[New data on the effectiveness of Tadalafil alone and in combination with NeyroDoz in treating erectile dysfunction associated with secondary premature ejaculation].
To compare the effectiveness of the phosphodiesterase type 5 inhibitor (PDE-5i) tadalafil alone and in combination with a biologically active dietary supplement (BADS) NeyroDoz, containing the precursors of serotonin in patients with erectile dysfunction (ED) associated with secondary premature ejaculation (SPE). 105 patients (mean age 36.2+/-9.1 years) with concomitant ED and SPE were included in a prospective study and divided into 2 groups. The patients of group 1 (n=47) received PDE-5i 5 mg daily for 1 month. In patients of group 2 (n=58) PDE-5i was co-administered with BADS 2 capsules twice daily. Treatment efficacy was evaluated using "Criteria for premature ejaculation" (CriPE) and IIEF-5 questionnaires at baseline and on completion of the treatment course. Besides, a polymorphism in the serotonin transporter gene (5-HTTLPR) was tested. The treatment was effective in 35 (74.5%) and 48 (82.7%) patients of group 1 and 2, respectively (p<0.0001) with similar statistically significant (p<0.001) improvement in erectile function. According to CriPE scores, 6.4, 8.5, 23.4, 10.6 and 12.8% patients of group 1 and 10.3, 1.7, 40.0, 25.9, 10.3 and 31.0% patients of group 2 with LaLa, LaLg, LgLg, Sla, SLg, SS genotypes were rendered free of SPE, respectively. Treating ED-associated SPE with the combination of serotonin precursors and tadalafil can better improve ejaculatory function recovery compared with PDE-5i monotherapy.


Effects of S-1 combined with radiotherapy in the treatment of advanced esophageal cancer: A systematic review and meta-analysis protocol.
Esophageal cancer is one of the worst malignant digestive neoplasms with poor treatment outcomes. Definitive concurrent chemoradiotherapy (CRT) has become the standard nonsurgical treatment option for locally advanced esophageal cancer. The chemotherapeutic drugs 5-fluorouracil and cisplatin have been most commonly used in CRT of esophageal cancer. However, radiotherapy combined with 5-FU/cisplatin often delivers severe toxicity to patients. S-1 as an oral chemotherapeutic drug exhibits higher anti-tumor activity, less adverse effects, and better biological availability. S-1 also has excellent effects as a CRT regimen for esophageal cancer. A systematic literature search will be performed through January 2018 using MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and Google Scholar for relevant articles published in any language. Randomized controlled trials, prospective comparative studies will be included. All meta-analyses will be performed using Review Manager software. The quality of the studies will be evaluated using the guidelines listed in the Cochrane Handbook. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements will be followed until the findings of the systematic review and meta-analysis are reported. The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. Our study will draw an objective conclusion of the effects of S-1 combined with radiotherapy in the treatment of unresectable esophageal cancer and provide level I evidence for clinical decision makings.


Idiopathic myocardial vasculitis presenting as restrictive cardiomyopathy.
A previously unreported case of small-vessel myocardial vasculitis presenting as restrictive cardiomyopathy and congestive heart failure is described. The hemodynamic study, showing severely increased and equalized diastolic pressures in atrial and ventricular chambers, and cardiac MRI, showing normal pericardium and ventricular endomyocardial biopsy, not including myocardial vascular component, were insufficient to make a diagnosis. This made a thoracotomy and surgical cardiac biopsy necessary. Steroids and cyclophosphamide, introduced after histologic evidence of necrotizing vasculitis, unassociated with a systemic disease, became available and improved the clinical profile and the diastolic dysfunction at two-dimensional echocardiographic Doppler analysis.


High glucose level as a modifier factor in CMT1A patients.
Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common type of hereditary neuropathy worldwide and diabetes mellitus (DM) is the most frequent cause of peripheral neuropathy in the Western world. CMT1A typically manifest as a predominant motor neuropathy, while, DM-related neuropathy often manifests as a predominant sensory disorder. There are some evidences that CMT1A patients that also had DM had a more severe neuropathy. Although the real frequency and the underlying mechanisms related to this association has not yet been addressed in the literature. We sought to characterize the phenotypic variability of CMT1A patients with persistent high glucose levels (DM or impaired glucose tolerance [IGT]). Nineteen patients with CMT1A and DM (CMTdiab), seven with CMT1A and IGT (CMTintol) and 27 with CMT1A without comorbidities were analyzed. They were evaluated through clinical assessment, application of the following scales: visual analogue scale, McGill, CMTNS, SF-36 and COMPASS 31 and electrophysiological studies. Patients CMTdiab had a more severe motor and sensory neuropathy, more intense autonomic symptoms and worse quality of life. Surprisingly, proximal weakness and temporal dispersion on nerve conduction studies are frequently observed in this group. Patients CMTintol also had a more severe neuropathy. Curiously, we observed that the association of CMT1A and glucose metabolism disorders (CMTglic) clustered in some families. Patients CMTglic develop a more severe neuropathy. As there is yet no cure to CMT1A, a strict blood sugar control may be a useful measure.


Adjusting for partial invariance in latent parameter estimation: Comparing forward specification search and approximate invariance methods.
Measurement invariance is the condition that an instrument measures a target construct in the same way across subgroups, settings, and time. In psychological measurement, usually only partial, but not full, invariance is achieved, which potentially biases subsequent parameter estimations and statistical inferences. Although existing literature shows that a correctly specified partial invariance model can remove such biases, it ignores the model uncertainty in the specification search step: flagging the wrong items may lead to additional bias and variability in subsequent inferences. On the other hand, several new approaches, including Bayesian approximate invariance and alignment optimization methods, have been proposed; these methods use an approximate invariance model to adjust for partial measurement invariance without the need to directly identify noninvariant items. However, there has been limited research on these methods in situations with a small number of groups. In this paper, we conducted three systematic simulation studies to compare five methods for adjusting partial invariance. While specification search performed reasonably well when the proportion of noninvariant parameters was no more than one-third, alignment optimization overall performed best across conditions in terms of efficiency of parameter estimates, confidence interval coverage, and type I error rates. In addition, the Bayesian version of alignment optimization performed best for estimating latent means and variances in small-sample and low-reliability conditions. We thus recommend the use of the alignment optimization methods for adjusting partial invariance when comparing latent constructs across a few groups.


Effects of Exercise on Falls, Balance, and Gait Ability in Parkinson's Disease: A Meta-analysis.
Postural instability and falls are complex and disabling features of Parkinson's disease (PD) and respond poorly to anti-Parkinsonian medication. There is an imperative need to evaluate the effectiveness of exercise interventions in enhancing postural stability and decreasing falls in the PD population. The objectives of our study were to determine the effects of exercise training on the enhancement of balance and gait ability and reduction in falls for people with PD and to investigate potential factors contributing to the training effects on balance and gait ability of people with PD. We included 25 randomized control trials of a moderate methodological quality in our meta-analysis. The trials examined the effects of exercise training on balance and gait ability and falls against no intervention and placebo intervention. The results showed positive effects of exercise intervention on enhancing balance and gait performance (Hedges' g = 0.303 over the short-term in 24 studies and 0.419 over the long-term in 12 studies; P < .05) and reducing the fall rate (rate ratio = 0.485 over the short-term in 4 studies and 0.413 over the long-term in 5 studies; P < .05). The longest follow-up duration was 12 months. There was no evidence that training decreased the number of fallers over the short- or long-term (P > .05). The results of our metaregression and subgroup analysis showed that facility-based training produced greater training effects on improving PD participants' balance and gait ability (P < .05). The findings support the application of exercise training to improve balance and gait ability and prevent falls in people with PD.


Total RNA concentration as an index of microbial activity and oxygen supply in an oxidation ditch.
Total RNA and chromosomal DNA concentrations at a municipal wastewater treatment plant with an oxidation ditch (OD) were monitored for 1.5 years using commercial extraction kits for DNA and RNA. No parameters correlated with the chromosomal DNA concentration. The total RNA concentration exhibited better correlation than the solids retention time and the mixed liquor suspended solids with the removal rate of total organic carbon, and can be regarded as an index of microbial activity. The total RNA concentration varied with a cycle of one year and increased at lower water temperatures in this OD. When diffusion theory was taken into account, it was found that the oxygen dissolution rate increased at lower temperature, and a small change in the oxygen dissolution rate caused a large variation in microbial activity and also affected nitrification and denitrification. The information was insufficient to clarify the various reaction relationships, but total RNA concentration will likely be useful as an index of microbial activity in actual wastewater treatment reactors.


What can be done about home health fieldwork?
The literature indicates that health care is moving away from institutional care and specialization to the community and home where providers need generalist competencies. As educators strive to prepare students for this environment, fieldwork experiences in the community and home are opportunities for students to develop generalist competencies. Because of the current scarcity of fieldwork sites, in general, scheduling placements is difficult. As educators seek new sites, home health settings and therapists who provide home health care as a component of their service need to be considered. Home health occupational therapy requires a practitioner to adopt a holistic perspective in order to assist clients to function optimally in their home environment. Because a large number of students work in addition to taking classes, they can be encouraged to find jobs as home health aides or chore providers as part-time employment before and during their didactic education. This work experience can help them to acculturate to the home setting. By encouraging students' participation in home health experiences, educators are helping to facilitate generalist competencies.


FDA drug approval summary: nelarabine (Arranon) for the treatment of T-cell lymphoblastic leukemia/lymphoma.
To describe the clinical trials leading to U.S. Food and Drug Administration (FDA) approval of nelarabine (Arranon), a new purine analogue, for the treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. Two phase II trials, one conducted in pediatric patients and the other in adult patients, were reviewed. Patients were in their first or subsequent relapse and/or were refractory to first-line therapy. The dose and schedule of i.v. nelarabine in the pediatric and adult studies were 650 mg/m2 per day daily for 5 days and 1,500 mg/m2 i.v. on days 1, 3, and 5, respectively. Treatments were repeated every 21 days. Study endpoints were the rates of complete response (CR) and CR with incomplete hematologic or bone marrow recovery (CR*). The pediatric efficacy population consisted of 39 patients who had relapsed after, or had been refractory to, two or more induction regimens. CR to nelarabine treatment was observed in five patients (13%) and CR+CR* was observed in nine patients (23%). The adult efficacy population consisted of 28 patients. CR to nelarabine treatment was observed in five patients (18%) and CR+CR* was observed in six patients (21%). Neurologic toxicity was dose limiting for both pediatric and adult patients. Other severe toxicities included hematologic, hepatic, and metabolic laboratory abnormalities in pediatric patients and gastrointestinal and pulmonary toxicities in adults. On October 28, 2005, the FDA granted accelerated approval for nelarabine for treatment of patients with relapsed or refractory T-ALL/T-LBL after at least two prior regimens. This use is based on the induction of CR. The applicant will conduct postmarketing clinical trials to demonstrate clinical benefit, for example, survival prolongation.


Assimilation of alkanes and alkenes by fungi.
A group of filamentous fungi were assayed for their ability to utilize a series of n-alkanes and 1-alkenes as the sole source of carbon. Although strains of Cunninghamella exhibited profuse growth on most of the hydrocarbons tested, the majority of fungi tested were able to produce definite growth on one or more of the compounds. The hydrocarbons with a 14-carbon chain length appeared to be more consistently utilized than any other. Strains of Aspergillus appeared to differ in their capacity to utilize individual members of the hydrocarbon series. Thin-layer chromatographic analyses of ether extracts from C. blakesleeana grown on n-tetradecane and 1-tetradecene were similar and revealed the presence of a monocarboxylic acid, a primary alcohol, and a secondary alcohol.


Domain cross-talk within a bifunctional enzyme provides catalytic and allosteric functionality in the biosynthesis of aromatic amino acids.
Because of their special organization, multifunctional enzymes play crucial roles in improving the performance of metabolic pathways. For example, the bacterium Prevotella nigrescens contains a distinctive bifunctional protein comprising a 3-deoxy-d-arabino heptulosonate-7-phosphate synthase (DAH7PS), catalyzing the first reaction of the biosynthetic pathway of aromatic amino acids, and a chorismate mutase (CM), functioning at a branch of this pathway leading to the synthesis of tyrosine and phenylalanine. In this study, we characterized this P. nigrescens enzyme and found that its two catalytic activities exhibit substantial hetero-interdependence and that the separation of its two distinct catalytic domains results in a dramatic loss of both DAH7PS and CM activities. The protein displayed a unique dimeric assembly, with dimerization solely via the CM domain. Small angle X-ray scattering (SAXS)-based structural analysis of this protein indicated a DAH7PS-CM hetero-interaction between the DAH7PS and CM domains, unlike the homo-association between DAH7PS domains normally observed for other DAH7PS proteins. This hetero-interaction provides a structural basis for the functional interdependence between the two domains observed here. Moreover, we observed that DAH7PS is allosterically inhibited by prephenate, the product of the CM-catalyzed reaction. This allostery was accompanied by a striking conformational change as observed by SAXS, implying that altering the hetero-domain interaction underpins the allosteric inhibition. We conclude that for this C-terminal CM-linked DAH7PS, catalytic function and allosteric regulation appear to be delivered by a common mechanism, revealing a distinct and efficient evolutionary strategy to utilize the functional advantages of a bifunctional enzyme.


Rapid In Situ MRI Traceable Gel-forming Dual-drug Delivery for Synergistic Therapy of Brain Tumor.
Preventing tumor recurrence after surgical resection of a brain tumor is a significant clinical challenge because current methods deliver chemotherapeutic agents in a rapid manner and are not effective against the residual tumor cells. To overcome this drawback, we report a simple method to prepare magnetic resonance imaging (MRI) traceable ultra-thermosensitive hydrogels with rapid gelation ability from aqueous solution within 4 s at 28 °C for hydrophilic (epirubicin, EPI) and hydrophobic (paclitaxel, PTX) drugs co-delivery with bovine serum albumin nanoparticles (BSA NPs) incorporation. The results showed the average survival of gliosarcoma-bearing (MBR 614 or U87) mice receiving BSA/PTX NPs incorporated hydrogelGd/EPI increased to 63 days or 69 days with no tumor recurrence observed. Our synergistic strategy presents a new approach to the development of a local drug delivery system for the prevention of brain tumor recurrence.


A constitutively active dioxin/aryl hydrocarbon receptor promotes hepatocarcinogenesis in mice.
The dioxin/aryl hydrocarbon receptor (AhR) functions as a ligand-activated transcription factor regulating transcription of a battery of genes encoding enzymes involved in drug metabolism. Known ligands include polycyclic aromatic hydrocarbons, certain polychlorinated biphenyls, and the polyhalogenated dioxins including 2,3,7,8-tetrachlorodibenzo-p-dioxin. Both polyhalogenated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin are potent promoters of rodent hepatocarcinogenesis in two-stage initiation-promotion experiments. Although several lines of evidence indicate the involvement of the AhR in toxic effects mediated by polyhalogenated biphenyls and dioxins, its involvement in tumor promotion has not been unequivocally proven. In the present study, a transgenic mouse line expressing a constitutively active AhR (CA-AhR) has been used to investigate the role of the AhR in hepatocarcinogenesis. Male AhR wild-type and CA-AhR-transgenic B6C3F1-mice were treated with a single injection of the hepatocarcinogen N-nitrosodiethylamine at 6 weeks of age and were subsequently kept untreated on control diet. Thirty five weeks after carcinogen treatment, mice were sacrificed, and the prevalence and multiplicity of liver tumors were determined. Whereas only 1 small liver tumor was observed in 15 AhR-wild-type mice, 19 tumors (two >1 cm in diameter) were present in 18 CA-AhR-transgenic mice. This result demonstrates the oncogenic potential of the activated AhR and implicates an important role of the receptor in promotion of hepatocarcinogenesis. A microarray-based gene expression-profiling analysis revealed down-regulation in the liver of CA-AhR-transgenic mice of a cluster of genes encoding heat shock proteins, including GRP78/BiP, Herp1, Hsp90, DnaJ (Hsp40) homologue B1, and Hsp105, which are important for protein folding and quality control.


Effects of low-potassium diet on N-ethylmaleimide-sensitive ATPase in the distal nephron segments.
The present study was undertaken to investigate whether or not potassium deficiency influences N-ethylmaleimide (NEM)-sensitive ATPase in the distal nephron segments of the rat. One group of animals was fed a low-K diet, whereas the normal K-group was given the same diet after supplementation with KCl. The nephron segments examined were: the medullary and cortical thick ascending limbs, the distal convoluted tubule, and the cortical, outer and inner medullary collecting ducts. NEM-sensitive ATPase activity in microdissected segments was measured by a fluorometric microassay. The plasma K+ concentration in the low-K group was 3.1 +/- 0.3 mEq/l compared with 4.2 +/- 0.1 mEq/l in the normal-K group. NEM-sensitive ATPase activity in the outer medullary collecting duct of low-K diet animals was significantly greater than in normal-K animals. There was no significant difference in NEM-sensitive ATPase activity between the two groups of animals in the other nephron segments examined. It is suggested that NEM-sensitive H-ATPase activity in the outer medullary collecting duct is modulated by the potassium status of the animal.


Age and sex differences in mitotic activity within the zebra finch telencephalon.
Brain regions associated with song learning in zebra finches are larger and contain more neurons in males than females. Differences in cell proliferation, migration, survival, and specification may all contribute to the divergent development of the song-control system in developing birds. This study quantified levels of cell proliferation within the telencephalic ventricular zone (VZ) of juvenile and adult birds to look for both age and sex differences in mitotic activity that might contribute to the construction of song-control circuits. A single pulse of [(3)H]thymidine was administered to juveniles and adults of both sexes, and animals were killed 2 hr later. Analysis of thymidine labeling within the telencephalic VZ at the levels of area X, the anterior commissure, and high vocal center (HVC) revealed two major findings: (1) levels of mitotic activity decreased as a function of age in both males and females because of a reduction in the number of dividing cells within the VZ, and (2) sex differences in thymidine labeling occurred in restricted, localized segments of the VZ at the levels of area X and the anterior commissure in juveniles but not adults. Thus, overall proliferative activity decreases as birds mature, and the incidence of cell division in all regions of the VZ becomes equivalent in both sexes, such that no regions of sexually dimorphic proliferation are evident by adulthood. These data suggest that regions of sexually dimorphic proliferation within the VZ may contain precursor cells that give rise to song-control neurons, such that higher rates of mitotic activity in juvenile males could contribute to the growth of song-control nuclei such as HVC and area X.


Surface functionalized 3D printed metal structures as next generation recyclable SERS substrates.
Combining the design flexibility and rapid prototyping capabilities of additive manufacturing with photocatalytic and plasmonic functionalities is promising for the development of next-generation SERS applications such as point of care diagnostics and in situ monitoring of chemical reactions in fuels and chemical processing. Laser powder bed fusion (LPBF) is a well-matured additive manufacturing technique which generates metallic structures through localised melting and joining of metal powders using a laser. LPBF reduces material wastage during manufacturing, is applicable to a wide range of metals and alloys, and allows printing of complex internal structures. This feature article elaborates the use of soot templating, chemical vapour deposition and electroless plating techniques for grafting plasmonic and semiconductor nanoparticles on the surface of LPBF manufactured metallic substrates. The capability to fabricate different types of intricate metallic lattices using additive manufacturing is demonstrated and technical challenges in their adequate functionalization are elaborated. The developed methodology allows tailoring of the substrate structure, composition, morphology, plasmonic and photocatalytic activities and thus unveils a new class of recyclable SERS substrates.


Potential Drug interactions with Drugs used for Bipolar Disorder: A Comparison of 6 Drug Interaction Database Programs.
Patients with bipolar disorder frequently experience polypharmacy, putting them at risk for clinically significant drug-drug interactions (DDI). Online drug interaction database programs are used to alert physicians, but there are no internationally recognized standards to define DDI. This study compared the category of potential DDI returned by 6 commercial drug interaction database programs for drug interaction pairs involving drugs commonly prescribed for bipolar disorder. The category of potential DDI provided by 6 drug interaction database programs (3 subscription, 3 open access) was obtained for 125 drug interaction pairs. The pairs involved 103 drugs (38 psychiatric, 65 nonpsychiatric); 88 pairs included a psychiatric and nonpsychiatric drug; 37 pairs included 2 psychiatric drugs. Every pair contained at least 1 mood stabilizer or antidepressant. The category provided by 6 drug interaction database programs was compared using percent agreement and Fleiss kappa statistic of interrater reliability. For the 125 drug pairs, the overall percent agreement among the 6 drug interaction database programs was 60%; the Fleiss kappa agreement was slight. For drug interaction pairs with any category rating of severe (contraindicated), the kappa agreement was moderate. For drug interaction pairs with any category rating of major, the kappa agreement was slight. There is poor agreement among drug interaction database programs for the category of potential DDI involving psychiatric drugs. Drug interaction database programs provide valuable information, but the lack of consistency should be recognized as a limitation. When assistance is needed, physicians should check more than 1 drug interaction database program.


A crosstalk between extracellular ATP and jasmonate signaling pathways for plant defense.
Damage-associated molecular patterns (DAMPs), such as extracellular ATP, act as danger signals in response to biotic and abiotic stresses. Extracellular ATP is perceived by a plant purinoceptor, P2 receptor kinase 1 (P2K1), inducing downstream signaling for defense responses. How ATP induces these defense responses has not been well studied. A recent study by Tripathi et al. (Plant Physiology, 176: 511-523, 2018) revealed a synergistic interaction between extracellular ATP and jasmonate (JA) signaling during plant defense responses. This signaling crosstalk requires the formation of secondary messengers, i.e., cytosolic calcium, reactive oxygen species, and nitric oxide. This finding has given a new direction towards understanding the defense signals activated by DAMPs. In this addendum, we discuss possible insights into how extracellular ATP signaling interacts with the JA signaling pathway for plant defense responses.


An Interesting Case of Hypothyroidism Associated Acute Kidney Injury.
Muscle involvement is common in hypothyroidism. However, hypothyroidism as a causal factor for severe rhabdomyolysis and acute kidney injury (AKI) is rarely reported. We report a case of a 56-year-old Arab male who presented with unexplained acute worsening of chronic kidney disease. The patient was detected to have hypothyroidism and rhabdomyolysis on laboratory investigations. However, thyroxine replacement led to partial recovery of renal function. CPK also improved with vigorous hydration and thyroxine replacement. Although this is a rare association, in the absence of other causes of rhabdomyolysis, hypothyroidism should be suspected in patients presenting with AKI and high creatinine phospho-kinase.


Two randomized controlled trials of virucidal nasal tissues in the prevention of natural upper respiratory infections.
Two six-month randomized, controlled double-blind trials of the efficacy of virucidal nasal tissues in the prevention of natural colds were conducted in Charlottesville, Virginia, between 1983 and 1986. Tissues impregnated with malic and citric acids and sodium lauryl sulfate were used in both trials. Placebo tissues contained saccharin in the first trial and a mixture including succinic acid in the second. A total of 186 families were evaluable after completion of trial I, and 98 families were evaluable in trial II. The antiviral tissues were associated with 14 and 5% relative reductions in the overall rate of colds in the first and second trials, respectively. In the first study, this appeared to be due to an appropriate fall in secondary illnesses with a relative reduction in the ratio of secondary to primary illnesses of 32%. In trial II, however, the small and statistically insignificant reduction was primarily due to a drop in the rate of primary illness (which cannot be attributed to tissue efficacy), and the ratio of secondary to primary illness was actually 5% higher in the group with active tissues than in the placebo group. We conclude that when rigorously used in a study protocol, virucidal tissues may offer a modest reduction of secondary colds in the home, but for reasons currently unknown, do not have a major effect on the overall rate of colds.


Pharmacology and toxicology of chemical warfare agents.
Toxic chemicals have been used as weapons of war and also as means of terrorist attacks on civilian populations. The main classes of chemical weapons are: a) nerve agents, b) vesicant agents and c) blood agents. If an exposure to nerve agents is anticipated, prophylactic pyridostigmine may be used. Once exposure has occurred, the management strategy is to reduce cholinergic activity through the use of atropine as well as to attempt to regenerate acetylcholinesterase with pralidoxime. Convulsions may be managed using diazepam. Exposure to vesicant agents may be reduced through the use of protective gear, but once exposure has occurred, no specific treatment is available. Treatment remains symptomatic and supportive. Lethal atmospheric concentrations of hydrogen cyanide gas, a blood agent, is seldom achieved except in enclosed spaces. Sub-lethal exposure to hydrogen cyanide may be managed using sodium nitrite, sodium thiosulphate and VitB12.


Sodium channel in human malignant hyperthermia.
The abundance of a specific sodium channel subunit (SkM2) appeared to be altered in vitro in cell cultures from persons susceptible to malignant hyperthermia. This study sought to determine whether these findings are artifacts of cell culture or whether they may be relevant to malignant hyperthermia. Regulation of transcript levels of SkM2, a specific sodium channel alpha-subunit, was determined by mRNA analysis. Functional SkM2 protein was estimated in biopsy sections of vastus lateralis muscle by inhibiting the directly elicited muscle twitch by tetrodotoxin, which can differentiate at least three sodium currents in skeletal muscle. The transcript levels of SkM2 were depressed by 115-fold in six of seven persons susceptible to malignant hyperthermia; and the functional expression of the SkM2 protein, based on the tetrodotoxin sensitivity of the directly elicited twitch, was decreased by at least fourfold in muscle from persons susceptible to malignant hyperthermia compared with persons who were not susceptible. As in previous studies in cell culture, altered mRNA and/or the functional expression of a specific subunit of the sodium channel (SkM2) was found in biopsy sections of muscle from all 12 persons examined who were susceptible to malignant hyperthermia but in none of the 16 nonsusceptible participants. Human malignant hyperthermia is a heterogeneous disorder, and the down-regulation of SkM2 may be involved in the final common pathway through which mutations in any one of several proteins, including the ryanodine receptor, could render a person susceptible.


Food allergy.
Food allergy is an immunologically mediated hypersensitivity reaction that occurs in 1% to 2% of the general population and in about 8% of children. Reactions mediated by IgE antibodies are the most common type of food allergy and can cause asthma, rhinitis, atopic dermatitis, urticaria, and anaphylaxis, which can be lethal. A proper diagnosis can be established through a careful history and physical examination, tests for IgE antibodies specific for food antigens, a favorable response to an allergen elimination diet, and, if necessary, blinded and controlled allergen challenge. The only effective therapy is avoidance of the problem foods. Resolution of the sensitivity over time is more common in younger patients than in adults and for some foods more than others. Most adverse food reactions are due to nonimmunologic intolerance and can be managed differently.


PICKLE is required for SOLITARY-ROOT/IAA14-mediated repression of ARF7 and ARF19 activity during Arabidopsis lateral root initiation.
Lateral root (LR) formation in Arabidopsis is regulated by auxin signaling through AUXIN RESPONSE FACTOR transcriptional activators, ARF7 and ARF19, and auxin/indole-3-acetic acid (Aux/IAA) repressors, including SOLITARY-ROOT (SLR)/IAA14. Previous studies have strongly suggested that, in the gain-of-function slr-1 mutant, stabilized mutant IAA14 (mIAA14) protein inactivates ARF7/19 functions, thereby completely blocking LR initiation. However, the mechanism of inactivation is still unknown. We have now identified an extragenic suppressor mutation of slr-1, suppressor of slr2 (ssl2), which specifically restores LR formation in the slr-1 mutant, and have found that SSL2 negatively regulates the auxin-induced pericycle cell divisions required for LR initiation. The SSL2 gene encodes PICKLE (PKL), a homologue of the animal chromatin-remodeling factor CHD3/Mi-2, and LR formation restored in pkl/ssl2 slr-1 mutants depends on ARF7/19 functions, suggesting that ARF7/19-dependent transcription takes place if there is a pkl/ssl2 mutation in slr-1. In animals, Mi-2 represses transcription as a subunit of the NuRD/Mi-2 complex containing histone deacetylases (HDACs). Inhibition of HDAC activity by trichostatin A also results in LR formation in the slr-1 mutant, but not in the slr-1 arf7 arf19 triple mutant, suggesting that normal HDAC activity is required for the mIAA14-mediated inactivation of ARF7/19 functions in LR initiation. Taken together, our data suggest that PKL/SSL2-mediated chromatin remodeling negatively regulates auxin-mediated LR formation in Arabidopsis.


The Code for Facial Identity in the Primate Brain.
Primates recognize complex objects such as faces with remarkable speed and reliability. Here, we reveal the brain's code for facial identity. Experiments in macaques demonstrate an extraordinarily simple transformation between faces and responses of cells in face patches. By formatting faces as points in a high-dimensional linear space, we discovered that each face cell's firing rate is proportional to the projection of an incoming face stimulus onto a single axis in this space, allowing a face cell ensemble to encode the location of any face in the space. Using this code, we could precisely decode faces from neural population responses and predict neural firing rates to faces. Furthermore, this code disavows the long-standing assumption that face cells encode specific facial identities, confirmed by engineering faces with drastically different appearance that elicited identical responses in single face cells. Our work suggests that other objects could be encoded by analogous metric coordinate systems. PAPERCLIP.


[A new trial assessment of left ventricular function before and after aorto coronary bypass surgery--application of ejection vector (E.V.)].
In 34 patients underwent aorto coronary bypass, left ventriculography was analyzed and ejection indexes (E.F. 100, E.F. 50, E.V. = 2 X E.F. 50/E.F. 100) were calculated. There was not difference in ejection indexes of patients between who had been complicated with preoperative myocardial infarction and not. E.F. 100 was not changed postoperatively, otherwise, E.F. 50 and E.V. showed significant increase. In 15 patients whose quality of life remarkably was improved postoperative period, E.F. 100 was not changed but E.F. 50 and E.V. were significantly increased. Four patients could not perform exercise test to full dose because of intractable ischemic calf pain. In twelve patients, whose left ventricular function was improved at postoperative exercise test, their E.F. 100 was found to be unchanged, but in contrast, E.F. 50 and E.V. were increased significantly. In conclusion, we found that E.V. could become to be more sensitive indicator of left ventricular function compared with E.F. 100 before and after aorto coronary bypass surgery.


Restoration of leukemia virus-suppressed immunocytes in vitro by peritoneal exudate cells.
Depressed antibody responsiveness to sheep erythrocytes in mice infected with Friend leukemia virus continued in vitro when spleen cell cultures from infected animals were cultured in the presence of antigen. Addition of PE cells from normal donor mice to the immunologically depressed splenocyte cultures resulted in a marked restoration of antibody responsiveness. Restoration of the immune response was PE cell dose-dependent; a ratio of 1 PE cell per 10 splenocytes resulted in the largest numbers of PFC's. These results suggest that impaired antibody responsiveness by spleen cell cultures from FLV-infected mice may be due, in part, to effects on antigen-processing macrophages, since restoration of immune responsiveness occurs by PE cell supplements.


Juvenile methylphenidate modulates reward-related behaviors and cerebral blood flow by decreasing cortical D3 receptors.
Attention deficit hyperactivity disorder is associated with reduced cortical blood flow that is reversible with exposure to the psychostimulant methylphenidate (MPH). D3 dopamine receptors modulate stimulant-induced changes in blood flow and are associated with reward processing during young adulthood, but their role in the enduring effects of MPH during development is unknown. Rats were given vehicle (VEH) or MPH (2 mg/kg between postnatal days 20-35) and assessed in young adulthood for regional cerebral blood volume (rCBV) after MPH challenge and mRNA expression levels of dopamine receptors. To probe D3 receptor involvement, juvenile subjects were exposed to VEH, MPH, the D3-preferring agonist +/-7-OHDPAT (0.3 mg/kg), the D3 antagonist nafadotride (Naf; 0.05, 0.5 or 5.0 mg/kg) or a Naf (0.05 mg/kg)/MPH combination, and assessed biochemically and behaviorally. Juvenile MPH exposure increased MPH-induced rCBV in the cingulate and medial prefrontal cortex and thalamus in adulthood. Behaviorally, juvenile MPH- or +/-7-OHDPAT-exposed subjects demonstrated an aversion to cocaine-associated environments, which was prevented by juvenile co-treatment with MPH and Naf, or with adult cortical microinjections of +/-7-OHDPAT. Cortical D3 mRNA levels significantly decreased by 23.8 +/- 6.7% in MPH-treated subjects and normalized with combined Naf/MPH treatment, with no change in the other dopamine receptors. Enhanced cortical responsiveness to psychostimulants may occur through a reduction in D3 receptors, which in turn reduces drug-seeking behavior. These data provide evidence for a postnatal sensitive period when juvenile MPH exposure is able to alter cortical development.


A cross-sectional analysis of the relationship between diabetes and health access barriers in an urban First Nations population in Canada.
This study explores the relationship between health access barriers and diabetes in an urban First Nations population in Canada. Data from a self-identified urban First Nations population were collected using respondent-driven sampling (RDS). As no clear approach for regression modelling of RDS data is available, two logistic regression modelling approaches, including survey-based logistic and generalised linear mixed models, were used to explore the relationship between diabetes and health barriers of interest, including access to healthcare, food, housing and socioeconomic factors. Hamilton, Ontario, Canada. This cross-sectional study used data collected from the Our Health Counts study, in partnership with the De dwa da dehs nye>s Aboriginal Health Centre, which recruited 554 First Nations adults living in Hamilton using RDS. After adjusting for covariates, multivariable regression techniques showed a statistically significant relationship between a self-reported diagnosis of diabetes and a lack of culturally appropriate care among urban First Nations peoples (OR: 12.70, 95% CI 2.52 to 57.91). There was also a trend towards a relationship between diabetes and not having a doctor available in the area, feeling that healthcare provided was inadequate and a lack of available healthcare services in the area. Urban First Nations peoples who felt the health service they received was not culturally appropriate were more likely to have diabetes, compared with those who did not feel the service they received was culturally inappropriate. Establishing more healthcare services that integrate First Nations cultures and traditions could improve access to care and the course of treatment for urban First Nations peoples living with diabetes.


MeCP2 regulates ethanol sensitivity and intake.
We have investigated the expression of chromatin-regulating genes in the prefrontal cortex and in the shell subdivision of the nucleus accumbens during protracted withdrawal in mice with increased ethanol drinking after chronic intermittent ethanol (CIE) vapor exposure and in mice with a history of non-dependent drinking. We observed that the methyl-CpG binding protein 2 (MeCP2) was one of the few chromatin-regulating genes to be differentially regulated by a history of dependence. As MeCP2 has the potential of acting as a broad gene regulator, we investigated sensitivity to ethanol and ethanol drinking in MeCP2(308/) (Y) mice, which harbor a truncated MeCP2 allele but have a milder phenotype than MeCP2 null mice. We observed that MeCP2(308/) (Y) mice were more sensitive to ethanol's stimulatory and sedative effects than wild-type (WT) mice, drank less ethanol in a limited access 2 bottle choice paradigm and did not show increased drinking after induction of dependence with exposure to CIE vapors. Alcohol metabolism did not differ in MeCP2(308/) (Y) and WT mice. Additionally, MeCP2(308/) (Y) mice did not differ from WT mice in ethanol preference in a 24-hour paradigm nor in their intake of graded solutions of saccharin or quinine, suggesting that the MeCP2(308/) (Y) mutation did not alter taste function. Lastly, using the Gene Set Enrichment Analysis algorithm, we found a significant overlap in the genes regulated by alcohol and by MeCP2. Together, these results suggest that MeCP2 contributes to the regulation of ethanol sensitivity and drinking.


Introduction to the special issue on diversity and leadership.
Theories of leadership have neglected diversity issues. As the population within the United States and in countries throughout the world becomes increasingly diverse, the contexts in which leadership occurs within institutions and communities will also become increasingly diverse. Attention to diversity is not simply about representation of leaders from diverse groups in the ranks of leadership. Attention to diversity means paradigm shifts in our theories of leadership so as to make them inclusive; it means incorporating explanations of how dimensions of diversity shape our understanding of leadership. It means paying attention to the perceptions and expectations of diverse leaders by diverse followers and to how bias influences the exercise of leadership. Although leadership theories have evolved and reflect changing social contexts, they remain silent on issues of equity, diversity, and social justice. Theories of leadership need to be expanded to incorporate diversity if they are to be relevant for the 21st century amidst new social contexts, emerging global concerns, and changing population demographics.


The mother-daughter-sister triad: The role of female family members in predicting body image and eating behaviour in young women.
Familial influence, specifically from mothers and sisters, may impact the development of body dissatisfaction and disordered eating in young women. Guided by the Tripartite Influence Model, the present study recruited 422 young Australian women for a survey to determine how appearance pressures and fat talk, exhibited by mothers and sisters, and mediational mechanisms (comparisons and internalisation), are associated with body dissatisfaction, and in turn, disordered eating symptomatology. We also explored differences in perceived ratings of mother versus sister appearance pressures and fat talk. Findings were in the hypothesised directions. Greater appearance pressures and fat talk from mothers and sisters was associated with greater body dissatisfaction, restriction and bulimic behaviours. Furthermore, appearance pressures from mothers and sisters was related to young women's likelihood of engaging in appearance comparisons and thin-ideal internalisation, which was associated with body dissatisfaction, and in turn, disordered eating symptomatology. Finally, participants perceived more appearance pressures from their mothers than their sisters, and perceived their mothers to exhibit greater fat talk than their sisters. The findings extend previous research in an important and novel way by investigating individual agents of female familial influence in addition to the role of fat talk in predicting body dissatisfaction and disordered eating.


Gene expression profiling of anticancer immune responses.
Anticancer immune responses can be enhanced by immune manipulation, however, the biological mechanism responsible for these immune responses remains largely unexplained. Conventional immunology researchers have extensively studied specific interactions between immune and cancer cells, and additional investigations have identified co-factors that may enhance the effectiveness of such interactions. As the molecular understanding of individual interactions increases, it is becoming apparent that no single mechanism can explain the phenomenon of tumor rejection. The contribution of several components of the innate and adaptive immune response is likely to be required for successful tumor rejection. These components may be variably recruited and activated by molecules with immune modulatory properties being produced by tumor and bystander cells within the tumor micro-environment. Such complexity can only be appreciated and solved by high-throughput tools capable of providing a global view of biological processes as they occur. This review will present selected examples of how high-throughput gene expression profiling may contribute to the understanding of anticancer immune responses. As reviews on technological aspects of the genomic analysis of cancer are already available, this review will provide a speculative discussion about their potential usefulness.


Hydrocarbon recovery and biocompatibility of solvents for extraction from cultures of Botryococcus braunii.
Various water-immiscible solvents were tested for biocompatibility and hydrocarbon recovery under different contact conditions with the hydrocarbon-rich microalga Botryococcus braunii. Eighteen solvents were first selected from a database of 1500 compounds (compiled for solvent selection for ethanol recovery from Saccharomyces cerevisiae fermentation). Nine of these candidate solvents were shown to be biocompatible with B. braunii following short contact times. This biocompatibility tends to be associated with high molecular weights and high boiling points but strongly depends on solvent chemical structure. A low polarity is essential to biocompatibility and calculated octanol-water partition coefficients, or capacity factors determined by reversed-phase high-performance liquid chromatography (HPLC), are suitable predictors of biocompatibility with B. braunii. High recoveries of hydrocarbons directly from the algal culture require relatively polar solvents and are, therefore, inimical with maintenance of cell viability. The inaccessibility of weakly polar solvents to the cell surface appears to protect the algae but also prevents substantial recovery of the hydrocarbons stored in B. braunii outer walls. In order to achieve a high recovery, contact with the solvent must be carried out on algae concentrated by filtration. Then, a large fraction of B. braunii hydrocarbons can be recovered, after a short contact time, without impairing cell viability. Under these conditions, the pertinent solvent property is affinity for the nonpolar hydrocarbons, and the highest recovery yield, approximately 70% after contact for 30 min, is achieved with hexane.


High positive predictive value of specific antibodies cross-reacting with a 28-kDa Drosophila antigen for diagnosis of ankylosing spondylitis.
Diagnosis of ankylosing spondylitis (AS) can be difficult, and a specific laboratory test has not yet been introduced as a routine diagnostic tool. Our aim was to evaluate the diagnostic value of antibodies specifically binding to a recombinant 28-kDa antigen for the diagnosis of AS. Blinded sera were tested for antibodies binding to the procaryotically expressed 28-kDa protein using an enzyme-linked immunosorbent assay (ELISA). This purified 28-kDa protein is produced by a specific clone from an embryonic Drosophila hydei Xgtl I c-DNA library and is bound by human antibodies cross-reacting with both a 36-kDa protein of chromosomes from Drosophila melanogaster and a 69-Da HeLa S3 protein potentially involved in signal transduction pathways. Serum concentrations of antibodies cross-reacting with this specific antigen were increased in 371 patients with AS compared with 37 healthy controls (39.5 vs 22.6 U/ml; P = 0.004). The positive predictive values of this ELISA test for AS were between 95.1% (95% confidence interval 90.6-97.9%) for a cut-off level of 50 U/ml and 97.4% (92.7-99.5%) for a cut-off level of 75 U/ml, and the sensitivities were between 42.1% (37.0-47.3%) for a cut-off level of 50 U/ml and 30.7% (26.1-35.7%) for a cut-off level of 75 U/ml. Serum ELISA tests for antibodies cross-reacting with the 28-kDa antigen show a high positive predictive value for AS of more than 95%.


Unimolecular Decay of the Dimethyl-Substituted Criegee Intermediate in Alkene Ozonolysis: Decay Time Scales and the Importance of Tunneling.
We used the steady-state master equation to model unimolecular decay of the Criegee intermediate formed from ozonolysis of 2,3-dimethyl-2-butene (tetramethylethylene, TME). Our results show the relative importance and time scales for both the prompt and thermal unimolecular decay of the dimethyl-substituted Criegee intermediate, (CH3)2COO. Calculated reactive fluxes show the importance of quantum mechanical tunneling for both prompt and thermal decay to OH radical products. We constrained the initial energy distribution of chemically activated (CH3)2COO formed in TME ozonolysis by combining microcanonical rates k(E) measured experimentally under collision-free conditions and modeled using semiclassical transition-state theory (SCTST) with pressure-dependent yields of stabilized Criegee intermediates measured with scavengers in flow-tube experiments. Thermal decay rates under atmospheric conditions k(298 K, 1 atm) increase by more than 1 order of magnitude when tunneling is included. Accounting for tunneling has important consequences for interpreting pressure dependent yields of stabilized Criegee intermediates, particularly with regard to the fraction of Criegee intermediates formed in the zero-pressure limit.


Maternal attachment behavior and the mother's self-concept: the effect of early skin-to-skin contact.
The problem was to determine the effect of skin-to-skin contact between mother and infant during the first hour following delivery on later maternal attachment behavior and self concept. Twenty primiparous women were randomly assigned skin-to-skin contact with their infant during the first hour after birth. There were no significant differences in 36-hour or three-month attachment behaviors or in prenatal or three month self-concept scores. For most mothers, first time motherhood appeared to have a positive effect on their self-concepts.


Development and Evaluation of Azelaic Acid-Loaded Microemulsion for Transfollicular Drug Delivery Through Guinea Pig Skin: A Mechanistic Study.
Purpose: Azelaic acid is a natural keratolytic, comedolytic, and antibacterial drug that is used to treat acne. The topical application of azelaic acid is associated with problems such as irritation and low permeability. For dissolving, the problem is that microemulsion (ME) is used as a drug carrier. The aim of this study was to increase the azelaic acid affinity in the follicular pathway through ME. Methods: Azelaic acid-loaded MEs were prepared by the water titration method. The properties of the MEs included formulation stability, particle size, drug release profile, thermal behavior of MEs, the diffusion coefficient of the MEs and skin permeability in the non-hairy ear skin and hairy abdominal skin of guinea pig were studied in situ. Results: The MEs demonstrated a mean droplet size between 5 to 150 nm. In the higher ratios of surfactant/co-surfactant, a more extensive ME zone was found. All MEs increased the azelaic acid flux through both hairy and non-hairy skin compared with an aqueous solution of azelaic acid as a control. This effect of the ME was mainly dependent on the droplet diffusion coefficient and hydrodynamic radius. MEs with a higher diffusion coefficient demonstrated higher azelaic acid flux through hairy and non-hairy skin. Drug flux through both skins was affected by the surfactant/co-surfactant ratio in that the higher ratio increased the azelaic acid affinity into the follicular pathway. Conclusion: Finally, the ME with the highest droplet diffusion coefficient and the lowest surfactant/co-surfactant ratio was the best ME for azelaic acid delivery into the follicular pathway.


Ultrasound enhances transforming growth factor beta-mediated chondrocyte differentiation of human mesenchymal stem cells.
In clinical studies and animal models, low-intensity ultrasound (US) promotes fracture repair and increases mechanical strength. US also promotes cartilage healing by increasing glycosaminoglycan synthesis of chondrocytes. As mesenchymal stem cells (MSCs) have the ability to differentiate into chondrocytes, US may promote their differentiation. Here, we evaluated the effects of US on the differentiation of MSCs toward chondrocytes and cartilage matrix formation. When human MSCs cultured in pellets were treated with transforming growth factor beta (TGF-beta, 10 ng/mL), they differentiated into chondrocytes as assessed by alcian blue staining and immunostaining for aggrecan, but nontreated cell pellets did not. Furthermore, when low-intensity US was applied for 20 min every day to the TGF-beta-treated cell pellets, chondrocyte differentiation was enhanced. Biochemically, aggrecan deposition was increased by 2.9- and 8.7-fold by treatment with TGF-beta alone, and with both TGF-beta and US, respectively. In contrast, cell proliferation and total protein amount appeared unaffected by these treatments. These results indicate that low-intensity US enhances TGF-beta-mediated chondrocyte differentiation of MSCs in pellet culture and that application of US may facilitate larger preparations of chondrocytes and the formation of mature cartilage tissue.


Novel Mechanism for an Old Drug: Phenazopyridine is a Kinase Inhibitor Affecting Autophagy and Cellular Differentiation.
Phenazopyridine is a widely used drug against urinary tract pain. The compound has also been shown to enhance neural differentiation of pluripotent stem cells. However, its mechanism of action is not understood. Based on its chemical structure, we hypothesized that phenazopyridine could be a kinase inhibitor. Phenazopyridine was investigated in the following experimental systems: 1) activity of kinases in pluripotent stem cells; 2) binding to recombinant kinases, and 3) functional impact on pluripotent stem cells. Upon addition to pluripotent stem cells, phenazopyridine induced changes in kinase activities, particularly involving Mitogen-Activated Protein Kinases, Cyclin-Dependent Kinases, and AKT pathway kinases. To identify the primary targets of phenazopyridine, we screened its interactions with 401 human kinases. Dose-inhibition curves showed that three of these kinases interacted with phenazopyridine with sub-micromolar binding affinities: cyclin-G-associated kinase, and the two phosphatidylinositol kinases PI4KB and PIP4K2C, the latter being known for participating in pain induction. Docking revealed that phenazopyridine forms strong H-bonds with the hinge region of the ATP-binding pocket of these kinases. As previous studies suggested increased autophagy upon inhibition of the phosphatidyl-inositol/AKT pathway, we also investigated the impact of phenazopyridine on this pathway and found an upregulation. In conclusion, our study demonstrates for the first time that phenazopyridine is a kinase inhibitor, impacting notably phosphatidylinositol kinases involved in nociception.


Organization and function of the YsiA regulon of Bacillus subtilis involved in fatty acid degradation.
The organization and function of the Bacillus subtilis YsiA regulon involved in fatty acid degradation were investigated. Northern and primer extension analyses indicated that this regulon comprises five operons, i.e. lcfA-ysiA-B-etfB-A, ykuF-G, yhfL, yusM-L-K-J, and ywjF-acdA-rpoE. YusJ and AcdA, YsiB and YusL, and YusK presumably encode acyl-CoA dehydrogenases, 3-hydroxyl-CoA dehydrogenase/enoyl-CoA hydratase complexes, and acetyl-CoA C-acyltransferase, respectively, which are directly involved in the fatty acid beta-oxidation cycle. In addition, LcfA and YhfL are likely to encode long chain acyl-CoA ligases. On gel retardation and footprinting analyses involving the purified YsiA protein, we identified cis-sequences for YsiA binding (YsiA boxes) in the promoter regions upstream of ysiA, ykuF, yusL, yhfL, and ywjF, the equilibrium dissociation constants (K(d)) for YsiA binding being 20, 21, 37, 43, and 65 nm, respectively. YsiA binding was specifically inhibited by long chain acyl-CoAs with 14-20 carbon atoms, acyl-CoAs with 18 carbon atoms being more effective; out of long chain acyl-CoAs tested, monounsaturated oleoyl-CoA, and branched chain 12-metyltetradecanoyl-CoA were most effective. These in vitro findings were supported by the in vivo observation that the knock-out of acyl-CoA dehydrogenation through yusJ, etfA, or etfB disruption resulted in YsiA inactivation, probably because of the accumulation of long chain acyl-CoAs in the cells. Furthermore, the disruption of yusL, yusK, yusJ, etfA, etfB, or ykuG affected the utilization of palmitic acid, a representative long chain fatty acid. Based on this work, ysiA, ysiB, ykuF, ykuG, yhfL, yusM, yusL, yusK, yusJ, and ywjF can be renamed fadR, fadB, fadH, fadG, lcfB, fadM, fadN, fadA, fadE, and fadF.


Associations between the number of natural teeth and the maternal age at childbirth or history of parity in postmenopausal women: The 2010-2012 Korea national health and nutrition examination survey.
The relationship between reproductive factors, including pregnancy and delivery, and the number of teeth in postmenopausal women remains to be revealed. The aim of this study was to evaluate the relationship between age at first and last delivery, parity and the number of natural teeth in postmenopausal women, using nationally representative data. Data from the Korea National Health and Nutrition Examination Survey between 2010 and 2012 were used, and the analysis in this study was confined to a total of 4,060 respondents who had gone through menopause and had no missing values for the reproductive factors and outcome variables. The total number of natural teeth was then calculated after excluding third molars, and frequency of tooth brushing was recorded as oral health behavior. Univariate and multivariate logistic regression analyses were used to assess the associations between the number of natural teeth and reproductive factors. Both a woman's age at her last childbirth and the number of pregnancies had statistically significant effects on the number of natural teeth remaining after menopause. With each one-year increase of age at a woman's last delivery, the number of natural teeth decreased by a value of 0.12 (p < 0.05). Similar trends were seen with increases in parity, which resulted in decreases in the number of natural teeth by 0.65 (p < 0.05). The odds ratios of the percentage of individuals with a 20 or fewer teeth tended to increase with increases in the woman's age at her last childbirth. This study identified an association between the number of natural teeth and a woman's age at her last childbirth as well as between the number of natural teeth and parity. Higher ages at last childbirth and higher parity were found to be potential risk indicators for tooth loss in postmenopausal women.


Vasoepididymostomy to the head of the epididymis: a comparative study of two microsurgical techniques in the rabbit.
In an experimental animal study, two different microsurgical techniques of vasoepididymostomy to the caput epididymidis are compared: an end-to-side anastomosis with the epididymal tubule and an end-to-end anastomosis with a section of a cluster of the epididymal tubule. The patency rates are respectively 50 per cent and 26.3 per cent, as controlled by deferentography and histology. Examination with scanning electron microscopy, shows that the superiority of the first method is due to the better apposition of both mucosas .


Favorable first-pass recanalization rates with NeVa™ thrombectomy device in acute stroke patients: Initial clinical experience.
The NeVa™ thrombectomy device (Vesalio LLC, Nashville, USA) has been reported to succeed in large vessel occlusion thrombectomy in animal, in-vitro, and clinical studies. Designed with Drop Zone technology, a closed distal tip, and strong expansive radial force, the device demonstrated particular efficiency in resistant "white" thrombi in preclinical research. Our goal is to determine the safety and performance of this novel stent retriever on first-pass rates and overall recanalization. The Interventional Neurology Database is a prospectively maintained database of anterior and posterior circulation stroke thrombectomy cases. We retrospectively analyzed cases where the NeVa™ thrombectomy device was used as the first-line treatment strategy. Data collection occurred between January 2019 and January 2020. First-pass recanalization, final recanalization, 90-day functional outcome, complication, and bleeding rates are reported. One hundred eighteen patients were treated with the NeVa™ thrombectomy device. The mean patient age was 69 ± 14 years, the median baseline National Institutes of Health Stroke Scale was 14, and the median initial Alberta Stroke Program Early Computed Tomography score was 8. The median time from groin puncture to successful recanalization was 29 min (interquartile range (IQR): 20-40). First-pass recanalization rates were 56.8% (modified treatment in cerebral infarction (mTICI) 2b/3) and 44.9% (mTICI 2c/3). Final successful recanalization rate was 95.8% (thrombolysis in cerebral infarction 2b/3). Favorable functional outcome (modified Rankin Scale 0-2) was 53% in the "first-pass" subgroup and 42.4% in the total patient population. The median number of passes to achieve the final recanalization score was 1 (IQR 1-2). The rate of embolization into new territory was 1.7%. Four patients (3.3%) had symptomatic hemorrhage. In our experience, the NeVa™ device demonstrated high first-pass and overall recanalization rates along with a good safety profile.


Role of Ultrasound in the Management of Thyroid Nodules and Thyroid Cancer.
The management of thyroid nodules can be classified into narrow-and broad-sense levels. The broad-sense procedures are used for special population and include screening,risk assessment of thyroid nodules,follow-up of benign thyroid nodules,surgical operation,post-operative follow-up,and assessment and treatment of recurrence and/or metastasis of thyroid cancer. The narrow-sense procedures are for individual patients and the whole process includes the assessment,supervision,treatment,and reassessment of thyroid lesion. Ultrasound plays different roles at different management stages. With the development of ultrasonic technology and improvement of diagnostic accuracy,ultrasound has gradually becoming an irreplaceable imaging tool in the diagnosis of thyroid nodules. In this article we review the history of thyroid ultrasound and the latest international guidelines on the management of thyroid nodules and differentiated thyroid cancer by focusing on the role of ultrasound throughout the management of thyroid nodules.


Clinical evidence based review and systematic scientific review in the identification of malignant transformation of inverted papilloma.
Inverted papilloma (IP) is an unusual type of benign tumor that has high recurrence rates and the potential to transform into squamous cell carcinomas (SCC). The mechanism of the transformation process from IP to IP-SCC is uncertain and there is no consensus regarding the best practice for IP-SCC detection. The goal of this study is to identify the best clinical methods to detect for IP-SCC. An evidence-based review was performed using Medline and Ovid to obtain all articles up to October 10th, 2019 pertaining to identification of IP malignant transformation. All manuscripts discussing clinical methods or biomarkers were included. Based on clinical research studies, convoluted cerebriform pattern and apparent diffusion coefficient values on Magnetic Resonance Imaging (MRI) can help differentiate benign IP from SCC and increased SUVmax on PET/CT is associated with higher probability of malignancy although not as specific. No consensus about the best biomarker for IP-SCC has been reached among researchers and continues to be exploratory. Endoscopy with biopsy is the gold standard practice to identify IP-SCC; however, MRI is the preferred imaging modality to recognize malignant transformation in cases where biopsy is difficult. Multiple biomarkers have shown positive results, but no single indicator with clinical significance for monitoring malignant transformation process has been found.


[Clinical and medication characteristics of senior hospitalized patients with chronic constipation].
To analyze the clinical features, risk factors and drug uses of senior hospitalized patients with chronic constipation. A total of 162 hospitalized patients aged 85 years and over at our hospital during the period of January-March 2012 conducted a questionnaire survey. There were 137 males and 25 females. And 112 cases of chronic constipation were diagnosed in accordance with the Rome III criteria. The survey included general condition, risk factors of constipation, spectrum of symptoms, associated symptoms, previous medication and medication for constipation after admission. The results were statistically analyzed by Logistic regression. Their average age was (90 ± 4) years old. And the total prevalence of chronic constipation was 69.1% (112/162). Logistic regression analysis showed that less activity (OR = 10.873) and diet (OR = 4.752) were the important risk factors. Defecation effort was the most common symptom (n = 85, 75.9%). A total of 88 cases (78.6%) took lactulose alone or lactulose plus other laxatives. The reasons of using lactulose were as follows: dietary restrictions (n = 31, 35.2%), aspiration prevention (n = 21, 23.9%) and poor efficacy of other laxatives (n = 36, 40.9%). Prevalence of constipation is high among senior hospitalized patients. Less activity and diet are the main risk factors. And lactulose should be a first-line therapy.


GALNT3 inhibits NF-κB signaling during influenza A virus infection.
Protein glycosylation, attaching glycans covalently onto amino acid side chains of protein by various glycosyltransferase, is the most common post-translational modification. The UDP-GalNAc transferase 3 (GANLT3), encoded by Galnt3, transfers N-acetyl-d-galactosamine to hydroxyl groups of the side chains of Ser/Thr residues, initiating mucin type O-glycosylation of proteins. Most researches as yet focus on the involvement and abnormal expression of GALNT3 in various tumors. In this study, we found that GALNT3 was significantly decreased in the lungs after influenza A virus (IAV) infection in mice. Overexpression of GALNT3 in cell lines markedly inhibited IAV replication. Further experiments demonstrated that GALNT3 inhibited NF-κB signaling by preventing the translocation of phosphorylated P65 into nucleus. Therefore, our results reveal an important role of GALNT3 in regulating host responses during IAV infection, indicating the broad functions of the GALNT family, and the direct involvement of GALNTs during viral infections.


Efficacy and Safety of Triple Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Patients With Cystic Fibrosis: A Meta-Analysis of Randomized Controlled Trials.
Background: Cystic fibrosis is a rare, recessive, progressive genetic disease caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Small molecules have recently been developed to treat the molecular consequences of CFTR mutations and restore CFTR protein function. However, the data on triple combination therapy (mainly from Vertex Pharmaceuticals, which is most tested in clinical trials) are limited. This meta-analysis was aimed to assess the efficacy and safety of this therapy according to different mutation genotypes and comparators. Methods: Relevant publications were identified through searching several medical databases before 31 December 2021. The primary outcomes of ppFEV1, sweat chloride concentration and Cystic Fibrosis Questionnaire-Revised (CFQ-R) score were pooled and analyzed. The secondary outcomes were adverse events in triple combination therapy. Results: Six randomized controlled trials were eligible for analysis. The total outcome of the ppFEV1 change was higher with triple combination therapy than triple placebo or active control (mean difference, MD, 13.6% and 8.74%, respectively). The pooled result of sweat chloride concentrations with triple combination therapy was lower than that of triple placebo or active control (MD, -44.13 and -39.26, respectively). The pooled estimate of the CFQ-R score was higher with triple combination therapy than triple placebo or active control (MD, 19.8% and 14.63%, respectively). No clear differences in adverse events were found between triple combination therapy and the control (placebo or active control). Conclusion: CFTR modulators in triple combination achieve better clinical results than placebo and active control, and result in comparable adverse events. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021293402, identifier PROSPERO 2021 CRD42021293402.


Combined Exposure to Alcohol and Tobacco Smoke Changes Oxidative, Inflammatory, and Neurotrophic Parameters in Different Areas of the Brains of Rats.
Devastating effects of exposure to alcohol and tobacco smoke on health are extensively reported in the literature. However, few studies have attempted to elucidate the consequences of their combined use on the central nervous system. Here we studied the effect of this combined use on some oxidative, inflammatory, and neurotrophic parameters in the hippocampus, striatum, and frontal cortex of rats. Adult Wistar rats were allocated into control (CT), alcohol (AL), tobacco smoke (TB), or combined (ALTB) groups. Rats were exposed to environmental air (CT and AL groups) or to the smoke from six cigarettes (TB and ALTB groups) immediately after tap water (CT and TB) or 2 g of alcohol/kg (AL and ALTB) oral gavage administration, twice a day, for 4 weeks. On day 28, rats were euthanized and areas of the brain were dissected to evaluate some cellular redox parameters, pro-inflammatory cytokine levels, and brain-derived neurotrophic factor (BDNF) levels. A one-way analysis of variance showed that the ALTB combined treatment significantly increased oxidative stress levels in the hippocampus. ALTB also increased interleukin-1β levels in the striatum and frontal cortex and tumoral necrosis factor-α levels in the frontal cortex compared with those of AL, TB, and CT rats. Combined treatment also decreased the BDNF levels in the frontal cortex of rats. Oxidative damage was found, more importantly, in the hippocampus, and inflammatory parameters were extended to all areas of the brain that were studied. Our results showed an interaction between alcohol and tobacco smoke according to the area of the brain, suggesting an additional risk of neural damage in alcoholics who smoke.


Exclusive breastfeeding and associated factors among mothers in Gozamin district, northwest Ethiopia: a community based cross-sectional study.
Exclusive breastfeeding is defined as feeding infants only breast milk, be it directly from breast or expressed, except drops or syrups consisting of vitamins, mineral supplements or medicine. Exclusive breastfeeding is one of the essential actions for infant development and survival. However, the prevalence of exclusive breastfeeding in Ethiopia has been estimated at 52% which is far less than the World Health Organization (WHO) recommendations. Moreover, there are inconsistencies among estimates in different districts of the country. Therefore, this study aimed to assess the prevalence and associated factors of exclusive breastfeeding among mothers in Gozamin district, northwest Ethiopia. Using the simple random sampling technique, seven kebeles (lowest administrative units) were selected as the primary sampling unit of the district. Sample mother-infant pairs were then selected using the systematic random sampling technique that involved our moving from house to house in each village. Data were collected from 506 mother-infant pairs using interviews. Factors associated with exclusive breastfeeding were determined using logistic regression. The measure of association used was the odds ratio, and statistical tests with p-values of less than 0.05 were considered as statistically significant. In this study, the prevalence of exclusive breastfeeding among mothers was 74.1% (95% CI 70.80, 79.10). For government employee mothers, the odds of exclusive breastfeeding were reduced by half compared to housewives (AOR 0.49, 95% CI 0.26, 0.94). Mothers who did not receive breastfeeding counseling after delivery were 0.43 times less likely to practice exclusive breastfeeding compared with mothers who received the services (AOR 0.43, 95% CI 0.25, 0.72). Mothers who gave birth at health institutions were more likely to practice exclusive breastfeeding. Even though the estimated prevalence is relatively high, more effort to meet WHO recommendations is still necessary. Therefore, we suggest health institutions encourage hospital birthing and increase breastfeeding counseling after delivery, and employers needs to give longer maternity leave to improve exclusive breastfeeding practice.


[How healthy is the lifestyle of adolescents in Germany?].
Studies on the health behaviour of adolescents mostly examine single health behaviour indicators in a separate manner for each one. However, health behaviours are not independently developed, but occur within a broader behavioural scheme acquired during socialisation. The aim of this study is to analyse the distribution of health-related behaviour patterns in adolescence by using a composite index made up of 6 single indicators allowing for sociodemographic and socioeconomic variables. The data are derived from a subsample of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), carried out by the Robert Koch Institute between May 2003 and May 2006 (age: 11-17 years, n=6 813). The creation of an additive healthy lifestyle index (HLI) is based upon data regarding smoking behaviour, body mass index, physical activity, use of electronic media, alcohol intake and fruit and vegetable consumption. The highest score of HLI is taken as a single indicator of a healthy lifestyle. Independent variables are socioeconomic status (SES) of the family of origin, school type and migration background. All analyses were done taking into account potential age and gender differences. Girls adhere more often to a recommended healthy lifestyle than boys (25.4% and 18.7%, respectively). The proportion of adolescents adhering to all 6 HLI categories decreases with every year of life. Adolescents with a low SES and adolescents from secondary general schools ("Hauptschule") reach to a significantly lower extent the highest score of HLI than peers with a middle or high SES and adolescents attaining other types of schools. The results of the created HLI refer to latent potentials for prevention and specific target groups for health promotion measures.


[Role of the membranes in lymphocyte interaction with mycoplasmas].
The interaction of Acheleplasma laidlawii cells, derived membranes and liposomes with mouse spleen lymphocytes does not require the energy and participation of electrostatic coupling. The absence of pinocytosis of mycoplasma is demonstrated. Specific membrane receptors don't participate in mycoplasma and lymphocyte binding. The exchange by membrane lipids occurs during the interaction of mycoplasma, membranes and liposomes with lymphocytes; mycoplasma, membranes and liposomes lose saturated fat acids and enrich with cholesterol. On the contrary, lymphocytes lose cholesterol, but absorb fat acids. The intensity of lipid exchange depends on the degree of unsaturation of fat acids in mycoplasma. The carbohydrate transport into lymphocytes is stimulated considerably as a result of interaction of both cells.


Studies of potato resistance to Globodera rostochiensis revealed novel alleles for 57R marker.
Globodera rostochiensis resistance has been an important trait in potato (Solanum tuberosum) breeding for decades. Our aim was to complement phenotypic testing with genetic marker analysis. We analysed the results of G. rostochiensis resistance greenhouse testing in 4601 tubers of 2918 breeding clones from 11 years. Applicability of H1 gene markers TG689 and 57R was compared. We implemented the latter with the positive predictive value of 99.1% and negative predictive value of 60.0% into the breeding scheme. The 57R marker alleles of 22 Estonian cultivars and 470 breeding clones were determined. Two unique 57R alleles, 57R-887 and 57R-1155, were found in Estonian cultivar 'Anti'. The 887 bp allele has two deletions (14 bp and 490 bp) accompanied by several other indels and SNPs within the 57R marker region. The 1155 bp allele has three deletions (7 bp, 20 bp and 210 bp) accompanied by several other indels and SNPs within the same region. Partial resistance to G. rostochiensis in 'Anti' suggests that the newly described alleles could affect the H1-mediated resistance directly or indirectly.


Disruptive Selection of Human Immunostimulatory and Immunosuppressive Genes Both Provokes and Prevents Rheumatoid Arthritis, Respectively, as a Self-Domestication Syndrome.
Using our previously published Web service SNP_TATA_Comparator, we conducted a genome-wide study of single-nucleotide polymorphisms (SNPs) within core promoters of 68 human rheumatoid arthritis (RA)-related genes. Using 603 SNPs within 25 genes clinically associated with RA-comorbid disorders, we predicted 84 and 70 candidate SNP markers for overexpression and underexpression of these genes, respectively, among which 58 and 96 candidate SNP markers, respectively, can relieve and worsen RA as if there is a neutral drift toward susceptibility to RA. Similarly, we predicted natural selection toward susceptibility to RA for 8 immunostimulatory genes (e.g., IL9R) and 10 genes most often associated with RA (e.g., NPY). On the contrary, using 25 immunosuppressive genes, we predicted 70 and 109 candidate SNP markers aggravating and relieving RA, respectively (e.g., IL1R2 and TGFB2), suggesting that natural selection can simultaneously additionally yield resistance to RA. We concluded that disruptive natural selection of human immunostimulatory and immunosuppressive genes is concurrently elevating and reducing the risk of RA, respectively. So, we hypothesize that RA in human could be a self-domestication syndrome referring to evolution patterns in domestic animals. We tested this hypothesis by means of public RNA-Seq data on 1740 differentially expressed genes (DEGs) of pets vs. wild animals (e.g., dogs vs. wolves). The number of DEGs in the domestic animals corresponding to worsened RA condition in humans was significantly larger than that in the related wild animals (10 vs. 3). Moreover, much less DEGs in the domestic animals were accordant to relieved RA condition in humans than those in the wild animals (1 vs. 8 genes). This indicates that the anthropogenic environment, in contrast to a natural one, affects gene expression across the whole genome (e.g., immunostimulatory and immunosuppressive genes) in a manner that likely contributes to RA. The difference in gene numbers is statistically significant as confirmed by binomial distribution (p < 0.01), Pearson's χ2 (p < 0.01), and Fisher's exact test (p < 0.05). This allows us to propose RA as a candidate symptom within a self-domestication syndrome. Such syndrome might be considered as a human's payment with health for the benefits received during evolution.


Painful Abdominal Lump in the Pediatric Age Group: A Diagnostic Dilemma.
Any cystic lesion occurring in the mesentery which may or may not extend into the retroperitoneum is referred to as a mesenteric cyst; they have an infrequent incidence rate in the pediatric age group. Definitive etiology of the cystic lymphatic malformations is still not known but there are multiple hypotheses. A young male child presented with acute onset abdominal pain and palpable intra-abdominal mass and ultrasonography revealed presence of two lesions, one of them as an encysted turbid fluid collection in the right lumbar region and the other as a dilated, tortuous, intercalated structure. On CT, the first one was identified definitively as a mesenteric cyst while the other as a possible neoplastic mass in close proximity to the first one. Histopathology confirmed the diagnosis as a cystic lymphatic malformation of the mesenteric cyst. The limited awareness of its existence along with its usually asymptomatic nature, are the likely reasons that it still remains an elusive diagnosis. Based on our case we discuss, the use of a multi-modality approach towards diagnosing cystic malformation disorders and how the use of MRI is under-utilised when it could prove decisive.


Surface-enhanced Raman spectroscopy to probe reversibly photoswitchable azobenzene in controlled nanoscale environments.
We apply in situ surface-enhanced Raman spectroscopy (SERS) to probe the reversible photoswitching of azobenzene-functionalized molecules inserted in self-assembled monolayers that serve as controlled nanoscale environments. Nanohole arrays are fabricated in Au thin films to enable SERS measurements associated with excitation of surface plasmons. A series of SERS spectra are recorded for azobenzene upon cycling exposure to UV (365 nm) and blue (450 nm) light. Experimental spectra match theoretical calculations. On the basis of both the simulations and the experimental data analysis, SERS provides quantitative information on the reversible photoswitching of azobenzene in controlled nanoscale environments.


[Optimal beam quality for chest digital radiography].
To investigate the optimal beam quality for chest computed radiography (CR), we measured the radiographic contrast and evaluated the image quality of chest CR using various X-ray tube voltages. The contrast between lung and rib or heart increased on CR images obtained by lowering the tube voltage from 140 to 60 kV, but the degree of increase was less. Scattered radiation was reduced on CR images with a lower tube voltage. The Wiener spectrum of CR images with a low tube voltage showed a low value under identical conditions of amount of light stimulated emission. The quality of chest CR images obtained using a lower tube voltage (80 kV and 100 kV) was evaluated as being superior to those obtained with a higher tube voltage (120 kV and 140 kV). Considering the problem of tube loading and exposure in clinical applications, a tube voltage of 90 to 100 kV (0.1 mm copper filter backed by 0.5 mm aluminum) is recommended for chest CR.


Special features of intestinal metaplasia and its relation to early gastric carcinoma in man: observation by a method in which leucine aminopeptidase activity is used.
The degree of intestinal metaplasia and its macroscopic distribution in gastric mucosa were examined by a new method in which leucine aminopeptidase (LAP) activity is used to investigate the relationship between intestinal metaplasia and gastric carcinoma. Since LAP is a specific enzyme of intestinal metaplasia, the area showing positive reaction for this enzyme corresponds strictly with the zone of intestinal metaplasia examined microscopically. Almost all metaplasia was demonstrated by this method. This method was used to examine 40 human gastric carcinomas confined to the mucosa. Gastric mucosa containing differentiated tubular-type carcinoma (60%) was associated with a high degree of metaplasia in comparison with the low degree of metaplasia in poorly differentiated carcinoma (40%). Differentiated tubular-type carcinoma was closely related to intestinal metaplasia. However, all carcinomas arising from the mucosa without intestinal metaplasia (18%) were poorly differentiated. Therefore, gastric carcinomas occurring in Japanese patients are frequently and closely related to intestinal metaplasias.


Compassion, medical humanities and medical education.
Compassion is central to person centred clinical care. Medical Humanities have developed both as an academic discipline and as a resource for education over the past 30 years. The article will discuss what compassion is in a clinical context, and explore whether compassionate clinical practice can be enhanced by using the humanities in medical education in primary care.


Clinical significance of intra-host variability of Dengue-1 virus in venous and capillary blood.
Dengue fever represents a major public health problem. Both viral and host immune factors are involved in severe infections. Humans and mosquito-vectors are infected with diverse viral populations that may play a role in viral adaptation and disease pathogenesis. Our objective was to analyse the intra-host genetic variability of dengue virus type 1 (DENV-1) in the venous and capillary blood and its relationships with the clinical presentation of dengue fever. Early serum samples were collected in 2009 from ten DENV-1-infected patients hospitalized in Santa Cruz de la Sierra, Bolivia. Partial viral envelope sequences were analysed at the inter-host and intra-host level. For each patient, an average of 56 clone sequences was analysed both in the venous sector and the capillary sector (from right and left hands). The ten consensus sequences were highly similar. The intra-host DENV-1 genetic variability was significantly lower in the venous sector than in the capillary sector, and in patients with haemorrhagic symptoms than in those without haemorrhagic symptoms, particularly in capillary samples. No relation was found with sex, age, dengue IgG-serological status, day of serum sampling, or viral load. Significant relationships were found between the clinical presentation of dengue fever and the variability of viral populations within hosts, particularly in capillary samples. The observed variability of envelope sequences at the early phase of dengue infection was not critically influenced by the previous dengue serological status of patients. An important part of viral microevolution may occur in the capillary sector and influence the mechanisms of severe forms.


Management of Male Patients With Occult Breast Cancer: Analysis of the National Cancer Database.
Occult breast cancer (OBC) consists of <0.1% of breast cancer cases in the United States. Male occult breast cancer (mOBC) has not been well-studied outside of case reports, and management is largely based on female OBC (fOBC) studies. We aim to examine the prevalence of mOBC among those in the National Cancer Database with breast cancer and describe treatment modalities received by mOBC compared to fOBC. The National Cancer Database was queried for patients with OBC from 2004 to 2018. Chi-Square test and Fisher's exact tests compared patient, clinical, and facility characteristics by sex. Treatment modalities [systemic therapy, radiation therapy, axillary lymph node dissection, modified radical mastectomy (MRM)] were compared. A subgroup analysis examined pathologic upstaging in patients who underwent MRM. Of 23,374 male patients with breast cancer, 0.13% were identified to have mOBC [versus 0.09% in fOBC]. cN2/N3 disease was significantly more prevalent in the mOBC cohort (61.3%) than in the fOBC cohort (30.7%, P < 0.001). Receipt of axillary lymph node dissection or MRM was not significantly different by sex. Male OBC (mOBC) patients were less likely to receive trimodality treatment than fOBC patients. In patients who underwent MRM, more mOBC patients [75%] were pathologically upstaged as T+ after mastectomy than fOBC patients [30%, P < 0.001], questioning the adequacy of diagnostic workup for mOBC compared to fOBC. This review confirms mOBC as an extremely rare disease. Multimodal treatments have been highly utilized to optimize care in this patient population. Further investigation is warranted to examine the survival benefit of treatment regimens for mOBC.


Salvage procedures for calcaneus fractures.
Salvage procedures reverse the anatomic factors that cause widening and mechanical misalignment of the hindfoot. Posttraumatic arthrosis of the subtalar joint is treated by arthrodesis, using techniques that improve alignment. The easily measured goal is to restore the normal plantar alignment of the talus (Meary's line) and return the calcaneal tuberosity to the weightbearing line beneath the talus. The subtalar joint is the joint most often treated by arthrodesis, although a triple arthrodesis is sometimes required when Chopart's joint is involved.


FNA of extraskeletal myxoid chondrosarcoma: cytomorphologic, EM, and X-ray microanalysis features.
Extraskeletal myxoid chondrosarcoma, an unusual soft tissue lesion which preferentially affects the extremities, is a prime candidate for "pathologist performed" fine-needle aspirates (FNA) because it preferentially affects the extremities [Enzinger and Shiraki, Hum Pathol 1972;3:421-435] and is usually an accessible lesion. Cytomorphologically, the neoplasm consists of clusters of fairly uniform cells, lacking cartilaginous differentiation, with a metachromatic matrix when stained with Diff-Quik (DQ). While subtle, this neoplasm has distinct features and must be distinguished for other neoplasms in the differential diagnosis because patient evaluation, prognosis, and therapy will vary greatly. We present a case characteristic of this tumor in which FNA derived material was subjected to light microscopy, X-ray microanalysis, and immunohistochemical studies; each modality provided data essential to the correct diagnosis.


T cell depletion in bone marrow transplantation.
Prior to the introduction of T cell depletion graft-versus-host disease (GVHD) was the major cause of transplant-related mortality. Why has the remarkable technical achievement of efficient T cell depletion, which has virtually eliminated severe GVHD over the last few years, failed to reduce mortality and increase disease-free survival? This review examines the value of T cell depletion based on recent clinical experience. It surveys the directions that are being pursued in an effort to solve the problems that have arisen and indicates how this is leading to a greater understanding of the mechanisms involved in GVHD and the graft-versus-leukaemia effect.


Regulation of lactate production at the onset of ischaemia is independent of mitochondrial NADH/NAD+: insights from in silico studies.
Ischaemia decreases mitochondrial NADH oxidation, activates glycolysis, increases the NADH/NAD+ ratio, and causes lactate production. The mechanisms that regulate anaerobic glycolysis and the NADH/NAD+ ratio during ischaemia are unclear. Although continuous measurements of metabolic fluxes and NADH/NAD+ in cytosol and mitochondria are not possible in vivo with current experimental techniques, computational models can be used to predict these variables by simulations with in silico experiments. Such predictions were obtained using a mathematical model of cellular metabolism in perfused myocardium. This model, which distinguishes cytosolic and mitochondrial domains, incorporates key metabolic species and processes associated with energy transfer. Simulation of metabolic responses to mild, moderate and severe ischaemia in large animals showed that mitochondrial NADH/NAD+ was rapidly reset to higher values in proportion to the reduced O2 delivery and myocardial oxygen consumption . Cytosolic NADH/NAD+, however, showed a biphasic response, with a sharp initial increase that was due to activation of glycogen breakdown and glycolysis, and corresponded with lactate production. Whereas the rate of glycolysis and the malate-aspartate shuttle had a significant effect on the cytosolic NADH/NAD+, their effects on the mitochondrial NADH/NAD+ were minimal. In summary, model simulations of the metabolic response to ischaemia showed that mitochondrial NADH/NAD+ is primarily determined by O2 consumption, while cytosolic NADH/NAD+ is largely a function of glycolytic flux during the initial phase, and is determined by mitochondrial NADH/NAD+ and the malate-aspartate shuttle during the steady state.


Comparative and evolutionary analysis of RIP kinases in immune responses.
The group of receptor-interacting protein (RIP) kinases has seven members (RIPK1-7), with one homologous kinase domain but distinct non-kinase regions. Although RIPK1-3 have emerged as key modulators of inflammation and cell death, few studies have connected RIPK4-7 to immune responses. The divergence in domain structures and paralogue information in the Ensembl database have raised question about the phylogeny of RIPK1-7. In this study, phylogenetic trees of RIPK1-7 and paralogues constructed using full-length amino acid sequences or Kinase domain demonstrate that RIPK6 and RIPK7 are distinct from RIPK1-5 and paralogues shown in the Ensembl database are inaccurate. Comparative and evolutionary analyses were subsequently performed to gain new clues about the potential functions of RIPK3-7. RIPK3 gene loss in birds and animals that undergo torpor, a common physiological phenomenon in cold environments, implies that RIPK3 may be involved in ischemia-reperfusion injury and/or high metabolic rate. The negligible expression of RIPK4 and RIPK5 in immune cells is likely responsible for the lack of studies on the direct role of these members in immunity; RIPK6 and RIPK7 are conserved among plants, invertebrates and vertebrates, and dominantly expressed in innate immune cells, indicating their roles in innate immunity. Overall, our results provide insights into the multifaceted and conserved biochemical functions of RIP kinases.


Establishment of Lipofection Protocol for Efficient miR-21 Transfection into Cortical Neurons In Vitro.
Dysregulated microRNAs in neurons could cause many nervous system diseases. The therapeutic manipulation of these pathogenic microRNAs necessitates novel, efficient delivery systems to facilitate microRNA modulators targeting neurons with minimal off-target effects. The study aimed to establish a lipofection protocol to upregulate expression levels of miR-21 in neurons under different conditions, including different serum-free medium, transfection conditions, and reagent concentration, by evaluating the expression levels of miR-21 and neuron injury. The expression levels of miR-21 were higher in neurons transfected by Neurobasal-A than by DMEM. Expression levels of miR-21 were already the highest at the ratio RNAiMAX:miR-21 = 3:5, but the increase of RNAiMAX's concentration had not caused the further upregulation of expression level of miR-21. Neuron injury was condition dependent and dose dependent after transfection. Compared to S-Neurobasal groups, neurons have a smaller injury in N-Neurobasal groups, and compared to ratios RNAiMAX:miR-21 = 4:5, 5:5, neuron injury was smaller at ratios of RNAiMAX:miR-21 = 1:5, 2:5, 3:5. Without the pretreatment of starvation in vitro, the lipofection protocol was that RNAiMAX/miR-21 agomir complexes were diluted in Neurobasal-A at the ratio of RNAiMAX:miR-21 = 3:5.


Postural and object-oriented experiences advance early reaching, object exploration, and means-end behavior.
The effects of 3 weeks of social (control), postural, or object-oriented experiences on 9- to 21-week-old infants' (N = 42) reaching, exploration, and means-end behaviors were assessed. Coders recorded object contacts, mouthing, fingering, attention, and affect from video. Postural and object-oriented experiences advanced reaching, haptic exploration of objects, and developing means-end behavior compared to social experience. Object-oriented experience best-advanced means-end behavior. The results suggest that the development of novel behaviors is dependent on multiple subsystems and can be similarly advanced by addressing a variety of these subsystems. They also suggest that past experiences with active object exploration can facilitate early information processing and the development of early knowledge.


New Guideline on Managing Colorectal Cancer.
A multidisciplinary panel of experts has issued guidelines that consolidate current evidence on testing for molecular biomarkers in colorectal cancer. The guidelines aim to standardize molecular testing for patients with colorectal cancer and help clinicians identify patients most likely to benefit from targeted treatments.


First synthesis of a stable isotope of Ochratoxin A metabolite for a reliable detoxification monitoring.
Due to its toxicity and presence in numerous food products, Ochratoxin A (OTA) has drawn attention for decades. This article summarizes the first synthesis of a labeled analogue of Ochratoxin α (OTα), one of the main products generated by the metabolization of OTA by microorganisms. This synthesis also led to a new labeled analogue of OTA with the deuteration located on the dihydroisocoumarin moiety allowing thus both the accurate quantification of OTA and OTα and the establishing of a reliable detoxification rate.