Barriers to conducting clinical research in reproductive medicine: India.
Research in India is evolving at a rapid pace. Ergo, we need faster approval processes and review timelines. Improvement in the quality of institutional review boards would also contribute to good research practices. Clinical research should be included as a part of the undergraduate medical and pharmacy curriculum, and leading hospitals and practitioners should openly endorse research.


Primary Care Use Among Commercially Insured Adolescents: Evidence From the 2018 Healthcare Effectiveness Data and Information Set.
Improving the utilization of preventive care among adolescents is important for achieving individual-level and population-level health goals. The Healthcare Effectiveness Data and Information Set reports data submitted by managed care health plans, capturing a large number of individuals in the U.S. Using Healthcare Effectiveness Data and Information Set from 2018, mean performance levels were calculated for 5 preventive care measures among adolescents. Differences in performance between states that use Healthcare Effectiveness Data and Information Set or Health Plan Accreditation and those that use neither were estimated. Analysis was conducted in January-July 2020. The sample included data from 39 states, with 32 that use Healthcare Effectiveness Data and Information Set or Health Plan Accreditation and 7 that do not. Adolescent vaccination coverage was 28% for the complete human papillomavirus series, 81% for meningococcal, and 88% for tetanus, diphtheria, and acellular pertussis. Access to a primary care practitioner (a 2-year measure) was 91%, and well-care visits (a 1-year measure) were 50%. When compared with states that do not use Healthcare Effectiveness Data and Information Set or Health Plan Accreditation, the mean performance of states that used either Healthcare Effectiveness Data and Information Set or Health Plan Accreditation was statistically significantly higher for 4 of the 5 assessed measures. Healthcare Effectiveness Data and Information Set measures can help public health officials to monitor progress toward health goals, such as Healthy People 2020, and identify poorly performing health plans and types of preventive services in greatest need of improvement. States using Healthcare Effectiveness Data and Information Set or Health Plan Accreditation were associated with better performance in some adolescent measures, which suggests that health plan accountability may have a role in achieving health outcomes and could be an important area for future research.


A novel test for determination of wild felid-domestic cat hybridization.
In October 2018, Colorado Parks and Wildlife seized an animal believed to be an illegally possessed bobcat. The owner claimed the animal was a bobcat/domestic cat hybrid, exempted from license requirements. Burden of proof lay with CPW to determine the lineage of the animal. Commercial microsatellite arrays and DNA barcoding have not been developed for identification of bobcat/domestic cat hybrids, and limited time and resources prevented development of such tests for this application. Instead, we targeted endogenous feline leukemia virus (enFeLV) to quickly and inexpensively demonstrate the absence of domestic cat DNA in the contested animal. Using this assay, we were able to confirm that the contested animal lacked enFeLV, and therefore was not a domestic cat hybrid.


Review and case report demonstrate that spontaneous spinal epidural abscesses are rare but dangerous in childhood.
A spinal epidural abscess (SEA) is a rare paediatric bacterial infection, with possible devastating neurological sequelae. We explored localisation in the cervical segment, which is unusual, but more dangerous, than other SEAs. We describe 22 cases (12 male) of paediatric SEAs without risk factors: 21 from a literature search from 2000 to 2017 and a 30-month-old boy with a spontaneous cervical SEA due to Group A Streptococcus. The average age was eight years and the symptoms were mainly fever, back pain and motor deficit, with an aetiological diagnosis in 68%. Methicillin-sensitive Staphylococcus aureus was isolated in six patients, methicillin-resistant Staphylococcus aureus in two, Staphylococcus aureus with unknown susceptibility patterns in three and Group A Streptococcus in four. All patients underwent gadolinium-enhanced magnetic resonance imaging and most abscesses were localised in the thoracic and lumbar areas. More than half (59%) underwent surgery to remove pus and granulation tissue and nine were just treated with antimicrobial therapy for an average of 5.3 weeks. Most patients had good outcomes. SEAs were underestimated in children due to the rarity and spectrum of differential diagnoses. Timely diagnosis, immediate antibiotics, spinal magnetic resonance imaging and prompt neurosurgical consultations were essential for favourable outcomes.


PROspective evaluation of coronary FLOW reserve and molecular biomarkers in patients with established coronary artery disease the PROFLOW-trial: cross-sectional evaluation of coronary flow reserve.
Survivors of myocardial infarction (MI) are at high risk of new major adverse cardiovascular events (MACE). Coronary flow reserve (CFR) is a strong and independent predictor of MACE. Understanding the prevalence of impaired CFR in this patient group and identifying risk markers for impaired CFR are important steps in the development of personalized and targeted treatment for high-risk individuals with prior MI. PROFLOW is a prospective, exploratory, cross-sectional open study. We used information from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) to identify high-risk patients with a history of type-1 MI. We measured CFR non-invasively in a left anterior descending artery (LAD) using transthoracic Doppler echocardiography. Coronary flow velocity was measured at rest and at maximal flow after induction of hyperemia by intravenous infusion of adenosine (140 μg/kg/min). Independent predictors of CFR were assessed with multiple linear regression. We included 619 patients. The median age was 69 (IQR 65-73), and 114 (18.4%) were women. Almost one-half of the patients, 285 (46.0%) had the multi-vessel disease, and 147 (23.7%) were incompletely revascularized. The majority were on optimal standard treatment eg ASA (93.1%), statins (90.0%), ACEI/ARB (82.6%) and beta-blockers (80.8%). The majority, 547 (88.4%) had no angina pectoris, and 572 (92.2%) were in NYHA class I. Evaluation of CFR was possible in 611 (98.7%) patients. Mean CFR was 2.74 (±0.79 (mean ± SD)). A substantial number of patients (39.7%) had CFR ≤2.5. In a multiple linear regression model age, dyslipidemia, smoking, hypertension, body mass index, incomplete revascularization, and treatment with angiotensin receptor blockers were independent predictors of CFR. In this high-risk group of patients with prior MI, the prevalence of impaired CFR was high. Further risk stratification with CFR in addition to traditional cardiovascular risk factors may improve predictive accuracy for future MACE in this patient population.


Effects of resin ligand density on yield and impurity clearance in preparative cation exchange chromatography. I. Mechanistic evaluation.
The effects of resin ligand density on cation exchange chromatography performance in preparative monoclonal antibody purification processes were evaluated. A set of agarose-based cation exchange resins spanning a relatively wide range of ligand densities was tested using three different monoclonal antibodies with unique impurity profiles. Experiments were performed in bind-and-elute mode using gradient elution at both intermediate protein loadings and near saturation capacity. Ligand density did not affect clearance of high molecular weight variants under any of the conditions tested; however, ligand density did affect resolution of a basic charge variant in one case and changed host cell protein clearance in another instance. In general, the results indicate that the relationships between ligand density, retention, and resolution are affected by both characteristic charge and protein surface charge distribution.


Immunological homologies between ribosomal proteins amongst lower eukaryotes.
Polyclonal antibodies were raised against the purified ribosomal proteins L1 and L2, the 5S rRNA binding protein L3, all from Saccharomyces cerevisiae, and against L1 and L2 from Schizosaccharomyces pombe (numbering according to Otaka and Osawa 1981; Otaka et al. 1983, respectively). For clarity prefixes Sc and Sp have been added to the numbering of proteins derived from S. cerevisiae and S. pombe, respectively. Ribosomal proteins from these yeasts and from Kluyveromyces marxianus, Rhodotorula glutinis, the slime mold Dictyostelium discoideum and the protozoan Tetrahymena thermophila were checked for antigenic cross-reactivity by the immunoblot technique. Anti-ScL1 bound to the largest ribosomal proteins of all organisms but not with equal strength. A fast migrating protein band from R. glutinis was also reactive. Anti-ScL2 reacted strongly with L2 or analogous proteins derived exclusively from the yeasts. Anti-ScL3 cross-reacted only with one protein band from K. marxianus, whereas anti-SpL1 cross-reacted with L1 or its analogues from the other organisms, but also with proteins of lower molecular weight. In S. cerevisiae, these proteins are located exclusively on the small ribosomal subunit. L2 or analogous ribosomal proteins of all organisms were recognized by anti-SpL2 but additionally the ribosomal protein YL28 of S. cerevisiae and fast migrating proteins of T. thermophila exhibited anti-SpL2 binding.


Promotional removal of oxygenated VOC over manganese-based multi oxides from spent lithium-ions manganate batteries: Modification with Fe, Bi and Ce dopants.
In this work, cathode materials of spent lithium-ions manganate batteries are recovered as the precursor of manganese-based oxides catalysts and furthermore, different amount of Fe, Bi, Ce are introduced to modify their properties. A series of MnOx(MS)-X Fe, MnOx(MS)-X Bi and MnOx(MS)-X Ce samples with crystal phase of Mn5O8 are synthesized using combustion method and then the catalytic behavior and physicochemical properties of prepared catalysts are investigated. Compared to binary MnOx-5% Fe, MnOx-15% Bi and MnOx-10% Ce samples, multi MnOx(MS)-5% Fe, MnOx(MS)-15 Bi and MnOx(MS)-10% Ce catalysts display enhanced catalytic performance significantly in the removal of oxygenated VOC, which could be attributed to larger specific surface area, higher concentration of surface active oxygen species and Mn4+ ions and better reducibility at low temperature. In-situ DRIFTS results imply that main oxygen-containing functional groups such as carbonyl (-C=O), carboxyl (-COO), hydroxyl (-OH) can be observed during VOC oxidation and by comparison, it can be found that gas-phase O2 plays a crucial role in facilitating the further oxidation of by-products into CO2. In addition, TD/GC-MS results point out that the main by-products are formaldehyde; 2-propanol, 1-methoxy-; ethanol, 2-methoxy-, acetate; 2-ethoxyethyl acetate; acetic acid during VOC oxidation.


Surface properties and early murine pre-osteoblastic cell responses of phosphoric acid modified titanium surface.
The present study investigated the surface properties and murine pre-osteoblast cell (MC3T3-E1) responses of phosphoric acid (H3PO4) treated commercially pure titanium. Titanium discs were treated with various concentration of H3PO4 (5%, 10%, and 20%; v/v) at 90 °C for 30 min. Surface properties were evaluated by profilometer, contact angle meter, and scanning electron microscopy (SEM) with energy dispersive X-rays. MC3T3-E1 attachment and spreading were evaluated by SEM and phalloidin immunohistochemistry staining. Surface roughness and wettability were not statistically difference among all experimental and control groups. Phosphate and oxygen were detected on H3PO4 treated surfaces. At 20 min, cell attachment was significantly higher in 10% and 20% H3PO4 treated groups compared to the control. Cells exhibited orientated-cytoskeleton fibers on 20% H3PO4 modified titanium surface. Though, there was no difference in cell spreading stage among all treatment groups. H3PO4 treatment on titanium may influence early cell response, particularly on attachment and spreading.


Multiple sclerosis, sleep latencies and HLA antigens.
The role of HLA antigens, and HLA-DR2 in particular, in the determination of mean sleep onset latencies (MSOLs) in multiple sclerosis (MS) was studied. It has been suggested that this antigen may play a part in the reduction of MSOLs, since nearly 100% of patients suffering from narcolepsy are DR2-positive. A multiple sleep latency test was performed in 37 patients suffering from MS without spontaneous complaints of sleep disturbances and who were typed for HLA-A, B, C, DR and DQ. The MSOL was reduced in a total of 21 patients, in only 7 of 15 DR2-positive patients and in 12 of 21 DQw1-positive patients. However, it was reduced in 13 of 16 B8- or B14-positive patients. In contrast with this, in the absence of an early sleep onset (MSOL greater than 30 min), no HLA antigens were found to be over-represented when considered individually; only those patients positive for a group of cross-reacting HLA antigens (B5, B15, B18, B21 or B35) had an MSOL greater than 30 min. These results suggest that the genes which code for the DR2 or DQw1 antigens, which are present in nearly 100% of narcoleptics, are not solely responsible for the appearance of an early sleep onset in MS.


A patient with Schinzel-Giedion syndrome and a review of 20 patients.
The Schinzel-Giedion syndrome is characterized by severe midface retraction, multiple skull anomalies, clubfeet, and cardiac and renal malformations. So far, 20 patients have been reported. This is the first report of the syndrome demonstrated in Oriental patients. In surviving patients, severe growth and developmental deficiency is a common finding.


Circadian fluctuation of plasma epinephrine in supine humans.
Previous studies have demonstrated circadian fluctuations of systemic catecholamines in man. However, methodological differences and conflicting results with epinephrine are apparent. In the present study, plasma and urinary epinephrine and norepinephrine and plasma cortisol were studied in healthy young adult males over 24 hr with 20 min plasma sampling and EEG monitoring of sleep. Plasma epinephrine did not have a circadian variation in supine subjects. Urinary epinephrine levels and small urinary circadian variations were increased by normal posture and activity. Sleep and sleep stage were not associated with different plasma epinephrine levels, and no ultradian fluctuation was observed. Levels of norepinephrine and cortisol were normal. Based on all studies to date, it appears that basal plasma epinephrine has either a very small amplitude or no circadian rhythm, but that changes in posture and activity or the rest/activity cycle may modify this pattern.


Prenatal expression of cholecystokinin (CCK) in the central nervous system (CNS) of mouse.
Cholecystokinin (CCK) is a peptide found in both gut and brain. Although numerous studies address the role of brain CCK postnatally, relatively little is known about the ontogeny of CCK expression in the central nervous system (CNS). Recent work revealed that CCK modulates olfactory axon outgrowth and gonadotropin-releasing hormone-1 (GnRH-1) neuronal migration, suggesting that CCK may be an important factor during CNS development. To further characterize the developmental expression of CCK in the nervous system, in situ hybridization experiments were performed. CCK mRNA expression was widely distributed in the developing mouse brain. As early as E12.5, robust CCK expression is detected in the thalamus and spinal cord. By E17.5, cells in the cortex, hippocampus, thalamus and hypothalamus express CCK. In addition, CCK mRNA was also detected in the external zone of the median eminence where axons of the neuroendocrine hypophysiotropic systems terminate. Our study demonstrates that CCK mRNA is expressed prenatally in multiple areas of the CNS, many of which maintain CCK mRNA expression postnatally into adult life. In addition, we provide evidence that regions of the CNS known to integrate hormonal and sensory information associated with reproduction and the GnRH-1 system, expressed CCK already during prenatal development.


Neural correlates of working memory function in euthymic people with bipolar disorder compared to healthy controls: A systematic review and meta-analysis.
Bipolar disorders (BD) are serious mental health disorders that impacts on cognitive and social functioning. We aimed to systematically review and conduct a meta-analysis of fMRI correlates of working memory in euthymic people with BD compared to healthy participants. Web of Science, Embase and PubMed databases were systematically searched to identify studies which examined the fMRI correlates of working memory function in euthymic people with BD and healthy participants. Relevant demographic, behavioral and functional MRI (fMRI) data was qualitatively and quantitatively assessed, and the quality of the included studies evaluated. Comparable studies which used the same working memory task were included in a meta-analysis using Seed-Based D Mapping software (SDM). Twenty-four studies were included in this systematic review. Consistent brain fMRI activity differences were found in key brain areas of the working memory network in euthymic people with BD compared to healthy participants including the ventromedial and dorsolateral prefrontal cortices. Cognitive performance was not significantly different between the two groups. Six studies were suitable to be included in the meta-analysis. There was no significant overlap in areas of brain activation after family-wise correction for multiple comparisons. Heterogeneity of task paradigms, small sample sizes and inherent difficulty in the interpretation of functional brain activity due to variations between studies were all limitations. The differences in working memory related fMRI activity identified by this study between people with BD and healthy participants are consistent with existing literature reporting impaired working memory performance in BD. This was not accompanied by significant differences in cognitive performance in the reviewed studies, likely due to small sample sizes. Further studies are needed to investigate the relationship between differential brain activity and working memory performance in people with BD.


An investigation into the removal of oil from rock utilising magnetic particle technology.
The application of magnetic particle technology to environmental remediation has tended to focus, up to now, upon the removal of oil contamination from plumage and fur. The present research demonstrates the potential of this technology to remove oil contamination from the surface of rock. Specifically, a single treatment has been demonstrated to remove more than 80% by weight of heavy bunker oil from the surface of a common foreshore rock type. A further three treatments have been shown to result in an optimum removal of up to 94% by weight. The results are highly reproducible and offer the possibility of achieving up to 100% removal with the appropriate use of pre-conditioners.


Prevalence and predictors of mental health outcomes in UK doctors and final year medical students during the COVID-19 pandemic.
The mental health of doctors is an ongoing concern, both prior to and during the COVID-19 pandemic. This study aimed to: i) assess the prevalence of symptoms of depression, anxiety, PTSD, and burnout in UK doctors and final year medical students during the pandemic, and ii) analyse the hypothesised relationships between psychological flexibility, intolerance of uncertainty and resilience with these mental health outcomes. A cross-sectional online study of UK-based doctors and final year medical students was conducted between 27/09/2020 and 31/01/2021. Outcomes were measured using the PHQ9, GAD7, PCL-5, and aMBI. Independent variables included the CompACT-SF, IUS-12, and CD-RISC-10. Descriptive statistics, between-group analyses, and multiple regression were performed. Prevalence of anxiety symptoms was 26.3%, depression 21.9%, PTSD 11.8%, and burnout 10.8%. Psychological flexibility negatively predicted all outcomes, apart from low personal achievement. Intolerance of uncertainty positively predicted anxiety and PTSD scores. Resilience negatively predicted scores on burnout subscales. Cross-sectional design and non-probability sampling method means that assumptions about causality cannot be made and may have implications for bias and generalisability of results. Doctors and medical students in the UK reported high levels of mental health symptoms during the pandemic, between September 2020 and January 2021. All three independent variables explained significant variance in mental health outcomes. Psychological flexibility was the most consistent predictor, over and above sociodemographic variables and other psychological predictors. These findings have implications for interventions to improve retention of our essential medical workforce, and for providing support at future times of national crisis.


Optimized hydration dynamics in mucoadhesive xanthan-based trilayer vaginal films for the controlled release of tenofovir.
Karaya gum, pectin and xanthan gum have been tested as candidates for manufacturing mucoadhesive trilayer films containing ethylcellulose and chitosan for the vaginal administration of the antiviral Tenofovir (TFV). The swelling profile correlated with the amount of mobile dipoles determined by impedance spectroscopy allows the determination of the hydration dynamics of these films. The fast water penetration has been demonstrated to favor the formation of polyelectrolyte complexes (PEC) via hydrogen or ionic bonds which would favor a controlled release. The incorporation of an inorganic drug release regulator induces the weakness of the polymeric chains thus enhancing the ionic mobility via the formation of low molecular weight PECs in films manufactured with karaya gum. Due to the different mechanical properties of the individual components, pectin-based films failed for a potential pharmaceutical formulation. However, mucoadhesive trilayer films produced with xanthan gum have demonstrated a moderate swelling, improved wettability and a controlled release of TFV.


Granivory and microhabitat use in Australian desert rodents: are seeds important?
The diet and microhabitat use of two species of native Australian desert rodents, the spinifex hoppingmouseNotomys alexis and sandy inland mousePseudomys hermannsburgensis, were studied in the Simpson Desert, south-western Queensland. Contrary to expectation, both species were confirmed from analyses of their stomach contents to be omnivorous. The diets of both species varied through time in a similar manner; seeds were important in summer and especially in winter, but in autumn invertebrates constituted nearly 50% and 60% of the diet ofN. alexis andP. hermannsburgensis, respectively. Other plant material (root, leaf, floral part, stem) was found in appreciable amounts in the stomach contents of both species, and fungi were identified from a small number of individuals. Both species showed a high degree of overlap in the broad types of food they ingested (seed, plant material, invertebrates); however, there was considerably less overlap in the species of seeds eaten. Analysis of microhabitat use suggested that this difference was due to differential foraging between the species; the larger, bipedalN. alexis forages in the open more than the smaller, quadrupedalP. hermannsburgensis, which is found more commonly in or under hummocks of spinifex grass. Although our findings parallel patterns of morphological specialisation and differential foraging on seeds that have been described within communities of North American heteromyid rodents, we found little evidence that the foraging economics ofN. alexis orP. hermannsburgensis should depend solely or primarily on the distribution patterns of seeds. In the absence of dietary information, we suggest that ecological studies of desert rodents which focus solely on granivory, and neglect other important aspects of rodent foraging, can lead to a misinterpretation of species coexistence and community structure.


Endoscopic versus surgical treatment for pancreatic pseudocysts: Systematic review and meta-analysis.
This systematic review and meta-analysis aims to compare surgical and endoscopic treatment for pancreatic pseudocyst (PP). The researchers did a search in Medline, EMBASE, Scielo/Lilacs, and Cochrane electronic databases for studies comparing surgical and endoscopic drainage of PP s in adult patients. Then, the extracted data were used to perform a meta-analysis. The outcomes were therapeutic success, drainage-related adverse events, general adverse events, recurrence rate, cost, and time of hospitalization. There was no significant difference between treatment success rate (risk difference [RD] -0.09; 95% confidence interval [CI] [0.20,0.01]; P = .07), drainage-related adverse events (RD -0.02; 95% CI [-0.04,0.08]; P = .48), general adverse events (RD -0.05; 95% CI [-0.12, 0.02]; P = .13) and recurrence (RD: 0.02; 95% CI [-0.04,0.07]; P = .58) between surgical and endoscopic treatment.Regarding time of hospitalization, the endoscopic group had better results (RD: -4.23; 95% CI [-5.18, -3.29]; P < .00001). When it comes to treatment cost, the endoscopic arm also had better outcomes (RD: -4.68; 95% CI [-5.43,-3.94]; P < .00001). There is no significant difference between surgical and endoscopic treatment success rates, adverse events and recurrence for PP. However, time of hospitalization and treatment costs were lower in the endoscopic group.


Self-healing, sensitive and antifreezing biomass nanocomposite hydrogels based on hydroxypropyl guar gum and application in flexible sensors.
In this manuscript, self-healing, highly flexible hydrogels based on hydroxypropyl guar gum (HPG) were prepared by adding dopamine-coated reduced-graphene oxide (rGO@PDA). The multiple reversible dynamic networks were simultaneously constructed by boron-oxygen and metal-ligand interactions. These multiple networks significantly improve the self-healing efficiency and mechanical strength of the biomass hydrogels. It is noteworthy that rGO@PDA can enhance conductivity and flexibility properties. Impressively, flexible sensor with these self-healing hydrogels have a large strain range (728%), high sensitivity (GF = 11.30) and fast response time (210 ms). The obtained flexible sensors can also detect human motion (such as sound vibrations and pulse rates) to large scales (such as knee flexion) over a wide temperature range (-20-30 °C). The signals of sensors have superior stability and repeatability, which show potential application prospect in the field of flexible wearable devices.


Fracture risk of patients suffering from dizziness: a retrospective cohort study.
Dizziness is known to be associated with the risk of falls. However, there is not much evidence for the increase of fractures caused by dizziness. The aim of the study was to investigate whether the symptom of dizziness is associated with an increased fracture rate. We performed a retrospective cohort study using a population-based administrative database in the Province of Quebec, Canada. A cohort of n = 2442 patients with at least one diagnosis of dizziness was compared to n = 16,125 unexposed patients. The main outcome measure was any kind of first fracture after the index date of dizziness. Analysis revealed a moderate effect of dizziness as an independent contributing factor to fractures (adjusted hazard ratio (HR) 1.26, 95% confidence interval 1.03 to 1.55). A fracture in the year before the index date was highly associated with the incidence of a subsequent fracture (HR 2.69, 2.09 to 3.47), and fractures were less frequent in women (HR 0.70, 0.60-0.82). Analysis further revealed that dizziness (HR 1.31, 1.05-1.64) and prior fractures (HR 2.41, 1.81-3.22) were associated with non-osteoporotic fractures, which were also less frequent in women (HR 0.59, 0.50-0.71). The incidence of fractures in sites typical for osteoporosis correlated with a precedent fracture (HR 3.91, 2.31-6.63), but not with dizziness (HR 1.10, 0.69-1.75). Besides the 'typical' elderly female patient being at risk of osteoporotic fractures, male patients suffering from dizziness should be carefully evaluated, and prevention strategies should be considered to minimise their risk of suffering non-osteoporotic fractures.


Understanding Mental Health Clinicians' Perceptions and Concerns Regarding Using Passive Patient-Generated Health Data for Clinical Decision-Making: Qualitative Semistructured Interview Study.
Digital health-tracking tools are changing mental health care by giving patients the ability to collect passively measured patient-generated health data (PGHD; ie, data collected from connected devices with little to no patient effort). Although there are existing clinical guidelines for how mental health clinicians should use more traditional, active forms of PGHD for clinical decision-making, there is less clarity on how passive PGHD can be used. We conducted a qualitative study to understand mental health clinicians' perceptions and concerns regarding the use of technology-enabled, passively collected PGHD for clinical decision-making. Our interviews sought to understand participants' current experiences with and visions for using passive PGHD. Mental health clinicians providing outpatient services were recruited to participate in semistructured interviews. Interview recordings were deidentified, transcribed, and qualitatively coded to identify overarching themes. Overall, 12 mental health clinicians (n=11, 92% psychiatrists and n=1, 8% clinical psychologist) were interviewed. We identified 4 overarching themes. First, passive PGHD are patient driven-we found that current passive PGHD use was patient driven, not clinician driven; participating clinicians only considered passive PGHD for clinical decision-making when patients brought passive data to clinical encounters. The second theme was active versus passive data as subjective versus objective data-participants viewed the contrast between active and passive PGHD as a contrast between interpretive data on patients' mental health and objective information on behavior. Participants believed that prioritizing passive over self-reported, active PGHD would reduce opportunities for patients to reflect upon their mental health, reducing treatment engagement and raising questions about how passive data can best complement active data for clinical decision-making. Third, passive PGHD must be delivered at appropriate times for action-participants were concerned with the real-time nature of passive PGHD; they believed that it would be infeasible to use passive PGHD for real-time patient monitoring outside clinical encounters and more feasible to use passive PGHD during clinical encounters when clinicians can make treatment decisions. The fourth theme was protecting patient privacy-participating clinicians wanted to protect patient privacy within passive PGHD-sharing programs and discussed opportunities to refine data sharing consent to improve transparency surrounding passive PGHD collection and use. Although passive PGHD has the potential to enable more contextualized measurement, this study highlights the need for building and disseminating an evidence base describing how and when passive measures should be used for clinical decision-making. This evidence base should clarify how to use passive data alongside more traditional forms of active PGHD, when clinicians should view passive PGHD to make treatment decisions, and how to protect patient privacy within passive data-sharing programs. Clear evidence would more effectively support the uptake and effective use of these novel tools for both patients and their clinicians.


MALDI-Imaging Mass Spectrometry: a step forward in the anatomopathological characterization of stenotic aortic valve tissue.
Aortic stenosis (AS) is the most common form of valve disease. Once symptoms develop, there is an inexorable deterioration with a poor prognosis; currently there are no therapies capable of modifying disease progression, and aortic valve replacement is the only available treatment. Our goal is to study the progression of calcification by matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) and get new insights at molecular level that could help in the understanding of this disease. In this work, we analyzed consecutive slices from aortic valve tissue by MALDI-IMS, to establish the spatial distribution of proteins and peptides directly from the surface of the histological sections. The analysis showed different structures corresponding to regions observed in conventional histology, including large calcification areas and zones rich in collagen and elastic fibers. Peptide extraction from the tissue, followed by liquid chromatography mass spectrometry analysis, provided the identification of collagen VI α-3 and NDRG2 proteins which correlated with the masses obtained by MALDI-IMS and were confirmed by immunohistochemistry. These results highlighted the molecular mechanism implied in AS using MALDI-IMS, a novel technique never used before in this pathology. In addition, we can define specific regions proving a complementary resolution of the molecular histology.


Insulin stimulation of phosphorylation of the beta subunit of the insulin receptor. Formation of both phosphoserine and phosphotyrosine.
Rat hepatoma cells were labeled with [32P]orthophosphate and the insulin receptor subunits were identified by immunoprecipitation and sodium dodecyl sulfate-acrylamide gel electrophoresis. In the basal state, only the Mr = 95,000 (beta) subunit of the insulin receptor was phosphorylated. The covalent labeling with 32P of this subunit was stimulated about 3-fold by insulin (10(-6) M). This stimulation was due to an increase in the content of phosphoserine, the appearance of phosphotyrosine, and a possible increase in phosphothreonine as well. These results suggest phosphorylation of the insulin receptor at multiple sites is an early event in insulin action.


Inactivation of the three GGA genes in HeLa cells partially compromises lysosomal enzyme sorting.
The Golgi-localized, gamma-ear containing, ADP-ribosylation factor-binding proteins (GGAs 1, 2, and 3) are multidomain proteins that bind mannose 6-phosphate receptors (MPRs) at the Golgi and play a role, along with adaptor protein complex 1 (AP-1), in the sorting of newly synthesized lysosomal hydrolases to the endolysosomal system. However, the relative importance of the two types of coat proteins in this process is still unclear. Here, we report that inactivation of all three GGA genes in HeLa cells decreased the sorting efficiency of cathepsin D from 97% to 73% relative to wild-type, with marked redistribution of the cation-independent MPR from peripheral punctae to the trans-Golgi network. In comparison, GNPTAB-/- HeLa cells with complete inactivation of the mannose 6-phosphate pathway sorted only 20% of the cathepsin D. We conclude that the residual sorting of cathepsin D in the GGA triple-knockout cells is mediated by AP-1.


Distribution and levels of 5-HT1B receptors in anterior cingulate cortex of patients with bipolar disorder, major depressive disorder and schizophrenia - An autoradiography study.
The serotonin 1B receptor has recently received more interest as a possible new target for pharmacological treatment of psychiatric disorders. However, the exact mechanisms of action remain unclear. This study aimed to examine the binding distribution and levels of the serotonin 1B receptor in-depth in the anterior cingulate cortex (ACC) and provide more insight in its functional role in bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia (SZ). Serotonin 1B receptor binding distribution was visualized with high resolution autoradiography (ARG), using the radioligand [3H]AZ10419369, in postmortem ACC tissue from patients diagnosed with BD (n=14), MDD (n=12), SZ (n=13) and healthy subjects (n=13). Moreover, a quantification of receptor binding was made with ARG, in relation to patient group, age and gender. In all subject groups a significantly higher specific binding of serotonin 1B receptor was measured in the outer ACC layers compared to the inner ACC layers. Correlation analysis with ARG binding patterns of several radioligands resulted in a significant correlation with glutamatergic N-methyl-D-aspartate receptor binding in the outer layers. No significant difference was found between subject groups in binding levels and distribution. In female subjects a significantly lower receptor binding was found than in male subjects, which was most profound in patients diagnosed with MDD. The binding distribution of the serotonin 1B receptor found in this study supports a role in glutamate transmission in the ACC and was not shown to be significantly altered in BD, MDD or SZ. A gender difference in serotonin 1B receptor binding was found.


Monodisk: device for percutaneous transcatheter closure of cardiac septal defects.
The Monodisk, a device to facilitate percutaneous closure of cardiac septal defects, was developed and tested in vitro and in vivo. Atrial septal defects (8-10 mm) were created in five dogs using transcatheter techniques. The defects were then closed with the Monodisk. The device was easily and successfully fixed in place in all dogs. The efficacy of the device was determined radiographically. No shunting of contrast medium was observed in any case. Animals were followed for 6 months. Results showed good biocompatibility and several advantages of the device: it requires only a simple one-step placement procedure; it utilizes a small delivery system; it is easy to place and detach; it is self-centering and stable; and it can be repositioned or retrieved prior to detachment. Its possible clinical applications include correction of atrial septal defects, ventricular septal defects, patent ductus arteriosus, as well as creating an aortopulmonary window.


Relationships among cushion type, backrest height, seated posture, and reach of wheelchair users with spinal cord injury.
Seated posture and trunk control are important factors affecting upper extremity (UE) function of wheelchair users. A stable pelvis and trunk are required to provide a base from which UE movement occurs, but, conversely, the ability to move one's trunk and pelvis can increase functional ranges of motion. For wheelchair users, balancing sufficient trunk support with adequate trunk mobility has important functional and medical consequences. To determine the effect of cushion and backrest height on posture and reach and to determine the relationship between posture and UE reach using a randomized 2 x 3 repeated-measures factorial design. Twenty-two subjects with spinal cord injury were tested in 6 configurations, including 3 types of cushions (segmented air, contoured viscous fluid/foam, and air/foam) and 2 of 3 backrest heights (referenced to T12, inferior scapular angle, and scapular spine) while performing unilateral and bilateral reaching tasks. Seated posture (pelvic tilt and torso angle) and American Spinal Injury Association (ASIA) score were also measured. Pelvic tilt and ASIA score were significant predictors of reach. No evidence was found indicating cushion type or backrest height affected reach or posture. No consistent patterns of posture were found across cushion types or backrest heights. The posture adopted by wheelchair users is a more important influence on UE reach than are the cushion or backrest height used. Sitting with increased posterior pelvic tilt enhanced stability and permitted greater reach. Because individuals adopt different postures when using different cushions and backrest heights, clinicians should monitor posture while assessing seating and function of wheelchair users.


Microbiological evaluation of LOCATOR® Legacy attachments: A cross-sectional clinical study.
This retrospective cross-sectional study aimed to evaluate quantitatively the oral microbiome in the tri-lobe central cavity of Locator Legacy attachment and verify whether it harbors a different, potentially more pathogenic, bacterial spectrum than the adjacent edentulous ridge. Edentulous patients rehabilitated with implant overdentures using Locator Legacy attachments were recruited for this study. The clinical examination comprised probing depths, mobility, peri-implant, and periodontal health along with intraoral swabs for microbiological evaluation, polymerase chain reaction (PCR) testing, and candida culture. The swabs were collected from the trilobed cavity of the attachment and the adjacent edentulous ridge. PCR was performed to detect six specific bacteria, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Treponema denticola, Prevotella intermedia, and Parvimonas micra. Statistical analyses were performed using McNemar's test and Wilcoxon's rank sum test with the significance set to p < .05. A total of 50 participants with a mean age of 71.5 ± 9.6 years participated in the study. No significant differences in the microbiome were found between samples from the ridge and the attachment. No significantly different numbers in the candida cultures were identified, and the presence of a removable prostheses did not demonstrate a significant association with the prevalence of candida. Within the limits of this study and the investigated bacterial species, the trilobed cavity of the attachment does not seem to increase the bacterial load.


Neonatal delivery weight and risk of future maternal diabetes.
To investigate associations between neonatal delivery weight and future risk of maternal type 1 or type 2 diabetes. Data included in the Swedish Medical Birth Registry and Swedish National Diabetes Registry were merged to include all women born during 1930-1989; patients with pre-existing diabetes or gestational diabetes were excluded. Cox regression analyses were performed to identify associations between the neonatal delivery weight from the most recent pregnancy and later occurrence of diabetes. There were 1 873 440 patients included in the analyses. An increased risk of type 1 (hazard ratio 3.60, 95% confidence interval [CI] 3.23-4.01) or type 2 diabetes (hazard ratio 2.77, 95% CI 2.68-2.87) was observed among patients who had a large for gestational age neonate compared with patients who had neonates within one standard definition of the mean weight for gestational age; the odds of developing type 1 (odds ratio 10.27, 95% CI 7.37-14.31) or type 2 diabetes (odds ratio 8.50, 95% CI 6.01-12.02) within 1 year of delivery was also increased compared with patients who had a neonate within one standard deviation of the mean weight for gestational age. Delivering a large for gestational age neonate was a potent risk factor for the later development of maternal type 1 or type 2 diabetes.


The regional hypothalamic distribution of type II 5'-monodeiodinase in euthyroid and hypothyroid rats.
The brain topographical distribution of type II 5'-monodeiodinase (5'D-II), which converts thyroxine (T4) to triiodothyronine (T3), was studied in euthyroid and hypothyroid rats. Low levels of 5'D-II activity were detected in the median eminence, but not in any other brain regions of euthyroid rats. The arcuate nucleus and median eminence were also the sites of highest 5'D-II activity in brains of hypothyroid rats. Under these conditions, the paraventricular nucleus contained almost no detectable 5'D-II, while intermediate enzyme activity was present in other medial basal hypothalamic sites.


Transcriptional behavior of silkmoth chorion genes in vivo and in injected Xenopus laevis oocytes.
A cloned fragment of Bombyx mori genomic DNA containing a pair of chorion genes was injected into Xenopus laevis oocytes. The RNA transcribed from the injected template was examined by primer extension analysis for the presence of transcripts initiated correctly from the two chorion genes. Using as primers a number of fragments derived from various parts of the injected DNA, we have found that transcription initiation around the cap sites of the chorion genes was considerably more frequent than that at other, seemingly random sites of the template. Injection of different quantities of template into the oocytes revealed that at high DNA concentrations, most transcripts were randomly initiated. However, when reduced amounts of DNA were injected into the oocytes, the extent of specific transcription increased dramatically while the proportion of nonspecific transcripts correspondingly decreased. The relative rates of specific initiation from the two chorion genes in injected oocytes resembled closely those observed in choriogenic follicles. Finally, the primer extension analysis revealed the presence of chorion antisense transcripts not only in injected oocytes but also in total RNA derived from follicular cells. The possible origin of these transcripts is discussed.


Targeting epigenetic deregulations for the management of esophageal carcinoma: recent advances and emerging approaches.
Ranking from seventh in incidence to sixth in mortality, esophageal carcinoma is considered a severe malignancy of food pipe. Later-stage diagnosis, drug resistance, and a high mortality rate contribute to its lethality. Esophageal squamous cell carcinoma and esophageal adenocarcinoma are the two main histological subtypes of esophageal carcinoma, with squamous cell carcinoma alone accounting for more than eighty percent of its cases. While genetic anomalies are well known in esophageal cancer, accountability of epigenetic deregulations is also being explored for the recent two decades. DNA methylation, histone modifications, and functional non-coding RNAs are the crucial epigenetic players involved in the modulation of different malignancies, including esophageal carcinoma. Targeting these epigenetic aberrations will provide new insights into the development of biomarker tools for risk stratification, early diagnosis, and effective therapeutic intervention. This review discusses different epigenetic alterations, emphasizing the most significant developments in esophageal cancer epigenetics and their potential implication for the detection, prognosis, and treatment of esophageal carcinoma. Further, the preclinical and clinical status of various epigenetic drugs has also been reviewed.


Imaging features of benign adenomyoepithelioma of the breast.
The purpose of our study was to evaluate the imaging features of benign adenomyoepithelioma of the breast with a focus on sonographic (US) appearances. Ten benign adenomyoepitheliomas in 9 patients were included in this study. Mammographic and US findings were analyzed retrospectively by 2 radiologists according to the Breast Imaging-Reporting and Data System (BI-RADS) lexicon. The BI-RADS final assessment category was also recorded. Of the 8 lesions for which mammography was available, 4 lesions presented with abnormal findings. Two lesions presented with an indistinct, irregular, isodense mass and a circumscribed, oval, isodense mass. The other 2 lesions presented with areas of focal asymmetry and asymmetry, respectively. On US, all of 10 lesions presented as a mass. The masses measured 0.5-1.2 cm (mean, 0.8 cm), were irregular (n = 8) or oval (n = 2) with microlobulated (n = 5), indistinct (n = 3), or angular (n = 2) margins. They were all hypoechoic, had non parallel orientation in 6 cases, and increased peripheral vascularity in 7 cases. The BI-RADS final assessment category was 4B in 6, and 4A in 4. Mammographic findings of benign adenomyoepithelioma were nonspecific. An irregular, non parallel orientation, microlobulated or indistinct margin, hypoechogenicity, and increased peripheral vascularity were the most frequent US features.


Preparation of a PM2.5-like reference material in sufficient quantities for accurate monitoring of anions and cations in fine atmospheric dust.
A reference material of a PM2.5-like atmospheric dust material has been prepared using a newly developed method. It is intended to certify values for the mass fraction of SO42-, NO3-, Cl- (anions) and Na+, K+, NH4+, Ca2+, Mg2+ (cations) in this material. A successful route for the preparation of the candidate reference material is described alongside with two alternative approaches that were abandoned. First, a PM10-like suspension was allowed to stand for 72 h. Next, 90% of the volume was siphoned off. The suspension was spiked with appropriate levels of the desired ions just prior to drop-wise shock-freezing in liquid nitrogen. Finally, freeze drying of the resulting ice kernels took place. In using this approach, it was possible to produce about 500 g of PM2.5-like material with appropriate characteristics. Fine dust in 150-mg portions was filled into vials under an inert atmosphere. The final candidate material approaches the EN12341 standard of a PM2.5-material containing the ions mentioned in Directive 2008/50/EC of the European Union. The material should be analysed using the CEN/TR 16269:2011 method for anions and cations in PM2.5 collected on filters. The method described here is a relatively rapid means to obtain large quantities of PM2.5. With access to smaller freeze dryers, still 5 to 10 g per freeze-drying cycle can be obtained. Access to such quantities of PM2.5-like material could potentially be used for different kinds of experiments when performing research in this field. Graphical abstract The novelty of the method lies in transformation of a suspension with fine particulate matter to a homogeneous and stable powder with characteristics similar to air-sampled PM2,5. The high material yield in a relatively short time is a distinct advantage in comparison with collection of air-sampled PM2,5.


Development of a prognostic gene signature based on an immunogenomic infiltration analysis of osteosarcoma.
Osteosarcoma is the most common primary malignant bone tumour predominantly occurring in children and adolescents with a high tendency of local invasion and early metastases. Currently, tumour immune microenvironment (TME) is becoming the focus of studying of malignant tumours.. However, no sound evidence shows a specific immune molecular target in osteosarcoma. We downloaded the gene expression profile and clinical data of osteosarcoma from the TARGET portal, and extracted and normalized via R software. Then, the immune cell infiltration assessed by CIBERSORT and ESTIMATE algorithms. Three survival-related immune cells and immune score were obtained via Kaplan-Meier survival analysis, and 232 immune-related genes were obtained as candidate genes. Enrichment and protein-protein interaction co-expression analyses were performed to identify 13 hub genes. Lastly, a seven gene prognostic signature was identified by univariate and multivariate Cox regression analyses. More importantly, our validations and TIMER algorithm suggested this immune-related prognostic signature a good predictive tool. Our findings have provided novel insights that could demonstrate new targets of immunotherapy in osteosarcoma.


Dysfunctional BRCA1 is only indirectly linked to multiple centrosomes.
A remarkable and yet unexplained phenomenon in cancer cells is the presence of multiple centrosomes, organelles required for normal cell division. Previously, it was demonstrated that the tumor suppressor BRCA1 is a component of centrosomes. This observation led to the hypothesis that defective BRCA1 results in malfunctioning centrosomes and faulty centrosomes are a possible cause of cancer. Using EGFP-tagged fusion proteins and BRCA1(-/-) cells we show that although some BRCA1 antibodies do label centrosomes under certain fixation conditions, BRCA1 is not a centrosomal protein. Therefore, it is unlikely that a mutation in BRCA1 directly alters centrosome structure and function. BRCA1 plays an established role in DNA damage repair and in G2/M checkpoint regulation. We present evidence that multiple centrosomes can arise in any cell when G2/M checkpoint fails and entrance into mitosis occurs in the presence of DNA damage.


Effect of a low intensity magnetic field on human motor behavior.
Extremely low frequency (ELF) magnetic fields (MF) are omnipresent in our modern daily environment, but their effects on humans are still not clearly established. The aim of this study was to determine the effect of a 50 Hz, 1,000 microT MF centered at the level of the head on human index finger micro-displacements. Twenty-four men recruited among the personnel of the French company, Electricité de France (EDF), completed the experiment. Their postural and kinetic tremors were recorded under four "field-on" and four "field-off" conditions, each tested during a real and a sham sequence. Eight postural and four kinetic tremor characteristics were calculated on recorded time series and were used for statistical analysis. No effect of the MF was found for kinetic tremor. Concerning postural tremor, the proportion of oscillations at low frequencies (between 2 and 4 Hz) was higher during the real than during the sham exposure sequence (P<.05). It suggests that MF could have a subtle delayed effect on human behavior, which is clearly not pathological. These results should be taken into account for the establishment of new exposure limits.


Thymic Stromal Lymphopoietin Induction Suppresses Lung Cancer Development.
Lung cancer is the leading cause of cancer deaths in the United States and across the world. Immunotherapies, which activate tumor-infiltrating cytotoxic T lymphocytes, have demonstrated efficacy for the treatment of advanced-stage lung cancer. However, the potential for harnessing the immune system against the early stages of lung carcinogenesis to prevent cancer development and recurrence remains unexplored. Using a mouse model of lung adenocarcinoma, we investigated the effects of thymic stromal lymphopoietin (TSLP) induction on early cancer development in the lungs. Herein, we demonstrate that systemic TSLP induction suppressed spontaneous lung cancer development in KrasG12D mice. TSLP drove a significant CD4+ T cell response to block lung cancer progression from atypical alveolar hyperplasia to adenocarcinoma. Our findings suggest that TSLP can be used in the early stages of lung cancer development to trigger a lasting immunity in the tissue and prevent the development of advanced disease.


[Depilation lasers and lamps].
Regardless of the actual method used, depilation is a process that has been present since antiquity and is found across all the continents. Thanks to the recent introduction of pulsed polychromatic lamps and lasers, long-lasting depilation is now possible. This article describes the theoretical basis for this new technology and discusses the various types of equipment available. Whether such devices are used for aesthetic or medical reasons, doctors must have a knowledge of the various techniques involved, as well as the limitations thereof. They must also be able to manage all potential adverse effects arising during or after depilation sessions.


Tardive dyskinetic movements over time.
Tardive dyskinetic (TD) movements have been noted to fluctuate in intensity throughout the hours of the day. There have been very few descriptive studies of this fluctuation; the resulting lack of knowledge has made treatment and monitoring procedures for TD problematic. This study sought to describe TD symptom variations across the hours of the day and between days and to relate these variations to control factors. This small study (eight subjects) identified several potentially important variations which need to be further examined in larger studies.


Repeated resection of colorectal cancer pulmonary oligometastases: pooled analysis and prognostic assessment.
Repeated resection of colorectal cancer pulmonary metastasis is associated with long-term survival. Nevertheless, very limited data addressing the best candidates for repeated pulmonary resection is available. We searched the PubMed database for retrospective studies evaluating lung metastasectomy for metastatic colorectal cancer (CRC). We included studies with available data about repeated pulmonary metastasectomy. Potential prognostic factors were analyzed for possible impact on survival following the second metastasectomy through univariate and multivariate analysis. Between 1983 and 2008, 944 lung metastasectomies were carried out on 759 patients. Of those, 148 patients had a second metastasectomy. The 5-year survival rate was 52 % for patients who had 1 metastasectomy and 57.9 % from the second metastasectomy for patients who had repeated resection. More than 2 metastatic pulmonary nodules and maximum diameter of largest pulmonary nodule ≥3 cm were the only independent factors associated with inferior survival following repeated pulmonary resection. In selected patients with metastatic CRC, repeated pulmonary metastasectomy offers an excellent chance for long-term survival and is associated with a quite low operative mortality. Patients with more than 2 metastatic nodules and a maximum diameter of the largest metastatic lung nodule of ≥3 cm have a significantly inferior survival.


Motor and non-motor improvements following short-term multidisciplinary day-clinic care in Parkinson´s disease.
Inpatient as well as outpatient care does often not meet PD-patients' individual needs. Day-clinic concepts encompassing a multidisciplinary team as well as therapy adjustments accompanying everyday demands aim at filling this gap. This is a retrospective study on short-term effects of a 3 week multidisciplinary rehabilitation program in patients with Parkinson´s disease (PD) embedded in a specialized movement disorder day-clinic. We analyzed short-term outcome of motor and non-motor symptoms (NMS) in 143 PD-patients (mean age 65.3 ± 11.9 years; Hoehn-and-Yahr-score 2.6 ± 0.7) after 3 weeks with 7.4 ± 1.8 active days of interdisciplinary day-care treatment. Participants attended the day-clinic in groups of five patients at a time. Improvements were evaluated by comparison of standardized physical therapy assessments, disease specific scores for motor symptoms (MDS-UPDRS III), mood (BDI), quality of life (PDQ39, SF36), sleep (PDSS, ESS), impulsiveness (QUIP), apathy (SAS), cognition (MMST), as well as change in medication before and directly after the intervention. MDS-UPDRS motor score improved significantly by 22.9 ± 21.5% (p < 0.001) and was accompanied by a significant reduction of imbalance, immobility, and weakness ranging between 6% and 17% in standardized physical therapy tests. In addition, all disease-specific non-motor scales improved significantly. A multidisciplinary day-clinic approach can support benefit on motor, non-motor symptoms and QoL in PD-patients. Given the increase in PD incidence and prevalence as well as the significant treatment effects shown here, more day-clinic treatment opportunities ought to be implemented to improve PD treatment adapted to everyday challenges while still reducing costs to the health care system.


Acceleration of orthodontic tooth movement and root resorption with near and distant surgical insults: An in-vivo study on a rat model.
The purpose of this study was to determine the effects of alveolar decortications (AD) closer and farther from the tooth on Orthodontic tooth movement (OTM) and root resorption. Twenty-four Wistar rats (age 17 weeks) were used in the study. Three groups were formed by randomly dividing the rats into: 1) Control Group (N=8): OTM (14 days) without any surgical insult; 2) Near Group (N=8) OTM (14 days)+Alveolar Decortications (AD) adjacent to roots of the maxillary first molar; 3) Far Group (N=8) OTM (14 days)+AD 5mm away from the roots of the maxillary first molar. OTM was performed using a closed coil Nickel-Titanium (NiTi) spring to apply a mesial force on maxillary first molars of 8-10 grams. AD was performed with high-speed quarter round bur on the palatal aspect of alveolar bone. The rats were euthanized after 2 weeks of OTM and microfocus computed tomography and histological analysis were performed. Near-AD and Far-AD groups exhibited significantly increased OTM and reduction of Bone volume fraction compared to control. The root volume was significantly decreased (increased root resorption) in the Near-AD group. Histological analysis showed no statistically significant difference between the groups. Alveolar decortications lead to a significant increase in the rate of OTM. Increased root resorption was observed when the alveolar decortications were performed close to the maxillary molar.


Dynamic lumbopelvic stabilization for treatment of stress urinary incontinence in women: Controlled and randomized clinical trial.
To compare the results of the dynamic lumbopelvic stabilization (DLS) exercises with exercises for the pelvic floor muscles (PFM) in women with stress urinary incontinence. Randomized controlled clinical trial comparing 17 women submitted to the DLS with 16 women submitted to the exercises for the PFM. The evaluated outcomes were incontinence severity, quality of life (QoL), and impression of improvement in three moments. Significance was set at 5%. For socio-demographic and clinical variables, only climacteric was more prevalent in the DLS group (82% vs. 44%, P = 0.02). Soon after the intervention, there was no difference between the groups in relation to the outcomes evaluated. In the evaluation after 90 days, the DLS group presented better values for the severity of the losses (4.1 ± 2.6 vs. 5.7 ± 2.4, P = 0.006, d = 0.64), daytime frequency (4.6 ± 0.4 vs. 6.2 ± 0.6, P < 0.001, d = 2.67), and nighttime frequency (0.4 ± 0.3 vs. 1.4 ± 0.5, P < 0.001, d = 2.50), QoL and impression of improvement (P < 0.001). After treatment, the DLS plus PFM exercise patients had results similar to those performing PFM exercises alone. However, the DLS plus PFM exercises were superior in the outcomes of incontinence severity, QoL, and impression of improvement in the post-90-day evaluation, showing longer lasting effect.


Interactions of staphylokinase with human platelets.
The interactions of recombinant staphylokinase (SakSTAR) with human platelets were investigated in a buffer milieu, in a human plasma milieu in vitro, and in plasma from patients with acute myocardial infarction (AMI) treated with SakSTAR. In a buffer milieu, the activation rate of plasminogen by SakSTAR or streptokinase (SK) was not significantly altered by addition of platelets. Specific binding of SakSTAR or SK to either resting or thrombin-activated platelets was very low. ADP-induced or collagen-induced platelet aggregation in platelet-rich plasma (PRP) was 94 +/- 2.7% or 101 +/- 1.7% of control in the presence of 0.1 to 20 microM SakSTAR, with corresponding values of 95 +/- 2.8% or 90 +/- 4.6% of control in the presence of 0.1 to 4 microM SK. No effects were observed on platelet disaggregation. ATP secretion following collagen-induced platelet aggregation was 4.3 +/- 0.26 microM for SakSTAR (at concentrations of 0.1 to 20 microM) and 4.4 +/- 0.35 microM for SK (at concentrations of 0.1 to 4 microM), as compared to 3.4 +/- 0.70 microM in the absence of plasminogen activator. Fifty % lysis in 2 h (C50) of 60 microliters 125I-fibrin labeled platelet-poor plasma (PPP) clots prepared from normal plasma or from plasma of patients with Glanzmann thrombasthenia and immersed in 0.5 ml normal plasma, was obtained with 12 or 16 nM SakSTAR and with 49 or 40 nM SK, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Selection of suitable marker genes for the development of cloning vectors and electroporation in different strains of Amycolatopsis mediterranei.
To select suitable genetic markers for optimizing electroporation efficiency in Amycolatopsis mediterranei, thiostrepton (tsr), erythromycin (ermE) and apramycin (am) resistance genes were used. Although tsr could not be suitably expressed in A. mediterranei, the cloning of ermE in pRL1 or its derivative (containing am) resulted in the development of cloning vectors pRLM20, pRLM30 and pRL90. In contrast to tsr and km (kanamycin resistance gene), ermE and am were suitably expressed in A. mediterranei strains and no spontaneous mutants were observed among transformants. Under optimum conditions, maximum electroporation efficiency of 1.2 x 10(4) transformants/micrograms DNA was achieved for A. mediterranei DSM 40,773. These plasmids could also be effectively transferred in other strains of A. mediterranei including F1/24 and T-195. With the cloning of ermE and am and their expression in different strains of Amycolatopsis, we have overcome the problem of the choice of suitable selectable markers for A. mediterranei and related species.


Associations between chewing and swallowing problems and physical and psychosocial health status of long-term care residents in taiwan: a pilot study.
Oral health is often overlooked in institutional elder care but may have an impact on general health and ability to communicate. We aimed to determine the factor associated with chewing and swallowing problems among long-term care residents in Taiwan. Staff nurses trained to evaluate oral health assessed 781 residents using relevant sections of the Minimum Data Set 2.1 for nursing homes (Chinese version), including the Cognitive Performance Scale, Index of Social Engagement, and Activities of Daily Living Scale. Individuals with chewing and swallowing problems (n = 345) tended to be women (odds ratio [OR] = 1.51, P = .019) in smaller facilities (OR = 4.18, P < .001) with fewer natural teeth (OR = 0.54, P = .011); more broken, loose, or carious teeth (OR = 1.74, P = .042); and with more frequently inflamed gums (OR = 2.72, P = .025) than residents without chewing and swallowing problems (n = 436). Residents' chewing and swallowing problems were significantly associated with parenteral/enteral intake, oral health status, nutritional status, concomitant disease and infection, cognitive function, and social engagement.


Essential fatty acid deficient hairless mouse: the effects of topical agents on the epidermis.
Essential fatty acid deficient (EFA deficient) hairless mice were used to test the ability of topical agents to reduce the high epidermal DNA synthesis and acanthosis present in EFA deficiency. An established therapeutic agent known to be effective in psoriasis (betamethasone 17-valerate) significantly reduced the epidermal DNA synthesis, mitotic count and epidermal cell thickness. Linoleic acid reduced DNA synthesis and returned epidermal histology towards that of normal skin. Prostaglandin E2 analogue (15 (S)-15-methyl PGE2 methyl ester) reduced epidermal DNA synthesis both in treated and distant skin sites. Prostaglandin E2 was less effective than the analogue but slightly reduced epidermal DNA synthesis and thickness. Prostaglandin F2alpha had no obvious effect on the epidermis. Chlorambucil reduced epidermal DNA synthesis and thickness. Vitamin A acid increased DNA synthesis and epidermal cell thickness but reduced the hyperkeratosis of EFA deficiency. A rapid epidermal cell transit was found in EFA deficient mice, approximately three times faster than in normal mouse epidermis.


Comparative study of fungal cell disruption--scope and limitations of the methods.
Simple and effective protocols of cell wall disruption were elaborated for tested fungal strains: Penicillium citrinum, Aspergillus fumigatus, Rhodotorula gracilis. Several techniques of cell wall disintegration were studied, including ultrasound disintegration, homogenization in bead mill, application of chemicals of various types, and osmotic shock. The release of proteins from fungal cells and the activity of a cytosolic enzyme, glucose-6-phosphate dehydrogenase, in the crude extracts were assayed to determine and compare the efficacy of each method. The presented studies allowed adjusting the particular method to a particular strain. The mechanical methods of disintegration appeared to be the most effective for the disintegration of yeast, R. gracilis, and filamentous fungi, A. fumigatus and P. citrinum. Ultrasonication and bead milling led to obtaining fungal cell-free extracts containing high concentrations of soluble proteins and active glucose-6-phosphate dehydrogenase systems.


Does professionalism change with different sociodemographic variables? A survey of Arab medical residents.
Medical professionalism reflects the commitment of physicians to their patients, society, themselves, and the profession. The study examined residents' attitudes towards professionalism and how these attitudes vary among the different demographic groups, namely gender, specialty, and year of residency. A proportionate random sampling strategy was used to select the study sample. Medical residents from six specialties at a large tertiary care teaching facility were invited to participate in an online survey. The survey used the modified Learners Attitude of Medical Professionalism Scale (LAMPS), which consists of five domains: respect, excellence, altruism, duty/accountability, and integrity. Chi-square, Student t-test, one-way ANOVA, factorial ANOVA, and post hoc analysis were used to examine the attitudinal differences towards professionalism among the different demographic factors. The overall response rate was 82.7%. Overall, the residents' self-reported attitudes towards professionalism was positive. The highest score was for the "respect" domain (4.61), and the lowest was for "altruism" (3.67). No significant association was found between the mean scores and the three studied variables, namely, gender, specialty (surgical/nonsurgical), and level (senior/junior). No significant differences were observed in the overall attitude towards professionalism among the residents regarding their year of residency, gender, and specialty. The low altruism score and absence of improvement of the total score regarding the residents' increasing experience in the profession are concerns that need remedial action. Therefore, we suggest that future research look for possible explanations by using multi-institutional surveys that explore not only the residents' attitudes, but also the trainers' attitudes and practice, work situations, the hidden curriculum, and culture. Key messagesAttitudes towards professionalism among different demographic groups of residents do not show similar variations as has been reported in the literature, albeit in different sociocultural contexts.The low altruism score and absence of improvement of the total score as the residents gained more experience in the profession are concerns that need remedial action.A longitudinal study involving more than one institution for both residents and their faculty members to compare faculty scores with those of residents, while controlling for specialty and gender, may help elucidate the factors affecting attitudes towards professionalism and suggest possible means of addressing unfavourable attitudes.


Ureteral stenosis as the sole manifestation of Wegener's granulomatosis.
In Wegener's granulomatosis, necrotizing lesions are typically located in the upper and lower respiratory tract and kidneys, and ureteral involvement is uncommon. We report 2 cases in which intrinsic ureteral stenosis was the sole manifestation of this small-vessel vasculitis. Excisional surgery evidenced characteristic granulomatous inflammation that allowed adjuvant elective medical treatment. Urologists, nephrologists, and internists should be aware of this atypical presentation of Wegener's granulomatosis. Thorough clinical and biologic assessments are warranted in the initial workup of isolated intrinsic ureteral stenosis.


Coadministration of oral levofloxacin with agents that impair its absorption: potential impact on emergence of resistance.
Coadministration of fluoroquinolones (FQs) with divalent or trivalent cation-containing compounds (DTCCs) inhibits FQ absorption. In a case-control study of 46 inpatients receiving oral levofloxacin and DTCCs, patients with a levofloxacin-resistant isolate had been previously exposed to nearly twice as many days of levofloxacin/DTCC coadministration (P = 0.04). There remained a borderline significant independent association between the number of days of coadministration and levofloxacin-resistant culture [adjusted odds ratio (95% confidence interval) = 1.26 (0.98, 1.63); P = 0.07], even after controlling for the length of the levofloxacin course and the duration of hospitalisation prior to initiation of levofloxacin. Efforts should be directed at modifying hospital policies for dosing of levofloxacin and DTCCs to prevent coadministration.


Mechanism of RNA synthesis initiation by the vesicular stomatitis virus polymerase.
The minimal RNA synthesis machinery of non-segmented negative-strand RNA viruses comprises a genomic RNA encased within a nucleocapsid protein (N-RNA), and associated with the RNA-dependent RNA polymerase (RdRP). The RdRP is contained within a viral large (L) protein, which associates with N-RNA through a phosphoprotein (P). Here, we define that vesicular stomatitis virus L initiates synthesis via a de-novo mechanism that does not require N or P, but depends on a high concentration of the first two nucleotides and specific template requirements. Purified L copies a template devoid of N, and P stimulates L initiation and processivity. Full processivity of the polymerase requires the template-associated N protein. This work provides new mechanistic insights into the workings of a minimal RNA synthesis machine shared by a broad group of important human, animal and plant pathogens, and defines a mechanism by which specific inhibitors of RNA synthesis function.


Docetaxel and gemcitabine combination in 133 advanced soft-tissue sarcomas: a retrospective analysis.
Advanced soft-tissue sarcomas are usually resistant to cytotoxic agents such as doxorubicin and ifosfamide. Antitumor activity has been observed for gemcitabine and docetaxel combination. We conducted a retrospective study on 133 patients (58 males/75 females) with unresectable or metastatic soft-tissue sarcoma. The median age at diagnosis was 51.7 (18-82), with 76 patients with leiomoyosarcoma and 57 patients with other histological subtypes. The initial localizations were limb (44), uterine (32), retroperitoneal (23) and organs or bone (34). Patients received 900 mg/m2 of gemcitabine (days 1 and 8) over 90 min plus 100 mg/m2 of docetaxel (day 8), intravenously every 21 days. Gemcitabine/docetaxel combination was well tolerated with an overall response of 18.4% and with no clear statistical difference between leiomyosarcomas and other histological subtypes (24.2% versus 10.4% (p=0.06)). No difference was found between uterine soft-tissue sarcomas versus others. The median overall survival was 12.1 months (1-28). Better overall survival was correlated with leiomyosarcoma (p=0.01) and with the quality of the response, even for patients with stable disease (p<10(-4)). No statistical difference was found for the initial localization. Response to treatment and overall survival were better for patients in World Health Organization (WHO) performance status classification (PS) 0 at baseline versus patients in WHO PS-1, 2 or 3 (p=0.023 and p<10(-4), respectively). Gemcitabine/docetaxel combination was tolerable and demonstrated better response and survival for leiomyosarcoma, especially for patients in WHO PS-0 at baseline. For the other histological subtypes, the response was not encouraging, but the survival for patients in response or stable suggests further investigation.


Influence of different treatment modalities on survival of patients with low-grade endometrial stromal sarcoma: A retrospective cohort study.
To assess the efficacy of different treatment modalities on the outcome of patients with low-grade endometrial stromal sarcoma (LG-ESS). Patients with LG-ESS who received hysterectomy from March 1991 to December 2013 were retrospectively analyzed. The associations between clinicopathologic variables and disease free survival (DFS) were evaluated. One hundred and fourteen patients met the eligibility requirements. All patients received hysterectomy as the main treatment, 17.5% (20/114) of patients received ovarian preservation, and 62.3% (71/114) of patients received lymphadenectomy. Fifty-six patients received chemotherapy, 36 patients received radiotherapy, and 11 patients received endocrine therapy. The median follow-up duration was 40 months. The 5-year and 10-year DFS rates were 91.8% and 77.4%, respectively. The 5-year and 10-year overall survival rates were 96.7% and 96.7%, respectively. Univariate analyses showed that there were no risk factors associated with DFS. Lymphadenectomy, lymph node status, ovarian preservation, chemotherapy, radiotherapy, and endocrine therapy had no significant effect on DFS. Hysterectomy has been the mainstay of treatment for LG-ESS. The optimal treatment strategy in LG-ESS remains to be determined.


The Six-Item Screener and AD8 for the detection of cognitive impairment in geriatric emergency department patients.
We evaluate the diagnostic test characteristics of the Six-Item Screener and the AD8 to detect cognitive dysfunction in adults older than 65 years and using the emergency department (ED) for any reason. We conducted an observational cross-sectional cohort study at a single academic urban university-affiliated hospital. Subjects were consenting, non--critically ill, English-speaking adults older than 65 years and receiving care in the ED. We quantitatively assessed the diagnostic test characteristics of the Six-Item Screener and AD8 by using the Mini-Mental State Examination score less than 24 as the criterion standard for cognitive dysfunction. The prevalence of cognitive dysfunction was 35%, but only 6% of charts noted a pre-existing deficit. The Six-Item Screener was superior to either the caregiver-administered AD8 or the patient-administered AD8 for the detection of cognitive dysfunction. The Six-Item Screener was superior to the caregiver- or patient-administered AD8 to identify older adults at increased risk for occult cognitive dysfunction.


The therapeutic use of the unconjugated monoclonal antibodies (MAb) 17-1A in combination with GM-CSF in the treatment of colorectal carcinoma (CRC).
Unconjugated monoclonal antibodies (MAb) and granulocyte macrophage-colony stimulating factor (GM-CSF) may induce tumor regression in patients. Antibody-dependent cellular cytotoxicity (ADCC) is considered to be one of the effector functions of MAb. Human peripheral blood mononuclear cells (PBMC) preincubated with GM-CSF and used as effector cells in an 18h ADCC assay with SW948 (human colorectal carcinoma cell line) as target cells and MAb 17-1A induced significant increase in the lytic capacity of the effector cells. Based on these findings the therapeutic effect of the combination of mouse MAb 17-1A (IgG2a) against colorectal carcinoma (CRC) cells and GM-CSF was evaluated in 20 patients with metastatic CRC. The patients received GM-CSF (250 micrograms/m2/day s.c.) for 10 days and a single i.v. infusion of MAb 17-1A (400 mg) at day 3 of the cycle. The cycles were repeated with an interval of one month. Four cycles were given. ADCC as well as Fc-receptor bearing mononuclear cells increased significantly during therapy. Two patients achieved CR (10%). One patient had an MR (5%) and a further three patients were considered to have SD > 3 months (15%). The two CR patients are still in CR, 35+ and 30+ months respectively after initiation of therapy. Patients with an ADCC activity at start of therapy above the median value of the total patient material survived significantly longer than those patients with an ADCC reactivity below this value (p = 0.002).


Short-acting testosterone appears to have lesser effect on male reproductive potential compared to long-acting testosterone in mice.
To compare the effect of exogenous short-acting and long-acting testosterone on male reproductive potential in mice. In vivo mouse model. University-based basic science research laboratory. A total of 30 wild-type C57BL/6 male and female mice were used for this experimentation. The male mice were used for control group and testosterone supplementation, while both male and female mice were used for the breeding portion of the study. Exogenous testosterone was administered either in short-acting formulation (Monday-Wednesday-Friday dosing schedule, testosterone propionate 0.2 mg/kg), or long-acting formulation (3-month dosing schedule - testosterone pellets 150 mg) to male mice. Time to pregnancy, Luteinizing hormone (LH) levels, and testicular weight. Mice treated with long-acting testosterone appear to have longer time to pregnancy when compared to wild-type (33 ± 11 vs 23 ± 2.6 days, p ≤ 0.05) and mice that received short-acting testosterone propionate (26 ± 5.9 days). Mice treated with long-acting testosterone had smaller testes weight when compared to control (0.08 ± 0.01 vs 0.11 ± 0.01g; p ≤ 0.01), while the short-acting testosterone treated mice had similar testis weight when compared to control (0.09 ± 0.02 vs 0.11 ± 0.01g; ns). The serum testosterone level was elevated in mice that received testosterone pellets (285.78 ng/dL) and testosterone propionate (122.16 ng/dL) versus control (68.4 ng/dL). In mice that received long-acting testosterone pellets, LH levels at 3 months were almost undetectable while those that received short-acting testosterone remained similar to control (0.017 ± 0.058 vs 0.348 ± 0.232 IU/L; p ≤ 0.01). Female reproductive potential parameters including litter size and pup weight were collected and observed to have no difference between groups. Through a mouse breeding study, mice that received short-acting testosterone were shown to have fertility potential similar to wild-type male mice. Long-acting exogenous testosterone appeared to impair male reproductive capacity and LH levels when compared to short-acting testosterone. Short-acting testosterone appeared to cause less LH suppression. Identifying strategies to increase testosterone while simultaneously preserving male fertility is important for treating young men with hypogonadism.


Enzymatic replacement therapy for Hunter disease: Up to 9 years experience with 17 patients.
Hunter disease is an X-linked lysosomal storage disorder characterized by progressive storage of glycosaminoglycans (GAGs) and multi-organ impairment. The central nervous system (CNS) is involved in at least 50% of cases. Since 2006, the enzymatic replacement therapy (ERT) is available but with no effect on the cognitive impairment, as the present formulation does not cross the blood-brain barrier. Here we report the outcome of 17 Hunter patients treated in a single center. Most of them (11) started ERT in 2006, 3 had started it earlier in 2004, enrolled in the phase III trial, and 3 after 2006, as soon as the diagnosis was made. The liver and spleen sizes and urinary GAGs significantly decreased and normalized throughout the treatment. Heart parameters improved, in particular the left ventricular mass index/m(2) decreased significantly. Amelioration of hearing was seen in many patients. Joint range of motion improved in all patients. However, no improvement on respiratory function, eye, skeletal and CNS disease was found. The developmental quotient of patients with a CNS involvement showed a fast decline. These patients were no more testable after 6 years of age and, albeit the benefits drawn from ERT, their quality of life worsened throughout the years. The whole group of patients showed a consistent residual disease burden mainly represented by persistent skeletal disease and frequent need of surgery. This study suggests that early diagnosis and treatment and other different therapies which are able to cross the blood-brain barrier, might in the future improve the MPS II outcome.


Testing privatization of "long arm" service of process.
The research addresses questions about the desirability of privatizing a key component of the child support enforcement process, namely, the serving of legal documents or "service of process" for cases in which the noncustodial parent is living in another state. Child support enforcement cases that require this type of "long arm" service of process were randomly assigned to a private vendor and to out-of-state sheriff offices using an experimental research design. The author finds that although there is no difference in the time it took the two groups to process cases, the private vendor was more successful, on average, at performing this function. Furthermore, he finds that the higher success rate of the private vendor is sufficient to produce a substantively important increase in collections in child support enforcement cases. Additional questions about the suitability of privatizing "service of process" and other like services are also discussed.


Morphologic shift associated with aberrant cytokeratin expression in a GIST patient after tyrosine kinase inhibitors therapy. A case report with a brief review of the literature.
After an initial benefit from tyrosine kinase inhibitors (TKI), most gastrointestinal stromal tumors (GISTs) eventually develop disease progression or secondary resistance. An altered tumor (immune)phenotype with anaplasia and morphological changes secondary to therapy have occasionally been described in the literature. We present a 52-year old patient, diagnosed with high risk, spindle-cell, GIST (CD117 positive, Pankeratin negative) in 2003, showing a c-Kit exon 11 mutation. After TKI therapy, he developed drug resistance and disease progression. Pathological assessment of the last surgical specimen showed a pure epithelioid/clear cell histology, without evidence of cellular anaplasia. Tumor cells were CD117 positive, DOG1 positive but also E-cadherin positive and Pankeratin positive, whereas molecular analysis confirmed the presence of the c-Kit exon 11 mutation, with no additional mutations. We describe an unusual case of GIST showing peculiar (immuno)phenotypic changes under therapy, different from the vast majority of therapy-driven changes, which include marked cellular pleomorphisms and KIT immunonegativity. Possible molecular explanations to understand these phenomena and a brief review of the literature are also addressed.


A Non-Invasive and Accurate Measurement of Gingival Thickness Using Cone-Beam Computerized Imaging for the Assessment of Planning Immediate Implant in the Esthetic Zone-A Pig Jaw Model.
The objective of the study is to compare the accuracy of the measurement of gingival thickness using cone-beam computerized tomography (CBCT) with direct clinical measurement on a pig jaw model, aiming to provide an alternate and precise method to aid assessment of the gingival biotype before immediate implant placement at the esthetic zone. Four pig mandibles were categorized separately into 14 different zones with each prominent tooth cusp as one. A high-resolution CBCT image was taken. Measurement of gingival thickness was performed using computer software and was compared with direct clinical measurements. Intraclass correlation coefficient between clinical and CBCT measurements were 0.995 (pig 1), 0.945 (pig 2), 0.966 (pig 3), and 0.932 (pig 4), which indicated a good match between 2 measuring methods. Independent t test showed no significant difference between 2 independent investigators in all aspect of measurements (P > 0.05). Measuring gingival thickness using CBCT is a predictable and accurate method to assess the gingival biotype of a patient, so as to predict the suitability of immediate implantation.


Chronic exposure to rotenone, a dopaminergic toxin, results in peripheral neuropathy associated with dopaminergic damage.
Rotenone, a widely used pesticide, causes a syndrome in rats that replicates, both pathologically and behaviorally, the symptoms of Parkinson's disease (PD). In the present study, we sought to determine if a chronic exposure to rotenone, resulting in dopaminergic loss, could also lead to peripheral neuronal damage related to motor dysfunction. Adult male Sprague-Dawley rats (n=14) were treated with rotenone (1 or 2mg/kg, s.c., once daily) on days 1, 3, 6, 8, 10, 13, 15, 17, 21, 22, and 27 to minimize mortality. Control rats received vehicle (DMSO) injections. Animals were weighed on the days of injection and monitored daily. A mortality of 21% was observed in rotenone treated rats. The motor nerve conduction velocity (MCV) was assessed using action potentials detected from the tail muscle through surface receiver electrodes installed around the distal portion of the tail. Rats exposed to rotenone often developed hind limb paresis with a significant decrease in MCV as detected in tail nerves (p<0.05). Animals were then sacrificed, either 24h after rotenone exposure on day 6 or 24h after the last dose of rotenone on day 27. The striatum and sciatic nerves were dissected on dry ice and flash-frozen and kept at -80°C until further analysis. Striatal dopamine (DA) was analyzed using HPLC-ECD and sciatic nerve pathology was analyzed for neurodegeneration. A time-dependent rotenone-induced striatal depletion of DA (60% after 7 days and 80% after 27 days) was observed. Furthermore, Neurofilament-neurofilament B, Flouro-Jade C and myelin basic protein analyses suggested a time-dependent rotenone-induced neurodegeneration in sciatic nerves. These data, for the first time, indicate an association between dopaminergic damage and peripheral motor nerve degeneration in an animal model of dopaminergic toxicity. Peripheral motor nerve dysfunction in rats following a chronic exposure to rotenone may serve not only as a relevant experimental model of motor neuropathy but also as a peripheral marker of dopaminergic neuronal damage to the central nervous system.


Cytochrome b-245 and its involvement in the molecular pathology of chronic granulomatous disease.
Cytochrome b-245 is an integral, and probably the terminal, component of the microbicidal oxidase electron transport chain of phagocytic cells. Current knowledge of the biochemistry and cell and molecular biology of this molecule is described. The molecular basis of chronic granulomatous disease, in which defective electron transport down this chain predisposes to infection and impaired digestion by phagocytes, is explained in terms of anomalies of the cytochrome b and related molecules.


Visible-light-induced indole synthesis via intramolecular C-N bond formation: desulfonylative C(sp2)-H functionalization.
Despite significant advances made on the synthesis of indole derivatives through photochemical strategies during the past several years, the requirement of equivalent amounts of oxidants, bases or other additional additives has limited their practical applications in the synthesis of natural products and pharmaceuticals as environment-friendly processes. Herein, we report LED visible-light-induced redox neutral desulfonylative C(sp2)-H functionalization for the synthesis of N-substituted indoles with a broad scope through γ-fragmentation under mild conditions in the absence of any additional additive. The reaction mechanism paradigm has been investigated on the basis of deuterium labeling experiments, kinetic analysis, Hammett plotting analysis and DFT calculations.


Do the benefits of screening mammography outweigh the harms of overdiagnosis and unnecessary treatment?--no.
No. Breast cancer researchers Robin Bell and Robert Burton believe that screening can result in overdiagnosis.


Visceral-to-subcutaneous fat ratio is a possible prognostic factor for type 1 endometrial cancer.
Associations have been observed between obesity defined by the body mass index (BMI) and the incidence of endometrial cancer. However, the impact of obesity on the prognosis of endometrial cancer is not yet clear. Recently, visceral fat has been considered to have a greater impact on malignant disease in obese patients than subcutaneous fat. In this study, we investigated the association between prognostic factors of type 1 and type 2 endometrial cancer and obesity parameters. The impacts of clinical factors on the progression-free survival (PFS) and overall survival (OS) were analyzed retrospectively in 145 primary endometrial cancer patients. The factors included age, BMI, pathological findings, Federation of Gynecology and Obstetrics (FIGO) stage, status of lymph node metastasis, and the amounts of visceral and subcutaneous fat obtained from computed tomography (CT) data. Only the visceral-to-subcutaneous fat ratio (V/S ratio) (cutoff value 0.5) corresponded to a significant difference in OS and PFS in type 1 endometrial cancer (p = 0.0080, p = 0.0053) according to the results of log-rank tests of Kaplan-Meier curves. The COX regression univariate analysis revealed that only the V/S ratio was a significant prognostic factor for PFS, but not OS (p = 0.033 and p = 0.270, respectively). A V/S ratio > 0.5 is a possible factor for poor prognosis in type 1 endometrial cancer. Further research is needed to investigate the preventive and therapeutic effects of reducing visceral fat on the prognosis of this type of cancer.


A two-year observational study assessing the safety of DepoFoam bupivacaine after augmentation mammaplasty.
Two-year safety outcomes in patients who received DepoFoam bupivacaine during two prior breast augmentation studies were evaluated. The authors assess the clinical sequelae observed during follow-up examination with respect to the integrity of the breast implants. In Study 1, patients received bupivacaine HCl (75 mg) in one breast pocket and DepoFoam bupivacaine (133 or 266 mg) in the other. In Study 2, patients received either bupivacaine HCl (200 mg) or DepoFoam bupivacaine (532 mg), divided equally into each breast pocket. Investigators and patients remained blinded to the treatment administered. Patients completed a questionnaire regarding breast pain, tenderness, tingling, numbness, burning, changes in sensation, and any relevant life events potentially affecting the implants. Patients were also assessed for postoperative healing and implant integrity. Ninety-four women were evaluated. Most patients in all groups had no change in breast size or shape and no changes in the skin or nipple. There were no reports of palpable hard knots or swelling. There was one report of irritation/implant leakage (in a patient who received bupivacaine HCl [75 mg] in the relevant breast). Most patients reported no breast pain, tenderness, tingling, numbness, burning, other changes in sensation, chest wall surgery or trauma, or life events affecting the implant. At a two-year follow-up assessment, DepoFoam bupivacaine was not associated with any complications that would compromise the integrity of the breast implants. There was no indication of an association between DepoFoam bupivacaine or bupivacaine HCl and changes in sensation or other abnormal findings in these patients. 2.


Morphologic changes and prognosis of the respiratory tract epithelium in inhalation injury and their relationship with clinical manifestations.
We set out to observe the morphologic changes and determine prognosis based on airway epithelial injury after inhalation injury of varying severity using a fiberbronchoscope and to explore the relationship between the severity of epithelial injury and its clinical manifestation. Sixty burn patients with an inhalation injury underwent fiberoptic bronchoscopy. Morphologic changes of the airway epithelium were observed, and the inhalation injury was divided into 3 categories based on the severity of the epithelial injury: first-degree injury, in which the airway epithelium had slight hyperemia and edema; second-degree injury, in which obvious epithelial hyperemia and edema, epithelial erosion, or petechial hemorrhage was observes; and third-degree, in which the airway epithelium had necrosis and exfoliation. For all groups, chest radiographs were examined. The duration of ventilation was recorded. Among 60 patients, 16 (27%) had first-degree injury, 33 (55%) had second-degree injury, and 11 (18%) had third-degree injury. Among this last group, 4 patients with epithelial exfoliation had airway hemorrhage. In this study, 38 of 60 (63%) patients presented with abnormal findings on lung radiographs and 9 of 60 (15%) developed pulmonary infections. The duration of ventilation averaged 2 days for second-degree injury and 14 days for third-degree injury. The recovery times for first-, second-, and third-degree injury were 7, 16, and 29 days, respectively. Fiberoptic bronchoscopy contributes to the accurate evaluation of tracheal epithelial injury severity. As the severity of inhalation injury increased, the clinical symptoms also increased. Severe complications (eg, bleeding and asphyxia caused by epithelial slough) may occur in patients with third-degree injury and should be closely observed by clinicians. The airway epithelium has a substantial potential for repair. Even if the airway epithelial injury is severe, the damaged epithelium will recover.


Latex allergy in a child with banana anaphylaxis.
Allergy to latex and to banana is probably uncommon. Cross-reactivity between these two antigens has been recently demonstrated, but the clinical association of allergic reactions to latex contact and banana ingestion is extremely rare. We report a 3-year-old boy who developed an anaphylactic reaction following banana ingestion and who presented an associated immediate hypersensitivity to latex.