A Cross-sectional Survey of Health Professionals Across Australia and New Zealand to Determine What Outcome Measures Are Important From a Clinical Perspective Post Hand Burn Injury.
Outcome measures are used in healthcare to evaluate clinical practice, measure efficiencies and to determine the quality of health care provided. The Burns Trauma Rehabilitation: Allied Health Practice Guidelines advocates for the collection of outcome measures post burn injuries across different time points. These guidelines recommend multiple tools which can be utilized when measuring outcomes post burn injuries. The aim of this study was to gather information from specialist clinicians regarding their clinical practice and the outcome measurement tools used post hand burn injuries. This cross-sectional study used a survey design to collect data at one given point in time across a sample population. A total of 43 clinical specialists allied health professionals responded to the survey. Respondents indicated that their patients considered hand dexterity was the most important outcome. Three months post burn injury was the most common timepoint for measurement (n = 31, 72.1%) followed by six months (n = 27, 62.8%). Patient report of hand function (n = 42, 97.7%) and observation (n = 41, 95.3%) were the most frequently reported assessment methods. The Jamar Dynamometer (n = 40, 93%), goniometer (n = 39, 90.7%) and pinch gauge (n = 36, 83.7) were the most frequency cited assessment tools. The findings of this study suggest that clinical specialist allied health collect some outcome measures in their routine practice. Based on the respondent's perceptions of barriers when using outcome measures and lack of reliable/validated tools to measure hand burn outcomes, there is a need for further studies in this area.


Influence of Weak Base Addition to Hole-Collecting Buffer Layers in Polymer:Fullerene Solar Cells.
We report the effect of weak base addition to acidic polymer hole-collecting layers in normal-type polymer:fullerene solar cells. Varying amounts of the weak base aniline (AN) were added to solutions of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The acidity of the aniline-added PEDOT:PSS solutions gradually decreased from pH = 1.74 (AN = 0 mol% ) to pH = 4.24 (AN = 1.8 mol %). The electrical conductivity of the PEDOT:PSS-AN films did not change much with the pH value, while the ratio of conductivity between out-of-plane and in-plane directions was dependent on the pH of solutions. The highest power conversion efficiency (PCE) was obtained at pH = 2.52, even though all devices with the PEDOT:PSS-AN layers exhibited better PCE than those with the pristine PEDOT:PSS layers. Atomic force microscopy investigation revealed that the size of PEDOT:PSS domains became smaller as the pH increased. The stability test for 100 h illumination under one sun condition disclosed that the PCE decay was relatively slower for the devices with the PEDOT:PSS-AN layers than for those with pristine PEDOT:PSS layers.


Ion mobility spectrometry - Mass spectrometry coupling for synthetic polymers.
This review covers applications of ion mobility spectrometry (IMS) hyphenated to mass spectrometry (MS) in the field of synthetic polymers. MS has become an essential technique in polymer science, but increasingly complex samples produced to provide desirable macroscopic properties of high-performance materials often require separation of species prior to their mass analysis. Similar to liquid chromatography, the IMS dimension introduces shape selectivity but enables separation at a much faster rate (milliseconds vs minutes). As a post-ionization technique, IMS can be hyphenated to MS to perform a double separation dimension of gas-phase ions, first as a function on their mobility (determined by their charge state and collision cross section, CCS), then as a function of their m/z ratio. Implemented with a variety of ionization techniques, such coupling permits the spectral complexity to be reduced, to enhance the dynamic range of detection, or to achieve separation of isobaric ions prior to their activation in MS/MS experiments. Coupling IMS to MS also provides valuable information regarding the 3D structure of polymer ions in the gas phase and regarding how to address the question of how charges are distributed within the structure. Moreover, the ability of IMS to separate multiply charged species generated by electrospray ionization yields typical IMS-MS 2D maps that permit the conformational dynamics of synthetic polymer chains to be described as a function of their length.


Light-mediated spatial control via photolabile fluorescently quenched peptide cassettes.
Light-regulatable compounds are finding increasing utility as spatial and temporal probes of biological behavior. An independent measure of successful light-induced structural change is possible when alteration (e.g., activation, deactivation, etc.) of the bioprobe can be directly linked to a fluorescent readout. We have identified a series of photolabile fluorescently quenched cassettes that display extraordinarily large fluorescence enhancements upon photolysis. A pair of cassettes has been inserted into mitochondrial localization sequences to assess an organelle-targeted light-mediated release strategy for controlling biological activity. The peptide constructs are readily absorbed by mitochondria and subsequently can be cleaved in a light-dependent fashion as assessed by the predicted changes in absorbance and fluorescence.


A tiered procedure for assessing the formation of biotransformation products of pharmaceuticals and biocides during activated sludge treatment.
Upon partial degradation of polar organic micropollutants during activated sludge treatment, transformation products (TPs) may be formed that enter the aquatic environment in the treated effluent. However, TPs are rarely considered in prospective environmental risk assessments of wastewater-relevant compound classes such as pharmaceuticals and biocides. Here, we suggest and evaluate a tiered procedure, which includes a fast initial screening step based on high resolution tandem mass spectrometry (HR-MS/MS) and a subsequent confirmatory quantitative analysis, that should facilitate consideration of TPs formed during activated sludge treatment in the exposure assessment of micropollutants. At the first tier, potential biotransformation product structures of seven pharmaceuticals (atenolol, bezafibrate, ketoprofen, metoprolol, ranitidine, valsartan, and venlafaxine) and one biocide (carbendazim) were assembled using computer-based biotransformation pathway prediction and known human metabolites. These target structures were screened for in sludge-seeded batch reactors using HR-MS/MS. The 12 TPs found to form in the batch experiments were then searched for in the effluents of two full-scale, municipal wastewater treatment plants (WWTPs) to confirm the environmental representativeness of this first tier. At the second tier, experiments with the same sludge-seeded batch reactors were carried out to acquire kinetic data for major TPs that were then used as input parameters into a cascaded steady-state completely-stirred tank reactor (CSTR) model for predicting TP effluent concentrations. Predicted effluent concentrations of four parent compounds and their three major TPs were corroborated by comparison to 3-day average influent and secondary effluent mass flows from one municipal WWTP. CSTR model-predicted secondary effluent mass flows agreed within a factor of two with measured mass flows and confidence intervals of predicted and measured mass flows overlapped in all cases. The observed agreement suggests that the combination of batch-determined transformation kinetics with a simple WWTP model may be suitable for estimating aquatic exposure to TPs formed during activated sludge treatment. Overall, we recommend the tiered procedure as a realistic and cost-effective approach to include consideration of TPs of wastewater-relevant compounds into exposure assessment in the context of prospective chemical risk assessment.


Identifying and injecting myofascial trigger points.
Myofascial pain syndrome is characterized by the presence of discreet, hypersensitive nodules known as trigger points. A myofascial trigger point is a hyperirritable locus within a taut band of skeletal muscle, located in the muscle and/or fascia (1). They are palpable within muscles as cord-like bands within a sharply circumscribed area of extreme tenderness. Trigger points are found most commonly in muscles involved in postural support.


Paleo-ENSO influence on African environments and early modern humans.
In this study, we synthesize terrestrial and marine proxy records, spanning the past 620 ky, to decipher pan-African climate variability and its drivers and potential linkages to hominin evolution. We find a tight correlation between moisture availability across Africa to El Niño Southern Ocean oscillation (ENSO) variability, a manifestation of the Walker Circulation, that was most likely driven by changes in Earth's eccentricity. Our results demonstrate that low-latitude insolation was a prominent driver of pan-African climate change during the Middle to Late Pleistocene. We argue that these low-latitude climate processes governed the dispersion and evolution of vegetation as well as mammals in eastern and western Africa by increasing resource-rich and stable ecotonal settings thought to have been important to early modern humans.


Limited heat tolerance in a cold-adapted seabird: implications of a warming Arctic.
The Arctic is warming at approximately twice the global rate, with well-documented indirect effects on wildlife. However, few studies have examined the direct effects of warming temperatures on Arctic wildlife, leaving the importance of heat stress unclear. Here, we assessed the direct effects of increasing air temperatures on the physiology of thick-billed murres (Uria lomvia), an Arctic seabird with reported mortalities due to heat stress while nesting on sun-exposed cliffs. We used flow-through respirometry to measure the response of body temperature, resting metabolic rate, evaporative water loss and evaporative cooling efficiency (the ratio of evaporative heat loss to metabolic heat production) in murres while experimentally increasing air temperature. Murres had limited heat tolerance, exhibiting: (1) a low maximum body temperature (43.3°C); (2) a moderate increase in resting metabolic rate relative that within their thermoneutral zone (1.57 times); (3) a small increase in evaporative water loss rate relative that within their thermoneutral zone (1.26 times); and (4) a low maximum evaporative cooling efficiency (0.33). Moreover, evaporative cooling efficiency decreased with increasing air temperature, suggesting murres were producing heat at a faster rate than they were dissipating it. Larger murres also had a higher rate of increase in resting metabolic rate and a lower rate of increase in evaporative water loss than smaller murres; therefore, evaporative cooling efficiency declined with increasing body mass. As a cold-adapted bird, murres' limited heat tolerance likely explains their mortality on warm days. Direct effects of overheating on Arctic wildlife may be an important but under-reported impact of climate change.


Dialkyl phosphates determination by gas chromatography: Evaluation of a microwave-assisted derivatization†.
Dialkyl phosphates are organophosphate insecticide metabolites and their urinary analysis is useful for assessing human exposure to these compounds. This study presents a sample preparation method with microwave-assisted derivatization for two dialkyl phosphates to make the process faster before gas chromatographic analysis. The optimized conditions for derivatization procedure were: 250 μL of 2,3,4,5,6-pentafluorobenzyl bromide 3% in acetonitrile for derivative; microwave for 5 min with intensity of 160 W. The electron ionization mass spectrometric analysis was performed using a gas chromatography with mass spectrometry QP-2010 from the Shimadzu(®) equipped with RTx(®) -5MS capillary column. Ions were monitored at selected-ion monitoring mode at m/z 350 for diethyl thiophosphate and m/z 366 for diethyl dithiophosphate. The developed method was linear for both metabolites. The intra-assay precision was the values ranged between 1.1 and 9.1%, for diethyl thiophosphate, and between 4.06 and 6.9%, for diethyl dithiophosphate. The interassay precision showed relative standard deviation between 10.3 and 15.1%, for diethyl thiophosphate and between 4.9 and 11.9%, for diethyl dithiophosphate. The results obtained suggests that derivatization assisted by microwave, before gas chromatography with mass spectrometry analysis, can be applied to monitoring of exposure to organophosphates once is fast, sensible, and precise method to determinate dialkyl phosphates.


Use of bactec 460 TB system in the diagnosis of tuberculosis.
To evaluate, the efficacy of BACTEC 460 TB system for the diagnosis of tuberculosis in a tertiary care hospital in Mumbai, India. We compared 12,726 clinical specimens using BACTEC 460 TB system and conventional method for detection of Mycobacterium tuberculosis over a period of six years. The overall recovery rate was 39% by BACTEC technique and 29% using Lowenstein-Jensen (LJ) medium. An average detection time for B actec0 460 TB system was found to be 13.3 days and 15.3 days as against 31.2 days and 35.3 days by LJ method for respiratory and nonrespiratory specimens respectively. The average reporting time for drug susceptibility results ranged from 6-10 days for the BACTEC 460 TB system. The BACTEC system is a good system for level II laboratories, especially in the diagnosis of extrapulmonary and smear negative tuberculosis.


Evaluation of short axial blood flow pattern in thoracic descending aorta by use of tagging cine magnetic resonance.
The authors, for the first time, evaluated the short axial blood flow profile by using tagging cine magnetic resonance (MR). Cine MR was performed on 15 healthy volunteers aged 51.5 +/- 23.1 (SD) years. The transverse plane of the thoracic descending aorta was imaged at the middle level of the left ventricle. Two or four radial tags, whose thickness was 3 mm width each, were established to the short axial image of the descending aorta at 2 msec and 300 msec following the R wave of the subjects' QRS complex on the electrocardiogram. They observed the flow patterns and measured the rotating flow velocity of the thoracic descending aorta in early systole and late systole from the following formula: v = d/t, (v = velocity, d = displacement of tags over the interval, t = time interval between the time of presaturation and the time of imaging). In the short axial image of the descending aorta, 13 subjects showed the clockwise rotation of tags in the supine position from the foot side view. Flow image of the other 2 subjects showed as undefined. Rotating flow velocity was 1.63 +/- 0.88 cm/sec in early systole and was 1.37 +/- 1.11 cm/sec in late systole. Tagging cine MR is useful to evaluate the blood flow profile in the thoracic descending aorta.


Biotransformation of magnetic nanoparticles as a function of coating in a rat model.
Long-term in vivo studies in murine models have shown that DMSA-coated nanoparticles accumulate in spleen, liver and lung tissues during extended periods of time (at least up to 3 months) without any significant signs of toxicity detected. During that time, nanoparticles undergo a process of biotransformation either by reducing the size or the particle aggregation or both. Using a rat model, we have evaluated the transformations of magnetic nanoparticles injected at low doses. Particles with two different coatings, dimercaptosuccinic acid (NP-DMSA) and polyethylene glycol (NP-PEG-(NH2)2) have been administered to animals, to evaluate the role of coating in the degradation of the particles. We have found that low doses of magnetic nanoparticles are quickly metabolized by the animals. In fact, using a nanoparticle dose four times lower than in previous experiments, NP-DMSA were not observed 24 h after the administration either in the liver or in the lungs. Interestingly, an increased amount of ferritin, the iron storage protein, was observed in liver tissues from rats that were treated with the low dose of NP-DMSA in comparison with the control ones, suggesting a rapid metabolization of the particles into ferritin iron. On the other side we have found that, NP-PEG-(NH2)2 are still detectable in several organs 24 h after their administration at low doses. Probably, due to the longer circulation times of the NP-PEG-(NH2)2, there is a delay in the arrival of the particles to the tissue and this is the reason why we are able to see the particles 24 h post-administration. PEG coating could also be protecting the nanoparticles from rapid degradation of the reticuloendothelial system. Knowledge on the biodistribution, circulation time and degradation processes is required to gain a better understanding of the safety evaluation of this kind of nanomaterial for biomedical applications.


Measuring progressive soft tissue change with nasoalveolar molding using a three-dimensional system.
For craniofacial orthodontics and surgery to progress, accurate temporal evaluation of soft tissue and skeletal change with treatment is necessary. Evolution in three-dimensional imaging eliminates certain inherent challenges in making such measurements in infants with facial clefts. The aim of this pilot study was to measure progressive three-dimensional changes in nasal form in a series of infants with facial clefts during the course of presurgical nasoalveolar molding. In 5 infants with unrepaired cleft lip and palate, three-dimensional photographs were obtained using the 3dMD system (3dMD, Inc, Atlanta, GA) at 2-week intervals during nasoalveolar molding treatment. Using the 3dMD Vultus software, temporal soft tissue changes were evaluated quantitatively based on three-dimensional linear measurements of 3 landmarks in the nasal area and qualitative changes in the surface shell. Increase in columellar length on the cleft side and decrease of the nostril floor on the noncleft side were observed in all subjects. Progressive changes were observed most significantly in week 4 (T3) into treatment. This pilot study describes an approach using the 3dMD photo system with Vultus software for measuring the progressive change in the nasal soft tissues. The 3dMD system was believed to be valuable for facial analysis in this setting.


Detailed analysis of the association between urate deposition and bone erosion in gout: a dual-energy computed tomography study.
This study aimed to analyze the effect of urate deposition (UD) on bone erosion and examine the association between the volume of monosodium urate (MSU) crystals and an improved bone erosion score method, as measured in the metatarsophalangeal (MTP) joints of patients with gout. Fifty-six patients diagnosed with gout using the 2015 European League Against Rheumatism and American College of Rheumatology criteria were enrolled. MSU crystals volume at each MTP joint was measured using dual-energy computed tomography (DECT) images. The degree of bone erosion was evaluated with the modified Sharp/van der Heijde (SvdH) erosion scoring system based on CT images. Differences in clinical features between patients with (UD group) and without (non-UD group) UD were assessed, and the correlation between erosion scores and urate crystal volume was analyzed. The UD and non-UD groups comprised 30 and 26 patients, respectively. Among the 560 MTP joints assessed, 80 showed MSU crystal deposition, and 108 showed bone erosion. Bone erosion occurred in both groups but was significantly less severe in the non-UD group (p <0.001). Both groups had equivalent levels of serum uric acid (p=0.200). Symptom duration was significantly longer in the UD group (p=0.009). The UD group also had a higher rate of kidney stones (p=0.023). The volume of MSU crystals was strongly and positively associated with the degree of bone erosion (r=0.714, p <0.001). This study found that patients with UD show significant increased bone erosion than those without UD. The volume of MSU crystals is associated with the improved SvdH erosion score based on CT images, regardless of serum uric acid level, demonstrating the potential of combining DECT and serum uric acid measurements in helping optimize the management of patients with gout.


[Sweet's syndrome complicating isotretinoin therapy in acne].
We report a case of juvenile acne aggravated in the form of Sweet's syndrome by isotretinoin treatment. The late onset of ulcerative-hemorrhagic rectocolitis in this patient raised doubts about a possible relationship between Sweet's syndrome, acne and inflammatory colitis. A 19 year-old male patient with no disease history of note was treated for juvenile polymorphous acne resistant to standard topical acne treatment using isotretinoin (Roaccutane) at a dose of 0.5 mg/kg/d. After one week of treatment, the patient presented a fever of 38.5 degrees C, joint pain and congestive, erythematous-edematous, maculopapular plaques in ring-like layout subsequently becoming pustular and necrotic. These lesions occurred on the face, neck and pinna of the ear. Some nodules were also noted on the lower limbs. Biological tests and histology examination of a skin biopsy were evocative of Sweet's syndrome. The outcome was rapidly favorable following discontinuation of isotretinoin and institution of systemic corticosteroids (0.5 mg/kg/d). Two years later, ulcerative-hemorrhagic rectocolitis was diagnosed with episodes of bloody diarrhea. Treatment of acne with isotretinoin can occasionally induce inflammatory episodes of acne. To date there have been no reported cases of isotretinoin-induced Sweet's syndrome. The subsequent onset of ulcerative-hemorrhagic rectocolitis provides an indication of the complexity of the pathogenic mechanisms involved.


[Tailgut cyst. Rare differential diagnosis of retrorectal tumors].
Tumors of the retrorectal space are rare entities. The case report of a retrorectal tailgut cyst serves to illustrate the clinical and diagnostic findings, differential diagnosis, and therapy of retrorectal tumors. Tumors in this area can be identified by palpation. The subsequent investigations include ultrasound, endosonography, endoscopy, and by choice computed tomography or magnetic resonance imaging. Usually tailgut cysts are characterized as cystic tumors, well delineated with multicystic formation. The diagnosis has to differentiate between carcinomas of the colorectum, hamartomas, lymphomas, teratomas, chordomas, abscess formation, dermoid cysts, epidermoid cysts, and enteral cysts. An elevated level of CEA may point to malignancy. Complete surgical resection is the therapy of choice.


RIA for serum holo-transcobalamin: method evaluation in the clinical laboratory and reference interval.
Decreased serum holo-transcobalamin (holoTC) could be the earliest marker of cobalamin (Cbl) deficiency, but there has been no method suitable for routine use. We evaluated a new commercial holoTC RIA, determined reference values, and assessed holoTC concentrations in relation to other biochemical markers of Cbl deficiency. The reference population consisted of 303 individuals 22-88 years of age, without disease or medication affecting Cbl or homocysteine metabolism. In elderly individuals (>or=65 years), normal Cbl status was further confirmed by total homocysteine (tHcy; <19 micro mol/L) and methylmalonic acid (MMA; <0.28 micro mol/L) concentrations within established reference intervals. HoloTC in Cbl deficiency was studied in a population of 107 elderly individuals with normal renal function. The Cbl deficiency was graded as potential (total Cbl <or=150 pmol/L or tHcy >or=19 micro mol/L), possible (total Cbl <or=150 pmol/L and either tHcy >or=19 micro mol/L or MMA >or=0.45 micro mol/L), and probable (tHcy >or=19 micro mol/L and MMA >or=0.45 micro mol/L). The intra- and between-assay imprecision (CV) for the holoTC RIA were 4-7% and 6-8%, respectively. A 95% central reference interval for serum holoTC was 37-171 pmol/L. All participants (n = 16) with probable Cbl deficiency, 86% of those with possible, and 30% of those with potential Cbl deficiency had holoTC below the reference limit (<37 pmol/L). The holoTC correlated with total Cbl (r(s) = 0.80; P <0.0001) and inversely with MMA (r(s) = -0.52; P <0.0001). HoloTC concentrations were significantly (P = 0.01) higher in women than in men. The new holoTC RIA is precise and simple to perform. Low holoTC is found in individuals with biochemical signs of Cbl deficiency, but the sensitivity and specificity of low holoTC in diagnosis of Cbl deficiency need to be further evaluated.


Cardiorespiratory interactions during periodic breathing in awake chronic heart failure patients.
We applied spectral techniques to the analysis of cardiorespiratory signals [instantaneous lung volume (ILV), instantaneous tidal volume (ITV), arterial O(2) saturation (Sa(O(2))) at the ear, heart rate (HR), systolic (SAP), and diastolic (DAP) arterial pressure] during nonapneic periodic breathing (PB) in 29 awake chronic heart failure (CHF) patients and estimated the timing relationships between respiratory and slow cardiovascular (<0.04 Hz) oscillations. Our aim was 1) to elucidate major mechanisms involved in cardiorespiratory interactions during PB and 2) to test the hypothesis of a central vasomotor origin of PB. All cardiovascular signals were characterized by a dominant (>/=84% of total power) oscillation at the frequency of PB (mean +/- SE: 0.022 +/- 0.0008 Hz), highly coherent (>/=0.89), and delayed with respect to ITV (ITV-HR, 2.4 +/- 0.72 s; ITV-SAP, 6.7 +/- 0.65 s; ITV-DAP, 3.2 +/- 0.61 s; P < 0.01). Sa(O(2)) was highly coherent with (coherence function = 0.96 +/- 0. 009) and almost opposite in phase to ITV. These findings demonstrate the existence of a generalized cardiorespiratory rhythm led by the ventilatory oscillation and suggest that 1) the cyclic increase in inspiratory drive and cardiopulmonary reflexes and 2) mechanical effects of PB-induced changes in intrathoracic pressure are the more likely sources of the HR and blood pressure oscillations, respectively. The timing relationship between ITV and blood pressure signals excludes the possibility that PB represents the effect of a central vasomotor rhythm.


Fluorescent Aptasensor for Highly Specific Detection of ATP Using a Newly Screened Aptamer.
Owing to the significant roles of adenosine triphosphate (ATP) in diverse biological processes, ATP level is used to research and evaluate the physiological processes of organisms. Aptamer-based biosensors have been widely reported to achieve this purpose, which are superior in their flexible biosensing mechanism, with a high sensitivity and good biocompatibility; however, the aptamers currently used for ATP detection have a poor ability to discriminate ATP from adenosine diphosphate (ADP) and adenosine monophosphate (AMP). Herein, an ATP-specific aptamer was screened and applied to construct a fluorescent aptasensor for ATP by using graphene oxide (GO) and strand displacement amplification (SDA). The fluorescence intensity of the sensor is linearly related to the concentration of ATP within 0.1 μM to 25 μM under optimal experimental conditions, and the detection limit is 33.85 nM. The biosensor exhibits a satisfactory specificity for ATP. Moreover, the experimental results indicate that the biosensor can be applied to determine the ATP in human serum. In conclusion, the screened aptamer and the biosensor have promising applications in the determination of the real energy charge level and ATP content in a complex biological system.


Books for free? How can this be? - A PubMed resource you may be overlooking.
The NCBI (National Center for Biotechnology Information) at the National Institutes of Health collects a wide range of molecular biological data, and develops tools and databases to analyse and disseminate this information. Many life scientists are familiar with the website maintained by the NCBI (http://www.ncbi.nlm.nih.gov), because they use it to search GenBank for homologues of their genes of interest or to search the PubMed database for scientific literature of interest. There is also a database called the Bookshelf that includes searchable popular life science textbooks, medical and research reference books and NCBI reference materials. The Bookshelf can be useful for researchers and educators to find basic biological information. This article includes a representative list of the resources currently available on the Bookshelf, as well as instructions on how to access the information in these resources.


Ion-channel modulators: more diversity than previously thought.
Ion-channel function can be modified in various ways. For example, numerous studies have shown that currents through voltage-gated ion channels are affected by pore block or modification of voltage dependence of activation/inactivation. Recent experiments performed on various ion channels show that allosteric modulation is an important mechanism for affecting channel function. For instance, in K(Ca)2 (formerly SK) channels, the prototypic "blocker" apamin prevents conduction by an allosteric mechanism, while TRPV1 channels are prevented from closing by a tarantula toxin, DkTx, through an interaction with residues located away from the selectivity filter. The recent evidence, therefore, suggests that in several ion channels, the region around the outer mouth of the pore is rich in binding sites and could be exploited therapeutically. These discoveries also suggest that the pharmacological vocabulary should be adapted to define these various actions.


Positive and negative appraisals of the consequences of activated states uniquely relate to symptoms of hypomania and depression.
Individuals may appraise internal states positively or negatively. Positive appraisals involve desiring or pursuing the state or experience, while negative appraisals involve dreading or avoiding the experience. The extent to which individuals make extreme positive or negative appraisals of high, activated, energetic states might determine whether they experience symptoms of high or low mood. This study extends the existing literature by considering the role of opposing appraisals and beliefs about the same internal states and by controlling for the potential correlation between depression and activation symptoms. Extreme, positive and negative appraisals of activated mood states related distinctly to experiences of activation and depression symptoms respectively, in an analogue sample (n=323). Positive appraisals of activated internal states were uniquely associated with elevated activation and hypomania symptoms. Negative appraisals of the same states were uniquely associated with elevated depression symptoms. Opposing appraisals of internal states may underlie mood swing symptoms.


Daptomycin-reversible rifampicin resistance in vancomycin-resistant Enterococcus faecium.
In a previous study, we observed marked synergy between daptomycin and rifampicin against 73% of rifampicin-resistant, vancomycin-resistant Enterococcus faecium (VRE), with approximately 100-fold reductions in rifampicin MICs observed at one-eighth to one-fourth daptomycin MIC. The purpose of this study was to determine whether the synergy between daptomycin and rifampicin could be explained by enhanced entry of rifampicin into the cell or was related to amino acid substitutions in the rifampicin-binding site in the beta subunit (rpo beta) of the RNA polymerase. We developed a bioassay for rifampicin to measure cell-bound rifampicin levels as well as metabolic inactivation of rifampicin. In addition, we sequenced the rifampicin-binding site in the rpo beta of VRE strains with and without synergy between daptomycin and rifampicin. Cell-bound rifampicin levels were the same in rifampicin-susceptible VRE as in rifampicin-resistant VRE showing daptomycin synergy and were not affected by the presence of daptomycin. In contrast, rifampicin-resistant VRE without daptomycin synergy had undetectable cell-bound rifampicin. Sequencing the rpo beta rifampicin-binding site revealed that the synergistic strains had the same sequence as rifampicin-susceptible wild-type E. faecium. The daptomycin synergy-resistant strains all had mutations in known rifampicin-binding sites. Daptomycin is able to reverse rifampicin resistance in some strains of VRE, but the mechanism could not be explained by an effect of daptomycin on entry of rifampicin into or transport out of the cell, by inactivation of rifampicin or by mutation involving the rifampicin-binding site.


Detection of trace mercury ions in water with a bovine-serum-albumin-modified Au@SiNWA surface-enhanced-Raman-scattering sensor.
Accurate detection of mercury ions (Hg2+) in water is of great importance for environmental protection. Here, a surface-enhanced Raman scattering (SERS) sensor using bovine-serum-albumin-modified gold-silicon nanowire arrays (Au@SiNWAs) is used to detect the ions. The SiNWAs were grown via chemical etching; the addition of modified gold particles on the surface formed Au@SiNWAs to increase the surface activity. The Raman enhancement factor was as large as ∼2.52 × 105, which was also confirmed with finite-difference time-domain simulations. The detection limit for Hg2+ ions in water was as low as ∼10-12 M, which is much lower than that stipulated by the United States Environmental Protection Agency's maximum residue requirements for drinking water. Furthermore, the SERS intensity was linear with the log of the Hg2+ concentration between 1 pM and 100 nM, with a correlation coefficient of 0.992. There was no significant interference when other metal ions were present, which shows the excellent selectivity of the SERS sensor. Unknown Hg2+ concentrations in water can be readily determined in an accurate and reliable manner, with a relative standard deviation of ∼9.21%.


NAFLD Preclinical Models: More than a Handful, Less of a Concern?
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases ranging from simple steatosis to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and/or hepatocellular carcinoma. Due to its increasing prevalence, NAFLD is currently a major public health concern. Although a wide variety of preclinical models have contributed to better understanding the pathophysiology of NAFLD, it is not always obvious which model is best suitable for addressing a specific research question. This review provides insights into currently existing models, mainly focusing on murine models, which is of great importance to aid in the identification of novel therapeutic options for human NAFLD.


Inhibition of Growth and Aflatoxin Production of Aspergilli in Medium Containing Phosphates.
Mycelial growth and mycotoxin production of Aspergillus flavus and A. parasiticus were studied in Sabouraud dextrose agar containing pure or blended pyro-, poly- or meta-phosphates during 9 d of incubation at 30°C. Pure tetrasodium pyrophosphate (TSPP) and sodium polyphosphate, glassy (SPG, formerly hexametaphosphate), as well as a commercial phosphate blend and three combinations all containing various proportions of sodium acid pyrophosphate (SAPP), TSPP and SPG were tested. Inhibition of growth of aspergilli was observed in media containing 2.0% TSPP and 1.0 and 2.0% SPG and 2.0% of the commercial phosphate blend. Lower concentrations of single or blended phosphates allowed only limited, atypical mycelial growth. Sporulation was totally inhibited by 2.0% concentrations of single or blended phosphates, and so was production of aflatoxins B1 and G1. TSPP or SPG at 1.0% reduced (P<0.05) aflatoxin production from parts per million (controls) to parts per billion.


Differential in vitro cellular response induced by exposure to synthetic vitreous fibers (SVFs) and asbestos crocidolite fibers.
In this study, we analyzed the effects of synthetic vitreous fibers (SVFs) on a mesothelial (MeT5A) and a fibroblast cell line (NIH3T3), compared to those exerted by crocidolite asbestos fibers. SVFs (glass wool, rock wools) do not induce significant changes in cell mortality, whereas crocidolite asbestos fibers caused a dose-dependent cytotoxicity. We investigated the correlation between the fiber-induced cytotoxicity and the extent and type of interaction of the fibers with the cell surface, and we observed that SVFs, unlike crocidolite asbestos fibers, establish few and weak interactions. Moreover, after internalization, crocidolite asbestos fibers are often found free in the cytoplasm, whereas glass wool fibers are mainly localized inside cytoplasmic vacuoles. After treatments, we also detected signs of oxidative stress, revealed by an increased reactive oxygen species (ROS) production and by an induction of superoxide dismutase (SOD) activity. The lipoperoxidative damage was characterized by a decrease in polyunsaturated fatty acids (PUFA), an increase in the content of thiobarbituric reactive species (TBARS) and a consumption of vitamin E, as a lipophilic antioxidant. Furthermore, we investigated the effect of fiber exposure on cell proliferation. and it was found that, unlike crocidolite asbestos fibers, SVFs did not induce a significant increase in DNA synthesis.


Heterogeneous nucleation and growth of the β(Ti) phase in the Ti-Al system-experiments and model calculations.
The barrier to heterogeneous nucleation of the β(Ti) phase on TiB(2) and other borides has been evaluated using the plane to plane matching model. The results are compared to the known nucleation of the α(Ti) phase on the β(Ti) phase. According to this comparison, the barrier to heterogeneous nucleation of the β(Ti) phase on TiB(2) can be judged to be small. This is in agreement with inoculation experiments. The addition of a Ti-Al-TiB(2) master composite to a β(Ti) solidifying TiAl based alloy leads to a significantly refined microstructure. Microsegregations enable us to attribute this refinement to refined equiaxed β(Ti) dendrites. However, model calculations based on the hemispherical cap model predict that the refinement via heterogeneous β(Ti) nucleation should be more potent. First calculations indicate that structural imperfections of TiB(2) particles limit the nucleation site diameter. Thereby, the nucleation barrier is increased and the refinement is less pronounced.


Psychometric evaluation of the leg activity measure (LegA) for outcome measurement in people with brain injury and spasticity.
The aim of this study is to evaluate the properties of the Leg Activity measure according to COnsensus-based Standards for the selection of health Measurement INstruments. Participants were assessed at baseline, one day, 6 weeks and 12 weeks, following treatment for leg spasticity with botulinum toxin and physical interventions. In stage 1, 64 participants were recruited to evaluate the initial psychometric properties of Leg Activity measure. In stage 2, 100 additional participants were recruited, to evaluate the scaling properties. Total sample of 164 participants was used. Construct validity was supported for "passive function", "active function" and "impact on quality of life". Cronbach's alpha was 0.86, 0.97 and 0.87 respectively for the scales. Item level test-retest agreement ranged from 91-97% (Kappa 0.75-0.95). Following treatment for spasticity (n = 64), the Leg Activity measure "passive function" and "impact on life" scales were responsive to change. Principal components analysis confirmed the constructs and a unidimensional Rasch Partial Credit Model was subsequently established for each scale. Transformation to an interval scale was achieved. Using the ordinal-to-interval conversion tables, parametric statistical analysis may be used. The study provides support for the Leg Activity measure being valid, reliable and responsive.Implications for rehabilitationThe Leg Activity measure is the only published self-report measure in the current literature that addresses passive and active function as well as impact on quality of life, of the paretic leg in a comprehensive manner.The initial evaluation of Leg Activity measure psychometric properties, in relation to the COnsensus-based Standards for the selection of health Measurement INstruments checklist and Medical Outcomes Trust Quality Criteria, supports its measurement properties for clinical and research use.The Leg Activity measure as a valid, reliable and responsive tool for the evaluation of treatment in leg spasticity including condition specific (spasticity) quality-of-life.


Autoimmune Gastritis.
Autoimmune gastritis (AG) is a corpus-restricted chronic atrophic gastritis associated with intrinsic factor deficiency, either with or without pernicious anemia. Autoimmune gastritis is a microscopic disease because patients present with no or vague symptoms, and clinicians rarely find endoscopic changes. Autoimmune gastritis only becomes a clinical disease when pathologists diagnose it in gastric biopsies performed for a variety of clinical indications. Unfamiliarity with this disease can result in misdiagnosis of patients, and thus inadequate patient management. To review the pathogenesis, clinical features, diagnostic criteria, differential diagnoses, sequelae, and surveillance recommendations for AG. The sources of the study include a review of the pertinent literature for AG. Autoimmune gastritis is an important disease characterized by a loss of oxyntic mucosa and presence of metaplastic epithelium and enterochromaffin-like cell hyperplasia. Awareness and proper diagnosis are critical to prevent mismanagement of patients.


[Analysis on the development strategy for hearing aid fitting].
Based on the investigation and analysis of the current situation for hearing aid fitting, some analysis results and suggestions for the development of the industry are presented, including manufacturer, association for medical devices industry and supervision division.


Exogenous Bioactive Peptides Have a Potential Therapeutic Role in Delaying Aging in Rodent Models.
In recent years, some exogenous bioactive peptides have been shown to have promising anti-aging effects. These exogenous peptides may have a mechanism similar to endogenous peptides, and some can even regulate the release of endogenous active peptides and play a synergistic role with endogenous active peptides. Most aging studies use rodents that are easy to maintain in the laboratory and have relatively homogenous genotypes. Moreover, many of the anti-aging studies using bioactive peptides in rodent models only focus on the activity of single endogenous or exogenous active peptides, while the regulatory effects of exogenous active peptides on endogenous active peptides remain largely under-investigated. Furthermore, the anti-aging activity studies only focus on the effects of these bioactive peptides in individual organs or systems. However, the pathological changes of one organ can usually lead to multi-organ complications. Some anti-aging bioactive peptides could be used for rescuing the multi-organ damage associated with aging. In this paper, we review recent reports on the anti-aging effects of bioactive peptides in rodents and summarize the mechanism of action for these peptides, as well as discuss the regulation of exogenous active peptides on endogenous active peptides.


Is Mild Cognitive Impairment a Precursor of Alzheimer's Disease? Short Review.
Mild Cognitive Impairment (MCI) may be a precursor of Alzheimer's disease (AD). There is a boundary area between normal aging and dementia. In practice, the term "age related cognitive decline" has been used interchangeably with "normal aging". Alternatively, the term "aging associated cognitive decline" was introduced and defined by a performance on a standardized cognitive scale focused on learning and memory, attention and cognitive speed, language, or visuoconstructional abilities. The term "mild cognitive impairment" was adopted by Petersen in 2004 to describe a period in the course of neurodegenerative disease where cognition is no longer normal relative to age expectations, however, daily functions are not sufficiently disrupted to correlate with the diagnosis of dementia. Most of the literature refers to the amnestic form of MCI, which is likely a precursor of AD. The rate of conversion from amnestic form of MCI to AD is estimated to reach 10-15% per year. That is why MCI generated a great deal of research. When considering MCI a precursor of AD, it seems reasonable to study AD genetic markers in the MCI patients. In AD, association studies focus on genetic polymorphisms assumed to have an effect on the expression and modulation function of genes associated with AD pathogenesis (ApoE, APP, presenilin 1, presenilin 2, tau protein), and on polymorphisms related to metabolism of the aforementioned proteins (splicing, degradation). Neuropsychological assesment plays a substantial role in the diagnosis of MCI, especially in the case of identification of different MCI subtypes or typical profiles of cognitive performance in prodromal phases of neurodegenerative diseases. The optimal composition of diet may increase an average age and prevent impairment of cognitive functions at the same time. Despite the progress in early diagnosis of MCI and dementia, further research is needed on differential diagnosis and treatment. In amnestic subtype of MCI some genetic markers may already be present, predicting possible future development of AD. Pointing to the need of secondary prevention, lifestyle modifications and possible early treatment could be implemented.


Vectorial loading of processive motor proteins: implementing a landscape picture.
Individual processive molecular motors, of which conventional kinesin is the most studied quantitatively, move along polar molecular tracks and, by exerting a force F = (F(x),F(y),F(z)) on a tether, drag cellular cargoes, in vivo, or spherical beads, in vitro, taking up to hundreds of nanometre-scale steps. From observations of velocities and the dispersion of displacements with time, under measured forces and controlled fuel supply (typically ATP), one may hope to obtain insight into the molecular motions undergone in the individual steps. In the simplest situation, the load force F may be regarded as a scalar resisting force, F(x)<0, acting parallel to the track: however, experiments, originally by Gittes et al (1996 Biophys. J. 70 418), have imposed perpendicular (or vertical) loads, F(z)>0, while more recently Block and co-workers (2002 Biophys. J. 83 491, 2003 Proc. Natl Acad. Sci. USA 100 2351) and Carter and Cross (2005 Nature 435 308) have studied assisting (or reverse) loads, F(x)>0, and also sideways (or transverse) loads [Formula: see text]. We extend previous mechanochemical kinetic models by explicitly implementing a free-energy landscape picture in order to allow for the full vectorial nature of the force F transmitted by the tether. The load-dependence of the various forward and reverse transition rates is embodied in load distribution vectors, [Formula: see text] and [Formula: see text], which relate to substeps of the motor, and in next order, in compliance matrices [Formula: see text] and [Formula: see text]. The approach is applied specifically to discuss the experiments of Howard and co-workers (1996 Biophys. J. 70 418) in which the buckling of partially clamped microtubules was measured under the action of bound kinesin molecules which induced determined perpendicular loads. But in the normal single-bead assay it also proves imperative to allow for F(z)>0: the appropriate analysis for kinesin, suggesting that the motor 'crouches' on binding ATP prior to stepping, is sketched. It yields an expression for the velocity, V (F(x),F(z);[ATP]), needed to address the buckling experiments.


Retinoic acid inhibits junctional communication between animal cells.
Retinoic acid inhibits junctional communication between a variety of vertebrate cell types in culture. It reduces the intercellular transfer of 3H-nucleotides between Syrian hamster kidney fibroblasts (BHK 21/13), Chinese hamster lung fibroblasts (V79), rat liver epithelial cells (BRL), Swiss mouse embryo fibroblasts (3T3), rainbow trout gonadal fibroblasts (RTG2) and Xenopus embryo fibroblasts (Xen). It also reduces metabolic cooperation between hypoxanthine-guanine phosphoribosyl transferase deficient mutant and wild-type BHK cells. The inhibition is rapid (intercellular transfer of iontophoretically injected Lucifer Yellow CH between BRL cells is completely blocked after the cells have been exposed to 10(-4) M retinoic acid for 5 min), and is fully reversed when the drug is removed. Based on these results and the observation that the amount of gap junctional protein isolated from cells grown in the presence of retinoic acid for 1 h is the same and after 24 h is increased (1.3- to 3.1-fold) compared with the amount isolated from untreated cells, we suggest that the inhibitory effect is mediated by the reversible closure of junctional channels.


Plasticity of recurring spatiotemporal activity patterns in cortical networks.
How do neurons encode and store information for long periods of time? Recurring patterns of activity have been reported in various cortical structures and were suggested to play a role in information processing and memory. To study the potential role of bursts of action potentials in memory mechanisms, we investigated patterns of spontaneous multi-single-unit activity in dissociated rat cortical cultures in vitro. Spontaneous spikes were recorded from networks of approximately 50 000 neurons and glia cultured on a grid of 60 extracellular substrate- embedded electrodes (multi-electrode arrays). These networks expressed spontaneous culture- wide bursting from approximately one week in vitro. During bursts, a large portion of the active electrodes showed elevated levels of firing. Spatiotemporal activity patterns within spontaneous bursts were clustered using a correlation-based clustering algorithm, and the occurrences of these burst clusters were tracked over several hours. This analysis revealed spatiotemporally diverse bursts occurring in well-defined patterns, which remained stable for several hours. Activity evoked by strong local tetanic stimulation resulted in significant changes in the occurrences of spontaneous bursts belonging to different clusters, indicating that the dynamical flow of information in the neuronal network had been altered. The diversity of spatiotemporal structure and long-term stability of spontaneous bursts together with their plastic nature strongly suggests that such network patterns could be used as codes for information transfer and the expression of memories stored in cortical networks.


Synthetic Life and the Value of Life.
If humans eventually attain the ability to create new life forms, how will it affect the value of life? This is one of several questions that can be sources of concern when discussing synthetic life, but is the concern justified? In an attempt to answer this question, I have analyzed some possible reasons why an ability to create synthetic life would threaten the value of life in general (that is, not just of the synthetic creations), to see if they really give us reason to worry. The main conclusion is that it is unlikely that a future human ability to create life will really have a great negative impact on these characteristics of life. It therefore seems unlikely that the value of life will be negatively affected by the ability to create synthetic life, though it is possible that the properties in question will be less salient in the synthetic life and thus that the value of the synthetic life will be lower than that of existing life, which in turn can lead to a disturbing difference in value between different kinds of life.


Regulation of AMH and SCF expression in human granulosa cells by GnRH agonist and antagonist.
With the progress of cancer treatment, fertility preservation has become an urgent requisition. Gonadotropin-releasing hormone agonist (GnRH-a) and antagonist (GnRH-ant) have been used to protect fertility for these patients. However, studies showed that although GnRH-a and GnRH-ant had a comparable down-regulating effect on the pituitary, GnRH-ant could not preserve ovarian function. Moreover, GnRH-ant alone could deplete primordial follicles. It might be speculated that an additional intraovarian system existed except the pituitary system. Anti-Müerian hormone (AMH) and Stem cell factor (SCF) proved to be the key factors in follicle recruitment and development. The balance between AMH and SCF was tightly related to ovarian reserve. To investigate the intraovarian effect of GnRH-a or GnRH-ant on ovarian reserve, we examined AMH and SCF expression in human granulosa cells (hGCs). GCs were isolated from follicular aspirates after oocyte removal from the patients undergoing assisted reproduction techniques. After pretreated with GnRH-a (triptorelin) or GnRH-ant (cetrorelix) for 48 h, mRNA and protein of AMH and SCF were analyzed by Real-time PCR and Immunoblot assay respectively. The results indicated that AMH mRNA and protein expressions were down-regulated in the GnRH-ant groups, SCF mRNA and protein expressions were up-regulated in the high-dose GnRH-ant group. There was no difference of AMH and SCF expression in the GnRH-a group or GnRH-a + GnRH-ant group compared with control. These results suggested the effects of GnRH-a and GnRH-ant on the regulation of AMH and SCF were different, which may provide insight into the mechanism of GnRH-a and GnRH-ant interventions on ovarian reserve.


Nucleoli from two-cell embryos support the development of enucleolated germinal vesicle oocytes in the pig.
Recent research has shown that nucleoli of oocytes at the germinal vesicle (GV) stage (GV nucleoli) are not necessary for oocyte maturation but are essential for early embryonic development. Nucleoli of 2-cell embryos (2-cell nucleoli) have morphology similar to that of nucleoli in oocytes at the GV stage. In this study, we examined the ability of 2-cell nucleoli to substitute for GV nucleoli in terms of supporting early embryonic development by nucleolus aspiration (enucleolation) and transfer into metaphase II (MII) oocytes or 2-cell embryos that were derived from enucleolated oocytes at the GV stage in the pig. When 2-cell embryos were centrifuged to move the lipid droplets to one side of the blastomere, multiple nucleoli in the nucleus fused into a single nucleolus. The nucleoli were then aspirated from the 2-cell embryos by micromanipulation. The injection of 2-cell nucleoli to GV enucleolated oocytes at the MII stage rescued the embryos from the early embryonic arrest, and the resulting oocytes developed to blastocysts. However, the injection of 2-cell and GV nucleoli to 2-cell embryos derived from GV enucleolated oocytes rarely restored the development to blastocysts. These results indicate that 2-cell nucleoli support early embryonic development as GV nucleoli and that the presence of nucleoli is essential for pig embryos before the 2-cell stage.


School superintendents' perceptions of schools assisting students in obtaining public health insurance.
Superintendents' perceptions regarding the effect of health insurance status on academics, the role schools should play in the process of obtaining health insurance, and the benefits/barriers to assisting students in enrolling in health insurance were surveyed. Superintendents' basic knowledge of health insurance, the link between health and learning, and specific school system practices for assisting students were also examined. A 4-page questionnaire was sent to a national random sample of public school superintendents using a 4-wave postal mailing. Only 19% of school districts assessed the health insurance status of students. School districts' assistance in helping enroll students in health insurance was assessed using Stages of Change theory; 36% of superintendents' school districts were in the action or maintenance stages. The schools most often made health insurance materials available to parents (53%). The perceived benefits identified by more than 80% of superintendents were to keep students healthier, reduce the number of students with untreated health problems, reduce school absenteeism, and improvement of students' attention/concentration during school. The 2 most common perceived barriers identified by at least 50% of superintendents were not having enough staff or financial resources. Most superintendents believed schools should play a role in helping students obtain health insurance, but the specific role was unclear. Three fourths of superintendents indicated overwhelmingly positive beliefs regarding the effects of health insurance status on students' health and academic outcomes. School personnel and public policy makers can use the results to support collaboration in getting students enrolled in health insurance.


Does Population Aging Impact China's Economic Growth?
The rapid aging of the population presents great challenges in terms of China's social security expenditure and economic growth. This paper uses the entropy method to comprehensively measure the provincial population aging index in 2008-2019 and constructs an intermediary effect model with it as the core explanatory variable. The results show that the population aging has a significant positive impact on economic growth and on the promotion of the economic growth of more developed areas; it also has a positive impact on the endowment insurance expenditure and medical and health expenditure and on the promotion of economically backward areas. Endowment spending and health spending fully mediate the relationship between population aging and economic growth.


Synthesis and structure elucidation of triarylmethyl radicals with anthryl substitution.
Two stable triarylmethyl radicals with one or two anthryl substitutions are synthesized in gram scale, and are isolated in the crystalline state. Detailed structural elucidation with X-ray crystallographic analysis and DFT calculations revealed that the twisted structure is more energetically favorable than the folded structure, and consequently, the spin density is mainly localized at the methyl carbon. The spin distribution leads to unique physical properties, making them promising open-shell organic materials.


A conceptual model of second language pronunciation in communicative contexts: Implications for children's bilingual education.
Second language (L2) pronunciation patterns that differ from those of first language (L1) speakers can affect communication effectiveness. Research on children's L2 pronunciation in bilingual education that involves non-English languages is much needed for the field of language acquisition. Due to limited research in these specific populations and languages, researchers often need to refer to literature on L2 pronunciation in general. However, the multidisciplinary literature can be difficult to access. This paper draws on research from different disciplines to provide a brief but holistic overview of L2 pronunciation. A conceptual model of L2 pronunciation is developed to organize multidisciplinary literature, including interlocutors' interactions at three layers: the sociopsychological, acquisitional, and productive-perceptual layers. Narrative literature review method is used to identify themes and gaps in the field. It is suggested that challenges related to L2 pronunciation exist in communication. However, the interlocutors share communication responsibilities and can improve their communicative and cultural competencies. Research gaps are identified and indicate that more studies on child populations and non-English L2s are warranted to advance the field. Furthermore, we advocate for evidence-based education and training programs to improve linguistic and cultural competencies for both L1 speakers and L2 speakers to facilitate intercultural communication.


Observing the NICEties of hypertension management.
National Institute for Health and Clinical Excellence guidance for the clinical management of hypertension, published last year, proposes a step change in UK clinical practice.1 Although broadly helpful, there are some concerns about its implementation. Ambulatory blood pressure monitoring for diagnosis of hypertension, though logical, will place an additional financial burden on primary care at a time of austerity. Home blood pressure measurement may be a more practical option. Previous guidance recommended the used of thiazide diuretics as a first-line treatment option.2 Five years later, the new guidelines propose a major change, with an initial emphasis on the use of calcium channel blockers and angiotensin converting enzyme inhibitors/angiotensin receptor blockers, moving the use of thiazide-like diuretics to a third-line option. In addition, bendroflumethiazide, the mainstay of treatment in the UK over many years, has been replaced with chlortalidone, the starting doses of which are not readily available in this country. Cost-effectiveness analysis and a presumed risk of metabolic disorders has guided the rationale for these changes to the therapeutic algorithm, however this may not be robust. Importantly, unless there are special circumstances, reducing the blood pressure in hypertensive patients is more important than the means used to lower it. In future, it will be important to 'personalise' treatment more effectively and base management on lifetime risk.


Sanctification of Parenting, Moral Socialization, and Young Children's Conscience Development.
Religion is important to most U.S. families, but is often overlooked in research on children's development. This study examined parental religious beliefs about the sanctification of parenting, parental disciplinary strategies, and the development of young children's conscience in a sample of 58 two-parent families with a preschool child. Fathers were more punitive and used less induction when disciplining their children than did mothers. Maternal and paternal reports of the sanctification of parenting were positively related to positive socialization/praise and the use of induction. When mothers and fathers in the family were both using induction, children had higher scores on moral conduct. Parents' use of positive socialization combined with a belief in the sanctification of parenting predicted children's conscience development.


Number and size of motoneurons in a forelimb motor nucleus of normal and dystrophic (C57BL/6J dy2j/dy2j) mice.
The method of retrograde axonal transport of horseradish peroxidase (HRP) was used to identify the motoneurons that innervate the distal forelimb muscles via the ulnar nerve in normal and dystrophic (C56BL/6J dy2j/dy2j) mice. In both normal and dystrophic mice this motor nucleus was located in spinal segments C6 through T1. No clear division, on the basis of size, into alpha and gamma motoneuron populations was apparent. The motoneurons of dystrophic mice were fewer in number (26.5 vs. 35) but larger in cross-sectional area (780 vs. 674 microns2) than those of age-matched control mice. These results are quantitatively similar to those reported for the hind limb soleus muscle of dystrophic mice and suggest that the motoneuronal changes are a reflection of the dystrophic process rather than the associated spontaneous action potential generation seen in the dystrophic hind limb muscles.


Si-H···Se Chalcogen-Hydride Bond Quantified by Diffraction and Topological Analyses.
The Si-H···Se contact in 1-mesitylselanyl-8-(dimethylsilyl)naphthalene (1), which exhibits the spatial arrangement of a δ-agostic interaction from geometric considerations, was investigated. Is this just enforced by close 1,8-proximity or is this a favorable interaction? Charge density studies are best suited to investigate the exact origin of the interaction and to quantify the properties. Hence, they are most elucidating. High-resolution X-ray diffraction data of 1 were collected, and a multipole refinement followed by a topological analysis using Bader's quantum theory of atoms in molecules was employed. The resulting bond properties were set in relation to high-level computational parameters. The comparison to Si-H···[M] agostics, hydride bonding, chalcogen bonds, and charge-inverted hydrogen bonds qualified the Si-H···Se noncovalent interaction to be best classified as a chalcogen-hydride bond.


Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injury.
The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an increased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deficits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells.


Endomyocardial fibrosis in Sudan: clinical and echocardiographic features.
Endomyocardial fibrosis (EMF) is a rare disease and is often an underdiagnosed and forgotten cardiomyopathy. The objective of this study was to document the current frequency of EMF in Sudan by defining and selecting cases from patients attending the echocardiography laboratory. Additionally we aimed to create an EMF registry for Sudan. The study started in January 2007 and is on-going. All the patients attending our echocardiography clinics in four different hospitals in Khartoum, Sudan, were included. Transthoracic echocardiography was used as the main diagnostic and selection tool. The diagnosis of EMF was based on predefined criteria and definitions, and was further supported by additional clinical, ECG, laboratory and chest X-ray findings. Out of 4 332 cases studied, 23 (0.5%) were found to have features of EMF. Females constituted 52% and the age range was 24 to 67 years. All patients presented with dyspnoea grades III-IV. Advanced heart failure with gross fluid overload was seen in 54% of cases and ascites was seen in 30%. EMF was biventricular in 53%, left ventricular in 29% and right ventricular in 18% of cases. Apical and ventricular wall fibrosis was found in all cases, followed by atrial enlargement, atrioventricular valve incompetence, ventricular cavity obliteration, restrictive flow pattern and pericardial effusion. Additional echocardiographic features are defined and discussed. Although a rare disease, cases of EMF can be identified in Sudan if a high index of suspicion is observed. New echocardiographic features of ventricular wall layering, endocardial fibrous shelf and endomyocardiopericarial fibrosis were identified and are discussed.


Case for diagnosis. Atypical genital lesion.
We present a case of a penile lesion with a clinical appearance similar to Mondor penile disease (thrombosis of the dorsal vein of the penis) or penile sclerosing lymphangitis. Laboratory evaluation, however, showed a solid lesion, with no vascular component to Doppler ultrasonography and no treponema to immunohistochemistry. Histological and serological tests were compatible with secondary syphilis. The authors reinforce the need for the inclusion of syphilis in the differential diagnosis of penile cord injuries.


Interleukin-17A modulates retinal inflammation by regulating microglial activation via the p38 MAPK pathway in experimental glaucoma neuropathy.
As a prototypical member of the IL-17 family, interleukin-17A (IL-17A) has received increasing attentions for its potent proinflammatory role as well as potential to be a key therapeutic target in human autoimmune inflammatory diseases; however, its roles in other pathological scenarios like neuroinflammations are not fully elucidated yet but appear essentially correlating and promising. Glaucoma is the leading cause of irreversible blindness with complicated pathogenesis still to be understood, where neuroinflammation was reported to be critically involved in its both initiation and progression. Whether IL-17A takes part in the pathogenesis of glaucoma through interfering neuroinflammation due to its potent proinflammatory effect is still unknown. In the present study, we investigated the role of IL-17A in the pathological process of glaucoma neuropathy as well as its relationship with the predominant immune inflammation mediator microglia in retina, trying to elucidate the underlying mechanisms from the view of inflammation modulation. In our study, RNA sequencing was performed for the retinas of chronic ocular hypertension (COH) and control mice. Western blot, RT-PCR, immunofluorescence, and ELISA were used to evaluate the microglial activation and proinflammatory cytokines release at conditioned levels of IL-17A, along with assessment of optic nerve integrity including retinal ganglion cells (RGCs) counting, axonal neurofilament quantification, and flash visual-evoked potential (F-VEP) examination. And the possibly involved signaling pathways were screened out to go through further validation in scenarios with conditioned IL-17A. Subsequently, IL-17A was found to be significantly upregulated in COH retina. Furthermore, suppression of IL-17A effectively diminished the loss of RGCs, improved axonal quality, and F-VEP performance in COH mice. Mechanistically, IL-17A promoted microglial activation and proinflammatory cytokines release along with enhanced phenotypic conversion of activated microglia to M2-type in early stage and to M1-type in late stage in glaucomatous retinas. Microglia elimination decreased the proinflammatory factors secretion, enhanced the RGCs survival and axonal quality mediated by IL-17A. Furthermore, IL-17A-induced the overactivation of microglia in glaucomatous condition was alleviated after blocking the p38 MAPK pathway. Taken together, IL-17A is involved in the regulation of retinal immune response and RGCs cell death in experimental glaucoma by essentially promoting retinal microglial activation via p38 MAPK signaling pathway. IL-17A dynamically regulates the phenotypic conversion of retinal microglia in experimental glaucoma partly depending on the duration of elevated intraocular pressure. Suppression of IL-17A contributes to alleviate glaucoma neuropathy and exhibits promising potential as an innovative target for therapeutic strategy in glaucoma.


The extent and causes of malnutrition in children in the Tsolo district of Transkei.
A survey of children under 5 years old living in a rural Transkei village was carried out. It was found that 36% of the children were below the Boston third percentile (BTP) (including 57% of those children between the ages of 18 and 32 months), and that nearly 30% die before the age of 2 years. The relative importance of education, dietary understanding and socio-economic status in accounting for this situation is assessed.


Simultaneous trapping of high and low refractive index particles using a single-fiber optical trap with coexisting LP01 and LP11 modes.
We propose and demonstrate a fiber optical trap based on the coexistence of LP01 and LP11 modes for the simultaneous trapping of both high refractive index particles and low refractive index particles. Since different mode beams have different propagation constants, they exhibit different focused light fields. We fabricated a tapered fiber probe using thermal fusion to converge the beam, which generates a strong gradient force field near the fiber tip, as well as a dark trap along the axial direction. High refractive index particles are attracted near the fiber tip by a strong gradient force, and low refractive index particles are trapped in the dark cage along the axial direction. The proposed optical trap, which can simultaneously trap particles with different refractive indices, makes it easier to manipulate cells or molecules with different properties and explore multi-molecule interactions, which can facilitate research related to biology and chemistry.


Identification and In Silico Characterization of a Genetically Distinct Avian Rotavirus D Capsid Gene, VP7.
Rotavirus D (RV-D) is gaining importance as a cause of gastroenteritis and runting and stunting syndrome (RSS) in poultry. To date, information is scarce on the molecular analysis of RV-D isolates worldwide. In this study, the VP7 gene, a major constituent of outer capsid structural protein, from a RV-D isolate (UKD48) obtained from Uttarakhand state was analyzed. Phylogenetically, the RV-D isolate was found to be closely related to a South Korean strain, and the nucleotide percent identity varied from 80.4–84.2% with other RV-D strains available globally. Furthermore, domain investigation within 21 aligned amino acid sequences of the VP7 gene affirmed that this gene has several domains: a conserved glycosylation site (N–I–T) having an important role in protein folding; a N-terminal signal peptide ("ITG") for endoplasmic reticulum retention; and two hydrophobic sites for elucidating transmembrane portions, antigenic structures, and so forth. The findings suggest that the VP7 gene of the Indian RV-D isolate is genetically distinct from those of other avian RV-Ds. Although biological evidence is still needed to prove the functional characteristics of these domains in outer capsid structural proteins, the present study adds new knowledge and derives the need for further investigation.


Evaluation of a continuing education course for occupational therapy practitioners on the use of applied behavior analysis.
A three hour continuing education course combining occupational therapy practice and behavior analysis strategies related to children with autism spectrum disorders was developed and delivered to 24 occupational therapy practitioners. Participants completed evaluations pre-course, post-course, and one month follow up on their self-efficacy, knowledge, and skills in managing challenging behaviors of children with autism spectrum disorders. Overall, ratings scores showed an increase in participants' self-efficacy and knowledge and skill at post-course and one-month follow-up. Despite this increase, participants continued to implement sensory strategies to decrease challenging behaviors due to increased self-efficacy in using sensory strategies and the lack of support in implementing behavior techniques outside their session time.


Modeling and Simulation of Pretomanid Pharmacokinetics in Pulmonary Tuberculosis Patients.
Pretomanid is a nitroimidazole antibiotic in late-phase clinical testing as a component of several novel antituberculosis (anti-TB) regimens. A population pharmacokinetic model for pretomanid was constructed using a Bayesian analysis of data from two phase 2 studies, PA-824-CL-007 and PA-824-CL-010, conducted with adult (median age, 27 years) patients in Cape Town, South Africa, with newly diagnosed pulmonary TB. Combined, these studies included 63 males and 59 females administered once-daily oral pretomanid doses of 50, 100, 150, 200, 600, 1,000, or 1,200 mg for 14 days. The observed pretomanid plasma concentration-time profiles for all tested doses were described by a one-compartment model with first-order absorption and elimination and a sigmoidal bioavailability dependent on dose, time, and the predose fed state. Allometric scaling with body weight (normalized to 70 kg) was used for volume of distribution and clearance, with the scaling exponents equal to 1 and 3/4, respectively. The posterior population geometric means for the clearance and volume of distribution allometric constants were 4.8 ± 0.2 liters/h and 130 ± 5 liters, respectively, and the posterior population geometric mean for the half-maximum-effect dose for the reduction of bioavailability was 450 ± 50 mg. Interindividual variability, described by the percent coefficient of variation, was 32% ± 3% for clearance, 17% ± 4% for the volume of distribution, and 74% ± 9% for the half-maximum-effect dose. This model provides a dose-exposure relationship for pretomanid in adult TB patients with potential applications to dose selection in individuals and to further clinical testing of novel pretomanid-containing anti-TB regimens.


Holdase/Foldase Mimetic Nanochaperone Improves Antibody-Based Cancer Immunotherapy.
Despite unprecedented successes of antibody-based cancer immunotherapy, the serious side effects and rapid clearance following systemic administration remain big challenges to realize its full potential. At the same time, combination immunotherapy using multiple antibodies has shown particularly promising in cancer treatment. It is noticed that the working mechanisms of natural holdase and foldase chaperone are desirable to overcome the limitations of therapeutic antibodies. Holdase chaperone stabilizes unfolded client and prevents it from activation and degradation, while foldase chaperone assists unfolded client to its native state to function. Here a holdase/foldase mimetic nanochaperone (H/F-nChap) to co-delivery two types of monoclonal antibodies (mAbs), αCD16 and αPDL1, and resiquimod (R848) is developed, which significantly improves cancer immunotherapy. The H/F-nChap presents holdase activity in blood and normal tissues that hides and protects mAbs from unnecessary targeted activation and degradation, thereby prolonging blood circulation and reducing immunotoxicity in vivo. Furthermore, H/F-nChap switches to foldase activity in the tumor microenvironment that exposes mAbs and releases R848 to enhance the engagement between NK cells and tumor cells and promote immune activation, respectively. The H/F-nChap represents a strategy for safe and spatiotemporal delivery of multiple mAbs, providing a promising platform for improved cancer immunotherapy.


Theoretical study of the structural properties of plutonium(IV) and (VI) complexes.
The structural properties of several plutonium(IV) and (VI) complexes have been examined in the gaseous and aqueous phases using Kohn-Sham density functional theory calculations with scalar relativistic effective core potentials and the polarizable continuum solvation model. The aquo and nitrate complexes of PuO(2)(2+) and Pu(4+) were considered in addition to the aquo-chloro complexes of PuO(2)(2+). The nitrate and chloro- complexes formed with triphenylphosphine oxide (TPPO) and tributylphosphate (TBP) respectively were also studied. The structural parameters of the plutonyl complexes were compared to their uranyl and neptunyl analogues. The bond lengths and vibrational frequencies of the plutonyl complexes can generally be computed with sufficient accuracy with the pure PBE density functional with shorter bond lengths being predicted by the B3LYP functional. The structural parameters of the [PuO(2)Cl(2)L(2)] systems formed with TPPO and TBP as well as the aqueous [PuO(2)Cl(2)(H(2)O)(3)] complex are matched to previous experimental results. Overall, the inclusion of ligands in the equatorial region results in significant changes in the stretching frequency of the plutonyl group. The structural features of the plutonyl (VI) systems are rather similar to those of their 5f(0) uranyl and 5f(1) neptunyl counterparts. For the Pu(IV) aquo and nitrate complexes, the average of the calculated Pu-OH(2) and Pu-O(nitrate) bond lengths are generally within 0.04 Å of the reported experimental values. Overall Kohn-Sham DFT can be used successfully in predicting the structures of this diverse set of Pu(VI) and Pu(IV) complexes.


Deciphering the molecular nature of ovarian cancer biomarker CA125.
The ovarian cancer biomarker CA125 has been extensively investigated over the last 30 years. The knowledge about the exact molecular nature of this protein, however, remains fragmented. This review provides an overview of the structural research regarding CA125, and presents an orthogonal verification method to confirm the identity of this molecule. The need for independent identification of CA125 is exemplified by several reports where mutually exclusive data concerning the existence of isoforms and the glycan moieties is presented. Mass spectrometry can overcome the pitfalls of a single detection/identification method such as antibody probing. Independent verification of CA125 identity in characterization studies will help establish a refined model of its molecular structure that will promote the development of new approaches for diagnosis, prognosis and therapy of ovarian cancer.


[Interrelations of NAD and adenosine transformation in the rat liver].
The interrelationship of NAD and adenosine (inosine) conversions in the rat liver is investigated. The ratio of products of NAD+ conversions (ADP-ribose, inosine, hypoxanthine and ribose phosphates) are established. AMP and adenosine are not detected, which indicates an availability of different activities of the corresponding enzymes. It is shown that under conditions of the high inorganic phosphate concentration (33 mM) ribose-1-phosphate, formed in the purine nucleoside phosphorylase reaction, is accumulated due to the phosphoribomutase inhibition, but in the presence of NAD+ the utilization of ribose phosphate increases significantly. Nicotinamide inhibits the NAD+-glycohydrolase reaction in the system containing 33 mM phosphate, NAD+ and adenosine and simultaneously it lowers the utilization of ribose.


Development and Characterization of Carbon-Based Adsorbents Derived from Agricultural Wastes and Their Effectiveness in Adsorption of Heavy Metals in Waste Water.
The current work focuses on peanut shells and agricultural wastes richly in many nations subjected to pyrolysis treatment at various temperatures in the range of 500-800°C to determine the feasible physiochemical characteristics of the biochar. The biochars with the high surface area were employed to adsorb Pb2+ (lead) ions, the heaviest pollutants in the water bodies. The raw material, biochar, and pyrolyzed biochar were characterized by SEM, FTIR, partial and elemental analysis, and BET tests. The adsorption characteristics of the biochar, pre- and postpyrolysis treatment, were studied with the assistance of batch adsorption tests under varying test conditions. Adsorbing conditions were determined by evaluating the effects of adsorbing parameters like initial concentration of the lead in water, pH of the adsorbent, contact time, and mixing speed on the effective adsorption of Pb2+ ions from water. Langmuir, Freundlich, and Themkin isotherm expressions were employed to study the experimental results. The adsorption kinetics study showed that the synthesized biochars were chemically stable enough to adsorb the Pb ions onto the surface.


Twinfilin is required for actin-dependent developmental processes in Drosophila.
The actin cytoskeleton is essential for cellular remodeling and many developmental and morphological processes. Twinfilin is a ubiquitous actin monomer-binding protein whose biological function has remained unclear. We discovered and cloned the Drosophila twinfilin homologue, and show that this protein is ubiquitously expressed in different tissues and developmental stages. A mutation in the twf gene leads to a number of developmental defects, including aberrant bristle morphology. This results from uncontrolled polymerization of actin filaments and misorientation of actin bundles in developing bristles. In wild-type bristles, twinfilin localizes diffusively to cytoplasm and to the ends of actin bundles, and may therefore be involved in localization of actin monomers in cells. We also show that twinfilin and the ADF/cofilin encoding gene twinstar interact genetically in bristle morphogenesis. These results demonstrate that the accurate regulation of size and dynamics of the actin monomer pool by twinfilin is essential for a number of actin-dependent developmental processes in multicellular eukaryotes.


Limited significance of asymmetric adrenal visualization on dexamethasone-suppression scintigraphy.
To assess whether a single measurement of the adrenal uptake of 6 beta-[131I]-iodomethylnorcholesterol (NP-59) on constant dexamethasone suppression would allow discrimination of adenoma from normal and bilateral hyperplasia, the adrenal uptake of 6 beta-[131I]iodomethylnorcholesterol (NP-59) was determined in 50 patients with primary aldosteronism (30 adenoma, 20 hyperplasia) and in 13 with hyperandrogenism (six adenoma, seven hyperplasia). Bilateral adrenal NP-59 activity at 5 days was seen in 14 of 36 patients with adenoma (normal to adenoma ratio of greater than or equal to 0.5), whereas marked asymmetric uptake of NP-59 was seen in six of 27 patients with hyperplasia (uptake ratio of less than or equal to 0.5). Thus the level of adrenal NP-59 uptake does not alone serve to distinguish either adenoma from the normal, contralateral adrenal or the adrenal glands in bilateral hyperplasia in all cases. It appears that the pattern of adrenal imaging, early unilateral or early bilateral NP-59 activity (less than 5 days after NP-59 on 4 mg dexamethasone), best serves to separate adrenal adenoma from bilateral hyperplasia.


Tracking the pipeline: immunoinformatics and the COVID-19 vaccine design.
With the onset of the COVID-19 pandemic, the amount of data on genomic and proteomic sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stored in various databases has exponentially grown. A large volume of these data has led to the production of equally immense sets of immunological data, which require rigorous computational approaches to sort through and make sense of. Immunoinformatics has emerged in the recent decades as a field capable of offering this approach by bridging experimental and theoretical immunology with state-of-the-art computational tools. Here, we discuss how immunoinformatics can assist in the development of high-performance vaccines and drug discovery needed to curb the spread of SARS-CoV-2. Immunoinformatics can provide a set of computational tools to extract meaningful connections from the large sets of COVID-19 patient data, which can be implemented in the design of effective vaccines. With this in mind, we represent a pipeline to identify the role of immunoinformatics in COVID-19 treatment and vaccine development. In this process, a number of free databases of protein sequences, structures and mutations are introduced, along with docking web servers for assessing the interaction between antibodies and the SARS-CoV-2 spike protein segments as most commonly considered antigens in vaccine design.


Tenderness as measured by pressure pain thresholds extends beyond the pelvis in chronic pelvic pain syndrome in men.
Urological Chronic Pelvic Pain Syndrome (UCPPS) in men is a common complaint, and causes significant impairment in quality of life. Until recently, the focus of research has primarily been on pain symptoms or underlying prostate pathology. However, new clinical phenotyping demonstrates pelvic tenderness to be an important component of UCPPS. Unfortunately, mechanisms underlying tenderness remain to be understood, and tenderness itself has not been well quantified. To validate the use of pressure pain thresholds as a method of measuring tenderness in UCPPS and to demonstrate that tenderness extends beyond the pelvis. Fifty-five men diagnosed with UCPPS and 46 healthy controls were recruited through referrals and advertisements. Each participant filled out questionnaires and was assessed by a structured interview. In addition, all UCPPS men underwent urological assessment. Demographic information was collected as well as the National Institutes of Health-Chronic Prostatitis Symptom Index. Using a digital algometer, pressure pain thresholds on 10 genito-pelvic and one control site (deltoid) were measured. The four-glass test was used for all UCPPS men. UCPPS men had reliably lower pain thresholds compared to controls in all locations, including the deltoid. UCPPS men also demonstrated consistently lower overall pain thresholds regardless of location. Furthermore, pressure pain thresholds were able to correctly distinguish patients from controls 77% of the time. Prostate infection did not influence pain thresholds. Lower pelvic and nonpelvic thresholds suggest the involvement of a central mechanism in UCPPS. Overall, the data confirm the move away from a prostate-based view of UCPPS. This is supported by the failure to find threshold differences related to prostate infection. Pressure pain thresholds appear to be a promising method of assessing tenderness in UCPPS.


Response surface methodology as an approach to determine the optimal activities of xylose reductase and xylitol dehydrogenase enzymes from Candida Mogii.
A central composite experimental design leading to a set of 16 experiments with different combinations of pH and temperature was performed to attain the optimal activities of xylose reductase (XR) and xylitol dehydrogenase (XDH) enzymes from Candida mogii cell extract. Under optimized conditions (pH 6.5 and 38 degrees C), the XR and XDH activities were found to be 0.48 U/ml and 0.22 U/ml, respectively, resulting in an XR to XDH ratio of 2.2. Stability, cofactor specificity and kinetic parameters of the enzyme XR were also evaluated. XR activity remained stable for 3 h under 4 and 38 degrees C and for 4 months of storage at -18 degrees C. Studies on cofactor specificity showed that only NADPH-dependent XR was obtained under the cultivation conditions employed. The XR present in C. mogii extracts showed a superior Km value for xylose when compared with other yeast strains. Besides, this parameter was not modified after enzyme extraction by aqueous two-phase system.


Validity and reliability of the Miller Forensic Assessment of Symptoms Test (M-FAST): comment on Veazey, et al. (2005).
Confidence intervals are provided for the validity coefficients calculated by Veazey, et al. for the M-FAST. Two coefficients alpha are also presented along with suggestions for different approaches to calculating the M-FAST internal consistency reliability.


Evaluation of an inspiratory muscle trainer in healthy humans.
The Powerbreathe is an inspiratory muscle trainer promoted as improving inspiratory muscle strength (and consequently exercise performance) in athletes and patients with respiratory disease. No published evidence supports its efficacy. We performed a prospective randomized controlled study in which 12 normal subjects received either Powerbreathe training or sham training for a 6-week period. The primary outcome measure was diaphragm strength evaluated as twitch transdiaphragmatic pressure (Tw Pdi) but secondary outcome measures were provided by full respiratory muscle assessment and cardiopulmonary exercise testing. An advantage to training was observed when outcome was assessed by maximal static inspiratory mouth pressure (mean advantage 14.5 cm H2O, 95% CI 2.2-26.9 cm H2O, P=0.025). However. no significant difference was observed between the groups in any other parameter. In particular the deltaTw Pdi was not different between groups (mean 'advantage' 0.7 cmH2O, 95% CI- 7.0+/-5.5 cmH2O, P=0.8). The continued sale and use of the Powerbreathe device is not justified by our data. A sample size calculation showed that 234 subjects would need to be randomized to definitively refute the hypothesis that Powerbreathe improves Tw Pdi and we argue that such a study is required.


Significance of radiation dose in medical imaging.
Publicized cases of errant high radiation exposure delivered to patients undergoing diagnostic imaging have led to heightened awareness and scrutiny of the costs and benefits of imaging by physicians, the public, and policymakers.The statistical risks associated with the ever-increasing utilization of modalities employing damaging ionizing radiation across the population are compounded by the development of the latest generation of devices, which are capable of delivering greater radiation doses than their predecessors for comparable diagnostic applications.This article reviews the fundamental concepts and risks of medical radiation exposure, trends in imaging utilization, and the role of radiologists and their physician colleagues in managing and appropriately utilizing imaging for patient diagnosis.


Efficacy of Integrated Online Mindfulness and Self-compassion Training for Adults With Atopic Dermatitis: A Randomized Clinical Trial.
Quality of life (QOL) of patients with atopic dermatitis (AD) is reported to be the lowest among skin diseases. To our knowledge, mindfulness and self-compassion training has not been evaluated for adults with AD. To evaluate the efficacy of mindfulness and self-compassion training in improving the QOL for adults with AD. This randomized clinical trial conducted from March 2019 through October 2022 included adults with AD whose Dermatology Life Quality Index (DLQI) score, a skin disease-specific QOL measure, was greater than 6 (corresponding to moderate or greater impairment). Participants were recruited from multiple outpatient institutes in Japan and through the study's social media outlets and website. Participants were randomized 1:1 to receive eight 90-minute weekly group sessions of online mindfulness and self-compassion training or to a waiting list. Both groups were allowed to receive any dermatologic treatment except dupilumab. The primary outcome was the change in the DLQI score from baseline to week 13. Secondary outcomes included eczema severity, itch- and scratching-related visual analog scales, self-compassion and all of its subscales, mindfulness, psychological symptoms, and participants' adherence to dermatologist-advised treatments. The study randomized 107 adults to the intervention group (n = 56) or the waiting list (n = 51). The overall participant mean (SD) age was 36.3 (10.5) years, 85 (79.4%) were women, and the mean (SD) AD duration was 26.6 (11.7) years. Among participants from the intervention group, 55 (98.2%) attended 6 or more of the 8 sessions, and 105 of all participants (98.1%) completed the assessment at 13 weeks. The intervention group demonstrated greater improvement in the DLQI score at 13 weeks (between-group difference estimate, -6.34; 95% CI, -8.27 to -4.41; P < .001). The standardized effect size (Cohen d) at 13 weeks was -1.06 (95% CI, -1.39 to -0.74). All secondary outcomes showed greater improvements in the intervention group than in the waiting list group. In this randomized clinical trial of adults with AD, integrated online mindfulness and self-compassion training in addition to usual care resulted in greater improvement in skin disease-specific QOL and other patient-reported outcomes, including eczema severity. These findings suggest that mindfulness and self-compassion training is an effective treatment option for adults with AD. https://umin.ac.jp/ctr Identifier: UMIN000036277.


Stabilization of Near Identical Hydrogen Bonded Octameric Water Clusters in Crystal Structures of Three Distinct Non-Charged Polyamide Macrocyclic Host Molecules.
In this paper, we present a comparative analysis of the solid state structures of three well-resolved hydrates of macrocyclic host molecules 1a, 1b, and 2 containing an intrannular amide-aryl substituent (lariat arm) connected to a fixed 26-membered ring in a normal (-NHCOAr, hosts 1a and 1b) or reverse manner (-CONHAr, host 2). Despite different chemical structures, these hosts crystallize as isostructural tetrahydrates in the same P-1 space group. Moreover, their crystals exhibit identical hydrogen bond motifs resulting in a stabilization of an almost identical unusual octameric water cluster built from the cyclic tetramer core and four water molecules, attached sequentially in an "up-and-down" manner. Further analysis reveals that, among the series, the structure of host 2 provides the most suitable environment for the accommodation of this type of water cluster.


Brain Pharmacokinetics and the Pharmacological Effects on Striatal Neurotransmitter Levels of Pueraria lobata Isoflavonoids in Rat.
Isoflavonoids are putatively active components of Pueraria lobata and has been demonstrated prominent neuro-protection effect against cerebrovascular disorders, hypertension or Parkinson's disease (PD). However, the molecular basis for the beneficial effect of Pueraria lobata on nervous systems has not been well revealed. The present study aims to assess striatum exposure to main active isoflavonoids and changes of striatal extracellular neurotransmitters levels in rat brain after intravenous administration of Pueraria lobata isoflavonoids extracts (PLF), to further elucidate its' substantial bases for neuro activities. Fifteen rats were divided into 3 groups (five rats in each group) to receive a dose of PLF at 80 or 160 mg/kg or normal saline (vehicle), respectively. An LC-MS/MS method was employed to determine the concentrations of five main isoflavonoids and multiple neurotransmitters in microdialysate from striatal extracellular fluid (ECF) of the rats. The exposed quantities of puerarin (PU), 3'-methoxypuerarin (MPU), daidzein-8-C-apiosyl-(1-6)-glucoside (DAC), and 3'-hydroxypuerarin (HPU) in striatum were dose-dependent. The content of daidzein (DAZ) was too low to be detected in all dialysate samples through the experiment. Optimal dose PLF (80 mg/kg) promoted DA metabolism and inhibited 5-HT metabolism. No obvious change in the level of GLu was determined. The concentration of GABA presented a temporary decline firstly and then a gradual uptrend followed by a further downtrend. Higher dose (160 mg/kg) PLF could enhance the metabolism of both DA and 5-HT, and lower the extracellular level of GLu, without changing GABA concentrations, which might result in alleviation on excitatory toxicity under conditions, such as ischemia. The results infer that different dose of PLF should be chosen to achieve appropriate neurochemical modulation effects under conditions, such as hypertension or ischemia/stroke. These findings may significantly contribute to a better understanding of the neuroprotective effect of Pueraria lobata and provide new insights into its application toward neuro-degenerative diseases in the future.