Practices and challenges in community aphasia groups in Australia: Results of a national survey.
This study reports on practices and challenges in developing community aphasia groups in Australia. A 24-item web-based survey addressed the structure of existing community aphasia groups, funding models, group activities, facilitator satisfaction, challenges to group development and maintenance and suggestions for improvement. A total of 156 surveys were completed, mostly by speech-language pathologists (SLPs), with 66% urban and 34% regional/rural/remote participants representing all Australian states/territories consistent with their populations. Seventy respondents indicated running a total of 86 groups, reflecting a substantial under-representation of service in proportion to the population of people with aphasia. Further, 23.6% of respondents reported dissatisfaction with aspects of their groups. The primary barriers to achieving satisfaction relate to limited resources and staffing, inability to run sufficient numbers of groups and to tailor them effectively, dispersed populations beyond major cities, group dynamics and a lack of group promotion and referral to groups. Respondents suggested means for improvement including changes to group structure, improved SLP training, dedicated funding and staffing, development of specific resources and better liaison and promotion. The major features differentiating the community aphasia groups run in Australia from those running overseas are discussed and practical ways to achieve service improvement are suggested.


Discovery of thienopyrrolotriazine derivatives to protect mitochondrial function against Aβ-induced neurotoxicity.
Recovery of mitochondrial dysfunction has gained increasing attention as an alternative therapeutic strategy for Alzheimer's disease (AD). Recent studies suggested that the 18 kDa mitochondrial translocator protein (TSPO) has the potential to serve as a drug target for the treatment of AD. In this study, we generated a structure-based pharmacophore model and virtually screened a commercial library, identifying SVH07 as a virtual hit, which contained a tricyclic core structure, thieno[2',3':4,5]pyrrolo[1,2-d][1,2,4]triazine group. A series of SVH07 analogues were synthesized and their effects on the mitochondrial membrane potential and ATP production were determined by using neuronal cells under Aβ-induced toxicity. Among these analogues, compound 26 significantly recovered mitochondrial membrane depolarization and ATP production. In vitro binding assays indicated that SVH07 and 26 showed high affinities to TSPO with the IC50 values in a nanomolar range. We believe that compound 26 is a promising lead compound for the development of TSPO-targeted mitochondrial functional modulators with therapeutic potential in AD.


The role of stereotactic radiosurgery in the management of patients with newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline.
Should patients with newly-diagnosed metastatic brain tumors undergo stereotactic radiosurgery (SRS) compared with other treatment modalities? Target population These recommendations apply to adults with newly diagnosed solid brain metastases amenable to SRS; lesions amenable to SRS are typically defined as measuring less than 3 cm in maximum diameter and producing minimal (less than 1 cm of midline shift) mass effect. Recommendations SRS plus WBRT vs. WBRT alone Level 1 Single-dose SRS along with WBRT leads to significantly longer patient survival compared with WBRT alone for patients with single metastatic brain tumors who have a KPS > or = 70.Level 1 Single-dose SRS along with WBRT is superior in terms of local tumor control and maintaining functional status when compared to WBRT alone for patients with 1-4 metastatic brain tumors who have a KPS > or =70.Level 2 Single-dose SRS along with WBRT may lead to significantly longer patient survival than WBRT alone for patients with 2-3 metastatic brain tumors.Level 3 There is class III evidence demonstrating that single-dose SRS along with WBRT is superior to WBRT alone for improving patient survival for patients with single or multiple brain metastases and a KPS<70 [corrected].Level 4 There is class III evidence demonstrating that single-dose SRS along with WBRT is superior to WBRT alone for improving patient survival for patients with single or multiple brain metastases and a KPS < 70. SRS plus WBRT vs. SRS alone Level 2 Single-dose SRS alone may provide an equivalent survival advantage for patients with brain metastases compared with WBRT + single-dose SRS. There is conflicting class I and II evidence regarding the risk of both local and distant recurrence when SRS is used in isolation, and class I evidence demonstrates a lower risk of distant recurrence with WBRT; thus, regular careful surveillance is warranted for patients treated with SRS alone in order to provide early identification of local and distant recurrences so that salvage therapy can be initiated at the soonest possible time. Surgical Resection plus WBRT vs. SRS +/- WBRT Level 2 Surgical resection plus WBRT, vs. SRS plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (>3 cm) or for those causing significant mass effect (>1 cm midline shift). Level 3: Underpowered class I evidence along with the preponderance of conflicting class II evidence suggests that SRS alone may provide equivalent functional and survival outcomes compared with resection + WBRT for patients with single brain metastases, so long as ready detection of distant site failure and salvage SRS are possible. SRS alone vs. WBRT alone Level 3 While both single-dose SRS and WBRT are effective for treating patients with brain metastases, single-dose SRS alone appears to be superior to WBRT alone for patients with up to three metastatic brain tumors in terms of patient survival advantage.


In Vitro Anti-inflammatory Effects of the Phenylbutyric Acid Metabolite Phenylacetyl Glutamine.
Sodium 4-phenylbutyrate (PBA), which exerts a wide range of anti-inflammatory effects, is rapidly cleared from the body (approximately 98%) by urinary excretion by 24 h after oral treatment in humans. PBA was almost entirely excreted to urine as phenylacetyl glutamine (PAGln). However, no data describe the potential anti-inflammatory effects of PAGln. The purpose of this study was to evaluate the anti-inflammatory effects of PAGln on mouse spleen cells and peritoneal cavity cells, and explore the potential mechanism underlying this effect. PAGln was added to mouse spleen cell cultures stimulated by concanavalin A, or mouse peritoneal cavity cell cultures stimulated by lipopolysaccharide. After 72 h of culture, levels of inflammatory cytokines in culture supernatants were measured using a sandwich enzyme-linked immunosorbent assay system, and levels of inflammatory proteins were assessed by Western blotting. PAGln significantly inhibited inflammatory cytokine (interferon-γ, interleukin-6, and tumor necrosis factor-α) production, decrease of cell number in the spleen cell, and suppressed the expression of inflammatory proteins (nuclear factor κB, and inducible nitric oxide synthase). These results suggest that PAGln possesses anti-inflammatory activity via inhibition of T cell activation and Toll-like receptor 4 signaling. This study of the anti-inflammatory mechanism of PAGln provides useful information about its potential for therapeutic applications.


A survey of carbonic anhydrase mRNA expression in enamel cells.
Enamel formation requires rigid control of pH homeostasis during all stages of development to prevent disruptions to crystal growth. The acceleration of the generation of bicarbonate by carbonic anhydrases (CA) has been suggested as one of the pathways used by ameloblasts cells to regulate extracellular pH yet only two isozymes (CA II and CA VI) have been reported to date during enamel formation. The mammalian CA family contains 16 different isoforms of which 13 are enzymatically active. We have conducted a systematic screening by RT-PCR on the expression of all known CA isoforms in mouse enamel organ epithelium (EOE) cells dissected from new born, in secretory ameloblasts derived from 7-day-old animals, and in the LS8 ameloblast cell line. Results show that all CA isoforms are expressed by EOE/ameloblast cells in vivo. The most highly expressed are the catalytic isozymes CA II, VI, IX, and XIII, and the acatalytic CA XI isoform. Only minor differences were found in CA expression levels between 1-day EOE cells and 7-day-old secretory-stage ameloblasts, whereas LS8 cells expressed fewer CA isoforms than both of these. The broad expression of CAs by ameloblasts reported here contributes to our understanding of pH homeostasis during enamel development and demonstrates its complexity. Our results also highlight the critical role that regulation of pH plays during the development of enamel.


Crocin treatment decreased pancreatic atrophy, LOX-1 and RAGE mRNA expression of pancreas tissue in cholesterol-fed and streptozotocin-induced diabetic rats.
Objective Oxidative stress in diabetic mellitus is a consequence of oxidative stress, which plays a critical role in the pathogenesis of diabetic tissue damage. Receptors for advanced glycation end products and for oxidized low-density lipoproteins (LDL) have critical contribution in oxidative tissue damage. The present study investigated whether anti-diabetic effects of Crocin via modulation of mRNA expression of RAGE and LOX-1 receptors in diabetic rats. Methods In the current study, high-fat cholesterol (HFC) and streptozotocin (40 mg/kg) used to induce type II diabetes. Experimental groups as follows: (Group 1: control); (Group 2: control treatment [Crocin]); (Group 3: DM [STZ]); (Group 4: DM treatment [STZ + Crocin]); (Group 5; DM + HFC [STZ + HFC]); (Group 6; DM + HFC treatment [STZ + HFC + Crocin]). Crocin (20 mg/kg/day, i.p.) administered in treatment groups for 60 days. Serum glucose and cholesterol levels evaluated on days 5, 30 and 60 after induction of DM. Pancreatic tissue from all group removed on day 60 for histological and RT-PCR analysis. Results Application of Crocin significantly decreased serum cholesterol levels on day 60 after induction of DM in diabetic + HFC rats. Moreover, Crocin significantly decreased serum glucose levels on days 30 and 60 both in diabetic and diabetic + HFC rats. Crocin partially prevented the atrophic effects of STZ on both exocrine and endocrine parts of pancreas. Additionally, Crocin significantly decreased LOX-1 and RAGE mRNA expression OF pancreas in diabetic rats. Conclusion The current study suggested that Crocin suppressed atrophic change of the pancreas by decrease of LOX-1 and RAGE mRNA expression in diabetic rats.


Nutritional support of the hospitalized patient.
Malnutrition is being recognized more frequently in hospitalized patients. Clinically significant malnutrition is defined as nutritional deficits that have serious adverse effects on the treatment and outcome of illness. The anergic metabolic profile is a simple method of assessing nutritional status. New techniques of enteral and parenteral nutritional support can stop or reverse the progression of malnutrition.


Genetic Disruption of 21-Hydroxylase in Zebrafish Causes Interrenal Hyperplasia.
Congenital adrenal hyperplasia is a group of common inherited disorders leading to glucocorticoid deficiency. Most cases are caused by 21-hydroxylase deficiency (21OHD). The systemic consequences of imbalanced steroid hormone biosynthesis due to severe 21OHD remains poorly understood. Therefore, we developed a zebrafish model for 21OHD, which focuses on the impairment of glucocorticoid biosynthesis. A single 21-hydroxylase gene (cyp21a2) is annotated in the zebrafish genome based on sequence homology. Our in silico analysis of the 21-hydroxylase (Cyp21a2) protein sequence suggests a sufficient degree of similarity for the usage of zebrafish cyp21a2 to model aspects of human 21OHD in vivo. We determined the spatiotemporal expression patterns of cyp21a2 by whole-mount in situ hybridization and reverse transcription polymerase chain reaction throughout early development. Early cyp21a2 expression is restricted to the interrenal gland (zebrafish adrenal counterpart) and the brain. To further explore the in vivo consequences of 21OHD we created several cyp21a2 null-allele zebrafish lines by using a transcription activator-like effector nuclease genomic engineering strategy. Homozygous mutant zebrafish larvae showed an upregulation of the hypothalamic-pituitary-interrenal (HPI) axis and interrenal hyperplasia. Furthermore, Cyp21a2-deficient larvae had a typical steroid profile, with reduced concentrations of cortisol and increased concentrations of 17-hydroxyprogesterone and 21-deoxycortisol. Affected larvae showed an upregulation of the HPI axis and interrenal hyperplasia. Downregulation of the glucocorticoid-responsive genes pck1 and fkbp5 indicated systemic glucocorticoid deficiency. Our work demonstrates the crucial role of Cyp21a2 in glucocorticoid biosynthesis in zebrafish larvae and establishes an in vivo model allowing studies of systemic consequences of altered steroid hormone synthesis.


[The short term prognosis in alcoholic liver disease with metabolic acidosis].
Alcoholic liver disease with metabolic acidosis may have possible causes such as alcoholic ketoacidosis, diabetic ketoacidosis, lactic acidosis. Salicylate, methanol, and ethylene glycol intoxication should also be considered. The aim of this study was to investigate the short-term prognostic factors in patients with alcoholic liver disease with metabolic acidosis. Clinical data related to twenty-nine patients with alcoholic liver disease and metabolic acidosis was analysed retrospectively. Patients were divided into two groups according to the outcome (survival or death). Past medical history, and physical, laboratory and radiologic data at admission were compared. The amount of daily alcohol intake differed significantly between the two groups (P=0.034), but duration and total amount of alcohol intake did not differ significantly between the two groups (P=0.128; P=0.360). The presence of ascites differed significantly between two the groups (P=0.019). On laboratory testing, the following differed significantly: base excess (P=0.038), hemoglobin (P=0.019), platelet (P=0.040), total bilirubin (P=0.007), albumin (P=0.012), creatinine (P=0.014), phosphorus (P=0.021), chloride (P=0.010), ammonia (P=0.003), prothrombin time (P=0.033), fibrinogen (P=0.011) and D-dimer (P=0.024). Review of the medical history of the patients showed diabetes (10/29), cirrhosis (10/29), and hepatocellular carcinoma (1/29). Combined conditions at admission were sepsis (8/29), pneumonia (7/29), acute renal failure (6/29), rhabdomyolysis (5/29), gastrointestinal hemorrhage (4/29), acute pancreatitis (3/29), acute respiratory distress syndrome (2/29), and acute myocardial infarction (1/29). The amount of daily alcohol intake, base excess, hemoglobin, platelet, total bilirubin, albumin, creatinine, phosphorus, chloride, ammonia, prothrombin time, fibrinogen and D-dimer seemed to be useful parameters in predicting short-term prognosis of patients with alcoholic liver disease with metabolic acidosis. Further study is needed to define the significance of these factors.


Conserved RNA secondary structures promote alternative splicing.
Pre-mRNA splicing is carried out by the spliceosome, which identifies exons and removes intervening introns. Alternative splicing in higher eukaryotes results in the generation of multiple protein isoforms from gene transcripts. The extensive alternative splicing observed implies a flexibility of the spliceosome to identify exons within a given pre-mRNA. To reach this flexibility, splice-site selection in higher eukaryotes has evolved to depend on multiple parameters such as splice-site strength, splicing regulators, the exon/intron architecture, and the process of pre-mRNA synthesis itself. RNA secondary structures have also been proposed to influence alternative splicing as stable RNA secondary structures that mask splice sites are expected to interfere with splice-site recognition. Using structural and functional conservation, we identified RNA structure elements within the human genome that associate with alternative splice-site selection. Their frequent involvement with alternative splicing demonstrates that RNA structure formation is an important mechanism regulating gene expression and disease.


Cholecystokinin knockout mice are resistant to high-fat diet-induced obesity.
Cholecystokinin (CCK) is a satiation peptide released during meals in response to lipid intake; it regulates pancreatic digestive enzymes that are required for absorption of nutrients. We proposed that mice with a disruption in the CCK gene (CCK knockout [CCK-KO] mice) that were fed a diet of 20% butter fat would have altered fat metabolism. We used quantitative magnetic resonance imaging to determine body composition and monitored food intake of CCK-KO mice using an automated measurement system. Intestinal fat absorption and energy expenditure were determined using a noninvasive assessment of intestinal fat absorption and an open circuit calorimeter, respectively. After consuming a high-fat diet for 10 weeks, CCK-KO mice had reduced body weight gain and body fat mass and enlarged adipocytes, despite the same level of food intake as wild-type mice. CCK-KO mice also had defects in fat absorption, especially of long-chain saturated fatty acids, but pancreatic triglyceride lipase did not appear to have a role in the fat malabsorption. Energy expenditure was higher in CCK-KO than wild-type mice, and CCK-KO mice had greater oxidation of carbohydrates while on the high-fat diet. Plasma leptin levels in the CCK-KO mice fed the high-fat diet were markedly lower than in wild-type mice, although levels of insulin, gastric-inhibitory polypeptide, and glucagon-like peptide-1 were normal. CCK is involved in regulating the metabolic rate and is important for lipid absorption and control of body weight in mice placed on a high-fat diet.


Vision-related quality of life comparison for emmetropes, myopes after refractive surgery, and myopes wearing spectacles or contact lenses.
To compare the vision-related quality of life among emmetropes, myopes who had refractive surgery, and myopes who wore spectacles and/or contact lenses. This cross-sectional study assessed vision-related quality of life using the Vision Quality of Life Index. Participants were age 18 years or older with a presenting visual acuity of 20/40 or better and no other ocular pathology. Responses were compared among three groups: emmetropes (spherical equivalent [SE] < 0.50 to > -0.50 diopters [D]), myopes (SE < or = -0.50 D) who wore spectacles and/or contact lenses, and myopes who had refractive surgery. The study population included 64 emmetropes, 66 myopes who wore spectacles and/or contact lenses, and 65 myopes who had refractive surgery. No significant differences were found between the refractive surgery and emmetropic groups. In contrast, the spectacle and/or contact lens group had significantly increased odds of having concerns about injuring themselves (odds ratio = 11.5, 95% confidence interval [CI] 2.3, 57.1), difficulties coping with demands in life (odds ratio = 23.6, 95% CI 23.8, 198.1), difficulties fulfilling roles (odds ratio = 5.6, 95% CI 1.4, 22.1), and less confidence joining in everyday activities (odds ratio = 30.6, 95% CI 3.2, 292.3) compared to emmetropes. Myopia corrected with spectacles or contact lenses had a negative impact on some areas of vision-related quality of life. However, individuals with myopia who had refractive surgery enjoyed the same vision-related quality of life as those with emmetropia. The potential improvement in vision-related quality of life should be considered when recommending treatment for myopia.


Assessment of cytologic follow-up as the recommended management for patients with atypical squamous cells of undetermined significance or low grade squamous intraepithelial lesions.
The optimal management of low grade Papanicolaou (Pap) smear abnormalities remains controversial. This center's experience with recommending cytologic follow-up for women with atypical cells of undetermined significance (ASCUS) or low grade squamous intraepithelial lesions (LSIL) was reviewed to determine outcome and patient/physician compliance. The records were reviewed on women with Pap smears reported as either ASCUS (320) or LSIL (112) who did not have a history of dysplasia. The cytologic and colposcopic follow-up for a 2-year period was obtained from the laboratory data base that includes the colposcopy and cancer referrals for this region. Repeat Pap smear in 6 months was recommended. If patients subsequently demonstrated high grade SIL (HSIL) or persistent ASCUS or LSIL over three time intervals, colposcopic evaluation was recommended. The outcome was determined by the most significant diagnosis among the follow-up Pap smears or colposcopic biopsies. 29% of patients were lost to follow-up. Of the remaining patients, 70.5% reverted to normal or benign cellular changes, 25.3% persisted as ASCUS or LSIL, and 5.2% progressed to HSIL. The majority of patients (68%) were referred for colposcopy for persistent mildly abnormal Pap smears. The timing of referral ranged from 3-30 months. These results suggest that cytologic follow-up of women with low grade Pap smear abnormalities will identify a large number whose smears will regress to normal. A small but significant proportion of women showed subsequent HSIL. Most HSIL was detected within 1 year of the initial abnormal Pap smear and the majority of intervening Pap smears also were abnormal. Approximately one third of patients did not have follow-up within the study system and their outcome was uncertain. Although the recommendations are standard, patterns of follow-up and referral to colposcopy varied widely, suggesting that the guidelines need to be reinforced to both patients and physicians. [See editorial on pages 1-4, this issue.]


Chromophobe renal cell carcinoma: a morphologic and immunohistochemical study of 45 cases.
The aim of this study was to evaluate the morphological spectrum of chromophobe renal cell carcinoma (CRCC) and diagnostic utility of a panel of three immunohistochemical stains. All cases of CRCC reported between 2002 and 2012 in the Section of Histopathology, Aga Khan University Hospital, were retrieved. A total of 45 cases were identified. Slides were reviewed and immunohistochemical stains (CK7, CD117, and vimentin) were performed. Ages ranged from 18 to 90 years (mean, 48.5 years). Male-to-female ratio was 0.8:1. The tumor was located in the left kidney in 24 patients and the right kidney in 20 patients. The tumor size ranged from 3.5 to 22 cm (mean 10 cm). Histologically, 4 were classic, 22 were eosinophilic, 16 were mixed, and 3 were sarcomatoid type. Morphologic patterns included broad alveolar, solid, nested, tubular, tubulocystic, trabecular, papillary, and microglandular. Binucleation and perinuclear halos were seen in all cases. Nuclear grooves and pseudoinclusions were seen in 17 and 6 cases, respectively. Multinucleated cells were seen in 19 cases. Mitoses ranged from 1 to 11/10 HPFs (mean 3/10 HPFs). Hyalinized stroma was seen in 38 cases and calcification in 26 cases. Necrosis was seen in 18 cases. Palisading of smaller cells around the broad alveolar pattern was noted in 5 cases. The Furhman's nuclear grade was I (11), II (26), III (5), and IV (3). Hale's colloidal iron was positive in all cases. Immunohistochemical stain CK7 and CD117 were positive in 100% and 95.5% of cases respectively. Vimentin was negative in all cases, except in the sarcomatoid areas of 3 cases. In conclusion, chromophobe renal cell carcinoma has certain unique morphological features and immunohistochemical profile which help to distinguish it from conventional renal cell carcinoma and oncocytoma. We identified nuclear pseudoinclusions, microglandular pattern and palisading of smaller cells, which have not been reported earlier.


[Assessment of the contribution of complex and simple Purkinje cell impulses to local potentials of the cerebellar cortex].
Potentials amplitude decrement with the distance between referent cell and test electrode is estimated by means of potential averaging synchronous with complex and simple spikes of the referent Purkinje cell. Anisotropy of recorded fields in accordance with natural planes of anisotropy of cerebellar cortex and temporal parameters of complex and simple spikes has been described. Use of synchronous averaging for increase of a probability of finding of Purkinje cells pairs controlled with the same climbing fiber is discussed.


Resolution of the phylogenetic position of the Congo peafowl, Afropavo congensis: a biogeographic and evolutionary enigma.
Afropavo congensis, the Congo peafowl, has long fascinated ornithologists because of its uncertain phylogenetic position and unusual geographic distribution. While some researchers have placed Afropavo as a sister taxon to the true peafowl, Pavo species, others have suggested relationships with the guineafowl or an Old World partridge, Francolinus. These divergent opinions are due, at least in part, to (i) the unique morphological characteristics, lack of elaborate ornamentation, and monogamous mating system in Afropavo which differentiates it from Pavo; and (ii) the restricted distribution of Afropavo in Zaire, which is far removed from the Asian distribution of all other pheasant species. We obtained complete cytochrome b and partial D-loop sequences of Afropavo and compared them to Pavo, guineafowl, Francolinus and other galliform taxa. Our results strongly support a close relationship between Afropavo and Pavo, and we were able to reject alternative phylogenetic hypotheses. Molecular clock estimates of the divergence time place the separation of Afropavo and Pavo in the late Miocene. We also discuss other relatives of Afropavo and Pavo and use this information to propose hypotheses regarding the evolution of ornamentation and sexual dimorphism within this group of pheasants.


Biphasic effect of aspirin on apoptosis of bovine vascular endothelial cells and its molecular mechanism.
To investigate the effect of aspirin on the apoptosis of cultured bovine aortic endothelial cells (BAEC) and the signal pathways involved in this process. BAEC were cultured and passaged in Dulbecco's modified Eagle's medium culture medium. Morphologic changes and quantification of apoptotic cells were determined using fluorescence microscope after staining the cells with Hoechst 33258. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide (MTT) method. DNA fragmentation was visualized by agarose gel electrophoresis. Phospho-p38 mitogen-activated protein kinase (MAPK) expression was detected by Western blotting. Aspirin at low concentrations from 1X10( -10) mol/L to 1X10( -8) mol/L decreased the apoptosis and p38 MAPK phosphorylation induced by H2O2 in BAEC, while high doses of aspirin (1X10( -7)-1X10( -4) mol/L) induced typical apoptotic changes in BAEC and stimulated the expression of phospho-p38 MAPK in a concentration-dependent manner. SB203580, a specific p38 MAPK inhibitor, blocked such effects. Aspirin exhibits a biphasic effect on the apoptosis in BAEC, reducing apoptosis at low concentration and inducing apoptosis at high concentration. p38 MAPK may be an important signal molecule mediating the effects of aspirin.


[Early tracheal intubation and mechanical ventilation in the treatment of pulmonary edema secondary to ischemic heart disease].
Forty patients with overt pulmonary edema secondary to ischemic heart disease were treated in the emergency room with iv ouabain and furosemide; 20 patients in Group A received sublingual nifedipine before undergoing early tracheal intubation and mechanical ventilation with 100% FiO2 during 15 min. and then 50% FiO2; 20 patients in Group B received iv aminophylline, rotating tourniquets and IPPB by mask with 60% FiO2. All patients in Group A were extubated after 66 +/- 10.8 min. in the emergency room; 7 in Group B improved but 13 had to undergo tracheal intubation and mechanical ventilation. Upon arrival at the ICCU all had a Swan-Ganz catheter installed and received comparable therapy for ischemic heart disease. Statistically significant differences in favor of patients in Group A as compared to the 7 improved in B were seen in heart rate, arrhythmias, diastolic blood pressure, mean and wedge pulmonary pressures, systemic resistances, arterial pH and PaO2; when compared to the 13 patients undergoing late tracheal intubation and mechanical ventilation, parameters were more or less similar but improvement appeared later and extubation took place after 1.94 +/- 1.24 days (P less than 0.05). Three patients in Group B died in the emergency room, 3 in Group A and 4 in B died in the ICCU (P less than 0.01). Early tracheal intubation and mechanical ventilation in patients with overt pulmonary edema secondary to ischemic heart disease produce better results due to early improvement in pulmonary and systemic hemodynamics and should be considered in all such patients arriving at the emergency room.


Influence of turbulence strength on temporal correlation of scintillation.
Through extensive laboratory experimentation we demonstrate that the temporal frequency content of turbulence-induced scintillation strongly depends on the temperature gradient exerted at the propagation path of a collimated laser beam. We find a power law relating the turbulence strength induced by convection with the vertical temperature gradient and we show that the cutoff frequency of scintillation shows an approximately linear growth with turbulence strength, measured by angle-of-arrival fluctuations. The impact of these findings are discussed in the context of free-space optical communications.


Measuring Mental Health Recovery: An Application of Rasch Modeling to the Consumer Recovery Measure.
As the need for recovery-oriented outcomes increases, it is critical to understand how numeric recovery scores are developed. In the current article, the modern Rasch modeling techniques were applied to establish numeric scores of consumers' perceptions of recovery. A sample of 1,973 adult consumers at a community-based mental health center (57.5% male; average age of 47 years old) completed the 15-item Consumer Recovery Measure. A confirmatory factor analysis revealed the unidimensional nature of the Consumer Recovery Measure and provided construct validity evidence. The Rasch analysis displayed that the items produced acceptable model fit, reliability, and identified the difficulty of the items. The conclusion emphasizes the value of Rasch modeling regarding the measurement of recovery and its relevance to consumer-derived assessments in the clinical decision-making process.


Accuracy of colposcopy-directed biopsy vs dynamic spectral imaging directed biopsy in correctly identifying the grade of cervical dysplasia in women undergoing conization: A methodological study.
Dynamic spectral imaging (DSI) colposcopy has previously been found to improve sensitivity of CIN2+ detection. The aim of this study was to compare the histological diagnosis of colposcopic-directed biopsies (CDB) with that of DSI-directed biopsies in women undergoing conization, using the histological diagnosis of the conization specimen as gold standard. Women referred for colposcopy were included in a prospective cohort study at Randers Regional Hospital, Denmark, from January 2016 to February 2019. All women had four cervical punch biopsies taken. The first biopsy was taken from the area that appeared most abnormal by conventional colposcopy (ie, CDB) and the second biopsy from the area that appeared most abnormal using the DSI map. An additional two biopsies were taken either from other visible lesions or as random biopsies. Biopsies were analyzed separately. If any biopsies revealed cervical dysplasia of such a degree that excisional treatment was recommended, the patient was referred for conization. Subsequently, we compared the histological diagnosis of CDB and DSI-directed biopsies with that of the cone biopsy. A total of 573 women were enrolled, 170 of which underwent conization. In women with an adequate colposcopy and representative biopsies (n = 124) there was an overall agreement rate between the worst biopsy diagnosis (of any four) and the conization diagnosis in 95.2% (95% CI 89.8-98.2) of women. CDB diagnosis agreed with the cone diagnosis in 80.6% (95% CI 72.6-87.2) of women. DSI-directed biopsy agreed with the cone diagnosis in 83.9% (95% CI 76.2-89.9) of women. The difference in detection rate between the CDB and the DSI-directed biopsy was, however, not significant (P = .54). Taking four biopsies increases the detection rate of cervical dysplasia to 95.2%, which was a significant increase from both CDB alone (P = .0008) and DSI-directed biopsy alone (P = .0053). We found no significant difference in the ability to identify the cervical dysplasia grade between CDB and DSI-directed biopsies. A higher detection rate of cervical dysplasia was achieved with four biopsies than with one CDB biopsy or one DSI-directed biopsy.


Imbalanced spontaneous brain activity in orbitofrontal-insular circuits in individuals with cognitive vulnerability to depression.
The hopelessness theory of depression posits that individuals with negative cognitive styles are at risk of developing depression following negative life events. The purpose of this work was to examine whether individuals with cognitive vulnerability to depression (CVD) exhibit similar spontaneous brain activity patterns as compared to patients with major depressive disorder (MDD). Subjects with CVD (N=32), drug-naïve first-episode patients with major depressive disorder (N=32), and sex-, age- and education-matched healthy controls (HCs; N=35) were subjected to resting state functional magnetic resonance imaging (RS-fMRI) and amplitudes of low-frequency fluctuation (ALFF) was compared between the groups. Pearson correlation analysis was performed between regional ALFFs and psychometric scores, namely the Cognitive Style Questionnaire (CSQ) and the Center for Epidemiologic Studies Depression (CES-D) scale scores. Significant group differences in ALFF values were observed bilaterally in the orbitofrontal cortex (OFC) and insular cortex (IC), and in the left fusiform gyrus (FFG). Compared to HCs, CVD subjects had reduced ALFFs in the bilateral OFC and increased ALFF in the bilateral IC and the left FFG, which were similar to the differences observed between the HCs and MDD patients. Compared to MDD patients, CVD subjects showed significant reduced ALFF values in right IC. Additionally, CSQ scores for the CVD group correlated with ALFF values in the left IC. We did not conduct a longitudinal study. Our findings were limited in cross-sectional analysis. A hypoactive OFC and hyperactive IC in a resting-state may underlie an imbalance in the spontaneous brain activity in orbitofrontal-insular circuits, and these differences may represent a trait-related marker of vulnerability to depression.


Tissue-engineered collateral ligament composite allografts for scapholunate ligament reconstruction: an experimental study.
In patients with chronic scapholunate (SL) dissociation or dynamic instability, ligament repair is often not possible, and surgical reconstruction is indicated. The ideal graft ligament would recreate both anatomical and biomechanical properties of the dorsal scapholunate ligament (dorsal SLIL). The finger proximal interphalangeal joint (PIP joint) collateral ligament could possibly be a substitute ligament. We harvested human PIP joint collateral ligaments and SL ligaments from 15 cadaveric limbs. We recorded ligament length, width, and thickness, and measured the biomechanical properties (ultimate load, stiffness, and displacement to failure) of native dorsal SLIL, untreated collateral ligaments, decellularized collateral ligaments, and SL repairs with bone-collateral ligament-bone composite collateral ligament grafts. As proof of concept, we then reseeded decellularized bone-collateral ligament-bone composite grafts with green fluorescent protein-labeled adipo-derived mesenchymal stem cells and evaluated them histologically. There was no difference in ultimate load, stiffness, and displacement to failure among native dorsal SLIL, untreated and decellularized collateral ligaments, and SL repairs with tissue-engineered collateral ligament grafts. With pair-matched untreated and decellularized scaffolds, there was no difference in ultimate load or stiffness. However, decellularized ligaments revealed lower displacement to failure compared with untreated ligaments. There was no difference in displacement between decellularized ligaments and native dorsal SLIL. We successfully decellularized grafts with recently described techniques, and they could be similarly reseeded. Proximal interphalangeal joint collateral ligament-based bone-collateral ligament-bone composite allografts had biomechanical properties similar to those of native dorsal SLIL. Decellularization did not adversely affect material properties. These tissue-engineered grafts may offer surgeons another option for reconstruction of chronic SL instability.


Consistency of participation over time among persons aging with physical disability as measured by a tool designed for use among community-based organizations.
Community participation measures for persons aging with disability were developed and evaluated to support community-based organizations (CBOs) with efficient assessment of change in participation and need for supports/services to facilitate participation. To evaluate a set of nine activity domain measures to broadly assess community participation and change in participation over time. A community-based sample (N = 323) of persons ages 45-65 responded to a survey with repeated measures three times annually (T1, T2, T3) between 2019 and 2022. Nine activity domain measures were developed based on extant research and evaluated with assistance from community-based support service providers. Statistical analyses employed T-tests and chi-square tests to assess change in participation over time, perceptions of participation satisfaction, and assistance needed to facilitate participation. Participants were asked if they thought changes were attributable to aging, the COVID-19 pandemic, or other factors. Findings showed varying levels of participation across the nine activity domains, with the lowest participation rate for employment and the highest participation rates for personal leisure and managing medications across T1, T2, and T3. Change in participation over the three-year period was limited; most change was reported as activity reduction. In general, respondents indicated that reduction was due to their aging or the COVID-19 pandemic. Personal assistance, transportation, environmental modifications, and improved health were identified as factors needed to help increase participation levels. The activity domain measures demonstrated efficiency in identifying participation rates and change. CBOs may deem them useful for assessing support and service needs to facilitate participation.


Women in family farming: Evidence from a qualitative study in two Portuguese inner regions.
The importance of family farming in food systems worldwide is recognized by different international bodies, as well as the leading role played by women and the inequalities they face in this sector of activity. The most recent data from Portugal highlight the importance of this type of agriculture in this Southern European country. In 2019, 68% of the total agricultural workforce in the country was concentrated in family farming, with almost half of them being women. This high permanence of women in agriculture is the result of a long process of feminization on this sector that is similar to other contexts. Despite this strong feminization of family farming, there are few studies that portrait agricultural activity from the women's viewpoint, since the voice of men is always predominant in all references. Based on the exploratory qualitative data from two focus groups, carried out in two Portuguese inner regions, we intend to address the perceptions and meanings of a small group of women farmers regarding their activity, the role taken by them in agriculture and the difficulties they experience. Issues such as changes in agriculture and the sexual division of labor will also be addressed in this article. Within these groups, women work in agriculture is perceived as long, solitary and uncertain. Also, the public/private dichotomy is evident, with decision-making and public places dominated by men. A prevalence of the discourse of "masculinization" still exists with certain tasks being attributed to men (e.g., operations with machinery). Younger women (34 and 40 years old) tend to overcome these gender differences choosing agriculture as a profession and healthy and sustainable life for their families.


Clinical Features of COVID-19 on Patients With Neuromyelitis Optica Spectrum Disorders.
To describe the clinical features and disease outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorder (NMOSD). The Neuroimmunology Brazilian Study Group has set up the report of severe acute respiratory syndrome (SARS-CoV2) cases in patients with NMOSD (pwNMOSD) using a designed web-based case report form. All neuroimmunology outpatient centers and individual neurologists were invited to register their patients across the country. Data collected between March 19 and July 25, 2020, were uploaded at the REDONE.br platform. Inclusion criteria were as follows: (1) NMOSD diagnosis according to the 2015 International Panel Criteria and (2) confirmed SARS-CoV2 infection (reverse transcription-polymerase chain reaction or serology) or clinical suspicion of COVID-19, diagnosed according to Center for Disease Control / Council of State and Territorial Epidemiologists (CDC/CSTE) case definition. Demographic and NMOSD-related clinical data, comorbidities, disease-modifying therapy (DMT), COVID-19 clinical features, and severity were described. Among the 2,061 pwNMOSD followed up by Brazilian neurologists involved on the registry of COVID-19 in pwNMOSD at the REDONE.br platform, 34 patients (29 women) aged 37 years (range 8-77), with disease onset at 31 years (range 4-69) and disease duration of 6 years (range 0.2-20.5), developed COVID-19 (18 confirmed and 16 probable cases). Most patients exhibited mild disease, being treated at home (77%); 4 patients required admission at intensive care units (severe cases); and 1 patient died. Five of 34 (15%) presented neurologic manifestations (relapse or pseudoexacerbation) during or after SARS-CoV2 infection. Most NMOSD patients with COVID-19 presented mild disease forms. However, pwNMOSD had much higher odds of hospitalization and intensive care unit admission comparing with the general Brazilian population. The frequency of death was not clearly different. NMOSD disability, DMT type, and comorbidities were not associated with COVID-19 outcome. SARS-CoV2 infection was demonstrated as a risk factor for NMOSD relapses. Collaborative studies using shared NMOSD data are needed to suitably define factors related to COVID-19 severity and neurologic manifestations.


Comprehensive analysis of iron utilization by Mycobacterium tuberculosis.
Iron is essential for nearly all bacterial pathogens, including Mycobacterium tuberculosis (Mtb), but is severely limited in the human host. To meet its iron needs, Mtb secretes siderophores, small molecules with high affinity for iron, and takes up iron-loaded mycobactins (MBT) and carboxymycobactins (cMBT), from the environment. Mtb is also capable of utilizing heme and hemoglobin which contain more than 70% of the iron in the human body. However, many components of these iron acquisition pathways are still unknown. In this study, a high-density transposon mutagenesis coupled with deep sequencing (TnSeq) showed that Mtb exhibits nearly opposite requirements for 165 genes in the presence of heme and hemoglobin versus MBT and cMBT as iron sources. The ESX-3 secretion system was assessed as essential for siderophore-mediated iron uptake and, surprisingly, also for heme utilization by Mtb. Predictions derived from the TnSeq analysis were validated by growth experiments with isogenic Mtb mutants. These results showed that (i) the efflux pump MmpL5 plays a dominant role in siderophore secretion, (ii) the Rv2047c protein is essential for growth of Mtb in the presence of mycobactin, and (iii) the transcriptional repressor Zur is required for heme utilization by Mtb. The novel genetic determinants of iron utilization revealed in this study will stimulate further experiments in this important area of Mtb physiology.


Getting angry matters: Going beyond perspective taking and empathic concern to understand bystanders' behavior in bullying.
The present study examined the relations between different empathic dimensions and bystanders' behavior in bullying. Specifically, the indirect effects of empathic concern and perspective taking via empathic anger on defending and passive bystanding were tested in a sample of Italian young adolescents (N = 398; Mage = 12 years, 3 months, 47.2% girls). Path analysis confirmed the direct and indirect effects, via empathic anger, of empathic concern and perspective taking on bystanders' behavior, with the exception of the direct association between perspective taking and passive bystanding that was not significant. Our findings suggest that considering empathic anger together with empathic concern and perspective taking could help researchers to better understand the links between empathic dispositions and bystanders' behavior in bullying.


When the world collapses: changed worldview and social reconstruction in a traumatized community.
Traumatic experience can affect the individual's basic beliefs about the world as a predictable and safe place. One of the cornerstones in recovery from trauma is reestablishment of safety, connectedness, and the shattered schema of a worldview. This study explored the role of negatively changed worldview in the relationship between war-related traumatization and readiness for social reconstruction of intergroup relations in a post-conflict community measured by three processes: intergroup rapprochement, rebuilding trust, and need for apology. It was hypothesized that more traumatized people are less supportive of social reconstruction and that this relationship is mediated by the changed worldview. The study included a community random sample of 333 adults in the city of Vukovar, Croatia, that was most devastated during the 1991-1995 war. Six instruments were administered: Stressful Events Scale, Impact of Event Scale-Revised, Changed Worldview Scale, and three scales measuring the post-conflict social reconstruction processes: Intergroup Rapprochement, Intergroup Trust and Need for Apology. Mediation analyses showed that the worldview change fully mediated between traumatization and all three aspects of social reconstruction. In a population exposed to war traumatization the worldview change mediates post-conflict social recovery of community relations.


Donor-Acceptor-Collector Ternary Crystalline Films for Efficient Solid-State Photon Upconversion.
It is pivotal to achieve efficient triplet-triplet annihilation based photon upconversion (TTA-UC) in the solid-state for enhancing potentials of renewable energy production devices. However, the UC efficiency of solid materials is largely limited by low fluorescence quantum yields that originate from the aggregation of TTA-UC chromophores and also by severe back energy transfer from the acceptor singlet state to the singlet state of the triplet donor in the condensed state. In this work, to overcome these issues, we introduce a highly fluorescent singlet energy collector as the third component of donor-doped acceptor crystalline films, in which dual energy migration, i.e., triplet energy migration for TTA-UC and succeeding singlet energy migration for transferring energy to a collector, takes place. To demonstrate this scheme, a highly fluorescent singlet energy collector was added as the third component of donor-doped acceptor crystalline films. An anthracene-based acceptor containing alkyl chains and a carboxylic moiety is mixed with the triplet donor Pt(II) octaethylporphyrin (PtOEP) and the energy collector 2,5,8,11-tetra- tert-butylperylene (TTBP) in solution, and simple spin-coating of the mixed solution gives acceptor films of nanofibrous crystals homogeneously doped with PtOEP and TTBP. Interestingly, delocalized singlet excitons in acceptor crystals are found to diffuse effectively over the distance of ∼37 nm. Thanks to this high diffusivity, only 0.5 mol % of doped TTBP can harvest most of the singlet excitons, which successfully doubles the solid-state fluorescent quantum yield of acceptor/TTBP blend films to 76%. Furthermore, since the donor PtOEP and the collector TTBP are separately isolated in the nanofibrous acceptor crystals, the singlet back energy transfer from the collector to the donor is effectively avoided. Such efficient singlet energy collection and inhibited back energy transfer processes result in a large increase of UC efficiency up to 9.0%, offering rational design principles toward ultimately efficient solid-state upconverters.


What are the correlates of intention to be physically active in Brazilian adolescents? A network analysis.
The current study aimed to explore the association of individual characteristics, social and environmental factors - school and region - in the intention to be physically active in Brazilian adolescents. This is a cross sectional study based on the third edition of the National School Health Survey. The study included a total of 53,937 adolescents. To assess the intention to be physically active, only who engaged in less than 300 min of physical activity per week were included. Participants were asked: "If you had the opportunity to practice physical activity most days of the week, what would your attitude be?" Individual characteristics, physical activity domains, social factors, school, and regional environments were used as exposures. Network analysis was utilized to evaluate the associations. We observed that boys had higher intentions to be physically active compared to their peers, as did adolescents who perceived themselves as fat. In addition, students from private schools show a higher intention to regularly engage in physical activities, and in general, private schools offer more extracurricular physical activities. In conclusion, individual factors such as sex and body image perception, and environmental factors such as school administrative dependency and availability of extracurricular activities had a significant contribution to the intention to be physically active among Brazilian adolescents.


The Sorghum (Sorghum bicolor) Brown Midrib 30 Gene Encodes a Chalcone Isomerase Required for Cell Wall Lignification.
In sorghum (Sorghum bicolor) and other C4 grasses, brown midrib (bmr) mutants have long been associated with plants impaired in their ability to synthesize lignin. The brown midrib 30 (Bmr30) gene, identified using a bulk segregant analysis and next-generation sequencing, was determined to encode a chalcone isomerase (CHI). Two independent mutations within this gene confirmed that loss of its function was responsible for the brown leaf midrib phenotype and reduced lignin concentration. Loss of the Bmr30 gene function, as shown by histochemical staining of leaf midrib and stalk sections, resulted in altered cell wall composition. In the bmr30 mutants, CHI activity was drastically reduced, and the accumulation of total flavonoids and total anthocyanins was impaired, which is consistent with its function in flavonoid biosynthesis. The level of the flavone lignin monomer tricin was reduced 20-fold in the stem relative to wild type, and to undetectable levels in the leaf tissue of the mutants. The bmr30 mutant, therefore, harbors a mutation in a phenylpropanoid biosynthetic gene that is key to the interconnection between flavonoids and monolignols, both of which are utilized for lignin synthesis in the grasses.


Annotated primary scientific literature: A pedagogical tool for undergraduate courses.
Annotated primary scientific literature is a teaching and learning resource that provides scaffolding for undergraduate students acculturating to the authentic scientific practice of obtaining and evaluating information through the medium of primary scientific literature. Utilizing annotated primary scientific literature as an integrated pedagogical tool could enable more widespread use of primary scientific literature in undergraduate science classrooms with minimal disruption to existing syllabi. Research is ongoing to determine an optimal implementation protocol, with these preliminary iterations presented here serving as a first look at how students respond to annotated primary scientific literature. The undergraduate biology student participants in our study did not, in general, have an abundance of experience reading primary scientific literature; however, they found the annotations useful, especially for vocabulary and graph interpretation. We present here an implementation protocol for using annotated primary literature in the classroom that minimizes the use of valuable classroom time and requires no additional pedagogical training for instructors.


F-18 fluorodeoxyglucose positron emission tomography in the non-invasive staging of non-small cell lung cancer.
Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG), a glucose analogue, as a metabolic tumour marker, has been proposed for the non-invasive staging of oncological disease. Tumours demonstrate increased glycolytic activity and thereby, FDG PET can differentiate benign from malignant lesions. To determine its role in the mediastinal staging of patients with suspected non-small cell lung cancer, a prospective study of FDG PET and computed tomography (CT) compared to surgery and pathology was performed. The analysis group consists of 50 patients, 37 men and 13 women, mean age 64 years (range, 41-78 years). A nuclear physician, blind to the clinical and CT data, graded the FDG PET studies qualitatively on a five-point scale, based on the intensity of glucose uptake, for the presence of mediastinal nodal tumour involvement. Scores of four or greater were considered positive for tumour. An experienced radiologist interpreted the patients' CT scans blind to the other data. The CT criterion for tumour involvement was a nodal long axis diameter of 10 mm or greater. All patients underwent either thoracotomy or mediastinoscopy to obtain surgical specimens. The PET, CT, surgery and pathology were mapped according to the American Thoracic Society nodal classification resulting in 201 nodal stations evaluated. The imaging studies were analysed for N2 or N3 tumour involvement compared to histology or dissection of nodal stations. All patients had proven non-small cell lung carcinoma. PET excluded tumour in 175 of 181 nodal stations (specificity 97%) compared to 162 of 181 (specificity 90%) by CT. PET correctly identified 16 of 20 (sensitivity 80%) nodal stations with tumour compared to 13 of 20 by CT (sensitivity 65%). Overall, PET correctly staged 191 of 201 nodal stations (accuracy 95%) compared to 175 of 201 by CT (accuracy 87%). By the McNemar test, PET was significantly more specific than CT in excluding nodal tumour involvement (X2 = 5.5, P < 0.05). FDG PET is more specific than computed tomography in the non-invasive mediastinal staging of non-small cell lung cancer and has an important clinical role in the pre-operative staging of lung cancer patients.


Genetic Engineering of Therapeutic Phages Using Type III CRISPR-Cas Systems.
The functional characterization of "hypothetical" phage genes is a major bottleneck in basic and applied phage research. To compound this issue, the most suitable phages for therapeutic applications-the strictly lytic variety-are largely recalcitrant to classical genetic techniques due to low recombination rates and lack of selectable markers. Here we describe methods for fast and effective phage engineering that rely upon a Type III-A CRISPR-Cas system. In these methods, the CRISPR-Cas system is used as a powerful counterselection tool to isolate rare phage recombinants.


Not just females and males: unravelling the complex sex determinism of the hemp palm Trachycarpus fortunei.
The Asian palm Trachycarpus fortunei (Arecaceae: Coryphoideae) is an ornamental species that is widely planted in temperate regions. In Europe, it has spread outside of gardens, particularly on the southern side of the Alps. Sexual expression in the species is complex, varying from dioecy to polygamy. This study investigated (1) sexual floral development and (2) genetic markers implicated in sex determinism. The morphology and anatomy of floral organs at different developmental stages were studied using SEM observations and anatomical sections. Sex determinism was explored using a Genome-Wide Association Study (GWAS) approach, searching for correlations between 31'000 SNP markers and sex affiliation of 122 palms from 21 wild populations. We observed that sexual differentiation appears late in floral development of T. fortunei. Morpho-anatomical characters of flowers conducive to panmixia were observed, such as well-differentiated septal nectaries that are thought to promote cross-pollination. At the molecular level, homozygous and heterozygous allelic systems with closely linked regions were found for sex determinism in individuals with female and 'dominant-male' phenotypes, respectively. Through our wide sampling in the southern Alps, the closely linked genetic regions in males suggest that at least fifteen percent of wild palms are the direct offspring of 'males' that can also produce fertile pistillate flowers. Trachycarpus fortunei is a further example of unstable sexual expression found in the family Arecaceae and represents an evolutionary path towards an XY genetic system. Our structural and genetic results may explain the high species dispersal ability in the southern Alps. This article is protected by copyright. All rights reserved.


Cup-disc ratio and ischemic optic neuropathy.
Cup-disc ratios in the fellow eyes of 26 patients with unilateral, nonarteritic, anterior ischemic optic neuropathy were compared with the ratios in fellow eyes of 29 patients with unilateral idiopathic or demyelinative optic neuritis. The ratios in both groups were also compared with the ratios of a large group of normal subjects evaluated in a population survey. Observers measured the cup-disc ratio by viewing color stereophotographs. The cup-disc ratios of the fellow eyes of patients with anterior ischemic optic neuropathy were significantly smaller on average than were those of the fellow eyes of patients with optic neuritis and the normal subjects. Eyes with small cup-disc ratios may be more vulnerable to infarction than are eyes with large cup-disc ratios.


Cesarean Section Is Associated with an Increased Risk of Acute Lymphoblastic Leukemia and Hepatoblastoma in Children from Minnesota.
In recent decades, Cesarean section (C-section) rates have increased. C-section is hypothesized to negatively impact the developing immune system by altering activation of the hypothalamic-pituitary-adrenal axis and the infant microbiome, among other mechanisms, thereby potentially modulating childhood cancer risk. Using linked birth and cancer registry data from Minnesota (1976-2014), we included individuals ages 0-14 at diagnosis with one of 19 cancers. Cases and controls were frequency matched by birth year. We used logistic regression to estimate ORs and 95% confidence intervals (95% CI) as the measure of association between C-section and cancer. We assessed sex-C-section interactions for each cancer and conducted stratified analyses in acute lymphoblastic leukemia (ALL) for birth year, age at diagnosis, and maternal race. There were 3,166 cases and 20,589 controls. One third (n = 1,174) of controls born during 2004-2014 were delivered via C-section compared with 42.2% of cases (n = 285). C-section was associated with ALL (n = 819; OR: 1.20; 95% CI: 1.01-1.43) and hepatoblastoma (n = 50; OR: 1.89; 95% CI: 1.03-3.48), particularly among females (ALL OR: 1.34; 95% CI: 1.04-1.72; hepatoblastoma OR: 3.87; 95% CI: 1.30-11.57). The risk of ALL was highest during 2005-2014 (OR: 1.62; 95% CI: 1.11-2.34) and among children ages 1-5 years (OR: 1.28; 95% CI: 1.02-1.61). C-section was associated with an increased risk of ALL and hepatoblastoma. These associations require investigation to determine causality and rule out confounding by indication or reverse causality. The mechanisms underlying these associations may depend on neonatal immune system processes altered during C-section deliveries.


Vertical distribution, flight behaviour and evolution of wing morphology in Morpho butterflies.
1. Flight is a key innovation in the evolution of insects that is crucial to their dispersal, migration, territoriality, courtship and predator avoidance. Male butterflies have characteristic territoriality and courtship flight behaviours, and females use a characteristic flight behaviour when searching for host plants. This implies that selection acts on wing morphology to maximize flight performance for conducting important behaviours among sexes. 2. Butterflies in the genus Morpho are obvious components of neotropical forests, and many observations indicate that they show two broad categories of flight behaviour and flight height. Although species can be categorized as using gliding or flapping flight, and flying at either canopy or understorey height, the association of flight behaviour and flight height with wing shape evolution has never been explored. 3. Two clades within Morpho differ in flight behaviour and height. Males and females of one clade inhabit the forest understorey and use flapping flight, whereas in the other clade, males use gliding flight at canopy level and females use flapping flight in both canopy and understorey. 4. We used independent contrasts to answer whether wing shape is associated with flight behaviour and height. Given a single switch to canopy habitation and gliding flight, we compared contrasts for the node at which the switch to canopy flight occurred with the distribution of values in the two focal clades. We found significant changes in wing shape at the transition to canopy flight only in males, and no change in size for either sex. A second node within the canopy clade suggests that other factors may also be involved in wing shape evolution. Our results reinforce the hypothesis that natural selection acts differently on male and female butterfly wing shape and indicate that the transition to canopy flight cannot explain all wing shape diversity in Morpho. 5. This study provides a starting point for characterizing evolution of wing morphology in forest butterflies in the contexts of habitat selection and flight behaviour. Further, these observations suggest that exploring wing shape evolution for canopy and understorey species in other insects may help understand the effects of habitat destruction on biological diversity.


[The physical and health status of runaway slaves announced in Jornal do Commercio (RJ) in 1850].
The article examines the state of health of a population of runaway slaves, based on announcements published in Rio de Janeiro's Jornal do Commercio in 1850. Two strategies were used. The first entailed analysis of the slaves' physical characteristics, as described by their masters. Taking into account the slave's health, the second step was to describe his or her physical problems as viewed by the era's medical or folk knowledge. This evidence can be traced to procedures found in the slave system, which sought to maximize use of captives.


Spectroscopic scanning near-field optical microscopy with a free electron laser: CH2 bond imaging in diamond films.
Hydrogen chemistry in thin films and biological systems is one of the most difficult experimental problems in today's science and technology. We successfully tested a novel solution, based on the spectroscopic version of scanning near-field optical microscopy (SNOM). The tunable infrared radiation of the Vanderbilt free electron laser enabled us to reveal clearly hydrogen-decorated grain boundaries on nominally hydrogen-free diamond films. The images were obtained by SNOM detection of reflected 3.5 microm photons, corresponding to the C-H stretch absorption, and reached a lateral resolution of 0.2 microm, well below the lambda/2 (lambda = wavelength) limit of classical microscopy.


[Relationship between job satisfaction and patient safety culture].
To evaluate the relationship between safety culture and job satisfaction in a medium-stay hospital, showing the relationships between the dimensions that define both constructs and identifying the dimensions with the greatest impact on both variables. Cross-sectional study conducted in 2015, using the Basque Health Service Job Satisfaction Survey and the Spanish version of the «Hospital Survey on Patient Safety» questionnaire (Agency for Healthcare Research and Quality). Result Variables: high job satisfaction and high degree of perceived security (score ≥75th percentile). Predictor variables: socio-demographic characteristics and perception of the evaluated dimensions. The association between variables was quantified by adjusted odds ratio (OR) and the 95% confidence interval. The mean job satisfaction was 7.21 (standard deviation [SD]: 2.01) and the mean of perceived safety was 7.48 (SD=1.98). The 75th percentile of the distribution in both cases was 9. The socio-demographic variables had little significance, while a positive perception of many of the considered dimensions, was associated with high perception of the result variables. In the data analysis were obtained multiple significant correlations and cross-relations between the dimensions that define both constructs, as well as between the degree of satisfaction of the dimensions considered and the outcome variables. The results obtained evidenced the relationship between job satisfaction and safety culture and quantify the association degree between the studied variables. The adjusted OR identifies the variables most strongly associated with the effect and helps to select improvement areas.


Platelets induce apoptosis during sepsis in a contact-dependent manner that is inhibited by GPIIb/IIIa blockade.
End-organ apoptosis is well-described in progressive sepsis and Multiple Organ Dysfunction Syndrome (MODS), especially where platelets accumulate (e.g. spleen and lung). We previously reported an acute sepsis-induced cytotoxic platelet phenotype expressing serine protease granzyme B. We now aim to define the site(s) of and mechanism(s) by which platelet granzyme B induces end-organ apoptosis in sepsis. End-organ apoptosis in murine sepsis (i.e. polymicrobial peritonitis) was analyzed by immunohistochemistry. Platelet cytotoxicity was measured by flow cytometry following 90 minute ex vivo co-incubation with healthy murine splenocytes. Sepsis progression was measured via validated preclinical murine sepsis score. There was evident apoptosis in spleen, lung, and kidney sections from septic wild type mice. In contrast, there was a lack of TUNEL staining in spleens and lungs from septic granzyme B null mice and these mice survived longer following induction of sepsis than wild type mice. In co-incubation experiments, physical separation of septic platelets from splenocytes by a semi-permeable membrane reduced splenocyte apoptosis to a rate indistinguishable from negative controls. Chemical separation by the platelet GPIIb/IIIa receptor inhibitor eptifibatide decreased apoptosis by 66.6±10.6% (p = 0.008). Mice treated with eptifibatide in vivo survived longer following induction of sepsis than vehicle control mice. In sepsis, platelet granzyme B-mediated apoptosis occurs in spleen and lung, and absence of granzyme B slows sepsis progression. This process proceeds in a contact-dependent manner that is inhibited ex vivo and in vivo by the platelet GPIIb/IIIa receptor inhibitor eptifibatide. The GPIIb/IIIa inhibitors and other classes of anti-platelet drugs may be protective in sepsis.


Factors Associated With Medical and Nursing Students' Willingness to Donate Organs.
Malaysia suffers from a chronic shortage of human organs for transplantation. Medical and nursing students (MaNS) are future health professionals and thus their attitude toward organ donation is vital for driving national donation rates. This study investigates MaNS' willingness to donate organs upon death and the factors influencing their willingness. A cross-sectional design was used with a sample of 500 students (264 medical and 236 nursing) at the University of Malaya. A self-administrated questionnaire was used. The responses were analyzed by using descriptive statistics and multiple logistic regression. Of all respondents, 278 (55.6%) were willing to donate organs upon death, while the remaining 222 (44.4%) were unwilling to donate. Only 44 (8.8%) had donor cards. The multiple logistic regression revealed that the minorities ethnic group was more willing to donate organs than Malay respondents (adjusted odds ratio [aOR] = 1.98, P = 0.010). In addition, medical students were more willing to donate than nursing students (aOR = 2.53, P = 0.000). Respondents who have a family member with a donor card were more willing to donate than respondents who do not (aOR = 3.48, P = 0.006). MaNS who believed that their religion permits deceased donation were more willing to donate than their counterparts (aOR = 4.96, P = 0.000). Household income and sex were not significant predictors of MaNS' willingness to donate organs upon death. MaNS have moderate willingness, but low commitment toward deceased organ donation. Strategies for improving MaNS' attitude should better educate them on organ donation, targeting the most the Malay and nursing students, and should consider the influence of family attitude and religious permissibility on MaNS' willingness.


Central cord syndrome after total hip arthroplasty: a patient report.
Case report. To present a patient with central cord syndrome injury after total hip arthroplasty performed under general endotracheal anesthesia. Central cord syndrome, a common injury usually sustained as a result of an extension injury to the cervical spine, often occurs in geriatric patients with underlying spondylotic changes. The injury results in weakness and sensory changes, which are more pronounced in the upper than in the lower extremities. Patients with this syndrome experience variable return of function, but some degree of residual deficit and spasticity is likely. The medical record, including the intraoperative anesthesia records, operative notes, progress notes, discharge summary, clinic notes, and radiology studies and reports, was reviewed. The patient developed signs of central cord syndrome after total hip arthroplasty. Despite nonoperative intervention, including physiotherapy, the patient's upper and lower extremity weakness continued. Magnetic resonance imaging revealed evidence of cervical cord compression, and the patient underwent a cervical laminectomy, which produced mild improvement in his symptoms. To avoid life-altering complications, it is important to evaluate the cervical spine (especially in the elderly), avoid neck extension during intubation, and use careful airway management in patients with suspected stenosis/spondylosis.


Expression of ACC oxidase promoter-GUS fusions in tomato and Nicotiana plumbaginifolia regulated by developmental and environmental stimuli.
The enzyme ACC oxidase, catalysing the last step in the biosynthesis of the plant hormone ethylene, is encoded by a small multigene family in tomato, comprising three members, LEACO1, LEACO2 and LEACO3. LEACO1 is the major gene expressed during ripening, leaf senescence, and wounding (Barry et al., 1996). To investigate the transcriptional regulation of ACC oxidase gene expression, chimeric fusions between the beta-glucuronidase reporter gene and 97 bp of 5' UTR plus 124, 396 and 1825 bp, respectively, of 5' untranscribed LEACO1 sequence were constructed and introduced into Lycopersicon esculentum (Mill cv. Ailsa Craig) and Nicotiana plumbaginifolia. Analysis of transgenic tomatoes indicated that the region containing nucleotides -124 to +97 of the LEACO1 gene is sufficient to confer a marked increase in GUS activity during fruit ripening, albeit at very low levels. Fusion of 396 and 1825 bp of LEACO1 upstream sequence resulted in strong and specific induction of GUS expression in situations known to be accompanied by enhanced ethylene production. Reporter gene expression was similar to that of the endogenous LEACO1 gene, with major increases especially during fruit ripening, senescence and abscission of leaves and, to a lesser extent, of flowers. Analysis of transgenic N. plumbaginifolia plants confirmed the pattern of LEACO1 promoter activity detected in tomato leaves and flowers. Reporter gene expression was also induced following wounding, treatment with ethylene, and pathogen infection. Histochemical analysis illustrated localized GUS activity in the pericarp of ripening fruit, abscission zones of senescent petioles and unfertilized flowers, and at wound sites. These results demonstrate that ACC oxidase is regulated at the transcriptional level in a wide range of cell types at different developmental stages and in response to several external stimuli.


Hypoxia inducible factor-1alpha inactivation unveils a link between tumor cell metabolism and hypoxia-induced cell death.
Hypoxia and the acquisition of a glycolytic phenotype are intrinsic features of the tumor microenvironment. The hypoxia inducible factor-1alpha (HIF-1alpha) pathway is activated under hypoxic conditions and orchestrates a complex transcriptional program that enhances cell survival. Although the consequences of HIF-1alpha inactivation in cancer cells have been widely investigated, only a few studies have addressed the role of HIF-1alpha in the survival of cancer cells endowed with different glycolytic capacities. In this study, we investigated this aspect in ovarian cancer cells. Hypoxia-induced toxicity was increased in highly glycolytic cells compared with poorly glycolytic cells; it was also associated with a sharp decrease in intracellular ATP levels and was prevented by glucose supplementation. Stable HIF-1alpha silencing enhanced hypoxia-induced cell death in vitro due to a lack of cell cycle arrest. Tumors bearing attenuated HIF-1alpha levels had similar growth rates and vascularization as did controls, but tumors showed higher proliferation levels and increased necrosis. Moreover, tumors formed by HIF-1alpha deficient cells had higher levels of lactate and lower ATP concentrations than controls as shown by metabolic imaging. The findings that such metabolic properties can affect the survival of cancer cells under hypoxic conditions and that these properties contribute to the determination of the consequences of HIF-1alpha inactivation could have important implications on the understanding of the effects of anti-angiogenic and HIF-1alpha-targeting drugs in cancer.


Biosynthesis of collagen crosslinks: in vivo labelling of neonatal skin, tendon, and bone in rats.
Collagen crosslinks in neonatal rats were labelled in vivo by a single intraperitoneal injection of 200 microCi of [14C]lysine. Rats were killed at times ranging from 30 minutes to 10 weeks after injection. Whole skin, tendon, and bone were analyzed, after reduction and hydrolysis, for collagen crosslink content by HPLC. Crosslinks and amino acids were visualized by their incorporation of radioactivity from [14C]lysine and also fluorometrically by post-column derivatization with o-phthalaldehyde. The incorporation of 14C from labelled lysine into the principal difunctional reducible crosslinks, N6.6'-dehydro-5,5'-dihydroxylysinonorleucine and N6.6'-dehydro-5-hydroxylysinonorleucine, increased most rapidly between 4 and 12 hours after injection, results similar to those observed by others studying crosslink biosynthesis in vitro. Incorporation of 14C into the tetrafunctional crosslink histidinohydroxymerodesmosine proceeded more slowly than it did for the difunctional crosslinks. Values for the amount of radioactivity incorporated into the various crosslinks reached an apparent constant value between 3 and 5 days after injection for all three tissues studied. These values remained approximately constant for the duration of the experiment except for HHMD in tendon, which showed an increase in incorporated radioactivity at 8 and 10 weeks after injection. Direct chemical quantification of these same crosslinks by determination of the fluorescence of their o-phthalaldehyde adducts was also performed. We conclude that in vivo labelling of collagen crosslinks can be studied, at least in rapidly growing neonates, after a single injection of radioactive lysine. The results of such studies support previous suggestions by others about the rate of formation of difunctional crosslinks based upon studies using in vitro systems. Our results further suggest that formation of the tetrafunctional reducible crosslink histidinohydroxymerodesmosine proceeds relatively rapidly in vivo. Finally, we conclude that such labelled crosslinks are apparently quite stable after biosynthesis, suggesting the possibility of studies of the metabolic fate of collagen crosslinks over appreciable fractions of the lifetime of a rat.


Telomerase enzyme activity as a diagnostic tool to distinguish effusions of malignant and benign origin.
Telomerase enzyme activity is high in populations of cells that are dividing, and is low or undetectable in quiescent cell populations. Activation of telomerase in tissues that normally lack the capacity for self-renewal is strongly correlated with neoplasia. Telomerase activity can be detected in samples containing very small numbers of cells and studies of human patients suggest that measurement of telomerase activity may be useful for the evaluation of samples that can be obtained in a minimally invasive manner. This study compares the presence or absence of telomerase activity with cytologic evaluation of body cavity effusions, to determine if neoplasia is the underlying cause for the effusion in dogs and cats. Detection of telomerase in effusions was no more sensitive than cytologic evaluation for the identification of underlying neoplasia, and was less specific (telomerase assay: sensitivity = 50%, specificity = 83%; cytology: sensitivity = 50%, specificity = 100%). We conclude that although the telomerase assay may constitute a useful adjunctive test for the diagnosis of neoplasia in some dogs and cats with body cavity effusions, the results of this assay are not sufficiently reliable to be used as a sole diagnostic test.


A new postural stability-indicator to predict the level of fear of falling in Parkinson's disease patients.
Fear of falling (FoF) is defined as a lasting concern about falling that causes a person to limit or even stop the daily activities that he/she is capable of. Seventy percent of Parkinson's disease (PD) patients report activity limitations due to FoF. Timely identification of FoF is critical to prevent its additional adverse effects on the quality of life. Self-report questionnaires are commonly used to evaluate the FoF, which may be prone to human error. In this study, we attempted to identify a new postural stability-indicator to objectively predict the intensity of FoF and its related behavior(s) in PD patients. Thirty-eight PD patients participated in the study (mean age, 61.2 years), among whom 10 (26.32%) were identified with low FoF and the rest (73.68%) with high FoF, based on Falls Efficacy Scale-International (FES-I). We used a limit of stability task calibrated to each individual and investigated the postural strategies to predict the intensity of FoF. New parameters (FTRis; functional time ratio) were extracted based on the center of pressure presence pattern in different rectangular areas (i = 1, 2, and 3). The task was performed on two heights to investigate FoF-related behavior(s). FTR1/2 (the ratio between FTR1 and FTR2) was strongly correlated with the FES-I (r = - 0.63, p < 0.001), Pull test (r = - 0.65, p < 0.001), Timed Up and Go test (r = - 0.57, p < 0.001), and Berg Balance Scale (r = 0.62, p < 0.001). The model of FTR1/2 was identified as a best-fitting model to predicting the intensity of FoF in PD participants (sensitivity = 96.43%, specificity = 80%), using a threshold level of ≤ 2.83. Using the proposed assessment technique, we can accurately predict the intensity of FoF in PD patients. Also, the FTR1/2 index can be potentially considered as a mechanical biomarker to sense the FoF-related postural instability in PD patients.


Accuracy of the Pediatric End-stage Liver Disease Score in Estimating Pretransplant Mortality Among Pediatric Liver Transplant Candidates.
Fair allocation of livers between pediatric and adult recipients is critically dependent on the accuracy of mortality estimates afforded by the Pediatric End-stage Liver Disease (PELD) and Model for End-stage Liver Disease, respectively. Widespread reliance on exceptions for pediatric recipients suggests that the 2 systems may not be comparable. To evaluate the accuracy of the PELD score in estimating 90-day pretransplant mortality among pediatric patients on the United Network for Organ Sharing (UNOS) waiting list. Patients who were listed from February 27, 2002, to March 31, 2014, for primary liver transplant were included in this retrospective analysis and were followed up for at least 2 years through June 17, 2016. The study analyzed 2 cohorts using the UNOS Standard Transplant Analysis and Research data files. The full cohort comprised 4298 patients (<18 years of age) who had chronic liver disease (excluding cancer). The reduced cohort (n = 2421) excluded patients receiving living donor transplantation or PELD exception points. Observed and expected 90-day pretransplant mortality rates evaluated at 10-point interval PELD levels. Among the 4298 patients in the full cohort (mean [SD] age, 2.5 [4.2] years; 2251 [52.4%] female; 2201 [51.2%] white), PELD scores and mortality were concordant (C statistic, 0.8387 [95% CI, 0.8191-0.8584] for the full cohort and 0.8123 [95% CI, 0.7919-0.8327] for the reduced cohort). However, the estimated 90-day mortality using the PELD score underestimated the actual probability of death by as much as 17%. With use of the PELD score, the ranking of risk among children was preserved, but direct comparisons between adult and pediatric candidates were not accurate. Children with chronic liver disease who are in need of transplant may be at a disadvantage compared with adults in a similar situation.


Morphometric and genetic evidence for four species of gentoo penguin.
Gentoo penguins (Pygoscelis papua) are found across the Southern Ocean with a circumpolar distribution and notable genetic and morphological variation across their geographic range. Whether this geographic variation represents species-level diversity has yet to be investigated in an integrative taxonomic framework. Here, we show that four distinct populations of gentoo penguins (Iles Kerguelen, Falkland Islands, South Georgia, and South Shetlands/Western Antarctic Peninsula) are genetically and morphologically distinct from one another. We present here a revised taxonomic treatment including formal nomenclatural changes. We suggest the designation of four species of gentoo penguin: P. papua in the Falkland Islands, P. ellsworthi in the South Shetland Islands/Western Antarctic Peninsula, P. taeniata in Iles Kerguelen, and a new gentoo species P. poncetii, described herein, in South Georgia. These findings of cryptic diversity add to many other such findings across the avian tree of life in recent years. Our results further highlight the importance of reassessing species boundaries as methodological advances are made, particularly for taxa of conservation concern. We recommend reassessment by the IUCN of each species, particularly P. taeniata and P. poncetii, which both show evidence of decline.


Effects of postanesthetic sedation with romifidine or xylazine on quality of recovery from isoflurane anesthesia in horses.
To test the hypothesis that postanesthetic sedation with romifidine would dose-dependently improve recovery quality of recovery from isoflurane anesthesia in horses more than postanesthetic sedation with xylazine. Prospective, randomized, blinded clinical trial. 101 healthy adult horses examined at the University of California-Davis Veterinary Medical Teaching Hospital from 2007 to 2009. Horses were sedated with xylazine, and anesthesia was induced with guaifenesin, diazepam, and ketamine via a standardized drug protocol. Anesthesia for surgical or diagnostic procedures was maintained with isoflurane in oxygen for 1 to 4 hours. At the end of anesthesia, horses were moved to a padded stall for recovery. Once the breathing circuit was disconnected and the patient was spontaneously breathing, either xylazine (100 or 200 μg/kg [45 or 91 μg/lb]) or romifidine (10 or 20 μg/kg [4.5 or 9.1 μg/lb]) was administered i.v.. Objective patient, surgical, and anesthesia data were recorded. Subjective visual analog scale (VAS) scores of recovery quality were assigned by a single individual who was unaware of the treatment received. A stepwise linear regression model was used to correlate patient and procedure factors with the VAS score. Painful procedures, longer anesthesia times, and the Arabian horse breed were associated with poorer VAS scores. Adjustment for these factors revealed an improved VAS recovery score associated with the use of a romifidine dose of 20 μg/kg. In healthy adult horses anesthetized with isoflurane for > 1 hour, the results of this study supported the use of 20 μg of romifidine/kg, i.v., rather than lower romifidine doses or xylazine, for postanesthetic sedation to improve recovery quality.


Posterior collagenous layer of the cornea. Ultrastructural classification of abnormal collagenous tissue posterior to Descemet's membrane in 30 cases.
We studied the transmission electron microscopy of the abnormal collagenous tissue posterior to Descemet's membrane in 30 human corneas that represented 19 different diseases. We named this abnormal tissue the "posterior collagenous layer" of the cornea and classified it into three morphologic types: (1) banded posterior collagenous layer, characterized by 110-nm wide-spacing material, (2) fibrillar posterior collagenous layer, characterized by loose meshwork of collagenous fibrils 20 to 30 nm in diameter, and (3) fibrocellular posterior collagenous layer, characterized by fibroblasts in connective tissue. The published ultrastructural studies of 88 corneas that represented 13 different clinical disorders fit this classification well. The posterior collagenous layers often formed multiple lamellae, but no pattern was invariably associated with a specific clinical disorder. We think these multiple layers represent successive periods of deposition of collagen by a stressed corneal endothelium and provide a lifelong record of senescent and pathologic events.


Insect Repellants During Pregnancy in the Era of the Zika Virus.
Health care providers must be equipped to provide appropriate advice to reproductive-aged patients for protection against the potentially devastating consequences of prenatal Zika virus exposure. The goal of this commentary is to summarize what is known about the safety and toxicity of N,N-diethyl-meta-toluamide (DEET) as a topical insect repellant and the pyrethroid permethrin for treatment of fabric, endorsed in the fight against Zika virus. Reviews assessing the safety and toxicity of DEET conducted by the U.S. Environmental Protection Agency and the Canadian Pest Management Regulatory Agency conclude that DEET has low acute toxicity and does not appear to pose a significant health concern to humans when used as directed. Some experimental animal and limited epidemiologic data suggest that prenatal pyrethroid exposure may adversely affect learning and behavior, but this level of evidence pales in comparison to the known risks of Zika virus to the fetal brain. The available evidence has led to the strong recommendation by the Centers for Disease Control and Prevention for use of these products by pregnant women as personal protection against mosquito bites in the fight against Zika virus infection. This message has been affirmed by our obstetrics and gynecology professional organizations. Because Zika virus is unlikely to be the last disease requiring vector control, those with environmental health expertise must continue to join with infectious disease specialists to communicate the potential vulnerability of our youngest (fetuses, infants, and young children) to vector-borne disease, both to the disease itself and to the strategies employed to mitigate the spread of such disease.


Exploring the link between stuttering and phonology: a review and implications for treatment.
Three lines of research have been pursued in the literature to study the link between phonology and stuttering: (1) effects of phonological complexity on the location (loci) of stutter events; (2) outcomes of standardized test measures in children who do and do not stutter; and (3) studies of phonological encoding in children and adults who stutter. This review synthesizes findings from these three lines of research to address the purported link between phonology and stuttering and its potential implications for stuttering treatment. Results from the loci studies offer some support for the role of phonological complexity in the occurrence of stuttering. Studies of performance in standardized tests of phonology have not identified differences between children who do and do not stutter. Studies of phonological encoding have been equivocal in reporting differences between children and adults who stutter and those who do not stutter. Several cautions are raised in interpreting the findings from the discussed studies, and despite the mixed findings, some implications for treatments are considered.


(η(6)-p-Cymene)(1,3-dimesityl-2,3-dihydro-1H-imidazol-2-yl-idene)bis-(pentafluorobenzoato-κO)ruthenium(II) dichloro-methane disolvate.
The title compound, [Ru(C7F5O2)2(C10H14)(C21H24N2)]·2CH2Cl2, is formed as an orange crystalline powder by the reaction of RuCl2(p-cymene)(IMes) and AgOCOC6F5 in anhydrous tetra-hydro-furan (IMes = 1,3-dimesityl-2,3-di-hydro-1H-imidazol-2-yl-idene). The asymetric unit consists of two independent [Ru(C6F5COO)2(η(6)-p-cymene)(IMes)] com-plexes and four dichloro-methane solvent mol-ecules. In each complex molecule, the Ru atom presents a pseudo-octa-hedral environment with the p-cymene ligand occupying three facial coordination sites, while the remaining coordination positions are occupied by the O atoms of the penta-fluoro-benzoate ligands and by the imidazolyl-idene ligand.


Human immunodeficiency virus infection induces both polyclonal and virus-specific B cell activation.
Peripheral blood lymphocytes (PBL) were obtained from HIV-1-infected patients at different stages of disease. The absolute number of IgM-, IgG-, and IgA-producing lymphocytes per 10(6) PBL was increased 2.8-, 3.4-, and 1.9-fold, respectively, compared with normal controls. 2-17% of IgG-secreting patient cells reacted with the gp160 envelope glycoprotein of HIV-1 (a 737-fold increase over background), while 1-9% reacted with p24 (140-fold over background). In addition to this HIV-specific B cell activation, the number of lymphocytes reactive with nonviral antigens such as DNA, myosin, actin, trinitrophenylated keyhole limpet hemocyanin, and ovalbumin was increased by a mean of 17.9-fold. Evidence suggests that the latter changes reflect an HIV-induced polyclonal B cell activation unrelated to the production of anti-HIV antibodies. For example, the proportion of IgG anti-gp160- and anti-p24-secreting lymphocytes declined in patients with advanced disease, whereas the number of B cells producing antibodies to non-HIV antigens rose. Moreover, CD4 cell count and T4/T8 ratio showed a significant inverse correlation with the degree of polyclonal activation but not with anti-HIV responsiveness. These observations demonstrate that both quantitative and qualitative changes in B cell activation accompany (and may be predictive of) disease progression in HIV-infected individuals.


Training family to assist with physiotherapy for older people transitioning from hospital to the community: a pilot randomized controlled trial.
To investigate the safety and effectiveness of augmenting physiotherapy with family-assisted therapy, to inform a future, fully powered trial. Parallel pilot randomized controlled trial. Transition Care Program. Thirty-five older adults with multimorbidity, recently hospitalized, with a mean age of 84.1 years (SD = 6.1 years) and mean Modified Barthel Index of 67.8 units (SD = 19.2 units), and 40 family members. The control group (n = 18) received usual physiotherapy care. The experimental group (n = 17) received usual physiotherapy care and family-assisted therapy from a family member trained by a physiotherapist. Primary outcomes were falls-related self-efficacy measured by the Short Falls Efficacy Scale - International and falls during the intervention period. Secondary outcomes included daily steps, EQ-5D-3L (three-level version of the EuroQoL five-dimensional health-related quality of life questionnaire) and ICECAP-O (ICEpop CAPability measure for Older people), Modified Barthel Index and Modified Caregiver Strain Index. There were no between-group differences for falls-related self-efficacy. Relative to the control group, the experimental group was observed to have a reduced risk of falling (relative risk = 0.38, 95% confidence interval (CI) = 0.09-1.60) and a reduced falls rate (incidence rate ratio = 0.22, 95% CI = 0.04-1.20) was of borderline statistical significance. The experimental group walked a mean of 944 daily steps more than the control group (95% CI = 139-1748) and had a significant reduction in activity limitation. There were no between-group differences for quality of life or caregiver strain. Augmenting physiotherapy with family-assisted therapy is feasible for older people transitioning from hospital to the community. A fully powered randomized controlled trial is indicated.


Synthesis and study of a molecularly imprinted polymer for the specific extraction of indole alkaloids from Catharanthus roseus extracts.
Two molecularly imprinted polymers (MIP) for catharanthine and vindoline have been synthesized in order to specifically extract these natural indole alkaloids from Catharanthus roseus by solid-phase extraction (SPE). Each MIP was prepared by thermal polymerisation using catharanthine (or vindoline) as template, methacrylic acid (or itaconic acid) as functional monomer, ethylene glycol dimethacrylate (EDMA) as cross-linking agent and acetonitrile (or acetone) as porogenic solvent. For catharanthine-MIP, a SPE protocol (ACN-AcOH 99/1 washing and MeOH-AcOH 90/10 elution) allows a good MIP/NIP selectivity (imprinting factor 12.6). The specificity of catharanthine-MIP versus related bisindole alkaloids was assessed by cross-reactivity study. The catharanthine-MIP specifically retained catharanthine and its N-oxide analogue but displayed a weak cross-reactivity for other Vinca alkaloids (vinorelbine, vincristine, vinblastine, vindoline, vinflunine). It appears that the catharanthine-like unit of these molecules are hardly trapped in catharanthine cavities located in the MIP, probably due to the sterical hindrance of the vindoline moiety. Finally, the MIP-SPE applied to C. roseus extract enabled quantitative recovery of catharanthine (101%) and the total removal of vindoline. Its capacity was determined and was equal to 2.43 μmol g(-1). Vindoline is a weaker base than catharanthine, so the vindoline-MIP was achieved with a strong acidic monomer (itaconic acid) to increase vindoline-monomer interactions and a modified washing solvent (ACN-HCOOH 99/1) to reduce non-specific interactions. The influence of the amount of HCOOH (protic modifier) percolated during the washing step upon the elution yield and the imprinting factor for vindoline was investigated. This preliminary optimisation of the washing step, and in particular the number of moles of acid percolated, seems useful to emphasize the use of MIP in conditions of high selectivity or high yield. A compromise was obtained with an imprinting factor equal to 7.6 and an elution recovery of 33%. However MIP-vindoline failed to achieve a specific extraction of vindoline since catharanthine was also extracted probably because of strong non-specific interactions occurring between catharanthine and the sorbent.


Biochemical characterization of psychrophilic Mn-superoxide dismutase from newly isolated Exiguobacterium sp. OS-77.
Many types of superoxide dismutases have been purified and characterized from various bacteria, however, a psychrophilic Mn-superoxide dismutase (MnSOD) has not yet been reported. Here, we describe the purification and the biochemical characterization of the psychrophilic MnSOD from Exiguobacterium sp. strain OS-77 (EgMnSOD). According to 16S rRNA sequence analysis, a newly isolated bacterium strain OS-77 belongs to the genus Exiguobacterium. The optimum growth temperature of the strain OS-77 is 20 °C. The EgMnSOD is a homodimer of 23.5 kDa polypeptides determined by SDS-PAGE and gel filtration analysis. UV-Vis spectrum and ICP-MS analysis clearly indicated that the homogeneously purified enzyme contains only a Mn ion as a metal cofactor. The optimal reaction pH and temperature of the enzyme were pH 9.0 and 5 °C, respectively. Notably, the purified EgMnSOD was thermostable up to 45 °C and retained 50% activity after 21.2 min at 60 °C. The differential scanning calorimetry also indicated that the EgMnSOD is thermostable, exhibiting two protein denaturation peaks at 65 and 84 °C. The statistical analysis of amino acid sequence and composition of the EgMnSOD suggests that the enzyme retains psychrophilic characteristics.