Nasal Airflow Dynamics following LeFort I Advancement in Cleft Nasal Deformities: A Retrospective Preliminary Study.

Unilateral cleft lip and palate (UCLP) nasal deformity impacts airflow patterns and pressure distribution, leading to nasal breathing difficulties. This study aims to create an integrated approach using computer-aided design (CAD) and computational fluid dynamics (CFD) to simulate airway function and assess outcomes in nasal deformities associated with unilateral cleft lip and palate (UCLP) after LeFort I osteotomy advancement. Significant alterations were observed in nasal geometry, airflow velocity, pressure dynamics, volumetric flow rate, and nasal resistance postoperatively, indicating improved nasal airflow. The cross-sectional area increased by 26.6%, airflow rate by 6.53%, and nasal resistance decreased by 6.23%. The study offers quantitative insights into the functional impacts of such surgical interventions, contributing to a deeper understanding of UCLP nasal deformity treatment and providing objective metrics for assessing surgical outcome.

Improving water, sanitation, and hygiene (WASH), with a focus on hand hygiene, globally for community mitigation of COVID-19.

Continuity of key water, sanitation, and hygiene (WASH) infrastructure and WASH practices-for example, hand hygiene-are among several critical community preventive and mitigation measures to reduce transmission of infectious diseases, including COVID-19 and other respiratory diseases. WASH guidance for COVID-19 prevention may combine existing WASH standards and new COVID-19 guidance. Many existing WASH tools can also be modified for targeted WASH assessments during the COVID-19 pandemic. We partnered with local organizations to develop and deploy tools to assess WASH conditions and practices and subsequently implement, monitor, and evaluate WASH interventions to mitigate COVID-19 in low- and middle-income countries in Latin America and the Caribbean and Africa, focusing on healthcare, community institution, and household settings and hand hygiene specifically. Employing mixed-methods assessments, we observed gaps in access to hand hygiene materials specifically despite most of those settings having access to improved, often onsite, water supplies. Across countries, adherence to hand hygiene among healthcare providers was about twice as high after patient contact compared to before patient contact. Poor or non-existent management of handwashing stations and alcohol-based hand rub (ABHR) was common, especially in community institutions. Markets and points of entry (internal or external border crossings) represent congregation spaces, critical for COVID-19 mitigation, where globally-recognized WASH standards are needed. Development, evaluation, deployment, and refinement of new and existing standards can help ensure WASH aspects of community mitigation efforts that remain accessible and functional to enable inclusive preventive behaviors.

Impact assessment of the reduction or removal of ionophores used for controlling coccidiosis in the UK broiler industry.

Coccidiosis is a complex parasitic disease ubiquitous in all types of poultry production. It can have both a direct effect on bird health and welfare with significant negative impacts on the production parameters and indirect effect as it predisposes to other pathogens. Ionophore coccidiostats have been used safely for over 45 years by poultry producers. Concerns have been raised that their use in livestock production could promote the development of antibiotic resistance, but their unique mode of action makes it unlikely. Conversely their removal can result in increased use of therapeutic antibiotics to treat disease posing a greater risk of antibiotic resistance development. Economic and environmental models examining the impact of the removal of ionophore coccidiostats from UK production suggest the annual cost to the broiler sector would be between £68.02-£109.95 million and result in an additional 84,000 tonnes CO2 e being produced per annum. Any cost increase would make this wholesome and affordable animal protein less affordable to poorer sectors of society. Increased greenhouse gas production, demand for water and land as a result of less efficient production will impact on climate change targets.

Risk Factors for Surgical Site Infection after Minor Dermatologic Surgery.

BACKGROUND: Surgical site infection (SSI) after dermatologic surgery is associated with poor outcomes including increased recovery time, poor cosmesis, and repeat visits to doctors. Prophylactic antibiotics are prescribed to reduce these adverse outcomes. Identifying risk factors for SSI will facilitate judicious antibiotic prophylaxis. OBJECTIVE: To identify risk factors for SSI after minor dermatologic surgery. METHODS: Individual patient data from four large randomized controlled trials were combined to increase statistical power. A total of 3,819 adult patients requiring minor skin procedures at a single facility were recruited over a 10-year period. The main outcome measure was SSI. MAIN RESULTS: A total of 298 infections occurred, resulting in an overall incidence of 7.8% (95% confidence interval [CI], 5.8-9.6), although the incidence varied across the four studies (P = .042). Significant risk factors identified were age (relative risk [RR], 1.01; 95% CI, 1.001-1.020; P = .008), excisions from the upper limbs (RR, 3.03; 95% CI, 1.76-5.22; P = .007) or lower limbs (RR, 3.99; 95% CI, 1.93-8.23; P = .009), and flap/two-layer procedures (RR, 3.23; 95% CI, 1.79-5.85; P = .008). Histology of the excised lesion was not a significant independent risk factor for infection. CONCLUSIONS: This study demonstrated that patients who were older, underwent complex excisions, or had excisions on an extremity were at higher risk of developing an SSI. An awareness of such risk factors will guide evidence-based and targeted antibiotic prophylaxis.

Evolution of the Research Literature and the Scientific Community of Alzheimer's Disease from 1983-2017: A 35-Year Survey.

This study surveys the development of Alzheimer's disease (AD) in the research literature, the scientific community, and the journals containing AD papers over a 35-year period. Research papers on AD published from 1983 to 2017 in journals indexed in the Web of Science were analyzed in seven five-year periods. The number of AD papers increased from 1,095 in 1983-1987 to 50,532 by 2013-2017 and in the same time period, the number of participating countries went from 27 to 152. The US was the most prolific country throughout, followed by several European countries, Canada, Australia, and Japan. Asian countries have emerged and by 2013-2017, China surpassed all but the US in productivity. Countries in Latin America and Africa have also contributed to AD research. Additionally, several new non-governmental institutions (e.g., ADNI, ADI) have emerged and now play a key role in the fight against AD. Likewise the AD scientific publishing universe evolved in various aspects: an increase in number of journals containing AD papers (227 journals in 1983-1987 to 3,257 in 2013-2017); appearance of several AD-focused journals, e.g., Alzheimer's & Dementia, Journal of Alzheimer's Disease; and the development of special issues dedicated to AD. Our paper complements the numerous extant papers on theoretical and clinical aspects of AD and provides a description of the research landscape of the countries and journals contributing papers related to AD.

Structural water and disordered structure promote aqueous sodium-ion energy storage in sodium-birnessite.

Birnessite is a low-cost and environmentally friendly layered material for aqueous electrochemical energy storage; however, its storage capacity is poor due to its narrow potential window in aqueous electrolyte and low redox activity. Herein we report a sodium rich disordered birnessite (Na0.27MnO2) for aqueous sodium-ion electrochemical storage with a much-enhanced capacity and cycling life (83 mAh g-1 after 5000 cycles in full-cell). Neutron total scattering and in situ X-ray diffraction measurements show that both structural water and the Na-rich disordered structure contribute to the improved electrochemical performance of current cathode material. Particularly, the co-deintercalation of the hydrated water and sodium-ion during the high potential charging process results in the shrinkage of interlayer distance and thus stabilizes the layered structure. Our results provide a genuine insight into how structural disordering and structural water improve sodium-ion storage in a layered electrode and open up an exciting direction for improving aqueous batteries.

Alcoholic versus aqueous chlorhexidine for skin antisepsis: the AVALANCHE trial.

BACKGROUND: Preoperative skin antisepsis is routine practice. We compared alcoholic chlorhexidine with aqueous chlorhexidine for skin antisepsis to prevent surgical site infection after minor skin excisions in general practice. METHODS: We conducted this prospective, multicentre, randomized controlled trial in 4 private general practices in North Queensland, Australia, from October 2015 to August 2016. Consecutive adult patients presenting for minor skin excisions were randomly assigned to undergo preoperative skin antisepsis with 0.5% chlorhexidine in 70% ethanol (intervention) or 0.5% chlorhexidine aqueous solution (control). Our primary outcome was surgical site infection within 30 days of excision. We also measured the incidence of adverse reactions. RESULTS: A total of 916 patients were included in the study: 454 underwent antisepsis with alcoholic chlorhexidine and 462 with aqueous chlorhexidine. Of these, 909 completed follow-up. In the intention-to-treat analysis of cases available at follow-up, there was no significant difference in the incidence of surgical site infection between the alcoholic chlorhexidine arm (5.8%, 95% confidence interval [CI] 3.6% to 7.9%) and the aqueous chlorhexidine arm (6.8%, 95% CI 4.5% to 9.1%). The attributable risk reduction was 0.010 (95% CI -0.021 to 0.042), the relative risk was 0.85 (95% CI 0.51 to 1.41), and the number needed to treat to benefit was 100. Per protocol and sensitivity analyses produced similar results. The incidence of adverse reactions was low, with no difference between groups (p = 0.6). INTERPRETATION: There was no significant difference in efficacy between alcoholic and aqueous chlorhexidine for the prevention of surgical site infection after minor skin excisions in general practice. Trial registration: https://www.anzctr.org.au, no. ACTRN12615001045505.

Structural water engaged disordered vanadium oxide nanosheets for high capacity aqueous potassium-ion storage.

Aqueous electrochemical energy storage devices using potassium-ions as charge carriers are attractive due to their superior safety, lower cost and excellent transport properties compared to other alkali ions. However, the accommodation of potassium-ions with satisfactory capacity and cyclability is difficult because the large ionic radius of potassium-ions causes structural distortion and instabilities even in layered electrodes. Here we report that water induces structural rearrangements of the vanadium-oxygen octahedra and enhances stability of the highly disordered potassium-intercalated vanadium oxide nanosheets. The vanadium oxide nanosheets engaged by structural water achieves high capacity (183 mAh g-1 in half-cells at a scan rate of 5 mV s-1, corresponding to 0.89 charge per vanadium) and excellent cyclability (62.5 mAh g-1 in full cells after 5,000 cycles at 10 C). The promotional effects of structural water on the disordered vanadium oxide nanosheets will contribute to the exploration of disordered structures from earth-abundant elements for electrochemical energy storage.

Snoring and Obstructive Sleep Apnea: Objective Efficacy and Impact of a Chairside Fabricated Mandibular Advancement Device.

PURPOSE: Obstructive sleep apnea (OSA) has been described as a common sleep respiratory disorder. Its prevalence in the adult population has been reported to be high, varying from 3% to 28%. Dental practitioners play a key role in the treatment of this disease, using tailor-made mandibular advancement devices (MADs). This pilot study assessed the efficacy and compliance of a custom-fitted thermoplastic MAD for the treatment of moderate to severe OSA syndrome. MATERIALS AND METHODS: In this open study without a control group, OSA syndrome sufferers were enrolled by four centers. One specific MAD was custom fitted to the patients. Polysomnography, Epworth, and snoring scales were administered from inclusion to 45 days postinclusion. RESULTS: The study population consisted of 33 men and 8 women; 35 patients completed the study. Patient response was high with 69% of them considered as responders, and 60% showing a complete response. Also, 77.3% of patients with moderate OSA syndrome presented a complete response. An improvement was observed in the apnea hypopnea index, which decreased from 34.1 ± 18.9 to 12.8 ± 14.1. The Epworth Sleepiness Scale score, snoring, and quality of sleep scores decreased with the device (p < 0.0001). Compliance rates were high, with patients wearing the device 6.5 nights a week. Side effects and patient complaints were minor and transient. CONCLUSION: This custom-fitted MAD improved respiratory and somnolence parameters, with response rates similar to those published in the literature with other devices.

Growth of Headache Research: A 1983-2014 bibliometric study.

Aim This study charts the growth of the scientific journal literature on headache for 30+ years (1983-2014). Methods Using the Web of Science, articles published in four two-year periods (1983-1984, 1993-1994, 2003-2004, 2013-2014) from journals indexed in the Science Citation Index Expanded database were retrieved and analyzed. Results From 1983-1984 to 2013-2014, the scientific literature on headache increased nearly fourfold (3.8) from 468 to 1776 articles; the number of participating countries more than doubled (26 to 67); and the two most prolific countries in each period were the USA and Italy. While several European countries (Italy, Germany, UK and Denmark) were among the top 10 in each period, the notable appearance of Turkey, China and Brazil among the top 10 in 2013-2014 indicates the growing geographic spread of publications on headache research. Meanwhile, the comet-like distribution of journals has not changed: two journals, Headache and Cephalalgia, persist throughout as the nucleus, with the tail increasing more than threefold from 141 journals in 1983-1984 to 462 in 2013-2014. Conclusion Our study follows the recent growth and spread of the scientific literature on headache research and should stimulate further bibliometric investigation in this field.

A Diacylglycerol Transferase 1 Inhibitor Is a Potent Hepatitis C Antiviral in Vitro but Not in Patients in a Randomized Clinical Trial.

Hepatitis C virus (HCV) infection is a significant cause of liver disease affecting 80-150 million people globally. Diacylglycerol transferase 1 (DGAT-1), a triglyceride synthesis enzyme, is important for the HCV life cycle in vitro. Pradigastat, a potent DGAT-1 inhibitor found to lower triglycerides and HgbA1c in patients, was investigated for safety and efficacy in patients with HCV. This was a two-part study. In the in vitro study, the effect of pradigastat on virus production was evaluated in infected cells in culture. In the clinical study ( https://clinicaltrials.gov/ct2/show/NCT01387958 ), 32 patients with HCV infection were randomized to receive pradigastat or placebo (26:6) once daily for 14 days. Primary efficacy outcomes were serum viral RNA and alanine aminotransferase levels. In vitro, pradigastat significantly reduced virus production, consistent with inhibition of viral assembly and release. However, the clinical study was prematurely terminated for lack of efficacy. There was no significant change in serum viral RNA levels after dosing with pradigastat or placebo for 14 days. Pradigastat was safe and well-tolerated in this population. Most treatment-emergent adverse events were gastrointestinal; there were no hepatic adverse events. Although pradigastat had a potent antiviral effect in vitro, no significant antiviral effect was observed in patients at predicted efficacious exposures.

Bivalence Mn5O8 with hydroxylated interphase for high-voltage aqueous sodium-ion storage.

Aqueous electrochemical energy storage devices have attracted significant attention owing to their high safety, low cost and environmental friendliness. However, their applications have been limited by a narrow potential window (∼1.23 V), beyond which the hydrogen and oxygen evolution reactions occur. Here we report the formation of layered Mn5O8 pseudocapacitor electrode material with a well-ordered hydroxylated interphase. A symmetric full cell using such electrodes demonstrates a stable potential window of 3.0 V in an aqueous electrolyte, as well as high energy and power performance, nearly 100% coulombic efficiency and 85% energy efficiency after 25,000 charge-discharge cycles. The interplay between hydroxylated interphase on the surface and the unique bivalence structure of Mn5O8 suppresses the gas evolution reactions, offers a two-electron charge transfer via Mn2+/Mn4+ redox couple, and provides facile pathway for Na-ion transport via intra-/inter-layer defects of Mn5O8.

Globe stability during simulated vitrectomy with valved and non-valved trocar cannulas.

PURPOSE: To compare the effects of valved and non-valved cannulas on intraocular pressure (IOP), fluid leakage, and vitreous incarceration during simulated vitrectomy. METHODS: Three-port pars plana incisions were generated in six rubber eyes using 23-, 25-, and 27-gauge valved and non-valved trocar cannulas. The models were filled with air and IOP was measured. Similar procedures were followed for 36 acrylic eyes filled with saline solution. Vitreous incarceration was analyzed in eleven rabbit and twelve porcine cadaver eyes. RESULTS: In the air-filled model, IOP loss was 89%-94% when two non-valved cannulas were unoccupied versus 1%-5% when two valved cannulas were unoccupied. In the fluid-filled model, with non-valved cannulas, IOP dropped while fluid leaked from the open ports. With two open ports, the IOP dropped to 20%-30% of set infusion pressure, regardless of infusion pressure and IOP compensation. The IOP was maintained in valved cannulas when one or two ports were left open, regardless of IOP compensation settings. There was no or minimal fluid leakage through open ports at any infusion pressure. Direct microscopic analysis of rabbit eyes showed that vitreous incarceration was significantly greater with 23-gauge non-valved than valved cannulas (P<0.005), and endoscopy of porcine eyes showed that vitreous incarceration was significantly greater with 23-gauge (P<0.05) and 27-gauge (P<0.05) non-valved cannulas. External observation of rabbit eyes showed vitreous prolapse through non-valved, but not valved, cannulas. CONCLUSION: Valved cannulas surpassed non-valved cannulas in maintaining IOP, preventing fluid leakage, and reducing vitreous incarceration during simulated vitrectomy.

Hepatic portal venous gas and portal venous thrombosis following colonoscopy in a patient with terminal ileal Crohn's disease.

A 27-year-old man developed extensive hepatic portal venous gas (HPVG) shortly after staging colonoscopy for active, ulcerating, terminal ileal Crohn's disease. Non-operative management was instigated with broad-spectrum antibiotics and thromboprophylaxis. Radiology at 72 h demonstrated resolution of HPVG but revealed fresh non-occlusive left portal vein thrombus. Anticoagulation with warfarin was continued for 1 year, during which the thrombus initially progressed and then organised with recanalisation of the portal vein. There were no long-term clinical consequences. HPVG has previously been documented as a rare complication of inflammatory bowel disease and endoscopic intervention. We hypothesise that the barotrauma sustained during endoscopy, in association with active ulceration and mucosal friability, predisposes to the influx of gas and bacteria into the portal system. We describe successful non-operative management of HPVG in this setting and draw attention to an additional complication of portal venous thrombosis, highlighting the importance of thromboprophylaxis and serial radiological examination.

Effect of the DGAT1 inhibitor pradigastat on triglyceride and apoB48 levels in patients with familial chylomicronemia syndrome.

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare lipid disease caused by complete lipoprotein lipase (LPL) deficiency resulting in fasting chylomicronemia and severe hypertriglyceridemia. Inhibition of diacylglycerol acyltransferase 1 (DGAT1), which mediates chylomicron triglyceride (TG) synthesis, is an attractive strategy to reduce TG levels in FCS. In this study we assessed the safety, tolerability and TG-lowering efficacy of the DGAT1 inhibitor pradigastat in patients with FCS. METHODS: Six FCS patients were enrolled in an open-label clinical study. Following a 1-week very low fat diet run-in period patients underwent baseline lipid assessments, including a low fat meal tolerance test. Patients then underwent three consecutive 21 day treatment periods (pradigastat at 20, 40 & 10 mg, respectively). Treatment periods were separated by washout periods of ≥4 weeks. Fasting TG levels were assessed weekly through the treatment periods. Postprandial TGs, ApoB48 and lipoprotein lipid content were also monitored. RESULTS: Following once daily oral dosing, steady-state exposure was reached by Day 14. There was an approximately dose proportional increase in pradigastat exposure at studied doses. Pradigastat was associated with a 41% (20 mg) and 70% (40 mg) reduction in fasting triglyceride over 21 days of treatment. The reduction in fasting TG was almost entirely accounted for by a reduction in chylomicron TG. Pradigastat treatment also led to substantial reductions in postprandial TG as well as apo48 (both fasting and postprandial). Pradigastat was safe and well tolerated, with only mild, transient gastrointestinal adverse events. CONCLUSION: The novel DGAT1 inhibitor pradigastat substantially reduces plasma TG levels in FCS patients, and may be a promising new treatment for this orphan disease. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01146522 .

Anti-tumour necrosis factor agent and liver injury: literature review, recommendations for management.

Abnormalities in liver function tests, including transient and self-limiting hypertransaminasemia, cholestatic disease and hepatitis, can develop during treatment with anti-tumour-necrosis-factor (TNF) therapy. The optimal management of liver injury related to anti-TNF therapy is still a matter of debate. Although some authors recommend discontinuing treatment in case of both a rise of alanine aminotransferase more than 5 times the upper limit of normal, or the occurrence of jaundice, there are no standard guidelines for the management of anti-TNF-related liver injury. Bibliographical searches were performed in PubMed, using the following key words: inflammatory bowel disease (IBD); TNF inhibitors; hypertransaminasemia; drug-related liver injury; infliximab. According to published data, elevation of transaminases in patients with IBD treated with anti-TNF is a common finding, but resolution appears to be the usual outcome. Anti-TNF agents seem to be safe with a low risk of causing severe drug-related liver injury. According to our centre experience, we found that hypertransaminasemia was a common, mainly self-limiting finding in our IBD cohort and was not correlated to infliximab treatment on both univariate and multivariate analyses. An algorithm for the management of liver impairment occurring during anti-TNF treatment is also proposed and this highlights the need of a multidisciplinary approach and suggests liver biopsy as a key-point in the management decision in case of severe rise of transaminases. However, hepatic injury is generally self-limiting and drug withdrawal seems to be an exception.

Paraventricular hypothalamic regulation of trigeminovascular mechanisms involved in headaches.

While functional imaging and deep brain stimulation studies point to a pivotal role of the hypothalamus in the pathophysiology of migraine and trigeminal autonomic cephalalgias, the circuitry and the mechanisms underlying the modulation of medullary trigeminovascular (Sp5C) neurons have not been fully identified. We investigated the existence of a direct anatomo-functional relationship between hypothalamic excitability disturbances and modifications of the activities of Sp5C neurons in the rat. Anterograde and retrograde neuronal anatomical tracing, intrahypothalamic microinjections, extracellular single-unit recordings of Sp5C neurons, and behavioral trials were used in this study. We found that neurons of the paraventricular nucleus of the hypothalamus (PVN) send descending projections to the superior salivatory nucleus, a region that gives rise to parasympathetic outflow to cephalic and ocular/nasal structures. PVN cells project also to laminae I and outer II of the Sp5C. Microinjections of the GABAA agonist muscimol into PVN inhibit both basal and meningeal-evoked activities of Sp5C neurons. Such inhibitions were reduced in acutely restrained stressed rats. GABAA antagonist gabazine infusions into the PVN facilitate meningeal-evoked responses of Sp5C neurons. PVN injections of the neuropeptide pituitary adenylate cyclase activating peptide (PACAP38) enhance Sp5C basal activities, whereas the antagonist PACAP6-38 depresses all types of Sp5C activities. 5-HT1B/D receptor agonist naratriptan infusion confined to the PVN depresses both basal and meningeal-evoked Sp5C activities. Our findings suggest that paraventricular hypothalamic neurons directly control both spontaneous and evoked activities of Sp5C neurons and could act either as modulators or triggers of migraine and/or trigeminal autonomic cephalalgias by integrating nociceptive, autonomic, and stress processing mechanisms.

Sensing behavior of atomically thin-layered MoS2 transistors.

Most of recent research on layered chalcogenides is understandably focused on single atomic layers. However, it is unclear if single-layer units are the most ideal structures for enhanced gas-solid interactions. To probe this issue further, we have prepared large-area MoS2 sheets ranging from single to multiple layers on 300 nm SiO2/Si substrates using the micromechanical exfoliation method. The thickness and layering of the sheets were identified by optical microscope, invoking recently reported specific optical color contrast, and further confirmed by AFM and Raman spectroscopy. The MoS2 transistors with different thicknesses were assessed for gas-sensing performances with exposure to NO2, NH3, and humidity in different conditions such as gate bias and light irradiation. The results show that, compared to the single-layer counterpart, transistors of few MoS2 layers exhibit excellent sensitivity, recovery, and ability to be manipulated by gate bias and green light. Further, our ab initio DFT calculations on single-layer and bilayer MoS2 show that the charge transfer is the reason for the decrease in resistance in the presence of applied field.

Assessment and management of chronic orofacial pain associated with a disease in children: a multidisciplinary approach.

UNLABELLED: To summarize the diversity of assessment and management for chronic orofacial pain associated with a disease (COFPAD) in children. We performed a review of the literature up to May 2012. Hetero-evaluation and self-assessment are used according to age of children. Strict management of the cause is not sufficient for children with COFPAD without a multidisciplinary approach combining pharmacotherapy, psychology and physiotherapy. CONCLUSION: The multidisciplinary approach is the key of management for children with COFPAD.

Expression vectors for Acinetobacter baylyi ADP1.

Acinetobacter baylyi ADP1 is naturally competent and proficient at homologous recombination, so it can be transformed without restriction digests or ligation reactions. Expression vectors for this system, however, are not yet widely available. Here we describe the construction and characterization of inducible expression vectors that replicate as plasmids in A. baylyi or integrate into a nonessential part of its chromosome. These tools will facilitate the engineering of genes and genomes in this promising model organism.