Modulation of Altered Immune Parameters IL-2 and TNF-α in Diabetic Animal Models: A Therapeutic Insinuation of Metformin Beyond Diabetes.
Immunomodulatory drugs target the overall immune system, hence producing numerous toxic effects on the other organs with serious health manifestations. Due to these safety concerns, there is a need to introduce or repurpose a new drug with immunomodulatory effects with good safety, efficacy, and better tolerance. Metformin, a standard antidiabetic drug, was evaluated for its immunomodulatory effects in diabetic models in the current study. The diabetic model was developed by intraperitoneal (IP) administration of streptozotocin (60 mg/kg). The experimental rats were divided into six groups (three diabetic and three non-diabetic) with six rats in each group. Metformin (50 mg/kg and 80 mg/kg) was given orally to both diabetic and non-diabetic groups, once a day, for 42 days. Immunomodulatory cytokines interleukin (IL)-2, IL-4, IL-5, tumor necrosis factor (TNF)-α, and interferon gamma (INF-ɣ) were analyzed from blood samples by BD FCAP flow cytometer. The results revealed a significant (p=0.002) decrease in IL-2 and TNF-α in diabetic groups in comparison to control rats. However, no significant changes were observed in IL-4, IL-5, and INF-ɣ levels. Importantly, the treatment of metformin at both doses, i.e., 50 and 80 mg/kg, significantly reduced the elevated levels of IL-2 and TNF-α when compared to untreated diabetic groups. Metformin may be considered as an optimum drug candidate to reduce pro-inflammatory cytokines, IL-2 and TNF-α, that can lead to the reduction of long-term diabetic complications.


Tick Haller's Organ, a New Paradigm for Arthropod Olfaction: How Ticks Differ from Insects.
Ticks are the vector of many human and animal diseases; and host detection is critical to this process. Ticks have a unique sensory structure located exclusively on the 1st pairs of legs; the fore-tarsal Haller's organ, not found in any other animals, presumed to function like the insect antennae in chemosensation but morphologically very different. The mechanism of tick chemoreception is unknown. Utilizing next-generation sequencing and comparative transcriptomics between the 1st and 4th legs (the latter without the Haller's organ), we characterized 1st leg specific and putative Haller's organ specific transcripts from adult American dog ticks, Dermacentor variabilis. The analysis suggested that the Haller's organ is involved in olfaction, not gustation. No known odorant binding proteins like those found in insects, chemosensory lipocalins or typical insect olfactory mechanisms were identified; with the transcriptomic data only supporting a possible olfactory G-protein coupled receptor (GPCR) signal cascade unique to the Haller's organ. Each component of the olfactory GPCR signal cascade was identified and characterized. The expression of GPCR, Gαo and β-arrestin transcripts identified exclusively in the 1st leg transcriptome, and putatively Haller's organ specific, were examined in unfed and blood-fed adult female and male D. variabilis. Blood feeding to repletion in adult females down-regulated the expression of all three chemosensory transcripts in females but not in males; consistent with differences in post-feeding tick behavior between sexes and an expected reduced chemosensory function in females as they leave the host. Data are presented for the first time of the potential hormonal regulation of tick chemosensation; behavioral assays confirmed the role of the Haller's organ in N,N-diethyl-meta-toluamide (DEET) repellency but showed no role for the Haller's organ in host attachment. Further research is needed to understand the potential role of the GPCR cascade in olfaction.


Postoperative Mortality of Indigenous Populations Compared With Nonindigenous Populations: A Systematic Review.
A range of factors have been identified as possible contributors to racial/ethnic differences in postoperative mortality that are also likely to hold true for indigenous populations. Yet despite its severity as an outcome, death in the period following a surgical procedure is underresearched for indigenous populations. To describe postoperative mortality experiences for minority indigenous populations compared with numerically dominant nonindigenous populations and examine the factors that drive any differences observed. This review was conducted according to PRIMSA guidelines and registered on PROSPERO. Articles were identified through searches of the Embase, Ovid MEDLINE, Scopus, and Cumulative Index to Nursing and Allied Health Literature databases, with manual review of references and gray literature searches conducted. Eligible articles included those that reported associations between ethnicity/indigeneity and mortality up to 90 days following surgery and published in English between January 1, 1990, and March 26, 2019. Data on the study design, setting, participants (including indigeneity), and results were extracted. A modified Newcastle-Ottawa Quality Assessment Scale was used to determine study quality. A total of 442 abstracts were screened, 92 articles were reviewed in full text, and 21 articles (from 20 studies) and 7 reports underwent data extraction. All included studies were cohort studies (3 prospective and the remainder retrospective) investigating a wide range of surgical procedures in the US, Australia, or New Zealand. Seven studies were from single facilities, while the remainder used data from national databases. Sample sizes ranged, with indigenous sample sizes ranging from 20 to 3052 patients and a number of studies reporting less than 10 indigenous deaths. The postoperative mortality experience for minority indigenous populations compared with the nonindigenous populations was mixed. There was evidence from several studies that indigenous populations may be more likely to die following cardiac procedures. However, the available evidence has overall poor study quality, with methods to identify the indigenous populations being a major limitation of most of the studies. Postoperative mortality experiences for indigenous populations should not be interpreted in isolation from the broader context of inequities across the health care pathway and must take into account the quality of data used for indigenous identification.


New Plastic Crack-Tip Opening Displacement Tool Based on Digital Image Correlation for Estimating the Fatigue-Crack-Growth Law on 316L Stainless Steel.
This work presents a new approach for studying crack growth resulting from fatigue, which utilizes the plastic contribution of crack-tip opening displacement (CTODp). CTODp is used to predict austenitic stainless-steel crack propagation. Unlike linear elastic fracture mechanics analysis, the method presented here is also helpful for tasks other than small-scale yielding. The approach was based on correlating full-field displacement information with post-processing digital images. This work describes a detailed post-processing protocol that can be used to calculate CTODp. The results for steel compact-tension specimens were especially promising. Of note, there was a linear relationship between the propagation rate of fatigue cracks and the CTODp range.


Temporally distinct regulatory pathways coordinate thermo-responsive storage organ formation in potato.
Tuberization is an important developmental process in potatoes, but it is highly affected by environmental conditions. Temperature is a major environmental factor affecting tuberization, with high temperatures suppressing tuber development. However, the temporal aspects of thermo-responsive tuberization remain elusive. In this study, we show that FT homolog StSP6A is suppressed by temporally distinct regulatory pathways. Experiments using StSP6A-overexpressing plants show that post-transcriptional regulation plays a major role at the early stage, while transcriptional regulation is an important late-stage factor, suppressing StSP6A at high temperatures in leaves. Overexpression of StSP6A in leaves restores tuber formation but does not recover tuber yield at the late stage, possibly because of suppressed sugar transport at high temperatures. Transcriptome analyses lead to the identification of potential regulators that may be involved in thermo-responsive tuberization at different stages. Our work shows that potato has temporally distinct molecular mechanisms that finely control tuber development at high temperatures.


Physiological Monitoring During Augmented Reality Exercise Confirms Advantages to Health and Well-Being.
Augmented reality (AR) is a versatile tool that is changing the way we interact with the world. One way is through exergaming, integrating AR, and gaming with traditional exercise programs. This study aimed to test three different AR systems to determine their ability to elicit physiological responses similar to those experienced while exercising or performing rehabilitation exercises. The systems tested included a head-mounted display experience (Teapots), a Sony EyeToy game (Slap Stream), and a prototype of a PC-camera-based system (Drums). Physiological recordings show that Slap Stream and Drums produced significant increases (p < 0.05) in heart rate (HR) and skin conductance, and all three games produced nonsignificant increase in respiratory rate. Of the three games, Slap Stream produced the highest rates of low- (∼28 percent), moderate- (17 percent), and high-intensity (∼22 percent) HRs. This study successfully showed that inexpensive easy-to-use AR systems can effectively contribute to exercise programs. Future game design recommendations, including feedback, mixed reality, and stress tracking, are discussed.


Effects of captopril on cardiorenal hemodynamics in patients with severe chronic congestive heart failure.
The effects of captopril on cardiorenal function were studied in patients with chronic congestive heart failure. A single oral dose of captopril in 16 patients significantly increased cardiac indices and decreased total systemic vascular resistance. These changes were greater in subjects with higher baseline plasma renin activity (PRA). The increase in PRA and decrease in plasma aldosterone were also greater in this group. During 7 days of captopril therapy, renal plasma flow distinctly increased in 10 patients in whom renal function was followed. The increase in renal blood flow was greater in subjects with higher PRA. Simultaneous infusion of aprotinin in eight of these subjects did not affect the captopril-induced increase in renal plasma flow: these responses were the same in both PRA subgroups. The results suggest that captopril reduces total systemic vascular resistance in patients with chronic congestive heart failure through the inhibition of the renin-angiotensin system and the preferential renal vasodilating effect of captopril seems exclusively to be the sole result of this inhibition, with the kallikrein-kinin system or kinin-mediated prostaglandins not playing a major role.


Continuous positive airway pressure effects on regional lung aeration in patients with COPD: a high-resolution CT scan study.
The effects of nasal continuous positive airway pressure (CPAP) on the lung parenchyma of patients with COPD, to our knowledge, have never been assessed by high-resolution CT (HRCT) scanning. HRCT scans were obtained at the apex, hilum, and basis of the lungs at functional residual capacity while on spontaneous respiration and at the end of CPAP trials of 5 cm water (H(2)O), 10 cm H(2)O, and 15 cm H(2)O in 11 stable patients with COPD and eight healthy volunteers. Lung aeration was assessed by quantitative density parameters and by qualitative analysis of each CT image after processing by means of a density-based color-mask computational algorithm. The quantitative parameters were density histograms, the relative area of the lungs with attenuation values < -950 Hounsfield units (percentage of hyperaerated areas) and the 15th percentile (the density value separating the 15% voxels of least density). A CPAP of 5 cm H(2)O caused little increase in lung aeration in both groups, but in some patients with COPD, CPAP deflated some regions of the lungs. CPAP levels of 10 cm H(2)O and 15 cm H(2)O increased the emphysematous zones in all sectors of the lungs, including dorsal and apical regions in patients with COPD compared to little hyperaeration predominantly in the ventral areas in healthy volunteers. Nasal CPAP causes variable effects on regional lung aeration in relation to the applied pressure and the regional distribution of emphysema in patients with COPD. Low pressure levels may cause regional lung deflation in some patients. High levels increase the emphysematous areas wherever they are located inside the lungs.


Cell mediated cross-reactivity in vivo and in vitro to purified dermatophyte antigen preparations in sensitized guinea pigs.
Guinea pigs were sensitized to either Trichophyton rubrum, Trichophyton mentagrophytes, or Epidermophyton floccosum. Cross-reactivity experiments were performed in vivo and in vitro with purified antigen preparations prepared from the respective dermatophyte according to the ethylene glycol method. All sensitized animals responded with delayed-type skin reactions to all three antigen preparations, although the strongest reactivity observed was to the homologous antigen. Spleen and blood lymphocytes from many (but not all) animals were stimulated by these antigens and the response to the homologous antigen was always more pronounced. The findings indicate the presence of a common group-specific dermatophyte antigen as well as the possibility of species-specific antigens in the experimental system studied.


Camphene as a Mild, Bio-Derived Porogen for Near-Ambient Processing and 3D Printing of Porous Thermoplastics.
Porous structures are ubiquitous in nature due to their advantageous mechanical and transport properties. These structures have inspired various synthetic porous polymer technologies, including lightweight structural materials and membranes. While many manufacturing processes have been developed to generate porous thermoplastics, these usually include hazardous processes, such as high pressures and temperatures, or chemical components. Furthermore, few are compatible with additive manufacturing methods, such as 3D printing. Herein, we introduce bio-derived terpene camphene as a solvent and porogen for the freeze-casting of thermoplastic parts under mild conditions. Enabled by a low melting point (50 °C), camphene is used as a solvent for melt processing camphene-polymer solutions at moderate temperatures that later undergo room-temperature crystallization to template polymer-rich domains. Due to its high vapor pressure, camphene can be sublimed directly from these biphasic structures, resulting in an interconnected microporous polymer structure. Various polymers are demonstrated to be soluble in camphene, including polystyrene, an olefinic elastomer, a polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene elastomer, a cyclic olefin copolymer, and poly(ethyl methacrylate). Porous samples of each polymer were generated from camphene mixtures via compression molding, cooling, and subsequent vacuum annealing at room temperature to remove camphene. The porosity and pore structures were dependent on solution composition, including both the polymer type and polymer loading. Across the compositions investigated, porosity decreased monotonically from 93 to 65% with increasing polymer content. In the case of polystyrene, samples with pore diameters varying from ∼20 to <5 μm were generated. Rheological measurements were conducted on a series of polystyrene-camphene solutions to understand and optimize the formulation and conditions for direct ink write 3D printing. Porous parts with complex structures were successfully printed under mild conditions. These results underscore the advantages of camphene as a sustainable, nontoxic porogen and will inform future development of porous polymer systems derived from these methods.


Direct transport of 2',3'-didehydro-3'-deoxythymidine (D4T) and its ester derivatives to the cerebrospinal fluid via the nasal mucous membrane in rats.
We investigated the absorption and transport of 2',3'-didehydro-3'-deoxythymidine (D4T) and its ester prodrugs from the nasal cavity in rats. The absorption of D4T and its acetate (C2-D4T) was rapid and almost complete, although the hemi-succinate (Suc-D4T) was absorbed rather slowly; the plasma concentrations of the prodrug, Suc-D4T, and regenerated D4T remained unchanged throughout the experimental period (180 min). Concentrations in the cerebrospinal fluid (CSF) following intravenous (i.v.) and intranasal (i.n.) administration were also measured. After i.n. administration, drug concentrations were higher in the fraction derived from the subarachnoid space located close to the nasal mucosa than those in the fractions located far from the nasal cavity. This difference was not found following the i.v. administration of the drugs. Following nasal administration, the intact Suc-D4T was found in the CSF at a concentration higher than that of D4T, although transport of the intact prodrug to the CSF was not observed following i.v. administration. These results suggest that direct transport of the drugs from the nasal cavity to the CSF significantly contributes to the higher concentrations in CSF of D4T and/or its ester prodrugs, and indicate the possible value of nasal administration for the treatment of patients with AIDS dementia.


Hindsight bias in political elections.
Two studies on political hindsight bias were conducted on the occasions of the German parliament election in 1998 and the Nordrhein-Westfalen state parliament election in 2000. In both studies, participants predicted the percentage of votes for several political parties and recalled these predictions after the election. The observed hindsight effects were stronger than those found in any prior study on political elections (using percentage of votes as the dependent variable). We argue that the length of the retention interval between original judgement and recollection is mainly responsible for this difference. In our second study, we investigated possible artifacts in political hindsight biases using a control-group design where half of the participants recalled their predictions shortly before or after the election. Hindsight bias was preserved, reinforcing the results of earlier studies with non-control-group designs. Finally, we discuss the possibility that the hindsight experience (in political judgement and in general) actually consists of three different, partly independent components.


Rib-to-spine and rib-to-pelvis magnetically controlled growing rods: does the law of diminishing returns still apply?
The Law Of Diminishing Returns (LODR) has been demonstrated for traditional growing rods, but there is conflicting data regarding the lengthening behavior of Magnetically Controlled Growing Rods (MCGR). This study examines a cohort of patients with early-onset scoliosis (EOS) with rib-to-spine or rib-to-pelvis-based MCGR implants to determine if they demonstrate the LODR, and if there are differences in lengthening behaviors between the groups. A prospectively collected multicenter EOS registry was queried for patients with MCGR with a minimum 2-year follow-up. Patients with rib-based proximal anchors and either spine- or pelvis-based distal anchors were included. Patients with non-MCGR, unilateral constructs, < 3 lengthenings, or missing > 25% datapoints were excluded. Patients were further divided into Primary-MCGR (pMCGR) and Secondary-MCGR (sMCGR). 43 rib-to-spine and 31 rib-to-pelvis MCGR patients were included. There was no difference in pre-implantation, post-implantation and pre-definitive procedure T1-T12 height, T1-S1 height, and major Cobb angles between the groups (p > 0.05). Sub-analysis was performed on 41 pMCGR and 19 sMCGR rib-to-spine patients, and 31 pMCGR and 17 sMCGR rib-to-pelvis patients. There is a decrease in rod lengthenings achieved at subsequent lengthenings for each group: rib-to-spine pMCGR (rho = 0.979, p < 0.001), rib-to-spine sMCGR (rho = 0.855, p = 0.002), rib-to-pelvis pMCGR (rho = 0.568, p = 0.027), and rib-to-pelvis sMCGR (rho = 0.817, p = 0.007). Rib-to-spine pMCGR had diminished lengthening over time for idiopathic, neuromuscular, and syndromic patients (p < 0.05), with no differences between the groups (p > 0.05). Rib-to-pelvis pMCGR neuromuscular patients had decreased lengthening over time (p = 0.01), but syndromic patients had preserved lengthening over time (p = 0.65). Rib-to-spine and rib-to-pelvis pMCGR and sMCGR demonstrate diminished ability to lengthen over subsequent lengthenings.


[Bases for the selection of pharmacological treatment in attention deficit hyperactivity disorder].
To collect some factors that can help the clinician to design a plan of pharmacologic treatment for children and adolescents with attention deficit hyperactivity disorder (ADHD). We did a literature search of current available studies on the pharmacological treatment of ADHD. Treatment of ADHD requires the design of a comprehensive and individualized plan for each patient, family and environment, which includes three main parts: psychoeducation and behavioral management training, academic support, and medication. Stimulants (methylphenidate) and non-stimulants (atomoxetine) are the two drugs approved in Spain for children and adolescents and then treatment in adults with ADHD. The effect size of stimulants (1.0) is higher than for atomoxetine (0.7-0.8). The methodology of the study, especially the duration, may affect the effect size. The range of NNT is 1.9 to 5.3, higher than other drugs for other disorders (antidepressants or antipsychotics). Some factors that impact the choice of medication for ADHD are: comorbidity, potential adverse effects (especially low appetite, insomnia, tics and potential abuse of medication), parental preference and patient need for action along the day or at specific times of day, need rapid onset of action, and any visa price of medication. There are some factors related to the patient and the features of ADHD, drug, and the patient's situation or environment which should be considered when selecting a treatment for ADHD.


High-resolution small-angle x-ray diffraction study of long-range order in hard-sphere colloidal crystals.
The long-range order parameters in single crystals of hard colloidal spheres grown in sediments of colloid-polymer mixtures are determined using synchrotron small-angle x-ray diffraction with a resolution of 10(-6) of the wave vector. The interplanar positional order derived from the width of lattice reflections extends over at least 500 lattice planes. The lattice planes are orientationally correlated within approximately 0.1 degrees throughout the crystals, whereas the stacking of hexagonal planes remains random.


Enhancement of tofu isoflavone recovery by pretreatment of soy milk with koji enzyme extract.
Isoflavones are novel nutraceutical constituents of soybeans, but considerable amounts are lost in the whey during conventional tofu manufacturing. In this study, in a small-scale process, 2 mL of koji enzyme extract (soybean koji/deionized water, 1/3, w/v) was combined with 600 mL of soy milk, and 30 mL aliquots were incubated at 35 degrees C for 0, 30, 60, 120, and 300 min, for enzyme pretreatment. After each treatment time, soy milk was heated to 85 degrees C, CaSO4 was added to aggregate protein, and the mixture was centrifuged to separate the solids (tofu) from the whey. The tofu yield and moisture contents from soy milk treated for 30 or 60 min were higher than those from soy milk treated for 0 (control), 120, or 300 min. The protein content of freeze-dried tofu varied in a limited range, and native PAGE and SDS-PAGE patterns revealed slight quantitative and qualitative variations among products. Soy milk daidzein and genistein contents increased while daidzin and genistin contents decreased as the time of enzyme pretreatment of the soy milk increased. After 30 min of pretreatment, daidzin, genistin, daidzein, and genistein contents recovered in tofu products were higher than those of the control. In a pilot-scale process, aliquots (3 L) of soy milk were enzyme-treated for 30 min, aggregated with CaSO4, and hydraulically pressed to remove the whey. As in pretreatments, soy milk daidzein and genistein contents increased while daidzin and genistin contents decreased. In a comparison of the control and enzyme-treated tofu products, the total recoveries of daidzin, genistin, daidzein, and genistein in the tofu products increased from 54.9% to 64.2%. When the tofu products were subjected to a sensory panel test, both products were judged acceptable.


Prenatal transfer of decabromodiphenyl ether (BDE-209) results in disruption of the thyroid system and developmental toxicity in zebrafish offspring.
Decabromodiphenyl ether (BDE-209) was one of most widely-used polybrominated diphenyl ether (PBDE) flame retardants and is frequently detected in both abiotic and biotic samples from environment. However, knowledge of its transgenerational risks is limited. Here, 4-month-old zebrafish were exposed to various concentrations of BDE-209 (0, 3, 30 or 300μg/L) for 28days and spawned in clean water without BDE-209. Concentrations of triiodothyronine (T3) and thyroxine (T4) as well as expressions of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were measured in offspring after exposure of adult zebrafish to BDE-209. BDE-209 was accumulated in adult fish and F1 eggs, which suggests transfer of this compound from adult fish to their offspring. Exposure of BDE-209 to parents resulted in developmental abnormalities in offspring and a significant decrease in T4 concentrations in F1 larvae 120h post-fertilization (hpf). Furthermore, expressions of several genes involved in the HPT axis were also altered. Expressions of thyroid hormone receptor α (tr-α), thyrotropin releasing hormone (trh), thyroid stimulating hormone β (tsh-β) and deiodinase 1 (dio 1) were significantly down-regulated in F1 individuals, while expressions of thyroid stimulating hormone receptor (tshr) and transthyretin (ttr) were significantly up-regulated. These results suggest that exposure of parent zebrafish to BDE-209 can cause developmental toxicity in offspring and disruption of the thyroid endocrine system of offspring.


Nursing competence in CRRT: creation and validation of a measurement tool.
Acute Renal Failure is an essential condition frequently encountered in intensive care units and requires targeted treatment. The nursing team must be adequately trained in the management of the patient undergoing CRRT. To build and validate the CRRT-MCT (Continuous Renal Replacement Therapy -Measurement Competency Tool), which aims to measure nursing competence in managing patients undergoing renal replacement techniques. The most current guidelines for CRRT techniques were used to create an instrument to measure nursing competence. A pool of 10 experts evaluated this instrument. The pilot study examined content and face validity. Test-retest reliability with r-Person correlation and internal consistency reliability with Crombach's was assessed. The CRRT-MCT achieved good content and face validity (S-CVI= 0.96; I-CVI=70%-100%), good internal consistency reliability (Crombach's = 0.83). Two hundred and forty nurses employed in intensive care units did pilot testing and test-retesting. The t-test showed no significant difference between test and retest results, confirming the stability of the tool (Pearson's r = 0.984) CONCLUSIONS: The instrument assesses nursing competence concerning CRRT techniques in the ICU and is valid, reliable and understandable. The creation and validation of this tool enables nurses to understand their level of competence for the care of patients undergoing CRRT with the ultimate aim of becoming aware of their gaps and undertaking training to fill them to provide the best possible nursing care.


Inducing rapid polysulfide transformation through enhanced interfacial electronic interaction for lithium-sulfur batteries.
Sluggish dynamics of polysulfide (LiPS) conversion leads to reduced utilization of active sulfur and rapid capacity decay. Introducing catalysts into lithium-sulfur battery systems is a feasible and imperative strategy to tackle this problem. Previous research studies have mainly been focused on selecting new catalysts and design functional structures to improve performance, and ignoring the interaction between catalysts and their carriers. Herein, by simply fabricating a high-efficiency ZnS quantum dot@graphene nanosheet catalyst (ZnS QD@rGO), we utilized enhanced interfacial electronic interaction to accelerate polysulfide conversion for high energy density Li-S batteries. With the smaller size of ZnS, the interfacial electronic interaction becomes more enhanced, which was evidenced by DFT calculations and XPS experiments. After mixing with sulfur, the electrodes achieved a high capacity of 857.8 mA h g-1 at 1 C and a retention of 91.2% after 300 cycles. Also, a sulfur cathode with a high actual capacity of ∼4.0 mA h cm-2 could be obtained, with no obvious capacity decay within 100 cycles. We believe that this strategy represents a new perspective on designing efficient high-load electrodes for Li-S batteries.


Closed-form expressions of quantum electron transfer rate based on the stationary-phase approximation.
Closed-form rate expressions are derived on the basis of the stationary-phase approximation for the Fermi golden rule expression of the quantum electron-transfer (ET) rate. First, on the basis of approximate solutions of the stationary-phase points near DeltaG = 0, -lambda, and lambda, where DeltaG is the reaction free energy and lambda is the reorganization energy, three closed-form rate expressions are derived, which are respectively valid near each value of DeltaG. Numerical tests for a model Ohmic spectral density with an exponential cutoff demonstrate good performance of the derived expressions in the respective regions of their validity. In particular, the expression near DeltaG = -lambda, which differs from the semiclassical approximation only by a prefactor quadratic in DeltaG, works substantially better than the latter. Then, a unified formula is suggested, which interpolates the three approximate expressions and serves as a good approximation in all three regions. We have also demonstrated that the interpolation formula can serve as a good quantitative means for understanding the temperature dependence of the quantum ET rate.


Assessing noncognitive domains of respiratory therapy applicants: Messick's framework appraisal of the multiple mini-interview.
Educators who assess incoming applicants into a health professional training program are looking for a wide array of cognitive and noncognitive skills that best predict success in the program and as a future practicing professional. While aptitude tests generally measure cognitive skills, noncognitive constructs are more difficult to measure appropriately. The traditional method of measuring noncognitive constructs has been the panel interview. Panel interviews have been described as inconsistent in measuring noncognitive domains and consistently reported as unreliable and susceptible to bias. An alternate interview method used in many health professions schools is the multiple mini-interview (MMI) that was specifically designed to assess noncognitive domains in health professions education. This paper discusses the purpose of using the MMI, how the MMI is conducted, specific domains of focus for the MMI, and the feasibility of creating an MMI. Finally, the paper uses Messick's framework on validity to guide the consideration of the MMI.


EMG Processing Based Measures of Fatigue Assessment during Manual Lifting.
Manual lifting is one of the common practices used in the industries to transport or move objects to a desired place. Nowadays, even though mechanized equipment is widely available, manual lifting is still considered as an essential way to perform material handling task. Improper lifting strategies may contribute to musculoskeletal disorders (MSDs), where overexertion contributes as the highest factor. To overcome this problem, electromyography (EMG) signal is used to monitor the workers' muscle condition and to find maximum lifting load, lifting height and number of repetitions that the workers are able to handle before experiencing fatigue to avoid overexertion. Past researchers have introduced several EMG processing techniques and different EMG features that represent fatigue indices in time, frequency, and time-frequency domain. The impact of EMG processing based measures in fatigue assessment during manual lifting are reviewed in this paper. It is believed that this paper will greatly benefit researchers who need a bird's eye view of the biosignal processing which are currently available, thus determining the best possible techniques for lifting applications.


Optical coherence tomography-angiographic vascular densities in Familial Mediterranean Fever (FMF) Patients with M694V Mutations.
Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disease with accompanying findings of amyloidosis and vasculitis. M694V is one of the most common mutations associated with amyloidosis. This study compared the macular optical coherence tomography angiography measurements in FMF patients who were genetically verified to carry the M694V mutation of the MEFV gene to those in healthy controls. The vessel densities (VDs) of superficial (SVP) and deep vascular plexus (DVP) of the retina, and choriocapillaris, foveal avascular zone (FAZ) perimetry, foveal VD 300µ around the FAZ (FD-300), acirculatory index (AI) and non-flow area were measured with optical coherence tomography angiography (OCT-A). The FMF and control groups were matched for age and gender. Compound heterozygous pathogenic variants were excluded. Thirty-eight FMF patients with M694V mutations (28 heterozygous and 10 homozygous) and 40 healthy controls were included. The two groups were similar with the regard to age and gender (P=0.88 and P=0.49, respectively). None of the investigated parameters, including the vessel densities of the SVP and DVP, and choriocapillaris, FAZ perimetry, FD-300, AI, and non-flow area showed a statistically significant difference between the FMF and control groups. The macular vessel density measurements and FAZ parameters of FMF patients with M694V mutations do not differ from age- and sex-matched healthy controls.


Changes in the Time-Domain of Heart Rate Variability and Corticosterone after Surgical Trauma to the Nasal Septum in Rats.
The aim of the work was to study changes in the time range of heart rate variability (HRV) against the background of changes in the concentration of corticosterone in blood plasma in rats after surgical trauma to the nasal septum. Septoplasty was simulated in 30 mature male Wistar rats weighing 210-290 g. ECG was recorded with subsequent analysis of the time domain of HRV, as well as blood sampling to estimate changes in the concentration of corticosterone in the blood plasma was performed. As a result, SDNN significantly increased in comparison with the control on days 2 and 3 (p < 0.001) but decreased on days 4-5 (p < 0.001) and 6 (p < 0.01). rMSSD changed in waves with two irregular peaks on days 1 and 6. SDNN/rMSSD, in comparison with the 1st day of the postoperative period, increased on the 2nd day, continued to increase (p < 0.05), and then began to decrease on day 4 (p < 0.01). The total HRV power of was low throughout the postoperative period (p < 0.001), except for day 3, when it was equal to the control data. The increase in the total power index fell on day 3 after the operation (p <0.01), after which its decline was observed again. The concentration of corticosterone in the blood plasma in rats was significantly higher than before (p < 0.001). On postoperative day 2 to 4, its plateau was determined. Simulation of septoplasty leads to changes in the time range of HRV, an increase in the concentration of corticosterone in the blood plasma in rats with its maximum at the time of surgery and 24 h later, and the formation of a "plateau" on postoperative days 2 to 4, which coincides with the changes in HRV.


Synthesis of substituted thienopyrimidine-4-ones.
The parallel solution-phase synthesis of more than 3000 substituted thienopyrimidin-4-ones has been accomplished. Key reactions include assembly of the 2-thioxopyrimidin-4-one ring by condensation of isomeric aminothiophenecarboxylates or their appropriate reactive derivatives (isothiocyanates or dithiocarbamates) with the corresponding isothiocyanates or amines. The libraries from libraries were then obtained in good yields and purities using solution-phase alkylation and acylation methodologies. Simple manual techniques for parallel reactions using special CombiSyn synthesizers were coupled with easy purification procedures (crystallization from the reaction mixtures) to give high-purity final products. The scope and limitations of the developed approach are discussed.


Staphylococcus aureus Survives in Cystic Fibrosis Macrophages, Forming a Reservoir for Chronic Pneumonia.
Staphylococcus aureus plays an important role in sepsis, pneumonia, wound infections, and cystic fibrosis (CF), which is caused by mutations of the cystic fibrosis transmembrane conductance regulator (Cftr). Pulmonary S. aureus infections in CF often occur very early and prior to colonization with other pathogens, in particular Pseudomonas aeruginosa Here, we demonstrate that CF mice are highly susceptible to pulmonary infections with S. aureus and fail to clear the pathogen during infection. S. aureus is internalized by Cftr-deficient macrophages in the lung, but these macrophages are unable to kill intracellular bacteria. This failure might be caused by a defect in the fusion of phagosomes with lysosomes, while this process occurs rapidly in wild-type macrophages and serves to kill intracellular pathogens. Transplantation of infected Cftr-deficient alveolar macrophages into the lungs of noninfected CF mice is sufficient to induce pneumonia. This suggests that intracellular survival of S. aureus in macrophages may allow the pathogen to chronically infect CF lungs.


Proteomic profiling of primary breast cancer predicts axillary lymph node metastasis.
To determine if protein expression in primary breast cancers can predict axillary lymph node (ALN) metastasis, we assessed differences in protein expression between primary breast cancers with and without ALN metastasis using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Laser capture microdissection was performed on invasive breast cancer frozen sections from 65 patients undergoing resection with sentinel lymph node (SLN) or level I and II ALN dissection. Isolated proteins from these tumors were applied to immobilized metal affinity capture (IMAC-3) ProteinChip arrays and analyzed by SELDI-TOF-MS to generate unique protein profiles. Correlations between unique protein peaks and histologically confirmed ALN status and other known clinicopathologic factors were examined using ANOVA and multivariate logistic regression. Two metal-binding polypeptides at 4,871 and 8,596 Da were identified as significant risk factors for nodal metastasis (P = 0.034 and 0.015, respectively) in a multivariate analysis. Lymphovascular invasion (LVI) was the only clinicopathologic factor predictive of ALN metastasis (P = 0.0038). In a logistic regression model combining the 4,871 and 8,596 Da peaks with LVI, the area under the receiver operating characteristic curve was 0.87. Compared with patients with negative ALN, those with > or =2 positive ALN or non-SLN metastases were significantly more likely to have an increased peak at 4,871 Da (P = 0.016 and 0.0083, respectively). ProteinChip array analysis identified differential protein peaks in primary breast cancers that predict the presence and number of ALN metastases and non-SLN status.


Patient Preferences in Diagnostic Imaging: A Scoping Review.
As new diagnostic imaging technologies are adopted, decisions surrounding diagnostic imaging become increasingly complex. As such, understanding patient preferences in imaging decision making is imperative. We aimed to review quantitative patient preference studies in imaging-related decision making, including characteristics of the literature and the quality of the evidence. The Pubmed, Embase, EconLit, and CINAHL databases were searched to identify studies involving diagnostic imaging and quantitative patient preference measures from January 2000 to June 2022. Study characteristics that were extracted included the preference elicitation method, disease focus, and sample size. We employed the PREFS (Purpose, Respondents, Explanation, Findings, Significance) checklist as our quality assessment tool. A total of 54 articles were included. The following methods were used to elicit preferences: conjoint analysis/discrete choice experiment methods (n = 27), contingent valuation (n = 16), time trade-off (n = 4), best-worst scaling (n = 3), multicriteria decision analysis (n = 3), and a standard gamble approach (n = 1). Half of the studies were published after 2016 (52%, 28/54). The most common scenario (n = 39) for eliciting patient preferences was cancer screening. Computed tomography, the most frequently studied imaging modality, was included in 20 studies, and sample sizes ranged from 30 to 3469 participants (mean 552). The mean PREFS score was 3.5 (standard deviation 0.8) for the included studies. This review highlights that a variety of quantitative preference methods are being used, as diagnostic imaging technologies continue to evolve. While the number of preference studies in diagnostic imaging has increased with time, most examine preventative care/screening, leaving a gap in knowledge regarding imaging for disease characterization and management.


[Pseudoreplication in ecological research: the problem overlooked by Russian scientists].
The use of differential statistics to test for treatment effect with data from experiments where either treatments were not replicated (though samples may be) or replicates are not statistically independent leads to serious methodological problem. This problem, discovered by Hurbert (1984), is called pseudoreplication. Due to unknown reasons, pseudoreplication issue was completely overlooked by the Russian ecologists, in spite of the fact that the international scientific community is aware of pseudoreplication for almost twenty years. As the result, up to 47% of the experimental ecological papers, published in six Russian academic journals (Botanicheskij zhurnal, Ekologia, Izvestija RAN Ser. Biol., Lesovedenie, Zhurnal Obshchei Biologii, Zooligicheskij zhurnal) in 1998-2001, are pseudoreplicated; this proportion is nearly twice as high as the proportion of pseudoreplicated studies in international journals during 1960-1980, e.g. before the problem was discovered by Hurlbert (1984). This situation is alarming, especially because a substantial part of pseudoreplication arise from incorrect use of statistics, not from incorrect designing of experiments. By using several examples from the recent papers of Russian ecologists I shortly review the situations where pseudoreplication may occur and discuss some aspects of the experimental design, which are critical for correct processing and interpretation of ecological data.


Problems associated with using in vivo proton (1H) magnetic resonance spectroscopy to quantify liver fat.
In-vivo 1H magnetic resonance (MR) spectra of the liver were obtained in 8 patients admitted for liver biopsy. These patients had abnormal liver function and the presumptive diagnosis of fatty liver prior to biopsy. Two patients with NIDDM were also studied but liver biopsies were not performed as liver function was normal. The MR spectra, obtained on a 60 cm clear-bore 1.9 tesla superconducting magnet showed two 1H resonances, one from water and the other from repeating methylene protons - (CH2)n - in triglyceride. The lipid: water signal ratio was used to characterize tissues as subcutaneous fat (high lipid:water ratio), normal liver (low lipid: water ratio) and fatty liver (intermediate lipid: water ratio). The spectra obtained at the greatest depth from the probe surface ~4.5 cm) was used as it was most likely to represent liver tissue. Although all 8 patients were expected to have fatty liver only 2 had evidence of significant fatty changes on microscopy. This was assessed by counting the vacuoles of fat over the area of the biopsy specimen and quantitated as 'fat vacuoles per high power field' (f/hpf). In the 2 patients with NIDDM, unusual stack plots suggested technical difficulties with 1H MR spectroscopy for in-vivo assessment of fatty liver. The first patient, PT had a significant increase in lipid:water ratio on the spectra thought to represent liver (lipid:water ~ 65% cf levels <3% in norma liver and 12.6% + 26.5% in those patients subsequently found to have fat on biopsy). This was later found on MR imaging to represent omental fat lying between the liver and muscle layer. The second patient, OM had a large amount of subcutaneous fat overlying the area assessed. As seen on the stack plot, the probe depth was not great enough to pass through the subcutaneous fat and muscle layer to penetrate liver tissue. There was a significant correlation between the lipid:water signal ratio and visible fat on biopsy in those patients who underwent liver biopsy. Difficulties experienced with probe depth suggests imaging would be necessary prior to spectroscopy to ensure liver tissue is actually assessed.


Influence of implantable cardioverter-defibrillators on the long-term prognosis of survivors of out-of-hospital cardiac arrest.
Survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction are at high risk for recurrent cardiac arrest and sudden cardiac death. The impact of the implantable cardioverter-defibrillator on long-term prognosis in these patients is uncertain. Three hundred thirty-one survivors of out-of-hospital cardiac arrest (age, 56 +/- 13.7 years) underwent electrophysiologically guided therapy. Implantable defibrillators were placed in 150 patients (45.3%), and 181 patients (54.7%) received pharmacological and/or surgical therapy alone. Left ventricular ejection fraction was 35.2 +/- 16.6% in defibrillator recipients and 45.3 +/- 18.2% in nondefibrillator patients. Median patient follow-up was 24 months in the defibrillator group and 46 months in the nondefibrillator group. In a proportional hazards model, the independent predictors of total cardiac mortality were left ventricular ejection fraction of less than 0.40 (relative risk, 4.55; 95% confidence interval, 2.44 to 8.33; P = .0001), absence of an implantable defibrillator (relative risk, 2.70; confidence interval, 1.41 to 5.00; P = .017), and persistence of inducible sustained ventricular tachycardia (relative risk, 1.84; 95% confidence interval, 0.97 to 3.49; P = .045). The 1- and 5-year probabilities of survival free of cardiac mortality in patients with left ventricular ejection fraction of less than 0.40 were 94.3% and 69.6% with a defibrillator and 82.1% and 45.3% without a defibrillator, respectively. For patients with left ventricular ejection fraction of 0.40 or more, the 1- and 5-year probabilities of survival free of cardiac mortality were 97.7% and 94.6% with a defibrillator and 95.4% and 86.9% without a defibrillator, respectively. In survivors of out-of-hospital cardiac arrest, the implantable defibrillator is associated with a reduction in cardiac mortality, particularly in patients with impaired left ventricular function.


Acute experimental suppurative pancreatitis in the rat.
Acute pancreatitis was induced in rats by infusing sodium taurodeoxycholate with or without Escherichia coli and Bacteroides fragilis into the bile-pancreatic duct. Survival did not differ between the 'noninfected bile group' (NIB) and the 'infected bile group' (IB). At standardized macroscopic evaluation, pancreatitis was more severe in the IB group (p less than 0.05). Histologic examination on day 7 showed suppuration of pancreatic tissue in 6/7 IB and 3/14 NIB rats (p less than 0.05). Bacteriologic culture of pancreatic tissue was positive in 6/8 IB and 3/17 NIB rats (p less than 0.01). Bacterial culture of blood, peritoneal fluid of pulmonary tissue was seldom positive. Concordance between microscopically observed suppuration and positive bacterial culture was almost total. Recall antigen skin testing indicated anergy in the IB group, while the NIB group showed moderately diminished reaction (p less than 0.001). Similar increase of S-fibrinogen was found on day 3 in both groups, but complement factor C3 was reduced only in the IB group. This experimental model, with suppurative pancreatitis induced by intraductal infusion of an infected bile salt, may be useful for studies of systemic complications in acute pancreatitis.


Vectorial secretion of a kallikrein-like enzyme by cultured renal cells. I. General properties.
Urinary kallikreins are proteolytic enzymes known to be secreted by distal nephron tubules. In this study, we demonstrate (using the chromogenic tripeptide substrate S 2266) that the renal cell line A6 from Xenopus laevis secretes a kallikrein-like enzyme. Secretion is present only when the cells are grown on filters, and enzyme is secreted only into the apical membrane bathing solution. Enzyme secretion consists of two components, one soybean trypsin inhibitor (SBTI) sensitive (SSBTI) and the other insensitive to SBTI (ISBTI). Both enzymes were inhibited by aprotinin, a kallikrein-like enzyme inhibitor. Using a bioassay, only the ISBTI enzyme produced a hypotensive effect on blood pressure and is thus a kallikrein-like enzyme. The apical membrane of cells grown on filters contains both enzyme species, whereas the basolateral membrane contains only the ISBTI (kallikrein-like) enzyme. Both enzymes were present in the apical membrane of cells grown on plastic. Initiation of enzyme secretion occurred after the cells formed electrically tight monolayers and the increase in membrane activity always preceded enzyme secretion. Using an irreversible inhibitor of the apical membrane-bound enzymes, the turnover rate for the SSBTI and ISBTI enzymes (cells on filters) was 3 and 7 h, respectively. Because the recovery of enzyme secretion was proportional to the recovery of membrane-bound enzyme activities, this suggests that enzyme secretion is due to the release of membrane-bound enzyme.


Effect of Zinc Foliar Fertilization Alone and Combined with Trehalose on Maize (Zea mays L.) Growth under the Drought.
Maize (Zea mays L.) is one of the most widely grown cereals in the world. Its cultivation is affected by abiotic stress caused by climate change, in particular, drought. Zinc (Zn) supplied by foliar nutrition can increase plant resistance to water stress by enhancing physiological and enzymatic antioxidant defence mechanisms. One of the possibilities to reduce the effect of drought on plant production is also the utilization of trehalose. In order to confirm the effect of the foliar application of selected forms of Zn (0.1% w/v solution)-zinc oxide micro- (ZnO) and nanoparticles (ZnONP), zinc sulphate (ZnSO4) and zinc chelate (ZnEDTA)-a pot experiment in controlled conditions was conducted in combination with trehalose (1% w/v solution) on selected growth parameters of maize exposed to the drought stress. A significant effect of coapplication of Zn and trehalose on chlorophyll content, chlorophyll fluorescence parameters, root electrical capacity, weight of maize aboveground biomass (AGB) and Zn content in AGB was found. At the same time, the hypothesis of a positive effect of carbohydrates on increasing the uptake of foliar-applied Zn was confirmed, especially for the ZnEDTA and ZnSO4. This paper presents the first empirical evidence of the trehalose addition to sprays for zinc foliar fertilization of maize proving to be an effective way of increasing the resistance of maize grown under drought stress conditions.


Clinical Outcomes of 3-column Osteotomy at Growing Rod Graduation.
Several different strategies were described on how to graduate a patient when skeletal maturity is reached after growing rod treatment. A final instrumentation and fusion is commonly performed, but the stiffness of the spine after numerous lenghthenings can be a major problem. When correction is needed in a severe and rigid curve, 3-column osteotomies (3CO) can be used as a method of bringing the spine back to a well-balanced position. This study aims to evaluate the clinical outcomes of 3CO osteotomies at growing rod graduation. A retrospective search of the database was performed between 1996 and 2018. Inclusion criteria were: diagnosis of early-onset scoliosis, underwent 3CO at the final fusion procedure, and ≥1 year of follow-up. Indications for this osteotomy were: significant sagittal and/or coronal off-balance or severe crankshaft deformity or significant distal and/or proximal adding-on. Clinical, radiographic, and operative data were analyzed. Complications were classified according to the modified Clavien-Dindo-Sink system. Eight patients were included in the study with a mean age of 13.5 at graduation (male/female: 2/6). The mean scoliosis angle significantly reduced from 65.6 to 39 degrees (P=0.012). Mean T1-T12 height increased from 19 to 20.5 (P=0.084) and T1-S1 from 29.6 to 31.6 (P=0.144). Five patients had a staged surgery. Average operative time was 338 minutes and blood loss was 1321 mL. Four grade 1, 1 grade 2, and 1 grade 3 complications occurred. This is the first case-series in the literature reporting on the use of 3CO at growing rod graduation. These procedures can be safely and effectively used to overcome significant multiplanar deformity and/or off-balance in the graduation of patients with early-onset scoliosis and significant correction can be achieved on these severe and rigid curves. Level IV-case series.


Induction of colon tumors in 1,2-dimethylhydrazine-resistant Lobund Wistar rats by methylazoxymethanol acetate.
Sprague-Dawley and Lobund Wistar rats, which were sensitive and resistant to induction of colon tumors by 1,2-dimethylhydrazine (DMH), respectively, were treated with methylazoxymethanol (MAM), the product of DMH metabolism by the microsomal mixed-function oxidase system. Although the colon tissue in both stocks of rats had similar NAD+-dependent dehydrogenase activities that are considered necessary to activate MAM to an ultimate carcinogen, still a sevenfold greater incidence of colon tumors was found in the Sprague-Dawley rats, and their tumors were more extensive. The results indicated that the difference in susceptibility to colon tumor induction between the rat stocks was partially related to metabolic activation of the DMH and to other, as yet undetermined, endogenous factors.


Use of Fluorescent Dyes in Endoscopy and Diagnostic Investigation.
The advancement of innovative endoscopic technology in terms of improving the visualization of the mucosa has been of significant benefit. Advancements in image resolution, software processing, and optical filter technology have resulted in several techniques complemental to traditional white light endoscopy. These new techniques provide a real-time optical diagnosis as well as virtual histology of detected lesions. Optical molecular imaging permits a functional assessment within cells. Optical molecular imaging provides an understanding of cellular processes and permits validation of the specificity of fluorescent tracers and the possibility of quantifying the signal.


Fe3O4 nanoparticles as robust photothermal agents for driving high barrier reactions under ambient conditions.
Magnetite nanoparticles (MNPs) show remarkable stability during extreme photothermal heating (≥770 K), displaying no change in size, crystallinity, or surfactants. The heat produced is also shown as chemically useful, driving the high-barrier thermal decomposition of polypropylene carbonate. This suggests MNPs are better photothermal agents (compared to gold nanoparticles), for photothermally driving high-barrier chemical transformations.


Hypopituitarism associated with neurofibromatosis type 1: report of one case.
Neurofibromatosis type 1 (NF-1) is an autosomal dominant disorder with a wide range of clinical manifestations. Hydrocephalus unrelated to brain tumors is rare in neurofibromatosis type 1. A 16-year-and-6-month-old girl with primary amenorrhea was found to have hydrocephalus associated with neurofibromatosis type 1. After endocrine and brain imaging study, the cause of primary amenorrhea was proven to be hypopituitarism due to hydrocephalus. She entered puberty soon after relieving the hydrocephalus with a ventriculoperitoneal shunt. However, arrest of puberty was noted three months later. Therefore estrogen replacement therapy was given. Early detection of hydrocephalus was difficult in this patient. From the experience of our case, MRI study of brain is indicated in patient with neurofibromatosis type 1 and endocrine dysfunction.


Perceptions of a "good death" in acute hospitals.
Despite the fact that half of all deaths occur in hospital, there is a lack of literature on general nurses' experiences of caring for end-of-life patients on general hospital wards. To ascertain general nurses' perceptions and experiences of a good death in an acute hospital setting. In-depth interviews were conducted with 13 general nurses working in an acute hospital. Six themes were identified as important in facilitating a good death: good communication/awareness of expected death; time (to care); environment; support; knowledge; symptom management. Participants felt that failing to communicate a diagnosis of dying adversely affected the quality of death. As such the focus of future end-of-life care education needs to include how general nurses can facilitate communication and handle difficult questions to enable a good death for patients and their families.


Understanding Childhood Constipation through the Prism of the Caretaker.
Childhood constipation is presenting with increasing frequency at pediatric surgical clinics. The caregiver's role in prevention and management is pivotal. This study aimed at determining mothers' knowledge, attitudes, and practices with regard to childhood constipation and the association of these with demographic variables. This was a survey-based descriptive study conducted at a tertiary care hospital in South India. Randomly selected mothers of children aged 1-10 years consulting for any problem other than constipation were included in the study. Data collection was done by means of a pretested and prevalidated questionnaire. There were 169 mothers with a median age of 30 years. Over half were homemakers and of a rural background. Urban mothers scored better than their rural counterparts in the attitude section (P = 0.034). Mothers with greater knowledge had better attitude (P = 0.001) and practice (P = 0.020) scores. Those with higher attitude scores also fared better in the practice section (P = 0.04). Knowledge, attitude and practice concerning childhood constipation are connected to each other. South Indian mothers are sufficiently aware of the nuances surrounding childhood constipation, but focused large-scale outreach programs and health education are necessary to bridge the gaps.


Insight into the Effect of Sulfonation Techniques on the Adsorption Properties of -SO3H Surface-Functionalized Coal as Adsorbent for Malachite Green Dye: Steric and Energetic Investigation.
Natural coal (N.C) was sulfonated with sulfuric acid by normal stirring (MS.C) and sonication waves (SS.C) to obtain -SO3H functionalized coal as enhanced adsorbents of malachite green dye (MG). The sulfonated products exhibit enhanced surface area (MS.C (27.2 m2/g) and SS.C (45.8 m2/g)) as compared to N.C. SS.C achieved higher acid density (14.2 mmol/g) and sulfur content (13.2 wt. %) as compared to MS.C. The impact of the sulfonation processes on the adsorption of MG was assessed based on the monolayer isotherm model of one energy. The MG Q sat of N.C (121.3 mg/g), MS.C (226.3 mg/g), and SS.C (296.4 mg/g) validate the significant effect of the sulfonation processes by the sonication waves. This is in agreement with the active site densities that reflect the saturation of SS.C by more active sites (180.74 mg/g) than MS.C (120.38 mg/g) and N.C (70.84 mg/g). The MS.C and SS.C can adsorb three MG molecules as compared to two molecules per site of N.C. The Gaussian energy (<8 kJ/mol) and adsorption energy (<40 kJ/mol)) reflects the physisorption of MG involving van der Waals forces, hydrogen bonding, and dipole bonding forces. The thermodynamic functions demonstrate the uptake of MG by exothermic, spontaneous, feasible reactions.


The Meaning of Occupation for Adults With Advanced Cancer: A Scoping Review.
In this scoping review, we explore the meaning of occupation for people with advanced cancer to develop and improve occupation-based services in oncology. To identify the meaning(s) of occupation for adults with advanced cancer through relevant peer-reviewed literature. Scopus, CINAHL, Medline, and PubMed were used to identify peer-reviewed articles published between 2011 and 2021. Inclusion criteria comprised research studies in English and on meaningful occupations as well as participants age 19 yr or older and diagnosed with advanced cancer. Exclusion criteria comprised non-English publications, studies with participants in an early stage of cancer, and gray literature or nonreviewed articles. Thirteen articles matched the inclusion criteria: 9 qualitative studies, 1 mixed-methods study, 1 case study, 1 pilot study (pretest-posttest design), and 1 retrospective study (review of clinical data). Four themes emerged from the thematic analysis: occupation benefits important relationships and connections with others, occupation as a source of physical or psychological comfort, managing one's identity through occupation, and occupation as a religious expression. This scoping review highlights the value of participating in an occupation for people with advanced cancer. It also shows the importance of meaningful occupations to the quality of life and well-being of adults with advanced cancer. What This Article Adds: This scoping review identifies meanings of occupation linked to the health and well-being of adults with advanced cancer to develop and improve occupation-based services in oncology.


Pharmacogenomics in asthma therapy: where are we and where do we go?
The response to drug treatment in asthma is a complex trait and is markedly variable even in patients with apparently similar clinical features. Pharmaco-genomics, which is the study of variations of human genome characteristics as related to drug response, can play a role in asthma therapy. Both a traditional candidate-gene approach to conducting genetic association studies and genome-wide association studies have provided an increasing list of genes and variants associated with the three major classes of asthma medications: β2-agonists, inhaled corticosteroids, and leukotriene modifiers. Moreover, a recent integrative, systems-level approach has offered a promising opportunity to identify important pharmacogenomics loci in asthma treatment. However, we are still a long way away from making this discipline directly relevant to patients. The combination of network modeling, functional validation, and integrative omics technologies will likely be needed to move asthma pharmacogenomics closer to clinical relevance.


Reducing the flexibility of retinal restores a wild-type-like photocycle in bacteriorhodopsin mutants defective in protein-retinal coupling.
The thermal re-isomerization of retinal from the 13-cis to the all-trans state is a key step in the final stages of the photocycle of the light-driven proton pump, bacteriorhodopsin. This step is greatly slowed upon replacement of Leu-93, a residue in van der Waals contact with retinal. The most likely role of this key interaction is that it restricts the flexibility of retinal. To test this hypothesis, we have exchanged native retinal in Leu-93 mutants with bridged retinal analogs that render retinal less flexible by restricting free rotation around either the C10-C11 (9,11-bridged retinal) or C12-C13 (11,13-bridged retinal) single bonds. The effect of the analogs on the photocycle was then determined spectroscopically by taking advantage of the previous finding that the decay of the O intermediate in the Leu-93 mutants provides a convenient marker for retinal re-isomerization. Time-resolved spectroscopic studies showed that both retinal analogs resulted in a dramatic acceleration of the photocycling time by increasing the rate of decay of the O intermediate. In particular, exchange of native retinal in the Leu-93 --> Ala mutant with the 9,11-bridged retinal resulted in an acceleration of the decay of the O intermediate to a rate similar to that seen in wild-type bacteriorhodopsin. We conclude that the protein-induced restriction of conformational flexibility in retinal is a key structural requirement for efficient protein-retinal coupling in the bacteriorhodopsin photocycle.


Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases.
Neutrophils play an essential role in the body's innate defense against pathogens and are one of the primary mediators of the inflammatory response. To defend the host, neutrophils use a wide range of microbicidal products, such as oxidants, microbicidal peptides, and lytic enzymes. The generation of microbicidal oxidants by neutrophils results from the activation of a multiprotein enzyme complex known as the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which is responsible for transferring electrons from NADPH to O2, resulting in the formation of superoxide anion. During oxidase activation, cytosolic oxidase proteins translocate to the phagosome or plasma membrane, where they assemble around a central membrane-bound component known as flavocytochrome b. This process is highly regulated, involving phosphorylation, translocation, and multiple conformational changes. Originally, it was thought that the NADPH oxidase was restricted to phagocytes and used solely in host defense. However, recent studies indicate that similar NADPH oxidase systems are present in a wide variety of nonphagocytic cells. Although the nature of these nonphagocyte NADPH oxidases is still being defined, it is clear that they are functionally distinct from the phagocyte oxidases. It should be noted, however, that structural features of many nonphagocyte oxidase proteins do seem to be similar to those of their phagocyte counterparts. In this review, key structural and functional features of the neutrophil NADPH oxidase and its protein components are described, including a consideration of transcriptional and post-translational regulatory features. Furthermore, relevant details about structural and functional features of various nonphagocyte oxidase proteins will be included for comparison.


Resting state connectivity in alcohol dependent patients and the effect of repetitive transcranial magnetic stimulation.
Alcohol dependence is thought to result from an overactive neural motivation system and a deficient cognitive control system, and rebalancing these systems may mitigate excessive alcohol use. This study examines the differences in functional connectivity of the fronto-parietal cognitive control network (FPn) and the motivational network (striatum and orbitofrontal cortex) between alcohol dependent patients (ADPs) and healthy controls (HCs), and the effect of repetitive transcranial magnetic stimulation (rTMS) on these networks. This randomized controlled trial included 38 ADPs and 37 HCs, matched on age, gender and education. Participants were randomly assigned to sham or right dorsolateral prefrontal cortex (dlPFC) stimulation with rTMS. A 3T resting state functional Magnetic Resonance Imaging (fMRI) scan was acquired before and after active or sham 10Hz rTMS. Group differences of within and between network connectivity and the effect of rTMS on network connectivity was assessed using independent component analysis. Results showed higher connectivity within the left FPn (p=0.012) and the left fronto-striatal motivational network (p=0.03) in ADPs versus HCs, and a further increase in connectivity within the left FPn after active stimulation in ADPs. ADPs also showed higher connectivity between the left and the right FPns (p=0.025), and this higher connectivity was related to fewer alcohol related problems (r=0.30, p=0.06). The results show higher within and between network connectivity in ADPs and a further increase in fronto-parietal connectivity after right dlPFC rTMS in ADPs, suggesting that frontal rTMS may have a beneficial influence on cognitive control and may result in lower relapse rates.


Non-metastatic ductal adenocarcinoma of the prostate: pattern of care from an uro-oncology multidisciplinary group.
To retrospectively review our 20 year experience of multidisciplinary management of non-metastatic ductal prostate cancer (dPC), a rare but aggressive histological subtype of prostate cancer whose optimal therapeutic approach is still controversial. Histologically confirmed dPC patients undergoing primary, curative treatment [radical prostatectomy (RP), external beam radiotherapy (EBRT), and androgen deprivation therapy (ADT)] were included, and percentage of ductal and acinar pattern within prostate samples were derived. Survival outcomes were assessed using the subdistribution hazard ratio (SHR) and Fine-and-Gray model. From January 1997 to December 2016, 81 non-metastatic dPC fitted selection criteria. Compared to surgery alone, SHR for progression-free survival and cancer-specific mortality were 2.8 (95% CI 0.6-13.3) and 1.3 (95% CI 0.1-16.2) for exclusive EBRT, 2.7 (95% CI 0.6-13.0) and 6.5 (95% CI 0.6-69.8) for adjuvant EBRT, 4.9 (95% CI 0.7-35.5) and 5.8 (95% CI 0.5-65.6) for salvage EBRT post-prostatectomy recurrence, and 3.2 (95% CI 0.7-14.0) and 3.9 (95% CI 0.3-44.1) for primary ADT (P = 0.558; P = 0.181), respectively. Comparing multimodal treatment and monotherapy confirmed the above trends. Local recurrence more typically occurred in pure dPC patients, mixed histology more frequently produced metastatic spread (29.6% relapse in total, P = 0.026). Albeit some limitations affected the study, our findings support the role of local treatment to achieve better disease control and improve quality of life. Different behavior, with typical local growth in pure dPC, higher distant metastatization in the mixed form, might influence treatment response. Given its poor prognosis, we recommend multidisciplinary management of dPC.


Management of giant cell tumor of the tarsal bones: a report of nine cases and a review of the literature.
Giant cell tumor of the tarsal bones is uncommon and therapeutic options are ill defined. We report on nine cases of giant cell tumors of the tarsal bones treated by excision of the complete bone in 6 cases, partial excision in 1 case, and curettage and bone grafting in two cases. There was no recurrence at an average 25.8-month follow-up. Function after calcanectomy was satisfactory. Excision of the talus may or may not be followed by arthrodesis, but arthrodesis is essential after excision of all the other tarsal bones except the calcaneus. We advocate aggressive surgical measures in these cases; amputation should be reserved for recurrences only. Satisfactory function may be expected after excision of tarsal bones.


The molecular mechanisms of skeletal muscle wasting: implications for therapy.
Skeletal muscle wasting is an important systemic manifestation of a wide range of diseases, including trauma, sepsis and cancer. The clinical consequences of muscle wasting undoubtedly include significant patient morbidity and worsened survival. Recently, there has been important progress in our understanding of the molecular mechanisms behind muscle wasting. In this review, the common systemic mediators, intracellular signalling pathways and effector mechanisms of skeletal muscle wasting are discussed with particular reference to different models of wasting and the development of novel therapeutic strategies.


Tyzzer's Disease in Free-Ranging Passerine Birds in California, USA.
Tyzzer's disease was diagnosed as the cause of mortality in free-ranging hatch-year passerine birds in Southern California, US. Birds presented with ataxia, tremors, and opisthotonos and died or were euthanized. Postmortem examination of four birds identified encephalitis on microscopy with characteristic stacked, slender bacterial rods visible with special stains. Infection with Clostridium piliforme was confirmed by real-time PCR.


Joint molecule resolution requires the redundant activities of MUS-81 and XPF-1 during Caenorhabditis elegans meiosis.
The generation and resolution of joint molecule recombination intermediates is required to ensure bipolar chromosome segregation during meiosis. During wild type meiosis in Caenorhabditis elegans, SPO-11-generated double stranded breaks are resolved to generate a single crossover per bivalent and the remaining recombination intermediates are resolved as noncrossovers. We discovered that early recombination intermediates are limited by the C. elegans BLM ortholog, HIM-6, and in the absence of HIM-6 by the structure specific endonuclease MUS-81. In the absence of both MUS-81 and HIM-6, recombination intermediates persist, leading to chromosome breakage at diakinesis and inviable embryos. MUS-81 has an additional role in resolving late recombination intermediates in C. elegans. mus-81 mutants exhibited reduced crossover recombination frequencies suggesting that MUS-81 is required to generate a subset of meiotic crossovers. Similarly, the Mus81-related endonuclease XPF-1 is also required for a subset of meiotic crossovers. Although C. elegans gen-1 mutants have no detectable meiotic defect either alone or in combination with him-6, mus-81 or xpf-1 mutations, mus-81;xpf-1 double mutants are synthetic lethal. While mus-81;xpf-1 double mutants are proficient for the processing of early recombination intermediates, they exhibit defects in the post-pachytene chromosome reorganization and the asymmetric disassembly of the synaptonemal complex, presumably triggered by crossovers or crossover precursors. Consistent with a defect in resolving late recombination intermediates, mus-81; xpf-1 diakinetic bivalents are aberrant with fine DNA bridges visible between two distinct DAPI staining bodies. We were able to suppress the aberrant bivalent phenotype by microinjection of activated human GEN1 protein, which can cleave Holliday junctions, suggesting that the DNA bridges in mus-81; xpf-1 diakinetic oocytes are unresolved Holliday junctions. We propose that the MUS-81 and XPF-1 endonucleases act redundantly to process late recombination intermediates to form crossovers during C. elegans meiosis.


EPR evidence for α-triphenylstannylvinyl radicals in the O-directed hydrostannation of dialkylacetylenes with Ph3SnH/cat. Et3B/O2.
Here we provide definitive EPR evidence for the existence of α-triphenylstannylvinyl radicals in the low temperature O-directed free radical hydrostannation of dialkyl propargylic alcohols with Ph3SnH/cat. Et3B and O2 in PhMe. Isotropic hyperfine splitting patterns and spectral simulations confirm the assignments made. In the case of the α-triphenylstannylvinyl radical (Z)-2, an isotopic 119/117Sn hyperfine coupling constant of 9.5 mT (95 G) was measured along with a 1Hβ hyperfine coupling constant of 1.1 mT.


Condom use and its association with bacterial vaginosis and bacterial vaginosis-associated vaginal microflora.
Previous studies have been inconsistent with regard to whether condom use is associated with bacterial vaginosis. We evaluated this association using case-crossover analyses. A total of 871 women at high risk for sexually transmitted diseases were followed for a median of 3 years. At baseline and at 6, 12, 24, and 36 months thereafter, vaginal swabs were obtained for gram stain diagnosis of bacterial vaginosis, culture of microflora, and DNA amplification of Neisseria gonorrhoeae and Chlamydia trachomatis. Case-crossover analyses using incident and recurrent incident case periods were used to assess the associations among condom use, bacterial vaginosis, and vaginal microflora. Consistent condom use (10 out of 10 sexual encounters) was associated with a decreased frequency of bacterial vaginosis (adjusted odds ratio = 0.55 [95% confidence interval 0.35-0.88]). When we excluded women with intermediate flora, consistent condom use was even more strongly protective against bacterial vaginosis (0.37 [0.20-0.70]). Consistent condom use was similarly protective against carriage of anaerobic gram-negative pigmented rods (0.58 [0.36-0.94]). Results were similar when analyses were repeated to capture only first occurrences of outcomes among women without bacterial vaginosis at baseline, suggesting a protective effect against the acquisition of bacterial vaginosis. Consistent condom use was associated with a decrease in the risk for bacterial vaginosis and associated vaginal microflora.


Microscale Structures Arising from Nanoscale Inhomogeneities in Nematics Made of Bent-Shaped Molecules.
Nanoscale structures in fluid media normally require techniques such as freeze fracture electron microscopy and atomic force microscopy for their visualization. As demonstrated in the present study, the surface modification due to nanoscale clusters occurring intrinsically in nematics made of bent-shaped molecules with either rigid or flexible cores leads to microscale structures, which are visible in an optical microscope. The underlying physical mechanism proposed here involves a quasiperiodic change in anchoring conditions on untreated glass plates for the medium made of islands of clusters surrounded by unclustered molecules. The resulting pattern of stripes outlines the director-normal field around line defects in the well-known schlieren texture. The instability, which is seen over most of the nematic range, with increasing visibility under continued cooling of the sample, sets the nematics made of bent-shaped molecules apart from the classical nematics of rod-shaped molecules.


Water adsorption and dissociation processes on small Mn-doped TiO2 complexes.
Metal oxide complexes have high catalytic potential in many fields, such as oxidation, dehydrogenation, dehydration, reductive coupling, etc. The adsorption of molecules is a fundamental process in catalytic reactions on the metal oxide complex. In this study, water adsorption and dissociation processes on small Mn-doped TiO2 complexes are investigated at the density functional theory (DFT) level of theory. Water adsorption at terminal Mn atoms is typically found to have an energy around -0.7 eV, which is smaller than the -1.2 eV observed at terminal Ti atoms. Dissociation energies at Mn atoms are determined to be about -0.6 eV, which are also smaller than the approximately -1.2 eV dissociation energies at Ti atoms. Molecular adsorption without dissociation is favorable in energy after water adsorbs at each metal atom. Mn doping reduces the reaction energy; the reaction energy of the doped system is not similar to that of the pure manganese oxide complex.


Mechanism of DNA binding to the gene 5 protein of bacteriophage fd.
A model for the bimolecular complex arising from the interaction of single-stranded DNA with the gene 5 DNA binding protein (G5BP) of bacteriophage fd is proposed on the basis of difference Fourier analyses and the correlation between structural and physicochemical data. The essential DNA binding element is the G5BP dimer which provides two antiparallel DNA binding channels, each constructed from amino acid contributions of both monomers within the pair. These channels display identical bonding environments but opposite polarities as a consequence of the inherent dyad symmetry within each dimer unit. The two channels are separated by 30 A, and each is 10 A wide and 40 A long. We propose that DNA binding is a consequence of two general sets of interactions. Aromatic side chains of G5BP stack upon nucleic acid bases, and the DNA phosphate backbone is bound by a series of appropriately positioned lysyl and arginyl side chains. The DNA conformation is fully extended, and each binding channel can accommodate up to five nucleotides. Only minor conformational changes in the native G5BP structure are required to optimize the binding of DNA. The G5BP-DNA complexation model presented here serves to explain some of the mechanistic features associated with the role this protein plays in the formation of a nucleoprotein helix during the bacteriophage fd life cycle.


Systematic editing of synthetic RIG-I ligands to produce effective antiviral and anti-tumor RNA immunotherapies.
Retinoic acid-inducible gene I (RIG-I) recognizes double-stranded viral RNAs (dsRNAs) containing two or three 5' phosphates. A few reports of 5'-PPP-independent RIG-I agonists have emerged, but little is known about the molecular principles underlying their recognition. We recently found that the bent duplex RNA from the influenza A panhandle promoter activates RIG-I even in the absence of a 5'-triphosphate moiety. Here, we report that non-canonical synthetic RNA oligonucleotides containing G-U wobble base pairs that form a bent helix can exert RIG-I-mediated antiviral and anti-tumor effects in a sequence- and site-dependent manner. We present synthetic RNAs that have been systematically modified to enhance their efficacy and we outline the basic principles for engineering RIG-I agonists applicable to immunotherapy.


Measurements of impurity ion temperature and velocity distributions via active charge-exchange recombination spectroscopy in C-2W.
In TAE Technologies' C-2W experiment, electrode biasing is utilized for boundary control of a field-reversed configuration (FRC) plasma embedded in a magnetic mirror. Understanding the underlying physics associated with FRC rotation, stabilization, and heating is crucial for improving machine performance. Impurity ion rotation and temperature are sensitive to biasing effects, and measurements of these quantities can provide insight into important plasma dynamics and overall effectiveness of the biasing system. To this end, a charge-exchange recombination spectroscopy (ChERS) diagnostic was developed and deployed to measure local impurity ion temperature and velocity in the confinement vessel of C-2W. The system utilizes a new diagnostic neutral beam (40 keV, 8.5 A) and a fiber-coupled spectrometer with an image-intensified high-speed camera to measure beam-induced spectral line emission at multiple lines-of-sight. Design details and the first experimental results obtained with this new diagnostic are presented and discussed.


Bilingual children with language impairment: A comparison with monolinguals and second language learners.
The purpose of this study is twofold: (a) to examine whether English finite morphology has the potential to differentiate children with and without language impairment (LI) from Spanish-speaking backgrounds and different levels of English proficiency in comparison to Hispanic English speakers and (b) to investigate the extent to which children who are bilingual exhibit differences in their grammatical performance because of cross-linguistic influence from their first language. Seventy-one children between the ages of 4 years, 5 months and 6 years, 5 months were distributed into the following five groups: English as a first language (EL1) speakers with typical language development (TLD), EL1 speakers with LI, Spanish-English bilinguals with TLD, Spanish-English bilinguals with LI, and English as a second language (EL2) learners with TLD were compared on regular verb finiteness and nominative subject use using spontaneous narrative samples. The EL1 children with LI had significantly lower verb accuracy rates than the EL1 controls with TLD. Verb finiteness marking was also a significant discriminator for the bilinguals with LI. There was no evidence of cross-linguistic influence, however. The analysis indicated no significant differences between EL1 and bilingual children on subject or verb use. The EL2 group only presented difficulties with finite verb use. The typological differences between English and Spanish for overt subject use did not seem to affect the performance of either typical or atypical bilingual learners. The findings underscore the need for addressing language dominance in future bilingual studies.


Effect of secondary flows on Taylor-Aris dispersion.
We study theoretically the effects of secondary (transverse) flows on the Taylor-Aris dispersion of pressure-driven, open column flow in a conduit with a rectangular cross section and account for the interaction of solutes with the retentive coating on the conduit's surface. A few plausible means of inducing secondary flows (that are independent of the primary, pressure-driven, axial flow) are described. The Taylor-Aris dispersion coefficient is computed as a function of the secondary flow's pattern and intensity. By inducing secondary flows, one can significantly reduce dispersion.


Intercellular Transfer of Oncogenic KRAS via Tunneling Nanotubes Introduces Intracellular Mutational Heterogeneity in Colon Cancer Cells.
Mutated forms of the RAS oncogene drive 30% of all cancers, but they cannot be targeted therapeutically using currently available drugs. The molecular and cellular mechanisms that create a heterogenous tumor environment harboring both mutant and wild-type RAS have not been elucidated. In this study, we examined horizontal transfer of mutant KRAS (Kirsten Rat Sarcoma Virus) between colorectal cancer (CRC) cells via a direct form of cell-to-cell communication called tunneling nanotubes (TNTs). TNT formation was significantly higher in CRC cell lines expressing mutant KRAS than CRC cell lines expressing wild-type RAS; this effect was most pronounced in metastatic CRC cell lines with both mutant KRAS and deficiency in mismatch repair proteins. Using inverted and confocal fluorescence time-lapse and fluorescence recovery after photobleaching (FRAP)-based microscopy, we observed GFP-tagged mutant KRASG12D protein trafficking between CRC cells through TNTs within a span of seconds to several minutes. Notably, acquisition of mutant KRAS increased Extracellular Signal-regulated Kinase (ERK) phosphorylation and upregulated tunneling nanotube formation in recipient wildtype CRC cells. In conclusion, these findings suggest that intercellular horizontal transfer of RAS can occur by TNTs. We propose that intercellular transfer of mutant RAS can potentially induce intratumoral heterogeneity and result in a more invasive phenotype in recipient cells.


Gambling-Related Intimate Partner Violence Against Women: A Grounded Theory Model of Individual and Relationship Determinants.
This study aimed to examine how problem gambling interacts with gendered drivers of intimate partner violence (IPV) against women to exacerbate this violence. Interviews were conducted with 48 female victims of IPV linked to a male partner's gambling; 24 female victims of IPV linked to their own gambling; and 39 service practitioners from 25 services. Given limited research into gambling-related IPV, but a stronger theoretical base relating to IPV against women, this study used an adaptive grounded theory approach. It engaged with existing theories on gendered drivers of violence against women, while also developing a grounded theory model of individual and relationship determinants based on emergent findings from the data. Gambling-related IPV against women was found to occur in the context of expressions of gender inequality, including men's attitudes and behaviors that support violence and rigid gender expectations, controlling behaviors, and relationships condoning disrespect of women. Within this context, the characteristics of problem gambling and the financial, emotional and relationship stressors gambling causes intensified the IPV. Alcohol and other drug use, and co-morbid mental health issues, also interacted with gambling to intensify the IPV. Major implications. Reducing gambling-related IPV against women requires integrated, multi-level interventions that reduce both problem gambling and gendered drivers of violence. Gambling operators can act to reduce problem gambling and train staff in responding to IPV. Financial institutions can assist people to limit their gambling expenditure and families to protect their assets. Service providers can be alert to the co-occurrence of gambling problems and IPV and screen, treat, and refer clients appropriately. Public education can raise awareness that problem gambling increases the risk of IPV. Reducing gender inequality is also critical.


Effects of rumen-protected methionine and other essential amino acid supplementation on milk and milk component yields in lactating Holstein cows.
Objectives of this study were to investigate the effects of supplementing rumen-protected methionine (RP-Met), threonine (RP-Thr), isoleucine (RP-Ile), and leucine (RP-Leu) individually or jointly to a low-protein diet, on the performance of lactating dairy cows, as well as to determine the effects of these amino acids (AA) on the mammalian target of rapamycin (mTOR) in vivo. Ten lactating Holstein cows were randomly allocated to a repeated 5 × 5 Latin square experiment with five 19-d periods. Treatments were high-protein diet (16% crude protein, positive control; HP), low-protein diet (12% crude protein, negative control; LP), LP plus RP-Met (LPM), LP plus RP-Met and RP-Thr (LPMT), and LP plus RP-Met, RP-Thr, RP-Ile, and RP-Leu (LPMTIL). The dry matter intakes (DMI) of the LP, LPM, and LPMT diets were lower than that of the HP diet, whereas the DMI of the LPMTIL diet was intermediate between the HP diet and the other LP diets. Supplementing RP-Met to the LP diet increased the yields of milk and milk protein, increased the content of milk urea N, and tended to increase milk N efficiency. Co-supplementation of RP-Thr with RP-Met resulted in no further milk production increase. Co-supplementation of all 4 rumen-protected amino acids (RP-AA) increased milk and lactose yields to the level of the HP diet and tended to increase milk protein yield compared with the LPMT diet. We found no significant differences in the contents and yields of milk components between the LPMTIL and HP diets except for a lower milk urea N content in the LPMTIL diet. Venous concentrations of the measured AA were similar across the LP and LP diets supplemented with RP-AA. Relative to levels of the HP diet, LP diets had higher venous concentrations of Met and Gly and tended to have higher Phe concentration and lower concentrations of Val and BCAA. The LPMTIL diet had higher venous concentrations of Arg, Lys, Met, Phe, and Glu, and a lower Val concentration. Phosphorylation status of the measured mTOR components in LPM and LPMT treatments were similar to those in the LP treatment but phosphorylation status of mTOR and eIF4E-binding protein 1 (4eBP1) in LPMTIL treatment were higher. The phosphorylation rates of eukaryotic elongation factor 2 (eEF2) in the 4 LP and LP plus RP-AA diets were higher than that of the HP diet. Overall, results of the present study supported the concept that under the relatively short time of this experiment, supplementing RP-AA, which are believed to stimulate the mTOR signal pathway, can lead to increased milk protein yield. This increase appears to be due to increased DMI, greater mTOR signaling, and greater eEF2 activity.


Phenylalanine binding is linked to dimerization of the regulatory domain of phenylalanine hydroxylase.
Analytical ultracentrifugation has been used to analyze the oligomeric structure of the isolated regulatory domain of phenylalanine hydroxylase. The protein exhibits a monomer-dimer equilibrium with a dissociation constant of ~46 μM; this value is unaffected by the removal of the 24 N-terminal residues or by phosphorylation of Ser16. In contrast, phenylalanine binding (Kd = 8 μM) stabilizes the dimer. These results suggest that dimerization of the regulatory domain of phenylalanine hydroxylase is linked to allosteric activation of the enzyme.


EDHF, but not NO or prostaglandins, is critical to evoke a conducted dilation upon ACh in hamster arterioles.
Vasomotor reactions upon focal stimulation of arterioles have been shown to be conducted along the vascular wall. Such a conduction, which is assumed to reflect the spread of electrical signals, may contribute to coordination of responses within a vascular segment. We aimed to identify which endothelial autacoid(s) act as mediators of the local and conducted dilator responses, respectively. To this end, arterioles in the hamster cremaster microcirculation were locally stimulated with endothelium-dependent [acetylcholine (ACh)] or endothelium-independent dilators [sodium nitroprusside (SNP)], and the resulting changes in diameter were measured using a videomicroscopy technique at the site of application and up to 1.4 mm upstream at distant sites. Experiments were also performed after blockade of nitric oxide (NO) synthase, cyclooxygenase, P-450 monooxygenase, or K(+) channels. Dilations upon ACh (71 +/- 3%) were conducted rapidly (<1 s) to upstream sites (at 1.4 mm: 37 +/- 5%). Although the NO donor SNP induced a similar local dilation (71 +/- 7%), this response was not conducted. Maximal amplitudes of ACh-induced dilations were not attenuated after inhibition of NO synthase and cyclooxygenase at the local and remote sites. However, additional treatment with a P-450 monooxygenase blocker (sulfaphenazole) strongly attenuated the local response (from 62 +/- 9 to 17 +/- 5%) and abrogated dilations at distant sites (at 0.67 mm: from 23 +/- 4% to 4 +/- 3%). Likewise, 17-octadecynoic acid strongly attenuated local and remote responses. Blockers of Ca(2+)-dependent K(+) channels (charybdotoxin or iberiotoxin) attenuated dilations at the local and remote sites after focal application at the ACh stimulation site. In marked contrast, treatment of the upstream site with these blockers was without any effect. We conclude that upon local stimulation with ACh, a cytochrome P-450 monooxygenase product is generated that induces local dilation via the activation of Ca(2+)-dependent K(+) channels and initiates conduction of the dilation. In contrast to the local site, neither activation of these K(+) channels nor the synthesis of NO or prostaglandins is necessary to dilate the arterioles at remote, distant sites. This suggests that endothelium-derived hyperpolarizing factor serves as an important mediator to initiate conducted dilations and, by doing so, may act as a key player in the coordination of arteriolar behavior in the microcirculatory network.


Centrifuges and inertial shear forces.
Centrifuges are often used in biological studies for 1 x g control samples in space flight microgravity experiments as well as in ground based research. Using centrifugation as a tool to generate an Earth like acceleration introduces unwanted inertial shear forces to the sample. Depending on the centrifuge and the geometry of the experiment hardware used these shear forces may contribute as much as 99% to the total force acting on the cells or tissues. The inertial shear force artifact should be dealt with for future experiment hardware development for Shuttle and the International Space Station (ISS) as well as for the interpretation of previous spaceflight and on-ground research data.


Liver biopsy: ultrasonography guidance is not superior to the blind method.
The aim of this study was to evaluate our experience with adequate liver biopsy samples and compare the complication rates of blind and US-guided biopsies, as well as to compare the histological yield of blind and US-guided biopsy specimens. We retrospectively analyzed 205 consecutive patients that underwent liver biopsies during a 12-month period. Liver biopsy was performed via the blind method in 152 patients, and via US-guidance in 53 patients. Biopsy specimens were evaluated according to length, presence of fragmentation, crush artifacts, adequacy for diagnosis, and the number of portal tracts and central veins. We also evaluated the rates of mortality and major life-threatening complications. All the biopsy specimens were adequate for histological evaluation, except in 8 cases, of which 4 were in the blind biopsy group (2.63%) and 4 were in the US-guided biopsy group (7.54%) (P>0.05). There were no statistically significant differences between the two groups in terms of the specimen fragmentation, or number of portal tracts and central veins in each specimen. Mean specimen length in the US-guided liver biopsy group was 12.58+/-5.59 mm, and in the blind biopsy group 16.22+/-9.91 mm (P<0.005) . There was no mortality or major complications in either of the two study groups. US-guided biopsy was not superior to blind biopsy, an unexpected result. Gastroenterologists/hepatologists should be encouraged to perform liver biopsies via the blind method.