Prenatal ethanol intoxication and maternal intubation stress alter cell survival and apoptosis in the postnatal development of rat hippocampus.
It is well known that the fetal ethanol exposure and prenatal stress may have adverse effects on brain development. Interestingly, some morphological and functional recovery from their teratogenic effects that take place during brain maturation. However, mechanisms that underlie this recovery are not fully elucidated. The aim of this study was to examine whether the postnatal attenuation of fetal alcohol - and maternal stress‑induced morphological and functional deficits correlates with compensatory changes in the expression/activation of the brain proteins involved in inflammation, cell survival and apoptosis. In this project, we investigated the hippocampus which belongs to the brain regions most susceptible to the adverse effects of prenatal ethanol exposure. Pregnant rat dams were administered ethanol (A) or isocaloric glucose solution (IC) by a gastric intubation during gestational days 7-20. The pure control group received ad libitum laboratory chow and water with no other treatment. The hippocampi of fetal-ethanol and control pups were examined at the postnatal day (PD)1, PD10, PD30 and PD60. Moderate fetal-ethanol exposure and prenatal intubation stress caused a significant increase in molecular factors relating to inflammation (iNOS) and cell survival/apoptosis pathways (PTEN, GSK-3 and ERK) at birth, with a rapid compensation from these developmental deficits upon removal of alcohol at PD10. Indeed, an increase in ERK1/2 and JNK1/2 activation at PD30 was observed with ethanol consumption. It indicates that the recovery process in A and IC brains started soon after the birth upon the ethanol and stressor withdrawal and continued until the adulthood.


Completion report: Effect of Comprehensive Yogic Breathing program on type 2 diabetes: A randomized control trial.
Yoga has been shown to be beneficial in diabetes in many studies, though randomized control trials are few. The aim of this randomized control trial was to see the effect of Sudarshan Kriya and related practices (comprehensive yogic breathing program) on quality of life, glycemic control, and cardiac autonomic functions in diabetes. Diabetes mellitus is a risk factor for sudden cardiac death. Cardiac autonomic neuropathy has been implicated in the causation of sudden cardiac death. Therefore, a maneuver to prevent progression of cardiac autonomic neuropathy holds significance. A total of 120 patients of diabetes on oral medication and diet and exercise advice were randomized into two groups: (1) Continued to receive standard treatment for diabetes. (2) Patients administered comprehensive yogic breathing program and monitored to regularly practice yoga in addition to standard treatment of diabetes. At 6 months, quality of life and postprandial plasma glucose significantly improved in the group practicing yoga compared to baseline, but there was no significant improvement in the fasting plasma glucose and glycated hemoglobin. On per protocol analysis, sympathetic cardiac autonomic functions significantly improved from baseline in the group practicing comprehensive yogic breathing. This randomized control trial points towards the beneficial effect of yogic breathing program in preventing progression of cardiac neuropathy. This has important implications as cardiac autonomic neuropathy has been considered as one of the factors for sudden cardiac deaths.


Life at the top: rank and stress in wild male baboons.
In social hierarchies, dominant individuals experience reproductive and health benefits, but the costs of social dominance remain a topic of debate. Prevailing hypotheses predict that higher-ranking males experience higher testosterone and glucocorticoid (stress hormone) levels than lower-ranking males when hierarchies are unstable but not otherwise. In this long-term study of rank-related stress in a natural population of savannah baboons (Papio cynocephalus), high-ranking males had higher testosterone and lower glucocorticoid levels than other males, regardless of hierarchy stability. The singular exception was for the highest-ranking (alpha) males, who exhibited both high testosterone and high glucocorticoid levels. In particular, alpha males exhibited much higher stress hormone levels than second-ranking (beta) males, suggesting that being at the very top may be more costly than previously thought.


Safety and Efficacy of Gamma Knife Radiosurgery for the Management of Koos Grade 4 Vestibular Schwannomas.
Gamma Knife radiosurgery (GKRS) is commonly used in treating small vestibular schwannomas; however, its use for larger vestibular schwannomas is still controversial. To assess the long-term safety and efficacy of treating eligible Koos grade 4 vestibular schwannomas with GKRS. We conducted a single-center, retrospective evaluation of patient undergoing GKRS for Koos grade 4 vestibular schwannomas. We evaluated clinical, imaging, and treatment characteristics and assessed treatment outcome. Inclusion criteria were tumor size of ≥4 cm and follow-up of at least 6 months. Patients with neurofibromatosis type 2 were excluded. Primary outcomes measured were tumor control rate, hearing and facial function preservation rate, and complications. All possible factors were analyzed to assess clinical significance. Sixty-eight patients met inclusion criteria. Median follow-up was 47 months (range, 6-125 months). Baseline hearing was serviceable in 60%. Median tumor volume at radiosurgery was 7.4 cm (range, 4-19 cm). The median marginal dose used was 12 Gy at the 50% isodose line. Actuarial tumor control rates were 95% and 92% at 2 and 10 years, respectively. Actuarial serviceable hearing preservation rates were 89% and 49% at 2 and 5 years, respectively. Facial nerve preservation was 100%. Clinical complications included balance disturbance (11%), facial pain (10%), facial numbness (5%), and tinnitus (10%). Most complications were mild and transient. Hydrocephalus occurred in 3 patients, requiring ventriculoperitoneal shunt insertion. Larger tumor size was significantly associated with persisting symptoms post-treatment. Patients with Koos grade 4 vestibular schwannomas and minimal symptoms can be treated safely and effectively with GKRS.


Temporal Coherence Strategies for Augmented Reality Labeling.
Temporal coherence of annotations is an important factor in augmented reality user interfaces and for information visualization. In this paper, we empirically evaluate four different techniques for annotation. Based on these findings, we follow up with subjective evaluations in a second experiment. Results show that presenting annotations in object space or image space leads to a significant difference in task performance. Furthermore, there is a significant interaction between rendering space and update frequency of annotations. Participants improve significantly in locating annotations, when annotations are presented in object space, and view management update rate is limited. In a follow-up experiment, participants appear to be more satisfied with limited update rate in comparison to a continuous update rate of the view management system.


Clostridium leptum group bacteria abundance and diversity in the fecal microbiota of patients with inflammatory bowel disease: a case-control study in India.
Alterations in the fecal bacterial flora occur in inflammatory bowel disease (IBD). We examined the abundance and diversity of Clostridium leptum group, an important group of carbohydrate-fermenting bacteria, in the feces of patients with IBD and compared them with healthy controls. Seventeen healthy controls (HC), 20 patients with Crohn's disease (CD) and 22 patients with ulcerative colitis (UC) participated in the study. DNA extracted from fecal samples was amplified by PCR targeting 16S rRNA gene sequences specific to C. leptum group. The PCR product was subjected to temporal temperature gradient electrophoresis (TTGE) and the number and position of individual bands were noted and diversity was estimated. The identity of bands at different positions was confirmed by cloning and sequencing. Real time quantitative PCR with Mesa Green, targeted at specific 16S rRNA gene sequences, was used to quantitate C. leptum group and its most prominent constituent, Faecalibacterium prausnitzii. Twenty five different operational taxonomic units (OTUs, equivalent to species) were identified constituting the C. leptum group in these participants. Their sequences were deposited in GenBank [accession numbers GQ465348 to GQ465370]. OTU number was significantly reduced in CD (7.7 ± 3.7, mean ± SD) and UC (9.0 ± 3.0) compared to HC (11.9 ± 2.2) (P=0.0005). The Simpson D index of alpha diversity was not significantly different between the three groups. Total numbers of C. leptum group bacteria and F. prausnitzii were reduced in both CD and UC compared to HC (P=0.0036 and P<0.0001 respectively). Disease activity did not influence numbers of C. leptum or F. prausnitzii in patients with CD or UC. C. leptum numbers and diversity were significantly reduced in both CD and UC suggesting that alterations noted were not specific to one disease. This could contribute to reduced short chain fatty acid production in IBD.


Keratoconjunctival effects of diabetes mellitus in dogs.
To compare Schirmer tear test (STT) values, corneal sensitivity, tear film break up times (TFBUTs), and tear glucose concentrations in relation to conjunctival microflora, and conjunctival cytologic and histologic findings among diabetic cataractous, nondiabetic cataractous, and nondiabetic noncataractous dogs. Procedures Fifteen dogs in each category underwent neuro-ophthalmic examination; aerobic, anaerobic and fungal conjunctival cultures; assessment of corneal touch threshold (CTT), STT, tear glucose, TFBUT; and conjunctival cytology and histology (in certain cases only). Degree of cataract and uveitis were critically graded. Glycemic control was estimated using serum fructosamine and glycosylated hemoglobin. STT values were significantly lower in diabetic cataractous than nondiabetic noncataractous dogs. CTT of diabetic cataractous dogs was significantly lower than that of nondiabetic noncataractous dogs. Mean TFBUTs were significantly less in diabetic cataractous dogs than nondiabetic cataractous and nondiabetic noncataractous dogs. Tear glucose concentrations were significantly higher in diabetic cataractous dogs than nondiabetic cataractous and nondiabetic noncataractous dogs. Conjunctival microbial isolates did not differ among groups. There were no significant differences in degree of cataract or uveitis between diabetic cataractous and nondiabetic cataractous groups. There was mild submucosal inflammatory infiltrate in conjunctival specimens from diabetic dogs. Conjunctival epithelial dysplasia and/or squamous metaplasia was/were detected in conjunctival biopsies of 5/7 diabetic dogs. Reductions in conjunctival goblet cell (GC) densities were noted in 4/7 diabetic dogs; there were no significant differences in mean GC densities among the three groups. Diabetic cataractous dogs have significantly altered keratoconjunctival characteristics compared to nondiabetic cataractous and nondiabetic noncataractous dogs.


Primary and secondary prevention of stroke and systemic embolism with rivaroxaban in patients with non-valvular atrial fibrillation : Sub-analysis of the EXPAND Study.
The EXPAND Study examined the real-world efficacy and safety of rivaroxaban for the prevention of stroke and systemic embolism (SE) in Japanese patients with non-valvular atrial fibrillation (NVAF). In this sub-analysis, we compared the differences in efficacy and safety between patients with and those without history of stroke or transient ischemic attack (TIA). This multicenter, prospective, non-interventional, observational, cohort study was conducted at 684 medical centers in Japan. A total of 7141 NVAF patients aged ≥ 20 years [mean age 71.6 ± 9.4 (SD) years] who were being or planned to be treated with rivaroxaban (10 mg/day, 43.5%; 15 mg/day, 56.5%) were followed for a mean period of 897.1 ± 206.8 days with a high follow-up rate (99.7%). The primary prevention group comprised patients without history of ischemic stroke or TIA (n = 5546, 77.7%), and the secondary prevention group comprised those with history of ischemic stroke or TIA (n = 1595, 22.3%). In the primary and secondary prevention groups, the incidence rate of stroke or SE (primary efficacy endpoint) was 0.7 and 2.2%/year, respectively (P < 0.001), and the incidence rate of major bleeding (primary safety endpoint) was 1.2 and 1.5%/year, respectively (P = 0.132). For major bleeding events, the incidence rate of intracranial bleeding was 0.4 and 0.8%/year (P = 0.002) in the primary and secondary prevention groups, respectively. This sub-analysis of the EXPAND Study showed that the Japan-specific dosages of rivaroxaban were effective and safe in Japanese NVAF patients with and those without ischemic stroke or TIA in routine clinical practice.


Change in brain volume and cortical thickness after behavioral and surgical weight loss intervention.
Obesity is associated with reduced cortical thickness and brain volume, which may be related to poor nutrition. Given that brain atrophy in anorexia nervosa recovers with nutritional improvements and weight gain, it is worth examining how brain structure changes at the other end of the weight spectrum with weight loss. Thus, this study aimed to examine change in cortical thickness and brain volume in 47 patients with severe obesity who participated in no treatment, behavioral weight loss, or bariatric surgery. T1-weighted MRI scans were conducted pre-treatment and approximately four months later. Measures of cortical thickness, gray matter volume, and white matter volume were compared between time points. Despite overall reduction in BMI, there was no significant change in cortical thickness. There was a significant increase in left hemisphere gray matter and white matter volumes across the sample. At baseline and follow-up, there was no relationship between cortical thickness or brain volumes and BMI. This study is the first to examine changes in cortical thickness and brain volume with weight loss in adults with obesity and the findings show partial support for the hypotheses that weight loss results in increased cortical gray and white matter.


Lipoprotein LptE is required for the assembly of LptD by the beta-barrel assembly machine in the outer membrane of Escherichia coli.
Most Gram-negative bacteria contain lipopolysaccharide (LPS), a glucosamine-based phospholipid, in the outer leaflet of the outer membrane (OM). LPS is unique to the bacterial OM and, in most cases, essential for cell viability. Transport of LPS from its site of synthesis to the cell surface requires eight essential proteins, MsbA and LptABCDEFG. Although the key players have been identified, the mechanism of LPS transport and assembly is not clear. The stable LptD/E complex is present at the OM and functions in the final stages of LPS assembly. Here, we have identified the mutant allele lptE6, which causes a two-amino-acid deletion in the lipoprotein LptE that affects its interaction with LptD. Highly specific suppressor mutations were isolated not only in lptD but also in bamA, which encodes the central component of the β-barrel assembly machine. We show that lptE6 and both suppressor mutations affect the assembly of the LptD/E complex and suggest that the lipoprotein LptE interacts with LptD while this protein is being assembled by the β-barrel assembly machine.


Long-Term Mechanical Insufflation-Exsufflation Cough Assistance in Neuromuscular Disease: Patterns of Use and Lessons for Application.
Mechanical insufflation-exsufflation (MI-E) devices increase expiratory air flow and thereby promote increased cough peak flow (CPF) in conjunction with a cough. There is little research looking at long-term use of MI-E in subjects with neuromuscular disease (NMD), and no long-term study has reported CPF, MI-E device settings, and adherence. We evaluated 181 patient records (130 adults, 51 children) of individuals who received a MI-E device from our center between February 2014 and February 2018. Median age (interquartile range [IQR]) was 27 (14-51) y. Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA), and amyotrophic lateral sclerosis (ALS) were the 3 most common diagnoses. MI-E devices were provided to the weakest subjects with a CPF < 160 L/min. Median (IQR) settings were insufflation, 25 (23-30) cm H2O, exsufflation -35 (-30 to -40) cm H2O, insufflation time 1.5 (1.3-1.7) s, exsufflation time 1.8 (1.5-2.0) s, and pause 1.5 (1.3-2.0) s. The inspiratory flow profile was set to high in all subjects, and no subject used supplemental oxygen with the MI-E device. When comparing insufflation pressures to exsufflation pressures, a greater negative pressure was used relative to positive pressure (P < .001). When comparing insufflation to exsufflation time, there was a significantly longer exsufflation duration (P < .001). Median (IQR) CPF at the start of MI-E was 60 (10-100) L/min. There was no correlation between either insufflation or exsufflation pressures and CPF. Median (IQR) usage for the group was 60% (13.5-100%) of days for the total days. Subjects with tracheostomies or SMA type I had the greatest adherence to treatment. Median (IQR) duration of MI-E use was 17 (8.5-32) months. Ninety-six percent of subjects were receiving ventilatory support. Greater exsufflation pressures than insufflation pressures, together with a shorter insufflation time than exsufflation time, were used. Predicting good adherence among the subjects was difficult. Subjects who produced daily secretions were more likely to use MI-E every day.


Targeted transgenic expression of an osteoclastic transmembrane protein-tyrosine phosphatase in cells of osteoclastic lineage increases bone resorption and bone loss in male young adult mice.
This study evaluated whether transgenic expression of PTP-oc (osteoclastic transmembrane protein-tyrosine phosphatase) in cells of the osteoclast lineage would affect bone resorption and bone density in young adult mice. Transgenic mice were generated with a transgenic construct using a tartrate-resistant acid phosphatase exon 1C promoter to drive expression of rabbit PTP-oc in osteoclastic cells. pQCT evaluation of femurs of young adult male progeny of three lines showed that transgenic mice had reduced bone volume and area, cortical and trabecular bone mineral content, and density. Histomorphometric analyses at secondary spongiosa of the femur and at metaphysis of the L4 vertebra confirmed that male transgenic mice had decreased trabecular surface, reduced percentage of trabecular area, decreased trabecular number, increased trabecular separation, and increased osteoclast number per bone surface length. Consistent with an increase in bone resorption, the serum C-telopeptide level was 25% higher in transgenic mice than in wild-type littermates. However, the bone phenotype was not readily observed in female young adult transgenic mice. This could in part be due to potential interactions between estrogen and PTP-oc signaling, since the bone loss phenotype was seen in young adult ovariectomized transgenic mice by microcomputed tomography analysis. In vitro, the average pit area per resorption pit created by marrow-derived transgenic osteoclasts was approximately 50% greater than that created by wild-type osteoclasts. Transgenic osteoclasts showed a lower c-Src phosphotyrosine 527 level, greater c-Src kinase activity, and increased tyrosine phosphorylation of paxillin. In summary, this study provides compelling in vivo evidence that PTP-oc is a positive regulator of osteoclasts.


Informing the Tolerability of Cancer Treatments Using Patient-Reported Outcome Measures: Summary of an FDA and Critical Path Institute Workshop.
The US Food and Drug Administration and the Critical Path Institute's Patient-Reported Outcome (PRO) Consortium convened a cosponsored workshop on the use of PRO measures to inform the assessment of safety and tolerability in cancer clinical trials. A broad array of international stakeholders involved in oncology drug development and PRO measurement science provided perspectives on the role of PRO measures to provide complementary clinical data on the symptomatic side effects of anticancer agents. Speakers and panelists explored the utility of information derived from existing and emerging PRO measures, focusing on the PRO version of the National Cancer Institute's Common Terminology Criteria for Adverse Events. Panelists and speakers discussed potential ways to improve the collection, analysis, and presentation of PRO data describing symptomatic adverse events to support drug development and better inform regulatory and treatment decisions. Workshop participants concluded the day with a discussion of possible approaches to the patient-reported assessment of an investigational drug's overall side effect burden as a potential clinical trial end point. The Food and Drug Administration reiterated its commitment to collaborate with international drug development stakeholders to identify rigorous methods to incorporate the patient perspective into the development of cancer therapeutics.


Exploratory modeling and simulation to support development of motesanib in Asian patients with non-small cell lung cancer based on MONET1 study results.
The motesanib phase III MONET1 study failed to show improvement in overall survival (OS) in non-small cell lung cancer, but a subpopulation of Asian patients had a favorable outcome. We performed exploratory modeling and simulations based on MONET1 data to support further development of motesanib in Asian patients. A model-based estimate of time to tumor growth was the best of tested tumor size response metrics in a multivariate OS model (P < 0.00001) to capture treatment effect (hazard ratio, HR) in Asian patients. Significant independent prognostic factors for OS were baseline tumor size (P < 0.0001), smoking history (P < 0.0001), and ethnicity (P < 0.00001). The model successfully predicted OS distributions and HR in the full population and in Asian patients. Simulations indicated that a phase III study in 500 Asian patients would exceed 80% power to confirm superior efficacy of motesanib combination therapy (expected HR: 0.74), suggesting that motesanib combination therapy may benefit Asian patients.


Nasal glioma.
Nasal gliomas are uncommon congenital lesions arising from abnormal embryonic development. Clinically, these masses are firm and incompressible. Histologically, they are made up of astrocytes and neuroglial cells, embedded in fibrous and vascular connective tissue. Proper management of a nasal glioma requires a multidisciplinary approach including an otorhinolaryngologist, radiologist, and neurosurgeon. Radiological investigations such as computed tomography or magnetic resonance imaging should be performed to exclude intracranial extension. The mainstay of treatment is conservative surgical excision because nasal gliomas are slow-growing, rarely recurrent, and have no malignant potential. We report one case of nasal glioma in a Chinese infant. He had an uncomplicated surgical intervention with a good cosmetic result. A review of the clinical features of and diagnostic approach to nasal gliomas is also presented.


Development of intraoperative electrochemical detection: wireless instantaneous neurochemical concentration sensor for deep brain stimulation feedback.
Deep brain stimulation (DBS) is effective when there appears to be a distortion in the complex neurochemical circuitry of the brain. Currently, the mechanism of DBS is incompletely understood; however, it has been hypothesized that DBS evokes release of neurochemicals. Well-established chemical detection systems such as microdialysis and mass spectrometry are impractical if one is assessing changes that are happening on a second-to-second time scale or for chronically used implanted recordings, as would be required for DBS feedback. Electrochemical detection techniques such as fast-scan cyclic voltammetry (FSCV) and amperometry have until recently remained in the realm of basic science; however, it is enticing to apply these powerful recording technologies to clinical and translational applications. The Wireless Instantaneous Neurochemical Concentration Sensor (WINCS) currently is a research device designed for human use capable of in vivo FSCV and amperometry, sampling at subsecond time resolution. In this paper, the authors review recent advances in this electrochemical application to DBS technologies. The WINCS can detect dopamine, adenosine, and serotonin by FSCV. For example, FSCV is capable of detecting dopamine in the caudate evoked by stimulation of the subthalamic nucleus/substantia nigra in pig and rat models of DBS. It is further capable of detecting dopamine by amperometry and, when used with enzyme linked sensors, both glutamate and adenosine. In conclusion, WINCS is a highly versatile instrument that allows near real-time (millisecond) detection of neurochemicals important to DBS research. In the future, the neurochemical changes detected using WINCS may be important as surrogate markers for proper DBS placement as well as the sensor component for a "smart" DBS system with electrochemical feedback that allows automatic modulation of stimulation parameters. Current work is under way to establish WINCS use in humans.


The multi-dimensional nature of active coping: differential effects of effort and enhanced control on cardiovascular reactivity.
Some studies show that enhanced control increases cardiovascular reactivity; other studies show decreases. This disparity may be due to a confound: enhanced control may reduce reactivity, but effort accompanying active coping may increase it. The present study was designed to vary level of control and availability of active coping responses, while maintaining effort constant. Sixty female undergraduates performed word-search puzzles while blood pressure and heart rate were monitored. They were divided into three groups: In condition 1, reinforcement was contingent on the subjects' performance only; in conditions 2 and 3, reinforcement was contingent on the joint performance of the subject and a poorly performing confederate. In condition 2, subjects could help their partners (active coping); in condition 3, they could not (passive coping). Effort was constant across groups. Cardiovascular responses were significantly greater in the passive coping condition than in the other two, indicating that with effort held constant, enhanced control diminishes reactivity.


Elevation of serum triacylglycerol concentration in association with hepatic microsomal enzyme induction after treatment with phenylbutazone and diclofenac sodium in rats.
1. The relationship between serum triacylglycerol concentration and hepatic microsomal enzyme activity was examined in rats. 2. Two groups of rats were injected with diclofenac sodium at doses of 2.5 and 5 mg day-1 kg-1. A third group was injected with phenylbutazone at a dose of 20 mg day-1 kg-1. The treatment was continued for 15 days and the rats were killed 24 h after the last dose. 3. In all drug-treated rats, the serum triacylglycerol concentration and the hepatic microsomal activities of aminopyrine N-demethylase and aniline hydroxylase were significantly increased as compared with the corresponding values in control rats. The correlations between the serum triacylglycerol concentrations and the activities of the two enzymes, as indices of the hepatic microsomal activity, were highly significant. 4. These results indicate that the possibility of hypertriglyceridaemia as an adverse effect of the induction of the hepatic microsomal enzymes after the administration of phenylbutazone and diclofenac sodium should be considered.


Characteristics of the iodide/triiodide redox mediator in dye-sensitized solar cells.
Dye-sensitized solar cells (DSCs) have gained widespread interest because of their potential for low-cost solar energy conversion. Currently, the certified record efficiency of these solar cells is 11.1%, and measurements of their durability and stability suggest lifetimes exceeding 10 years under operational conditions. The DSC is a photoelectrochemical system: a monolayer of sensitizing dye is adsorbed onto a mesoporous TiO(2) electrode, and the electrode is sandwiched together with a counter electrode. An electrolyte containing a redox couple fills the gap between the electrodes. The redox couple is a key component of the DSC. The reduced part of the couple regenerates the photo-oxidized dye. The formed oxidized species diffuses to the counter electrode, where it is reduced. The photovoltage of the device depends on the redox couple because it sets the electrochemical potential at the counter electrode. The redox couple also affects the electrochemical potential of the TiO(2) electrode through the recombination kinetics between electrons in TiO(2) and oxidized redox species. This Account focuses on the special properties of the iodide/triiodide (I(-)/I(3)(-)) redox couple in dye-sensitized solar cells. It has been the preferred redox couple since the beginning of DSC development and still yields the most stable and efficient DSCs. Overall, the iodide/triiodide couple has good solubility, does not absorb too much light, has a suitable redox potential, and provides rapid dye regeneration. But what distinguishes I(-)/I(3)(-) from most redox mediators is the very slow recombination kinetics between electrons in TiO(2) and the oxidized part of the redox couple, triiodide. Certain dyes adsorbed at TiO(2) catalyze this recombination reaction, presumably by binding iodine or triiodide. The standard potential of the iodide/triiodide redox couple is 0.35 V (versus the normal hydrogen electrode, NHE), and the oxidation potential of the standard DSC-sensitizer (Ru(dcbpy)(2)(NCS)(2)) is 1.1 V. The driving force for reduction of oxidized dye is therefore as large as 0.75 V. This process leads to the largest internal potential loss in DSC devices. We expect that overall efficiencies above 15% might be achieved if half of this internal potential loss could be gained. The regeneration of oxidized dye with iodide leads to the formation of the diiodide radical (I(2)(-*)). The redox potential of the I(2)(-*)/I(-) couple must therefore be considered when determining the actual driving force for dye regeneration. The formed I(2)(-*) disproportionates to I(3)(-) and I(-), which leads to a large loss in potential energy.


Disinfection by-products exposure and intra-uterine growth restriction: Do genetic polymorphisms of CYP2E1or deletion of GSTM1 or GSTT1 modify the association?
Exposure to disinfection by-products (DBPs) during pregnancy was associated with reduced foetal growth. Genetic susceptibility might play a role, especially for genes encoding for the Cytochrome P450 (CYP2E1) and Glutathione S-Transferase (GST) enzymes, involved in metabolism and activation of DBPs. Few epidemiological studies evaluated these gene-environment interactions and their results were never replicated. This study aims to examine interactions between trihalomethanes (THM) or haloacetic acids (HAA) exposure and genetic polymorphisms on small for gestational age (SGA) neonates by investigating single nucleotide polymorphisms (SNPs) in CYP2E1 gene and GSTM1 and GSTT1 deletions in mothers-children pairs. A population-based case-control study of 1549 mothers and 1455 children was conducted on SGA and THM/HAA exposure. DNA was extracted from blood or saliva cells. Targeted SNPs and deletions were genotyped. Statistical interaction between SNPs/deletions and THMs or HAAs in utero exposure with regard to SGA occurrence was evaluated by unconditional logistic regression with control of potential confounders. Previously reported positive modification of the effect of THM uterine exposure by mothers or newborns CYP2E1 rs3813867 C allele or GSTM1 deletion was not replicated. However interactions with CYP2E1 rs117618383 and rs2515641 were observed but were not statistically significant after correction for multiple testing. Previous positive interactions between THMs exposure and CYP2E1 and GSTM1 were not replicated but interactions with other CYP2E1 polymorphisms are reported.


Antioxidative dietary compounds modulate gene expression associated with apoptosis, DNA repair, inhibition of cell proliferation and migration.
Many dietary compounds are known to have health benefits owing to their antioxidative and anti-inflammatory properties. To determine the molecular mechanism of these food-derived compounds, we analyzed their effect on various genes related to cell apoptosis, DNA damage and repair, oxidation and inflammation using in vitro cell culture assays. This review further tests the hypothesis proposed previously that downstream products of COX-2 (cyclooxygenase-2) called electrophilic oxo-derivatives induce antioxidant responsive elements (ARE), which leads to cell proliferation under antioxidative conditions. Our findings support this hypothesis and show that cell proliferation was inhibited when COX-2 was down-regulated by polyphenols and polysaccharides. Flattened macrophage morphology was also observed following the induction of cytokine production by polysaccharides extracted from viili, a traditional Nordic fermented dairy product. Coix lacryma-jobi (coix) polysaccharides were found to reduce mitochondrial membrane potential and induce caspase-3- and 9-mediated apoptosis. In contrast, polyphenols from blueberries were involved in the ultraviolet-activated p53/Gadd45/MDM2 DNA repair system by restoring the cell membrane potential. Inhibition of hypoxia-inducible factor-1 by saponin extracts of ginsenoside (Ginsen) and Gynostemma and inhibition of S100A4 by coix polysaccharides inhibited cancer cell migration and invasion. These observations suggest that antioxidants and changes in cell membrane potential are the major driving forces that transfer signals through the cell membrane into the cytosol and nucleus, triggering gene expression, changes in cell proliferation and the induction of apoptosis or DNA repair.


Regulation of proliferation and Ras localization in transformed cells by products of mevalonate metabolism.
Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl (HMG) CoA reductase, and 6-fluoromevalonate (Fmev), an inhibitor of diphosphomevalonate decarboxylase, blocked the synthesis of downstream mevalonate products, including prenyl-derived lipids, and prevented membrane localization of Ras in the myeloid cell line U-937. In contrast to lovastatin, which induced cytosol localization of Ras in U-937 cells, Fmev failed to increase cytosolic Ras and also completely prevented the proliferation of U-937 cells. Growth of U-937 cells was restored by the addition of lovastatin to Fmev-blocked cells. These results implied that a product of mevalonate metabolism proximal to isopentenyl diphosphate was responsible for the suppression of proliferation. To delineate the action of this endogenous inhibitor of cell proliferation and determine the relationship between its impact on Ras localization and cell proliferation, the effect of Fmev on a variety of leukemia- and lymphoma-derived cells was examined. Whereas Fmev blocked the growth of these cell lines, there were more than 50-fold differences in the concentrations required to inhibit the growth of individual cell lines by 90%. Regardless of its effect on cell proliferation, the biochemical effect of Fmev was similar. Thus, Fmev uniformly prevented the conversion of radiolabeled mevalonate to isopentenyl diphosphate and other downstream products, including synthesis of sterol and nonsterol lipids and prenylation of proteins. A correlation was noted between higher intrinsic rates of mevalonate synthesis by a cell and susceptibility to inhibition by Fmev. Thus, sensitivity of a cell line to inhibition by Fmev was associated with markedly increased rates of HMG CoA reductase activity that were further increased by incubation with Fmev. Whereas Fmev depleted cellular levels of the prenylated protein Ras in the sensitive cell line U-937, there was no depletion of cellular Ras levels in the resistant cell line EL-4, but rather, there was a shift of Ras from membrane to cytosol, as expected for inhibition of prenylation. These results suggest that leukemic cells with increased HMG CoA reductase activity produce increased levels of an endogenous mevalonate-derived inhibitor that leads to Ras depletion and suppression of cell growth. As a result, inhibition of the growth of these transformed cells might be specifically accomplished by Fmev.


Initial T cell frequency dictates memory CD8+ T cell lineage commitment.
Memory T cells can be divided into central memory T cell (T(CM) cell) and effector memory T cell (T(EM) cell) subsets based on homing characteristics and effector functions. Whether T(EM) and T(CM) cells represent interconnected or distinct lineages is unclear, although the present paradigm suggests that T(EM) and T(CM) cells follow a linear differentiation pathway from naive T cells to effector T cells to T(EM) cells to T(CM) cells. We show here that naive T cell precursor frequency profoundly influenced the pathway along which CD8+ memory T cells developed. At low precursor frequency, those T(EM) cells generated represented a stable cell lineage that failed to further differentiate into T(CM) cells. These findings do not adhere to the present dogma regarding memory T cell generation and provide a means for identifying factors controlling memory T cell lineage commitment.


Management of exposed pacemaker caused by burns.
Annual implants of cardiovascular implantable devices (CIEDs) are increasing, thus increasing the risk of device exposure. This case presents CIED management issues following traumatic thermal injury. A 59-year-old female presented to intensive care with 42% total body surface area burn involving tissue over her pacemaker generator. Electrophysiologists interrogated and reprogrammed the pacer and observed the patient over 72 hours without pacing. Serratia bacteremia developed and cardiology recommended device removal. The pacemaker generator and leads were removed by cardiothoracic and burn surgery. Postoperatively, asystole required emergency transvenous pacing wire placement. During bacteremia treatment, cardiology planned to pace with an active-fixation screw-in lead with long-term plans to place a single right ventricular chamber leadless pacemaker because of the extensive burns. The patient developed fungemia and the family opted for comfort care. This case report discusses the management of a CIED exposed after a traumatic thermal burn, including device extraction.


Paradoxical effect of obesity on hemorrhagic transformation after acute ischemic stroke.
Among the patients with established coronary artery diseases, obese patients tend to have a more favorable prognosis, which is called as obesity paradox. Interestingly, mildly obese patients who underwent coronary revascularization had a lower risk of bleeding. In this context, we have investigated the association between obesity and hemorrhagic transformation (HTf) after acute ischemic stroke. A total of 365 patients with first-ever acute ischemic stroke were included in this study. Demographic, clinical and radiological information was collected and HTf was evaluated through follow-up T2*-weighted gradient-recalled echo MRI performed usually within 1 week after occurrence of stroke. Body mass index was calculated, and obesity was defined using the World Health Organization Western Pacific Regional Office criteria. The HTf was identified in 59 patients (16.2%). As the severity of obesity increased, the occurrence of HTf decreased. Compared with the normal weight group and after controlling possible confounders including acute and previous treatment, stroke severity and subtype, the risk of HTf decreased significantly in the obese group (odds ratio, 0.39; 95% confidence interval, 0.17-0.87). The better outcome for HTf seen in obese patients suggests the existence of a "bleeding-obesity paradox" in acute ischemic stroke.


A wheat homologue of PHYTOCLOCK 1 is a candidate gene conferring the early heading phenotype to einkorn wheat.
An X-ray mutant showing an early flowering phenotype has been identified in einkorn wheat (Triticum monococcum L.), for which a major QTL for heading time was previously mapped in the telomeric region on the long arm of chromosome 3A. Recent advances in Triticeae genomics revealed that the gene order in this region is highly conserved between wheat and barley. Thus, we adopted a hypothetical gene order in barley, the so-called GenomeZipper, to develop DNA markers for fine mapping the target gene in wheat. We identified three genes tightly linked to the early heading phenotype. PCR analysis revealed that early-flowering is associated with the deletion of two genes in the mutant. Of the two deleted genes, one is an ortholog of the LUX ARRHYTHMO (LUX)/PHYTOCLOCK 1 (PCL1) gene found in Arabidopsis, which regulates the circadian clock and flowering time. We found distorted expression patterns of two clock genes (TOC1 and LHY) in the einkorn pcl1 deletion mutant as was reported for the Arabidopsis lux mutant. Transcript accumulation levels of photoperiod-response related genes, a photoperiod sensitivity gene (Ppd-1) and two wheat CONSTANS-like genes (WCO1 and TaHd1), were significantly higher in the einkorn wheat mutant. In addition, transcripts of the wheat florigen gene (WFT) accumulated temporally under short-day conditions in the einkorn wheat mutant. These results suggest that deletion of WPCL1 leads to abnormally higher expression of Ppd-1, resulting in the accumulation of WFT transcripts that triggers flowering even under short-day conditions. Our observations from gene mapping, gene deletions, and expression levels of flowering related genes strongly suggest that WPCL1 is the most likely candidate gene for controlling the early flowering phenotype in the einkorn wheat mutant.


A qualitative evaluation of occupational therapy-led work rehabilitation for people with inflammatory arthritis: Patients' views.
This qualitative study, nested in a pilot feasibility randomised controlled trial, explored the views of working people with inflammatory arthritis on the impact of a work rehabilitation programme received. Thirty-two participants, drawn from the 55 participants in the associated randomised controlled trial, were recruited from secondary care in the United Kingdom. Semi-structured telephone and face-to-face interviews were conducted at six (n = 32) and nine months follow-up (n = 31). Interviews were audio-recorded, transcribed, and analysed using a constant comparative approach, under the theoretical framework of critical realism. Three overarching themes emerged: (1) intervention group participants valued the work rehabilitation programme received, and highlighted the benefits of occupational therapy; (2) control group participants reported no benefits in relation to the written work advice pack, and lacked future aspirations to stay employed; (3) the majority of participants reported not reading the written work advice pack provided, which was the only work advice received by the control group. Working people with inflammatory arthritis highly valued the practical support received from the therapists, and emphasised the value of the therapeutic relationship in the rehabilitation process. A tailor-made work rehabilitation programme, which incorporates cognitive-behavioural strategies into patient education, may help to reduce work instability in people with inflammatory arthritis, and increase their perceived self-efficacy.


Tracking echovirus eleven outbreaks in Guangdong, China: a metatranscriptomic, phylogenetic, and epidemiological study.
In April 2019, a suspect cluster of enterovirus cases was reported in a neonatology department in Guangdong, China, resulting in five deaths. We aimed to investigate the pathogen profiles in fatal cases, the circulation and transmission pattern of the viruses by combining metatranscriptomic, phylogenetic, and epidemiological analyses. Metatranscriptomic sequencing was used to characterize the enteroviruses. Clinical and environmental surveillance in the local population was performed to understand the prevalence and genetic diversity of the viruses in the local population. The possible source(s), evolution, transmission, and recombination of the viruses were investigated by incorporating genomes from the current outbreak, from local retrospective surveillance, and from public databases. Metatranscriptomic analysis identified Echovirus 11 (E11) in three fatal cases. Seroprevalence of neutralization antibody to E11 was 35 to 44 per cent in 3-15 age groups of general population, and the viruses were associated with various clinical symptoms. From the viral phylogeny, nosocomial transmissions were identified and all E11 2019 outbreak strains were closely related with E11 strains circulating in local population 2017-19. Frequent recombination occurred among the 2019 Guangdong E11 outbreak strains and various genotypes in enterovirus B species. This study provides an example of combining advanced genetic technology and epidemiological surveillance in pathogen diagnosis, source(s), and transmission tracing during an infectious disease outbreak. The result highlights the hidden E11 circulation and the risk of viral transmission and infection in the young age population in China. Frequent recombination between Guangdong-like strains and other enterovirus genotypes also implies the prevalence of these emerging E11 strains.


Evaluation of Implementation of Intermittent Screening and Treatment for Control of Malaria in Pregnancy in Jharkhand, India.
This study evaluated intermittent screening and treatment during pregnancy (ISTp) for malaria using rapid diagnostic tests (RDTs) at antenatal care (ANC) compared with passive case detection within the routine health system. The mixed-method evaluation included two cross-sectional household surveys (pre- and post-implementation of ISTp), in-depth interviews with health workers, and focus group discussions (FGDs) with pregnant women. Differences in proportions between surveys for a number of outcomes were tested; 553 and 534 current and recently pregnant women were surveyed (pre- and post-implementation, respectively). In-depth interviews were conducted with 29 health providers, and 13 FGDs were held with pregnant women. The proportion of pregnant women who received an RDT for malaria at ANC at least once during their pregnancy increased from pre- to post-implementation (19.2%; 95% CI: 14.9, 24.3 versus 42.5%; 95% CI: 36.6, 48.7; P < 0.0001), and the proportion of women who had more than one RDT also increased (16.5%; 95% CI: 13.1, 20.5 versus 27.7%; 95% CI: 23.0, 33.0; P = 0.0008). Post-implementation, however, only 8% of women who had completed their pregnancy received an RDT on three visits to ANC. Health workers were positive about ISTp mainly because of their perception that many pregnant women with malaria were asymptomatic. Health workers perceived pregnant women to have reservations about ISTp because of their dislike of frequent blood withdrawal, but pregnant women themselves were more positive. Intermittent screening and treatment during pregnancy was not sufficiently adopted by health workers to ensure the increased detection of malaria infections achievable with this strategy in this setting.


The risk of penetration or aspiration during videofluoroscopic examination of swallowing varies depending on food types.
Videofluoroscopic examination of swallowing (VF) is the gold standard in diagnosis and management of dysphagia. During VF, the patient ingests radiopaque foods and liquids, and oral, pharyngeal, and esophageal stages of swallowing physiology are observed and evaluated. Aspiration is defined as passage of materials through the vocal folds, and laryngeal penetration is defined as passage of materials into the larynx, but not through the vocal folds. In this study, we compared the risk of laryngeal penetration or aspiration during VF using various liquid volumes and food consistencies. Between January 2006 and September 2008, 229 patients with suspected dysphagia each were fed at least 2 out of 6 types of liquids or foods during VF in an upright posture without compensatory maneuvers. The 6 types were pudding-thick barium of 4 ml (PD), thin liquid barium of 4 ml (LQ4) and 10 ml (LQ10), one swallow of thin liquid barium from a cup (CUP), corned beef hash (8 g) with barium (CB), and a two-phase mixture of corned beef hash (4 g) with barium and thin liquid barium of 5 ml (MX). The paired comparisons revealed that laryngeal penetration risk increased in the following order: PD, CB, LQ4, LQ10, MX and CUP, while aspiration risk after PD increased in the following order: CB, LQ4, LQ10, CUP and MX. Thus, risk of laryngeal penetration or aspiration varies, depending on food types. In conclusion, risk of aspiration is highest with the two-phase food, and multi-textured foods should be used with caution in individuals with dysphagia.


Suicide Prevention.
Suicide is a public health problem affecting people across the lifespan. It is currently the 10th leading cause of death, with rates having remained relatively flat for the past century. This article summarizes the problem of suicide and suicidal behavior along with suicide prevention efforts in the United States. Part 1 provides an overview of the epidemiology of suicide, including groups most at risk of suicide and suicidal behavior. Part 2 provides a review of common risk factors, organized by developmental life stage. A brief discussion of the lesser well-researched area of protective factors follows. Part 3 provides an overview of suicide prevention today, including the major types of prevention strategies, their successes, including means restriction, quality improvement in behavioral services, and comprehensive programs; and limitations to date, such as a lack of evidence for impact on actual deaths or behavior, small sample sizes, and low base rates. Finally, part 4 discusses challenges and future directions with an eye toward the great many opportunities that exist for prevention.


Long-term thermostabilization of live poxviral and adenoviral vaccine vectors at supraphysiological temperatures in carbohydrate glass.
Live recombinant viral vectors based on adenoviruses and poxviruses are among the most promising platforms for development of new vaccines against diseases such as malaria, tuberculosis, and HIV-AIDS. Vaccines based on live viruses must remain infectious to be effective, so therefore need continuous refrigeration to maintain stability and viability, a requirement that can be costly and difficult, especially in developing countries. The sugars sucrose and trehalose are commonly used as stabilizing agents and cryoprotectants for biological products. Here, we have exploited the ability of these sugars to vitrify on desiccation to develop a thermostabilization technique for live viral vaccine vectors. By slowly drying vaccines suspended in solutions of these disaccharide stabilizers onto a filter-like support membrane at ambient temperature, an ultrathin glass is deposited on the fibers of the inert matrix. Immobilization of two recombinant vaccine vectors-E1/E3-deleted human adenovirus type 5 and modified vaccinia virus Ankara-in this glass on the membranes enabled complete recovery of viral titer and immunogenicity after storage at up to 45 degrees C for 6 months and even longer with minimal losses. Furthermore, the membrane carrying the stabilized vaccine can be incorporated into a holder attached to a syringe for almost simultaneous reconstitution and injection at point of use. The technology may potentially be developed for the deployment of viral vector-based biopharmaceuticals in resource-poor settings.


Development of a novel wavelength selection method for the trace determination of chlorpyrifos on Au@Ag NPs substrate coupled surface-enhanced Raman spectroscopy.
A novel wavelength selection method, namely interval combination population analysis-minimal redundancy maximal relevance (ICPA-mRMR), was employed for the trace level detection of chlorpyrifos (CPS) coupled surface-enhanced Raman spectroscopy (SERS). Herein, a highly sensitive SERS enhancement substrate, Au@Ag nanoparticles (NPs), was synthesized possessing strong enhancement of Raman signals for CPS quantification (enhancement factor: 2.5 × 106). Compared with other established methods such as partial least squares (PLS), synergy interval partial least squares-genetic algorithm (siPLS-GA) and competitive adaptive reweighted sampling-partial least squares (CARS-PLS), ICPA-mRMR yielded the best results with higher correlation coefficients (Rc = 0.9917, RP = 0.9895), ratios of performance to deviation (RPD = 6.8797), and lower root mean square errors (RMSEC = 0.1998, RMSEP = 0.2271). The proposed method was employed for the determination of trace level CPS in tea samples, and the recovery percentages were in the range 90%-108%. Meanwhile, this method was validated using a standard GC-MS method indicating no significant difference (P > 0.05). The proposed methodology offers a rapid, sensitive and powerful analytical platform for the detection of pesticide residues in food.


The transmembrane domain is sufficient for Sbh1p function, its association with the Sec61 complex, and interaction with Rtn1p.
The Sec61 protein translocation complex in the endoplasmic reticulum (ER) membrane is composed of three subunits. The alpha-subunit, called Sec61p in yeast, is a multispanning membrane protein that forms the protein conducting channel. The functions of the smaller, carboxyl-terminally tail-anchored beta subunit Sbh1p, its close homologue Sbh2p, and the gamma subunit Sss1p are not well understood. Here we show that co-translational protein translocation into the ER is reduced in sbh1Delta sbh2Delta cells, whereas there is a limited reduction of post-translational translocation and no effect on export of a mutant form of alpha-factor precursor for ER-associated degradation in the cytosol. The translocation defect and the temperature-sensitive growth phenotype of sbh1Delta sbh2Delta cells were rescued by expression of the transmembrane domain of Sbh1p alone, and the Sbh1p transmembrane domain was sufficient for coimmunoprecipitation with Sec61p and Sss1p. Furthermore, we show that Sbh1p co-precipitates with the ER transmembrane protein Rtn1p. Sbh1p-Rtn1p complexes do not appear to contain Sss1p and Sec61p. Our results define the transmembrane domain as the minimal functional domain of the Sec61beta homologue Sbh1p in ER translocation, identify a novel interaction partner for Shb1p, and imply that Sbh1p has additional functions that are not directly linked to protein translocation in association with the Sec61 complex.


Bend propagation in the flagella of migrating human sperm, and its modulation by viscosity.
A pre-requisite for sexual reproduction is successful unification of the male and female gametes; in externally-fertilising echinoderms the male gamete is brought into close proximity to the female gamete through chemotaxis, the associated signalling and flagellar beat changes being elegantly characterised in several species. In the human, sperm traverse a relatively high-viscosity mucus coating the tract surfaces, there being a tantalising possible role for chemotaxis. To understand human sperm migration and guidance, studies must therefore employ similar viscous in vitro environments. High frame rate digital imaging is used for the first time to characterise the flagellar movement of migrating sperm in low and high viscosities. While qualitative features have been reported previously, we show in precise spatial and temporal detail waveform evolution along the flagellum. In low viscosity the flagellum continuously moves out of the focal plane, compromising the measurement of true curvature, nonetheless the presence of torsion can be inferred. In high viscosities curvature can be accurately determined and we show how waves propagate at approximately constant speed. Progressing waves increase in curvature approximately linearly except for a sharper increase over a distance approximately 20-27 microm from the head/midpiece junction. Curvature modulation, likely influenced by the outer dense fibres, creates the characteristic waveforms of high viscosity swimming, with remarkably effective cell progression against greatly increased resistance, even in high viscosity liquids. Assessment of motility in physiological viscosities will be essential in future basic research, studies of chemotaxis and novel diagnostics.


Management of high blood pressure in Blacks: an update of the International Society on Hypertension in Blacks consensus statement.
Since the first International Society on Hypertension in Blacks consensus statement on the "Management of High Blood Pressure in African American" in 2003, data from additional clinical trials have become available. We reviewed hypertension and cardiovascular disease prevention and treatment guidelines, pharmacological hypertension clinical end point trials, and blood pressure-lowering trials in blacks. Selected trials without significant black representation were considered. In this update, blacks with hypertension are divided into 2 risk strata, primary prevention, where elevated blood pressure without target organ damage, preclinical cardiovascular disease, or overt cardiovascular disease for whom blood pressure consistently <135/85 mm Hg is recommended, and secondary prevention, where elevated blood pressure with target organ damage, preclinical cardiovascular disease, and/or a history of cardiovascular disease, for whom blood pressure consistently <130/80 mm Hg is recommended. If blood pressure is ≤10 mm Hg above target levels, monotherapy with a diuretic or calcium channel blocker is preferred. When blood pressure is >15/10 mm Hg above target, 2-drug therapy is recommended, with either a calcium channel blocker plus a renin-angiotensin system blocker or, alternatively, in edematous and/or volume-overload states, with a thiazide diuretic plus a renin-angiotensin system blocker. Effective multidrug therapeutic combinations through 4 drugs are described. Comprehensive lifestyle modifications should be initiated in blacks when blood pressure is ≥115/75 mm Hg. The updated International Society on Hypertension in Blacks consensus statement on hypertension management in blacks lowers the minimum target blood pressure level for the lowest-risk blacks, emphasizes effective multidrug regimens, and de-emphasizes monotherapy.


Contribution of comparative fish studies to general endocrinology: structure and function of some osmoregulatory hormones.
Fish endocrinologists are commonly motivated to pursue their research driven by their own interests in these aquatic animals. However, the data obtained in fish studies not only satisfy their own interests but often contribute more generally to the studies of other vertebrates, including mammals. The life of fishes is characterized by the aquatic habitat, which demands many physiological adjustments distinct from the terrestrial life. Among them, body fluid regulation is of particular importance as the body fluids are exposed to media of varying salinities only across the thin respiratory epithelia of the gills. Endocrine systems play pivotal roles in the homeostatic control of body fluid balance. Judging from the habitat-dependent control mechanisms, some osmoregulatory hormones of fish should have undergone functional and molecular evolution during the ecological transition to the terrestrial life. In fact, water-regulating hormones such as vasopressin are essential for survival on the land, whereas ion-regulating hormones such as natriuretic peptides, guanylins and adrenomedullins are diversified and exhibit more critical functions in aquatic species. In this short review, we introduce some examples illustrating how comparative fish studies contribute to general endocrinology by taking advantage of such differences between fishes and tetrapods. In a functional context, fish studies often afford a deeper understanding of the essential actions of a hormone across vertebrate taxa. Using the natriuretic peptide family as an example, we suggest that more functional studies on fishes will bring similar rewards of understanding. At the molecular level, recent establishment of genome databases in fishes and mammals brings clues to the evolutionary history of hormone molecules via a comparative genomic approach. Because of the functional and molecular diversification of ion-regulating hormones in fishes, this approach sometimes leads to the discovery of new hormones in tetrapods as exemplified by adrenomedullin 2.


Hepatic Src homology phosphatase 2 regulates energy balance in mice.
The Src homology 2 domain-containing protein-tyrosine phosphatase Src homology phosphatase 2 (Shp2) is a negative regulator of hepatic insulin action in mice fed regular chow. To investigate the role of hepatic Shp2 in lipid metabolism and energy balance, we determined the metabolic effects of its deletion in mice challenged with a high-fat diet (HFD). We analyzed body mass, lipid metabolism, insulin sensitivity, and glucose tolerance in liver-specific Shp2-deficient mice (referred to herein as LSHKO) and control mice fed HFD. Hepatic Shp2 protein expression is regulated by nutritional status, increasing in mice fed HFD and decreasing during fasting. LSHKO mice gained less weight and exhibited increased energy expenditure compared with control mice. In addition, hepatic Shp2 deficiency led to decreased liver steatosis, enhanced insulin-induced suppression of hepatic glucose production, and impeded the development of insulin resistance after high-fat feeding. At the molecular level, LSHKO exhibited decreased hepatic endoplasmic reticulum stress and inflammation compared with control mice. In addition, tyrosine and serine phosphorylation of total and mitochondrial signal transducer and activator of transcription 3 were enhanced in LSHKO compared with control mice. In line with this observation and the increased energy expenditure of LSHKO, oxygen consumption rate was higher in liver mitochondria of LSHKO compared with controls. Collectively, these studies identify hepatic Shp2 as a novel regulator of systemic energy balance under conditions of high-fat feeding.


Haptoglobin genotype and outcome after aneurysmal subarachnoid haemorrhage.
After aneurysmal subarachnoid haemorrhage (aSAH), extracellular haemoglobin (Hb) in the subarachnoid space is bound by haptoglobin, neutralising Hb toxicity and helping its clearance. Two exons in the HP gene (encoding haptoglobin) exhibit copy number variation (CNV), giving rise to HP1 and HP2 alleles, which influence haptoglobin expression level and possibly haptoglobin function. We hypothesised that the HP CNV associates with long-term outcome beyond the first year after aSAH. The HP CNV was typed using quantitative PCR in 1299 aSAH survivors in the Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study, a retrospective multicentre cohort study with a median follow-up of 18 months. To investigate mediation of the HP CNV effect by haptoglobin expression level, as opposed to functional differences, we used rs2000999, a single nucleotide polymorphism associated with haptoglobin expression independent of the HP CNV. Outcome was assessed using modified Rankin and Glasgow Outcome Scores. SAH volume was dichotomised on the Fisher grade. Haemoglobin-haptoglobin complexes were measured in cerebrospinal fluid (CSF) of 44 patients with aSAH and related to the HP CNV. The HP2 allele associated with a favourable long-term outcome after high-volume but not low-volume aSAH (multivariable logistic regression). However rs2000999 did not predict outcome. The HP2 allele associated with lower CSF haemoglobin-haptoglobin complex levels. The CSF Hb concentration after high-volume and low-volume aSAH was, respectively, higher and lower than the Hb-binding capacity of CSF haptoglobin. The HP2 allele carries a favourable long-term prognosis after high-volume aSAH. Haptoglobin and the Hb clearance pathway are therapeutic targets after aSAH.


Microinjection of the vehicle dimethyl sulfoxide (DMSO) into the periaqueductal gray modulates morphine antinociception.
Dimethyl sulfoxide (DMSO) is commonly used as a solvent for water-insoluble drugs. Given that DMSO has varying cellular and behavioral effects ranging from increased membrane permeability to toxicity, microinjection of DMSO as a vehicle could confound the effects of other drugs. For example, DMSO is often used as a vehicle for studies examining the neurochemical mechanisms underlying morphine antinociception. Given that the ventrolateral periaqueductal gray (vlPAG) plays a major role in morphine antinociception and tolerance, the effects of DMSO on morphine antinociception mediated by the vlPAG needs to be evaluated. The present experiment tested whether co-administration of DMSO (0, 0.2, 2, or 20%) would alter the antinociceptive effect of microinjecting morphine into the vlPAG. DMSO had no effect on nociception when microinjected into the vlPAG alone, but 2% DMSO enhanced morphine potency when co-administered with morphine. In contrast, twice daily microinjections of DMSO (5 or 20%) for two days reduced the potency of subsequent microinjections of morphine into the vlPAG--an effect that persisted for at least one week. A similar rightward shift in the morphine dose-response curve was caused by morphine tolerance. Co-administration of morphine and DMSO during the pretreatment did not cause a greater shift in the morphine dose-response curve compared to morphine pretreated alone. In conclusion, DMSO can alter morphine antinociception following both acute (enhancement) and chronic (inhibition) administration depending on the concentration. These data reinforce the need to be cautious when using DMSO as a vehicle for drug administration.


[Clinical, serological and parasitological aspects of an outbreak of human trichinellosis in Villa Mercedes, San Luis, Argentina. The acute and chronic phases of the infection].
Clinical and serological features of individuals undergoing the acute (n: 54) and chronic (n: 32) phases of trichinellosis belonging to an outbreak originated by the consumption of pork products of a commercial source, arisen in Argentina, are described. Epidemiological data, signs, symptoms, and laboratory studies were assessed. Parasitological studies were performed in patients and pork products. Results showed that: a) the parasite burden of pork products was 200.0 +/- 18.3 larvae/g; b) muscle larvae were demonstrated in 10 out of the 11 patients studied; c) during the acute phase, fever (94%), eosinophilia (90%), myalgia (85%), headache (81%), facial edema (54%), diarrhoea (52%) and anti-Trichinella antibodies (64%) were observed; d) 15% of the patients had to be hospitalized, 7% having complications; e) during the chronic phase, myalgia (72%), sight abnormalities (22%), gastrointestinal disorders (31%) and the persistence of antibodies (77%) were observed. This study highlights the socioeconomical impact of trichinellosis due to the clinical characteristics of the acute phase and the presence of symptoms in the chronic phase.


High test-retest reliability of checkerboard reversal visual evoked potentials (VEP) over 8 months.
The inter-individual variation in the shape of a visual evoked potential (VEP) is large even for simple stimuli. We compared the inter-individual variation in VEP waveform to the intra-individual stability. We recorded VEP with checkerboard stimulation in 10 women aged 19-29years in two sessions. We determined the latencies and the peak-to-peak amplitude of N75 and P100. As a new approach in VEP research, we regressed VEP waveforms pairwise onto each other and calculated a t-value between all sessions. The maximal t-value was taken to indicate recognition for all 19 comparisons performed with one session. The recognition rate was cross-validated in a generalized linear regression model (GLM). The number of sessions correctly matched to the correct subject was 19 of 20 (true positives) leading to a sensitivity of 95.0% with confidence interval [75.1% 99.9%] for the method. The number of true negatives was 359 of 360 leading to a specificity of 99.7% [98.5% 100.0%]. The VEP waveform shows high intra-individual stability compared to the inter-individual variation in healthy women. With a new statistical approach the effect of external factors on the VEP waveform can now be contrasted against the normal variability over time in longitudinal studies.


Genomic epidemiology reveals multiple introductions of SARS-CoV-2 from mainland Europe into Scotland.
Coronavirus disease 2019 (COVID-19) was first diagnosed in Scotland on 1 March 2020. During the first month of the outbreak, 2,641 cases of COVID-19 led to 1,832 hospital admissions, 207 intensive care admissions and 126 deaths. We aimed to identify the source and number of introductions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into Scotland using a combined phylogenetic and epidemiological approach. Sequencing of 1,314 SARS-CoV-2 viral genomes from available patient samples enabled us to estimate that SARS-CoV-2 was introduced to Scotland on at least 283 occasions during February and March 2020. Epidemiological analysis confirmed that early introductions of SARS-CoV-2 originated from mainland Europe (the majority from Italy and Spain). We identified subsequent early outbreaks in the community, within healthcare facilities and at an international conference. Community transmission occurred after 2 March, 3 weeks before control measures were introduced. Earlier travel restrictions or quarantine measures, both locally and internationally, would have reduced the number of COVID-19 cases in Scotland. The risk of multiple reintroduction events in future waves of infection remains high in the absence of population immunity.


A SNP-Based Linkage Map Revealed QTLs for Resistance to Early and Late Leaf Spot Diseases in Peanut (Arachis hypogaea L.).
Cultivated peanut (Arachis hypogaea L.) is an important oilseed crop that is grown extensively in Africa, Asia and America. The diseases early and late leaf spot severely constrains peanut production worldwide. Because multiple genes control resistance to leaf spot diseases, conventional breeding is a time-consuming approach for pyramiding resistance genes into a single genotype. Marker-assisted selection (MAS) would complement and accelerate conventional breeding once molecular markers tightly associated with the resistance genes are identified. In this study, we have generated a large number of SNPs through genotyping by sequencing (GBS) and constructed a high-resolution map with an average distance of 1.34 cM among 2,753 SNP markers distributed on 20 linkage groups. QTL mapping has revealed that major QTL within a confidence interval could provide an efficient way to detect putative resistance genes. Analysis of the interval sequences has indicated that a major QTL for resistance to late leaf spot anchored by two NBS-LRR resistance genes on chromosome B05. Two major QTLs located on chromosomes A03 and B04 were associated with resistance genes for early leaf spot. Sequences within the confidence interval would facilitate identifying resistance genes and applying marker-assisted selection for resistance.


The effect of ApoE e4 on blood pressure in patients with and without depression.
Depression is considered an independent risk factor for hypertension, particularly for people with recurrent episodes or a long history of depression. Another risk factor for cardiovascular disease is the Apolipoprotein E e4 allele (ApoE e4). The aim of this study was to examine how ApoE e4 was related to blood pressure (BP) in patients with depression and a control group. A total of 78 patients, 49 with depression and 29 without, all recruited from the same hospital, underwent ApoE e genotyping (24 had at least one ApoE e4 allele) and examination of BP. In the depression group, but not in the control group, both systolic and diastolic BP were significantly higher in patients with ApoE e4 than in those without. The effect of ApoE e4 on BP differed significantly between the two groups. Our findings showed that the effect of ApoE e4 on BP differed between the patients with depression and the control group. In patients with depression, ApoE e4 was associated with an increase in BP. We suggest that patients with depression and ApoE e4-positive status are particularly prone to develop BP elevation.


[Application of artificial DNA-binding proteins and artificial nucleases to prevention of virus infection: development of virus-resistant plants and protein-based anti-viral drugs].
Various DNA viruses are known to cause severe infectious diseases in both plants and mammals, including humans. For many of these infectious diseases, we have yet to find an effective prevention or treatment. Therefore, new methodologies for the prevention of virus infections in both agricultural crops and humans have been vigorously sought for a long time. One attractive approach to the prevention is inhibition of virus replication. We first inhibited virus replication by blocking binding of a viral replication protein, which initiates virus replication, to its replication origin, with using an artificial DNA-binding protein. We demonstrated that this new methodology was very effective in plants and mammalian cells: especially, we created transgenic plants that were immune to a geminivirus. We also developed novel protein-based antiviral drugs by fusing a cell-penetrating peptide to an artificial DNA-binding protein. Furthermore, we successfully generated a more effective protein-based antiviral, which was one hundred thousand times more active than the antiviral chemical drug Cidofovia, by alternatively fusing an DNA-cleaving enzyme to an artificial DNA-binding protein. Since this artificial protein has little cytotoxicity, it is expected that it will be used as a new antiviral drug.


The COVID-19 pandemic: Clinical practice advice for gastroenterologists, hepatologists, and liver transplant specialists.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel acute infectious disease that has rapidly reached staggering pandemic proportions. This review addresses gastroenterologists, hepatologists, liver transplant (LT) specialists, and health-care professionals working in the field of liver diseases and liver transplantation. It has been written based on a limited number of publications, recommendations of national and international liver and organ transplantation societies, and experiences of patients with COVID-19 around the world. The purpose of this review is to provide information addressing questions and concerns about COVID-19, to reveal the effects of the novel disease on patients with chronic liver disease and LT recipients, and to share information about ways in which this pandemic will affect clinical practices. We, the Turkish Association for the Study of the Liver (TASL), would like to remind you that this text is actually not a practical guide. It is imperative to act according to the standards set by health-care institutions and the Ministry of Health, Republic of Turkey.


Pregnancy outcome among working women.
The influence of occupational factors on the outcome of pregnancy was investigated in a prospective study of 3901 women who worked during their pregnancy and received prenatal care in Orebro County from October 1980 to June 1983. Data on occupational factors, social circumstances, and life-style factors were obtained from questionnaires. There were no significant differences in the incidence of adverse pregnancy outcome (spontaneous abortion, perinatal death, birth defects, or low birthweight) between the nine occupational categories used when nonoccupational factors were accounted for. No increased risk was found for exposure to organic solvents, but the adjusted risk ratio of adverse outcome was 1.28 (95% CI 0.91-1.80) for "other chemical exposures." The work conditions in this county have been generally favorable in recent years, and the results therefore cannot be generalized to conditions with higher exposures. Methodological problems such as misclassification of exposure and the possible bias resulting from different rates of legal abortions among occupational groups are discussed.


Successful anaesthesia management of a child with hunter syndrome for adenotonsillectomy.
Airway management in a child with hunter syndrome is a challenge to the anesthetists. Various methods to achieve this are reported in literature. Here we describe another method in a three year old male child posted for adenotonsillectomy and myringotomy. After check videolaryngoscopy with C Mac blade size 2, vocal cords were not visible even with various monoevres. Thus a larger blade size 3 was used to place it under the epiglottis after which posterior part of vocal cords became visible and bougie guided endotracheal intubation was successful. Thus we recommend that in a child with hunter syndrome if vocal cords are not visible, a larger blade can be utilized to place under the epiglottis to visualize the vocal cords for successful endotracheal intubation.


Physiological responses in thermal stressed Jersey cows subjected to different management strategies.
The effects of cooling and recombinant bovine somatotropin (rbST) on milk yield, reproductive performance, and health of Jersey cattle during summer thermal stress were measured for 2 yr. Cows were assigned to one of two groups based upon days in milk (DIM), parity, and genetic index. Year 1 and year 2 control cows (n = 143, n = 183, respectively) were housed in a pen with only shades. Cooled treatment cows each year (n = 142, n = 180) were housed with a spray and fan system for evaporative cooling. Cows were assigned at various days postpartum, not before d 63, coincident with commencement of rbST injections. One half of cows in each group received rbST on d 63 postpartum. Cows were assigned to the shade trial ranging from d 63 to 190. Cooled versus noncooled DIM were similar at the start of the trial. Trials began on July 1, 1999, and July 1, 2000, and concluded on September 30, 1999, and September 25, 2000. The ANOVA of daily milk weight data was conducted utilizing a 2 x 2 factorial design with cooling and rbST treatments as main effects. Cooling in combination with rbST increased milk yield compared with no cooling and no rbST for 1999 and 2000 (25.5 versus 21.8 kg/d, and 23.7 versus 20.5 kg/d, respectively). In general, cooling improved health and reproductive performance.


Sinks as limited resources? A new indicator for evaluating anthropogenic material flows.
Besides recyclables, the use of materials inevitably yields non-recyclable materials such as emissions and wastes for disposal. These flows must be directed to sinks in a way that no adverse effects arise for humans and the environment. The objective of this paper is to present a new indicator for the assessment of substance flows to sinks on a regional scale. The indicator quantifies the environmentally acceptable mass share of a substance in actual waste and emission flows, ranging from 0% as worst case to 100% as best case. This paper consists of three parts: first, the indicator is defined. Second, a methodology to determine the indicator score is presented, including (i) substance flows analysis and (ii) a distant-to-target approach based on an adaptation of the Ecological Scarcity Method 2006. Third, the metric developed is applied in three case studies including copper (Cu) and lead (Pb) in the city of Vienna, and perfluorooctane sulfonate (PFOS) in Switzerland. The following results were obtained: in Vienna, 99% of Cu flows to geogenic and anthropogenic sinks are acceptable when evaluated by the distant-to-target approach. However, the 0.7% of Cu entering urban soils and the 0.3% entering receiving waters are beyond the acceptable level. In the case of Pb, 92% of all flows into sinks prove to be acceptable, and 8% are disposed of in local landfills with limited capacity. For PFOS, 96% of all flows into sinks are acceptable. 4% cannot be evaluated due to a lack of normative criteria, despite posing a risk for human health and the environment. The examples demonstrate the need (i) for appropriate data of good quality to calculate the sink indicator and (ii) for standards, needed for the assessment of substance flows to urban soils and receiving waters. This study corroborates that the new indicator is well suited as a base for decisions regarding the control of hazardous substances in waste and environmental management.


Transcription factor SOHLH1 potentially associated with primary ovarian insufficiency.
To investigate whether gene variants of SOHLH1 exist in Chinese and Serbian patients with primary ovarian insufficiency (POI). Case-control genetic study. University hospitals. A total of 364 Han Chinese and 197 Serbian women with nonsyndromic POI and ethnically matched controls. None. SOHLH1 gene sequencing. We found 10 novel heterozygous variants in our cohorts of 561 women with POI but none in the 600 ethnically matched controls. Statistical and bioinformatic analyses indicated that three of the eight variants in Chinese POI cases are potentially disease causing. They comprise two missense variants (p.Ser317Phe and p.Glu376Lys) that might each change activity of the SOHLH1 protein as a transcription factor and one variant (c.*118C>T) located in the 3' untranslated region of the SOHLH1 gene, which might generate a new binding site for the microRNA hsa-miR-888-5p. Of the two variants in the Serbian POI cases, both were synonymous, and no missense variant was identified. The allele frequencies of some known single-nucleotide polymorphisms were statistically significantly different between patients and controls in both the Chinese and Serbian groups. Our results suggest that SOHLH1 may be regarded as a new candidate gene for POI.


Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein.
This paper presents the results of experiments that determine the chromosomal location of the mouse gene encoding CCAAT/enhancer binding protein (C/EBP) and measure its expression as a function of tissue type and temporal period of development in mice and rats. Three alleles of the C/EBP gene were identified according to restriction fragment length polymorphisms. The strain distribution pattern of the three alleles was determined in recombinant inbred mouse strains and compared to that of other mouse genes. These results mapped the gene to a position within 2.5 centimorgans (cM) of the structural gene encoding glucose phosphate isomerase on chromosome 7 of the mouse. The expression pattern of the C/EBP gene was studied by a combination of nucleic acid hybridization and antibody staining assays. High levels of C/EBP mRNA were observed in tissues known to metabolize lipid and cholesterol-related compounds at uncommonly high rates. These included liver, fat, intestine, lung, adrenal gland, and placenta. More detailed analysis of two of these tissues, liver and fat, showed that C/EBP expression was limited to fully differentiated cells. Moreover, analysis of the temporal pattern of expression of C/EBP mRNA in two tissues, liver and intestine, revealed a coordinated induction just prior to birth. These observations raise the possibility that the synthesis of C/EBP may be responsive to humoral factors and that modulation in C/EBP expression might mediate coordinated changes in gene expression that facilitate adaptive challenges met during development or during the fluctuating physiological states of adult life.


Development and validation of a tool to assess emergency physicians' nontechnical skills.
Nontechnical skills are "the cognitive, social and personal resource skills that complement technical skills, and contribute to safe and efficient task performance." Our research team developed and evaluated the task of developing and validating a behavioral marker system for the observational assessment of emergency physicians' nontechnical skills. The development of the tool was divided into 3 phases and used triangulation of data from a number of sources. During phase 1, a provisional assessment tool was developed according to published literature and curricula. Phase 2 used analysis of staff interviews and field observations to determine whether the skill list contained any significant omissions. These studies were also used to identify behavioral markers linked to nontechnical skills in the context of the emergency department (ED) and establish whether skills included in the tool were observable. Phase 3 involved evaluating the content validity index of exemplar behaviors, using a survey of experts. A behavioral marker system was developed that comprised 12 emergency medicine-specific nontechnical skills, grouped into 4 categories. Content validity was assessed with a survey of 148 emergency medicine staff, and 75% of items achieved the recommended content validity index greater than 0.75. Data from the survey enabled further refinement of the behavioral markers to produce a final version of the tool. Although further evaluative studies are needed, this behavioral marker system provides a structured approach to the assessment and training of nontechnical skills in the ED.


Evaluation of rapid radiometric method for drug susceptibility testing of Mycobacterium tuberculosis.
A total of 106 isolates of Mycobacterium tuberculosis were tested for drug susceptibility by the conventional 7H11 plate method and by a new rapid radiometric method using special 7H12 liquid medium with 14C-labeled substrate. Results obtained by the two methods were compared for rapidity, sensitivity, and specificity of the new test method. There was 98% overall agreement between the results obtained by the two methods. Of a total of 424 drug tests, only 8 drug results did not agree, mostly in the case of streptomycin. This new procedure was found to be rapid, with 87% of the tests results reportable within 4 days and 98% reportable within 5 days as compared to the usual 3 weeks required with the conventional indirect susceptibility test method. The results of this preliminary study indicate that the rapid radiometric method seems to have the potential for routine laboratory use and merits further investigations.


hOGG1 gene polymorphism and breast cancer risk: A systematic review and meta-analysis study.
To address the effect of hGGO1 (rs1052133) gene polymorphism on the risk of breast cancer, a meta-analysis was performed. We pooled adjusted odds ratios (OR) as overall and three subgroups (menopausal status, ethnicity, and study setting). In overall analysis, we found a significant association when the model of inheritance was homozygote (pooled OR 1.14; 95% CI 1.01, 1.29). Subgroup analysis showed significant association for homozygote genetic models among postmenopause women (OR 1.23; 95% CI 1.01, 1.49) and Asian population (OR 1.17; 95% CI 1.01, 1.35). This study suggested that the carrier of Ser326Cys polymorphism of hOGG1, Cys/Cys vs Ser/Ser, are at higher risk for breast cancer, independent of other hormonal and environmental risk factors.


Impact of interlaminar graft materials on the fusion status in atlantoaxial transarticular screw fixation.
Structural interlaminar graft materials were used for atlantoaxial transarticular screw fixation (TSF), and its impact on the fusion status was investigated. Forty-two patients (10 men, 32 women, mean age 51 years, mean follow-up period 45 months; 30 with rheumatoid arthritis, and 12 with os odontoideum) underwent TSF and modified Brooks posterior wiring involving titanium cables. As interlaminar graft materials, autologous bone from posterior iliac crest alone was used in 20 patients (Group A), and a structural spacer (13 ceramic spacers, nine titanium mesh cages) in 22 (Group B). Lateral radiographs were evaluated to determine bone fusion, alignment of the cervical spine, and wire loosening. Solid osseous fusion was obtained in 95% of Group A and 96% of Group B patients. The mean atlantoaxial angle was 19.1+/-9.7 degrees and 16.7+/-10.4 degrees before surgery (p = 0.45), and 27.4+/-7.8 degrees and 22.1+/-5.5 degrees after surgery (p = 0.02) in Groups A and B, respectively. Atlantoaxial hyperlordosis (atlantoaxial angle > or = 30 degrees) was observed in 32% of Group A and 18% of Group B patients (p = 0.26). Postoperative kyphosis occurred in 40% of Group A and 23% of Group B patients (p = 0.28). Loosening of the cable was demonstrated in 50% of Group A and 36% of Group B patients(p = 0.37). In Group B patients maintenance of cervical lordosis was more likely than in those in Group A, although the differences did not reach statistical significance. These results indicate that structural interlaminar spacers can maintain proper cervical alignment without a decease in the fusion rate; the authors recommend their use in conjunction with TSF.


Cryptic speciation patterns in Iranian rock lizards uncovered by integrative taxonomy.
While traditionally species recognition has been based solely on morphological differences either typological or quantitative, several newly developed methods can be used for a more objective and integrative approach on species delimitation. This may be especially relevant when dealing with cryptic species or species complexes, where high overall resemblance between species is coupled with comparatively high morphological variation within populations. Rock lizards, genus Darevskia, are such an example, as many of its members offer few diagnostic morphological features. Herein, we use a combination of genetic, morphological and ecological criteria to delimit cryptic species within two species complexes, D. chlorogaster and D. defilippii, both distributed in northern Iran. Our analyses are based on molecular information from two nuclear and two mitochondrial genes, morphological data (15 morphometric, 16 meristic and four categorical characters) and eleven newly calculated spatial environmental predictors. The phylogeny inferred for Darevskia confirmed monophyly of each species complex, with each of them comprising several highly divergent clades, especially when compared to other congeners. We identified seven candidate species within each complex, of which three and four species were supported by Bayesian species delimitation within D. chlorogaster and D. defilippii, respectively. Trained with genetically determined clades, Ecological Niche Modeling provided additional support for these cryptic species. Especially those within the D. defilippii-complex exhibit well-differentiated niches. Due to overall morphological resemblance, in a first approach PCA with mixed variables only showed the separation between the two complexes. However, MANCOVA and subsequent Discriminant Analysis performed separately for both complexes allowed for distinction of the species when sample size was large enough, namely within the D. chlorogaster-complex. In conclusion, the results support four new species, which are described herein.


Being a pedestrian with dementia: A qualitative study using photo documentation and focus group interviews.
The aim of the study was to identify problematic situations in using zebra crossings. They were identified from photo documentations comprising film sequences and the perspectives of people with dementia. The aim was also to identify how they would understand, interpret and act in these problematic situations based on their previous experiences and linked to the film sequences.A qualitative grounded theory approach was used. Film sequences from five zebra crossings were analysed. The same film sequences were used as triggers in two focus group interviews with persons with dementia. Individual interviews with three informants were also performed.The core category, the hazard of meeting unfolding problematic traffic situations when only one layer at a time can be kept in focus, showed how a problematic situation as a whole consisted of different layers of problematic situations. The first category, adding layers of problematic traffic situations to each other, was characterized by the informants' creation of a problematic situation as a whole. The different layers were described in the subcategories of layout of streets and zebra crossings, weather conditions, vehicles and crowding of pedestrians. The second category, actions used to meet different layers of problematic traffic situations, was characterized by avoiding problematic situations, using traffic lights as reminders and security precautions, following the flow at the zebra crossing and being cautious pedestrians.In conclusion, as community-dwelling people with dementia commonly are pedestrians, it is important that health care professionals and caregivers take their experiences and management of problematic traffic situations into account when providing support.


Chemoprevention of breast cancer.
Trials with tamoxifen have clearly shown that the risk of developing oestrogen receptor positive breast cancer can be reduced at a late stage in the natural history with prophylactic agents. About half of the oestrogen receptor positive cases were prevented, but there was no beneficial effect on ER-negative cancers. The current challenge is to find new agents which achieve this or better efficacy but with fewer side effects. Recent results indicate that the SERM raloxifene has similar efficacy to tamoxifen, but leads to fewer endometrial cancers, gynaecologic symptoms, and thromboembolic events. Results for contralateral tumours in adjuvant trials suggest that aromatase inhibitors may be able to prevent up to 70-80% of ER-positive breast cancers, and this is currently being investigated in two large prevention trials, one using anastrozole (IBIS-II) and the other exemestane (MAP.3). New agents are needed, for receptor negative breast cancer and several possibilities are currently under investigation.


Antipsychotic switching in schizoaffective disorder: A systematic review.
To systematically review the evidence about the switching of antipsychotics in SZA in acute and maintenance treatment. A systematic review following the PRISMA statement identifying studies specifically conducted on, or including, SZA patients. One analysis considered uniquely a SZA population, 13 more studies including an adequate SZA subsample were considered. Most of the studies were aimed at switching antipsychotic treatments to improve tolerability issues. Despite the absolute lack of trials specifically conducted on SZA populations, we found limited evidence on the use of aripiprazole, lurasidone, and, to a lesser extent, risperidone and ziprasidone as possible agents to substitute previous treatments whereas efficacy or, more frequently, tolerability issues arise. Evidence supports also the switch to risperidone long-acting injectable when the adherence to oral treatment may be a concern. Antipsychotic switching in SZA is a neglected topic that would need better profiling. Clinicians should keep in mind the receptor binding characteristics of drugs in order to optimize transitions. Evidence supports the switch to aripiprazole and lurasidone, less strongly to risperidone and ziprasidone. The switch to risperidone long-acting injectable is supported, especially in patients with limited treatment adherence to oral therapy.


Elevated expression of TcHMA3 plays a key role in the extreme Cd tolerance in a Cd-hyperaccumulating ecotype of Thlaspi caerulescens.
Cadmium (Cd) is a highly toxic heavy metal for plants, but several unique Cd-hyperaccumulating plant species are able to accumulate this metal to extraordinary concentrations in the aboveground tissues without showing any toxic symptoms. However, the molecular mechanisms underlying this hypertolerance to Cd are poorly understood. Here we have isolated and functionally characterized an allelic gene, TcHMA3 (heavy metal ATPase 3) from two ecotypes (Ganges and Prayon) of Thlaspi caerulescens contrasting in Cd accumulation and tolerance. The TcHMA3 alleles from the higher (Ganges) and lower Cd-accumulating ecotype (Prayon) share 97.8% identity, and encode a P(1B)-type ATPase. There were no differences in the expression pattern, cell-specificity of protein localization and transport substrate-specificity of TcHMA3 between the two ecotypes. Both alleles were characterized by constitutive expression in the shoot and root, a tonoplast localization of the protein in all leaf cells and specific transport activity for Cd. The only difference between the two ecotypes was the expression level of TcHMA3: Ganges showed a sevenfold higher expression than Prayon, partly caused by a higher copy number. Furthermore, the expression level and localization of TcHMA3 were different from AtHMA3 expression in Arabidopsis. Overexpression of TcHMA3 in Arabidopsis significantly enhanced tolerance to Cd and slightly increased tolerance to Zn, but did not change Co or Pb tolerance. These results indicate that TcHMA3 is a tonoplast-localized transporter highly specific for Cd, which is responsible for sequestration of Cd into the leaf vacuoles, and that a higher expression of this gene is required for Cd hypertolerance in the Cd-hyperaccumulating ecotype of T. caerulescens.