A small molecule BCL6 inhibitor as chemosensitizers in acute myeloid leukemia.
BCL6 is a transcriptional repressor that regulates multiple genes involved in immune cell differentiation, DNA damage repair, cell cycle, and apoptosis, and is a carcinogenic factor in acute myeloid leukemia (AML). AML is one of the four major types of leukemia with the 5-year survival rate of patients is less than 20% and chemotherapy resistance remains the major obstacle to the treatment failure of AML. We identified WK499, a small molecule compound that can bind to BCL6BTB structure. Treatment with WK499 hinders the interactions between BCL6 with its corepressor proteins, resulting in a remarkable change of BCL6 downstream genes and anti-proliferative effects in AML cells, and inducing cell cycle arrest and apoptosis. We verified that AraC and DOXo could induce BCL6 expression in AML cells, and found that WK499 had a synergistic effect when combined with chemotherapeutic drugs. We further proved that WK499 and AraC could achieve a better result of inhibiting the growth of AML in vivo. These findings indicate that WK499, a small molecule inhibitor of BCL6, not only inhibits the proliferation of AML, but also provides an effective therapeutic strategy for increasing AML sensitivity to chemotherapy.


Enzymic glycosphingolipid synthesis on polymer supports. III. Synthesis of GM3, its analog [NeuNAcalpha(2-3)Galbeta(1-4)Glcbeta(1-3)Cer] and their lyso-derivatives.
Two water-soluble polymers, carrying 0.24 meq g(-1) of lactosyl-beta(1-1)-sphingosine (7) and 0.13 meq g(-1) of lactosyl-beta(1-3)-sphingosine (8) were prepared. The polymers served as acceptors in the alpha-(2-3)-sialyltransferase reaction (up to 55.3 and 38.5% transfer yields, respectively). Subsequent photolysis, released compounds 11 (lyso-GM3) and 12 (lyso-GM3 analog), respectively; acylation and chromatography afforded (5-acetamido-3,5-dideoxy-D-glycero-alpha-galacto-2-nonulopyranosyloni c acid)-(2-3)-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl-(1-1)-(2 S, 3R, 4E)-2-octadecanoylamino-4-octadecene-1,3-diol (13, GM3) and (5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylo nic acid)-(2-3)-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl-(1-3)-(2 S, 3R, 4E)-2-octadecanoylamino-4-octadecene-1,3-diol (14, GM3 analogue), respectively, thus presenting a route to glycosphingolipids possessing the unusual glycosyl-beta(1-3)-spingosine linkage.


Pandemic fatigue impact on COVID-19 spread: A mathematical modelling answer to the Italian scenario.
The COVID-19 outbreak has generated, in addition to the dramatic sanitary consequences, severe psychological repercussions for the populations affected by the pandemic. Simultaneously, these consequences can have related effects on the spread of the virus. Pandemic fatigue occurs when stress rises beyond a threshold, leading a person to feel demotivated to follow recommended behaviours to protect themselves and others. In the present paper, we introduce a new susceptible-infected-quarantined-recovered-dead (SIQRD) model in terms of a system of ordinary differential equations (ODE). The model considers the countermeasures taken by sanitary authorities and the effect of pandemic fatigue. The latter can be mitigated by fear of the disease's consequences modelled with the death rate in mind. The mathematical well-posedness of the model is proved. We show the numerical results to be consistent with the transmission dynamics data characterising the epidemic of the COVID-19 outbreak in Italy in 2020. We provide a measure of the possible pandemic fatigue impact. The model can be used to evaluate the public health interventions and prevent with specific actions the possible damages resulting from the social phenomenon of relaxation concerning the observance of the preventive rules imposed.


Brain-derived neurotrophic factor and Alzheimer's disease: physiopathology and beyond.
Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system where it plays several pivotal roles in synaptic plasticity and neuronal survival. As a consequence, BDNF became a key target in the physiopathology of several neurological and psychiatric diseases. Recent studies have reported altered levels of BDNF in the circulation, i.e. serum or plasma, of patients with Alzheimer's disease (AD), and low BDNF levels in the CSF as predictor of future cognitive decline in healthy older subjects. Altered BDNF circulating levels have also been reported in other neurodegenerative and psychiatric disorders, hampering its use as a specific biomarker for AD. Therefore, BDNF seems to be an unspecific biomarker of neuropsychiatric disorders marked by neurodegenerative changes.


Optimising the sensing volume of OPM sensors for MEG source reconstruction.
Magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs) has been hailed as the future of electrophysiological recordings from the human brain. In this work, we investigate how the dimensions of the sensing volume (the vapour cell) affect the performance of both a single OPM-MEG sensor and a multi-sensor OPM-MEG system. We consider a realistic noise model that accounts for background brain activity and residual noise. By using source reconstruction metrics such as localization accuracy and time-course reconstruction accuracy, we demonstrate that the best overall sensitivity and reconstruction accuracy are achieved with cells that are significantly longer and wider that those of the majority of current commercial OPM sensors. Our work provides useful tools to optimise the cell dimensions of OPM sensors in a wide range of environments.


Association of Metabolic Syndrome with Serum Adipokines in Community-Living Elderly Japanese Women: Independent Association with Plasminogen Activator-Inhibitor-1.
Associations between metabolic syndrome (MetS) with serum adipokines and basal lipoprotein lipase mass (serum LPL) have not been extensively studied in elderly Asians, who in general have lower body mass index than European populations. A cross-sectional analysis was conducted including 159 community-living elderly Japanese women whose age averaged 77 years. MetS was defined by the modified National Cholesterol Education Program Adult Treatment Panel III criteria, but using a body mass index ≥25 kg/m(2) instead of waist circumference. Serum LPL, leptin, adiponectin, plasminogen activator inhibitor 1 (PAI-1), interleukin-6, tumor necrosis factor-alpha, and high-sensitivity C-reactive protein were measured. Both the presence of MetS and the number of MetS components were associated with higher homeostasis assessment of insulin resistance, serum levels of leptin, PAI-1, and tumor necrosis factor-alpha and with lower serum levels of LPL and adiponectin (all P < 0.05), but not with high-sensitivity C-reactive protein and interleukin-6. Among six biomarkers of MetS, PAI-1 remained associated with MetS independent of fat mass index and insulin resistance. Although proinflammatory, prothrombotic, and anti-inflammatory states were associated with MetS, higher PAI-1 was associated with MetS independent of fat mass index and insulin resistance in elderly Japanese women, in whom obesity is rare.


A novel synthetic trivalent single chain variable fragment (tri-scFv) construction platform based on the SpyTag/SpyCatcher protein ligase system.
Advances in antibody engineering provide strategies to construct recombinant antibody-like molecules with modified pharmacokinetic properties. Multermerization is one strategy that has been used to produce antibody-like molecules with two or more antigen binding sites. Multimerization enhances the functional affinity (avidity) and can be used to optimize size and pharmacokinetic properties. Most multimerization strategies involve genetically fusing or non-covalently linking antibody fragments using oligomerization domains. Recent studies have defined guidelines for producing antibody-like molecules with optimal tumor targeting properties, which require intermediates size (70-120 kDa) and bi- or tri-valency. We described a highly modular antibody-engineering platform for rapidly constructing synthetic, trivalent single chain variable fragments (Tri-scFv) using the SpyCatcher/SpyTag protein ligase system. We used this platform to construct an anti-human epidermal growth factor receptor 3 (HER3) Tri-scFv. We generated the anti-HER3 Tri-scFv by genetically fusing a SpyCatcher to the C-terminus of an anti-HER3 scFv and ligating it to a synthetic Tri-SpyTag peptide. The anti-HER3 Tri-scFv bound recombinant HER3 with an apparent KD of 2.67 nM, which is approximately 12 times lower than the KD of monomeric anti-HER3 scFv (31.2 nM). Anti-HER3 Tri-scFv also bound endogenous cell surface expressed HER3 stronger than the monomer anti-HER3 scFv. We used the SpyTag/SpyCatcher protein ligase system to ligate anti-HER3 scFv fused to a SpyCatcher at its C-termini to a Tri-SpyTag to construct Tr-scFv. This system allowed the construction of a Tri-scFv with all the scFv antigen-binding sites pointed outwards. The anti-HER3 Tri-scFv bound recombinant and endogenously expressed HER3 with higher functional affinity (avidity) than the monomeric anti-HER3 scFv. The Tri-scFv had the size, valency, and functional affinity that are desired for therapeutic and imaging applications. Use of the SpyTag/SpyCatcher protein ligase system allows Tri-scFvs to be rapidly constructed in a simple, modular manner, which can be easily applied to scFvs or other antibody fragments targeting other antigens.


Mitigating biomass composition uncertainties in flux balance analysis using ensemble representations.
The biomass equation is a critical component in genome-scale metabolic models (GEMs): it is used as the de facto objective function in flux balance analysis (FBA). This equation accounts for the quantities of all known biomass precursors that are required for cell growth based on the macromolecular and monomer compositions measured at certain conditions. However, it is often reported that the macromolecular composition of cells could change across different environmental conditions and thus the use of the same single biomass equation in FBA, under multiple conditions, is questionable. Herein, we first investigated the qualitative and quantitative variations of macromolecular compositions of three representative host organisms, Escherichia coli, Saccharomyces cerevisiae and Cricetulus griseus, across different environmental/genetic variations. While macromolecular building blocks such as RNA, protein, and lipid composition vary notably, changes in fundamental biomass monomer units such as nucleotides and amino acids are not appreciable. We also observed that flux predictions through FBA is quite sensitive to macromolecular compositions but not the monomer compositions. Based on these observations, we propose ensemble representations of biomass equation in FBA to account for the natural variation of cellular constituents. Such ensemble representations of biomass better predicted the flux through anabolic reactions as it allows for the flexibility in the biosynthetic demands of the cells. The current study clearly highlights that certain component of the biomass equation indeed vary across different conditions, and the ensemble representation of biomass equation in FBA by accounting for such natural variations could avoid inaccuracies that may arise from in silico simulations.


Virus-induced lesions and the fetal brain: examples of the transmission of HIV-1 and CMV from mother to offspring.
Human immunodeficiency virus 1 (HIV-1) and cytomegalovirus (CMV) are among the most frequently transmitted viruses from an infected mother to her offspring. The clinical consequences of transmission depend heavily on the time of transmission, the virus concerned, and maternal status. This chapter describes first the natural course of neurological aspects of HIV-1 infection and the way in which it has been modified by HAART in developed countries. It then describes the situation in the African context (taking Cameroon as an example) where HAART is not readily available and the natural course of the disease may be different. Finally, we consider the possible toxic effects on the developing central nervous system of antiretroviral drug administration during pregnancy. Congenital CMV infection leads to a wide spectrum of symptoms and is not always apparent at birth. When CMV infection occurs early during gestation, it disturbs the neurogenesis of the central nervous system while late-onset CMV infection affects brain growth and the development of the white matter, leading to leukomalacia and cyst formation, usually associated with intraparenchymatous calcifications. Neurosensory hearing loss frequently occurs and may be the only symptom in cases of perinatal infection.


Resveratrol protects against atherosclerosis, but does not add to the antiatherogenic effect of atorvastatin, in APOE*3-Leiden.CETP mice.
Resveratrol is a major constituent of traditional Asian medicinal herbs and red wine and is suggested to be a potential antiatherosclerotic drug due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate whether resveratrol protects against atherosclerosis development in APOE*3-Leiden.CETP (E3L.CETP) mice and adds to the antiatherogenic effect of mild statin treatment, currently the most widely used antiatherogenic therapy. E3L.CETP mice were fed a cholesterol-rich diet without (control) or with resveratrol (0.01% w/w), atorvastatin (0.0027% w/w) or both for 14 weeks. During the study plasma lipid, inflammatory and oxidative stress parameters were determined. Resveratrol reduced atherosclerotic lesion area (-52%) in the aortic root, comparable to atorvastatin (-40%) and the combination of both drugs (-47%). The collagen/macrophage ratio in the atherosclerotic lesion, a marker of plaque stability, was increased by resveratrol (+108%), atorvastatin (+124%) and the combination (+154%). Resveratrol decreased plasma cholesterol levels (-19%) comparable to atorvastatin (-19%) and the combination (-22%), which was completely confined to (very)low-density lipoprotein cholesterol levels in all groups. Post hoc analyses showed that the antiatherogenic effect of atorvastatin could be explained by cholesterol lowering, while the antiatherosclerotic effect of resveratrol could be attributed to factors additional to cholesterol lowering. Markers of inflammation and oxidative stress were not different, but resveratrol improved macrophage function. We conclude that resveratrol potently reduces atherosclerosis development and induces a more stable lesion phenotype in E3L.CETP mice. However, under the experimental conditions tested, resveratrol does not add to the antiatherogenic effect of atorvastatin.


A Novel Web-Based and Mobile Application to Measure Real-Time Moral Distress: An Initial Pilot and Feasibility Study.
Moral distress (MoD) is a vital clinical indicator linked to clinician burnout and provider concerns about declining patient care quality. Yet it is not routinely assessed. Earlier, real-time recognition may better target interventions aimed at alleviating MoD and thereby increase provider well-being and improve patient care quality. Combining two validated MoD instruments (the Moral Distress Thermometer [MDT] and the Measure of Moral Distress for Healthcare Professionals [MMD-HP]), the authors developed a novel mobile and Web-based application environment to measure and report levels MoD and their associated causes. This app was tested for basic feasibility and acceptability in two groups: graduate nursing students and practicing critical care nurses. The MDT app appears feasible and acceptable for future use. All participants (n = 34) indicated the MDT app was satisfying to use, and 91.2% (n = 31) indicated the app was "very appropriate" for measuring MoD. In addition, 84.2% (n =16) of practicing nurses indicated the app fit either "somewhat well" (47.4%, n = 9) or "very well" (36.8%, n = 7) into their typical workday, and 68.4% (n = 13) said they were either "extremely likely" or "somewhat likely" to use the app daily in clinical practice. Education about moral distress and its associated causes proved important to the MDT app's success. It is ready for future validity and reliability testing, as well as examining usability beyond nursing, longitudinal data monitoring, and possible leveraging to pre- and postintervention evaluation studies.


Prediction of biopersistence of hydrocarbons using a single parameter.
Aerobic biodegradation is an important attenuation process for petroleum hydrocarbons (PHCs) in the natural environment. It has also been frequently used in engineered systems to remediate PHC-contaminated sites. A model such as a quantitative structure property relationship (QSPR) that can predict the biodegradation rate of PHCs would be helpful prior to implementing any extensive environmental measurements and bioremediation strategies. Existing QSPRs either have a large number of predictor variables that may cause overfitting or are based on a small dataset of PHCs. The goal of this study is to develop a simple, portable QSPR that has only a few predicator variables but can accurately predict the biodegradation half-lives of a large group of PHCs. To this end, more than 500 molecular variables were screened, and candidate variables were refined by a feature selection method and fitted to biodegradation data of a group of structurally heterogeneous PHCs (n = 173). The model was established by means of hierarchical clustering and classification and regression tree algorithms, which was optimized by an internal validation procedure and validated by an external dataset. The optimal QSPR model, containing only one predictor variable (the number of bonds that do not contain hydrogen), was able to accurately predict biodegradation half-lives for a wide variety of PHCs. The internal validation test indicated an overall prediction accuracy of 93%, and predictions applied to an independent external set of 64 PHCs yielded 95% accuracy. The new model is transparent and easily portable from one user to another.


Physical activity and menopausal symptoms in women who have received menopause-inducing cancer treatments: results from the Women's Wellness After Cancer Program.
This randomized controlled trial tested a digitally-delivered whole-of-lifestyle program for women previously treated for cancer. We investigated (1) associations between self-reported physical activity (PA) and menopausal symptoms and (2) if the intervention was associated with beneficial changes in PA and menopausal symptoms. Women were randomized to intervention (n = 142) or control (n = 138). The intervention targeted lifestyle behavior including PA. Self-reported PA (International Physical Activity Questionnaire - Short Form) and menopausal symptom (Green Climacteric Scale, GCS) data were collected at baseline, with measures repeated at 12 weeks (end of intervention) and 24 weeks (to assess sustainability). Generalized estimating equation models explored associations between PA and GCS scores. Mixed-effects generalized equation models analyzed changes within and between groups in PA and GCS scores. Total GCS scores were 1.83 (95% CI: 0.11-3.55) and 2.72 (95% CI: 1.12-4.33) points lower in women with medium and high levels of PA, respectively, than in women with low levels of PA. Total average GCS scores were 1.02 (0.21-2.26) and 1.61 (0.34-2.87) points lower in those undertaking moderate or vigorous intensity PA, respectively. Time spent walking, and performing moderate and vigorous PA were not different between intervention and control. The average GCS decrease of 0.66 points (95% CI: 0.03-1.29; p time = 0.03) over 24 weeks was not different between groups. This exploratory study established a stepwise association between moderate and vigorous PA and a lower total menopausal symptom score. The intervention did not appear to increase self-reported PA in women treated for early stage breast, reproductive, and blood cancers.


Erratum to "Prevalence and Associated Factors of Tuberculosis in Prisons Settings of East Gojjam Zone, Northwest Ethiopia".
[This corrects the article DOI: 10.1155/2017/3826980.].


Analysis of Telomere-Homologous DNA with Different Conformations Using 2D Agarose Electrophoresis and In-Gel Hybridization.
In mammalian cells, in addition to double-stranded telomeric DNA at chromosome ends, extra telomere-homologous DNA is present that adopts different conformations, including single-stranded G- or C-rich DNA, extrachromosomal circular DNA (T-circle), and telomeric complex (T-complex) with an unidentified structure. The formation of such telomere-homologous DNA is closely related to telomeric DNA metabolism and chromosome end protection by telomeres. Conventional agarose gel electrophoresis is unable to separate DNA based on conformation. Here, we introduce the method of two-dimensional (2D) agarose electrophoresis in combination with in-gel native/denatured hybridization to determine different conformations formed by telomere-homologous DNA.


Fas ligand enhances malignant behavior of tumor cells through interaction with Met, hepatocyte growth factor receptor, in lipid rafts.
Many late-stage cancer cells express Fas ligand (FasL) and show high malignancy with metastatic potential. We report here a novel signaling mechanism for FasL that hijacks the Met signal pathway to promote tumor metastasis. FasL-expressing human tumor cells express a significant amount of phosphorylated Met. The down-regulation of FasL in these cells led to decreased Met activity and reduced cell motility. Ectopic expression of human FasL in NIH3T3 cells significantly stimulated their migration and invasion. The inhibition of Met and Stat3 activities reverted the FasL-associated phenotype. Notably, FasL variants activated the Met pathway, even though most of their intracellular domain or Fas binding sites were deleted. FasL interacted with Met through the FasL(105-130) extracellular region in lipid rafts, which consequently led to Met activation. Knocking down Met gene expression by RNAi technology reverted the FasL-associated motility to basal levels. Furthermore, treatment with synthetic peptides corresponding to FasL(117-126) significantly reduced the FasL/Met interaction, Met phosphorylation, and cell motility of FasL(+) transfectants and tumor cells. Finally, the transfectants of truncated FasL showed strong anchorage-independent growth and lung metastasis potential in null mice. Collectively, our results establish the FasL-Met-Stat3 signaling pathway and explains the metastatic phenotype of FasL-expressing tumors.


Gamma-hydroxybutyrate in the treatment of schizophrenia.
Gamma-Hydroxybutyrate (GHB) inhibits firing of dopaminergic neurons and is thus potentially useful in the treatment of schizophrenia. GHB was administered to 10 schizophrenics concurrently with low-dose fluphenazine in a 6-week double-blind crossover study. No antipsychotic efficacy of GHB was noted. GHB had little if any effect on plasma prolactin levels after a single administration and caused few side effects. Trials with higher doses of GHB may be warranted.


"Auricular reconstruction: A sociocultural, surgical and scientific perspective".
The functional and sociocultural role of the auricle has been prevalent in art, literature and history for millennia. It is no surprise, therefore, that auricular anomalies can be associated with affective disorders and impaired academic performance in children. The challenge of auricular reconstruction has captured the attention of surgical innovators for millennia with the earliest records of auricular reconstruction documented in the Edwin Smith Surgical Papyrus dating back to 3000 BCE. Since the 19th century, however, the interest in the ambition partial and total auricular reconstruction witnessed a rebirth, with refinements in frame construction, projection and skin coverage improving exponentially over the last two centuries. The gold standard auricular reconstruction practices today have their roots in these historical milestones, and form a solid foundation for the introduction of technological advancements such as 3D bioprinting and composite tissue allotransplantation into future auricular reconstruction practice. The aim of this review is to outline the sociocultural role of the auricle, the history and evolution of auricular reconstruction surgery and to provide an insight into potential future avenues of restoring auricular form and function.


Evidence for adenosine A2b receptors in the rat pineal gland.
We describe the effects of 5'-N-ethylcarboxamidoadenosine (NECA), a mixed A2a/A2b adenosine receptor agonist and 2-[p-(carboxyethyl)-phenylethylamino]-5'-N-ethylcarboxamidoaden osin e (CGS 21680), a selective A2a agonist, on cyclic AMP and N-acetylserotonin synthesis in rat pineal gland. NECA, 1 and 10 microM, increased cyclic AMP by 5- and 25-fold and N-acetylserotonin by 40- and 60-fold respectively, whereas CGS 21680 at the same concentrations was ineffective. These results argue for the presence of adenosine A2b receptors in rat pinealocytes.


Bioactivities and Structure-Activity Relationships of Fusidic Acid Derivatives: A Review.
Fusidic acid (FA) is a natural tetracyclic triterpene isolated from fungi, which is clinically used for systemic and local staphylococcal infections, including methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci infections. FA and its derivatives have been shown to possess a wide range of pharmacological activities, including antibacterial, antimalarial, antituberculosis, anticancer, tumor multidrug resistance reversal, anti-inflammation, antifungal, and antiviral activity in vivo and in vitro. The semisynthesis, structural modification and biological activities of FA derivatives have been extensively studied in recent years. This review summarized the biological activities and structure-activity relationship (SAR) of FA in the last two decades. This summary can prove useful information for drug exploration of FA derivatives.


Systematic review of lung function and COPD with peripheral blood DNA methylation in population based studies.
Epigenetic variations in peripheral blood have potential as biomarkers for disease. This systematic review assesses the association of lung function and chronic obstructive pulmonary disease (COPD) with DNA methylation profiles in peripheral blood from population-based studies. Online databases Medline, Embase, and Web of Science were searched. Google Scholar was searched to identify grey literature. After removing duplicate articles, 1155 articles were independently screened by two investigators. Peer reviewed reports on population-based studies that examined peripheral blood DNA methylation in participants with measured lung function (FEV1, FEV1/FVC ratio) or known COPD status were selected for full-text review. Six articles were suitable for inclusion. Information regarding study characteristics, designs, methodologies and conclusions was extracted. A narrative synthesis was performed based on published results. Three of the six articles assessed the association of COPD with DNA methylation, and two of these also included associations with lung function. Overall, five reports examined the association of lung function with DNA methylation profiles. Five of the six articles reported 'significant' results. However, no consistent CpG sites were identified across studies for COPD status or lung function values. DNA methylation patterns in peripheral blood from individuals with reduced lung function or COPD may be different to those in people with normal lung function. However, this systematic review did not find any consistent associations of lung function or COPD with differentially methylated CpG sites. Large studies with a longitudinal design to address reverse causality may prove a more fruitful area of research. PROSPERO 2016: CRD42016037352 .


A comparison of onlay versus inlay glenoid component loosening in total shoulder arthroplasty.
Glenoid component loosening is common in total shoulder arthroplasty (TSA), often resulting from the mechanical interaction of glenohumeral components. This cadaveric study was performed to evaluate and to compare commercially available onlay and inlay glenoid prosthetic designs with respect to loading characteristics and loosening. Sixteen prescreened cadaveric shoulders (8 matched pairs) underwent either onlay or inlay TSA. We created a custom glenohumeral loading model and used cycles of 5 mm anterior-posterior humeral translation to simulate a rocking-horse loosening mechanism for all testing. Articular TekScan measurements were performed with 9.1 kg (88.9 N) of glenohumeral compression before and after TSA. Fatigue testing was performed with 34.0 kg (333.6 N) of glenohumeral compression using high-definition video to document gross glenoid loosening. Testing ended with gross loosening or a maximum of 4000 cycles. Mean contact area, pressure, and joint reaction force were used to compare the 2 glenoid designs. In both implant types, contact area decreased and pressure increased after TSA (P < .0001). Force increased at the onlay component edge only (P = .0012) compared with native glenoid testing. Force was greater in the onlay vs. the inlay implants (P < .0001). During fatigue testing, all onlay glenoid components exhibited gross loosening at a mean of 1126 cycles (range, 749-1838), whereas none of the inlay glenoid components exhibited gross loosening (P < .0001). The inlay glenoid implant exhibited biomechanical characteristics favoring stability and decreased loosening compared with the onlay glenoid implant in this cadaveric model.


Frailty status and increased risk for falls: The role of anticholinergic burden.
Frailty leads to serious adverse outcomes including falls. The relationship between frailty and falls has not been evaluated in the context of the side effects of drugs with anticholinergic properties. The aim of this study was to examine the potential association of anticholinergic burden (ACB) with the risk of falls among frail older adults. Community-dwelling older adults were consecutively selected from the geriatrics outpatient clinic. Based on a fall history in the last 12 months, the participants were grouped as fallers and non-fallers. Frailty status was assessed by Fried's phenotype method. Exposure to anticholinergic medications was estimated using the ACB scale, and the participants were classified into ACB_0 (none), ACB_1 (possible) and ACB_2+ (definite). The study included 520 older adults (mean age 77.7 years, 62.7 % female), with a fall prevalence of 25.8 % 12 months past. The proportions of frailty and pre-frailty were 33.1 % and 57.4 %, respectively. After adjustment for study confounders, receiving at least 1 drug with either possible or definite anticholinergic properties was independently associated to falls in frail [OR = 3.84 (1.48-9.93), p = 0.006] and pre-frail participants [OR = 2.71 (1.25-5.89); p = 0.012], but not in robust subjects. Moreover, ACB was significantly associated with the frailty components on adjusted analysis (p's<0.05). Current study showed that the use of any drugs with possible or definite anticholinergic properties was associated with an increased risk of falls in frail older adults. The results emphasize the importance of medication management with respect to fall prevention in these patients.


Management of neurogenic bladder in infancy and childhood.
Sixty-two patients, age twelve years and under, were treated for incontinence due to neurogenic bladder secondary to spina bifida (58) or trauma (4) with a follow-up period of three to thirty-two months (mean, ten months). In early life, patients were managed with the Credé maneuver (18 patients). Older children were managed with intermittent clean catheterization (44 patients) with or without pharmacologic agents. Continence was achieved with intermittent clean catheterization in 77 per cent, thus enabling these children to be more acceptable to their peers and in many cases attend schools from which they had previously been excluded because of urinary incontinence. With the Credé maneuver, renal deterioration was noted in 11 per cent on follow-up IVP, and in 2 per cent of the patients on intermittent clean catheterization. Recurrent asymptomatic bacteriuria occurred in 33 per cent of those with the Credé maneuver and in 55 per cent of the patients using intermittent clean catheterization. The use of antibiotic bladder irrigations reduced this incidence to 5 per cent. All patients with renal deterioration except one responded to intermittent clean catheterization; this patient was treated with cutaneous vesicostomy. Urodynamic assessment was performed in 15 patients, and this diagnostic tool assisted in the therapeutic management of these children.


An improved tensile deformation model for in-situ dendrite/metallic glass matrix composites.
With regard to previous tensile deformation models simulating the tensile behavior of in-situ dendrite-reinforced metallic glass matrix composites (MGMCs) [Qiao et al., Acta Mater. 59 (2011) 4126; Sci. Rep. 3 (2013) 2816], some parameters, such as yielding strength of the dendrites and glass matrix, and the strain-hardening exponent of the dendrites, are estimated based on literatures. Here, Ti48Zr18V12Cu5Be17 MGMCs are investigated in order to improve the tensile deformation model and reveal the tensile deformation mechanisms. The tensile behavior of dendrites is obtained experimentally combining nano-indentation measurements and finite-element-method analysis for the first time, and those of the glass matrix and composites are obtained by tension. Besides, the tensile behavior of the MGMCs is divided into four stages: (1) elastic-elastic, (2) elastic-plastic, (3) plastic-plastic (work-hardening), and (4) plastic-plastic (softening). The respective constitutive relationships at different deformation stages are quantified. The calculated results coincide well with the experimental results. Thus, the improved model can be applied to clarify and predict the tensile behavior of the MGMCs.


Stochastic activation of a DNA damage response causes cell-to-cell mutation rate variation.
Cells rely on the precise action of proteins that detect and repair DNA damage. However, gene expression noise causes fluctuations in protein abundances that may compromise repair. For the Ada protein in Escherichia coli, which induces its own expression upon repairing DNA alkylation damage, we found that undamaged cells on average produce one Ada molecule per generation. Because production is stochastic, many cells have no Ada molecules and cannot induce the damage response until the first expression event occurs, which sometimes delays the response for generations. This creates a subpopulation of cells with increased mutation rates. Nongenetic variation in protein abundances thus leads to genetic heterogeneity in the population. Our results further suggest that cells balance reliable repair against toxic side effects of abundant DNA repair proteins.


Chronic kidney disease begets heart failure and vice versa: temporal associations between heart failure events in relation to incident chronic kidney disease in type 2 diabetes.
To investigate the interplay of incident chronic kidney disease (CKD) and/or heart failure (HF) and their associations with prognosis in a large, population-based cohort with type 2 diabetes (T2DM). Patients aged ≥18 years with new-onset T2DM, without renal disease or HF at baseline, were identified from the territory-wide Clinical Data Analysis Reporting System between 2000 and 2015. Patients were followed up until December 31, 2020 for incident CKD and/or HF and all-cause mortality. Among 102 488 patients (median age 66 years, 45.7% women, median follow-up 7.5 years), new-onset CKD occurred in 14 798 patients (14.4%), in whom 21.7% had HF. In contrast, among 9258 patients (9.0%) with new-onset HF, 34.6% had CKD. The median time from baseline to incident CKD or HF (4.4 vs. 4.1 years) did not differ. However, the median (interquartile range) time until incident HF after CKD diagnosis was 1.7 (0.5-3.6) years and was 1.2 (0.2-3.4) years for incident CKD after HF diagnosis (P < 0.001). The crude incidence of CKD was higher than that of HF: 17.6 (95% confidence interval [CI] 17.3-17.9) vs. 10.6 (95% CI 10.4-10.9)/1000 person-years, respectively, but incident HF was associated with a higher adjusted-mortality than incident CKD. The presence of either condition (vs. CKD/HF-free status) was associated with a three-fold hazard of death, whereas concomitant HF and CKD conferred a six to seven-fold adjusted hazard of mortality. Cardiorenal complications are common and are associated with high mortality risk among patients with new-onset T2DM. Close surveillance of these dual complications is crucial to reduce the burden of disease.


Serum carnitine levels in patients with tumoral cachexia.
Cachexia is a serious complication of many cancers that is common in cancer and AIDS patients. However, the key factors and mechanisms involved in the development of cachexia are not yet understood. There is little data currently available regarding carnitine metabolism in patients with neoplasm and cachexia. Forty-six neoplastic patients with different localizations of their primary disease gave signed, informed consent before enrolling in the present study. They underwent routine laboratory investigation, including examination of the levels of the various forms of carnitine present in serum (i.e., long-chain acylcarnitine, short-chain acylcarnitine, soluble acid acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 30 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. In the comparison of serum plasma carnitine of cachectic patients versus controls, the difference in free carnitine was - 8.20 micromol/L (p=0.000); the difference in short-chain acylcarnitine - 2.60 micromol/L (p=0.029); the difference in soluble acid carnitine - 10.80 micromol/L (p=0.000); the difference in long-chain acylcarnitine - 0.40 micromol/L (p=0.036); and the difference in total carnitine -11.20 micromol/L (p=0.000). In the comparison of serum plasma carnitine of cachectic versus neoplastic patients in good nutritional status, the difference in free carnitine was -5.80 micromol/L (p=0.006); the difference in soluble acid carnitine - 7.20 micromol/L (p=0.000); and the difference in total carnitine - 7.50 micromol/L (p=0.000). Our study showed that, in the multifactorial pathogenesis of cachexia, the low serum levels of carnitine in terminal neoplastic patients, which are due to a decreased dietary intake as well as to an impaired endogenous synthesis of this substance, could play an important role. These low serum carnitine levels may also contribute to the development of cachexia in cancer patients.


Comparing the long-term retention of a physiology course for medical students with the traditional and problem-based learning.
The rapid improvements in medical sciences and the ever-increasing related data, however, require novel methods of instruction. One such method, which has been given less than due attention in Iran, is problem-based learning (PBL). In this study, we aimed to evaluate the impact of study skills and the PBL methods on short and long-term retention of information provided for medical students in the course of respiratory physiology and compare it with traditional learning method. In this study, 39 medical students from Medical School of Kerman University of Medical Sciences, Kerman, Iran (2006-2010) were enrolled in the study and allocated randomly in three equal groups (13 in each group). All groups underwent a pre-test to be assessed for their basic information regarding respiratory physiology. Two groups were instructed using the traditional method, and one group used PBL. Among the two groups of the traditional method, one was instructed about study skills and the other was not. Once the PBL group took the study skill workshop, they were aided by tutors for their education. In the final term test, those students who had learned study skills and were instructed with the traditional method scored higher compared to other groups (p < 0.05). However, in the 1 year (p < 0.05) and 4 year (p < 0.01) interval examinations, the PBL group achieved significantly higher scores. Despite the fact that PBL had no positive effect on the final term exam of our students, it yielded a more profound and retained understanding of the subject course. Moreover, considering the positive effect of study skills on long-term student scores, we recommend students to receive instructions regarding the appropriate study skills when initiated into universities.


EXERCISES AND NEUROMUSCULAR ELECTRIC STIMULATION FOR MEDIAL LONGITUDINAL ARCH: CLINICAL TRIAL.
The extrinsic muscles, such as the posterior tibialis and long flexor of the hallux and the intrinsic of the foot, are part of the active subsystem of the central system of the foot and play an essential role in the control of the medial longitudinal arch resulting from difficulty in contracting the muscle, neuromuscular electrostimulation (NMES) becomes a resource combined with strengthening and recommended for rehabilitation. T this work aims to evaluate the effectiveness of NMES associated with exercise in deforming the medial longitudinal arch. This is a randomized blind clinical trial. 60 asymptomatic participants were divided into three groups: NMES, exercise and control. The NMES and exercise group performed seven exercises for the intrinsic and extrinsic muscles twice a week for 6 weeks, and the NMES group used an NMES associated with five exercises. Navicular height and medial longitudinal arch angle were taken before and after the intervention period. No statistically significant differences existed between groups for navicular height and medial longitudinal arch angle. NMES associated with exercise does not change the characteristics of the medial longitudinal arch in association with asymptomatic. Level of Evidence I; Randomized clinical trial.


Response competition better explains Stroop interference than does response exclusion.
Researchers debate whether Stroop interference from an incongruent word in color-naming response time is caused by response competition or by response exclusion. According to the former account, the interference reflects competition in lexical response selection during color name planning, whereas according to the latter, the interference reflects the removal of a motor program for the incongruent word from an articulatory buffer after planning. Here, numerical predictions about the magnitude of Stroop interference as a function of stimulus onset asynchrony were derived from these accounts. These predictions were then tested on representative data in the literature. Measures of goodness-of-fit showed that the numerical predictions of a response competition account are closer to the empirical data than those of the response exclusion account. These results indicate that response competition provides a better explanation of interference in naming than does response exclusion.


The influence of lightning activity on NOx and O3 in the Pearl River Delta region.
Extremely high-temperature lightning generates NOx by electrolyzing nitrogen and oxygen molecules, regulating ozone concentration. The Pearl River Delta (PRD) is located in the world's high-value area of lightning density, and lightning-generated NOx (LNOx) cannot be ignored. Using the flash data from Guangdong-Hong Kong-Macao Lightning Location System and multi-site atmospheric composition data, we estimate the NOx variations in lightning activity and its impact on O3 across the PRD region. The cloud-to-groud (CG) frequency from 2013 to 2021 shows a decreasing trend driven by urban regions. We observe that the lightning density is steadily decreasing from the south-central part of Guangzhou City to the surrounding area. A comparison of the different sites with lightning days and non-lightning days shows that a significant amount (13. 84-20. 47 %) of ground-level NOx concentration at urban stations can be attributed to lightning NOx emissions. A lower lightning frequency and low background concentration observed at suburban sites indicated a limited contribution of LNOx. The average decrease in O3 concentration at urban stations (15.92-25.06 %) was significantly higher than that at suburban stations (5.34-8.95 %) due to the influence of titration and lower actinic radiation. There was a greater fluctuation in NOx and O3 concentrations during the cases, and the surface NOx concentration displayed the most significant responsiveness to LNOx under direct lightning striking in the tall tower. This phenomenon has not been reported, however, it is consistent with the laboratory-based observations suggesting the amount of LNO increases with peak current. LNOx significantly impacts air quality in the PRD during the high convective season. Further in situ and vertical distribution observations are necessary to explore the ground-level impact of LNOx.


Involvement of Holotrichia parallela odorant-binding protein 3 in the localization of oviposition sites.
Organic fertilizers-derived volatiles attract Holotrichia parallela during oviposition. However, the mechanisms underlying the perception of oviposition cues in H. parallela remain unclear. Here, H. parallela odorant-binding protein 3 (HparOBP3) was identified as a key OBP. Bioinformatics analysis showed that HparOBP3 clustered together with Holotrichia oblita OBP8. HparOBP3 was mainly expressed in the antennae of both sexes. Recombinant HparOBP3 exhibited distinct binding affinities towards 22 compounds released by organic fertilizers. After 48 h of RNA interference (RNAi), the expression of HparOBP3 in male and female antennae was decreased by 90.77 % and 82.30 %, respectively. In addition, silencing of HparOBP3 significantly reduced the electrophysiological responses and tropism of males to cis-3-hexen-1-ol, 1-hexanol, and (Z)-β-ocimene as well as females to cis-3-hexen-1-ol, 1-hexanol, benzaldehyde, and (Z)-β-ocimene. Molecular docking indicated that hydrophobic residues Leu-83, Leu-87, Phe-108, and Ile-120 of HparOBP3 were important amino acids for interacting with ligands. Mutation of the key residue, Leu-83, significantly diminished the binding ability of HparOBP3. Furthermore, acrylic plastic arena bioassays showed that the attraction and oviposition indexes of organic fertilizers to H. parallela were reduced by 55.78 % and 60.11 %, respectively, after silencing HparOBP3. These results suggest that HparOBP3 is essential in mediating the oviposition behavior of H. parallela.


Cardiomyopathy in children.
| Cardiomyopathy in children is a rare but serious disease leading to heart failure with a high mortality rate. Dilated cardiomyopathy (DCM) and hypertrophic cardio-myopathy (HCM) are more common than restrictive cardiomyopathy (RCM). Arrhythmogenic right ventricular dysplasia (ARVD) is extremely rare in pediatric age groups. Treatment should be targeted at the cause of the cardiomyopathy, if identified. Nutritional deficiencies, metabolic disorders, and inborn errors of metabolism should be corrected if possible. Immunosuppressive therapy may be considered in patients with lymphocytic myocarditis. Maximal medical therapy with inotropic drugs or cardiac glycosides, diuretic drugs, and angiotensin-converting enzyme inhibitors improve heart failure symptoms in patients with DCM. Beta-blocker therapy in adults with DCM is well established and is being evaluated in children with DCM. High-dosage beta-blocker or calcium channel blocker therapy improves the survival rate in children with HCM. The cautious use of diuretics and angiotensin-converting enzyme inhibitors in patients with RCM improves symptoms. Anticoagulation to prevent thromboembolism in patients with DCM and RCM is indicated. Antiarrhythmia therapy is needed in patients with DCM- or HCM-associated dysrhythmia. Cardiac transplant is indicated in patients with progressive deterioration.


Detecting interactions in association studies by using simple allele recoding.
This paper aims to describe the benefits of using data recoding methods for the analysis of genetic interactions. By changing the representation of the input data it is possible to model non-additive genetic effects in association analysis software, which has been primarily designed to analyse only additive genetic effects. Similar treatment can be applied also for general-purpose statistical search algorithms available in general statistical packages. Data recoding is illustrated for several interaction models using hypothetical examples and by presenting gene-gene interaction analysis in a real cystic fibrosis dataset using the BAMA software.


Special classroom placements for EMR children: guidelines for community mental health personnel.
Community mental health personnel have become increasingly involved in public school interventions for mildly retarded children. Previous research, legal findings, and ethical principles regarding the most common intervention, special class placement, are reviewed. Advantages and disadvantages of special placement are presented. Finally, a process model is proposed as offering guidelines to the mental health professional who is involved in establishing treatment programs for EMR children in the public school.


Inappropriate manipulation and drainage exacerbate post-operative pain and prolong the hospital stay after laparoscopic appendectomy for pediatric complicated appendicitis.
This study examined whether drain placement or not is associated with the postoperative outcomes of pediatric patients following trans-umbilical single-port laparoscopic appendectomy (TUSPLA) for complicated appendicitis. The medical records of pediatric patients undergoing TUSPLA for acute complicated appendicitis from January 2012 to September 2018 in Kaohsiung Chang Gung Memorial Hospital were reviewed retrospectively. They were classified according to whether they received passive drainage with a Penrose drain (Penrose group) (19), active drainage with a Jackson-Pratt drain with a vacuum bulb (JP group) (16), or no drain (non-drain group) (86). The postoperative outcomes of the three groups were compared. Postoperative visual analog scale pain score was significantly higher in the non-drain group than in either the JP group or Penrose group. Patients in the Penrose group had a significantly longer postoperative hospital stay than those in the non-drain group and a higher rate of intra-abdominal abscess, while patients in the JP group had a significantly shorter postoperative hospital stay; moreover, no patient in JP group developed a postoperative intra-abdominal abscess. Compared to passive drainage with a Penrose drain or no drain, active drainage with a JP drain shorter the postoperative hospital stay and decreased the risk of postoperative intra-abdominal abscess.


Enhanced genomic stability of new miRNA-regulated oncolytic coxsackievirus B3.
Genetic modification of coxsackievirus B3 (CVB3) by inserting target sequences (TS) of tumor-suppressive and/or organ-selective microRNAs (miRs) into viral genome can efficiently eliminate viral pathogenesis without significant impacts on its oncolytic activity. Nonetheless, reversion mutants (loss of miR-TS inserts) were identified as early as day 35 post-injection in ∼40% immunodeficient mice. To improve the stability, here we re-engineered CVB3 by (1) replacing the same length of viral genome at the non-coding region with TS of cardiac-selective miR-1/miR-133 and pancreas-enriched miR-216/miR-375 or (2) inserting the above miR-TS into the coding region (i.e., P1 region) of viral genome. Serial passaging of these newly established miR-CVB3s in cultured cells for 20 rounds demonstrated significantly improved stability compared with the first-generation miR-CVB3 with 5'UTR insertion of miR-TS. The safety and stability of these new miR-CVB3s was verified in immunocompetent mice. Moreover, we showed that these new viruses retained the ability to suppress lung tumor growth in a xenograft mouse model. Finally, we observed that miR-CVB3 with insertion in P1 region was more stable than miR-CVB3 with preserved length of the 5'UTR, whereas the latter displayed significantly higher oncolytic activity. Overall, we presented here valid strategies to enhance the genomic stability of miR-CVB3 for virotherapy.


The public health response to a case of Lassa fever in London in 2000.
Evaluation of the Department of Health 1996 guidance, the Memorandum on the Management and Control of Viral Haemorrhagic Fevers. Description of the public health management in 2000 of the fifth UK patient confirmed to have Lassa fever. Delayed risk categorisation of the patient occurred for a variety of reasons. DH Guidance was followed once infection control advice was sought. Active surveillance of 125 contacts was extremely resource intense, involving over 3000 communications. Self-monitoring by healthcare workers should be considered in future. Advice on use of ribavirin prophylaxis is not included in the Memorandum, nor advice or templates for information sheets for contacts. Information sheets are now available from the Health Protection Agency in the event of future cases. International aspects not adequately addressed include the need for reliable risk assessment to be carried out before patients are medically evacuated from the country of origin, and the steps required to repatriate UK nationals. Effective and efficient communication is required between national and international organisations involved in such incidents. If guidelines are unclear or impracticable they will not be followed. It is important that lessons are learned and documented and that national guidance be regularly reviewed.


Absence of clinical benefit of FDG PET-CT in staging T1 part-solid lung adenocarcinoma.
To assess the rates of nodal and metastatic disease and change in management when staging part-solid T1 lung adenocarcinomas using integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)-computed tomography (CT) in a UK population. This was a retrospective review of PET-CT examinations performed to stage radiologically suspected T1 part-solid lung adenocarcinoma (n=58) from two different centres. Rates of detection of nodal and metastatic disease, change in management, and final patient outcome were recorded. PET-CT changed the stage in one patient from N0 to N1. It did not change final management in any patient. In this UK population, PET-CT had minimal additional diagnostic benefit in staging patients with T1 part-solid lung adenocarcinoma. Especially given its cost, the inclusion of PET-CT for this indication in guidelines should be reviewed.


RIDB: A Dataset of fundus images for retina based person identification.
The paper describes a dataset, entitled Retina Identification Database (RIDB). The stated dataset contains Retinal fundus images acquired using Fundus imaging camera TOPCON-TRC 50 EX. The abovementioned dataset holds a significant position in retinal recognition and identification. Retinal recognition is considered as one of the reliable biometric recognition features. Biometric recognition has become an integral part of any organization's security department. Before biometrics, the information was secured through passwords, pin keys, etc. However, the fear of decryption and hacking retained. Biometric verification includes behavioural (voice, signature, gait), morphological (Fingerprint, face, palm print, retina) and biological (Odour, saliva, DNA) features [1]. Amongst all of them, retina based identification is considered as the spoof proof and most accurate identification system. Since the retina is embedded inside the eye thus is least affected by the outer environment and retain in its original state. Moreover, the vascular pattern in the retina is unique and remains unchanged during the entire life span. The data presented in the paper is composed of 100 retinal images of 20 individuals (5 images were captured from each patient). The dataset is supported by research work [2] and [7]. These research papers proposed retinal recognition algorithms for biometric verification and identification. The proposed method utilized both vascular and non-vascular features for identification and yields recognition rates of 100 % and 92.5% respectively.


Central myelin gene expression during postnatal development in rats exposed to nicotine gestationally.
Abnormal myelin gene expression in the central nervous system (CNS) is associated with many mental illnesses, including psychiatric disorders and drug addiction. We have previously shown that prenatal exposure to nicotine, the major psychoactive component in cigarette smoke, alters myelin gene expression in the CNS of adolescent rats. To examine whether this effect is specific for adolescents, we examined myelin gene expression in the CNS of juveniles and adults. Pregnant Sprague-Dawley rats were treated with nicotine (3 mg/kg/day; GN) or saline (GS) via osmotic mini pumps from gestational days 4-18. Both male and female offspring were sacrificed at postnatal day P20-21 (juveniles), P35-36 (adolescents), or P59-60 (adults). Three limbic brain regions, the prefrontal cortex (PFC), caudate putamen (CPu), and nucleus accumbens (NAc), were dissected. The expression of genes encoding major myelin components was evaluated using quantitative RT-PCR. We found that GN altered myelin gene expression in juveniles with brain region and sex differences. The pattern of alteration was different from that observed in adolescents. Although these genes were expressed normally in male adults, we observed decreased expression in GN-treated female adults, especially in the CPu. Thus, GN altered myelin gene expression throughout postnatal development and adulthood. The effect on adolescents was quite different from that at other ages, which correlated with the unique symptoms of many psychiatric disorders during adolescence.


Effect of the haptic anchors during balancing and walking tasks in older adults: A systematic review.
Older adults are benefited from the continuous tactile information to enhance postural control. Therefore, the aim was to evaluate the effect of the haptic anchors during balancing and walking tasks in older adults. The search strategy (up to January 2023) was based on the PICOT (older adults; anchor system during balance and walking tasks; any control group; postural control measurements; short and/or long-term effect). Two pairs of reviewers independently examined all titles and abstracts for eligibility. The reviewers independently extracted data from the included studies, assessed the risk of bias, and certainty of the evidence. Six studies were included in the qualitative synthesis. All studies used a 125-g haptic anchor system. Four studies used anchors when standing in a semi-tandem position, two in tandem walking on different surfaces, and one in an upright position after plantar flexor muscle fatigue. Two studies showed that the anchor system reduced body sway. One study showed that the ellipse area was significantly lower for the 50% group (reduced frequency) in the post-practice phase. One study showed that the reduction in the ellipse area was independent of the fatigue condition. Two studies observed reduced trunk acceleration in the frontal plane during tandem waking tasks. The studies had low to moderate certainty of evidence. Haptic anchors can reduce postural sway during balance and walking tasks in older adults. Also, positive effects were seen during the delayed post-practice phase after the removal of anchors only in individuals who used a reduced anchor frequency.


Nutritional immunomodulation in burn patients.
A series of laboratory experiments in thermally injured guinea pigs has shown that feeding by the enteral route immediately after injury results in a decreased metabolic response by preventing loss of the GI barrier to the entrance of intestinal endotoxin and bacteria. Feeding by the iv route or giving crystalline amino acids instead of intact protein does not prevent atrophy of the intestine, nor does it prevent the hypermetabolic response. Optimal diets for nutritional support of burn patients contain 20% of energy from whey protein, 2% from arginine, 0.5% from cysteine, and 0.5% from histidine. Lipids comprise 15% of nonprotein calories with 50% fish oil (high in omega-3 fatty acids) and 50% safflower oil (high in linoleic acid). In a prospective clinical study, administration of this new diet was found to reduce wound infection (p less than .03), shorten hospital stay (p less than .02), and reduce death (p less than .06) when compared to other standard enteral formulations.


The effects of interferon beta-1a on proton MR spectroscopic imaging in patients with multiple sclerosis, a controlled study, preliminary results.
To evaluate the effects of interferon beta-1a(INFbeta-1a) on brain metabolites in patients with multiple sclerosis (MS), we performed Magnetic Resonance Spectroscopy Imaging (MRSI) on five patients treated with INFbeta-1a (Rebif 44 microg), and on five untreated patients. Six healthy volunteers were used as controls. Patients were evaluated at the beginning, in the first, third, sixth, and twelfth month. There were no significant differences in normal appearing white matter (NAWM) metabolite peaks of the control group and patients with MS. However, in white matter lesions (WML) and NAWM there was significant differences between the basal and the other months' metabolic peaks (p < 0.05) in the treatment group although no differences emerged in the untreated group. These data suggest that INFbeta-1a has a favorable effect on restoration of metabolites in MS lesions.


[A study of the patency of postoperatively irradiated vascular anastomoses in rats and their histologic results].
The influence of radiation on microvascular anastomoses were investigated on the femoral artery and vein of the rat. In an increasing number of operations free transplantations after tumor resections of the head and neck are performed. In advanced tumors postoperative radiation would be desired as early as possible. The histological changes and the patency of the vessels were investigated. The results indicate that an immediate postoperative radiation is possible even after an free microvascular transplantation.


Intestinal transport of cefuroxime axetil in rats: absorption and hydrolysis processes.
Studies were performed using three cefuroxime axetil solutions (11.8, 118 and 200 microM) in three selected intestinal segments and one cefuroxime axetil solution (118 microM) in colon of anaesthetized rats. First-order absorption rate pseudoconstants, k(ap) and effective permeability coefficients, P(eff), were calculated in each set. Absorption of cefuroxime axetil can apparently be described as a carrier-mediated transport, which obeys Michaelis-Menten and first order kinetics in the proximal segment of the small intestine and a passive diffusion mechanism in the mean and distal segments. The absorption kinetic parameters for cefuroxime axetil were obtained: Vm=0.613 (0.440) microM min-1; Km=31.49(28.31) microM and ka=0.011(0.003) min-1. Parameters characterizing degradation of the prodrug were obtained in each intestinal segment: proximal segment k(dp)=0.0049(0.0003) min-1, mean segment, k(dm)=0.0131(0.0007) min-1 and distal segment k(dd)=0.019(0.0009) min-1. Therefore, in situ intestinal absorption of cefuroxime axetil in the proximal segment of the rat in the presence of variable concentrations of cefadroxil has been investigated in order to examine the inhibitory effect of cefadroxil on cefuroxime axetil transport. The data suggest that cefadroxil and cefuroxime axetil share the same intestinal carrier.


Primary care workforce composition and population, professional, and system outcomes: a retrospective cross-sectional analysis.
The diversification of types of staff delivering primary care may affect professional, population, and system outcomes. To estimate associations between workforce composition and outcomes. Cross-sectional analysis of 6210 GP practices from a range of geographical settings across England in 2019. A multivariable regression analysis was undertaken, relating numbers of staff in four groups - GPs, nurses, healthcare professionals, and health associate professionals - to patient access and satisfaction, quality of clinical care and prescribing, use of hospital services, GP working conditions (subsample of practices), and costs to the NHS. Data were obtained from the GP Patient Survey 2019, Quality and Outcomes Framework, prescribing data, the Hospital Episode Statistics database, the NHS Payments to General Practice 2019/2020, and the Tenth National GP Worklife Survey 2019. Having additional GPs was associated with higher levels of satisfaction for the GPs themselves and for patients, whereas additional staff of other types had opposite associations with these outcomes. Having additional nurses and health associate professionals was associated with lower costs per prescription but more prescribing activity than having additional staff from the other two groups. Having more GPs was associated with higher costs per prescription and lower use of narrow-spectrum antibiotics compared with the other staff groups. Except for health associate professionals, greater staff numbers were associated with more hospital activity. Professional, population, and system outcomes showed a variety of associations with primary care workforce composition. Having additional nurses was associated with lower quality in some aspects, and higher costs and activity. The association between additional healthcare professionals or health associate professionals and higher costs was less than that for additional GPs, but was also linked to lower patient and GP satisfaction.


Endogenous intoxication in helminthic invasion in men of reproductive age.
Helminthes have a systemic effect on the human body: the people in infested occur pathological changes in organs and tissues, violated the enzymatic, hormonal function and childbearing, suffering intestinal microflora develops immune deficiency, which affects the body's adaptive capabilities. Research aim: ?stimate endogenous intoxication of helminthiasis at molecular level at people of reproductive age. We examined 110 men of reproductive age. Of these, 50 men entered the control group, 60 men suffering with ascaridiasis invasion. To determine the content of middle molecules in the blood of persons investigated using the methodology Kovalevsky A.N. and Nifanteva O.E. Average mass concentration of molecules in the blood of men under 36 years with ascaridiasis invasion ranged from 0.44 to 8.9 standard units, men 36-45 years - from 0.41 to 5.21 standard units 30% of men with ascaridiasis invasion under 36 years, the level of middle molecules in the blood exceeds 3.00 standard units, while men older age group of middle molecules content exceeding 3.00 standard units, was observed only in 11% of cases. Thus, the concentration of middle molecules in the blood ascaridiasis invasion of men aged 35-45 years were significantly higher than in healthy individuals, indicating that expressed endogenous intoxication caused by helminthes invasions. Endogenous intoxication is more pronounced in those aged 18-35 years, having a larger, compared with the older age group, the reproductive potential. Perhaps this phenomenon is associated with more intense metabolic processes, typical for the age group 18-35 years.


Non tuberculous mycobacterial lesion of the parotid gland and facial skin in a 4year old girl: A proposed treatment strategy.
We report a case of a parotid-facial caseating granulomatous infection caused by atypical mycobacteria (Mycobacterium avium) in an immuno-competent child. The size and depth of the lesion and its proximity to the facial nerve present a challenge for a purely surgical treatment strategy. An alternative treatment strategy is developed to avoid severe disfigurement. Atypical mycobacterial infection of the parotid region in a 5 year old girl: timeline and definition of a planned combined treatment strategy with antibiotics and surgical excision. Cervicofacial infections caused by non-tuberculous mycobacteria (NTM) may present surgical challenges due to the size and depth of the lesion and its proximity to the facial nerve and major vascular structures. Even minor scars are highly visible and poorly tolerated. Close clinical monitoring combined with judicious treatment strategies is necessary for successful treatment and good cosmesis. Recent literature provides insufficient guidance in formulating the best treatment strategy for the individual patient. Comparisons of antibiotic therapy with variations of surgical excision are abundant but poorly formulated. Our case presented with a lesion involving skin, superficial and deep lobe of the parotid gland. Lesion was in immediate proximity to the distribution of the facial nerve through the parotid gland. The risk of surgical damage to the facial nerve in the acute phase of the inflammation and the required extent of skin excision were significant. We decided to start treatment with combination antimycobacterial antibiotics in close cooperation with the pediatric infectious disease specialists. We observed and documented the regress and executed a delayed surgical excision when the lesion was reduced to skin only. In our opinion this was the best treatment strategy that helped us avoid extensive dissection in the vicinity of the facial nerve as well as a parotidectomy. Excision of the involved skin with the deep portion was performed 6.5 months after initial diagnosis.


Nicotine inhibits cytokine synthesis by mouse colonic mucosa.
We examined the in vivo effect of nicotine on the synthesis of (pro)inflammatory mediators by mouse colonic mucosa. The synthesis of lipid mediators such as the prostanoids prostaglandin E2, 6-keto-prostaglandin F1 alpha and thromboxane B2, the 5-lipoxygenase products leukotriene B4 and leukotriene C4 and the platelet activating factor was not affected, whereas the synthesis of the pro-inflammatory cytokines interleukin-1 beta and tumor necrosis factor alpha was completely abolished. The beneficial effects of smoking and nicotine in ulcerative colitis could be attributed to this inhibition.


Molecular species of phosphatidylcholine from rat gastric mucosa.
Phosphatidylcholine of rat gastric mucosa were found to constitute about half of the total phospholipids. The composition of 20 molecular species accounting for approx. 90% of the total phosphatidylcholine was determined by specific enzymic hydrolyses and AgNO3 thin-layer and gas-liquid chromatography. Disaturated (dipalmitoyl) phosphatidylcholine made up about 31% of the total phosphatidylcholines. Other species which occurred in significant concentrations included 16:0/18:1, 18:0/18:1, 16:0/18:2, 18:0/18:2, 16:0/18:3, 18:0/18:3, 16:0/20:4, and 18:0/20:4. These results indicate that rat gastric mucosa is similar to lung in that both contain elevated amounts of dipalmitoyl phosphatidylcholine. Other similarities between these two tissues are discussed.


Hyperlipidemia management in diabetes: First line or supportive therapy?
Coronary heart disease (CHD) is the most important cause of morbidity and mortality in type 2 diabetes. Current therapeutic approach has changed from glucocentric to vasculoprotective. This brief review highlights importance of management of hyperlipidemia (raised LDL cholesterol and triglycerides) on CHD outcomes in diabetes. Literature seach was done till March 2022 (Pubmed, Google scholar) using following search words; lipids, cholesterol, statins, triglycerides, fibrates, omega-3 polyunsaturated fatty (Omega-3 PUFAs) acids, LDL, diabetes, coronary heart disease. Meta-analyses of randomized controlled trials have reported that LDL cholesterol lowering using moderate to high intensity statins significantly reduces adverse CHD outcomes in diabetes. Evidence of triglyceride reduction using fenofibrate or omega-3 PUFAs is not very robust although a trial of a purified omega-3 PUFAs has shown significant benefit. Lipid lowering with statins along with comprehensive lifestyle changes in addition to glucose control is recommended as first-line therapy to reduce CHD mortality and morbidity in diabetes.


Non-Maxwellian velocity distribution functions for Coulombic systems out of equilibrium.
The velocity distribution function (VDF) of ions in the solar wind, as observed by spacecraft at 1 AU and elsewhere in the heliosphere, exhibits a consistent trend: at low energies in the solar wind frame, the distribution is largely Maxwellian-the core; at higher but still modest energies in the solar wind frame, the distribution follows a power law (f ∝ v -γ , where f is the VDF, v is the speed in the solar wind frame, and γ is an arbitrary spectral index parameter)-the tail-with a spectral index of γ ≈ 5 being extremely common. Several theories have been proposed to explain this common index. Among these theories is that the tail is a natural consequence of an ensemble of particles obeying Coulomb's law (Randol & Christian 2014, 2016). In this study, we derive a general analytical formula for the distribution of electric fields, and find that it always exhibits a power law tail with a spectral index of exactly 9/2, or 4.5, due to the spatial power law index of Coulomb's law. We then show how the VDF is a convolution of the distribution of electric fields with a pre-existing VDF, and that for small values of time after being created, the ion VDF always exhibits a γ = 9/2 power law, wherein the probability of the tail relative to the core depends on particle density, n, and inversely on the pre-existing VDF thermal speed, v th . Finally, we compare our results with previous works, and find good agreement but with important distinctions.


The antibacterial and anticancer properties of zinc oxide coated iron oxide nanotextured composites.
Core-shell α-Fe2O3-ZnO structures of different nanotextured morphology were synthesized through wet chemical routes using different solvents like ethanol, ethanolamine, water and acetaldehyde. Morphological tuning using different solvents resulted in the formation of different shapes, such as disc, spindle, rod and sphere (abbreviated as FZ-ND, FZ-NSP, FZ-NR and FZ-NS, respectively). Structural, morphological and compositional characterization of these nanoparticles (NPs) has been carried out. Antibacterial efficacy of the synthesized NPs was checked against Gram negative V. cholerae N16961 (VcN16961) and Gram positive S. aureus bacteria by recording optical density (OD) at different time points. Among the NPs tested, FZ-NSP was found to be the most effective against VcN16961, while FZ-NR showed maximum efficacy against S. aureus, implying the importance of nanotextured surface as well as the morphology in the manifestation of antibacterial activity. The kinetics of growth for both the bacteria has been modelled using logistic approach. Cytotoxicity was evaluated through MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide) assay against human breast adenocarcinoma cell line (MCF-7), human hepatocarcinoma cell line (HepG2) and against normal human embryonic kidney cell line (HEK-293). The lesser toxicity of α-Fe2O3-ZnO towards HEK-293 and the potent anticancer activity against MCF-7 and HepG2 cells underline its applicability as anticancer agent. With continued improvement of nanotechnology, this study may pave the way for designing and construction of various morphologically diverse, nanotextured materials with desired functional attributes.


Sex differences in the effectiveness of buprenorphine to decrease rates of responding in rhesus monkeys.
Sex differences in μ-opioid receptor (MOR) agonist-induced antinociception have been reported in nonhuman primates. The degree to which μ-opioid receptor agonist sex differences in nonhuman primates extend to other behavioral endpoints remains unknown. The present study compared the behavioral effects of three MOR ligands (fentanyl, buprenorphine, and naltrexone) that varied in efficacy to stimulate [S]-GTPγS binding (from highest to lowest: fentanyl, buprenorphine, and naltrexone) in male and female rhesus monkeys. Male (n=3) and female (n=3) monkeys were trained to respond under a fixed-ratio 10 schedule of food presentation during daily sessions consisting of multiple components. Once rates of responding were stable, cumulative dose-effect functions were determined for intramuscular fentanyl (0.00032-0.032 mg/kg), buprenorphine (0.001-1 mg/kg), and naltrexone (0.01-0.1 mg/kg). Fentanyl dose-dependently decreased rates of responding in both sexes and the corresponding ED50 values were not significantly different. Buprenorphine dose-dependently decreased rates of responding in females, but not males. Naltrexone did not significantly alter behavior in either females or males. Overall, these results suggest that the expression of sex differences in MOR pharmacology depends upon both the efficacy of the MOR ligand and the behavioral endpoint.


Lymphovascular space invasion is highly associated with lymph node metastasis and recurrence in endometrial cancer.
Lymphovascular space invasion (LVSI) has been evaluated as a predictor for nodal metastasis or poor survival in endometrial adenocarcinoma. To evaluate whether LVSI is a prognostic factor for lymph node metastasis and relapse of disease in endometrial adenocarcinoma. We retrospectively analysed the medical records of 438 women with endometrial adenocarcinoma treated by surgical staging, including pelvic and paraaortic lymph node dissection, between January 1996 and July 2011. One hundred sixty-three women (37.2%) were LVSI-positive and 275 (62.8%) were negative. LVSI-positive women were significantly older and showed more advanced stage, poorer differentiation, and a higher frequency of non-endometrioid histology type, myometrial invasion, and positive peritoneal cytology than LVSI-negative women. Surgeries by laparotomy rather than laparoscopy and more adjuvant therapies were conducted in LVSI-positive women. The median number of pelvic and paraaortic lymph nodes removed were not different, but LVSI-positive patients showed more lymph node metastases. The LVSI-positive group also showed a higher recurrence of disease and lower survival rates than the LVSI-negative group. Negative predictive values of LVSI for lymph node metastasis and recurrence of disease were 96.4 and 97.1%, respectively. In multivariate analysis, LVSI did not influence overall or disease-free survival after adjusting for several confounding factors. In the cases that the nodal status has not been assessed in endometrial adenocarcinoma, the presence of LVSI may be a reasonable surrogate in addition to other risk factors, in determining the need for adjuvant therapy.


Patient self-reported instruments for assessing symptoms in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic joint autoimmune disease with a higher prevalence of depressive symptoms due to the burden of the disease. There are several patient-self-depression scales used for the assessment and a wide range of variations in the prevalence of depression could be related to this. No evidence was found that reports the most accurate, sensitive, and specific depression instrument through an extensive review in the literature. To determine the most precise depression instrument to evaluate RA patients. A systematic review search was directed, considering type of study, prevalence of depressive symptoms, usage of validated depression scales, and reported scale performance measurements. The data extraction followed the PRISMA guidelines, and the risk of bias was assessed using RoB 2, ROBINS-I, and QUADAS-2. From a total of 1958, only 28 articles included in the analysis. The total number of patients analyzed was 6405, with a mean age of 56.53 years, 4474 women (75.22%), and a mean prevalence of depressive symptoms of 27.4%. The most frequent and the best scale used was the CES-D (n = 12), considering all characteristics. The CES-D reported the best psychometric properties, and it was the most frequently used tool.


Maternal prenatal depression is associated with dysregulation over the first five years of life moderated by child polygenic risk for comorbid psychiatric problems.
Dysregulation is a combination of emotion, behavior, and attention problems associated with lifelong psychiatric comorbidity. There is evidence for the stability of dysregulation from childhood to adulthood, which would be more fully characterized by determining the likely stability from infancy to childhood. Early origins of dysregulation can further be validated and contextualized in association with environmental and biological factors, such as prenatal stress and polygenic risk scores (PRS) for overlapping child psychiatric problems. We aimed to determine trajectories of dysregulation from 3 months to 5 years (N = 582) in association with maternal prenatal depression moderated by multiple child PRS (N = 232 pairs with available PRS data) in a prenatal cohort. Mothers reported depression symptoms at 24-26 weeks' gestation and child dysregulation at 3, 6, 18, 36, 48, and 60 months. The PRS were for major depressive disorder, attention deficit hyperactivity disorder, cross disorder, and childhood psychiatric problems. Covariates were biological sex, maternal education, and postnatal depression. Analyses included latent classes and regression. Two dysregulation trajectories emerged: persistently low dysregulation (94%), and increasingly high dysregulation (6%). Stable dysregulation emerged at 18 months. High dysregulation was associated with maternal prenatal depression, moderated by PRS for child comorbid psychiatric problems. Males were at greater risk of high dysregulation.


Can self-management programmes change healthcare utilisation in COPD?: A systematic review and framework analysis.
The study aims to evaluate the ability of self-management programmes to change the healthcare-seeking behaviours of people with Chronic Obstructive Pulmonary Disease (COPD), and any associations between programme design and outcomes. A systematic search of the literature returned randomised controlled trials of SMPs for COPD. Change in healthcare utilisation was the primary outcome measure. Programme design was analysed using the Theoretical Domains Framework (TDF). A total of 26 papers described 19 SMPs. The most common utilisation outcome was hospitalisation (n = 22). Of these, 5 showed a significant decrease. Two theoretical domains were evidenced in all programmes: skills and behavioural regulation. All programmes evidenced at least 5 domains. However, there was no clear association between TDF domains and utilisation. Overall, study quality was moderate to poor. This review highlights the need for more alignment in the goals, design, and evaluation of SMPs. Specifically, the TDF could be used to guide programme design and evaluation in future. Practices have a reasonable expectation that interventions they adopt will provide patient benefit and value for money. Better design and reporting of SMP trials would address their ability to do so.


Thiophilic ring-opening and rearrangement reactions of epoxyketone natural products.
Thiol additions to the highly functionalized core structures of aranorosin- and manumycin-type antibiotics reveal the general reactivity patterns of epoxyketone natural products. Rapid hemiacetal and hydrate formations decrease the reactivity of the epoxyketone moiety in aqueous media toward the cellular scavenger glutathione, and secondary 1,2-shift, elimination, aromatization and intramolecular aldol reactions provide novel reaction pathways. In a hydrophobic environment, the thiol-capture function of the ketone moiety facilitates electrophilic attack.


Collateral ligament injuries of the metacarpophalangeal joints of the fingers.
Although complete collateral ligament tear and instability involving the metacarpophalangeal joints of the fingers, especially those on the radial aspect of the index finger, are rare, they may be underdiagnosed, underestimated, and potentially disabling. Awareness and suspicion of the injury, coupled with careful physical and imaging examinations, confirm the diagnosis and its extent. Early operative repair results in favorable outcomes in most cases. Chronic instability may lead to pain, weakness, and arthritis. Late ligament repair or reconstruction is typically slightly less reliable than acute repair, yet often improves outcomes. Arthritic joints may require reconstruction.


The impact of normal range estimated glomerular filtration rate on mortality in selected patients undergoing coronary angiography - a long-term follow-up.
Estimated glomerular filtration rate (eGFR) predicts mortality and adverse cardiovascular events in people with chronic kidney disease. The significance of eGFR within the normal range and its long-term effect on clinical adverse events is unknown. We examined the effect of normal range or mildly reduced eGFR on long-term mortality in a large prospective registry. The study included consecutive patients undergoing clinically-driven coronary angiography who had an eGFR ≥60 ml/min/1.73 m2. Baseline clinical characteristics were assessed, and patients were followed-up for the occurrence of all-cause mortality. Cox regression analysis was used to evaluate the impact of eGFR. A total of 4186 patients were recruited. Median follow-up time was 2883 days (7.9 years). Mean age was 62.0 ± 11.3 years with 77.4% males. Clinical presentation included acute coronary syndrome and stable angina. In a multivariable model adjusted for possible confounding factors, decreasing eGFR within the normal and mildly reduced range was inversely associated with long-term all-cause mortality with a hazard ratio (HR) of 1.32 for every decrease of 10 ml/min/1.732 in eGFR. Compared to eGFR > 100 ml/min/1.732, there was a graded association between lower eGFR values and increased long term mortality with a HR of 1.16 (0.59-2.31) for eGFR 90-100 ml/min/1.732, HR 1.54 (0.81-2.91) for eGFR 80-90 ml/min/1.732, HR 2.62 (1.41-4.85) for eGFR 70-80 ml/min/1.732 and HR 2.93 (1.58-5.41) for eGFR 60-70 ml/min/1.732. eGFR within the normal and mildly reduced range is an independent predictor of long-term all-cause mortality in selected patients undergoing clinically driven coronary angiography.


Cerium-based nanoparticles triggered catalytic reaction for the colorimetric and ratiometric fluorimetric dual-signal sensing of vitamin C.
The construction of multi-modal detection methods has attracted widespread attention in the field of biosensing due to their high sensitivity and strong anti-interference ability. In this manuscript, we developed colorimetric and ratiometric fluorescence dual-signal optical methods based on cerium-based nanoparticles (Ce NPs) for the sensitive detection of vitamin C (VC). The catalysis of Ce NPs with excellent peroxidase-like activity upon the reaction of H2O2 with OPD was occurred, promoting the oxidation of o-phenylenediamine (OPD) to generate 2,3-diaminophennazine (OPDox) with an obvious absorption peak at 420 nm and an emission peak at 565 nm. In the presence of VC, VC not only inhibited the generation of OPDox, but also induced the formation of quinoxaline with an obvious absorption peak at 336 nm and an emission peak at 430 nm. This can be visually observed and monitored by measuring the absorbance of peak at 336 nm (A336) and the ratiometric fluorescence intensity (F430/F565). Therefore, the dual-signal methods are constructed for the detection of VC. The detection lower detection limits are 8.0 μM and 8.4 μM when using the fluorescence and colorimetric signals, respectively. Furthermore, the proposed methods are successfully applied to the detection of VC in practical samples with satisfactory results.


Nutrigenetics/Nutrigenomics, Personalized Nutrition, and Precision Healthcare.
The purposes of the present review are to examine the emergence of nutrigenetics/nutrigenomics, to analyze the relationship between nutrigenetics and nutrigenomics, to explore the impact of nutrigenetics/nutrigenomics on healthcare with respect to noncommunicable diseases, and to discuss the challenges facing the implementation of nutrigenetics/nutrigenomics within healthcare. Nutrigenetics/nutrigenomics is certainly a thriving specialty given the sharp increase of publications over the last two decades. The relationship between nutrigenetics and nutrigenomics is proposed as complementary. The current clinical and research literature supports the significant impact nutrigenetics/nutrigenomics has on treating and preventing noncommunicable diseases. Although several challenges face the implementation of nutrigenetics/nutrigenomics into healthcare, they are not insurmountable. Nutrigenetics/nutrigenomics plays an important role not only in treating diseases and illnesses but also in promoting health and wellness through both basic and clinical research; and it is critical for the future of both personalized nutrition and precision healthcare.


Characterization of the need for galactofuranose during the Neurospora crassa life cycle.
Galactofuranose is a constituent of the cell walls of filamentous fungi. The galactofuranose can be found as a component of N-linked oligosaccharides, in O-linked oligosaccharides, in GPI-anchored galactomannan, and in free galactomannan. The Neurospora genome contains a single UDP-galactose mutase gene (ugm-1/NCU01824) and two UDP-galactofuranose translocases used to import UDP-galactofuranose into the lumen of the Golgi apparatus (ugt-1/NCU01826 and ugt-2/NCU01456). Our results demonstrate that loss of galactofuranose synthesis or its translocation into the lumen of the secretory pathway affects the morphology and growth rate of the vegetative hyphae, the production of conidia (asexual spores), and dramatically affects the sexual stages of the life cycle. In mutants that are unable to make galactofuranose or transport it into the lumen of the Golgi apparatus, ascospore development is aborted soon after fertilization and perithecium maturation is aborted prior to the formation of the neck and ostiole. The Neurospora genome contains three genes encoding possible galactofuranosyltransferases from the GT31 family of glycosyltransferases (gfs-1/NCU05878, gfs-2/NCU07762, and gfs-3/NCU02213) which might be involved in generating galactofuranose-containing oligosaccharide structures. Analysis of triple KO mutants in GT31 glycosyltransferases shows that these mutants have normal morphology, suggesting that these genes do not encode vital galactofuranosyltransferases.


Effect of neck extension on intraocular pressure in paediatric patients undergoing palatoplasty.
Intraocular pressure (IOP) can increase with postural changes, which can cause ocular complications. Neck extension is commonly used during palatoplasty to improve surgical angulation. This study evaluates whether neck extension affects IOP during palatoplasty. In this prospective observational study, IOP was measured using a rebound tonometer at four specific time points: T1, 10 min after anaesthesia while in the supine position; T2, 5 min after neck extension; T3, at completion of palatoplasty with neck extended; and T4, 5 min after returning to the supine position. The primary outcome was the IOP at T2, and the secondary outcomes were the IOPs at T3 and T4. Haemodynamic and respiratory variables were also measured at each time point. Thirty-seven patients were included. IOP at T2 was significantly higher than at T1 (15.8 ± 3.4 mmHg vs 10.5 ± 2.8 mmHg, P < 0.001), and IOPs at T3 and T4 were also significantly higher than at T1 (T3 vs T1: 18.9 ± 3.6 mmHg vs 10.5 ± 2.8 mmHg, P < 0.001; T4 vs T1: 13.3 ± 3.7 mmHg vs 10.5 ± 2.8 mmHg, P < 0.001). However, no significant differences were observed for the haemodynamic and respiratory variables at any time point. Our findings indicate that the intraoperative neck extension position during palatoplasty significantly increases IOP in paediatric cleft palate patients undergoing a palatoplasty.


Clinicopathologic characteristics of nontuberculous mycobacterial lung disease in Taiwan.
Taiwan is an endemic area for tuberculosis (TB), and the incidence of pulmonary infection caused by nontuberculous mycobacteria (NTMs) is also increasing. This study aims to investigate the clinicopathologic characteristics of patients with NTM lung disease during 1998 to 2007 at a medical center in Taiwan. The medical records of patients with confirmed NTM pulmonary infections who underwent open lung surgery in a medical center were reviewed. Twenty-four patients with confirmed NTM pulmonary infections were identified. These patients were histologically classified into 4 types: fibrocavitary/tuberculoid (n = 10), nodular bronchiectatic (n = 4), sarcoidal (n = 6), and other (n = 4). The fibrocavitary/tuberculoid type usually (90%) develops in the upper lobes of old patients with preexisting lung disease. Pulmonary TB (n = 7, 70%) was the major underlying disease before 2003. Nodular bronchiectatic type occurred mainly in the middle lobe of middle-aged women without preexisting lung disease. Sarcoidal type was usually associated with Mycobacterium avium complex infection and develops in middle-aged women. Immunoreactive bacilli were detected in 21 patients (87 %) by immunohistochemical staining using a polyclonal antibody against Mycobacterium tuberculosis and other mycobacterial species (M. avium-intracellulare, Mycobacterium phlei, and Mycobacterium parafortuitum), whereas conventional acid-fast staining was positive in only 21% of patients. In conclusion, TB was the major underlying disease in patients with NTM lung disease in Taiwan. The different histologic types of pulmonary NTM infection suggest each had a distinct pathogenesis.


Clinical effects of transcatheter hepatic arterial embolization with holmium-166 poly(L-lactic acid) microspheres in healthy pigs.
The aim of this study is to evaluate the toxicity of holmium-166 poly(L-lactic acid) microspheres administered into the hepatic artery in pigs. Healthy pigs (20-30 kg) were injected into the hepatic artery with holmium-165-loaded microspheres ((165)HoMS; n=5) or with holmium-166-loaded microspheres ((166)HoMS; n=13). The microspheres' biodistribution was assessed by single-photon emission computed tomography and/or MRI. The animals were monitored clinically, biochemically, and ((166)HoMS group only) hematologically over a period of 1 month ((165)HoMS group) or over 1 or 2 months ((166)HoMS group). Finally, a pathological examination was undertaken. After microsphere administration, some animals exhibited a slightly diminished level of consciousness and a dip in appetite, both of which were transient. Four lethal adverse events occurred in the (166)HoMS group due either to incorrect administration or comorbidity: inadvertent delivery of microspheres into the gastric wall (n=2), preexisting gastric ulceration (n=1), and endocarditis (n=1). AST levels were transitorily elevated post-(166)HoMS administration. In the other blood parameters, no abnormalities were observed. Nuclear scans were acquired from all animals from the (166)HoMS group, and MRI scans were performed if available. In pigs from the (166)HoMS group, atrophy of one or more liver lobes was frequently observed. The actual radioactivity distribution was assessed through ex vivo (166m)Ho measurements. It can be concluded that the toxicity profile of HoMS is low. In pigs, hepatic arterial embolization with (166)HoMS in amounts corresponding with liver-absorbed doses of over 100 Gy, if correctly administered, is not associated with clinically relevant side effects. This result offers a good perspective for upcoming patient trials.


Reaching for wellness in schizophrenia.
Coronary heart disease (CHD) is a major cause of mortality in people who have schizophrenia, and it is caused by many factors relating to lifestyle choices, antipsychotic treatment, and other medical comorbidities. This article focuses on modifiable risk factors such as cigarette smoking, diabetes, hyperlipidemia, hypertension, and the metabolic syndrome, all of which occur more frequently in patients who have schizophrenia than in the general population. Although treatment of risk factors for CHD is still far from ideal, all attempts should be made to strive for wellness to improve patients' long-term outcomes.


Aromatase inhibitors with or without gonadotropin-releasing hormone analogue in metastatic male breast cancer: a case series.
Data regarding the safety and effectiveness of aromatase inhibitors (AIs) as monotherapy or combined with gonadotropin-releasing hormone (GnRH) analogue in male breast cancer are scarce. In this retrospective chart review, cases of male breast cancer patients treated with AIs with or without a GnRH analogue were evaluated. Twenty-three men were included into this case series. Aromatase inhibitors in combination with or without a GnRH analogue were given as first-line therapy in 60.9% and as second-line therapy in 39.1% of patients, respectively. All patients had visceral metastases, whereas in five of them bone lesions coexisted. In all cases AIs were tolerated well, and no case of grade 3 and 4 adverse events was reported. A partial response was observed in 26.1% of patients and stable disease in 56.5%. Median overall survival (OS) was 39 months and median progression-free survival (PFS) was 13 months. Regarding OS and PFS, no significant effects of GnRH analogue co-administration or type of AI were noted. Our study shows that AIs with or without GnRH analogues may represent an effective and safe treatment option for hormone-receptor positive, pretreated, metastatic, male breast cancer patients.