Isolation and characterization of Nicotiana plumbaginifolia nitrate reductase-deficient mutants: genetic and biochemical analysis of the NIA complementation group.
Two hundred and eleven nitrate reductase-deficient mutants (NR-) were isolated from mutagenized Nicotiana plumbaginifolia protoplast cultures by chlorate selection and regenerated into plant. More than 40% of these clones were classified as cnx and presumed to be affected in the biosynthesis of the molybdenum cofactor, the remaining clones being classified as nia mutants. A genetic analysis of the regenerated plants confirmed this proportion of nia and cnx clones. All mutants regenerated were found to carry monogenic recessive mutations that impaired growth on nitrate as sole nitrogen source. Mutants propagated by grafting on N. tabacum systematically displayed a chlorotic leaf phenotype. This chlorosis was therefore related to the NR deficiency. The observation of leaves with NR- chlorotic sectors surrounded by NR+ wild-type tissues suggests that an NR deficiency is not corrected by diffusible factors. Periclinal chimeras between wild-type tobacco and the NR- graft were also observed. In this type of chimeric tissue chlorosis was no longer detectable when NR+ cells were in the secondmost (L2) layer, but was still detectable when NR- cells were in the secondmost layer. The genetic analysis of nia mutants revealed that they belong to a single complementation group. However three nia mutants were found to complement some of the other nia mutants. The apoenzyme of nitrate reductase was immunologically detected in several nia mutants but not in other members of this complementation group. Some of the nia mutants, although they were NR-, still displayed methylviologen-nitrate reductase activity at a high level. These data show that the nia complementation group corresponds to the structural gene of nitrate reductase. Some of the mutations affecting this structural gene result in the overproduction of an inactive nitrate reductase, suggesting a feedback regulation of the level of the apoenzyme in the wild type.


Local regulatory factors in regulation of ovarian function: role of prorenin-renin-angiotensin-system.
During reproductive life in the female, there is a continuous flow of growth, maturation and demise of ovarian follicles, unless pregnancy occurs. Although ovarian function is primarily controlled by the hypothalamus-pituitary-axis, there is no doubt that a hormonal microenvironment specific for each individual follicle is established, that finally determines whether a follicle ovulates and becomes a corpus luteum or undergoes atresia. In this respect, autocrine and paracrine factors that act alone or modulate gonadotropins action are of paramount importance. In this article, we want to introduce the ovarian prorenin-renin-angiotensin-system (PRAS) and summarize what is actually known about its involvement in ovarian physiology and pathology.


From haematopoietic stem cells to complex differentiation landscapes.
The development of mature blood cells from haematopoietic stem cells has long served as a model for stem-cell research, with the haematopoietic differentiation tree being widely used as a model for the maintenance of hierarchically organized tissues. Recent results and new technologies have challenged the demarcations between stem and progenitor cell populations, the timing of cell-fate choices and the contribution of stem and multipotent progenitor cells to the maintenance of steady-state blood production. These evolving views of haematopoiesis have broad implications for our understanding of the functions of adult stem cells, as well as the development of new therapies for malignant and non-malignant haematopoietic diseases.


A Systematic Review of Closed Head Injury Models of Mild Traumatic Brain Injury in Mice and Rats.
Mild TBI (mTBI) is a significant health concern. Animal models of mTBI are essential for understanding mechanisms, and pathological outcomes, as well as to test therapeutic interventions. A variety of closed head models of mTBI that incorporate different aspects (i.e., biomechanics) of the mTBI have been reported. The aim of the current review was to compile a comprehensive list of the closed head mTBI rodent models, along with the common data elements, and outcomes, with the goal to summarize the current state of the field. Publications were identified from a search of PubMed and Web of Science and screened for eligibility following PRISMA guidelines. Articles were included that were closed head injuries in which the authors classified the injury as mild in rats or mice. Injury model and animal-specific common data elements, as well as behavioral and histological outcomes, were collected and compiled from a total of 402 articles. Our results outline the wide variety of methods used to model mTBI. We also discovered that female rodents and both young and aged animals are under-represented in experimental mTBI studies. Our findings will aid in providing context comparing the injury models and provide a starting point for the selection of the most appropriate model of mTBI to address a specific hypothesis. We believe this review will be a useful starting place for determining what has been done and what knowledge is missing in the field to reduce the burden of mTBI.


Thermoanalytical and Fourier transform infrared spectral curve-fitting techniques used to investigate the amorphous indomethacin formation and its physical stability in Indomethacin-Soluplus® solid dispersions.
The amorphous form of a drug has higher water solubility and faster dissolution rate than its crystalline form. However, the amorphous form is less thermodynamically stable and may recrystallize during manufacturing and storage. Maintaining the amorphous state of drug in a solid dosage form is extremely important to ensure product quality. The purpose of this study was to quantitatively determine the amount of amorphous indomethacin (INDO) formed in the Soluplus® solid dispersions using thermoanalytical and Fourier transform infrared (FTIR) spectral curve-fitting techniques. The INDO/Soluplus® solid dispersions with various weight ratios of both components were prepared by air-drying and heat-drying processes. A predominate IR peak at 1683cm(-1) for amorphous INDO was selected as a marker for monitoring the solid state of INDO in the INDO/Soluplus® solid dispersions. The physical stability of amorphous INDO in the INDO/Soluplus® solid dispersions prepared by both drying processes was also studied under accelerated conditions. A typical endothermic peak at 161°C for γ-form of INDO (γ-INDO) disappeared from all the differential scanning calorimetry (DSC) curves of INDO/Soluplus® solid dispersions, suggesting the amorphization of INDO caused by Soluplus® after drying. In addition, two unique IR peaks at 1682 (1681) and 1593 (1591)cm(-1) corresponded to the amorphous form of INDO were observed in the FTIR spectra of all the INDO/Soluplus® solid dispersions. The quantitative amounts of amorphous INDO formed in all the INDO/Soluplus® solid dispersions were increased with the increase of γ-INDO loaded into the INDO/Soluplus® solid dispersions by applying curve-fitting technique. However, the intermolecular hydrogen bonding interaction between Soluplus® and INDO were only observed in the samples prepared by heat-drying process, due to a marked spectral shift from 1636 to 1628cm(-1) in the INDO/Soluplus® solid dispersions. The INDO/Soluplus® solid dispersions prepared by both drying processes could keep the amorphous state of INDO in the INDO/Soluplus® solid dispersions at the accelerated storage condition.


PET/CT Limitations and Pitfalls in Urogenital Cancers.
Hybrid FDG PET/CT plays a vital role in oncologic imaging and has been widely adopted for the staging and restaging of a variety of malignancies. Its diagnostic value in urogenital malignancies is less well-known, not at least because of the variable FDG avidity of these tumor entities, the sites of these tumors, and technical challenges associated with sequential imaging of CT and PET. PET/CT interpretation thus can be especially challenging and is associated with many pitfalls, which can lead to both false-positive and false-negative diagnoses as well as incorrect assessment of metabolic change following therapy. Currently, FDG PET/CT is not the standard of care for the initial diagnosis or staging of early-stage or low-risk urogenital cancers; however, it can help evaluate distant metastatic disease, response to therapy, and disease recurrence in high-risk patients. Knowledge of imaging features of tumor metabolic avidity and pitfalls is essential for accurate interpretation.


To Assess the Serum and Salivary Biomarkers in People with and Without Diabetes.
The study was conducted to assess the serum and salivary biomarkers in people with and without diabetes. Among the 100 participants in this cross-sectional comparative study, 59 men and 61 women aged 32 to 59 years old were randomly assigned to category I (consisting of 50 diabetes mellitus (DM) patients of both types 1 and 2) or category II (consisting of 50 healthy volunteers) to serve as comparisons. Since there is no difference in the amounts of salivary biomarkers across the various types of diabetes, they are all grouped together. Several biochemical indicators were measured by measuring the amounts in the participants' saliva and serum samples. There was little to no difference between the two categories when comparing saliva and serum levels. Although there was a strong correlation between serum and salivary glucose, amylase, total proteins, albumin, and globulin levels in DM patients, there was also a strong correlation between diabetics and non-diabetics for these same markers.


Dilated cardiomyopathy: the role of genetics, highlighted in a family with Filamin C (FLNC) variant.
Dilated cardiomyopathy (DCM) is a heterogenous group of disorders characterised by left ventricular dilatation and dysfunction, in the absence of factors affecting loading conditions such as hypertension or valvular disease, or significant coronary artery disease. The prevalence of idiopathic DCM is estimated between 1:250 and 1:500 individuals. Determining the aetiology of DCM can be challenging, particularly when evaluating an individual and index case with no classical history or investigations pointing towards an obvious acquired cause, or no clinical clues in the family history to suggest a genetic cause. We present a family affected by DCM associated with Filamin C variant, causing sudden cardiac death at a young age and heart failure due to severe left ventricular impairment and myocardial scarring. We review the diagnosis and treatment of DCM, its genetic associations and potential acquired causes. Thorough assessment is mandatory to risk stratify and identify patients who may benefit from primary prevention implantable cardioverter defibrillator therapy according to international guidelines. Genetic testing has some limitations, and is positive in only 20%-35% of DCM, but should be considered in specific cases to identify families who may benefit from cascade screening after appropriate counselling. The management of often complex familial cardiomyopathy requires specialist input for every case, and the appropriate infrastructure to coordinate investigations.


Vitamin B12 and its binding proteins in the serum of some wild game species.
The concentration of vitamin B12 and its binding proteins was measured in the impala, nyala, wildebeest, zebra, bushpig, warthog, and rhino, all existing in their natural state. Marked differences were found between some species. The variations observed are probably true species differences, unrelated to environmental factors.


C1 lateral mass screw insertion using cannulated, navigated screws: preliminary results of a novel technique.
The upper cervical spine region is densely populated by neural and vascular structures impeding the approach for fusion surgery. Technological advancement simplify the approach to C1-C2 fusion, thus reduce risks. The current paper purpose is to describe initial experience with a novel technique modification for C1 lateral screw insertion that incorporates cannulated-navigated screw system with intra-operative 3D imaging. A single-center single surgeon database was reviewed to identify all patients who underwent placement of C1 lateral mass screw insertion using the novel technique modification described below, on 2020. This cohort was retrospectively analyzed and compared with a cohort of patients who were operated on by the same surgeon with non-cannulated, navigated screws with intra-operative 3D imaging (O-arm, Medtronic, USA) between 2011 and 2019. Following navigated starting hole and drilling of the C1 lateral mass, a blunt guide-wire is used to palpate the hole and cannulated screw is advanced to the correct position over the wire. After initial purchase, a navigated screw driver is used for final screw depth position. Twelve C1 lateral mass screws were inserted in six patients using this novel cannulated-navigated screw placement technique and compared to 24 patients operated using navigated non-cannulated screws. Minimal Estimated Blood Loss (EBL) was recorded in five of six cases undergoing the novel cannulated navigated placement of C1 lateral mass screws. Comparison to non-cannulated cohort demonstrated an EBL of 83CC vs. 354CC (Not significant). Mean surgery time was 97min and 118min for the cannulated-navigated and navigated only procedures (p = 0.03, statistically significant) respectively. In the current cohort, all screws were rated in optimal position and no repositioning procedures were performed. The new method presented allows for faster and possibly safer and more accurate C1 lateral mass screw insertion.


Persistent and recurrent conductive deafness following stapedotomy.
Stapedotomy produces the best hearing results of any otological operation. However, in a small number of cases the air-bone gap is not successfully closed, or conductive hearing loss recurs. To investigate the proportion of cases in the senior author's series which required revision surgery and to determine the medium to long term success rate of surgery, taking into account the results of revision surgery. Review of a series of 233 primary stapedotomy operations and 100 revision procedures carried out by one surgeon over a 20-year period. Closure of the air-bone gap to within 10 dB was achieved in 80 per cent of cases following the primary procedure. Fifteen per cent of patients developed a recurrence of conductive hearing loss. When the results of revision surgery were taken into account, the proportion of ears with a mean air-bone gap of less than 10 dB was 86 per cent. However, of the patients undergoing revision surgery, air-bone gap closure to within 10 dB was only achieved in 52 per cent of cases. The best chance of obtaining a successful outcome in stapedotomy is to achieve this for the first procedure. However, revision surgery does increase the medium to long term success rate.


Pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD) decreases the risk for substance abuse: findings from a longitudinal follow-up of youths with and without ADHD.
Findings from a previously published longitudinal follow-up of adolescents with and without attention-deficit/hyperactivity disorder (ADHD) were reanalyzed to determine the extent to which pharmacotherapy for ADHD is associated with substance use disorders, including abuse and dependence. Using naturalistic data from 140 people with ADHD and 120 controls, researchers returned to previously accumulated data to determine whether exposure to stimulant therapy had increased rates of substance use disorder among ADHD patients. Findings included confirmation that, in fact, stimulant therapy protected medicated ADHD patients against substance use disorder, which occurred at rates that were 3 to 4 times greater among people with untreated ADHD.


A probable case of peduncular hallucinosis secondary to a cerebral peduncular lesion successfully treated with an atypical antipsychotic.
Peduncular hallucinosis is a rare phenomenon that has been reported in case reports and case series. The exact pathophysiology is unclear, but is postulated to involve disruption and dysregulation of the visual neuronal pathways in the brain. A case of complex visual hallucinations in an elderly man with no previous history of psychosis is discussed. Magnetic resonance imaging of the patient's brain revealed a discrete peduncular lesion that was the likely cause of the hallucinations. The lesion was not present on a previous brain magnetic resonance imaging that predated the onset of the hallucinations. The patient was started on low-dose risperidone, which resulted in the complete resolution of the visual hallucinations. It is important to consider discrete rostral brainstem lesions as a potential cause of new onset visual hallucinations in patients being evaluated for visual hallucinations.


pH control in biological systems using calcium carbonate.
Due to its abundance, calcium carbonate (CaCO3) has high potentials as a source of alkalinity for biotechnological applications. The application of CaCO3 in biological systems as neutralizing agent is, however, limited due to potential difficulties in controlling the pH. The objective of the present study was to determine the dominant processes that control the pH in an acid-forming microbial process in the presence of CaCO3. To achieve that, a mathematical model was made with a minimum set of kinetically controlled and equilibrium reactions that was able to reproduce the experimental data of a batch fermentation experiment using finely powdered CaCO3. In the model, thermodynamic equilibrium was assumed for all speciation, complexation and precipitation reactions whereas, rate limited reactions were included for the biological fatty acid production, the mass transfer of CO2 from the liquid phase to the gas phase and the convective transport of CO2 out of the gas phase. The estimated pH-pattern strongly resembled the measured pH, suggesting that the chosen set of kinetically controlled and equilibrium reactions were establishing the experimental pH. A detailed analysis of the reaction system with the aid of the model revealed that the pH establishment was most sensitive to four factors: the mass transfer rate of CO2 to the gas phase, the biological acid production rate, the partial pressure of CO2 and the Ca(+2) concentration in the solution. Individual influences of these factors on the pH were investigated by extrapolating the model to a continuously stirred-tank reactor (CSTR) case. This case study indicates how the pH of a commonly used continuous biotechnological process could be manipulated and adjusted by altering these four factors. Achieving a better insight of the processes controlling the pH of a biological system using CaCO3 as its neutralizing agent can result in broader applications of CaCO3 in biotechnological industries.


Application of bioluminescence ATP measurement for evaluation of fungal viability of foxing spots on old documents.
An adenosine triphosphate (ATP) bioluminescence-based protocol was tested to assess the viability of fungal species in old documents damaged by foxing. Foxing appears as scattered yellow brownish-red stains, damaging the aesthetics of documents and their long-term readability. In the field of cultural heritage conservation, the debate over the mechanism of foxing is ongoing. Previous studies found evidence of mold-like structures in some coloured areas; however, many species have not yet been identified and their role in the phenomenon is not understood. To better understand their involvement in this type of paper decay, we focused our attention first on their viability. We demonstrated the reliability and sensitivity of the ATP bioluminescence assay compared with conventional methods based on cultivation, which has rarely given rise to in vitro growth from foxed papers. From nine books dating back from the 19th and 20th centuries, the mean ATP amount of foxed spots ranged from 0.29 to 3.63 ng/cm(2), suggesting the presence of strains inside the brownish spots and providing evidence of their viability. Outside the spots, ATP content was considered negligible, with a mean ATP amount of 0 to 0.03 ng/cm(2). ATP assay appears to be a useful and robust method for the detection and quantification of viable elements in foxing spots.


BiVO4 -TiO2 Composite Photocatalysts for Dye Degradation Formed Using the SILAR Method.
Composite photocatalyst films have been fabricated by depositing BiVO4 upon TiO2 via a sequential ionic layer adsorption reaction (SILAR) method. The photocatalytic materials were investigated by XRD, TEM, UV/Vis diffuse reflectance, inductively coupled plasma optical emission spectrometry (ICP-OES), XPS, photoluminescence and Mott-Schottky analyses. SILAR processing was found to deposit monoclinic-scheelite BiVO4 nanoparticles onto the surface, giving successive improvements in the films' visible light harvesting. Electrochemical and valence band XPS studies revealed that the prepared heterojunctions have a type II band structure, with the BiVO4 conduction band and valence band lying cathodically shifted from those of TiO2 . The photocatalytic activity of the films was measured by the decolourisation of the dye rhodamine 6G using λ>400 nm visible light. It was found that five SILAR cycles was optimal, with a pseudo-first-order rate constant of 0.004 min(-1) . As a reference material, the same SILAR modification has been made to an inactive wide-band-gap ZrO2 film, where the mismatch of conduction and valence band energies disallows charge separation. The photocatalytic activity of the BiVO4 -ZrO2 system was found to be significantly reduced, highlighting the importance of charge separation across the interface. The mechanism of action of the photocatalysts has also been investigated, in particular the effect of self-sensitisation by the model organic dye and the ability of the dye to inject electrons into the photocatalyst's conduction band.


An in vitro evaluation of microleakage in class I preparations using 5th, 6th and 7th generation composite bonding agents.
The intent of this study was to evaluate microleakage of newer generations of dentinal bonding systems of Class I restorations filled with the same resin based composites. Eighty extracted human premolar and molar teeth were randomly assigned to four groups for bonding: the 5th generation bonding system (Optibond Solo), the 6th generation bonding system (Prompt-L-Pop) and the 7th generation bonding system (iBond), and a control group that was used with no dentinal bonding system. Cavities were prepared 3 mm in width, 2 mm in depth and 2 mm in length. Margins of the cavities were chamfered using a high-speed hand piece with water spray and a #1/2 round diamond bur. The cavities were restored with resin based composites after the application of the dentinal bonding systems according to the instructions of the manufacturer. Upon drying of the teeth, two coats of nail varnish were applied covering the surface of the tooth, excluding the tooth-restoration interface. Samples were thermocycled and immersed in methylene blue dye (0.05%). Each sample was sectioned with an Isomet and evaluated, for microleakage using light microscopy under a measuring microscope at 50x magnification Statitical significance was determined using the Chi-Square Test. Among the three dentinal adhesive systems used in this study the 5th generation outperformed both the 6th and 7th generation bonding systems.


A comparison of fenoldopam with dopamine and sodium nitroprusside in patients undergoing cross-clamping of the abdominal aorta.
Fenoldopam, a selective dopamine-1-receptor agonist, decreases arterial blood pressure rapidly, with a brief duration of action similar to sodium nitroprusside (SNP), but in contrast to SNP, it increases renal blood flow. We compared the hemodynamic and renal effects of fenoldopam in patients undergoing abdominal aortic surgery requiring cross-clamping of the aorta with another therapeutic option, dopamine and SNP. Fenoldopam or 2 mcg x kg(-1) x min(-1) of dopamine and SNP was infused before incision in 60 randomly selected patients in a double-blind fashion. Hemodynamic variables were recorded before incision, immediately before clamping the aorta, 5 min after cross-clamp release and upon completion of surgery. Urine output, serum creatinine, and creatinine clearance were measured intraoperatively and postoperatively. Characteristics were compared between groups using two-sample rank sum test for continuous variables and Fisher's exact test for discrete variables. The occurrence of severe hypotension, maximum systolic blood pressure, and need for additional antihypertensive drugs were not different between the groups. Most intraoperative hemodynamic variables and all indices of renal function did not differ according to treatment. Therefore, fenoldopam has no therapeutic advantage compared with similar therapies in patients undergoing major vascular surgery involving cross-clamping of the aorta.


Analysis of protein/ligand interactions with NMR diffusion measurements: the importance of eliminating the protein background.
Pulsed-field gradient nuclear magnetic resonance (PFG-NMR) is a well-established method for the determination of translational diffusion coefficients. Recently, this method has found applicability in the combinatorial arena with the introduction of affinity NMR for characterizing protein/ligand interactions. Although affinity NMR has been reported to be an effective method for the identification of active compounds in a complex mixture, there are limitations of this method. We have developed a simple mathematical model to predict optimum concentration ratios of the ligand and protein in order to observe maximum changes in the ligand diffusion coefficient upon protein binding. The ligand/protein systems of L-tryptophan and ibuprofen binding to human serum albumin were chosen to demonstrate the usefulness of this model. However, even when the conditions of the mathematical model are satisfied, the spectral background arising from the protein in proton-detected experiments can be problematic. To this end, we have employed spectral subtraction of the protein spectrum to yield ligand diffusion coefficients that are in agreement with those predicted by simulation.


Direct and indirect effects of dominant plants on ecosystem multifunctionality.
Biodiversity is essential for the provision of multiple ecosystem functions simultaneously (ecosystem multifunctionality EMF). Yet, it remains unclear whether and how dominant plant species impact EMF. Here, we aimed at disentangling the direct from indirect above- and belowground pathways by which dominant plant species influence EMF. We evaluated the effects of two dominant plant species (Dasiphora fruticosa, and the toxic perennial plant Ligularia virgaurea) with expected positive and negative impacts on the abiotic environment (soil water content and pH), surrounding biological communities (plant and nematode richness, biomass, and abundance in the vicinity), and on the EMF of alpine meadows, respectively. We found that the two dominant plants enhanced EMF, with a positive effect of L. virgaurea on EMF greater than that of D. fruticosa. We also observed that dominant plants impacted on EMF through changes in soil water content and pH (indirect abiotic effects), but not through changes in biodiversity of surrounding plants and nematodes (indirect biotic pathway). Our study suggests that dominant plants may play an important role in promoting EMF, thus expanding the pervasive mass-ratio hypothesis originally framed for individual functions, and could mitigate the negative impacts of vegetation changes on EMF in the alpine meadows.


Utility of Serum Albumin for Predicting Incident Metabolic Syndrome according to Hyperuricemia.
Serum albumin and uric acid have been positively linked to metabolic syndrome (MetS). However, the association of MetS incidence with the combination of uric acid and albumin levels has not been investigated. We explored the association of albumin and uric acid with the risk of incident MetS in populations divided according to the levels of these two parameters. In this retrospective longitudinal study, 11,613 non-MetS participants were enrolled among 24,185 individuals who had undergone at least four annual check-ups between 2006 and 2012. The risk of incident MetS was analyzed according to four groups categorized by the sex-specific medians of serum albumin and uric acid. During 55,407 person-years of follow-up, 2,439 cases of MetS developed. The risk of incident MetS increased as the uric acid category advanced in individuals with lower or higher serum albumin categories with hazard ratios (HRs) of 1.386 (95% confidence interval [CI], 1.236 to 1.554) or 1.314 (95% CI, 1.167 to 1.480). However, the incidence of MetS increased with higher albumin levels only in participants in the lower uric acid category with a HR of 1.143 (95% CI, 1.010 to 1.294). Higher levels of albumin were associated with an increased risk of incident MetS only in individuals with lower uric acid whereas higher levels of uric acid were positively linked to risk of incident MetS regardless of albumin level.


Role of integrin-linked kinase in the hypoxia-induced phenotypic transition of pulmonary artery smooth muscle cells: Implications for hypoxic pulmonary hypertension.
The phenotypic transition of pulmonary artery smooth muscle cells (PASMCs) from a contractile/differentiated to synthetic/de-differentiated phenotype is an important mechanism for the occurrence and development of hypoxic pulmonary hypertension (HPH). Integrin-linked kinase (ILK) is an early hypoxic response factor whose kinase activity is significantly affected during early hypoxia. Myocardin and ETS-like protein 1 (Elk-1) are co-activators of serum response factor (SRF) and can bind to SRF to mediate the phenotypic transition of PASMCs. However, little is known about the role of ILK on the phenotypic transition of these PASMCs. Thus, in our study, we explored the role of ILK in this process. We found that the expression of ILK and myocardin decreased gradually with the increase in hypoxia exposure time in the pulmonary arteries of rats. We observed that hypoxia exposure for 1 h caused an increase in the phosphorylation of Elk-1 but did not affect the expression of ILK, myocardin, or SRF. Exposure to hypoxic treatment for 1 h decreased ILK kinase activity and caused Elk-1 to suppress myocardin binding to SRF and the smooth muscle (SM) α-actin gene promoters. In addition, hypoxia exposure for 24 h decreased the expression of ILK, myocardin, SM α-actin, and calponin but increased the expression of osteopontin. Silencing of the myocardin gene significantly decreased the expression of SM α-actin and calponin but increased the expression of osteopontin. Silencing of the ILK gene significantly decreased the expression of myocardin, SM α-actin, and calponin but increased the expression of osteopontin. ILK overexpression reversed the effects of 24 h of hypoxia on the expression of myocardin, SM α-actin, calponin, and osteopontin and reversed the decrease in binding of myocardin to the SM α-actin promoter caused by 24 h of hypoxia exposure. Thus, our results suggest that ILK initiates the phenotypic transition of PASMCs. The underlying mechanism may involve hypoxia downregulating ILK kinase activity and protein expression, causing Elk-1 to compete with myocardin for binding to the SM α-actin promoter, which downregulates the expression of the downstream target myocardin and results in the phenotypic transition of PASMCs from a contractile to a synthetic phenotype. This may be an important mechanism in the development of HPH.


Localization studies of ioactive cyclic peptides in the ascidian Lissoclinum patella.
A Palauan specimen of the ascidian Lissoclinum patella contained the cyclic peptides patellamides A-C. In contrast to previous reports concerning the location of cyclic peptides in L. patella and L. bistratum, it has been demonstrated that these cyclic peptides were not located in the symbiotic cyanobacterium Prochloron sp. but were instead distributed throughout the ascidian tunic. The relevance of these results with respect to the biosynthetic origins of the patellamides is discussed.


The antimicrobial properties of a urea-based handwash lotion with triclosan.
The purpose of this study was to determine and compare the antimicrobial action of a urea-based handwash lotion with triclosan with a lipid-depleting detergent-based handwash product with 4% chlorhexidine gluconate. The zones of inhibition produced by the two handwash lotions and the one produced by the positive control were similar against all strains of bacteria tested, indicating that a urea-based handwash lotion with triclosan is as effective as a lipid-depleting handwash lotion in inhibiting bacterial activity.


Contribution to the study of diaphragm innervation in Nelore bovines.
The phrenic nerves, in Nelore bovines, divide more frequently (60%) in a dorsal branch and a ventrolateral trunk, in both left and right sides. Another division, in trifurcation, giving off dorsal, lateral and ventral branches occurred in 23.3% of cases in the right side and in 30% left side. The division in ventral branch and dorsolateral trunk was observed in 16.6% of cases in the right side and 10% left side. The dorsal branches, both left and right, were distributed among their corresponding lumbar portions in all the cases verified. In 3% of the muscles studied, the right dorsal branch sent a nervous twig to caudal vena cava, and in 73.3% of the muscles, the left dorsal branch innervated the left lumbar portion and also sent some twigs which, after crossing the middle line, distributed in the right lumbar portion, ventral to esophageal hiatus. The lateral and ventral branches, in both left and right sides, innervated corresponding parts of the muscle. Connections (anastomosis) were observed between left lateral and dorsal branches in 10% of cases, and between dorsal left and right branches in 6.7% of cases.


Deceased elderly in-patients with pulmonary embolism.
Pulmonary embolism (PE) in the elderly is an immediate threat of life. Especially in old age clinical signs of PE are non-specific and could be both underestimated and overestimated. The retrospective long-term study was aimed at conducting an analysis and comparison of pertinent influence of age, gender and immobility on occurrence of PE and sudden death. Between 1995 and 2012 years we had altogether 12,746 elderly patients of an average age 80.6 ± 7.0 y (range 65-103 y) hospitalized at the Department of Geriatrics. All in-patients 65+ y were randomly admitted for internal hospitalization from the catchment area of Brno city (100,000 inhabitants). The subject of our interest was to study the documentation of deaths (including autopsy findings), which was caused by PE. Out of this number there were 8,540 women (66.3 %) and 4,206 men (33.7 %). Among all hospitalized patients PE in 700 cases (5.5 % of all admitted patients) was shown in a medical report. Among them there were 424 survivors (60.6 %; 134 men and 290 women). The high occurrence of PE (particularly silent form) has crucial importance in the elderly mortality. Our recommendations would like to emphasize the need of no underestimation of this fact and to carry out preventive measures in all age groups (including the "oldest old" and frail persons) (Tab. 3, Ref. 41).


Impact of MALDI-TOF MS identification on anaerobic species and genus diversity in routine diagnostics.
Introduction of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has revolutionized bacterial identification in the last decade. In 2013, MALDI-TOF MS was implemented for the identification of anaerobic bacteria at our laboratory. This study analyzed the impact of MALDI-TOF MS on the number of different anaerobic genera and species identified in diagnostics. 155 anaerobic human clinical isolates, representing the most frequently isolated anaerobic species at our laboratory, were identified by conventional biochemical methods and by a Bruker MALDI Biotyper (Bruker Daltonics, Bremen, Germany). Discrepancies were resolved by partial 16S rRNA gene sequence analysis. In addition, we compared the frequencies of anaerobic genera and species prior to the implementation of MALDI-TOF MS from 2008 to 2012 to the frequencies of anaerobes from 2013 to 2020 when MALDI-TOF MS was used for identification. The diversity of anaerobic bacteria increased from 12 genera and 20 species in 2012, before the introduction of MALDI-TOF MS, to 16 genera and 31 species in 2013 and to 20 genera and 41 species in 2020 when MALDI-TOF MS was used as primary identification method. MALDI-TOF MS allowed species assignment within closely related species such as the Bacteroides fragilis group in accordance with 16S identification, and correctly identified newly described anaerobic species. Introduction of MALDI-TOF MS identification increased genus and species diversity of the reported anaerobes at our laboratory. Updates to the MALDI-TOF MS database and new species descriptions will further increase the diversity of anaerobic bacteria isolated from infectious processes.


Simultaneous Occurrence of Borrelia miyamotoi, Borrelia burgdorferi Sensu Lato, Anaplasma phagocytophilum and Rickettsia helvetica in Ixodes ricinus Ticks in Urban Foci in Bratislava, Slovakia.
Questing Ixodes ricinus ticks were collected in two urban parks (Železná studienka and Horský park) of the capital city of Slovakia, Bratislava, during two consecutive years in 2011 and 2012. A total of 932 ticks were analyzed for the presence of tick-borne agents: B. miyamotoi, B. burgdorferi s.l., A. phagocytophilum and R. helvetica. PCR analysis confirmed the presence of all pathogens at both localities. The overall infection prevalence of B. miyamotoi, B. burgdorferi s.l., A. phagocytophilum and R. helvetica was 0.75, 13.2, 5.6 and 8.9%, respectively. B. burgdorferi s.l. positive samples were represented by six genospecies. The most frequent one was B. afzelii followed by B. garinii and B. valaisiana. Our study confirms the presence of I. ricinus ticks and at least nine tick-borne bacterial agents in city forest parks, which are used for recreational purposes. Ordination analysis revealed significant differences in the composition of pathogens with respect to study site location, time of season and ambient temperature, despite the fact that both sites are located relatively close to one another within the city.


Electron spin density on the axial His ligand of high-spin and low-spin nitrophorin 2 probed by heteronuclear NMR spectroscopy.
The electronic structure of heme proteins is exquisitely tuned by the interaction of the iron center with the axial ligands. NMR studies of paramagnetic heme systems have been focused on the heme signals, but signals from the axial ligands have been rather difficult to detect and assign. We report an extensive assignment of the (1)H, (13)C and (15)N resonances of the axial His ligand in the NO-carrying protein nitrophorin 2 (NP2) in the paramagnetic high-spin and low-spin forms, as well as in the diamagnetic NO complex. We find that the high-spin protein has σ spin delocalization to all atoms in the axial His57, which decreases in size as the number of bonds between Fe(III) and the atom in question increases, except that within the His57 imidazole ring the contact shifts are a balance between positive σ and negative π contributions. In contrast, the low-spin protein has π spin delocalization to all atoms of the imidazole ring. Our strategy, adequately combined with a selective residue labeling scheme, represents a straightforward characterization of the electron spin density in heme axial ligands.


Less Invasive Surgical Approaches for Left Ventricular Assist Device Implantation.
For several years, the standard implantation strategy of ventricular assist devices has involved a full sternotomy approach. However, less invasive implantation techniques are now becoming increasingly popular as they are associated with reduction of trauma, blood loss, and arrhythmogenic complications, as well as a decreased duration of intensive care unit and in-hospital stay. Thus, due to miniaturization and increasing technical improvement of ventricular assist devices, less invasive strategies for implantation, explantation, exchange, and concomitant cardiac procedures are on the rise. In this review article, we report on the state of the art of less invasive techniques for implantation, explantation, exchange, and combined cardiac procedures of ventricular assist devices.


Life-threatening hypoglycemia associated with intentional insulin ingestion.
There are reports of insulin overdose by injection, yet little is known regarding the potential harms of intentional oral ingestion of insulin. In this report, we describe a case of massive insulin ingestion and ensuing hypoglycemia. To our knowledge, there are no previously published cases of hypoglycemia caused by intentional insulin ingestion. A 51-year-old man intentionally ingested three 10-ml vials (total of 3000 units) of various insulins: one vial each of insulin aspart, lispro, and glargine. Four symptomatic hypoglycemic episodes, with blood glucose levels of 48, 25, 34, and 40 mg/dl, occurred approximately 1, 3, 4, and 5 hours, respectively, after ingestion. The hypoglycemia could not be explained other than the ingestion of the insulins. The patient was admitted for observation, and euglycemia occurred within 24 hours without any additional hypoglycemic episodes. Hypoglycemia treatment is reviewed in this case report, and factors that may affect systemic response of orally ingested insulin, including gastrointestinal absorption and insulin sensitivity, are discussed. In addition, the findings of our case report may provide useful insight into the development of novel oral insulin products that are currently in research. Despite poor bioavailability (1%) when taken orally, insulin may produce symptomatic hypoglycemia with a massive ingestion. Vigilant blood glucose monitoring, supportive care with glucose replacement therapy, and admission to the hospital for observation may be required.


Loss of Pla2r1 decreases cellular senescence and age-related alterations caused by aging and Western diets.
Cellular senescence is induced by many stresses including telomere shortening, DNA damage, oxidative, or metabolic stresses. Senescent cells are stably cell cycle arrested and they secrete many factors including cytokines and chemokines. Accumulation of senescent cells promotes many age-related alterations and diseases. In this study, we investigated the role of the pro-senescent phospholipase A2 receptor 1 (PLA2R1) in regulating some age-related alterations in old mice and in mice subjected to a Western diet, whereas aged wild-type mice displayed a decreased ability to regulate their glycemia during glucose and insulin tolerance tests, aged Pla2r1 knockout (KO) mice efficiently regulated their glycemia and displayed fewer signs of aging. Loss of Pla2r1 was also found protective against the deleterious effects of a Western diet. Moreover, these Pla2r1 KO mice were partially protected from diet-induced senescent cell accumulation, steatosis, and fibrosis. Together these results support that Pla2r1 drives several age-related alterations, especially in the liver, arising during aging or through a Western diet.


Fibrous capsule formation of the peritoneal catheter tip in ventriculoperitoneal shunt: Two case reports.
A fibrous capsule formation of a peritoneal catheter tip has not previously been researched as a complication of ventriculoperitoneal (VP) shunts. Two adult patients who had undergone a VP shunt for communicative hydrocephalus following subarachnoid hemorrhage caused by a ruptured aneurysm have been identified with malfunction of the VP shunt system by mild disturbance of consciousness and gait disturbance or loss of appetite. Hydrocephalus was diagnosed by computed tomography and the obstruction of the peritoneal catheter was revealed by shuntgraphy. Laparoscopy was performed and the peritoneal catheter tips were obstructed by fibrous white capsules that covered them. One was a thin membranous capsule like a stocking with two small endoluminal granulomas of the peritoneal catheter, and other one was a fibrous glossy white capsule like a sock. These fibrous capsules were excised by laparoscopy forceps without the conversion to a new peritoneal catheter. Following the procedure, the shunt functioned normally. The pathological diagnoses were peritoneum with foreign body reaction or hyalinization of membranous tissue surrounded by fibrous tissue. These fibrous capsules might be formed by the peritoneal reaction to cerebrospinal fluid as a foreign material. As such, a periodic medical check should be scheduled since a fibrous capsule of the peritoneal catheter tip might be formed again.


Noninvasive imaging for staging of prostate cancer: magnetic resonance imaging, computed tomography, and ultrasound.
The diagnosis of prostate carcinoma by imaging is still fraught with problems, even with the advent of highly sophisticated techniques. Despite enthusiastic preliminary reports, no one imaging method reliably screens for this condition. The staging of prostate carcinoma is feasible, but the best imaging method remains a subject of debate. The transabdominal sonographic approach lacks the resolution required for detailed intraglandular anatomic delineation. The transrectal sonographic approach excels in guiding needle biopsy and in evaluating transcapsular and seminal vesicle extension of known tumors. Computed tomography lags behind other tomographic imaging modalities in its accuracy for local tumor staging, but it is excellent, although nonspecific, in the detection of lymph node enlargement. Magnetic resonance detects abnormalities in the prostate in a high percentage of cases but is nonspecific. However, it can stage prostate carcinoma and detect lymphadenopathy reliably.


Bisphosphonates for the prevention of fractures in osteogenesis imperfecta: meta-analysis of placebo-controlled trials.
Bisphosphonates are widely used off-label in the treatment of patients with osteogenesis imperfecta (OI) with the intention of reducing the risk of fracture. Although there is strong evidence that bisphosphonates increase bone mineral density in osteogenesis imperfecta, the effects on fracture occurrence have been inconsistent. The aim of this study was to gain a better insight into the effects of bisphosphonate therapy on fracture risk in patients with osteogenesis imperfecta by conducting a meta-analysis of randomized controlled trials in which fractures were a reported endpoint. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials in which the effects of bisphosphonates on fracture risk in osteogenesis imperfecta were compared with placebo and conducted a meta-analysis of these studies using standard methods. Heterogeneity was assessed using the I2 statistic. Six eligible studies were identified involving 424 subjects with 751 patient-years of follow-up. The proportion of patients who experienced a fracture was not significantly reduced by bisphosphonate therapy (Relative Risk [RR] = 0.83 [95% confidence interval 0.69-1.01], p = 0.06) with no heterogeneity between studies (I2 = 0). The fracture rate was reduced by bisphosphonate treatment when all studies were considered (RR = 0.71 [0.52-0.96], p = 0.02), but with considerable heterogeneity (I2 = 36%) explained by one study where a small number of patients in the placebo group experienced a large number of fractures. When this study was excluded, the effects of bisphosphonates on fracture rate was not significant (RR = 0.79 [0.61-1.02], p = 0.07, I2 = 0%). We conclude that the effects of bisphosphonates on fracture prevention in osteogenesis imperfecta are inconclusive. Adequately powered trials with a fracture endpoint are needed to further investigate the risks and benefits of bisphosphonates in this condition.


Discriminated punishment: avoidable and unavoidable shock.
Warning stimuli for two punishment conditions were alternated with periods of appetitive responding by rats. In either warning stimulus, the first response produced a brief shock, terminated the stimulus, and started an interval during which the baseline appetitive schedule was in effect. Not responding resulted in stimuli of random duration, which terminated with a shock under one condition and without a shock under the other. Each subject was exposed to several shock intensities, with trials for the two conditions programmed during alternate portions of the session. In general, response frequency in the warning signal for either condition decreased with increasing intensity; however, at a given intensity, responding was more frequent in the stimulus invariably terminating with shock than in the stimulus terminating without shock when no response was made. The frequency difference was greatest at intensities intermediate between those producing minimal and maximal suppression.


The mec-3 gene contains cis-acting elements mediating positive and negative regulation in cells produced by asymmetric cell division in Caenorhabditis elegans.
The homeo box-containing genes mec-3 and unc-86 are necessary to specify the fate of a defined set of mechanoreceptors in Caenorhabditis elegans. Previous experiments have shown that mec-3 expression can be divided into two phases: initial synthesis mediated in part by unc-86, and continued synthesis that requires mec-3 itself. We now identify sequences that have been conserved during Caenorhabditis evolution and are necessary for establishment, maintenance, and repression of mec-3 expression. Upstream of the start codon for the mec-3-coding sequence are four segments (regions I-IV) of 71, 29, 28, and 24 bp, which are almost identical between C. elegans and Caenorhabditis vulgarensis. Region I is the only conserved sequence that effects establishment of mec-3 synthesis. Maintenance of mec-3 expression is mediated primarily by region II. Repression appears to be controlled by several segments: Mutation of region III, region IV, and parts of region I in a mec-3-lacZ fusion results in beta-galactosidase expression in some non-mec-3-expressing sisters of mec-3-positive cells. These results indicate that the mec-3 5' region contains target sequences that mediate a genetic switch between alternative fates expressed by sister cells in a stereotyped cell lineage.


[Rapid nuclear magnetic resonance tomography. Initial results of studies using the new gradient echo sequence].
In 60 patients with intracerebral lesions, examined by MRI, a new gradient-echo sequence was employed. This imaging technique uses excitation pulse angles smaller than 90 degrees and echoes are produced by an inversion of the read gradient. Since no 180 degrees pulse between successive excitations is necessary, very short repetition times can be used. Depending on matrix-size and signal averaging, MR imaging time can be reduced to approximately 5 to 40 seconds for single slice scan. For comparison, conventional T1- and T2-weighted spin-echo images were performed. Diagnostic results of the T1-weighted fast gradient-echo images corresponded with T1-weighted spin-echo images in 30% of cases. Diagnostic information was lower in 40% of cases. In the remainder of cases (30%) lesions were not detected with the gradient-echo technique. This especially applied to multiple sclerosis, infarctions and low-grade gliomas. Due to image artefacts and low contrast, visualization of small pathologic lesions was limited. Significant improvement of tumor visualization on gradient-echo scans was observed after injection of Gd-DTPA (0.1 mmol/kg).


Distribution of genes encoding iron uptake systems among enteroaggregative Escherichia coli strains isolated from adults with irritable bowel syndrome.
The distribution of genes encoding different iron acquisition systems in enteroaggregative Escherichia coli (EAEC) from adults with irritable bowel syndrome and from healthy controls was examined using a PCR assay. As many as 95.5% of EAEC carried the chuA gene coding for a haem receptor, and the majority of these strains also had yersiniobactin-encoding genes. Apart from yersiniobactin, enterobactin was the siderophore most frequently associated with EAEC among those strains examined. Genes encoding aerobactin and salmochelin siderophores were less frequent in the group of EAEC.


Pediatric Tracheal Rhabdomyosarcoma Masquerading as a Granuloma.
We describe a posterior wall intratracheal embryonal rhabdomyosarcoma (RMS) arising in a 6-year-old tracheostomized child masquerading as reactive granulation tissue and review all reported cases of pediatric intratracheal RMS. The child underwent laser debulking of the tumor and postoperative radiation and chemotherapy with no evidence of recurrence at 2-year follow-up. A literature review revealed four previous cases of pediatric primary tracheal or intratracheal RMS, and remission was achieved in all but one case with surgery, chemotherapy, and radiation. Pathologic evaluation of tracheal mucosal granulation tissue may merit consideration, particularly in patients with increased risk factors.


Diagnostic performance of capillary and venous blood samples in the detection of Loa loa and Mansonella perstans microfilaraemia using light microscopy.
Loa loa and Mansonella perstans-the causative agents of loiasis and mansonellosis-are vector-borne filarial parasites co-endemic in sub-Saharan Africa. Diagnosis of both infections is usually established by microscopic analysis of blood samples. It was recently established that the odds for detecting Plasmodium spp. is higher in capillary (CAP) blood than in venous (VEN) blood. In analogy to this finding this analysis evaluates potential differences in microfilaraemia of L. loa and M. perstans in samples of CAP and VEN blood. Recruitment took place between 2015 and 2019 at the CERMEL in Lambaréné, Gabon and its surrounding villages. Persons of all ages presenting to diagnostic services of the research center around noon were invited to participate in the study. A thick smear of each 10 microliters of CAP and VEN blood was prepared and analysed by a minimum of two independent microscopists. Differences of log2-transformed CAP and VEN microfilaraemia were computed and expressed as percentages. Furthermore, odds ratios for paired data were computed to quantify the odds to detect microfilariae in CAP blood versus in VEN blood. A total of 713 participants were recruited among whom 52% were below 30 years of age, 27% between 30-59 years of age and 21% above 60 years of age. Male-female ratio was 0.84. Among 152 participants with microscopically-confirmed L. loa infection median (IQR) microfilaraemia was 3,650 (275-11,100) per milliliter blood in CAP blood and 2,775 (200-8,875) in VEN blood (p<0.0001), while among 102 participants with M. perstans this was 100 (0-200) and 100 (0-200), respectively (p = 0.44). Differences in linear models amount up to an average of +34.5% (95% CI: +11.0 to +63.0) higher L. loa microfilaria quantity in CAP blood versus VEN blood and for M. perstans it was on average higher by +24.8% (95% CI: +0.0 to +60.5). Concordantly, the odds for detection of microfilaraemia in CAP samples versus VEN samples was 1.24 (95% CI: 0.65-2.34) and 1.65 (95% CI: 1.0-2.68) for infections with L. loa and M. perstans, respectively. This analysis indicates that average levels of microfilaraemia of L. loa are higher in CAP blood samples than in VEN blood samples. This might have implications for treatment algorithms of onchocerciasis and loiasis, in which exact quantification of L. loa microfilaraemia is of importance. Furthermore, the odds for detection of M. perstans microfilariae was higher in CAP than in VEN blood which may pre-dispose CAP blood for detection of M. perstans infection in large epidemiological studies when sampling of large blood quantities is not feasible. No solid evidence for a higher odds of L. loa microfilariae detection in CAP blood was revealed, which might be explained by generally high levels of L. loa microfilaraemia in CAP and VEN blood above the limit of detection of 100 microfilariae/ml. Yet, it cannot be excluded that the study was underpowered to detect a moderate difference.


Novel method to analyze post-yield mechanical properties at trabecular bone tissue level.
Tissue level mechanics is a key factor to be investigated to improve the knowledge of how the overall trabecular structure reacts to loading and overloading. The aim of this study was to develop a new device for measuring the mechanical competence of single trabeculae in the post-yield region for both tensile and bending tests, characterized by high accuracy and precision, and to assess the effect of testing mode, donor age and material composition. A novel approach for measuring the displacement and deformation was developed (accuracy error of 0.3% and a precision of 2.7%). A total of 30 samples from two bovine femora of different ages (from <3-year-old and 14-year-old cows) were tested in tension or bending, while average material properties have been acquired by means of Raman spectroscopy. A group of trabeculae was tested in bending after treatment for collagen degradation. As a result, a complete set of post-yield properties has been reported. The results highlight significant differences between tensile and bending groups, with higher values for the bending test mode for yield strain, ultimate strain and post-yield work and lower for the elastic modulus. Significant higher values were found for the old donor (differences in the range of 30-60%) for elastic modulus, yield stress and ultimate stress as well as for material properties measured by Raman spectroscopy. We quantified that changes in materials properties induced by collagen degradation corresponded to a substantial decrease (up to 120% for post-yield work) of mechanical competence, both in the elastic and inelastic region.


Increase in oxidative stress in kidneys of diabetic Akita mice.
New biomarkers for oxidative damage, were used to identify whether hyperglycemia caused oxidative stress in diabetic Akita mice. At 13 weeks of age, the tissues of these mice were obtained, and the levels of N(epsilon)-(hexanonyl)lysine (HEL) and dityrosine (DT) were measured, these being related to lipid peroxide-derived protein covalent modification and protein cross-linking. The levels of HEL and DT in the kidneys of Akita mice were significantly increased compared with the control mice without any accumulation of thiobarbituric acid reactive substances and 4-hydroxy-2-nonenal-modified protein. Immunopositive staining was clearly observed in the kidneys of the Akita mice when using the anti-HEL antibody or anti-DT antibody. These results suggest that hyperglycemia in Akita mice induced oxidative stress and increased these markers in the kidneys.


The relationship between symptoms, depression, and quality of life in peritoneal dialysis patients.
Measurement of patient outcome by mental and social indexes such as quality of life (QOL) in addition to survival is a growing trend. We examined the feasibility of using a single global QOL question in peritoneal dialysis (PD) patients. We also examined the relationship that QOL has with uremic symptoms and depression in these patients. During a clinic visit, each PD patient completed a single-question QOL measure (0-10 scale, 10 being best). Patients' symptoms were assessed using a 10-symptom checklist, with each symptom scored on a Likert scale of 0 (none) to 5 (severe). We evaluated for depression using two questions from the Primary Care Evaluation of Mental Disorders. Serum albumin, hemoglobin, and phosphorus were obtained, but only phosphorus was associated with QOL on univariate analysis (p = 0.05) and therefore included in the multivariate model. Results (checklist score, depression, phosphorus, age, diabetes, and race) were analyzed using a sequential multivariate analysis with QOL as the dependent variable. The study population consisted of 64 PD patients [mean age: 47 +/- 16 years; 25% black; 23% with diabetes; 31% incident (< or =3 months)]. The median score on the single QOL question was 7 (range: 1-10). Patients scored a median of 9 (range: 0-31) out of 50 on the total symptom checklist. Among responding patients, 34% answered yes to at least one depression question. The sequential incremental r2 values associated with a poorer QOL were higher checklist score (r2 = 0.16, p < 0.02), presence of depression (r2 = 0.13, p < 0.00002), younger age (r2 = 0.06, p < 0.03), and presence of diabetes (r2 = 0.04, p < 0.05). In this model, PO4 and race were nonsignificant. Total r2 in the model was 0.48. The single measure of QOL, the checklist score, and the depression screening score were simple and easy to obtain during a routine clinic visit. We conclude that physical symptoms and depression are strongly associated with a simple single measure of QOL. The extent to which symptoms and depression can be improved by clinical intervention, and the subsequent effect on quality of life and survival, should be examined in longitudinal studies.


Integration of Mobile Health Technology in the Treatment of Chronic Pain: A Critical Review.
This article provides a critical overview and best-evidence synthesis of the use of mobile health (mHealth) technology among persons with chronic pain and their health care providers and examines the future benefits and barriers of implementing mHealth technology in clinical care. We critically review articles about electronic pain diaries, pain assessment programs, text messaging, and smartphone pain apps for management of persons with pain. Also presented are findings on the utility of activity trackers and use of telehealth to deliver cognitive behavioral therapy. Finally, barriers, study gaps, and future challenges of incorporating mobile technology for chronic pain are discussed. Although the future of mHealth technology and telemedicine in clinical practice is promising, this critical review highlights the need for rigorous studies to establish an association of the use of mHealth technology with improved quality of life, functional autonomy, and decreased hospital use.


The joint effect and hemodynamic mechanism of PA and PM2.5 exposure on cognitive function: A randomized controlled trial study.
While PM2.5 has been shown to impair cognitive function, physical activity (PA) is known to enhance it. Nonetheless, considering the increased inhalation of PM2.5 during exercise, the potential of PA to counteract the detrimental effects of PM2.5, along with the underlying hemodynamic mechanisms, remains uncertain. We conducted a double-blinded, randomized controlled trial among healthy young adults in Beijing, China. Ninety-three participants were randomly allocated to groups experiencing different intensities of PA interventions, and either subjected to purified or unpurified air conditions. Cognitive function was measured by the Color-Word Matching Stroop task, and the hemodynamic response was measured using functional near-infrared spectroscopy during participants performed the Stroop task both before and after the intervention. Linear mixed-effect models were used to estimate the impact of PA and PM2.5 on cognitive function and hemodynamic response. The reaction time for congruent and incongruent Stroop tasks improved by - 80.714 (95% CI: -136.733, -24.695) and - 105.843 (95% CI: -188.6, -23.085) milliseconds after high-intensity interval training (HIIT) intervention. PM2.5 and HIIT had interaction effects on cognition, such that every 1 μg/m3 increase in PM2.5 attenuated the benefits of HIIT on reaction time by 2.231 (95% CI: 0.523, 3.938) and 3.305 (95% CI: 0.791, 5.819) milliseconds for congruent and incongruent Stroop tasks. Moreover, we divided participants into high and low PM2.5 exposure groups based on average PM2.5 concentration (32.980 μg/m3), and found that HIIT intervention in high PM2.5 concentration led to 69.897 (95% CI: 9.317, 130.476) and 99.269 (95% CI: 10.054, 188.485) milliseconds increased in the reaction time of congruent and incongruent Stroop, compared with the control group among low PM2.5. Furthermore, we found a significant interaction effects of PM2.5 and moderate-intensity continuous training (MICT) on the middle frontal gyrus (MFG) and dorsolateral superior frontal gyrus (DLPFC). PM2.5 and HIIT had a significant interaction effect on the DLPFC. HIIT improved cognitive function, but the cognitive benefits of HIIT were attenuated or even reversed under high PM2.5 exposure. The activation of the DLPFC and MFG could serve as hemodynamic mechanisms to explain the joint effect of PA and PM2.5.


Beta-2-microglobulin in hemodialysis patients. Effects of different dialyzers and different dialysis procedures.
beta 2-Microglobulin (beta 2m) has been identified as the major constituent of dialysis-related amyloid. Although there is no clear correlation between absolute beta 2m levels and amyloidosis-related symptoms, elevated serum levels are thought to be the basis for tissue deposition of beta 2m. Besides diminished renal excretion and insufficient removal during hemodialysis, a dialysis-related induction of beta 2m production is discussed as the major cause of elevated serum beta 2m levels. In order to evaluate the influence of hemodialysis membranes and the hemodialysis procedure on beta 2m levels we determined serum beta 2m levels in patients on chronic intermittent hemodialysis. Polymethylmethacrylate 2.0 m2, cuprophane and cellulose acetate dialyzers led to increasing beta 2m levels during dialysis, which was in excess of what could be accounted for by hemoconcentration. The polymethylmethacrylate 1.6 m2 dialyzer did not result in a significant rise of beta 2m levels during dialysis. This indicates that production of beta 2m is not only dependent on the membrane material but also on the surface area of the dialyzer. The use of polysulfone and hemophane low-flux dialyzers did not induce an increase in beta 2m levels during dialysis but a significant clearance of beta 2m was not demonstrable either. Volume-controlled dialysis with high-flux membranes (polysulfone 0.65 m2 and polysulfone 1.25 m2) lowered beta 2m; clearance values, however, were significantly higher when these dialyzers were used in a hemodiafiltration procedure. We conclude from our study that some dialysis membranes appear to induce beta 2m production, whereas others do not.(ABSTRACT TRUNCATED AT 250 WORDS)


Chick embryo metanephros: the glycosylation pattern as revealed with lectin conjugates.
Fragments of metanephros were taken from chick embryos and studied from the 7th to the 21st d of incubation. A battery of 7 different horseradish peroxidase-labelled lectins (PNA, ConA, DBA, SBA, LTA, WGA and UEA I) was used to analyse the distribution and changes of carbohydrate moieties in glycoconjugates along the metanephric nephron from the S-shaped body stage onwards. DBA and SBA reacted for a short time at some sites during the considered period of incubation. Provided WGA and ConA reacted with most of the nephric components, the almost ubiquitous presence of N-acetyl-D-glucosamine and alpha-D-mannose was demonstrated. SBA and LTA were found to be good markers of the proximal tubule. On the 12th d of incubation, sialic acid was found in the podocytes, capillary walls, and the connecting and collecting ducts. On the same day, other oligosaccharides were present at the nephric tubular components. The simultaneous presence of sialic acid and other sugar residues may be significant for the identification of the exact stage of incubation at which metanephric activity starts. The possible role of some sugar residues for the regulation of metanephric activity is discussed.


Magnetically recoverable Ni/C catalysts with hierarchical structure and high-stability for selective hydrogenation of nitroarenes.
Here we report that magnetic Ni/C catalysts with hierarchical structure can be fabricated from a mixture of nickel acetate, polyethylene glycol-200 and furfural by a one-step hydrothermal method, followed by calcination. It has been found that the calcination temperature is the key factor affecting the structure, morphology and the catalytic performance of the Ni/C catalysts. Of the as-made catalysts, the Ni/C sample calcined at 300 °C features small-size metallic Ni particles with high dispersion in the carbon matrix and a unique hierarchical structure, and has the highest rate of conversion of o-chloronitrobenzene with high selectivity to o-chloroanilines. The concerned Ni/C catalysts are magnetic due to the presence of metallic Ni particles, which makes their recovery easy after the reaction by an external magnetic field. The recovered Ni/C catalysts can be recycled at least ten times without obvious loss both in Ni loading and the catalytic performance. This kind of catalyst is also active for the selective hydrogenation of other nitroarenes to the corresponding anilines.


Late recurrence of nonseminomatous germ cell tumor successfully treated with intensity-modulated radiation therapy.
We report the case of a 41-year-old man with a late recurrence of nonseminomatous germ cell tumor, which was successfully treated with intensity-modulated radiation therapy. For the residual retrocrural tumor invading the 11th and 12th thoracic vertebrae with an abnormal level of tumor marker (α-fetoprotein: 23.2 ng/ml) after salvage chemotherapy, chemotherapy could not be continued due to its neurotoxicity, and surgery could not be performed due to the location. In this situation, intensity-modulated radiation therapy achieved a complete response of tumor marker. The patient remained in complete clinical remission after 3 years. The efficacy of radiotherapy, especially intensity-modulated radiation therapy, for a nonseminomatous germ cell tumor is discussed.


Mutational analysis of the mitochondrial tRNA genes and flanking regions in umbilical cord tissue from uninfected infants receiving AZT-based therapies for prophylaxis of HIV-1.
A sensitive vertical denaturing gradient gel electrophoresis (DGGE) method, using 13 unipolar psoralen-clamped PCR primer pairs, was developed for detecting sequence variants in the 22 tRNA genes and flanking regions (together spanning approximately 21%) of the human mitochondrial genome. A study was conducted to determine (i) if mitochondrial DNA (mtDNA) polymorphisms and/or mutations were detectable in healthy newborns and (ii) if prepartum 3'-azido-2',3'-dideoxythymidine (AZT) based HIV-1 prophylaxis was associated with significant increases in mtDNA mutations and changes in the degree of heteroplasmy of sequence variants in uninfected infants born to HIV-1-infected mothers. DGGE analysis of umbilical cord tissue (where vascular endothelium and smooth muscle cells are the major source of mtDNA) showed that mtDNA sequence variants were significantly elevated by threefold in AZT-treated infants compared with unexposed controls (P < 0.001), with 24 changes observed in 19/52 (37%) treated newborns (averaging 0.46 changes/subject) versus only eight changes found in 7/55 (13%) unexposed newborns (averaging 0.15 changes/subject). Six distinct sequence variants occurring in unexposed controls were predominately synonymous and homoplasmic, representing previously reported polymorphisms. Uninfected infants exposed to a combination of AZT and 2',3'-dideoxy-3'-thiacytidine and "maternal HIV-1" had a significant shift in the spectrum of mutations (P = 0.04) driven by increases in nonsynonymous heteroplasmic sequence variants at polymorphic sites (10 distinct variants) and novel sites (four distinct variants). While the weight of evidence suggests that prepartum AZT-based prophylaxis produces mtDNA mutations, additional research is needed to determine the degree to which fetal responses to maternal HIV-1 infection, in the absence of antiretroviral treatment, contribute to prenatal mtDNA mutagenesis.


Postnephrectomy arteriovenous fistula.
A new case of postnephrectomy arteriovenous fistula is reported. This is an uncommon acquired complication of a common surgical procedure. Clinical features, diagnostic procedures, surgical treatment and results are analysed and discussed. In this case, a direct communication between the right renal artery and the inferior vena cava was found.


Resistance to subcutaneous infection with Mycobacterium lepraemurium is controlled by more than one gene.
The resistance of C57BL (high) and BALB/c (low) mice, their F1 hybrids, and the offspring derived from backcrosses of the F1 to both parental strains was assessed at 20 weeks after subcutaneous infection with 10(7) Mycobacterium lepraemurium organisms. The numbers of bacilli recovered from the infected foot and draining lymph node indicated that resistance to subcutaneous infection is controlled by more than one non-H-2-linked gene of intermediate dominance. In general, female mice were more resistant than males.


Crystal structure of the kinase domain of human protein tyrosine kinase 6 (PTK6) at 2.33 Å resolution.
Human Protein tyrosine kinase 6 (PTK6) (EC:22.214.171.124), also known as the breast tumor kinase (BRK), is an intracellular non-receptor Src-related tyrosine kinase expressed in a majority of human breast tumors and breast cancer cell lines, but its expression is low or completely absent in normal mammary glands. In the recent past, several studies have suggested that PTK6 is a potential therapeutic target in cancer. To understand its structural and functional properties, the PTK6 kinase domain (PTK6-KD) gene was cloned, overexpressed in a baculo-insect cell system, purified and crystallized at room temperature. X-ray diffraction data to 2.33 Å resolution was collected on a single PTK6-KD crystal, which belonged to the triclinic space group P1. The Matthews coefficient calculation suggested the presence of four protein molecules per asymmetric unit, with a solvent content of ∼50%.The structure has been solved by molecular replacement and crystal structure data submitted to the protein data bank under the accession number 5D7V. This is the first report of apo PTK6-KD structure crystallized in DFG-in and αC-helix-out conformation.


Asthma in Head Start children: prevalence, risk factors, and health care utilization.
1. To identify the prevalence and severity of asthma in a Massachusetts Head Start program; 2. To identify associated risk factors for children with asthma; 3. To assess factors associated with health care utilization for asthma management. Parents of 316 Head Start children were interviewed using a close-ended survey questionnaire. Survey A was used for demographics and general health screening. Survey B documented more specific asthma information. There was a 35% prevalence rate of asthma in this preschool Head Start population. Most children had mild to moderate degrees of severity. Atopy, environmental triggers, and tobacco smoke exposure were common risk factors. Seventy-four percent of these children with asthma had used the emergency department at least once in their lifetime for asthma management. Forty-one percent had been hospitalized at least one time for asthma. These findings are consistent with previous studies that support the need for asthma outreach and interventions in at-risk Head Start preschool populations.


[Effects of p53 in benzo (a) pyrene induced p21 and E2F-1 expression and cell cycle changes].
To investigate the roles of p53 in cell cycle changes on human embryo lung fibroblasts (HELF) induced by benzo(a) pyrene[ B(a) P], and relationships between p53 and p21, E2F-1. Cells transfected with p53 siRNA plasmid (p53-H) and CMV vector (HELF/CMV) were cultured with serum-free R/MINI-1640 for 48 hours, then treated with 2 micromol/L B(a)P for 24 hours. Flow cytometry assay was used for detecting the cell cycle alteration after being exposed to B(a)P. Changes of p53 and p21 expressions were checked using Western blot assay, and the cytoplasmic and nuclear extraction was used to observe the subcellular localizations of p53 and p21. The immunofluorescence assay was used to check changes of E2F-1 expression and the distribution of E2F-1 in nuclear and cytoplasm after exposed to B (a)P. p53siRNA plasmid and the chemical inhibitor of p53 [pifithrin-alpha (PFT)] were used to observe effects of p53 in B(a)P induced cell cycle changes and the relationships of p53 and p21, E2F-1. After 2 micromol/L B(a)P exposure, the ratio of G1 phase cells (71 +/- 5)% was decreased to (39 +/- 4)% (P < 0.05). p53, p21 and E2F-1 expressions were increased significantly, and over expressed proteins were mostly located in nuclear after B(a)P treatment. When p53 expression was inhibited by p53 siRNA or PFT, the decreases of G1 phase in response to B(a)P treatment still existed, and over expression of p21 induced by B(a)P was attenuated, especially in nuclear, but E2F-1 over expression was not changed significantly. B(a)P could induce cell cycle changes through p53 independent pathways. And p53 could regulate p21 expression positively, but not E2F-1.


Orthopaedic care of the aging athlete.
Increasing numbers of middle-aged and older adults participate in sports, and athletes wish to remain active as they age. Understanding the anatomic, physiologic, and psychosocial differences between older and younger athletes can help aging athletes maintain function. Athletic capacity may be sustained well into advanced age, and many of the physiologic consequences of aging may be mitigated or reversed by regular exercise. Most injuries in older athletes are chronic and overuse injuries that result in diminished flexibility and endurance. In addition, many aging athletes have medical and musculoskeletal problems that mandate tailoring athletic activity to the patient's general health and functional requirements.


Chronic obstructive pulmonary disease assessment test: usefulness for monitoring recovery and predicting poor course of disease after exacerbations.
To assess the usefulness of the chronic obstructive pulmonary disease (COPD) assessment test (CAT) for evaluating recovery from an acute exacerbation of chronic COPD. To assess whether the CAT score used along with a COPD exacerbation severity scale can better predict risk of a poor course of disease. Prospective multicenter cohort study enrolling patients who attended hospital emergency departments with symptoms of exacerbated COPD. We recorded sociodemographic and clinical data and information from 2 questionnaires: the CAT and the modified dyspnea scale of the Medical Research Council (mMRC). Measures of clinical outcome in this study were the CAT score 2 months after the COPD exacerbation and poor course of disease during the hospital stay or 1 week after discharge from the emergency department if patients were not hospitalized. The cohort included 501 patients. The median (interquartile range) CAT score was 13 (7-18) on the day before the exacerbation, 25 (19-30) during emergency care for the exacerbation, and 13 (7-18) 2 months later. The difference between the CAT scores before the exacerbation and 2 months later was not statistically significant when the cohort was stratified by severity of baseline COPD (mild, moderate, and severe/very severe) (P=.585, P=.419, and P=.4357). The short-term course of disease was poor for 91 patients (18.16%). Combining the mMRC and the CAT scores to predict poor short-term outcome gave an area under the receiver operating characteristic curve (AUC) of 0.701 (95% CI, 0.640-0.762). The AUC for the mMRC score without the CAT score was 0.667 (95% CI, 0.616- 0.737). The difference between the AUCs was not statistically significant (P=.088). The CAT score may be useful for monitoring recovery from a COPD exacerbation. Combining the CAT score and a COPD severity score may be useful for predicting clinical course after an exacerbation.


APOEε4 and slow wave sleep in older adults.
Slow wave (or stage N3) sleep has been linked to a variety of cognitive processes. However, the role of stage N3 in the elderly is debated. The link between stage N3 and episodic memory may be weakened or changed in the older adult population, possibly due to several altered mechanisms impacting the cellular structure of the brain. The bases for the age-related dissociation between stage N3 and cognition are not understood. Since APOEε4 status is the strongest genetic risk factor for cognitive decline, we assessed whether the ε4 allele is associated with stage N3 sleep. Participants were from the population-based Osteoporotic Fractures in Men (MrOS) cohort with polysomnography and APOEε4 genotype data (n = 2,302, 100% male, mean age 76.6 years). Sleep stages were objectively measured using overnight in-home polysomnography and central electroencephalogram data were used to score stage N3 sleep. Cognitive function was assessed using the Modified Mini Mental State Exam (3MS). The APOE rs429358 single nucleotide polymorphism, which defines the APOEε4 allele, was genotyped using a custom genotyping array. Total time in stage N3 sleep was significantly higher (p<0.0001) among the 40 MrOS participants carrying two copies of the ε4 allele (62±5.2 minutes) compared with 43±1.5 minutes for carriers of one ε4 allele (n = 515) and 40±0.8 minutes for ε4 non-carriers (n = 1747). All results were independent of sleep efficiency, number of sleep cycles, and apnea hypopnea index. These findings support an association between APOEε4 genotype and sleep stage N3 in the elderly. Increased total stage N3 duration among ε4/ε4 carriers does not appear to reflect compensation for prior cognitive decline and may reflect overactive downscaling of synapses during sleep. If confirmed, these results might in part explain the high risk of age-related cognitive decline and AD among APOE ε4/ε4 carriers.


Platelets from WAS patients show an increased susceptibility to ex vivo phagocytosis.
The thrombocytopenia of Wiskott-Aldrich syndrome (WAS) is thought to be due to both reduced platelet production and accelerated platelet consumption. We have previously demonstrated that platelets from WASP-deficient mice are consumed more rapidly in vivo than are WT platelets, and that opsonization accelerates their uptake by bone marrow- derived macrophages more than it does that of WT platelets. Here we asked whether platelets from WAS patients show similar features. We show that ex vivo phagocytosis by activated THP-1 cells of DIO-labeled platelets from a series of WAS or XLT patients is increased in comparison to that of normal control platelets. Using a numerical analysis method, we distinguish this effect from a concurrent effect on the amount of detectable fluorescent signal transferred to the macrophage per phagocytosed platelet. We show that the latter quantity is reduced by platelet WASP deficiency, as might be expected if the fluorescence transferred from these smaller platelets is more rapidly quenched. We are unable to detect a differential effect of opsonization with anti-CD61 antibody on the uptake of WASP(-) vs. WT platelets. However, the high probability of phagocytosis per adsorbed WASP(-) platelet could limit the sensitivity of the assay in this case. We also see no effect of sera from WAS patients on the uptake of normal control platelets, suggesting that in vivo opsonization is not the cause of increased uptake of WASP(-) platelets. Finally, we show little, if any, increase in the reticulated platelet fraction in WAS patients, suggesting that impaired production of reticulated platelets contributes to the thrombocytopenia. Our findings suggest that rapid in vivo platelet consumption contributes significantly to the thrombocytopenia of WAS. They also demonstrate the feasibility of routinely performing functional assays of phagocytosis of small numbers of platelets obtained at remote locations, a method which should be applicable to the study of other types of thrombocytopenia such as ITP.


Human Botfly: A Case Report and Overview of Differential Diagnosis.
Dermatobia hominis, commonly known as the human botfly, is native to Tropical America. As such, cutaneous infestation by its developing larvae, or myiasis, is quite common in this region. The distinct dermatological presentation of D hominis myiasis allows for its early recognition and noninvasive treatment by locals. However, it can prove quite perplexing for those unfamiliar with the lesion's unique appearance. Common erroneous diagnoses include the following: folliculitis, benign dermatocyst, and embedded foreign body with localized infection. We present a patient who acquired D hominis while she was in Belize. In this report, we discuss the presentation, differential diagnosis, diagnostic tests, and therapeutic approaches of human botfly lesion to raise the awareness about human botfly.


p66 Shc tumor levels show a strong prognostic correlation with disease outcome in stage IIA colon cancer.
Most stage IIA colon cancer patients receive no adjuvant therapy despite an estimated 15% risk of disease-related death within 5 years of resection. Prognostication of disease outcome would benefit the clinician by categorizing patients with stage IIA disease by risk. The abundance of the signal transduction proteins p66 Shc and tyrosine-phosphorylated (PY)-Shc in tumor cells is a prognostic indicator of disease outcome in breast cancer, suggesting that Shc analysis may provide prognostic information in stage IIA colon cancer. Immunohistochemical staining of p66 Shc and PY-Shc was examined in resection specimens from 240 chemotherapy-naïve patients with stage IIA (T(3)N(0)M(0)) colon cancer from two independent (130 and 110 cases, respectively) retrospective cohorts. Staining was scored on a 0 to 5 scale and correlated with relapse-free survival and disease-specific survival in a multivariate analysis to obtain hazard ratios (HR) for both outcomes. In a pooled analysis of both cohorts, p66 Shc score was a significant prognostic indicator of relapse-free survival (full-range HR, 13.0; P = 0.012) and disease-specific survival (full-range HR, 36.6; P = 0.004) when analyzed as a continuous variable in a multivariate Cox proportional hazards model stratified by study site and adjusted for age, sex, grade, and lymphovascular involvement. PY-Shc in this multivariate Cox model, however, did not achieve statistical significance for either outcome. Measuring p66 Shc tumor levels provides a unique and simple tool for stratifying stage IIA colon cancer patients by risk of recurrence and disease-specific death and may assist in determining treatment strategies for these patients.


Acute and chronic changes in rat soleus muscle after high-fat high-sucrose diet.
The effects of obesity on different musculoskeletal tissues are not well understood. The glycolytic quadriceps muscles are compromised with obesity, but due to its high oxidative capacity, the soleus muscle may be protected against obesity-induced muscle damage. To determine the time-course relationship between a high-fat/high-sucrose (HFS) metabolic challenge and soleus muscle integrity, defined as intramuscular fat invasion, fibrosis and molecular alterations over six time points. Male Sprague-Dawley rats were fed a HFS diet (n = 64) and killed at serial short-term (3 days, 1 week, 2 weeks, 4 weeks) and long-term (12 weeks, 28 weeks) time points. Chow-fed controls (n = 21) were killed at 4, 12, and 28 weeks. At sacrifice, animals were weighed, body composition was calculated (DXA), and soleus muscles were harvested and flash-frozen. Cytokine and adipokine mRNA levels for soleus muscles were assessed, using RT-qPCR Histological assessment of muscle fibrosis and intramuscular fat was conducted, CD68+ cell number was determined using immunohistochemistry, and fiber typing was assessed using myosin heavy chain protein analysis. HFS animals demonstrated significant increases in body fat by 1 week, and this increase in body fat was sustained through 28 weeks on the HFS diet. Short-term time-point soleus muscles demonstrated up-regulated mRNA levels for inflammation, atrophy, and oxidative stress molecules. However, intramuscular fat, fibrosis, and CD68+ cell number were similar to their respective control group at all time points evaluated. Therefore, the oxidative capacity of the soleus may be protective against diet-induced alterations to muscle integrity. Increasing oxidative capacity of muscles using aerobic exercise may be a beneficial strategy for mitigating obesity-induced muscle damage, and its consequences.


Determination of cut-off cycle threshold values in routine RT-PCR assays to assist differential diagnosis of norovirus in children hospitalized for acute gastroenteritis.
Norovirus (NV) is an important cause of acute gastroenteritis in children, but is also frequently detected in asymptomatic children, which complicates the interpretation of NV detection results in both the clinical setting and population prevalence studies. A total of 807 faecal samples from children aged <5 years hospitalized for acute gastroenteritis were collected in Thai Binh, Vietnam, from January 2011 to September 2012. Real-time RT-PCR was used to detect and quantify NV-RNA in clinical samples. A bimodal distribution of cycle threshold (Ct) values was observed in which the lower peak was assumed to represent cases for which NV was the causal agent of diarrhoea, whereas the higher peak was assumed to represent cases involving an alternative pathogen other than NV. Under these assumptions, we applied finite-mixture modelling to estimate a threshold of Ct <21·36 (95% confidence interval 20·29-22·46) to distinguish NV-positive patients for which NV was the likely cause of diarrhoea. We evaluated the validity of the threshold through comparisons with NV antigen ELISA results, and comparisons of Ct values in patients co-infected with rotavirus. We conclude that the use of an appropriate cut-off value in the interpretation of NV real-time RT-PCR results may improve differential diagnosis of enteric infections, and could contribute to improved estimates of the burden of NV disease.


SARS-CoV-2 Infection Inducing Immune Thrombocytopenic Purpura: Case Series.
Background: Immune thrombocytopenic purpura (ITP) refers to immune-mediated destruction of platelets. Viral infections have been proposed as an etiology of ITP; antibodies developed in response to infection may cross-react with normal platelets and result in their destruction. Case Series: We report 2 cases in which coronavirus disease 2019 (COVID-19) likely induced severe ITP. Conclusion: ITP may also play a role in the thrombocytopenia observed in some patients with COVID-19. ITP in this patient population may be more prevalent than currently documented.


A Case of Flecainide-Induced Hyponatremia.
The complex classification for the diagnosis and treatment illustrates that hyponatremia is a very heterogeneous disorder. However, data on hyponatremia induced by flecainide, an often-prescribed antiarrhythmic agent, are scarce in the literature. A 78-year-old man with a recent history of recurrent hyponatremia and symptomatic paroxysmal atrial fibrillation presented with the complaints of dizziness and fatigue. During his repeated hospital admissions, the patient was treated with hypertonic saline, which temporarily improved serum sodium levels, but hyponatremia recurred without sustained clinical improvement. After discontinuation of the drug, the sodium levels remained stable. Doctors should be aware of not only the electrocardiographic changes associated with flecainide, but also the less-often found clinical manifestations linked with hyponatremia.


Efficient Pd-Catalyzed Regio- and Stereoselective Carboxylation of Allylic Alcohols with Formic Acid.
Formic acid is efficiently used as a C1 source to directly carboxylate allylic alcohols in the presence of a low loading of palladium catalyst and acetic anhydride as additive to afford β,γ-unsaturated carboxylic acids with excellent chemo-, regio-, and stereoselectivity. The reaction proceeds through a carbonylation process with in situ-generated carbon monoxide under mild conditions, avoiding the use of high-pressure gaseous CO. A bisphosphine ligand with a large bite angle (4,5-bis{diphenylphosphino}-9,9-dimethylxanthene, Xantphos) was found to be uniquely effective for this transformation. The regio- and stereoconvergence of this reaction is ascribed to the thermodynamically favored isomerization of the allylic electrophile in the presence of the palladium catalyst.


Relationship of VH and VL genes encoding three idiotypic families of anti-p-azobenzenearsonate antibodies.
We describe here an intrastrain, cross-reactive idiotype (CRI), CRID, associated with anti-p-azobenzenearsonate antibodies of the A/J strain of mouse and distinguishable, by some but not by all of its idiotopes, from the major anti-p-azobenzenearsonate idiotype (CRIA). Molecules carrying the CRID idiotype have heavy chain variable-segment sequences that are identical or nearly identical to that of the germ-line-encoded heavy chain variable sequence of CRIA. Their light chain variable sequences are very similar to those present in a third idiotypic family, CRIC, that is a minor CRI in the A/J strain but a major CRI in BALB/c. This appears to represent a form of combinational diversity, in which the heavy and light chain variable region genes of two unrelated idiotypic families interact to form a third family, all involving antibodies of the same antigen-binding (anti-p-azobenzenearsonate) specificity. The D region of CRID, in the six monoclonal representatives studied (three IgMs, three IgGs), is unusual in that it comprises a single amino acid--arginine or serine; there are eight amino acids in the D region of CRI+A antibodies. Three different heavy chain joining regions, JH1, JH2, and JH3, are utilized. A serological reagent was developed that identifies CRID; it was used to show that the idiotype is present in relatively high concentration, comparable to that of CRIA, in anti-p-azobenzenearsonate antibodies taken soon after primary immunization. In serum taken later CRIA greatly predominates, but CRID persists at low levels.


Angular and energy distribution of fragment ions in dissociative double photoionization of acetylene molecules at 39 eV.
The two-body dissociation reactions of the dication, C(2)H(2)(2+), produced by 39.0 eV double photoionization of acetylene molecules, have been studied by coupling photoelectron-photoion-photoion coincidence and ion imaging techniques. The results provide the kinetic energy and angular distributions of product ions. The analysis of the results indicates that the dissociation leading to C(2)H(+)+H(+) products occurs through a metastable dication with a lifetime of 108±22 ns, and a kinetic energy release (KER) distribution exhibiting a maximum at ∼4.3 eV with a full width at half maximum (FWHM) of about 60%. The reaction leading to CH(2)(+)+C(+) occurs in a time shorter than the typical rotational period of the acetylene molecules (of the order of 10(-12) s). The KER distribution of product ions for this reaction, exhibits a maximum at ∼4.5 eV with a FWHM of about 28%. The symmetric dissociation, leading to CH(+)+CH(+), exhibits a KER distribution with a maximum at ∼5.2 eV with a FWHM of 44%. For the first two reactions the angular distributions of ion products also indicate that the double photoionization of acetylene occurs when the neutral molecule is mainly oriented perpendicularly to the light polarization vector.


When does modifying the protocol go too far? Considerations for implementing evidence-based treatment in practice.
The majority of evidence-based psychological treatments (EBTs) are packaged as manuals that provide guidance regarding when and how to deliver specific interventions (e.g., cognitive restructuring, exposure). However, clinical practice regularly necessitates flexibility in the timing and delivery of treatment strategies. Indeed, research on the dissemination and implementation of EBTs has highlighted the need to adapt these treatments to fit the needs of specific settings or patient populations. Adapting a treatment also means changing it from its original, evidence-based format, raising questions about how much or in which ways a treatment can be altered before it is no longer reflective of the original EBT. The purpose of this article is to discuss factors that contribute to the challenge of adapting EBTs, highlight considerations for clinicians with regard to modifying EBTs, and propose directions for future research that can provide guidelines for adapting EBTs in the future. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Rapid head-pose detection for automated slice prescription of fetal-brain MRI.
In fetal-brain MRI, head-pose changes between prescription and acquisition present a challenge to obtaining the standard sagittal, coronal and axial views essential to clinical assessment. As motion limits acquisitions to thick slices that preclude retrospective resampling, technologists repeat ~55-second stack-of-slices scans (HASTE) with incrementally reoriented field of view numerous times, deducing the head pose from previous stacks. To address this inefficient workflow, we propose a robust head-pose detection algorithm using full-uterus scout scans (EPI) which take ~5 seconds to acquire. Our ~2-second procedure automatically locates the fetal brain and eyes, which we derive from maximally stable extremal regions (MSERs). The success rate of the method exceeds 94% in the third trimester, outperforming a trained technologist by up to 20%. The pipeline may be used to automatically orient the anatomical sequence, removing the need to estimate the head pose from 2D views and reducing delays during which motion can occur.