Estimation of optimal b-value sets for obtaining apparent diffusion coefficient free from perfusion in non-small cell lung cancer.
The purpose of this study was to determine optimal sets of b-values in diffusion-weighted MRI (DW-MRI) for obtaining monoexponential apparent diffusion coefficient (ADC) close to perfusion-insensitive intravoxel incoherent motion (IVIM) model ADC (ADCIVIM) in non-small cell lung cancer. Ten subjects had 40 DW-MRI scans before and during radiotherapy in a 1.5 T MRI scanner. Respiratory triggering was applied to the echo-planar DW-MRI with TR ≈ 4500 ms, TE = 74 ms, eight b-values of 0-1000 μs μm(-2), pixel size = 1.98 × 1.98 mm(2), slice thickness = 6 mm, interslice gap = 1.2 mm, 7 axial slices and total acquisition time ≈6 min. One or more DW-MRI scans together covered the whole tumour volume. Monoexponential model ADC values using various b-value sets were compared to reference-standard ADCIVIM values using all eight b-values. Intra-scan coefficient of variation (CV) of active tumour volumes was computed to compare the relative noise in ADC maps. ADC values for one pre-treatment DW-MRI scan of each of the 10 subjects were computed using b-value pairs from DW-MRI images synthesized for b-values of 0-2000 μs μm(-2) from the estimated IVIM parametric maps and corrupted by various Rician noise levels. The square root of mean of squared error percentage (RMSE) of the ADC value relative to the corresponding ADCIVIM for the tumour volume of the scan was computed. Monoexponential ADC values for the b-value sets of 250 and 1000; 250, 500 and 1000; 250, 650 and 1000; 250, 800 and 1000; and 250-1000 μs μm(-2) were not significantly different from ADCIVIM values (p > 0.05, paired t-test). Mean error in ADC values for these sets relative to ADCIVIM were within 3.5%. Intra-scan CVs for these sets were comparable to that for ADCIVIM. The monoexponential ADC values for other sets-0-1000; 50-1000; 100-1000; 500-1000; and 250 and 800 μs μm(-2) were significantly different from the ADCIVIM values. From Rician noise simulation using b-value pairs, there was a wide range of acceptable b-value pairs giving small RMSE of ADC values relative to ADCIVIM. The pairs for small RMSE had lower b-values as the noise level increased. ADC values of a two b-value set-250 and 1000 μs μm(-2), and all three b-value sets with 250, 1000 μs μm(-2) and an intermediate value approached ADCIVIM, with relative noise comparable to that of ADCIVIM. These sets may be used in lung tumours using comparatively short scan and post-processing times. Rician noise simulation suggested that the b-values in the vicinity of these experimental best b-values can be used with error within an acceptable limit. It also suggested that the optimal sets will have lower b-values as the noise level becomes higher.


[Changes in the nigrostriatal dopamine receptor compartment after continuous dopaminergic infusions in Parkinson disease].
Motor fluctuations often complicate chronic levodopa treatment of Parkinson's disease. Pharmacologically, these phenomena are characterized by a progressive shortening of the duration of action of levodopa and a gradual narrowing of the range of "optimally effective" doses, able to improve parkinsonian akinesia without inducing abnormal involuntary movements. The effects of a continuous intravenous infusion of levodopa lasting 9 +/- 0.3 days on these clinical-pharmacological indices have been studied in 12 parkinsonian patients. Continuous infusion therapy gradually ameliorated motor fluctuations by more than 40%, and this improvement lasted for at least 6 days after resuming standard oral therapy. Moreover, levodopa duration of action was prolonged by about 30%, and the range of "optimally effective" dose was widened by about 50%. The above data suggest the possibility of plastic modifications of the pathogenetic mechanisms underlying motor fluctuations in Parkinson's disease, and a potential deleterious effect of intermittent oral therapy. Consequently, continuous dopaminergic stimulation, when used in the early stages of the disease, might theoretically have a prophylactic role on the development or worsening of motor fluctuations.


Patellar tendon structure responds to load over a 7-week preseason in elite male volleyball players.
The purpose of this study was to investigate the relation between external and internal load and the response of the patellar tendon structure assessed with ultrasound tissue characterization (UTC) in elite male volleyball players during preseason. Eighteen players were followed over 7 weeks, measuring four load parameters during every training and match: volume (minutes played), rating of perceived exertion (RPE) (ranging from 6 to 20), weekly load (RPE*volume), and jump frequency (number of jumps). Patellar tendon structure was measured biweekly using UTC, which quantifies tendon matrix stability resulting in four different echo types (I-IV). On average, players spent 615 min/wk on training and matches with an RPE of 13.9 and a jump frequency of 269. Load evaluation shows significant changes over the 7 weeks: Volume and weekly load parameters were significantly higher in week 3 than week 7 and in week 4 than week 2. Weekly load performed in week 4 was significantly higher than week 7. No significant changes were observed in tendon structure. On the non-dominant side, no significant correlations were found between changes in load parameters and echo types. At the dominant side, a higher weekly volume and weekly load resulted in a decrease of echo type I and a higher mean RPE in an increase of echo type II. The results of this study show that both external and internal load influence changes in patellar tendon structure of elite male volleyball players. Monitoring load and the effect on patellar tendon structure may play an important role in injury prevention.


The factorial structure of the Mini-Mental State Examination (MMSE) in Japanese dementia patients.
The Mini-Mental State Examination (MMSE) is one of the most commonly used instruments in the evaluation of global cognitive status. Few studies have investigated the relationship among its components in terms of factorial structure in Japanese individuals suffering from dementia. The aims of this study were: 1) to analyze the factorial structure of MMSE in Japanese dementia patients, 2) to clarify the MMSE static structure in identifying different cognitive profiles and understanding how these profiles are related to levels of dysfunction in subsets of dementia patients. 30,895 consecutive outpatients with dementia were evaluated. The 11 subtests composing the MMSE and the global MMSE score were analyzed. Factor analysis based on principal component analysis with Promax rotation was applied to the data representing the frequency of failures in each subtest as identified by the MMSE. Factor analysis identified three factors that explained approximately 44.57% of the total variance. The first factor, immediate memory, essentially constituted a simple index of the reading and writing subtests. The second factor, orientation and delayed recall, expressed the ability to handle new information. The third factor, working memory, was most closely related to the severity of dementia at the time of test administration. Japanese dementia patients appear to develop difficulty handling new information in the early stages of their disease. This finding, and our finding that there is a factor associated with disease severity, suggest that understanding the specific factors related to subtest items, which underlie the total MMSE score may be useful to clinicians in planning interventions for Japanese patients in the early stages of dementia.


Understanding Resilience and Preventing and Treating PTSD.
Resilience is defined as the dynamic ability to adapt successfully in the face of adversity, trauma, or significant threat. Some of the key early studies of resilience were observational studies in children. They were followed by research in adults, studies testing interventions to promote resilience in different populations, and a recent upsurge of studies on the underlying genomic and neurobiological mechanisms. Neural and molecular studies in preclinical models of resilience are also increasingly identifying active stress adaptations in resilient animals. Knowledge gained from animal and human studies of resilience can be harnessed to develop new preventive interventions to enhance resilience in at-risk populations. Further, treatment interventions focused on enhancing potentially modifiable protective factors that are consistently linked to psychological resilience can enrich currently available treatment interventions for individuals with posttraumatic stress disorder (PTSD). Translating our expanding knowledge of the neurobiology of resilience additionally promises to yield novel therapeutic strategies for treating this disabling condition. This review summarizes the vast field of resilience research spanning genomic, psychosocial, and neurobiological levels, and discusses how findings have led and can lead to new preventive and treatment interventions for PTSD.


Duloxetine-induced hyponatremia in an elderly patient treated with thiazide diuretics.
Hyponatremia is a known adverse effect of duloxetine, and it can lead to potentially life-threatening complications. Administration of thiazide diuretics also has been the cause of hyponatremia. We report a case of duloxetine-induced hyponatremia in an elderly patient treated with thiazide diuretics. An 86-year-old woman treated with the trichlormethiazide was admitted for vertebral compression fracture with disorientation and nausea on the 6(th) day of treatment with duloxetine. Laboratory findings revealed hyponatremia, hypo-osmolality, concentrated urine, and increased urine sodium. Syndrome of inappropriate antidiuretic hormone was considered, therefore, duloxetine, and trichlormethiazide was discontinued and treated with fluid restriction, furosemide and sodium chloride administered orally. Disorientation and nausea were improved after correction of hyponatremia. Health care practitioners should be aware of the possibility of duloxetine-induced hyponatremia, particularly in patients treated with thiazide diuretics.


Evaluation of a novel enzyme-linked immunosorbent assay for serological diagnosis of porcine proliferative enteropathy.
A specific enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to the porcine pathogen Lawsonia intracellularis was developed and evaluated using sera from naïve, naturally infected as well as experimentally infected pigs. On the basis of 37 serum samples collected from experimentally infected pigs and 62 serum samples from naturally infected pigs the sensitivity of the ELISA was calculated to 98.0%. The specificity of the test was 99.3%, calculated on the basis of 273 serum samples collected in six herds free of L. intracellularis after medicated eradication. The novel ELISA was a specific and sensitive method for detecting specific antibodies, and may be a good alternative to the existing serological tests for L. intracellularis. It may be usable for diagnosis of proliferative enteropathy and for determination of a herd's epidemiologic status.


Sleeping through anything: The effects of unpredictable disruptions on mouse sleep, healing, and affect.
Many aspects of the laboratory environment are not tailored to the needs of rodents, which may cause stress. Unpredictable stressors can cause ulcers, prolonged pituitary-adrenal activation, and anhedonia. Similarly, pain has been demonstrated to slow wound healing, and mice experiencing pain exhibit altered behavior. However it is unknown how husbandry, which occurs when the mice are inactive, and lack of analgesia, specifically in a punch biopsy procedure, effects animal physiology, behavior, and welfare, particularly as it relates to sleep fragmentation. We hypothesized that sleep fragmentation, induced by unpredictable husbandry and lack of pain management will slow wound healing. Two main treatments were tested in a factorial design in C57BL/6 mice of both sexes (64 mice total); 1) analgesia (carprofen and saline) and 2) sleep disruptions (random and predictable). Mice were singly housed in a non-invasive sleep monitoring apparatus on arrival (Day -4). Disruption treatments were applied from Day -3 to 2. All mice received a punch biopsy surgery (Day 0) with topical lidocaine gel and their analgesic treatment prior to recovery, and on Days 1 and 2. Nesting behavior was assessed daily and a sugar cereal consumption test, as a measure of anhedonia, was conducted on Days -1 to 2. On Day 3, mice were euthanized and wound tissue and adrenal glands were collected. We found that the disruption predictability had no effect on mouse sleep, wound healing, or adrenal cortex:medulla ratio. It's possible that the disruption period was not long enough to induce chronic stress. However, male mice who received analgesia slept more than their female counterparts; this may be related to sex differences in pain perception. Overall, it does not appear that the predictability of disturbance effects sleep fragmentation or stress responses, indicating that husbandry activities do not need to occur at set predictable times to improve welfare.


Nanodiamonds as a state-of-the-art material for enhancing the gamma radiation resistance properties of polymeric membranes.
We report, for the first time, the development of gamma radiation resistant polysulfone (Psf)-nanodiamond (ND) composite membranes with varying concentrations of NDs, ranging up to 2 wt% of Psf. Radiation stability of the synthesized membranes was tested up to a dose of 1000 kGy. To understand the structure-property correlationship of these membranes, multiple characterization techniques were used, including field-emission scanning electron microscopy, atomic force microscopy, drop shape analysis, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, gel permeation chromatography, positron annihilation spectroscopy, and small angle X-ray scattering. All the composite membranes exhibited enhanced radiation resistance properties, with 0.5% loading of NDs as the optimum. Compared to the radiation stability of Psf membranes up to a dose of 100 kGy, the optimum composite membranes are found to be stable up to a radiation dose of 500 kGy, owing to the unique surface chemistry of NDs and interfacial chemistry of Psf-ND composites. Experimental findings along with the Monte Carlo simulation studies confirmed a five times enhanced life-span of the composite membranes in an environment of the intermediate level radioactive waste, compared to the control Psf membrane.


How to build an integrated biobank: the Washington University Translational Cardiovascular Biobank & Repository experience.
Translational studies that assess and extend observations made in animal models of human pathology to elucidate relevant and important determinants of human diseases require the availability of viable human tissue samples. However, there are a number of technical and practical obstacles that must be overcome in order to perform cellular and electrophysiological studies of the human heart. In addition, changing paradigms of how diseases are diagnosed, studied and treated require increasingly complex integration of rigorous disease phenotyping, tissue characterization and detailed delineation of a multitude of "_omics". Realizing the need for quality-controlled human cardiovascular tissue acquisition, annotation, biobanking and distribution, we established the Translational Cardiovascular Biobank & Repository at Washington University School of Medicine. Several critical details are essential for the success of cardiovascular biobanking including coordinated, trained and dedicated staff members; adequate, nonrestrictive informed consent protocols; and fully integrated clinical data management applications for annotating, tracking and sharing of tissue and data resources. Labor and capital investments into growing biobanking resources will facilitate collaborative efforts aimed at limiting morbidity and mortality due to heart disease and improving overall cardiovascular health.


Addressing the Social Needs of Medicaid Enrollees Through Managed Care: Lessons and Promising Practices from the Field.
With growing recognition of the adverse health impacts of unmet social needs, Medicaid managed care organizations (MMCOs) are increasingly focusing on addressing the social needs of Medicaid enrollees as part of a holistic approach to care. Information and knowledge sharing among MMCOs pertaining to lessons learned and promising practices from their social determinants of health (SDOH) targeted efforts can help identify successful practical approaches for navigating common challenges, developing robust SDOH programming, and effectively delivering whole-person care. Using data from interviews with 28 representatives of 8 national and regional MMCOs, this qualitative study describes the perspectives of MMCO representatives on the lessons learned and emerging promising practices from addressing SDOH among their Medicaid enrollees. Participants discussed the importance of member and community-centeredness, structured programming, and delivery system realignment in the effective delivery of whole person care. Ten lessons learned and emerging promising practices are discussed. Findings from this study suggest that success in addressing the social needs of Medicaid beneficiaries may be achieved through adaptive, data-driven, member- and community-centric efforts by MMCOs, facilitated by system-level changes that formally integrate social services within health care. Lessons learned and promising practices can serve as a foundation for identifying and evaluating best practices and guidelines for effective MMCOs' SDOH-related programming.


[Cardiac remodeling in the light of immune status changes in patients with chronic obstructive pulmonary disease].
The degree of structural and functional heart changes was evaluated by means of Doppler echocardiography in 120 patients with chronic obstructive pulmonary disease (COPD) of different degrees of severity. Conventional immunological laboratory techniques were used in all the patients to evaluate the condition of cell-mediated, humoral, and cytokine-mediated immunity; inflammatory process activity and the degree of endotoxicosis were evaluated by measuring blood levels of acute phase proteins and medium mass molecules. The study showed that the character of heart remodeling depended on COPD severity. Only severe COPD was associated with a significant right atrial enlargement, as well as structural and functional changes in the left heart. The results demonstrated a distinct correlation between the variables of structural and functional condition of the heart and immunity parameters in COPD patients. The variables of right and left ventricular function moderately correlated with inflammatory and endotoxicosis indices. Decompensation of patients with severe COPD and cor pulmonale is accompanied by a pronounced immunodeficiency. An increase in blood levels of cytokines, tumor necrosis factor alpha in particular, may serve as a marker of early stages of chronic heart failure, while an increase in blood levels of interleukin-6 may be a marker of its severity.


Fast inactivation of Nav current in rat adrenal chromaffin cells involves two independent inactivation pathways.
Voltage-dependent sodium (Nav) current in adrenal chromaffin cells (CCs) is rapidly inactivating and tetrodotoxin (TTX)-sensitive. The fractional availability of CC Nav current has been implicated in regulation of action potential (AP) frequency and the occurrence of slow-wave burst firing. Here, through recordings of Nav current in rat CCs, primarily in adrenal medullary slices, we describe unique inactivation properties of CC Nav inactivation that help define AP firing rates in CCs. The key feature of CC Nav current is that recovery from inactivation, even following brief (5 ms) inactivation steps, exhibits two exponential components of similar amplitude. Various paired pulse protocols show that entry into the fast and slower recovery processes result from largely independent competing inactivation pathways, each of which occurs with similar onset times at depolarizing potentials. Over voltages from -120 to -80 mV, faster recovery varies from ∼3 to 30 ms, while slower recovery varies from ∼50 to 400 ms. With strong depolarization (above -10 mV), the relative entry into slow or fast recovery pathways is similar and independent of voltage. Trains of short depolarizations favor recovery from fast recovery pathways and result in cumulative increases in the slow recovery fraction. Dual-pathway fast inactivation, by promoting use-dependent accumulation in slow recovery pathways, dynamically regulates Nav availability. Consistent with this finding, repetitive AP clamp waveforms at 1-10 Hz frequencies reduce Nav availability 80-90%, depending on holding potential. These results indicate that there are two distinct pathways of fast inactivation, one leading to conventional fast recovery and the other to slower recovery, which together are well-suited to mediate use-dependent changes in Nav availability.


Angioplasty and Stenting for Intracranial Stenosis.
Of the patients enrolled in the Japanese Registry of Neuroendovascular Therapy (JR-NET), a surveillance study in Japanese, 1133 patients who underwent intracranial percutaneous transluminal angioplasty (PTA)/stenting for intracranial stenosis during the period from 2005 to 2009 were investigated. A technical success was achieved in 98.3% of the patients, and 70.5% and 7.5% had a residual stenosis of <30% and ≥50%, respectively. The incidence of ischemic complications and hemorrhagic complications was as low as 7.7% and 2.5%, respectively, but tended to increase in patients who underwent stenting. While a significant correlation with ischemic complications was observed in previously untreated patients and patients who underwent stenting followed by post-dilatation, a significant correlation with hemorrhagic complications was observed in patients who received emergency treatment and those treated between 24 hours and 14 days of the onset. Flexible intracranial stents are expected to contribute to improvement in the treatment outcome.


Magnetic thin-film insulator with ultra-low spin wave damping for coherent nanomagnonics.
Wave control in the solid state has opened new avenues in modern information technology. Surface-acoustic-wave-based devices are found as mass market products in 100 millions of cellular phones. Spin waves (magnons) would offer a boost in today's data handling and security implementations, i.e., image processing and speech recognition. However, nanomagnonic devices realized so far suffer from the relatively short damping length in the metallic ferromagnets amounting to a few 10 micrometers typically. Here we demonstrate that nm-thick YIG films overcome the damping chasm. Using a conventional coplanar waveguide we excite a large series of short-wavelength spin waves (SWs). From the data we estimate a macroscopic of damping length of about 600 micrometers. The intrinsic damping parameter suggests even a record value about 1 mm allowing for magnonics-based nanotechnology with ultra-low damping. In addition, SWs at large wave vector are found to exhibit the non-reciprocal properties relevant for new concepts in nanoscale SW-based logics. We expect our results to provide the basis for coherent data processing with SWs at GHz rates and in large arrays of cellular magnetic arrays, thereby boosting the envisioned image processing and speech recognition.


Mosquito frequency and feeding habits in an enzootic canine dirofilariasis area in Niterói, state of Rio de Janeiro, Brazil.
Heartworm, a chronic fatal mosquito-borne canine disease, is frequently diagnosed in dogs from the State of Rio de Janeiro, where its prevalence is 29.7% in the city of Niterói. Nevertheless it is rarely detected in cats (0.8%) from the same state. Dogs are the primary source of infection to mosquitoes. because cats either do not demonstrate microfilaremia or it is too low and transient for transmission. A mosquito survey was conducted in Itacoatiara, Niterói, from March 1995 to February 1996, using canine, feline and human baits. A total of 21 mosquito species (3,888 females) was collected and biting frequency was higher at dusk. The four species collected most frequently (88.9%) were: Aedes taeniorhynchus (30% of the total catch; with the peak in May/June); Culex quinquefasciatus (22.5%; August/October); Aedes scapularis (19.4%; August, October/November and January) and Culex declarator (17%; November/January). Human baits were attractive to these species and dogs were significantly more attractive to them than cats. Ae. taeniorhynchus, Cx. quinquefasciatus, Ae. scapularis, Cx. declarator and Cx. nigripalpus are the most likely mosquito species to transmit Dirofilaria immitis parasites to dogs and may transit the parasite to humans. It is also suggested that the vector to cats belongs to the games Culex.


Treat Now or Treat Later: Comparative Effectiveness of Adjuvant Therapy in Resected Stage IIIA Melanoma.
Adjuvant therapy for most sentinel-node-positive (stage IIIA) melanoma may have limited clinical benefit for older patients given the competing risk of non-cancer death. The objective of this study is to model the clinical effect and cost of adjuvant therapy in stage IIIA melanoma across age groups. A Markov decision analysis model simulated the overall survival of patients with resected stage IIIA melanoma treated with adjuvant therapy vs observation. In the adjuvant approach, patients are modeled to receive adjuvant pembrolizumab (BRAF wild type) or dabrafenib/trametinib (BRAF mutant). In the observation approach, treatment is deferred until recurrence. Transition variables were derived from landmark randomized trials in adjuvant and salvage therapy. The model was analyzed for age groups spanning 40 to 89 years. The primary outcome was the number needed to treat (NNT) to prevent one melanoma-related death at 10 years. Cost per mortality avoided was estimated using Medicare reimbursement rates. Projections for NNT among BRAF wild type patients increased by age from 14.71 (age 40 to 44) to 142.86 (age 85 to 89), with patients in cohorts over the age of 75 having an NNT over 25. The cost per mortality avoided ranged from $2.75 million (M) (age 40 to 44) to $27.57M (age 85 to 89). Corresponding values for BRAF mutant patients were as follows: NNT 18.18 to 333.33; cost per mortality avoided ranged from $2.75M to $54.70M. Universal adjuvant therapy for stage IIIA melanoma is costly and provides limited clinical benefit in patients older than 75 years.


Caryophyllene Oxide, the Active Compound Isolated from Leaves of Hymenaea courbaril L. (Fabaceae) with Antiproliferative and Apoptotic Effects on PC-3 Androgen-Independent Prostate Cancer Cell Line.
Cancer treatment frequently carries side effects, therefore, the search for new selective and effective molecules is indispensable. Hymenaea courbaril L. has been used in traditional medicine in South America to treat several diseases, including prostate cancer. Leaves' extracts from different polarities were evaluated using the 3-(4,5-methyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) cell viability assay to determine the cytotoxicity in prostate p53-null cells, followed by bio-guided fractionations to obtain the most cytotoxic fraction considering the selectivity index. The most cytotoxic fraction was analyzed by GC/MS to identify the active compounds. The majority compound, caryophyllene oxide, induced early and late apoptosis, depolarized the mitochondrial membrane, leading to several morphological changes and shifts in apoptotic proteins, and caspases were evidenced. Depolarization of the mitochondrial membrane releases the pro-apoptotic protein Bax from Bcl-xL. The apoptosis process is caspase-7 activation-dependent. Caryophyllene oxide is a safe anti-proliferative agent against PC-3 cells, inducing apoptosis with low toxicity towards normal cells.


Integrated electrooptic Bragg modulator modules for matrix-vector and matrix-matrix multiplications.
Successful fabrication of high performance microlenses and microlens arrays using the titanium-indiffusion and proton-exchange technique has enabled realization of a variety of integrated electrooptic Bragg modulator modules in the LiNbO(3) channel-planar composite waveguides of 0.2- x 1.0- x 1.8-cm(3) substrate size. These integrated optic device modules have been utilized successfully to perform matrix-vector and matrix-matrix multiplications. Through the channel-waveguide and the linear microlens arrays, the very large channel capacities that are inherent in the diode laser and the optical fiber as well as the photodotcctor arrays may be conveniently exploited. Consequently, such integrated optic device modules should facilitate realization of multichannel optical computing as well as communication and rf signal processing systems.


Perceptions of Mobile Apps for Smoking Cessation Among Young People in Community Mental Health Care: Qualitative Study.
Young adults with serious mental illness are over twice as likely to have tobacco use disorder than those in the general population and are less likely to utilize proven treatment methods during quit attempts. However, little research has evaluated the efficacy of interventions for this group. Smartphone apps may be an underutilized tool for tobacco use disorder among young adults with serious mental illness. The aim of this study was to explore attitudes toward smoking cessation apps and preferences regarding app design in young adult smokers with serious mental illness. Five focus groups involving 25- to 35-year-old adults with serious mental illness receiving treatment at a community mental health center were conducted between May 2019 and August 2019. Three researchers independently coded transcripts and identified themes using thematic analysis. Participants (n=22) were individuals who smoke daily: 10 (46%) self-identified as female, 18 (82%) self-identified as White, and 9 (41%) had psychotic disorders. Key themes that emerged included a general interest in using health apps; a desire for apps to provide ongoing motivation during a quit attempt via social support, progress tracking, and rewards; a desire for apps to provide distraction from smoking; concerns about app effectiveness due to a lack of external accountability; and concerns that apps could trigger cravings or smoking behavior by mentioning cigarettes or the act of smoking. Apps have the potential to support smoking cessation or reduction efforts among young adults with serious mental illness. However, they may require tailoring, optimization, and clinical support to effectively promote cessation in this population.


Prevalence of abomasal lesions in Danish Holstein cows at the time of slaughter.
Abomasal lesions in cattle are challenging to diagnose because the clinical signs are often subtle and nonspecific. An increasing number of studies suggests that abomasal lesions are commonly found in cattle of all ages, but the number of recent prevalence studies in dairy cows is limited. The main objective of this study was to estimate the prevalence of abomasal lesions in a population of Danish Holstein dairy cattle in Denmark. An abattoir survey of 1,327 dairy cows apparently suitable for slaughter was performed in 2016 and 2017. Abomasal lesions are usually classified using a standardized protocol with the following types: abomasal ulcer type I: erosions and nonperforating ulcers; type II: ulcers with arterial bleeding; type III: perforating ulcer with localized peritonitis; and type IV: perforating ulcer with diffuse peritonitis. A further subdivision of the nonperforating abomasal ulcers type I were classified as subtype Ia: erosions; subtype Ib: small ulcers with localized hemorrhage; subtype Ic: ulcers with a crater-like appearance; and subtype Id: retention of the mucosa due to tissue loss with either radial wrinkles converging at a central point or perforations of the spiral folds. Type I abomasal lesions were found in 84% of the examined cows. No ulcers with arterial bleeding (type II) or perforating ulcers with diffuse peritonitis (type IV) were found, but one perforating abomasal ulcer (type III) was observed. The total number of lesions found was 7,418 and when the lesion subtypes were evaluated individually the majority of subtypes Ia and Ic were found in the pyloric area (85 and 94%, respectively), whereas lesion subtypes Ib and Id dominated the fundus/corpus area (71 and 67%, respectively). When considering lesion subtypes according to parity, there was a high prevalence of subtype Ib across the 3 groups of parity (51, 58, and 55% for parity 1, 2, and ≥3, respectively). The prevalence of lesion subtype Id seemed to increase with increasing parity, and the prevalence of lesion subtype Ia seemed to decrease with increasing parity. The prevalence of abomasal lesions was higher than that shown in similar studies of cattle at the time of slaughter. However, the expectedly most painful cases were rare, with only one perforating and no arterial bleeding ulcers found. The etiology of the different subtype I lesions is still unknown, and further investigations are needed to establish the possible influence these lesions might have on welfare and production.


Browning of Subcutaneous White Adipose Tissue in Humans after Severe Adrenergic Stress.
Since the presence of brown adipose tissue (BAT) was confirmed in adult humans, BAT has become a therapeutic target for obesity and insulin resistance. We examined whether human subcutaneous white adipose tissue (sWAT) can adopt a BAT-like phenotype using a clinical model of prolonged and severe adrenergic stress. sWAT samples were collected from severely burned and healthy individuals. A subset of burn victims were prospectively followed during their acute hospitalization. Browning of sWAT was determined by the presence of multilocular adipocytes, uncoupling protein 1 (UCP1), and increased mitochondrial density and respiratory capacity. Multilocular UCP1-positive adipocytes were found in sWAT samples from burn patients. UCP1 mRNA, mitochondrial density, and leak respiratory capacity in sWAT increased after burn trauma. Our data demonstrate that human sWAT can transform from an energy-storing to an energy-dissipating tissue, which opens new research avenues in our quest to prevent and treat obesity and its metabolic complications.


The Structural Properties of Major White Matter Tracts in Strabismic Amblyopia.
In order to better understand whether white matter structural deficits are present in strabismic amblyopia, we performed a survey of the tissue properties of 28 major white matter tracts using diffusion and quantitative magnetic resonance imaging approaches. We used diffusion-based tensor modeling and a new quantitative T1 protocol to measure fractional anisotropy (FA), mean diffusivity (MD), and myelin-sensitive T1 values. We surveyed tracts in the occipital lobe, including the vertical occipital fasciculus (VOF)-a newly rediscovered tract that bridges dorsal and ventral areas of the occipital lobe, as well as tracts across the rest of the brain. Adults with long-standing strabismic amblyopia show tract-specific elevations in MD. We rank-ordered the tracts on the basis of their MD effect-size. The four most affected tracts were the anterior frontal corpus callosum (ACC), the right VOF, the left inferior longitudinal fasciculus (ILF) and the left optic radiation. The results suggest that most white matter tissue properties are relatively robust to the early visual insult caused by strabismus. However, strabismic amblyopia does affect MD, not only in occipital tracts, such as the VOF and optic radiation, but also in long range association tracts connecting visual cortex to the frontal and temporal lobes (ILF) and connecting the two hemispheres (ACC).


Smith-Magenis syndrome and Moyamoya disease in a patient with del(17)(p11.2p13.1).
Chromosomal rearrangements causing microdeletions and microduplications are a major cause of congenital malformation and mental retardation. Because they are not visible by routine chromosome analysis, high resolution whole-genome technologies are required for the detection and diagnosis of small chromosomal abnormalities. Recently, array-comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) have been useful tools for the identification and mapping of deletions and duplications at higher resolution and throughput. Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation syndrome caused by deletion or mutation of the retinoic acid induced 1 (RAI1) gene and is often associated with a chromosome 17p11.2 deletion. We report here on the clinical and molecular analysis of a 10-year-old girl with SMS and moyamoya disease (occlusion of the circle of Willis). We have employed a combination of aCGH, FISH, and MLPA to characterize an approximately 6.3 Mb deletion spanning chromosome region 17p11.2-p13.1 in this patient, with the proximal breakpoint within the RAI1 gene. Further, investigation of the genomic architecture at the breakpoint intervals of this large deletion documented the presence of palindromic repeat elements that could potentially form recombination substrates leading to unequal crossover.


Cardiac impairment in rabbits fed a high-fat diet is counteracted by dehydroepiandrosterone supplementation.
The biochemical and structural cardiac oxidative-dependent damage induced by high-fat (HF) diet was examined in a rabbit model, together with the role of dehydroepiandrosterone (DHEA) in contrasting tissue damage. New Zealand white rabbits fed a HF diet supplemented or not with DHEA (0.02%) were utilized for 12 weeks. Oxidative stress, inflammatory and necrosis parameters, fatty deposition, heavy-chain myosin isoforms (MHC) expression and papillary muscle functionality were examined in the left ventricle of rabbits. Rabbits fed a HF diet that showed hyperglycemia, insulin resistance and dyslipidemia together with increase of oxidative stress and of advanced end-glycation product levels have been observed. Concerning pro-inflammatory insults, there was increased p65-NFkB activation and increased tumor necrosis factor-alpha and C-reactive protein expressions. Cellular damage induced by the HF diet was detected through the switch of expression of MHC isoforms, indicating impairment of cardiac contractility, confirmed by altered of basal parameters of papillary muscle functionality. Rabbits fed the HF diet supplemented with DHEA showed a partial reduction of oxidative stress and the inflammatory state. Cardiac necrosis, the shift of MHC isoforms, and cardiac functionality, were also partially counteracted. Rabbits fed with a HF diet showed a beneficial effect when low-dose DHEA was added to the diet. The steroid, without affecting high plasma glucose level or insulin resistance, restored oxidative balance, lowered lipid levels and inflammation insults, preventing cellular and functional alterations of cardiac tissue and thus delaying the onset of cardiac damage.


Activation of a plant nucleotide binding-leucine rich repeat disease resistance protein by a modified self protein.
Nucleotide binding-leucine rich repeat (NB-LRR) proteins function as intracellular receptors for the detection of pathogens in both plants and animals. Despite their central role in innate immunity, the molecular mechanisms that govern NB-LRR activation are poorly understood. The Arabidopsis NB-LRR protein RPS5 detects the presence of the Pseudomonas syringae effector protein AvrPphB by monitoring the status of the Arabidopsis protein kinase PBS1. AvrPphB is a cysteine protease that targets PBS1 for cleavage at a single site within the activation loop of PBS1. Using a transient expression system in the plant Nicotiana benthamiana and stable transgenic Arabidopsis plants we found that both PBS1 cleavage products are required to activate RPS5 and can do so in the absence of AvrPphB. We also found, however, that the requirement for cleavage of PBS1 could be bypassed simply by inserting five amino acids at the PBS1 cleavage site, which is located at the apex of the activation loop of PBS1. Activation of RPS5 did not require PBS1 kinase function, and thus RPS5 appears to sense a subtle conformational change in PBS1, rather than cleavage. This finding suggests that NB-LRR proteins may function as fine-tuned sensors of alterations in the structures of effector targets.


Cytotoxic and antibacterial effect of a red propolis mouthwash, with or without fluoride, on the growth of a cariogenic biofilm.
To evaluatein vitro the antibacterial activity, the antibiofilm effect and the cytotoxic potential of mouthwashes containing Brazilian red propolis with or without fluoride. The minimum inhibitory and bactericidal concentrations (MIC and MBC) against S. mutans, S. sanguinis, S. salivarius and L. casei were determined for RPE mouthwashes. A cariogenic biofilm with the aforementioned bacteria was formed over cellulose membrane disks (N = 30, 13 mm), which were submitted for 1 min to the following mouthwashes: plain mouthwash base; 0.05% NaF; 0.8% RPE; 0.8% RPE + 0.05% NaF and 0.12% chlorhexidine (CHX). The bacterial viability and the production of extracellular polysaccharide (EPS) were measured. Cytotoxic potential of the mouthwashes was also evaluated. For bacterial viability and EPS production, Mann-Withney and one-way ANOVA tests were performed followed by Tukey, with results considered significant when p ≤ 0.05. MIC and MBC values of RPE mouthwashes ranged from 7.44 to 29.76 mg/mL and from 7.44 to ≥59.52 mg/mL, respectively, presenting better action against S. salivarius. RPE mouthwashes showed 44% of viable cells after 1 min of contact with fibroblasts. RPE (7.74) had the greatest reduction of viable total microorganisms and did not differ from the RPE + NaF (7.95) (p = 0.292). CHX (7.54) was the most effective in reducing Streptococcus spp, but did not differ from RPE (p = 0.521) and RPE + NaF (p = 0.238). There was no difference between the treatments regarding EPS production. RPE and RPE + NaF mouthwash showed similar antibacterial activity, toxicity level and antibiofilm effect compared to CHX.


Prevalence of deep venous thrombosis among patients in medical intensive care.
OBJECTIVE--To determine the frequency of deep venous thrombosis (DVT) in medical intensive care unit (MICU) patients. DESIGN--Prospective ultrasound case series. SETTING--An MICU in a large tertiary care hospital in Boston, Mass. SUBJECTS--Patients older than 18 years of age admitted to the MICU with an anticipated stay of more than 48 hours. MAIN OUTCOME MEASURE--Deep venous thrombosis as detected by ultrasonography with color Doppler imaging performed twice weekly in the MICU and once within 1 week of discharge from the MICU. RESULTS--Deep venous thrombosis was detected in 33% (95% confidence interval, 24% to 43%) of 100 eligible patients during the 8-month study period. Forty-eight percent (16/33) were proximal lower extremity DVT, and 15% (5/33) were upper extremity DVT associated with central venous catheters, with one patient having both upper and proximal lower extremity DVT. Ultrasound examination results led to inferior vena cava filter placement in three patients, initiation of full-dose anticoagulation in four patients, initiation or continuation of low-dose subcutaneous heparin in 10 patients, follow-up ultrasound studies in three patients, central line removal in one patient, and no intervention in 10 patients due to active bleeding, prior filter, or heparin-induced thrombocytopenia. Two patients remained anticoagulated for other reasons. In this series, there was no difference in age, gender, body mass index, diagnosis of cancer, recent surgery, duration of hospitalization prior to DVT detection, and DVT prophylaxis between patients with DVT and those without. CONCLUSIONS--An unexpectedly high rate of DVT was detected by ultrasound in these MICU patients despite prophylaxis in 61%. Traditionally recognized DVT risk factors failed to identify patients who developed DVT. Routine ultrasound surveillance or more intensive prophylaxis regimens may be warranted in this patient population if these DVT rates are confirmed in other settings.


Regulation of immature cartilage growth by IGF-I, TGF-beta1, BMP-7, and PDGF-AB: role of metabolic balance between fixed charge and collagen network.
Cartilage growth may involve alterations in the balance between the swelling tendency of proteoglycans and the restraining function of the collagen network. Growth factors, including IGF-I, TGF-beta1, BMP-7, and PDGF-AB, regulate chondrocyte metabolism and, consequently, may regulate cartilage growth. Immature bovine articular cartilage explants from the superficial and middle zones were incubated for 13 days in basal medium or medium supplemented with serum, IGF-I, TGF-beta1, BMP-7, or PDGF-AB. Variations in tissue size, accumulation of proteoglycan and collagen, and tensile properties were assessed. The inclusion of serum, IGF-I, or BMP-7 resulted in expansive tissue growth, stimulation of proteoglycan deposition but not of collagen, and a diminution of tensile integrity. The regulation of cartilage metabolism by TGF-beta1 resulted in tissue homeostasis, with maintenance of size, composition, and function. Incubation in basal medium or with PDGF-AB resulted in small volumetric and compositional changes, but a marked decrease in tensile integrity. These results demonstrate that the phenotype of cartilage growth, and the associated balance between proteoglycan content and integrity of the collagen network, is regulated differentially by certain growth factors.


Mitochondrial and nuclear DNA phylogeography of European grayling (Thymallus thymallus): evidence for secondary contact zones in central Europe.
Mitochondrial and microsatellite DNA markers were applied to infer the phylogeography, intraspecific diversity and dynamics of the distributional history of European grayling (Thymallus thymallus) with focus on its central and northern European distribution range. Phylogenetic and nested clade analyses revealed at least four major mtDNA lineages, which evolved in geographical isolation during the Pleistocene. These lineages should be recognized as the basic evolutionary significant units (ESUs) for grayling in central and northern Europe. In addition, and in contrast to previous work on grayling, the results of Bayesian analysis of individual admixture coefficients, two-dimensional scaling analysis and spatial analysis of molecular variance provided evidence for a high level of admixture among major lineages in contact zones between drainages (e.g. the low mountain range of Germany), most likely resulting from glacial perturbations and ancient river connections between drainages during the Pleistocene glaciations. Even within river systems, a high level of differentiation among populations was revealed as indicated by the microsatellite data. Grayling sampled from 29 sites displayed high levels of differentiation (overall F(ST) = 0.367), a high number of private alleles and high bootstrap support for the genetic distance-based population clusters across 12 loci. We specifically discuss our results in context of phylogeograpic studies on other European freshwater fish species with habitat preferences similar to those of grayling. Our study shows that both large-scale phylogeographical and detailed genetic analyses on a fine scale are mandatory for developing appropriate conservation guidelines of endangered species.


The effects of dimethyl sulfoxide and retinoic acid on the cell growth and the phenotype of ovarian cancer cells.
We have compared the in vitro effects of the differentiation inducers dimethyl sulfoxide (DMSO) and retinoic acid (RA) on a polyclonal human ovarian cancer cell line (HOC-7). Density gradient fractionation of untreated cells reveals that a proportion of rapidly growing, polygonal cells with medium density is capable of spontaneous reversion into a slowly growing low-density phenotype with flattened morphology similar to non-transformed human ovarian surface epithelial cells. Clonal expansion of these low-density cells proves that the observed characteristics are stable for prolonged culture periods. Exposure of HOC-7 cells to DMSO and RA or removal of the serum from the medium is effective in enhancing the proportion of these low-density cells. Application of DMSO causes the cells to become flattened and elongated, and to develop rod-like protrusions. In these cytoplasmic extensions thick filament bundles are dominant. Immunofluorescence studies demonstrate that both untreated low-density subclones and DMSO-treated polyclonal cells are much more reactive for cytokeratin than medium-density subclones or untreated parental cells. Furthermore, immunocytochemistry and fixed-cell ELISA reveal 2- to 5-fold greater amounts of desmoplakins I and II and of fibronectin in low-density subclones and in DMSO-treated cells as compared to medium-density subclones and control cultures. RA exerts weaker effects on the phenotype of the cells. Both inducers reduce DNA synthesis and inhibit the anchorage-dependent and the anchorage-independent cell growth in a dose- and time-dependent manner. The restoration of the original morphology and growth rate after removal of the differentiation-inducing agents proves that the observed changes are reversible; this indicates that the cells do not become terminally differentiated.(ABSTRACT TRUNCATED AT 250 WORDS)


Blood meal enhanced onchocerca development and its correlation with fecundity in laboratory reared blackflies (Diptera, Simuliidae).
Simulium ornatum s.l. is a natural vector of Onchocerca lienalis in Britain. These studies investigated the role of the blood meal on the development of the parasite in the thoracic musculature. Infection was by the standard technique of intrathoracic injection, allowing precise doses of microfilariae to be administered. Prior to infection flies were fed on bovine blood through a chick skin membrane. In 3 trials the number of O. lienalis larvae developing in non-blood fed flies was between 60.2 and 68.4% lower than in blood fed insects. The mean number of eggs recovered per fly ranged from 131.7 to 187.5 in infected groups. In uninfected control groups the levels ranged from 315.4 to 378.1 per fly. This represents reductions in fecundity of between 50.4 and 51.7% in infected groups of simuliids. It appears that in order to maintain relatively high levels of transmission an intermediate blood meal, between uptake of microfilariae and release of infective stage larvae, may be important. Furthermore, great care must be taken when using fecundity to assess the age of simuliids. Levels of parasitic infection may affect egg production to a much greater extent.


Aging, abstinence, and medical risk factors in the prediction of neuropsychologic deficit among long-term alcoholics.
Halstead-Reitan assessments were conducted with 71 male alcoholics sober for four weeks, 65 alcoholics sober for four years, and 68 nonalcoholics. Recently detoxified alcoholics showed learning and problem-solving difficulties, as did older persons in all groups. Aging, not alcoholism, was related to psychomotor slowing. There were no age-alcohol interactions for any neuropsychologic test. Time since last drink predicted neuropsychologic performance modestly, as did head injury, age, and education. Long-term sober alcoholics were indistinguishable from controls. Our results suggest that alcoholics abstinent one month suffer a subacute alcohol-related organic mental disorder that might resolve with prolonged abstinence, that the neuropsychologic findings in such alcoholics are more consistent with an "independent decrements" rather than "premature aging" hypothesis, and that neuromedical and other risk factors must be considered before permanent neuropsychologic deficit among alcoholics can be attributed solely to neurotoxic effects of alcohol.


Risk in Relatives, Heritability, SNP-Based Heritability, and Genetic Correlations in Psychiatric Disorders: A Review.
The genetic contribution to psychiatric disorders is observed through the increased rates of disorders in the relatives of those diagnosed with disorders. These increased rates are observed to be nonspecific; for example, children of those with schizophrenia have increased rates of schizophrenia but also a broad range of other psychiatric diagnoses. While many factors contribute to risk, epidemiological evidence suggests that the genetic contribution carries the highest risk burden. The patterns of inheritance are consistent with a polygenic architecture of many contributing risk loci. The genetic studies of the past decade have provided empirical evidence identifying thousands of DNA variants associated with psychiatric disorders. Here, we describe how these latest results are consistent with observations from epidemiology. We provide an R tool (CHARRGe) to calculate genetic parameters from epidemiological parameters and vice versa. We discuss how the single nucleotide polymorphism-based estimates of heritability and genetic correlation relate to those estimated from family records.


Prevalence of type 2 diabetes in psychiatric disorders: an umbrella review with meta-analysis of 245 observational studies from 32 systematic reviews.
Estimates of the global prevalence of type 2 diabetes vary between 6% and 9%. The prevalence of type 2 diabetes has been investigated in psychiatric populations but a critical appraisal of the existing evidence is lacking, and an overview is needed. This umbrella review summarises existing systematic reviews of observational studies investigating the prevalence of type 2 diabetes in people with a psychiatric disorder. We searched PubMed, EMBASE, PsycINFO and the Cochrane Database of Systematic Reviews from inception to 17 January 2021 and screened reference lists of included systematic reviews. On the basis of prespecified criteria, we included systematic reviews investigating the prevalence of type 2 diabetes in adults (aged ≥18 years) with a psychiatric disorder. Titles and abstracts of 5155 identified records and full texts of 431 selected studies were screened by two independent reviewers, based on predefined eligibility criteria and an a priori developed extraction form, following the PRISMA and MOOSE guidelines. Risk of bias was assessed with the ROBIS instrument. Data extracted from primary studies were synthesised using random-effects meta-analyses. A total of 32 systematic reviews with 245 unique primary studies were identified and met inclusion criteria. Twelve had low risk of bias. They reported type 2 diabetes prevalence estimates ranging from 5% to 22% depending on the specific psychiatric disorder. We meta-analysed data for ten categories of psychiatric disorders and found the following prevalence estimates of type 2 diabetes: in people with a sleep disorder: 40%; binge eating disorder: 21%; substance use disorder: 16%; anxiety disorder: 14%; bipolar disorder: 11%; psychosis: 11%; schizophrenia: 10%; a mixed group of psychiatric disorders: 10%; depression: 9%; and in people with an intellectual disability 8%. All meta-analyses revealed high levels of heterogeneity. Type 2 diabetes is a common comorbidity in people with a psychiatric disorder. Future research should investigate whether routine screening for type 2 diabetes and subsequent prevention initiatives for these people are warranted. PROSPERO registration no. CRD42020159870.


[Serum antibodies against corneal and internal ear tissues in Cogan's syndrome].
Using the indirect immunofluorescence technique, IgG and IgA antibodies against human cornea and IgG antibodies against human inner ear tissue (stria vascularis, Reissner's membrane, spiral ligament, dark cell area) were demonstrated in the serum of a patient with cogan's syndrome. Sera of controls (healthy individuals) did not show positive reactions. Additionally the serum of two patients suffering from "idiopathic" progressive sensorineural hearing loss contained antibodies (IgG) which reacted with human inner ear tissue only but not with human cornea. A possible autoimmune mechanism in Cogan's syndrome is discussed.


Mitochondrial Calcium Regulation of Redox Signaling in Cancer.
Calcium (Ca2+) uptake into the mitochondria shapes cellular Ca2+ signals and acts as a key effector for ATP generation. In addition, mitochondria-derived reactive oxygen species (mROS), produced as a consequence of ATP synthesis at the electron transport chain (ETC), modulate cellular signaling pathways that contribute to many cellular processes. Cancer cells modulate mitochondrial Ca2+ ([Ca2+]m) homeostasis by altering the expression and function of mitochondrial Ca2+ channels and transporters required for the uptake and extrusion of mitochondrial Ca2+. Regulated elevations in [Ca2+]m are required for the activity of several mitochondrial enzymes, and this in turn regulates metabolic flux, mitochondrial ETC function and mROS generation. Alterations in both [Ca2+]m and mROS are hallmarks of many tumors, and elevated mROS is a known driver of pro-tumorigenic redox signaling, resulting in the activation of pathways implicated in cellular proliferation, metabolic alterations and stress-adaptations. In this review, we highlight recent studies that demonstrate the interplay between [Ca2+]m and mROS signaling in cancer.


CRITICAL FREQUENCY OF FLICKER AS A FUNCTION OF INTENSITY OF ILLUMINATION FOR THE EYE OF THE BEE.
The bee's characteristic response to a movement of its visual field is used for the study of the relation between critical frequency of flicker and illumination. The critical flicker frequency varies with illumination in such a way that with increasing flicker frequency the intensity of illumination must be increased to produce a threshold response in the bee. The illuminations required to give a response in a bee at different flicker frequencies closely correspond to the intensities for threshold response in visual acuity tests. This is due to the different thresholds of excitability of the elements of the ommatidial mosaic. An analysis of the variation of the values for threshold intensities at the several flicker frequencies shows that the variation depends upon flicker frequency and upon the number of elements functioning at different intensities.


Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents.
Berberis aristata is an edible plant employed in the South Asian Traditional Medicine, particularly its fruits being used as a tonic remedy for liver and heart. In this investigation, berberine, a known compound from this plant, was studied for its possible antihepatotoxic action in rats. Pretreatment of animals with berberine (4 mg/kg; orally twice daily for 2 days) prevented the acetaminophen- or CCl4-induced rise in serum levels of alkaline phosphatase (ALP) and aminotransaminases (AST and ALT), suggestive of hepatoprotection. Post-treatment with three successive oral doses of berberine (4 mg/kg every 6 h) reduced the hepatic damage induced by acetaminophen, while CCl4-induced hepatotoxicity was not modified, suggesting a selective curative effect against acetaminophen. Pretreatment of animals with a single oral dose of berberine (4 mg/kg) induced prolongation of the pentobarbital (60 mg/kg, i.p.)-induced sleeping time as well as increased strychnine (0.3 mg/kg; i.p.)-induced toxicity, suggestive of inhibitory effect on microsomal drug metabolizing enzymes, cytochrome P450s (CYPs).


Dual Phase Synergy Enabled Large Elastic Strains of Nanoinclusions in a Dislocation Slip Matrix Composite.
Freestanding nanomaterials (such as nanowires, nanoribbons, and nanotubes) are known to exhibit ultralarge elastic strains and ultrahigh strengths. However, harnessing their superior intrinsic mechanical properties in bulk composites has proven to be difficult. A recent breakthrough has overcome this difficulty by using a martensitic phase transforming matrix in which ultralarge elastic strains approaching the theoretical limit is achieved in Nb nanowires embedded in the matrix. This discovery, breaking a long-standing challenge, still limits our ability of harnessing the exceptional properties of nanomaterials and developing ultrahigh strength bulk materials to a narrow selection of phase transforming alloy matrices. In this study, we investigated the possibility to harness the intrinsic mechanical properties of nanoinclusions in conventional dislocation slip matrix based on a principle of synergy between the inclusion and the matrix. The small spacing between the densely populated hard and dislocation-impenetrable nanoinclusions departmentalize the plastic matrix into small domains to effectively impede dislocation motion within the matrix, inducing significant strengthening and large local elastic strains of the matrix, which in turn induced large elastic strains in the nanoinclusions. This dual phase synergy is verified in a Ti3Sn inclusions/B2-NiTi(Fe) plastic matrix model materials system. The maximum elastic strain of Ti3Sn inclusion obtained in the dislocation slip matrix is comparable to that achieved in a phase transforming matrix. This finding opens new opportunities for the development of high-strength nanocomposites.


Ventricular arrhythmias during the first year after acute myocardial infarction: influence of long-term treatment with metoprolol.
Three hundred and one patients who had been hospitalized for acute myocardial infarction, were less than 70 years old, were in sinus rhythm, and did not have complete bundle branch block were stratified before discharge according to age, size of infarction, and type of ventricular arrhythmias as determined on a 6 hr electrocardiogram (ECG). They were thereafter randomly assigned to double-blind treatment with 100 mg bid metoprolol or placebo. Repeat 6 hr ECGs were recorded 3 days and 1, 6, and 12 months after treatment had begun. In the placebo group there was a significant increase in the proportion of patients with complex premature ventricular complexes (PVCs) (i.e., multiform, paired and R-on-T PVCs, or ventricular tachycardia) as well as increased numbers of PVCs in the patients during the follow-up. In contrast, an initial decrease in the number of PVCs (p less than .001) was found in the metoprolol group, whereas the complexity of PVCs was constant in those patients who continued on metoprolol therapy throughout the follow-up period. We conclude that the increase in complexity and number of PVCs that is part of the natural clinical course after myocardial infarction is counteracted by long-term treatment with metoprolol.


Comparison of incremental and constant load tests of inspiratory muscle endurance in COPD.
The aim of the present study was to determine the relative value of incremental and constant load tests in detecting changes in inspiratory muscle endurance following high-intensity inspiratory muscle training (H-IMT) in chronic obstructive pulmonary disease. In total, 16 subjects (11 males; forced expiratory volume in one second (FEV(1)) 37.4+/-12.5%) underwent H-IMT. In addition, 17 subjects (11 males; FEV(1) 36.5+/-11.5%) underwent sham inspiratory muscle training (S-IMT). Training took place three times a week for 8 weeks. Baseline and post-training measurements were obtained of maximum threshold pressure sustained during an incremental load test (P(th,max)) and time breathing against a constant load (t(lim)). Breathing pattern was unconstrained. H-IMT increased P(th,max) and t(lim) relative to baseline and to any change seen following S-IMT. The effect size for P(th,max) was greater than for t(lim). Post-training tests were accompanied by changes in breathing pattern, including decreased duty cycle, which may have served to decrease inspiratory work and thereby contribute to the increase in P(th,max) and t(lim) in both groups. When assessing inspiratory muscle function in chronic obstructive pulmonary disease via tests in which the pattern of breathing is unconstrained, the current authors recommend incremental load tests be used in preference to constant load tests. However, to attribute changes in these tests to improvements in inspiratory muscle endurance, breathing pattern should be controlled.


Does recycling in germinal centres exist?
A general criterion is formulated to decide if the recycling of B cells exists in germinal centre (GC) reactions. The criterion is independent of the selection and affinity maturation process and based solely on total centroblast population arguments. An experimental test is proposed to verify whether the criterion is fulfilled.


Protective efficacy in mice of post-exposure vaccination with vaccinia virus recombinant expressing either rabies virus glycoprotein or nucleoprotein.
Mice vaccinated intraperitoneally (i.p.) with 10(7) p.f.u. of a vaccinia virus recombinant expressing either the glycoprotein (rVac-G) or nucleoprotein (rVac-N) of rabies virus 3 weeks before challenge were protected against peripheral lethal infection. Similarly, by post-exposure vaccination in which mice were first infected with rabies virus and subsequently vaccinated i.p. with the recombinant, rVac-G conferred protection when given immediately following infection and up to 24 h after infection. Prior treatment of those mice with anti-CD8 monoclonal antibodies (MAb) did not significantly affect the outcome of the infection. In contrast, rVac-N failed to confer protection even with higher doses (10(8) p.f.u.) of the virus or even when administered by the intradermal route. Anti-nucleoprotein antibody production by these mice was not suppressed by prior rabies virus infection and the levels and the time of antibody production were similar to those of anti-glycoprotein antibody production in mice vaccinated with rVac-G after rabies virus infection. The cytotoxic T lymphocyte response was also not down-regulated by rabies virus in the mice that were given rVac-N. Possible mechanism(s) for the ineffectiveness of rVac-N by post-exposure vaccination in contrast to pre-exposure vaccination was discussed.


Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus.
Rhinoviruses are the major trigger of acute asthma exacerbations and asthmatic subjects are more susceptible to these infections. To investigate the underlying mechanisms of this increased susceptibility, we examined virus replication and innate responses to rhinovirus (RV)-16 infection of primary bronchial epithelial cells from asthmatic and healthy control subjects. Viral RNA expression and late virus release into supernatant was increased 50- and 7-fold, respectively in asthmatic cells compared with healthy controls. Virus infection induced late cell lysis in asthmatic cells but not in normal cells. Examination of the early cellular response to infection revealed impairment of virus induced caspase 3/7 activity and of apoptotic responses in the asthmatic cultures. Inhibition of apoptosis in normal cultures resulted in enhanced viral yield, comparable to that seen in infected asthmatic cultures. Examination of early innate immune responses revealed profound impairment of virus-induced interferon-beta mRNA expression in asthmatic cultures and they produced >2.5 times less interferon-beta protein. In infected asthmatic cells, exogenous interferon-beta induced apoptosis and reduced virus replication, demonstrating a causal link between deficient interferon-beta, impaired apoptosis and increased virus replication. These data suggest a novel use for type I interferons in the treatment or prevention of virus-induced asthma exacerbations.


The susceptibility of trypanosomatid pathogens to PI3/mTOR kinase inhibitors affords a new opportunity for drug repurposing.
Target repurposing utilizes knowledge of "druggable" targets obtained in one organism and exploits this information to pursue new potential drug targets in other organisms. Here we describe such studies to evaluate whether inhibitors targeting the kinase domain of the mammalian Target of Rapamycin (mTOR) and human phosphoinositide-3-kinases (PI3Ks) show promise against the kinetoplastid parasites Trypanosoma brucei, T. cruzi, Leishmania major, and L. donovani. The genomes of trypanosomatids encode at least 12 proteins belonging to the PI3K protein superfamily, some of which are unique to parasites. Moreover, the shared PI3Ks differ greatly in sequence from those of the human host, thereby providing opportunities for selective inhibition. We focused on 8 inhibitors targeting mTOR and/or PI3Ks selected from various stages of pre-clinical and clinical development, and tested them against in vitro parasite cultures and in vivo models of infection. Several inhibitors showed micromolar or better efficacy against these organisms in culture. One compound, NVP-BEZ235, displayed sub-nanomolar potency, efficacy against cultured parasites, and an ability to clear parasitemia in an animal model of T. brucei rhodesiense infection. These studies strongly suggest that mammalian PI3/TOR kinase inhibitors are a productive starting point for anti-trypanosomal drug discovery. Our data suggest that NVP-BEZ235, an advanced clinical candidate against solid tumors, merits further investigation as an agent for treating African sleeping sickness.


[Transient hyperglycemia in acute myocardial infarct: the short- and long-term risk factor for mortality].
To evaluate the prevalence and prognostic significance of hyperglycemia in acute myocardial infarction, we studied 700 patients (mean age 63.3 +/- 10.97) subsequently admitted to the UCIC of Tradate Hospital during the period January 1976 to December 1987. Patients were followed up for a median period of four years. On the basis of fasting blood glycaemia values in the first five days of hospitalization, excluding the admission day, patients were divided into groups: 401 patients (57.0%) with constantly normal glycaemia; 84 patients (12.0%) with glycaemia equal or superior to 120 mg/100 ml, and with subsequent normalization; and 215 patients (31.0%) with diabetes mellitus diagnosed before hospitalization and/or with persistent hyperglycaemia. The overall mortality was 284 (40.5%) and cardiovascular deaths were 90.8%. Within the first month of myocardial infarction 98 patients died. The mortality rate was 9.4% in normoglycaemic patients and 20.2% in transient hyperglycaemic patients, similar to the value observed in diabetic patients (20.0%). During the follow-up 186 patients died. Late mortality after the first month is higher in diabetic patients (40%) and patients with transient hyperglycaemia (37%) compared to normoglycaemic patients (25.3%). Multivariate analysis shows that independent predictive variables are: for mortality in the first month, Killip class only; and after the first month, Killip class, metabolic classification, sex and supraventricular arrhythmias. The present study shows that transient hyperglycaemia has a low prevalence in the first days of acute myocardial infarction. Transient hyperglycaemia could be attributed not only to increased sympathetic tone elicited by acute myocardial infarction, but is probably a pathologic condition with an adverse outcome to which multiple factors contribute.


Metal-Organic Frameworks Based Nano/Micro/Millimeter-Sized Self-Propelled Autonomous Machines.
Synthetic nano/micro/millimeter-sized machines that harvest energy from the surrounding environment and then convert it to motion have had a significant impact on many research areas such as biology (sensing, imaging, and therapy) and environmental applications. Autonomous motion is a key element of these devices. A high surface area is preferable as it leads to increased propellant or cargo-loading capability. Integrating highly ordered and porous metal-organic frameworks (MOFs) with self-propelled machines is demonstrated to have a significant impact on the field of nano/micro/millimeter-sized devices for a wide range of applications. MOFs have shown great potential in many research fields due to their tailorable pore size. These fields include energy storage and conversion; catalysis, biomedical application (e.g., drug delivery, imaging, and cancer therapy), and environmental remediation. The marriage of motors and MOFs may provide opportunities for many new applications for synthetic nano/micro/millimeter-sized machines. Herein, MOF-based micro- and nanomachines are reviewed with a focus on the specific properties of MOFs.


Prognostic Significance of Short-Term Blood Pressure Variability in Acute Stroke: Systematic Review.
Blood pressure variability (BPV) may be an important prognostic factor acutely after stroke. This review investigated the existing evidence for the effect of BPV on outcome after stroke, also considering BPV measurement techniques and definitions. A literature search was performed according to a prespecified study protocol. Two reviewers independently assessed study eligibility and quality. Where appropriate, meta-analyses were performed to assess the effect of BPV on poor functional outcome. Eighteen studies from 1359 identified citations were included. Seven studies were included in a meta-analysis for the effect of BPV on functional outcome (death or disability). Systolic BPV was significantly associated with poor functional outcome: pooled odds ratio per 10-mm Hg increment, 1.2; confidence interval (1.1-1.3). A descriptive review of included studies also supports these findings, and in addition, it suggests that systolic BPV may be associated with increased risk of intracranial hemorrhage in those treated with thrombolytic therapy. This systematic review and meta-analysis suggest that greater systolic BPV, measured early from ischemic stroke or intracerebral hemorrhage onset, is associated with poor longer-term functional outcome. Future prospective studies should investigate how best to measure and define BPV in acute stroke, as well as to determine its prognostic significance.


The effect of saponins from Ampelozizyphus amazonicus Ducke on the renal Na+ pumps' activities and urinary excretion of natriuretic peptides.
In a previous study, we showed that a saponin mixture isolated from the roots of Ampelozizyphus amazonicus Ducke (SAPAaD) reduces urine excretion in rats that were given an oral loading of 0.9 % NaCl (4 ml/100 g body weight). In the present study, we investigated whether atrial natriuretic peptides (ANP) and renal ATPases play a role in the SAPAaD- induced antidiuresis in rats. To evaluate the effect of SAPAaD on furosemide-induced diuresis, Wistar rats (250-300 g) were given an oral loading of physiological solution (0.9 % NaCl, 4 ml/100 g body weight) to impose a uniform water and salt state. The solution containing furosemide (Furo, 13 mg/kg) was given 30 min after rats were orally treated with 50 mg/kg SAPAaD (SAPAaD + Furo) or 0.5 ml of 0.9 % NaCl (NaCl + Furo). In the SAPAaD + NaCl group, rats were pretreated with SAPAaD and 30 min later they received the oral loading of physiological solution. Animals were individually housed in metabolic cages, and urine volume was measured every 30 min throughout the experiment (3 h). To investigate the role of ANP and renal Na(+) pumps on antidiuretic effects promoted by SAPAaD, rats were given the physiological solution (as above) containing SAPAaD (50 mg/kg). After 90 min, samples of urine and blood from the last 30 min were collected. Kidneys and atria were also removed after previous anesthesia. ANP was measured by radioimmunoassay (RIA) and renal cortical activities of Na(+)- and (Na(+),K(+))-ATPases were calculated from the difference between the [32P] Pi released in the absence and presence of 1 mM furosemide/2 mM ouabain and in the absence and presence of 1 mM ouabain, respectively. It was observed that SAPAaD inhibited furosemide-induced diuresis (at 90 min: from 10.0 ± 1.0 mL, NaCl + Furo group, n = 5, to 5.9 ± 1.0 mL, SAPAaD + Furo group n = 5, p < 0.05), increased both Na(+)-ATPase (from 25.0 ± 5.9 nmol Pi.mg(-1).min(-1), control, to 52.7 ± 8.9 nmol Pi.mg(-1).min(-1), p < 0.05) and (Na(+),K(+))-ATPase (from 47.8 ± 13.3 nmol Pi.mg(-1).min(-1), control, to 79.8 ± 6.9 nmol Pi .mg(-1).min(-1), p < 0.05) activities in the renal cortex. SAPAaD also lowered urine ANP (from 792 ± 132 pg/mL, control, to 299 ± 88 pg/mL, p < 0.01) and had no effect on plasma or atrial ANP. We concluded that the SAPAaD antidiuretic effect may be due to an increase in the renal activities of Na(+)- and (Na(+),K(+))-ATPases and/or a decrease in the renal ANP.


The role of nurse practitioners in primary healthcare.
The employment of more nurse practitioners (NPs) is one of the most promising ways to expand the capacity of medical group practices. The objective of this study was to determine the association of NPs with patient-level cost and quality of care. Eighty-five primary care medical group practices were matched with 315,000 Medicare patients. Per beneficiary per year total costs and quality of care were calculated from Medicare claims data. Data were analyzed using multivariate regression analysis. A national sample of primary care medical group practices based on responses to the 2009 Medical Group Management Association Performance Survey. The cost variable was annual risk-adjusted Medicare expenditures per capita for patients attributed to a practice. There were 5 quality of care measures. Employing NPs in primary care practices is associated with increased risk-adjusted patient cost for up to 1 NP for every 2 physicians, but cost decreases as the number of NPs per physician increases. There was little evidence of systematic association of NPs with quality of care or the practice's net revenue. Primary care medical group practices need to evaluate the alternate clinical roles of their NPs and develop models that optimize cost and quality of care. Practices that have employed more than 1 NP for every 2 physicians appear to have lower per capita Medicare spending with no adverse effects on quality. Research now needs to explore these causalities.


Cloning and characterization of a growth factor-inducible cyclooxygenase gene from rat intestinal epithelial cells.
Growth factors have been shown to play a role in intestinal epithelial growth regulation and transformation. Utilizing standard differential cloning techniques, we have isolated a growth factor-inducible gene (RS-2) from rat intestinal epithelial cells that has approximately 95% homology to the mouse mitogen-inducible cyclooxygenase (COX-2) at the amino acid level. This cDNA hybridizes to a approximately 4.5-kb mRNA from transforming growth factor (TGF)-alpha-stimulated rat intestinal epithelial (RIE-1) cells and is constitutively expressed in vivo in adult rat kidney and brain. Nuclear run-on experiments demonstrate that the increase of RS-2 mRNA after TGF-alpha stimulation is in part due to an increased transcription rate of the gene. The coding region for RS-2 was subcloned into a pCMV-2 expression vector, and the RS-2 protein was expressed in COS-1 cells. Microsomal fractions isolated from the COS-1 cells transfected with the RS-2 expression vector contained cyclooxygenase activity. In addition to the production of prostaglandins, the recombinant RS-2 protein also catalyzed the formation of three other eicosanoid products. In summary, we have cloned a mitogen-inducible cyclooxygenase gene from rat intestinal cells that is induced following growth factor stimulation.


[Classification of pancreatic pseudocysts].
Pancreatic pseudocysts were observed in 50 patients and created in the experiment in 48 dogs. Depending on cyst communication with the pancreatic ducts, their patency and outflow through them of a pancreatic secret into the duodenum, the progressive, stable and intermittent pancreatic pseudocysts have been distinguished.


A small-molecule modulator of the tumor-suppressor miR34a inhibits the growth of hepatocellular carcinoma.
Small molecules that restore the expression of growth-inhibitory microRNAs (miRNA) downregulated in tumors may have potential as anticancer agents. miR34a functions as a tumor suppressor and is downregulated or silenced commonly in a variety of human cancers, including hepatocellular carcinoma (HCC). In this study, we used an HCC cell-based miR34a luciferase reporter system to screen for miR34a modulators that could exert anticancer activity. One compound identified as a lead candidate, termed Rubone, was identified through its ability to specifically upregulate miR34a in HCC cells. Rubone activated miR34a expression in HCC cells with wild-type or mutated p53 but not in cells with p53 deletions. Notably, Rubone lacked growth-inhibitory effects on nontumorigenic human hepatocytes. In a mouse xenograft model of HCC, Rubone dramatically inhibited tumor growth, exhibiting stronger anti-HCC activity than sorafenib both in vitro and in vivo. Mechanistic investigations showed that Rubone decreased expression of cyclin D1, Bcl-2, and other miR34a target genes and that it enhanced the occupancy of p53 on the miR34a promoter. Taken together, our results offer a preclinical proof of concept for Rubone as a lead candidate for further investigation as a new class of HCC therapeutic based on restoration of miR34a tumor-suppressor function.


Contralateral prophylactic mastectomy (CPM): A systematic review of patient reported factors and psychological predictors influencing choice and satisfaction.
Conduct a systematic review of quantitative and qualitative studies exploring patient reported factors and psychological variables influencing the decision to have contralateral prophylactic mastectomy (CPM), and satisfaction with CPM, in women with early stage breast cancer. Studies were identified via databases: Medline, CINAHL, Embase and PsycINFO. Data were extracted by one author and crosschecked by two additional authors for accuracy. The quality of included articles was assessed using standardised criteria by three authors. Of the 1346 unique citations identified, 17 were studies that met the inclusion criteria. Studies included were primarily cross-sectional and retrospective. No study utilised a theoretical framework to guide research and few studies considered psychological predictors of CPM. Fear of breast cancer was the most commonly cited reason for CPM, followed by cosmetic reasons such as desire for symmetry. Overall, women appeared satisfied with CPM, however, adverse/diminished body image, poor cosmetic result, complications, diminished sense of sexuality, emotional issues and perceived lack of education regarding alternative surveillance/CPM efficacy were cited as reasons for dissatisfaction. Current literature has begun to identify patient-reported reasons for CPM; however, the relative importance of different factors and how these factors relate to the process underlying the decision to have CPM are unknown. Of women who considered CPM, limited information is available regarding differences between those who proceed with or ultimately decline CPM.


Dose-dependent tolerance to ozone. I. Tracheobronchial epithelial reorganization in rats after 20 months' exposure.
Two salient features of the pulmonary response to reactive oxidant air pollutants such as ozone are the heterogeneity of response by site within the respiratory tract and the development of tolerance to injury with repeated exposure. The purpose of this study was to establish whether the development of tolerance to long-term exposure is associated with changes in the tracheobronchial epithelium. Male F344-N rats were exposed to 0, 0.12, 0.5, or 1.0 ppm ozone 6 hours/day for 5 days/week for 20 months and killed 1 week post-exposure. Samples for light microscopic morphometry were obtained by microdissection from each infusion-fixed trachea and left lung lobe and included: 1) a cranial bronchus with short path length (generation no. 4 to 5) and small diameter; 2) a central bronchus with short path length (generation no. 4 to 5) and large diameter; and 3) a caudal bronchus with long path length (generation no. 10 to 12) and small diameter. In addition, three sites within the central acinus were examined from cranial, central, and caudal regions. These sites included terminal bronchiole, 0.5 to 1 mm proximal to terminal bronchiole and bronchiolarized alveolar duct. Intraepithelial mucin storage (AB/PAS-positive material quantified by image analysis) within the trachea decreased with dose. Mucin storage was unchanged in the central bronchus, increased threefold with dose in the caudal bronchus, and was six times higher in the cranial bronchus at 1.0 ppm ozone. Epithelial composition was unchanged in trachea or any bronchi; however, we noted a significant dose-dependent increase in nonciliated cell mass and volume fraction in terminal bronchioles in all three regions. There was also a significant increase in nonciliated cell mass in the bronchiolarized alveolar ducts. Bronchiolar nonciliated cells were identified greater than fourfold further into alveolar ducts in 1.0 ppm exposed than in 0 ppm animals. Nonciliated cells occurred almost 200 microns deeper into alveolar ducts in cranial regions than in caudal regions. We conclude: 1) that the development of tolerance to injury produced by long-term exposure to ozone involves changes in airway epithelium and 2) that these changes are site specific and involve alterations in both secretory activity and cellular composition.


The retained cervical stump. A 25-year experience.
During a 25-year period on one service at the Mayo Clinic, 262 cervical stumps were removed surgically: 208 vaginally and 54 abdominally. In this series, 46 patients had malignancy of the cervical stump. When a cervical stump is present, it most often can be expeditiously removed during the course of additional vaginal repairs with extremely few risks and complications, and low morbidity.


A splint designed for easy fixation and release during orthognathic surgery.
Orthognathic correction of jaw deformity may require a period of inter-maxillary fixation (IMF) at operation or during the post-operative period. A splint has been designed which may be used for both fixation and localisation of the jaws and which employs a quick release mechanism designed for use during surgery. It may be used also by the patient when intermittent fixation is required post-operatively and by non-medical staff in the event of an emergency such as airway obstruction.


Modelling heat and mass exchange of buried avian eggs.
The eggs of the Megapodiidae are incubated while buried in a substrate with which they exchange heat and water. The eggs may be buried in sand or in a mound composed in part or totally of organic material. We have analyzed the heat and water exchange of these buried eggs by constructing egg heat and mass balances. The equations are used to examine changes in egg temperature and water exchange during incubation in different environments. The thermal conductivities of the substrates are likely to vary by a factor of 5 to 10, with sand having the greatest thermal conductivity and organic litter the smallest. We predict that eggs incubated in sand will increase in temperature by 1 degree C or less, whereas eggs incubated in organic material will increase in temperature by 4 degrees C or more. Mound temperatures should remain low (less than 35 degrees C) to prevent overheating of eggs and hatchlings. Eggs can be incubated in sand at higher temperatures with less risk of overheating. Egg water loss in mounds is likely to be variable depending on mound humidity and considerably greater than 0 even in very high humidities. We expect that the rate of water loss by the eggs will increase many fold during incubation because of the low thermal conductivity of the mound material and the consequent increase in egg temperature.


Associations of the dietary approaches to stop hypertension (DASH) diet with pregnancy complications in Project Viva.
The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to improve cardiometabolic outcomes in non-pregnant populations. Little is known regarding the impact of this diet on health during pregnancy. The objective of this research is to examine associations of adherence to the DASH diet with hypertensive disorders of pregnancy (HDP) and other pregnancy outcomes. We conducted analyses with data that came from 1760 women in Project Viva, a Boston-area longitudinal cohort recruited in early pregnancy 1999-2002. We derived a DASH score using data from a food frequency questionnaire (FFQ) administered at median 11.1 weeks gestation. Next, we used multivariable linear regression models that accounted for the woman's age at enrollment, pre-pregnancy body mass index (BMI), education, smoking habits, race/ethnicity, gestational weight gain (GWG) up until the time of the FFQ, and total energy intake to examine associations of the DASH score with HDP, gestational diabetes, preterm delivery (<37 weeks), birth size, and GWG from FFQ to delivery. Models for HDP and GDM were additionally mutually adjusted for each other. Because pre-pregnancy weight status may modify these relationships, we tested for interactions between pre-pregnancy BMI and the DASH score. Mean ± SD age of the women was 32.2 ± 4.9 years; 71.9% were white. Overall, the DASH diet score (mean: 24.0, SD: 5.0) was not associated with any of the pregnancy outcomes or complications. However, we found a positive association between the DASH diet and subsequent GWG among women who were obese before pregnancy (0.19 [95% CI: 0.05, 0.34], P ≤ 0.05 kg higher GWG per 1 unit DASH score). Adherence to DASH diet during early pregnancy does not appear to be protective against HDP or other adverse pregnancy outcomes.


Computation of the binding free energy of peptides to graphene in explicit water.
The characteristic properties of graphene make it useful in an assortment of applications. One particular application--the use of graphene in biosensors--requires a thorough understanding of graphene-peptide interactions. In this study, the binding of glycine (G) capped amino acid residues (termed GXG tripeptides) to trilayer graphene surfaces in aqueous solution was examined and compared to results previously obtained for peptide binding to single-layer free-standing graphene [A. N. Camden, S. A. Barr, and R. J. Berry, J. Phys. Chem. B 117, 10691-10697 (2013)]. In order to understand the interactions between the peptides and the surface, binding enthalpy and free energy values were calculated for each GXG system, where X cycled through the typical 20 amino acids. When the GXG tripeptides were bound to the surface, distinct conformations were observed, each with a different binding enthalpy. Analysis of the binding energy showed the binding of peptides to trilayer graphene was dominated by van der Waals interactions, unlike the free-standing graphene systems, where the binding was predominantly electrostatic in nature. These results demonstrate the utility of computational materials science in the mechanistic explanation of surface-biomolecule interactions which could be applied to a wide range of systems.


A case approach: the pathophysiology of thyroid storm.
As is illustrated in the case report presented here, disorders other than malignant hyperthermia can lead to fever and tachydysrhythmias. Should such symptoms develop in a patient with a previous history of thyrotoxicosis, the possibility of thyroid storm should be considered. Careful monitoring must not cease with the termination of the operation, because this complication usually develops after surgery. Should the complication occur, a successful outcome is dependent upon an understanding of the pathophysiology of the disease process, aggressive monitoring, and appropriate pharmacological management.


Null Hypotheses, Interval Estimation, and Bayesian Analysis.
Hypothesis testing using a frequentist approach is the mainstay of biostatistics and forms the foundation for assessing the significance of study results. This classical method has well-understood advantages as it determines whether data are statistically improbable and provides a threshold (ie, the P value) for delineating significance. Alternative statistical approaches have been proposed, including Bayesian analysis. This technique incorporates a prior probability as to what is already known clinically with the observed data. It is important for otolaryngologists to understand the advantages and disadvantages of these 2 approaches to conduct the most appropriate analyses.


Job satisfaction among multiple sclerosis certified nurses.
Several studies document high levels of job satisfaction among certified nurses, but no study has examined job satisfaction and factors influencing job satisfaction of certified multiple sclerosis (MS) nurses. This study tested a theoretical model proposing that two organizational factors, colleague relationships and benefits, will predict job satisfaction. Job satisfaction was represented by four factors: autonomy, professional status, professional growth, and time efficiency. Participants included MS nurses certified for 6 months or more practicing mostly in three countries (Canada, Great Britain, and the United States) who anonymously completed the Misener Nurse Practitioner Job Satisfaction Scale, an overall job satisfaction rating, and demographic information. Findings indicate that colleague relationships and benefits significantly estimated organization structure and that autonomy, professional status, professional growth, and time efficiency significantly estimated job satisfaction; furthermore, organization factors such as colleague relationships and benefits significantly predict job satisfaction. Among the countries, several statistically significant differences were observed between job satisfaction factors as well as items in both organization and job satisfaction subscales. Average factor scores among the countries were mostly rated satisfactory. The International Organization of Multiple Sclerosis Nurses Executive Board plans to use the study findings to see how it needs to focus efforts as an organization toward enhancing and standardizing MS care and develop MS nurse professionalism worldwide.


Elucidation of nucleus-cytoplasm interaction: change in ability of the nucleus to express sexuality according to clonal age in Paramecium.
The expression of sexual activity in Paramecium caudatum is repressed for about 50 fissions after conjugation. The ability of the macronucleus to affect the expression of sexual activity according to the age of clonal development was investigated using the macronuclear fusion-reorganization method. When a mature macronucleus was transplanted into an immature cell and fused with a macronucleus in the immature cell, the clones derived from the recipient showed sexual immaturity. In a reverse experiment, an immature macronucleus was transplanted into a mature cell, and the clones also showed sexual immaturity. The ability of the macronucleus to transform mature cells to immature cells was clonal age-dependent. The characteristics of the immature-mature hybrid macronucleus indicate that the immature macronucleus is dominant over the mature macronucleus with respect to the ability to express sexual activity. On the other hand, in cells of the early immaturity period, the micronucleus, known as the germ nucleus, shows the ability to undergo meiosis and eventually to produce progeny under control of the mature macronucleus. The expression of sexual activity is thought to be governed by the clonal age of the macronucleus and not by the clonal age of the micronucleus or cytoplasm. The macronucleus seems to determine the ability to express sexual activity by counting post-conjugation divisions and keeping track of the age of the clone.


Combined Score of Perivascular Space Dilatation and White Matter Hyperintensities in Patients with Normal Cognition, Mild Cognitive Impairment, and Dementia.
Background and Objectives: Cerebral perivascular spaces (PVS) are part of the cerebral microvascular structure and play a role in lymphatic drainage and the removal of waste products from the brain. White matter hyperintensities (WMH) are hyperintense lesions on magnetic resonance imaging that are associated with cognitive impairment, dementia, and cerebral vascular disease. WMH and PVS are direct and indirect imaging biomarkers of cerebral microvascular integrity and health. In our research, we evaluated WMH and PVS enlargement in patients with normal cognition (NC), mild cognitive impairment (MCI), and dementia (D). Materials and Methods: In total, 57 participants were included in the study and divided into groups based on neurological evaluation and Montreal Cognitive Assessment results (NC group 16 participants, MCI group 29 participants, D group 12 participants). All participants underwent 3T magnetic resonance imaging. PVS were evaluated in the basal ganglia, centrum semiovale, and midbrain. WMHs were evaluated based on the Fazekas scale and the division between deep white matter (DWM) and periventricular white matter (PVWM). The combined score based on PVS and WMH was evaluated and correlated with the results of the MoCA. Results: We found statistically significant differences between groups on several measures. Centrum semiovale PVS dilatation was more severe in MCI and dementia group and statistically significant differences were found between D-MCI and D-NC pairs. PVWM was more severe in patients with MCI and dementia group, and statistically significant differences were found between D-MCI and D-NC pairs. Furthermore, we found statistically significant differences between the groups by analyzing the combined score of PVS dilatation and WMH. We did not find statistically significant differences between the groups in PVS dilation of the basal ganglia and midbrain and DWM hyperintensities. Conclusions: PVS assessment could become one of neuroimaging biomarkers for patients with cognitive decline. Furthermore, the combined score of WMH and PVS dilatation could facilitate diagnostics of cognitive impairment, but more research is needed with a larger cohort to determine the use of PVS dilatation and the combined score.