A Healthy Life for African American Women Caregivers: A Concept Mapping Study.
African American women experience a higher burden of caregiving, but they are often underrepresented in studies on caregiver health. This study used a participatory process to elucidate how African American women caring for older adults view health and factors that influence health. We invited African American women ages 24-64 years old who reported caring for an older adult for group concept mapping, a process consisting of five steps: 1) preparation, 2) idea generation, 3) sorting and rating, 4) creating maps, and 5) interpreting maps. Participants (n = 29) first completed idea generation by responding to the focus prompt "A healthy life for a caregiver includes _____." Participants then sorted ideas into clusters based on conceptual similarity and rated each idea on desirability and importance. Data were managed via The Concept System Global MAX Software. Idea generation identified 512 ideas that reduced to 99 unique ideas. Using the 99 ideas, a cluster map with 12 outcome domains best fit the data. Identified clusters included spirituality, maintaining relationships, good character, taking action to cope, preserving oneself, support, personal empowerment, resources, striving for peace, handling emotions, wellness, and taking care of self and place. Forty-three ideas representing 10 of the 12 domains were rated high for desirability and importance. A participatory research method was used to integrate the voices of African American women caregivers and provide a rich set of elements necessary for their health and well-being. We also identified potential focus areas for interventions aimed at promoting the health of these caregivers.


Enhanced Dielectric and Hydrophobic Properties of Poly(vinylidene fluoride-trifluoroethylene)/TiO2 Nanowire Arrays Composite Film Surface Modified by Electrospinning.
In this research, we designed a feasible method to prepare composite films with high permittivity and significantly enhanced hydrophobic performance, which showed huge potential in the electrowetting field. TiO2 nanowire arrays were prepared by a one-step hydrothermal process, and poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) was spin-coated on the nanowire arrays to form composite, the surface of which was modified by electrospinning. Due to the great orientation of TiO2 nanowires, dipoles and space charges are in ordered arrangement along the electric field, and this strongly reinforced the Maxwell-Wagner-Sillars (MWS) polarization, thus the permittivity of the composite (TiO2 nanowire length/film thickness is 0.769) reaches 53 at 1 kHz, which is nearly 3 times higher than pure P(VDF-TrFE). Meanwhile the composite film possesses low dielectric loss (0.07) and low conductivity (2.69 × 10-9 S/cm), showing good insulation. The contact angle of the composite after electrospinning (about 137°) was greatly enhanced from pure P(VDF-TrFE) spin-coated film (about 89°), which can be attributed to the microrough structure built by P(VDF-TrFE) nanofibers.


Stress and developmental responses of terpenoid biosynthetic genes in Cistus creticus subsp. creticus.
Plants, and specially species adapted in non-friendly environments, produce secondary metabolites that help them to cope with biotic or abiotic stresses. These metabolites could be of great pharmaceutical interest because several of those show cytotoxic, antibacterial or antioxidant activities. Leaves' trichomes of Cistus creticus ssp. creticus, a Mediterranean xerophytic shrub, excrete a resin rich in several labdane-type diterpenes with verified in vitro and in vivo cytotoxic and cytostatic activity against human cancer cell lines. Bearing in mind the properties and possible future exploitation of these natural products, it seemed interesting to study their biosynthesis and its regulation, initially at the molecular level. For this purpose, genes encoding enzymes participating in the early steps of the terpenoids biosynthetic pathways were isolated and their gene expression patterns were investigated in different organs and in response to various stresses and defence signals. The genes studied were the CcHMGR from the mevalonate pathway, CcDXS and CcDXR from the methylerythritol 4-phosphate pathway and the two geranylgeranyl diphosphate synthases (CcGGDPS1 and 2) previously characterized from this species. The present work indicates that the leaf trichomes are very active biosynthetically as far as it concerns terpenoids biosynthesis, and the terpenoid production from this tissue seems to be transcriptionally regulated. Moreover, the CcHMGR and CcDXS genes (the rate-limiting steps of the isoprenoids' pathways) showed an increase during mechanical wounding and application of defence signals (like meJA and SA), which is possible to reflect an increased need of the plant tissues for the corresponding metabolites.


Postoperative hypothermia and blood loss after the neonatal arterial switch procedure.
Numerous studies have demonstrated that mild hypothermia helps reduce hypoxic/ischemic brain injury that may occur during neonatal cardiac procedures. However, traditional intensive care practices emphasize aggressive rewarming, and the risk of excessive bleeding that may be related to hypothermia. An analysis was conducted of prospectively collected temperature and blood loss data on 47 neonates (30 boys, 17 girls) with transposition of the great arteries who underwent an arterial switch operation at median age 6 days (range, 2 to 23 days) and a mean weight of 3.6 +/- 0.6 kg. Blood loss was compared between 26 patients with mean temperatures below 35.5 degrees C for first 6 hours after operation (mild hypothermia group) and 21 patients at 35.5 degrees C or higher (normothermia group). Repeated-measures analysis of variance and regression modeling were used to evaluate the association between temperature and blood loss and to detect outliers. Total postoperative blood loss was 31 +/- 28 mL in the first 6 hours and 61 +/- 37 mL at 24 hours (range, 15 to 238 mL). Postoperative blood loss between two groups at 6 or 24 hours did not differ significantly. After two outliers were removed, no significant relationship remained between body temperature at 6 hours and cumulative blood loss at 24 hours. Mild postoperative hypothermia does not increase blood loss in neonates after the arterial switch operation. Lack of a difference between the two groups is not likely due to the study being underpowered. We recommend avoidance of aggressive rewarming, which might exacerbate potential neurologic injury.


The effect of nutritional supplementation and stunting on morbidity in young children: the Jamaican study.
Infection and undernutrition in young children are thought to act synergistically. However, studies of the relationship between low height-for age (stunting) and morbidity in young children have had inconsistent findings and there are few adequate data on the effects of nutritional supplementation on morbidity. 129 stunted and 21 non-stunted children aged between 9 and 24 months, from poor Kingston neighbourhoods, identified from a house-to-house survey, were studied. The stunted children were randomly assigned to supplementation or no supplementation. Every week for 24 months the mothers were asked about the occurrence of any symptoms of illness. Supplementation had no consistent effect on the incidence or duration of symptoms. The stunted children had significantly more attacks of diarrhoea, fever, anorexia and apathy than the non-stunted children. The differences remained after controlling for social background and previous attacks of diarrhoea. There was also some indication of more severe illness in the stunted than in the non-stunted children.


Corrigendum to: Analytical evaluation of the new Seal Autoanalyzer 3 High Resolution for urinary iodine determination.
[This corrects the article DOI: 10.11613/BM.2019.020711.].


[μ-Bis(diphenyl-arsan-yl)methane-1:2κAs:As']nona-carbonyl-1κC,2κC,3κC-[tris-(biphenyl-4-yl)arsane-3κAs]-triangulo-triruthenium(0).
In the title triangulo-triruthenium compound, [Ru(3)(C(25)H(22)As(2))(C(36)H(27)As)(CO)(9)], the bis-(diphenyl-arsan-yl)methane ligand bridges an Ru-Ru bond and the monodentate arsine ligand bonds to the third Ru atom. Both arsine ligands are equatorial with respect to the Ru(3) triangle. In addition, each Ru atom carries one equatorial and two axial terminal carbonyl ligands. The phenyl rings of biphenyl are twisted from each other by dihedral angles of 50.5 (2), 44.5 (2) and 27.8 (2)°. The arsine-substituted phenyl rings make dihedral angles of 61.56 (18), 89.36 (18) and 83.27 (18)° with each other. The dihedral angles between the two benzene rings are 87.5 (2) and 81.95 (19)° for the two diphenyl-arsanyl groups. In the crystal, mol-ecules are linked into dimers by inter-molecular C-H⋯O hydrogen bonds. Weak inter-molecular C-H⋯π and π-π [centroid-centroid distance = 3.601 (3) Å] inter-actions stabilize the crystal structure.


Drug utilization review on a tertiary palliative care unit.
Drugs are indispensable for the management of symptoms in palliative care patients, and account for a significant proportion of expenditures on a Tertiary Palliative Care Unit (TPCU). Drug expenditures for Edmonton's TPCU increased by 40% in 2002 compared to 2001. Fifty-five percent of the increase was attributable to injectable fentanyl, oral and injectable ondansetron, and total parenteral nutrition (TPN). As there was no increase in the unit cost of these drugs between 2001 and 2002, the increased expenditures reflected increased utilization. The hypothesis of this study was that the increased utilization of these drugs reflected appropriate prescribing. The objective was to compare the indications for prescribing these drugs in 2002 against evidence- and consensus-based criteria. Patients who received these drugs while admitted to the TPCU from January 1 to December 31, 2002 were identified through the pharmacy database. Evidence- and consensus-based criteria for drug utilization were developed. Prescribing indications were retrospectively compared against the criteria. Drug prescriptions were categorized as follows: (1) meeting criteria, (2) not meeting criteria, or (3) uncertain. The drugs under study were prescribed during 48 out of 234 admissions to the TPCU in 2002. Prescriptions for fentanyl met criteria in 26 of 29 cases. Indications were unsuccessful therapy with morphine, hydromorphone, and oxycodone (20), requirement for rapid titration from fentanyl patch (5), renal failure (2), and sublingual administration for breakthrough pain (1). Prescriptions for ondansetron met criteria in 19 of 21 cases. Indications were nausea refractory to metoclopramide and dexamethasone (13), and nausea related to radiotherapy or chemotherapy (6). Prescriptions for TPN met criteria for initiation in only one of five cases. However, in all cases, TPN had been started prior to admission. In cases where death was considered imminent, TPN was continued pending consultation with the patient and family regarding discontinuation. These data indicate that the increased prescribing of fentanyl and ondansetron on the TPCU satisfied evidence- and consensus-based criteria in most cases, apparently justifying the associated increase in drug expenditures. This type of analysis may be useful whenever increased drug utilization requires review. A cost effectiveness analysis would be the next step in evaluating the costs vs. the benefits. The issue of discontinuing TPN in palliative care patients requires further investigation.


Forensic psychiatry in France: the Outreau case and false allegations of child sexual abuse.
During the Outreau case in France, 13 individuals were falsely accused of child sexual abuse and incarcerated. The author of this article testified as a psychiatric expert when the convictions were appealed. He explains how purposeful false statements by adults, inept expert witnesses, and the judicial assumption that children do not lie converged to create a tragic legal outcome. This article explains how psychiatric experts should conduct evaluations in cases of alleged child sexual abuse.


Smoking History as a Predictor of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Non-Small Cell Lung Cancer Harboring EGFR Mutations.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKIs) therapy has been recognized as the standard treatment for patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, resistance to EGFR-TKIs has been observed in certain subpopulations of these patients. We aimed to evaluate the impact of smoking history on the efficacy of EGFR-TKIs. The records of patients (n = 248) with NSCLC harboring activating EGFR mutations who were treated with gefitinib or erlotinib at our institution between March 2010 and June 2016 were retrospectively reviewed, and the treatment outcomes were evaluated. The overall response rate and median progression-free survival (PFS) were 59.7% and 10.7 months, respectively. The overall response rate was significantly higher in the ex- and nonsmokers than in the current smokers (64.6 vs. 51.1%, p = 0.038). PFS also differed significantly between the current smokers and the ex- and nonsmokers (12.4 vs. 7.4 months, p = 0.016). Multivariate analysis identified smoking history as an independent predictor of PFS and overall survival. The clinical data obtained in this study provide a valuable rationale for considering smoking history as a predictor of the efficacy of EGFR-TKI in NSCLC patients harboring activating EGFR mutations.


Effect of self-esteem on social interactions during the Ultimatum Game.
Self-esteem is an attitude formed by self-evaluation based on positive and negative aspects of oneself. Low self-esteem is a risk factor for psychiatric disorders and is especially associated with social difficulties. Recently, behavioral economics has allowed the quantitative study of social interactions. We investigated the association between self-esteem and interpersonal problems and whether self-esteem modulates behavior and emotions during an economic task, the Ultimatum Game (UG). In this task participants accept or reject fair/unfair monetary offers from others. Low (LSE, n=40) and high (HSE, n=45) self-esteem participants were assessed in their interpersonal problems and psychiatric symptoms using self-reported questionnaires, and were compared on their decision making and emotional response during the UG. LSE was associated with depression and anxiety symptoms. In addition, LSE was associated with interpersonal problems, especially in the domains of socially inhibited, nonassertive, overly accommodating, self-sacrificing and cold/distant. During the UG, LSE women reported more anger towards unfair offers than HSE women. Our findings suggest that low self-esteem individuals experience high distress by interpersonal problems in several domains. Importantly, low self-esteem in women seems to be associated with an accentuated emotional response to unfair social exchanges. These results may contribute to treat social difficulties in this population.


The relationship of puberty to other maturity indicators and body composition in man.
The purpose of this paper is to examine the relationship between sexual development and other maturational processes in children. The word "puberty" is used as a general term to include the development of the secondary sex characters and the attainment of reproductive competence.


catena-Poly[[[[2-(2-pyridyl-κN)-1H-benzimidazole-κN]copper(II)]-μ-l-methio-ninato-κN,O:O'] perchlorate].
The structure of the title compound, {[Cu(C(5)H(10)NO(2)S)(C(12)H(9)N(3))]ClO(4)}(n), has ortho-rhom-bic symmetry. The chain structure is constructed from square-pyramidally coordinated Cu(II) atoms linked through l-methio-nate ligands. The chains propagate along the a-axis direction and are linked to perchlorate anions via N-H⋯O hydrogen bonds.


A recombinant C-terminal toxin fragment provides evidence that membrane insertion is important for Clostridium perfringens enterotoxin cytotoxicity.
Clostridium perfringens enterotoxin (CPE) is believed to be involved in several important gastrointestinal illnesses. Recent studies have identified a number of distinct molecular events which occur after CPE treatment of eukaryotic cells or isolated membranes. Additional studies are underway to determine the temporal order and intrinsic importance of each CPE event for cytotoxicity. We now demonstrate that a truncated CPE fragment binds to membranes, but is unable to insert into membranes or cause any other subsequent post-insertion event. This is the first experimental evidence supporting the importance of membrane insertion for CPE cytotoxicity. Binding of the CPE fragment is also shown to be irreversible, strongly suggesting that the irreversible binding of wild-type CPE is not due solely to insertion of CPE into membranes.


Management of symptomatic ascites and post-operative lymphocysts with an easy-to-use, patient-controlled, vascular catheter.
Malignant ascites (MA) can be managed with paracentesis, diuretics, shunt-systems, chemotherapy, and targeted therapies. Some treatments are ineffective; others are associated with complications, involve inpatient procedures, or are not cost-effective. Postoperative lymphocysts (LCs) are managed with inpatient drainage and sclerotherapy or surgery. We tested the use of a vascular catheter in the management of symptomatic MA and LC. Fifty-five patients with primary or recurrent cancers with ascites or LCs were managed for symptom relief. A central venous 14-Ga 16-cm catheter (Arrow) was inserted into the abdominal cavity or LC, followed by drainage. The catheter was safely inserted with ultrasound guidance in 43 patients with MA (39 with ovarian cancer: 9 before primary cytoreduction, 30 with recurrence; 4 non-gynecological cancers), and 12 patients with LCs (10 retroperitoneal, 2 bilateral inguinal). All procedures were performed in the outpatient department under local anesthesia, without insertion-related complications. Within a mean of 30 days after catheter placement (range: 7-90 days), no grade 3 infection, peri-drain leakage, or self-removal was noted. In three patients with recurrent ovarian mucinous ascites and one patient with an inguinal LC, some drain obstruction was noted. In cases before primary cytoreduction for ovarian cancer, drainage enabled better nutritional and anesthiological outcomes. Patients with chronic ascites were able to self-monitor the amount of evacuated fluid. Twelve patients whose ascites were drained had chemotherapy at the time, and they reported better well-being, and we estimated better performance status. LC drainage followed by sclerotherapy enabled symptom control and LC radical treatment. The use of the vascular catheter is safe, easy, and cost-effective in the management of symptomatic MA and LC.


Twelve weeks treatment with the DPP-4 inhibitor, sitagliptin, prevents degradation of peptide YY and improves glucose and non-glucose induced insulin secretion in patients with type 2 diabetes mellitus.
To examine the effects of 12 weeks of treatment with the DPP-4 inhibitor, sitagliptin, on gastrointestinal hormone responses to a standardized mixed meal and beta cell secretory capacity, measured as glucose and non-glucose induced insulin secretion during a hyperglycaemic clamp, in patients with type 2 diabetes. A double-blinded, placebo-controlled study over 12 weeks in which 24 patients with T2DM were randomized to receive either sitagliptin (Januvia) 100 mg qd or placebo as an add-on therapy to metformin. In week 0, 1 and 12 patients underwent a meal test and a 90-min 20 mM hyperglycaemic clamp with 5 g of l-arginine infusion. Main outcome measure was postprandial total glucagon-like peptide 1 (GLP-1) concentration. Additional measures were insulin and C-peptide, glycaemic control, intact and total peptide YY (PYY) and glucose-dependent insulinotropic polypeptide (GIP), and intact glucagon-like peptide 2 (GLP-2) and GLP-1. All patients [sitagliptin n = 12, age: 59.5 (39-64) years, HbA1c: 8.0 (7.3-10.0)%, BMI: 33.2 (29.3-39.4); placebo n = 12, age: 60 (31-72) years, HbA1c: 7.7 (7.1-9.8)%, BMI: 30.7 (25.7-40.5)] [median (range)] completed the trial. Sitagliptin treatment improved glycaemic control, had no effect on total GLP-1, GIP or intact GLP-2, but reduced total PYY and PYY(3- 36), and increased PYY(1- 36) and intact incretin hormones. Sitagliptin improved first and second phases of beta cell secretion and maximal secretory capacity. All effects were achieved after 1 week. No significant changes occurred in the placebo group. The postprandial responses of total GLP-1 and GIP and intact GLP-2 were unaltered. PYY degradation was prevented. Glucose and non-glucose induced beta cell secretion was improved. There was no difference in responses to sitagliptin between 1 and 12 weeks of treatment.


Macropinocytosis: an endocytic pathway for internalising large gulps.
Macropinocytosis is a regulated form of endocytosis that mediates the non-selective uptake of solute molecules, nutrients and antigens. It is an actin-dependent process initiated from surface membrane ruffles that give rise to large endocytic vacuoles called macropinosomes. Macropinocytosis is important in a range of physiological processes; it is highly active in macrophages and dendritic cells where it is a major pathway for the capture of antigens, it is relevant to cell migration and tumour metastasis and it represents a portal of cell entry exploited by a range of pathogens. The molecular basis for the formation and maturation of macropinosomes has only recently begun to be defined. Here, we review the general characteristics of macropinocytosis, describe some of the regulators of this pathway, which have been identified to date and highlight strategies to explore the relevance of this endocytosis pathway in vivo.


Selection acting directly on an enzyme polymorphism.
A biochemical approach is utilised in the study of the maintenance of variation at the Adh locus in Drosophila melanogaster. There is a direct correlation between biochemical findings and the results of competition experiments. The relevance of these findings to the study of other enzyme polymorphisms is discussed.


Growth, substrate consumption, and product formation kinetics of Phanerochaete chrysosporium and Schizophyllum commune mixed culture under solid-state fermentation of fruit peels.
Kinetic analysis of solid-state fermentation (SSF) of fruit peels with Phanerochaete chrysosporium and Schizophyllum commune mixed culture was studied in flask and 7 kg capacity reactor. Modified Monod kinetic model suggested by Haldane sufficiently described microbial growth with co-efficient of determination (R 2) reaching 0.908 at increased substrate concentration than the classical Monod model (R 2 = 0.932). Leudeking-Piret model adequately described product synthesis in non-growth-dependent manner (R 2 = 0.989), while substrate consumption by P. chrysosporium and S. commune fungal mixed culture was growth-dependent (R 2 = 0.938). Hanes-Woolf model sufficiently represented α-amylase and cellulase enzymes synthesis (R 2 = 0.911 and 0.988); α-amylase had enzyme maximum velocity (V max) of 25.19 IU/gds/day and rate constant (K m) of 11.55 IU/gds/day, while cellulase enzyme had V max of 3.05 IU/gds/day and K m of 57.47 IU/gds/day. Product yield in the reactor increased to 32.65 mg/g/day compared with 28.15 mg/g/day in shake flask. 2.5 cm media thickness was adequate for product formation within a 6 day SSF in the tray reactor.


Three-tesla MRI biphasic angiography: a method for preoperative assessment of the vascular supply in renal tumours: a surgical perspective.
The new generation of 3TMRI has improved spatial and time resolutions, which are favourable in imaging of the renal vasculature. In this study, we have compared the imaging findings of the renal blood vessels using 3TMRI and CT with intraoperative assessment of the renal vasculature as gold standard. This prospective study was approved by the local ethical committee. Between 4/2011 and 12/2011, 80 patients with renal tumours underwent 3TMRA (angiography) (Magnetom SKYRA 3T, Siemens). Twenty of the patients were also examined with CT AG. The results of the CTA- and MRA-imaging studies were correlated with the intraoperative assessment of the renal vessels. Seventy patients (87.5 %) had a detailed intraoperative assessment of the renal vessels. The sensitivities for CTA and MRA were 88.2 and 88.6 %, respectively. All discrepancies between imaging studies and intraoperative findings were due to inability to identify small polar vessels. The results of MRA were concordant with CTA in 85.0 % of cases. The (three) discrepancies between MRI and CT were due to failure of MRI in identifying small polar vessels. (1) 3TMRA gives detailed information about the renal vasculature including its topographical anatomy. (2) With MRI, small aberrant vessels are more frequently missed than with CTA. (3) CTA remains the gold standard. However, MRA may be used for planning of laparoscopic operations. (4) The quality of the 3D reconstruction is highly depending on the skills of the radiologist.


[The flexure of on-eye rigid gas permeable contact lenses and its relationship with anterior corneal surface].
To investigate the effect of corneal irregularity on on-eye rigid gas permeable (RGP) contact lenses and the corneal shape changed by RGP contact lenses. Corneal topography was taken for 42 bare eyes of 22 subjects before and 1 month after wearing of the RGP contact lens. Off-eye and on-eye wavefront aberrations of the anterior surface of the RGP contact lens were also measured by corneal topography for the same 42 eyes. Zernike aberrations of the RGP contact lens were examined and compared to those of baseline anterior corneal surface. For bare eyes, C4, C5, C7 and C8 were significantly different from the baseline 30 minutes after the RGP contact lens was removed. For the on-eye RGP contact lens, three mean Zernike aberrations were significantly different from those off-eye. These were defocus C4 [OD: (1.003 ± 0.131) µm off-eye and (1.065 ± 0.160) µm on-eye, P = 0.015; OS: (1.003 ± 0.130) µm off-eye and 1.069 (0.851, 1.594) µm on-eye, P = 0.017], main axis astigmatism C5 [OD: (0.072 ± 0.083) µm off-eye and (-0.312 ± 0.232) µm on-eye, P < 0.001; OS: (0.066 ± 0.056) µm off-eye and (-0.349 ± 0.242) µm on-eye, P < 0.001], and spherical aberration C12 [OD: (0.264 ± 0.039) µm off-eye and (0.295 ± 0.048) µm on-eye, P < 0.001; OS: (0.266 ± 0.035) µm off-eye and 0.290 (0.215, 0.471) µm on-eye, P < 0.001]. All these three Zernike aberrations of on-eye RGP contact lenses were significantly correlated to those of the baseline corneas (OD: rc4=0.557, rc5=0.596, rc12=0.581, P < 0.01; OS: rc4=0.684, rc5=0.497, rc12=0.543, P < 0.01). The results suggest that the surface shape of on-eye RGP contact lenses is not rigid, and its change depends on irregularity of the anterior corneal surface, even if the cornea itself is changed by the RGP contact lens. It is better not to fit for RGP so flatter than the average curvature of the cornea.


Characterization the mitochondrial genome of Acrossocheilus Labiatus (Cypriniformes, Acrossocheilus) and its phylogeny.
The first complete mitochondrial genome of Acrossocheilus Labiatus from the Qingshui River were reported in this study with accession number MG878098. The overall nucleotide composition was 31.13% A, 25.10% T, 27.52% C, 16.24% G, respectively. Phylogenetic analysis shows that the A. parallens and A. Hemispinus showed a closest phylogenetic relationship, then clustal with A. Labiatus.


Persistent bactericidal defect in neutrophils from a young woman who recovered from toxic shock syndrome.
We have previously found transient menstruation-associated abnormalities in the in vitro bactericidal function of neutrophils from females who have recovered from toxic shock syndrome (TSS). We now report the case of a young woman who has also recovered from TSS, but who has a persistent, non-menstruation-associated defect in the ability of her neutrophils to kill Staphylococcus aureus in vitro.


Prevalence of and risk factors associated with alcohol abuse in Moshi, northern Tanzania.
This study aimed to assess the prevalence of and risk factors associated with alcohol abuse among women and men in Moshi in northern Tanzania. Alcohol abuse was measured by a CAGE score of 2-4, versus 0-1 for no alcohol abuse (Ewing, 1984). Crude and adjusted logistic regression models determined odds ratios (OR) and 95% confidence intervals (95% CI) of alcohol abuse by characteristics of, respectively, women with partners (n=1200), women without partners (n=614) and men (n=788) (women's partners). Prevalence of alcohol abuse was 7.0% (95% CI: 5.6-8.4) among women with partners, 9.3% (95% CI: 7.0-11.6) among women without partners, and more than double among men at 22.8% (95% CI: 19.9-25.8). In general, Christians had higher alcohol abuse than Muslims or other religions, as did Chagga men compared with men of other ethnic groups. Other socio-demographic characteristics, such as education or income, were not significant. Sexual behaviours were significant predictors of alcohol abuse. For example, women without partners who reported more than two partners in the last year had higher alcohol abuse compared with women reporting no partners (OR=8.75; 95% CI: 2.37-32.31), as did men reporting it is 'OK to hit a partner' for any reason (OR=1.79; 95% CI: 1.16-2.77) compared with men who did not. HIV-1 infection was not significantly associated with alcohol abuse by women or men. The Christian Church in Moshi should consider raising awareness about the harmful effects of high alcohol use among its adherents. Comprehensive programmes focusing on reducing number of partners and alcohol use, particularly by men, are needed in this community.


The Detection, Evaluation, and Management of Dyslipidemia in Children and Adolescents: A Canadian Cardiovascular Society/Canadian Pediatric Cardiology Association Clinical Practice Update.
Atherosclerosis begins in youth and is directly linked with the presence and severity of cardiovascular risk factors, including dyslipidemia. Thus, the timely identification and management of dyslipidemia in childhood might slow atherosclerotic progression and decrease the risk of cardiovascular disease in adulthood. This is particularly true for children with genetic disorders resulting in marked dyslipidemia, including familial hypercholesterolemia, which remains frequently undiagnosed. Universal and cascade screening strategies can effectively identify cases of pediatric dyslipidemia. In the clinical evaluation of children with dyslipidemia, evaluating for secondary causes of dyslipidemia, including medications and systemic disorders is essential. The first line therapy generally centres around lifestyle modifications, with dietary changes specific to the dyslipidemia phenotype. Indications for medication depend on the severity of dyslipidemia and an individualized assessment of cardiovascular risk. Despite an expanding evidence base supporting the detection and timely management of pediatric dyslipidemia, numerous knowledge gaps remain, including a sufficient evidence base to support more widespread screening, thresholds for initiation of pharmacotherapy, and treatment targets. Further studies on the most appropriate age for statin initiation and long-term safety studies of statin use in youth are also required. The most pressing matter, however, is the development of knowledge translation strategies to improve the screening and detection of lipid disorders in Canadian youth.


Clinical analysis of patients with systemic lupus erythematosus complicated with liver failure.
The objective of this study is to analyze and summarize the characteristics of the clinical data of patients with systemic lupus erythematosus (SLE) complicated with liver failure, and to improve the cognition of the disease. The clinical data of patients with SLE complicated with liver failure hospitalized in Beijing Youan Hospital from January 2015 to December 2021 were collected retrospectively, including general information and laboratory examination data, and the clinical characteristics of the patients were summarized and analyzed. Twenty-one SLE patients with liver failure were analyzed. The diagnosis of liver involvement was earlier in 3 cases than that of SLE, and later in 2 cases. Eight patients were diagnosed with SLE and autoimmune hepatitis at the same time. The medical history is between 1 month and 30 years. This was the first case report of SLE complicated with liver failure. We found that: (1) among the 21 patients, organ cysts (liver and kidney cysts) were more common and the proportion of cholecystolithiasis and cholecystitis was higher than that in previous studies, but the proportion of renal function damage and joint involvement was lower. (2) The inflammatory reaction was more obvious in SLE patients with acute liver failure. The degree of liver function injury in SLE patients with autoimmune hepatitis was less than that in patients with other liver diseases. (3) The use of glucocorticoid in SLE patients with liver failure was worthy of further discussion. Key Points • Patients with SLE complicated with liver failure have a lower proportion of renal impairment and joint involvement. • The study firstly reported SLE patients with liver failure. • Glucocorticoids in the treatment of SLE patients with liver failure are worthy of further discussion.


Multiyear life energy and life cycle assessment of orange production in Iran.
Increasing agricultural production requires the application of more chemical inputs during the growth of different crops. This study aims at assessing the energy indicators and environmental impacts during the initial 7-year growth of orange orchards. Through the life cycle assessment (LCA) technique, the hotspots in 11 environmental indicators of the orange orchard growth were determined for different years. The system boundaries were considered to be the orange orchard gates, and the functional units were 1 kg of orange and 1-h orange orchard. The energy input of nitrogen fertilizer, diesel, and human labor has the biggest share in the total energy inputs. The total average energy input and energy output (in 7 years) were calculated as 62,917.027 MJ/ha and 47,618.17 MJ/ha, respectively. The results showed that the energy indices (energy efficiency and net energy) were increasing from year first to seventh and also the share of renewable energy increased. According to the results, with respect to the highest share for production of 1 kg orange in different criteria, nitrogen fertilizer was the main contributor to abiotic depletion and human toxicity, orchard field emissions and nitrogen fertilizer had the highest shares in global warming and photochemical oxidation, fossil fuels and nitrogen fertilizer were the highest contributors to ozone layer depletion, whereas ecotoxicity was mainly affected by chemical fertilizers and orchard surface emissions. Finally, the main contributor for acidification and eutrophication was surface emissions. In the study of environmental impacts from the first to the seventh year, it should be noted that if the functional unit is considered mass based (1 kg orange), due to the unproductive of the trees in the first to third years (low fruit production), the environmental effects are high and then it decreases after the third year due to increasing the yield of the product. Generally, with consideration of the tree growth period, the useful data of energy and environmental impacts for production horticultural products can be provided so that we can avoid multiple interpretations of results associated to reporting annual energy and environmental impact variations.


Health promotion and the knowledge-attitude-behavior continuum.
Influencing health behavior through informational campaigns, followed by the expectation of attitude change and subsequent desired behavior changes, is examined. Prior literature in this area indicates that the correlations between information level and overt behavior or between attitude and overt behavior are generally positive though low. Two major approaches to improving the relationships between knowledge, attitude, and behavior are discussed: the approach taken by M. Fishbein and his associates, which argues for the use of measures of behavior intention rather than generalized attitudes, and the approach of W.J. McGuire and other proponents of an information-processing model, which argues that moving between the elements of the knowledge-attitude-behavior continuum demands processing time on the part of individuals and attention to a set of elements within a communication matrix. The five central elements of the communication process--source, message, channel, receiver, destination--and the independent variables involved are examined. The information-processing model is seen as particularly appropriate to health promotion campaigns and is recommended for further careful study in health promotion situations.


[A study of the interaction of immobilized delipidized rhodopsin with G-proteins].
It was shown that delipidated rhodopsin immobilized on concanavalin A-Sepharose (Rimm) binds with high selectivity transducin from total extracts of rod outer segment protein as well as the regulatory GTP-binding Gi- and Go-like proteins from solubilized membranes of bovine brain. The Rimm-bound proteins are eluted in the presence of the nonionic detergent, octyl glucoside, and GTP. This suggests that Rimm can be used as an affinity adsorbent for the isolation and purification of G-proteins.


The empty rectum on plain X-ray. Does it have any significance in the neonate?
The absence of rectal gas is said to be a sign of Hirschsprung's disease, especially when there is also gaseous distension of the bowel proximally. This paper reviews 136 neonates who had plain abdominal radiographs. There were 83 patients with multiple examinations, of which 52 (63%) showed variability in the presence of rectal gas on the radiographs. Fifty-seven of the total babies (42%) had significant bowel distension and of these 42 (74.5%) had absence of rectal gas. Only one of these cases had Hirschsprung's disease, most of the remaining having either generalized sepsis (42%) or necrotizing enterocolitis (25.5%).


Levels of SERPIN family proteins in peri-implant crevicular fluid in patients with peri-implantitis.
Serine protease inhibitors (SERPINs) family has been discovered in many disorders with proteolysis mechanisms. Our study determined the SERPINBs protein expression via public-based GEO databases and further validated by peri-implant crevicular fluid (PICF) of peri-implantitis patients and healthy recruiters. This study is a retrospective analysis. A total of 123 participants of Fujian Medical University Fujian Stomatological Hospital, consisting of 58 cases of peri-implantitis and 65 samples of healthy control were retrospectively analyzed by ELISA assays and explored the gene enrichment pathways and clinical significance of SERPINBs expression accompanied by two different cytokines (IL-6 and TNF-α). Moreover, the clinical significance of SERPINBs was evaluated in peri-implantitis patients with PICF samples by the receiver operating curve (ROC) using the area under the curve (AUC). KEGG database showed that Starch and sucrose metabolism, Retrograde endocannabinoid signaling, Prion diseases, Pentose phosphate pathways, and Olfactory pathways are up-regulated; GO database showed that synapse organization, synapse assembly, sequestering of triglyceride, sensory perception of smell, and regulation of synapse organization pathways are up-regulated. SERPINBs were overexpressed in peri-implant tissues and peri-implantitis patients with PICF. SERPINBs was positively correlated to IL-6 and TNF-α in peri-implantitis patients with PICF. The ROC-AUCs of SERPINBs achieved a significantly higher range from 0.895 to 0.939 in peri-implantitis patients with PICF. Therefore, certain SERPINBs expressions were not only perceived through PICF and peri-implant tissues but also showed potential significance in peri-implantitis. SERPINBs play an influential role in the pathogenesis of peri-implantitis via binding with other inflammatory cytokines.


The major impacts of James Black's drug discoveries on medicine and pharmacology.
James Black has many claims to pharmacological fame as the creator of two new classes of drugs (beta-blockers and H2 antihistamines) and as a tireless innovator in drug discovery strategies and analytical procedures. The latter attributes in particular assisted Black in the invention of the prototypes for the two major classes of drugs for which he is best known, propranolol and cimetidine. The clinical impact of these drugs on both morbidity and mortality has been profound. In addition, the application of his analytical approach to drug discovery and pharmacology led others in the field to create many other new classes of drugs. Shortly before he died in 2010, Black wrote a retrospective review of his research career that provides insight into his innovative thinking and career success. This overview affords readers a very personal picture of the man, his ideas and his contributions.


Aryl benzofuran derivatives from the stem bark of Calpocalyx dinklagei attenuate inflammation.
Calpocalyx dinklagei Harms (Fabaceae) is a tropical medicinal tree, which is indigenous to Western Africa. A phytochemical study of this local plant species from its stem bark has led to the isolation of two previously undescribed aryl benzofuran derivatives, named dinklagein A and B, together with eight known compounds. Their chemical structures were elucidated by use of extensive spectroscopic methods (IR, HREI-MS and 1D and 2D NMR). Among all isolates, dinklagein A displayed remarkably potent inhibitory activity against the production of nitric oxide (NO) in the lipopolysaccharide (LPS) induced RAW264.7 macrophages. SAR and molecular docking investigations on iNOS and previously undescribed compounds (dinklagein A and B) supported experimental data. Furthermore, dinklagein A dose dependently suppressed the LPS-stimulated iNOS expression at both mRNA and protein level. It also attenuated IL-1β release, mRNA expressions of IL-1β and COX-2 at low doses. These results suggest that dinklagein A can be developed as natural, multi-target agent against several inflammatory diseases.


Enrichment strategies for glycopeptides.
In order to understand glycoprotein functionality, information on the structure of both the core proteins and the glycan moieties is necessary. From a practical viewpoint, glycopeptides rather than whole glycoproteins are the general targets for structural analysis, which is primarily carried out by employing mass spectrometry (MS). Using the "glycoproteomics" concept, several techniques have recently been developed to allow the preparation of a series of reference glycopeptides. In this chapter, we describe two selective capturing methods for glycopeptides, i.e., lectin-affinity chromatography and polysaccharide hydrophilic affinity physicochemical chromatography. The combined use of these methods effectively removes non-glycosylated peptides, the inclusion of which substantially interferes with glycopeptide ionization in MS analysis.


Focal [Ca2+]i increases detected by aequorin but not by fura-2 in histamine- and caffeine-stimulated swine carotid artery.
1. We hypothesized that the homogeneity of intracellular [Ca2+] ([Ca2+]i) varies and is regulated in arterial smooth muscle. 2. We evaluated this hypothesis by exploiting the different characteristics of several [Ca2+]i indicators: (1) aequorin, which theoretically can measure focal increases in [Ca2+]i, (2) fura-2, which is predominantly a measure of mean cytoplasmic [Ca2+], and (3) myosin light chain phosphorylation and force, which reflect increases in [Ca2+] near the contractile apparatus. 3. From the differences in the observed aequorin and fura-2 signals, we developed an index of the relative degree of [Ca2+]i homogeneity as the ratio of the aequorin signal and fura-2 signal. 4. Stimulation with intermediate concentrations of histamine (1 and 10 microM) or high [K+]o (25 and 40 mM) increased [Ca2+]i and contractile stress. Relative [Ca2+]i homogeneity, estimated from the aequorin/fura-2 ratio, remained similar to levels observed in unstimulated tissues. 5. Higher concentrations of histamine (100 microM) also increased [Ca2+]i and stress, but the aequorin/fura 2 ratio declined , indicating increased [Ca2+]i homogeneity. Similarly, the aequorin/fura-2 ratio decreased when extracellular Ca2+ was removed. 6. Stimulation with histamine in low extracellular [Ca2+] transiently increased [Ca2+]i and the aequorin/fura-2 ratio. Similarly, in tissues treated with low extracellular [Ca2+], restoration of extracellular Ca2+ transiently increased both [Ca2+]i and the aequorin/fura-2 ratio. Although both of these experiments demonstrated a transient decrease in [Ca2+]i homogeneity, only histamine stimulation led to increased myosin light chain phosphorylation and force. These results indicate that the focal increases in [Ca2+]i observed with histamine stimulation and Ca2+ restoration occurred in different cellular regions. 7. Addition of caffeine (20 mM) increased [Ca2+]i and [cAMP], but this was not accompanied by sustained increased myosin light chain phosphorylation or contraction. Phosphorylation of myosin light chain kinase did not appear to underlie the lack of increase in myosin light chain phosphorylation. Rather, caffeine induced a sustained increase in the aequorin/fura-2 ratio, suggesting that caffeine inhibits smooth muscle contraction by localizing increases in [Ca2+]i to a region distant from the contractile apparatus. 8. These data suggest that there can be transient and sustained focal increases in [Ca2+]i. Aequorin detected increased [Ca2+]i in small regions of the cytoplasm during release from and refilling of the intracellular Ca2+ store and with caffeine stimulation. Dual use of aequorin and fura-2 permits determination of relative [Ca2+]i homogeneity in smooth muscle.


Haemodynamic and metabolic effects of surface rewarming after coronary revascularization.
Cardiac surgery is often associated with a postoperative increase in the patient's metabolic rate; surface rewarming has been suggested to decrease the energy expenditure by preventing hypothermia. Thirty patients, undergoing coronary revascularization, were randomly divided into two groups; after surgery group A was rewarmed by a new device that acts by both conduction and convection, while group B was just covered with cotton blankets. Blood, oesophagus and skin (thigh and foot) temperatures were recorded on admission to the intensive care unit (ICU) and 30, 60, 90, 180, 270, and 450 min later. Haemodynamic parameters, oxygen delivery, calculated oxygen consumption, and plasma lactate concentration were assessed as well. Group A warmed up quicker than group B as far as the skin was concerned while the core temperature was unaffected. Group A was also characterized by lower cardiac indices and oxygen consumption. As the occurrence of a dependence of oxygen consumption on delivery could be reasonably ruled out in warmed patients because blood lactate levels were lower than in the controls, we conclude that surface rewarming might have some positive effect in decreasing metabolic demand after cardiac surgery even if the patient's core temperature is little affected. The inhibition of skin temperature receptors could possibly explain this finding.


A Library of Atomically Thin 2D Materials Featuring the Conductive-Point Resistive Switching Phenomenon.
Non-volatile resistive switching (NVRS) is a widely available effect in transitional metal oxides, colloquially known as memristors, and of broad interest for memory technology and neuromorphic computing. Until recently, NVRS was not known in other transitional metal dichalcogenides (TMDs), an important material class owing to their atomic thinness enabling the ultimate dimensional scaling. Here, various monolayer or few-layer 2D materials are presented in the conventional vertical structure that exhibit NVRS, including TMDs (MX2 , M = transitional metal, e.g., Mo, W, Re, Sn, or Pt; X = chalcogen, e.g., S, Se, or Te), TMD heterostructure (WS2 /MoS2 ), and an atomically thin insulator (h-BN). These results indicate the universality of the phenomenon in 2D non-conductive materials, and feature low switching voltage, large ON/OFF ratio, and forming-free characteristic. A dissociation-diffusion-adsorption model is proposed, attributing the enhanced conductance to metal atoms/ions adsorption into intrinsic vacancies, a conductive-point mechanism supported by first-principle calculations and scanning tunneling microscopy characterizations. The results motivate further research in the understanding and applications of defects in 2D materials.


The development of ommatidial patterning in metamorphosed eye imaginal discs implants ofDrosophila melanogaster.
The development of the rhabdomeric pattern in the compound eye ofDrosophila has been studied using combined transplantation and electron microscope techniques. In a first series of experiments eye imaginal discs of increasing age were implanted into larvae ready to pupate, thus losing variable amounts of the normal time for development. A sequence of differentiative abilities was found in the metamorphosed test pieces. As far as the photoreceptor cells are concerned, the most prominent steps of this sequence are: ability to form groups with other similar elements, anatomical polarization of microvilli, establishment of the rhabdomeric pattern and formation of an equator line. The stability of determination of the equator line was tested in a second experimental series. Fragment of different topographical origin within the mature eye anlage were brought to metamorphosis by implantation into larvae ready to pupate. It was found that an equator line differentiates only in those pieces which according to the published anlage maps contain the prospective equator region prior to metamorphosis. The mitotic abilities of implanted eye imaginal discs were investigated by means of "in vitro"3H-thymidine pulse-labelling and light microscope autoradiography of the differentiated test pieces. During the third larval stage the eye anlage is traversed by two consecutive mitotic waves, each one of them producing different categories of receptor cells. The first, anterior wave predominantly produces cells oriented toward the poles of the eye within the ommatidia, while the second, posterior wave gives rise to elements exclusively in an equatorial position. The dynamics of this proliferation are discussed in relation to the findings in the implantation experiments. Silver-grain counts support the possibility that at least two successive cell divisions occur in the eye anlage between labeling with tritiated thymidine and beginning of morphological differentiation. The relevance of this finding for the understanding of the concept of acquisition of competence is discussed.


Using a Posterolateral Portal to Pass and Tie the Suture of the Inferior Anchor During Arthroscopic Bankart Repair.
Using a posterolateral portal in passing and tying the inferior knot allows good labral reduction and adequate capsular shift to treat anterior shoulder instability. In this technique, the most inferior anchor is placed through a low anterolateral portal. A penetrating grasper is introduced from a posterolateral portal situated 2 to 3 cm distal and lateral to the viewing portal. This portal is used to pass the 2 limbs of the anchor suture as inferior as possible through the labrum and capsule close to 6 o'clock position to form the 2 limbs of the first mattress suture. Finally, knot tying is performed through this posterolateral portal, thus allowing better superior shift of the capsulolabral tissue. The other 2 anchor sutures are passed and tied through the low anterolateral portal.


Risk factors in gestational trophoblastic disease, and consequences for primary treatment.
Treatment with methotrexate (MTX) for two patients with gestational choriocarcinoma proved to be inadequate; subsequently both patients received a combination of cis-platinum, cyclophosphamide, actinomycin D and etoposide. These histories demonstrate the need for better prediction of the efficacy of MTX treatment. Baghshawe and Goldstein developed scoring systems to recognize patients requiring primary combination chemotherapy. The Dutch Working Group for Trophoblastic Tumors recently introduced a simplified scoring system to classify these patients. In order to compare these three scoring systems to predict the effect of primary treatment with MTX a retrospective study was made of 37 patients. MTX treatment failures were predictable in 8 out of 13 patients using Bagshawe's system and 6 out of 13 by the Dutch scoring system. The specificity was 88 and 92%, respectively. Goldstein's scoring system proved to be the least sensitive, but very specific.


Altered platelet serotonin 5-HT2A receptor density but not second messenger inositol trisphosphate levels in drug-free schizophrenic patients.
The 5-HT2A receptor binding parameters using [3H]ketanserine and its intracellular signal inositol 1,4,5 trisphosphate (IP3) concentrations were determined in platelets from schizophrenic patients so as to assess differences with respect to a control group and to a standardized antipsychotic drug treatment. Seventy-five antipsychotic-free patients with a DSM-IV diagnosis of paranoid schizophrenia were included in the study. Blood samples were collected before the onset of antipsychotic treatment (baseline values) and after 3 weeks of treatment. Antipsychotic-free schizophrenic patients showed significantly increased basal 5-HT2A densities in comparison to the control group, together with a significantly increase (23%) in the 5-HT2A binding density in those patients treated with risperidone. These changes could be attributed to an up-regulation of 5-HT2A receptors caused by previous treatment with antipsychotic drugs, which is consistent with the chronic effect of 5-HT2A antagonists to up-regulate the number of binding sites. With regard to second messenger IP3 concentrations, basal concentrations in schizophrenic patients were not significantly different from control values, nor was there any significant difference between basal vs. posttreatment values. These results are possibly related to failure of second messenger systems of 'translating' extracellular messages generated presynaptically into effective neurotransmitter signals in schizophrenic patients.


Antitumor imidazotetrazines. 20. Preparation of the 8-acid derivative of mitozolomide and its utility in the preparation of active antitumor agents.
The preparation of 3-(2-chlorethyl)-4-oxo-3H-imidazo[5,1-d]-1,2,3,5- tetrazine-8-carboxylic acid, a key derivative of mitozolomide in our exploration of the structure-activity relationships of this class of antitumor agents, is described. The facile conversion to the 8-carbonyl chloride gave a derivative that reacted preferentially with nucleophiles at the 8-position rather than at the reactive 4-oxo group, allowing the preparation of a wide range of ester, thioester, amide (including an amide derived from an amino acid), hydroxamic acid, hydrazide and sulfoximide, azide and diazoacetyl derivatives. The in vivo activity is presented of a range of these compounds against TLX5 lymphoma and L1210 leukemia cell lines.


Frequency dependence of attenuation and backscatter coefficient of ex vivo human lymphedema dermis.
Radio-frequency (RF) signals from the most dominant scatterer in a dermis, i.e., collagen fibers, are collected as backscattered signals. We aim to confirm the frequency dependence of the spatial distribution of features in ultrasound images, as well as the attenuation coefficient (AC) and backscatter coefficient (BSC) of skin tissue without [LE (-)] and with lymphedema [LE (+)]. Measurement samples (n = 13) were excised from human skin tissue with LE (-) and middle severity LE (+). A laboratory-made scanner and single-element concave transducers (range 9-47 MHz) were used to measure RF data. A localized AC was computed from the normalized power spectrum using the linear least squares technique. The reflector method and compensation technique of the attenuation of tissue were applied to calculate the BSC. In addition, effective scatterer diameter (ESD), effective acoustic concentration (EAC), and integrated BSC (IBS) were calculated from the BSC as the benchmark to differentiate LE (-) and LE (+) tissues. High-frequency ultrasound displayed different echogenicity and texture compared between LE (-) and LE (+) in all transducers. The AC for LE (-) (0.22 dB/mm/MHz) and LE (+) (0.29 dB/mm/MHz) was comparable. BSC in LE (-) and LE (+) increased linearly with each transducer. The difference of intercept of the BSC between LE (-) and LE (+) indicated that both EAC and IBS of LE (+) were higher than that of LE (-). In contrast, ESD correlated with the slope of the BSC demonstrated the same tendency for both LE (-) and LE (+). These tendencies appeared for each transducer independent of the frequency bandwidth. Frequency independence of AC and BSC in LE (-) and LE (+) was confirmed. Several 9- to 19-MHz ultrasound beams are sufficient for BSC analysis to discriminate LE (-) and LE (+) in terms of the penetration depth of the ultrasound.


A checklist of the helminth parasites of sympatric rodents from two Mayan villages in Yucatán, México.
In this survey, 19 species of helminths including Cestoda (Davaineidae, Hymenolepididae, and Taeniidae), Acanthocephala (Oligacanthorhynchidae), and Nematoda (Trichuridae, Ornithostrongylidae, Heligmonellidae, Oxyuridae, and Gongylonematidae) from Rattus rattus, Mus musculus, Sigmodon toltecus, Heteromys gaumeri, and Peromyscus yucatanicus in two Mayan villages in Yucatán, México, were recorded. Ten species of helminths were collected in both localities. The highest species richness was recorded in R. rattus from Xkalakdzonot (6 taxa). Twelve species are new records for Yucatán and two are registered for the first time in México. This survey constitutes the first checklist of helminth parasites in small rodents in the south-southeast of México.


Transvaginal repair of anterior vaginal wall prolapse with polyvinylidene fluoride (PVDF) mesh: an alternative for previously restricted materials?
To study the mid-term safety and functional outcomes of transvaginal anterior vaginal wall prolapse repair using polyvinylidene fluoride (PVDF) mesh (DynaMesh®-PR4) by the double trans-obturator technique (TOT). Between 2015 and 2020, we prospectively included women with symptomatic high-stage anterior vaginal wall prolapse with or without uterine prolapse or stress urinary incontinence (SUI) in the study. The patients underwent transvaginal repair of the prolapse using PVDF mesh in two medical centers. We followed all patients for at least 12 months. We recorded the characteristics of vaginal and sexual symptoms, urinary incontinence, and prolapse stage pre- and postoperatively using International Consultation on Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS), International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF), and Pelvic Organ Prolapse Quantification (POP-Q) system, respectively. One hundred eight women were included in the final analysis with a mean follow-up time of 34.5 ± 18.6 months. The anatomical success was achieved in 103 (95.4%) patients. There was a significant improvement in patients' vaginal symptoms, urinary incontinence, and quality of life scores postoperatively (p < 0.0001). Only six patients (5.5%) had mesh extrusion, five of whom were managed successfully. The total rates of complications and de novo urinary symptoms were 21.3% and 7.4%, respectively. Significant pain was reported in 17 cases (15.7%). Our findings show that using PVDF mesh in the double TOT technique for anterior vaginal wall prolapse repair is a safe procedure with high anatomic and functional success rates and acceptable complication rates in mid-term follow-up.


Microsurgical transplantation of nonvascularized segments of the fallopian tube in the rabbit.
Microsurgical nonvascularized transplantation of a 1-cm segment of fallopian tube was performed using the rabbit as a model. Autograft experiments showed survival of a 1-cm tubal segment for as long as 10 months postoperatively. Allografts survived equally as well, and one rabbit became pregnant.


Laxative treatment with polyethylene glycol does not affect lipid absorption in rats.
Polyethylene glycol (PEG) is a frequently used laxative agent. It is unknown, however, whether PEG affects the absorptive capacity of the intestine. Reduced lipid (dietary fat and cholesterol) absorption induced by long-term PEG treatment could negatively affect growth in children. We tested whether PEG accelerates gastrointestinal transit and alters lipid absorption and plasma lipid levels. Wistar rats were administered drinking water with or without PEG (7%) for 2 weeks. We studied whole gut transit time by recording the first appearance of red feces after intragastric carmine red administration. We measured plasma concentrations of cholesterol and triglycerides, dietary fat absorption by 48-hour fat balance and by plasma appearance of intragastrically administered stable-isotope labeled fats, and cholesterol absorption with a dual stable isotope technique. PEG decreased whole gut transit time by 20% (P=0.028) without causing diarrhea. PEG treatment did neither affects overall dietary fat balance nor fat uptake kinetics, cholesterol absorption, or plasma lipid concentrations. PEG does not affect lipid absorption nor steady-state plasma lipid levels in rats, although it accelerates the gastrointestinal transit.


Oral Candida colonization and candidiasis in patients with psoriasis.
The objective of this study was to investigate oral Candida colonization and candidosis in a group of patients with psoriasis and controls. A total of 100 patients with psoriasis and matched controls underwent the concentrated oral rinse test for Candida isolation. Candida species were identified by the VITEK 2 Identification System. Categorical variables were evaluated using the χ(2) test. The median Candida count was compared using the Mann-Whitney U test. Oral candidiasis was diagnosed in 3% of the patients with psoriasis. The Candida count and prevalence were significantly higher in the patients with psoriasis compared with controls (69% vs 44%, P < .001), but with no relationship to the severity or treatment of psoriasis. Oral Candida was significantly higher in late-onset (at age ≥30 years) compared with early-onset psoriasis (at age <30 years). Patients with psoriasis have increased oral Candida colonization and candidiasis. Further studies are needed to clarify the predisposing factor(s) for oral Candida in patients with psoriasis.


The association of air temperature with cardiac arrhythmias.
The body response to meteorological influences may activate pathophysiological mechanisms facilitating the occurrence of cardiac arrhythmias in susceptible patients. Putative underlying mechanisms include changes in systemic vascular resistance and blood pressure, as well as a network of proinflammatory and procoagulant processes. Such a chain reaction probably occurs within the time window of several hours, so use of daily average values of meteorological elements do not seem appropriate for investigation in this area. In addition, overall synoptic situation, and season-specific combinations of meteorological elements and air pollutant levels probably cause the overall effect rather than a single atmospheric element. Particularly strong interrelations have been described among wind speed, air pressure and temperature, relative air humidity, and suspended particulate matter. This may be the main reason why studies examining the association between temperature and ventricular arrhythmias have found linear positive, negative, J-shaped or no association. Further understanding of the pathophysiological adaptation to atmospheric environment may help in providing recommendations for protective measures during "bad" weather conditions in patients with cardiac arrhythmias.


Prolonged cyclic strain impairs the fibrinolytic system in cultured vascular endothelial cells.
We previously reported that patients with primary hypertension have an impaired ability to release tissue-type plasminogen activator acutely from the vascular endothelium, and recently found that lowering blood pressure can restore this capacity. We hypothesized that the suppression of the fibrinolytic system is caused by the chronic pressure-induced increased haemodynamic load on the endothelium. This study investigated the effect of the tensile force component of blood pressure by exposing cultured human aortic endothelial cells to 10% cyclic strain for 6-72 h. Messenger RNA levels of tissue-type plasminogen activator, urokinase-type plasminogen activator, and plasminogen activator inhibitor 1 were analysed using Taqman real-time reverse transcriptase-polymerase chain reaction and protein release by enzyme-linked immunosorbent assay. Tensile stimulation resulted in a transient initial upregulation of tissue-type plasminogen activator mRNA at 6 h (53%), which declined with time, and at 48 h had switched to a 28% downregulation. The reduction was sustained after 72 h. Tissue-type plasminogen activator protein secretion showed a similar but somewhat delayed response, with a transient increase in release at 6 h (60%), declining to a final 12% reduction at 72 h. A similar pattern was observed for urokinase-type plasminogen activator mRNA. By contrast, plasminogen activator inhibitor 1 mRNA expression and protein secretion increased at all timepoints (16-47%). Prolonged tensile stimulation impairs fibrinolytic activity in human aortic endothelial cells by a dual action, with suppression of plasminogen activator expression and increased inhibitor production. This effect of tensile stress may contribute to the reduced fibrinolytic capacity observed in patients with hypertension.


Prospective study of treatment outcome of implant retained mandibular overdenture: Two years follow-up.
The aim of this study is to evaluate the treatment outcome of immediately loaded Implants in the interforaminal region of anterior mandible. A total of 15 completely edentulous patients aged between 50 and 70 years were selected satisfying certain inclusion and exclusion criteria. Two implants were placed in 33 and 43 region (B and D location) and the implants were loaded immediately by mandibular overdenture retained with O-ring attachments. The implants were evaluated for various clinical parameters at 6 months, 1 year, 1.5 years, and 2 years intervals after initial placement. There was increased marginal bone loss around implants during the 1(st) year after that the bone loss was insignificant. Clinical stability of immediately loaded implants was lower initially for 6 months, but improved by the end of 1(st) year. Survival rate for immediately loaded implants was 96.6% at the end of the period of study. Immediate loading of interforaminal mandibular implants demonstrated a highly acceptable clinical success at the end of 2 years. However, initially the marginal bone level and clinical stability were significantly lower which showed improvement with time.


The Wandering Nerve: Positional Variations of the Cervical Vagus Nerve and Neurosurgical Implications.
The vagus ("wandering") nerve is the longest cranial nerve with the largest territory of innervation in the human body. Injury during various operative procedures involving the anterior or lateral neck may lead to serious complications. Per "textbook" descriptions, the cervical vagus nerve (CVN) commonly locates within the carotid sheath, in between the common carotid artery (CCA) and internal jugular vein (IJV). However, anatomic variations in its positioning may occur more often than expected and intraoperative identification may anticipate potential surgical pitfalls. A literature review was conducted per PRISMA guidelines for all studies describing positional variations of the CVN within the carotid sheath. A rare and potentially dangerous variation, occurring in only 0.7% of all reported cases, is illustrated with a cadaveric case. Overall, 10 anatomic CVN variations have been described across 971 specimens. The non-textbook variations (26.5%) consist of: lateral (4.7%), anterolateral (8.7%), posteromedial (0.2%), posterior (5.8%), anterior (3.1%), medial (0.7%), and anteromedial (0.4%) to the CCA, as well as posterolateral (0.3%) and posterior (2.6%) to IJV. The "textbook" anatomic location is posterolateral to CCA (73.5%). Moreover, an increase in variability is reported on the left side (17.1%) compared with the right (11.3%). Our cadaveric dissection revealed a right-sided CVN directly medial to the CCA. Positional variations of the CVN occur in over 26% of patients and may add difficulty to an array of surgical procedures. Knowledge of these variations and their prevalence may aid the surgeon in conducting a more precise dissection possibly preventing significant potential adverse sequelae.


[The control of the effect of the electrical stimulation for the callus formation by means of conductance measurement in the rabbit tibia after osteotomy].
The measurement of the resistance between the electrodes for stimulation during the operation shows the electrical field strength in the osteotomie. This one will recommend for the comparison of the results of stimulation experiments. The measurement in the course of healing shows faults at the electrodes and the contacts, whereas as the assertions about the process of healing are slightly.


C-reactive protein in general practice--how commonly is it used and why?
C-reactive protein (CRP) is a well-known diagnostic tool in general practice. The scope of this study was to assess how frequently CRP is used by general practitioners and to evaluate the reasons for using it. A retrospective part based on data from a laboratory database system, and a prospective part with a questionnaire-based registration. 30 general practice clinics in the catchment area of Vejle County Central Hospital. Retrospectively, all patients from general practice serviced by the laboratory for one year. Prospectively, 1190 patients from whom a blood sample was taken for CRP-measurement during a 2 month study period. The frequency of using CRP and the reason requesting it; A) diagnosing a new disease, B) monitoring a well-known disease, or C) "screening". Furthermore; 1) infections, 2) chronic inflammatory disease, 3) malignant disease, or 4) others. CRP-measurements were ordered in 3.7% of all consultations in general practice and for 34.1% of all patients whose blood sample was analysed at the central laboratory. The use of CRP was as follows: A-1: 28.6%, A-2: 6.7%, A-3,4: 9.3%, B-1: 8.2%, B-2: 12.4%, B-3,4: 6.5%, C-1: 5.7%, C-2: 3.2%, C-3: 3.5% and C-4: 15.2%. Diagnosing a new (infectious) disease was the most frequent single reason for CRP-measurement. There was major interpractice variation. CRP is frequently used in general practice, mostly (65.4%) in the field of infections and chronic inflammatory diseases. Because of major interpractice variation, the most correct way of using CRP should be evaluated and guidelines should be provided.


PINK1 signalling in cancer biology.
PTEN-induced kinase 1 (PINK1) was identified initially in cancer cells as a gene up-regulated by overexpression of the major tumor suppressor, PTEN. Loss-of-function mutations in PINK1 were discovered subsequently to cause autosomal recessive Parkinson's disease. Substantial work during the past decade has revealed that PINK1 regulates several primary cellular processes of significance in cancer cell biology, including cell survival, stress resistance, mitochondrial homeostasis and the cell cycle. Mechanistically, PINK1 has been shown to interact on a number of levels with the pivotal oncogenic PI3-kinase/Akt/mTOR signalling axis and to control critical mitochondrial and metabolic functions that regulate cancer survival, growth, stress resistance and the cell cycle. A cytoprotective and chemoresistant function for PINK1 has been highlighted by some studies, supporting PINK1 as a target in cancer therapeutics. This article reviews the function of PINK1 in cancer cell biology, with an emphasis on the mechanisms by which PINK1 interacts with PI3-kinase/Akt signalling, mitochondrial homeostasis, and the potential context-dependent pro- and anti-tumorigenic functions of PINK1.


Autoimmunity, anergy, lentiviral immunity and disease.
Autoimmune antibodies and autoimmune responses have been characterized in both human HIV infection and the rhesus macaque (RM) non-human primate model of SIV infection and reasoned to contribute to the pathogenesis of AIDS. Many theories for the induction and maintenance of such responses have been entertained including molecular mimicry between HIV proteins and self molecules, CD4+ T cell loss accompanied by loss of normal immune regulation that dictate self-non-self-reactivity, defective negative/positive selection of T cells to name a few. The precise mechanisms that lead to such immune dysfunction is difficult to study in humans. Our lab has been studying such autoimmune responses in both SIV-infected RM and sooty mangabeys (SM), a species from Africa that are naturally infected with SIV but do not display any detectable signs of immune deficiency or autoimmunity. We submit that this model is an important model since it allows for narrowing down those mechanisms and pathways that are a result of lentiviral infection per se from those that specifically cause disease including autoimmunity. During the course of these studies, we have ruled out a role for plasma and cellular viral loads, anti-viral humoral responses and a variety of cell signaling pathways. We have identified select pathways that appear to play roles in the pathogenesis of lentiviral infection and disease. These include pathways involved in innocent bystander killing by apoptosis of CD4+ T cells, role for differential regulation of the cell cycle, and a role for distinct host proteins that get incorporated by the virions as they are assembled and either bud out of CD4+ T cells or exit the cells in the form of multi-vesicular endosomal particles from monocytes/macrophages from SIV-infected disease susceptible RM and disease-resistant SM. We present our current working model and hypotheses that are designed to elucidate differences that are responsible for such distinct outcomes of lentiviral infection, autoimmunity and disease. We believe that such findings have important implications for the design of vaccines against human HIV infection.


The impact of Vision 2020 on global blindness.
Recent data suggest that there are 37 million blind people and 124 million with low vision, excluding those with uncorrected refractive errors. The main causes of global blindness are cataract, glaucoma, corneal scarring (from a variety of causes), age-related macular degeneration, and diabetic retinopathy. It would appear that the global Vision 2020 initiative is having an impact to reduce avoidable blindness particularly from ocular infections, but more needs to be done to address cataract, glaucoma, and diabetic retinopathy.


Changes in the survival of adult patients with metastasized melanoma with the approval of immune checkpoint inhibitors: A retrospective study from the United States database.
Immune-checkpoint inhibitors (ICI) have revolutionized the treatment of metastatic melanoma. Ipilimumab and Ipilimumab-Nivolumab combination therapies were approved by the United States Food and Drug Administration in 2011 and 2015, respectively. We aimed to evaluate potential changes in the survival of patients with metastatic melanoma following the approval of these agents. We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database (Nov 2021 submission). All patients aged 20 and above who were diagnosed with 'distant' melanoma (per 'combined summary stage') from 2007 through 2018 were included in the study. This time period was further sub-categorized into 2007-2010 (pre-ICI era), 2011-2014 (single-agent ICI era), and 2015-2018 (combination ICI era) based on the approval timeline of ICI. The median overall survival (OS) was 8, 10, and 14 months in the pre-ICI, single-agent ICI, and combination ICI eras respectively (log-rank test, χ² = 189.03, p < 0.001). On Cox-proportional hazard analysis, patients diagnosed in the single-agent and combination ICI eras had a significantly lower risk of dying [HR 0.82 (95% CI 0.78-0.87) and 0.67 (0.64-0.71), respectively] compared to patients diagnosed in the pre-ICI era. Patients who were of the male gender, aged ≥ 65 years, and those receiving chemotherapy and/or radiotherapy were at a significantly higher risk of dying. Married individuals had a significantly lower risk of dying compared to patients who were divorced, separated, or widowed at the time of diagnosis. There was no significant difference in survival demonstrated among non-Hispanic blacks versus non-Hispanic whites. Survival of patients with metastatic melanoma has improved in the era of immune checkpoint inhibitors. It implies that the survival of patients reported in trials can be correlated at a population level as well. Future analysis from the SEER database is needed when new data becomes available to see if there is a further increase in OS.


The determinants of stability and folding in evolutionarily diverged cytochromes c.
Cytochrome c has served as a paradigm for the study of protein stability, folding, and molecular evolution, but it remains unclear how these aspects of the protein are related. For example, while the bovine and equine cytochromes c are known to have different stabilities, and possibly different folding mechanisms, it is not known how these differences arise from just three amino acid substitutions introduced during divergence. Using site-selectively incorporated carbon-deuterium bonds, we show that like the equine protein, bovine cytochrome c is induced to unfold by guanidine hydrochloride via a stepwise mechanism, but it does not populate an intermediate as is observed with the equine protein. The increased stability also results in more similar free energies of unfolding observed at different sites within the protein, giving the appearance of a more concerted mechanism. Furthermore, we show that the differences in stability and folding appear to result from a single amino acid substitution that stabilizes a helix by allowing for increased solvation of its N-terminus.


A novel method to produce immobilised biomolecular concentration gradients to study cell activities: design and modelling.
It is well known that many cell functions are activated by chemical signals with a time and space-dependent profile. To mimic these profiles in vitro, it is necessary to develop a system that is able to generate concentration gradients with a resolution similar to that perceived by cells, which is around nanomolar with a spatial resolution of a few tens of microns. Many devices capable of generating steady-state concentration gradients have been developed using continuous flow micro-fluidic techniques. However, these systems cannot reproduce the immobilised concentration gradients that are present in the extracellular matrix. For this reason, we have developed a new gradient generator to enable precise and reproducible studies on the effects of immobilised concentration gradients on cell behaviour. A well-known gradient of a desired molecule was generated on the bottom surface of a hydrogel, which was then used as a stamp to immobilise the molecule on a functionalised substrate. A concentration gradient was thus obtained using a simple silane-based chemical reaction. To validate the method, image analysis was performed on glass slides printed with fluorescein isothiocyanate (FITC)- collagen and FITC-poly-lysine concentration gradients. Preliminary cell adhesion tests were also carried out by seeding NIH-3T3 and mesencephalic cells on lab-glass slides printed with concentration profiles of collagen and poly-lysine, respectively.


Strategies to maintain a family-centered care approach in the era of COVID-19: Experiences of a Canadian pediatric cardiology program.
The COVID-19 pandemic has resulted in strict provincial guidelines to prevent its spread. Physical distancing requirements, the postponement of elective pediatric cardiac surgeries and non-invasive cardiac interventions, and hospital visitor restrictions have significantly impacted services provided by our pediatric cardiac program. Rapid modifications to current inpatient and outpatient practices were required to maintain a family-centered care approach. Strategies our team used to maintain a family-centered care approach focused on six key areas including inpatient care, outpatient pediatric cardiology clinics, family meetings, discharge planning and teaching, the connection of inpatient pediatric patients to the outside world, and social support. The majority of our strategies are adaptable to other pediatric cardiology programs and some may prove useful after the pandemic and as restrictions lift. These strategies each have their own limitations and challenges that must be considered when adapting them to other pediatric cardiology programs and continuing their use after the pandemic has resolved.


Surgery of intraabdominal giant dedifferentiated liposarcoma of ascending colon mesentery: A rare case report.
Liposarcoma, a lipogenic tumor of large deep-seated connective tissue space, presents the most common type of soft tissue sarcoma arising in the retroperitoneum. Liposarcoma that arises from colonic mesentery is especially a very rare disease. The present case describes a surgery of giant dedifferentiated liposarcoma at ascending colon mesentery. A 47-year-old South Korean man was admitted and presented with palpable abdominal mass. Abdominal pelvic computed tomography scan revealed a huge mass at his right sided abdomen (about 25 × 19 cm sized mass at right abdomen with encapsulation). After the surgery, the entire mass was completely excised en bloc with the ascending colon. The specimen consisted of multinodular, pinkish tanned, focally myxoid tissue, which measured up to 25.5 × 19 × 12.5 cm. Final pathological analysis reported dedifferentiated liposarcoma (high grade sarcoma) with MDM2 and CDK2 (+) in immunohistochemistry. The present case report concerns a 47-year-old male with giant dedifferentiated liposarcoma arising from colonic mesentery and achieved en-bloc resection of liposarcoma with right hemicolectomy.


Temporal trends in Black-White disparities in cancer surgery and cancer-specific survival in the United States between 2007 and 2015.
The American Society of Clinical Oncology (ASCO) has strived to address racial/ethnic disparities in cancer care since 2009. Surgery plays a pivotal role in cancer care; however, it is unclear whether and how racial/ethnic disparities in cancer surgery have changed over time. This cohort study included 1,113,256 White and Black cancer patients across 9 years (2007-2015) using patient data extracted from the Surveillance, Epidemiology, and End Results (SEER)-18 registries. Patient data were included from 2007 to adjust insurance status and by 2015 to obtain at least a 3-year survival follow-up (until 2018). The primary outcome was a surgical intervention. The secondary outcomes were the use of (neo)adjuvant chemotherapy and cancer-specific survival (CSS). Adjusted associations of the race (Black/White) with the outcomes were measured in each cancer type and year. The gap between surgery rates for Black and White patients narrowed overall, from an adjusted odds ratio (aOR) of 0.621 (0.592-0.652) in 2007 to 0.734 (0.702-0.768) in 2015. However, the racial gap persisted in the surgery rates for lung, breast, prostate, esophageal, and ovarian cancers. In surgically treated patients with lymph node metastasis, Black patients with colorectal cancer (CRC) were less likely to receive (neo)adjuvant chemotherapy than White patients. Black patients undergoing surgery were more likely to have a worse CSS rate than White patients undergoing surgery. In breast cancer patients, the overall trend was narrow, but continuously present, with an adjusted hazard ratio (aHR) of 1.224 (1.278-1.173) in 2007 and 1.042 (1.132-0.96) in 2015. Overall, progress has been made toward narrowing the Black-White gap in cancer surgical opportunity and survival. Future efforts should be directed toward those specific cancers for which the Black-White gap continues. Additionally, it is worth addressing the Black-White gap regarding the use of (neo)adjuvant chemotherapy for CRC treatment.


[Testosterone content of the blood in women with Itsenko-Cushing disease].
The paper is concerned with the results of a study of the testosterone content in the blood of 68 women with the Itsenko-Cushing disease at different stages of therapy. The testosterone level was elevated in the blood of untreated patients at the stage of exacerbation and remission following various therapeutic modalities including khloditan and returned to normal after bilateral total adrenalectomy. It is assumed that the source of testosterone hyperproduction in the Itsenko-Cushing disease is the adrenals.


Replacement of a chlorine with a methylsulfonyl group in the metabolism of propachlor (2-chloro-N-isopropylacetanilide).
Urine from rats and sheep given single doses of [14C]propachlor contained 14C metabolites in which the chlorine of propachlor was replaced by a methylsulfonyl group. Methylsulfonyl-containing metabolites were also isolated from the urine of rats given an intraperitoneal dose of the cysteine conjugate of [14C]propachlor; this indicated that the methylsulfonyl-containing metabolites resulted from metabolic reactions subsequent to the mercapturic acid pathway.


Urinary catecholamines as markers of hypothermia.
Although raised urinary CA levels provide good supportive evidence of prolonged agonal stress in hypothermic deaths, the CA index is not, in our experience, of particular diagnostic significance.


[Laugier-Hunziker syndrome : A rare differential diagnosis of mucocutaneous hyperpigmentation].
Laugier-Hunziker syndrome (LHS) is characterized by lentiginous hyperpigmentation of the oral mucosa and lips. In addition, longitudinal melanonychia and palmoplantar hyperpigmented lesions may occur. LHS is a clinical diagnosis of exclusion. Herein, we report the case of a 66-year-old woman with LHS. The clinical and histopathologic features of LHS are presented and important differential diagnoses are discussed.


Insulin and IGF receptor signalling in neural-stem-cell homeostasis.
Neural stem cells (NSCs) are found in two regions in the adult brain: the subgranular zone (SGZ) in the hippocampal dentate gyrus and the subventricular zone (SVZ) adjacent to the lateral ventricles. Similarly to other somatic stem cells, adult NSCs are found within specialized niches that are organized to facilitate NSC self-renewal. Alterations in stem-cell homeostasis can contribute to the consequences of neurodegenerative diseases, healthy ageing and tissue repair after damage. Insulin and the insulin-like growth factors (IGFs) function in stem-cell homeostasis across species. Studies in the mammalian central nervous system support essential roles for IGF and/or insulin signalling in NSC self-renewal, neurogenesis, cognition and sensory function through distinct ligand-receptor interactions. IGF-II is of particular interest as a result of its production by the choroid plexus and presence in cerebrospinal fluid (CSF). CSF regulates and supports the development, division and migration of cells in the adult brain and is required for NSC maintenance. In this Review, we discuss emerging data on the functions of IGF-II and IGF and/or insulin receptor signalling in the context of NSC regulation in the SVZ and SGZ. We also propose a model for IGF-II in which the choroid plexus is a major component of the NSC niche.


Computational investigation of possible inhibitors of the winged-helix domain of MUS81.
The methyl methanesulfonate and ultraviolet sensitive 81 (MUS81) is a structure-specific endonuclease that is highly conserved in eukaryotes and essential for homologous recombination repair. The winged-helix domain at the N-terminus of MUS81 (wMUS81) can bind DNA substrates and regulate the endonuclease activity. The repression of MUS81 activity could enhance the sensitivity to antitumor compounds of different tumour cells. Thus, MUS81 is a potential therapeutic target in cancer therapy. However, specific inhibitors of MUS81 have remained elusive. Here, for the first time, we attempt to discover the compounds disrupting the wMUS81 activity. The binding affinity of available drugs to wMUS81 was first estimated by molecular docking. pKa values were taken into consideration to eliminate unlikely protonation states of the ligands. Top-lead compounds were then estimated the binding affinity using the fast pulling ligand simulations. Finally, the free energy perturbation method accurately defined the absolute binding free energy of the top four ligands, revealing the most potential inhibitors of wMUS81 including simeprevir and nilotinib. Binding of simeprevir destabilizes the β-hairpin region of wMUS81, likely disturbing the wMUS81 function. The van der Waals free binding energy majorly modulates the ligand-binding mechanism. The two conserved residues Leu189 and Arg196 are likely important in monitoring the interacting process of simeprevir to wMUS81.


The diagnostic value of sleep and vigilance tests in central disorders of hypersomnolence.
This retrospective cross-sectional observational study explored the diagnostic value of selected sleep and vigilance tests (SVT) beyond the multiple sleep latency test to differentiate between various central disorders of hypersomnolence (CDH) and fatigue syndromes. Data from patients who underwent the multiple sleep latency test and at least one additional SVT were extracted from the Bern sleep database (1997-2018). One thousand three hundred fifty-two patients with a CDH (106 narcolepsy type 1, 90 narcolepsy type 2, 119 idiopathic hypersomnia, 192 nonorganic hypersomnia, 205 insufficient sleep syndrome), fatigue syndromes (n = 183), and a subgroup of patients with sleep apnea (n = 457) were analyzed. Classification based on SVT parameters was compared with the final clinical diagnosis serving as a reference. An overall model predicted the final diagnosis in 49.5% of patients. However, for the pairwise differentiation of two clinically suspected diagnoses, many SVT parameters showed a sensitivity and specificity above 70%. While the overall discrimination power of the multiple sleep latency test was slightly better than the one of the maintenance of wakefulness test, the latter differentiated best between narcolepsy and idiopathic hypersomnia with prolonged sleep need. Disproportionally poor results in reaction tests (e.g. steer clear test), despite comparable or lower sleepiness levels (SLAT, WLAT), were valuable for differentiating nonorganic hypersomnia from idiopathic hypersomnia/sleep insufficiency syndrome. This study demonstrates how the combination of a careful clinical assessment and a selection of SVTs can improve the differentiation of CDH, whereas it was not possible to establish an overall prediction model based on SVTs alone.


Determination of dye intermediates in oxidative hair dyes by fused-silica capillary gas chromatography.
A fused-silica capillary gas chromatographic method is described for the determination of dye intermediates in oxidative hair dyes. An appropriate amount of hair dye sample is dissolved in 10 ml of methanol containing 0.25 g of ammonium thioglycolate and an appropriate amount of 2-amino-4-methylphenol as an internal standard. This solution is directly injected into a gas chromatograph. A fused-silica capillary column with cross-linked methyl silicone OV-1 or SE-54 as a liquid phase yields excellent resolution of dye intermediates. Some factors affecting the quantitation of dye intermediates are discussed. The proposed method gave good recoveries and reproducibilities, and permits simultaneous determination of various types of dye intermediates without any pretreatment. The use of a nitrogen-phosphorus detector allows the selective detection of nitrogen-containing dye intermediates. This simple and versatile method is applicable for the determination of dye intermediates in commercial hair dyes.


Correlation of side chain mobility with cholesterol retention by phospholipid vesicles.
Multilamellar vesicles were prepared from choline phospholipids with various fatty acyl chains, singly and in mixtures, with and without cholesterol. Mobility of acyl side chains for each type of vesicle was measured by fluorescence polarization with diphenylhexatriene, and the amounts of cholesterol and phospholipid retained by them after extraction with a nonpolar solvent were determined. The data suggest that structures of acyl chains determine the extractability of cholesterol. Phosphatidylcholines with unsaturated or short saturated side chains above transition temperature retain less cholesterol upon extraction with petroleum ether than phosphatidylcholines with saturated side chains below transition temperature. Correlation of cholesterol retention with side chain mobility showed that cholesterol is more easily removed from vesicles with mobile acyl side chains than from vesicles with rigid side chains. The presence of cholesterol also alters extractability of phospholipids from vesicles and suggests that sterol affects the polarity rather than spacing of headgroups on vesicle surfaces.


[Antiplatelet agents and proton pump inhibitors. How can the risk-benefit balance be optimized in patients at risk for cardiovascular disease and gastrointestinal bleeding?].
Antiplatelet agents are routinely used in both primary and secondary prevention of cardiovascular events. The development of new antiplatelet agents and the strong growth of interventional cardiology have led to this therapy being more widely prescribed and for longer periods. The most important secondary effect is the rise in the incidence of hemorrhagic complications, the most prevalent being gastrointestinal bleeding. In this context, the balance between the cardiovascular benefits and bleeding risk of these agents must be optimized. This review provides specific management recommendations and highlights important practical aspects related to antiplatelet therapy, including the interaction between clopidogrel and proton pump inhibitors. The benefits and hazards in distinct clinical settings are outlined within the context of optimizing the balance between the cardiovascular benefits and bleeding risk of antiplatelet therapy.


Ischemia-reperfusion injury-induced pulmonary mitochondrial damage.
Mitochondrial dysfunction is a key factor in solid organ ischemia-reperfusion (IR) injury. Impaired mitochondrial integrity predisposes to cellular energy depletion, free radical generation, and cell death. This study analyzed mitochondrial damage induced by warm pulmonary IR. Anesthetized Wistar rats received mechanical ventilation. Pulmonary clamping was followed by reperfusion to generate IR injury. Rats were subjected to control, sham, and to 2 study group conditions: 30 minutes of ischemia without reperfusion (IR30/0), or ischemia followed by 60 minutes of reperfusion (IR30/60). Pulmonary edema was quantified by wet/dry-weight ratio. Polarography determined activities of respiratory chain complexes. Mitochondrial viability was detected by using Ca(2+)-induced swelling, and integrity by citrate synthase assay. Enzyme-linked immunosorbent assay determined cytochrome C content. Mitochondrial membrane potential (ΔΨm) stability was analyzed by flow cytometry using JC1, inflammation by myeloperoxidase (MPO) activity, and matrix-metalloproteinase-9 (MMP-9) activity by gel zymography, respectively. In IR30/60 rats, tissue water content was elevated from 80.6 % (sham) to 86.9%. After ischemia, ΔΨm showed hyperpolarization and rapid decline after uncoupling compared with controls. IR, but not ischemia alone, impaired respiratory chain function complexes I, II and III (p < 0.05). Mitochondrial viability (p < 0.001) and integrity (p < 0.01) was impaired after ischemia and IR, followed by mitochondrial cytochrome C loss (p < 0.05). Increased activation of MPO (p < 0.01) and MMP-9 (p < 0.001) was induced by reperfusion after ischemia. Ischemia-related ΔΨm hyper-polarization induces reperfusion-associated mitochondrial respiratory chain dysfunction in parallel with tissue inflammation and degradation. Controlling ΔΨm during ischemia might reduce IR injury.


Contradictory Effect of Coronary Collateral Circulation on Regional Myocardial Perfusion That Assessed by Quantitative Myocardial Perfusion Scintigraphy.
Previous studies showed conflicting results about the contribution of coronary collateral circulation (CCC) to myocardial perfusion and function. The aim of this study was to investigate these contradictory problems by gated myocardial perfusion scintigraphy (gated MPS) for the first time. The current cohort was retrospectively selected among patients who underwent gated MPS and coronary angiography within 2 months. Two different groups including 96 patients were assessed by gated MPS to detect the understanding of the miscellaneous effect of CCC on myocardial perfusion. Group 1 consisted of those who had collateral arteries that were not-well-developed (Rentrop grade 0 - 1) (n = 58), while group 2 consisted of those who had collateral arteries that were well-developed (Rentrop grade 2 - 3) (n = 38). There was no statistically significant difference between groups 1 and 2 in terms of perfusion and functional parameters obtained from gated MPS. Furthermore, no statistically significant difference was found in the phase analysis parameters which is a novel technique to evaluate left ventricular synchronization. On the other hand the left ventricular mass index values were high and quite close to the statistically significant value (P = 0.059) in group 2. The current results that obtained by using the gated MPS technique for the first time in the evaluation of CCC showed that the well-developed collateral circulation has a positive effect on myocardial perfusion and function, but this effect was not statistically significant. Results need to be supported by large scale of patients' size.