Amorphous calcium carbonate controls avian eggshell mineralization: A new paradigm for understanding rapid eggshell calcification.
Avian eggshell mineralization is the fastest biogenic calcification process known in nature. How this is achieved while producing a highly crystalline material composed of large calcite columnar single crystals remains largely unknown. Here we report that eggshell mineral originates from the accumulation of flat disk-shaped amorphous calcium carbonate (ACC) particles on specific organic sites on the eggshell membrane, which are rich in proteins and sulfated proteoglycans. These structures known as mammillary cores promote the nucleation and stabilization of a amorphous calcium carbonate with calcitic short range order which predetermine the calcite composition of the mature eggshell. The amorphous nature of the precursor phase was confirmed by the diffuse scattering of X-rays and electrons. The nascent calcitic short-range order of this transient mineral phase was revealed by infrared spectroscopy and HRTEM. The ACC mineral deposited around the mammillary core sites progressively transforms directly into calcite crystals without the occurrence of any intermediate phase. Ionic speciation data suggest that the uterine fluid is equilibrated with amorphous calcium carbonate, throughout the duration of eggshell mineralization process, supporting that this mineral phase is constantly forming at the shell mineralization front. On the other hand, the transient amorphous calcium carbonate mineral deposits, as well as the calcite crystals into which they are converted, form by the ordered aggregation of nanoparticles that support the rapid mineralization of the eggshell. The results of this study alter our current understanding of avian eggshell calcification and provide new insights into the genesis and formation of calcium carbonate biominerals in vertebrates.


Systemic lupus erythematosus in patients with chronic cutaneous (discoid) lupus erythematosus. Clinical and laboratory findings in seventeen patients.
The presence of the discoid lupus erythematosus (DLE) skin lesion in a patient with systemic lupus erythematosus (SLE) has been suggested to be a marker of less frequent and less severe renal disease. The clinical and laboratory features of seventeen patients who were seen in a dermatology practice and who had DLE as a manifestation of SLE (DLE-SLE) are reported. DLE preceded the diagnosis of SLE in eight patients. In six patients, the onset was concurrent, whereas in three the SLE was present prior to the discoid skin lesions. Five of the patients had lesions of subacute cutaneous lupus erythematosus (SCLE), and Raynaud's phenomenon occurred in eight patients. Clinical evidence of a renal abnormality was present in six patients (hematuria in three, proteinuria in five, and abnormal renal function in two). Antibodies to nuclear and/or cytoplasmic components were abnormal in all patients. Antibody subsets did not correlate well with clinical findings; only half of those with Raynaud's phenomenon demonstrated a positive ribonucleoprotein; only one patient with SCLE demonstrated anti-Ro (SSA) antibody, but four of the six patients with a renal abnormality had an elevated anti-native deoxyribonucleic acid antibody titer. The cutaneous lesions were eventually widespread in all patients, although two had initial disease that was localized to the head and neck. Although renal disease occurs in this group, it is less common and usually milder than in previous groups of unselected SLE patients.


Lifetime prevalence and impact of stalking in a European population: epidemiological data from a middle-sized German city.
There is a lack of community-based studies on prevalence rates of stalking and the impact of stalking on victims in European countries. To examine lifetime and point prevalence rates of stalking, behavioural and psychological consequences for victims, and the impact of stalking on current psychological well-being in a German community sample. A postal survey was conducted with a sample randomly selected from the population of a middle-sized German city; 679 people (400 women, 279 men) responded. The survey included a stalking questionnaire and the WHO-5 well-being scale. Almost 12% of the respondents (n=78, 68 women, 10 men) reported having been stalked. A multiple regression analysis revealed a significant effect of victimisation on psychological well-being. This study identified a high lifetime prevalence of stalking in the community. Effects on victims' psychological health are significant, suggesting that the phenomenon deserves more attention in future community mental health research.


Ambient air quality in the vicinity of a works manufacturing sulphuric acid, phosphoric acid and sodium tripolyphosphate.
Airborne concentrations of sulphur dioxide, nitrogen dioxide, sulphate and fluorides have been determined in the vicinity of a large industrial producer of sulphuric acid, phosphoric acid and sodium tripolyphosphate. The results indicate that the Works does not contribute significantly to 24-h average levels of nitrogen dioxide or sulphuric acid, but does cause an elevation in local sulphur dioxide and fluoride concentrations. Measurements of phosphate deposition demonstrate that the Works is a source of both condensed phosphate and orthophosphate emissions. It is concluded that ambient air pollution concentrations are well within accepted standards for human health, but that alleged damage to garden plants may be due to airborne fluorides and/or phosphate deposition.


Pre-procedure intravenous lidocaine administration on propofol consumption for endoscopic retrograde cholangiopancreatography: A prospective, randomized, double-blind study.
The endoscopic retrograde cholangiopancreatography (ERCP) procedure is generally performed in patients with high comorbidity. We aimed to reduce the consumption of propofol by adding lidocaine before ERCP. Eighty ERCP patients with ASA I-III, aged between 45-75 years, were randomly divided into two groups. Lidocaine group (group L, n = 40), received 1-mg midazolam, 1.5 mg/kg lidocaine, and 1 mg/kg propofol intravenously. The control group (group C, n = 40) received 1-mg midazolam, saline in the same volume as the lidocaine group, and 1 mg/kg propofol intravenously. Propofol was administered with intermittent bolus doses. Propofol consumption, oropharyngeal reflex, recovery time, endoscopist satisfaction, ketamine need, and side-effects were recorded. Propofol consumption during the procedure was statistically lower in group L than in the control group (157.25 ± 39.16 mg vs 228.75 ± 64.62 mg respectively, P < 0.001). Additionally, recovery time was statistically faster in group L compared with the control group (7.78 ± 3.95 min vs 11.92 ± 3.24 min respectively, P < 0.001). The oropharyngeal reflex was less in group L than control group (6/40 vs 15/40 respectively, P = 0.042). There was no significant difference between the two groups regarding visual analogue scale scores and endoscopist satisfaction (P > 0.05). We recommend the use of intravenous lidocaine before the ERCP procedure as it reduces propofol consumption, recovery times, and oropharyngeal reflex.


Molecular Biology, Composition and Physiological Functions of Cuticle Lipids in Fleshy Fruits.
Fleshy fruits represent a valuable resource of economic and nutritional relevance for humanity. The plant cuticle is the external lipid layer covering the nonwoody aerial organs of land plants, and it is the first contact between fruits and the environment. It has been hypothesized that the cuticle plays a role in the development, ripening, quality, resistance to pathogen attack and postharvest shelf life of fleshy fruits. The cuticle's structure and composition change in response to the fruit's developmental stage, fruit physiology and different postharvest treatments. This review summarizes current information on the physiology and molecular mechanism of cuticle biosynthesis and composition changes during the development, ripening and postharvest stages of fleshy fruits. A discussion and analysis of studies regarding the relationship between cuticle composition, water loss reduction and maintaining fleshy fruits' postharvest quality are presented. An overview of the molecular mechanism of cuticle biosynthesis and efforts to elucidate it in fleshy fruits is included. Enhancing our knowledge about cuticle biosynthesis mechanisms and identifying specific transcripts, proteins and lipids related to quality traits in fleshy fruits could contribute to the design of biotechnological strategies to improve the quality and postharvest shelf life of these important fruit crops.


Non-rigid image registration with anatomical structure constraint for assessing locoregional therapy of hepatocellular carcinoma.
Assessing the treated region with locoregional therapy (LT) provides valuable information for predicting hepatocellular carcinoma (HCC) recurrence. The commonly used of assessment method is inefficient because it only compares two-dimensional CT images manually. In our previous work, we automatically aligned the two CT volumes to evaluate the therapeutic efficiency using registration algorithms. The non-rigid registration is applied to capture local deformation, however, it usually destroys internal structure. Taking these into consideration, this paper proposes a novel non-rigid registration approach for evaluating LT of HCC to maintain the image integrity. In our registration algorithm, a global affine transformation combined with localized cubic B-spline is used to estimate the significant non-rigid motions of two livers. The proposed method extends a classical non-rigid registration based on mutual information (MI) that uses an anatomical structure term to constrain the local deformation. The energy function can be defined based on the total one associated with the anatomical structure and deformation information. Optimal transformation is obtained by finding the equilibrium state in which the total energy is minimized, indicating that the anatomical landmarks have found their correspondences. Thus, we can use the same transformation to automatically transform the ablative region to the optimal position. Registration accuracy is evaluated using the clinical data. Improved results are obtained with respect to all criteria in our proposed method (MI-LC) than those in the MI-based non-rigid registration. The landmark distance error (LDE) of MI-LC is decreased by an average of 3.93mm compared to the case of MI-based registration. Moreover, it could be found regardless of how many landmarks applied in our proposed method, a significant reduction in LDE values using registrations based on MI-LC compared with those based on MI is confirmed. Our proposed approach can guarantee the continuity, the accuracy and the smoothness of structures by constraining the anatomical features. The results clearly indicate that our method can retain the local deformation of the image. In addition, it assures the anatomical structure stability.


Salvianolic acids from Salvia miltiorrhiza Bunge and their anti-inflammatory effects through the activation of α7nAchR signaling.
Cardiovascular disease (CVD) is a serious disease with a high incidence rate and mortality. Inflammation is closely related to the occurrence of CVDs. As an essential medicine of promoting blood circulation and removing blood stasis in China, Salvia miltiorrhiza Bunge (Danshen) is widely used to treat CVDs due to its anti-inflammatory and cardiovascular protective effects. Salvianolic acids are the most abundant component in the water extract of S. miltiorrhiza, which has a significant effect on the treatment of CVDs. However, due to the complex composition of salvianolic acids, the active molecules and their underlying mechanisms have not been fully explored. The present study aims to isolate and identify salvianolic acids from Danshen with anti-inflammatory activity and explore the potential mechanisms of isolates. The structures of isolated salvianolic acids were elucidated by UV, IR, NMR, MS and electronic circular dichroism (ECD) calculations. Then anti-inflammatory activities of isolates were screened out by the zebrafish inflammation models. The most active compound was further used to explore the anti-inflammatory mechanisms on LPS-stimulated RAW 264.7 cells. The key inflammatory cytokines IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). The protein expression levels of STAT3, p-STAT3 (Tyr705), NF-κB p65, IκBα, p-IκBα (Ser32) and α7nAchR were determined by Western blotting. The nuclear translocation of p-STAT3 (Tyr705) and NF-κB p65 was evaluated by immunofluorescence assays. Finally, the in vivo anti-inflammatory mechanisms were investigated by observation of neutrophil migration, H&E staining, survival analysis and quantitative PCR (Q-PCR) in LPS-microinjected zebrafish. Two new and four known compounds were isolated from Danshen. Among them, isosalvianolic acid A-1 (C1) and ethyl lithospermate (C5) inhibited neutrophil migrations in three zebrafish inflammation models and C1 with the best activities decreased the secretion of IL-6 and TNF-α and inhibited the expression level of p-IκBα (Ser32) in LPS stimulated RAW 264.7 cells. In addition, C1 also reduced the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705). Moreover, C1 significantly upregulated the protein expression of α7nAchR, and the knockdown of α7nAchR counteracted the effects of C1 on the production of IL-6 and TNF-α and the expression levels of p-STAT3 (Tyr705), NF-κB p65 and p-IκBα (Ser32). In vivo experiments, C1 decreased the migration and infiltration of inflammatory cells, increased the survival ratio and inhibited the mRNA level of IL-6, TNF-α, STAT3, NF-κB and IκBα in LPS-microinjected zebrafish. Two new and four known compounds were isolated from Danshen. Among them, C1 exerted anti-inflammatory activities by activating α7nAchR signaling and subsequently inhibiting STAT3 and NF-κB pathways. This study provided evidence for the clinical application of Danshen and contributed to the development of C1 as a novel in the treatment of cardiovascular disease.


Effects of Root Maturation and Thickness Variation in Coronal Mineral Trioxide Aggregate Plugs Under Traumatic Load on Stress Distribution in Regenerative Endodontic Procedures: A 3-dimensional Finite Element Analysis Study.
Regenerative endodontic procedures (REPs) are the best biological-based treatment choice for managing necrotic immature permanent teeth. This study aimed to evaluate the stress distribution of immature maxillary permanent incisors and periodontal tissues under a traumatic load after root maturation achieved by REP with thickness variation in coronal mineral trioxide aggregate (MTA) plugs. Five different mathematical 3-dimensional finite element analysis models of an immature permanent maxillary incisor were created. These involved immediate postoperative models after REP with varying coronal MTA plug thickness (model 1: 3-mm MTA and model 2: 5-mm MTA), postoperative models after REP with varying coronal MTA plug thickness with 15% volumetric root maturation (model 3: 3-mm MTA and model 4: 5-mm MTA), and a control model (model 5: a mature, healthy maxillary incisor). After the modeling procedures, a traumatic horizontal force load of 400 N was applied, and 3-dimensional finite element analysis was performed. The minimum principal, maximum principal, and von Mises stress criteria were calculated for evaluation. Regardless of the coronal MTA plug thickness, tensile stress in cervical root surfaces decreased with root maturation after REP. Using the 5-mm MTA plug reduced all types of stress in the middle third of the root. In bone tissue, the difference in MTA thickness did not affect stress values. However, stress decreased in most of the bony surfaces with root maturation after REP. Using the 5-mm coronal MTA plug may help in providing biomechanical advantages regarding stress transmission. Also, because root maturation after REP provided a more favorable stress distribution as mentioned, regenerative treatments can be recommended for immature permanent maxillary incisors for a good prognosis.


Alterations of DNA damage response pathway: Biomarker and therapeutic strategy for cancer immunotherapy.
Genomic instability remains an enabling feature of cancer and promotes malignant transformation. Alterations of DNA damage response (DDR) pathways allow genomic instability, generate neoantigens, upregulate the expression of programmed death ligand 1 (PD-L1) and interact with signaling such as cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling. Here, we review the basic knowledge of DDR pathways, mechanisms of genomic instability induced by DDR alterations, impacts of DDR alterations on immune system, and the potential applications of DDR alterations as biomarkers and therapeutic targets in cancer immunotherapy.


Brain Reserve, Resilience, and Cognitive Stimulation Across the Lifespan: How Do These Factors Influence Risk of Cognitive Impairment and the Dementias?
In the absence of effective treatments for dementia, maintaining cognitive health in old age is one of the major challenges facing aging societies. Interventions for cognitive health that are tailored to the person are more likely to bring the best benefits with a minimum burden. We review the existing literature on this topic and discuss the role of the primary care physician.


Conventional IVF revisited: Is ICSI better for non-male factor infertility? Randomized controlled double blind study.
Is ICSI better than conventional IVF for non-male factor infertility? IVF should be the choice of assisted reproductive technique in non-male factor infertility cases. Although total fertilization failure is a major concern for patients and professionals, the overall risk/benefit analysis favors conventional IVF in non-male factor infertility cases. However, according to the ESHRE EIM database pertaining to 1997-2012, the use of IVF has been continuously decreasing in favor of ICSI. Randomized controlled double-blind study involving 138 women undergoing ART in a private Center. All couples with a female partner ≤42 years of age and without severe male factor (total progressive motile sperm with normal morphology >10.000) were included in the study. Exclusion criteria were: history of total fertilization failure, less than 6 cumulus oocyte complexes (COC) available for fertilization, prenatal genetic testing (PGT) cycles, unwillingness to participate and couples undergoing total cryopreservation for any indication. On the day of oocyte pick up, sibling COCs were randomly allocated to fertilization with IVF or denudation followed by ICSI to MII oocytes. The decision to transfer IVF or ICSI embryo(s) depended on embryo quality. Women receiving two embryos were given only IVF or ICSI embryos. Neither the clinician performing the transfer nor the patients were aware of the fertilization method used to generate the embryos transferred. Main outcome parameters were fertilization, clinical pregnancy, implantation and miscarriage rates. Demographic variables, ovarian reserve and infertility etiology, duration of stimulation, total gonadotropin consumption, peak estradiol levels were similar for IVF-ET and ICSI-ET groups. Mean number of COCs (18.95 vs 19.24), number of embryos transferred (1,81 vs 1,81), the ratio of good quality embryos/total embryos (56.89 % and 55.97 %), clinical pregnancy rates (63 % vs 49 %), implantation rates (31 % vs 28 %), and abortion rates (12,5 % vs 8,1 %) were also similar. A total of 1306 COCs were allocated for IVF while 1331 COCs were denuded for ICSI. Fertilization rate per inseminated oocyte was significantly higher in ICSI group (56,20 % vs 63,78 %). There were ten cases of total fertilization failure, all in the IVF group. Although overall fertilization rate was higher for ICSI, it was similar in both groups when cases with total fertilization failure were excluded. The non-availability of live birth rates is a limitation. Randomization of sibling oocytes, not patients requires careful interpretation of pregnancy and implantation rates. Lower cost, ease of application and similar clinical outcome makes IVF the choice of fertilization method in non-male factor infertility cases.


Application of Laser Correlation Spectroscopy for Measuring Virus Size.
Dynamic light scattering method or laser correlation spectroscopy was applied to evaluation of the size of viruses. We measured correlation functions of the light scattered by human immunodeficiency viruses (HIV) and hepatitis A viruses (HAV) and found that size of HIV-1 (subtype A and B) and HAV virions were 104 nm and 28 nm, respectively. Comparison of these findings with electron microscopy data for fixed samples of the same viruses showed good agreement of the results.


Purification of contracture-inducing insect toxins from Buthinae scorpion venoms by immunoaffinity and high pressure liquid chromatography.
A method of rapid and selective detection and purification of contracture-inducing insect toxins from Buthinae scorpion venoms is described in this paper. It consists of two main steps: the first one is specific as it uses immunoaffinity chromatography with antibodies against Androctonus australis Hector IT; the second, reverse phase high pressure liquid chromatography, allows the final separation of the different toxins present in each of the three venoms studied. Two, three and four insect toxins have been purified, respectively, from the venoms of Androctonus australis Hector, Buthus occitanus mardochei and Leiurus quinquestriatus quinquestriatus. This work demonstrates that, in Buthinae venoms, contracture-inducing insect toxins antigenically related to AaH IT, the first one purified, constitute the most important and, in some cases, the only toxins present.


Coronary angioplasty versus bypass grafting. Cost-benefit considerations.
Both PTCA and CABG are effective strategies for coronary revascularization. The initial cost of PTCA is 60% to 75% less than that of CABG. PTCA patients, however, often require repeat procedures secondary to restenosis and incomplete revascularization. Despite this, the cost of PTCA is still approximately half that of CABG at 1 year but approaches that of CABG at 3 years. The BARI SEQOL trial will be available in 1996 and will analyze cost differences as well as quality of life for PTCA versus CABG up to 5 years after revascularization. Patients with single-vessel disease can be treated effectively with PTCA or medications. Although PTCA is more expensive, patients have less angina and better exercise tolerance. Many patients with single-vessel disease are now treated with PTCA, who in the past would have been treated medically. Undoubtedly, this change has added to the increasing cost of health care. Although certain patient groups, such as those with three-vessel disease and low ejection fraction and left-main disease, have a significant mortality advantage when revascularized surgically, many patients with symptomatic two-vessel and three-vessel disease can be treated either with CABG or PTCA with no difference in mortality and MI. To reach this equivalent outcome, however, PTCA patients require more interventional procedures. As a result, at 3 years, there is no cost savings with PTCA. Physicians in the United States have been able to choose the mode of revascularization for patients based on clinical judgment and preference, which has been financed by third-party payers. Given the escalating costs of health care in a country with limited resources, physicians failing to consider costs and benefits may find their choices limited secondary to lack of funding and restrictive policies. Future treatment of CAD will most likely be influenced by aggressive lipid-lowering therapy to prevent secondary cardiac events and possibly by gene therapy to prevent restenosis.


Grey and white matter differences in brain energy metabolism in first episode schizophrenia: 31P-MRS chemical shift imaging at 4 Tesla.
Altered high energy and membrane metabolism, measured with phosphorus magnetic resonance spectroscopy (31P-MRS), has been inconsistently reported in schizophrenic patients in several anatomical brain regions implicated in the pathophysiology of this illness, with little attention to the effects of brain tissue type on the results. Tissue regression analysis correlates brain tissue type to measured metabolite levels, allowing for the extraction of "pure" estimated grey and white matter compartment metabolite levels. We use this tissue analysis technique on a clinical dataset of first episode schizophrenic patients and matched controls to investigate the effect of brain tissue specificity on altered energy and membrane metabolism. In vivo brain spectra from two regions, (a) the fronto-temporal-striatal region and (b) the frontal-lobes, were analyzed from 12 first episode schizophrenic patients and 11 matched controls from a (31)P chemical shift imaging (CSI) study at 4 Tesla (T) field strength. Tissue regression analyses using voxels from each region were performed relating metabolite levels to tissue content, examining phosphorus metabolite levels in grey and white matter compartments. Compared with controls, the first episode schizophrenic patient group showed significantly increased adenosine triphosphate levels (B-ATP) in white matter and decreased B-ATP levels in grey matter in the fronto-temporal-striatal region. No significant metabolite level differences were found in grey or white matter compartments in the frontal cortex. Tissue regression analysis reveals grey and white matter specific aberrations in high-energy phosphates in first episode schizophrenia. Although past studies report inconsistent regional differences in high-energy phosphate levels in schizophrenia, the present analysis suggests more widespread differences that seem to be strongly related to tissue type. Our data suggest that differences in grey and white matter tissue content between past studies may account for some of the variance in the literature.


Lysis of trypanosomes by peptidyl fluoromethyl ketones.
Peptidyl fluoromethyl ketones, improved reagents for inactivating cysteinyl and serine proteinases, have provided unexpected results when applied to intact trypanosomes. A lethal effect was observed but limited to the infectious phase of the parasitic growth cycle. Since the inhibitors are known only to act on proteases, the result implies the existence of a protease of critical importance during the infectious phase. A labelled inhibitor, Cbz-Ala-[3H]Phe-CH2F, indicated that the killing effect correlated with the labelling of a 68 kd protein in the trypomastigotes which we deduce is an essential protease.


Systematic Review and Network Meta-Analysis on the Efficacy of Evolocumab and Other Therapies for the Management of Lipid Levels in Hyperlipidemia.
The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low-density lipoprotein cholesterol (LDL-C) when added to statin therapy in patients who need additional LDL-C reduction. We conducted a systematic review and network meta-analysis of randomized trials of lipid-lowering therapies from database inception through August 2016 (45 058 records retrieved). We found 69 trials of lipid-lowering therapies that enrolled patients requiring further LDL-C reduction while on maximally tolerated medium- or high-intensity statin, of which 15 could be relevant for inclusion in LDL-C reduction networks with evolocumab, alirocumab, ezetimibe, and placebo as treatment arms. PCSK9 inhibitors significantly reduced LDL-C by 54% to 74% versus placebo and 26% to 46% versus ezetimibe. There were significant treatment differences for evolocumab 140 mg every 2 weeks at the mean of weeks 10 and 12 versus placebo (-74.1%; 95% credible interval -79.81% to -68.58%), alirocumab 75 mg (-20.03%; 95% credible interval -27.32% to -12.96%), and alirocumab 150 mg (-13.63%; 95% credible interval -22.43% to -5.33%) at ≥12 weeks. Treatment differences were similar in direction and magnitude for PCSK9 inhibitor monthly dosing. Adverse events were similar between PCSK9 inhibitors and control. Rates of adverse events were similar between PCSK9 inhibitors versus placebo or ezetimibe. PCSK9 inhibitors added to medium- to high-intensity statin therapy significantly reduce LDL-C in patients requiring further LDL-C reduction. The network meta-analysis showed a significant treatment difference in LDL-C reduction for evolocumab versus alirocumab.


Genetic effects of 5-azacytidine in Saccharomyces cerevisiae.
The base analog 5-azacytidine induced a variety of genetic and epigenetic effects in different organisms. It was tested in two diploid strains of the yeast Saccharomyces cerevisiae to study the induction of point mutation, mitotic reciprocal crossing-over, mitotic gene conversion (strain D7) and mitotic aneuploidy (strain D61.M). It was used on cells growing in its presence for 4-5 generations. There was a strong induction of both types of mitotic recombination and point mutation. However, there was no induction of mitotic chromosomal malsegregation under the same conditions.


Does refractive error change twice as fast as corneal power in orthokeratology?
We analyzed data from 4 orthokeratology studies of refractive error change (deltaRE) and keratometer-reading change (deltaK). Instead of the reported deltaRE/deltaK ratio of 2:1, we calculated from linear-regression analysis a ratio (slope) of 2:3. The ordinate intercept of the straight line fitted to the data (N = 181 eyes) indicates that when deltaK = 0, deltaRE = 0.72. The correlation between deltaK and deltaRE is poor (+0.63). Causes and interpretations of these results are discussed.


Favorable Safety Outcomes of Delayed Primary Closure of Large Fournier's Gangrene Skin Defects.
To assess the feasibility and safety of delayed primary closure (DPC) in Fournier's gangrene (FG) patients with large genital defects. A single institution retrospective review was performed from October 2020 to December 2022 of adult males that underwent DPC for FG. All patients underwent standard medical management and were assessed for DPC eligibility by the urology service. Clinical data on patient factors and outcomes were collected, and descriptive statistics were assessed. Of 16 patients that underwent DPC, the average age was 61.1years and body mass index was 34.6 kg/m2. Median Charlson Comorbidity Index was 3.5 (IQR 2-5.3) and Fournier's Gangrene Severity Index was 6.5 (IQR 4.8-8). Median number of debridements was 2.5 (IQR 2-3), with a time to closure of 6.5days (IQR 3-11) and length of stay of 13days (IQR 9-16.3). Mean genital defect size was 119 cm2 (range 44-346 cm2). Eight patients (50%) were closed using scrotal flaps alone while other patients had advancement flaps using the inner thigh, lower abdomen, and perineum. The majority of patients were discharged home directly (63%). There were four Clavien-Dindo III complications: two partial flap necrosis, one wound dehiscence, and one instance of bleeding. Of patients with follow-up, 6/15 (40.0%) had no known complications. DPC is safe and effective for a range of patients presenting with FG. Patients with large defects may benefit from less complex wound management and direct discharge home.


The role of the N-terminal tail for the oligomerization, folding and stability of human frataxin.
The N-terminal stretch of human frataxin (hFXN) intermediate (residues 42-80) is not conserved throughout evolution and, under defined experimental conditions, behaves as a random-coil. Overexpression of hFXN56-210 in Escherichia coli yields a multimer, whereas the mature form of hFXN (hFXN81-210) is monomeric. Thus, cumulative experimental evidence points to the N-terminal moiety as an essential element for the assembly of a high molecular weight oligomer. The secondary structure propensity of peptide 56-81, the moiety putatively responsible for promoting protein-protein interactions, was also studied. Depending on the environment (TFE or SDS), this peptide adopts α-helical or β-strand structure. In this context, we explored the conformation and stability of hFXN56-210. The biophysical characterization by fluorescence, CD and SEC-FPLC shows that subunits are well folded, sharing similar stability to hFXN90-210. However, controlled proteolysis indicates that the N-terminal stretch is labile in the context of the multimer, whereas the FXN domain (residues 81-210) remains strongly resistant. In addition, guanidine hydrochloride at low concentration disrupts intermolecular interactions, shifting the ensemble toward the monomeric form. The conformational plasticity of the N-terminal tail might impart on hFXN the ability to act as a recognition signal as well as an oligomerization trigger. Understanding the fine-tuning of these activities and their resulting balance will bear direct relevance for ultimately comprehending hFXN function.


Disruption of xCT inhibits cell growth via the ROS/autophagy pathway in hepatocellular carcinoma.
xCT, the functional subunit of the system x(c)(-) which plays an important role in maintaining intracellular glutathione (GSH) levels, is expressed in various malignant tumors. Here, we demonstrated that xCT expression is often elevated in HCC and is associated with poor prognosis in HCC patients; moreover, disruption of xCT suppressed HCC cell growth both in vitro and in vivo. xCT dysfunction has also been shown to increase intracellular reactive oxygen species (ROS) levels, thus in turn led to autophagic cell death of HCC cells. Taken together, these findings suggest that xCT may be a promising therapeutic target for human HCC.


Phenylpropanolamine: effects on subjective and cardiovascular variables at recommended over-the-counter dose levels.
Two controlled clinical studies evaluated the effects of phenylpropanolamine HCL (PPA) on measures of blood pressure, pulse, and subjective state (mood). One hundred fifty subjects participated in a parallel groups design that compared a 75-mg sustained release (SR) preparation with a 25-mg tid. dosing regimen and placebo. Fifty-nine of these subjects participated in an additional cross-over component that compared SR PPA 75 mg with placebo. Measures of blood pressure, pulse, and subjective drug effect were obtained nine times throughout the course of a 12-hour session. Data analysis revealed no clinically and few statistically significant effects due to drug treatment. As expected, most measures showed circadian changes on both the cardiovascular and mood variables, which were not related to drug treatment. No euphorogenic or "amphetamine-like" effects were noted. Although further work is warranted regarding the effects of chronic or higher-than-normal doses of PPA, the current studies suggest that PPA, at currently recommended dose levels, is not associated with adverse effects on either cardiovascular or subjective functioning.


Non-adherence to Haemodialysis, Interdialytic weight gain and cardiovascular mortality: a cohort study.
Patients with chronic kidney diseases (CKD) on haemodialysis (HD) have high morbidity and mortality rates, which are also due to the inherent risks associated with nephropathy. Non-adherence (NA) to the different demands of the treatment can have consequences for the outcome of patients undergoing HD; nevertheless, there are still doubts about such repercussions. This study was conducted to evaluate the association between NA to conventional HD and all-cause mortality and cardiovascular mortality. We prospectively evaluated mortality in a 6-year period in a cohort of 255 patients on HD in northeast Brazil. The evaluated parameters of NA to HD were interdialytic weight gain (IDWG) ≥ 4% of dry weight (DW), hyperphosphatemia and regular attendance at treatment, assessed as the correlation between the periods on HD completed and those prescribed. We used the Cox multivariate regression model to analyse survival and the predictors of all-cause mortality and cardiovascular mortality. With a median follow-up period of 1493 days and a mortality rate of 9.1 per 100 people-years, there were 87 deaths, of which 54% were cardiovascular deaths. IDWG ≥4% of DW was associated with a risk of all-cause mortality however presenting a borderline outcome for cardiovascular mortality, with hazard ratios of 2.02 (CI 95% 1.17-3.49, p = 0.012) and 2.09 (CI 95% 1.01-4.35, p = 0.047), respectively. No significant association was found between other parameters of NA and mortality. Subgroup analysis showed that for patients with IDWG ≥4% of DW, malnutrition, age and diagnosis of cardiovascular and cerebrovascular diseases were associated with higher all-cause mortality. IDWG ≥4% of DW was identified as an independent predictor of all-cause mortality and demonstrated a borderline outcome for cardiovascular mortality in patients on conventional HD. The occurrence of excessive IDWG in the presence of malnutrition represented a significant increase in the risk of death, indicating a subgroup of patients with a worse prognosis.


The use of indoramin to induce hypotension during general anaesthesia.
The alpha-blocker indoramin had only modest hypotensive action in the normotensive anaesthetised, paralysed patient undergoing major surgical intervention but had a greater effect in the hypertensive patient. The absence of deleterious cardiac effects even with intravenous doses as high as 1 mg/kg. supports previous findings as to the safety of this compound. It is possible that indoramin potentiates the hypotensive action of halothane but there is no evidence to suggest that an adverse interaction might arise when halothane is used to anaesthetise a patient receiving indoramin treatment.


Predictors of glycemic control in Japanese subjects with type 2 diabetes mellitus.
The purpose of this study was to investigate which pathophysiological and demographic characteristics of Japanese subjects with type 2 diabetes mellitus were associated with poor glycemic control and to propose a statistical model for predicting their glycemic control. A total of 220 subjects with type 2 diabetes mellitus were enrolled in this study. Frequently sampled intravenous glucose tolerance test was performed to determine the first-phase C-peptide secretion rate (CS1) and insulin sensitivity index. Multiple regression analysis in a stepwise manner was carried out to identify independent regulators of glycemic control. Upon stepwise linear regression analysis with hemoglobin A1c as a dependent parameter, fasting plasma glucose concentration (FPG), CS1, and onset age remained as predictors, explaining 41.0% of glycemic control. The young-onset group (onset age < or =48 years) had significantly higher hemoglobin A1c than the old-onset group (onset age >48 years) (P = .0148), although the present age was significantly older in the old-onset group; and there were no significant differences in duration of diabetes, treatment, body mass index, FPG, fasting insulin level, homeostasis model assessment of insulin resistance, CS1, and log(insulin sensitivity index) between them. Worsening factors of glycemic control in Japanese subjects with type 2 diabetes mellitus were elevated FPG, impaired first-phase insulin secretion, and young age of onset of the disease. Because glycemic control in the subjects with young-onset diabetes tends to be worse, early and aggressive intervention should be required for those with young-onset diabetes to prevent long-term complications.


Promoting the wellbeing of lesbian, gay, bisexual and transgender forced migrants in Canada: providers' perspectives.
Researchers are beginning to document the experiences of lesbian, gay, bisexual and transgender (LGBT) forced migrants in settlement. However, studies exploring the perceptions of service providers working with this vulnerable population are limited. These may shed light on the challenges of meeting the needs of LGBT forced migrants, especially mental health issues and problems. This qualitative study elicited the views of 22 Canadian service providers, including advocates, lawyers and mental health practitioners, who serve LGBT forced migrants. Grounded theory analysis revealed the following four themes: facilitating safety, buffering rejection; tracking avoidance patterns; interpreting mental health; and negotiating identity paradigms. Participants' accounts suggest that LGBT forced migrants may be best served by providers who understand the exigencies of establishing trust and safety for their clients; recognise their clients' nuanced social support needs; facilitate the refugee claims process; grasp the complexity of their clients' mental health challenges; and interrogate their own cultural biases regarding sexual orientations and gender identities.


Loss of thalamic serotonin transporters in early drug-naïve Parkinson's disease patients is associated with tremor: an [(123)I]beta-CIT SPECT study.
In vitro studies revealed serotonin transporter (5-HTT) decline in Parkinson's disease (PD). Yet, few studies investigated thalamic 5-HTT in vivo and its effect on PD heterogeneity. We analyzed thalamic [(123)I]beta-CIT binding (mainly reflecting 5-HTT binding) in 32 drug-naïve PD patients and 13 controls with SPECT. Twenty-six patients were examined twice (17 months apart). Based on UPDRS scores, we identified subgroups of patients with moderate/severe tremor (PD(T)) and without tremor (PD(WT)) at the time of clinical diagnosis. Additionally, depressive symptoms were evaluated using the Beck Depression Inventory (BDI) at baseline. Mean thalamic specific to non-specific [(123)I]beta-CIT binding ratio was lower in patients when compared to controls, and further decreased during follow-up. At baseline, average thalamic ratio was significantly lower in the PD(T) than in the PD(WT) subgroup. No correlation was found between BDI scores and thalamic binding ratios. Our findings show decline of [(123)I]beta-CIT binding to thalamic 5-HTT in PD and its possible contribution to tremor onset.


Duodenal infusion of soy protein hydrolysate activates cAMP signaling and hypothalamic neurotransmitter synthesis in pigs.
Neurotransmitters in the brain are important for cognition and memory. As bioactive substrates, whether increased soy protein levels in pigs can promote hypothalamic neurotransmitter synthesis remains unclear. The effect of increased soy protein hydrolysate (SPH) levels in the small intestine of pigs on neurotransmitter precursor supply, hypothalamic neurotransmitter synthesis and underlying molecular processes was investigated by using sixteen pigs (35.2 ± 0.3 kg) infused either with SPH (70 g day-1) or sterile saline (control) twice daily for 15 days via a duodenal fistula. It demonstrated that SPH infusion increased the expression of the neutral amino acid transporter B0AT1 in the jejunal mucosa, the serum tyrosine/large neutral amino acid ratio, the concentrations of serum tyrosine, hypothalamic tyrosine, dopamine and brain-derived neurotrophic factor (BDNF) (P < 0.05). It also increased the jejunal and serum choline, hypothalamic choline and acetylcholine levels (P < 0.05). Hypothalamic transcriptome revealed that differential genes were significantly enriched in the cholinergic synapse, dopaminergic synapse and cyclic adenosine monophosphate (cAMP) signalling pathways, and that the expression of key enzyme genes in the synthesis of acetylcholine and dopamine and dopamine receptors 1 (DRD1) was upregulated by SPH (P < 0.05). Western blotting showed that SPH infusion activated the hypothalamic cAMP signalling pathways. Overall, SPH infusion promoted the synthesis of hypothalamic dopamine and acetylcholine, and the synthesised dopamine promoted BDNF production most likely through the activation of the cAMP signalling pathways by the DRD1.


Bioaccumulation and physiological effects of tetrabromobisphenol A in coontail Ceratophyllum demersum L.
Tetrabromobisphenol A (TBBPA) is one of the most widely used brominated flame retardants. In the present study, the accumulation of TBBPA and its consequent biological responses were examined in coontail (Ceratophyllum demersum L.) over 14 days' exposure. Most of the TBBPA was accumulated after 4d exposure and TBBPA concentration in plant increased with increasing TBBPA concentration in growth solution (R(2)=0.99). By using electron paramagnetic resonance (EPR), we found that the TBBPA exposure significantly increased total free radicals generation in the plants. A good positive relationship (R(2)=0.99) was found between the free radicals formation and accumulation level of TBBPA in plant. Lipid peroxidation was enhanced and chlorophyll content showed declined after TBBPA exposure. The activities of superoxide dismutase (SOD), peroxidase (POD), and the contents of glutathione were also detected. The results suggest that TBBPA accumulation in C. demersum induces oxidative stress and the level of tolerance depends on the antioxidative capacity of the plants.


Basic mechanisms of urinary acidification.
This article has examined the process of urinary acidification from the perspective of events occurring at the cellular and single nephron level. Accordingly, the reabsorption of filtered HCO3- and the titration of urine buffers can be ascribed to the fundamental process of H+ secretion. The precise mechanism of H+ secretion by the tubule cells, the rate by which this occurs, and the factors regulating transport differ between nephron segments. Despite these differences, the cellular process of urinary acidification can be viewed as the extrusion of H+ against an electrochemical gradient across the luminal cell membrane and the movement of an HCO3- equivalent across the basolateral cell membrane. In the proximal tubule (convoluted and straight portions) approximately 90 per cent of the filtered load of HCO3- is reabsorbed. This occurs without the development of large lumen-to-blood pH gradients. The secretion of H+ across the luminal membrane occurs primarily via an electrically neutral Na-H exchange mechanism. Since it is the lumen-to-cell Na+ gradient which provides the energy, the secretion of H+ is a "secondary active" process dependent on the function of the Na-K-ATPase located in the basolateral cell membrane. During the elaboration of an acid urine, the distal nephron (distal convoluted tubule and collecting duct) reabsorbs that portion of the filtered HCO3- escaping proximal reabsorption, titrates luminal buffers, and lowers urine pH. The secretion of H+ occurs by a "primary active" mechanism, which involves the extrusion of H+ across the luminal cell membrane by an electrogenic H+ pump driven by the hydrolysis of ATP. The rate at which H+ is secreted depends on the electrochemical gradient for H+ across the luminal membrane. Thus, changes in both lumen pH and potential will effect H+ secretion, with low lumen pH inhibiting transport and large lumen-negative potentials stimulating transport. In some animals, depending on their homeostatic needs, secretion of HCO3- by the distal nephron can also occur. This process is localized to the distal convoluted tubule and the cortical collecting duct and appears to represent a transport system distinct from that responsible for H+ secretion.


Cancer metabolism: current perspectives and future directions.
Cellular metabolism influences life and death decisions. An emerging theme in cancer biology is that metabolic regulation is intricately linked to cancer progression. In part, this is due to the fact that proliferation is tightly regulated by availability of nutrients. Mitogenic signals promote nutrient uptake and synthesis of DNA, RNA, proteins and lipids. Therefore, it seems straight-forward that oncogenes, that often promote proliferation, also promote metabolic changes. In this review we summarize our current understanding of how 'metabolic transformation' is linked to oncogenic transformation, and why inhibition of metabolism may prove a cancer's 'Achilles' heel'. On one hand, mutation of metabolic enzymes and metabolic stress sensors confers synthetic lethality with inhibitors of metabolism. On the other hand, hyperactivation of oncogenic pathways makes tumors more susceptible to metabolic inhibition. Conversely, an adequate nutrient supply and active metabolism regulates Bcl-2 family proteins and inhibits susceptibility to apoptosis. Here, we provide an overview of the metabolic pathways that represent anti-cancer targets and the cell death pathways engaged by metabolic inhibitors. Additionally, we will detail the similarities between metabolism of cancer cells and metabolism of proliferating cells.


Anaerobic Metabolism in T4 Acanthamoeba Genotype.
Members of the genus Acanthamoeba are of the most common protozoa that has been isolated from a variety of environment and affect immunocompromised individuals, causing granulomatous amoebic encephalitis and skin lesions. Acanthamoeba, in immunocompetent patients, may cause a keratitis related to corneal microtrauma. These free-living amoebas easily adapt to the host environment and wield metabolic pathways such as the energetic and respiratory ones in order to maintain viability for long periods. The energetic metabolism of cysts and trophozoites remains mostly unknown. There are a few reports on the energetic metabolism of these organisms as they are mitochondriate eukaryotes and some studies under aerobic conditions showing that Acanthamoeba hydrolyzes glucose into pyruvate via glycolysis. The aim of this study was to detect the energetic metabolic pathways with emphasis on anaerobic metabolism in trophozoites of three isolates of Acanthamoeba sp belonging to the T4 genotype. Two samples were collected in the environment and one was a clinical sample. The evaluation of these microorganisms proceeded as follows: rupture of trophozoites (7.5 × 103 parasites/ml) and biochemical analysis with high performance liquid chromatography and spectrophotometry. The anaerobic glycolysis was identified through the detection of glucose, pyruvate, and lactate. The protein catabolism was identified through the detection of fumarate, urea, and creatinine. The fatty acid oxidation was identified through the detection of acetate, beta-hydroxybutyrate, and propionate. The detected substances are the result of the consumption of energy reserves such as glycogen and lipids. The anaerobic glycolysis and protein catabolism pathways were observed in all three isolates: one clinical and two environmental. This study represents the first report of energetic pathways used by trophozoites from different isolates of the T4 genotype Acanthamoeba.


Free radical damage in neonatal rat cardiac myocyte cultures: effects of alpha-tocopherol, Trolox, and phytol.
A number of investigations have implicated free radicals in the progression of ischemic/reperfusion injury. alpha-Tocopherol has been found to attenuate alterations due to ischemia and reperfusion in an isolated heart model. The present study was intended to directly examine neonatal rat cardiac ventricular cell cultures exposed to a free radical generating system catalyzed by xanthine oxidase. The effectiveness of alpha-tocopherol in the attenuation of the resultant changes and the mechanism by which the effects of alpha-tocopherol may be exerted were evaluated. Cultures were either nontreated or pretreated for 18 h with 20 microM alpha-tocopherol or the subcomponents of the alpha-tocopherol molecule, phytol and Trolox. Exposure of cell cultures to free radicals resulted in significant increases in lipid peroxidation products, release of both lactate dehydrogenase and 3H-arachidonate, and structural alterations. Pretreatment with alpha-tocopherol showed significant attenuation of the changes associated with exposure to free radicals. Trolox and phytol at equal molar doses were not as effective as alpha-tocopherol in protecting the myocytes against injury. Thus, alpha-tocopherol seems beneficial in its ability to reduce free radical-mediated changes by functioning as a lipophilic antioxidant. Additionally, the intact, native alpha-tocopherol molecule exceeded the protective capabilities of either of its subcomponents.


Differences in physical functioning between relatively active and passive patients with Chronic Fatigue Syndrome.
According to the Cognitive behavioral therapy (CBT) protocol for patients with Chronic Fatigue Syndrome (CFS), therapists are advised to categorize patients in relatively active and passive patients. However, evidence to support the differences in physical functioning between these subgroups is limited. Using the baseline data from a multicentre randomized controlled trial (FatiGo), the differences in actual and perceived physical functioning between active and passive patients with CFS were evaluated. Sixty patients, who received CBT during the FatiGo trial were included. Based on the expert opinion and using the definitions of subgroups defined in the CBT protocols, the therapist categorized the patient. Data from an activity monitor was used to calculate actual physical functioning, physical activity, daily uptime, activity fluctuations and duration of rest during daily life. Perceived physical functioning was assessed by measuring physical activity, physical functioning and functional impairment with the Checklist Individual Strength, Short Form-36 and Sickness-Impact Profile 8. Relatively active patients have a significantly higher daily uptime and show significantly less fluctuations in activities between days. Passive patients experience a significantly lower level of physical functioning and feel more functionally impaired in their mobility. However, no significant differences were found in the other actual or perceived physical functioning indices. A clear difference in actual and perceived physical functioning between relatively active and passive patients with CFS as judged by their therapists could not be found. Future research is needed to form a consensus on how to categorize subgroups of patients with CFS.


Effects of cereals and culture filtrate of Trichoderma viride on lipid metabolism of swine.
Swine were fed corn- or barley-based diets with, or without, culture filtrate (CF) of Trichoderma viride for 21 days. Weight gains were nonsignificantly but slightly increased by CF. The activities of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase, acetyl-CoA carboxylase (ACX), fatty acid synthetase (FAS) and other lipogenic enzymes in several tissues were determined. Significant decreases in the activities of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase in all tissues of swine fed the CF-diets were observed. The major site for the regulation of cholesterol biosynthesis was adipose tissue followed by the intestine, liver, lung and muscle in order of activity. The concentrations of cholesterol in serum and muscle were decreased 27% and 23%, respectively, by CF. ACX and FAS activities increased ca. 2-fold when CF was fed with either of the cereal-based diets. The major sites for fatty acid synthesis was the adipose tissue and, to a lesser extent, the liver. Very low rates of synthesis were detected in intestine, lung and muscle. Similar distributions of activities were found for related lipogenic enzymes.


Highlights in basic autonomic neurosciences: central adenosine A1 receptor - the key to a hypometabolic state and therapeutic hypothermia?
The positive outcome that hypothermia contributes to brain and cardiac protection following ischemia has stimulated research in the development of pharmacological approaches to induce a hypothermic/hypometabolic state. Here we review three papers to highlight the role of the adenosine 1 receptor (A1AR) as a potential mediator and physiological regulator of a hypothermic state in both hibernating and non-hibernating mammals. We would like to emphasize the importance of comparative studies between hibernating and non-hibernating species that could lead to important discoveries on the mechanisms inducing hibernation and how they might be translated to induce a clinically useful hypothermic state.


[Dynamics of cytoskeleton microtubules in higher plant meiosis. I. The perinuclear band of microtubules and the meiotic spindle formation].
A planar meridional perinuclear band of microtubules was observed at the late meiotic prophase I in a range of higher plant species. A distinct high-organized structure and a long time of existence allow to consider it as a new class of MTs dependent on the cell cycle in plant meiosis. MTs of the perinuclear band convert into meiotic spindle through a complex process of spatial rearrangements.


Estimation of global rating changes in quality of life and marital satisfaction among reproductive age women in Iran and Afghanistan before and after COVID-19 pandemic.
Quality of life and marital satisfaction are important components of reproductive-age women's health. This study aimed to compare the quality of life and marital satisfaction in women of reproductive age in Iran and Afghanistan before and after the COVID-19 pandemic. This was a cross-sectional study on a sample of Iranian and Afghan women of reproductive age. To collect the data, the 12-item short-form health survey (SF-12) and the Enrich marital satisfaction scale were used to assess the quality of life and marital satisfaction, respectively. In addition, the Global Rating of Change (GRC) was used in order to evaluate the quality of life and marital satisfaction compared to before the COVID-19 pandemic. Data were evaluated descriptively through statistics including sing t-test, and chi-square, Logistic regression was performed to assess the relationship between outcome variables and independent variables. In all 599 reproductive-age women (300 Iranian, and 299 Afghan) were studied. After adjusting for demographic variables, no significant difference was observed between the two groups for the physical component (P = 0.05) and mental component summary scores of quality of life (P = 0.166) as measured by the SF-12. The majority of Iranian women reported that their quality of life was worsened compared to before the pandemic (57.2%), while in the Afghan group, a higher percentage declared that it was unchanged (58.9%). The mental component of quality of life had no significant relationship with any of the independent variables including nationality. In contrast, the physical component quality of life had a significant relationship with nationality (P = 0.01). Iranian women had more marital satisfaction than Afghan women (P<0.001) and marital satisfaction had a significant relationship with nationality (P<0.001). Most women in both groups (70% of Iranian and 60% of Afghan women) declared that their marital satisfaction unchanged compared to before the COVID-19 pandemic. The results showed that the quality of life of Iranian and Afghan women of reproductive age was almost the same before and after the pandemic. However, Iranians scored lower on the mental component summary and Afghans reported lower scores on the physical component summary. Marital satisfaction of Afghan women was much lower than that of Iranian women. The findings suggest the need for serious attention by health care authorities. Providing a supportive environment might be considered a primary step towards a better quality of life for these populations.


A blood pressure lowering effect of lesions of the caudal periaqueductal gray: relationship to basal pressure.
Basal mean arterial pressure (MAP) measured one week following placement of pontine lesions was markedly lower (-27.85 mm Hg) in cats with bilateral lesions of the caudal periaqueductal gray than in cats with bilateral lesions of the area anteroventral to the locus coeruleus. Regression models of the relationship between basal arterial pressure (MAPbasal) and the change in arterial pressure (MAPchange) after the lesions indicate that lesions of the caudal periaqueductal gray led to a marked decrease in MAP in animals with an elevated basal MAP (MAPchange = MAPbasal x (-1.182) + 139.433; r = -0.902; P less than 0.002). In contrast, lesions of the area anteroventral to the locus coeruleus had no such effect (MAPchange = MAPbasal x (-0.363) + 56.49; r = -0.375; P greater than 0.1). The region of the caudal periaqueductal gray affecting MAP appears anterior to the locus coeruleus and through intrinsic neurons or fibers of passage may play a critical role in control of arterial pressure.


Practical investigation of the factors that affect the selectivity in hydrophilic interaction chromatography.
Retention data for a series of 29 compounds comprising acids, bases and neutrals were obtained on six different hydrophilic interaction (HILIC) columns including bare silica, zwitterionic and those bonded with neutral bonded ligands. The principal aim of the work was to evaluate the effect of various experimental variables such as the nature of the stationary phase, buffer pH, buffer concentration, organic solvent and its concentration, and temperature, in order to determine which factors gave the most effect on the selectivity of the separation. The influence of solute properties on the separation, such as logD values, was also considered. In this way, it was hoped to provide a practical guide to aid in the selection of conditions to achieve a separation in HILIC. The nature of the stationary phase was found to have the greatest effect on selectivity.


Role of cuproptosis in understanding diseases.
Cell death is involved in a wide range of physiological and pathological processes. Recently, the term "cuproptosis" was coined to describe a novel type of cell death. This type of cell death, characterized by copper accumulation and proteotoxic stress, is a copper-dependent manner of death. Despite the progress achieved toward a better understanding of cuproptosis, mechanisms and related signaling pathways in physiology and pathology across various diseases remain to be proved. This mini review summarizes current research on cuproptosis and diseases, providing insights into prospective clinical therapies via targeting cuproptosis.


Tofacitinib as the potent treatment for refractory pemphigus: A possible alternative treatment for pemphigus.
Pemphigus is a rare, but life-threatening autoimmune disease with a high rate of morbidity and mortality, if left untreated. After the development of corticosteroid therapy in the 1950s, the death rate for pemphigus has significantly decreased. However, finding more potent therapeutic options for refractory patients has remained a controversial topic. In the recent years, rituximab has increasingly been used for the treatment of refractory pemphigus, but some patients do not well-respond. In addition, there is a paucity of evidence to support the risk of diseases exacerbation after rituximab therapy. In this study, as a JAK1 and JAK3 inhibitor, tofacitinib has been proposed for the treatment of refractory pemphigus patients.


Morphological and elemental properties of urban aerosols among PM events and different traffic systems.
Morphology and elemental composition of individual fine ambient particles varied among types of PM events and between two different urban environments having different major transportation systems (gasoline/diesel vehicles versus motorcycles). Carbonaceous particles were the most dominant in PM events, whereas S-rich particles were the highest in non-events at urban Gwangju in Korea. The aged soot, semi-volatile organic (SVO), and non-volatile organic (NVO) particles were more abundant in the polluted-long range transport (LTP) event than those in the dust-LTP event and non-event. In the dust-LTP event, the aged mineral dust particles outnumbered the fresh ones, suggesting the mineral dust particles were aged during their long-range transport. At HoChiMinh (HCM) in Vietnam, the fraction of carbonaceous particles was much higher than Gwangju (66% versus 30%) possibly due to more abundant two-stroke motor vehicles at HCM. Of the carbonaceous particles, combustion soot (19%) was the highest, followed by NVO (18%), SVO (17%), and biological particles (11%) at HCM, whereas SVO (11%) and NVO (10%) particles were the highest, followed by combustion soot particles (8%) at Gwangju. The higher fraction of mineral dust particles was also observed at HCM, indicating the sampling site was influenced by dust from unpaved roads and construction sites.


Global prevalence of sexual dysfunction among diabetic patients from 2008 to 2022: Systematic review and meta-analysis.
Both men and women can have a wide range of physical, emotional, and sexual issues as a result of diabetes. One of them is sexual dysfunction, which has an effect on marital relationships as well as the effectiveness of therapy and can develop into a serious social and psychological condition. As a result, the purpose of this study was to identify the global prevalence of sexual dysfunction among diabetic patients. Science Direct, Scopus, Google Scholar, and PubMed were all searched for information. Data were extracted using Microsoft Excel (v. 14), STATA statistical software, and STATA. Publication bias was investigated by a forest plot, rank test, and Egger's regression test. To detect heterogeneity, I2 was calculated and an overall estimated analysis was performed. Subgroup analysis was done by study region and sample size. The pooled odds ratio was also computed. The study was able to include 15 of the 654 publications that were evaluated since they met the criteria. 67,040 people participated in the survey in all. The pooled global prevalence of sexual dysfunction among diabetic patients was 61.4% (95% CI: 51.80, 70.99), I2 = 71.6%. The frequency of sexual dysfunction was highest in the European region (66.05%). For males, the prevalence of sexual dysfunction was 65.91%, while for females, it was 58.81%. Patients with type 2 diabetes mellitus were more likely (71.03%) to experience sexual dysfunction. Finally, sexual dysfunction was fairly common all across the world. There were variations in the prevalence of sexual dysfunction depending on the sex, type of diabetes, and location of the study participant. Our findings imply that screening and appropriate treatment are required for diabetes persons exhibiting sexual dysfunction.


Effects of dietary arginine supplementation on production performance, serum biochemicals, antioxidant capacity, and immunity of laying Wulong geese.
This study investigated the effects of dietary arginine supplementation on the production performance, serum biochemicals, antioxidant capacity, and immunity of laying Wulong geese. A total of 150 Wulong geese (34-wk old) with similar body weights were randomly divided into 6 groups with 5 replicates and 5 geese each (1 male and 4 female). The geese in the control group were fed a corn-rapeseed meal basal diet, and the geese in the treatment groups were fed the basal diet supplemented with 0.1, 0.2, 0.3, 0.4, and 0.5% arginine. The experiment lasted for 17 wk. Our results showed that dietary arginine increased the egg production rate (LR) and average egg weight (AEW) of geese in a quadratic manner (P < 0.05). Dietary arginine had a quadratic effect on the contents of total protein (TP) and triglyceride (TG) (P < 0.05) in the serum. Dietary arginine quadratically decreased the content of malondialdehyde (MDA) and increased the activity of total superoxide dismutase (T-SOD) (P < 0.05). Dietary arginine supplementation linearly and quadratically increased the contents of immunoglobulin A (IgA) and immunoglobulin G (IgG), and linearly increased the content of nitric oxide (NO) (P < 0.05). In conclusion, dietary arginine supplementation can significantly improve the production performance, serum biochemicals, antioxidant capacity, and immunity of laying Wulong geese. Therefore, 0.3% arginine (actual content: 1.02%) is recommended in the diet.


In vivo and In vitro function of the intracellular proteolytic apparatus in nongrowing bacillus megaterium under heat stress
In Bacillus megaterium sporulating at 35 degreesC, up to 90% of 10-min pulse-labeled proteins were degraded. Degradation proceeded in two waves. Short-lived proteins, i.e., intrinsically labile proteins and proteins made short-lived because of starvation, were mostly degraded during the reversible sporulation phase. Their amount corresponded to 20% or slightly more during 2 h. The second wave of protein degradation, which followed during the irreversible sporulation phase at 35 degreesC, increased the amount of total degradable pulse-labeled proteins to about 90%. This wave was absent in the isogenic asporogenic mutant 27-36 or in the wild strain, whose sporulation was inhibited by increased temperature. The proportion of degradable proteins was thus reduced to less than 40% in the asporogenic mutant incubated at 35 degreesC and to 46% in the wild strain whose sporulation was suppressed by the temperature of 47 degreesC. Unlike sporulating cells, these cells were thus capable of degrading short-lived and denatured proteins, but were not able to degrade most of other proteins. The in vitro protein degradation was substantially enhanced by increasing the Ca2+ concentration, suggesting a role of Ca2+-dependent proteinase(s) in the process.


Headspace solid-phase microextraction of halogenated toluenes in environmental aqueous samples with polypropylene microporous membranes.
The optimization of the polypropylene microporous membrane based solid-phase microextraction (MMSPE) of several halogenated (Cl(-) and Br(-)) toluenes was carried out. The influence of several factors such as sampling mode, sample volume, stirring rate, ionic strength, exposure time, etc. on the performance of the microextraction process was thoroughly investigated. Under optimized conditions, analytes were concentrated onto a 2-cm long membrane exposed to the headspace (HS) of the sample vial containing 80mL of water with a 30% of sodium chloride. Equilibrium was achieved after a sampling period of 1h, at room temperature and vigorous magnetic stirring. After analytes desorption, with just 250 microL of n-hexane, they were determined by gas chromatography with micro-electron capture detection (GC-mu-ECD). The developed methodology was characterized and validated also by gas chromatography-mass spectrometry (GC-MS). The proposed approach presented good precision (RSDs of 6-15% and 2-8% under reproducibility and repeatability conditions, respectively) and linear responses (R(2): 0.990-0.999) over more than two order of magnitude concentration ranges for di- to penta-substituted species either with GC-MS or GC-mu-ECD detection. The absolute extraction efficiency was directly related with the lipophilic nature of the studied species and their volatile character, ranging between 27% and 47% for di- to pentahalotoluenes. Despite being an adsorption based methodology, no matrix effects were observed for complex environmental water matrices such as river water or treated wastewater. The proposed approach provided a very simple and low-cost microextraction alternative rendering adequate limits of quantification, in the low/sub ngL(-1) level, for environmental sample analysis of poly-halogenated toluenes.


Strategies for cytokine utilisation in tumor therapy.
The state of the art with regard to the employment of various cytokine-based tumor immunotherapy strategies and their mechanisms of action are critically reviewed. As matters now stand, adoptive transfer of LAK cells or tumor infiltrating lymphocytes together with high doses of IL-2 constitutes the only immunologic way to hinder tumor growth in advanced stages of cancer. On the other hand, many experimental data show that the local presence of cytokines, either injected repeatedly at tumor site or released by cytokine-gene engineered tumor cells, arouses immunogenicity in apparently nonimmunogenic spontaneous tumors. By strengthening the notion that most tumors are potentially immunogenic, these findings offer substantial evidence to stress the potential use of cytokines as a component of new tumor vaccines.


Midwives' occupational wellbeing and its determinants. A cross-sectional study among newly qualified and experienced Dutch midwives.
Internationally, about 40 percent of midwives report symptoms of burnout, with young and inexperienced midwives being most vulnerable. There is a lack of recent research on burnout among Dutch midwives. The aim of this study was to examine the occupational wellbeing and its determinants of newly qualified and inexperienced midwives in the Netherlands. The majority of practicing Dutch midwives are aged under 40, which could lead to premature turnover. A cross-sectional study was conducted using an online questionnaire that consisted of validated scales measuring job demands, job and personal resources, burnout symptoms and work engagement. The Job Demands-Resources model was used as a theoretical model. We recruited Dutch midwives who were actually working in midwifery practice. A total of N=896 midwives participated in this study, representing 28 percent of practicing Dutch midwives. Data were analysed using regression analysis. Seven percent of Dutch midwives reported burnout symptoms and 19 percent scored high on exhaustion. Determinants of burnout were all measured job demands, except for experience level. Almost 40 percent of midwives showed high work engagement; newly qualified midwives had the highest odds of high work engagement. Master's or PhD-level qualifications and employment status were associated with high work engagement. All measured resources were associated with high work engagement. A relatively small percentage of Dutch midwives reported burnout symptoms, the work engagement of Dutch midwives was very high. However, a relatively large number reported symptoms of exhaustion, which is concerning because of the risk of increasing cynicism levels leading to burnout. In contrast to previous international research findings, being young and having less working experience was not related to burnout symptoms of Dutch newly qualified midwives. The recognition of job and personal resources for midwives' occupational wellbeing must be considered for a sustainable midwifery workforce. Midwifery Academies need to develop personal resources of their students that will help them in future practice.


Polymorphism of monocyte chemoattractant protein 1 in Crohn's disease.
The chemokine MCP-1 is thought to be important for the recruitment of mononuclear cells and the maintenance of inflammation in inflammatory bowel disease. We investigated whether MCP-1 protein expression is correlated with the degree of mucosal inflammation in patients with Crohn's disease. Furthermore, we studied whether a functional single nucleotide polymorphism (G or A) located in the distal regulatory region of the MCP-1 gene is associated with Crohn's disease and/or its phenotype. MCP-1 concentration in tissue homogenates was analyzed in mucosal biopsy specimens of 31 patients with Crohn's disease and 48 controls by enzyme-linked immunosorbent assay, and the correlation with an endoscopic macroscopic score was analyzed. In 179 patients with Crohn's disease and 189 controls MCP-1 genotyping was carried out by polymerase chain reaction restriction fragment length polymorphism technique. Subgroup phenotypic analysis was performed according to the Vienna classification. MCP-1 tissue concentrations were significantly associated with the macroscopic degree of inflammation. The gene frequency of the different MCP-1 alleles did not differ from healthy controls. However, the G/A and G/G genotype was significantly decreased in patients with a later onset of the disease and both genotypes presented also less frequently with a fistulizing disease behavior. The degree of intestinal inflammation in Crohn's disease is associated with MCP-1 tissue levels. Furthermore there is evidence for an association of different disease behavior with different MCP-1 genotypes.


MRI-biochemical follow up measurements of lumbar intervertebral disc in patients with leg length discrepancy: Is it possible to alter cartilage damage with conservative therapy?
Effect of conservative therapy on intervertebral discs (IVD) in patients with leg-length-discrepancy (LLD). Seventy lumbar IVDs of 14 participants (five with LLD 10-20 mm) were examined using a 3T-MRI-scanner. Morphological (Pfirrmann) and molecular (glycosaminoglycan-chemical-exchange-saturation-transfer, gagCEST) grading was assessed before and after a four-month therapy (physiotherapy and shoe inlays). Significantly lower GAG values in patients with LLD were found (L5/S1, p = 0.02). After therapy, a trend towards higher gagCEST values in patients with LLD was observed (2.48 ± 1.77% vs. 1.79 ± 0.79%; p > 0.05). LLD represents a risk factor for molecular alterations of lumbar IVDs. Only minor effects of conservative therapy on these alterations could be found.


EPC-DARTS: Efficient partial channel connection for differentiable architecture search.
With weight-sharing and continuous relaxation strategies, the differentiable architecture search (DARTS) proposes a fast and effective solution to perform neural network architecture search in various deep learning tasks. However, unresolved issues, such as the inefficient memory utilization, and the poor stability of the search architecture due to channels randomly selected, which has even caused performance collapses, are still perplexing researchers and practitioners. In this paper, a novel efficient channel attention mechanism based on partial channel connection for differentiable neural architecture search, termed EPC-DARTS, is proposed to address these two issues. Specifically, we design an efficient channel attention module, which is applied to capture cross-channel interactions and assign weight based on channel importance, to dramatically improve search efficiency and reduce memory occupation. Moreover, only partial channels with higher weights in the mixed calculation of operation are used through the efficient channel attention mechanism, and thus unstable network architectures obtained by the random selection operation can also be avoided in the proposed EPC-DARTS. Experimental results show that the proposed EPC-DARTS achieves remarkably competitive performance (CIFAR-10/CIFAR-100: a test accuracy rate of 97.60%/84.02%), compared to other state-of-the-art NAS methods using only 0.2 GPU-Days.


Accuracy of estrogen receptor, progesterone receptor, and HER2 status between core needle and open excision biopsy in breast cancer: a meta-analysis.
Accurate determination of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2) status was very important in selecting breast cancer treatment. Discordance of ER, PR, and HER2 status between core needle biopsy (CNB) and open excision biopsy (OEB) varied among reported studies. We performed a meta-analysis to compare the accuracy of CNB with that of OEB for ER, PgR, and HER2 status detection in breast cancer. Medical subject heading (MeSH) terms (Breast Neoplasm) and key words (biopsy OR mammotome) AND (incision OR excision OR surgery) AND (estrogen OR progesterone OR HER2 OR hormone). Patients with HER2 immunohistochemical 3+ or fluorescence in situ hybridization positive were classified into HER2[b] group. A total of 27 studies were eligible in this study. Aggregate positive ER and PgR rate was 80.0 and 69.5% for CNB; and 77.7 and 66.2% for OEB, respectively. The HER2 positive rate difference between CNB and OEB was only 0.2%. The pooled sensitivity of evaluating ER, PgR, and HER2 status in CNB compared with OEB was 0.970, 0.911, and 0.799 (0.813 for HER2[b]), respectively. All of AUC values for these status determination were larger than 0.9. Heterogeneity between studies was introduced by various factors in PgR and HER2[b] analysis. Subgroup analysis showed that the specificity and OR of CNB in studies with ER positive rate >78% was lower than studies with ER positive rate ≤78% (P < 0.05). This meta-analysis indicated that CNB had high diagnostic accuracy in evaluating ER, PgR, and HER2 status compared with OBE in breast cancer patients. In terms of 2-3% positive rate difference, ER and PgR status should be detected both on CNB and OEB samples, especially to retest their expression on CNB in patients with hormonal receptor negative tumors in OEB.


Overexpression of the Wilms' tumor gene WT1 in colorectal adenocarcinoma.
Expression of the Wilms' tumor gene WT1 was examined in 59 cases of colorectal adenocarcinoma to examine the involvement of WT1 in tumorigenesis. Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) showed that WT1 mRNA was expressed in the range from 7.2 x 10(-5) to 4.9 x 10(-1) levels (WT1 expression level in K562 leukemic cells was defined as 1.0) in all (100%) of the 28 cases of colorectal adenocarcinoma examined, and that the WT1 mRNA expression levels were higher in 20 (71%) of the 28 cases compared to those of normal-appearing mucosal tissues examined. Immunohistochemical analysis using an anti-WT1 antibody was performed on 46 cases of colorectal adenocarcinoma (15 of the 28 cases with WT1 mRNA expression and 31 newly collected cases), and the expression of WT1 protein was detected in 41 (89%) of the 46 cases. The direct sequencing analysis of the WT1 genomic DNA showed no mutations in any of the 10 exons of the WT1 gene in any of 5 different colorectal adenocarcinomas. These results may indicate an important role of the wild-type WT1 gene in tumorigenesis of colorectal adenocarcinoma.


Gas chromatography vacuum ultraviolet spectroscopy: A review.
Accelerated technological progress and increased complexity of interrogated matrices imposes a demand for fast, powerful, and resolutive analysis techniques. Gas chromatography has been for a long time a 'go-to' technique for the analysis of mixtures of volatile and semi-volatile compounds. Coupling of the several dimensions of gas chromatography separation has allowed to access a realm of improved separations in the terms of increased separation power and detection sensitivity. Especially comprehensive separations offer an insight into detailed sample composition for complex samples. Combining these advanced separation techniques with an informative detection system such as vacuum ultraviolet spectroscopy is therefore of great interest. Almost all molecules absorb the vacuum ultraviolet radiation and have distinct spectral features with compound classes exhibiting spectral signature similarities. Spectral information can be 'filtered' to extract the response in the most informative spectral ranges. Developed algorithms allow spectral mixture estimation of coeluting species. Vacuum ultraviolet detector follows Beer-Lambert law, with the possibility of calibrationless quantitation. The purpose of this article is to provide an overview of the features and specificities of gas chromatography-vacuum ultraviolet spectroscopy coupling which has gained interest since the recent introduction of a commercial vacuum ultraviolet detector. Potentials and limitations, relevant theoretical considerations, recent advances and applications are explored.


The periaqueductal gray projections to the rat spinal trigeminal, raphe magnus, gigantocellular pars alpha and paragigantocellular nuclei arise from separate neurons.
Possible collateral branches of periaqueductal gray axons which distribute to the nucleus raphe magnus, nucleus reticularis paragigantocellularis, nucleus reticularis gigantocellularis pars alpha and the spinal trigeminal nucleus were analyzed with the double fluorescent retrograde tracer technique. With the exception of a small number of double-labeled neurons observed in the periaqueductal gray following injections of fluorescent dyes into the nuclei reticularis paragigantocellularis and gigantocellularis pars alpha, no double-labeled cells were found in this midbrain region following injections of tracers into various combinations of the above 4 nuclear groups. The results of this investigation indicate that these 4 brainstem nuclei are innervated predominantly by separate neuronal populations within the periaqueductal gray.


Effects of multiple firings on metal-ceramic bond strength of Co-Cr alloy fabricated by selective laser melting.
Selective laser melting (SLM) is a new technique for fabricating dental restorations, but the metal-ceramic bond strength of the restorations after multiple firings must be considered because adequate bond strength is a clinical requirement for long-term performance. The purpose of this study was to investigate the effects of repeated firing on the metal-ceramic bond strength of an SLM Co-Cr alloy. Thirty-six SLM-fabricated (Group SLM) and conventional lost wax cast (Group Cast) Co-Cr metal bars were prepared. Eighteen bars from each group were molded into dimensions of 25×3×0.5 mm, following International Organization for Standardization (ISO) standard 9693:2012. In the center of each bar, a 1.1-mm thickness of porcelain was fused onto an 8×3-mm rectangular area. In each group, specimens were divided into 3 subgroups based on the number of firing cycles (3, 5, 7) for the veneering process. Metal-ceramic bond strength, fracture mode analysis, and area fraction of adherence porcelain (AFAP) of each subgroup was evaluated with a 3-point bend test and by measuring the Si content of specimens with scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDS). The results were statistically analyzed first with the Shapiro-Wilk test, where a P value of .364 was considered normally distributed, and then with the Student t test to determine significant differences (α=.05). Student t test results showed no statistical differences between the metal-ceramic bond strength of SLM and that of conventionally cast groups after firing 3, 5, and 7 times (P>.05). However, after SEM/EDS analyses, the SLM group showed significantly more porcelain adherence than that of the control group (P<.05) after 5 or 7 firings. The SLM group showed superior metal-ceramic bond strength that exceeded ISO 9691:1999 (E) requirements at all firing periods. Also, the bond showed better behavior in terms of AFAP than the conventional cast group, especially after 5 or 7 firings.


[Options and limits of leg length correction in paediatric orthopaedics].
For paediatric orthopaedic surgeons treating leg length discrepancy, knowledge of the available procedures and their options and limits is just as important as mastery of the very different surgical methods and implants, as well as the possible complications, in order to be able to advise and treat the children and adolescents and their parents comprehensively and in the best interests. Both the growth inhibiting procedures and the complex bone lengthening procedures require a great deal of experience to successfully guide patients and families through what is often a lengthy and sometimes complicated treatment process. Careful preoperative indications and planning, precise surgical techniques with suitable instruments and implants, and attentive postoperative check-ups are mandatory prerequisites for the desired therapeutic success.


Expression pattern and functional role of Phc2 during activation of helper T cells after antigenic stimulation.
Polycomb group (PcG) proteins, which are conserved from invertebrates to mammals, are associated with epigenetic regulation of many cell fates. The activities of PcG proteins are largely associated with modulation of specific immune reactions. However, no study has attempted to explore the role of Phc2, a subunit of polycomb repressive complex 1, on helper T (Th) cell activation. Presently, Phc2 expression was down-regulated in activated Th cells. The ectopic expression of Phc2 in Th cells inhibited Th cell proliferation and secretion of interleukin-2 from Th cells upon antigen-specific activation. Phc2 may act as a negative regulator that inhibits the activity of Th cells.


Atopic Dermatitis in Israeli Adolescents from 1998 to 2013: Trends in Time and Association with Migraine.
Recent data have shown an increasing occurrence of atopic dermatitis (AD) in children and adolescents, as well as in adults. Most of the epidemiologic research on AD is limited to pediatric and youth populations and is based on self-reported questionnaires. A nationwide, population-based, cross-sectional retrospective study of adolescents with AD was performed to estimate its prevalence, trends, and association with demographic factors and comorbidities. The study included all Israeli teens going through medical evaluation as part of the assessment before being conscripted into the military from 1998 to 2013. A total of 1,187,757 adolescents were included in the study population, with an overall prevalence of AD of 0.64% in boys and 0.9% in girls. Over the study period, the prevalence of AD steadily increased, especially in the mild disease group. A greater risk of AD was found in subjects with high predicted socioeconomic status (male: odds ratio [OR] 1.14 [95% confidence interval {CI} 1.11, 1.16]; female: OR 1.08, [95% CI 1.05, 1.10]) and Israeli-born subjects (male: OR 1.34 [95% CI 1.21, 1.48]; female: OR 1.12 [95% CI 1.01, 1.23]). Allergic conditions such as asthma, conjunctivitis, and contact dermatitis were more prevalent in subjects with AD. There was a significantly higher prevalence of migraine in patients with AD (male: OR 1.35 [95% CI 1.18, 1.54]; female: OR 1.51 [95% CI 1.30, 1.74]). This large cross-sectional study demonstrates the increasing prevalence of AD in adolescents and its relation to other allergic diseases and migraine. It is hoped that greater awareness of the distinctive epidemiologic characteristics of this population will lead to better recognition and management of the disease and its comorbidities.


Human pregnancy serum inhibits proliferation of T8-depleted cells and their interleukin-2 synthesis in mixed lymphocyte cultures.
T8-depleted and unfractionated T lymphocytes allogeneically stimulated and cultured in the presence of pregnancy sera exhibit an inhibition of cellular proliferation and interleukin-2 synthesis, respectively. Unfractionated T cells show a decrease in their cytotoxicity in the presence of these sera. The inhibition of cytotoxicity could be due to the deficit of IL-2 observed since if exogenous IL-2 is added to the cultures T4/LEU3a-depleted allogeneically stimulated cells reach the same degree of cytotoxicity whether cultured in normal human serum or pregnancy serum. A possible mechanism to explain the inhibition of mixed lymphocyte cultures by pregnancy serum could therefore be decrease of cellular proliferation of the T8-depleted subpopulation with a decrease in IL-2 synthesis, implying an inhibition of cytotoxic effector cells.


What is a useful marker for predicting survival in patients with high-grade soft tissue sarcoma who have non-inflammatory conditions?
The modified Glasgow prognostic score (mGPS) is a reliable system for identifying patients at high risk of death among patients with soft tissue sarcoma (STS). The scoring systems use a combination of C-reactive protein (CRP) and albumin levels. Although patients with high-grade STS are at risk of metastasis and death, even if their mGPS is 0, the prognostic indicators in these patients are unknown. Therefore, we investigated useful prognostic indicators for survival and the development of metastasis in patients with high-grade STS and an mGPS of 0. One hundred and four patients with CRP and albumin levels of <1.0 mg/dl and >3.5 g/dl, respectively, indicating an mGPS of 0, were included. The mean follow-up period was 79 months. The 5-year disease-specific survival (DSS) rate was 79.2%. Cox proportional analysis showed that tumor size and absolute neutrophil count (ANC) were prognostic variables in multivariate analyses. Patients with higher ANC (ANC>3370/μl) had a worse DSS than those with lower ANC. The 5-year DSS was 74.7% vs. 91.7%, respectively (p = 0.0207). The 5-year metastasis-free survival was 67.2%. Tumor size and ANC remained significant variables for predicting the development of metastasis in the multivariate analysis. Patients with higher ANC had a worse metastasis-free survival than those with lower ANC. The 5-year metastasis-free survival was 59.5% vs. 87.3%, respectively (p = 0.00269). When patients with high-grade STS have an mGPS of 0, the ANC and tumor size should be carefully evaluated. A higher neutrophil count and larger tumor size may increase the risk of metastasis development.


Comparative pathogenicity of Fusarium graminearum isolates from China revealed by wheat coleoptile and floret inoculations.
Fusarium head blight (FHB) or scab caused by Fusarium species is an economically important disease on small grain cereal crops worldwide. Accurate assessments of the pathogenicity of fungal isolates is a key obstacle toward a better understanding of the Fusarium-wheat scab system. In this study, a new laboratory method for inoculation of wheat coleoptiles was developed, which consists of cutting off the coleoptile apex, covering the cut apex with a piece of filter paper soaked in conidial suspension, and measuring the lengths of brown lesions 7 days post inoculation. After coleoptile inoculation, distinct brown lesions in the diseased stems were observed, in which the presence of the fungus was verified by PCR amplification with F. graminearum Schwable-specific primers. Coleoptile inoculation of six wheat varieties indicated that a highly susceptible wheat variety was more suitable as a differentiating host for the pathogenicity assay. Analysis of the coleoptiles inoculated with a set of 58 different isolates of F. graminearum showed a significant difference in the lengths of the lesions, forming the basis by which pathogenicity of the isolates was assessed. Field inoculation of florets of three wheat varieties over 2 years revealed significant differences in pathogenicity among the 58 isolates, and that the highly resistant and highly susceptible wheat varieties were more appropriate and stable for pathogenicity assessment in field trials. Comparative analyses of eight inoculation experiments of wheat with 58 F. graminearum isolates showed significant direct linear correlations (P<0.001) between coleoptile and floret inoculations. These results indicate that the wheat coleoptile inoculation is a simple, rapid and reliable method for pathogenicity studies of F. graminearum in wheat.


Effect of huperzine A, a novel acetylcholinesterase inhibitor, on radial maze performance in rats.
Rats were trained to run in a spatial, radial arm maze using a procedure to determine two memory functions, working and reference memory. The muscarinic antagonist, not the nicotinic antagonist, impaired both working and reference memory of rats. Scopolamine (0.125, 0.15, and 0.2 mg/kg, IP, 30 min before a session) significantly impaired choice accuracy in the eight-arm maze. In contrast, mecamylamine (5, 10, and 15 mg/kg) did not affect the performance. Huperzine A (0.1, 0.2, and 0.3 mg/kg, IP, 30 min before testing) and physostigmine (0.3 mg/kg, IP, 20 min before testing) could reverse scopolamine-induced deficits in the task. Chronic treatment with huperzine A (0.25 mg/kg, PO, once a day) for 8 consecutive days was as potent as acute treatment on attenuating the scopolamine-induced amnesia.


Effectiveness of legislative changes obligating notification of prolonged sickness absence and assessment of remaining work ability on return to work and work participation: a natural experiment in Finland.
Policies have been introduced to reduce sickness absence, but their effectiveness is largely unknown. In a natural experiment, we examined effects of legislative changes on return to work and work participation. The source population consisted of up to 72,164 Finnish public sector employees with a permanent job contract in 2008-2011 (before) and in 2013-2014 (after). We used employees with a continuous sickness absence of at least 30 calendar-days (n=5708-6393), 60 compensated days (n=1481-1655) and 90 compensated days (n=766-932). We examined sustainable return to work (a minimum of 28 consecutive working days) with survival analysis as well as monthly work participation after a sickness absence, and annual gain in work participation after the intervention, using trajectory analyses. Sustainable return to work after 60 days of sickness absence occurred earlier after the legislative changes (p value 0.017), although the effect reduced towards the end of the follow-up. There were no differences in return to work after a 30 or 90 days of sickness absence. The largest annual gain, postintervention versus preintervention, in monthly work participation was observed among employees with 60 days of sickness absence and was 230.9 person-years/10,000 employees. The corresponding annual gains among those with 30 days and 90 days of sickness absence were 51.8 and 39.6, respectively. Our findings suggest that the legislative changes, obligating early notification of prolonged sickness absences as well as assessment of remaining work ability and possibilities to continue working, may enhance sustainable return to work in the short term. Other measures will be needed to enhance work participation, especially in the long term.


Odontogenic tumours in Istanbul: 527 cases.
We retrieved and analysed the records of 527 odontogenic tumours from a total of 62,565 cases in the department of tumour pathology in the Institute of Oncology, University of Istanbul, from 1971 to 2003. Of these 527 tumours, 521 were benign and 6 were malignant. The most common lesions were ameloblastomas (n=133) followed by odontomas (n=109), odontogenic myxomas (n=83) and others. There were more female patients (n=278, 53%) than male, and nearly half the patients (n=253, 48%) were between the ages of 10 and 29 years. The posterior mandible was the commonest site (n=184, 35%), followed by the premolar area of the mandible (n=98, 19%), and the anterior maxilla (n=84, 16%).


1-(Benz-yloxy)naphthalene.
In the title compound, C(17)H(14)O, the dihedral angle between the naphthyl ring system and the benzyl group is 83.22 (4)°. Both of these moieties are planar, with mean deviations from their least-squares planes, defined by the naphthyl ring C atoms and the O atom, and the phenyl ring C atoms and the benzyl α-C atom, of 0.0176 (1) and 0.0024 (13) Å, respectively. The crystal structure is stabilized by C-H⋯π and π-π inter-actions [centroid-centroid distance = 3.7817 (10) Å].