Patient-Reported Outcome and Experience Measures Administered by Dietitians in the Outpatient Setting: Systematic Review.
Understanding how patients perceive their health and the experience with the dietitian is fundamental to providing patient-centred care. The types of patient reported measures (PRMs) used by outpatient dietitians is unclear. Guidance about use of PRMs for dietitians is also lacking. The aim of this systematic review was to synthesise evidence regarding the use of PRMs by dietitians in the outpatient setting and evaluate the methodological quality of studies evaluating the psychometric properties of PRMs. Eight databases were searched systematically for studies of dietitians working in the outpatient setting and administering a PRM. Forty-four studies were evaluated and described 58 different PRMs. These included direct nutrition related (n = 12 studies), clinical (n = 21 studies), and health-related quality of life PRMs (n = 24 studies); 1 study documented use of a patient-reported experience measure. A large range of PRMs are used by outpatient dietitians. Of the most common PRMs, the majority are administered in similar populations to the original validation study. Dietitians should use a combination of 3 PRMs: a generic health-related quality of life tool, an experience measure, and at least 1 clinical or direct nutrition-related measure. This will enable dietitians to fully capture the impact of their care on patients.


The efficacy of urinalysis, plain films, and spiral CT in ED patients with suspected renal colic.
We determined the diagnostic value of urinalysis and plain films in patients with suspected renal colic presenting to an emergency department (ED). Over a 1-year period, 138 patients presented to the ED during the daytime with suspected renal colic, but for technical reasons the diagnostic modalities used in the study could be completed for only 99 patients, and 34 patients were lost to follow-up. A urinalysis; kidney, ureter, and bladder film; and spiral computed tomography (CT) were performed on each patient. The presence of urinary tract stones was determined by their definite presence on helical CT and/or passage of a stone on clinical follow-up (average follow-up = 3 months). A urinary stone was visualized on spiral CT or passed in the urine in 54 of the patients. Using helical CT findings or passage of a stone as the gold standard, plain radiography had a sensitivity of 69% and specificity of 82%. Urinalysis had a sensitivity of 69% and specificity of 27%. The sensitivity increased to 89% if either test was positive, but the specificity remained low at 27%. The sensitivity and specificity of CT in the diagnosis of urinary stones was 91%. Urinalysis and plain films are much less accurate than helical CT for confirming the diagnosis of acute urolithiasis. Further evaluation of the clinical and cost-effectiveness of helical CT should be done to determine its role in the work-up of these patients.


[Limits of prosthetic restoration of the hip joint and possibilities of recovery in failures].
The Authors report on treatment of patients with total prosthesis of the hip, in whom mobilisation of the prosthesis or one or both its components has occurred. In particular, stress is put on the results of the operation of removal of the prosthesis, which finds its major indications in cases of acute or remote, deep sepsis, and in case of aseptic mobilisation when the theoretical presuppositions allowing its substitution do not exist.


[Comparative study of indirect immunofluorescence (IIF) and ELISA techniques in the detection of parvovirus B19].
To determine the seroprevalence of IgG and IgM antibodies against Parvovirus B19 (P. B19), we studied the sera of 53 patients with different hematologic disorders and the sera of 15 controls using indirect immunofluorescence (IFI) and the ELISA method. The prevalence of IgG in the control group was 46.6%, in patients with aplastic crisis was 83.3% (IFI) and 66.7% (ELISA) and, in patients without crisis was 68.9% (IFI) and 72.4% (ELISA). IgM was negative except for patients with crisis: 8.3% (IFI) and 29.1% (ELISA). The higher seroprevalence (IgG) found in patients in comparison with controls might be due to a greater exposure of of patients to the virus. The agreement for both techniques was 81%(IgG) and 93% (IgM) however ELISA technique was more sensitive for detecting IgM of P. B19. In spite of serologic evidence and evaluating a simple serum sample per patient, we could establish an association between aplastic crisis and viral infection for IgM ELISA but not for IgG between hematologic disorders and infection for the P. B19.


The role of good governance in the race for global vaccination during the COVID-19 pandemic.
Governments have developed and implemented various policies and interventions to fight the COVID-19 pandemic. COVID-19 vaccines are now being produced and distributed globally. This study investigated the role of good governance and government effectiveness indicators in the acquisition and administration of COVID-19 vaccines at the population level. Data on six World Bank good governance indicators for 172 countries for 2019 and machine-learning methods (K-Means Method and Principal Component Analysis) were used to cluster countries based on these indicators and COVID-19 vaccination rates. XGBoost was used to classify countries based on their vaccination status and identify the relative contribution of each governance indicator to the vaccination rollout in each country. Countries with the highest COVID-19 vaccination rates (e.g., Israel, United Arab Emirates, United States) also have higher effective governance indicators. Regulatory Quality is the most important indicator in predicting COVID-19 vaccination status in a country, followed by Voice and Accountability, and Government Effectiveness. Our findings suggest that coordinated global efforts led by the World Health Organization and wealthier nations may be necessary to assist in the supply and distribution of vaccines to those countries that have less effective governance.


Drug eluting stents versus bare metal stents for the treatment of extracranial vertebral artery disease: a meta-analysis.
While a growing number of reports offer evidence for the potential of drug eluting stents (DES) in treating atherosclerotic stenosis of the extracranial vertebral artery, their efficacy when compared with bare metal stents (BMS) is uncertain due to the lack of a large prospective randomized trial. A search strategy using the terms 'stents', 'drug-eluting stents', 'atherosclerosis', 'vertebral artery', and 'vertebrobasilar insufficiency' was employed through Medline. Five studies met the criteria for a comparative meta-analysis. The technical/clinical success, periprocedural complications, target vessel revascularization (TVR), rates of restenosis, recurrent symptoms, and overall survival were compared. There was no significant difference in the technical success (OR=1.528, p=0.622), clinical success (OR=1.917, p=0.274), and periprocedural complications (OR=0.741, p=0.614) between the two groups. An OR of 0.388 for no restenosis in the BMS to DES arms (p=0.001) indicated a significantly higher restenosis rate in the BMS group relative to the DES group (33.57% vs 15.49%). When compared with the DES group, the BMS group had a significantly higher rate of recurrent symptoms (2.76% vs 11.26%; OR=3.319, p=0.011) and TVR (4.83% vs 19.21%; OR=4.099, p=0.001). A significantly lower rate of restenosis, recurrent symptoms, and TVR was noted in the DES group compared with the BMS group.


Association of body mass index with longitudinal rates of retinal atrophy in multiple sclerosis.
Studies evaluating associations between body mass index (BMI) and optical coherence tomography (OCT) measures in multiple sclerosis (MS) are lacking. To assess whether elevated BMI is associated with accelerated retinal atrophy. In this observational study, 513 MS patients were followed with serial spectral-domain OCT for a median of 4.4 years. Participants were categorized as normal weight (BMI: 18.5-24.9 kg/m2), overweight (BMI: 25-29.9 kg/m2), and obese (BMI: ⩾30 kg/m2). Participants with diabetes mellitus or uncontrolled hypertension and eyes with optic neuritis (ON) ⩽6 months prior to baseline OCT or during follow-up were excluded. Statistical analyses were performed with mixed-effects linear regression. Obese patients (n = 146) exhibited accelerated rates of ganglion cell + inner plexiform layer (GCIPL) atrophy relative to normal weight patients (n = 214; -0.57%/year (95% confidence interval (CI): -0.65% to -0.48%) versus -0.42%/year (95% CI: -0.49% to -0.35%); p = 0.012). GCIPL atrophy rate did not differ between overweight (n = 153) and normal weight patients (-0.47%/year vs -0.42%/year; p = 0.41). Each 1 kg/m2 higher BMI was associated with accelerated GCIPL (-0.011%/year; 95% CI: -0.019% to -0.004%; p = 0.003) atrophy. Multivariable analyses accounting for age, sex, race, MS subtype, and ON history did not alter the above findings. Elevated BMI, in the absence of overt metabolic comorbidities, may be associated with accelerated GCIPL atrophy. Obesity, a modifiable risk factor, may be associated with accelerated neurodegeneration in MS.


Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia.
This study is aimed at investigating the effects of shikonin, a pyruvate kinase M2 (PKM2) inhibitor, on the functions of myeloid dendritic cells (mDCs) in a mouse model of severe aplastic anemia (AA) generated by total body irradiation and lymphocyte infusion. Flow cytometry and qPCR were used to determine the proportions of PKM2+ mDCs and other immune indicators in the AA mice. Glucose consumption level, pyruvate generation level, and ATP content were used to determine the level of glycolytic metabolism in the mDCs. The survival rates of AA mice were evaluated after the administration of shikonin or the immunosuppressive agent cyclosporin A. The AA mice displayed pancytopenia, decreased CD4+/CD8+ cell ratio, increased perforin and granzyme levels in CD8+ cells, increased costimulatory CD80 and CD86 expressions, and inadequate regulatory T cell number. In vivo animal experiments showed that the shikonin-mediated inhibition of the PKM2 expression in mice was associated with high survival rates. In addition, the administration of cyclosporin A or shikonin decreased the expression of cytotoxic molecules and costimulatory CD80 and CD86 on CD8+ cells. Taken together, the results of this study indicated that shikonin could inhibit the activation and proliferation of mDCs as well as the activation of downstream cytotoxic T cells by reducing the PKM2 level in mDCs.


Immunosuppressive therapy in high-risk transplant patients: dose-dependent efficacy of mycophenolate mofetil in African-American renal allograft recipients. U.S. Renal Transplant Mycophenolate Mofetil Study Group.
Numerous studies have demonstrated that renal allograft survival is reduced in African-Americans (AAs). This posthoc racial subgroup analysis (AAs vs. non-AAs) tested whether mycophenolate mofetil (MMF) might have favorable implications for the treatment of AA renal allograft recipients. Patients received a triple therapy regimen of corticosteroids, cyclosporine, and azathioprine (AZA) 1-2 mg/kg/day, MMF 2 g/day (MMF 2 g), or MMF 3 g/day (MMF 3 g). AAs in the AZA group had the highest biopsy-proven rejection/treatment failure (BPR/TF) rate (57.5% vs. 43.5% for non-AAs). AAs in the MMF 3 g group showed a significant reduction in BPR/TF (57.5% vs. 24.2%, P=0.0008). BPRs were more frequent for AAs in either the AZA (47.5%) or MMF 2 g group (31.8%) than in the MMF 3 g group (12.1%), whereas rejections were reduced for non-AAs receiving either MMF dosage (AZA, 35.5%; MMF 2 g, 15.7%; MMF 3 g, 18.8%). AAs in the AZA group experienced BPR/TF earlier than AAs in the MMF 3 g group (median onset at 64 days vs. > 183 days, P=0.0012). But AAs in the MMF 3 g experienced BPR/TF the latest among the six subgroups of treatment and race. AAs had more severe rejection episodes and higher serum creatinine levels at 6 months after transplant, regardless of treatment group. Dose-dependent prevention of acute rejection in AAs is best afforded by a dosage of MMF at 3 g/day, whereas 2 g/day provides a superior benefit/risk ratio for non-AAs. MMF at 3 g/day thus provides an improvement over conventional immunosuppressive strategies in reducing the frequency of acute rejections in this immunologically high-risk group.


Vertical dielectric screening of few-layer van der Waals semiconductors.
Vertical dielectric screening is a fundamental parameter of few-layer van der Waals two-dimensional (2D) semiconductors. However, unlike the widely-accepted wisdom claiming that the vertical dielectric screening is sensitive to the thickness, our first-principles calculation based on the linear response theory (within the weak field limit) reveals that this screening is independent of the thickness and, in fact, it is the same as the corresponding bulk value. This conclusion is verified in a wide range of 2D paraelectric semiconductors, covering narrow-gap ones and wide-gap ones with different crystal symmetries, providing an efficient and reliable way to calculate and predict static dielectric screening of reduced-dimensional materials. Employing this conclusion, we satisfactorily explain the tunable band gap in gated 2D semiconductors. We further propose to engineer the vertical dielectric screening by changing the interlayer distance via vertical pressure or hybrid structures. Our predicted vertical dielectric screening can substantially simplify the understanding of a wide range of measurements and it is crucial for designing 2D functional devices.


Virtual Exertions: a user interface combining visual information, kinesthetics and biofeedback for virtual object manipulation.
Virtual Reality environments have the ability to present users with rich visual representations of simulated environments. However, means to interact with these types of illusions are generally unnatural in the sense that they do not match the methods humans use to grasp and move objects in the physical world. We demonstrate a system that enables users to interact with virtual objects with natural body movements by combining visual information, kinesthetics and biofeedback from electromyograms (EMG). Our method allows virtual objects to be grasped, moved and dropped through muscle exertion classification based on physical world masses. We show that users can consistently reproduce these calibrated exertions, allowing them to interface with objects in a novel way.


Behavioural effects of acute tryptophan depletion in healthy male volunteers.
Acute tryptophan depletion (ATD) studies have been used to assess the role of the serotonergic system in various aspects of human behaviour. Changes in mood have already been described in selected groups of individuals submitted to ATD. The present study was a randomized, double-blind, cross-over trial designed to evaluate the effects of ATD on mood, memory, attention and induced anxiety in normal male volunteers. Twelve healthy male volunteers were submitted to two separate sessions of ATD, 1 week apart. Drinks containing either a balanced mixture of amino acids (B) or a similar mixture devoid of tryptophan (T-) were administered in each session. Mood was assessed using self-rating scales. Attention and memory were assessed using a battery of psychological tests. Anxiety induction was carried out using a simulation of public speaking. Blood levels of tryptophan were assessed before and after the B and T- drinks. Results showed that ATD markedly decreased plasma tryptophan (p < 0.0001). Mood ratings, memory and attention were not changed by the T- drink. There was no difference among the anxiety levels measured under T- or B mixtures. These data supports the notion that ATD does not change mood and cognitive function in healthy subjects.


Characteristics of plasmalemma alkaline phosphatase of rat mesenteric artery.
General characteristics of alkaline phosphatase activity of the plasma membrane-enriched fraction isolated from rat mesenteric arteries were investigated. The vascular smooth muscle plasmalemma alkaline phosphatase is a metalloenzyme which is strongly inhibited by chelating agents and this inhibition can be completely overcome by addition of Mg2+ or Ca2+. Zn2+ only partially reactivates the enzyme in the presence of low concentrations of EDTA. The enzymatic hydrolysis of p-nitrophenyl phosphate, beta-glycerophosphate, alpha-glycerophosphate, or 3'-adenosine monophosphate showed an optimal activity in the alkaline region between pH 9 and 11. The alkaline phosphatase activity is distinctly different from the plasmalemma ATPase and 5'-nucleotidase activities with respect to their pH dependence, influence by added divalent metal ions and stability against heat inactivation. Vanadate ion, being structurally similar to the transition state analog of the phosphoryl group, potently inhibits alkaline phosphatase with an apparent Ki of 1.5 microM. The altered alkaline phosphatase activity of vascular smooth muscle in relation to its possible physiological function and pathophysiological manifestation associated with hypertensive disease are discussed.


Oxidative Fluorination of Cu/ZnO Methanol Catalysts.
The influence of a mild difluorine treatment on Cu/ZnO precatalysts for methanol synthesis was investigated. It led to the incorporation of 1.2…1.3±0.1 wt % fluoride into the material. Fluorination considerably increased the amount of ZnOx related defect sites on the catalysts and significantly increased the space-time yields. Although the apparent activation energy EA,app for methanol formation from CO2 and H2 was almost unchanged, the EA,app for the reverse water-gas shift (rWGS) reaction increased considerably. Overall, fluorination led to a significant gain in methanol selectivity and productivity. Apparently, also the quantity of active sites increased.


An investigation of free-energy-averaged (coarse-grained) potentials for fluid adsorption on heterogeneous solid surfaces.
Coarse-grained, two-body fluid-solid potentials provide a simple way to describe the interaction between a fluid molecule and a solid in adsorption theories, and also a means to reduce the computational expense in molecular simulations, compared to those employing full atomistic detail. Here we investigate the applicability of a recently proposed mapping procedure to obtain free-energy-averaged (FEA) fluid-solid interactions for fluids on various heterogeneous surfaces. Methane and graphite are chosen as the fluid and the solid, respectively, and the surface graphene layer is modified to create chemical and geometrical heterogeneities; for the latter surfaces, the FEA mapping is appropriately modified to account for vacancies. Adsorption isotherms and fluid density profiles are obtained by performing grand canonical Monte Carlo (GCMC) simulations for explicit-solid and FEA-potential representations, and are compared to gain insights about the applicability and limitations of the FEA potentials. For solids with homogeneous and chemically heterogeneous surfaces, adsorption isotherms and density profiles obtained using FEA potentials are in good agreement with those obtained using an explicit-solid representation. For surfaces containing vacancies, isotherms and density profiles obtained using the unmodified FEA potential differ significantly from their explicit-surface analogues. When using the FEA potential obtained with the modified mapping procedure some deviations are still seen at very high pressure, however, at low to moderate pressures, agreement is, once again, good.


The evolutionary young miR-1290 favors mitotic exit and differentiation of human neural progenitors through altering the cell cycle proteins.
Regulation of cellular proliferation and differentiation during brain development results from processes requiring several regulatory networks to function in synchrony. MicroRNAs are part of this regulatory system. Although many microRNAs are evolutionarily conserved, recent evolution of such regulatory molecules can enable the acquisition of new means of attaining specialized functions. Here we identify and report the novel expression and functions of a human and higher primate-specific microRNA, miR-1290, in neurons. Using human fetal-derived neural progenitors, SH-SY5Y neuroblastoma cell line and H9-ESC-derived neural progenitors (H9-NPC), we found miR-1290 to be upregulated during neuronal differentiation, using microarray, northern blotting and qRT-PCR. We then conducted knockdown and overexpression experiments to look at the functional consequences of perturbed miR-1290 levels. Knockdown of miR-1290 inhibited differentiation and induced proliferation in differentiated neurons; correspondingly, miR-1290 overexpression in progenitors led to a slowing down of the cell cycle and differentiation to neuronal phenotypes. Consequently, we identified that crucial cell cycle proteins were aberrantly changed in expression level. Therefore, we conclude that miR-1290 is required for maintaining neurons in a differentiated state.


Chiral diphosphine and monodentate phosphorus ligands on a spiro scaffold for transition-metal-catalyzed asymmetric reactions.
The preparation of chiral compounds in enantiomerically pure form is a challenging goal in modern organic synthesis. The use of chiral metal complex catalysis is a powerful, economically feasible tool for the preparation of optically active organic compounds on both laboratory and industrial scales. In particular, the metals coordinated by one or more chiral phosphorus ligands exhibit amazing enantioselectivity and reactivity. Many chiral phosphorus ligands have been synthesized and used in transition-metal-catalyzed asymmetric reactions in past decades. However, a large number of reactions still lack effective chiral ligands, and the enantioselectivities in many reactions are substrate-dependent. The development of effective chiral phosphorus ligands, especially ligands having novel chiral backbones, is still an important task in the area of asymmetric catalysis. Molecules containing a spirocyclic framework are ubiquitous in nature. The synthesis of molecules with this spiro structure can be traced back to 100 years ago. However, the use of this spirocyclic framework to construct chiral phosphorus ligands is a recent event. This Account outlines the design and synthesis of a new family of chiral spiro phosphorus ligands including spiro diphosphines and spiro monodentate phosphorus ligands with 1,1'-spirobiindane and 9,9'-spirobifluorene backbone and their applications in transition-metal-catalyzed asymmetric hydrogenation and carbon-carbon bond formation reactions. The chiral spiro diphosphine lgands SDP with a 1,1'-spirobiindane backbone and SFDP with a 9,9'-spirobifluorene backbone, and the spiro monophosphorus ligands including phosphoramidites, phosphites, phosphonites, and phospholane with a 1,1'-spirobiindane backbone were synthesized in good yields from enantiomerically pure 1,1'-spirobiindane-7,7'-diol and 9,9'-spirobifluoren-1,1'-diol. The ruthenium complexes of chiral spiro diphosphine ligands proved to be very effective catalysts for asymmetric hydrogenations of ketones, alpha-arylaldehydes and alpha,beta-unsaturated acids. The rhodium complexes of chiral spiro monophosphorus ligands are highly enantioselective for the asymmetric hydrogenations of alpha- and beta-dehydroamino acid derivatives, alpha-arylethenyl acetamides and non- N-acyl enamines. The spiro monophosphorus ligands were demonstrated to be highly efficient for the Rh-catalyzed asymmetric addition of arylboronic acids to aldehydes and N-tosylarylimines, Pd-catalyzed asymmetric allylation of aldehydes with allylic alcohols, Cu-catalyzed asymmetric ring opening reactions with Grignard reagents, and Ni-catalyzed asymmetric hydrovinylation of styrene derivatives with ethylene. The chiral spiro phosphorus ligands show high enantioselectivities for a wide range of transition-metal-catalyzed asymmetric reactions. In most of these transformations, the enantioselectivities of spiro phosphorus ligands are superior to those obtained by using the corresponding phosphorus ligands with other backbones. These results arise from the intriguing chiral inducement of spiro structures of the ligands.


Beat perception in polyrhythms: Time is structured in binary units.
In everyday life, we group and subdivide time to understand the sensory environment surrounding us. Organizing time in units, such as diurnal rhythms, phrases, and beat patterns, is fundamental to behavior, speech, and music. When listening to music, our perceptual system extracts and nests rhythmic regularities to create a hierarchical metrical structure that enables us to predict the timing of the next events. Foot tapping and head bobbing to musical rhythms are observable evidence of this process. In the special case of polyrhythms, at least two metrical structures compete to become the reference for these temporal regularities, rendering several possible beats with which we can synchronize our movements. While there is general agreement that tempo, pitch, and loudness influence beat perception in polyrhythms, we focused on the yet neglected influence of beat subdivisions, i.e., the least common denominator of a polyrhythm ratio. In three online experiments, 300 participants listened to a range of polyrhythms and tapped their index fingers in time with the perceived beat. The polyrhythms consisted of two simultaneously presented isochronous pulse trains with different ratios (2:3, 2:5, 3:4, 3:5, 4:5, 5:6) and different tempi. For ratios 2:3 and 3:4, we additionally manipulated the pitch of the pulse trains. Results showed a highly robust influence of subdivision grouping on beat perception. This was manifested as a propensity towards beats that are subdivided into two or four equally spaced units, as opposed to beats with three or more complex groupings of subdivisions. Additionally, lower pitched pulse trains were more often perceived as the beat. Our findings suggest that subdivisions, not beats, are the basic unit of beat perception, and that the principle underlying the binary grouping of subdivisions reflects a propensity towards simplicity. This preference for simple grouping is widely applicable to human perception and cognition of time.


Purine nucleoside analogs in indolent non-Hodgkin's lymphoma.
This article details both the contribution of the purine nucleoside analogs to the current management of relapsed indolent non-Hodgkin's lymphoma (NHL) and the role of pentostatin (Nipent) in that management. Of the three purine nucleoside analogs, pentostatin has received the least attention with regard to the management of indolent NHL. Although data in the literature appear to indicate that fludarabine (Fludara) and 2-chlorodeoxyadenosine (cladribine [Leustatin]) are more active in NHL, this conclusion could be flawed because many of the studies investigating pentostatin in indolent NHL have contained a large number of patients previously treated with the other purine analogs. As these agents are most likely cross-resistant, it is unfair to conclude that pentostatin is less active. Recently, there has been interest in using a new, more protracted schedule of 2 mg/m2/d of pentostatin for 5 days. Although the schedule used in the trials conducted in indolent NHL might not be optimal, pentostatin has nevertheless shown significant activity in these disorders.


Effect of trabeculectomy on ocular higher-order aberrations in patients with open angle glaucoma.
The aim of this study was to evaluate the effect of trabeculectomy on ocular higher-order aberrations following surgery in a group of patients with open angle glaucoma. In this prospective study, patients with primary open angle glaucoma underwent wavefront aberrometry before trabeculectomy with mitomycin-C. Coma-like, spherical-like, and total ocular higher-order aberrations were measured as root mean square values. The measurements were repeated 1 month and 3 months after the procedure. A total of 20 eyes from 20 patients were examined. There was a significant decrease in intraocular pressure following surgery at 1 month and 3 months postoperatively. However, there was no statistically significant change in the spherical equivalent of the eyes. One month after surgery, a significant change in coma-like, spherical-like, and total higher-order aberrations of the eyes was observed. However, the repeated measurements performed 3 months after procedure revealed no significant difference compared to the baseline values. Ocular higher-order aberrations increased 1 month following trabeculectomy surgery. However, this effect seems to be transient, as the values returned to the preoperative measurement 3 months after the procedure.


Do measures of surgical effectiveness at 1 year after lumbar spine surgery accurately predict 2-year outcomes?
OBJECTIVE With the recent passage of the Patient Protection and Affordable Care Act, there has been a dramatic shift toward critical analyses of quality and longitudinal assessment of subjective and objective outcomes after lumbar spine surgery. Accordingly, the emergence and routine use of real-world institutional registries have been vital to the longitudinal assessment of quality. However, prospectively obtaining longitudinal outcomes for patients at 24 months after spine surgery remains a challenge. The aim of this study was to assess if 12-month measures of treatment effectiveness accurately predict long-term outcomes (24 months). METHODS A nationwide, multiinstitutional, prospective spine outcomes registry was used for this study. Enrollment criteria included available demographic, surgical, and clinical outcomes data. All patients had prospectively collected outcomes measures and a minimum 2-year follow-up. Patient-reported outcomes instruments (Oswestry Disability Index [ODI], SF-36, and visual analog scale [VAS]-back pain/leg pain) were completed before surgery and then at 3, 6, 12, and 24 months after surgery. The Health Transition Index of the SF-36 was used to determine the 1- and 2-year minimum clinically important difference (MCID), and logistic regression modeling was performed to determine if achieving MCID at 1 year adequately predicted improvement and achievement of MCID at 24 months. RESULTS The study group included 969 patients: 300 patients underwent anterior lumbar interbody fusion (ALIF), 606 patients underwent transforaminal lumbar interbody fusion (TLIF), and 63 patients underwent lateral interbody fusion (LLIF). There was a significant correlation between the 12- and 24-month ODI (r = 0.82; p < 0.0001), SF-36 Physical Component Summary score (r = 0.89; p < 0.0001), VAS-back pain (r = 0.90; p < 0.0001), and VAS-leg pain (r = 0.85; p < 0.0001). For the ALIF cohort, patients achieving MCID thresholds for ODI at 12 months were 13-fold (p < 0.0001) more likely to achieve MCID at 24 months. Similarly, for the TLIF and LLIF cohorts, patients achieving MCID thresholds for ODI at 12 months were 13-fold and 14-fold (p < 0.0001) more likely to achieve MCID at 24 months. Outcome measures obtained at 12 months postoperatively are highly predictive of 24-month outcomes, independent of the surgical procedure. CONCLUSIONS In a multiinstitutional prospective study, patient-centered measures of surgical effectiveness obtained at 12 months adequately predict long-term (24-month) outcomes after lumbar spine surgery. Patients achieving MCID at 1 year were more likely to report meaningful and durable improvement at 24 months, suggesting that the 12-month time point is sufficient to identify effective versus ineffective patient care.


The NS1 protein of influenza A virus blocks RIG-I-mediated activation of the noncanonical NF-κB pathway and p52/RelB-dependent gene expression in lung epithelial cells.
Influenza A virus (IAV) infection of epithelial cells activates NF-κB transcription factors via the canonical NF-κB signaling pathway, which modulates both the antiviral immune response and viral replication. Since almost nothing is known so far about a function of noncanonical NF-κB signaling after IAV infection, we tested infected cells for activation of p52 and RelB. We show that the viral NS1 protein strongly inhibits RIG-I-mediated noncanonical NF-κB activation and expression of the noncanonical target gene CCL19.


Changes in regional cerebral blood flow demonstrated by 99mTc-HMPAO SPECT in euthymic bipolar patients.
Single photon emission computed tomography (SPECT) with 99mTc-HMPAO was used to compare regional cerebral blood flow (rCBF) in patients with bipolar disorder and in healthy controls. The sample of this study consisted of 16 euthymic bipolar patients who met the DSM-IV criteria and 10 healthy control subjects. The mean regional cerebral blood flow values of the bipolar euthymic patients were significantly lower than those of the controls in the bilateral medial-basal temporal, occipital; medial frontal; parietal regions and in the cingulate gyrus; the hypoperfusion in the cingulate had the highest significant P value (.001, Bonferroni correction). No significant differences in rCBF emerged between right and left-brain regions. The most important findings of the current study are the presence of regional cerebral perfusion alterations, particularly in the cingulate gyrus in the euthymic bipolar patients. Our results imply that underlying brain dysfunction may be independent from manic or depressive episodes in bipolar disorder. Because of the small number of subjects, however, this finding should be viewed as preliminary.


Vegetable Intake in College-Aged Adults Is Explained by Oral Sensory Phenotypes and TAS2R38 Genotype.
Taste and oral sensations vary in humans. Some of this variation has a genetic basis, and two commonly measured phenotypes are the bitterness of propylthiouracil (PROP) and the number of fungiform papillae on the anterior tongue. While the genetic control of fungiform papilla is unclear, PROP bitterness associates with allelic variation in the taste receptor gene, TAS2R38. The two common alleles are AVI and PAV (proline, alanine, valine, and isoleucine); AVI/AVI homozygotes taste PROP as less bitter than heterozygous or homozygous PAV carriers. In this laboratory-based study, we determined whether taste of a bitter probe (quinine) and vegetable intake varied by taste phenotypes and TAS2R38 genotype in healthy adults (mean age=26 years). Vegetable intake was assessed via two validated, complementary methods: food records (Food Pyramid servings standardized to energy intake) and food frequency questionnaire (general intake question and composite vegetable groups). Quinine bitterness varied with phenotypes but not TAS2R38; quinine was more bitter to those who tasted PROP as more bitter or had more papillae. Nontasters by phenotype or genotype reported greater consumption of vegetables, regardless of type (i.e., the effect generalized to all vegetables and was not restricted to those typically thought of as being bitter). Furthermore, nontasters with more papillae reported greater vegetable consumption than nontasters with fewer papillae, suggesting that when bitterness does not predominate, more papillae enhance vegetable liking. These findings suggest that genetic variation in taste, measured by multiple phenotypes or TAS2R38 genotype, can explain differences in overall consumption of vegetables, and this was not restricted to vegetables that are predominantly bitter.


Assessing the validity and applicability of the French 3-year prognostic score in the UK cystic fibrosis population - a national cohort study.
Models that predict outcomes, aid prognostication and inform the assessment of urgency for lung transplantation (LT) in CF are in demand. A prognostic score derived from the French adult CF registry to predict death or LT over 3-year follow-up was described in 2017 and validated using Canadian CF registry data. We assessed its performance in the UK CF population. The French prognostic score was applied to untransplanted adults with CF. The index year (2014) and outcomes (Death or LT) were evaluated to 2017. Receiver operator characteristics plots and area under curve (AUC) was computed. 4407 adults with CF met the inclusion criteria. After 3 years, 7.1% (P < 0.001) were dead or had received LT compared to the French (12.8%) and Canadian (9.4%) cohorts. The French score deemed 592 (26.2%) 'High-risk' - death/LT occurred in 189/592 (30.2%), less than previously reported in France and Canada (P < 0.0001). The discriminatory power of the French score was lower (AUC 0.830) than reported. Recalibration yielded only marginal improvement in model performance (AUC 0.833). The French prognostic score does not perform as well in the UK as reported elsewhere. Bespoke UK scores are needed to aid prognostication and inform LT decision-making.


Material-Selective Polydopamine Coating in Dimethyl Sulfoxide.
Polydopamine coating is known to be performed in a material-independent manner and has become a popular tool when designing a surface-functionalization strategy of a given material. Studies to improve polydopamine coatings have been reported, aiming to reduce the coating time (by transition metals, oxidants, applied voltages, or microwave irradiation), control surface roughness using catechol derivatives, and vary the ad-layer molecules formed on an underlying polydopamine layer. However, none of the techniques have changed the most important intrinsic property of polydopamine, the surface-independent coating. Currently, no method has been reported to modify this property to create a material-selective 'smart' polydopamine coating. Herein, we report a method with polydopamine to differentiate the chemistry of surfaces. We found that the polydopamine coating was largely inhibited on silicon-containing surfaces such as Si wafers and quartz crystals in a dimethyl sulfoxide (DMSO)/phosphate-buffered saline (PBS) cosolvent, while the coating properties on other materials remained mostly unchanged. Among the various interface bonding mechanisms of coordination, namely, cation-π, π-π stacking, and hydrogen-bonding interactions, the DMSO/PBS cosolvent effectively inhibits hydrogen-bond formation between catechol and SiO2, resulting in surface-selective 'smart' polydopamine coatings. The new polydopamine coating is useful for functionalizing patterned surfaces such as Au patterns on SiO2 substrates. Considering that Si wafer is the most widely used substrate, the surface-selective polydopamine coating technique described herein opens up a new direction in surface functionalization and interface chemistry.


MoMA-LoopSampler: a web server to exhaustively sample protein loop conformations.
MoMA-LoopSampler is a sampling method that globally explores the conformational space of flexible protein loops. It combines a large structural library of three-residue fragments and a novel reinforcement-learning-based approach to accelerate the sampling process while maintaining diversity. The method generates a set of statistically likely loop states satisfying geometric constraints, and its ability to sample experimentally observed conformations has been demonstrated. This paper presents a web user interface to MoMA-LoopSampler through the illustration of a typical use-case. MoMA-LoopSampler is freely available at: https://moma.laas.fr/applications/LoopSampler/. We recommend users to create an account, but anonymous access is possible. In most cases, jobs are completed within a few minutes. The waiting time may increase depending on the server load, but it very rarely exceeds an hour. For users requiring more intensive use, binaries can be provided upon request. Supplementary data are available at Bioinformatics online.


Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY): protocol of a prospective, multicentre, observational study.
Recurrence rate following radical therapy for lung cancer remains high, potentially reflecting occult metastatic disease, and better staging tools are required. Minimal pleural effusion (mini-PE) is associated with particularly high recurrence risk and is defined as an ipsilateral pleural collection (<1/3 hemithorax on chest radiograph), which is either too small to safely aspirate fluid for cytology using a needle, or from which fluid cytology is negative. Thoracoscopy (local anaesthetic thoracoscopy (LAT) or video-assisted thoracoscopic surgery (VATS)) is the gold-standard diagnostic test for pleural malignancy in patients with larger symptomatic effusions. Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY) will prospectively evaluate thoracoscopic staging in lung cancer associated-mini-PE for the first time. STRATIFY is a prospective multicentre observational study. Recruitment opened in January 2020. The primary objective is to determine the prevalence of detectable occult pleural metastases (OPM). Secondary objectives include assessment of technical feasibility and safety, and the impact of thoracoscopy results on treatment plans, overall survival and recurrence free survival. Inclusion criteria are (1) suspected/confirmed stages I-III lung cancer, (2) mini-PE, (3) Performance Status 0-2 (4), radical treatment feasible if OPM excluded, (5) ≥16 years old and (6) informed consent. Exclusion criteria are any metastatic disease or contraindication to the chosen thoracoscopy method (LAT/VATS). All patients have LAT or VATS within 7 (±5) days of registration, with results returned to lung cancer teams for treatment planning. Following an interim analysis, the sample size was reduced from 96 to 50, based on a lower-than-expected OPM rate. An MRI substudy was removed in November 2022 due to pandemic-related site setup/recruitment delays. These also necessitated a no-cost recruitment extension until October 2023. Protocol approved by the West of Scotland Research Ethics Committee (Ref: 19/WS/0093). Results will be published in peer-reviewed journals and presented at international meetings. ISRCTN13584097.


Regulation of per and cry genes reveals a central role for the D-box enhancer in light-dependent gene expression.
Light serves as a key environmental signal for synchronizing the circadian clock with the day night cycle. The zebrafish represents an attractive model for exploring how light influences the vertebrate clock mechanism. Direct illumination of most fish tissues and cell lines induces expression of a broad range of genes including DNA repair, stress response and key clock genes. We have previously identified D- and E-box elements within the promoter of the zebrafish per2 gene that together direct light-induced gene expression. However, is the combined regulation by E- and D-boxes a general feature for all light-induced gene expression? We have tackled this question by examining the regulation of additional light-inducible genes. Our results demonstrate that with the exception of per2, all other genes tested are not induced by light upon blocking of de novo protein synthesis. We reveal that a single D-box serves as the principal light responsive element within the cry1a promoter. Furthermore, upon inhibition of protein synthesis D-box mediated gene expression is abolished while the E-box confers light driven activation as observed in the per2 gene. Given the existence of different photoreceptors in fish cells, our results implicate the D-box enhancer as a general convergence point for light driven signaling.


Why is the choice of future climate scenarios for species distribution modelling important?
Species distribution models (SDMs) are common tools for assessing the potential impact of climate change on species ranges. Uncertainty in SDM output occurs due to differences among alternate models, species characteristics and scenarios of future climate. While considerable effort is being devoted to identifying and quantifying the first two sources of variation, a greater understanding of climate scenarios and how they affect SDM output is also needed. Climate models are complex tools: variability occurs among alternate simulations, and no single 'best' model exists. The selection of climate scenarios for impacts assessments should not be undertaken arbitrarily - strengths and weakness of different climate models should be considered. In this paper, we provide bioclimatic modellers with an overview of emissions scenarios and climate models, discuss uncertainty surrounding projections of future climate and suggest steps that can be taken to reduce and communicate climate scenario-related uncertainty in assessments of future species responses to climate change.


Sexual dysfunction in the elderly: Prevalence and impact on quality of life.
Sexual functioning is a major component of the overall human wellbeing. However, data on the sexual disorders among the elderly remain few. Determine the prevalence of sexual dysfunction among 100 elderly Tunisian subjects and evaluate the impact on quality of life and depression. The rate of sexual dysfunction was 88% without significant gender differences. Erectile dysfunction was the most common disorder in men (84.2%). Disorders of sexual arousal and pain were the most frequent disorders in women. The presence of sexual dysfunction was correlated with worse quality of life scores (p <0.001). A statistically significant correlation was not found with the depression score. The improvement of the quality of life among the elderly should include systematic sexual dysfunction assessment and management. Sexual education programs should be carried out.


Comparative genetics of capsular polysaccharide biosynthesis in Streptococcus pneumoniae types belonging to serogroup 19.
The genetic basis for the structural diversity of capsule polysaccharide (CPS) in Streptococcus pneumoniae serogroup 19 (consisting of types 19F, 19A, 19B, and 19C) has been determined for the first time. In this study, the genetic basis for the 19A and 19C serotypes is described, and the structures of all four serogroup 19 cps loci and their flanking sequences are compared. Transformation studies show that the structural difference between the 19A and 19F CPSs is likely to be a consequence of differences between their respective polysaccharide polymerase genes (cps19aI and cps19fI). The CPS of type 19C differs from that of type 19B by the addition of glucose. We have identified a single gene difference between the two cps loci (cps19cS), which is likely to encode a glucosyl transferase. The arrangement of the genes within the cps19 loci is highly conserved, with 13 genes (cps19A to -H and cps19K to -O) common to all four serogroup 19 members. These cps genes encode functions required for the synthesis of the shared trisaccharide component of the group 19 CPS repeat unit structures. Furthermore, the genetic differences between the group 19 cps loci identified are consistent with the CPS structures of the individual serotypes. Functions have been assigned to nearly all of the cps19 gene products, based on either gene complementation or similarity to other proteins with known functions, and putative biosynthetic pathways for production of all four group 19 CPSs have been proposed.


Sodium-lithium countertransport and hypertension in Rochester, Minnesota.
The objectives of the present study were to determine whether increased sodium-lithium countertransport is associated with essential hypertension in the general Caucasian population and to determine whether this association is independent of the effects of gender, age, body size, and plasma lipids. We studied 543 men and 589 women from the population of Rochester, Minnesota. Mean sodium-lithium countertransport was higher in hypertensive than in normotensive subjects in men (370 +/- 147 [mean +/- SD] versus 315 +/- 110 mumol/l red blood cells [RBC]/hr, p less than 0.001) and in women (339 +/- 114 versus 269 +/- 92 mumol/l RBC/hr, p less than 0.001). Interindividual differences in plasma triglycerides, body mass index (wt/[ht]2), and plasma total cholesterol explained 13.0% of sodium-lithium countertransport variation in men (p less than 0.001) and 20.2% in women (p less than 0.001). Age did not predict additional sodium-lithium countertransport variation in either gender. Slopes of the regressions of sodium-lithium countertransport on plasma triglycerides, body mass index, and plasma total cholesterol did not differ between diagnostic groups in men (p = 0.31) or in women (p = 0.29). After adjustment to remove sodium-lithium countertransport variation attributable to these covariates, mean sodium-lithium countertransport remained significantly higher in hypertensive than in normotensive subjects in men (354 +/- 139 versus 319 +/- 104 mumol/l RBC/hr, p less than 0.01) and in women (311 +/- 103 versus 278 +/- 83 mumol/l RBC/hr, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Discovery of enzyme modulators via high-throughput time-resolved FRET in living cells.
We have used a "two-color" SERCA (sarco/endoplasmic reticulum calcium ATPase) biosensor and a unique high-throughput fluorescence lifetime plate reader (FLT-PR) to develop a high-precision live-cell assay designed to screen for small molecules that perturb SERCA structure. A SERCA construct, in which red fluorescent protein (RFP) was fused to the N terminus and green fluorescent protein (GFP) to an interior loop, was stably expressed in an HEK cell line that grows in monolayer or suspension. Fluorescence resonance energy transfer (FRET) from GFP to RFP was measured in the FLT-PR, which increases precision 30-fold over intensity-based plate readers without sacrificing throughput. FRET was highly sensitive to known SERCA modulators. We screened a small chemical library and identified 10 compounds that significantly affected two-color SERCA FLT. Three of these compounds reproducibly lowered FRET and inhibited SERCA in a dose-dependent manner. This assay is ready for large-scale HTS campaigns and is adaptable to many other targets.


Residual outcome expectations and relapse in ex-smokers.
From a social cognitive theoretical point of view, strong positive outcome expectations of smoking are a cause of relapse in smoking cessation, working in concert with self-efficacy. This study investigated whether and to what extent this could be verified in a sample of ex-smokers. Some (N = 324) ex-smokers were followed for 7 months. At Time 1 (T1) and Time 2 (T2), participants filled in a self-report questionnaire assessing residual outcome expectations (ROEs), self-efficacy, craving for tobacco, and smoking behavior, which was sent and returned by mail. First, prospective analyses showed that ROEs assessed at T1 predicted relapse reported at T2 over and above self-efficacy. Second, the influence of ROEs (and self-efficacy) on relapse was mediated by craving experience. Third, the hypothesized interactions between ROEs and self-efficacy were significant and meaningful.


Facet joint disorders: from diagnosis to treatment.
One of the most common sources of spinal pain syndromes is the facet joints. Cervical, thoracic, and lumbar facet joint pain syndromes comprise 55%, 42%, and 31% of chronic spinal pain syndromes, respectively. Common facet joint disorders are degenerative disorders, such as osteoarthritis, hypertrophied superior articular process, and facet joint cysts; septic arthritis; systemic and metabolic disorders, such as ankylosing spondylitis or gout; and traumatic dislocations. The facet pain syndrome from osteoarthritis is suspected from a patient's history (referred pain pattern) and physical examination (tenderness). Other facet joint disorders may cause radicular pain if mass effect from a facet joint cyst, hypertrophied superior articular process, or tumors compress the dorsal root ganglion. However, a high degree of morphological change does not always provoke pain. The superiority of innervating nerve block or direct joint injection for diagnosis and treatment is still a controversy. Treatment includes facet joint injection in facet joint osteoarthritis or whiplash injury provoking referred pain or decompression in mass effect in cases of hypertrophied superior articular process or facet joint cyst eliciting radicular pain. In addition, septic arthritis is treated using a proper antibiotic, based on infected tissue or blood culture. This review describes the diagnosis and treatment of common facet joint disorders.


The adaptor protein APPL2 inhibits insulin-stimulated glucose uptake by interacting with TBC1D1 in skeletal muscle.
Insulin stimulates glucose uptake by promoting the trafficking of GLUT4 to the plasma membrane in muscle cells, and impairment of this insulin action contributes to hyperglycemia in type 2 diabetes. The adaptor protein APPL1 potentiates insulin-stimulated Akt activation and downstream actions. However, the physiological functions of APPL2, a close homolog of APPL1, in regulating glucose metabolism remain elusive. We show that insulin-evoked plasma membrane recruitment of GLUT4 and glucose uptake are impaired by APPL2 overexpression but enhanced by APPL2 knockdown. Likewise, conditional deletion of APPL2 in skeletal muscles enhances insulin sensitivity, leading to an improvement in glucose tolerance. We identified the Rab-GTPase-activating protein TBC1D1 as an interacting partner of APPL2. Insulin stimulates TBC1D1 phosphorylation on serine 235, leading to enhanced interaction with the BAR domain of APPL2, which in turn suppresses insulin-evoked TBC1D1 phosphorylation on threonine 596 in cultured myotubes and skeletal muscle. Substitution of serine 235 with alanine diminishes APPL2-mediated inhibition on insulin-dependent TBC1D1 phosphorylation on threonine 596 and the suppressive effects of TBC1D1 on insulin-induced glucose uptake and GLUT4 translocation to the plasma membrane in cultured myotubes. Therefore, the APPL2-TBC1D1 interaction is a key step to fine tune insulin-stimulated glucose uptake by regulating the membrane recruitment of GLUT4 in skeletal muscle.


Exploring and dissecting genome-wide gene expression responses of Penicillium chrysogenum to phenylacetic acid consumption and penicillinG production.
Since the discovery of the antibacterial activity of penicillin by Fleming 80 years ago, improvements of penicillin titer were essentially achieved by classical strain improvement through mutagenesis and screening. The recent sequencing of Penicillium chrysogenum strain Wisconsin1255-54 and the availability of genomics tools such as DNA-microarray offer new perspective. In studies on beta-lactam production by P. chrysogenum, addition and omission of a side-chain precursor is commonly used to generate producing and non-producing scenarios. To dissect effects of penicillinG production and of its side-chain precursor phenylacetic acid (PAA), a derivative of a penicillinG high-producing strain without a functional penicillin-biosynthesis gene cluster was constructed. In glucose-limited chemostat cultures of the high-producing and cluster-free strains, PAA addition caused a small reduction of the biomass yield, consistent with PAA acting as a weak-organic-acid uncoupler. Microarray-based analysis on chemostat cultures of the high-producing and cluster-free strains, grown in the presence and absence of PAA, showed that: (i) Absence of a penicillin gene cluster resulted in transcriptional upregulation of a gene cluster putatively involved in production of the secondary metabolite aristolochene and its derivatives, (ii) The homogentisate pathway for PAA catabolism is strongly transcriptionally upregulated in PAA-supplemented cultures (iii) Several genes involved in nitrogen and sulfur metabolism were transcriptionally upregulated under penicillinG producing conditions only, suggesting a drain of amino-acid precursor pools. Furthermore, the number of candidate genes for penicillin transporters was strongly reduced, thus enabling a focusing of functional analysis studies. This study demonstrates the usefulness of combinatorial transcriptome analysis in chemostat cultures to dissect effects of biological and process parameters on gene expression regulation. This study provides for the first time clear-cut target genes for metabolic engineering, beyond the three genes of the beta-lactam pathway.


[The mechanism of antiarrhythmic action of the endogenous ORL1 receptor agonist nociceptin].
Prophylactic intravenous (i.v.) injections of a selective agonist of ORL1 receptors nociceptin (orphanin FQ) in a dose of 0.4 mg/kg prevented the development of aconitine-induced arrhythmia in rats narcotized with diethyl ether or chloralose. Pretreatment with L-NAME (50 mg/kg) completely abolished this effect of orphanin FQ, while the pretreatment with indomethacin (10 mg/kg) only attenuated the agonist effect, rather than abolished it completely. At the same time, pretreatment with hexamethonium (10 mg/kg) or glibenclamide (3 mg/kg) had no effect on the nociceptin-dependent cardiac tolerance to the arrhythmogenic action of aconitine. Intracerebroventricular (i.c.v.) infusion of orphanin FQ (36 microg) also prevented the onset of aconitine-induced arrhythmia, but this effect was completely abolished by hexamethonium. It is concluded that the antiarrhythmic action of nociceptin with respect to aconitine-induced arrhythmia upon i.v. and i.c.v. administration is explained by different mechanisms. In the former case, the effect of orphanin FQ is related to the activation of NO synthase and cyclooxygenase, while the central action involves the vegetative nervous system.


Heart Rate Reduction with Ivabradine Prevents Cardiac Rupture after Myocardial Infarction in Mice.
Cardiac rupture is a fatal complication following myocardial infarction (MI). An increase in heart rate (HR) is reportedly an independent risk factor for cardiac rupture during acute MI. However, the role of HR reduction in cardiac rupture after MI remains to be fully elucidated. We aimed to evaluate the therapeutic efficacy of HR reduction with ivabradine (IVA) on post-MI cardiac rupture in mice. We induced MI in mice by ligating the left anterior descending coronary artery. Subsequently, we subcutaneously implanted osmotic pumps filled with IVA solution or vehicle (Veh) in the surviving MI mice at 24 h postoperatively. We biochemically analyzed the myocardium on day 5, additionally observed the mice for 10 days, and analyzed the rates of cardiac rupture and non-cardiac rupture death, and survival after MI. HR was significantly lower in the IVA-treated mice, whereas blood pressure was comparable between the two groups. Compared to the Veh-treated mice, apoptosis was significantly reduced in the MI border zone in the IVA-treated mice. Although there were no differences in the infarct size of the surviving MI mice between the two groups, HR reduction with IVA significantly reduced cardiac rupture (rupture rate 26 and 8% in the Veh-treated and IVA-treated groups, respectively) and improved survival after MI. Our findings suggest that HR reduction with IVA prevents cardiac rupture after MI. This may be particularly effective in MI patients with a high HR who are either unable to adequately tolerate β-blockers or whose HR remains high despite receiving β-blockers.


Topology and mental processes.
The study reported here considers the effect of rotation on the decision time taken to compare nonrigid objects, presented as like and unlike pairs of knots and unknots. The results for 48 subjects, 21 to 45 years old, support the notion that images which have a characteristic 'foundation part' are more easily stored and accessed in the brain. Also, there is evidence that the comparison of deformable objects is processed by mental strategies other than self-evident mental rotation.


Machine learning approach for classification of ADHD adults.
Machine learning techniques that combine multiple classifiers are introduced for classifying adult attention deficit hyperactivity disorder (ADHD) subtypes based on power spectra of EEG measurements. The analyzed sample includes 117 adults (67 ADHD, 50 controls). The measurements are taken for four different conditions: two resting conditions (eyes open and eyes closed) and two neuropsychological tasks (visual continuous performance test and emotional continuous performance test). We divide the sample into four data sets, one for each condition. Each data set is used for training of four different support vector machine classifiers, while the output of classifiers is combined using logical expression derived from the Karnaugh map. The results show that this approach improves the discrimination between ADHD and control groups, as well as between ADHD subtypes.


Modulating risk-taking behavior with theta-band tACS.
Although risk is prevalent in decision-making, the specific neural processes underlying risk-taking behavior remain unclear. Previous studies have suggested that frontal theta-band activity plays a crucial role in modulating risk-taking behavior. The functional relevance of theta in risk-taking behavior is yet to be clearly established and studies using noninvasive brain stimulation have yielded inconsistent findings. We aimed to investigate this relevance using transcranial alternating current stimulation (tACS) over right or left dorsolateral prefrontal cortex (DLPFC). We also studied the influence of stimulation intensity on risk-taking behavior and electrophysiological effects. We applied theta-band (6.5 Hz) tACS over the left (F3) and right (F4) DLPFC with lower (1.5 mA) and higher (3 mA) tACS intensities. We employed a single-blinded, sham-controlled, within-subject design and combined tACS with electroencephalography (EEG) measurements and the Maastricht Gambling Task (MGT) to elicit and evaluate risk-taking behavior. Our results show an increase in risk-taking behavior after left DLPFC stimulation at both intensities and a reduction of risk-taking behavior after 3 mA (and not 1.5 mA) right DLPFC stimulation compared to sham. Further analyses showed a negative correlation between resting-state frontal theta-power and risk-taking behavior. Overall, frontal theta-power was increased after left, but not right, theta-band tACS independent of stimulation intensity. Our findings confirm the functional relevance of frontal theta-band activity in decision-making under risk and the differential role of left and right DLPFC. We also were able to show that stimulation intensity did have an effect on behavioral responses, namely risk-taking behavior. Significant right hemisphere stimulation effects were observed only after high-intensity stimulation. Nevertheless, electrophysiological effects were only significant after left DLPFC stimulation, regardless of tACS intensity. Furthermore, the results indicate the role of the baseline frontal theta-power in the direction of behavioral effects after theta-band tACS.


A physiologically based toxicokinetic model of P-glycoprotein transporter-mediated placenta perfusion of dexamethasone in the pregnant rat.
The present dosage of Dexamethasone (DEX) administered to pregnant women may pose a risk of toxicity to their unborn offspring. We aimed to develop a maternal-fetal physiologically based toxicokinetic (PBTK) model for DEX in pregnant rats, with a specific focus on the role of the P-glycoprotein (P-gp) transporter in placenta perfusion, and finally facilitate the optimization of clinical DEX dosage. We conducted animal experiments to determine DEX concentrations in various rat tissues, and constructed the PBTK model using MATLAB software. Sensitivity analysis was performed to assess input parameters and the model stability, with fold error (FE) values serving as evaluation indices. Our results indicate the successful construction of the PBTK model, with the fitting key parameters such as the absorption rate constant (Ka), intrinsic hepatic clearance (CLh,int) and intrinsic P-gp clearance (CLint,P-gp). The median concentration of DEX in maternal plasma, fetal plasma, fetal lung, and fetal brain were determined, which allowed us to fit the tissue-to-plasma partition coefficients for the fetal lung (Kp,lung,f) and fetal brain (Kp,brain,f). After making adjustments, all calculated FE values were found to be less than 2, demonstrating the acceptability and accuracy of our model's predictions. Our model integrated external literature data and internal animal experimentation to comprehensively evaluate the maternal-fetal PK characteristics of DEX. These findings provide valuable support for the optimization of clinical DEX dosing.


The child as held in the mind of the mother: The influence of prenatal maternal representations on parenting behaviors.
Using a longitudinal design, this study examined the relationship of a mother's prenatal representation of her child and her parenting behavior with that child at 1 year of age in a sample of women who were either exposed or not exposed to intimate partner violence (IPV) (N = 164; M child age = 1.1 years, SD = .11 years; 52% male). Controlling for prenatal IPV, a MANCOVA analysis revealed that prenatal representational typology was significantly related to parenting behavior 1 year postpartum. Mothers whose representations were affectively deactivated (disengaged) were more behaviorally controlling with their children. Mothers whose representations were affectively overactivated (distorted) were more hostile with their children. Mothers with balanced representations demonstrated more positive parenting. Exposure to IPV did not moderate this relationship. There was no direct association between prenatal or postnatal IPV and parenting behavior. These findings suggest that prenatal representations influence postnatal parenting behavior in significant and theoretically consistent ways and that this relationship functions similarly for both abused and nonabused women. Results add to the growing literature that internal representations serve to guide behavior throughout development and suggest that maternal working models may be one important link in the intergenerational transmission of attachment relationships.


A state-of-the-art review on biomass-derived carbon materials for supercapacitor applications: From precursor selection to design optimization.
Biomass-derived carbon materials have the characteristics of a wide range of precursor sources, controllable carbon nano-dimension, large specific surface area and abundant heteroatoms doping. At present, biomass-derived carbon materials have been widely used in electrochemical energy storage devices, especially the research and development of biomass-derived carbon materials for supercapacitors has become mature and in-depth. Therefore, it is of importance to summarize the advanced technologies and strategies for optimizing biomass-derived carbon materials for supercapacitors, which will effectively promote the further development of high-performance supercapacitors. In this review, the recent research progress of biomass-derived carbon materials is provided in detail, including the selection of biomass precursors, the design of carbon nano-dimension and the theory of heteroatom doping. Besides, the preparation methods of biomass-derived carbon materials and the related processes of optimizing the electrochemical performance are also summarized. This review ends with the perspectives for future research directions and challenges in the field of biomass-derived carbon materials for electrochemical applications. This review aims to provide helpful reference information for the nano-dimensional design and electrochemical performance optimization of biomass-derived carbon materials for the practical application of supercapacitors.


Physiologic hypoxia and oxygen homeostasis in the healthy intestine. A Review in the Theme: Cellular Responses to Hypoxia.
In recent years, the intestinal mucosa has proven to be an intriguing organ to study tissue oxygenation. The highly vascularized lamina propria juxtaposed to an anaerobic lumen containing trillions of metabolically active microbes results in one of the most austere tissue microenvironments in the body. Studies to date have determined that a healthy mucosa contains a steep oxygen gradient along the length of the intestine and from the lumen to the serosa. Advances in technology have allowed multiple independent measures and indicate that, in the healthy mucosa of the small and large intestine, the lumen-apposed epithelia experience Po2 conditions of <10 mmHg, so-called physiologic hypoxia. This unique physiology results from a combination of factors, including countercurrent exchange blood flow, fluctuating oxygen demands, epithelial metabolism, and oxygen diffusion into the lumen. Such conditions result in the activation of a number of hypoxia-related signaling processes, including stabilization of the transcription factor hypoxia-inducible factor. Here, we review the principles of mucosal oxygen delivery, metabolism, and end-point functional responses that result from this unique oxygenation profile.


TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants.
While numerous life-extending manipulations have been discovered in the nematode Caenorhabditis elegans, one that remains most enigmatic is disruption of oxidative phosphorylation. In order to unravel how such an ostensibly deleterious manipulation can extend lifespan, we sought to identify the ensemble of nuclear transcription factors that are activated in response to defective mitochondrial electron transport chain (ETC) function. Using a feeding RNAi approach, we targeted over 400 transcription factors and identified 15 that, when reduced in function, reproducibly and differentially altered the development, stress response, and/or fecundity of isp-1(qm150) Mit mutants relative to wild-type animals. Seven of these transcription factors--AHA-1, CEH-18, HIF-1, JUN-1, NHR-27, NHR-49 and the CREB homolog-1 (CRH-1)-interacting protein TAF-4--were also essential for isp-1 life extension. When we tested the involvement of these seven transcription factors in the life extension of two other Mit mutants, namely clk-1(qm30) and tpk-1(qm162), TAF-4 and HIF-1 were consistently required. Our findings suggest that the Mit phenotype is under the control of multiple transcriptional responses, and that TAF-4 and HIF-1 may be part of a general signaling axis that specifies Mit mutant life extension.


Why don't women with diabetes plan their pregnancies?
To determine why women with diabetes generally do not plan their pregnancies, consequently entering their pregnancies with poor blood glucose control and greatly increasing the risk of birth defects in their infants. A population-based sample of 85 women with diabetes diagnosed before the index pregnancy were recruited within 6 months postpartum from 15 hospitals in the state of Washington. Women with planned and unplanned pregnancies were compared using qualitative and quantitative analysis of personal interviews, self-administered questionnaires, and medical record review. Although most women (79%) knew they should optimize their blood glucose levels before conception, fewer than half (41%) of their pregnancies were planned. Women with planned pregnancies had significantly higher income and more education; were more likely to have private health insurance, to see an endocrinologist before pregnancy, to be happily married, and to be Caucasian; and were less likely to use tobacco. Most unplanned pregnancies were not contraceptive failures, but may have been consciously or subconsciously intended. Women with planned pregnancies generally described an ongoing and positive relationship with their health care providers. Women who felt that their doctors discouraged pregnancy were more likely to have an unplanned pregnancy than were women who had been reassured they could have a healthy baby. Many women with diabetes still perceive negative messages about pregnancies and become pregnant without optimal planning. We believe there are many opportunities for increasing the proportion of women with diabetes who plan their pregnancies, particularly in the areas of prepregnancy information, support that women are given, and the quality of the relationships they experience within the health care system. It is crucial that couples be reassured that with pre-conception glucose control, almost all women with diabetes can have healthy babies.


Enzyme replacement therapy for mucopolysaccharidosis VI: Growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase.
BACKGROUND AND METHODS: Growth failure is characteristic of untreated mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome). Growth was studied in fifty-six MPS VI patients (5 to 29 years old) prior to and for up to 240 weeks of weekly infusions of recombinant human arylsulfatase B (rhASB) at 1 mg/kg during Phase 1/2, Phase 2, Phase 3 or Phase 3 Extension clinical trials. Height, weight, and Tanner stage data were collected. Pooled data were analyzed to determine mean height increase by treatment week, growth impacts of pubertal status, baseline urinary GAG, and age at treatment initiation. Growth rate for approximately 2 years prior to and following treatment initiation was analyzed using longitudinal modeling. RESULTS: Mean height increased by 2.9 cm after 48 weeks and 4.3 cm after 96 weeks on enzyme replacement therapy (ERT). Growth on ERT was not correlated with baseline urinary GAG. Patients under 16 years of age showed greatest increases in height on treatment. Model results based on pooled data showed significant improvement in growth rate during 96 weeks of ERT when compared to the equivalent pretreatment time period. Delayed pubertal onset or progression was noted in 10 patients entering the clinical trials; all of whom showed progression of at least one Tanner stage during 2 years on ERT, and 6 of whom (60%) completed puberty. CONCLUSION: Analysis of mean height by treatment week and longitudinal modeling demonstrate significant increase in height and growth rate in MPS VI patients receiving long-term ERT. This impact was greatest in patients aged below 16 years. Height increase may result from bone growth and/or reduction in joint contractures. Bone growth and resolution of delayed puberty may be related to improvements in general health, bone cell health, nutrition, endocrine gland function and reduced inflammation.


The changes of heart rate variability after unilateral stellate ganglion block.
The effect of the unilateral stellate ganglion block (SGB) on cardiovascular regulation remains controversial. We wished to evaluate the changes in heart rate variability (HRV) after a unilateral stellate ganglion block in patients with head and neck pain in the present study. Patients with head and neck pain (n = 89) were studied. HRV was determined before and after a C6 unilateral stellate ganglion block (right-sided SGB, 40; left-sided SGB, 49) using a paratracheal technique with 1% mepivacaine (6 ml). There were no significant differences in HRV indices before and after right-sided SGB. The log scale of power in the high frequency range (lnHF) was increased and ratio of power in the low frequency range (LF) to power in the high frequency range (HF) ratio was decreased after left-sided SGB. These results demonstrated that left-sided SGB increased parasympathetic activities in patients with head and neck pain.


Characterization of oleic acid-induced acute respiratory distress syndrome model in rat.
Animal studies using oleic acid (OA) model to produce acute respiratory distress syndrome (ARDS) have been inconsistent. Therefore, the present study was undertaken to establish an acute model of ARDS in rats using OA and to characterize its effect on cardio-respiratory parameters and lethality. The trachea, jugular vein and femoral artery of anesthetized adult rats were cannulated. A dose of OA (30-90 microL; iv) was injected in each animal and changes in respiratory frequency (RF), heart rate (HR) and mean arterial pressure (MAP) were recorded. Minute ventilation and PaO2/FiO2 (P/F) ratio were also determined. At the end, lungs were excised for determination of pulmonary water content and histological examination. At all doses of OA, there was immediate decrease followed by increase in RF, however at 75 and 90 microL of OA, RF decreased abruptly and the animals died by 63 +/- 8.2 min and 19 +/- 6.3 min; respectively. In all the groups, HR and MAP changes followed the respiratory changes. The minute ventilation increased in a dose-dependent manner while the values of P/F ratio decreased correspondingly. Pulmonary edema was induced at all doses. Histological examination of the lung showed alveolar damage, microvascular congestion, microvascular injury, infiltration of inflammatory cells, pulmonary edema and necrosis in a dose-dependent manner. With these results, OA can be used to induce different grades of ARDS in rats and OA doses of 50, 60 and 75 microL resemble mild, moderate and severe forms of ARDS respectively. Hence, OA model serves as a useful tool to study the pathophysiology of ARDS.


Life events and disability in rheumatoid arthritis: a European cohort.
The objective was to study the relationship between life events (LE) and the clinical status of patients suffering from recently diagnosed rheumatoid arthritis (RA) in a 2 yr follow-up. As part of a multicentre European cohort study, 370 French and Dutch patients were questioned three times at 1 yr intervals about LE which had occurred in the previous year. Three criteria were used to quantify the degree of disease activity (Ritchie's index), the level of functional disability [Health Assessment Questionnaire (HAQ)] and perceived health [Overall Evaluation of Health (OEH)]. Total LE and desirable LE showed a weak negative correlation with the HAQ scores. On the other hand, death-related LE did not seem to modify patient status. The higher the number of health-associated LE, the greater the deterioration in HAQ and OEH scores. The results indicate that LE do not affect the course of early RA in a spectacular manner.


Land-based birds as potential disseminators of avian mammalian reassortant influenza A viruses.
Chickens, quail, and other land-based birds are extensively farmed around the world. They have been recently implicated in zoonotic outbreaks of avian influenza in Hong Kong. The possibility that land-based birds could act as mixing vessels or disseminators of avian/mammalian reassortant influenza A viruses with pandemic potential has not been evaluated. In this report, we investigated whether chickens and Japanese quail are susceptible to a mammalian influenza virus (A/swine/Texas/4199-2/98 [H3N2]). This virus did not grow in chickens and replicated to low levels in Japanese quail but did not transmit. Replacing the H3 gene of this virus for one of the avian H9 viruses resulted in transmission of the avian/swine reassortant virus among quail but not among chickens. Our findings demonstrated that Japanese quail could provide an environment in which viruses like the A/swine/Texas/4199-2/98 [H3N2] virus could further reassort and generate influenza viruses with pandemic potential.


The urgency of the development of CO2 capture from ambient air.
CO(2) capture and storage (CCS) has the potential to develop into an important tool to address climate change. Given society's present reliance on fossil fuels, widespread adoption of CCS appears indispensable for meeting stringent climate targets. We argue that for conventional CCS to become a successful climate mitigation technology--which by necessity has to operate on a large scale--it may need to be complemented with air capture, removing CO(2) directly from the atmosphere. Air capture of CO(2) could act as insurance against CO(2) leaking from storage and furthermore may provide an option for dealing with emissions from mobile dispersed sources such as automobiles and airplanes.


Depressive symptoms, anatomical region, and clinical outcomes for patients seeking outpatient physical therapy for musculoskeletal pain.
Clinical guidelines advocate the routine identification of depressive symptoms for patients with pain in the lumbar or cervical spine, but not for other anatomical regions. The purpose of this study was to investigate the prevalence and impact of depressive symptoms for patients with musculoskeletal pain across different anatomical regions. Design This was a prospective, associational study. Demographic, clinical, depressive symptom (Symptom Checklist 90-Revised), and outcome data were collected by self-report from a convenience sample of 8,304 patients. Frequency of severe depressive symptoms was assessed by chi-square analysis for demographic and clinical variables. An analysis of variance examined the influence of depressive symptoms and anatomical region on intake pain intensity and functional status. Separate hierarchical multiple regression models by anatomical region examined the influence of depressive symptoms on clinical outcomes. Prevalence of severe depression was higher in women, in industrial and pain clinics, and in patients who reported chronic pain or prior surgery. Lower prevalence rates were found in patients older than 65 years and those who had upper- or lower-extremity pain. Depressive symptoms had a moderate to large effect on pain ratings (Cohen d=0.55-0.87) and a small to large effect on functional status (Cohen d=0.28-0.95). In multivariate analysis, depressive symptoms contributed additional variance to pain intensity and functional status for all anatomical locations, except for discharge values for the cervical region. Rates of depressive symptoms varied slightly based on anatomical region of musculoskeletal pain. Depressive symptoms had a consistent detrimental influence on outcomes, except on discharge scores for the cervical anatomical region. Expanding screening recommendations for depressive symptoms to include more anatomical regions may be indicated in physical therapy settings.


A Method for Physical Analysis of Recombination Intermediates in Saccharomyces cerevisiae.
Meiosis is a process through which diploid cells divide into haploid cells, thus promoting genetic diversity. This diversity arises from the formation of genetic crossovers (COs) that repair DNA double-strand breaks (DSBs), through homologous recombination (HR). Deficiencies in HR can lead to chromosomal abnormality resulting from chromosomal nondisjunction, and genetic disorders. Therefore, investigating the mechanisms underlying effective HR is crucial for reducing genome instability. Budding yeast serves as an ideal model for studying HR mechanisms due to its amenability to gene modifications and the ease of inducing synchronized meiosis to yield four spores. During meiosis, at the DNA level, programmed DSBs are repaired as COs or non-crossovers (NCOs) through structural alterations in the nascent D-loop, involving single-end invasions (SEIs) and double-Holliday junctions (dHJs). This repair occurs using homologous templates rather than sister templates. This protocol, using Southern blotting, allows for the analysis and monitoring of changes in DNA structures in the recombination process. One-dimensional (1D) gel electrophoresis is employed to detect DSBs, COs, and NCOs, while two-dimensional (2D) gel electrophoresis is utilized to identify joint molecules (JMs). Therefore, physical analysis is considered the most effective method for investigating the HR mechanism. Our protocol provides more comprehensive information than previous reports by introducing conditions for obtaining a greater number of cells from synchronized yeast and a method that can analyze not only meiotic/mitotic recombination but also mitotic replication.


The changing face of crises and aid in the Asia-Pacific.
Both US foreign policy and global attention attest to the strategic, economic, and political importance of Asia. Yet, the region faces urgent challenges that must be addressed if it is to remain stable and prosperous. The densely populated countries of the Asia-Pacific are beleaguered by poverty, population displacement, decreasing access to potable water and adequate sanitation, and high rates of disease morbidity and mortality. New and reemerging diseases known to have originated in Asia over the past decades have spread globally by international trade, tourism, worker migration, and agricultural exportation. Unremitting naturally occurring and man-made disasters have strained Southeast Asia's already fragile disaster and public health response infrastructures and the essential services they provide (eg, surveillance, vaccination, maternal and child health, and mental health programs). Following disasters, governments often contract with the broader humanitarian community (eg, indigenous and international NGOs) and seek the assistance of militaries to provide essential services. Yet, their roles and capabilities in addressing acute and chronic health issues in the wake of complex disasters remain unclear. Current mechanisms of nation-state and outside organization interaction, including dissimilar operational platforms, may limit true partnership on behalf of the health security mission. Additionally, concerns regarding skill sets and the lack of standards-based training raise questions about the balance between developing internal response capabilities and professionalizing external, deployable resources. Both the mega-disasters that are forecast for the region and the global health security threats that are expected to emanate from them require an increased focus on improving the Asia-Pacific's emergency preparedness and response posture.


External cortical landmarks and measurements for the temporal horn: Anatomic study with application to surgery of the temporal lobe.
The location of the temporal horn is important to neurosurgeons during procedures such as amygdalohippocampectomy and intraventricular electrode placement for temporal lobe seizure monitoring. However, sometimes the temporal horn is difficult to localize, especially without neuronavigation. The authors aimed to better localize this structure using superficial anatomic landmarks. Twenty-two brain halves were dissected from the midline, and the fornix identified and followed toward the left and right temporal horns. Once the temporal horn was isolated from a mesial approach, 6-cm long needles were placed into its anterior and posterior walls of the temporal horn and passed laterally from the axial plane to the cortical surface. Pin exit sites were marked externally and measurements taken between the outer temporal lobe cortex and the underlying temporal horn. No statistical differences were noted between left and right sides. The temporal horn was generally directed anteroinferiorly and best marked externally by the inferior temporal sulcus. The mean length of the temporal horn was 4.4 cm. Mean distance from anterior temporal tip to anterior wall of the temporal horn was 3.3 cm. The mean distance from the anterior temporal tip to the posterior wall of the temporal horn was 7 cm. The anterior wall of the temporal horn was a mean of 3 mm superior to the inferior temporal sulcus. The posterior wall was a mean of 1.2 cm superior to the inferior temporal sulcus. These landmarks and measurements may help neurosurgeons better localize this part of the lateral ventricular system.


Mental Health Impacts of Wildfire, Flooding and COVID-19 on Fort McMurray School Board Staff and Other Employees: A Comparative Study.
Fort McMurray, a city in northern Alberta, Canada, has experienced multiple traumas in the last five years, including the 2016 wildfire, the 2020 floods, and the COVID-19 pandemic. Eighteen months after the wildfire, major depressive disorder (MDD), generalized anxiety disorder (GAD), and Post Traumatic Stress Disorder (PTSD) symptoms were elevated among school board employees in the city. This study aimed to compare employees of the school board and other employees of Fort McMurray in respect to the impact the 2016 wildfires, the 2019 COVID pandemic, and the 2020 floods had on their mental health. A quantitative cross-sectional survey was conducted in Fort McMurray from 24 April to 2 June 2021. Online questionnaires were administered through REDCap and were designed to capture socio-demographic characteristics, clinical as well as wildfire, COVID-19, and flooding-related variables. Mental health outcome variables were captured using self-reported standardized assessment scales. Data were analysed with descriptive statistics, Chi-square/Fisher's Exact tests, and binary regression analysis. Of the 249 residents who accessed the online survey, 186 completed the survey, giving a response rate of 74.7%. Of these respondents, 93.5% (174) indicated their employment status and were included in the Chi-square analysis. Most of the respondents were female (86.2%, (150)), above 40 years (53.4%, (93)), and were in a relationship (71.3%, (124)). The prevalence values for MDD, GAD and PTSD among respondents were 42.4%, 41.0, and 36.8%, respectively. There was a statistically significant difference between employees of the school board and other employees with respect to likely PTSD prevalence (28% vs. 45%, respectively, p < 0.05), although with other factors controlled for, in a binary logistic regression model, employer type did not significantly predict likely PTSD. The study has established that likely PTSD symptoms were significantly higher in other employees compared to those of school board employees. Greater exposure to the traumatic events and a greater perceived lack of support from other employers might have contributed to the significantly higher prevalence of PTSD in other employees.


Oestrogen-induced enhancement of myeloperoxidase activity in human polymorphonuclear leukocytes--a possible cause of oxidative stress in inflammatory cells.
Micromolar concentrations of beta-estradiol, estrone, 16-alpha-hydroxyestrone and estriol enhance the oxidative metabolism of activated human PMNL's. The corresponding 2-hydroxylated estrogens 2-OH-estradiol, 2-OH-estrone and 2-OH-estriol act on the contrary as powerful inhibitors of cell activity. Equilenine, a naturally occurring steroid hormone structurally closely related to estrone, removes the estrogen-induced increase in oxidative metabolism of activated PMNL's without diminishing cell activity determined in the absence of enhancing hormone. A number of other female and male sexual hormones were without potentiating effect. The cell response to hormone treatment was assayed as increase (or decrease) in LU-dependent CL of activated PMNL's. When assaying LUC-dependent CL of the cells no stimulatory effects of the estrogens could be detected. This fact may imply that the myeloperoxidase enzyme system of the cells is the target for the hormonal action. Various inhibition experiments using activated PMNL's or purified MPO confirmed this conclusion. The efficicious hormones induced approximately a doubling of CL of activated cells and a tenfold increase of the activity of purified MPO. If cell activity was initiated by the additions of low concentrations of hydrogen peroxide, the presence of estrogens caused a remarkable enhancement of the luminol-dependent chemiluminescence. PMNL's activated with fMLP release MPO activity into the surrounding cell medium. It has been found here that the presence of estrogens in micromolar concentrations greatly increases such enzyme release. Release of MPO activity from the cells could be achieved by the mere addition of estrogenic hormones. Estrogen-induced release of enzyme activity was abrogated by the simultaneous presence of equilenine in the cell suspension. Released enzyme responded vigorously to estrogens in the presence of chloride ions and its substrate, hydrogen peroxide. About a tenfold increase in enzyme activity could be measured in the presence of 5 microM beta-estradiol or esteriol. The activity of the released enzyme (as well of purified MPO) was effectively inhibited by small amounts of anti-MPO antibodies. This observation together with other inhibition experiments was taken as evidence for the view that the released enzyme was identical with myeloperoxidase.


Voltammetric techniques for low-cost on-site routine analysis of thymol in the medicinal plant Ocimum gratissimum.
The composition of essential oils varies according to culture conditions and climate, which induces a need for simple and inexpensive characterization methods close to the place of extraction. This appears particularly important for developing countries. Herein, we develop an analytical strategy to determine the thymol content in Ocimum Gratissimum, a medicinal plant from Benin. The protocol is based on electrochemical techniques (cyclic and square wave voltammetry) implemented with a low cost potentiostat. Thymol is a phenol derivative and was directly oxidized at the electrode surface. We had to resort to submillimolar concentrations (25-300 μM) in order to minimize production of phenol oligomers that passivate the electrode. We worked first on two essential oils and realized that in one of them the thymol concentration was below our detection method. These results were confirmed by gas chromatography - mass spectrometry. Furthermore, we optimized the detection protocol to analyze an infusion made directly from the leaves of the plant. Finally, we studied whether the cost of the electrochemical cell may also be minimized by using pencil lead as working and counter electrodes.


Drosophila model of myosin myopathy rescued by overexpression of a TRIM-protein family member.
Myosin is a molecular motor indispensable for body movement and heart contractility. Apart from pure cardiomyopathy, mutations in MYH7 encoding slow/β-cardiac myosin heavy chain also cause skeletal muscle disease with or without cardiac involvement. Mutations within the α-helical rod domain of MYH7 are mainly associated with Laing distal myopathy. To investigate the mechanisms underlying the pathology of the recurrent causative MYH7 mutation (K1729del), we have developed a Drosophila melanogaster model of Laing distal myopathy by genomic engineering of the Drosophila Mhc locus. Homozygous MhcK1728del animals die during larval/pupal stages, and both homozygous and heterozygous larvae display reduced muscle function. Flies expressing only MhcK1728del in indirect flight and jump muscles, and heterozygous MhcK1728del animals, were flightless, with reduced movement and decreased lifespan. Sarcomeres of MhcK1728del mutant indirect flight muscles and larval body wall muscles were disrupted with clearly disorganized muscle filaments. Homozygous MhcK1728del larvae also demonstrated structural and functional impairments in heart muscle, which were not observed in heterozygous animals, indicating a dose-dependent effect of the mutated allele. The impaired jump and flight ability and the myopathy of indirect flight and leg muscles associated with MhcK1728del were fully suppressed by expression of Abba/Thin, an E3-ligase that is essential for maintaining sarcomere integrity. This model of Laing distal myopathy in Drosophila recapitulates certain morphological phenotypic features seen in Laing distal myopathy patients with the recurrent K1729del mutation. Our observations that Abba/Thin modulates these phenotypes suggest that manipulation of Abba/Thin activity levels may be beneficial in Laing distal myopathy.


Growth advantage and enhanced toxicity of Escherichia coli adherent to tissue culture cells due to restricted diffusion of products secreted by the cells.
This study was undertaken to examine whether Escherichia coli adherent to tissue cells gain advantages over nonadherent bacteria due to their proximity to the cells. We used tissue culture cells and isogenic derivatives of a proline auxotrophic strain of E. coli that were fimbriated (Fim+) or nonfimbriated (Fim-), and were heat-labile enterotoxin producing (Tox+) or toxin nonproducing (Tox-). We found that the Fim+ bacteria; which were capable of adhering to tissue culture cells, initiated growth much sooner than did nonadherent Fim- bacteria; the adherent bacteria used tissue cell-derived proline, which was available at high concentrations only in the zone of bacterial adherence. Likewise, cyclic AMP secreted by adherent (Fim+) bacteria was maintained at high concentration on the tissue cell surfaces. As few as 2 X 10(5) adherent Fim+ Tox+ bacteria exert toxic activity upon Y1 adrenal cells, whereas toxin secreted in the medium by 6 X 10(6) Fim- Tox+ bacteria was undetectable. The results suggest that the growth advantage and enhanced toxicity of adherent E. coli is due to restricted diffusion of products secreted by the tissue culture and bacterial cells, respectively.


Sepsis, signals, and surgical sequelae (a hypothesis).
Cytokines, products of the bodies on cells, are the major signals that orchestrate the host's response to bacterial infection. Those signals generated following infection include interleukins 1, 2, and 6, interferon gamma, and tumor necrosis factor (or cachectin). Tumor necrosis factor is the only cytokine, to date, that has been shown to fulfill Koch's postulates and, thus, be casually related to host responses. Host responses to cytokines vary because of alterations in the genetic mechanism that controls cytokine production, because of an alteration in the responsiveness of the reticuloendothelial system at the time of signal induction and because of alterations in cell surface receptors. Only now are techniques evolving that can detect cytokine concentrations or production rates to relate these molecules to varying aspects of human disease. A major therapeutic goal in the future will be directed toward blocking the deleterious effects of cytokines while maintaining their protective or beneficial effects.