Detailed descriptions of physical activity patterns among individuals with diabetes and prediabetes: the Lolland-Falster Health Study.
This study aimed to describe objectively measured physical activity patterns, including daily activity according to day type (weekdays and weekend days) and the four seasons, frequency, distribution, and timing of engagement in activity during the day in individuals with diabetes and prediabetes and compared with individuals with no diabetes. This cross-sectional study included data from the Danish household-based, mixed rural-provincial population study, The Lolland-Falster Health Study from 2016 to 2020. Participants were categorized into diabetes, prediabetes, and no diabetes based on their glycated hemoglobin level and self-reported use of diabetes medication. Outcome was physical activity in terms of intensity (time spent in sedentary, light, moderate, vigorous, and moderate to vigorous physical activity (MVPA) intensities), adherence to recommendations, frequency and distribution of highly inactive days (<5 min MVPA/day), and timing of engagement in activity assessed with a lower-back worn accelerometer. Among 3157 participants, 181 (5.7 %) had diabetes and 568 (18.0 %) had prediabetes. Of participants with diabetes, 63.2% did not adhere to the WHO recommendations of weekly MVPA, while numbers of participants with prediabetes and participants with no diabetes were 59.5% and 49.6%, respectively. Around a third of participants with diabetes were highly inactive daily (<5 min MVPA/day) and had >2 consecutive days of inactivity during a 7-days period. Mean time spent physically active at any intensity (light, moderate, and vigorous) during a day was lower among participants with diabetes compared with participants with no diabetes and particularly from 12:00 to 15:00 (mean difference of -6.3 min MVPA (95% CI -10.2 to -2.4)). Following adjustments, significant differences in physical activity persisted between diabetes versus no diabetes, but between participants with prediabetes versus no diabetes, results were non-significant after adjusting for body mass index. Inactivity was highly prevalent among individuals with diabetes and prediabetes, and distinct daily activity patterns surfaced when comparing these groups with those having no diabetes. This highlights a need to optimize current diabetes treatment and prevention to accommodate the large differences in activity engagement.


"I wasn't texting; I was just reading an email …": a qualitative study of distracted driving enforcement in Washington State.
In response to the rise of distracted driving, many countries and most US states have adopted laws to restrict the use of handheld phones for drivers. Specific provisions of each law and the overall social mores of distracted driving influence enforceability and impact. Identify multilevel interdependent factors that influence distracted driving enforcement through the perspective of police officers. We conducted focus group discussions with active duty law enforcement officers from three large Washington State counties. Our thematic analysis used descriptive and pattern coding that placed our findings within a social ecological framework to facilitate targeted intervention development. Participants reported that the distracted driving law posed challenges for consistent and effective enforcement. They emphasised the need to change social norms around distracted driving, similar to the shifts seen around impaired driving. Many participants were themselves distracted drivers, and their individual knowledge, attitude and beliefs influenced enforcement. Participants suggested that law enforcement leaders and policymakers should develop and implement policies and strategies to prioritise and motivate increased distracted driving enforcement. Individual, interpersonal, organisational and societal factors influence enforcement of distracted driving laws. Targeted interventions should be developed to address distracted driving and sustain effective enforcement.


Non-alcoholic steatofibrosis (NASF) can independently predict mortality in patients with non-alcoholic fatty liver disease (NAFLD).
Hepatic fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) independently predicts mortality. Given liver biopsy's invasive nature, non-invasive method to assess hepatic steatosis and fibrosis provides NAFLD risk stratification algorithm in clinical practice. NAFLD fibrosis score (NFS) is simple and non-invasive predictive model recommended by American Association for the Study of Liver Disease (AASLD) Guideline to identify patients with NAFLD with fibrosis risk. The aim of this study is to assess long-term outcomes of subjects with significant non-alcoholic steatofibrosis (NASF) as established by ultrasound (US) and NFS. Used National Health and Nutrition Examination Survey (NHANES III) with National Death Index-linked Mortality Files. NAFLD diagnosis established by the presence of moderate to severe hepatic steatosis on US without other causes of chronic liver disease (alcohol consumption <20 gr/day, hepatitis B surface-antigen negative, anti-hepatitis C virus antibody negative, transferrin saturation <50%). Significant hepatic fibrosis was estimated by high NFS (>0.676) and calculated with previously published formula. Subjects with NAFLD and high NFS have significant NASF. NHANES III included 20 050 adult participants. 2515 participants complete data and NAFLD with 5.1% (n=129) meeting criteria for significant SF. Subjects with significant SF were older, had higher body mass index, waist circumference and the homeostasis model assessment (HOMA) scores and higher rates of comorbidities (diabetes, congestive heart failure (CHF), stroke; all p<0.001). After median of 207 months of follow-up, overall mortality in NAFLD cohort was 30.0% (n=754). Crude mortality higher in subjects with significant SF (67.4% vs 28.0%, p<0.001). In multivariate survival analysis, predictors of overall mortality included significant SF (adjusted HR (aHR): 1.37; 95% CI 1.07 to 1.76, p=0.01), older age (aHR:1.08; 95% CI 1.07 to 1.09 per year), male gender (aHR:1.44; 95% CI 1.24 to 1.67), black race (aHR:1.24; 95% CI 1.04 to 1.48)), history of hypertension (aHR:1.40; 95% CI 1.20 to 1.64), diabetes (aHR:1.69; 95% CI 1.43 to 2.00), CHF (aHR:1.77; 95% CI 1.38 to 2.261), stroke (aHR:1.84; 95% CI 1.38 to 2.48) and smoking (aHR:1.74; 95% CI 1.47 to 2.07) (all p<0.02). Sensitivity analysis showed that the best association of SF with mortality is higher at NFS threshold of 0.80 (aHR:1.41; 95% CI 1.09 to 1.83, p=0.01). Significant NASF determined non-invasively is an independent predictor of mortality. These data should help clinicians to easily risk-stratify patients with NAFLD for close monitoring and treatment considerations in clinical trial setting.


Effect of reserpine pretreatment on mechanical responsiveness and [125I]Iodohydroxybenzylpindolol binding sites in the guinea-pig right atrium.
The inotropic and chronotropic responses of the guinea-pig right atrium to several pharmacologic agents were measured after acute (0.1 mg/kg/day x 1) and chronic (0.1 mg/kg/day x 7) reserpine administration. A small increase in the sensitivity of the pacemaker to isoproterenol occurred after acute reserpine treatment which was followed by a much greater change in sensitivity to the beta agonist when pretreatment was extended for 7 days. Chronotropic responsiveness to calcium, histamine and pilocarpine was not altered by reserpine pretreatment. The acute administration of reserpine resulted in a slight inotropic supersensitivity of paced right atria to isoproterenol, calcium and histamine. Pretreatment for 7 days produced an additional increase in inotropic sensitivity to isoproterenol but did not affect contractile responses to the other agents. The catecholamine-specific nature of the supersensitivity induced by chronic reserpine treatment suggested that a change in the number and/or affinity of beta adrenergic receptors was involved. The radiolabeled beta adrenoceptor antagonist [125]iodohydroxybenzylpindolol (I-HYP) was used to test this hypothesis. Preliminary experiments revealed the presence of a single class of noninteracting (nH = 0.99), high affinity (Kd = 100 pM) binding sites which exhibited stereospecificity and saturability (47.2 fmol/mg of protein). The agonist potency series for the inhibition of I-HYP binding was identical to the series for mediating mechanical responses. Taken collectively this information suggests that the high affinity I-HYP binding site in the guinea-pig right atrium represents the beta adrenergic receptor. As determined by Scatchard analyses, neither acute (1-day) nor chronic (7-day) low-dose (0.1 mg/kg/day) reserpine administration altered the number or affinity of I-HYP binding sites. It is concluded that changes in beta receptor characteristics are not responsible for reserpine-induced supersensitivity in this tissue.


Local striatal reward signals can be predicted from corticostriatal connectivity.
A defining feature of the basal ganglia is their anatomical organization into multiple cortico-striatal loops. A central tenet of this architecture is the idea that local striatal function is determined by its precise connectivity with cortex, creating a functional topography that is mirrored within cortex and striatum. Here we formally test this idea using both human anatomical and functional imaging, specifically asking whether within striatal subregions one can predict between-voxel differences in functional signals based on between-voxel differences in corticostriatal connectivity. We show that corticostriatal connectivity profiles predict local variation in reward signals in bilateral caudate nucleus and putamen, expected value signals in bilateral caudate nucleus, and response effector activity in bilateral putamen. These data reveal that, even within individual striatal regions, local variability in corticostriatal anatomical connectivity predicts functional differentiation.


Model-Independent Observation of Exotic Contributions to B^{0}→J/ψK^{+}π^{-} Decays.
An angular analysis of B^{0}→J/ψK^{+}π^{-} decays is performed, using proton-proton collision data corresponding to an integrated luminosity of 3 fb^{-1} collected with the LHCb detector. The m(K^{+}π^{-}) spectrum is divided into fine bins. In each m(K^{+}π^{-}) bin, the hypothesis that the three-dimensional angular distribution can be described by structures induced only by K^{*} resonances is examined, making minimal assumptions about the K^{+}π^{-} system. The data reject the K^{*}-only hypothesis with a large significance, implying the observation of exotic contributions in a model-independent fashion. Inspection of the m(J/ψπ^{-}) vs m(K^{+}π^{-}) plane suggests structures near m(J/ψπ^{-})=4200 and 4600 MeV.


Velopharyngeal Incompetence in Children With 22q11.2 Deletion Syndrome: Velar and Pharyngeal Dimensions.
The surgical management of velopharyngeal incompetence (VPI) in children with 22q11.2 deletion syndrome (22q11.2 DS) is challenging. There are numerous approaches and children often undergo more than one operation. Our aim was to develop a method using images from routine lateral videofluoroscopy to study the dimensions of the velopharynx in this cohort.We analyzed 22 pre-operative lateral videofluoroscopy recordings of children with 22q11.2 DS and VPI. Fourteen had a submucous cleft palate (SMCP) and 8 had no obvious palatal abnormality but who were subsequently labelled as having an occult submucous cleft palate (OSMCP). The control data were 10 historic records of children with cleft lip and an intact palate. The authors identified key points on radiographs of the velum at rest and when elevated to measure the total velar length, functional velar length and pharyngeal depth and compared them ratiometrically.The intra-observer reliability was > 0.9 whereas the inter-observer reliability was > 0.74. The velopharyngeal depth/total velar length was significantly greater in 22q11.2 DS than the control group P < 0.001. There was no difference between SMCP and OSMCP patients, P = 0.556. There was no difference in the functional velar length/total velar length between 22q11.2 DS and controls (P = 0.763).In this study, the authors demonstrate a reliable method to gain useful ratiometric measurements of the velopharynx. This may help with treatment planning. Children with 22q11.2 DS and VPI have a larger velopharyngeal depth/total velar length ratio that may explain some of the difficulty in management.


Aquaporin-4 gene disruption in mice protects against impaired retinal function and cell death after ischemia.
Water channel aquaporin (AQP)-4 is expressed in Muller cells in retina, which are similar to astroglial cells in the central nervous system, where AQP4 deletion protects against cytotoxic brain edema after cerebral ischemia. A transient ischemia-reperfusion model was used to determine whether AQP4 deletion in mice protects the retina. Retinal function and morphology were assessed in wild-type versus AQP4-deficient mice after ischemic damage produced by a 45- to 60-minute elevation of intraocular pressure to 120 mm Hg. Retinal function was assessed by electroretinography, and retinal structure by light microscopy. Extracellular space (ECS) size in fluorescently stained retinal slices was assessed by fluorescence recovery after photobleaching. Retinal function and cell survival were significantly improved in AQP4-deficient mice in both inbred (C57/bl6) and outbred (CD1) genetic backgrounds. By electroretinography, b-wave amplitude was reduced by 75% to 83% at 1 to 4 days after ischemia in wild-type mice versus 48% to 51% in AQP4-null CD1 mice. Reductions were 53% to 72% versus <34% in C57/bl6 mice. Retinal structure and cell count were preserved in AQP4-null mice, particularly in the inner nuclear and plexiform layers of the retina, where Müller cells are concentrated. At 4 days after ischemia, inner retinal thickness was thinned by 43% in wild-type mice versus 11% in AQP4-null mice. Several mechanisms for retinal protection were investigated, including ECS expansion, reduced early swelling, and altered Kir4.1 K(+) channel expression. AQP4 deletion in mice is neuroprotective in a transient ischemia model of retinal injury, suggesting the possible use of AQP4 inhibitors in retinal vascular occlusive and ischemic diseases.


Effectiveness of Airborne Fungi Removal by using a HEPA Air Purifier Fan in Houses.
Few studies have evaluated the performance of air purifiers in removing airborne fungi in houses. Here, we evaluated the ability of a HEPA air purifier fan to remove airborne fungi in six houses in Japan. In each house, the number of airborne fungi decreased more rapidly when the air purifier fan was on (test measurement) than when it was off (control) , demonstrating its ability to decrease the fungal concentration. The number of airborne fungi decreased between 1.5 and 6 times faster when the air purifier fan was on than when it was off (spontaneous decrease) . Clean air change rates, calculated from measurements taken 15 min after the test equipment operation began, ranged from 2.9 to 5.4 (h-1) , indicating adequate air cleaning. One of the six test houses contained a much greater concentration of airborne fungi than the standard set by the Architectural Institute of Japan. When the air purifier fan was operated in the house, the indoor/outdoor (I/O) ratio decreased from 77.5, equating to a fungal concentration of 53,000 cfu/m3 at 0 min to 0.72 or 620 cfu/m3 after 45 min, which is below the standard. This reduction clearly demonstrated the antifungal effect of the air purifier fan.


A Newly Described, Highly Prevalent Arterial Pedicle Perfuses Both Gracilis and Profunda Artery Perforator Flap Tissues: An Angiographic Study of the Medial Thigh.
Novel secondary flap options are paramount for patients who are not candidates for common reconstructive methods. The purpose of this study is to identify the prevalence of single arterial pedicle supplying both the gracilis muscle and medial thigh tissue carried in a profunda artery perforator (PAP) flap. Such a pedicle could allow the creation of a chimeric gracilis and PAP flap with a single-arterial anastomosis. We conducted a retrospective review of 157 lower extremity computed tomography (CT) angiograms to assess the vasculature of the thigh soft tissues. Imaging evaluation was supervised by a board-certified musculoskeletal radiologist. Prevalence of a single-arterial pedicle to a gracilis and PAP flap in each patient was 59% (31% within the right leg and 28% in the left leg). Furthermore, 16% of patients had a common arterial pedicle in both lower extremities. Existence of a single-arterial pedicle to both the gracilis muscle and PAP flap tissues is frequently present in most patients in at least one lower extremity. This chimeric flap configuration could serve as a reconstructive avenue for patients, particularly those who have exhausted other more common flap options. Screening angiography is warranted in patients looking for this anatomic variation to establish its presence.


Contents of antenatal care services in Afghanistan: findings from the national health survey 2018.
Maternal and newborn mortality is a public health concern in low- and middle-income countries (LMICs), including Afghanistan, where the evolving socio-political circumstances have added new complexities to healthcare service delivery. Birth outcomes for both pregnant women and their newborns are improved if women receive benefits of quality antenatal care (ANC). This study aimed to assess the contents of ANC services and identify predictors of utilization of services by pregnant women during ANC visits to health facilities in Afghanistan. In this cross-sectional study, we used data from the Afghanistan Health Survey 2018 (AHS2018). We included a total of 6,627 ever-married women, aged 14-49 years, who had given birth in the past 2 years or were pregnant at the time of survey and had consulted a health worker for ANC services in a health facility. The outcome was defined as 1-4 services and 5-8 services that a pregnant woman received during an ANC visit. The services were (i) taking a pregnant woman's blood pressure, (ii) weighing her, (iii) testing her blood, (iv) testing her urine, (v) providing advice on nutrition, (vi) advising about complicated pregnancy, (vii) advising about the availability of health services, and (viii) giving her at least one dose of Tetanus Toxoid (TT) vaccine. The binary outcome (1-4 services versus 5-8 services) was used in a multivariable logistic regression model. Of all 6,627 women, 31.4% (2,083) received 5-8 services during ANC visits. Only 1.3% (86) received all 8 services, with 98.7% (6,541) receiving between 1 and 7 services, and 71.6% (4,745) women had their blood pressure measured during ANC visits. The likelihood (adOR = Adjusted Odds Ratio) of receiving 5-8 services was higher in women who could read and write (adOR = 1.33: 1.15-1.54), in women whose husbands could read and write (adOR = 1.14: 1.00-1.28), in primipara women (adOR = 1.42: 1.02-1.98), in women who knew one danger sign (adOR = 5.38: 4.50-6.45), those who knew 2 danger signs (adOR = 8.51: 7.12-10.19) and those who knew ≥ 3 danger signs (adOR = 13.19: 10.67-16.29) of complicated pregnancy, and in women who had almost daily access to TV (adOR = 1.16: 1.01-1.33). However, the likelihood of receiving 5-8 services was lower in women who used private clinics (adOR = 0.64: 0.55-0.74) and who received services from nurses (adOR = 0.27 (0.08-0.88). Our findings have the potential to influence the design and implementation of ANC services of health interventions to improve the delivery of services to pregnant women during ANC visits.


Abnormal cervical smears: are we in for an epidemic?
A retrospective study was conducted to examine the pattern of a disturbing increase in abnormal cervical smears in one health district. Past records over fifteen years (1965-79) were analysed to produce pick up rates according to age, screening state, severity of lesion, and area of residence. Main findings included an increased pick up rate in unscreened (5.8 to 12.9/1000 smears) and screened (0.9 to 3.6/1000 smears) women. The order of increase was proportionately much higher in women under 40 years. The only significant epidemiological variable in the catchment area was a substantial population increase, overweighted by the younger age groups. The principal conclusion of the study was that the increased pick up rates of abnormal cervical smears in the district reflected a true increase in the incidence of premalignant lesions of the cervix. Screening efforts aided by computerisation should be examined nationwide in order to reach high risk groups and thus try to prevent an increase in carcinoma of the cervix.


The Role of Psychiatry in the Management of Acute Trauma Surgery Patients.
BACKGROUND: Trauma is a leading cause of death and disability in the United States, with high prevalence and recidivism in individuals with psychiatric and substance abuse disorders. Half of these disorders go undiagnosed by the trauma team, resulting in adverse public health and economic consequences. METHOD: In a 16-week pilot study in the emergency department of an inner-city tertiary care hospital, a psychiatrist was integrated into the trauma surgery team by responding to all traumas and rounding with the staff 1 shift per week (March 1, 2000, through June 31, 2000). During this 16-week period, 375 patients passed through the trauma surgery service. Data on the frequency of psychiatric consultations were compared with those for a retrospectively selected control group consisting of all 360 patients passing through the trauma surgery service during the corresponding 16 weeks of the previous year (March 1, 1999, through June 31, 1999). To determine the prevalence of psychopathology, eligible patients seen during the psychiatrist's shift (N = 28) were assessed with a semistructured interview, and charts for eligible patients seen in the corresponding shift during the previous year (N = 18) were assessed according to the same criteria. Before the study, a 10-item, self-report questionnaire was completed by 16 (73%) of the 22 emergency medicine physicians who serve as front-line staff members. The survey assessed physicians' attitudes toward psychiatric consultation for psychopathology and addictions in trauma patients. RESULTS: Based on DSM-IV screening criteria, the prevalence of preexisting psychopathology was 68% (19/28), but before the psychiatrist's involvement, only 12% (2/16) of physicians surveyed had considered consulting psychiatry, even for patients with gross psychopathology. Before the psychiatrist's integration into the 16-week study period, 75% (9/12) of trauma patients were discharged without psychiatric consultation despite the fact that more than half had documented substance abuse. After the psychiatrist joined the team, staff awareness of psychopathology sharpened. The number of patients treated for a psychiatric disorder that was often the proximal cause of the traumatic event nearly doubled, even on shifts not covered in the study. CONCLUSIONS: The ability to identify and treat coexisting psychopathology requires trauma surgeons to routinely incorporate a psychiatrist into their evaluation and treatment algorithm. Such a change in physician awareness and motivation hinges on a psychiatrist's visible presence (even if brief) and regular, active participation in the emergency department.


Accounting for polarization cost when using fixed charge force fields. I. Method for computing energy.
Although it is not currently standard practice, the cost to change the electronic polarization from one appropriate for the gas phase to that implied by the charge model should be considered when deriving force fields based on fits to certain types of experimental data and for using force fields to compute observables that involve changes in molecular polarization. We present mathematical expressions and a method to estimate this polarization cost implied by a fixed charge model force field, where the fixed charge model can be any combination of point charges, higher-order multipoles, or even distributed charge densities, as long as they do not change in response to environment. These expressions illuminate the relationship between polarization costs associated with fixed charge models, self-polarization energies of polarizable models, and quantum chemical based approaches that use continuum representations of the solvent, such as the self-consistent reaction field and polarizable continuum models. The technique takes account of the tensorial nature of the polarizabilities and includes quadrupole as well as dipole polarization. The consistency of this approach to one that estimates polarization cost using an implicit solvent quantum chemistry method (PCM) is demonstrated.


[Methods of improvement of diagnosis of thyroid cancer].
Duplex ultrasonography in combination with fine-needle aspiration biopsy (NBA) were used for early diagnosis of thyroid cancer. Main sonographic symptoms of thyroid cancer permitted to select patients for NBA. Diagnostic mistakes were analyzed on each stage of diagnosis based on complex of clinical and morphological features of thyroid epithelium. This approach in diagnosis of thyroid cancer permits to make accurate diagnosis before hospitalization and to plan treatment and surgical policy correctly.


Effect of Macromolecular Structure on Phase Separation Regime in 3D Printed Materials.
In this study, the fabrication of 3D-printed polymer materials with controlled phase separation using polymerization induced microphase separation (PIMS) via photoinduced 3D printing is demonstrated. While many parameters affecting the nanostructuration in PIMS processes are extensively investigated, the influence of the chain transfer agent (CTA) end group, i.e., Z-group, of macromolecular chain transfer agent (macroCTA) remains unclear as previous research has exclusively employed trithiocarbonate as the CTA end group. Herein, the effect of macroCTAs containing four different Z-groups on the formation of nanostructure of 3D printed materials is explored. The results show that the different Z-groups lead to distinct network formation and phase separation behaviors between the resins, influencing both the 3D printing process and the resulting material properties. Specifically, less reactive macroCTAs toward acrylic radical addition, such as O-alkyl xanthate and N-alkyl-N-aryl dithiocarbamate, result in translucent and brittle materials with macrophase separation morphology. In contrast, more reactive macroCTAs such as S-alkyl trithiocarbonate and 4-chloro-3,5-dimethylpyrazo dithiocarbamate produce transparent and rigid materials with nano-scale morphology. Findings of this study provide a novel approach to manipulate the nanostructure and properties of 3D printed PIMS materials, which can have important implications for materials science and engineering.


[Comparison of Clinical Effects of Electroacupuncture of Abdominal and Limb Acupoints in the Treatment of Acute Pancreatitis].
To compare the difference of therapeutic efficacy of electroacupuncture (EA) stimulation of abdominal acupoints and limb acupoints in the treatment of acute pancreatitis (AP), so as to provide a reference for EA treatment of AP. A total of 60 patients with AP were equally and randomly divided into abdominal acupoint group and limb acupoint group. On the basis of retention enema of Chaiqin Chengqi Decoction (containing Radix Bupleurum, Radix Scutellaria, etc.), and abdominal external application of Liuhe Powder ointment (containing Cinnabaris, pearl powder, etc.), patients of the two groups were also treated with acupuncture stimulation of acupoints at the abdomen or limbs. The abdominal acupoints were Shangwan (CV 13), Zhongwan (CV 12), Xiawan(CV 10), Liangmen (ST 21, left), Taiyi(ST 23, left), Chengman (ST 20, left), Fu'ai (SP 16, left), Yindu(KI 19, right), and the limb acupoints were Hegu(LI 4), Neiguan(PC 6), Zusanli(ST 36), Shangjuxu(ST 37), Xiajuxu(ST 39), and Yinlingquan(SP 9) which were punctured with filiform needles by retaining the needles for 30 min after twirling for a while. CV 12 - ST 21, CV 10- SP 16 of the abdomen group, and bilateral PC 6 and ST 36 of the limb group were administered EA (2 Hz/15 Hz, 1 mA and duration of 30 min). The treatment was conducted once daily for 5 days. The abdominal pain severity and distension severity were assessed using the visual analogue scale (VAS), and the abdominal girth was measured by using a soft ruler. Following the treatment, the abdominal pain and distension symptom scores in the lightest and most severe phases of AP and the abdominal girth levels were considerably decreased on the 5th day in the two groups in comparison with their own pre-treatment in the same one group (P < 0.05); and the abdominal pain scores on the 2nd, 3rd and 4th day in the lightest phase, and those on the 2nd, 3rd, 4th and 5th day in the most severe phase were markedly lower in the abdomen acupoint group than in the limb acupoint group (P<0.05). No significant differences were found between two groups in the abdominal distension symptom scores and abdominal circumference levels in the lightest and most severe phases of AP (P>0.05). In addition, no adverse events were found in both groups. EA has a good curative effect in the treatment of AP patients. The curative effect of acupuncture of the abdominal acupoints is significantly superior to that of limb acupoints in relieving abdominal pain.


Activation of mitogen-activated protein kinase and p70S6 kinase is not correlated with cerebellar granule cell survival.
We have investigated the role of mitogen-activated protein (MAP) kinase in the survival of cerebellar granule cells in primary culture. Brain-derived neurotrophic factor (BDNF) and insulin, but not epidermal growth factor (EGF), promoted the survival of P6 cerebellar granule neurons. BDNF promoted a sustained activation of MAP kinase, whereas that induced by EGF was only transient. Insulin promoted a small but transient activation of MAP kinase that was completely blocked by PD98059, an inhibitor of MAP kinase kinase activation. PD98059 had no effect on the insulin- or BDNF-induced survival of cerebellar granule cells. We also investigated the role of p70S6 kinase in survival. The activation of p70S6 kinase by EGF was transient, whereas BDNF and insulin promoted a sustained activation of p70S6 kinase. Rapamycin, which blocked p70S6 kinase activation, had no effect on the BDNF- or insulin-induced survival of cerebellar granule cells. We conclude that sustained activation of MAP kinase is not correlated with the survival response of cerebellar granule cells; indeed insulin-mediated survival is independent of MAP kinase. Survival of cerebellar granule cells is also independent of the activation of p70S6 kinase.


Pharmacological mechanism of angiotensin II receptor antagonists: implications for the treatment of elevated systolic blood pressure.
Systolic hypertension is a major risk factor for cardiovascular disease. The determinants of systolic blood pressure are peripheral resistance and arterial compliance. Arterial vasoconstriction, vascular growth and fluid retention, induced by the renin-angiotensin system directly or indirectly by enhancing sympathetic nervous system activity, are important factors in increasing peripheral resistance, decreasing arterial compliance and, consequently, elevating systolic blood pressure. Selective blockade of the angiotensin II type 1 (AT1) receptor represents a novel mechanism for interrupting the renin-angiotensin system. This provides the additional benefit of blocking angiotensin II generated by non-angiotensin-converting-enzyme pathways without altering either bradykinin metabolism or the potential beneficial effects of AT2 receptor stimulation. Eprosartan is a potent (1.4 nmol/l) AT1 receptor antagonist that inhibits angiotensin-II-induced vascular contraction in a competitive manner. Eprosartan is effective in reducing disease progression in animal models of hypertension, heart failure, renal disease and stroke. Furthermore, eprosartan causes a large increase in arterial compliance in hypertensive rats fed high-salt and high-fat diets. Eprosartan also possesses sympathoinhibitory activity as demonstrated by an inhibition of the pressor responses induced by activation of sympathetic outflow through spinal cord stimulation in pithed rats. In contrast, other angiotensin II receptor antagonists, such as losartan, used at equivalent angiotensin II blocking activity, do not appear to alter sympathetic nervous system activity. Angiotensin II receptor antagonists, such as eprosartan, that have the ability to block both the direct effects of angiotensin II and the indirect effects mediated by enhanced sympathetic neurotransmission, may represent an important advance in the treatment of elevated systolic blood pressure.


Risk factors of late-onset neonatal sepsis in Taiwan: A matched case-control study.
Infants in a neonatal intensive care unit (NICU) have a higher incidence of bloodstream infections (BSIs) than any other pediatric or adult population. The predisposing factors have not been comprehensively evaluated in this population in Taiwan. A retrospective matched case-control study was conducted in the NICUs of a teaching hospital in Taiwan. The case patients were identified from a staff-maintained electronic database containing the records of BSIs from July 2003 to June 2006. The case patients and the control patients (who did not develop BSI during their NICU stay) were 1:1 matched by birth weight, gestational age, gender, Apgar score, and date of birth. A total of 164 infants with culture-proven BSI were identified. Of these, 74 (45.1%) infants were female. The mean gestational age and birth weight were 30.7 ± 0.7 weeks and 1512 ± 804 g, respectively. The common etiologic pathogens included coagulase-negative staphylococci (28.7%), Staphylococcus aureus (16.5%), and Klebsiella pneumoniae (14.6%). Candida spp. accounted for 11 (6.7%) episodes. Two independent factors associated with BSIs in the neonates, as identified by multivariate analysis using conditional logistic regression, were the use of parenteral nutrition (matched odds ratio [mOR], 6.07; 95% confidence interval [CI], 1.14-32.32; p = 0.034) and intraventricular hemorrhage (mOR, 2.68; 95% CI, 1.20-5.99; p = 0.017). Parenteral nutrition was a significant and independent risk of late-onset neonatal sepsis. This risk should be considered when implementing early parenteral nutrition in NICUs.


Mottling score and skin temperature in septic shock: Relation and impact on prognosis in ICU.
Mottling score, defined by 5 areas over the knee is developed to evaluate tissue perfusion at bedside. Because of the subjective aspect of the score, we aimed to compare mottling score and skin temperature in septic shock with infrared thermography in ICU and the correlation to survival. We conducted a prospective and observational study in a teaching hospital in France during 8 months in ICU. All patients with sepsis requiring vasoactive drugs were included. We recorded epidemiologic data, hemodynamic parameters, mottling score and skin temperature with a thermic camera of the 5 mottling areas around the knee (temperatures recorded with FLIR™ software) at bedside. Measures were performed at ICU admission (H0) and six hours after initial resuscitation (H6). 46 patients were included. Median age was 69 (60-78), SOFA score 11 (8-12) mean SAPS II was 57±20 and 28-day mortality rate was 30%. Patients with mottling (score≥1), had a skin temperature of the knee significantly lower (30.7 vs 33,2°C p = 0.01 at H6) than patients without mottling (score = 0). Skin temperatures of the knee in mottling groups 1 to 5 were similar at H0 and H6. Neither mottling score nor skin temperature of the knee were associated with prognostic regarding day-28 mortality. Skin temperature measured with infrared thermography technology around the knee is lower when mottling sign is present and sign microcirculation alterations. This method, compared to standard mottling score is objective and allows data collections. However, this method failed to predict mortality in ICU patients.


Postantifungal Effect of Micafungin against the Species Complexes of Candida albicans and Candida parapsilosis.
Micafungin is an effective antifungal agent useful for the therapy of invasive candidiasis. Candida albicans is the most common cause of invasive candidiasis; however, infections due to non-C. albicans species, such as Candida parapsilosis, are rising. Killing and postantifungal effects (PAFE) are important factors in both dose interval choice and infection outcome. The aim of this study was to determinate the micafungin PAFE against 7 C. albicans strains, 5 Candida dubliniensis, 2 Candida Africana, 3 C. parapsilosis, 2 Candida metapsilosis and 2 Candida orthopsilosis. For PAFE studies, cells were exposed to micafungin for 1 h at concentrations ranging from 0.12 to 8 μg/ml. Time-kill experiments (TK) were conducted at the same concentrations. Samples were removed at each time point (0-48 h) and viable counts determined. Micafungin (2 μg/ml) was fungicidal (≥ 3 log10 reduction) in TK against 5 out of 14 (36%) strains of C. albicans complex. In PAFE experiments, fungicidal endpoint was achieved against 2 out of 14 strains (14%). In TK against C. parapsilosis, 8 μg/ml of micafungin turned out to be fungicidal against 4 out 7 (57%) strains. Conversely, fungicidal endpoint was not achieved in PAFE studies. PAFE results for C. albicans complex (41.83 ± 2.18 h) differed from C. parapsilosis complex (8.07 ± 4.2 h) at the highest tested concentration of micafungin. In conclusion, micafungin showed significant differences in PAFE against C. albicans and C. parapsilosis complexes, being PAFE for the C. albicans complex longer than for the C. parapsilosis complex.


Hybrid vascular intervention for a giant cervical carotid artery aneurysm in a clopidogrel-hyporesponsive child.
Aneurysms of the extracranial internal carotid artery (ICA) in pediatric patients are rare and mostly treated surgically. The authors present the case of a child with a giant extracranial ICA aneurysm presenting with gradual airway compression. A plan was made to explore the aneurysm surgically and straighten the associated carotid artery kinks during the operation to enable further endovascular treatment if primary reconstruction of the carotid artery proved not to be possible. Finally, the aneurysm was successfully treated with staged hybrid intervention, which consisted of surgical correction of parent artery kinks followed by endovascular implantation of stent grafts. The child tolerated the procedure well without adverse events. A craniocervical CT angiogram at 5 months showed patency of the stent construct and relief of airway compression. However, a follow-up CT angiogram at 14 months showed total occlusion of the ipsilateral carotid artery without clinical sequelae and complete cessation of airway compression. The management of this was unique since the patient is the first reported case of clopidogrel hyporesponsiveness in a child undergoing neurovascular intervention with prasugrel monotherapy. Point-of-care testing-based adjustment of prasugrel necessitated education of the patient's family regarding the loss of effect of the prasugrel tablets upon crushing and contact with air.


Disease burden in Brazil: an investigation into alcohol and non-viral cirrhosis.
Alcohol use/dependence are an important risk factor for cirrhosis of the liver. The article aims to describe and conduct a comparative analysis of Disability Adjusted Life Years (DALY), Years of Life Lost (YLL) and Years Lived with Disability (YLD) of alcohol use disorders and non-viral cirrhosis in Brazil in 2008. DALY was calculated as the sum of YLL and YLD. For YLL estimates, the mean number of deaths from 2007- 2009 in the country was considered. After revision of epidemiological data, prevalence of each disease was modelled with the DisMod tool, which generated incidence data for YLD estimates. Alcohol and non-viral cirrhosis were responsible for 3% and 1% of total DALYs, respectively. In both diseases, men contributed to a greater proportion of DALYs. Among the first ten causes of DALYs, alcohol use disorders occupied the second, third and sixth positions at the ages of 15-29, 30-44 and 45- 59, respectively. Non-viral cirrhosis was the eighth cause of DALY in the 30-44 age group in men; the fifth, in the 45-59 group and the eighth, in the 60-69 group. Age distribution suggests that interventions directed against alcohol use/dependence would have effects on the burden of alcoholic cirrhosis in the country.


Using the Physical Examination to Diagnose Patients with Acute Dizziness and Vertigo.
Emergency department (ED) patients who present with acute dizziness or vertigo can be challenging to diagnose. Roughly half have general medical disorders that are usually apparent from the context, associated symptoms, or initial laboratory tests. The rest include a mix of common inner ear disorders and uncommon neurologic ones, particularly vertebrobasilar strokes or posterior fossa mass lesions. In these latter cases, misdiagnosis can lead to serious adverse consequences for patients. Our aim was to assist emergency physicians to use the physical examination effectively to make a specific diagnosis in patients with acute dizziness or vertigo. Recent evidence indicates that the physical examination can help physicians accurately discriminate between benign inner ear conditions and dangerous central ones, enabling correct management of peripheral vestibular disease and avoiding dangerous misdiagnoses of central ones. Patients with the acute vestibular syndrome mostly have vestibular neuritis, but some have stroke. Data suggest that focused eye movement examinations, at least when performed by specialists, are more sensitive for detecting early stroke than brain imaging, including diffusion-weighted magnetic resonance imaging. Patients with the triggered episodic vestibular syndrome mostly have benign paroxysmal positional vertigo (BPPV), but some have posterior fossa mass lesions. Specific positional tests to provoke nystagmus can confirm a BPPV diagnosis at the bedside, enabling immediate curative therapy, or indicate the need for imaging. Emergency physicians can effectively use the physical examination to make a specific diagnosis in patients with acute dizziness or vertigo. They must understand the limitations of brain imaging. This may reduce misdiagnosis of serious central causes of dizziness, including posterior circulation stroke and posterior fossa mass lesions, and improve resource utilization.


The pneumonia severity index predicts time to clinical stability in patients with community-acquired pneumonia.
A total of 33 hospitals in 13 countries in North America, Europe, Africa, Asia and Latin America. To investigate the relationship between the pneumonia severity index (PSI) and the time to clinical stability from intravenous to oral antibiotic therapy in hospitalized adult patients with community-acquired pneumonia (CAP). An international, retrospective, observational study of random adult patients meeting the definition of CAP between June 2001 and May 2004. The risk class (RC) according to the PSI was calculated for all patients. The criteria to define when a patient is clinically stable were evaluated daily during the first 7 days of hospitalization in all patients. The mean time to clinical stability for 254 patients in RC I was 4.2 days, for 233 patients in RC II it was 3.9 days, for 395 patients in RC III it was 4.6 days, for 644 patients in RC IV it was 5.0 days and for 296 patients in RC V it was 6.0 days. Significant positive correlations were observed between RC and time to clinical stability (P < 0.0001). The PSI is a tool that can be used to predict time to clinical stability (i.e., time to antimicrobial switch therapy) in hospitalized patients with CAP.


Mutations in PMR1 stimulate xylose isomerase activity and anaerobic growth on xylose of engineered Saccharomyces cerevisiae by influencing manganese homeostasis.
Combined overexpression of xylulokinase, pentose-phosphate-pathway enzymes and a heterologous xylose isomerase (XI) is required but insufficient for anaerobic growth of Saccharomyces cerevisiae on d-xylose. Single-step Cas9-assisted implementation of these modifications yielded a yeast strain expressing Piromyces XI that showed fast aerobic growth on d-xylose. However, anaerobic growth required a 12-day adaptation period. Xylose-adapted cultures carried mutations in PMR1, encoding a Golgi Ca2+/Mn2+ ATPase. Deleting PMR1 in the parental XI-expressing strain enabled instantaneous anaerobic growth on d-xylose. In pmr1 strains, intracellular Mn2+ concentrations were much higher than in the parental strain. XI activity assays in cell extracts and reconstitution experiments with purified XI apoenzyme showed superior enzyme kinetics with Mn2+ relative to other divalent metal ions. This study indicates engineering of metal homeostasis as a relevant approach for optimization of metabolic pathways involving metal-dependent enzymes. Specifically, it identifies metal interactions of heterologous XIs as an underexplored aspect of engineering xylose metabolism in yeast.


The risk of bias in observational studies of exposures (ROBINS-E) tool: concerns arising from application to observational studies of exposures.
Systematic reviews, which assess the risk of bias in included studies, are increasingly used to develop environmental hazard assessments and public health guidelines. These research areas typically rely on evidence from human observational studies of exposures, yet there are currently no universally accepted standards for assessing risk of bias in such studies. The risk of bias in non-randomised studies of exposures (ROBINS-E) tool has been developed by building upon tools for risk of bias assessment of randomised trials, diagnostic test accuracy studies and observational studies of interventions. This paper reports our experience with the application of the ROBINS-E tool. We applied ROBINS-E to 74 exposure studies (60 cohort studies, 14 case-control studies) in 3 areas: environmental risk, dietary exposure and drug harm. All investigators provided written feedback, and we documented verbal discussion of the tool. We inductively and iteratively classified the feedback into 7 themes based on commonalities and differences until all the feedback was accounted for in the themes. We present a description of each theme. We identified practical concerns with the premise that ROBINS-E is a structured comparison of the observational study being rated to the 'ideal' randomised controlled trial. ROBINS-E assesses 7 domains of bias, but relevant questions related to some critical sources of bias, such as exposure and funding source, are not assessed. ROBINS-E fails to discriminate between studies with a single risk of bias or multiple risks of bias. ROBINS-E is severely limited at determining whether confounders will bias study outcomes. The construct of co-exposures was difficult to distinguish from confounders. Applying ROBINS-E was time-consuming and confusing. Our experience suggests that the ROBINS-E tool does not meet the need for an international standard for evaluating human observational studies for questions of harm relevant to public and environmental health. We propose that a simpler tool, based on empirical evidence of bias, would provide accurate measures of risk of bias and is more likely to meet the needs of the environmental and public health community.


Design Parameters in Multimodal Games for Rehabilitation.
Objectives: The repetitive and sometimes mundane nature of conventional rehabilitation therapy provides an ideal opportunity for development of interactive and challenging therapeutic games that have the potential to engage and motivate the players. Certain game design parameters that may encourage patients to actively participate by making the games more enjoyable have been identified. In this article, we describe a formative study in which we designed and evaluated some of these parameters with healthy subjects. Materials and Methods: The "operant conditioning" and "scoring" design parameters were incorporated in a remake of a classic labyrinth game, "Marble Maze." A group of participants (n=37) played the game twice: Once in the control condition without both modalities and then with either one of the parameters or with both. Measures of game duration and number of fails in the game were recorded along with survey questionnaires to measure player perceptions of intrinsic motivation on the game. Results: Longer playtimes, higher levels of interest/enjoyment, and effort to play the game were recorded with the introduction of these parameters. Conclusions: This study provides an understanding on how game design parameters can be used to motivate and encourage people to play longer. With these positive results, future aims are to test the parameters with stroke patients, providing much clearer insight as to what influences these parameters have on patients undergoing therapy. The ultimate goal is to utilize game design in order to maintain longer therapeutic interaction between a patient and his or her therapy medium.


Factors associated with symptoms of depression among informal caregivers of people with systemic sclerosis: a cross-sectional study.
Purpose: Our study aimed to identify caregiver characteristics (gender, age, occupational status, educational attainment, relation to care recipient), care recipient characteristics (age, disease subtype), and caregiving factors (hours of care, perceived caregiving burden) associated with symptoms of depression among informal caregivers of persons with systemic sclerosis (also known scleroderma).as Materials and methods: A questionnaire was developed and administered online from December 2016 to June 2017 to informal caregivers of people with scleroderma, including the Patient Health Questionnaire-9 to assess depressive symptoms. Multiple linear regression was used to identify factors associated with depressive symptoms.Results: Caregivers (n = 202) were 60.9% male. Average age was 57.2 years (standard deviation = 14.4 years). Most caregivers were partners (72.3%), children (11.9%), or parents (7.4%), of care recipients. Self-reported caregiving burden (standardized regression coefficient [Formula: see text] = 0.54, p < 0.001) and hours of care per week ([Formula: see text] = 0.17, p = 0.005) were significantly associated with greater symptoms of depression.Conclusions: Depressive symptoms were primarily associated with caregiving burden among a sample of scleroderma caregivers. There is need to develop interventions targeting caregivers in scleroderma. Rehabilitation professionals should consider the specific needs of scleroderma caregivers and should provide or refer to support services as appropriate.Implications for RehabilitationMost people diagnosed with scleroderma are cared for by an informal caregiver and the majority of these caregivers experience mild symptoms of depression.For caregivers that experience moderate to severe symptoms of depression, the ability to provide care to a loved one with scleroderma may be more difficult.Rehabilitation professionals should be aware of the burden faced by caregivers of persons with scleroderma and provide support services or referrals as appropriate.


Impact of Bit Errors in Digitized RF Data on Ultrasound Image Quality.
This article quantitatively analyzes the impact of bit errors in digitized RF data on ultrasound image quality. The quality of B-mode images in both linear array and phased array imaging is evaluated by means of three objective image quality metrics: peak signal-to-noise ratio, structural similarity index, and contrast-to-noise ratio, when bit errors are introduced to the RF data with different bit-error rates (BERs). The effectiveness of coding schemes for forward error detection and correction to improve the image quality is also studied. The results show that ultrasound imaging is inherently resilient to high BER. The image quality suffers unnoticeable degradation for BER lower than 1E-6. Simple 1-bit parity coding with 9% added redundancy helps to retain similar image quality for BER up to 1E-4, and Hamming coding with 33.3% added redundancy allows the BER to increase to 1E-3. These results can serve as a guideline in the datalink design for ultrasound probes with in-probe receive digitization. With much more relaxed BER requirements than in typical datalinks, the design can be optimized by allowing fewer cables with higher data rate per cable or lower power consumption with the same cable count.


Determinants of premature infant pain responses to heel sticks.
The exposure of premature infants to stressors, such as pain intended to ensure their survival, may instead alter their brain development and contribute to several learning and behavioral difficulties observed in later childhood. The objective of this descriptive, cross-sectional study was to compare the pain responses of 72 preterm infants to a heel stick procedure taking into consideration a variety of factors, including the use of opioids and sedatives. The pain scores assessed on the Preterm Infant Pain Profile (PIPP) scale were highest for the lowest gestational age (GA) group. Multiple linear regression analysis with the four predictor variables noted to be correlated with the PIPP scores (GA, type of needle, severity of illness, and behavioral state) indicated a significant overall relationship (F [5/66] = 5.62, p < 0.01) and accounted for 44% of the variance. All but severity of illness did not add significantly to the variance. Gender, postnatal age, amount, opioids, and sedatives used were not correlated to the PIPP scores. It was concluded that sick premature infants and those who have been exposed to a variety of painful procedures may not manifest behavioral or physiological signs of pain, but may be the most to benefit from precise pain assessment and prudent management.


Mal de debarquement syndrome: new insights.
Mal de Debarquement Syndrome (MdDS) is an enigmatic neurotological disorder with high morbidity, psychosocial burden, and few treatment options. Fortunately, there has been recent growth in scientific interest in understanding the biological basis of and in treating MdDS. Recent studies using functional neuroimaging have shown increased glucose metabolism in the left entorhinal cortex (EC) and amygdala in the setting of decreased prefrontal and temporal cortex metabolism in subjects with persistent MdDS. The EC is a key player in processing and gating spatial information to be stored in the hippocampus and is a major driver of brain oscillations. A limbic focus may also be key to spontaneous MdDS-like symptoms occurring in individuals with a history of anxiety or chronic stress. Treatment with repetitive transcranial magnetic stimulation over the dorsolateral prefrontal cortex can decrease the rocking dizziness of MdDS, with successful responses associated with decreases in the coherence between brain networks with nodes in the parietal and occipital lobes. A new theory of MdDS is proposed as pathology secondary to entrainment of intrinsic brain networks driven by oscillatory motion exposure coupled with an inability to subsequently desynchronize the activity of these nodes. Future treatment strategies may be directed toward unyoking these networks.


Caregiver support for women during childbirth.
Social support may include advice or information, tangible assistance and emotional support. The objective of this review was to assess the effects of continuous support during labour (provided by health care workers or lay people) on mothers and babies. I searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. Date of last search: April 1999. Randomised trials comparing continuous support during labour with usual care. Trial quality was assessed. Study authors were contacted for additional information. Fourteen trials, involving more than 5000 women, are included in the Review. The continuous presence of a support person reduced the likelihood of medication for pain relief, operative vaginal delivery, caesarean delivery, and a 5-minute Apgar score less than 7. Continuous support was also associated with a slight reduction in the length of labour. Six trials evaluated the effects of support on mothers' views of their childbirth experiences; while the trials used different measures (overall satisfaction, failure to cope well during labour, finding labour to be worse than expected, and level of personal control during childbirth), in each trial the results favoured the group who had received continuous support. Continuous support during labour from caregivers (nurses, midwives or lay people) appears to have a number of benefits for mothers and their babies and there do not appear to be any harmful effects.


Frequency, potential risk and therapeutic intervention in end-stage renal disease patients with antiphospholipid antibody syndrome: a multicenter study.
Antiphospholipid antibody syndrome (APAS) is characterized by the presence of anticardiolipin antibodies (ACA) in association with thrombotic disorders of arterial and/or venus systems, spontaneous abortion(s) or thrombocytopenia. In this multicenter study, 502 end-stage renal disease (ESRD) patients awaiting renal transplants were screened to determine the frequency of APAS, the potential risk associated with APAS, and strategies for therapeutic intervention. Ninety-three patients (19%) had high titers of ACA. Twenty-three patients had documented evidence of one or more of the thrombotic disorders such as lupus, frequent abortions, frequent thrombosis of arteriovenous shunts, biopsy-proven microrenal angiopathy, or thrombocytopenia and thus were diagnosed with APAS. Of these 23 patients, 11 received kidney transplants either with (4 patients) or without (7 patients), concomitant anticoagulation therapy. All seven of the patients with APAS not treated with anticoagulation therapy lost their allografts within 1 week as a result of renal thrombosis. In contrast, three out of four transplant patients with APAS treated with anticoagulation therapy maintained their allografts for over 2 years. The fourth patient lost his graft within a week because of thrombosis. Of the remaining 70 patients with high titers of ACA but no evidence of thrombotic disorders, 37 received kidney transplants. None lost their allografts as a result of thrombosis. Our data suggest that, although 19% of our ESRD patients exhibit high titer of ACA, only 5% of the patients have APAS. In conclusion, our data suggest that the patients with APAS are at high risk of posttransplant renal thrombosis. Anticoagulation therapy could prevent patients from posttransplant thrombosis in patients with APAS.


A Diagnostic Marker to Discriminate Childhood Apraxia of Speech From Speech Delay: IV. The Pause Marker Index.
Three previous articles provided rationale, methods, and several forms of validity support for a diagnostic marker of childhood apraxia of speech (CAS), termed the pause marker (PM). Goals of the present article were to assess the validity and stability of the PM Index (PMI) to scale CAS severity. PM scores and speech, prosody, and voice precision-stability data were obtained for participants with CAS in idiopathic, neurogenetic, and complex neurodevelopmental disorders; adult-onset apraxia of speech consequent to stroke and primary progressive apraxia; and idiopathic speech delay. Three studies were completed including criterion and concurrent validity studies of the PMI and a temporal stability study of the PMI using retrospective case studies. PM scores were significantly correlated with other signs of CAS precision and stability. The best fit of the distribution of PM scores to index CAS severity was obtained by dividing scores into 4 ordinal severity classifications: mild, mild-moderate, moderate-severe, and severe. Severity findings for the 4 classifications and retrospective longitudinal findings from 8 participants with CAS supported the validity and stability of the PMI. Findings support research and clinical use of the PMI to scale the severity of CAS.


Tracheal autograft prefabrication using microfibrillar collagen and bone morphogenetic protein.
To investigate the feasibility of prefabricating a tracheal autograft capable of microvascular free tissue transfer using microfibrillar collagen (Avitene) as a carrier for bone morphogenetic protein (BMP). Using heterotopic bone induction and soft tissue molding, an attempt was made to prefabricate a homologous tracheal autograft in a rodent free flap model. In 12 male Sprague-Dawley rats, linear troughs were dissected along the length of the gracillis muscle, filled with BMP-saturated microfibrillar collagen, molded around a silicone tracheal stent, and left pedicled on the femoral vessels. Untreated microfibrillar collagen was buried in muscle at a distant control site in 3 animals. Autografts were susequently evaluated for lumen integrity, vascular patency, and bone induction at 3 weeks. With the exception of 2 nonviable grafts, rings of heterotopic bone were created in all 10 animals. Rings spanning at least one third of the tracheal circumference maintained a noncollapsible lumen. Microfibrillar collagen was replaced by cancellous bone that reproduced the exact shape and volume of the collagen carrier. The lumen was lined by smooth fibroplasia, and there was no significant inflammatory response, bone exposure, or overgrowth. Soft tissue between rings allowed longitudinal flexibility, homologous to the native trachea. Bone induction did not occur in any of the control sites. Microfibrillar collagen is an effective carrier for BMP and may serve as the ideal substrate for tracheal reconstruction without the need for stenting. The potential use of BMP to bioengineer microvascular free flaps with intrinsic skeletal support has an unlimited potential and will add a new dimension to head and neck reconstruction.


A Clickable Oxysterol Photolabel Retains NMDA Receptor Activity and Accumulates in Neurons.
Oxysterol analogs that modulate NMDA receptor function are candidates for therapeutic development to treat neuropsychiatric disorders. However, the cellular actions of these compounds are still unclear. For instance, how these compounds are compartmentalized or trafficked in neurons is unknown. In this study, we utilized a chemical biology approach combining photolabeling and click chemistry. We introduce a biologically active oxysterol analog that contains: (1) a diazirine group, allowing for the permanent labeling of cellular targets, and (2) an alkyne group, allowing for subsequent in situ visualization using Cu2+ catalyzed cycloaddition of an azide-conjugated fluorophore. The physiological properties of this analog at NMDA receptors resemble those of other oxysterols, including occlusion with other oxysterol-like compounds. Fluorescent imaging reveals that the analog accumulates diffusely in the cytoplasm of neurons through an energy-independent mechanism. Overall, this work introduces a novel chemical biology approach to investigate oxysterol actions and introduces a tool useful for further cell biological and biochemical studies of oxysterols.


Skewness in the literature on infectious livestock diseases in an emerging economy - the case of Vietnam.
Livestock production has increased in many emerging economies, but productivity is often substantially impaired by infectious diseases. The first step towards improved livestock health and productivity is to map the presence of livestock diseases. The objective of this review was to summarize studies conducted on such diseases in an emerging economy, Vietnam, and thereby identifying knowledge gaps that may inform the design of surveillance and control programs. Few studies were found to evaluate the distribution of infectious livestock diseases other than avian influenza. Also, many regions with dense livestock populations had received little attention in terms of disease investigation. A large proportion of the studies dealt with zoonoses and food-borne infections which might be due to funding agencies priorities. On the contrary, studies targeting infections that affect livestock and their productivity were few. We think that this limitation in scientific reports on infectious diseases that only affect livestock productivity is a common phenomenon in low and lower middle income countries. More science-based data on such diseases would help policymakers to prioritize which livestock diseases should be subject to animal health programs aimed to support rural livelihoods and economic development.


Probable reasons for expressed agitation in persons with dementia.
Nursing home patients with dementia were videotaped in three previous studies. Sixty sequences of nine patients exhibiting agitated behaviors were examined to identify the most probable antecedents to agitation. Probable reasons were interpreted and applied to the Progressively Lowered Stress Threshold model, which suggests that agitation is stress related. Analysis suggests that agitation often serves as a form of communication. Two underlying reasons seem to be that the patient had loss of control over the situation and deficient autonomy. The most common causes for expressed agitation were interpreted as discomfort, a wish to be served immediately, conflict between patients or with nursing staff, reactions to environmental noises or sound, and invasion of personal space. It is recommended that nursing staff promote autonomy and independency for this group of patients whenever possible. By evaluating probable reasons for expressed agitation, the nursing staff can take steps to prevent or alleviate agitation.


Measuring lung water following major lung resection.
Following the acute changes of lung resection surgery, does the ratio of intrathoracic blood volume (ITBV) to global end diastolic volume (GEDV) remain constant? If it does this could validate a single thermo dilution (STD) technique in the measurement of extravascular lung water index (EVLWI) in patients undergoing lung resection surgery. EVLWI was derived using both double dye technique (DDT) and single thermo dilution technique (STD) in four patients undergoing thoracotomy selected for major lung resection surgery. Regular measurements were made for up to 12 h after surgery. After the first two hours following lung resection surgery, the ratio of blood volume ITBV/GEDV shows little variation for up to 12 h. EVLWI measurements measured by STD correlate well with those of DDT. This preliminary study suggests that EVLWI measurements by STD could be used to measure changes in EVLW following major lung resection. An assessment of EVLW could be useful in early diagnosis, management and treatments of the devastating condition of postoperative acute lung injury.


Modelling homosexual and heterosexual transmissions of hepatitis B virus in China.
Studies have shown that sexual transmission, both heterosexually and homosexually, is one of the main ways of HBV infection. Based on this fact, we propose a mathematical model to study the sexual transmission of HBV among adults by classifying adults into men and women and considering both same-sex and opposite-sex transmissions of HBV in adults. Firstly, we calculate the basic reproduction number R0 and the disease-free equilibrium point E0. Secondly, by analysing the sensitivity of R0 in terms of model parameters, we find that the infection rate among people who have same-sex partners, the frequency of homosexual contact and the immunity rate of adults play important roles in the transmission of HBV. Moreover, we use our model to fit the reported data in China and forecast the trend of hepatitis B. Our results demonstrate that popularizing the basic knowledge of HBV among residents, advocating healthy and reasonable sexual life style, reducing the number of adult carriers, and increasing the immunization rate of adults are effective measures to prevent and control hepatitis B.


The Portuguese plastic carrier bag tax: The effects on consumers' behavior.
Marine litter from lightweight plastic bags is a global problem that must be solved. A plastic bag tax was implemented in February 2015 to reduce the consumption of plastic grocery bags in Portugal and in turn reduce the potential contribution to marine litter. This study analyzes the effect of the plastic bag tax on consumer behavior to learn how it was received and determine the perceived effectiveness of the tax 4months after its implementation. In addition, the study assessed how proximity to coastal areas could influence behaviors and opinions. The results showed a 74% reduction of plastic bag consumption with a simultaneously 61% increase of reusable plastic bags after the tax was implemented. Because plastic bags were then reused for shopping instead of garbage bags, however, the consumption of garbage bags increased by 12%. Although reduction was achieved, the tax had no effect on the perception of marine litter or the impact of plastic bags on environment and health. The majority of respondents agree with the tax but view it as an extra revenue to the State. The distance to the coast had no meaningful influence on consumer behavior or on the perception of the tax. Although the tax was able to promote the reduction of plastics, the role of hypermarkets and supermarkets in providing alternatives through the distribution of reusable plastic bags was determinant to ensuring the reduction.


Photosynthetic antenna-reaction center mimicry by using boron dipyrromethene sensitizers.
Various molecular and supramolecular systems have been synthesized and characterized recently to mimic the functions of photosynthesis, in which solar energy conversion is achieved. Artificial photosynthesis consists of light-harvesting and charge-separation processes together with catalytic units of water oxidation and reduction. Among the organic molecules, derivatives of BF2-chelated dipyrromethene (BODIPY), "porphyrin's little sister", have been widely used in constructing these artificial photosynthetic models due to their unique properties. In these photosynthetic models, BODIPYs act as not only excellent antenna molecules, but also as electron-donor and -acceptor molecules in both the covalently linked molecular and supramolecular systems formed by axial coordination, hydrogen bonding, or crown ether complexation. The relationships between the structures and photochemical reactivities of these novel molecular and supramolecular systems are discussed in relation to the efficiency of charge separation and charge recombination. Femto- and nanosecond transient absorption and photoelectrochemical techniques have been employed in these studies to give clear evidence for the occurrence of energy- and electron-transfer reactions and to determine their rates and efficiencies.


Distinguishing infectivity in patients with pulmonary tuberculosis using deep learning.
This study aimed to develop and assess a deep-learning model based on CT images for distinguishing infectivity in patients with pulmonary tuberculosis (PTB). We labeled all 925 patients from four centers with weak and strong infectivity based on multiple sputum smears within a month for our deep-learning model named TBINet's training. We compared TBINet's performance in identifying infectious patients to that of the conventional 3D ResNet model. For model explainability, we used gradient-weighted class activation mapping (Grad-CAM) technology to identify the site of lesion activation in the CT images. The TBINet model demonstrated superior performance with an area under the curve (AUC) of 0.819 and 0.753 on the validation and external test sets, respectively, compared to existing deep learning methods. Furthermore, using Grad-CAM, we observed that CT images with higher levels of consolidation, voids, upper lobe involvement, and enlarged lymph nodes were more likely to come from patients with highly infectious forms of PTB. Our study proves the feasibility of using CT images to identify the infectivity of PTB patients based on the deep learning method.


Skin properties associated with skin tears in older adults: A case-control study.
The world population is growing rapidly and skin problems such as skin tears (STs) are more common in aging skin due to changes in the epidermis and dermis. Identification of ageing related skin properties, which are risk factors for STs, is essential for the development of ST prevention protocols. The aim of this study was to reveal the skin properties related to epidermal function and dermal associated with STs. A prospective case-control study was conducted with a sample of 36 older adults, 18 participants with ST and 18 participants without ST, in two elderly care centers. Tewameter TM 210 was used to measure transepidermal water loss, the Sebumeter SM810 was used to measure sebum, and Cutometer Dual MPA 580 was used to measure skin viscoelasticity (R0-R9). The differences of skin properties between groups were analyzed using the independent t-test and Mann-Whitney U test. The case group had a mean age of 77,17 ± 9,7 and the control group had a mean age of 75,33 ± 6,8. It was determined that there were more ecchymosis (p < 0.000), hematoma (p = 0.008), and ST history (p = 0.001) in the case group. Older adults in the case group were more frail than the control group (p = 0.044). Regarding the score of the skin properties, the case group showed that the TEWL levels of the older adults in the case group were lower (p = 0.031) compared to the control groups. There was a significant difference between the groups and R0, R2, R5, and R7. While R0 was higher in the case group, R2, R5, and R7 were lower than the control group. Older adults with ST showed differences in skin properties compared to those without ST, especially transepidermal water loss, and viscoelasticity (R0, R2, R5, R7). The results of this study suggest that some changes in skin properties may be a risk factor for STs.


Diagnosing mild traumatic brain injury: where are we now?
The brain acoustic monitor (BAM), an indicator of cerebral autoregulation, has previously shown high sensitivity but low specificity for computed tomographic (CT) abnormality in patients following the clinical diagnosis of traumatic brain injury. We assessed the utility of the BAM in diagnosing mild TBI (mTBI) in patients with and without normal findings of CT scan, a population for which there are a few objective markers of disease. We prospectively studied 369 patients with mechanism of injury consistent with TBI. The diagnosis was evaluated by five methods: (a) study enrollment (i.e., mechanism of injury), (b) signs of head trauma, (c) expert physician assessment, (d) presence of initial symptoms (loss of consciousness [LOC]; amnesia), and (e) BAM. All patients had a head CT scan. We compared the BAM screen results with the diagnosis of mTBI and BAM data from 50 normal volunteers and 49 trauma control patients not thought to have TBI. None of the diagnostic methods correlated well with the others. Correlation between the methods ranged from 21% to 71%. BAM discriminated between patients with mTBI versus without TBI (p<0.01) and patients with mTBI versus normal subjects (p<0.001). There were 14 patients with new abnormal findings of CT scans. A history of LOC and physical signs of head injury were associated with a new abnormality on head CT (p<0.05 and p<0.01, respectively), whereas an abnormal BAM signal was suggestive (p=0.08). The sensitivity of BAM abnormality for head CT abnormality was 100%, with a specificity of 30.14%. There is no gold standard for the diagnosis of mTBI. BAM screening is a useful diagnostic adjunct in patients with mTBI and may facilitate decision making. An abnormal BAM reading adds significance to LOC as a predictor of a new abnormality on head CT. In our study, opting not to CT scan patients with a normal BAM signal would have missed no new CT findings and no patients who required medical intervention for TBI, at a cost savings of $202,950.


Cobalamin (Cbl) C/D deficiency: clinical, neurophysiological and neuroradiologic findings in 14 cases.
The early onset type of cobalamin (Cbl) C/D deficiency is characterised by feeding difficulties, failure to thrive, hypotonia, seizures, microcephaly and developmental delay. It has an unfavourable outcome, often with early death and significant neurological impairment in survivors. While clinical and biochemical features of Cbl C/D deficiency are well known, only a few isolated case reports are available concerning neurophysiological and neuroimaging findings. We carried out clinical, biochemical, neurophysiological and neuroradiologic investigations in 14 cases with early-onset of the Cbl CID defect. Mental retardation was identified in most of the cases. A variable degree of supratentorial white matter atrophy was detected in 11 cases by MR imaging and tetraventricular hydrocephalus was present in the remaining 3 patients. Waking EEG showed a clear prevalence of epileptiform abnormalities, possibly related to the high incidence of seizures in these cases. Increased latency of evoked responses and/or prolongation of central conduction time were the most significant neurophysiological abnormalities. The selective white matter involvement, shown both by neuroradiologic and neurophysiological studies, seems to be the most consistent finding of Cbl C/D deficiency and may be related to a reduced supply of methyl groups, possibly caused by the dysfunction in the methyl-transfer pathway.


Studies on antibody-producing cells. IV. Ultrastructue of plaque-forming cells of rabbit lymph.
Efferent lymph of the popliteal lymph nodes of rabbits was collected 4 days after a single footpad injection of SRBC. Thin-layer agar plating was done to isolate plaque-forming cells of the lymph for electron microscope examination, and the numbers of plaque-forming cells (PFC) in cells from the lymph and lymph nodes were determined. Of 71 PFC of lymph isolated and examined, 93% were lymphocytes, most of them with signs of substantial levels of physiologic activity. The cytoplasm showed an abundance of free ribosomes and many finger-like projections. The endoplasmic reticulum (ER) was barely detectable in most of the active lymphocytic PFC, and in some, a few short narrow channels of ER could be seen. Approximately one-fifth of the lymphocytic PFC presented an appearance of senescence, with signs of degeneration: rounded cells, with amorphous nuclear chromatin, and very few microvilli. The remaining 7% of the PFC of the lymph showed an unusual combination of features: small round cells with a narrow ring of cytoplasm which, however, contained well-organized channels of ER. Such cells had been found only among PFC of peripheral blood of the rabbit. The number of PFC per million cells was higher in the lymph than in the suspensions of lymph node cells. In both the contralateral lymph node and its efferent lymph, the number of PFC was less than 1% that of the injected side.


[Congenital hereditary corneal dystrophy associated with various extraoculary anomalies].
Two subjects (brother and sister), children of consanguineous parents, showed a typical congenital corneal dystrophy associated with mental retardation and a bilateral malformation of the little finger. One of them, a boy of 10, was fat and showed a hearing loss for high tones. His corneal opacity diminished during 7 years observation. Seeing that the affected tissues were of mesenchymal origin, the authors conclude that the syndrome was mesodermal.


Health Care Costs by Type of Expenditure across eGFR Stages among Patients with and without Diabetes, Cardiovascular Disease, and Heart Failure.
CKD is associated with higher health care costs that increase with disease progression. However, research is lacking on the type of health care costs associated with CKD across all stages in a general population with a substantial comorbidity burden. Using electronic medical records of an integrated delivery system, we evaluated health care costs by expenditure type in general and in patients with CKD by eGFR and presence of comorbidities. We categorized 146,132 patients with eGFR data in 2016 or 2017 and examined nonmutually exclusive groups according to presence of diabetes mellitus, cardiovascular disease, or heart failure. We used 1 year of follow-up data to calculate outpatient, inpatient, emergency, pharmaceutical, dialysis, and total health care costs by eGFR (Kidney Disease Improving Global Outcomes-defined eGFR categories), adjusted for age, sex, and nonwhite race. Mean total health care costs among patients with CKD without comorbidities were 31% higher than among patients without CKD ($7374 versus $5631, respectively). Hospitalizations accounted for 35% of total costs among those with CKD and no comorbidities but up to 55% among patients with CKD and heart failure. The proportion of costs attributable to hospitalizations accelerated with declining kidney function, reaching as high as 66%. Poorer kidney function and the presence of diabetes mellitus, cardiovascular disease, or heart failure drive substantial health care costs and increase the proportion of costs attributable to inpatient care. The large contribution of inpatient costs begins in earlier stages of CKD and escalates as kidney function declines. Additional therapies to reduce CKD incidence, slow CKD progression, and lower hospitalization risk are needed to benefit patients and reduce CKD's economic burden.


Safety and Efficacy of Ultrasound-Guided Percutaneous Core Needle Biopsy of Pancreatic and Peripancreatic Lesions Adjacent to Critical Vessels.
To evaluate the safety and efficacy of ultrasound-guided percutaneous core needle biopsy (USPCB) of pancreatic and peripancreatic lesions adjacent to critical vessels. Data were collected retrospectively from 162 patients who underwent USPCB of the pancreas (n = 98), the peripancreatic area adjacent to the portal vein, the paraaortic area adjacent to pancreatic uncinate (n = 34), and lesions on the third duodenal portion (n = 30) during a 10-year period. An automated biopsy gun with an 18-gauge needle was used for biopsies under US guidance. The USPCB results were compared with those of the final follow- up imaging performed postoperatively. The diagnostic accuracy and major complication rate of the USPCB were calculated. Multiple factors were evaluated for the prediction of successful biopsies using univariate and multivariate analyses. The histopathologic diagnosis from USPCB was correct in 149 (92%) patients. The major complication rate was 3%. Four cases of mesenteric hematomas and one intramural hematoma of the duodenum occurred during the study period. The following factors were significantly associated with successful biopsies: a transmesenteric biopsy route rather than a transgastric or transenteric route; good visualization of targets; and evaluation of the entire US pathway. In addition, the number of biopsies required was less when the biopsy was successful. USPCB demonstrated high diagnostic accuracy and a low complication rate for the histopathologic diagnosis of pancreatic and peripancreatic lesions adjacent to critical vessels.


Reliability and Validity of Assessing User Satisfaction With Web-Based Health Interventions.
The perspective of users should be taken into account in the evaluation of Web-based health interventions. Assessing the users' satisfaction with the intervention they receive could enhance the evidence for the intervention effects. Thus, there is a need for valid and reliable measures to assess satisfaction with Web-based health interventions. The objective of this study was to analyze the reliability, factorial structure, and construct validity of the Client Satisfaction Questionnaire adapted to Internet-based interventions (CSQ-I). The psychometric quality of the CSQ-I was analyzed in user samples from 2 separate randomized controlled trials evaluating Web-based health interventions, one from a depression prevention intervention (sample 1, N=174) and the other from a stress management intervention (sample 2, N=111). At first, the underlying measurement model of the CSQ-I was analyzed to determine the internal consistency. The factorial structure of the scale and the measurement invariance across groups were tested by multigroup confirmatory factor analyses. Additionally, the construct validity of the scale was examined by comparing satisfaction scores with the primary clinical outcome. Multigroup confirmatory analyses on the scale yielded a one-factorial structure with a good fit (root-mean-square error of approximation =.09, comparative fit index =.96, standardized root-mean-square residual =.05) that showed partial strong invariance across the 2 samples. The scale showed very good reliability, indicated by McDonald omegas of .95 in sample 1 and .93 in sample 2. Significant correlations with change in depressive symptoms (r=-.35, P<.001) and perceived stress (r=-.48, P<.001) demonstrated the construct validity of the scale. The proven internal consistency, factorial structure, and construct validity of the CSQ-I indicate a good overall psychometric quality of the measure to assess the user's general satisfaction with Web-based interventions for depression and stress management. Multigroup analyses indicate its robustness across different samples. Thus, the CSQ-I seems to be a suitable measure to consider the user's perspective in the overall evaluation of Web-based health interventions.


Determination of volatile organic compound emissions and ozone formation from spraying solvent-based pesticides.
Large-scale agricultural activities have come under scrutiny for possible contributions to the emission of ozone precursors. The San Joaquin Valley (SJV) of California is an area with intense agricultural activity that exceeds the federal ozone standards for more than 30 to 40 d yr(-1) and the more stringent state standards for more than 100 d yr(-1). Pesticides are used widely in both agricultural and residential subregions of the SJV, but the largest use, by weight of "active ingredient," is in agriculture. The objective of the study was to determine the role of pesticide application on airborne volatile organic compounds (VOC) concentrations and ozone formation in the SJV. The ozone formation from the pesticide formulation sprayed on commercial orchards was studied using two transportable smog chambers at four application sites during the summers of 2007 and 2008. In addition to the direct measurements of ozone formation, airborne VOC concentrations were measured before and after pesticide spraying using canister and sorbent tube sampling techniques. Soil VOC concentrations were also measured to understand the distribution of VOCs between different environmental compartments. Numerous VOCs were detected in the air and soil samples throughout the experiment but higher molecular weight aromatic hydrocarbons were the primary compounds observed in elevated concentrations immediately after pesticide spraying. Measurements indicate that the ozone concentration formed by VOC downwind of the orchard may increase up to 15 ppb after pesticide application, with a return back to prespray levels after 1 to 2 d.


Cognitive Behavioral Therapy Reduces Benzodiazepine Anxiolytics Use in Japanese Patients with Mood and Anxiety Disorders: A Retrospective Observational Study.
Benzodiazepines (BZDs) are prescribed to treat psychiatric diseases. However, many guidelines recommend limiting the use of BZDs because of side effects and lack of evidence regarding long-term efficacy. Moreover, reducing BZDs' use is difficult because of dependency and the severity of withdrawal symptoms. The efficacy of cognitive behavioral therapy (CBT) for mood and anxiety disorders has been demonstrated. However, there is scant evidence that CBT has effectively reduced BZDs use, especially in Japan, where the BZDs prescription rate is high. Therefore, we sought to examine the impact of CBT on reducing BZDs use in a Japanese psychiatric setting. Participants were outpatients with mood and anxiety disorders who were prescribed BZD anxiolytics. We retrospectively reviewed changes in BZD anxiolytics prescription dosages during CBT (66 patients; mean number of CBT sessions, 14.6) from our hospital record between April 2015 and September 2017. We checked prescriptions at four time points: at first interview for judging adaptation of CBT (baseline), at the first CBT session, at the last CBT session, and 3 months after the last CBT session. A total of 13 of 66 patients discontinued BZD anxiolytics during CBT, and 21 of 66 reduced their prescribed dosage by 50%. The association between discontinuation and dose-reduction and assessment period was modeled simultaneously using Bayesian hierarchical hurdle model. Results from the modeling showed a significant discontinuation at post-CBT and at 3 months post-CBT session compared to baseline (estimated median odds ratio [OR] post-CBT = 9.79 [95% CI: 4.65-20.45]; OR at 3 months post-CBT = 11.53 [95% CI: 6.06-22.33]). Moreover, a significant dose reduction was observed post-intervention (estimated median relative risk = 0.845 [95% CI: 0.729-0.982]), with a median reduction of 1.7 mg (diazepam conversion) in BZD use. Our results suggest that CBT possibly aids in reducing and discontinuing BZD anxiolytics use for Japanese patients.


[Anorectal fistulas in Crohn disease].
Anorectal fistulas don't follow the same rules as idiopathic anorectal fistulas do. Their cause and treatment is completely different. Almost 40% of all patients suffering from Crohn's disease show anorectal manifestations. In 10-15% of the cases the anorectal manifestation is the first sign of Crohn's disease at all. 30% of all fistulas heal at least for a while spontaneously. The diagnostic procedures include nowadays anal endosonography and MRI as most sensitive ones and should be added for every work-up of anorectal Crohn. We differ a conservative from a radical therapy. To our opinion every therapy should be adopted to the individual needs of each patient. The most important principle in anorectal Crohn's disease is laying open of the fistula tract and excision of all the diseased tissue. This should be followed either by a drainage seton or by a definitive plastic closure of the fistula (mucosa-muscle flap). For a mucosa-muscle-flap there is only in otherwise disease-free patients and there only for high transsphincteric fistulas an indication. In our own series we treated of 69 patients 59 with a drainage seton and 10 with a mucosa-muscle flap. Recurrence occurred in 6/59 respectively 2/10 of the treated patients. Anovaginal fistulas should due to the high recurrence rate of surgically closed fistulas (> 50%) only be operated if there are serious symptoms such as recurrent vaginal infection, vaginal flatus and permanent vaginal defecations.


Integrating data-mining support into a brain-image database using open-source components.
Previously, we described our implementation of a brain-image database (braid), based on the proprietary object relational database-management system (ORDBMS) Illustra [1]. In conjunction with our collaborators, we have used this database to manage and analyze image and clinical data from what we call image-based clinical trials (IBCTs). Herein we describe the results of redesigning braid using open-source components, and integrating support for mining image and clinical data from braid's user interface. We re-designed and re-implemented braid using open-source components, including PostgreSQL, gcc, and PHP. We integrated data-mining algorithms into braid, based on PL/R, a PostgreSQL package to support efficient communication between R and PostgreSQL. We present a sample clinical study to demonstrate how clinicians can perform queries for visualization, statistical analysis, and data mining, using a web-based interface. We have developed a database system with data-mining capabilities for managing, querying, analyzing and visualizing brain-MR images. We implemented this system using open-source components, with the express goal of wide dissemination throughout the neuroimaging research community.


Long-term persistence of structured habitats: seagrass meadows as enduring hotspots of biodiversity and faunal stability.
Ecological studies indicate that structurally complex habitats support elevated biodiversity, stability and resilience. The long-term persistence of structured habitats and their importance in maintaining biodiverse hotspots remain underexplored. We combined geohistorical data (dead mollusc assemblages, 'DA') and contemporary surveys (live mollusc assemblages, 'LA') to assess the persistence of local seagrass habitats over multi-centennial timescales and to evaluate whether they acted as long-term drivers of biodiversity, stability and resilience of associated fauna. We sampled structured seagrass meadows and open sandy bottoms along Florida's Gulf Coast. Results indicated that: (i) LA composition differed significantly between the two habitat types, (ii) LA from seagrass sites were characterized by significantly elevated local biodiversity and significantly higher spatial stability, (iii) DA composition differed significantly between the two habitat types, and (iv) fidelity between LA and DA was significantly greater for seagrass habitats. Contemporary results support the hypotheses that local biodiversity and spatial stability of marine benthos are both elevated in structured seagrass habitats. Geohistorical results suggest that structured habitats persist as local hotspots of elevated biodiversity and faunal stability over centennial-to-millennial timescales; indicating that habitat degradation and concomitant loss within structurally complex marine systems is a key driver of declining biodiversity and resilience.


Participation of histamine in the step-through active avoidance response and its inhibition by H1-blockers.
The effects of intravenous and intracerebroventricular administrations of certain H1-blockers on the active avoidance response in rats were studied. Among the classic H1-blockers used in this study: pyrilamine, diphenydramine, promethazine and chlorpheniramine, promethazine was the most effective and chlorpheniramine the least in inhibiting the active avoidance response; namely, a variation of prolongation in the response latency of the avoidance response. Meanwhile, ketotifen most potently inhibited the active avoidance response when the drugs were administered intracerebroventricularly. Mequitazine, astemizole and oxatomide were weak depressants when administered by either route. Azelastine was less effective than the classic H1-blockers by intravenous injection, while by intracerebroventricular injection, the inhibition was almost identical to those induced by the classic H1-blockers. Intracerebroventricular injection of histamine was antagonized the prolonged latency in the avoidance response induced by pyrilamine or diphenhydramine. A similar effect was also produced by 2-methylhistamine, but 4-methylhistamine had no effect. Intracerebroventricular injection of acetylcholine was restored the retarded avoidance response induced by pyrilamine, but a dose 20 times greater than that of histamine was required. From these findings, it can be concluded that inhibition of the active avoidance response induced by H1-blockers may be exerted through interaction with H1-receptors in the brain.


Effects of iodoacetate and fluoride on islate respiration and insulin biosynthesis.
Fluoride and iodoacetate inhibited the oxidation of glucose by islets of Langerhans isolated from the rat pancreas. Fifty % inhibition occurred with either 17 mM fluoride or 0.5 mM iodoacetate. The rate of insulin biosynthesis was more strongly inhibited by these inhibitors, especially fluoride. Fifty % inhibition occurred with approximately 1.5 mM fluoride. At high concentrations of iodoacetate and fluoride, the inhibitory effect on insulin synthesis was not reversed to a significant degree by the addition of pyruvate in the incubation medium. In addition to inhibiting the glycolysis and depriving islets of energy essential for the biosynthesis of insulin, fluoride probably exerts a direct inhibitory influence on the biosynthetic mechanism. A separate experiment with [6-14C]glucose indicated that 0.2 mM iodoacetate does not inhibit glycolysis completely.


Protein synthesis in chloroplasts. Characteristics and products of protein synthesis in vitro in etioplasts and developing chloroplasts from pea leaves.
The function of plastid ribosomes in pea (Pisum sativum L.) was investigated by characterizing the products of protein synthesis in vitro in plastids isolated at different stages during the transition from etioplast to chloroplast. Etioplasts and plastids isolated after 24, 48 and 96h of greening in continuous white light, use added ATP to incorporate labelled amino acids into protein. Plastids isolated from greening leaves can also use light as the source of energy for protein synthesis. The labelled polypeptides synthesized in isolated plastids were analysed by electrophoresis in sodium dodecyl sulphate-ureapolyacrylamide gels. Six polypeptides are synthesized in etioplasts with ATP as energy source. Only one of these polypeptides is present in a 150 000g supernatant fraction. This polypeptide has been identified as the large subunit of Fraction I protein (3-phospho-D-glycerate carboxylyase EC 188.8.131.52) by comparing the tryptic 'map' of its L-(35S)methionine-labelled peptides with the tryptic 'map' of large subunit peptides from Fraction I labelled with L-(35S)methionine in vivo. The same gel pattern of six polypeptides is seen when plastids isolated from greening leaves are incubated with either added ATP or light as the energy source. However, the rates of synthesis of particular polypeptides are different in plastids isolated at different stages of the etioplast to chloroplast transition. The results support the idea that plastid ribosomes synthesize only a small number of proteins, and that the number and molecular weight of these proteins does not alter during the formation of chloroplasts from etioplasts.