Disuse rescues the age-impaired adaptive response to external loading in mice.
We aimed to determine whether aged bone's diminished response to mechanical loading could be rescued by modulating habitual activity. By reducing background loading, aged bone's response to loading increased to a level no different to young mice. This suggests, given the right stimulus, that ageing bone can respond to mechanical loading. Age-related decline in bone mass has been suggested to represent an impaired ability of bone to adapt to its mechanical environment. In young mice, the tibia's response to external mechanical loading has been shown to increase when habitual activity is reduced by sciatic neurectomy. Here we investigate if neurectomy can rescue bone's response to loading in old mice. The effect of tibial disuse, induced by unilateral sciatic neurectomy (SN), on the adaptive response to a single peak magnitude of dynamic load-engendered mechanical strain was assessed in 19-month-old (aged) mice. In a second experiment, a range of peak loads was used to assess the load magnitude-related effects of loading on a background of disuse in young adult and aged mice. Bone architecture was analysed using micro-computed tomography (μCT) and dynamic histomorphometry. In the first experiment, SN in aged mice was associated with a significant periosteal osteogenic response to loading not observed in sham-operated mice (7.98 ± 1.7 vs 1.02 ± 2.2 % increase in periosteally enclosed area, p < 0.05). In the second experiment, SN abrogated the expected age-related difference in the bones' osteogenic response to peak strain magnitude (p > 0.05). These data suggest that bones' age-related decline in osteogenic responsiveness to loading does not originate in bone cells to either assess, or appropriately respond to strain, but rather is likely to be due to inhibitory "averaging" effects derived from the habitual strains to which the bone is already adapted. If such "strain averaging" is applicable to humans, it suggests that gentle exercise may degrade the beneficially osteogenic effects of short periods of more vigorous activity.


Attention-deficit/hyperactivity disorder is associated with baseline child sport concussion assessment tool third edition scores in child hockey players.
The objectives of this study were to report baseline, preseason data for the Child-SCAT3, stratified by attention deficit hyperactivity disorder (ADHD) status, and examine group differences in Child-SCAT3 performance between children with and without ADHD. Cross-sectional study. Young male hockey players (n = 304), aged 8-12 years, were administered the Child-SCAT3 during pre-season. Child-SCAT3 measures included a 20-item symptom scale, a Standardised Assessment of Concussion Child Version (SAC-C), a modified Balance Error Scoring System (m-BESS), a tandem gait task, and a coordination test. Children with ADHD (n = 20) endorsed significantly more symptoms (d = 0.95) and greater symptom severity (d = 1.13) compared to children without ADHD. No statistically significant differences were found between groups on Child-SCAT3 measures of cognitive or physical functioning (e.g. balance and coordination). ADHD should be considered when interpreting Child-SCAT3 scores, especially symptom reporting, in the context of concussion assessment. Better understanding of symptom reporting in uninjured child athletes with ADHD can inform the clinical interpretation of symptoms at baseline and following an actual or suspected concussion. Normative data for the Child-SCAT3 that is not stratified by or otherwise accounts for ADHD status should be used with caution when appraising performance of children with ADHD.


Efficiency and key functional genera responsible for simultaneous methanation and bioelectricity generation within a continuous stirred microbial electrolysis cell (CSMEC) treating food waste.
This study reveals the efficient treatment of high strength food waste under varying hydraulic retention times (48 h, 36 h and 24 h) in a continuous stirred tank reactor (CSTR) integrated with microbial electrolysis cell (MEC) to become a continuous stirred microbial electrolysis cell (CSMEC). COD removal efficiency in the CSMEC surpassed 92% with OLR ranging from 0.4 to 21.31 kg COD/m3·d compared to that of the CSTR. The maximum current density (based on the cathode surface area) was 1125.35 ± 81 mA/m2 in the CSMEC. Biogas yield and methane production rates increased by 16.5% and 19.3% in the CSMEC respectively compared to the CSTR. CSMEC was 1.52 times better in performance compared to the CSTR. Firmicutes, Synergistetes, Bacteroidetes, Thermotogae, Chloroflexi and Proteobacteria were the dominant phyla associated with both CSMEC and CSTR. Archaeal microbial community analysis showed Methanosaeta, Methanobacterium, Methanosarcina and Methanocorpusculum as the dominant populations associated with the CSMEC.


AMPA receptors in the synapse turnover by monomer diffusion.
The number and subunit compositions of AMPA receptors (AMPARs), hetero- or homotetramers composed of four subunits GluA1-4, in the synapse is carefully tuned to sustain basic synaptic activity. This enables stimulation-induced synaptic plasticity, which is central to learning and memory. The AMPAR tetramers have been widely believed to be stable from their formation in the endoplasmic reticulum until their proteolytic decomposition. However, by observing GluA1 and GluA2 at the level of single molecules, we find that the homo- and heterotetramers are metastable, instantaneously falling apart into monomers, dimers, or trimers (in 100 and 200 ms, respectively), which readily form tetramers again. In the dendritic plasma membrane, GluA1 and GluA2 monomers and dimers are far more mobile than tetramers and enter and exit from the synaptic regions. We conclude that AMPAR turnover by lateral diffusion, essential for sustaining synaptic function, is largely done by monomers of AMPAR subunits, rather than preformed tetramers.


Noradrenaline turnover in the tissues of uraemic rats.
In female Wistar rats with acute renal failure a decrease of noradrenaline concentration in the heart, spleen and kidney was ascertained. Noradrenaline concentration after alpha-methyl-p-tyrosine and 6-hydroxydopamine in the heart, spleen and kidney was significantly lower than in the control group. In the adrenals a decrease of catecholamine level after alpha-methyl-p-tyrosine and 6-hydroxydopamine has been noted in the controls. The changes in tissue noradrenaline concentration are evidence of a dysfunction in the adrenergic nervous system in uraemic rats.


On the particle formation of leucine in spray drying of inhalable microparticles.
The particle formation of L-leucine, a dispersibility-enhancing amino acid used in the spray drying of inhalable pharmaceutical aerosols, was extensively studied using three experimental methods, and the results were interpreted with the aid of theory. A comparative-kinetics electrodynamic balance was used to study the shell formation behavior in single evaporating microdroplets containing leucine and trehalose. Different concentration thresholds of solidification and shell formation were determined for trehalose and leucine, which were then used in the particle formation model to predict the properties of spray-dried particles. Furthermore, a droplet chain instrument was used to study the particle morphologies and particle densities that were not accessible in the single particle experiments. Lab-scale spray drying was also used to produce powders typical for actual pharmaceutical applications. Raman spectroscopy confirmed that a glass former, such as trehalose, can inhibit the crystallization of leucine. The surface compositions of these spray-dried powders were analyzed via time-of-flight secondary ion mass spectrometry. The leucine surface coverage in a polydisperse powder was determined to be a function of the particle size or the initial droplet diameter of each respective particle. This observation confirms the important role of leucine crystallization kinetics in its shell-forming capabilities. A critical supersaturation ratio of 3.5 was also calculated for leucine, at which it is assumed to instantaneously nucleate out of solution. This ratio was used as the threshold for the initiation of crystallization. Crystallinity predictions for the leucine-trehalose particles based on this supersaturation ratio were in good agreement with the solid-state characterizations obtained by Raman spectroscopy. This study improves the fundamental understanding of the particle formation process of leucine-containing formulations, which can apply to other crystallizing systems and potentially facilitate the rational design of such formulations with reduced experimental effort.


[Extramembranous glomerulitis associated with visceral tumours. Clinical and histological study based upon 10 cases and a review of the literature (author's transl)].
The frequency of the association between extramembranous glomerulopathy and a visceral tumour suggests the responsibility of various antigen-antibody systems related to malignancy, at the origin of the nephropathy. In a number of special cases, the role of these systems has been more precisely demonstrated. The cases reported here emphasise the need to seek a visceral tumour when the onset of extramembranous glomerulitis occurs after the age of 40 years, in particular since the onset of proteinuria may precede the first clinical signs of the tumour by several months. The presence of polynuclear cells in the glomerular capillary loops, associated with extramembranous deposits, is an additional element of orientation in the direction of neoplastic aetiology.


Acute idiopathic scrotal oedema in association with diabetic septic foot.
Acute idiopathic scrotal oedema was observed in three adult diabetic patients with septic foot following life saving above knee guillotine amputation. This is a previously unreported association as far as we know and no clue to the pathogenesis could be obtained.


Mouse liver P450Coh: genetic regulation of the pyrazole-inducible enzyme and comparison with other P450 isoenzymes.
Genetic experiments with two inbred strains of mice, AKR/J and DBA/2N, show a single major gene inheritance of additive mode for pyrazole-inducible coumarin 7-hydroxylase. Intragroup variation in the enzyme activity further suggests the contribution of minor modifying genes to the final enzyme activity. Western blot analysis with a polyclonal antibody raised against the purified isozyme P450Coh (highly active in the 7-hydroxylation of coumarin) showed that a difference in the amounts of P450Coh protein between the D2 and AKR mice is the reason for the differences in the enzyme activity between the two mouse strains. Accordingly, changes at the regulatory level rather than at the structural gene would explain the genetic difference in the activity of coumarin 7-hydroxylase. This hypothesis is further supported by the identical Km values of the basal and induced enzyme. The inducibility of coumarin 7-hydroxylase by phenobarbital (PB) and its genetic regulation have been previously studied by A. W. Wood and colleagues ((1974) Science 185, 612-614; (1979); J. Biol. Chem. 254, 5641-5646 and 5647-5651). Our present experiments show that the regulation is the same for the pyrazole-inducible enzyme. Furthermore the experiments with anti-P450Coh antibody show that the PB- and pyrazole-inducible proteins have the same molecular weight and are immunologically indistinguishable. This suggests that PB and pyrazole may induce the same enzyme. Immunoinhibition of microsomal coumarin 7-hydroxylase is practically 100% for control animals and after pretreatment with pyrazole or PB. This suggests that in each case the same or immunologically closely related proteins are metabolizing coumarin and that the P450Coh may be the only P450 isoenzyme in mouse liver microsomes catalyzing the 7-hydroxylation of coumarin. The N-terminal amino acid sequence of P450Coh was found to be identical with those from Type I and Type II genes of the mouse P45015 alpha family for the first 21 amino acids. With rat PB-inducible P450b the homology is only 33%. Also the immunological properties of P450Coh are different from those of P450b. This may suggest that P450Coh has a closer association to the steroid 15 alpha-hydroxylase gene family than to the P450IIB subfamily of phenobarbital-inducible isoenzymes.


Studies of structure activity relationship of flavonoids for the anti-allergic actions.
The structure activity relationship of flavonoids for anti-allergic actions was studied by determining the IC50 values for the degranulation. The hexosaminidase release from RBL-2H3 cells (degranulation marker) was employed as an estimate for the anti-allergic actions. Among 22 flavonoid compounds tested, luteolin, apigenin, diosmetin, fisetin, and quercetin were found to be most active with IC50 values less than 10 microM.


Chemoproteomic mapping of the glycolytic targetome in cancer cells.
Hyperactivated glycolysis is a metabolic hallmark of most cancer cells. Although sporadic information has revealed that glycolytic metabolites possess nonmetabolic functions as signaling molecules, how these metabolites interact with and functionally regulate their binding targets remains largely elusive. Here, we introduce a target-responsive accessibility profiling (TRAP) approach that measures changes in ligand binding-induced accessibility for target identification by globally labeling reactive proteinaceous lysines. With TRAP, we mapped 913 responsive target candidates and 2,487 interactions for 10 major glycolytic metabolites in a model cancer cell line. The wide targetome depicted by TRAP unveils diverse regulatory modalities of glycolytic metabolites, and these modalities involve direct perturbation of enzymes in carbohydrate metabolism, intervention of an orphan transcriptional protein's activity and modulation of targetome-level acetylation. These results further our knowledge of how glycolysis orchestrates signaling pathways in cancer cells to support their survival, and inspire exploitation of the glycolytic targetome for cancer therapy.


(E)-3-[4-(Di-fluoro-meth-oxy)-3-hy-droxy-phen-yl]-1-phenyl-prop-2-en-1-one.
In the title compound, C16H12F2O3, the plane of the phenyl ring makes a dihedral angle of 3.22 (8)° with that of the benzene ring. The mol-ecule has an E conformation about the C=C bond. In the crystal, mol-ecules are linked via pairs of O-H⋯O hydrogen bonds, forming inversion dimers which are further consolidated by a pair of C-H⋯O hydrogen bonds. The dimers are linked via C-H⋯O hydrogen bonds, forming columns along the b-axis direction.


The importance of context in understanding behavior and promoting health.
Behavior, the roles of behavior in health, health promotion, health, quality of life, and death are all context-dependent. This paper begins with a review of behavioral and ecological models, emphasizing their shared emphasis on context. It then turns to genetics and the importance of contexts in understanding genetic influences. Jumping from genes to geography, it examines how spatial analysis provides both a model and framework for considering contextual influence. Continuing with analytic models, it returns to genetics, and considers how it provide models for integrating our understanding of broad social and community influences. The paper extends this thinking through multilevel analysis and proposes "analytic multilevel designs" as a way of studying "context focused interventions" (as opposed to context independent interventions for which conventional experimental designs are often well-suited). It closes with reflections on ways in which we cultivate and extend our knowledge base and on the intellectual contexts of positivism and postmodernism that surround behavioral and ecological thinking.


Genetic variation, real-time PCR, metabolites and mycotoxins ofFusarium avenaceum and related species.
In this paper the latest studies dealing with genetic variation and mycotoxins ofF. avenaceum and related species are reviewed and compared to the data from chromatographic image analyses. Forty-three European strains ofFusarium avenaceum and related species were classified by chromatographic image analysis on full chromatographic matrices. The results were in most cases in agreement with those from morphological and molecular analyses and supported the separation betweenF. avenaceum, F. arthrosporioides andF. tricinctum and betweenF. avenaceum groups I and II. The mycotoxin profiles of the FinnishF. avenaceum, F. arthrosporioides andF tricinctum strains were very similar to each other. Moniliformin and enniatins were the main mycotoxins produced. A fluorogenic TaqMan PCR assay (qPCR) was used for the detection ofF. avenaceum/ F. arthrosporioides DNA in Finnish barley and wheat. The qPCR results obtained from grain samples were compared to mycotoxin levels. A correlation was found betweenF. avenaceum/F. arthrosporioides DNA and moniliformin (MON) and enniatin (ENNs) levels in barley. A correlation was also found between the combinedF. avenaceum/F. arthrosporioides/F. tricinctum contamination and MON and ENNs levels in barley in 2002, but not in 2003. This was probably due to the higher MON and ENNs levels in 2002 than in 2003. It was possible to use the DNA levels ofF. avenaceum/F. arthrosporioides to distinguish between most barley samples containing high amounts of MON and ENNs from those containing low levels of the mycotoxins.


DEER and RIDME Measurements of the Nitroxide-Spin Labelled Copper-Bound Amine Oxidase Homodimer from Arthrobacter Globiformis.
In the study of biological structures, pulse dipolar spectroscopy (PDS) is used to elucidate spin-spin distances at nanometre-scale by measuring dipole-dipole interactions between paramagnetic centres. The PDS methods of Double Electron Electron Resonance (DEER) and Relaxation Induced Dipolar Modulation Enhancement (RIDME) are employed, and their results compared, for the measurement of the dipolar coupling between nitroxide spin labels and copper-II (Cu(II)) paramagnetic centres within the copper amine oxidase from Arthrobacter globiformis (AGAO). The distance distribution results obtained indicate that two distinct distances can be measured, with the longer of these at c.a. 5 nm. Conditions for optimising the RIDME experiment such that it may outperform DEER for these long distances are discussed. Modelling methods are used to show that the distances obtained after data analysis are consistent with the structure of AGAO. The online version contains supplementary material available at 10.1007/s00723-021-01321-6.


Structural basis for bending of organic crystals.
Bending is observed in organic crystals when the packing is anisotropic in such a way that strong and weak interaction patterns occur in nearly perpendicular directions.


[Somatic, biochemical and arterial pressure at the end of adolescence, according to weight at birth].
To investigate in young people differences among somatic measurements, biochemical issues and arterial tension, according to weight at birth. 53 youth born with body weight <2500 g, and 100 born with normal weight were studied. somatic measurements, arterial pressure, glucose, insulin, cholesterol and triglycerides. Insulin resistance and metabolic syndrome were also evaluated. Men born with normal weight had higher cholesterol and resistance to insulin. Differences persisted for odds ratio. Those born with <2500 g had a negative correlation among weight at birth and glucose level. Overweight-obesity was found in 30.0% (46/153) and the metabolic syndrome in 10% (14/140); the frequency of this syndrome increased with the IMC was higher: from 2.0% (2/100) in eutrophics to 30% (12/40) in those with overweight-obesity. The findings stand out the magnitude of the adiposity and of the metabolic syndrome in youths.


Role of average speed in N₂O exhaust emissions as greenhouse gas in a huge urban zone (MVMZ): would we need a cold sun?
Nowadays, the drastic pollution problems, some of them related with greenhouse gas emissions, have promoted important attempts to face and diminish the global warming effects on the Mexico Valley Metropolitan Zone (MVMZ) as well as on the huge urban zones around the world. To reduce the exhaust gas emissions, many efforts have been carried out to reformulate fuels and design new catalytic converters; however, it is well known that other variables such as socio-economic and transport structure factors also play an important role around this problem. The present study analyzes the roles played by several commonly-used three-way catalytic converters (TWC) and the average traffic speed in the emission of N(2)O as greenhouse gas. According to this study, by increasing the average traffic flow and avoiding constant decelerations (frequent stops) during common trips, remarkable environmental and economic benefits could be obtained due to the diminution of N(2)O and other contaminant emissions such as ammonia (NH(3)) and even CO(2) with the concomitant reduced fossil fuel consumption. The actions mentioned above could be highly viable to diminish, in general, the global warming effects and contamination problems.


Reduction in experimental autoimmune thyroiditis by IgG Fc fragments bearing regRF epitopes.
Previously, we identified a new immunoregulatory factor, the production of which provides rats with resistance to certain experimental autoimmune diseases. It has been named regulatory rheumatoid factor (regRF). RegRF inhibits the expansion of CD4 T lymphocytes by killing activated cells. CD4 T cells are essential for antibody production against a majority of antigens and for the generation of cytotoxic T cells; therefore, regRF is an attractive therapeutic biotarget for T-cell and antibody-mediated autoimmune diseases. RegRF is anti-idiotypic antibodies that have a shared paratope in addition to an individual paratope. Epitopes specific to the shared regRF paratope (regRF epitopes) can be obtained on conformers of IgG Fc fragments. Immunization with Fc fragments carrying regRF epitopes reduces rat collagen-induced arthritis and diminishes experimental autoimmune encephalomyelitis. The aim of this study was to determine whether IgG Fc fragments bearing regRF epitopes suppress experimental autoimmune thyroiditis (EAT). Four weeks after EAT induction, rats were immunized with IgG Fc fragments exhibiting regRF epitopes. Histology studies of the thyroid were performed 4 weeks later. Thyroid function and other parameters were also evaluated. Treatment of rats with Fc fragments bearing regRF epitopes decreased the number of rats affected by EAT, significantly decreased the extent of thyroid damage, prevented thyroid metaplasia, and restored normal thyroid hormone production. Therefore, RegRF is a promising biotarget in autoimmune thyroiditis, and Fc fragments bearing regRF epitopes are a potential therapeutic agent for that condition.


Critical role of the neural pathway from the intermediate medial mesopallium to the intermediate hyperpallium apicale in filial imprinting of domestic chicks (Gallus gallus domesticus).
Filial imprinting in precocial birds is a useful model for studying early learning and cognitive development, as it is characterized by a well-defined sensitive or critical period. We recently showed that the thyroid hormone 3,5,3'-triiodothyronine (T3) determines the onset of the sensitive period. Moreover, exogenous injection of T3 into the intermediate medial mesopallium (IMM) region (analogous to the associative cortex in mammals) enables imprinting even on post-hatch day 4 or 6 when the sensitive period has been terminated. However, the neural mechanisms downstream from T3 action in the IMM region remain elusive. Here, we analyzed the functional involvement of the intermediate hyperpallium apicale (IMHA) in T3 action. Bilateral excitotoxic ablation of the IMHA prevented imprinting in newly hatched chicks, and also suppressed the recovery of the sensitive period by systemic intra-venous or localized intra-IMM injection of T3 in day-4 chicks. In contrast to the effect in the IMM, direct injection of T3 into the IMHA did not enable imprinting in day-4 chicks. Moreover, bilateral ablation of IMHA after imprinting training impaired recall. These results suggest that the IMHA is critical for memory acquisition downstream following T3 action in the IMM and further, that it receives and retains information stored in the IMM for recall. Furthermore, both an avian adeno-associated viral construct containing an anterograde tracer (wheat-germ agglutinin) and a retrograde tracer (cholera toxin subunit B) revealed neural connections from the IMM to the IMHA. Taken together, our findings suggest that hierarchical processes from the primary area (IMM) to the secondary area (IMHA) are required for imprinting.


Portal hypertension. A fifteen year perspective.
Two hundred six consecutive patients were followed from 5 to 15 years after a distal splenorenal shunt operation. Nonalcoholic patients demonstrated nearly twice the survival rate when compared with alcoholic patients. The mean duration of life for the surviving nonalcoholics was 10 years and for the alcoholics, 9 years. We predict that approximately a third of the nonalcoholics will enjoy long-term survival. The operative mortality rate was similar in both groups, being about 4 percent. The risk of liver cancer was highest in the male alcoholics, and long-term survival was greater for women in both the alcoholic and nonalcoholic groups.


Zinc as modulator of oxygenation function and stabilizer of quaternary structure in earthworm hemoglobin.
Blood of the earthworm Pheretima hilgendorfi contains 10.7 mM Ca, 2.0 mM Mg, 75.5 mM Na, 5.9 mM K, 0.9 mM Zn and 0.3 mM Mn. Some of these cations cannot be removed completely from the blood by dialysis, and 36 atoms of Ca, 1-3 atoms of Mg and 1-2 atoms of Zn per 164 atoms of Fe were retained in purified preparation of the hemoglobin (Hb). At physiological pH, oxygen affinity and the Hill coefficient at half saturation (n1/2 value) of the Hb increased in the presence of 100 mM of Ca, Mg or Na. These effects were in the order of Ca > Mg > Na. At physiological concentration, however, the effect of each of these three cations on oxygenation was rather small. On the other hand, Zn gave a remarkable effect at less than 1 mM. This suggests a possibility that Zn acts as a primal modulator for the oxygenation function of the Hb in vivo. Oxygenation data at various pH values in the presence of each cation strongly suggest that Zn binds to a site different from those for the other three cations. Zn at a concentration of only 1 mM protected considerably the dissociation of the whole molecule to smaller components at alkaline pH and Zn thus contributes to the stabilization of the quaternary structure of the Hb.


Inflammatory Bowel Disease and Short Bowel Syndrome.
Short bowel syndrome / intestinal failure (SBS/IF) is a rare and debilitating disease process that mandates a multidisciplinary approach in its management. Inflammatory bowel disease (IBD), in particular Crohn's disease (CD), predisposes patients to development of SBS/IF. This review discusses SBS/IF from the perspective of IBD, with an emphasis on prevention and treatment in the setting of CD. The aims of this review are to emphasize the unique treatment goals of the newly diagnosed SBS/IF patient, and highlight the role of both medical and surgical therapies in the management of IBD-related SBS/IF, including intestinal transplantation.


Advances in field-effect biosensors towards point-of-use.
The future of medical diagnostics calls for portable biosensors at the point of care, aiming to improve healthcare by reducing costs, improving access, and increasing quality-what is called the 'triple aim'. Developing point-of-care sensors that provide high sensitivity, detect multiple analytes, and provide real time measurements can expand access to medical diagnostics for all. Field-effect transistor (FET)-based biosensors have several advantages, including ultrahigh sensitivity, label-free and amplification-free detection, reduced cost and complexity, portability, and large-scale multiplexing. They can also be integrated into wearable or implantable devices and provide continuous, real-time monitoring of analytesin vivo, enabling early detection of biomarkers for disease diagnosis and management. This review analyzes advances in the sensitivity, parallelization, and reusability of FET biosensors, benchmarks the limit of detection of the state of the art, and discusses the challenges and opportunities of FET biosensors for future healthcare applications.


Coronal fractures of the medial femoral condyle: a series of 6 cases and review of literature.
Isolated coronal fracture of medial femoral condyle with intact lateral femoral condyle is extremely rare. We present our experience with such 6 cases of coronal fractures of medial femoral condyle. We reviewed all case records of cases of coronal fractures of femoral condyle which presented to our centre from Jan 2000 to Jun 2009. Of 72 such cases, 56 were of lateral condyle, 9 were bicondylar, and 7 were only medial femoral condyle fractures. However, one of the 7 cases was a skeletally immature child with a physeal injury and hence excluded. All the 6 patients with medial femoral condyle fractures were retrospectively evaluated both clinically and radiologically. Of the 6 patients with medial condyle fractures, three patients had an isolated medial femoral condyle fracture, while three of them had associated fractures. Four of these patients were identified at the initial presentation. However, the fracture was missed during initial evaluation in one of the patients, while another patient presented with neglected medial Hoffa fracture after 6 months of injury. Mechanism of injury was direct impact to the medial side of knee in flexion in 4 out of 6 cases. All cases were operated through medial or antero-medial approach, and fixation was achieved in all with antero-posterior screws. All cases united at a mean period of 4.6 months. Coronal fractures of the medial femoral condyle are very rare, and there is a highly likelihood of these fractures being missed by an average orthopaedic surgeon. A high index of suspicion is necessary for early diagnosis especially in cases of undisplaced fractures. Being intra-articular, the ideal management includes open reduction and internal fixation. Medial or antero-medial approach with antero-posterior screws is the preferred method for fixation.


Underlying cardiac lesions in adults with infective endocarditis. The changing spectrum.
The spectrum of recognized cardiac lesions underlying infective endocarditis has been changing as a result of the decline in incidence of rheumatic heart disease, the recognition of the entity of mitral valve prolapse, and the improvement in cardiac diagnostic techniques. Sixty-three cases of native valve endocarditis diagnosed in Memphis hospitals between 1980 and 1984 were reviewed. All diagnoses of underlying cardiac lesions were confirmed by two-dimensional echocardiography, cardiac catheterization, and/or histopathologic examination of valve tissues. Major categories of underlying lesions were as follows: mitral valve prolapse, 29 percent; no underlying disease, 27 percent; degenerative lesions of the aortic or mitral valve, 21 percent; congenital heart disease, 13 percent; rheumatic heart disease, 6 percent. Thus, mitral valve prolapse and, in the elderly, degenerative lesions have displaced rheumatic and congenital heart diseases as the major conditions underlying endocarditis. Redundancy of the mitral valve leaflets was noted in 17 of 18 patients in whom endocarditis was superimposed upon mitral valve prolapse. The risk of infective endocarditis appears to be substantially increased in the subset of patients with mitral valve prolapse who exhibit valvular redundancy.


Humans pIKK-up NLRP3 to skip NEK7.
NLRP3 inflammasome regulation is essential for controlling cell death and inflammation. Mechanistic studies in murine cells suggest a two-step model of priming and activation with an indispensable role for NEK7. However, in a recent article in Immunity, Schmacke et al. report that, in humans, transcription-independent NLRP3 activation occurs by circumventing NEK7 via IKKβ.


Options for treatment of a small glottic gap.
Glottic insufficiency, or glottic gap as it is commonly called, is a common cause of dysphonia, producing symptoms of soft voice, decreased projection, and vocal fatigue. The etiology of glottic gap can occur from issues related to muscle atrophy, neurologic impairment, structural abnormalities, and trauma related causes. Treatment of glottic gap can include surgical and behavioral therapies or a combination of the two. When surgery is chosen, closure of the glottic gap is the primary goal. Options for surgical management include injection medialization, thyroplasty, and other methods of medializing the vocal folds. This manuscript reviews the current literature regarding the options for treatment of glottic gap. This manuscript discusses options for treatment of glottic gap, including the indications for temporary and permanent treatment modalities; the differences between the available materials for injection medialization laryngoplasty and how they affect the vibratory function of the vocal folds and vocal outcome; and the evidence that supports an algorithm for treatment of glottic gap. 3a-Systematic review of case-control studies.


Electroencephalographic spectral power in writer's cramp patients: evidence for motor cortex malfunctioning during the cramp.
We investigated cortical activation as reflected in task-related spectral power (TRPow) changes in 8 writer's cramp patients during writing on a digital board and during isometric contraction and compared them to those of 8 age-matched healthy subjects. Scalp EEG was recorded over the contralateral primary sensorimotor area (SM1(c)), and from the ipsilateral sensorimotor area (SM1(i)). The electromyogram (EMG) was recorded from the Extensor Digitorum Communis (Extensor), Flexor Digitorum Superficialis (Flexor), and First Dorsal Interosseous (FDI) muscles. We analyzed (1) handwriting performance, (2) changes in the TRPow confined to alpha and beta band, and (3) the EMG spectral power during both tasks, writing and isometric contraction. During writing, all patients developed writer's cramp. The handwriting in writer's cramp patients was associated with significantly less reduction of the beta-range TRPow and lower frequency of the TRPow reduction compared to controls. No significant differences between patients and controls for the alpha band TRPow reduction during handwriting were observed. During writing, the patients showed higher EMG spectral power than the controls but this difference was at the border of significance. The present results indicate disorder in the motor execution system, in writer's cramp patients, associated with impaired functional beta-network state of the contra- and ipsilateral sensorimotor cortices, most probably due to inadequate modulation of the intracortical inhibition associated with writing.


Epidemiological application of early markers of nephrotoxicity.
This paper is a review of epidemiological studies in which sensitive markers of nephrotoxicity have been used to detect the early effects of chemicals on the kidney. Most of the studies are cross-sectional, and their objective was either to identify potentially nephrotoxic chemicals (organic solvents, heavy metals) in the working or general environment or to establish dose-response/effect relationships from which safe exposure levels can be defined (e.g., for cadmium and mercury vapour). A few longitudinal studies were conducted to determine the persistence of renal disturbances and to get information on their predictive value (e.g., microproteinuria in cadmium workers). Nephrotoxicity tests, which have proved to be the most useful in these epidemiological studies, rely on the determination of specific urinary proteins which, according to their size, reflect the functional integrity of the proximal tubule (e.g., retinol-binding protein or beta 2-microglobulin) or the glomerulus (e.g., albumin, immunoglobulin G). An increased urinary excretion of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase has been reported in several studies (e.g., in lead-exposed workers), but the pathological significance of this finding remains to be clarified, particularly when it is not associated with changes in the urinary excretion of specific proteins. Further work is needed to assess the usefulness of tests introduced more recently such as the assay of renal antigens in urine and the use of red-blood-cell membrane negative charges as an index of the glomerular polyanion. With the exception of microproteinuria observed in chronic cadmium poisoning, no epidemiological data are available on the prognostic value of subclinical renal effects caused by nephrotoxic chemicals.


Specific and reversible activation and inactivation of the mitochondrial phosphate carrier by cardiolipin and nonionic detergents, respectively.
The phosphate carrier of pig heart mitochondria was solubilized with Triton X-100 and purified by chromatography on hydroxylapatite. Incubation of the phosphate carrier fraction with cardiolipin stimulated the reconstituted [32P]phosphate exchange activity in liposomes, whereas increased Triton X-100 concentrations inhibited it. The effects of cardiolipin and Triton X-100 are reversible. The activation by cardiolipin is highly specific and could not be obtained with any other applied phospholipid.


Calcium channelopathy mutants and their role in ocular motor research.
Thanks to technical advances in eye movement recording, the mouse is destined to become increasingly important in ocular motor research. An advantage of this species is the wide range of existing mutant strains and techniques to generate new mutations affecting specific cell types. Mutations of ion channels may be used to modulate the intrinsic properties of neurons, and this approach may generate insight into the degree to which neuronal computations depend upon those intrinsic properties as opposed to the properties of circuits of neurons. Dendritic calcium currents carried by P-type voltage-activated calcium channels have been widely postulated to perform important computational functions in cerebellar Purkinje cells. Mutations of this channel lead to human diseases, and several ataxic strains of mice are now known to harbor mutations of this calcium channel. Murine P-channel mutants such as rocker are ataxic, but have normal or near-normal numbers of cerebellar Purkinje cells and thus offer the opportunity to study the effects of biophysical perturbations as opposed to outright cell destruction or inactivation. Initial studies of rocker mice reveal an array of ocular motor abnormalities, including static hyperdeviation of the eyes and an attenuation of vestibulo-ocular reflex gains at high stimulus frequencies. The pattern of gain and phase abnormalities is entirely different in lurcher, an ataxic mutant in which Purkinje cells degenerate. The ocular motor abnormalities of rocker progress with animal age, underscoring the importance of careful attention to animal age when performing ocular motor studies in this short-lived species.


An incidental finding? Pneumatosis intestinalis after minor trauma.
Pneumatosis intestinalis (PI) refers to the identification of air within the wall of the gastrointestinal tract. This finding often marks serious underlying pathology, which can be potentially surgical in nature. However, this process may also occur within a benign context, for example, in patients who are chronically immunosuppressed. The prevalence of benign PI may be greater than previously anticipated, because its discovery is facilitated by the increasingly widespread use of computed tomography (CT) scanning. We will illustrate how widespread use of CT scanning after trauma leads to incidental findings, some of which are difficult to distinguish from acute pathologic findings. We will also discuss the differential diagnosis for PI and the associated clinical significance. A female patient with two autoimmune disorders requiring immunosuppression presented after minor trauma. Her clinical stability and benign examination led us to refrain from ordering a full radiographic evaluation, including an abdominal CT scan. She was safely discharged; however, per CT several days later, the incidental finding was made of PI with free intraperitoneal air. These findings after trauma commonly prompt an exploratory laparotomy. However, given her persistent stability, we attributed this to immunosuppression rather than to recent trauma. The indications for ordering CT scans after minor trauma must be carefully considered, and incidental findings must be interpreted in the context of the overall clinical scenario.


Effectiveness of Rex shunt for improving the abnormal portal hemodynamics and portal venous pathology in EHPVO animal model.
To investigate the feasibility of the re-patent EHPVO (r-EHPVO) as an animal model of Rex shunt and the effectiveness of Rex shunt in improving abnormal portal hemodynamics and portal venous pathology of EHPVO. A total of 18 New Zealand white rabbits were randomly divided into three groups: normal control (NC) group, extrahepatic portal venous obstruction (EHPVO) group, and r-EHPVO group. The main portal vein was dissected only in the NC group. The main portal vein was narrowed by a cannula in the EHPVO group. The cannula narrowing the main portal vein was removed to restore the portal blood flow into the liver on day 14 in the r-EHPVO group. The portal pressure, splenic size, blood flow velocity, and diameter of the portal vein were measured on days 14 and 28. The shear stress (SS) and circumferential stress (CS) of the portal vein were calculated. The proximal end of the main portal vein was collected on day 28 for further pathological analysis, and the thickness and area of the intima and media were measured by Image J software. The portal pressure, splenic size, SS, CS, intima and media thickness, the ratio of intimal to medial area (I/M), and the ratio of intimal area to the sum of intimal and medial area (I/I + M) were compared among the three groups. The correlation between SS and intimal thickness and between CS and medial thickness were analyzed. On day 28, the portal pressure of the EHPVO group was significantly higher than that of the NC and r-EHPVO groups, but no significant difference was detected in the portal pressure between r-EHPVO and NC groups. The length and thickness of the spleen in the EHPVO and r-EHPVO groups were significantly higher than those in the NC group (P < 0.01) but were significantly lower in the r-EHPVO group than those in the EHPVO group (P < 0.05). The SS was significantly lower in the EHPVO group than in NC and r-EHPVO groups (P < 0.05) but was significantly higher in the NC group than in the r-EHPVO group (P = 0.003). The CS was significantly higher in the EHPVO and r-EHPVO groups than that in the NC group (P < 0.05) but was significantly lower in the r-EHPVO group than that in the EHPVO group (P < 0.001). The intimal thickness, I/M, and I/I + M of the EHPVO group were significantly higher than those of the NC and r-EHPVO groups (P < 0.05), but no significant difference was observed between the NC and r-EHPVO groups (P > 0.05). The SS is negatively related to intimal thickness (r = - 0.799, P < 0.001). The r-EHPVO model is feasible as an animal model of the Rex shunt. The Rex shunt could be beneficial to improving the abnormal portal hemodynamic and portal venous intimal hyperplasia by restoring the portal blood flow into the liver.


[Treatment perspectives for critical limb ischemia: gene and cell therapy].
Critical limb ischemia is associated with a high risk of amputation and death. Several medical options have been tested on patients who cannot be revascularized surgically, but none has shown any effect on the amputation rate at 6 months.Gene and cell therapy intended to stimulate angiogenesis have been tested in phase I and II clinical trials. These innovative approaches appear both feasible and safe. Large randomized clinical trials are necessary to demonstrate their benefits and long-term safety.


Resistance gene analogs involved in tolerant cassava--geminivirus interaction that shows a recovery phenotype.
The current literature describes recovery from virus-induced symptoms as a RNA silencing defense, but immunity-related genes, including the structurally specific resistance gene analogs (RGAs) that may play a key role in tolerance and recovery is not yet reported. In this study, the transcriptome data of tolerant cassava TME3 (which exhibits a recovery phenotype) and susceptible cassava T200 infected with South African cassava mosaic virus were explored for RGAs. Putative resistance protein analogs (RPAs) with amide-like indole-3-acetic acid-Ile-Leu-Arg (IAA-ILR) and leucine-rich repeat (LRR)-kinase conserved domains were unique to TME3. Common responsive RPAs in TME3 and T200 were the dirigent-like protein, coil-coil nucleotide-binding site (NBS) and toll-interleukin-resistance, disease resistance zinc finger chromosome condensation-like protein (DZC), and NBS-apoptosis repressor with caspase recruitment (ARC)-LRR domains. Mutations in RPAs in the MHD motif of the NBS-ARC2 subdomain associated with the recovery phase in TME3 were observed. Additionally, a cohort of 25 RGAs mined solely during the recovery process in TME3 was identified. Phylogenetic and expression analyses support that diverse RGAs are differentially expressed during tolerance and recovery. This study reveals that in cassava, a perennial crop, RGAs participate in tolerance and differentially accumulate during recovery as a complementary defense mechanism to natural occurring RNA silencing to impair viral replication.


Solitary hepatic infantile hemangioendothelioma: dynamic gadolinium-enhanced MR imaging findings.
We report the MRI findings of a solitary hepatic infantile hemangioendothelioma (IHE) diagnosed in a 14-day-old girl. To the best of our knowledge, only one report has illustrated the dynamic gadolinium-enhanced MR imaging features of IHE previously. Compounding the rarity of presentation as a solitary mass, the gadolinium-enhanced MRI appearance in our case is unique, because the IHE showed an early rim-like pseudocapsular enhancement followed by progressive fill-in of the lesion on delayed imaging.


Effectiveness and outcomes of air travel-related TB incident follow-up: a systematic review.
The World Health Organization (WHO) recommends following up passengers after possible exposure to a case of infectious tuberculosis (TB) during air travel. This is time-consuming and difficult, and increasingly so with higher numbers each year of flights and passengers to and from countries with high TB endemicity. This paper systematically reviews the literature on contact tracing investigations after a plane exposure to active pulmonary TB. Evidence for in-flight transmission was assessed by reviewing the positive results of contacts without prior risk factors for latent TB.A search of Medline, EMBASE, BIOSIS, Cochrane Library and Database of Systematic Reviews was carried out, with no restrictions on study design, index case characteristics, duration of flight or publication date.In total, 22 papers were included, with 469 index cases and 15 889 contacts. Only 26.4% of all contacts identified completed screening after exposure. The yield of either a single positive tuberculin skin test (TST) or a TST conversion attributable to in-flight transmission was between 0.19% (95% CI 0.13%-0.27%) and 0.74% (95% CI 0.61%-0.88%) of all contacts identified (0.00%, 95% CI 0.00%-0.00% and 0.13%, 95% CI 0.00%-0.61% in random effects meta-analysis). The main limitation of this study was heterogeneity of reporting.The evidence behind the criteria for initiating investigations is weak and it has been widely demonstrated that active screening of contacts is labour-intensive and unlikely to be effective. Based on our findings, formal comprehensive contact tracing may be of limited utility following a plane exposure.


Switching off: The phenotypic transition to the uninduced state of the lactose uptake pathway.
The lactose uptake pathway of E. coli is a paradigmatic example of multistability in gene regulatory circuits. In the induced state of the lac pathway, the genes comprising the lac operon are transcribed, leading to the production of proteins that import and metabolize lactose. In the uninduced state, a stable repressor-DNA loop frequently blocks the transcription of the lac genes. Transitions from one phenotypic state to the other are driven by fluctuations, which arise from the random timing of the binding of ligands and proteins. This stochasticity affects transcription and translation, and ultimately molecular copy numbers. Our aim is to understand the transition from the induced to the uninduced state of the lac operon. We use a detailed computational model to show that repressor-operator binding and unbinding, fluctuations in the total number of repressors, and inducer-repressor binding and unbinding all play a role in this transition. Based on the timescales on which these processes operate, we construct a minimal model of the transition to the uninduced state and compare the results with simulations and experimental observations. The induced state turns out to be very stable, with a transition rate to the uninduced state lower than 2×10-9 per minute. In contrast to the transition to the induced state, the transition to the uninduced state is well described in terms of a 2D diffusive system crossing a barrier, with the diffusion rates emerging from a model of repressor unbinding.


Real economic benefits and environmental costs accounting of China-US trade.
A critical reason for China-United States trade friction is that China has a huge trade balance, especially the trade balance of goods. However, this huge trade balance is based on the results of official statistics and does not reflect the real economic benefits and environmental costs embodied in China-US trade, where both refer to trade in value-added and embodied CO2 emission costs, respectively. This paper calculates the trade in value-added and carbon emission transfer between China and the United States based on the World Input-Output Database. Results demonstrate that: (1) Gross trade statistics seriously overestimate China's benefits in China-US trade. The China-US trade surplus, based on gross trade statistics, is 20% higher than when based on trade in value-added accounting. (2) In China-US bilateral trade, China mainly adopts the trade model of importing intermediate products and exporting final products,whereas the United States mainly adopts the trade model of importing final products and exporting intermediate products. China's exports to the United States contain many of value-added in Korea, Taiwan, and Japan. (3) From 2000 through 2014, China maintained a large surplus of CO2 emissions exports to the United States, and China paid a huge environmental cost in its trade with the United States. (4) In China-US trade, China's environmental costs per unit value-added is 3.02 times that of the United States.


Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis.
Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia in patients with PSC. This inflammatory signature is characterized by antigen-driven interleukin-17A (IL-17A)+ forkhead box P3 (FOXP3)+ CD4 T cells that express a pathogenic IL-17 signature, as well as an expansion of IgG-secreting plasma cells. These results suggest that the mechanisms that drive the emergence of dysplasia in PSC and IBD are distinct and provide molecular insights that could guide prevention of colorectal cancer in individuals with PSC.


COVID-19's impact on the U.S. labor market as of September 2020.
This paper summarizes the impact of COVID-19 (through mid-September 2020) on the U.S. labor market through the lens of measures found in monthly Bureau of Labor Statistics' Employment Situation releases. It describes the pandemic's impact thus far by looking at payroll jobs, the unemployment rate, a broader measure of job disruptions, and disparities by race and sex. The conclusion discusses forces that will drive outcomes in the coming months. The findings are as follows: (1) The COVID-19 shock was very abrupt and deep by historical standards, and headline numbers understate the magnitude of job disruptions. (2) The pace of the jobs recovery has slowed markedly since June. (3) The share of disrupted workers with ties to employers, which began very high, is falling rapidly, dimming prospects for further rapid recovery. (4) Hispanic, African American and women workers' jobs were more disrupted than others'. (5) Prospects for a speedy jobs recovery depend strongly on the path of the pandemic and degree of fiscal stimulus, both aided by official statistics to guide decisions at all levels during this critical time.


Retinal ganglion cell death in glaucoma: mechanisms and neuroprotective strategies.
Various cellular and molecular mechanisms that may lead to apoptotic cell death of retinal ganglion cells in glaucoma are discussed. These cellular mechanisms include neurotrophic factor deprivation, ischemia, glial cell activation, glutamate excitotoxicity, and abnormal immune response. Based on experimental and clinical evidence, the rationale for various neuroprotective strategies is described.


A Multi-strain Potential Probiotic Formulation of GABA-Producing Lactobacillus plantarum 90sk and Bifidobacterium adolescentis 150 with Antidepressant Effects.
Today, a number of studies conclusively show that certain bacterial strains, mainly from the genera Lactobacillus and Bifidobacterium, influence the functioning of the central nervous system, leading to changes in beahvior, nociception and the cognitive abilities of humans and animals. Such strains serve as the basis for developing probiotics with a curative potential for the central nervous system - psychobioitcs. However, the question of how to find such strains and which criteria to use for their selection remains unanswered. Some compounds produced by bacteria, such as gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter of the central nervous system, are potential mediators between bacterial cells and the host. Previously, we established that some species of Lactobacillus and Bifidobacterium are capable of producing GABA. We presumed that GABA-producing Lactobacillus and Bifidobacterium strains are great candidates to use as psychobiotics. Therefore, we selected the strains Lactobacillus plantarum 90sk and Bifidobacterium adolescentis 150 as efficient GABA producers. The goal of this work was to assess the probiotic properties of the selected strains as well as their antidepressive effects in mice. We established that the ingestion of the probiotic composition based on the selected strains by BALB/c mice for 2 weeks reduced depressive-like behavior in the forced swimming test; the effect was similar to that of fluoxetine.


Guidelines for the management of children at risk of secondary bone fragility: Expert opinion of a French working group.
The current French national guidelines were elaborated by a working group consisting of experts in the field of pediatric endocrinology, rheumatology, hepatogastroenterology, nephrology, and pneumology. A systematic search was undertaken of the literature published between 2008 and 2018 and indexed in PubMed. The recommendations developed were then validated by an external evaluation group comprising representatives from the various highly specialized fields in pediatrics, representatives of the societies and groups supporting the development of the guidelines, and representatives of different healthcare professions. The objective of these guidelines was to detail the current optimal management of children at risk of secondary bone fragility.


Effects of expression of transcriptional factor AP-1 FOSL1 gene on psoriatic process.
We performed quantitative analysis of FOSL1 gene expression in lesional psoriatic skin. The expression of this gene in lesional psoriatic skin was significantly increased compared to that in unaffected areas. Enhanced FOSL1 expression significantly correlated with high psoriasis area and severity index (PASI). High level of FOSL1 gene expression was proposed to be a marker of pathological process activity in psoriasis.


[Opportunities for the evaluation of the secondary reaction of antituberculosis drugs by several indicators, determined in the blood of patients with tuberculosis of the lungs].
Some bioenergetic patterns were studied in blood and blood plasma of patients with pulmonary tuberculosis as well as--in rats after long-term daily administration of rifampycin and isoniazid at therapeutic doses. A series of bioenergetic patterns, estimated simultaneously, enabled to detect the side reactions caused by chemotherapy before occurrence of clinical symptoms. Correlation was analysed between these patterns and the routine biochemical tests used for evaluation of the drug side effects. A scheme describing relationship between amino acid transamination in blood plasma and reactions of energy metabolism is presented. The scheme shows the sequence of activation of various enzymatic reactions in blood plasma after an increase in consumption of tissue energy resources in various tissues.


Effect of Statistically Iterative Image Reconstruction on Vertebral Bone Strength Prediction Using Bone Mineral Density and Finite Element Modeling: A Preliminary Study.
Statistical iterative reconstruction (SIR) using multidetector computed tomography (MDCT) is a promising alternative to standard filtered back projection (FBP), because of lower noise generation while maintaining image quality. Hence, we investigated the feasibility of SIR in predicting MDCT-based bone mineral density (BMD) and vertebral bone strength from finite element (FE) analysis. The BMD and FE-predicted bone strength derived from MDCT images reconstructed using standard FBP (FFBP) and SIR with (FSIR) and without regularization (FSIRB0) were validated against experimental failure loads (Fexp). Statistical iterative reconstruction produced the best quality images with regard to noise, signal-to-noise ratio, and contrast-to-noise ratio. Fexp significantly correlated with FFBP, FSIR, and FSIRB0. FFBP had a significant correlation with FSIRB0 and FSIR. The BMD derived from FBP, SIRB0, and SIR were significantly correlated. Effects of regularization should be further investigated with FE and BMD analysis to allow for an optimal iterative reconstruction algorithm to be implemented in an in vivo scenario.


Cytotoxic ergostane-type steroids from Ganoderma lingzhi.
Two new ergostane-type steroids (1 and 2) have been isolated from the fruiting body of a medicinal macro fungus Ganoderma lingzhi. The structures including the absolute configurations of them were elucidated by a combination of different spectroscopic analyses especially 13C NMR and ECD calculations. Compound 2 features an unusual 1,2-dioxolane moiety. Our bioassays revealed that the two steroids showed remarkable cytotoxicity against human A549 (lung) and MCF-7 (breast) tumor cell lines, with IC50 values ranging from 5.15 to 8.57 μg/mL.


A study of glycoproteins in human serum and plasma reference standards (HUPO) using multilectin affinity chromatography coupled with RPLC-MS/MS.
The glycoproteome is a major subproteome present in human plasma. In this study, we isolated and characterized approximately 150 glycoproteins from the human plasma and serum samples provided by HUPO using a multilectin affinity column. The corresponding tryptic digest was separated by RP-HPLC coupled to an IT mass spectrometer (3-D LCQ). Also in this study, a new system, namely an Ettan MDLC system coupled to a linear ITLTQ, was compared with the previous LCQ platform and gave a greater number of protein identifications, as well as better quality. When we compared the composition of the glycoproteomes for the plasma and serum samples there was a close correlation between the samples, except for the absence of fibrinogen from the identified-protein list in the latter sample, which was presumably as a result of the clotting process. In addition, the analysis of the samples from three ethnic specimens, Caucasian American, Asian American, and African American, were very similar but showed a higher angiotensinogen plasma level and a lower histidine-rich glycoprotein level in Caucasian American samples, and a lower vitronectin level in African American blood samples.


Prognostic factors for response to treatment by corticosteroid injection or surgery in carpal tunnel syndrome (palms study): A prospective multicenter cohort study.
Studies of prognosis for surgery and corticosteroid injection for carpal tunnel syndrome (CTS) have considered only a limited range of explanatory variables for outcome. Data were prospectively collected on patient-reported symptoms, physical and psychological functioning, comorbidity, and quality of life at baseline and every 6 months for up to 2 years. Outcomes were patient-rated change over a 6-month period and symptom-severity score at 18 months. In total, 754 patients with CTS completed baseline questionnaires, and 626 (83%) completed follow-up to 18 months. Multivariable modeling identified, independent of symptom severity at outset, higher health utility, fewer comorbidities, and lower anxiety as significant predictors of better outcome from surgery. In patients treated by steroid injection, independent of symptom severity at outset, shorter duration of symptoms and having no prior injection were significant predictors of better outcome. These multivariable models of outcome may inform shared decision making about treatment for CTS. Muscle Nerve, 2019.


Orthopedic disorders in neonatal foals.
The first month of life is a vulnerable time for foals. They must adjust to their environment while they are still compromised immunologically, and their musculoskeletal system is rapidly growing and adjusting to stresses from an increasing amount of exercise. Therefore, if a foal is born with or acquires an abnormality or disease related to the musculoskeletal system, rapid adjustments must be made to allow the foal to grow and respond so that future athletic performance will not be compromised. Problems must be identified early, which requires thorough examinations. This article summarizes treatment options for orthopedic disorders that present or become clinically evident within the first month of life.


New biomedical strategies for HIV-1 prevention in women.
Novel HIV-1 prevention strategies continue to be urgently needed. This article reviews the current state of biomedical prevention against HIV-1, focusing on recently completed and ongoing clinical trials of new prevention interventions, particularly those relevant to prevention of HIV-1 in women. Male circumcision, cervical barrier devices, suppressive therapy against herpes simplex virus type 2, treatment of vaginal infections and other vaginal health interventions, pre-exposure antiretroviral prophylaxis, and topical vaginal microbicides are discussed.


Individual differences in saccharin acceptance predict rats' food intake.
Following previous results indicating that low acceptance of saccharin-sweetened yoghurt was associated with slower weight gain, the aim of this experiment was to determine which of three measures of individual differences would predict subsequent chow consumption, body weight gain, and fat mass. Pre-test measures consisted of amount of running in an activity wheel, amount of 0.1% saccharin solution consumed over 24h, and performance on an elevated plus maze (EPM). Rats were then maintained for three weeks on a diet of standard chow and water. Subsequent post-testing repeated the procedures used in pre-testing. The rats were then culled and fat pads excised and weighed. Pre-testing revealed a negative correlation between saccharin acceptance and activity, while neither measure correlated with anxiety in the EPM. Pre-test saccharin acceptance was positively correlated with subsequent chow consumption, percent weight gain, and g/kg fat mass. Multiple regression analyses including all three pre-test measures confirmed saccharin acceptance as a predictor of chow consumption and, marginally, of fat pad mass, while high anxiety predicted low percent body weight gain.


Controversies and hazards in the treatment of pit viper bites.
This paper discusses the pathology produced by pit viper venom and the pharmacologically active substances released by the action of venom on human tissue. The risks of many of the popular methods of treatment such as tourniquets, cryotherapy, incisions, excisions, and cortisone are also discussed. A prospective treatment plan was devised which was limited to measures of proven benefit, and 28 patients were treated with no mortality or tissue necrosis.


Preoperative long-acting octreotide treatment for invasive thyrotropin-secreting pituitary macroadenoma after previous radioiodine thyroid ablation.
We report a 33-year-old woman with invasive thyrotropin-secreting pituitary adenoma after previous thyroid ablation with radioiodine who was successfully treated with transsphenoidal surgery after pre-treatment with octreotide-LAR for 10 months. Since invasive and aggressive thyrotropin-secreting macroadenomas are more frequently observed in patients who have undergone thyroid ablation, we suggest preoperative treatment with somatostatin analogs should be considered in these patients to reduce serum thyrotropin and stabilize or reduce tumor size.


Efficacy of ivermectin against third-stage Dirofilaria immitis larvae in ferrets and dogs.
Ivermectin prevented maturation of Dirofilaria immitis when given per os to ferrets at a dosage of 0 X 1 mg ivermectin per kg bodyweight two days after inoculation with third stage heartworm larvae. Similar results were found in dogs treated one day after infection at a dosage of 0 X 05 mg ivermectin per kg. No heartworm were found in the hearts and lungs of five treated dogs compared to an average of 11 worms per dog in five control animals.


Gendered experiences of widowhood and depression across Europe: The role of loneliness and financial resources from a longitudinal perspective.
This study analyses the gendered experiences of widowhood and its relation to depressive symptoms in four European regions. A special focus lies on the question whether loneliness and reduced financial contribute to the detrimental effect of widowhood on mental health. Using waves 5,6 and 7 of the Survey of Health. Ageing and Retirement in Europe (SHARE), this study estimates fixed-effects linear regression models for the effect of widowhood on depressive symptoms with and without adjustment for potential mediating factors. There were no gender differences in the mental health consequences of widowhood irrespective of the regional context. Whereas loneliness was a major pathway through which widowhood exerts its negative consequences on mental health, reduced financial resources did not play a substiantial role. Moreover, the magnitude of the widowhood effect on depressive symptoms differed between European regions with stronger increases in Southern Europe. These regional differences were attenuated when accounting for inequalities in financial resources and loneliness. The findings support Attachment Theory, which postulates that it's mainly the loss of such an emotionally strong tie as one's spouse that leads to psychological distress following widowhood. Moreover, one can conclude that some contexts in Europe provide conditions that buffer the negative effect of widowhood on mental health at least to some extent.


Effects of antihistamines on centrifugal rotation-induced analgesia and conditioned flavor aversions.
Centrifugal rotation induces short lasting analgesia, as shown in tail flick tests conducted immediately afterwards, and apparently induces visceral upset that can support aversions for flavors ingested immediately beforehand, as indicated in later preference tests. Two experiments were performed with antihistamines to determine whether the analgesic and visceral effects of rotation were attributable to separate neurochemical systems. In each experiment four groups of rats were defined by factorial combination of UCS (rotation at 150 rpm vs. no rotation) and Drug (antihistamine vs. saline). In Experiment 1 the H1 blocker chlorpheniramine (20 mg/kg, IP) was found to be ineffective against analgesia and to block conditioned flavor aversions (CFAs). In Experiment 2 the H2 blocker cimetidine (100 mg/kg, IP) was found to have a nearly significant attenuating effect on analgesia and to have no effect on CFAs. The data support the idea that analgesia and visceral upset are attributable to separate mechanisms, both of which are activated by the same manipulations.


Bonding orthodontic acrylic resin to enamel.
Bonded acrylic orthodontic appliances are a recent alternative to banded methods. However, the physical properties demonstrated by bonding adhesives at the acrylic-enamel interphase have not been well documented. The purpose of this study was to use a laboratory testing model to evaluate the ultimate shear and tensile strengths and fracture sites of five bonding adhesives: unfilled (Bracketbond and Genie); filled (Unite, Excel, and Concise). One hundred bovine mandibular incisors were embedded in dental stone, labial surfaces ground flat for uniform acrylic-enamel adaptation, and stored in modified Fusyama's artificial saliva. Twenty 7-mm diameter acrylic cylinders were bonded in each group. Ten samples from each group were tested for shear strength and ten for tensile strength with an Instron testing machine. Bonding adhesive retained on the cylinder was measured by means of a Bioquant digitizer. Scanning electron microscopy was used to analyze fracture sites. The results showed that the percentage of bonding adhesive that remains on the acrylic surface after fracture is decreased by the addition of inorganic fillers to the adhesive and the use of separate liquid resin sealants, and is increased by the use of plastic bracket primers and bonding adhesives that are chemically similar to methylmethacrylate. Few significant differences in shear and tensile strengths were found among the bonding adhesives. Unfilled bonding adhesives cause less enamel damage and are indicated for clinical bonding of acrylic orthodontic appliances to enamel.


A comprehensive analysis and literature review of vertebral artery variation in craniovertebral junction using three-dimensional computed tomography angiography.
To describe vertebral artery (VA) variation in patients with or without osseous anomalies at congenital craniovertebral junction (CVJ). In the present study, we retrospectively analyzed 258 patients with VA variation who underwent three-dimensional computed tomography angiography (3D CTA) in our hospital from March 2017 to October 2019. Among 258 patients, 180 were accompanied by skeleton structural malformation, including 105 cases of occipital ossification of the atlas, 8 cases of the bipartite atlas, 7 cases of hypoplasia of the posterior arch of the atlas, 45 cases of C2/3 congenital fusion, 2 cases of C2/3/4 congenital fusion, and 13 cases of congenital os odontoid. VA variation was divided into type A (VA variation in the CVJ area without osseous anomalies) and type B (VA variation in the CVJ area with osseous anomalies). There are totally 10 subtypes, including type A1 (atlas occipitalization with VA entrance approach close to middle line, 20.2%); type A2 (atlas occipitalization with VA entrance approach far from middle line, 30.2%); type A3 (first intersegmental VA in C1-C2, 1.9%); type A4 (fenestration of the VA, 2.3%); type A5 (VA bulging type, 6.6%); type A6 (VA exposures with the absence of the posterior atlas arch, 2.3%); type A7 (C2 inner wall type, 0.4%); type A8 (single vertebral artery, 2.3%); type B1 (posterior ponticuli, 2.7%); and type B2 (high-riding VA, 31.4%). This study is expected to take the lead in the most comprehensive classification of VA variation.


Dissolved nitrogen in drinking water resources in Al-Mahareth village of Assir - Saudi Arabia.
A water quality study was carried out on ground water wells, which serve as drinking water sources in farming communities in Al-Mahareth village of Assir region of the Kingdom of Saudi Arabia. The objective of this research was to determine concentrations of different forms of nitrogen in drinking water samples. Water samples were collected from these sources every 3 months (from January to December 2008) and analyzed for ammonia, nitrate and nitrite using the Plaintest Photometer Method. Results indicated that the annual mean concentration of nitrate, nitrite and ammonia varied from 23.09 to 25.06 mg/l, 0.006 to 0.36 mg/l and 0.008 to 0.179 mg/l, respectively. An important observation was that, in general, higher nitrate and nitrite concentrations were found during the rainy season compared to the dry season. Concentrations of these potentially toxic substances were below WHO acceptable limits for surface and ground waters, indicating that these water resources appear safe for drinking from a dissolved nitrogen perspective.


Myocardial-vessel interaction: role of LV pressure and myocardial contractility.
Coronary heart disease is one of the most important health problems in Western society. The principal mechanism in this problem is the failure of sufficient blood supply to reach the heart muscle for cardiac metabolic needs and hence failure of the heart as a pump. Despite the magnitude of this health problem, the system of blood supply to the heart (the coronary circulation) remains poorly understood. The reason for this is that clinical work has largely focused on the diseased vessels (e.g., atherosclerosis) rather than on the dynamics of the coronary blood flow system as a whole. The latter requires a bioengineering understanding of both the highly complex system and associated mechanical determinants. Despite progress in this area, many issues remain unresolved. Advancements in high-performance computers make it possible now to attempt anatomically based computational (distributive) models rather than the "lumped" models used in the past, where the anatomical details of the coronary vascular system were ignored. Computer simulation and modeling are an important tool in this work because experimental avenues to the problem are highly limited, particularly in the circulation of the deeper layer of the heart which is not amenable to direct visualization. The mechanism of the effect of the cyclic contraction on coronary blood flow remains unresolved. This review will consider the major cardiac mechanical interactions with coronary blood flow including previous models, current hypotheses, and future directions. Experimental validation of present and future mechanical interaction models will be emphasized as well as the utility of the models to explain the mechanical propensity of the subendocardium to ischemia.


Polyethylene Incorporating Diels-Alder Comonomers: A "Trojan Horse" Strategy for Chemically Recyclable Polyolefins.
Polyolefins with periodic unsaturation in the backbone chain are sought after for synthesizing chemically recyclable polymers or telechelic polyolefin macromonomers. Here we introduce a bottom-up synthesis of unsaturated high-density polyethylene (HDPE) via copolymerization of ethylene with dimethyl 7-oxabicyclo[2.2.1]hepta-2,5-diene-3,5-dicarboxylate followed by post-polymerization retro-Diels-Alder to unveil hidden double bonds in the polymer backbone. The incorporation of this "Trojan Horse" comonomer was varied and a series of unsaturated HDPE polymers with block lengths of 1.2, 1.9, and 3.5 kDa between double bonds was synthesized. Cross metathesis of unsaturated HDPE samples with 2-hydroxyethyl acrylate yielded telechelic ester terminated PE macromonomers suitable for the preparation of ester-linked PE. These materials were depolymerized and repolymerized, making them suitable candidates for chemical recycling. The ester-linked PE displayed thermal and mechanical properties comparable to commercial HDPE.


Effect of chemoprophylaxis with avermectins on the immune response to gastrointestinal nematodes in first-season grazing calves.
The influence of chemoprophylaxis on the immune response to gastrointestinal nematodes was evaluated in three groups of ten first-season grazing calves. Group C functioned as untreated controls, whereas Group L received two treatments, one at turn-out and one 8 weeks later, with doramectin (200 micrograms kg-1) and Group H three treatments, 3, 8, and 13 weeks post turn-out, with ivermectin (200 micrograms kg-1). At housing, five calves of each group were randomly selected for necropsied for worm counts. The remaining calves were challenged with 50,000 Ostertagi and 100,000 Cooperia oncophora and necropsied 4 weeks later. During the grazing season, Group C suffered from an outbreak of parasitic gastroenteritis which necessitated two anthelmintic treatments. In both treated groups no clinical symptoms were observed and growth rates were normal. Pepsinogen levels and antibody concentrations indicated a moderate and low gastrointestinal nematode infection in Group L and Group H, respectively. The Ostertagia and Cooperia worm populations present in the calves necropsied at housing were reduced in both treated groups in comparison with Group C. In the challenged calves, egg output was significantly higher in Group H than in Group L and Group C. Ostertagia and Cooperia worm burdens after challenge were high in Group H, moderate to low in Group L and low in Group C. This study indicates that highly suppressive prophylactic programmes, such as the ivermectin 3, 8 and 13 weeks schedule, can impair immune development against gastrointestinal nematodes during the first grazing season.


The external domains of the HIV-1 envelope are a mutational cold spot.
In RNA viruses, mutations occur fast and have large fitness effects. While this affords remarkable adaptability, it can also endanger viral survival due to the accumulation of deleterious mutations. How RNA viruses reconcile these two opposed facets of mutation is still unknown. Here we show that, in human immunodeficiency virus (HIV-1), spontaneous mutations are not randomly located along the viral genome. We find that the viral mutation rate experiences a threefold reduction in the region encoding the most external domains of the viral envelope, which are strongly targeted by neutralizing antibodies. This contrasts with the hypermutation mechanisms deployed by other, more slowly mutating pathogens such as DNA viruses and bacteria, in response to immune pressure. We show that downregulation of the mutation rate in HIV-1 is exerted by the template RNA through changes in sequence context and secondary structure, which control the activity of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (A3)-mediated cytidine deamination and the fidelity of the viral reverse transcriptase.


Sex differences in predictors and outcomes of camouflaging: Comparing diagnosed autistic, high autistic trait and low autistic trait young adults.
Many autistic people use strategies that help them adapt in social situations and hide behaviours that may seem different to non-autistic individuals - this is called camouflaging. Camouflaging may help autistic people fit in socially; however, it might also lead to poorer well-being. It has been suggested that autistic females camouflage more than autistic males. This article explored differences between males and females who have an autism diagnosis, have characteristics of autism but no diagnosis and those with few autistic characteristics. It is important to include these groups as camouflaging may make it more difficult to get an autism diagnosis and therefore make it less likely a person will receive support. We found that autistic women camouflaged more than all other groups. The group with few autistic characteristics (males and females) camouflaged the least. Loneliness was found to be a possible reason for camouflaging for the diagnosed autistic group only. In terms of outcomes related to camouflaging, it was found that those who camouflaged most had a lower quality of life; this was true of all groups. This tells us that there may be different reasons to camouflage, and different outcomes related to camouflaging for those with many characteristics of autism (including those with a diagnosis), and those with few. It is important that clinicians, teachers, parents and other stakeholders are aware of the negative outcomes associated with camouflaging so that more support can be provided for those who need it.


Supersaturated amorphous solid dispersions of celecoxib prepared in situ by microwave irradiation.
This study investigated the ability of in situ amorphisation using microwave irradiation in order to prepare highly supersaturated ASDs, i.e. ASDs with drug loads higher than the saturation solubility in the polymer at ambient temperature. For this purpose, compacts containing the crystalline drug celecoxib (CCX) and polyvinylpyrrolidone (PVP), polyvinylpyrrolidone-vinyl acetate copolymer (PVP/VA), or polyvinyl acetate (PVAc), were prepared at drug loads between 30 and 90 % w/w. Sodium dihydrogen phosphate (NaH2PO4) monohydrate was included in all compacts, as a source of water, to facilitate the dielectric heating of the compacts upon dehydration during microwave irradiation. After processing, the samples were analysed towards their solid state using X-ray powder diffraction (XRPD) and modulated differential scanning calorimetry (mDSC). Complete amorphisation of CCX was achieved across all the investigated polymers and with a maximal drug load of 90, 80, and 50 % w/w in PVP, PVP/VA, and PVAc, respectively. These drug loads corresponded to a 2.3-, 2.4-, and 10.0-fold supersaturation in the investigated polymers at ambient temperature. However, dissolution experiments with the in situ prepared ASDs in fasted state simulated intestinal fluid (FaSSIF), showed a lower initial drug release (0-2 h) compared to equivalent physical mixtures of crystalline CCX and polymers or crystalline CCX alone. The lower drug release rate was explained by the fusion of individual drug and polymer particles during microwave irradiation and, subsequently, a lack of disintegration of the monolithic ASDs. Nevertheless, supersaturation of CCX in FaSSIF was achieved with the in situ amorphised ASDs with PVP and PVP/VA, albeit only after 3-24 h. Overall, the present study confirmed that it is feasible to prepare supersaturated ASDs in situ. However, in the current experimental setup, the monolithic nature of the resulting ASDs is considered a limiting factor in the practical applicability of this preparation method, due to limited disintegration and the associated negative effect on the drug release.


Age of onset and cumulative risk of mental disorders: a cross-national analysis of population surveys from 29 countries.
Information on the frequency and timing of mental disorder onsets across the lifespan is of fundamental importance for public health planning. Broad, cross-national estimates of this information from coordinated general population surveys were last updated in 2007. We aimed to provide updated and improved estimates of age-of-onset distributions, lifetime prevalence, and morbid risk. In this cross-national analysis, we analysed data from respondents aged 18 years or older to the World Mental Health surveys, a coordinated series of cross-sectional, face-to-face community epidemiological surveys administered between 2001 and 2022. In the surveys, the WHO Composite International Diagnostic Interview, a fully structured psychiatric diagnostic interview, was used to assess age of onset, lifetime prevalence, and morbid risk of 13 DSM-IV mental disorders until age 75 years across surveys by sex. We did not assess ethnicity. The surveys were geographically clustered and weighted to adjust for selection probability, and standard errors of incidence rates and cumulative incidence curves were calculated using the jackknife repeated replications simulation method, taking weighting and geographical clustering of data into account. We included 156 331 respondents from 32 surveys in 29 countries, including 12 low-income and middle-income countries and 17 high-income countries, and including 85 308 (54·5%) female respondents and 71 023 (45·4%) male respondents. The lifetime prevalence of any mental disorder was 28·6% (95% CI 27·9-29·2) for male respondents and 29·8% (29·2-30·3) for female respondents. Morbid risk of any mental disorder by age 75 years was 46·4% (44·9-47·8) for male respondents and 53·1% (51·9-54·3) for female respondents. Conditional probabilities of first onset peaked at approximately age 15 years, with a median age of onset of 19 years (IQR 14-32) for male respondents and 20 years (12-36) for female respondents. The two most prevalent disorders were alcohol use disorder and major depressive disorder for male respondents and major depressive disorder and specific phobia for female respondents. By age 75 years, approximately half the population can expect to develop one or more of the 13 mental disorders considered in this Article. These disorders typically first emerge in childhood, adolescence, or young adulthood. Services should have the capacity to detect and treat common mental disorders promptly and to optimise care that suits people at these crucial parts of the life course. None.


Hydrothermal modification of titanium surface in calcium solutions.
Hydrothermal modification of a titanium surface in calcium solutions was performed. The apatite precipitation on the modified surface in Hanks' solution, as a simulated body fluid, was evaluated and the surface microstructure changes after the modification were characterized by thin-film X-ray diffractometry (TF-XRD) and X-ray photoelectron spectroscopy (XPS). Hydrothermal modification in CaO solution enhanced the precipitation of apatite on the titanium surface. High pH, high pressure and high temperature of the CaO solution increased the thickness of the surface-modified layer and enhanced the synthesis of calcium titanate which possibly promoted the precipitation of apatite in Hanks' solution. Hydrothermal modification in CaCl2 solution, on the other hand, showed reverse effects. The modification of titanium in CaO solution with hydrothermal treatment is expected to result in excellent osteointegration and can be easily performed by using an autoclave, a clinical apparatus widely used.


Association of the MC4R rs17782313 polymorphism with plasma ghrelin, leptin, IL6 and TNFα concentrations, food intake and eating behaviors in morbidly obese women.
The rs17782313 variant of the MC4R gene plays an important role in the obesity phenotype. Studies that evaluate environmental factors and genetic variants associated with obesity may represent a great advance in understanding the development of this disease. This work seeks to assess the association of the polymorphism of MC4R rs17782313 on plasma parameters, including leptin, ghrelin, tumor necrosis factor (TNFα) and interleukin 6 (IL6), and on the eating behaviors of morbidly obese women. 70 adult women with BMI between 40 and 60 kg/m2 were recruited. Laboratory and anthropometric data were recorded. Using a visual analog scale (VAS), the feelings of hunger and satiety were evaluated. The presence or absence of binge eating was evaluated through the Binge Eating Scale (BES) questionnaire. Habitual food intake was analyzed using 3-day dietary records. TaqMan® assays were conducted using real-time PCR to assess genotype polymorphism variants from peripheral blood DNA. This study found that female patients with the MC4R rs17782313 polymorphism had high levels of ghrelin and reduced levels of IL6 in the postprandial period. We observed a higher prevalence of severe binge eating in more than 50% of women with at least one risk allele. Our hypothesis is that the MC4R rs17782313 polymorphism may influence the release of ghrelin, even without being associated with feelings of hunger and satiety. More than half of women with this polymorphism exhibited severe binge eating. Level III: case-control analytic study.


Lipid peroxidation and superoxide dismutase activity in muscle and erythrocytes in adult muscular dystrophies and neurogenic atrophies.
Lipid peroxidation (LP) and superoxide dismutase (SOD) activity were determined in erythrocytes and skeletal muscle obtained from patients with limb-girdle and facioscapulohumeral muscular dystrophies, neurogenic atrophies and from age-matched control subjects. Neither lipid peroxidation nor SOD activity in erythrocytes of patients differed from control values. SOD activity and LP in muscle specimens were also normal in types of neurogenic atrophy. Lipid peroxidation in the muscle from patients with adult types of muscular dystrophy had a tendency to be increased. The values were widely scattered, the highest being obtained in the older patients with long duration of disease.


Convenient synthesis of arabinonucleoside containing oligodeoxyribonucleotides.
C2 substituted arabinofuranosyluracil derivatives were synthesized and its incorporations into DNA were easily carried out by using post-synthetic modification.


M1 polarization of chicken macrophage HD11 can be activated by duck Tembusu virus via MyD88-NF-κB-mediated signaling pathway.
Duck Tembusu virus (DTMUV) has caused significant economic losses to the global duck industry since its outbreak in 2010. The macrophages act as the key immune cell, and its polarization in different functional states is very important for host's immune responses and microbial infections. Avian macrophages are the main target cells of DTMUV, its polarization induced by DTMUV and the underlying mechanisms were explored in this study. Through quantitative real-time PCR, nitrite assay, and flow cytometry analysis, we found that DTMUV caused severe inflammatory responses in chicken macrophage line HD11 by reprogramming the expression of M1- and M2-associated genes, leading to the polarization of HD11 macrophage to M1-type. In term of mechanism, transcriptomics was performed to analyze the M1-type polarization triggered by DTMUV, it was found that most differential genes were implicated in biological processes, and DTMUV infection significantly activated innate immune signaling pathways, including cytokine-cytokine receptor interaction, MAPK signaling pathway. Moreover, transcription factors NF-κB and AP1 also be activated after viral infection. However, further validation analysis by inhibitors and siRNAs of NF-κB and AP1 showed that NF-κB molecule was essential for DTMUV-induced M1 polarization in HD11 cell, but not AP1. Additionally, the inhibiting assays targeting MyD88 and TRIF molecules were conducted to determine their effect on NF-κB and M1-associated genes upregulated by DTMUV. The results showed that although the inhibition of both MyD88 and TRIF significantly downregulated the mRNA level of NF-κB, but the expression of M1-associated genes such as CD86 was lower in MyD88 inhibition group than in the other group, indicating that the role of MyD88 in mediating M1 polarization induced by DTMUV was more important. Overall, these results demonstrated that DTMUV infection induces M1-type polarization in chicken macrophage HD11 through MyD88-NF-κB signaling pathways. This finding will lay the foundation for further study the pathogenesis of DTMUV, and provide new insights into the prevention and control of this disease.


Analysis of metal artifact reduction tools for dental hardware in CT scans of the oral cavity: kVp, iterative reconstruction, dual-energy CT, metal artifact reduction software: does it make a difference?
Metal artifacts may negatively affect radiologic assessment in the oral cavity. The aim of this study was to evaluate different metal artifact reduction techniques for metal artifacts induced by dental hardware in CT scans of the oral cavity. Clinical image quality was assessed using a Thiel-embalmed cadaver. A Catphan phantom and a polymethylmethacrylate (PMMA) phantom were used to evaluate physical-technical image quality parameters such as artifact area, artifact index (AI), and contrast detail (IQFinv). Metal cylinders were inserted in each phantom to create metal artifacts. CT images of both phantoms and the Thiel-embalmed cadaver were acquired on a multislice CT scanner using 80, 100, 120, and 140 kVp; model-based iterative reconstruction (Veo); and synthesized monochromatic keV images with and without metal artifact reduction software (MARs). Four radiologists assessed the clinical image quality, using an image criteria score (ICS). Significant influence of increasing kVp and the use of Veo was found on clinical image quality (p = 0.007 and p = 0.014, respectively). Application of MARs resulted in a smaller artifact area (p < 0.05). However, MARs reconstructed images resulted in lower ICS. Of all investigated techniques, Veo shows to be most promising, with a significant improvement of both the clinical and physical-technical image quality without adversely affecting contrast detail. MARs reconstruction in CT images of the oral cavity to reduce dental hardware metallic artifacts is not sufficient and may even adversely influence the image quality.


Evaluation of new anti-infective drugs for the treatment of infection with human immunodeficiency virus. The European Working Party of the European Society of Clinical Microbiology and Infectious Diseases.
This guideline describes the preclinical documentation required for a new drug active against human immunodeficiency virus (HIV) and offers suggestions regarding the design and implementation of phase 1, 2, and 3 clinical trials. Drugs with a low level of potential toxicity, especially those that are not nucleoside analogues, should be evaluated in healthy individuals who are not infected with HIV before trials in HIV-infected patients commence. The guideline also discusses possible clinical and laboratory end points for efficacy and emphasizes the need for careful validation of all laboratory end points used. The approach of the guideline is deliberately general: more specific recommendations would soon become outdated in this field, which is characterized by extremely rapid developments.


Chemocentric informatics approach to drug discovery: identification and experimental validation of selective estrogen receptor modulators as ligands of 5-hydroxytryptamine-6 receptors and as potential cognition enhancers.
We have devised a chemocentric informatics methodology for drug discovery integrating independent approaches to mining biomolecular databases. As a proof of concept, we have searched for novel putative cognition enhancers. First, we generated Quantitative Structure-Activity Relationship (QSAR) models of compounds binding to 5-hydroxytryptamine-6 receptor (5-HT(6)R), a known target for cognition enhancers, and employed these models for virtual screening to identify putative 5-HT(6)R actives. Second, we queried chemogenomics data from the Connectivity Map ( http://www.broad.mit.edu/cmap/ ) with the gene expression profile signatures of Alzheimer's disease patients to identify compounds putatively linked to the disease. Thirteen common hits were tested in 5-HT(6)R radioligand binding assays and ten were confirmed as actives. Four of them were known selective estrogen receptor modulators that were never reported as 5-HT(6)R ligands. Furthermore, nine of the confirmed actives were reported elsewhere to have memory-enhancing effects. The approaches discussed herein can be used broadly to identify novel drug-target-disease associations.


Ability of rabeprazole to prevent gastric mucosal damage from clopidogrel and low doses of aspirin depends on CYP2C19 genotype.
Low doses of aspirin can injure the gastric mucosa. It is not clear whether other drugs such as the antiplatelet agent clopidogrel also cause gastric mucosal injury or exacerbate aspirin-induced injury, or whether proton pump inhibitors prevent damage. Twenty Japanese subjects with different CYP2C19 genotypes were randomly assigned to groups that were given a low dose of aspirin (100 mg; A), clopidogrel (75 mg; C), low dose of aspirin and clopidogrel (AC), or low dose of aspirin in combination with clopidogrel and rabeprazole (10 mg; ACR) once daily for 7 days. Subjects underwent gastroduodenoscopy and platelet tests on days 3 and 7; gastric mucosal damage was assessed by using the modified Lanza score (MLS). We performed 24-hour intragastric pH monitoring on day 7 of each regimen. We also analyzed the effects of the AC regimen on 30 patients with different CYP2C19 genotypes. Subjects in groups A, C, and AC had significantly higher levels of gastric mucosal damage on days 3 and 7, compared with baseline. The median MLS for the AC group was similar to that of the A group. Helicobacter pylori-negative subjects in the ACR group with different CYP2C19 genotypes had significant differences in MLS, intragastric pH, and platelet function. Gastric mucosal injury was inhibited equally among H pylori-positive subjects in the ACR group. Rabeprazole did not appear to affect platelet function or intragastric pH in subjects given clopidogrel. Clopidogrel and low doses of aspirin cause a similar degree of gastric mucosal damage. Rabeprazole prevented this damage without reducing the antiplatelet function of clopidogrel. However, its prophylactic effect varies with CYP2C19 genotype in H pylori-negative subjects.