β-Lactoglobulin as nanotransporter--Part I: Binding of organosulfur compounds.
The binding reaction of allicin and diallyl disulfide with β-lactoglobulin and the influence of pH value and protein denaturation on this reaction have been examined in the present study. Regardless of the structural similarity of both the organosulfur compounds, their binding behavior was significantly different. Both ligands were covalently bound by the free thiol group of the protein, whereas the affinity for allicin was significantly higher. In addition, diallyl disulfide was non-covalently bound. The binding reaction of both ligands was very sensitive to the pH value during incubation. The optimal pH range was between pH 8.0 and 9.0. Protein denaturation increased the reaction rate and reduced the number of binding sites for allicin, whereas the number of non-covalent binding sites increased for diallyl disulfide. Based on these findings, it can be proposed that the covalent modification of β-lactoglobulin functions as a specific transporter stabilizing allicin or diallyl disulfide.


Food and Drug Administration evaluation and cigarette smoking risk perceptions.
To examine the relationship between a belief about Food and Drug Administration (FDA) safety evaluation of cigarettes and smoking risk perceptions. A nationally representative, random-digit-dialed telephone survey of 1046 adult current cigarette smokers. Smokers reporting that the FDA does not evaluate cigarettes for safety (46.1%), exhibited greater comprehension of the health risks of smoking and were more likely (48.5%) than other participants (33.6%) to report quit intentions. Risk perceptions partially mediated the relationship between FDA evaluation belief and quit intentions. These findings highlight the need for proactive, effective communication to the public about the aims of new tobacco product regulations.


Cooling in the real world: therapeutic hypothermia in hypoxic-ischemic encephalopathy.
The benefits of therapeutic hypothermia have not been assessed from the perspective of the neurology clinic. We aimed to report the impact of the implementation of a local regional therapeutic hypothermia program on the neurodevelopmental outcomes of surviving hypoxic-ischemic encephalopathy (HIE) infants who were followed in the neonatal neurology clinic. Retrospective analysis of term infants referred to the neonatal neurology clinic after having been diagnosed with HIE and meeting eligibility criteria for therapeutic hypothermia between March 1999 and June 2010. Therapeutic hypothermia was implemented in September 2008. Outcome measures were dichotomously defined as: normal or adverse, which included cerebral palsy, global developmental delay, and epilepsy. Thirty infants were included in the pre-therapeutic hypothermia group. Thirty-one infants received therapeutic hypothermia and 27 were adequately followed and included in the post-therapeutic hypothermia group. The frequency of an adverse outcome was significantly higher in the pre-therapeutic hypothermia infants (19/30 [63%] versus 4/27 [15%]; OR = 0.10; 95% CI, 0.03-0.37; P < 0.001). Neonatal clinical seizures were more frequent in the pre-therapeutic hypothermia group (P = 0.012). There were no differences regarding frequency of fetal distress, rate of caesarean sections, Apgar scores, need of resuscitation, cord/initial blood gases, and degrees of encephalopathy between the two groups. The implementation of a regional therapeutic hypothermia program in our institution has vastly reduced the observed neurological morbidity of surviving HIE infants followed in our neonatal neurology clinic. A similar change in outcomes of infants with HIE can be anticipated by other centers and other clinics adopting this therapy.


Examination of autologous and embryonic cortical brain tissue transplantation to adult brain cortex in rats.
Autologous and embryonic cortical brain tissue was transplanted to adult rats in order to reconstruct experimentally degenerated cortical brain tissue. Rats were decapitated within 6 or 12 weeks. Viability of the graft tissues was studied by light and electron microscopy. Embryonic cortical brain tissue grafts became enlarged but adult cortical brain tissue grafts were found to be unaltered. Electron-microscopically observed mitochondria and other cell organellae and the newly vascularized areas clearly showed that the graft tissues were alive.


Analysis of canine cardiovascular therapeutic agent prescriptions using electronic health records in primary care veterinary practices in the United Kingdom.
Canine cardiovascular (CV) diseases are often managed in primary care settings. The objectives were to describe CV therapeutic agent (CVTA) prescribing patterns in primary care practices in the United Kingdom (UK) and to evaluate recorded clinical signs, diagnostic tests and justifications for use of torasemide, a recently marketed and authorised loop-diuretic in the UK. Electronic health records (EHRs) describing 3,579,420 consultations (1,043,042 unique dogs) were collated (1 April 2014 and 31 December 2018) by the Small Animal Veterinary Surveillance Network from 270 veterinary practices. Consultations prescribing at least one CVTA were identified. Annual variation in individual CVTA prescriptions was analysed using mixed-effects binomial regression models. Free-text clinical narratives were manually read to determine the first-prescribing event for torasemide. Twenty-nine thousand and seven consultations (0.81% of all consultations, 95% confidence interval [CI], 0.76-0.86) prescribed CVTA in 14,148 (1.36%) dogs. Furosemide (52.8% of CV-prescribing consultations, 95% CI 50.7-54.9) and pimobendan (51.9%, 95% CI 50.1-53.7) were most prescribed. Longitudinal analysis (2014-2018) showed a significant negative temporal trend for angiotensin-converting enzyme inhibitors (p < 0.001), and furosemide (p = 0.003) and a positive temporal trend for pimobendan (p = 0.020) and torasemide (p < 0.001). First prescriptions of torasemide were identified in 16.5% of torasemide-prescribing consultations. Where justification for prescription of torasemide was identified (32.5%), furosemide resistance was the most common (92.0%). EHRs can be used to temporally monitor prescribing habits, including responses to market authorisations. Despite authorisation in the UK for torasemide use as a first-line diuretic, it was most commonly prescribed after furosemide resistance.


Disease-modifying therapies and infectious risks in multiple sclerosis.
Immunomodulatory and immunosuppressive treatments for multiple sclerosis (MS) are associated with an increased risk of infection, which makes treatment of this condition challenging in daily clinical practice. Use of the expanding range of available drugs to treat MS requires extensive knowledge of treatment-associated infections, risk-minimizing strategies and approaches to monitoring and treatment of such adverse events. An interdisciplinary approach to evaluate the infectious events associated with available MS treatments has become increasingly relevant. In addition, individual stratification of treatment-related infectious risks is necessary when choosing therapies for patients with MS, as well as during and after therapy. Determination of the individual risk of infection following serial administration of different immunotherapies is also crucial. Here, we review the modes of action of the available MS drugs, and relate this information to the current knowledge of drug-specific infectious risks and risk-minimizing strategies.


Cloning and functional expression of the cDNA encoding rat lanosterol 14-alpha demethylase.
Lanosterol 14 alpha-demethylase (LDM) is a cytochrome P-450 enzyme in the biosynthetic pathway of cholesterol. As such, it represents a target for cholesterol-lowering drugs. Rat LDM (rLDM) has been purified from the livers of rats treated with cholestyramine. The purified protein was used to generate tryptic fragments which were then sequenced. The amino acid (aa) sequences were used to design oligodeoxyribonucleotide primers and a DNA fragment was generated by RT-PCR to probe a phagemid library. A clone encoding rLDM was isolated from the livers of cholestyramine-treated rats. The clone contains an open reading frame encoding a polypeptide of 486 aa and a predicted molecular mass of 55 045 Da. The deduced aa sequence shows a high degree of identity to the yeast LDM sequences, as well as sequences which match typical P-450 sequence motifs. When produced in a baculovirus/insect cell culture system, LDM activity was detected and inhibited by the specific inhibitor azalanstat with an IC50 value of less than 2 nM. The isolation of this full-length coding sequence should facilitate research into understanding the direct and indirect effects of LDM in the regulation of cholesterol biosynthesis and the search for cholesterol-lowering drugs.


Surgical options in the management of large omphaloceles.
Forty-six neonates with omphaloceles seen at the Children's Hospital and Medical Center in Seattle from 1975 to 1985 were reviewed. There was an 87 percent survival rate in those surgically managed. The 23 neonates who underwent primary closure all survived. The 13 neonates with giant omphaloceles with the liver in the defect who received silon chimneys had a 46 percent mortality rate and a high complication rate, with prolonged hospitalization. Two neonates with giant omphaloceles were managed by leaving the sac intact, and silver sulfadiazine cream was used as an escharotic agent. We believe it is a safer alternative than the silon chimney in neonates whose defects cannot be closed primarily.


Retreatment of full-thickness macular holes persisting after prior vitrectomy. A pilot study.
Vitrectomy with fluid-gas exchange has been shown to close more than one half of full-thickness macular holes, with improvement in visual acuity. By adding the appropriate dose of transforming growth factor-beta 2, a higher success rate has been reported. However, there still remain cases of macular holes that fail to close after vitreous surgery. The current pilot study is designed to determine whether reoperation may have a role in the management of cases that fail after vitreous surgery. Twelve eyes with persistent full-thickness macular holes that failed to close after an initial vitrectomy underwent reoperation using 1330 ng transforming growth factor-beta 2. After the second operation, closure occurred in 12 (100%) of 12 eyes. Follow-up ranged from 8 to 16 months. Visual acuity also improved by two or more lines in 5 (42%) of 12 patients. Increased nuclear sclerosis occurred in nine (90%) of the ten phakic eyes. Of the five eyes showing visual improvement, four required cataract extraction and intraocular lens implantation. Retreatment of persistent full-thickness macular holes with transforming growth factor-beta 2 appears to have a beneficial effect on both neurosensory retinal flattening and visual outcome.


Rapid, simple multi-locus variable number tandem repeat analysis: a reliable tool for Klebsiella pneumoniae outbreak screening.
Klebsiella pneumoniae causing nosocomial infections is increasingly multi-drug-resistant. Rapid and efficient typing tools are required for monitoring. To assess a simple, rapid (<5 h) multiplex polymerase chain reaction method based on multi-locus variable number tandem repeat analysis (MLVA) as a screening tool to determine whether or not K. pneumoniae strains are related. The global discriminatory power of the method was assessed on 72 unrelated K. pneumoniae isolates, including community carriage isolates, highly virulent strains causing liver abscess, and extended-spectrum beta-lactamase- and carbapenemase-producing strains. Suspected related strains from a suspected outbreak and a relapsed meningitis case were also studied. MLVA results were compared with whole-genome sequencing (WGS) analysis and multi-locus sequence typing (MLST). MLVA and MLST had similar discriminatory power, each distinguishing 54 profiles among the 72 unrelated isolates (Hunter-Gaston index 0.989). Each strain belonging to one sequence type (ST) or ST complex had its own MLVA type, with few exceptions. Two strains of ST268 and ST1119 shared the same MLVA profile, and two unrelated strains of ST307, ST86, ST45 and ST37 exhibited two different MLVA types each. Moreover, investigation of seven grouped cases of K. pneumoniae neonatal sepsis pointed to strong suspicion of a common source for five isolates, while two isolates with a different MLVA profile were excluded from this cluster. The MLVA approach is a useful, rapid and reliable tool for epidemiological investigation requiring only basic molecular biology equipment, and permits identification of sporadic isolates that are not part of an outbreak. However, analysis of strains sharing the same MLVA type by a highly discriminatory technique, such as WGS, remains necessary.


A Yoga-Based Program Decreases Physician Burnout in Neonatologists and Obstetricians at an Academic Medical Center.
Nearly half of U.S. pediatricians have symptoms of burnout. This pilot study examined the feasibility of a 6-week yoga-based program (RISE) for neonatologists and obstetricians at Brigham and Women's Hospital and studied the effects on burnout, professional fulfillment, and psychological health. Participants were recruited via email to participate either in both program and research study, or exclusively the program. RISE was delivered 1 hour/week during the workday for 6 consecutive weeks either in-person or remotely; 18 physicians participated, 12 completed post-program, and 11 completed 2-month follow-up. The questionnaires assessed burnout and measures of psychological health, professional fulfillment, work exhaustion, interpersonal disengagement/burnout (PFI), mindfulness (FFMQ), perceived stress (PSS), positive/negative affect (PANAS), resilience (RS), anxiety/depression/sleep disturbances (PROMIS), at baseline, post-program, and 2 months after RISE. Average attendance in-person was 2.8 sessions and remotely 1.4 sessions (4.2/6 sessions). Participants demonstrating total burnout reduced from 50.0% at baseline to 9.1% post-program. Participants demonstrating professional fulfillment were 8.3% at baseline and 27.3% post-program. Paired samples t-tests revealed statistically significant improvements in burnout, professional fulfillment, interpersonal disengagement, stress, resilience, anxiety, and depression at post-program compared with baseline (N = 12, all ps < .05). At 2-month follow-up, statistically significant improvements in interpersonal disengagement, resilience, and mindfulness (N = 11, all ps < .05) compared with baseline were reported. RISE is feasible within a workday and may address burnout and other psychological health measures in physicians with effects potentially sustainable over 2 months. Occupational health practitioners in health care should consider this type of intervention for their workers.


Distinct pharmacodynamics of insulin glargine and insulin detemir: crossover comparison in Type 1 and Type 2 diabetic patients on basal-bolus regimen.
We compared blood glucose profile when glargine or detemir was injected once daily before dinner in combination with pre-meal insulin lispro by a crossover design. Glargine showed lower post-dinner and bedtime glucose levels in Type 1 diabetes, and lower pre-dinner and post-dinner glucose levels in Type 2 diabetes than detemir.


Ocular anomalies in the alagille syndrome (arteriohepatic dysplasia).
The Alagille syndrome (arteriohepatic dysplasia) is a well-recognized multiple malformation syndrome consisting of a paucity of intrahepatic bile bile ducts, peripheral pulmonary artery hypoplasia with variable cardiac abnormalities, cholestatic facies, butterfly-like vertebral arch defects, and variable ocular anomalies, most commonly posterior embryotoxon and pigmentary retinopathy. The authors studied ocular findings in six patients from two families with Alagille syndrome to characterize more fully the spectrum of ocular anomalies in this disorder. Ocular anomalies consisted of a peculiar mosaic pattern of iris stromal hypoplasia in all patients, posterior embryotoxon and microcornea in five patients, anomalous optic discs in five patients, regional peripapillary retinal depigmentation in three patients, and a congenital maculopathy in one patient. The Alagille syndrome comprises a broad spectrum of ocular anomalies involving the cornea, iris, retina, and optic disc. In the setting of neonatal cholestasis, the findings of microcornea, posterior embryotoxon, mosaic iris stromal hypoplasia, regional peripapillary depigmentation, congenital macular dystrophy, and anomalous optic discs should suggest the diagnosis of Alagille syndrome.


Anaprox in dysmenorrhea: reduction of pain and intrauterine pressure.
In a double-blind parallel trial, 24 dysmenorrheic women received a single dose of Anaprox (1,100 mg) or placebo. Over the next 2 hours, pain intensity was scored and intrauterine pressure was measured using an immobilized microballoon. At the end of 2 hours, all 11 patients given Anaprox (but only three of the 13 given placebo) experienced complete pain relief (p = 0.0004). The resting intrauterine pressure (IUP) decreased from a mean of 51.4 to 26.8 mm Hg in the Anaprox-treated group, while in the placebo group the mean resting IUP values remained essentially unchanged ( drop from 55.4 to 51.9 mm Hg was observed). This difference between the two treatment groups was statistically significant in favor of Anaprox (p = 0.03). Several patients from each group were given 0.2 mg of ergonovine by intramuscular injection following the 2 hour trial. In both groups, the resting IUP increased within 30 minutes; the corresponding increase in pain intensity was more pronounced, however, in the placebo group. These results support the premise that a decrease in resting IUP is directly linked to the pain-relieving effects of Anaprox.


Shear-induced platelet activation and platelet microparticle formation in native human blood.
Shear-induced platelet activation and platelet microparticle formation are triggered in native human blood by high arterial shear or by a sudden increase in shear as introduced by a stenosis with potential consequences for collagen-induced platelet thrombus formation. Blood was drawn from healthy volunteers and directly perfused ex vivo over various well-defined eccentric stenoses. Shear-induced platelet activation was determined by using flow cytometry to assess: 1) GPIIb-IIIa activation by fluorescein isothiocyanate (FITC)-labeled Mab PAC-1; and 2) translocation of membrane aminophospholipids (procoagulant activity) by FITC-labeled Annexin V. Microparticle formation was measured by flow cytometry and FITC-labeled Mab Y2/51 directed against GPIIIa. Significant platelet activation and platelet microparticle formation were elicited when the wall shear rate reached 10,500 sec-1 for a period of 0.075 sec. Prolonged exposure to or a rapid increase in shear further enhanced activation and microparticle formation. Shear-induced platelet activation was associated with significantly increased collagen-induced platelet thrombus formation that was insensitive to aspirin ingestion. Exposure of native blood to very high shear thus activates platelets to express GPIIb-IIIa, renders the platelet membrane procoagulant and stimulates microparticle formation. These responses are associated with enhanced collagen-induced thrombus formation by prostaglandin-independent mechanisms.


circ-ZUFSP regulates trophoblasts migration and invasion through sponging miR-203 to regulate STOX1 expression.
Recurrent spontaneous abortion (RSA), defined as two or more consecutive pregnancy losses before 12 weeks of gestation with or without previous live births. Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs that play important roles in gene expression regulation and trophoblasts function during embryo development. This study aimed to evaluate the function mechanism of circRNAs regulating trophoblasts function in the occurrence and progression RSA. Through overexpression and down-regulation of circ-ZUFSP, we investigated the effect of circ-ZUFSP on the function of trophoblasts and found loss of circ-ZUFSP suppressed trophoblasts migration and invasion in vitro. Moreover, loss of circ-ZUFSP regulated trophoblasts migration and invasion via regulation of miR-203. Furthermore, STOX1 was revealed to a target of miR-203, and down-regulation of STOX1 reversed circ-ZUFSP enhanced cell invasion, suggesting that circ-ZUFSP might regulate STOX1 expression through sponging miR-203 in HTR-8/SVneo cells. In addition, low expression of circ-ZUFSP, STOX1 and high expression of miR-203 were testified in placental tissues of RSA mice. Our study demonstrated a molecular mechanism of circ-ZUFSP regulating trophoblasts migration and invasion, which might provide a novel indicator for early diagnosis and potential treatment of RSA.


Regulation of cyclic photophosphorylation in Rhodospirillum rubrum by the redox state of nicotinamide-adenine dinucleotide.
We have investigated the effect of the redox state of added NAD on the rates of anaerobic cyclic photophosphorylation which are supported by membrane vesicles isolated from Rhodospirillum rubrum. As the redox potential of NAD was lowered, the activity decreased according to a typical potentiometric titration. The Nernst plot showed an apparent midpoint potential (E'o) of -350 mV and had a slope which corresponded to a two-electron transition. Besides, an almost identical potentiometric relationship was found to exist between the extent of light-elicited ATP formation in anaerobic suspensions of intact R. rubrum cells and the redox potential of intracellular NAD. These results suggest that physiological photophosphorylation in R. rubrum requires the oxidized form of a membrane-bound constituent (E'o = -350 mV) whose redox state is controlled by the redox state of cytoplasmic NAD.


Refeeding after starvation in the rat: comparative effects of lipids, proteins and carbohydrates on jejunal and ileal mucosal adaptation.
To compare the tropic effect of different dietary nutrients on mucosal adaptation in the jejunum and ileum, adult rats were submitted to a 96-h period of starvation and refed isocaloric liquid diets (1.5 kcal ml-1) containing either protein (casein), carbohydrate (starch) or lipids. In the jejunum, 4 days of starvation caused mucosal hypoplasia, villus and crypt shortening and a decrease in the total activity of disaccharidases with the exception of lactase which was markedly enhanced. In contrast, mucosal hypoplasia was incomplete in the ileum which exhibited an increase in crypt depth and in the specific and total activities of disaccharidases and of aminopeptidase. Compared with protein and carbohydrates, lipids exerted the strongest stimulatory effect for mucosal regeneration. In the jejunum as well as in the ileum, mucosal mass parameters, villus length, crypt depth and lactase activity did reverse towards their initial value within 1-3 days of refeeding lipids, even though the animals received only one-third of their normal daily caloric intake. Our results indicate that the pattern of response to fasting differs between the proximal and distal small intestine, and that the intestinal changes induced by starvation are rapidly reversed by refeeding small amounts of a diet rich in fat.


Missense mutations in EDA and EDAR genes cause dominant syndromic tooth agenesis.
Hypohidrotic ectodermal dysplasia (HED) is the most common form of ectodermal dysplasia and is mainly associated with mutations in the EDA, EDAR, and EDARADD responsible for the development of ectodermal-derived structures. HED displays different modes of inheritance according to the gene that is involved, with X-linked EDA-related HED being the most frequent form of the disease. Two families with tooth agenesis and manifestations of HED underwent clinical examination and EDA, EDAR, and EDARADD genetic analysis. The impact of the novel variant on the protein was evaluated through bioinformatics tools, whereas molecular modeling was used to predict the effect on the protein structure. A novel missense variant was identified in the EDAR (c.287T>C, p.Phe96Ser) of a female child proband and her mother, accounting for autosomal dominant HED. The genetic variant c.866G>A (p.Arg289His) in EDA, which has been previously described, was observed in the male proband of another family confirming its role in X-linked HED. The inheritance model of the missense mutation showed a different relationship with X-linked HED and non-syndromic tooth agenesis. Our findings provide evidence of variable expression of HED in heterozygous females, which should be considered for genetic counseling, and different modes of inheritance related to tooth development.


The Evolution of the Clinical Use of Osmotic Therapy in the Treatment of Cerebral Edema.
For almost a century, it has been known that hypertonic solutions shrink cerebral tissue. Early attempts used hypertonic solutions of ions (sodium, magnesium) and sugars (glucose, dextrose, sucrose), concentrated albumin, and, later, urea. These early attempts were largely abandoned because the effect was short lived and often followed by a period of rebound edema. This was a result, to a great extent, of the osmotic agent either being metabolized or crossing the cell membrane.Renewed interest in osmotic therapy came in the 1960s, with the introduction of intracranial pressure monitoring in head injury and the use of mannitol as an osmotic agent. In the 1990s, use of hypertonic saline was reintroduced as an alternative to address concerns about mannitol. More recently, administration of hypertonic saline has transitioned from boluses to continuous infusions. The rationale for and data supporting the use of continuous infusions are presented.


[Incidence of undiagnosed skin cancers in a geriatric hospital].
The incidence of non melanoma skin cancers is closely correlated with age. The aim of this prospective study was to evaluate the prevalence of undiagnosed skin cancers among patients hospitalized in rehabilitation and long-term care units in a geriatric hospital. All the patients, resident in four rehabilitation and long-term care units and for whom no dermatological advice had been given, were systematically examined by a dermatologist. Clinical data included patient age at the time of the study, gender, relevant historical information, skin phototype and description of the cutaneous lesions. Biopsies were performed for all lesions of suspicious appearance. Three hundred and six patients (79.4% women and 20.6% men aged from 55 to 103 years) were included in the study. Among all the patients, 69.3% were hospitalized for more than one year. Skin phototype was clear for 93.5% of the patients. Thirty-two out of 306 patients (10.5%) presented 42 suspicious lesions and these were diagnosed by histological examination as 16 basal-cell carcinomas, seven squamous cell-carcinomas and two in situ melanomas. Skin cancers were localised on the head and neck in 80% of cases. The prevalence of patients with skin cancers was 5.6% in this population. The prevalence of skin cancers among patients hospitalized in geriatric hospitals justifies improved training of geriatricians regarding early recognition and dermatological assessment of cutaneous tumours.


Identification and molecular characterization of allergenic non-specific lipid-transfer protein from durum wheat (Triticum turgidum).
Common wheat (Triticum aestivum) and durum wheat (T. turgidum) are both involved in Baker's asthma (BA) and food allergy (FA) including wheat-dependent exercise-induced asthma (WDEIA). However, allergens in durum wheat have not been described, and the over-expression of T. turgidum non-specific lipid-transfer protein (nsLTPs) is considered to increase resistance to phytopathogens. To identify and assess the allergenicity of nsLTP from T. turgidum. Recombinant T. turgidum nsLTP Tri tu 14 was generated and tested for structural integrity (circular dichroism-spectroscopy) and purity (SDS-PAGE). Thirty-two wheat allergic patients were enrolled: 20 Spanish patients (BA) with positive bronchial challenge to wheat flour, and 12 Italian patients (wheat FA/WDEIA) with positive double-blind placebo-controlled food challenge/open food challenge (OFC) to pasta. IgE values to wheat, Tri tu 14, Tri a 14 (T. aestivum) and Pru p 3 (P. persica) were determined by ImmunoCAP testing. Allergenic potency (in vitro mediator release) and IgE cross-reactivity were investigated. Tri tu 14 was found to share 49% and 52% amino acid identity with Tri a 14 and Pru p 3, respectively. Among 25 Tri a 14 CAP positive sera, 23 (92%) were reactive to wheat extract, 22 (88%) to Tri tu 14 and 20 (80%) to Pru p 3. The correlation between Tri a 14 and Tri tu 14 specific IgE levels was r = 0.97 (BA) and r = 0.93 (FA/WDEIA), respectively. FA/WDEIA patients showed higher specific IgE values to Tri tu 14 and Pru p 3 than BA patients. Tri tu 14 displayed allergenic activity by mediator release from effector cells and IgE cross-reactivity with Pru p 3. The degree of IgE cross-reactivity between the two wheat nsLTPs varied between individual patients. Sensitization to Tri tu 14 likely appears to be more important in wheat FA/WDEIA than in BA. Over-expression of Tri tu 14 in wheat would represent a risk for patients with nsLTP-mediated FA.


Detection of cell-free foetal DNA fraction in female-foetus bearing pregnancies using X-chromosomal insertion/deletion polymorphisms examined by digital droplet PCR.
In families with X-linked recessive diseases, foetal sex is determined prenatally by detection of Y-chromosomal sequences in cell-free foetal DNA (cffDNA) in maternal plasma. The same procedure is used to confirm the cffDNA presence during non-invasive prenatal RhD incompatibility testing but there are no generally accepted markers for the detection of cffDNA fraction in female-foetus bearing pregnancies. We present a methodology allowing the detection of paternal X-chromosomal alleles on maternal background and the confirmation of female sex of the foetus by positive amplification signals. Using digital droplet PCR (ddPCR) we examined X-chromosomal INDEL (insertion/deletion) polymorphisms: rs2307932, rs16397, rs16637, rs3048996, rs16680 in buccal swabs of 50 females to obtain the population data. For all INDELs, we determined the limits of detection for each ddPCR assay. We examined the cffDNA from 63 pregnant women bearing Y-chromosome negative foetuses. The analysis with this set of INDELs led to informative results in 66.67% of examined female-foetus bearing pregnancies. Although the population data predicted higher informativity (74%) we provided the proof of principle of this methodology. We successfully applied this methodology in prenatal diagnostics in a family with Wiscott-Aldrich syndrome and in pregnancies tested for the risk of RhD incompatibility.


Pattern-reversal visual evoked potentials in photosensitive epilepsy.
VEPs to checkerboard pattern-reversal were recorded from 18 epileptic patients who had EEG photoparoxysmal responses to stroboscopic light. Patients were grouped according to whether seizures were precipitated by environmental light stimuli, or television viewing. Longitudinal studies were conducted on 8 patients treated with valproic acid. We concluded the following: (1) Latency of the major positive peak (P2) of the pattern-reversal VEP was shorter among photosensitive patients than among normal controls. This was especially true of television-sensitive patients. (2) Valproic acid, when effective in controlling seizures, lengthened the P2 latency and decreased VEP amplitude. Studies of drug effects on VEPs may help to elucidate neurochemical mechanisms of the visual cortex. (3) Because of overlap of values with normals, VEP measurements are not at present very sensitive in the diagnosis of photosensitivity. However, longitudinal studies in individuals parallel clinical changes and may be useful as objective measures of improvement.


Superficial ulnar artery originating from the brachial artery and its clinical importance.
We found a left superficial ulnar artery in the cadaver of a Japanese woman. This anomalous vessel originated from the brachial artery at a site 55 mm distal to the inferior border of the teres major muscle and medial to the median nerve, ran downward and medially superficial to the forearm flexor muscles, and then downward to enter the hand. It formed superficial and deep palmar arches with the radial artery. The clinical importance of the anomalous ulnar artery is discussed.


Impact of contamination from scattered photons in singles-mode transmission data on quantitative small-animal PET imaging.
In previous work, we described and validated a method of scatter correction for singles-mode transmission data using experimental preinjection data acquired with a dedicated rodent PET scanner. In the current work, we investigated the impact that our method has on the quantitative accuracy of small-animal PET. This investigation had 3 stages. We first confirmed the general validity of our method by applying it to preinjection transmission data from a different imaging system (a larger dedicated primate scanner). For these data, we evaluated the accuracy of the reconstructed distributions of linear attenuation coefficients (mu-values). In the second stage, we applied our attenuation-map reconstruction and scatter correction procedure for postinjection transmission data acquired with the dedicated rodent scanner. For these studies, we investigated the quantitative accuracy of reconstructed emission images that use attenuation correction derived from postinjection transmission data. In the third stage, we compared our scatter correction method with 2 more commonly used alternatives (automated rescaling and segmentation of the attenuation-map images). For the primate scanner data, the average reconstructed mu-values with scatter correction were within 3% of the expected values for water and soft tissue, whereas uncorrected values were 19%-26% lower than their expected values. For the postinjection transmission studies, we found that the correct average mu-values and reconstructed activity concentrations consistent with well-counter measurements were obtained only when scatter correction and emission contamination correction were applied to the transmission data. We also found that our transmission scatter correction provides more accurate mu-values and better image quantification than either rescaling or segmentation. Using different imaging systems (primate and rodent) and different scanning protocols (before and after injection), we found that our transmission scatter correction is more accurate (for both reconstructed mu-values and activity concentrations) than the existing alternatives.


Effect of 6-minute walk test on neuromuscular properties of patients with chronic obstructive pulmonary disease.
The objective of this study was to evaluate the neuromechanical properties of the knee extensor muscles before and after the 6-minute walk test (6MWT) in chronic obstructive pulmonary disease (COPD) patients and control subjects. COPD patients from the Department of Pulmonology of the Hospital de Clinicas de Porto Alegre and age- and sex-matched control volunteers without COPD were included in this study. Body composition and lower limb strength assessed by maximal voluntary isometric contraction (MVIC) of the knee extensors) were assessed before and after the 6MWT. The total reaction time (TRT), premotor time (PMT) and motor time (MT) were assessed using surface electromyography of the rectus femoris and vastus lateralis knee extensor muscles. Eighteen patients COPD patients (10 men, FEV1 36 ± 12% of predicted) and 8 control subjects (5 men, FEV1 82 ± 7% of predicted) were included. COPD patients had lower muscle strength before (21.77 ± 7.86 kg) and after the 6MWT (11.16 ± 4.70 kg) compared with control subjects (33.50 ± 14.01 kg before; 29.25 ± 16.66 kg after). After the 6MWT, COPD patients showed a significant reduction in the MVIC and a significant increase in the TRT and PMT, which did not occur in control subjects. The reaction time parameters were higher in COPD patients after the 6MWT compared with control subjects. The TRT (r = -0.535, P < 0.005) and PMT (r = -0.549, P < 0.005) were inversely correlated with the MVIC after the 6MWT. Neuromuscular changes associated with upper motor neuron activation contribute to MVIC impairment in COPD patients after performing a functional test.


Imaging of pelvic rhabdomyosarcoma by bone scintigraphy.
Urinary tract distortion caused by pelvic rhabdomyosarcoma was imaged during 99mTc-oxidronate bone scintigraphy for suspected metastatic disease. This appearance correlated well with the anatomy defined on other imaging modalities. Bone scanning also proved valuable in detecting an otherwise occult osseous metastasis from this unusual tumor.


Comparing the electronic properties and docking calculations of heme derivatives on CYP2B4.
Cytochrome P-450 is a group of enzymes involved in the biotransformation of many substances, including drugs. These enzymes possess a heme group (1) that when it is properly modified induces several important physicochemical changes that affect their enzymatic activity. In this work, the five structurally modified heme derivatives 2-6 and the native heme 1 were docked on CYP2B4, (an isoform of P450), in order to determine whether such modifications alter their binding form and binding affinity for CYP2B4 apoprotein. In addition, docking calculations were used to evaluate the affinity of CYP2B4 apoprotein-heme complexes for aniline (A) and N-methyl-aniline (NMA). Results showing the CYP2B4 heme 4- and heme 6-apoprotein complexes to be most energetically stable indicate that either hindrance effects or electronic properties are the most important factors with respect to the binding of heme derivatives at the heme-binding site. Furthermore, although all heme-apoprotein complexes demonstrated high affinity for both A and NMA, the CYP2B4 apoprotein-5 complex had higher affinity for A, and the heme 6 complex had higher affinity for NMA. Finally, surface electronic properties (SEP) were calculated in order to explain why certain arginine residues of CYP2B4 apoprotein interact with polarizable functionalities, such as ester groups or sp ( 2 ) carbons, present in some heme derivates. The main physicochemical parameter involved in the recognition process of the heme derivatives, the CYP2B4 apoprotein and A or NMA, are reported.


Hemorheological effects of pentoxifylline on disturbed flow behavior of blood in patients with cerebrovascular insufficiency.
The influence of pentoxifylline (11-18 mg/kg orally, Trental 400) on impaired hemorheologic conditions has been investigated in a total of 73 patients with CVI. Throughout a treatment period of 4 weeks, there was a significant improvement in red cell behavior and a significant inhibition of increased platelet aggregation; moreover, a fall in plasma fibrinogen and of blood viscosity has also been observed.


Differentiation of effector/memory Vdelta2 T cells and migratory routes in lymph nodes or inflammatory sites.
Vdelta2 T lymphocytes recognize nonpeptidic antigens without presentation by MHC molecules and mount both immediate effector functions and memory responses after microbial infection. However, how Vdelta2 T cells mediate different facets of a memory response remains unknown. Here, we show that the expression of CD45RA and CD27 antigens defines four subsets of human Vdelta2 T cells with distinctive compartmentalization routes. Naive CD45RA+CD27+ and memory CD45RA-CD27+ cells express lymph node homing receptors, abound in lymph nodes, and lack immediate effector functions. Conversely, memory CD45RA-CD27- and terminally differentiated CD45RA+CD27- cells, which express receptors for homing to inflamed tissues, are poorly represented in the lymph nodes while abounding at sites of inflammation, and display immediate effector functions. These observations and additional in vitro experiments indicate a lineage differentiation pattern for human Vdelta2 T cells that generates naive cells circulating in lymph nodes, effector/memory cells patrolling the blood, and terminally differentiated effector cells residing in inflamed tissues.


Ulnar Collateral Ligament Internal Bracing Repair Technique for High-Grade Partial Proximal Tears in the Throwing Athlete.
The use of ulnar collateral ligament (UCL) repair with concomitant internal bracing for throwing athletes is a viable treatment option, but must take into account tear location, ligament quality, the expected length of the athlete's career, desire to advance to the next level of competition, and age. There has been increased interest in repair of UCL injuries in overhead athletes due to advancements in surgical technique, as well as improved technologies of anchor and suture material. In addition, return to sport can be accelerated compared to reconstruction. In this Technical Note, we demonstrate an ulnar collateral ligament repair technique, with internal bracing augmentation for high-grade partial proximal tears in the throwing athlete that is reliable, strong, and easily reproducible.


Diversity of beet curly top Iran virus isolated from different hosts in Iran.
Beet curly top Iran virus (BCTIV) is a major pathogen of sugar beet in Iran. In order to study diversity of BCTIV, we sampled 68 plants in Iran during the summer of 2010 with curly top disease symptoms on beans (Phaseolus vulgaris), cowpeas (Vigna unguiculata), tomatoes (Solanum lycopersicum L.), sea beets (Beta vulgaris subsp. maritima), and sugar beets (Beta vulgaris). Plant samples showing leaf curling, yellowing, and/or swelling of veins on the lower leaf surfaces were collected from various fields in Khorasan Razavi, Northern Khorasan (north-eastern Iran), East Azarbayejan, West Azarbayejan (north-western Iran), and Fars (southern Iran) provinces. Using rolling circle amplification coupled with restriction digests, cloning, and Sanger sequencing, we determined the genomes of nine new BCTIV isolates from bean, cowpea, tomato, sea beet, and sugar beet in Iran. Our analysis reveals ~11 % diversity amongst BCTIV isolates and we detect evidence of recombination within these genomes.


Expression and immunodetection of aquaporin 1 (AQP1) in canine spermatozoa.
The permeability of water and cryoprotectants through the plasma membrane is very important for cryopreservation of mammalian cells. Aquaporin 1 (AQP1) is one of the water channel proteins localized on the membranes of various cells including reproductive organs, allowing water to flow rapidly across the plasma membranes in the direction of osmotic gradients. Although mRNA expression of AQP1 was reported in the mammalian testis by reverse transcription polymerase chain reaction (RT-PCR), protein and mRNA expressions of AQP1 have not been confirmed to date in the sperm of any species. The present study was conducted to determine whether AQP1 mRNA is expressed and AQP1 protein exists in canine spermatozoa. Results from RT-PCR showed that AQP1 mRNA was expressed in canine spermatozoa as well as the testis. The size was similar to the one from canine genomic DNA as a positive control. In sperm, AQP1 protein was also detected by canine AQP1 specific antibody. From these results, both AQP1 mRNA and protein are expressed in male gamete in the dog. Expression of AQP1 may be involved in the flux of water during the cryopreservation of spermatozoa.


Interferon inhibits progression of liver fibrosis and reduces the risk of hepatocarcinogenesis in patients with chronic hepatitis C: a retrospective multicenter analysis of 652 patients.
A retrospective multicenter analysis of 652 patients with chronic hepatitis C who have been treated with interferon (IFN) was performed to assess the effects of IFN on the clinical course and development of HCC. During a mean follow-up of 54.8 months, hepatocellular carcinoma (HCC) developed in 7.0% of the patients. The rate was significantly higher in the patients who did not respond to IFN treatment than in those with sustained virological response and those who obtained a normalization of alanine aminotransferase levels despite the presence of HCV RNA (incomplete response) (P < 0.01). Using multivariate Cox's proportional hazard model, alcohol abuse (P < 0.05) and a higher level of fibrosis (P < 0.05) before treatment were the significant background factors associated with HCC development in the patients who did not respond to IFN. Interestingly, a significant increase in the rate of HCC development occurred in patients who had a histological finding of progressive fibrosis (F3). In addition, patients with low histological staging scores were likely to have an incomplete response, even if a sustained virological response was not obtained. IFN produced an improvement in histological activity and fibrosis stage in the second biopsy specimens irrespective of the clinical outcome when compared against untreated subjects.


Post-treatment neutrophil-to-lymphocyte ratio (NLR) predicts response to anti-PD-1/PD-L1 antibody in SCLC patients at early phase.
Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) have been identified as predictors of treatment response in a variety of cancers. We conducted a retrospective analysis to investigate the usefulness of NLR, PLR and SII at baseline and at 6 weeks post-treatment as predictors of response to anti-PD-1/PD-L1 antibody treatment in small cell lung cancer (SCLC). Data of 41 SCLC patients receiving immunotherapy as second- or later-line treatment were analyzed. The overall median progression-free survival (PFS) was 5.1 months (95% CI 3.2-6.2). The median PFS was significantly longer in patients with NLR < 5 than in patients with NLR ≥ 5 at 6 weeks post treatment (HR = 0.29, 95%CI 0.09-0.96, P = 0.04). However, median PFS was comparable between patients with NLR < 5 and patients with NLR ≥ 5 at baseline (HR = 0.75, 95% CI 0.24-2.26, P = 0.56). The median PFS was similar between patients with PLR < 169 and those with PLR ≥ 169 at baseline (HR = 0.67, 95% CI 0.25-1.80, P = 0.43) and at 6 weeks post treatment (HR = 0.69, 95% CI 0.25-1.86, P = 0.46). No statistically different PFS was found between patients with SII < 730 and those with SII ≥ 730 at baseline (HR = 0.70, 95% CI 0.26-1.89, P = 0.48) and at 6 weeks post treatment (HR = 0.38, 95% CI 0.013-1.09, P = 0.07). In conclusion, NLR at 6 weeks after start of treatment appears to be a biomarker of response in the early phase in SCLC patients treated with anti-PD-1/PD-L1 antibodies as second- or later-line treatment.


Psychiatric nursing: what does biology have to do with it?
There is a plethora of research that investigates the mind/body connection. This article provides a review of the advances in biological psychiatry, which includes the areas of psychobiology and psychoneuroimmunology (PNI). Psychobiology is the branch of biological psychiatry that examines the biology of thoughts, feelings, and behavior. Current research findings that illuminate the neurotransmitter systems of the brain are highlighted. Psychoneuroimmunology is a relatively new branch of science that strives to show the connections between psychology, neurology, and immunology. Research in the area of PNI has yielded much information useful to nursing. Implications of this knowledge for psychiatric nursing are addressed.


Expression of heat shock protein 90 genes during early development and infection in Megalobrama amblycephala and evidence for adaptive evolution in teleost.
Heat shock protein 90 (HSP90) are highly conserved molecular chaperones, playing a pivotal role in cellular progress. In this study, we reported the characterization of the Hsp90α and Hsp90β genes in Megalobrama amblycephala, the expression profiling during early development, in various healthy tissues and in response to bacterial infection, and the assessment of their adaptive evolution. The Hsp90α cDNA contains an open reading frame (ORF) of 2193 bp encoding 731 amino acids and the Hsp90β cDNA has an ORF of 2184 bp encoding 728 amino acids. Using quantitative real-time PCR (qRT-PCR) analysis, the mRNA of both Hsp90α and Hsp90β reached the highest level at 15th day post-hatch. Using qRT-PCR and Western blot, both Hsp90α and Hsp90β were widely expressed in various healthy tissues and significantly higher in blood than in other tissues. Expression of both Hsp90α and Hsp90β were up-regulated upon bacterial infection and reached the peak level at 4 h post infection. Site model analysis indicated that one positive selection site (T717) in Hsp90α was found, while no positive selection site was observed in Hsp90β. Branch-site model test showed that there were adaptively evolutionary evidences in the branches of Salmoniformes and Gasterosteiformes for Hsp90α gene, and in the branch of Salmoniformes for Hsp90β gene.


Aging- and smoking-associated alteration in the relative content of mitochondrial DNA in human lung.
mtDNA mutations and oxidative DNA damage has been observed to accumulate in the lung and other tissues in human aging. Thus, it is of interest to know whether the content of mtDNA is changed in aging tissues of the human. Using a competitive PCR method, we determined the relative content of mtDNA in the lung tissues of 49 subjects aged 16-85 years. The results showed that the relative content of mtDNA (with respect to the beta-actin gene) in the lung tissues was significantly increased with age (P < 0.005). The average mtDNA content in the lung tissues of the subjects over 80 years of age was found to be about 2.6-fold higher than that of the subjects below age 20. However, the relative content of mtDNA was slightly increased in the lung tissues of light smokers but significantly decreased in heavy smokers. Moreover, we found a significant increase with age in the level of oxidative damage to DNA as indicated by the ratio of 8-OH-dG/dG in total DNA (P < 0.0005). These results together with our previous findings suggest that the increase in mtDNA content of aging tissues may be effected through a feedback mechanism to compensate for the functional decline of mitochondria in human aging and that smoking may modulate the mechanism.


[Anaesthetic Implications of Psychotropic and Neurologic Agents].
More than a third of all patients undergoing surgery take psychotropic agents on a regular basis. Aside from classical indications like depression and psychosis these drugs are often prescribed for treatment of pain, anxiety and panic disorder. Over the last 30 years the frequency of prescription of psychotropic drugs increased by seven times. Of note, drug interactions of psychoactive medications and anaesthetic agents are common, and the therapeutic range is narrow. Since not all of these agents can be stopped uncritically, careful assessment of risks and benefits is obligatory. The anaesthesiologist has to take special care or avoid the use of certain medications.Medical treatment is crucial for the treatment of several neurological disorders. Frequently, anaesthesiologists are faced with common diseases like seizure disorders, Parkinson's disease and Myasthenia gravis. Perioperative withdrawal of specific medication implies the risk of recurrence of the neurological symptoms. Therefore, these drugs should be continued postoperatively as soon as possible.


Selection and drift reduce genetic variation for milk yield in Manech Tête Rousse dairy sheep.
Decreases in genetic variance over generations reduce future genetic gain. We studied the evolution of genetic variance in the dairy sheep breed Manech Tête Rousse, which has been selected for increasingly complex objectives, including, in this order, milk yield, milk contents, scrapie resistance, and somatic cell score. We estimated base population genetic variance and genetic variance by sex and per year of birth from 1981 to 2014. The data consisted of 1,842,295 milk yield records (from 1978 to 2017) and a pedigree including 530,572 females (96% of them with records) and 3,798 artificial insemination males. As a measure of drift, we computed average relationships for each cohort from which we derived expected reduction of variance due to increased relationships. The difference between observed and expected reductions in genetic variances is the reduction in genetic variance due to selection. Average relationships increased steadily but slowly in both sexes. For females, genetic variance reduced with time until a plateau was reached at around 90% of the initial genetic variance. The reduction due to relationships (roughly 3% cumulated in 30 yr) was smaller than that due to selection (roughly 10% across the last years). A smaller loss due to selection was seen in recent years, possibly due to a change in selection objectives. These results agree well with theoretical expectations. The pattern of the evolution of genetic variance in males was similar to that for females but with a stronger reduction because of strong selection of AI males at birth. We conclude that the reductions in genetic variation due to selection and drift agree with expectations, and none of the reductions are very strong in this population because of control of inbreeding and smooth changes in selection objectives over time.


Defining the competencies of those conducting pharmacovigilance.
The absence of agreed competencies in pharmacovigilance and patient risk management is a key factor hindering the development of training and a curriculum in these interrelated disciplines. If competencies were to be developed, they could be tailored to the different roles and responsibilities of the various staff involved. We describe a simple theoretical model of functional and behavioural competencies that is based on an organisation with three levels of staff: evidence collectors and gatherers, evidence processors and distillers, and decision makers. To stimulate discussion about how to enhance the progress already being made in pharmacovigilance and patient risk management, we have proposed functional and behavioural competencies for pharmacovigilance as a way of identifying and measuring scientific and personal skills pertinent to pharmacovigilance. Competencies should, we believe, be agreed and adopted by all those seeking to improve pharmacovigilance. We invite discussion of these proposals.


Frequent consulting and multiple morbidity: a qualitative comparison of 'high' and 'low' consulters of GPs.
Frequent consulting is associated with multiple and complex social and health conditions. It is not known how the impact of multiple conditions, the ability to self-manage and patient perception of the GP consultation combines to influence consulting frequency. To investigate reasons for frequent consultation among people with multiple morbidity but contrasting consulting rates. Qualitative study with in-depth interviews in the west of Scotland. Participants were 23 men and women aged about 50 years with four or more chronic illnesses; 11 reported consulting seven or more times in the last year [the frequent consulters (FCs)] and 12, three or fewer times [the less frequent consulters (LFCs)]. The main outcome measures were the participants' accounts of their symptoms, self-management strategies and reasons for consulting a GP. All participants used multiple self-management strategies. FCs described: more disruptive symptoms, which were resistant to self-management strategies; less access to fewer treatments and resources and more medical monitoring, for unstable conditions and drug regimens. The LFCs reported: less severe and more containable symptoms; accessing more efficacious self-management strategies and infrequent GP monitoring for stable conditions and routine drug regimens. All participants conveyed consulting as a 'last resort'. However, the GP was seen as 'ally', for the FCs, and as 'innocent bystander', for the LFCs. This qualitative investigation into the combined significance of multiple morbidities and self-management on the GP consultation suggests that current models of self-management might have limited potential to reduce utilization rates among this vulnerable group. Severity of symptoms, stability of condition and complexity of drug regimens combine to influence the availability of effective resources and influence frequency of GP consultations.


ATP produced by oxidative phosphorylation is channeled toward hexokinase bound to mitochondrial porin (VDAC) in beetroots (Beta vulgaris).
Mitochondrial porins or voltage-dependent anion channels (VDAC) are the main route for solute transport through outer mitochondrial membranes (OMM). In mammals, hexokinase (HK) binds to VDAC, which allows the channeling of ATP synthesized by oxidative phosphorylation toward HK. In plants, although HK has been found associated with OMM, evidence for an interaction with VDAC is scarce. Thus, in this work, we studied the physical and functional interaction between these proteins in beetroot mitochondria. To observe a physical interaction between HK and VDAC, OMM presenting HK activity were prepared from purified mitochondria. Protein complexes were solubilized from OMM with mild detergents and separated by centrifugation in glycerol gradients. Both HK activity and immunodetected VDAC were found in small (9S-13S) and large (>40S) complexes. OMM proteins were also separated according to their hydropathy by serial phase partitioning with Triton X-114. Most of HK activity was found in hydrophobic fractions where VDAC was also present. These results indicated that HK could be bound to VDAC in beetroot mitochondria. The functional interaction of HK with VDAC was demonstrated by observing the effect of apyrase on HK-catalyzed glucose phosphorylation in intact mitochondria. Apyrase, which hydrolyzes freely soluble ATP, competed efficiently with hexokinase for ATP when it was produced outside mitochondria (with PEP and pyruvate kinase), but not when it was produced inside mitochondria by oxidative phosphorylation. These results suggest that HK closely interacts with VDAC in beetroot mitochondria, and that this interaction allows the channeling of respiratory ATP toward HK through VDAC.


Aneurysmal deformity of the basal interventricular septum secondary to impinging turbulent transprosthetic eccentric flow jets.
Cases of aneurysm of basal muscular interventricular septum are very uncommon. This report describes a rare case of a young man in which aneurysmal deformity was an incidental finding during follow-up after thrombolysis of the obstructed mitral prosthesis.


The genus Meiothrips Priesner (Thysanoptera, Phlaeothripidae, Idolothripinae) with a key and a new species from China.
The genus Meiothrips Priesneris reviewed, with Meiothrips fuscicrussp. n., and Meiothrips nepalensis Kudo & Ananthakrishnan recorded and described from China, and a key provided to the five known species. COI sequences of the new species and Meiothrips nepalensis are also provided.


Epidemiology and environmental risk in hairy cell leukemia.
Hairy cell leukaemia (HCL) is an orphan subtype of leukaemia which constitutes less than 2% of all leukaemia's, with an incidence of less than 1 per 100,000 persons per annum. Median age at presentation is 55 years and it is 3-4 times more frequent in males. It is also more frequently encountered in whites and less in Asians, Africans and Arabs. The epidemiologic data are multi-factorial and influenced by ethnicity and geographical factors. Other reported associations relate to some environmental exposures and possible occupational factors. Smoking appears to have an inverse correlation with the development of hairy cell leukaemia, while farming and exposure to pesticides, petroleum products, diesel and ionizing radiation have also been reported to be associated with an increased risk. National and international collaborative efforts are needed in order to undertake more extensive studies involving larger patient cohorts, aiming to determine the role of occupational and environmental risk factors in the development of this rare form of chronic leukaemia.


Intraoperative Esketamine Is Effective at Reducing Acute Postoperative Pain in Bariatric Surgery Patients: a Randomized Control Trial.
The analgesic effect and postoperative effects of esketamine are not yet clear in bariatric surgeries. Many bariatric surgery patients suffer from acute abdominal pain after surgery which leads to increased opioid use. This study aimed to determine whether intraoperative use of esketamine could reduce acute postoperative pain in bariatric surgery patients. We designed a randomized double-blinded controlled trial. Included patients between the ages of 18 and 50 years with a body mass index ≥27 kg/m2 and American Society of Anesthesiologists Physical Status of I-III, scheduled to undergo sleeve gastrectomy. We divided them into two groups, the control group which received a placebo, and the esketamine group which received a loading dose of esketamine 0.2 mg/kg and a maintenance dose of 0.2 mg/(kg·h) along with other anesthetic drugs during the surgery. After the surgery, they were assessed for Numerical Rating Scale (NRS) pain scores and Post Operative Nausea and Vomiting (PONV) scores, while other surgical data were recorded during the surgery. We enrolled 68 patients, 52 females, and 16 males. The 0.5 h, 1 h, 2 h, 6 h, and 12 h NRS scores were significantly lower in the esketamine group compared to the control group, and the extra painkillers administered were significantly lower in the esketamine group (p<0.05). Intraoperative use of esketamine can reduce acute postoperative pain in bariatric surgery patients. Further studies should explore whether the reduced pain is due to the anti-depressive effect of esketamine or purely the analgesic effect. Chinese Clinical Trial Registry (ChiCTR2100054038, https://www.chictr.org.cn/com/25/showproj.aspx?proj=142806 ).


Serum TNF-α, sTNFR1, IL-6, IL-8 and IL-10 levels in hemorrhagic fever with renal syndrome.
It is generally accepted that the pathogenesis of hantavirus infections is the result of virus-mediated host immune response. Hantaviruses, and mainly Dobrava-Belgrade virus, are present in Greece, and cause to humans hemorrhagic fever with renal syndrome (HFRS). Serum IL-6, IL-8, IL-10, TNF-α and sTNFR1 levels were measured in 29 HFRS Greek patients. Significant higher sTNFR1, IL-6, IL-8 and IL-10 levels were observed in severe than in mild/moderate cases, while TNF-α did not seem to be associated with disease severity. Correlations between cytokine levels and their fluctuation over time after onset of the illness, along with comparisons from previously published data on the field, led in building an immune response pattern for HFRS.


Insulin and glucose profiles during continuous subcutaneous insulin infusion compared with injection of a long-acting insulin in Type 2 diabetes.
To compare insulin and glucose profiles during basal continuous subcutaneous infusion of a rapid-acting insulin analogue and once daily subcutaneous injection of a long-acting insulin analogue in Type 2 diabetes. Twenty-one patients with Type 2 diabetes treated with oral glucose-lowering agents were randomized in this two-period crossover study to an equivalent 24-h dose of continuous subcutaneous infusion of insulin aspart and subsequently once-daily bedtime subcutaneous injection of insulin glargine, or vice versa, for eight consecutive days. Plasma profiles of insulin and glucose were recorded. On the last day of each treatment period, the area under the curve (AUC) for glucose was 10% lower on the continuous subcutaneous infusion regimen compared with the insulin injection regimen (P = 0.002). This was accomplished by a flat exogenous insulin infusion profile compared with a peaking profile with injected insulin (AUC was 74% higher after injection compared with pre-injection levels (P = 0.001)). During the last 6 days in each treatment period, the intra-subject variability of exogenous fasting insulin levels in the mornings was 41% lower during insulin infusion compared with insulin injection (P = 0.012). The corresponding intra-subject variability for fasting glucose only showed a tendency to be lower during infusion as compared to the injection regimen (28%; P = 0.104). Thirteen symptomatic-only or minor hypoglycaemic episodes were recorded during the entire infusion period compared with three episodes during the injection period. Basal continuous subcutaneous infusion of a rapid-acting insulin analogue improved plasma insulin (more flat insulin profile with a lower variability) and glucose (lower AUC) profiles compared with once-daily subcutaneous injection of a long-acting insulin analogue in Type 2 diabetes.


Effect of diagnostic ultrasound during the fetal period on learning and memory in mice.
An experiment was conducted to find out whether in utero exposure to diagnostic ultrasound leads to changes in postnatal behavior in adult mice. A total of 15 pregnant Swiss albino mice were exposed to diagnostic levels of ultrasound (3.5 MHz, 65 mW/cm(2), intensity((spatial peak-temporal peak)) (I(SPTP))=1 mW/cm(2), intensity((spatial average-temporal average)) (I(SATA))=240 mW/cm(2)) for 30 min on day 14 or 16 of gestation. All exposed as well as control animals were left to complete gestation and parturition. Their offspring were used in our further studies. They were monitored during early postnatal life for standard developmental markers (such as pinna detachment, eye opening and fur development) and postnatal mortality was recorded up to 6 weeks of age. The litters were subjected to behavioral tests for learning and memory at 4 months of age. Representative animals from each group were sacrificed and the hippocampal region of the brain was assayed for biogenic amines, noradrenaline, dopamine, serotonin (5-HT) and 5-HT's metabolite, 5-hydroxy indoleacetic acid (5-HIAA), in order to determine whether ultrasound exposure produced any biochemical changes in the hippocampal region of the brain. Coronal sections from the dorsal hippocampus from the representative animals from each group were processed for staining and the number of neurons was counted. Neither the standard developmental markers (such as pinna detachment, eye opening and fur development) nor the postnatal mortality was affected by ultrasound exposure. However, there was a significant impairment in learning (hole board test) and memory functions (shuttle box test) in both the exposure groups. Significant reductions in the biogenic amines and the decrease in the neuronal density were found only in day 14th pc ultrasound-exposed group compared with the control animals. The 16th day exposure group is relatively resistant to ultrasound-induced impairment of brain functions. The results suggest that the early fetal brain is highly susceptible to induction of neurobehavioral changes by ultrasound exposure.


Relations between the effects of histamine, pheniramin and metiamide on spontaneous motility and the formation of cyclic AMP in the isolated rat uterus.
Histamine (5 X 10(-6) to 10(-3) M) depressed the spontaneous motility of the isolated rat uterus in a dose-dependent manner. Under these conditions uterine cyclic AMP was raised up to 92%. Both effects, uterine relaxation and cyclic AMP accumulation after 2 min could be inhibited dose dependently by the H2-antihistaminic compound metiamide (1.7 X 10(-6) M to 1.7 X 10(-4) M). By contrast, the H1-antagonist pheniramin (4.4 X 10(-5) M) was ineffective. It was concluded that the histamine-induced inhibition of rat uterine motility is mediated by cyclic AMP which is formed in response to stimulation of H2-histaminergic receptors.


Validation of a pre-established triage protocol for critically ill patients in a COVID-19 outbreak under resource scarcity: A retrospective multicenter cohort study.
In case of COVID-19 related scarcity of critical care resources, an early French triage algorithm categorized critically ill patients by probability of survival based on medical history and severity, with four priority levels for initiation or continuation of critical care: P1 -high priority, P2 -intermediate priority, P3 -not needed, P4 -not appropriate. This retrospective multi-center study aimed to assess its classification performance and its ability to help saving lives under capacity saturation. ICU patients admitted for severe COVID-19 without triage in spring 2020 were retrospectively included from three hospitals. Demographic data, medical history and severity items were collected. Priority levels were retrospectively allocated at ICU admission and on ICU day 7-10. Mortality rate, cumulative incidence of death and of alive ICU discharge, length of ICU stay and of mechanical ventilation were compared between priority levels. Calculated mortality and survival were compared between full simulated triage and no triage. 225 patients were included, aged 63.1±11.9 years. Median SAPS2 was 40 (IQR 29-49). At the end of follow-up, 61 (27%) had died, 26 were still in ICU, and 138 had been discharged. Following retrospective initial priority allocation, mortality rate was 53% among P4 patients (95CI 34-72%) versus 23% among all P1 to P3 patients (95CI 17-30%, chi-squared p = 5.2e-4). The cumulative incidence of death consistently increased in the order P3, P1, P2 and P4 both at admission (Gray's test p = 3.1e-5) and at reassessment (p = 8e-5), and conversely for that of alive ICU discharge. Reassessment strengthened consistency. Simulation under saturation showed that this two-step triage protocol could have saved 28 to 40 more lives than no triage. Although it cannot eliminate potentially avoidable deaths, this triage protocol proved able to adequately prioritize critical care for patients with highest probability of survival, hence to save more lives if applied.


Intracoronary 166Holmium brachytherapy combined with cutting balloon angioplasty for the treatment of in-stent restenosis.
Brachytherapy is the only effective treatment for in-stent restenosis (ISR). The preliminary data regarding cutting balloon angioplasty (CBA) are encouraging and suggest a possible additive effect of CBA with combination with vascular brachytherapy. Hence, in this study, we evaluated the efficacy, feasibility and safety of cutting balloon angioplasty followed by intracoronary Holmium (166Ho) brachytherapy for the treatment of in-stent restenosis. Fifty-six patients with in-stent restenosis were treated with cutting balloon angioplasty and intracoronary 166Ho brachytherapy. For irradiation, a balloon approximately 10 mm longer than the initially deployed stent was filled with liquid 166Ho and placed at the in-stent restenosis lesion. The patients were followed angiographically at 6 months and clinically for 19.0+/-9.8 months. The initial procedures were successful in all of the patients. The preprocedural average minimal luminal diameter (MLD) and stenosis rate were 0.57+/-0.30 mm and 80.2+/-11.6%, respectively. The MLD and residual stenosis immediately after the procedure was 2.43+/-0.37 and 13.8+/-9.9%, respectively. Thirty-nine (69.6%) patients have completed their angiographic follow-up at 6 months. The MLD, late loss and loss index at follow-up were 1.97+/-0.79 mm, 0.72+/-0.69 mm and 0.36+/-0.34, respectively. The target lesion restenosis rate was 20.5% and the target lesion revascularization rate was 3.6%. None of these patients presented with adverse coronary events such as MI, sudden cardiac death or stent thrombosis during the follow up period. The combination therapy using cutting balloon angioplasty and intracoronary 166Ho brachytherapy may be an effective new treatment modality for in-stent restenosis.


A sensitive electrochemical aptasensor for thrombin detection based on exonuclease-catalyzed target recycling and enzyme-catalysis.
In the present study, a sensitive electrochemical aptasensor based on exonuclease-catalyzed target recycling and enzyme-catalysis was developed for thrombin (TB) detection. Firstly, the alcohol dehydrogenase (ADH) was abundantly embedded in the 3-(mercaptopropyl)trimethoxysilane (MPTS) sol with a 3-D network that exhibited tunable porosity and high thermal stability. ADH, as an alcohol oxidase, catalyzed the conversation of alcohol into acetaldehyde coupling with the production of NADH in the presence of NAD(+). Then the immobilized gold nanoparticles (AuNPs) could electrocatalyze the oxidation of NADH, finally promoting the redox reaction of the electroactive material methylene blue (MB) labeled on the hybrid double strand DNA (dsDNA). Furthermore, when the mixture of TB and RecJf exonuclease was introduced, TB combined with the thrombin aptamer II (TBA II) and the aptamer-TB complex was formed. And then, the RecJf exonuclease selectively degraded the TBA II from 5'→3', releasing the target TB into the solution. The free TB was reused to combine with other TBA II to accomplish the target recycling and realize the electrochemical signal amplification. In this way, excellent sensitivity of the aptasensor was obtained. The thrombin aptasensor achieved a detection limit of 1.7pM (defined as S/N=3) with a linear range from 5pM to 100nM. In addition, the proposed aptasensor had good stability and sensitivity, and would become a promising choice for the protein diagnostics in clinical analysis.


An implementation evaluation of the physical activity counseling for in-patients with major depressive disorder (PACINPAT) intervention: a randomized controlled trial.
The physical activity counseling for in-patients with major depression (PACINPAT) randomized controlled trial was launched to tackle physical inactivity for in-patients with major depressive disorder. Evidence shows that despite potential treatment effects, physical inactivity is prevalent in this population. To contribute to the assessment of how this in-person and remote, theory-based, individually tailored intervention was designed, received and effected behavior, the aim of this study was to evaluate its implementation. This implementation evaluation was conducted within a multi-center randomized controlled trial according to the Process Evaluation Framework by the Medical Research Council including the analysis of reach, dose, fidelity and adaptation. Data were collected from the implementers and the participants randomized to the intervention group of the trial. The study sample comprised 95 physically inactive in-patients (mean age: 42 years, 53% women) with diagnosed major depressive disorder. The intervention reached the intended population (N = 95 in-patients enrolled in the study). The intervention dose varied between early dropouts (counseling sessions, M = 1.67) and study completers with some participants receiving a low dose (counseling sessions, M = 10.05) and high dose (counseling sessions, M = 25.37). Differences in the attendance groups were recognizable in the first two counseling sessions (duration of counseling session about 45 min in early dropouts versus 60 min for study completers). Fidelity of the in-person counseling content was partly achieved and adapted, whereas that of the remote counseling content was well achieved. Participants (86% at follow up) reported satisfaction with the implementers of the intervention. Adaptations were made to content, delivery mode and dose. The PACINPAT trial was implemented in the intended population, in varying doses and with adaptations made to in-person counseling content and remote counseling dose. These findings are key to understanding outcome analyses within the PACINPAT trial, further developing interventions and contributing to implementation research among in-patients with depressive disorders. ISRCTN, ISRCTN10469580 , registered on 3rd September 2018.


Associations of genetic polymorphisms within MALAT1, UCA1, FAM211A-AS1 and AC000111.6 with genetic susceptibility to rheumatoid arthritis.
Recently, several long non-coding RNAs (lncRNAs) including MALAT1, UCA1, ENST00000483588, and ENST00000456270 have been implicated in the pathogenesis of rheumatoid arthritis (RA), and we hypothesized that polymorphisms within these lncRNA genes might be genetic modifiers for the development of RA. A total of 10 potentially functional single-nucleotide polymorphisms (SNPs) were selected and genotyped in 1198 participants, including 594 RA patients and 604 healthy controls. Significant associations of FAM211A-AS1 rs2882581 (G vs. A, OR = 1.31, 95%CI 1.07-1.62, p = .01; G/G + A/G vs. A/A, OR = 1.40, 95%CI 1.08-1.83, p = .01), rs3744281 (T vs. A, OR = 1.25, 95%CI 1.02-1.54, p = .03; T/T vs. A/T + A/A, OR = 1.69, 95%CI 1.01-2.82, p = 4.59 × 10-2), and rs3760235 (A vs. G, OR = 1.32, 95%CI 1.04-1.68, p = .02; A/A vs. A/G + G/G, OR = 1.32, 95%CI 1.00-1.74, p = 4.89 × 10-2) with RF-positive RA were found. Functional annotation results indicated that these identified polymorphisms might regulate the expression of FAM211A-AS1 and nearby genes via impacting on transcription factor binding. Taken together, our results indicated that FAM211A-AS1 rs2882581, rs3744281, and rs3760235 were involved in the genetic background of RF-positive RA.


Pneumococcal vaccine impact on otitis media microbiology: A New Zealand cohort study before and after the introduction of PHiD-CV10 vaccine.
We compared the microbiology of middle ear fluid (MEF) in two cohorts of children having ventilation tube (VT) insertion; the first in the era of 7-valent Streptococcus pneumoniae conjugate vaccine (PCV7) and the second following introduction of the ten-valent pneumococcal vaccine (PHiD-CV10). During 2011 (Phase 1) and again in 2014 (Phase 2) MEF and NP samples from 325 children and 319 children were taken at the time of VT insertion. A matched comparison group had NP swabs collected with 137 children (Phase 1) and 154 (Phase 2). Culture was performed on all NP and MEF samples with further molecular identification of Haemophilus species, serotyping of S. pneumoniae, and polymerase chain reaction (PCR) testing on all MEF samples. In Phase 2 immunisation coverage with ⩾3 doses of PHiD-CV10 was 93%. The rate and ratios of culture and molecular detection of the 3 main otopathogens was unchanged between Phase 1 and Phase 2 in both MEF and NP. Haemophilus influenzae was cultured in one quarter and detected by PCR in 53% of MEF samples in both time periods. S. pneumoniae and Moraxella catarrhalis were cultured in up to 13% and detected by PCR in 27% and 40% respectively of MEF samples. H. influenzae was the most common organism isolated from NP samples (61%) in the children undergoing VT surgery whilst M. catarrhalis (49%) was the most common in the non-otitis prone group. 19A was the most prominent S. pneumoniae serotype in both MEF and NP samples in Phase 2. Of Haemophilus isolates, 95% were confirmed to be non-typeable H. influenzae (NTHi) over both time periods. Following implementation of PHiD-CV10 in New Zealand, there has been no significant change in the 3 major otopathogens in NP or MEF in children with established ear disease. For these children non-typeable H. influenzae remains the dominant otopathogen detected.


Novel statistical methodology reveals that hip shape is associated with incident radiographic hip osteoarthritis among African American women.
Hip shape is a risk factor for the development of hip osteoarthritis (OA), and current methods to assess hip shape from radiographs are limited; therefore this study explored current and novel methods to assess hip shape. Data from a prior case-control study nested in the Johnston County OA Project were used, including 382 hips (from 342 individuals). Hips were classified by radiographic hip OA (RHOA) status as RHOA cases (baseline Kellgren Lawrence grade [KLG] 0 or 1, follow-up [mean 6 years] KLG ≥ 2) or controls (KLG = 0 or 1 at both baseline and follow-up). Proximal femur shape was assessed using a 60-point model as previously described. The current analysis explored commonly used principal component analysis (PCA), as well as novel statistical methodologies suited to high dimension low sample size settings (Distance Weighted Discrimination [DWD] and Distance Projection Permutation [DiProPerm] hypothesis testing) to assess differences between cases and controls. Using these novel methodologies, we were able to better characterize morphologic differences by sex and race. In particular, the proximal femurs of African American women demonstrated significantly different shapes between cases and controls, implying an important role for sex and race in the development of RHOA. Notably, discrimination was improved with the use of DWD and DiProPerm compared to PCA. DWD with DiProPerm significance testing provides improved discrimination of variation in hip morphology between groups, and enables subgroup analyses even under small sample sizes.


An optimized total focusing method based on delay-multiply-and-sum for nondestructive testing.
Total focusing method (TFM) attracts much interest because of high image resolution and large inspection coverage. However, the synthetic focusing approach based on delay-and-sum beamforming employs only the defect information contained in the dataset while ignoring the spatial information of the array signals, leading to limited imaging performance mixed with artifacts and noise. In addition, the signal-to-noise ratio (SNR) suffers due to single-element emission of full matrix capture. This work combines a modified delay-multiply-and-sum (DMAS) beamforming approach with conventional synthetic focusing in the TFM algorithm, to achieve optimization of TFM imaging performance. DMAS-based TFM is able to take full advantage of the defect and spatial information in the array dataset, and to generate new frequency components for better image reconstruction. As demonstrated on a series of comparative simulation and experimental results, the imaging results of the optimized TFM provide a considerable improvement in SNR. Better lateral spatial resolution is also achieved due to the increased number of equivalent transducer elements and second harmonic component. Therefore, this work provides a quite promising alternative solution for the post-processing of ultrasonic phased array with improved imaging performance.


Stability of ethyl glucuronide in urine, post-mortem tissue and blood samples.
The stability of ethyl glucuronide (EtG) under conditions of degradation was examined in urine samples of nine volunteers and in post-mortem tissue (liver, skeletal muscle) and blood taken from seven corpses at autopsies. Analysis was performed via LC-MS/MS. EtG concentrations in urine samples ranged from 2.5 to 296.5 mg/l. When stored at 4 degrees C in airtight test tubes, EtG concentrations remained relatively constant; when stored at room temperature (RT) for 5 weeks in ventilated vials, variations of EtG concentrations ranged from a 30% decrease to an 80% increase, with an average of 37.5% increase. Liver and skeletal muscle tissue of three corpses with positive blood alcohol concentrations (BAC; ranging from 0.106 to 0.183 g%) were stored for 4 weeks and analysed periodically. EtG concentrations decreased 27.7% on average in 4 weeks storage at RT but EtG was still detectable in all samples with initial EtG concentrations higher than 1 mug/g. Blood and liver samples of four corpses with negative BACs were stored at RT after addition of 0.1 g% ethanol, and no new formation of EtG was observed.


On the fabrication of atom probe tomography specimens of Al alloys at room temperature using focused ion beam milling with liquid Ga ion source.
In this work, a simple rectangular milling technique was demonstrated to prepare needle shape atom probe tomography (APT) specimens from Al alloys by focused-ion-beam (FIB) milling using Ga+ ions at room temperature. Ga has high miscibility in Al owing to which electropolishing technique is preferred over Ga+ ion FIB instruments for the fabrication of APT specimens. Although, site specific sample preparation is not possible by the electropolishing technique. This led to the motivation to demonstrate a new rectangular milling technique using Ga+ FIB instrument that resulted a significant reduction of Ga+ ion impregnation into the specimens. This is attributed to the reduction of milling time (<30 s at 30 kV acceleration voltage) and the use of lower currents (<0.3 nA) compared to the conventional annular milling method. The yield of specimens during field evaporation in APT was also significantly increased from around 8 million ions to more than 86 million ions due to the avoidance of Ga+ ion embrittlement. Therefore, the currently demonstrated rectangular milling technique can be used to prepare APT specimens from Al-alloys and obtained accurate compositions of matrix, phases, and hetero-phase interfaces with Ga < 0.1 at%. RESEARCH HIGHLIGHTS: Feasibility of using Ga+ ions for the preparation of needle shaped specimens at room temperature from aluminum alloys. Demonstration of using a rectangular milling technique instead of annular milling technique that led to a significant reduction in impregnation of Ga+ ions into the specimen needles. Due to very low Ga+ ion damage, the yield of the APT data increased by 10-12 times.


Rapid discrimination of H5 and H9 subtypes of avian influenza viruses and Newcastle disease virus by multiplex RT-PCR.
Avian influenza and Newcastle disease are the highly contagious and most economically important diseases in poultry industry throughout the world. A multiplex reverse transcription polymerase chain reaction (mRT-PCR) assay was developed for the rapid and specific discrimination of H5 and H9 subtypes of avian influenza viruses (AIV) and Newcastle disease virus (NDV). Three sets of specific primers were applied in the assay based on the sequences of the hemagglutinin gene of H5-AIV, H9-AIV and fusion protein gene of NDV. 59 clinical samples including the throat washes, oral swabs, and cloacal scrapings were detected by mRT-PCR and single RT-PCR (sRT-PCR), respectively. The results indicated that the sensitivity and specificity of mRT-PCR were in accordance with sRT-PCR. The mRT-PCR developed in this study may therefore provide a new avenue to rapid detection of these important pathogens in one reaction.


Surfactant driven flows overlying a hydrophobic epithelium: film rupture in the presence of slip.
Both for tear films and along the airways within the lung, one has an extremely thin fluid layer overlying a biological substrate; in both cases surfactants either of natural origin, or artificially introduced, are important in driving fluid flows. There is evidence that slip can occur when hydrophilic liquids, similar to mucus or aqueous tear films, overlie hydrophobic epithelium. Utilizing results from recent experimental findings we examine the possible influence of slip upon tear film rupture, important in so-called dry eye, and upon surfactant-induced flows within the lung, used in surfactant replacement therapy.


Applying educational gaming success to a nonsterile compounding escape room.
Serious educational gaming success has not been replicated in a nonsterile compounding practical skill-based course. The objective of this study was to create a nonsterile compounding escape room to evaluate third-year professional pharmacy students' (1) knowledge of nonsterile compounding and (2) perceptions of educational escape room gaming utilized in nonsterile compounding. The escape room gaming environment used puzzles focused on advanced topics of nonsterile compounding. To evaluate students' knowledge, all participating students completed a pre-assessment and post-assessment mapped to the course objectives. To assess student perceptions of educational escape room gaming, a previously-validated, 12-item survey on student perceptions of educational escape room gaming was modified and administered at the end of the activity. Additional influencing factors such as success in the activity and previous escape room gaming experience were collected. All thirty students completed the assessments and perception survey (100% response rate). Three out of four student teams successfully escaped the room. Students' knowledge improved or stayed the same for all questions of the assessment questions. Students perceived the escape room as helpful to their learning. Students' increased knowledge and positive perception were independent of their teams' escape success. Students were actively engaged in learning during a nonsterile compounding escape room. Escape room educational games may be successfully applied to nonsterile compounding to yield increased student knowledge and positive perceptions.


Positive nutrition: shifting the focus from nutrients to diet for a healthy lifestyle.
This summary is based on a scientific symposium organized by the Mediterranean Diet Roundtable and the American Italian Food Coalition titled, 'Positive Nutrition: shifting focus from nutrients to diet for a healthy lifestyle.' It was held at the Embassy of Italy in Washington DC in September of 2022. The panel of experts discussed how science can inform policy, what insights may be gleaned from different countries' approaches to healthy eating and what principles of the Mediterranean diet will inform strategies for a healthy future. Recognizing that isolated actions have limited impact on the complex relationship between diet and obesity, the panel discussed the importance of a system approach. In particular, the panel emphasized that focusing on single ingredients, isolated food categories and narrow approaches to policy have had limited success across the globe. The panel agreed that there is a need for change of perspective that embraces complexity and emphasizes more positive nutrition messaging and policies. V, Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.


Host-directed therapies for improving poor treatment outcomes associated with the middle east respiratory syndrome coronavirus infections.
Three years after its first discovery in Jeddah Saudi Arabia, the novel zoonotic pathogen of humans, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a major threat to global health security.(1) Sporadic community acquired cases of MERS continue to be reported from the Middle East. The recent nosocomial outbreaks in hospitals in Seoul, Korea and at the National Guard Hospital in Riyadh, Saudi Arabia indicate the epidemic potential of MERS-CoV. Currently there are no effective anti-MERS-CoV anti-viral agents or therapeutics and MERS is associated with a high mortality rate (40%) in hospitalised patients. A large proportion of MERS patients who die have a range of pulmonary pathology ranging from pneumonia to adult respiratory distress syndrome with multi-organ failure, compounded by co-morbidities, reflecting a precarious balance of interactions between the host-immune system and MERS-CoV. Whilst we wait for new MERS-CoV specific drugs, therapeutics and vaccines to be developed, there is a need to advance a range of Host-Directed Therapies. A range of HDTs are available, including commonly used drugs with good safety profiles, which could augment host innate and adaptive immune mechanisms to MERS-CoV, modulate excessive inflammation and reduce lung tissue destruction. We discuss the rationale and potential of using Host-Directed Therapies for improving the poor treatment outcomes associated with MERS. Carefully designed randomized controlled trials will be needed to determine whether HDTs could benefit patients with MERS. The recurrent outbreaks of MERS-CoV infections at hospitals in the Middle East present unique opportunities to conduct randomized clinical trials. The time has come for a more coordinated global response to MERS and a multidisciplinary global MERS-CoV response group is required to take forward priority research agendas.


Fabrication of Hierarchical Patterned Surfaces Using a Functionalized CeO2-EPDM Composite for Crevice Corrosion Prevention on High-Voltage Insulators.
Crevice corrosion accounts for 62% of the recorded breakdown of insulators utilized in transmission lines, which may interfere with the reliability of power utilities. To address these challenges, sustainable and resilient slippery lubricant-infused porous surfaces (SLIPS) are developed on insulators to prevent electrochemically/biochemically induced crevice corrosion especially occurring in tropical and coastal environments. The conventional way of developing SLIPS by chemical and physical etching might interfere with the mechanical stability of insulators composed of pin (galvanized steel), cement, and shell (porcelain). The current study proposes a noble concept of developing hierarchical patterned textured surfaces on insulators to fabricate a resilient SLIPS coating without physical/chemical etching. The proposed coating exhibits 99% antiadhesion performance against a mixed culture of bacterial strains, superior hydrophobicity (contact angle: 160°, contact angle hysteresis: 4°), and crevice corrosion resistance performance at elevated temperatures (25-75 °C) and humidity. This study could facilitate a new route for the development of sustainable and highly reliable SLIPS coatings in the future.


Using earthworms to test the efficiency of remediation of oil-polluted soil in tropical Mexico.
This study focuses on the medium-term effects of soil bioremediation on mortality and reproduction rates of Eisenia fetida (laboratory experiment) and of the tropical earthworm Polypheretima elongata (field experiment). We compared soils restored with the two bioremediation technologies landfarming (LF) and compost-bioremediation (BI) with control soils and with soils contaminated with 1% and 2% of petroleum. Control and restored soils both were fertile and showed low hydrocarbon contents. The mortality of E. fetida was not influenced by soil restoration and by contamination with 1% petroleum; it only increased in soils contaminated with 2% petroleum. However, the reproduction rate of E. fetida was significantly lower in the soils restored with LF and in those contaminated with 1% crude oil and significantly higher in the soils restored with BI. P. elongata showed the same reaction as E. fetida. We conclude that it is important to include reproduction or other sub-lethal tests for earthworms when estimating the efficiency of restoration techniques.


Multiple views to address diversity issues: an initial dialog to advance the chiropractic profession.
The purpose of this article is to provide expert viewpoints on the topic of diversity in the chiropractic profession, including cultural competency, diversity in the profession, educational and clinical practice strategies for addressing diversity, and workforce issues. Over the next decades, changing demographics in North America will alter how the chiropractic profession functions on many levels. As the population increases in diversity, we will need to prepare our workforce to meet the needs of future patients and society.


Management of NF-1 dystrophic scoliosis associated with rib heads dislocation into the spinal canal in neurological intact patients: a systematic literature review.
The management of scoliosis and kyphoscoliosis in patients with Type 1 Neurofibromatosis (NF-1) among spinal surgeons is still challenging due to the severity of the deformity especially in dystrophic deformity types. This rapid and progressive condition is likely to be associated with dislocated rib heads into the spinal canal, hence representing a real dilemma on the decision making between its resection versus not resection during the corrective surgery, especially in patients with normal neurological status. The objective of this publication is to discuss the management options in this patient population through a literature review. A comprehensive systematic literature search was performed for relevant studies using PubMed, Web of Science, and Scopus databases. Previous publications depicting neurologically intact patients with NF-1 and rib dislocation into the canal were reviewed. Articles reporting individual cases or case series/cohorts with patient-discriminated findings were included. The data collection retrieved a total of 55 neurologically intact patients with NF-1 dystrophic scoliosis and rib penetration into the canal who underwent spinal surgery. Among them, 37 patients underwent surgery without head rib resection and 18 patients with rib excision. No patient presented postoperative neurological deficit except for one case of late postoperative neurological deterioration reported in a patient within situ fusion in which the surgeons ignored the presence of previous spinal cord compression. Corrective surgery for patients with NF-1 and rib penetration into the canal in neurologically intact patients can be safely performed without the resection of the dislocated rib heads without a higher risk of neurological compromise.


The Effect of a Short-Term Occupational Therapy Intervention on the Participation and Personal Factors of Preschoolers with Developmental Disabilities.
Preschoolers with developmental disabilities are referred to occupational therapy due to their decreased participation in daily life occupations. The purpose of this study was to evaluate the improvement in preschoolers' participation and sensory-motor abilities following an occupational therapy intervention. A prospective cohort study of 38 preschoolers and their parents was conducted using an interrupted time-series design, including assessments at three time points: base line (upon referral to an occupational therapy assessment), pre-intervention, and post-intervention after 9-12 sessions of occupational therapy interventions. Children were evaluated with the Developmental Test of Visual-Motor Integration, as well as the balance and fine motor precision sub tests of the Bruininks-Oseretsky Test of Motor Proficiency. Parents completed the Children's Participation Questionnaire and the Child Performance Skills Questionnaire. Each intervention session was documented by the therapists using the Documentation of Occupational Therapy Session Intervention form. Significant improvement in children's sensory-motor abilities were found in balance, visual integration, and fine motor precision post-intervention. There were also improvements in the measures of diversity, children's independence, and parental satisfaction. A short-term occupational therapy intervention applied to preschoolers with developmental disabilities is effective in improving their sensory-motor abilities, as well as in promoting their participation in daily activities.