Prospective analysis of endoscopic vein harvesting.
Utilization of bridging vein harvesting (BVH) of saphenous vein grafts (SVG) for coronary artery bypass grafting (CABG) results in large wounds with great potential for pain and infection. Endoscopic vein harvesting (EVH) may significantly reduce the morbidity associated with SVG harvesting. A prospective database of 200 matched patients receiving EVH and BVH was compared. The patients all underwent CABG done over a period of 4 months (April to August 2000). Patients were excluded if they had prior vein harvesting. The EVH and BVH group included 100 patients each with similar demographics. The patients in the EVH group had significantly fewer wound complications, mean days to ambulation, and total length of stay (P <0.05). There was no difference in harvest time or vein injuries. Endoscopic vein harvesting results in significantly fewer wound complications, decrease in days to ambulation, and the total length of stay. EVH is superior to BVH in patients undergoing CABG.


Grazing effects of sea urchin Diadema savignyi on algal abundance and coral recruitment processes.
Herbivores control algae and promote coral dominance along coral reefs. However, the majority of previous studies have focused on herbivorous fish. Here we investigated grazing effects of the sea urchin Diadema savignyi on algal abundance and coral recruitment processes. We conducted an in situ cage experiment with three density conditions of D. savignyi (0, 8, 16 indiv. m-2) for three months during the main coral recruitment season in Taiwan. Results demonstrated a strong algal control by D. savignyi. At the end of the experiment, average algal cover was 95% for 0 indiv. m-2, compared to 47% for 8 indiv. m-2 and 16% for 16 indiv. m-2. Average algal biomass at 8 indiv. m-2 declined by one third compared to 0 indiv. m-2 and almost zero at 16 indiv. m-2. On the other hand, a negative grazing effect of D. savignyi was observed on coral recruitment processes. Notably, at 16 indiv. m-2, the density of coral recruits declined and mortality of small coral fragments (proxy of coral juveniles) increased. Our results confirm findings of previous studies and indicate the need to balance both positive (strong algal control) and negative (physical damage) influences of Diadema grazing to facilitate the coral recruitment process.


Vasopressin and epinephrine in the treatment of cardiac arrest: an experimental study.
Epinephrine remains the drug of choice for cardiopulmonary resuscitation. The aim of the present study is to assess whether the combination of vasopressin and epinephrine, given their different mechanisms of action, provides better results than epinephrine alone in cardiopulmonary resuscitation. Ventricular fibrillation was induced in 22 Landrace/Large-White piglets, which were left untreated for 8 minutes before attempted resuscitation with precordial compression, mechanical ventilation and electrical defibrillation. Animals were randomized into 2 groups during cardiopulmonary resuscitation: 11 animals who received saline as placebo (20 ml dilution, bolus) + epinephrine (0.02 mg/kg) (Epi group); and 11 animals who received vasopressin (0.4 IU/kg/20 ml dilution, bolus) + epinephrine (0.02 mg/kg) (Vaso-Epi group). Electrical defibrillation was attempted after 10 minutes of ventricular fibrillation. Ten of 11 animals in the Vaso-Epi group restored spontaneous circulation in comparison to only 4 of 11 in the Epi group (p = 0.02). Aortic diastolic pressure, as well as, coronary perfusion pressure were significantly increased (p < 0.05) during cardiopulmonary resuscitation in the Vaso-Epi group. The administration of vasopressin in combination with epinephrine during cardiopulmonary resuscitation results in a drastic improvement in the hemodynamic parameters necessary for the return of spontaneous circulation.


Quasi-Static Tests of Hybrid Adhesive Bonds Based on Biological Reinforcement in the Form of Eggshell Microparticles.
The paper is focused on the research of the cyclic loading of hybrid adhesive bonds based on eggshell microparticles in polymer composite. The aim of the research was to characterize the behavior of hybrid adhesive bonds with composite adhesive layer in quasi-static tests. An epoxy resin was used as the matrix and microparticles of eggshells were used as the filler. The adhesive bonds were exposed to cyclic loading and their service life and mechanical properties were evaluated. Testing was performed by 1000 cycles at 5-30% (165-989 N) and 5-70% (165-2307 N) of the maximum load of the filler-free bond in the static test. The results of the research show the importance of cyclic loading on the service life and mechanical properties of adhesive bonds. Quasi-static tests demonstrated significant differences between measured intervals of cyclic loading. All adhesive bonds resisted 1000 cycles of the quasi-static test with an interval loading 5-30%. The number of completed quasi-static tests with the interval loading 5-70% was significantly lower. The filler positively influenced the service life of adhesive bonds at a higher amount of quasi-static tests, i.e., the safety of adhesive bonds increased. The filler had a positive effect on adhesive bonds ABF2, where the strength significantly increased up to 20.26% at the loading of 5-30% against adhesive bonds ABF0. A viscoelasticity characteristic (creep) of the adhesive layer occurred at higher values of loading, i.e., between loading 5-70%. The viscoelasticity behavior did not occur at lower values of loading, i.e., between loading 5-30%.


The fluorescence decay kinetics of in vivo chlorophyll measured using low intensity excitation.
We report fluorescence lifetimes for in vivo chlorophyll a using a time-correlated single-photon counting technique with tunable dye laser excitation. The fluorescence decay of dark-adapted chlorella is almost exponential with a lifetime of 490 ps, which is independent of excitation from 570 nm to 640 nm. Chloroplasts show a two-component decay of 410 ps and approximately 1.4 ns, the proportion of long component depending upon the fluorescence state of the chloroplasts. The fluorescence lifetime of Photosystem I was determined to be 110 ps from measurements on fragments enriched in Photosystem I prepared from chloroplasts with digitonin.


Postoperative changes on functional mapping of the motor cortex in patients with brachial plexus injury: comparative study of magnetoencephalography and functional magnetic resonance imaging.
Using magnetoencephalography (MEG) and functional magnetic resonance imaging (f-MRI), we investigated the areas of the cerebral cortex that were activated when patients with brachial plexus injuries performed elbow flexion, a motion re-acquired through nerve transfer surgery. In all patients, elbow flexion on the operated side and on the unaffected side led to the activation of an area in the motor cortex, with these areas being located almost symmetrically on either side of the sagittal midline. These findings suggest that the activity center for the transferred intercostal nerves shifted to the motor cortex for the elbow, from the original intercostal nerve site.


Prenatal developmental toxicity evaluation of Verbena officinalis during gestation period in female Sprague-Dawley rats.
Verbena officinalis is widely used by women for maintaining general health and treating various gynaecological disorders during pregnancy. A case report has indicated that the consumption of V. officinalis induced an abortifacient effect. Hence, this study aimed to investigate the prenatal developmental toxicity of this plant according to OECD guideline (no. 414). A total of 50 pregnant female rats (dams) were distributed into five groups (n = 10); 500 mg/kg 1000 mg/2000 mg/kg and 3000 mg/kg of V. offcinalis extracts and the fifth group served as a normal control. All dams received their respective oral single daily treatment from the 6th to the 20th day of gestation. Maternal clinical toxicity signs, body weight and weight gain were recorded. Caesarean sections were performed on day 21 to evaluate embryo-foetal developmental toxicity. For dams, ovaries were harvested and weighed. The number of corpora lutea, implantation sites, and resorptions were recorded. No mortality was observed in dams, but their body weight gain was significantly reduced particularly in dams treated with 2000 and 3000 mg/kg V. officinalis. Asymmetrical distribution of implantation sites and embryos were observed. Embryo-fetotoxicity retardation was observed as evident by the decrease in foetal weight, head cranium, tail length, and higher incidence in the pre-and post-implantation loss. Some foetal skeleton abnormalities such as incomplete ossification of skull, sternebrae, and metatarsal bones were observed in foetuses of the 2000 and 3000 mg/kg V. officinalis-treated dams. LC/MS analysis identified the major constituents including geniposidic acid, tuberonic acid glucoside, luteolin 7, 3'-digalacturonide, iridotrial and apigenin. The glycosylated flavonoids such as apigenin and luteolin could be responsible for the reported prenatal developmental toxicity. In conclusion, the use of V. officinalis during pregnancy is not safe indicating evidence-based toxic effects on the reproductive performance of dams and dose-dependent risk potentials to the foetuses.


Autologous Platelet Lysate Is an Alternative to Fetal Bovine Serum for Canine Adipose-Derived Mesenchymal Stem Cell Culture and Differentiation.
The use of fetal bovine serum (FBS) in regenerative medicine raises serious ethical and scientific concerns. We have cultured and differentiated the canine mesenchymal stem cells (cMSCs) in five different media combinations of autologous platelet lysate (A-PL) and FBS; consisting of 0% A-PL and 10% FBS (M-1), 2.5% A-PL and 7.5% FBS (M-2), 5% A-PL and 5% FBS (M-3), 7.5% A-PL and 2.5% FBS (M-4), and 10% A-PL and 0% FBS (M-5). The cMSCs were evaluated for their doubling time, differentiation efficiency, and expression of CD73, CD90, CD105, and PDGFRα. The mRNA expression of NT5E, THY1, ENG, PPARγ, FABP4, FAS, SP7, BGLAP, and SPP1 was also assessed. The results indicated non-significant differences in cellular proliferation/viability; positive expression of surface markers, and PDGFRα with substantial adipo/osteogenic differentiation. The expression of adipogenic (PPARγ, FABP4, FAS), and osteogenic (SP7, BGLAP, SPP1) genes were higher (p < 0.05) in the M5 group. In conclusion, A-PL in cMSCs culture did not negatively affect cellular proliferation and viability but also enhanced their genetic potential for multilineage differentiation. Our results indicate that A-PL can be used as an alternative for FBS to develop potent cMSCs under good manufacturing practice protocol for regenerative medicine.


Down regulation of Fc and complement receptors on B cells in rheumatoid arthritis.
B cell tolerance is regulated by receptors that modulate B cell receptor signaling, such as Fc gamma receptor IIb (FcγRIIb; CD32b) and complement receptors (CR) 1 and 2. Deficiency in these receptors may contribute to autoimmunity. To address this we have investigated the receptor expression in healthy individuals in comparison with rheumatoid arthritis (RA) patients. In healthy subjects we found that women had overall lower FcγRIIb expression on B cells than men that significantly decreased with age. RA patients had fewer FcγRIIb, CR1 and CR2 positive B cells and decreased receptor expressions compared to healthy subjects. Further, the RA B cells displayed a significantly increased proliferative response when cultured with interleukin-2 in vitro. In summary, the dysregulated B cells in RA are associated with lower FcγRIIb, CR1 and CR2 levels. The reduced FcγRIIb expression on B cells in women may influence the increased frequency of autoimmunity in women.


Estimating photosynthetic electron transport via chlorophyll fluorometry without Photosystem II light saturation.
Estimates of thylakoid electron transport rates (J(e)) from chlorophyll fluorometry are often used in combination with leaf gas exchange measurements to provide detailed information about photosynthetic activity of leaves in situ. Estimating J(e) requires accurate determination of the quantum efficiency of Photosystem II (Phi(P)), which in turn requires momentary light saturation of the Photosystem II light harvesting complex to induce the maximum fluorescence signal (F(M)'). In practice, full saturation is often difficult to achieve, especially when incident photosynthetic photon flux density (Q) is high and energy is effectively dissipated by non-photochemical quenching. In the present work, a method for estimating the true F(M)' under high Q was developed, using multiple light pulses of varying intensity (Q'). The form of the expected relationship between the apparent F(M)' and Q' was derived from theoretical considerations. This allowed the true F(M)' at infinite Q' to be estimated from linear regression. Using a commercially available leaf gas exchange/ chlorophyll fluorescence measurement system, J(e) was compared to gross photosynthetic CO(2) assimilation (A(G)) under conditions where the relationship between J(e) and A(G) was expected to be linear. Both in C(4) leaves (Zea mays) in ambient air and also in C(3) leaves (Gossypium hirsutum) under non-photorespiratory conditions the apparent ratio between J(e) and A(G) declined at high Q when Phi(P) was calculated from F(M)' measured simply using the highest available saturating pulse intensity. When F(M)' was determined using the multiple pulse / linear regression technique, the expected relationship between J(e) and A(G) at high Q was restored, indicating that the Phi(P) estimate was improved. This method of determining F(M)' should prove useful for verifying when saturating pulse intensities are sufficient, and for accurately determining Phi(P) when they are not.


The Development of Cortical Microinfarcts Is Associated with Intracranial Atherosclerosis: Data from the Chinese Intracranial Atherosclerosis Study.
Little is known about the association between the cortical microinfarcts (CMIs) and intracranial atherosclerosis (ICAS) in Chinese patients with ischemic stroke. This study was designed to analyze the association and evaluate the role of CMIs in clinical outcomes. We evaluated 1421 consecutive patients who had experienced an acute cerebral ischemia within 7 days after symptom onset and evaluated the presence of CMIs and ICAS based on patients' 3.0-T magnetic resonance imaging and magnetic resonance angiography scans. Baseline characteristics, patient risk factors, and clinical outcomes were analyzed to investigate the different outcomes between the CMIs (n = 209) group and non-CMIs (n = 1212) group. CMIs were present in 14.7% persons. The following parameters were associated with risk of CMIs: advanced age, National Institutes of Health Stroke Scale score on admission, lower level of systemic blood pressure, lower triglycerides level, ICAS, and cerebral microbleeds (CMBs). On multivariate logistic regression analysis, ICAS remained an independent risk factor for the development of CMIs (adjusted odds ratio, 1.493; 95% confidence interval, 1.022-2.182; P = .038). At the time point of 1 year after stroke, the rates of poor outcome (modified Rankin Scale, 3-6) in CMIs group (33.5%) were statistically significantly different from the non-CMIs group (22.6%; P = .001). In addition, patients in CMIs group had a significantly higher stroke recurrence rate than patients in the non-CMIs group (6.7% versus 4%; P = .085). The development of CMIs is strongly associated with ICAS. CMIs are independent predictors of poor prognosis in patients with ischemic stroke.


TIOMAX: A Spanish Multicenter Registry of the real-world use of the TItanium OptiMAX® biostent: TIOMAX: Registro Español Multicéntrico Del Biostent De Titanio OptiMAX® En La Vida Real.
To compare the safety and efficacy of the new cobalt-chromium bioactive stent Titan Optimax® (Hexacath, France) with its predecessor, Titan-2® . The TIOMAX registry includes 784 patients who underwent percutaneous coronary intervention with these stents in 21 Spanish hospitals. Analysis of all patients in the registry without exclusion criteria, candidates for revascularization (March-2013/July-2014). Initially 273 patients received Titan-2® , and the next 511 received the Optimax® after its launch. Mean age was 65.8 ± 13.0 (78.1% men); 49.2% were STEACS patients (n = 322), 29.8% NSTEACS, and 27.3% had stable angina or silent ischemia. Most STEACS patients (76.4% of n = 322) were treated <24 hr after developing symptoms. All-cause death (D), cardiac death (CD), acute myocardial infarction (AMI), and stent thrombosis (ST) at 1 month were 1.1, 0.8, 0.1, and 0.5%, respectively, with no significant differences between groups. At 1 year, the death rate was 5.5% for Titan-2 vs. 4.1% for Optimax® , CD was 1.8% for both groups, ST 1.1 vs. 0.6%, new AMI 3.3 vs. 2.5% and target lesion revascularization (TLR) 3.7 vs. 2.9%. The primary endpoint of the composite event (CE) of D/AMI/TLR/ST occurred in 10.3% vs. 7.6% (p = 0.211). Patients with STEACS (N = 322: Titan-2/Optimax: 103/209) had better outcomes for secondary events, device-oriented failure CD/AMI/TLR (7.8% vs. 5.0%; p = 0.330), and non-fatal CE of AMI/ST/TLR (7.8% vs. 2.7%, p = 0.039). The Titan Optimax retains the efficacy and safety of Titan 2. It appears to perform better in the subgroup of STEACS patients, by reducing the non-fatal CE of AMI/ST/TLR.


Suspected antibody negative autoimmune limbic encephalitis: outcome of immunotherapy.
Whether and when to immunologically treat epilepsy patients with suggested autoantibody (AB)-negative limbic encephalitis (LE) is clinically challenging. Therefore, we evaluated the clinical outcome and eventual outcome predictors of immunotherapy in a group of AB-negative patients with recent-onset temporal lobe epilepsy (TLE), magnetic resonance imaging (MRI) indicators of LE, subjective cognitive decline, and/or psychiatric symptoms. This retrospective, observational, uncontrolled study monitored 28 TLE patients with suggested AB-negative LE along with methylprednisolone immunotherapy. All patients had seizures, amygdala and/or -hippocampal enlargement, subjective cognitive decline and/or behavioral problems. Eighty-six percent (24/28) were impaired in executive or memory functions, 39% (10/25) depressed, 81% were on antiepileptic drugs when pulse therapy started. After a median follow-up of 18 months, 46% (13/28) of the patients were seizure free (>2 months), 48% (13/27) showed MRI improvements (amygdala and/or hippocampal volume reduction), cognition improved in 57% (16/28), worsened in 32% (9/28), mood improved in 14% (4/25), and deteriorated in 11% (3/25). Immunotherapy was discontinued in 75% (21/28). Clinical changes did not correlate to each other. Outcomes could not be predicted. Immunological treatment of suggested AB-negative LE showed reasonable seizure control, MRI and cognitive improvements. Treatment success was not predictable from clinical features, nor definitely attributable to immunological treatment. Lacking biomarkers for the reliable diagnosis of AB-negative LE, we suggest that in presence of mild manifestations, and after initiating antiepileptic drug therapy, negative dynamics in MRI, seizures, cognition, and behavior should be documented before immunosuppressive treatment is initiated.


Structure of obsessive-compulsive symptoms in pediatric OCD.
It is unclear whether the structure of obsessive-compulsive disorder (OCD) symptoms seen in adults is preserved in pediatric samples. A total of 238 children and adolescents referred to a specialty pediatric OCD clinic were administered the Children's Yale-Brown Obsessive Compulsive Scale Symptom Checklist, and its 13 major symptom categories were subjected to exploratory principal components analysis. The resulting factors were correlated with relevant clinical variables. Principal components analysis identified four symptom dimensions explaining 55% of the total variance and broadly corresponding to those seen in adult samples. Boys were more likely to have sexual obsessions (34% vs. 18%, p = .01), whereas girls were more likely to endorse hoarding compulsions (53% vs. 36%, p=.009). High scores on the hoarding dimension were associated with increased levels of pervasive slowness, responsibility, indecisiveness, pathological doubt, depression and a variety of emotional difficulties, both self-rated and parent-rated. The structure of OCD symptoms is similar across the lifespan. Hoarding symptoms are prevalent in pediatric OCD, especially among girls, and are associated with greater levels of disability.


The demonstration of histamine release in clinical conditions: a review of past and present assay procedures.
Topics related to the measurement of histamine in human plasma and other body fluids are reviewed. These include (1) an overview of the data obtained by the biological, fluorometric and radioenzymatic assays over the past 45 years; (2) the various modifications of the radioenzymatic isotopic assay of histamine and the development of a single extraction step assay; (3) a compilation of values obtained in our laboratory by the radioenzymatic assay of histamine levels in various body fluids in disease states associated with abnormal histamine production or release; and (4) factors that affect histamine levels in plasma and some experimental considerations for monitoring changes in free histamine levels. The last topic includes a discussion of the halflife of histamine in the circulation, its clearance across various vascular beds, and the fact that capillary endothelial cells are one site of inactivation of circulating histamine.


Relevance of sleep and associated structural changes in GBA1 mouse to human rapid eye movement behavior disorder.
Rapid eye movement (REM) sleep behaviour disorder (RBD) is a REM parasomnia that often predicts the later occurrence of alpha-synucleinopathies. Variants in the gene encoding for the lysosomal enzyme glucocerebrosidase, GBA, strongly increase the risk of RBD. In a GBA1-mouse model recently shown to mimic prodromal stages of α-synucleinopathy, we now demonstrate striking REM and NREM electroencephalographic sleep abnormalities accompanied by distinct structural changes in the more widespread sleep neurocircuitry.


Assessment of biomarkers using multiplex assays in aqueous humor of patients with diabetic retinopathy.
With the high prevalence of type 2 diabetes, diabetic retinopathy (DR) has become a leading health problem worldwide. The pathogenesis of DR is complex and several vascular, inflammatory, and neuronal mechanisms are involved. The purpose of this study was to assess the levels of immune and inflammatory biomarkers in the aqueous humor of patients with different severities of DR and to analyze the correlations between Interleukin-6 (IL-6) and these biomarkers, and between IL-6 and the severity of the disease. Aqueous humor samples were obtained from 51 non-diabetic patients and 151 diabetic patients. Levels of 45 different cytokines, chemokines, and growth factors were measured using a multiplex bead immunoassay. IL-6, IL-8, Inducible Protein-10 (IP-10), leukemia inhibitory factor (LIF), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF)-A were significantly higher (p < 0.05) in the aqueous humor of the DR patients compared to the non-diabetic patients, while the concentrations of IL-1α, IL-4, IL-9, IL-21, IL-23, IL-27, IL-31, RANTES, interferon-α, growth regulated oncogene (GRO), and tumor necrosis factor (TNF)-α were significantly lower (p < 0.05) in the DR patients. The IL-6 levels increased as the severity of DR increased. In addition, the IL-6 level positively correlated with the IL-8, HGF and LIF levels, while negatively with the IL-31and GRO levels. These findings suggest that inflammation and immune response may contribute to the pathogenesis of DR, and these biomarkers may potentially be new therapeutic targets for DR.


The herpes simplex problem.
Most of the world's population is eventually infected with herpes simplex virus type 1, type 2, or both. Most infected persons harbor latent virus in nerve ganglia for the rest of their lives. True primary infections, nonprimary first-episode infections, and recurrent infections can be asymptomatic or clinical, but all of these are contagious. Past estimates of recurrent herpes affecting 20% to 40% of the population are probably low because of inadequate studies of asymptomatic shedding and genital recurrences. Herpes infections are spread primarily by close personal contact but some are contracted by fomites and medical-dental procedures. Latent virus harbored by almost everyone with frequent reactivation to produce symptomatic or asymptomatic, infectious recurrent disease poses a huge problem for control or eradication of herpes simplex infections. Public health measures will probably fail because they require too much alteration of the public's life-styles. So far, antiviral drugs do not eliminate latent virus from infected ganglia. That naturally infected persons can be reinfected, superinfected, or autoinoculated raises serious questions whether vaccines will eradicate the disease, although they might control some serious manifestations and limit some spreading. The problem of eradicating herpes is different from that of eradicating smallpox, where latent infections with infectious recurrences did not exist.


Association between shift work and hearing loss: The Dongfeng-Tongji cohort study.
The association between shift work and hearing loss is unclear. We aimed to evaluate this association in a Chinese population independently and in combination with occupational noise. A total of 11,196 participants of the Dongfeng-Tongji cohort study were included. Shift work was self-reported and hearing loss was defined as a pure-tone mean of 25 dB or higher at 0.5, 1, 2, and 4 kHz in any ear. The Robust Poisson method were used to assess the relationship between shift work and hearing loss, and the prevalence ratios (PRs) were calculated. Compared to individuals who reported no shift work, the PRs of bilateral hearing loss were significantly higher for a shift work duration of fewer than 10 years in women, (PR = 1.024, 95% confidence interval [CI] = 1.002-1.053), but not in men (PR = 1.016, 95% confidence interval [CI] = 0.998-1.035). The association between short duration of shift work and bilateral hearing loss was just statistically significant in women when those with occupational noise exposure were excluded (PR = 1.067, 95%CI = 1.015-1.122). When shift work and occupational noise exposure were combined, the PRs for hearing loss were highest among individuals with the longest shift work (≥10 years) and longest noise exposure (≥20 years) durations, whether for bilateral (PR = 1.114, 95%CI = 1.068-1.162) or any ear (PR = 1.065, 95%CI = 1.034-1.096). A short duration of shift work may be a risk factor for hearing loss in women and could increase the prevalence of hearing loss when combined with occupational noise.


Predictors of Virological Failure Among People Living with HIV Switching from an Effective First-Line Antiretroviral Regimen.
Aim of this study was to assess the predictors of virological failure (VF) among patients living with HIV (PLWHIV) switching from an effective first-line antiretroviral therapy (ART) regimen, and to evaluate the emergence of resistance-associated mutations. All adult patients enrolled in the Antiviral Response Cohort Analysis cohort who started ART after 2010, with at least 6 months of virological suppression (VS) before ART switch and with an available genotypic resistance test (GRT) at baseline were included. Thirty-two patients out of the 607 PLWHIV included (5.3%) experienced VF after a median of 11 months from ART switch. Younger age (adjusted Hazard Ratio [aHR] 0.96, 95% confidence interval [CI] 0.92-0.99, p = .023), being male who have sex with male (aHR 0.15, 95% CI 0.03-0.69, p = .014), and longer time from VS to ART switch (aHR 0.97, 95% CI 0.95-1.00, p = .021) resulted protective toward VF, while receiving a first-line regimen containing a backbone other than ABC/3TC or TXF/FTC (aHR 3.61, 95% CI 1.00-13.1, p = .050) and a boosted protease inhibitor as anchor drug (aHR 3.34, 95% CI 1.20-9.28, p = .021) were associated with higher risk of VF. GRT at the moment of VF was available only for 13 patients (40.6%). ART switch in patients with stable control of HIV infection is a safe practice, even if particular attention should be paid in certain cases of patients switching from regimens containing low-performance backbones or protease inhibitors.


Comparison of two bond strength testing methodologies for bilayered all-ceramics.
This study compared the shear bond strength (SBS) and microtensile (MTBS) testing methodologies for core and veneering ceramics in four types of all-ceramic systems. Four different ceramic veneer/core combinations, three of which were feldspathic and the other a fluor-apatite to their respectively corresponding cores, namely leucite-reinforced ceramic ((IPS)Empress, Ivoclar), low leucite-reinforced ceramic (Finesse, Ceramco), glass-infiltrated alumina (In-Ceram Alumina, Vita) and lithium disilicate ((IPS)Empress 2, Ivoclar) were used for SBS and MTBS tests. Ceramic cores (N=40, n=10/group for SBS test method, N=5 blocks/group for MTBS test method) were fabricated according to the manufacturers' instructions (for SBS: thickness, 3mm; diameter, 5mm and for MTBS: 10 mm x 10 mm x 2 mm) and ultrasonically cleaned. The veneering ceramics (thickness: 2mm) were vibrated and condensed in stainless steel moulds and fired onto the core ceramic materials. After trying the specimens in the mould for minor adjustments, they were again ultrasonically cleaned and embedded in PMMA. The specimens were stored in distilled water at 37 degrees C for 1 week and bond strength tests were performed in universal testing machines (cross-head speed: 1mm/min). The bond strengths (MPa+/-S.D.) and modes of failures were recorded. Significant difference between the two test methods and all-ceramic types were observed (P<0.05) (2-way ANOVA, Tukey's test and Bonferroni). The mean SBS values for veneering ceramic to lithium disilicate was significantly higher (41+/-8 MPa) than those to low leucite (28+/-4 MPa), glass-infiltrated (26+/-4 MPa) and leucite-reinforced (23+/-3 MPa) ceramics, while the mean MTBS for low leucite ceramic was significantly higher (15+/-2 MPa) than those of leucite (12+/-2 MPa), glass-infiltrated (9+/-1 MPa) and lithium disilicate ceramic (9+/-1 MPa) (ANOVA, P<0.05). Both the testing methodology and the differences in chemical compositions of the core and veneering ceramics influenced the bond strength between the core and veneering ceramic in bilayered all-ceramic systems.


24 Hours or Less Stay After Laparoscopic Minor Hepatectomy.
Laparoscopic liver resections can result in decreased length of stay. We looked at our hospital experience with 24 hours or less stay after minor laparoscopic liver resections. Patients who underwent laparoscopic minor hepatectomy (less than 3 hepatic segments resection) and stayed 24 hours or less in the hospital were selected from prospectively kept hepatobiliary surgery database. All were managed according to the established enhanced recovery after surgery protocol. 14 cases were identified and included 3 bisegmentectomies and 11 segmental resections. Length of surgery was between 29 and 210 minutes (median 80.5 minutes), and median blood loss was 50 cc (range 20-400 cc). 4 patients were discharged home the same day with 10 staying overnight. Selected group of patients undergoing minor laparoscopic hepatectomy can be discharged home the same day or less than 24 hours after surgery.


Clinical trial design in cancer.
The design of clinical trials in cancer is a subject which features reasonably often among FRCR (Part 1) examination questions, and as such should be of more than passing interest to oncologists. It is also a subject which is gaining in relevance since the number of trials is increasing annually due in part to the many chemotherapeutic regimes which are being proposed. This paper which is based on a lecture given in Cambridge at the Hospital Physicists' Association Annual Conference in September 1978, is intended to act as an introduction to clinical trial design. References for further reading are given and, in particular, the extensive report on randomised clinical trials to the Medical Research Council's Leukaemia Steering Committee (Peto et al., 1977, 1978) is recommended.


Antistaphylococcal activity of ceftobiprole, a new broad-spectrum cephalosporin.
Ceftobiprole (formerly BAL9141), the active component of the prodrug BAL5788 (ceftobiprole medocaril), is a novel cephalosporin with expanded activity against gram-positive bacteria. Among 152 Staphylococcus aureus isolates, including 5 vancomycin-intermediate and 2 vancomycin-resistant strains, MIC(50) and MIC(90) values for ceftobiprole were each 0.5 microg/ml against methicillin-susceptible strains and 2 mug/ml against methicillin-resistant strains. Against 151 coagulase-negative staphylococci (including 4 vancomycin-intermediate strains), MIC(50) and MIC(90) values were, respectively, 0.125 microg/ml and 1 microg/ml against methicillin-susceptible and 1 microg/ml and 2 microg/ml against methicillin-resistant strains. Teicoplanin was less active than vancomycin against coagulase-negative strains. Linezolid, quinupristin-dalfopristin, and daptomycin were active against all strains, whereas increased MICs for amoxicillin-clavulanate, cefazolin, minocycline, gentamicin, trimethoprim-sulfamethoxazole, levofloxacin, rifampin, mupirocin, fusidic acid, and fosfomycin were sometimes observed. At 2x MIC, ceftobiprole was bactericidal against 11 of 12 test strains by 24 h. Prolonged serial passage in the presence of subinhibitory concentrations of ceftobiprole failed to select for clones with MICs >4 times those of the parents; the maximum MIC achieved for ceftobiprole after 50 passages (in 1 of 10 strains) was 8 mug/ml. Single-passage selections showed very low frequencies of resistance to ceftobiprole irrespective of genotype or phenotype; the maximal ceftobiprole MIC of recovered clones was 8 mug/ml.


The Longer-term Unmet Needs after Stroke Questionnaire: Cross-Cultural Adaptation, Reliability, and Concurrent Validity in a Dutch Population.
Unmet needs are common after stroke. We aimed to translate the 22-item Longer-term Unmet Needs after Stroke (LUNS) Questionnaire and validate it in a Dutch stroke population. The LUNS was translated and cross-culturally adapted according to international guidelines. After field testing, the Dutch version was administered twice to a hospital-based cohort 5-8 years after stroke. Participants were also asked to complete the Frenchay Activity Index (FAI) and Short Form (SF)-12. To explore acceptability, the response and completion rates as well as number of missing items were computed. For concurrent validity, the differences in health status (FAI, SF-12) between groups who did and did not report an unmet need were calculated per item. To determine the 14-day test-retest reliability, the percentage of agreement between the first and the second administration was calculated for each item. Seventy-eight of 145 patients (53.8%) returned the initial Dutch LUNS (average age 68.3 [standard deviation 14.0] years, 59.0% male); 66 of these patients (84.6%) fully completed it. Of all items, 3.3% were missing. Among completers, the median number of unmet needs was 3.5 (2.0-5.0; 1.0-14.0). For 15 of 22 items, there was a significant association with the FAI or SF-12 Mental or Physical Component Summary scales. The percentage of agreement ranged from 69.8% to 98.1% per item. Among the 53.8% who completed the survey, the LUNS was concluded to be feasible, reliable, and valid; two-thirds of its items were related to activities and quality of life. Its usefulness and acceptability when administered in routine practice require further study.


Human MUC1 carcinoma-associated protein confers resistance to genotoxic anticancer agents.
The MUC1 transforming protein is overexpressed by most human carcinomas. The present studies demonstrate that the MUC1 C-terminal subunit (MUC1 C-ter) localizes to mitochondria in HCT116/MUC1 colon carcinoma cells and that heregulin stimulates mitochondrial targeting of MUC1 C-ter. We also show that MUC1 attenuates cisplatin-induced (1) release of mitochondrial apoptogenic factors, (2) activation of caspase-3, and (3) induction of apoptosis. Moreover, knockdown of MUC1 expression in A549 lung and ZR-75-1 breast carcinoma cells by MUC1siRNA was associated with increased sensitivity to genotoxic drugs in vitro and in vivo. These findings indicate that MUC1 attenuates the apoptotic response to DNA damage and that this oncoprotein confers resistance to genotoxic anticancer agents.


Biologically active tetralones from New Caledonian Zygogynum spp.
Bioassay guided purification of the ethyl acetate extracts of the bark and leaves of five New Caledonian Zygogynum species (Winteraceae) led to the isolation and characterization of four phenyl-3-tetralones (3,4-dihydronaphthalen-1(2H)-one). Their structures were determined by various NMR techniques and chemical studies. The absolute configuration of the compounds was established by circular dichroism. The compounds showed binding affinity for peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and significant inhibitory activity against KB cancer cell line.


Purification of a heat labile dermonecrotic toxin from culture fluid of Pasteurella multocida.
A highly pure heat-labile dermonecrotic toxin (DNT) of Pasteurella multocida was isolated from bacterium-free broth culture fluid. The protocol for the isolation included the following steps: ammonium sulphate precipitation, gel filtration, ion exchange chromatography and preparative polyacrylamide gel electrophoresis (PAGE). About 1 mg of purified DNT was recovered from 3 l of broth culture fluid. The final product was toxic for embryonic bovine lung (EBL) cells, lethal for mice, dermonecrotic in the guinea pig skin test and inactivated by heating at 56 degrees c. The recovery of biological activity was about 5% that of the original culture fluid and the specific activity had increased about 4000 times. After sodium dodecyl sulphate (SDS)-PAGE and silver staining a single band appeared, indicating that the purified DNT was free from contaminating proteins. The molecular weight of the toxin was approximately 125,000 daltons. The minimal toxic dose of DNT protein for embryonic bovine lung cells was about 2 ng, the minimal dermonecrotic dose in the guinea pig skin test was about 80 ng and the 50% lethal dose for mice about 300 ng.


Nonsurgical treatment of class III malocclusion with temporomandibular disorder comorbidity: A clinical report.
The treatment of a 57-year-old woman with combined skeletal and pseudo-class III malocclusion who was also suffering from chronic myofascial orofacial pain is described. The challenge was to treat the patient's malocclusion while simultaneously managing the temporomandibular disorder. After a successful 3-month occlusal device therapy, which substantially reduced the patient's discomfort, a nonsurgical therapy by using complete-mouth fixed restorations was planned. The treatment was first tested by using printed interim restorations before monolithic zirconia restorations were provided. Stable occlusion and a pain-free outcome were observed at the 3-month follow-up.


The spectrum of genital median raphe anomalies among infants undergoing ritual circumcision.
To evaluate the extent of genital median raphe (GMR) anomalies and their relation to other genitourinary anomalies, as well as the impact on performing ritual circumcision. This prospective study was designed to collect data from neonates coming for ritual circumcision in order to detect any associated congenital anomalies in their genitalia, particularly in the genital raphe. 2880 babies aged from 1 day to 7 weeks were examined, from 2006 to 2011. All doubtful cases were reevaluated and cases with GMR anomalies were investigated for detection of other congenital anomalies and enrolled in the study. 57 cases of GMR anomalies were detected with an overall incidence of 2%; 18 of them had hypospadias, 5 had renal anomalies and 3 had limb anomalies. Circumcision was postponed in 37 cases where further investigations were done, but routine circumcision was carried out in the remaining 20. It is crucial to examine every baby coming for circumcision to detect obvious or hidden congenital genital anomalies. Congenital anomalies of GMR are not so rare as thought, and some of these anomalies may necessitate surgical correction, and are commonly accompanied by urinary tract anomalies.


MicroRNA‑361‑5p suppresses cancer progression by targeting signal transducer and activator of transcription 6 in non‑small cell lung cancer.
The incidence of non‑small cell lung cancer (NSCLC) has significantly increased in China, while the prognosis of affected patients is poor. The pathogenesis of NSCLC is thought to be regulated by microRNAs (miRs). The present study used a miR array in order to determine the expression of miR‑361‑5p, which was significantly lower in NSCLC tissues compared with that in adjacent tissues, indicating a crucial role of miR‑361‑5p during the progression of NSCLC. Furthermore, the effects of transfection-induced upregulation of miR‑361‑5p on the NSCLC cell line H23 were assessed. Overexpression of miR‑361‑5p inhibited the proliferation and colony formation ability of H23 cells. In addition, apoptosis of H23 cells was induced by upregulation of miR‑361‑5p. Furthermore, signal transducer and activator of transcription 6 (STAT6) was confirmed as a direct target of miR‑361‑5p by a dual‑luciferase reporter assay. Moreover, inhibition of STAT6 by small interfering RNA or miR‑361‑5p also decreased the expression of B-cell lymphoma extra large (Bcl-xL). In vivo, miR‑361‑5p significantly reduced tumor growth in a nude mouse xenograft model, and suppressed STAT6 and Bcl-xL expression. In conclusion, the present study indicated that miR‑361‑5p may represent a novel molecular tool for therapeutic and diagnostic strategies in NSCLC.


[Specific cytoplasmic receptors for steroid homones in benign and malignant breast diseases, in normal glandular tissue and pectoral muscle].
An improvement to the DCC (destran-coated charcoal) method for determining receptors for 17-beta-oestradiol, 5-alpha-dihydrotestosterone and progesterone in benign and malignant breast conditions, normal glandular tissue and muscular tissue is reported. Preliminary results on 16 malignant cancers and 4 fibrocystic mastopathies are discussed together with a critical review of the technique employed and the results obtained in hormone competition.


Development and functionality of isoelastic dental implants of titanium alloys.
Two types of isoelastic endosseous dental implants were produced and their functionality was tested. One type consisted of a porous sintered TiTa30 alloy, the other had a special surface structure consisting of titanium wire loops. Their mechanical properties were optimized by the production parameter (sintering and diffusion bonding, respectively). The functionality was tested after insertion into an artificial jaw which had properties corresponding to the natural mandibular. The elastic properties of both implants were similar to the properties of the bone. In addition the implants have a safe anchorage bone ingrowth. In animal experiments using the implant with surface loops it was observed that the bone entered the loops and even extremely small surface cavities in the wire loops.


Chemical composition and trophic state of shallow saline steppe lakes in central Asia (North Kazakhstan).
The purpose of this study was to identify the prevailing chemical composition and trophic state of the shallow saline steppe lakes of North Kazakhstan along a wide size range (< 1-454 km2) and salinity gradient (2-322 g L-1) on a large spatial scale (1000 km), taking into account the potential effects of human disturbances. Water depth, Secchi disk transparency, temperature, pH, electric conductivity, major ions, total dissolved solids, total organic carbon, total nitrogen and phosphorus, nitrate, soluble reactive phosphorus, and chlorophyll a were measured. The equivalent percentage of major ions, Spearman rank correlation, multivariate analyses, equilibrium state of lakes, and spatial GIS autocorrelation were calculated. The impact of human disturbances (settlements, farms, and mines) on total organic carbon, nitrogen, phosphorus, and chlorophyll a were tested by Kruskal-Wallis ANOVA. The most common combinations of dominant ions were Na-Cl>SO4 and Na-Cl (n = 16; 64%); the Ca, Mg, HCO3, and SO4 ions precipitate with increasing salinity (2-322 g L-1); and ion composition shifts from Na>Mg-Cl>SO4 to Na-Cl. The most of the chemical variables positively, but chlorophyll a negatively, correlated with total dissolved solids, and the total phosphorus had no significant correlation with any variables. The trophic state of these lakes in most cases exceeded the hypertrophic level. The increase in salinity causes change in chemical composition and effects on the phytoplankton development independently from the size of water surface, and the human disturbances had negligible effect on the trophic state of shallow saline lakes in this region of Kazakhstan.


Cellulose hydrolysis by a methanogenic culture enriched from landfill waste in a semi-continuous reactor.
This study investigates the hydrolysis of cellulose by a mixed culture enriched from landfill waste in a continuous reactor operated under prolonged residence times to accommodate methanogenic conditions. Chemostat studies of hydrolysis under balance methanogenic conditions are rarely reported, despite the importance of hydrolysis under these conditions in waste management and renewable energy industries. Continuous digestion was studied in a 1.25l digester, fed with a 1% (w/v) slurry of 50mum cellulose in sterilized leachate drawn from a 220l digester operated on a feedstock of mixed municipal solid waste. Unsterilized leachate was used as the inoculum. Stable and rapid hydrolytic conditions were established at residence time of 2.5, 3.5 and 5d with a 1st order hydrolysis rate 0.45+/-0.07d(-1) and high methane yields ranging from 57% to 62% of solubilised cellulose on a COD basis. Biomass yields were between 32% and 35% of solubilised cellulose on a COD basis, over three times that observed with fermentative cultures. This is attributed to the diversity of the microbial population which fully converted solubilised COD to methane, as evident by VFA yields of less than 8% on a COD basis.


Individual and household risk factors for COVID-19 infection among household members of COVID-19 patients in home-based care in western Uganda, 2020.
To investigate factors associated with COVID-19 among household members of patients in home-based care (HBC) in western Uganda. We conducted a case-control and cohort study. Cases were reverse transcriptase-polymerase chain reaction-confirmed SARS-CoV-2 diagnosed 1-30 November 2020 among persons in HBC in Kasese or Kabarole districts. We compared 78 case-households (≥1 secondary case) with 59 control-households (no secondary cases). The cohort included all case-household members. Data were captured by in-person questionnaire. We used bivariate regression to calculate odds and risk ratios. Case-households were larger than control-households (mean 5.8 vs 4.3 members, P<0.0001). Having ≥1 household member per room (adjusted odds ratio (aOR)=4.5, 95% CI 2.0-9.9), symptom development (aOR=2.3, 95% CI 1.1-5.0), or interaction with primary case-patient (aOR=4.6, 95% CI 1.4-14.7) increased odds of case-household status. Households assessed for suitability for HBC reduced odds of case-household status (aOR=0.4, 95% CI=0.2-0.8). Interacting with a primary case-patient increased the risk of individual infection among household members (adjusted risk ratio=1.7, 95% CI 1.1-2.8). Household and individual factors influence secondary infection risk in HBC. Decisions about HBC should be made with these in mind.


[Neonatal hydrometrocolpos. A cause of immediate neonatal respiratory distress].
The authors report a case of acute fetal distress and immediate respiratory distress in a neonate presenting with large hydrometrocolpos. This diagnosis, infrequently concerned in such a situation, should be suggested in cases with abdominal tumors.


Impacts of increasing ozone on Indian plants.
Increasing anthropogenic and biogenic emissions of precursor compounds have led to high tropospheric ozone concentrations in India particularly in Indo-Gangetic Plains, which is the most fertile and cultivated area of this rapidly developing country. Current ozone risk models, based on European and North American data, provide inaccurate estimations for crop losses in India. During the past decade, several ozone experiments have been conducted with the most important Indian crop species (e.g. wheat, rice, mustard, mung bean). Experimental work started in natural field conditions around Varanasi area in early 2000's, and the use of open top chambers and EDU (ethylene diurea) applications has now facilitated more advanced studies e.g. for intra-species sensitivity screening and mechanisms of tolerance. In this review, we identify and discuss the most important gaps of knowledge and future needs of action, e.g. more systematic nationwide monitoring for precursor and ozone formation over Indian region.


Nocardia cyriacigeorgica is a significant pathogen responsible for nocardiosis in Japan and Thailand.
Nocardia cyriacigeorgica is a recently described species. During routine diagnostic testing of 121 clinical isolates, we found that about one fourth of the strains from Japan (19 isolates) and Thailand (8 isolates), which were identified in our laboratories as N. asteroides, in fact belong to N. cyriacigeorgica. To our knowledge, this is the first report of infection due to N. cyriacigeorgica in Japan and Thailand, and the third report of infection anywhere in the world. Although N. cyriacigeorgica is usually differentiated from other Nocardia species by utilization of glucose and gluconate, we found that it can also be differentiated by a characteristic synergistic effect between imipenem (IPM) and tobramycin (TOB).


Non-fistulous urinary leakage among women attending a Nigerian family planning clinic.
Urinary leakage is an important gynecological challenge, which has a substantial impact on quality of life. The aim of this study was to determine the prevalence and types of non-fistulous urinary leakage among women attending the family planning clinic of the University of Ilorin teaching hospital, Ilorin, Nigeria. The study was a cross-sectional study carried out between January 3 and April 25 2009. One hundred and two women experienced urinary leakage out of 333 women interviewed, giving a prevalence rate of 30.6%. Stress incontinence was the most common urinary leakage (prevalence rate 12.0%). This is followed by urge incontinence (10.8%), urinary incontinence (4.8%), and overflow incontinence (3.0%). None of the women afflicted sought medical help. Conclusively, this study has demonstrated that non-fistulous urinary leakage is a common problem among women of reproductive age in this environment.


Serum lipase active in the hydrolysis of the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate.
Sera from numerous animal sources contain enzymes that degrade the potent tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). The activity was present in rat, mouse, guinea pig, rabbit and goat, and absent in fetal bovine, bovine, porcine, horse, chicken and human sera. The enzyme shows a marked specificity for hydrolysis of the long-chain 12-O acyl group, which results in the formation of phorbol-13-monoacetate as the major product. Enzymatic catalysis displayed two pH optima (5.5 and 8.0) and was completely destroyed by heat inactivation (56 degrees C, 30 min) of the serum. N-Ethylmaleimide and p-chloromercuribenzoate were relatively weak inhibitors, whereas NaF (5.0 mM) produced an approximate 80% reduction of hydrolysis. Esterase-lipase substrates, such as cholesterol oleate, alpha-naphthylacetate, alpha-naphthylpalmitate, and monotetradecanoylglycerol, were not inhibitory when added to the reaction mixture. Porcine pancreatic lipase does not catalyze the removal of the acyl or the acetyl groups from TPA.


Peptoid - peptide hybrids that bind Syk SH2 domains involved in signal transduction.
Peptoid-peptide hybrids are oligomeric peptidomimetics that contain one or more N-substituted glycine residues. In these hybrids, the side chains of one or several amino acids are "shifted" from the alpha-carbon atom to the amide nitrogen atom. A library of phosphorylated peptoid-peptide hybrids derived from the sequence pTyr-Glu-Thr-Leu was synthesized and tested for binding to the tandem SH2 domain of the protein tyrosine kinase Syk. A considerable influence of the side chain position was observed. Compounds 19-21, 24, and 25 comprising a peptoid NpTyr and/or NGlu residue did not show any binding. Compounds 22, 23, and 26 containing an NhThr (hThr=homothreonine) and/or NLeu peptoid residue showed binding with IC(50) values that were only five to eight times higher than that of the tetrapeptide lead compound 18. These data show that side chain shifting is possible with retention of binding capacity, but only at the two C-terminal residues of the tetramer. This method of a peptoid scan using peptoid-peptide hybrids appears to be very useful to explore to what extent a peptide sequence can be transformed into a peptoid while retaining its affinity.


Augmentation Therapy for Severe Alpha-1 Antitrypsin Deficiency Improves Survival and Is Decoupled from Spirometric Decline-A Multinational Registry Analysis.
Rationale: Intravenous plasma-purified alpha-1 antitrypsin (IV-AAT) has been used as therapy for alpha-1 antitrypsin deficiency (AATD) since 1987. Previous trials (RAPID and RAPID-OLE) demonstrated efficacy in preserving computed tomography of lung density but no effect on FEV1. This observational study evaluated 615 people with severe AATD from three countries with socialized health care (Ireland, Switzerland, and Austria), where access to standard medical care was equal but access to IV-AAT was not. Objectives: To assess the real-world longitudinal effects of IV-AAT. Methods: Pulmonary function and mortality data were utilized to perform longitudinal analyses on registry participants with severe AATD. Measurements and Main Results: IV-AAT confers a survival benefit in severe AATD (P < 0.001). We uncovered two distinct AATD phenotypes based on an initial respiratory diagnosis: lung index and non-lung index. Lung indexes demonstrated a more rapid FEV1 decline between the ages of 20 and 50 and subsequently entered a plateau phase of minimal decline from 50 onward. Consequentially, IV-AAT had no effect on FEV1 decline, except in patients with a Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 lung index. Conclusions: This real-world study demonstrates a survival advantage from IV-AAT. This improved survival is largely decoupled from FEV1 decline. The observation that patients with severe AATD fall into two major phenotypes has implications for clinical trial design where FEV1 is a primary endpoint. Recruits into trials are typically older lung indexes entering the plateau phase and, therefore, unlikely to show spirometric benefits. IV-AAT attenuates spirometric decline in lung indexes in GOLD stage 2, a spirometric group commonly outside current IV-AAT commencement recommendations.


Elevated early follicular gonadotropin levels in women with unexplained infertility do not provide evidence for disordered gonadotropin-releasing hormone secretion as assessed by luteinizing hormone pulse characteristics.
To determine whether women with rigorously defined unexplained infertility demonstrated altered GnRH secretion, as reflected by serum LH secretion patterns. Prospective observational study. National Center for Infertility Research at Michigan. Nine women with rigorously defined unexplained infertility and 11 healthy, parous age-matched control women.Gonadotropin-releasing hormone (25 ng/kg) as a bolus injection. Daytime pulse patterns of LH secretion measured every 10 minutes; mean serum concentrations of LH, FSH, E(2), P, PRL, and cortisol; and response to a physiologic dose of GnRH in the early follicular, late follicular, mid-luteal, and late luteal phases of the same menstrual cycle. Serum LH pulse frequency and pulse amplitude and LH secretion in response to a physiologic bolus of GnRH were not significantly different in unexplained infertility patients at any phase of the cycle. Luteinizing hormone pulse frequency and amplitude, as well as response to GnRH, varied significantly across the cycle. Mean early follicular serum LH and FSH concentrations were significantly higher in unexplained infertility patients than in fertile control subjects (LH: 5.31 +/-.51 vs. 4.03 +/-.33 [mIU/mL +/- SEM]; FSH: 5.81 +/-.63 vs. 3.80 +/-.45) but were not different at any other phase of the cycle. These data do not support the hypothesis that unexplained infertility is caused by an abnormality in pulsatile GnRH secretion or abnormal pituitary sensitivity to GnRH. However, the results are consistent with a difference in negative feedback from the ovary to the pituitary in unexplained infertility patients that is suggestive of diminished ovarian reserve.


Prevalence of autism spectrum disorder in Asia: A systematic review and meta-analysis.
There has been an increased prevalence of the diagnosis of Autism Spectrum Disorder (ASD) globally during the last decade. An updated and overall estimate of ASD prevalence in Asia would assist health professionals to develop relevant public health strategies. We performed a systematic review by searching English databases (Medline, Embase, Web of Science, and Cochran Library) from inception date to August 6, 2018. Subgroup, sensitivity, and meta-regression analyses were performed to address heterogeneity. Publication bias was evaluated using Egger's test. A total of 2,195,497 subjects in Asia from 12 eligible studies were included in this meta-analysis. The pooled estimate of ASD prevalence among the included subjects was 0.36% (95% CI: 0.16-0.79%). The pooled ASD prevalence in males (0.45%, 95% CI: 0.19-1.04%) was higher than that in females (0.18%, 95% CI: 0.079-0.49%). ASD prevalence in East Asia, South Asia, and West Asia was 0.51% (95% CI: 0.06-4.22%), 0.31% (95% CI: 0.14-0.65%), and 0.35% (95% CI: 0.07-1.80%) respectively. The prevalence of ASD is increasing in Asia. Universal and standardized diagnostic processes for ASD should be adopted for the prevention and control programs of ASD in future.


Graphene oxide-silica composite coating hollow fiber solid phase microextraction online coupled with inductively coupled plasma mass spectrometry for the determination of trace heavy metals in environmental water samples.
In this work, a novel graphene oxide-silica (GO-silica) composite coating was prepared for hollow fiber solid phase microextraction (HF-SPME) of trace Mn, Co, Ni, Cu, Cd and Pb followed by on-line inductively coupled plasma mass spectrometry (ICP-MS) detection. The structure of the prepared graphene oxide and GO-silica composite was studied and elucidated by atomic force microscopy (AFM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). The GO-silica composite coated hollow fiber was characterized by scanning electron microscope (SEM), and the results show that the GO-silica composite coating possessed a homogeneous and wrinkled structure. Various experimental parameters affecting the extraction of the target metal ions by GO-silica composite coated HF-SPME have been investigated carefully. Under the optimum conditions, the limits of detection (LODs, 3σ) for Mn, Co, Ni, Cu, Cd and Pb were 7.5, 0.39, 20, 23, 6.7 and 28 ng L(-1) and the relative standard deviations (RSDs, c(Mn, Co, Cd)=0.05 μg L(-1), c(Ni, Cu, Pb)=0.2 μg L(-1), n=7) were 7.2, 7.0, 5.6, 7.3, 7.8 and 4.6%, respectively. The accuracy of the proposed method was validated by the analysis of Certified Reference Material of GSBZ 50009-88 environmental water and the determined values were in a good agreement with the certified values. The proposed method has been successfully applied for the determination of trace metals in real environmental water samples with recoveries ranging from 85 to 119%.


Conflicts in how interpreters manage their roles in provider-patient interactions.
Interpreters face challenges because of the various role expectations that others have placed on them and then adopt specific strategies to manage these conflicts. This study examines the conflicts in medical interpreters' role performances, the sources of these conflicts, and interpreters' strategies for resolving conflicts. It is based on in-depth interviews with 26 medical interpreters from 17 languages in the Midwestern area of the USA. The results showed that interpreters experienced four sources of conflicts in their role performances: (a) others' communicative practices, (b) changes in participant dynamics, (c) institutional constraints, and (d) unrealistic role expectations. To resolve conflicts, interpreters justified their roles by identifying the source and location of an assignment, (re)defining the relationships and identities of the provider and the patient, and adopting specific communicative strategies. This study highlights the importance of speaker and contextual factors on interpreters' communicative strategies and management of role conflicts.


Effects of substrate type on enhancing pollutant removal performance and reducing greenhouse gas emission in vertical subsurface flow constructed wetland.
Constructed wetlands (CWs), known as an alternative clean technology, have been widely used for sewage treatment. However, greenhouse gas (N2O, CH4 and CO2) emissions are the accompanying problem in CWs. To mitigate the net global warming potential (GWP) with the constant removal efficiency for contaminants is attracting wide attention recently. In this study, four CWs were established to explore the effects of substrate types (gravel, walnut shell, manganese ore and activated alumina) on contaminant removal and greenhouse gas emissions. CWs using manganese ore substrate with function of electronic exchange showed high removal efficiencies on COD (90.1%), TN (65.1%), TP (97.1%) and low greenhouse gas flux. The emission fluxes of N2O, CH4 and CO2 were 0.07-0.20, 2.00-252.30 and 337.54-782.57 mg m-2 h-1, respectively. Especially, the lowest average CH4 emission flux in the manganese ore CW was only 2.00 mg m-2 h-1 while those of N2O in walnut shell CW was only 0.07 mg m-2 h-1, which will make a significant contribution on the mitigation of GWP of CWs. High-throughput sequencing results indicated that microbial community diversity and richness changed significantly among different substrates. The high pmoA and low mcrA, caused by the introduction of manganese ore as substrate, also explained why there was little CH4 emission in CWs. Our study provided new insights into GWP mitigation and contaminant removal enhancement in CWs using optimal substrate.


Interaction of right and left ventricular filling pressures at the termination of cardiopulmonary bypass. Central venous pressure/pulmonary capillary wedge pressure ratio.
In 50 patients who underwent coronary bypass grafting, the interaction of left- and right-sided filling pressures were prospectively evaluated to determine whether restoration and/or maintainance of a normal central venous pressure/pulmonary capillary wedge pressure (CVP/PCWP) ratio could improve biventricular performance. In 40 patients, the CVP/PCWP ratio was normal (less than 1) and termination of cardiopulmonary bypass was uneventful. In 10 patients, during loading at the termination of extracorporeal circulation, CVP exceeded PCWP and the ratio was reversed (less than 1). Cardiac index and systolic arterial pressure were low. Restoration of normal ratio by emptying the right heart helped in the improvement of systolic arterial pressure and cardiac index. Thus, in the presence of reversed CVP/PCWP ratio at the termination of cardiopulmonary bypass, restoration of the ratio may prevent unnecessary pharmacologic and/or mechanical intervention, such as inotropic agents, balloon pumps, or assist devices.


Noninvasive control of adequate cerebral oxygenation during low-flow antegrade selective cerebral perfusion on adults and infants in the aortic arch surgery.
Real-time readings of the regional oxygen saturation (rSO(2)) using near-infrared spectroscopy (NIRS) during the aortic arch surgery can provide an early detection of perfusion or oxygenation abnormalities. Aortic arch repair techniques using low-flow antegrade selective cerebral perfusion have been standardized to a certain degree. However, some of the often-stated beneficial effects have never been proven. Especially, the existence of an adequate continuous flow in both cerebral hemispheres during the surgical procedure still remains unclear as the monitoring of an effective perfusion remains a nonstandardized technique. Seventeen patients underwent surgical reconstruction of the aortic arch due to aortic aneurysm surgery (adult group n = 8 patients) or of the hypoplastic aortic arch due to hypoplastic left heart syndrome (HLHS) or aortic coarctation (infant group n = 9 patients) under general anesthesia and mild hypothermia (adult group 28 degrees C; infant group 25 degrees C). Mean weights were 92.75 +/- 14.00 kg and 4.29 +/- 1.32 kg, and mean ages were 58.25 +/- 10.19 years and 55.67 +/- 51.11 days in the adult group and the infant group, respectively. The cerebral O(2) saturation measurement was performed by continuous plotting of the somatic reflectance oximetry of the frontal regional tissue on both cerebral hemispheres (rSO(2), INVOS; Somanetics Corporation, Troy, MI, USA). During low-flow antegrade perfusion via innominate artery, continuous plots with similar values of O(2) saturation (rSO(2)) in both cerebral hemispheres were observed, whereas a decrease in the rSO(2) values below the desaturation threshold correlated with a displacement or an incorrect positioning of the arterial cannula in the right subclavian artery. Continuous monitorization of the cerebral O(2) saturation during aortic arch surgery in adults and infants is a feasible technique to control an adequate cannula positioning and to optimize clinical outcomes avoiding neurological complications related to cerebral malperfusion.


Prognostic factors for quality of life after trochanteric fracture : Inter-regional study S.O.T.EST.
The aim of the study was to determine factors influencing functional ability and quality of life 6 months after surgically treated trochanteric fractures.A multicenter cohort included 459 patients (365 females, 103 males, mean age 80.5 years) in Eastern France. They presented with stable (62%) and unstable (38%) fractures. Six months after surgery, functional ability and quality of life were assessed by Merle d'Aubigné, Harris and Duke Health profile scores, or return to home.In logistic regression analysis, age was the most prominent factor predicting low functional ability and quality of life. The implant material similarly predicted poor functional ability and level of quality of life, probably through the different strategies for care management they involved. The quality of fracture reduction assessed on lateral radiograph as well as post-operative complications were predictors of a better functional ability. A delayed weight bearing was also suggested to predict better quality of life in these patients.


Mercury levels in hair are associated with reduced neurobehavioral performance and altered brain structures in young adults.
The detrimental effects of high-level mercury exposure on the central nervous system as well as effects of low-level exposure during early development have been established. However, no previous studies have investigated the effects of mercury level on brain morphometry using advance imaging techniques in young adults. Here, utilizing hair analysis which has been advocated as a method for biological monitoring, data of regional gray matter volume (rGMV), regional white matter volume (rWMV), fractional anisotropy (FA) and mean diffusivity (MD), cognitive functions, and depression among 920 healthy young adults in Japan, we showed that greater hair mercury levels were weakly but significantly associated with diminished cognitive performance, particularly on tasks requiring rapid processing (speed measures), lower depressive tendency, lower rGMV in areas of the thalamus and hippocampus, lower rWMV in widespread areas, greater FA in bilaterally distributed white matter areas overlapping with areas of significant rWMV reductions and lower MD of the widely distributed gray and white matter areas particularly in the bilateral frontal lobe and the right basal ganglia. These results suggest that even normal mercury exposure levels in Japan are weakly associated with differences of brain structures and lower neurobehavioral performance and altered mood among young adults.


A linkage between hereditary hyperferritinaemia not related to iron overload and autosomal dominant congenital cataract.
The only genetic disorder with elevated serum ferritin levels so far described is hereditary HLA-related haemochromatosis. On the other hand, hereditary cataract is both genotypically as well as phenotypically heterogenous, and no specific locus or any useful marker has been yet identified. We studied two Italian families in whom a combination of elevated serum ferritin not related to iron overload and congenital nuclear cataract is transmitted as an autosomal dominant trait. Affected individuals have normal serum iron and transferrin saturation, but high serum ferritin. Red cell counts are normal and venesection therapy rapidly produces iron-deficiency anaemia. This genetic disorder, which is characterized by hyperferritinaemia, differs from hereditary HLA-related haemochromatosis mostly for the absence of iron overload. A gene responsible for the congenital nuclear cataract likely maps on chromosome 19q close to the ferritin L-subunit gene. Within families with autosomal dominant congenital cataract, serum ferritin might be an early marker of disease.


Determination of Cost-Effectiveness Threshold for Health Care Interventions in Malaysia.
One major challenge in prioritizing health care using cost-effectiveness (CE) information is when alternatives are more expensive but more effective than existing technology. In such a situation, an external criterion in the form of a CE threshold that reflects the willingness to pay (WTP) per quality-adjusted life-year is necessary. To determine a CE threshold for health care interventions in Malaysia. A cross-sectional, contingent valuation study was conducted using a stratified multistage cluster random sampling technique in four states in Malaysia. One thousand thirteen respondents were interviewed in person for their socioeconomic background, quality of life, and WTP for a hypothetical scenario. The CE thresholds established using the nonparametric Turnbull method ranged from MYR12,810 to MYR22,840 (~US $4,000-US $7,000), whereas those estimated with the parametric interval regression model were between MYR19,929 and MYR28,470 (~US $6,200-US $8,900). Key factors that affected the CE thresholds were education level, estimated monthly household income, and the description of health state scenarios. These findings suggest that there is no single WTP value for a quality-adjusted life-year. The CE threshold estimated for Malaysia was found to be lower than the threshold value recommended by the World Health Organization.


Successful treatment of progressive disseminated histoplasmosis with amphotericin B methyl ester.
Amphotericin B methyl ester (AME) has been used to treat fungal infections, most often those caused by Coccidioides immitis. We describe the only patient with disseminated histoplasmosis who has been treated with AME. After having had alarming reactions to amphotericin B, the patient was treated and cured with AME without adverse drug effect or later relapse.


Trust, risk perception, and COVID-19 infections: Evidence from multilevel analyses of combined original dataset in China.
Previous studies have revealed medical, democratic, and political factors altering responses to unexpected infectious diseases. However, few studies have attempted to explore the factors affecting disease infection from a social perspective. Here, we argue that trust, which plays an important role in shaping people' s risk perception toward hazards, can also affect risk perception toward infections from a social perspective. Drawing on the indication that risk perception of diseases helps prevent people from being infected by promoting responsible behaviors, it can be further asserted that trust may alter the infection rate of diseases as a result of risk perception toward infectious diseases. This is an essential point for preventing the spread of infectious diseases and should be demonstrated. To empirically test this prediction, this study uses the COVID-19 outbreak in China as an example and applies an original dataset combining real-time big data, official data, and social survey data from 317 cities in 31 Chinese provinces to demonstrate whether trust influences the infection rate of diseases. Multilevel regression analyses reveal three main results: (1) trust in local government and media helps to reduce the infection rate of diseases; (2) generalized trust promotes a higher rather than lower infection rate; and (3) the effects of different types of trust are either completely or partly mediated by risk perception toward diseases. The theoretical and practical implications of this study provide suggestions for improving the public health system in response to possible infectious diseases.


The role of lactadherin in the phagocytosis of phosphatidylserine-expressing sickle red blood cells by macrophages.
Lactadherin is a phosphatidylserine-binding glycoprotein secreted by macrophages. Less than 0.5% of normal circulating red cells showed any binding to lactadherin. However, the red cells from patients with sickle cell disease showed 2 to 10-fold increases in lactadherin binding. Further, lactadherin stimulated the phagocytosis of sickle red blood cells by macrophages suggesting a potential role in sickle red cell clearance.


Water hydrogen uptake in biomolecules detected via nuclear magnetic phosphorescence.
We introduce a new symmetry-based method for structural investigations of areas surrounding water-exchanging hydrogens in biomolecules by liquid-state nuclear magnetic resonance spectroscopy. Native structures of peptides and proteins can be solved by NMR with fair resolution, with the notable exception of labile hydrogen sites. The reason why biomolecular structures often remain elusive around exchangeable protons is that the dynamics of their exchange with the solvent hampers the observation of their signals. The new spectroscopic method we report allows to locate water-originating hydrogens in peptides and proteins via their effect on nuclear magnetic transitions similar to electronic phosphorescence, long-lived coherences. The sign of long-lived coherences excited in coupled protons can be switched by the experimenter. The different effect of water-exchanging hydrogens on long-lived coherences with opposed signs allows to pinpoint the position of these labile hydrogen atoms in the molecular framework of peptides and proteins.


Glycation of Ribonuclease A affects its enzymatic activity and DNA binding ability.
Prolonged non-enzymatic glycation of proteins results in the formation of advanced glycation end products (AGEs) that cause several diseases. The glycation of Ribonuclease A (RNase A) at pH 7.4 and 37 °C with ribose, glucose and fructose has been monitored by UV-vis, fluorescence, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and matrix assisted laser desorption ionization spectroscopy-time of flight (MALDI-TOF) methods. The enzymatic activity and DNA binding ability of glycated RNase A was also investigated by an agarose gel-based assay. A precipitation assay examined the ribonucleolytic activity of the glycated enzyme. An increase in incubation time resulted in the formation of high molecular weight AGEs with a decrease in ribonucleolytic activity. Ribose exhibits the highest potency as a glycating agent and showed the greatest reduction in the ribonucleolytic activity of the enzyme. Interestingly, glycated RNase A was unable to bind with the ribonuclease inhibitor (RI) and DNA. The glycated form of the protein was also found to be ineffective in DNA melting unlike native RNase A.


Micronutrient special issue: coenzyme Q(10) requirements for DNA damage prevention.
Coenzyme Q(10) (CoQ(10)) is an essential component for electron transport in the mitochondrial respiratory chain and serves as cofactor in several biological processes. The reduced form of CoQ(10) (ubiquinol, Q(10)H(2)) is an effective antioxidant in biological membranes. During the last years, particular interest has been grown on molecular effects of CoQ(10) supplementation on mechanisms related to DNA damage prevention. This review describes recent advances in our understanding about the impact of CoQ(10) on genomic stability in cells, animals and humans. With regard to several in vitro and in vivo studies, CoQ(10) provides protective effects on several markers of oxidative DNA damage and genomic stability. In comparison to the number of studies reporting preventive effects of CoQ(10) on oxidative stress biomarkers, CoQ(10) intervention studies in humans with a direct focus on markers of DNA damage are limited. Thus, more well-designed studies in healthy and disease populations with long-term follow up results are needed to substantiate the reported beneficial effects of CoQ(10) on prevention of DNA damage.


Effects of Drinking Water Temperature and Flow Rate during Cold Season on Growth Performance, Nutrient Digestibility and Cecum Microflora of Weaned Piglets.
Although water is one of the most important nutrients and is essential for various physiological processes within the body, it does not receive adequate consideration when ensuring optimal nutrition and growth performance in piglets. This study was conducted to investigate the effects of drinking water temperature (DWT) and flow rate (DWF) on growth performance, nutrient digestibility and cecum microflora in weaned piglets during cold weather. Sixty-four piglets with an average body weight of 8.60 ± 0.5 kg were allotted into four groups with four replicates in each group and four pigs in each replicate. The DWT and DWF were set for each group as follows: (1) 13 °C + 300 mL/min, (2) 13 °C + 700 mL/min, (3) 30 °C + 300 mL/min and (4) 30 °C + 700 mL/min, respectively. All groups were fed the same diet during the 28 d trial. The body weight at day 0 and day 29, as well as daily feed intake, were recorded. Diarrhea severity was assessed every day. Fresh fecal samples were collected for four consecutive days at the end of the experiment for the digestibility test. Cecum content was collected after sacrifice for microbial composition analysis. The results indicated that: (1) DWT at 30 °C promoted the average daily gain (ADG) of weaned piglets considerably (p = 0.043) and decreased feed to weight ratio when compared with DWT at 13 °C (p = 0.045). DWF had no substantial effect on the growth performance of piglets (p > 0.05). (2) The 30 °C DWT groups had higher apparent digestibility of crude protein, crude fat and energy than the 13 °C DWT groups (p < 0.05), while DWF had no significant effect on the apparent digestibility of nutrients (p > 0.05). (3) DWT at 30 °C increased the Bacteroidetes abundance and decreased the Proteobacteria abundance in cecum digesta. The change in these two factors may be related to a decrease in diarrhea and the improvement of growth performance. Different DWF had no substantial effect on the cecum microbial structure. To sum up, providing a DWT of 30 °C to weaned piglets in cold weather reduced the abundance of harmful bacteria in the cecum and improved the apparent nutrient digestibility, which is beneficial for maintaining a healthy intestinal microenvironment and promoting growth performance. A lower DWF of 300 mL/min had no adverse effect on growth performance. Therefore, a combination of 30 °C + 300 mL/min is recommended for weaned piglets during cold weather for the consideration of animal welfare and production efficiency.


An exploratory investigation of schema modes in social anxiety disorder: Empirical findings and case conceptualization.
Current "gold standard" treatments for social anxiety disorder (SAD) are limited by the limited emphasis of key etiological factors in conceptualization, and many individuals with SAD experience residual symptoms posttreatment. Hence, the novel application of the Schema Therapy Mode Model may provide a helpful framework for extending clinical understanding and treatment options for SAD. This exploratory study aimed to investigate the presence and pattern of schema modes among SAD individuals. Forty individuals with SAD completed questionnaire measures of symptomatology, social anxiety-relevant cognitions, schema modes, childhood trauma, and parental style. Key maladaptive schema modes identified in SAD were Vulnerable Child, Punitive Critic, Demanding Critic, Compliant Surrender, and Detached Self-Soother. Outcomes provide the basis for a proposed schema mode case conceptualization for SAD and are hoped to provide a rationale for testing the applicability of Schema Therapy as a novel treatment for SAD. Key limitations are discussed.


The enhancement of growth and differentiation of rat adrenal nerve cells by the addition of conditioned medium from human fibroblast cultures.
The growth of rat adrenal nerve cells was remarkably enhanced by supplementing the cultured medium from the human fibroblast cell line, Hs 68. Maximum specific growth rate and length of the neurites were observed as 0.076 (1/hr) and 0.026 mm, respectively in 20% supplement of five day old medium. In adding more than 20% of the cultured medium both cell and neurite growth was severely decreased. It was interesting that the cultured medium from Hs 68 cells could play a role in the extension of the neurites rather than in the growth of neurite cells. It was also found that molecules lower than 50,000 daltons in the conditioned medium could improve the growth of neurite bearing cells and the extension of the neurites than larger molecules. The efficacy of the proteins (<50,000 MW) was similar to that of human nerve growth factor and much better than that of basic fibroblast growth factor which was mainly secreted from human fibroblast cells.


Macrocyclic diterpenoids from the seeds of Euphorbia peplus with potential activity in inducing lysosomal biogenesis.
The first phytochemical investigation of the seeds of Euphorbia peplus led to the isolation and characterization of five new (1-5), named euphopepluanones A-E, and five known diterpenoids (6-10). Their structures were established by extensive spectroscopic analysis and X-ray crystallographic experiments. Euphopepluanones A-E (1-3) feature a very rare 5/11/5-tricyclic skeleton, and euphopepluanones D-E (4-5) represent the first report of lathyrane type diterpenoids found in E. peplus. The new compounds 1-5 were assessed for their activities to induce lysosomal biogenesis through LysoTracker Red staining, in which compounds 1 and 3 could significantly induce lysosomal biogenesis. In addition, compounds 1 and 3 could promote the nuclear translocation of TFEB, a master transcriptional factor of lysosomal genes, indicating that compounds 1 and 3 induced lysosomal biogenesis through activation of TFEB.


Extremely high levels of alkaline phosphatase and pregnancy outcome: case series and review of the literature.
To evaluate the association between extremely elevated alkaline phosphatase (ALKP) levels (above 1000 U/L) and adverse perinatal outcome. A retrospective case series of all parturients with extremely elevated ALKP levels taken throughout pregnancy at a single university-affiliated medical center (2010-2018). Demographics and medical data were retrieved. Following literature review, previously reported similar cases were added to the cohort. We report perinatal outcome of our cohort as well as literature review. During study period 11 parturients with high ALKP were identified. Ten more cases were retrieved from PubMed search. Overall, median ALKP levels were 1880 (range 1052-4488 U/L). Reasons for evaluation were mostly nonspecific symptoms (pruritus, headache, abdominal pain) or routine obstetrical evaluation. In 10/12 (83%) cases, elevated ALKP levels were of placental origin; the rest had osteal origin. Median gestational age at delivery was 38 (range 35-41); four (19%) women had preterm delivery. Six patients (29%) had gestational diabetes mellitus and six (29%) had hypertensive disorders. Histopathology of the placenta was available in eight cases: three normal histology (38%) and five with different non-specific pathologies. We report the largest case series of extremely elevated levels of ALKP in pregnancy thus far. Our data suggest association with adverse perinatal outcome.


Exploring patient satisfaction after operative and nonoperative treatment for midshaft clavicle fractures: a focus group analysis.
There is no consensus on the optimal treatment for displaced midshaft clavicle fractures. Several studies indicate superior patient satisfaction in favour of operative reconstruction. It is unknown what drives superior satisfaction in this treatment group. The aim of this study was to explore patient satisfaction and identify contributors to patient satisfaction after operative and nonoperative treatment for displaced midshaft clavicle fractures in adults using a focus group approach. Four face-to-face and two web-based focus groups were hosted. A total of 24 participants who were treated nonoperatively (n = 14) or operatively (n = 10) agreed to participate. Participants were selected using purposive sampling, ensuring variation in gender, age, treatment complications and outcomes. A question script was developed to systematically explore patient expectations, attitudes and satisfaction with different dimensions of care. All focus groups were voice-recorded and transcribed at verbatim. Thematic analysis was conducted on all face-to-face and web-based transcripts. The main emerging themes across treatment groups were; need for more information, functional recovery, speed of recovery and patient-doctor interaction. There was no difference in themes observed between operative and nonoperative focus groups. The lack of information was the most important complaint in dissatisfied patients. Our study shows that informing patients about their injury, treatment options and expectations for recovery is paramount for overall patient satisfaction after treatment for a displaced midshaft clavicle fracture. Level III, focus group study.


Measurement of relative motion of the brain and skull in the mini-pig in-vivo.
The mechanical role of the skull-brain interface is critical to the pathology of concussion and traumatic brain injury (TBI) and may evolve with age. Here we characterize the skull-brain interface in juvenile, female Yucatan mini-pigs from 3 to 6 months old using techniques from magnetic resonance elastography (MRE). The displacements of the skull and brain were measured by a motion-sensitive MR imaging sequence during low-amplitude harmonic motion of the head. Each animal was scanned four times at 1-month intervals. Harmonic motion at 100 Hz was excited by three different configurations of a jaw actuator in order to vary the direction of loading. Rigid-body linear motions of the brain and skull were similar, although brain rotations were consistently smaller than corresponding skull rotations. Relative displacements between the brain and skull were estimated for voxels on the surface of the brain. Amplitudes of relative displacements between skull and brain were 1-3 μm, approximately 25-50% of corresponding skull displacements. Maps of relative displacement showed variations by anatomical region, and the normal component of relative displacement was consistently 25-50% of the tangential component. These results illuminate the mechanics of the skull-brain interface in a gyrencephalic animal model relevant to human brain injury and development.


Novel 13C direct detection experiments, including extension to the third dimension, to perform the complete assignment of proteins.
Carbon-13 direct detection NMR methods are feasible thanks to the improvements in probehead technology and to the development of new NMR experiments. We present here a complete set of experiments, based on C' direct detection, developed to perform protein complete assignment of backbone and side-chains (except for aromatic rings). This strategy offers alternative solutions for demanding situations (paramagnetic and/or large molecules) and can be useful in general in conjunction with conventional experiments.


Neuroprotective effects of 2,4-dinitrophenol in an acute model of Parkinson's disease.
Neurons depend on mitochondria for homeostasis and survival, and thus, mitochondrial dysfunction has been implicated in neurodegenerative diseases, including Parkinson's disease (PD). Increasing evidence indicates the mitochondrial uncoupler, 2,4-dinitrophenol (DNP), protects neurons against neurodegeneration and enhances neural plasticity. Here, the authors evaluated the protective effects of intraperitoneally (i.p.) administered low dose DNP in an acute mouse model of PD. Mice were administered DNP (1 or 5mg/kg) for 12 consecutive days, and then on day 13, MPTP (20mg/kg, i.p.) was administered four times (with 2h intervals between injections) to induce PD. It was found that MPTP-induced motor dysfunction was ameliorated in the DNP-treated mice versus vehicle-treated controls. Additionally, DNP effectively attenuated dopaminergic neuronal loss observed in MPTP treated mice. Moreover, in primary cultured neurons, DNP at 10μM, but not at 100μM, prevented MPP+-induced cell death and mitochondrial membrane potential (MMP) reduction. In addition, DNP was observed to cause the nuclear translocation of Nrf2 in primary neurons. Taken together, these findings of the present study suggest that DNP protects dopaminergic neurons against neurodegeneration and maintains MMP integrity in PD by activating adaptive stress responses.


Optical micturition interval monitor for experimental animals.
In the past several years, overactive bladder and urinary incontinence have become recognized as an unmet therapeutic need. Some new pharmacologic treatments have recently been described, and new approaches are in development by a number of companies. For preclinical studies, accurate assessment of micturition patterns over a long period of time is important for successful new drug development. Current methodologies rely upon collecting urine in cups positioned upon force displacement transducers and either collecting very large digitized data files, or producing long polygraph tracings. The methodology described in this paper utilized an optical device consisting of an infrared photodiode and a matched phototransistor as an electronic drop counter. The device can monitor the appearance of urine flow as it exits the bottom of a metabolic cage. Because the device only collects data when there is an event, the resulting data files are significantly smaller, and there is no need to assure that the urine collection cups do not fill-up and overflow. Data were collected using both methodologies and the results compared. In every experiment, the data derived from the optical device were in very close agreement with the actual micturition pattern recorded by the cup-force transducer method. This optical method represents a simple and reliable technique for monitoring micturition patterns in experimental animals.


The Medical Emergency Team in Italy: an overview of in-hospital emergencies response.
Medical Emergency Team (MET), implemented in many hospitals worldwide, aims to improve the safety of in-hospital patients whose condition is deteriorating. This study describes MET presence and organization in the Italian National Healthcare System Hospitals. A national survey with an online questionnaire was performed. The questionnaire, created ad hoc, was sent by e-mail to the nursing coordinators and MET referents of the Hospitals affiliated to the Italian National Healthcare System with an Anesthesia and Intensive Care service. One hundred-ninety-seven hospitals were interviewed (36.2% of the whole national network). A dedicated MET, composed at least by an intensivist and a nurse, was present only in 118 cases (59.9%). The team was composed by a non-dedicated staff (67.8% of doctors, 69.5% of nurses) and a minimum shared standard of education for the nurse component was absent. One third of the estimated hospitals did not use a warning score for emergency call activation. This survey showed a heterogenous and often lacking organization of in-hospital emergency management in Italy. MET system needs to be implemented in terms of presence in the Italian hospitals, and standardized for personnel structure and training, and equipment availability. A broader study is necessary to compare our data with those of other European Countries to better identify the specific areas which need to be improved more promptly.


Association of interleukin-18 gene polymorphisms with the outcomes of hepatitis C virus infection in high-risk Chinese Han population.
Interleukin 18 (IL-18) gene polymorphisms have been reported to be associated with the outcomes of hepatitis C virus (HCV) infection in Americans, Indians and Europeans. We aimed to investigate whether the association can be replicated in Chinese Han population. Three IL-18 variants, -656G>T, -137G>C and +105A>C, were genotyped in three independent Han cohorts consisting of 552 cases and 784 controls. By using logistic regression analysis and multiple testing, haplotype GCC were associated with a protection from susceptibility to HCV. After stratified analysis, both the carriage of -137C allele in the older or hemodialysis subgroup and the carriage of +105C allele in the younger subgroup were found to be significantly associated with a decreased risk of HCV susceptibility. By using logistic regression analysis and multiple testing for the resolution of HCV infection, our study showed that +105C allele and haplotype GGC displayed a negative effect on HCV persistence. After stratified analysis, a significantly decreased risk for HCV persistence was found in +105C allele in the subgroups of young, male or female, drug user or hemodialysis and HCV-1 or HCV mixed genotype. No significant association was observed between -656G>T and the outcomes of HCV infection. Our results demonstrated that the carriage of -137C allele, +105C allele, haplotype -656G/-137C/+105C and haplotype -656G/-137G/+105C of IL-18 gene may contribute to better outcomes of HCV infection in high-risk Chinese Han population.


[Analysis of functional properties of biologically active substances using eukaryotic cell models (review)].
This work presents an analysis of current data on the investigation into the functional properties of biologically active substances in model systems based on cultivated human cells. The knowledge regarding the practical application of cell cultures for the analysis of functional properties of bioactive substances is summarized, including antioxidant, immunomodulating, pro- and prebiotics, and chemoprevention properties. The most promising directions in cell culture model development for the investigation of functional properties, including three-dimensional models, are discussed.


Early Onset of Rapid Lesion Growth in an Acute Subdural Hematoma Model in Rats.
Acute subdural hematoma (ASDH) leads to the highest mortality rates of all head injuries with secondary brain damage playing a pivotal role in terms of morbidity and mortality. In patients with ASDH, a delay in surgery leads to disproportional mortality. The benefit of (very) early therapy is therefore, a target of ongoing research. As the process of delayed brain damage in ASDH has not yet been described, this study therefore aimed to examine secondary lesion growth in an experimental rat model of ASDH to define the ideal timing for testing potential neuroprotective therapies. Cerebral blood flow was monitored during ASDH induction with 300 μl of autologous blood. Lesion growth was characterized using Hematoxylin-Eosin- , Cresyl-Violet-, and Fluoro-Jade B-staining for early signs of neuronal degeneration. Histological evaluations were performed between 15 minutes and 24 hours after ASDH. There was a significant reduction of cerebral blood flow after ASDH. Fluoro-Jade B-positive cells were visible 15 minutes after ASDH in the lesioned hemisphere. Nonlinear growth of lesion volume from 3.7 ± 0.4 mm3 to 17.5 ± 0.6 mm3 was observed at 24 hours in Hematoxylin-Eosin-staining. The most damage develops between 15 minutes and 1 hour and again between 2 and 6 hours after ASDH. The time course of lesion growth supports the approach of early surgery for patients. It furthermore constitutes a basis for further ASDH research with more clearly defined time windows for therapy in animal models.


Withdrawal syndrome after donepezil cessation in a patient with dementia.
We describe a 62-year-old female diagnosed with Alzheimer's disease, who had been treated with donepezil for approximately 1 year. When she developed a low-grade fever and digestive complaints, her family physician interpreted these symptoms as side effects of the drug and ordered donepezil to be discontinued. Not only was there no improvement of the somatic symptoms after discontinuation of donepezil, but there was also a worsening of the dementia symptoms, culminating in delirium. When donepezil was re-prescribed, the delirium resolved and the patient's mental state stabilized. The authors urge great caution in discontinuing treatment with acetylcholinesterase inhibitors such as donepezil.