 vs 83.8 ± 7.7 years, p <0.001) and had higher incidences of coronary artery disease and renal failure. Mean aortic valve area was larger (0.73 ± 0.23 vs 0.53 ± 0.18 cm(2), p <0.001), while mean EF (26.4 ± 6.9% vs 30.5% ± 6.6%, p <0.001), cardiac output (3.7 ± 1.1 vs 4.1 ± 1.3 L/min, p = 0.04), and cardiac index (1.9 ± 0.5 vs 2.1 ± 0.6 L/min/m(2), p = 0.04) were lower in patients with lower gradients compared to those with higher gradients, respectively. Mortality was higher in patients with low gradients (53.8%) at a mean follow-up of 151 days compared to those with high gradients (41%) at a mean follow-up of 256 days (p = 0.01). In conclusion, patients with severe AS and low EF with low transvalvular gradients are at higher risk for worse outcomes compared to patients with high transvalvular gradients. Surgery or transcatheter aortic valve implantation treatment and high baseline transvalvular gradient are associated with EF improvement.


Bulbocavernosus muscle responses after suprapubic stimulation: analysis and measurement of suprapubic bulbocavernosus reflex latency.
Our objective was to describe pelvic floor responses with measurement of reflex latency after suprapubic mechanical stimulation. Twenty-one patients without neurological disease were studied. They were 14 women and seven men. The mean age was 51 (SD = 14.2). Motor responses were recorded with a needle electrode inserted in the left bulbocavernosus muscle. Stimulation was delivered with an electromechanical hammer, tapping directly on the suprapubic area. A polyphasic muscular response was always easily elicited in all patients. The man latency was 67.5 milliseconds (SD = 14.7). The reproducibility between the first and second mechanical responses was good with no statistical difference (r=0.966;P = 0.0001). In three patients who underwent cystometry, no rise in detrusor pressure was observed during mechanical stimulation of the suprapubic area. Our study clearly demonstrates a suprapubic bulbocavernosus reflex (SBR). Tapping the suprapubic area is a strong stimulus, reflexively mediated, used in the management of neurogenic bladder to determine a bladder contraction. However, the reflex consisting of pelvic floor muscle contraction after suprapubic stimulation was not specifically studied in humans. Many arguments can be put forth for a polysynaptic reflex (polyphasic response, habituation and short latency of the reflex, mean latency in the habitual values of R2 responses after electrical stimulation of the dorsal nerve of the penis). We hypothesize that the true stimulus is the stimulation of the bladder wall tensoreceptors, the integration level of the SBR is the sacral segments and the efferent limb the pudendal nerve, and afferent pathways could be conducted by pelvic nerve fibers. Competition between a preponderant (or exaggerated) SBR and a bladder contraction after suprapubic tapping may constitute an equivalent of detrusor-sphincter dyssynergia in some suprasacral bladders.


Primary structure of glucagon from the gut of the common dogfish (Scyliorhinus canicula).
The primary structure of glucagon isolated from the intestine of the common dogfish, Scyliorhinus canicula, was established as H S E G T F T S D Y S K Y M D N R R A K D F V Q W L M N T. The peptide shows four substitutions compared with human glucagon: Glu-3 for Gln, Met-14 for Leu, Asn-16 for Ser and Lys-20 for Gln. Glucagon represented the predominant molecular form of the glucagon-like immunoreactivity in the dogfish gut extracts demonstrating that the pathway of posttranslational processing of proglucagon in the gut of this fish differs markedly from the pathway in the mammalian gut.


Probable congenital melanocytic nevus of the oral mucosa: case report.
There are few case reports of congenital melanocytic nevi affecting the oral mucosa. We report the clinical and histologic features of an intraoral melanocytic lesion that in our opinion meets the criteria for the diagnosis.


Correction of discrepancies in dioxin quantification between immunoassay and gas chromatography-high-resolution mass spectrometry.
Due to the toxicity of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F), efforts are made to quantify their emission into the environment. Typically, this quantification is done using gas chromatography-high-resolution mass spectrometry (GC-HRMS). However, GC-HRMS is extremely expensive and time consuming, and GC-HRMS facilities are overly requested. In order to decrease the workload on GC-HRMS, another alternative is to use an enzyme-linked immunosorbent assay (ELISA) as a semi-quantitative screening tool. One problem of this solution is that ELISA measures the total PCDD/F content of a sample differently than GC-HRMS; a disparity exists between the two techniques. This paper introduces a congener correction factor that adjusts ELISA results for this incompatibility. The importance of the correction factor is explored by examining the congener profiles of 27 different dioxin sources. The congener profiles for many of these sources are such that large incompatibilities in predicted PCDD/F content would likely exist between uncorrected ELISA and GC-HRMS. The effect that the correction factor has on the correlation between ELISA and GC-HRMS for samples from a test site with dioxin-contaminated soils was also examined. The congener profile at this site was such that the inconsistencies between uncorrected ELISA and GC-HRMS results were relatively small. However, application of the congener correction factor still improved the correlation between ELISA and GC-HRMS by 11% when using sample-specific correction factors and by 5% when using an average site-wide correction factor. The findings of this paper suggest that application of the correction factor is necessary to remove incompatibilities between ELISA and GC-HRMS--particularly when the congener profile at a site would lead to incompatibilities that are large.


Insights into the harmful algal flora in northwestern Mediterranean coastal lagoons revealed by pyrosequencing metabarcodes of the 28S rRNA gene.
This study investigated the genetic diversity of phytoplankton communities in six shallow lagoons located on the French coast of the northwestern Mediterranean Sea that represented a trophic gradient ranging from oligotrophic to hypereutrophic. The phytoplankton communities were sampled once a month from spring (May) to the beginning of autumn (September/early October) in 2012 and fractionated by size. Metabarcodes were generated from cDNAs by targeting the D1-D2 region of the 28S rRNA gene and pyrosequenced using Roche 454 technology. Examination of the annotated barcodes revealed harmful algal species not previously documented in these lagoons. Three ichthyotoxic species belonging to Pfiesteriaceae were detected: Luciella masanensis was relatively widespread and abundant in many samples, whereas Pfiesteria piscicida and Stoeckeria changwonensis were found as single barcode sequences. Furthermore, a phylogenetic analysis of barcodes annotated as belonging to Pfiesteriaceae suggested the existence of two previously undescribed clades. The other toxic or potentially harmful dinoflagellates detected through rare barcodes were Dinophysis acuminata, Vulcanodinium rugosum, Alexandrium andersonii and A. ostenfeldii. The two most abundant dinoflagellate taxa were Gymnodinium litoralis and Akashiwo sanguinea with respect to sequence numbers. Four diatom species from the genus Pseudo-nitzschia that potentially produce domoic acid were identified (P. galaxiae, P. delicatissima, P. brasiliana and P. calliantha). These observations are discussed in terms of the literature and monitoring records related to the identified taxa in this Mediterranean area.


An overview of the management of adult ependymomas with emphasis on relapsed disease.
Ependymomas are rare neoplasms of the central nervous system. Disease-free survival after relapse is poor and approaches to treatment in recurrent disease often palliative. This overview summarises the management of primary disease for which broad consensus exists. We also extensively review treatment options in relapsed disease for which approaches to treatment are varied due to the paucity of literature evidence. Incorporated in this overview is a survey of UK neuro-oncology units to form a snapshot of current UK practise with respect to preferred systemic therapy regimens for patients with recurrent ependymoma. The outcome reflects a preference for mainly oral-based regimens. Universal guidance is lacking in the management of non-operable irradiated recurrent ependymoma and there are worthy therapeutic avenues for further investigation, in particular the role of radical re-irradiation and also the potential of bevacizumab in advanced disease. It is hoped that advances can be achieved by multicentre collaboration in future studies to overcome the difficulties posed by achieving meaningful data in such a rare tumour with extensive natural history.


Injection of Sca-1+/CD45+/CD31+ mouse bone mesenchymal stromal-like cells improves cardiac function in a mouse myocardial infarct model.
The objective of this study was to screen mouse bone marrow mesenchymal stromal cells (BMSCs) according to expression of cardiac stem cell (CSC) surface antigens and to assess the effects of resulting BMSC-like subsets on cardiac function after injection in a mouse myocardial infarct model. BMSCs were sorted by magnetic beads according to the expression of differentiation antigens on the surface of mouse CSCs, and four subsets were identified on the basis of CD45 and CD31 expression: stem cell antigen-1+ (Sca-1+)/CD45-/CD31-, Sca-1+/CD45-/CD31+, Sca-1+/CD45+/CD31-, and Sca-1+/CD45+/CD31+. When co-cultured with myocardial stem cells and 5-aza-2'-deoxycytidine for 14 days, each subset showed expression of cardiac markers α-actin, connexin 43, desmin, and cardiac troponin I; however, expression was greatest in Sca-1+/CD45+/CD31+ cells. To assess the ability of these cells to improve cardiac function, each subset was injected separately into mice with myocardial infarct induced by ligation of the left anterior descending coronary artery, and in vivo cardiac dual inversion recovery (DIR) imaging and Doppler echocardiography were performed 48 h, 96 h, and 7 days after injection. Results indicated that Sca-1+/CD45+/CD31+ cells were superior in improving cardiac function compared with the other subsets and with unsorted BMSCs. These results suggest that mouse BMSC cells are polyclonal and that the BMSC-like Sca-1+/CD45+/CD31+ subset was effective in directing cardiac differentiation and improving cardiac function in mice with myocardial infarcts.


Extended follow-up safety and effectiveness of the Endeavor zotarolimus-eluting stent in real-world clinical practice: two-year follow-up from the E-Five Registry.
To present data from the cohort of patients in the all-comers Endeavor zotarolimus-eluting stent (ZES) registry (E-Five) who underwent 2-year follow-up. The Endeavor ZES has been shown to be safe and efficacious for treatment of single, de novo lesions in patients with stable coronary artery disease. E-Five evaluated the ZES in over 8,000 real-world patients, at 188 sites followed to 1 year. A subset of sites continued follow-up through 2 years to evaluate late-term safety and effectiveness of the ZES in this population with diverse clinical and lesion characteristics. E-Five, a prospective, multicenter, nonrandomized global registry, collected 2-year outcomes for 2,116 patients from 26 centers. Sites were selected for participation based on patient accrual rates and the ability to continue follow-up activities for an additional year. Complete data was available for 2,054 patients. To observe whether or not a sustained benefit was achieved, data for all patients from the selected sites were included in the analysis. The outcomes in the 2-year cohort tracked with the results of randomized controlled trials using the Endeavor ZES. One year results were MACE 7.5%, TLR 4.5%, and ARC definite/probable stent thrombosis 0.6%. Outcomes at 2 years for MACE, TLR, and ARC definite/probable stent thrombosis were 8.5, 5.1, and 0.7%, respectively. Long-term efficacy and safety outcomes were maintained between 1 and 2 years for the 2-year patient cohort, with only a small number of additional MACE, TLR, and very late stent thrombosis events.


Occiput-to-Pelvis Spinal Arthrodesis: A Case Series.
Retrospective case series. To describe the indications, operative course, and outcomes in eight pediatric patients who underwent occiput-to-pelvis (O-P) spinal arthrodesis. Spinal arthrodesis from the occiput to pelvis is needed for some children with extensive spine deformity. There are few reports of patients with O-P arthrodesis. We reviewed records of pediatric patients who underwent spinal arthrodesis to treat spine deformity between 1987 and 2017 at one institution. Eight patients (six girls) who underwent staged O-P arthrodesis were identified. Underlying conditions, indications for surgery, medical comorbidities, operative courses, complications, and imaging of these patients were recorded. Diagnoses were neuromuscular disorders in five patients and syndromic disorders in three patients. Mean ages were 9.7 ± 4.1 years at index surgery and 16.8 ± 4.6 years at completion of O-P arthrodesis. Patients underwent a mean of three operations (range, two to five). Occipitocervical arthrodesis was the final operation in six of eight patients (all but the two patients with Loeys-Dietz syndrome). Mean follow-up after the last procedure was 8.5 ± 7.1 years. Two patients underwent revision for protruding occipital implants, and one patient underwent revision for thoracic pseudarthrosis. No patients developed postoperative infections or new neurologic deficits. At final follow-up, Scoliosis Research Society-22r questionnaire scores were lowest for Function (2.6 ± 1.0 of 5 possible points) and highest for Satisfaction (4.1 ± 1.4). O-P arthrodesis can benefit patients with extensive spine deformity from neuromuscular or syndromic causes. Patients were young at first operation, which may suggest that younger patients are at higher risk than older patients of major progression of deformity in other spinal regions after deformity correction. Health-related quality of life and radiographic outcomes suggest that patients who underwent O-P arthrodesis had satisfactory outcomes and maintenance of correction during a mean of 8.5 years of follow-up. Level IV, therapeutic study.


Two-day length of stay following open Roux-En-Y gastric bypass: is it feasible, safe and reasonable?
As our bariatric program matured, we noted that length of stay (LOS) steadily decreased. This led us to analyze our experience to identify factors contributing to this abbreviated LOS and to evaluate the safety of discharging patients with only a 2-day LOS. All patients undergoing open Roux-en-Y gastric bypass (RYGBP) from March, 1998 to December 31, 2002 were evaluated. Contrast swallow study was performed on Day 1. Patient demographics, complications, and readmission rates were reported for all patients. Discharge criteria included adequate oral intake, pain control with oral analgesia, and an adequate understanding of the operation and its effects demonstrated by a written test before discharge. 316 patients underwent open RYGBP with mean BMI 52.3. Operative time decreased from 241 minutes in 1998 to 156 minutes in 2002. No patient was discharged at 2 days during the first 2 years of the program. In 2000, 1 of 52 patients (2%) went home on the second day. In 2001, the year we fully enacted our multidisciplinary approach, 14 of 96 patients (15%) returned home on the second day. In 2002, 73 of 145 patients (50%) were discharged on the second postoperative day, with no increase in readmission rates. Three of the 73 patients (4.1%) required readmission within 30 days of discharge. No difference in co-morbid diseases or BMI was noted between groups. Our data support the hypothesis that patients undergoing open RYGBP can be discharged safely at Day 2, provided that aggressive preoperative education and screening are performed.


Unusual retrograde movement of a safety-pin ingested by an infant.
Here we present the first reported case of an ingested open safety-pin in a 7-mo-old boy that migrated from the stomach to the oesophagus. This rare complication is probably due to a gastro-oesophageal reflux effect, and for this reason we propose that all infants with safety-pins and other sharp objects in the stomach should be positioned in a semi-upright position.


How do patients perceive resident participation in facial cosmetic treatment?
The main objective of this study was to determine patient attitudes toward resident participation in their facial cosmetic treatment. The study design was a cross-sectional study which consisted of an anonymous questionnaire regarding the patient's opinion of resident involvement in their care. Patients who presented to a single academic center seeking facial cosmetic care were surveyed over a period of 10 months. The primary outcome variables were degree of training, analysis of resident involvement impacting quality of care, and resident gender. Fifty patients were surveyed. All participants agreed that they would be comfortable if a resident observed their consultation or treatment and 94% agreed they would be comfortable if a resident interviewed and examined before meeting with the surgeon (n = 47). When asked if they would prefer a resident to be far along in their training if they were involved in the surgical care, the majority, 68% (n = 34), agreed. Only 18% (n = 9) of the patients reported feeling a resident's involvement in their surgery may lower the quality of their care. Patient perception of resident participation in their cosmetic treatment is favorable, but it appears patients do prefer that residents be well into their training years.


Scedosporium boydii CatA1 and SODC recombinant proteins, new tools for serodiagnosis of Scedosporium infection of patients with cystic fibrosis.
Scedosporium species rank the second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF), after Aspergillus fumigatus. In CF, these fungi may cause various respiratory infections similar to those caused by A. fumigatus, including bronchitis and allergic broncho-pulmonary mycoses. Diagnosis of these infections relies on the detection of serum antibodies using crude antigenic extracts. However, many components of these extracts are common to Scedosporium and Aspergillus species, leading to cross-reactions. Here, 5 recombinant proteins from S. apiospermum or S. boydii were produced, and their value in serodiagnosis of Scedosporium infections was investigated by enzyme-linked immunosorbent assay. Two of them, corresponding to the Scedosporium catalase A1 or cytosolic Cu,Zn-superoxyde dismutase, allowed the detection of Scedosporium infection, and the differentiation with an Aspergillus infection. These recombinant proteins therefore may serve as a basis for the development of a standardized serological test.


Association of IL6ST (gp130) Polymorphism with Functional Outcome Following Spontaneous Intracerebral Hemorrhage.
Genes associated with the inflammatory response and cytostructural integrity may influence recovery following a brain injury. To examine this in the setting of spontaneous intracerebral hemorrhage (ICH), selected single nucleotide polymorphisms (SNPs) were assessed for associations with patient outcome. A cohort of 54 patients with supratentorial ICH were enrolled. Based on known involvement with neuroinflammation and cytostructural integrity, 10 preselected SNPs from 6 candidate genes were tested for associations with 6-month functional outcome (modified Rankin Scale [mRS] ≥ 3), mortality, and in-hospital deterioration (Glasgow Coma Scale decrease by >2 within 7 days of admission) following ICH. Fisher's exact test and logistic regression with adjustment for race and ICH score were performed. SNP rs10940495 (gp130 G/A) within the gp130 gene was the only SNP significantly associated with lower odds of an unfavorable 6-month functional outcome (odds ratio = .16 for mRS ≥ 3; 95% confidence interval, .03-.87, P = .03). Compared with major allele (A) homozygotes, minor allele (G) carriers in the IL6 signal transducer gene (gp130) locus were 84% less likely to have a poor outcome (mRS ≥ 3) at 6 months following spontaneous ICH. The SNP rs10940495 (gp130 G/A) and SNP rs3219119 (PARP-1 A/T) were associated with 6-month mortality (P = .02 and .04, respectively) only on univariate analysis. None of the SNPs examined were associated with in-hospital deterioration. In this exploratory study, SNP rs10940495 in the gp130 locus was associated with functional outcome at 6 months following spontaneous ICH. These findings, which should be validated through a larger study, suggest that inflammation plays an important role in mediating outcomes after ICH.


Clinical assessments as predictors of one year survival after hospitalization: implications for prognostic stratification.
In clinical trials measuring the short term survival of patients, prognostic stratification is important to avoid susceptibility bias. Demographic and disease specific clinical features are commonly used to established similarity, but these may not insure prognostic comparability. To identify the generic predictors of one year survival after hospitalization, a cohort of 559 patients admitted to the medical service at New York Hospital was studied. Among all of the clinical and demographic information available at the time of admission, only three were independent predictors of the time until death: functional ability, severity of illness and extent of comorbid disease. The overall one year survival rate was 66%. Six subgroups composed of patients with different combinations of the predictors of prognosis had mortality rates ranging from 97% to 14%. Illness severity was a predictor only in the less functional patients, and only severe comorbidity was associated with a decreased survival after taking into account functional ability and illness severity. Prospective estimates of severity of illness, functional ability and extent of comorbidity can be used to stratify a diverse group of patients according to their probability of one year survival after hospitalization.


The role of surgeon's learning on the outcomes of alveolar bone graft for cleft repair.
Teaching cleft repair in the operating room may not sufficiently prepare craniofacial residents to perform the procedure self-reliantly. This study aimed to assess the influence of surgeons' experience level on the operative time and graft survival ratio after alveolar bone grafts for cleft repair. This was a retrospective review of 100 consecutive alveolar bone graft patients treated for unilateral alveolar cleft by one craniofacial surgeon between 2012 and 2019. An alveolar bone graft from the iliac bone was performed using the lateral sliding flap. Sex, age, cleft width, cleft defect volume, and operative time were recorded, and the 1-year postoperative graft survival ratio was calculated. Multiple regression analysis was performed to identify factors that affect the operative time and survival ratio. Factors affecting the operative time were the experience level of the surgeon and the presence of a cleft palate. Factors affecting the graft survival ratio were the cleft defect volume and experience level of the surgeon. In cleft lip and alveolus, the survival ratio was constant, and the operative time stabilised after approximately 20 cases. In cleft lip and palate, more experience was required to master the technique, and the operative time and survival ratio were stabilised only after approximately 40 cases. Surgeons' experience level influenced the outcomes of alveolar bone grafting. Although surgical training is currently undergoing a paradigm shift from on-the-job training to simulation-based training, clinical experience is critical to be self-sufficient.


Matrix-derived combination effect and risk assessment for estragole from basil-containing plant food supplements (PFS).
Basil-containing plant food supplements (PFS) can contain estragole which can be metabolised into a genotoxic and carcinogenic 1'-sulfoxymetabolite. This study describes the inhibition of sulfotransferase (SULT)-mediated bioactivation of estragole by compounds present in basil-containing PFS. Results reveal that PFS consisting of powdered basil material contain other compounds with considerable in vitro SULT-inhibiting activity, whereas the presence of such compounds in PFS consisting of basil essential oil was limited. The inhibitor in powdered basil PFS was identified as nevadensin. Physiologically based kinetic (PBK) modeling was performed to elucidate if the observed inhibitory effects can occur in vivo. Subsequently, risk assessment was performed using the Margin of Exposure (MOE) approach. Results suggest that the consequences of the in vivo matrix-derived combination effect are significant when estragole would be tested in rodent bioassays with nevadensin at ratios detected in PFS, thereby increasing MOE values. However, matrix-derived combination effects may be limited at lower dose levels, indicating that the importance of matrix-derived combination effects for risk assessment of individual compounds should be done on a case-by-case basis considering dose-dependent effects. Furthermore, this study illustrates how PBK modeling can be used in risk assessment of PFS, contributing to further reduction in the use of experimental animals.


Pretreatment with 5-hydroxymethyl-2-furaldehyde blocks scopolamine-induced learning deficit in contextual and spatial memory in male mice.
5-Hydroxymethyl-2-furaldehyde (5-HMF) is a compound derived from the dehydration of certain sugars. The aim of the present study was to evaluate the effect of 5-HMF on the cognitive impairment induced by scopolamine, a muscarinic receptor antagonist. To measure various cognitive functions, we conducted the step-through passive avoidance task, the Y-maze task and the Morris water maze task. A single administration of 5-HMF (5 or 10mg/kg, p.o.) significantly attenuates scopolamine-induced cognitive impairment in these behavioral tasks without changes in locomotor activity, and the effect of 5-HMF on scopolamine-induced cognitive impairment was significantly reversed by a sub-effective dose of MK-801, an NMDA receptor antagonist. In addition, a single administration of 5-HMF (10mg/kg, p.o.) enhanced the cognitive performance of normal naïve mice in the passive avoidance task. Furthermore, Western blot analysis revealed that the levels of phosphorylated Ca(2+)/calmodulin-dependent protein kinase II-α (CaMKII) and extracellular signal-regulated kinases (ERK) were significantly enhanced by the single administration of 5-HMF in the hippocampal tissues. Taken together, the present study suggests that 5-HMF may block scopolamine-induced learning deficit and enhance cognitive function via the activation of NMDA receptor signaling, including CaMKII and ERK, and would be an effective candidate against cognitive disorders, such as Alzheimer's disease.