Family-Centered Care at Pediatric Cardiac Intensive Care Units in Germany and the Relationship With Parent and Infant Well-Being: A Study Protocol.
Rationale and Aim: Infants with Congenital Heart Disease (CHD) are at risk for neurodevelopmental delays, emotional, social and behavioral difficulties. Hospitalization early in life and associated stressors may contribute to these challenges. Family-centered Care (FCC) is a health care approach that is respectful of and responsive to the needs and values of a family and has shown to be effective in improving health outcomes of premature infants, as well as the mental well-being of their parents. However, there is limited empirical data available on FCC practices in pediatric cardiology and associations with parent and infant outcomes. Methods and Analysis: In this cross-sectional study, we will explore FCC practices at two pediatric cardiac intensive care units in Germany, assess parent satisfaction with FCC, and investigate associations with parental mental well-being and parenting stress, as well as infant physical and mental well-being. We will collect data of 280 infants with CHD and their families. Data will be analyzed using multivariate statistics and multilevel modeling. Implications and Dissemination: The study protocol was approved by the medical ethics committees of both partner sites and registered with the German registry for clinical trials (NR DRKS00023964). This study serves as a first step to investigate FCC practices in a pediatric cardiology setting, providing insight into the relationship between FCC and parent and infant outcomes in a population of infants with CHD. Results will be disseminated in peer-reviewed journals.


MR of a nasal glioma in a young infant.
We describe MR findings of a nasal glioma in a 5-week-old male infant with feeding difficulties and symptoms of respiratory distress. Endoscopic examination revealed a soft tissue mass in the nasal cavity. In T1- and T2-weighted images, the gyral structure of grey matter was visible. In T1-weighted images, a tissue component with a lower signal intensity equal to that of white matter was also well distinguishable. Edge enhancement of the tumour was due to the nasal mucosal epithelium covering the tumour. MR images were useful to rule out intracranial extension of the nasal cavity lesion and the brain, thus excluding the diagnosis of encephalocele. The lesion was excised and histologically characterized as heterotopic brain tissue.


Bacteriuria in a geriatric hospital: impact of an antibiotic improvement program.
To prospectively evaluate a management approach to bacteriuria including advice from an infectious diseases consultant (IDC) in geriatric inpatients. Prospective study from July 1, 2003, to June 30, 2004. A 205-bed geriatric university-affiliated hospital. Consecutive hospitalized patients with positive urine cultures. The hospital's infection control department developed recommendations about antimicrobial use for bacteriuria, which were discussed at staff meetings. Treatments for bacteriuria prescribed by ward physicians were reviewed by an IDC, who suggested changes where appropriate. Physicians were free to follow or to disregard the IDC's suggestions. Patients with positive urine cultures (UC) were classified as having asymptomatic bacteriuria (AB), urinary tract infection (UTI) or pyelonephritis (PN). Prescribed and actual treatments were compared. Of 252 consecutive positive UCs in 181 patients, 124 (49%) were classified as AB, 88 (35%) as UTI, and 38 (15%) as PN; 2 cases of prostatitis were excluded. The total number of prescribed antimicrobial days before IDC advice was 729 and the actual number (after IDC advice) was 577, for a 152-day (21%) reduction. Most of the reduction was generated by shortening the treatment duration. Intervention of an IDC resulted in reduced antimicrobial use in older inpatients with bacteriuria.


Development and Optimization of Indirect ELISAs for the Detection of Anti-Capripoxvirus Antibodies in Cattle, Sheep, and Goat Sera.
Sheeppox (SPP), goatpox (GTP), and lumpy skin disease (LSD) are economically significant pox diseases of ruminants, caused by sheeppox virus (SPPV), goatpox virus (GTPV), and lumpy skin disease virus (LSDV), respectively. SPPV and GTPV can infect both sheep and goats, while LSDV mainly affects cattle. The recent emergence of LSD in Asia and Europe and the repeated incursions of SPP in Greece, Bulgaria, and Russia highlight how these diseases can spread outside their endemic regions, stressing the urgent need to develop high-throughput serological surveillance tools. We expressed and tested two recombinant truncated proteins, the capripoxvirus homologs of the vaccinia virus C-type lectin-like protein A34 and the EEV glycoprotein A36, as antigens for an indirect ELISA (iELISA) to detect anti-capripoxvirus antibodies. Since A34 outperformed A36 by showing no cross-reactivity to anti-parapoxvirus antibodies, we optimized an A34 iELISA using two different working conditions, one for LSD in cattle and one for SPP/GTP in sheep and goats. Both displayed sound sensitivities and specificities: 98.81% and 98.72%, respectively, for the LSD iELISA, and 97.68% and 95.35%, respectively, for the SPP/GTP iELISA, and did not cross-react with anti-parapoxvirus antibodies of cattle, sheep, and goats. These assays could facilitate the implementation of capripox control programs through serosurveillance and the screening of animals for trade.


A minimally invasive surgical technique for the treatment of posttraumatic trigeminal neuropathic pain with peripheral nerve stimulation.
Facial pain occurring after traumatic injury of the facial branches of the trigeminal nerve is a medical condition that is often very difficult to treat. Patients are quite disabled by their symptoms and most therapies are ineffective in relieving this pain. Peripheral nerve stimulation has been used as a treatment to provide pain relief for this type of intractable atypical facial pain. To describe a minimally invasive peripheral nerve stimulation surgical technique for treating posttraumatic trigeminal neuralgia. Case report based on a patient seen in a university setting with posttraumatic trigeminal neuropathic pain who underwent a minimally invasive technique for the placement of a peripheral nerve stimulator. University-based outpatient clinic. A patient with a clinical picture suggestive of trigeminal neuropathic pain secondary to trauma involving the V1 and V2 branches of the trigeminal nerve was selected. Conservative management was attempted with no improvement before peripheral nerve stimulation was tried with a minimally invasive surgical technique. We recorded the patient's subjective assessment of pain and daily function before and after the procedure. Following the procedure, the patient's pain score decreased approximately 50% and the patient reported a better quality of life with improvement in daily function as well as a more positive outlook on her condition. There were no complications after the procedure and the patient reported no complaints with the device. Case report. This surgical technique for placing peripheral nerve stimulators allows for a minimally invasive approach for the treatment of intractable posttraumatic trigeminal neuralgia with potentially less risk of facial nerve damage. This case confirms the need for further studies to be done in the future to prove the safety and effectiveness of this technique.


Why Psychology Needs to Stop Striving for Novelty and How to Move Towards Theory-Driven Research.
Psychological science is maturing and therefore transitioning from explorative to theory-driven research. While explorative research seeks to find something "new," theory-driven research seeks to elaborate on already known and hence predictable effects. A consequence of these differences is that the quality of explorative and theory-driven research needs to be judged by distinct criterions that optimally support their respective development. Especially, theory-driven research needs to be judged by its methodological rigor. A focus on innovativeness, which is typical for explorative research, will instead incentivize bad research practices (e.g., imprecise theorizing, ignoring previous research, parallel theories). To support the advancement of psychology, we must drop the innovation requirement for theory-driven research and instead require the strongest methods, which are marked by high internal and external validity. Precise theorizing needs to substitute novelty. Theories are advanced by requiring explicit, testable assumptions, and an explicit preference for one theory over another. These explicit and potentially wrong assumptions should not be silenced within the peer-review process, but instead be scrutinized in new publications. Importantly, these changes in scientific conduct need to be supported by senior researchers, especially, in their roles as editors, reviewers, and in the hiring process. An important obstacle to further theory-driven research is to measure scientific merit using researchers' number of publications, which favors theoretically shallow and imprecise writing. Additionally, it makes publications the central target of scientific misconduct even though they are the main source of information for the scientific community and the public. To advance the field, researchers should be judged by their contribution to the scientific community (e.g., exchange with and support of colleagues, and mentoring). Another step to advance psychology is to clearly differentiate between measurement model and theory, and not to overgeneralize based on few stimuli, incidences, or studies. We will use ideas from the theory of science to underline the changes necessary within the field of psychology to overcome this existential replication crisis.


[Medical service of the Red Army in Vislo-Oder strategic offensive].
Was characterized work of medical service of the Red Army in Vislo-Oder strategic offensive. To the beginning of the operation in divisions of the first echelon were deployed medical aid stations in dugouts and blindages in 1.5-3 km from the front line. Sanitarium casualties of troops of the 1st Byelorussian Front were 60 310 persons, 5.8% of it's quantity, including wounded--5.3%, ill persons--0.5%; of the 1st Ukrainian Front--89 564 persons, 8.3%, including wounded--7.5%, ill persons--0.8%. It's important to mark, that casualties on first fronts are more then 2 times, and on the second fronts are one and half times less than was supposed. On both fronts casualties of main group of troops achieved 60% of all casualties during the 1st stage of operation.


Interactions between the adducin 2 gene and antihypertensive drug therapies in determining blood pressure in people with hypertension.
As part of the NHLBI Family Blood Pressure Program, the Genetic Epidemiology Network of Arteriopathy (GENOA) recruited 575 sibships (n = 1583 individuals) from Rochester, MN who had at least two hypertensive siblings diagnosed before age 60. Linkage analysis identified a region on chromosome 2 that was investigated using 70 single nucleotide polymorphisms (SNPs) typed in 7 positional candidate genes, including adducin 2 (ADD2). To investigate whether blood pressure (BP) levels in these hypertensives (n = 1133) were influenced by gene-by-drug interactions, we used cross-validation statistical methods (i.e., estimating a model for predicting BP levels in one subgroup and testing it in a different subgroup). These methods greatly reduced the chance of false positive findings. Eight SNPs in ADD2 were significantly associated with systolic BP in untreated hypertensives (p-value < 0.05). Moreover, we also identified SNPs associated with gene-by-drug interactions on systolic BP in drug-treated hypertensives. The TT genotype at SNP rs1541582 was associated with an average systolic BP of 133 mmHg in the beta-blocker subgroup and 148 mmHg in the diuretic subgroup after adjusting for overall mean differences among drug classes. Our findings suggest that hypertension candidate gene variation may influence BP responses to specific antihypertensive drug therapies and measurement of genetic variation may assist in identifying subgroups of hypertensive patients who will benefit most from particular antihypertensive drug therapies.


Gender differences in self-reported use, perceived efficacy, and interest in future use of nicotine-dependence treatments: A cross-sectional survey in adults at a tertiary care center for nicotine dependence.
Clinical trials have assessed the effectiveness of nicotine-dependence treatments (NDTs), alone or in combination, and reported that men and women have variable responses to these treatments. The variations in therapeutic responses highlight the need to explore gender-specific preferences for NDTs, including complementary and alternative medicine (CAM), which has become increasingly popular in the US population for the cessation of tobacco use. The aim of this study was to assess gender differences in the self-reported use, perceived efficacy, and interest in future use of NDTs, including CAM, in an outpatient setting. This cross-sectional survey was conducted in men and women at a tertiary care NDT clinic. The primary inclusion criterion was the willingness and ability of the patients to participate in the survey. Data from 1171 patients were included (599 men, 572 women; mean age: men, 46.2 years; women, 46.5 years). Of these, 68% of women and 65% of men reported use of nicotine-replacement therapy (NRT), other prescription medication, or counseling/group support. In men and women, NRT was the most commonly used type of pharmacologic treatment, of which the patch was the most popular (77% and 75%). A significantly greater proportion of women than men perceived the nicotine inhaler to be efficacious (67% vs 50%; P = 0.027). No other significant gender differences were found among NRTs. Among non-NRT methods, bupropion sustained release (SR) and counseling/group support were used by significantly more women than men (53% vs 43% [P = 0.007] and 16% vs 11% [P = 0.026], respectively). Compared with men, significantly greater proportions of women reported current or previous use of CAM for nicotine abstinence and expressed an interest in future use of CAM (34% vs 22% [P < 0.001] and 71% vs 64% [P = 0.006]). In this sample of patients at an NDT clinic, significantly more women than men reported previous use of bupropion SR, counseling, and CAM. More women than men expressed an interest in the future use of CAM. Based on these findings, an improved understanding of gender-based differences in the use of conventional and nonconventional NDTs might improve the rates of success of nicotine-cessation efforts among women.


Cornell's Depression for Dementia Scale: A psychometric study among Norwegian nursing home residents.
Depression is common among residents in long term-care facilities. Therefore, access to a valid and reliable measure of depressive symptoms among nursing home (NH) residents is highly warranted. The aim of this study was to test the psychometrical properties of the Norwegian version of the Cornell Scale for Depression in Dementia (CSDD). A sample of 309 NH residents were assessed for depressive symptoms using the CSDD in 2015-2016. Data on CSDD were missing for 64 residents, giving an effective sample of 245 (79.3%). Principal component and confirmatory factor analysis were used. A five-dimensional solution yielded the best fit with the data (χ2=174.927, df=94, χ2/df=1.86, p=0.0001, RMSEA=0.058, p-value for test of close fit=0.152, CFI=0.94, TLI=0.92 and SRMR=0.056). As expected, higher depressive symptoms correlated positively with higher scores on the Minimum Data Set Depression Rating Scale (MDSDRS) and correlated negatively with Quality of life assessed with the Quality of Life in Late Stage-Dementia Scale. The excluded residents (n=64, 20.7%) had lower cognitive function, which may limit the generalizability of the study results. This study suggests a five-dimensional solution of the CSDD scale. Sixteen of the 19 original items showed highly significant loadings, explaining a notable amount of the variation in the CSDD-construct. Further development and testing of a well-adapted scale assessing depression in the nursing home population with and without dementia is required.


Patterns of nicotinic receptor antagonism: nicotine discrimination studies.
Evaluation of the discriminative stimulus effects of drugs is a useful procedure for identification of receptor mediation of in vivo drug effects. This assay can be enhanced when the stimulus effects of different doses of agonist are evaluated. In the present study, rats were trained to discriminate small or large doses of nicotine from saline, and interactions of these effects with nicotinic receptor antagonists and partial agonists were determined. The insurmountable nicotine antagonist mecamylamine blocked both the discriminative stimulus and response rate-reducing effects of nicotine but was less effective against the large dose of nicotine. The α4β2*-selective, competitive antagonist dihydro-β-erythrodine (DHβE) antagonized the discriminative stimulus effects of both doses but was less effective against the larger training dose of nicotine. Schild analyses of DHβE suggested that different nicotinic receptor populations may be mediating the stimulus effects of large and small doses of nicotine. This suggestion was supported by observations that the discriminative stimulus effects of the partial agonist cytisine were more like those of the large dose than of the small dose of nicotine and that cytisine antagonized the effects of only the small nicotine dose. Varenicline produced nicotine-like effects in both training dose groups but reduced the discriminative stimulus effects of intermediate doses of nicotine in the group trained to the small dose of nicotine. Overall, these results suggest that small doses of nicotine produce their stimulus effects via α4β2* nicotine receptors, whereas larger doses of nicotine recruit additional nicotine receptor subtypes, as revealed by drug discrimination assays in rats.


Clinical and Epidemiological Characteristics of COVID-19 Patients in Chongqing China.
Objectives: To study in-depth the clinical and epidemiological characteristics of pneumonia resulting from COVID-19 and provide evidence for effective public health decisions. Methods: This was a retrospective, single-center research study. Participants were enrolled from patients presenting at the Chongqing Public Health Medical Treatment Center from Jan 24 to Feb 7, 2020, and were confirmed as having COVID-19. Results: A total of 114 COVID-19 patients (99 mild, 4 severe, 11 critical) of which 56 (56/114; 49.1%) were male, 58 (58/114; 50.9%) were female with a mean age of 46.05 years. Twenty nine (29/114; 25.44%) patients suffered from chronic diseases. Neutrophils counts in 23.68% (27/114) of patients were abnormally low and abnormally high in 21.05% (24/114). Erythrocyte sedimentation rate and the C-reactive protein levels were abnormally elevated in 76.5% (62/81) and 62.9% (66/105) of patients, respectively. Creatine kinase isoenzymes (CK-MB), pro-brain natriuretic peptide (pro-BNP) and troponin levels were above the normal range in 7.10% (8/112), 66.7% (10/15), and 100% of patients, respectively. The percentage of patients in which the partial pressure of oxygen (PaO2)/fraction of inspired O2(FiO2) ratio exceeded 200 was 60%. A total of 91 (91/114; 79.82%) patients displayed severe bilateral pneumonia, 52 (52/114; 45.61%) exhibited ground-glass opacity, and pulmonary consolidation was observed in 4 (3.51%) patients. Differences in shortness of breath, insomnia, inappetence, the procalcitonin (PCT) levels, FiO2 and PaO2/FiO2 among the three groups were statistically significant (p < 0.05). Differences between the mild and severe groups was observed in neutrophil and lymphocyte counts, CD4 expression, and levels of C-reactive protein, alanine aminotransferase, aspartate aminotransferase and albumin (P < 0.05). Between the mild and critical groups, differences were observed in neutrophils, platelets, and CD4 expression (P < 0.05). A difference in C-reactive protein levels between severe and critical groups was also found (P < 0.05). Conclusions: In the majority of cases no gender differences were observed and mostly the symptoms were mild. Evidence of efficient human-to-human virus transmission was found. The elderly with comorbidities were more prone to develop into severe or critical illness. Age and comorbidity may be risk factors for poor outcome.


Polysaccharide-based hydrogels with tunable composition as 3D cell culture systems.
To date, cell cultures have been created either on 2-dimensional (2D) polystyrene surfaces or in 3-dimensional (3D) systems, which do not offer a controlled chemical composition, and which lack the soft environment encountered in vivo and the chemical stimuli that promote cell proliferation and allow complex cellular behavior. In this study, pectin-based hydrogels were developed and are proposed as versatile cell culture systems. Pectin-based hydrogels were produced by internally crosslinking pectin with calcium carbonate at different initial pH, aiming to control crosslinking kinetics and degree. Additionally, glucose and glutamine were added as additives, and their effects on the viscoelastic properties of the hydrogels and on cell viability were investigated. Pectin hydrogels showed in high cell viability and shear-thinning behavior. Independently of hydrogel composition, an initial swelling was observed, followed by a low percentage of weight variation and a steady-state stage. The addition of glucose and glutamine to pectin-based hydrogels rendered higher cell viability up to 90%-98% after 1 hour of incubation, and these hydrogels were maintained for up to 7 days of culture, yet no effect on viscoelastic properties was detected. Pectin-based hydrogels that offer tunable composition were developed successfully. They are envisioned as synthetic extracellular matrix (ECM) either to study complex cellular behaviors or to be applied as tissue engineering substitutes.


Harmful Elements (Al, Cd, Cr, Ni, and Pb) in Wild Berries and Fruits Collected in Croatia.
Fruits and vegetables are considered a beneficial contribution to the human diet. Especially, berries contain a great deal of bioactive compounds, such as anthocyanins, organic acids, tannins, phenols, and antioxidants. Apart from organic substances, inorganic nutrients are also present in fruits. Some metals and metalloids are essential for humans, whilst others may exhibit harmful effects. Wild grown berries, collected in so-called unpolluted areas, are considered to be free of any potentially toxic ingredients. However, due to transmission processes pollutants can also reach remote areas and, furthermore, metal uptake from the soil via roots has to be taken into account. Thus, the presented study focused on the determination of Al, Cd, Cr, Ni, and Pb in lingonberries, blueberries, and rose hips collected in a non-polluted area in Croatia. Neither Cd nor Cr could be found in any sample. Ni levels were mainly up to 25 mg/kg, in a comparable range to the literature data. No health threat is to be expected by eating these fruits and berries regarding Cd, Cr, and Ni. Rose hips, however, contain Pb beyond the stipulated limit in fruits, and also Al is present at a high level (8 mg/g).


Two new 'legumoviruses' (genus Begomovirus) naturally infecting soybean in Nigeria.
Two new 'legumoviruses' (genus Begomovirus; family Geminiviridae) naturally infecting soybean (Glycine max L. Merr.) in Nigeria were molecularly characterized. Based on characteristic symptoms in soybean, the two viruses are provisionally designated as Soybean mild mottle virus (SbMMV) and Soybean chlorotic blotch virus (SbCBV). SbCBV has a bipartite genome, whereas SbMMV has only a DNA A component. The DNA A component of SbMMV is 2,768 nucleotides (nt) long and the DNA A and DNA B components of SbCBV are 2,708 and 2,647 nt long, respectively. In pairwise comparisons, the DNA A component of SbMMV and SbCBV showed 62% nt sequence identity, indicating that these two viruses are distinct. Whereas the DNA A of SbMMV contains two virion- and four complementary-sense open reading frames, that of SbCBV lacks the virus-sense AV2, a signature gene present in 'Old World' begomoviruses. A pairwise comparison with the corresponding nucleotide sequence of other begomoviruses in the databases indicated that SbCBV had a maximum of 74% identity with cowpea golden mosaic virus and SbMMV had a maximum of 65% identity with mungbean yellow mosaic India virus and kudzu mosaic virus. Phylogenetic analysis of the DNA A component of SbCBV and SbMMV together with those of other begomoviruses available in the databases showed clustering of the two viruses within the 'legumovirus' clade of the begomovirus phylogenetic tree. In addition, the DNA A and B components of SbCBV from Centrosema pubescens Benth were found to be identical to those from soybean, indicating that leguminous wild species are a potential alternative host for the virus. Since soybean is an introduced crop, the identification of two distinct begomoviruses naturally infecting soybean in Nigeria suggests the occurrence of 'legumoviruses' in plant species indigenous to Africa and underscores their potential threat to sustainable cultivation of soybean on the African continent.


Roles of Organic Anion Transporting Polypeptide 2A1 (OATP2A1/SLCO2A1) in Regulating the Pathophysiological Actions of Prostaglandins.
Solute carrier organic anion transporter family member 2A1 (OATP2A1, encoded by the SLCO2A1 gene), which was initially identified as prostaglandin transporter (PGT), is expressed ubiquitously in tissues and mediates the distribution of prostanoids, such as PGE2, PGF2α, PGD2 and TxB2. It is well known to play a key role in the metabolic clearance of prostaglandins, which are taken up into the cell by OATP2A1 and then oxidatively inactivated by 15-ketoprostaglandin dehydrogenase (encoded by HPGD); indeed, OATP2A1-mediated uptake is the rate-limiting step of PGE2 catabolism. Consequently, since OATP2A1 activity is required for termination of prostaglandin signaling via prostanoid receptors, its inhibition can enhance such signaling. On the other hand, OATP2A1 can also function as an organic anion exchanger, mediating efflux of prostaglandins in exchange for import of anions such as lactate, and in this context, it plays a role in the release of newly synthesized prostaglandins from cells. These different functions likely operate in different compartments within the cell. OATP2A1 is reported to function at cytoplasmic vesicle/organelle membranes. As a regulator of the levels of physiologically active prostaglandins, OATP2A1 is implicated in diverse physiological and pathophysiological processes in many organs. Recently, whole exome analysis has revealed that recessive mutations in SLCO2A1 cause refractory diseases in humans, including primary hypertrophic osteoarthropathy (PHO) and chronic non-specific ulcers in small intestine (CNSU). Here, we review and summarize recent information on the molecular functions of OATP2A1 and on its physiological and pathological significance.


Role of histamine produced by bone marrow-derived vascular cells in pathogenesis of atherosclerosis.
To clarify the role of histamine-producing cells and its origin in atherosclerosis, we investigated histidine decarboxylase (HDC; histamine-producing enzyme) expression in murine arteries with vascular injuries after the animal had received transplanted bone marrow (BM) from green fluorescent protein (GFP)-transgenic mice. The neointima in the ligated carotid arteries contained BM-derived HDC+ cells that expressed macrophage (Mac-3) or smooth muscle cell antigen (alpha-SMA). In contrast, the HDC+ BM-derived cells, which were positive for Mac-3, were mainly located in the adventitia in the cuff replacement model. In apolipoprotein E-knockout mice on a high cholesterol diet, BM-derived cells expressing Mac-3 in the atheromatous plaques were also positive for HDC. In comparison with wild-type mice, HDC-/- mice showed reduced neointimal thickening and a decreased intima-to-media ratio after ligation and cuff replacement. These results indicate that histamine produced from BM-derived progenitor cells, which could transdifferentiate into SMC- or macrophage-like cells, are important for the formation of neointima and atheromatous plaques.


Methods of pushing during vaginal delivery and pelvic floor and perineal outcomes: a review.
Over the past 20 years, several randomized studies have compared Valsalva and spontaneous pushing techniques during vaginal delivery. This review summarizes current medical knowledge concerning their maternal and fetal consequences, focusing on pelvic and perineal outcomes. We selected nine randomized controlled trials comparing Valsalva and spontaneous pushing, and a secondary analysis of a randomized controlled trial comparing different methods of perineal protection. Two trials showed that spontaneous pushing reduces the risk of perineal tears, but no firm conclusions can be drawn given the heterogeneity and inconsistent results of these studies. Conflicting results have been reported regarding the duration of the second stage of labor. Pushing technique does not seem to affect episiotomy, instrumental delivery or cesarean rates. Maternal satisfaction seems to be better after spontaneous pushing. Spontaneous pushing appears to have no adverse effects on neonatal well being, and one study showed a significant improvement in prenatal fetal parameters during the expulsive phase. Valsalva and spontaneous pushing techniques currently appear comparable in terms of duration, pelvic floor, perineal, and neonatal outcomes. In the absence of strong evidence in favor of either technique, the decision should be guided by patient preference and the clinical situation. Additional, well-designed randomized controlled trials are required.


The pulmonary lesion of smoke inhalation in an ovine model.
Inhalation injury was induced in chronically instrumented sheep (n = 9) by insufflating them with smoke from burning cotton cloth. Sham animals (n = 9) were insufflated with air. There were no temporal changes in any measured parameter of the sham animals. Smoke induced a depression in PaO2. There was a threefold elevation in protein-rich pulmonary lymph which was sustained for over 48 hours. The lymph-to-plasma oncotic pressure ratio was increased. The cardiac index, left atrial pressure, and pulmonary arterial pressure remained unchanged in both groups. After smoke inhalation, the interstitial levels of neutrophils increased while interstitial antiprotease activity was depressed. The lung lymph concentration of 6-keto prostaglandin F1a, the major metabolite of prostacyclin, was increased. These data suggest that the pulmonary injury following smoke inhalation is the result of an increase in lung microvascular permeability to protein with resultant pulmonary edema. The mechanisms responsible for these changes appear to be related to direct injury to the tracheobronchial tree by cytotoxic agents in the smoke; polymorphonuclear leukocytes; and, possibly, eicosanoids.


Troglitazone inhibits progesterone production in porcine granulosa cells.
Troglitazone (a thiazolidinedione that improves insulin resistance) lowers elevated androgen concentrations in women with polycystic ovarian syndrome. In this study, we assessed the direct effects of troglitazone on steroidogenesis in porcine granulosa cells. Troglitazone inhibited progesterone production in a dose- and time-dependent manner (earliest effects at 4 h, maximum at 24 h) without affecting cell viability. Progesterone production was also inhibited by troglitazone in the presence of 25-hydroxycholesterol, indicating that the drug does not affect intracellular cholesterol transport. Troglitazone also inhibited FSH- and forskolin-stimulated progesterone secretion. The reduced progesterone production was accompanied by marked elevations of pregnenolone concentrations, suggesting inhibition of 3beta-hydroxysteroid dehydrogenase (3beta-HSD). The activity of 3beta-HSD in troglitazone-treated granulosa cells was decreased by more than 60%, compared with controls after 24 h. Troglitazone did not affect aromatase activity in porcine granulosa cells. In summary, troglitazone has direct effects on porcine granulosa cell steroidogenesis. The drug specifically inhibits 3beta-HSD activity, resulting in impaired progesterone production. The clinical relevance of this direct in vitro effect on steroidogenesis needs further investigation.


Spatial epidemiology of American cutaneous leishmaniasis in a municipality of west São Paulo State, Brazil.
In the last decade, in the state of São Paulo, 5898 cases of cutaneous leishmaniasis (CL) were reported. This study was undertaken to analyze the epidemiology of CL in the municipality of Teodoro Sampaio, in São Paulo State, Brazil, based on a geographic approach, as very little is known of the relationship between CL and the spatial transformation process. This is a population-based quantitative, descriptive and cross-sectional case study. Surveys of the official notifications in the healthcare center and official sources from 1998 to 2011 were analysed. The data were described based on statistics and the Kernel method to detect hotspots of transmission. The age group between 21 and 40 yr was most affected, with 24 cases (57.9%). Of the 41 cases reported between 1998 and 2011, 33 cases were having low education status and 31 cases (75.6%) were males. The spatial and temporal distribution was aggregated in three-year periods which permitted the identification of two microfoci, in periods I (1998-2000) and III (2005-2007). The disease has presented, in recent years, a pattern of sporadic transmission or microfoci, and continues to maintain enzootic cycles of Leishmania in a sylvatic environment, ensuring the perpetuation of the pathogen in nature, and the risk of emergence of new cases of CL in domestic animals and humans.


Intravenous anaesthesia in horses by guaiphenesin-ketamine-detomidine infusion: some effects.
The effects of total intravenous anaesthesia with an intravenous infusion of a combination of guaiphenesin, ketamine and detomidine were studied in 10 patients scheduled for elective surgery. Anaesthesia was maintained by the infusion of guaiphenesin (100 mg/ml), ketamine (2 mg/ml) and detomidine (0.02 mg/ml). The infusion rate was 1 ml/kg/hr. During anaesthesia, pulse rate and mean arterial blood pressure were continuously recorded. Arterial blood gases and pH were determined immediately after induction and at stated times during anaesthesia. Venous blood was sampled to determine plasma glucose, lactate, lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and aspartate aminotransferase (AST) concentrations. Values were compared with those determined in blood sampled before the premedication. All determined parameters with the exception of the plasma glucose concentration, the arterial oxygen tension and the AST concentration did not change significantly and remained within normal ranges. The plasma glucose concentration increased significantly after the induction of anaesthesia compared to the control value but decreased to normal values during anaesthesia. The arterial oxygen tension was on average 30% lower than normally wished. Compared to the control value the plasma concentration of AST was significantly decreased at the end of anaesthesia. Based upon the results of this study an infusion of guaiphenesin, ketamine and detomidine appears to be useful for the maintenance of total anaesthesia in horses.


PSMA PET for Detection of Recurrence.
Prostate cancer (PC) is a significant health concern worldwide, with high incidence and mortality rates. Early and accurate detection and localization of recurrent disease at biochemical recurrence (BCR) is critical for guiding subsequent therapeutic decisions and improving patient outcomes. At BCR, conventional imaging consisting of CT, MRI, and bone scintigraphy are recommended by US and European guidelines, however, these modalities all bear certain limitations in detecting metastatic disease, particularly in low-volume relapse at low prostate-specific antigen (PSA) levels. Molecular imaging with PET/CT or PET/MRI using prostate-specific membrane antigen (PSMA) targeting radiopharmaceuticals has revolutionized imaging of PC. Particularly at BCR PC, PSMA PET has shown better diagnostic performance compared to conventional imaging in detecting local relapse and metastases, even at very low PSA levels. The most recent version of the National Comprehensive Cancer Network (NCCN) guideline has included PSMA-targeted PET/CT or PET/MRI for the localization of BCR PC. There are several different PSMA-targeting radiopharmaceuticals labeled with different radioisotopes, each with slightly different characteristics, but overall similar high sensitivity and specificity for PC. PSMA-targeted PET has the potential to significantly impact patient care by guiding personalized treatment decisions and thus improving outcomes in BCR PC patients.


Arthroscopic Determination of Cartilage Proteoglycan Content and Collagen Network Structure with Near-Infrared Spectroscopy.
Conventional arthroscopic evaluation of articular cartilage is subjective and insufficient for assessing early compositional and structural changes during the progression of post-traumatic osteoarthritis. Therefore, in this study, arthroscopic near-infrared (NIR) spectroscopy is introduced, for the first time, for in vivo evaluation of articular cartilage thickness, proteoglycan (PG) content, and collagen orientation angle. NIR spectra were acquired in vivo and in vitro from equine cartilage adjacent to experimental cartilage repair sites. As reference, digital densitometry and polarized light microscopy were used to evaluate superficial and full-thickness PG content and collagen orientation angle. To relate NIR spectra and cartilage properties, ensemble neural networks, each with two different architectures, were trained and evaluated by using Spearman's correlation analysis (ρ). The ensemble networks enabled accurate predictions for full-thickness reference properties (PG content: ρin vitro, Val= 0.691, ρin vivo= 0.676; collagen orientation angle: ρin vitro, Val= 0.626, ρin vivo= 0.574) from NIR spectral data. In addition, the networks enabled reliable prediction of PG content in superficial (25%) cartilage (ρin vitro, Val= 0.650, ρin vivo= 0.613) and cartilage thickness (ρin vitro, Val= 0.797, ρin vivo= 0.596). To conclude, NIR spectroscopy could enhance the detection of initial cartilage degeneration and thus enable demarcation of the boundary between healthy and compromised cartilage tissue during arthroscopic surgery.


First-principles calculations combined with experiments to study the gas-sensing performance of Zn-substituted SnS.
Two-dimensional group-IV monochalcogenides MX (M = Ge, and Sn; X = S, and Se) are explored for their potential in gas-sensing applications. In this work, a combined theoretical and experimental study on pure SnS and Zn-substituted SnS for promising methanol sensors is performed. The adsorption characteristics of methanol on pure and Zn-substituted SnS were first calculated using first-principles based on density functional theory (DFT). It is clarified theoretically that the incorporation of Zn dopant could enhance the adsorption capability of the SnS surface to methanol molecules, thus achieving obvious response enhancement and selectivity improvement. Further experimental investigation is carried out based on the successful synthesis of pure and Zn-substituted SnS with hierarchical architecture via a one-step solvothermal process. Gas-sensing measurement indicates that the Zn-substituted SnS sensor is promising for selective detection of rarefied methanol. At room temperature, the as-synthesized hierarchical SnS with an appropriate amount of Zn-doping can sense methanol vapor of as low as 100 ppb. In particular, Zn-doping can enhance the sensing response of methanol significantly, with a 32.8-fold increase in response value achieved in comparison to that of the pure SnS. The underlying mechanism for the response enhancement of Zn-substituted SnS is also analyzed and demonstrated in detail. The present work demonstrates that Zn-doping is highly effective for improving the response and selectivity of SnS towards methanol vapor, and the Zn-substituted SnS is promising for highly sensitive methanol sensors with low consumption.


Glucose hypometabolism and neuropathological correlates in brains of dementia with Lewy bodies.
Cerebral glucose metabolism using positron emission tomography (PET) with (18)F-fluorodeoxyglucose was examined in 11 patients with probable Alzheimer's disease (AD), 6 patients with probable, and 1 patient with autopsy-confirmed dementia with Lewy bodies (DLB) as well as in 10 age-matched normal control subjects. Among widespread cortical regions showing glucose hypometabolism in the DLB group, the metabolic reduction was most pronounced in the visual association cortex compared to that in the AD group. Using a metabolic ratio of 0.92 in the visual association cortex as a cutoff (mean-2 SD of normal control subjects), DLB could be distinguished from AD with a sensitivity of 86% and a specificity of 91%. In contrast, apolipoprotein E4 allele frequency and cerebrospinal fluid tau levels did not differ significantly between the two groups. In order to further dissect out neuropathological correlates of the dysfunctional occipital lobe, postmortem brains from 19 patients with AD and 17 with DLB as well as 11 brains from normal controls were examined. A distinct and extensive spongiform change with coexisting gliosis was variably noted throughout cerebral white matter with relative sparing of gray matter in DLB. Notably, the white matter spongiform change and gliosis was most prominently and consistently found in the occipital region of DLB, and the severity of the spongiform change in each brain region generally paralleled to the regional difference in reduced glucose metabolism between the living AD and DLB patients. These findings suggest that (1) among several potential antemortem biomarkers in the diagnosis of DLB, measures of the glucose metabolism in the occipital cortex may be an informative diagnostic aid to distinguish DLB from AD; and (2) a pathological process that generates widespread spongiform change and gliosis in long projection fibers may contribute, at least in part, to the characteristic imaging features of DLB.


University students' online habits and their use of the Internet for health information.
Studies have explored the use of the Internet for health information, but few have focused on the young adult population, a population that is known to have difficulties in accessing mainstream health services. It has been acknowledged that young people are active users of the Internet, and this mode of health service delivery warrants further exploration. This study aimed to determine university students' online habits and their use of the Internet for health information using a quantitative descriptive design. Data were collected from 922 university students in Ireland, aged between 18 and 24 years. The findings indicated that university students are active users of the Internet and of social networking sites, particularly for communication purposes. It was also found that 66.1% of participants had used the Internet to search for health information, for a variety of reasons, including information on specific illnesses, sexual health, and fitness and nutrition. It is concluded that the use of the Internet to communicate with young people in relation to their health needs to be explored.


Fingerprint indexing based on Minutia Cylinder-Code.
This paper proposes a new hash-based indexing method to speed up fingerprint identification in large databases. A Locality-Sensitive Hashing (LSH) scheme has been designed relying on Minutiae Cylinder-Code (MCC), which proved to be very effective in mapping a minutiae-based representation (position/ angle only) into a set of fixed-length transformation-invariant binary vectors. A novel search algorithm has been designed thanks to the derivation of a numerical approximation for the similarity between MCC vectors. Extensive experimentations have been carried out to compare the proposed approach against 15 existing methods over all the benchmarks typically used for fingerprint indexing. In spite of the smaller set of features used (top performing methods usually combine more features), the new approach outperforms existing ones in almost all of the cases.


In Vitro Monitoring of the Mitochondrial Beta-Oxidation Flux of Palmitic Acid and Investigation of Its Pharmacological Alteration by Therapeutics.
The present study was designed to validate the functional assay that enables rapid screening of therapeutic candidates for their effect on mitochondrial fatty acid oxidation. The two whole-cell systems (tissue homogenates and hepatocytes) have been evaluated to monitor the total beta-oxidation flux of physiologically important 3H-palmitic acid by measurement of tritiated water enrichment in incubations using UPLC coupled on-line to radioactivity monitoring and mass spectrometry. Our results with several known inhibitors of fatty acid oxidation showed that this simple assay could correctly predict a potential in alteration of mitochondrial function by drug candidates. Since the beta-oxidation of palmitic acid takes place almost exclusively in mitochondria of human hepatocytes, this model can be also utilized to distinguish between the mitochondrial and peroxisomal routes of this essential metabolic pathway in some cases. The present work offers a new in vitro screen of changes in mitochondrial beta-oxidation by xenobiotics as well as a model to study the mechanism of this pathway.


Role of umbilical Doppler velocimetry in the biophysical assessment of the growth-retarded fetus. Answers from neonatal morbidity and mortality.
We compared umbilical Doppler velocimetry with biophysical parameters, obstetrical management, and neonatal morbidity. The study of 85 pregnancies was prospective and blind both to the obstetric and pediatric staff. Our results show that under the same biophysical diagnosis, ie, abnormal fetal growth, oligohydramnios, and nonreactive cardiotocographics, the prevalence of neonatal morbidity was significantly higher in fetuses with associated abnormal umbilical pulsatility index (PI) in utero. Newborns with abnormal PI were delivered earlier, mostly for fetal indication, and were smaller and more asymmetrical than newborns with a normal PI in utero. The analysis of morbidity for homogeneous classes of weight showed that in the group of newborns between 1500 and 2500 g, newborns with normal umbilical PI did show only metabolic disturbances and one respiratory distress syndrome. On the contrary, newborns of the same gestational age and of the same weight with abnormal PI had more severe morbid episodes. In the class of weight between 1500 and 1000 g not only the severity but also the prevalence of neonatal morbidity was significantly higher in newborns with an abnormal PI in utero. None of the newborns delivered below 1000 g had a normal umbilical PI. Five died in the early neonatal period. Three suffered from mild neuromotor sequelae. Practical consequences of these findings on fetal management are the scheduled frequency of biophysical examinations, which must be closer and on an inpatient basis whenever abnormal, and the interpretation of other abnormal biophysical parameters, which must be considered as more severe whenever associated with an abnormal umbilical velocimetry.


Absence of Cardiolipin From the Outer Leaflet of a Mitochondrial Inner Membrane Mimic Restricts Opa1-Mediated Fusion.
Cardiolipin is a tetra-acylated di-phosphatidylglycerol lipid enriched in the matrix-facing (inner) leaflet of the mitochondrial inner membrane. Cardiolipin plays an important role in regulating mitochondria function and dynamics. Yet, the mechanisms connecting cardiolipin distribution and mitochondrial protein function remain indirect. In our previous work, we established an in vitro system reconstituting mitochondrial inner membrane fusion mediated by Opa1. We found that the long form of Opa1 (l-Opa1) works together with the proteolytically processed short form (s-Opa1) to mediate fast and efficient membrane fusion. Here, we extend our reconstitution system to generate supported lipid bilayers with asymmetric cardiolipin distribution. Using this system, we find the presence of cardiolipin on the inter-membrane space-facing (outer) leaflet is important for membrane tethering and fusion. We discuss how the presence of cardiolipin in this leaflet may influence protein and membrane properties, and future applications for this approach.


Consanguinity decreases risk of breast cancer--cervical cancer unaffected.
Marriages between third-degree and more distant relatives are common in many parts of the world. Offspring of consanguineous parents have increased morbidity and mortality related to recessive gene disorders. In a population with a high frequency of consanguinity, we examined the frequency of breast cancer (related in part to tumour genes) and cervical cancers (related to virus infection) among offspring of consanguineous and non-consanguineous parents. Study was done prospectively in the United Arab Emirates. Selected were married female citizens, ages 40-65, who attended 12 primary health care clinics for whatever reason. In a face-to-face interview, subjects were asked: (a) about consanguineous marriages in family; (b) if they have or have had breast or cervical cancer; (c) about family history of cancer, cancer screening and other parameters. Tumour diagnosis was confirmed by review of medical records. Of 1750 women invited into study, 1445 (79%) could be used in analysis. Among 579 (40%) women of consanguineous and 866 (60%) of non-consanguineous parents there were 24 and 54 with breast cancer, respectively (RR = 0.66, CI 0.42 - 1.06). In the 40 to 50 age group, breast cancer reported 13 of 446 women of consanguineous and 37 of 633 of non-consanguineous parents (RR = 0.50, Cl 0.27 - 0.93). Cervical cancer had 15 women in consanguineous and 32 in non-consanguineous group (RR = 0.70, Cl 0.38 - 1.28). Number of families with history of breast cancer in consanguineous and non-consanguineous group was 21 and 23, respectively (P = 0.29). The cancer screening rates and other variable values had fairly balanced distribution between the 2 groups. Having consanguineous parents decreases the risk of breast cancer especially in younger women, risk of cervical cancer being unaffected.


Parasitic myomas.
To report a large case series of parasitic myomas and to examine their causes, associations, and risk factors. Retrospective chart review was performed on 12 patients found to have parasitic myomas between August 2000 and April 2008. The following data were systematically collected: surgery date; indications for surgery; number, dates, and types of prior surgeries; prior use of morcellation; and locations of parasitic myomas. Pathologic confirmation of all specimens was obtained. Laparoscopic evaluation confirmed the presence of intraperitoneal and retroperitoneal myomas distinct from the uterus in 12 patients. Ten of the 12 patients had prior abdominal surgery. Eight patients had prior morcellation procedures; six performed laparoscopically, two performed by laparotomy. Three patients had multiple parasitic myomas, all of whom had a history of laparoscopic myomectomy with morcellation. The majority (14 of 15) of myomas were found in the pelvis, including two retroperitoneal myomas, one of which was embedded in the bladder. Six of 15 myomas were found along the gastrointestinal tract, and 1 of 15 was found in the upper abdomen. Parasitic myomas may occur spontaneously as pedunculated subserosal myomas lose their uterine blood supply and parasitize to other organs. More parasitic myomas may be iatrogenically created after surgery, particularly surgery using morcellation techniques. With increasing rates of laparoscopic procedures, surgeons should be aware of the potential for iatrogenic parasitic myoma formation, their likely increasing frequency, and intraoperative precautions to minimize occurrence. III.


Icescape-scale metabolomics reveals cyanobacterial and topographic control of the core metabolism of the cryoconite ecosystem of an Arctic ice cap.
Glaciers host ecosystems comprised of biodiverse and active microbiota. Among glacial ecosystems, less is known about the ecology of ice caps since most studies focus on valley glaciers or ice sheet margins. Previously we detailed the microbiota of one such high Arctic ice cap, focusing on cryoconite as a microbe-mineral aggregate formed by cyanobacteria. Here, we employ metabolomics at the scale of an entire ice cap to reveal the major metabolic pathways prevailing in the cryoconite of Foxfonna, central Svalbard. We reveal how geophysical and biotic processes influence the metabolomes of its resident cryoconite microbiota. We observed differences in amino acid, fatty acid, and nucleotide synthesis across the cap reflecting the influence of ice topography and the cyanobacteria within cryoconite. Ice topography influences central carbohydrate metabolism and nitrogen assimilation, whereas bacterial community structure governs lipid, nucleotide, and carotenoid biosynthesis processes. The prominence of polyamine metabolism and nitrogen assimilation highlights the importance of recycling nitrogenous nutrients. To our knowledge, this study represents the first application of metabolomics across an entire ice mass, demonstrating its utility as a tool for revealing the fundamental metabolic processes essential for sustaining life in supraglacial ecosystems experiencing profound change due to Arctic climate change-driven mass loss.


Long-term trends in the ambient PM2.5- and O3-related mortality burdens in the United States under emission reductions from 1990 to 2010.
Concentrations of both fine particulate matter (PM2.5) and ozone (O3) in the United States (US) have decreased significantly since 1990, mainly because of air quality regulations. Exposure to these air pollutants is associated with premature death. Here we quantify the annual mortality burdens from PM2.5 and O3 in the US from 1990 to 2010, estimate trends and inter-annual variability, and evaluate the contributions to those trends from changes in pollutant concentrations, population, and baseline mortality rates. We use a fine-resolution (36 km) self-consistent 21-year simulation of air pollutant concentrations in the US from 1990 to 2010, a health impact function, and annual county-level population and baseline mortality rate estimates. From 1990 to 2010, the modeled population-weighted annual PM2.5 decreased by 39 %, and summertime (April to September) 1 h average daily maximum O3 decreased by 9 % from 1990 to 2010. The PM2.5-related mortality burden from ischemic heart disease, chronic obstructive pulmonary disease, lung cancer, and stroke steadily decreased by 54% from 123 700 deaths year-1 (95% confidence interval, 70 800-178 100) in 1990 to 58 600 deaths year-1 (24 900-98 500) in 2010. The PM2.5-related mortality burden would have decreased by only 24% from 1990 to 2010 if the PM2.5 concentrations had stayed at the 1990 level, due to decreases in baseline mortality rates for major diseases affected by PM2.5. The mortality burden associated with O3 from chronic respiratory disease increased by 13% from 10 900 deaths year-1 (3700-17 500) in 1990 to 12 300 deaths year-1 (4100-19 800) in 2010, mainly caused by increases in the baseline mortality rates and population, despite decreases in O3 concentration. The O3-related mortality burden would have increased by 55% from 1990 to 2010 if the O3 concentrations had stayed at the 1990 level. The detrended annual O3 mortality burden has larger inter-annual variability (coefficient of variation of 12%) than the PM2.5-related burden (4%), mainly from the inter-annual variation of O3 concentration. We conclude that air quality improvements have significantly decreased the mortality burden, avoiding roughly 35 800 (38%) PM2.5-related deaths and 4600 (27%) O3-related deaths in 2010, compared to the case if air quality had stayed at 1990 levels (at 2010 baseline mortality rates and population).


Clients express preference for one-stop sexual health shop.
The concept of sexual health is becoming more prominent. However, health services relating to the maintenance of sexual health do not necessarily use the available resources to their best advantage. This paper examines developments in the area of sexual health and presents the results of a survey carried out in Eastbourne and Ipswich, which indicates that attenders of various clinics dealing with sexual health would welcome services such as family planning and genitourinary medicine being combined on one site.


Heme oxygenase-1 induction attenuates senescence in chronic obstructive pulmonary disease lung fibroblasts by protecting against mitochondria dysfunction.
Chronic obstructive pulmonary disease (COPD) is associated with lung fibroblast senescence, a process characterized by an irreversible proliferation arrest associated with secretion of inflammatory mediators. ROS production, known to induce senescence, is increased in COPD fibroblasts and mitochondria dysfunction participates in this process. Among the battery of cellular responses against oxidative stress damage, heme oxygenase (HO)-1 plays a critical role in defending the lung against oxidative stress and inflammation. Therefore, we investigated whether pharmacological induction of HO-1 by chronic hemin treatment attenuates senescence and improves dysfunctional mitochondria in COPD fibroblasts. Fibroblasts from smoker controls (S-C) and COPD patients were isolated from lung biopsies. Fibroblasts were long-term cultured in the presence or absence of hemin, and/or ZnPP or QC-15 (HO-1 inhibitors). Lung fibroblasts from smokers and COPD patients displayed in long-term culture a senescent phenotype, characterized by a reduced replicative capacity, an increased senescence and inflammatory profile. These parameters were significantly higher in senescent COPD fibroblasts which also exhibited decreased mitochondrial activity (respiration, glycolysis, and ATP levels) which led to an increased production of ROS, and mitochondria biogenesis and impaired mitophagy process. Exposure to hemin increased the gene and protein expression level of HO-1 in fibroblasts and diminished ROS levels, senescence, the inflammatory profile and simultaneously rescued mitochondria dysfunction by restoring mitophagy in COPD cells. The effects of hemin were abolished by a cotreatment with ZnPP or QC-15. We conclude that HO-1 attenuates senescence in COPD fibroblasts by protecting, at least in part, against mitochondria dysfunction and restoring mitophagy.


Neurosurgical correction of upper brachial plexus birth injuries.
The authors review the cases of 116 infants treated consecutively for birth-related brachial plexus injuries. Twenty-eight infants with upper brachial plexus lesions who showed no neurological improvement by 4 months of age were selected for early surgical reconstruction (at a mean age of 5 months). Neurological improvement of the affected arm was observed in more than 90% (p < 0.05) of the children examined longer than 9 months after brachial plexus reconstruction. A conservatively managed control subgroup of 44 children, first examined at less than 3 months of age, demonstrated neurological improvement by 4 months of age and continued to show improvement at 1 year of age. Early surgical reconstruction is recommended for infants with birth-related upper brachial plexus injury who show no neurological improvement by the age of 4 months.


Angiotensin-converting enzyme 2 regulates renal atrial natriuretic peptide through angiotensin-(1-7).
Deficiency of ACE2 (angiotensin-converting enzyme 2), which degrades Ang (angiotensin) II, promotes the development of glomerular lesions. However, the mechanisms explaining why the reduction in ACE2 is associated with the development of glomerular lesions have still to be fully clarified. We hypothesized that ACE2 may regulate the renoprotective actions of ANP (atrial natriuretic peptide). The aim of the present study was to investigate the effect of ACE2 deficiency on the renal production of ANP. We evaluated molecular and structural abnormalities, as well as the expression of ANP in the kidneys of ACE2-deficient mice and C57BL/6 mice. We also exposed renal tubular cells to AngII and Ang-(1-7) in the presence and absence of inhibitors and agonists of RAS (renin-angiotensin system) signalling. ACE2 deficiency resulted in increased oxidative stress, as well as pro-inflammatory and profibrotic changes. This was associated with a down-regulation of the gene and protein expression on the renal production of ANP. Consistent with a role for the ACE2 pathway in modulating ANP, exposing cells to either Ang-(1-7) or ACE2 or the Mas receptor agonist up-regulated ANP gene expression. This work demonstrates that ACE2 regulates renal ANP via the generation of Ang-(1-7). This is a new mechanism whereby ACE2 counterbalances the renal effects of AngII and which explains why targeting ACE2 may be a promising strategy against kidney diseases, including diabetic nephropathy.


Effect of Use of a Bougie vs Endotracheal Tube With Stylet on Successful Intubation on the First Attempt Among Critically Ill Patients Undergoing Tracheal Intubation: A Randomized Clinical Trial.
For critically ill adults undergoing emergency tracheal intubation, failure to intubate the trachea on the first attempt occurs in up to 20% of cases and is associated with severe hypoxemia and cardiac arrest. Whether using a tracheal tube introducer ("bougie") increases the likelihood of successful intubation compared with using an endotracheal tube with stylet remains uncertain. To determine the effect of use of a bougie vs an endotracheal tube with stylet on successful intubation on the first attempt. The Bougie or Stylet in Patients Undergoing Intubation Emergently (BOUGIE) trial was a multicenter, randomized clinical trial among 1102 critically ill adults undergoing tracheal intubation in 7 emergency departments and 8 intensive care units in the US between April 29, 2019, and February 14, 2021; the date of final follow-up was March 14, 2021. Patients were randomly assigned to use of a bougie (n = 556) or use of an endotracheal tube with stylet (n = 546). The primary outcome was successful intubation on the first attempt. The secondary outcome was the incidence of severe hypoxemia, defined as a peripheral oxygen saturation less than 80%. Among 1106 patients randomized, 1102 (99.6%) completed the trial and were included in the primary analysis (median age, 58 years; 41.0% women). Successful intubation on the first attempt occurred in 447 patients (80.4%) in the bougie group and 453 patients (83.0%) in the stylet group (absolute risk difference, -2.6 percentage points [95% CI, -7.3 to 2.2]; P = .27). A total of 58 patients (11.0%) in the bougie group experienced severe hypoxemia, compared with 46 patients (8.8%) in the stylet group (absolute risk difference, 2.2 percentage points [95% CI, -1.6 to 6.0]). Esophageal intubation occurred in 4 patients (0.7%) in the bougie group and 5 patients (0.9%) in the stylet group, pneumothorax was present after intubation in 14 patients (2.5%) in the bougie group and 15 patients (2.7%) in the stylet group, and injury to oral, glottic, or thoracic structures occurred in 0 patients in the bougie group and 3 patients (0.5%) in the stylet group. Among critically ill adults undergoing tracheal intubation, use of a bougie did not significantly increase the incidence of successful intubation on the first attempt compared with use of an endotracheal tube with stylet. ClinicalTrials.gov Identifier: NCT03928925


Streptococcal toxic shock-like syndrome.
After decades marked by a decrease in the incidence and severity of scarlet fever and streptococcal soft-tissue infections, invasive infections with group A streptococci have reemerged as a global public health problem. Sporadic outbreaks of a rapidly progressive disorder characterized by fever, shock, desquamating rash, and multiorgan system failure often associated with severe suppurative soft-tissue infection have recently been recognized in young, otherwise-healthy adults. Referred to as streptococcal toxic shock-like syndrome, this acute, progressive, often fatal illness appears to be related to an overall change in the virulence of group A streptococci and the reappearance of highly mucoid exotoxin-producing strains. However, the relationship between virulence factors, epidemiological features, and precise pathogenesis of these infections remains unclear. The 80% incidence of soft-tissue involvement in streptococcal toxic shock-like syndrome and the high frequency of progression to necrotizing fasciitis, myositis, or even death are unprecedented. The type and extent of tissue injury, systemic toxicity, and multiorgan system failure associated with this syndrome appear to be mediated by streptococcal pyrogenic exotoxins via the induction of biologically potent endogenous cytokines. The observed increase in the incidence and severity of invasive group A streptococcal infections coincides with the resurgence of genetically related, highly virulent strains of Staphylococcus pyogenes that express an invasive phenotype and carry a specific gene for pyrogenic exotoxin A. The changing spectrum of invasive group A streptococcal infections has prompted a reexamination of the microorganism and its diverse clinical manifestations. A clonal basis for increased virulence expression is supported epidemiologically. As the incidence of streptococcal toxic shock-like syndrome appears to be increasing, it is imperative that clinicians become familiar with the presentation of this syndrome so they can diagnose and treat it in a timely and effective manner.


Long-lasting muscle fatigue: partial disruption of excitation-contraction coupling by elevated cytosolic Ca2+ concentration during contractions.
The repeated elevation of cytosolic Ca(2+) concentration ([Ca(2+)](i)) above resting levels during contractile activity has been associated with long-lasting muscle fatigue. The mechanism underlying this fatigue appears to involve elevated [Ca(2+)](i) levels that induce disruption of the excitation-contraction (E-C) coupling process at the triad junction. Unclear, however, are which aspects of the activity-related [Ca(2+)](i) changes are responsible for the deleterious effects, in particular whether they depend primarily on the peak [Ca(2+)](i) reached locally at particular sites or on the temporal summation of the increased [Ca(2+)] in the cytoplasm as a whole. In this study, we used mechanically skinned fibers from rat extensor digitorum longus muscle, in which the normal E-C coupling process remains intact. The [Ca(2+)](i) was raised either by applying a set elevated [Ca(2+)] throughout the fiber or by using action potential stimulation to induce the release of sarcoplasmic reticulum Ca(2+) by the normal E-C coupling system with or without augmentation by caffeine or buffering with BAPTA. Herein we show that elevating [Ca(2+)](i) in the physiological range of 2-20 microM irreversibly disrupts E-C coupling in a concentration-dependent manner but requires exposure for a relatively long time (1-3 min) to cause substantial uncoupling. The effectiveness of Ca(2+) released via the endogenous system in disrupting E-C coupling indicates that the relatively high [Ca(2+)](i) attained close to the release site at the triad junction is a more important factor than the increase in bulk [Ca(2+)](i). Our results suggest that during prolonged vigorous activity, the many repeated episodes of relatively high triadic [Ca(2+)] can disrupt E-C coupling and lead to long-lasting fatigue.


Analysis of the correlation between non-alcoholic fatty liver disease and the risk of colorectal neoplasms.
This study aims at assessing the potential association between non-alcoholic fatty liver disease (NAFLD) and colorectal neoplasms (CRN). PubMed, Cochrane Library, and Embase were searched for cohort studies. 14 cohort studies with a total population of 38,761,773 were included for meta-analysis after selection. The results showed that NAFLD is related to an increased risk of CRN (OR = 1.23; 95% CI: 1.14-1.32; I2 = 70.7%, p < 0.001). In the subgroup analysis, NAFLD were found to be the independent risk factor of colorectal adenoma (CRA) (OR = 1.29; 95% CI = 1.15-1.45; I2 = 66.4%) and colorectal cancer (CRC) (OR = 1.13; 95% CI = 1.12-1.15; I2 = 69.4%). There is no close correlation between smoking status of NAFLD patients and CRN. Interestingly, bioinformatics analysis revealed that there were overlap of dysregulated gene sets among NAFLD, CRC, and two recently identified regulated cell death types, ferroptosis and cuproptosis, respectively. Our meta- and bioinformatics analysis shows that NAFLD increases the risk of CRN. Ferroptosis and cuproptosis may be the critical links between NAFLD and CRN, respectively. These findings here support that NAFLD is necessary to be considered as an emerging risk factor for CRN.


Prevention of football injuries.
Every sport has a unique profile of injury and risk of injury. In recent years, there have been numerous attempts at conducting injury prevention trials for specific injuries or for injuries within specific sports to provide evidence useful to the sports medicine and sport community. Football has been a focus of a number of randomized injury prevention trials. MEDLINE was searched with the first order keywords of "injury prevention" and "sport". This list was restricted to "clinical trial" or "randomized controlled trial" which had been conducted on children and adults whose goal was preventing common football injuries. Our objective was to find studies with an exercise-based training program, thus projects that used mechanical interventions were excluded. A structured, generalized warm-up has been shown to be effective at preventing common injuries in football, reducing injuries by about one-third. The huge participation numbers in the worldwide family of football would suggest that any reduction in injury should have a public health impact. Professionals in sports medicine need to promote injury prevention programs that have been shown to be effective.


Misdiagnosed paranasal gossypiboma: a 10-year experience with 21 cases at a tertiary center.
Different from rhinoliths, the paranasal gossypiboma is a foreign body, such as a surgical sponge, left in the nasal cavity. It is a rare, frequently misdiagnosed disease that has rarely been reported. We summarize its clinical characteristics, management, and possible risk factors. We reviewed medical records of confirmed paranasal gossypibomas at a tertiary medical center between 2005 and 2015. Clinical symptoms, age, sex, anatomic sites, endoscopic photography, computed tomography, intraoperative findings, and past medical history were reviewed. The study included 21 patients, each of whom had ultimately undergone two operations. Among them, 20 underwent endoscopic nasal surgery in primary hospitals, and 15 had been misdiagnosed during the second surgery. The average interval to discovery of a retained foreign body was 200 days. Predominant occurrence sites were the maxillary and ethmoid sinuses. Computed tomography showed paranasal gossypiboma as a heterogeneous cystic lesion with a thin calcified shell. A history of endoscopic nasal surgery, especially performed at a primary hospital, is a warning sign for clinicians. Computed tomography can add to the warning by showing a heterogeneous cystic lesion with a thin calcified shell. Clinicians should be aware of these characteristics to avoid misdiagnosing paranasal gossypiboma.


Fronto-ethmoidal and orbital osteomas with intracranial extension. Report of two cases.
Osteomas involving the anterior cranial base are quite rare lesions. Intracranial and orbital extension of these tumors, causing neurological and ophthalmological symptoms and signs is a rare event. Two such cases are reported. In the first one, the tumor arose from the frontal sinus and extended upward to the medial and superior wall of the right orbital cavity and the lower part of the right frontal convexity. In the second case the osteoma arose from the left orbital roof and extended to the lower part of the homolateral frontal convexity and the splenoid wing. After the operation the symptoms disappeared and the cosmetic deficits were corrected. Skull-films, CT and MR well define the bony extension and the displacement of the orbital and intracranial structures. Indications to the surgery include progressive ophthalmologic and neurologic signs and significant cosmetic deformations. The surgical techniques and the postoperative complications are briefly discussed.


Mononuclear cell line THP-1 internalizes bactericidal/permeability-increasing protein by a non-receptor-mediated mechanism consistent with pinocytosis.
Bactericidal/permeability-increasing protein (BPI) binds lipopolysaccharide and neutralizes its toxic effects in vitro and in endotoxemic animals. Our recent work identified physiologically significant interactions between BPI, lipopolysaccharide, and mononuclear cells. To determine whether the interaction between BPI and mononuclear cells is receptor mediated. Labeled BPI was incubated with THP-1 cells in the presence of up to 100-fold excess of unlabeled BPI. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting were performed to evaluate competitive binding and total uptake of BPI. Crosslinking was performed to determine whether BPI binds to a single protein entity. Acid washing experiments and flow cytometric analysis were performed to determine whether BPI remains on the cellular surface. Finally, flow cytometry analysis was used to determine whether BPI incubation with THP-1 cells affects the surface expression of the lipopolysaccharide-binding protein-lipopolysaccharide receptor CD14. Labeled BPI uptake was not inhibited by the presence of 100-fold excess of unlabeled BPI at 37 degrees C or 4 degrees C in the presence of azide. Uptake was not saturable under either condition with incubation concentrations up to 10 microgram/mL. Cross-linking did not show BPI bound to a single entity. Acid washing and flow cytometry experiments disclosed rapid internalization of BPI. Finally, BPI uptake by THP-1 cells had no effect on the surface expression of CD14. Bactericidal/permeability-increasing protein is rapidly internalized by mononuclear cells in a nonspecific fashion not saturable at very high doses, which is consistent with pinocytosis. This process may represent a disposal mechanism for lipopolysaccharide in closed-space infections and may be partially responsible for the rapid clearance of BPI from the peripheral circulation.


Influence of dressing changes on wound temperature.
When wound-tissue temperature falls below 33 degrees C neutrophil, fibroblast and epithelial cell activity decreases. This study examined the influence of dressing changes on wound temperature. The wound-bed temperatures of patients with a wound resulting from trauma or surgical debridement were measured immediately before and after dressing changes using a DermaTemp infrared body surface scanning device. The temperature on the surface of the dressing product was measured immediately before the dressing change and then every five minutes it until the pre-procedural temperature was reached. A total of 133 dressing episodes were measured, yielding 266 wound-bed temperature measurements and 619 external dressing temperature measurements. Pre-procedural temperatures showed that the wound beds were on average marginally below the 33 degrees C threshold immediately after dressing takedown (mean: 32.7 degrees C). This figure dropped two degrees on average as a result of the dressing-change procedure (mean: 29.9 degrees C). Reapplied wound-dressing products return to the pre-procedural temperature within 30 minutes (mean: 23 minutes). This study provides baseline data for future research aimed at promoting maintenance of a normothermic wound bed. None.


Efficient photochromism from the network of chemical reactions of 7,4'-dihydroxyflavylium in CTAB micelles.
Differently from water, efficient photochromism with a strong colour contrast has been observed for the multistate compound 7,4'-dihydroxyflavylium in the presence of cetyl trimethylammonium bromide (CTAB) micelles. Two states are responsible for the photochromism: trans-chalcone (inside the micelle) in the dark, and flavylium cation, AH(+), (in bulk water) upon irradiation. The kinetics of the system was characterized by flash photolysis and pH jumps. Evidence that the photochemical process leading to AH(+) occurs in the micelle was achieved. The best colour contrast is obtained at pH = 1.5, from a solution practically colourless in the dark, to an intense yellow upon irradiation (quantum yield 0.4). The system is completely reversible with a lifetime of 38 min at room temperature, and exhibits a reasonable stability. A kinetic model capable of fitting the data from thermal entrance of the compound into the micelle, its ejection to bulk water upon irradiation and quantum yields of the photochemical process is proposed.


Hunting bats adjust their echolocation to receive weak prey echoes for clutter reduction.
How animals extract information from their surroundings to guide motor patterns is central to their survival. Here, we use echo-recording tags to show how wild hunting bats adjust their sensory strategies to their prey and natural environment. When searching, bats maximize the chances of detecting small prey by using large sensory volumes. During prey pursuit, they trade spatial for temporal information by reducing sensory volumes while increasing update rate and redundancy of their sensory scenes. These adjustments lead to very weak prey echoes that bats protect from interference by segregating prey sensory streams from the background using a combination of fast-acting sensory and motor strategies. Counterintuitively, these weak sensory scenes allow bats to be efficient hunters close to background clutter broadening the niches available to hunt for insects.


Integrating plant physiology into simulation of fire behavior and effects.
Wildfires are a global crisis, but current fire models fail to capture vegetation response to changing climate. With drought and elevated temperature increasing the importance of vegetation dynamics to fire behavior, and the advent of next generation models capable of capturing increasingly complex physical processes, we provide a renewed focus on representation of woody vegetation in fire models. Currently, the most advanced representations of fire behavior and biophysical fire effects are found in distinct classes of fine-scale models and do not capture variation in live fuel (i.e. living plant) properties. We demonstrate that plant water and carbon dynamics, which influence combustion and heat transfer into the plant and often dictate plant survival, provide the mechanistic linkage between fire behavior and effects. Our conceptual framework linking remotely sensed estimates of plant water and carbon to fine-scale models of fire behavior and effects could be a critical first step toward improving the fidelity of the coarse scale models that are now relied upon for global fire forecasting. This process-based approach will be essential to capturing the influence of physiological responses to drought and warming on live fuel conditions, strengthening the science needed to guide fire managers in an uncertain future.


Relationship between Glycemic Load and Blood Lipid Level in Hospitalized Adult Chinese.
Metabolic diseases in China have been on the rise in recent decades, partially due to reduced cereal consumption and excessive intake of low glycemic index (GI) foods such as meat and oil. Although the relationship between dietary glycemic load (GL) and various metabolic diseases has been extensively studied worldwide, it is unclear whether dietary GL is related to blood lipid levels and dyslipidemia risk in Chinese. The aim of the present study was to investigate the relationship between dietary GL and blood lipid levels and dyslipidemia risk in hospitalized Chinese adults. Dietary GL in 2258 hospitalized Chinese adults was calculated based upon GI, carbohydrate content and daily intake of individual foods. In addition, fasting total cholesterol (TC), triglycerides (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) data were collected. Multiple regression and logistic regression analysis were used to determine the relationship between dietary GL and plasma lipid levels or dyslipidemia risk. Dietary GL remained inversely associated with blood total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (P<0.01). With increasing dietary GL, risks of hypercholesterolemia and high blood LDL-C were significantly reduced (P<0.01). In the meantime dietary GL remained negatively associated with blood triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) (P<0.01), but showed no significant influence on risk of hypertriglyceridemia and low blood HDL-C (P>0.05). High GL diet, as represented by traditional Chinese dietary pattern, may contribute to reduced risk of dyslipidemia in Chinese adults.


Low-dose creatine supplementation enhances fatigue resistance in the absence of weight gain.
We examined the effects of 6 wk of low-dose creatine supplementation on body composition, muscle function, and body creatine retention. Twenty healthy men and women (21 ± 2 y old) were randomized to receive creatine (0.03 g · kg(-1) · d(-1); n = 10, 4 women) or placebo (n = 10, 4 women) for 6 wk in a double-blind placebo-controlled fashion. Participants were tested on two occasions before supplementation to establish a reliable baseline, and then were retested after supplementation. Testing included body composition, maximal strength (three-repetition maximal concentric knee extension at 180 degrees/s), muscle fatigue (five sets of 30 concentric knee extensions at 180 degrees/s), and plasma creatine concentration. There were no significant differences in body mass, fat-free mass, fat mass, body fat percentage, total body water, or maximal strength in either group from before to after supplementation (all P > 0.05). After supplementation, plasma creatine increased significantly in the creatine group (+182%, P = 0.03), with no difference in the placebo group. Compared with baseline values, creatine-supplemented volunteers were more resistant to fatigue during sets 2 (7%), 3 (9%), 4 (9%), and 5 (11%) (all P < 0.05). In placebo-supplemented participants, there was no improvement in fatigue resistance during sets 2 (0%), 3 (1%), 4 (0%), and 5 (-1%) (all P > 0.05). Ingesting a low dose (≈2.3 g/d) of creatine for 6 wk significantly increased plasma creatine concentration and enhanced resistance to fatigue during repeated bouts of high-intensity contractions.


Policies and Management Interventions to Enhance Health and Care Workforce Capacity for Addressing the COVID-19 Pandemic: Protocol for a Living Systematic Review.
Countries and health systems have had to make challenging resource allocation and capacity-building decisions to promote proper patient care and ensure health and care workers' safety and well-being, so that they can effectively address the present COVID-19 pandemic as well as upcoming public health problems and natural catastrophes. As innovations are already in place and updated evidence is published daily, more information is required to inform the development and implementation of policies and interventions to improve health and care workforce capacity to address the COVID-19 pandemic response. The objective of this protocol review is to identify countries' range of experiences with policies and management interventions that can improve health and care workers' capacity to address the COVID-19 pandemic response and synthesize evidence on the effectiveness of the interventions. We will conduct a living systematic review of quantitative, qualitative, and mixed methods studies and gray literature (technical and political documents) published in English, French, Hindi, Portuguese, Italian, and Spanish between January 1, 2000, and March 1, 2022. The databases to be searched are MEDLINE (PubMed), Embase, SCOPUS, and Latin American and Caribbean Health Sciences Literature. In addition, the World Health Organization's COVID-19 Research Database and the websites of international organizations (International Labour Organization, Economic Co-operation and Development, and The Health System Response Monitor) will be searched for unpublished studies and gray literature. Data will be extracted from the selected documents using an electronic form adapted from the Joanna Briggs Institute quantitative and qualitative tools for data extraction. A convergent integrated approach to synthesis and integration will be used. The risk of bias will be assessed with Joanna Briggs Institute critical appraisal tools, and the certainty of the evidence in the presented outcomes will be assessed with the Grading of Recommendations, Assessment, Development and Evaluation. The database and gray literature search retrieved 3378 documents. Data are being analyzed by 2 independent reviewers. The study is expected to be published by the end of 2023 in a peer-reviewed journal. This review will allow us to identify and describe the policies and strategies implemented by countries and their effectiveness, as well as identify gaps in the evidence. PROSPERO CRD42022327041; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=327041. RR1-10.2196/50306.


Self care integrative treatment demonstrated in rural community setting improves health related quality of life of lymphatic filariasis patients in endemic villages.
This study assessed impact of community based self care integrative treatment provided through mass camps in villages of three districts of Kerala, India endemic for lymphatic filariasis (LF). Two most endemic Primary Health centres (PHCs) were selected from each of the three districts, where maximum concentration of LF patients is recorded. Fourteen one day LF camps, each attended by 30-40 patients were conducted. Trained Accredited Social Health Activists encouraged LF patients to attend camps. Skin wash and drying, care of bacterial entry points using dermatology drugs, and simple yoga and breathing exercises were demonstrated in these camps. Patients were advised to continue these self care activities daily at home for six months. The quality of life (QoL) of LF patients was determined for Indian life style domains using validated and pretested specific questionnaire (LF-specific QoL questionnaire-LFSQQ). It addressed conditions and state of individuals with reference to LF. The questionnaire had 7 domains and each domain consisted of a series of questions with likert scale (no problem, mild, moderate, severe, most severe). 446 patients attended one day camps to get training on integrative self care treatment. 425 patients (95.3%) were followed up after six months and QoL was reassessed. Each patient's QoL in mobility, self care, usual activity, pain and discomfort and social relationship significantly improved (P value <0.01). Psychological health showed no significant change. The disease burden, for the purpose of the study was measured by asking questions about history of painful redness, swelling and cellulitis of legs (filarial fever), foul smell (odor), itching (eczema/discharge from limb), wound (non healing ulcer) and weight/size of the limb. The difference in disease burden as recorded during the sixth month follow up was measured using dependent t test, reduced significantly (P value <0.01) in 409 (96.2%) patients. 103 (24.2%) patients experienced fever during follow up. Severity of inflammatory episodes reduced from severe problem to no problem, after six months of home based self care. There was significant relation between treatment regularity and QoL status (P value=0.003). The community based one day camps that trained LF patients on skin care and daily yoga and breathing practices improved QoL.


Effects of storage temperature on the contents of sugars and free amino acids in tubers from different potato cultivars and acrylamide in chips.
To clarify the effects of storage temperature on potato components and acrylamide in chips, tubers from five cultivars were stored at various temperatures (2, 6, 8, 10, and 18 degrees C) for 18 weeks, and the contents of sugars, free amino acids in tubers, and acrylamide in chips after frying were analyzed. At temperatures lower than 8 degrees C, the contents of reducing sugars increased markedly in all cultivars, with similar increases in the acrylamide level and dark brown chip color. Free amino acids showed little change at the storage temperatures tested and varied within certain ranges characteristic of each cultivar. The contents of reducing sugars correlated well with the acrylamide level when the fructose/asparagine molar ratio in the tubers was <2. When the fructose/asparagine ratio was >2 by low-temperature storage, the asparagine content, rather than the reducing sugar content, was found to be the limiting factor for acrylamide formation.


Insomnia and global sleep dissatisfaction in Finland.
The purpose of this study is to assess the prevalence of insomnia symptoms and diagnoses in the general population of Finland. A total of 982 participants, aged 18 years or older and representative of the general population of Finland, were interviewed by telephone using the Sleep-EVAL system. The participation rate was 78%. The questionnaire included the assessment of sleep habits, insomnia symptomatology according to Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) and International Classification of Sleep Disorders (ICSD), associated and sleep/mental disorders and daytime consequences. The overall prevalence of insomnia symptoms occurring at least three nights per week was 37.6%. Difficulty initiating sleep were mentioned by 11.9% of the sample, difficulty maintaining sleep by 31.6%, early morning awakenings by 11.0% and non-restorative sleep by 7.9% of the sample. Global dissatisfaction with sleep was found in 11.9% of the sample. Daytime consequences (fatigue, mood changes, cognitive difficulties or daytime sleepiness) were reported by 39.9% of participants with insomnia symptoms and 87.6% of those with sleep dissatisfaction. A deterioration of sleep in summer or winter was associated with more complaints of sleep dissatisfaction. Prevalence of any DSM-IV insomnia diagnosis was 11.7%. More specifically, DSM-IV diagnosis of primary insomnia had a prevalence of 1.6% and DSM-IV diagnosis of insomnia related to another mental disorder was at 2.1%. Insomnia was a symptom of another sleep disorder in about 16% of cases and of a mental disorder in about 17% of cases. As reported in other Nordic studies, sleep quality was worse in summer. Insomnia symptomatology was common and was reported by more than a third of Finnish participants. Compared with other European countries studied with the same methodology (France, the UK, Germany, and Italy), the prevalence of DSM-IV insomnia diagnosis was 1.5 to two times higher in Finland.


Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms.
The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied. Three modified-release formulations of aminophylline consisted of Carbopol® 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used. Commercial products were Aminofilin retard 350 mg tablets, Srbolek, Serbia (R-I) and Phyllocontin(®) 350, tablets Purdue Frederic, Canada (R-II). Calculated release rate constants and the ƒ2 values between R-I/F-I (84.1) and R-II/F-III (83.4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport. Higher Tmax, was found in the rabbits, dosed with F-II (12.00 h), F-III (10.50 h), and R-II (15.00 h) formulation. The highest Cmax (9.22 mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5.58 mg/L) and R-II (4.18 mg/L). Higher AUC values were detected for all three formulations (from 115.90 to 204.06 mgh/L) in relation to commercial products (105.33 and 113.25 mgh/L). The results demonstrated a good correlation of Level A (r(2) = 0.97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development.


The Frequency Response of Outer Hair Cell Voltage-Dependent Motility Is Limited by Kinetics of Prestin.
The voltage-dependent protein SLC26a5 (prestin) underlies outer hair cell electromotility (eM), which is responsible for cochlear amplification in mammals. The electrical signature of eM is a bell-shaped nonlinear capacitance (NLC), deriving from prestin sensor-charge (Qp) movements, which peaks at the membrane voltage, Vh, where charge is distributed equally on either side of the membrane. Voltage dependencies of NLC and eM differ depending on interrogation frequency and intracellular chloride, revealing slow intermediate conformational transitions between anion binding and voltage-driven Qp movements. Consequently, NLC exhibits low-pass characteristics, substantially below prevailing estimates of eM frequency response. Here we study in guinea pig and mouse of either sex synchronous prestin electrical (NLC, Qp) and mechanical (eM) activity across frequencies under voltage clamp (whole cell and microchamber). We find that eM and Qp magnitude and phase correspond, indicating tight piezoelectric coupling. Electromechanical measures (both NLC and eM) show dual-Lorentzian, low-pass behavior, with a limiting (τ2) time constant at Vh of 32.6 and 24.8 μs, respectively. As expected for voltage-dependent kinetics, voltage excitation away from Vh has a faster, flatter frequency response, with our fastest measured τ2 for eM of 18.2 μs. Previous observations of ultrafast eM (τ ≈ 2 μs) were obtained at offsets far removed from Vh We hypothesize that trade-offs in eM gain-bandwith arising from voltage excitation at membrane potentials offset from Vh influence the effectiveness of cochlear amplification across frequencies.SIGNIFICANCE STATEMENT Of two types of hair cells within the organ of Corti, inner hair cells and outer hair cells, the latter evolved to boost sensitivity to sounds. Damage results in hearing loss of 40-60 dB, revealing amplification gains of 100-1000× that arise from voltage-dependent mechanical responses [electromotility (eM)]. eM, driven by the membrane protein prestin, may work beyond 70 kHz. However, this speed exceeds, by over an order of magnitude, kinetics of typical voltage-dependent membrane proteins. We find eM is actually low pass in nature, indicating that prestin bears kinetics typical of other membrane proteins. These observations highlight potential difficulties in providing sufficient amplification beyond a cutoff frequency near 20 kHz. Nevertheless, observed trade-offs in eM gain-bandwith may sustain cochlear amplification across frequency.


Prolonged high iodine intake is associated with inhibition of type 2 deiodinase activity in pituitary and elevation of serum thyrotropin levels.
Our previous epidemiological study indicated that excessive intake of iodine could potentially lead to hypothyroidism. In the present study, we aimed to investigate the time and dose effect of iodine intake on serum thyrotropin (thyroid-stimulating hormone, TSH) levels and to explore the non-autoimmune regulation of serum TSH by pituitary type 2 deiodinase (D2). A total of 360 Wistar rats were randomly divided into five groups depending on administered iodine dosages (folds of physiological dose): normal iodine (NI), 3-fold iodine (3HI), 6-fold iodine (6HI), 10-fold iodine (10HI) and 50-fold iodine (50HI). At 4, 8, 12 and 24 weeks after administration of sodium iodide, blood was collected for serum TSH measurement by chemiluminescent immunoassay. Pituitaries were also excised for measurement of TSHβ subunit expression, D2 expression and activity, monocarboxylate transporter 8 (MCT8) and thyroid hormone receptor β2 isoform (TRβ2) levels. The results showed that iodine intake of 10HI and 50HI significantly increased pituitary and serum TSH levels from 8 to 24 weeks (P < 0·05 v. NI). Excess iodine had no effect on D2 mRNA or protein expression; however, 10HI and 50HI administration significantly inhibited pituitary D2 activities from 8 to 24 weeks (P < 0·05 v. NI). Iodine had no effect on MCT8 or TRβ2 protein levels. We conclude that prolonged high iodine intake inhibits pituitary D2 activity and induces elevation of serum TSH levels. These findings may provide a potential mechanism of iodine excess-induced overt and subclinical hypothyroidism.


Localization of MAP kinase activity in early Xenopus embryos: implications for endogenous FGF signaling.
We have used a sensitive assay for MAP kinase activity to investigate the role of endogenous fibroblast growth factor (FGF)-activated MAP kinase in early Xenopus embryonic patterning. MAP kinase activity is low during cleavage stages and increases significantly during gastrulation. The temporal profile of this activity correlates well with the expression pattern of Xenopus eFGF. Spatially, MAP kinase activity is lowest in animal pole tissue and higher in vegetal pole cells and the marginal zone. Endogenous MAP kinase activity is FGF receptor-dependent, demonstrating that FGF signaling is active in all three germ layers of the early embryo. This activity is necessary for normal expression of Mix.1, a mesoendodermal marker, in the endoderm as well as in the mesoderm, indicating that MAP kinase plays a functional role in patterning of both of these germ layers. Spatial and temporal changes in MAP kinase activation during gastrulation also suggest a role for FGF signaling in this process. In addition, we find that embryonic wounding during dissection results in significant stimulation of this pathway, providing a possible explanation for earlier observations of effects of surgical manipulation on cell fate in early embryos.