Excitation of Cortical nNOS/NK1R Neurons by Hypocretin 1 is Independent of Sleep Homeostasis.

We have proposed that cortical nNOS/NK1R interneurons have a role in sleep homeostasis. The hypocretins (orexins) are wake-promoting neuropeptides and hypocretin/orexin (Hcrt) neurons project to the cortex. Hcrt peptides affect deep layer cortical neurons, and Hcrt receptor 1 (Hcrtr1; Ox1r) mRNA is expressed in cortical nNOS/NK1R cells.

Pre- and postprandial variation in implicit attention to food images reflects appetite and sensory-specific satiety.

Implicit attentional processes are biased toward food-related stimuli, with the extent of that bias reflecting relative motivation to eat. These interactions have typically been investigated by comparisons between fasted and sated individuals. In this study, temporal changes in implicit attention to food were assessed in relation to natural, spontaneous changes in appetite occurring before and after an anticipated midday meal.

Piloting Direct Observation of Procedural Skills in Dental Education in India.

Context: Direct observation of procedural skills (DOPS) and corrective feedback are one of the most important tools to promote skill learning. Authentic and pedagogically effective feedback can come out only when based on direct observation of the learners' performance. Use of DOPS, particularly in dental education in India is very uncommon.

Problems and Progress regarding Sex Bias and Omission in Neuroscience Research.

Neuroscience research has historically ignored female animals. This neglect comes in two general forms. The first is sex bias, defined as favoring one sex over another; in this case, male over female.

Aspirin and the prevention of venous thromboembolism following total joint arthroplasty: commonly asked questions.

The number of arthroplasties being performed increases each year. Patients undergoing an arthroplasty are at risk of venous thromboembolism (VTE) and appropriate prophylaxis has been recommended. However, the optimal protocol and the best agent to minimise VTE under these circumstances are not known.

Prophylactic Supplementation of 5 Protects Mice from Ovariectomy-Induced Exacerbated Allergic Airway Inflammation and Airway Hyperresponsiveness.

Asthma is a chronic inflammatory disease that affects more females than males after puberty, and its symptoms and severity in women change during menstruation and menopause. Recently, evidence has demonstrated that interactions among the microbiota, female sex hormones, and immunity are associated with the development of autoimmune diseases. However, no studies have investigated if therapeutic gut microbiota modulation strategies could affect asthma exacerbation during menstruation and menopause.

Sleep/Wake Physiology and Quantitative Electroencephalogram Analysis of the Neuroligin-3 Knockout Rat Model of Autism Spectrum Disorder.

Study Objectives: Neuroligin-3 (NLGN3) is one of the many genes associated with autism spectrum disorder (ASD). Sleep dysfunction is highly prevalent in ASD, but has not been rigorously examined in ASD models. Here, we evaluated sleep/wake physiology and behavioral phenotypes of rats with genetic ablation of Nlgn3.

Contact lens trends over three decades in a hospital-based practice in India.

Background: Contact lens fittings in a hospital-based practice are different from those in private practices because of specialised conditions. Few studies have been published on material preferences of such wearers, especially in long-term wearers. The aim of this study is to document contact lens prescribing trends in a hospital-based practice among long-term lens wearers and to identify their demographic profile.

Gas-Phase Synthesis of the Elusive Cyclooctatetraenyl Radical (C H ) via Triplet Aromatic Cyclooctatetraene (C H ) and Non-Aromatic Cyclooctatriene (C H ) Intermediates.

The 1,2,4,7-cyclooctatetraenyl radical (C H ) has been synthesized for the very first time via the bimolecular gas-phase reaction of ground-state carbon atoms with 1,3,5-cycloheptatriene (C H ) on the triplet surface under single-collision conditions. The barrier-less route to the cyclic 1,2,4,7-cyclooctatetraenyl radical accesses exotic reaction intermediates on the triplet surface, which cannot be synthesized via classical organic chemistry methods: the triplet non-aromatic 2,4,6-cyclooctatriene (C H ) and the triplet aromatic 1,3,5,7-cyclooctatetraene (C H ). Our approach provides a clean gas-phase synthesis of this hitherto elusive cyclic radical species 1,2,4,7-cyclooctatetraenyl via a single-collision event and opens up a versatile, unconventional path to access this previously largely obscure class of cyclooctatetraenyl radicals, which have been impossible to access through classical synthetic methods.

Old Friends With New Faces: Are Sodium Channel Blockers the Future of Adjunct Pain Medication Management?

Unlabelled: Providers are being asked to decrease the emphasis and overutilization of long-term opioid therapy, but many are left without proper guidance on appropriate utilization of nonopioid therapies. Furthermore, therapeutic options are quite limited and many providers lack confidence in distinguishing available alternatives. When first-line therapy has failed in a patient, there is an apparent lack of knowledge on how to proceed with choosing subsequent therapy.

Eculizumab-C5 complexes express a C5a neoepitope in vivo: Consequences for interpretation of patient complement analyses.

The complement system has obtained renewed clinical focus due to increasing number of patients treated with eculizumab, a monoclonal antibody inhibiting cleavage of C5 into C5a and C5b. The FDA approved indications are paroxysmal nocturnal haemoglobinuria and atypical haemolytic uremic syndrome, but many other diseases are candidates for complement inhibition. It has been postulated that eculizumab does not inhibit C5a formation in vivo, in contrast to what would be expected since it blocks C5 cleavage.

A Free-Radical Pathway to Hydrogenated Phenanthrene in Molecular Clouds-Low Temperature Growth of Polycyclic Aromatic Hydrocarbons.

The hydrogen-abstraction/acetylene-addition mechanism has been fundamental to unravelling the synthesis of polycyclic aromatic hydrocarbons (PAHs) detected in combustion flames and carbonaceous meteorites like Orgueil and Murchison. However, the fundamental reaction pathways accounting for the synthesis of complex PAHs, such as the tricyclic anthracene and phenanthrene along with their dihydrogenated counterparts, remain elusive to date. By investigating the hitherto unknown chemistry of the 1-naphthyl radical with 1,3-butadiene, we reveal a facile barrierless synthesis of dihydrophenanthrene adaptable to low temperatures.

The Case-Based Collaborative Learning Peer Observation Worksheet and Compendium: An Evaluation Tool for Flipped Classroom Facilitators.

Introduction: In a flipped classroom, students learn basic concepts before class, allowing them time during class to apply newly gained knowledge to problem sets and cases. Harvard Medical School (HMS) has introduced a form of flipped classroom, called case-based collaborative learning (CBCL), during preclinical curricula. Finding few published resources, the HMS Academy's Peer Observation of Teaching Interest Group developed a guide for observations and feedback to CBCL facilitators.

Cortical nNOS/NK1 Receptor Neurons are Regulated by Cholinergic Projections From the Basal Forebrain.

Cholinergic (ACh) basal forebrain (BF) neurons are active during wakefulness and rapid eye movement (REM) sleep and are involved in sleep homeostasis. We have previously shown in adult animals that cortical neurons that express neuronal nitric oxide synthase (nNOS) and the receptor for Substance P (NK1R) are activated during non-REM (NREM) sleep in proportion to homeostatic sleep drive. Here, we show that BF neurons modulate cortical nNOS/NK1R cells.

Cntnap2 Knockout Rats and Mice Exhibit Epileptiform Activity and Abnormal Sleep-Wake Physiology.

Study Objectives: Although recent innovations have enabled modification of the rat genome, it is unclear whether enhanced utility of rodents as human disease models will result. We compared electroencephalogram (EEG) and behavioral phenotypes of rats and mice with homozygous deletion of Cntnap2, a gene associated with cortical dysplasia-focal epilepsy (CDFE) and autism spectrum disorders (ASD).

Methods: Male contactin-associated protein-like 2 (Cntnap2) knockout (KO) and wild-type (WT) rats and male Cntnap2 KO and WT mice were implanted with telemeters to record EEG, electromyogram, body temperature, and locomotor activity.

Priming in response to pro-inflammatory cytokines is a feature of adult synovial but not dermal fibroblasts.

Background: It has been hypothesized that chronic inflammatory diseases such as rheumatoid arthritis (RA) may be caused by a failure of negative feedback mechanisms. This study sought to examine negative feedback mechanisms in fibroblast-like synoviocytes (FLS), one of the most abundant cell types in the joint. We hypothesized that prior exposure of healthy FLS to an inflammatory stimulus would attenuate their responses to a second inflammatory stimulus, in the same way that negative feedback mechanisms desensitize macrophages to repeated stimulation by lipopolysaccharide.

Tissue-Associated Bacterial Alterations in Rectal Carcinoma Patients Revealed by 16S rRNA Community Profiling.

Sporadic and inflammatory forms of colorectal cancer (CRC) account for more than 80% of cases. Recent publications have shown mechanistic evidence for the involvement of gut bacteria in the development of both CRC-forms. Whereas, colon and rectal cancer have been routinely studied together as CRC, increasing evidence show these to be distinct diseases.

Oxidation of the para-Tolyl Radical by Molecular Oxygen under Single-Collison Conditions: Formation of the para-Toloxy Radical.

Crossed molecular beam experiments were performed to elucidate the chemical dynamics of the para-tolyl (CHCH) radical reaction with molecular oxygen (O) at an average collision energy of 35.3 ± 1.4 kJ mol.

Gas-Phase Synthesis of the Elusive Trisilicontetrahydride Species (SiH).

The bimolecular gas-phase reaction of ground-state atomic silicon (Si; P) with disilane (SiH; A) was explored under single-collision conditions in a crossed molecular beam machine at a collision energy of 21 kJ mol. Combined with electronic structure calculations, the results suggest the formation of SiH isomer(s) along with molecular hydrogen via indirect scattering dynamics through SiH collision complex(es) and intersystem crossing from the triplet to the singlet surface. The nonadiabatic reaction dynamics can synthesize the energetically accessible singlet SiH isomers in overall exoergic reaction(s) (-93 ± 21 kJ mol).

Microbial community structure and dynamics in thermophilic composting viewed through metagenomics and metatranscriptomics.

Composting is a promising source of new organisms and thermostable enzymes that may be helpful in environmental management and industrial processes. Here we present results of metagenomic- and metatranscriptomic-based analyses of a large composting operation in the São Paulo Zoo Park. This composting exhibits a sustained thermophilic profile (50 °C to 75 °C), which seems to preclude fungal activity.

Mega-earthquakes rupture flat megathrusts.

The 2004 Sumatra-Andaman and 2011 Tohoku-Oki earthquakes highlighted gaps in our understanding of mega-earthquake rupture processes and the factors controlling their global distribution: A fast convergence rate and young buoyant lithosphere are not required to produce mega-earthquakes. We calculated the curvature along the major subduction zones of the world, showing that mega-earthquakes preferentially rupture flat (low-curvature) interfaces. A simplified analytic model demonstrates that heterogeneity in shear strength increases with curvature.

Hyperandrogenism Accompanies Increased Intra-Abdominal Fat Storage in Normal Weight Polycystic Ovary Syndrome Women.

Context: Normal weight polycystic ovary syndrome (PCOS) women may have altered adipose structure-function underlying metabolic dysfunction.

Objective: This study examines whether adipose structure-functional changes exist in normal weight PCOS women and correlate with hyperandrogenism and/or hyperinsulinemia.

Design: This is a prospective cohort study.

Stress Increases Ethanol Self-Administration via a Shift toward Excitatory GABA Signaling in the Ventral Tegmental Area.

Stress is a well-known risk factor for subsequent alcohol abuse, but the neural mechanisms underlying interactions between stress and alcohol remain largely unknown. Addictive drug reinforcement and stress signaling involve common neural circuitry, including the mesolimbic dopamine system. We demonstrate in rodents that pre-exposure to stress attenuates alcohol-induced dopamine responses and increases alcohol self-administration.

Motorcycle helmet effectiveness in reducing head, face and brain injuries by state and helmet law.

Background: Despite evidence that motorcycle helmets reduce morbidity and mortality, helmet laws and rates of helmet use vary by state in the U.S.

Methods: We pooled data from eleven states: five with universal laws requiring all motorcyclists to wear a helmet, and six with partial laws requiring only a subset of motorcyclists to wear a helmet.

Formation of the 2,3-Dimethyl-1-silacycloprop-2-enylidene Molecule via the Crossed Beam Reaction of the Silylidyne Radical (SiH; X(2)Π) with Dimethylacetylene (CH3CCCH3; X(1)A1g).

We carried out crossed molecular beam experiments and electronic structure calculations to unravel the chemical dynamics of the reaction of the silylidyne(-d1) radical (SiH/SiD; X(2)Π) with dimethylacetylene (CH3CCCH3; X(1)A1g). The chemical dynamics were indirect and initiated by the barrierless addition of the silylidyne radical to both carbon atoms of dimethylacetylene forming a cyclic collision complex 2,3-dimethyl-1-silacyclopropenyl. This complex underwent unimolecular decomposition by atomic hydrogen loss from the silicon atom via a loose exit transition state to form the novel 2,3-dimethyl-1-silacycloprop-2-enylidene isomer in an overall exoergic reaction (experimentally: -29 ± 21 kJ mol(-1); computationally: -10 ± 8 kJ mol(-1)).