Water-soluble gold nanoparticles (AuNP) functionalized with a gadolinium(iii) chelate via Michael addition for use as a MRI contrast agent.
A contrast agent suitable for magnetic resonance imaging based on small, water soluble gold nanoparticles (AuNP) conjugated to over 50 Gd3+ chelators has been prepared by using an interfacial Michael addition in aqueous media. The resultant chelator-AuNP conjugates have been successfully characterised by 1H NMR spectroscopy, IR spectroscopy, ICP-OES, ζ-potential analysis, TEM and MRI. T1-weighted in vivo images of mouse kidney were obtained using the agent at 9.4 T. A preliminary in vivo experiment produced no ill effects and the clearance profile of the agent suggests it is suitable for animal testing at clinically relevant concentrations.


Urolithiasis and intracorporeal lithotripsy in 37 Military Hospital, Accra, Ghana.
The purpose of this study was to determine the indications and complications of intracorporeal lithotripsy in our institution. Retrospective study carried out at the urology unit of the 37 Military Hospital between 2012-2015. 42 patients had intracorporeal lithotripsy out of 359 patients who had surgery within the period. Records of all patients who had intracorporeal lithotripsy between December 2012 to December 2015 were collected and analysed. An endourology log sheet was used to record data of patient's name, age, sex, indication for operation, location of stone, intraoperative complications, type of instruments/materials used, stone analysis and follow-up dates. All patients between the ages of six months to seventy years presenting with urinary stones diseases within the period were included, whilst patients with urinary stone disease who were managed with open surgery were excluded.Ethical clearance was obtained from the 37 Military Hospital institutional review board. Lithotripsy constituted 42/359(11.7%) of the methods used in the surgical cases done within the period.The commonest age of presentation was between 31-40 years (26.2%), with a male to female ratio of 2:1. The commonest indications for lithotripsy were pain (92.8%) and hydronephrosis (61.9%). Ureteric stones are more common (50%), followed by renal stones (45%) with the commonest site being the proximal ureter. The commonest procedure was ureteroscopy. Ureteral mucosal injury (5/43) (11.62%), was the commonest intraoperative complication. Postoperative complications were reno-cutaneous fistula (1/43) (2.32%), severe bleeding (1/43) (2.32%) haematuria (4/43) (9.30%). Pain was the commonest indication for intra-corporeal lithotripsy (92.8%) and also the commonest post-operative complication (9.30%). None declared.


Computed tomography in osteochondritis dissecans of the patella.
Osteochondritis dissecans is a disorder which rarely involves the patella. It must be differentiated from chondromalacia, lateral marginal fracture due to direct injury, medial facet osteochondral fracture secondary to traumatic lateral dislocation and a dorsal defect of the patella. I report a patient in whom computed tomography (CT) helped confirm the diagnosis. Although usually diagnosable from plain films, in difficult patients CT should be considered.


Clinical assessment and treatment of leg length inequalities.
Controversy persists regarding the significance of leg length inequality, the diagnostic approach to the use of heel lifts, and the implementation of proper orthopedic support in treatment of anatomical leg length inequalities. The purpose of this paper is to review the literature and formulate a sequential examination for a patient with leg length discrepancy, then outline a formula for the treatment of the patient. The initial problem a practitioner faces in examining a patient with leg length inequality is to determine if a true (anatomical) leg deficiency exists. Through a series of measurements and pelvic assessments, an effective screening process can be accomplished before radiography (scanogram) is required. An understanding of the mechanics along the kinetic chain, anywhere from the foot to the lumbar spine, coupled with the information gained from radiographs, can provide a treatment plan detailing the size of the lift and location.


Postoperative hypertension in the management of patients with intracranial arterial aneurysms.
Elevation of systemic arterial pressure in seven patients with intracranial arterial aneurysms has been shown to be effective in alleviating ischemic symptoms attributed to cerebral vasospasm. Autoregulation is at least partially lost in patients with cerebral hemodynamic crisis. Blood volume expansion was used to augment vasopressors in maintenance of systemic hypertension. The management of these cases is discussed. Caution in the use of this technique is advised, since the regimen is not without risk.


Identifying genetic predictors of depression risk: 5-HTTLPR and BDNF Val66Met polymorphisms are associated with rumination and co-rumination in adolescents.
Despite research supporting moderate heritability of depression, efforts to replicate candidate gene associations to depression have yielded inconsistent results. We tested whether Val66Met and 5-HTTLPR exhibit utility as genetic markers of depression risk, testing for replicable associations to cognitive and interpersonal endophenotypes of depression (rumination and co-rumination), and further exploring developmental and sex moderation. In Study I, 228 youth (ages 8-14) of mothers with or without a history of MDD during the child's lifetime were recruited from the community. Replication tests were carried out in Study II, a sample of 87 youth with similar recruitment. In Study I, the Val66Met single-nucleotide polymorphism (SNP) was associated with rumination in adolescents, but not children, such that adolescents homozygous for the Val allele reported higher rumination levels. Further, a cumulative genetic score (CGS) (Val66Val and 5-HTTLPR) predicted higher levels of co-rumination, specifically among adolescent girls. Both genetic associations maintained significance after covarying for current depressive symptomology, and the other endophenotype. Finally, both genetic associations exhibited similar effect sizes in Study II, although results did not reach statistical significance. RESULTS replicate a previously reported association between the brain derived neurotrophic factor (BDNF) Val allele and rumination in adolescents, and provide preliminary support for a CGS predictive of co-rumination in adolescent girls. The current study indicates that candidate genes may demonstrate utility as consistent genetic markers of depression risk when focused on specific phenotypes, and supports the need to explore potential differential effects of developmental stage and sex. However, given the small sample sizes and possibility of chance findings, these results should be interpreted with caution pending replication.


Adenosine and acetylcholine reduce isoproterenol-induced protein phosphorylation of rat myocytes.
Adenosinergic and muscarinic agents have been shown to attenuate the catecholamine-induced augmentation of both protein phosphorylation and contractile state in perfused hearts. The attenuation by phenylisopropyl-adenosine (PIA) and carbamylcholine chloride (CARB) of the isoproterenol (ISO)-induced incorporation of 32P into protein substrates was examined in isolated rat ventricular myocytes. 32P-labelled myocytes exposed to ISO (0.1 microM, 30 s) demonstrated up to an eight-fold increase of 32P incorporation into three protein substrates (155, 31, 6 kD). When myocytes were pre-incubated with either PIA or CARB for 60 s, the ISO-induced 32P incorporation in the 31 kD and the 155 kD substrates was attenuated 37% and 25%, respectively by 1 microM PIA and only 23% and 11%, by 10 microM PIA. A concentration of 1 microM CARB produced a 24% and 17% reduction in these same substrates while 10 microM CARB produced a 44% and 50% reduction. The effects of ISO were antagonized by 10 microM propanolol. The inhibitory effects of PIA were antagonized by the theophylline, sulfophenyltheophylline and dipropylcyclopentylxanthine, whereas atropine antagonized the inhibitory effects of CARB. The 32P incorporation elicited by 1 microM forskolin was reduced more by CARB than PIA. Additionally, while PIA and CARB reduced the ISO-induced increase in cAMP-dependent protein kinase (PKA) activity by 48% and 41% respectively, only CARB attenuated the ISO-elicited increase in cAMP levels, attenuating this response by 58%. The results indicate that PIA was less effective in attenuating ISO-induced 32P incorporation at higher concentrations than at lower concentrations. Moreover, this compound was less potent than CARB at attenuating the effects of ISO. It is conceivable that this difference could be related to activation of stimulatory adenosine receptors (A2) and/or a greater density of muscarinic receptors including multiple inhibitory muscarinic pathways.


Effects of space allowance on the behavior and physiology of cattle temporarily managed on rubber mats.
Dairy cattle managed in some pasture-based systems, such as in New Zealand, are predominantly kept outdoors all year around but are taken off pasture for periods, especially in wet weather to avoid soil damage. The use of rubber matting for such stand-off practices is becoming more common to improve animal welfare, and our objective was to investigate the effects of different space allowances on cow behavior and physiology when managed temporarily on rubber mats during a weather-induced stand-off period. Thirty pregnant, nonlactating Holstein-Friesian dairy cows were divided into 6 groups of 5 and exposed to 6 treatments following a Williams designed 6×6 Latin square. The treatments consisted of 6 space allowances on a 24-mm rubber surface during a simulated weather-induced stand-off period: 3.0, 4.5, 6.0, 7.5, 9.0, and 10.5 m(2)/cow. The stand-off period consisted of 18 h in the treatment pens followed by 6 h at pasture to allow for their daily feed intake (no feed was available during stand-off, following normal farm practice), for 3 consecutive days, with 6 d of recovery on pasture between treatments. When cows had more space available during the stand-off period, they spent more time lying on the rubber mats and less time lying on pasture during their daily 6-h feed break. Mean lying times (24 h, pasture and rubber mats combined) for the different space allowances were for 3.0 m(2)=7.5 h, 4.5 m(2)=10.2 h, 6.0 m(2)=11.9 h, 7.5 m(2)=12.4 h, and 10.5 m(2)=13.8 h. At 6.0 m(2) of space allowance per cow, the animals spent similar times lying per 24 h as when the cows were on recovery on pasture in between treatments (11.9 and 11.2 h, respectively). Aggressive interactions and nonaggressive lying disturbances were more frequent at lower space allowances (aggressive interactions decreased by 35% from 3.0 to 4.5 m(2)/cow, with a slower decline thereafter). Cows were dirtier after the stand-off period, particularly at lower space allowances. All cows had higher gait scores after the stand-off period; however, this change was unaffected by space allowance and very minor. Stride length, plasma cortisol, and body weight were all unaffected by the stand-off period and space allowance. The results suggest that to reduce aggressive behavior and maintain adequate lying times, dairy cattle managed temporarily on rubber matting for up to 18 h per day, without feed, should have a space allowance of at least 4.5 to 6.0 m(2) per cow.


Headache burdens and bearers.
All elements of headache burden, and those who bear them, need to be identified if headache is to secure its rightful place in the priority queue for scarce healthcare resources. This paper sets out to do this. Illness manifesting as headache imposes substantial burdens on individual people and on society. Whilst different diagnostic categories of headache vary quantitatively in their impact, the elements of burden are similar for all common headaches. Migraine, being the most studied, is a good model. The AASH/IHS Consensus Symposium on Improving Migraine Management, held in Washington DC on October 2nd 1998, argued that, world-wide, migraine is both under-diagnosed and under-treated. Whilst improved allocation of healthcare resources to migraine and other headache illnesses will mitigate these burdens, this will not happen unless the size and full nature of the problem are recognised. Using rhetoric, I answer two questions: what are the burdens of headache, and who bears them? Migraine has a peculiar tendency to extend its burdens beyond attacks and to others than the immediate sufferer. In many cases it should be characterised as a chronic rather than episodic illness. Other categories of headache impose qualitatively similar and heavy and widely-placed burdens. Healthcare resources expended on better treatment are likely to be repaid several-fold by savings elsewhere.


Chemical conversion of nitrate and nitrite to nitrous oxide for nitrogen and oxygen isotopic analysis in freshwater and seawater.
We present a novel method for nitrogen and oxygen natural isotopic abundance analysis of nitrate and nitrite of seawater and freshwater at environmental concentrations. The method involves the reduction of nitrate to nitrite using spongy cadmium with further reduction to nitrous oxide using sodium azide in an acetic acid buffer. For separate nitrite analysis, the cadmium reduction step is simply bypassed. Nitrous oxide is purged from the water sample and trapped cryogenically using an automated system with subsequent release into a gas chromatography column. The isolated nitrous oxide is then analyzed on a continuous flow isotope ratio mass spectrometer via an open split. This paper describes the basic protocol and reaction conditions required to obtain reproducible natural abundance level nitrogen and oxygen isotopic ratios from nitrate, nitrite, or both, and the results obtained to support these conclusions. A standard deviation less than 0.2 per thousand for nitrogen and 0.5 per thousand for oxygen was found for nitrate samples ranging in concentration from 40 to 0.5 microM (better for nitrite), with a blank of 2 nmol for 50-mL samples. Nitrogen and oxygen isotopic fractionation and oxygen atom exchange were consistent within each batch of analysis. There was no interference from any seawater matrixes. Only one other method published to date can measure the nitrate oxygen isotopic abundance in seawater and none that do so for nitrite alone in the presence of nitrate. This method may prove to be simpler, faster, and obtain isotopic information for lower concentrations of nitrate and nitrite than other methods.


Dendritic cells in chronic myelomonocytic leukaemia.
Blood dendritic cells (DC) differentiate in vitro via two separate pathways: either directly from blood DC precursors (DCp) or from CD14+ monocytes. In chronic myelomonocytic leukaemia (CMML) abnormal bone marrow precursors contribute to blood monocyte development but DC development has not been studied previously. Monocytes comprised 60% of blood MNC in 15 CMML patients studied, compared with 20% in 16 age-matched controls. The increase in blood monocytes was accompanied by a reciprocal decrease in mean blood DC percentage (from 0.42% of MNC in normal individuals to 0.16% of MNC in CMML patients). Absolute blood DC numbers showed a minimal (non-significant) reduction from 9.8 x 10(6)/l in normal individuals to 7.5 x 10(6)/l in CMML patients. The CD14(low) WCD16+ monocyte subpopulation was not found in CMML patients. After culture in GM-CSF/IL-4, CMML CD14+ monocytes acquired the phenotype of immature monocyte derived DC (Mo-DC) with similar yields to normal blood Mo-DC generation. Addition of TNF-alpha or LPS induced both normal and CMML Mo-DC to express prominent dendritic processes, the CMRF44+ and CD83+ antigens and high levels of HLA-DR, CD80 and CD86. Treatment either with TNF-alpha or LPS increased the allostimulatory activity of normal Mo-DC, but had little effect on the allostimulatory activity of CMML Mo-DC, perhaps reflecting the underlying neoplastic changes in monocyte precursors. We conclude that the blood DC numbers are relatively unaffected in CMML, suggesting discrete regulation of monocyte and DC production.


Cell microenvironment engineering and monitoring for tissue engineering and regenerative medicine: the recent advances.
In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells' behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future.


Stimulation of acetylcholine release in myenteric plexus by calcitonin gene-related peptide.
The effects of calcitonin gene-related peptide (CGRP) on acetylcholine (ACh) release from myenteric plexus neurons in primary culture were investigated. CGRP (10(-12) to 10(-6) M) produced a dose-dependent increase in [3H]ACh release. The ACh release caused by CGRP was significantly inhibited (74 +/- 24%) by preincubation with dideoxyadenosine but was increased more than threefold by preincubation with theophylline. Incubation of myenteric plexus neurons with CGRP (10(-8) M) in the presence of diltiazem (10(-5) M) or in a calcium-free medium markedly reduced [3H]ACh release. CGRP potentiated [3H]ACh release stimulated by potassium or substance P but not by cholecystokinin octapeptide or forskolin. The results demonstrate that CGRP cause release of ACh from guinea pig myenteric plexus neurons and suggest that the peptide acts through an adenosine 3',5'-cyclic monophosphate-dependent mechanism that involves neuronal calcium channels.


A girl with type 1 diabetes and a yellowish appearance.
Type 1 diabetes mellitus in children has been associated with other autoimmune diseases, especially coeliac disease and autoimmune thyroiditis. This association may be the result of a common pathogenic background. We describe the case of a girl with type 1 diabetes mellitus who developed icterus due to autoimmune hepatitis, a disease rarely found in children. Thyroiditis-associated and diabetes-associated autoantibodies were also present. Human leucocyte antigen typing revealed DRB1*03 heterozygosity, which has been associated with the occurrence of both autoimmune hepatitis and type 1 diabetes. This finding implies that similar pathogenic pathways may be involved in different autoimmune diseases including type 1 diabetes and autoimmune hepatitis. The patient was successfully treated with prednisolone and azathioprine. Autoimmune hepatitis can be a serious co-occurring disease in patients with type 1 diabetes.


Functionally independent components of early event-related potentials in a visual spatial attention task.
Spatial visual attention modulates the first negative-going deflection in the human averaged event-related potential (ERP) in response to visual target and non-target stimuli (the N1 complex). Here we demonstrate a decomposition of N1 into functionally independent subcomponents with functionally distinct relations to task and stimulus conditions. ERPs were collected from 20 subjects in response to visual target and non-target stimuli presented at five attended and non-attended screen locations. Independent component analysis, a new method for blind source separation, was trained simultaneously on 500 ms grand average responses from all 25 stimulus-attention conditions and decomposed the non-target N1 complexes into five spatially fixed, temporally independent and physiologically plausible components. Activity of an early, laterally symmetrical component pair (N1aR and N1aL) was evoked by the left and right visual field stimuli, respectively. Component N1aR peaked ca. 9 ms earlier than N1aL. Central stimuli evoked both components with the same peak latency difference, producing a bilateral scalp distribution. The amplitudes of these components were no reliably augmented by spatial attention. Stimuli in the right visual field evoked activity in a spatio-temporally overlapping bilateral component (N1b) that peaked at ca. 180 ms and was strongly enhanced by attention. Stimuli presented at unattended locations evoked a fourth component (P2a) peaking near 240 ms. A fifth component (P3f) was evoked only by targets presented in either visual field. The distinct response patterns of these components across the array of stimulus and attention conditions suggest that they reflect activity in functionally independent brain systems involved in processing attended and unattended visuospatial events.


Near-infrared (NIR) emitting Nd/Yb(III) complexes sensitized by MLCT states of Ru(II)/Ir(III) metalloligands in the visible light region.
Four Ru(II)/Ir(III) metalloligands have been designed and synthesized from polypyridine and bibenzimidazole (BiBzIm) organic ligands, which show strong visible light absorption via metal-to-ligand charge transfer (MLCT) transitions. Nd/Yb(III) complexes were further assembled from these Ru(II)/Ir(III) metalloligands, and Ln(III)-centered NIR emissions can be efficiently sensitized by (3)MLCT states of the metalloligands in the visible-light region. The energy transfer rates for the complexes are generally in the order Nd > Yb, which is due to the better matching between (3)MLCT states of Ru(II)/Ir(III) metalloligands and densely distributed excited states of Nd(III) ions. Long decayed lifetimes on a μs scale and high quantum yields up to 1% are obtained in these lanthanide complexes, suggesting that the Ru(II)/Ir(III) metalloligands can serve as a good visible light harvesting antenna to efficiently sensitize Ln(III)-based NIR luminescence.


Patient-centered asthma care: a community-based multidisciplinary model.
In this first part of a three-part series, the authors discuss a treatment program for patients with chronic, severe asthma. Of all chronic diseases, asthma has proven to be one of the most expensive--financially, physically, and psychologically. Although the symptoms are usually reversible, they can be severe if left untreated. Physicians, nurses, and case managers across the country are recognizing the total value of treatment at "centers of excellence." In referring their toughest asthma cases to these centers, health care professionals and patients alike are experiencing the positive benefits received from a patient-centered, multidisciplinary approach.


Water formation at low temperatures by surface O2 hydrogenation I: Characterization of ice penetration.
Water is the main component of interstellar ice mantles, is abundant in the solar system and is a crucial ingredient for life. The formation of this molecule in the interstellar medium cannot be explained by gas-phase chemistry only and its surface hydrogenation formation routes at low temperatures (O, O(2), O(3) channels) are still unclear and most likely incomplete. In a previous paper we discussed an unexpected zeroth-order H(2)O production behavior in O(2) ice hydrogenation experiments compared to the first-order H(2)CO and CH(3)OH production behavior found in former studies on hydrogenation of CO ice. In this paper we experimentally investigate in detail how the structure of O(2) ice leads to this rare behavior in reaction order and production yield. In our experiments H atoms are added to a thick O(2) ice under fully controlled conditions, while the changes are followed by means of reflection absorption infrared spectroscopy (RAIRS). The H-atom penetration mechanism is systematically studied by varying the temperature, thickness and structure of the O(2) ice. We conclude that the competition between reaction and diffusion of the H atoms into the O(2) ice explains the unexpected H(2)O and H(2)O(2) formation behavior. In addition, we show that the proposed O(2) hydrogenation scheme is incomplete, suggesting that additional surface reactions should be considered. Indeed, the detection of newly formed O(3) in the ice upon H-atom exposure proves that the O(2) channel is not an isolated route. Furthermore, the addition of H(2) molecules is found not to have a measurable effect on the O(2) reaction channel.


Misfolded proteins and human diseases.
Though protein folding is a regular phenomenon inside the cellular milieu, slight differences in the folding pattern of proteins may lead to disease-causing forms. Many diseases have been identified that are caused by these misfolded macromolecules and a considerable amount of focus is still directed towards better understanding of the processes that lead to these misfolded structures. Further progress in the field of how soluble proteins begin to misfold and how resultant oligomers begin dysfunction offers exciting prospects for specific molecular intervention.


Phase Ib Pilot Study to Evaluate Reparixin in Combination with Weekly Paclitaxel in Patients with HER-2-Negative Metastatic Breast Cancer.
Purpose: Chemokine receptor 1 (CXCR1) is recognized as an actionable receptor selectively expressed by breast cancer stem cells (BCSCs). Reparixin is an investigational allosteric inhibitor of chemokine receptors 1 and 2 (CXCR1/2), and demonstrates activity against BCSCs in human breast cancer xenografts. This phase Ib clinical trial examined dose, safety, and pharmacokinetics of paclitaxel plus reparixin therapy, and explored effects of reparixin on BCSCs in patients with metastatic breast cancer (MBC) (trial registration ID: NCT02001974).Experimental Design: Eligible patients had MBC and were candidates for paclitaxel therapy. Study treatment included a 3-day run-in with reparixin oral tablets three times a day, followed by paclitaxel 80 mg/m2/week (days 1, 8, and 15 for 28-day cycle) + reparixin tablets three times a day for 21/28 days; three dose cohorts were examined in a 3+3 dose escalation schema. Additional patients were recruited into an expansion cohort at the recommended phase II dose to further explore pharmacokinetics, safety, and biological effects of the combination therapy.Results: There were neither G4-5 adverse events nor serious adverse events related to study therapy and no interactions between reparixin and paclitaxel to influence their respective pharmacokinetic profiles. A 30% response rate was recorded, with durable responses >12 months in two patients. Exploratory biomarker analysis was inconclusive for therapy effect on BCSCs.Conclusions: Weekly paclitaxel plus reparixin in MBC appeared to be safe and tolerable, with demonstrated responses in the enrolled population. Dose level 3, 1200 mg orally three times a day, was selected for further study in a randomized phase II trial (NCT02370238). Clin Cancer Res; 23(18); 5358-65. ©2017 AACR.


Length of intravenous antibiotic therapy and treatment failure in infants with urinary tract infections.
The goal was to determine the association between short-duration (< or =3 days) and long-duration (> or =4 days) intravenous antibiotic therapy and treatment failure in a cohort of young infants hospitalized with urinary tract infections (UTIs). We conducted a retrospective cohort study of infants <6 months of age who were hospitalized with UTIs between 1999 and 2004 at 24 children's hospitals in the Pediatric Health Information System. Our main model adjusted for all covariates, propensity scores, and clustering according to hospital to evaluate the effect of short versus long courses of inpatient intravenous antibiotic therapy on treatment failure, defined as readmission because of UTI within 30 days. Of the 12,333 infants who met the inclusion criteria, 240 (1.9%) experienced treatment failure. The treatment failure rates were 1.6% for children who received short-course intravenous antibiotic treatment and 2.2% for children who received long-course treatment. Treatment courses varied substantially across hospitals and with patient-level characteristics. After multivariate adjustment, including propensity scores, there was no significant association between treatment group and outcomes, with an odds ratio for long versus short treatment of 1.02 (95% confidence interval: 0.77-1.35). Known presence of genitourinary abnormalities, but not age, predicted treatment failure. Treatment failure for generally healthy young infants hospitalized with UTIs is uncommon and is not associated with the duration of intravenous antibiotic treatment. Treating more infants with short courses of intravenous antibiotic therapy might decrease resource use without affecting readmission rates.


Reducing heavy alcohol consumption in young restaurant workers.
Restaurant employees often have high rates of heavy drinking and problems with alcohol. This study evaluates reductions in drinking and associated problems at work, in connection with a new program for prevention and early intervention. The program, called Team Resilience, is designed for young restaurant workers. A cluster-randomized trial design was used, with 28 stores from a national casual-dining restaurant chain and 235 of their employees (54% male, 46% female). Fourteen stores received the Team Resilience training workshop, consisting of three 2-hour sessions held on 3 consecutive days. Sessions included group discussion, role-play and practice activities, and a learning game. Workers in trained stores reported significantly greater decreases in recurring heavy drinking (i.e., having five or more drinks on the same occasion, on 5 or more days in the past month) and work-related problems with alcohol than workers in control stores. In the intervention group, the odds of recurring heavy drinking declined by about one half and the number of work-related problem areas declined by one third following training. In addition, drinking behaviors and problems were tied to age and were most common among employees in their middle 20s. Findings support Team Resilience as an effective intervention for reducing drinking and associated problems among young restaurant workers, a population with substantial needs.


Entomophthoramycosis: An unusual cause of facial disfigurement.
Entomophthoramycosis is a rare fungal infection of nose, paranasal sinuses and subcutaneous tissues found in tropical and subtropical region. From India very few cases have been reported. Here we report a case of Entomophthoramycosis due to Conidiobolus coronatus from the eastern India who presented with slowly growing rhinofacial swelling and right sided nasal obstruction due to intranasal mass. The case was diagnosed by typical histopathological findings of broad aseptate hyphae with surrounding eosinophilic granular material (Splendore Hoeppli phenomenon) on microscopy of nasal biopsy material and confirmed by PCR assay of DNA and sequencing from biopsy tissue. Treatment with saturated solution of potassium iodide and itraconazole was successful and clinical cure was attained in 8 months.


Proto-oncogene expression in proliferating and differentiating cardiac and skeletal muscle.
We have examined the expression of 13 proto-oncogenes in proliferating and terminally differentiated cardiac and skeletal muscle. Total RNA was prepared from intact ventricular cardiac-muscle tissue and from purified ventricular cardiac-muscle cells of neonatal and adult rats and from cultured proliferating and terminally differentiated L6A1 rat skeletal-muscle cells. cDNA probes for histone H4, thymidine kinase, myosin heavy chain and M-creatine kinase were used to assess cellular proliferation and differentiation. Oncogenes c-myc, c-raf, c-erb-A, c-ras-H, c-ski, and c-sis were expressed in both proliferating and differentiated cardiac muscle tissue and cells, whereas c-myb expression was not observed in either. c-src was expressed only in neonatal cardiac muscle tissue and cells. c-fms, c-abl, and c-ras-K were expressed in tissue from both neonatal and adult animals but only in purified cells from neonatal animals. c-fes/fps was expressed only in neonatal cardiac muscles cells. c-fos expression was not observed in cardiac-muscle tissue from either neonatal or adult rats, but surprisingly was abundantly expressed in freshly isolated cardiac-muscle cells from animals of both ages. These results emphasize that biochemical analysis using intact cardiac-muscle tissue may not necessarily reflect muscle-specific cell processes. They also show that the expression of c-fos can be activated by the cell isolation procedure. c-myc, c-ski, c-ras-H, c-ras-K, c-abl, c-raf and c-erb-A were expressed in both proliferating and terminally differentiated skeletal-muscle cells, whereas c-myb, c-fos, c-src and c-fms transcripts were observed only in proliferating cells. c-fes/fps and c-sis were not expressed in dividing or fused skeletal-muscle cells. These results demonstrate unique tissue and cell-specific patterns of proto-oncogene expression and suggest that these genes may be involved with the regulation of cellular proliferation and terminal differentiation in striated muscle.


The effects of sotalol on ventricular repolarization during exercise.
Although after pacing animal and human studies have demonstrated a rate-dependent effect of sotalol on ventricular repolarization, there is little information on the effects of sotalol on ventricular repolarization during exercise. This study attempted to show the effects of sotalol on ventricular repolarization during physiological exercise. Thirty-one healthy volunteers (18 males, 13 females) were enrolled in the study. Each performed a maximal treadmill exercise test according to the Bruce protocol after random treatment with sotalol, propranolol and placebo. Sotalol significantly prolonged QTc (corrected QT) and JTc (corrected JT) intervals at rest compared with propranolol (QTc 324.86 ms vs 305.21 ms, P<0.001; JTc 245.04 ms vs 224.17 ms, P<0.001) and placebo (QTc 324.86 ms vs 314.06 ms, P<0.01; JTc 245.04 ms vs. 232.69 ms, P<0.001). The JTc percent reduction increased progressively with each stage of exercise and correlated positively with exercise heart rate (r=0.148, P<0.01). The JTc percent reduction correlation with exercise heart rate did not exist with either propranolol or placebo. These results imply that with sotalol ventricular repolarization is progressively shortened after exercise. Thus the specific class III antiarrhythmic activity of sotalol, present as delay of ventricular repolarization, may be attenuated during exercise. Such findings may imply the need to consider other antiarrythmic therapy during periods of stress-induced tachycardia.


Helminth communities of Leptodactylus latrans (Anura: Leptodactylidae) from the Atlantic rainforest, south-eastern Brazil.
The helminth fauna associated with Leptodactylus latrans, a large frog living in a disturbed environment of Atlantic rainforest in south-eastern Brazil, was evaluated. We found eight helminth taxa, including five nematode species, Falcaustra mascula, Oswaldocruzia subauricularis, Physaloptera sp., Rhabdias sp. and an unidentified cosmocercid, two trematodes, Gorgoderina parvicava and Haematoloechus fuelleborni, and one larval cestode. The overall prevalence of infection was 63.2% with a mean intensity of 11.3 ± 3.8. The cosmocercid nematode and O. subauricularis showed the highest prevalences, although the trematode G. parvicava was the most abundant and dominant parasite species. Host size positively influenced both the intensity of infection and parasite species richness. Our data suggest that the juvenile individuals of L. latrans are more susceptible to parasitic infection than the adults. The comparison of the similarity of this community component with that found in other studies in South America shows that, as well as the characteristics of the host, the sampling area also influences the parasitic fauna. Therefore, the results of this study agree that the helminth communities of frogs have relatively low species richness and dominance of generalist species.


Anti-SARS-CoV-2 antibodies in the CSF, blood-brain barrier dysfunction, and neurological outcome: Studies in 8 stuporous and comatose patients.
To investigate the pathophysiologic mechanism of encephalopathy and prolonged comatose or stuporous state in severally ill patients with coronavirus disease 2019 (COVID-19). Eight COVID-19 patients with signs of encephalopathy were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the serum and CSF using a Food and Drug Administration-approved and independently validated ELISA. Blood-brain barrier (BBB) integrity and immunoglobulin G (IgG) intrathecal synthesis were further tested using albumin and IgG indices. The CSF was also tested for autoimmune encephalitis antibodies and 14-3-3, a marker of ongoing neurodegeneration. All patients had anti-SARS-CoV-2 antibodies in their CSF, and 4 of 8 patients had high titers, comparable to high serum values. One patient had anti-SARS-CoV-2 IgG intrathecal synthesis, and 3 others had disruption of the blood-brain barrier. The CSF in 4 patients was positive for 14-3-3-protein suggesting ongoing neurodegeneration. In all patients, the CSF was negative for autoimmune encephalitis antibodies and SARS-CoV-2 by PCR. None of the patients, apart from persistent encephalopathic signs, had any focal neurologic signs or history or specific neurologic disease. High-titer anti-SARS-CoV-2 antibodies were detected in the CSF of comatose or encephalopathic patients demonstrating intrathecal IgG synthesis or BBB disruption. A disrupted BBB may facilitate the entry of cytokines and inflammatory mediators into the CNS enhancing neuroinflammation and neurodegeneration. The observations highlight the need for prospective CSF studies to determine the pathogenic role of anti-SARS-CoV-2 antibodies and identify early therapeutic interventions.


The effects of biotin supplementation on serum and liver tissue biotinidase enzyme activity and alopecia in rats which were administrated to valproic acid.
Valproic acid (VPA) is a widely used and well-tolerable antiepileptic drug in epileptic patients. However, VPA has many side effects dose-dependent or non-dose-dependent. It is reported that VPA treatment may lead to biotin deficiency and low serum and liver tissue biotinidase enzyme activity (BEA). Major clinical manifestations in biotin deficiency are seborrheic dermatitis, dry skin, fine and brittle hair, and alopecia. We aimed to investigate the effects of biotin supplementation on serum and liver tissue BEA and alopecia during VPA therapy. Rats were randomly divided into 4 groups, each consisted of 15 rats (VPA-B1, VPA-B2, VPA, and control). Except the control group, all groups were administrated VPA dose of 600 mg/kg/d per oral (PO) for 60 days with 12h intervals two divided doses. VPA-B1 was administrated biotin dose of 6 mg/kg/d and VPA-B2 was administrated biotin dose of 0.6 mg/kg/d. In the third week of the study, we determined alopecia in the study groups. Alopecia was seen in the subjects of 13.3% of VPA-B1 (n=2), 13.3% of VPA-B2 (n=2), and 40% of VPA (n=6). But statistical significant effect on alopecia by biotin supplementation was not able to be determined between the study groups. In the control group, alopecia was not observed. The ratios of alopecia in the study groups were statistically higher than the control group (p=0.028). Itchiness was more obvious in the study groups compared with the control group. Serum biotin levels of the biotin supplemented groups (VPA-B1 and VPA-B2) were higher than the other groups (VPA and control group). Serum biotin levels of the VPA group were lower than the control group. There were significant decreases in the levels of serum and liver tissue BEA of the study groups compared with the control group. In conclusion we showed that VPA usage reduced the serum and liver tissue BEA and impaired the biotin utilization by affecting the liver. Partial biotinidase deficiency may lead to alopecia. It might be prevented by biotin supplementation in the patients receiving VPA therapy. We considered that further studies are necessary to find out the effective and safe biotin dose.


Recurrent tonic-clonic seizures and coma due to ingestion of Type I pyrethroids in a 19-month-old patient.
Pyrethroids are synthetic pyrethrin analogues that induce sodium-channel depolarization and hyperexcitation. Severe pyrethroid poisoning is manifested by a "Tremor Syndrome" (Type I cyano-agents) or a "Choreoathetosis/Salivation Syndrome" (Type II non cyano-agents). Very few reports of neurotoxic effects caused by Type I pyrethroids ingestion are available, and no human data concerning Type I pyrethroid blood levels in pediatric poisoning are reported in the medical literature. A 19-month-old female patient presented with irritability and inconsolable crying that rapidly worsened to tonic-clonic seizures and coma (GCS 6). On admission vital signs including BP 110/70 mmHg, HR 110 beats/min, and SpO2 98% on room air were normal. Orotracheal intubation, oxygen administration, and midazolam infusion (4 μg/kg/min) were performed. Intravenous thiopental sodium, up to 18 mg/kg/hour, was administered to control convulsions. An inquiry revealed that 9 h before presentation the patient had ingested an unknown amount of an insecticide containing 7% piperonyl-butoxide and a mixture of the Type I pyrethroids bifenthrin (5%) and esbiothrin (3%). Consequently, gastric lavage was performed, followed by administration of activated charcoal and cathartics. On the subsequent 48 h, the patient returned progressively alert; she was extubated on day 4 and discharged asymptomatically 12 days after hospitalization. After 9, 48, and 72 h of ingestion, the plasma levels were 500, 95, and 40 ng/mL for bifenthrin and 1,640, 640, and 165 ng/mL for piperonyl-butoxide respectively. This pediatric case showed severe pyrethroid neurotoxicity associated with measurable plasma levels of bifenthrin and piperonyl-butoxide. In pediatric pyrethroid poisoning, coma and seizures may represent the main life-threatening features. First-aid therapy including airway maintenance and control of muscle fasciculation and seizures is of major importance. Benzodiazepines and high-dose thiopental sodium were effective treatments for convulsion.


Suppression of bilirubin production in the Crigler-Najjar type I syndrome: studies with the heme oxygenase inhibitor tin-mesoporphyrin.
The heme oxygenase inhibitor tin-mesoporphyrin was used to moderate hyperbilirubinemia in two 17-year-old boys with Crigler-Najjar type I syndrome. Both patients had histories of recent, progressive neurological deterioration and plasma bilirubin concentrations on admission to the hospital were 34.5 and 28.5 mg/dL. Throughout hospitalization lasting more than 400 days, both patients underwent 10 hours of phototherapy nightly and consumed constant weight-maintaining diets. They were treated with intermittent plasmapheresis and two periods of tin-mesoporphyrin therapy comprising, in the first study period, 40 doses of 0.5 mumol/kg body weight and in the second study period, 70 doses of 1.0 mumol/kg body weight. Plasma bilirubin concentrations were decreased in both patients to varying degrees as was the rebound hyperbilirubinemia which occurs after plasmapheresis. The prolonged treatments with the inhibitor were well-tolerated and no progression of the preexisting neurological impairments occurred during the clinical trials. The results of this study suggest that the clinical application of an effective heme oxygenase inhibitor can provide a potentially useful, pharmacological adjunct to presently available therapeutic modalities for controlling episodes of acute, severe jaundice in this but lethal disorder.


Validity and reliability of serologic immunophenotyping of multiple blood group systems by ORTHO Sera with fully automated procedure.
The increase of immunization against blood group antigens has reinforced the need for automated extensive blood typing. The aim of this study was to assess both the validity and reliability of red blood cell (RBC) automated agglutination technology in testing for antigens of Kidd (Jk), Duffy (Fy), and MNS (Ss) blood systems. ORTHO Sera (Ortho Clinical Diagnostics, Raritan, NJ) anti-Jka, anti-Jkb, Anti-Fya, anti-Fyb, anti-S, and anti-s reagents were each tested on RBC samples previously typed. Replicates were performed on three separate testing sessions with three consecutive repetitions within each session, thus obtaining 486 test results. Accuracy was assessed by aggregate analysis of sensitivity, specificity, and area under the receiver operating characteristics curve (AUC). Reliability was estimated by a cross-classified mixed-effect logistic model. All reagents tested yielded optimal accuracy (100% for sensitivity and specificity, and 1.00 for AUC), except for anti-S, for which performance was slightly lower (98%, 100%, and 0.99, respectively), owing to misclassification of one sample in a single replicate. Anomalous automated measurements were recorded in 38 of 486 tests (7.8%), which then needed additional manual interpretation. Different sessions and samples were the major contributors to measurement failures (38% and 18%, separately). Order of repetitions and antigen specificity across replicates did not contribute to the risk of failures, although weak evidence of enhanced risk was observed with Jk testing. Automated RBC typing with ORTHO Sera reagents against antigens in the Kidd, Duffy, and MNS blood group systems displayed nearly 100 percent accuracy. However, a sizable number of replicates needed additional ad hoc interpretation, thus suggesting that the reliability could still be improved. Automated agglutination technology represents a viable option for phenotyping large volumes of samples.


Gradient of extrajunctional acetylcholine receptors early after denervation of mammalian muscle.
After denervation, the number of acetylcholine receptors (AChR) found within the endplate band of skeletal muscle increases transiently by about twofold. In this study, we used EM autoradiography to show that this increased endplate band label is not due to an elevated site density of receptors at the junctional folds. Rather, AChR site density within 500 microns of the endplate was found to be 4 X higher than in non-endplate areas defined as greater than 2 mm from the endplate. This nonuniform distribution of extrajunctional AChR early after denervation could represent a transient gradient, similar to that reported shortly after innervation during development.


Selective oxidation on metallic carbon nanotubes by halogen oxoanions.
Chlorine oxoanions with the chlorine atom at different oxidation states were introduced in an attempt to systematically tailor the electronic structures of single-walled carbon nanotubes (SWCNTs). The degree of selective oxidation was controlled systematically by the different oxidation state of the chlorine oxoanion. Selective suppression of the metallic SWCNTs with a minimal effect on the semiconducting SWCNTs was observed at a high oxidation state. The adsorption behavior and charge transfer at a low oxidation state were in contrast to that observed at a high oxidation state. Density functional calculations demonstrated the chemisorption of chloro oxoanions at the low oxidation state and their physisorption at high oxidation states. These results concurred with the experimental observations from X-ray photoelectron spectroscopy. The sheet resistance of the SWCNT film decreased significantly at high oxidation states, which was explained in terms of a p-doping phenomenon that is controlled by the oxidation state.


Comparison of ribotyping, randomly amplified polymorphic DNA analysis, and pulsed-field gel electrophoresis in typing of Lactobacillus rhamnosus and L. casei strains.
A total of 24 strains, biochemically identified as members of the Lactobacillus casei group, were identified by PCR with species-specific primers. The same set of strains was typed by randomly amplified polymorphic DNA (RAPD) analysis, ribotyping, and pulsed-field gel electrophoresis (PFGE) in order to compare the discriminatory power of the methods. Species-specific primers for L. rhamnosus and L. casei identified the type strain L. rhamnosus ATCC 7469 and the neotype strain L. casei ATCC 334, respectively, but did not give any signal with the recently revived species L. zeae, which contains the type strain ATCC 15820 and the strain ATCC 393, which was previously classified as L. casei. Our results are in accordance with the suggested new classification of the L. casei group. Altogether, 21 of the 24 strains studied were identified with the species-specific primers. In strain typing, PFGE was the most discriminatory method, revealing 17 genotypes for the 24 strains studied. Ribotyping and RAPD analysis yielded 15 and 12 genotypes, respectively.


The fusion of trout spermatozoa with Chinese hamster fibroblasts.
Polyethylene glycol (PEG) was used to fuse trout sperm with Chinese hamster fibroblasts (CHW-1102). As judged by light microscopy, PEG significantly increased the number of associations between the two cell types. Electron microscopy revealed that the sperm nuclei were in the cytoplasm of CHW-1102 in cultures that had been treated with PEG and in phagosomes of CHW-1102 in cultures not treated with PEG. In the cytoplasm many sperm nuclei had an extensive network of fibres whereas before fusion the sperm nuclei contained chromatin blocks which were packed together tightly. In phagosomes they consisted of dispersed blocks of chromatin. The chromatin of the few sperm that were found outside CHW-1100 cells but in the same culture that was treated with PEG also lacked fibres and consisted of loosely packed blocks. Most nuclei were unaltered by PEG treatment alone although in a few the packing of the chromatin blocks was loosened. Thus the decondensation of sperm nuclei within CHW-1102 cells appears to be brought about by the mammalian cytoplasm rather than by digestion in phagosomes, the culture conditions, or the treatment used to induce fusion.


Sexual difference theory: mormon crickets show role reversal in mate choice.
Male Mormon crickets produce a large spermatophore that the female eats. Spermatophore proteins are important to female reproduction, and females compete for access to singing males. Males reject most receptive females as mates, and those accepted are more fecund than rejected individuals. This role reversal in courtship is in contrast to the behavior of the sexes in katydid species in which the males produce small spermatophores.


Pegylated granulocyte colony-stimulating factor conveys long-term neuroprotection and improves functional outcome in a model of Parkinson's disease.
Recent proof-of-principle data showed that the haematopoietic growth factor granulocyte colony-stimulating factor (filgrastim) mediates neuroprotection in rodent models of Parkinson's disease. In preparation for future clinical trials, we performed a preclinical characterization of a pegylated derivative of granulocyte colony-stimulating factor (pegfilgrastim) in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. We determined serum and cerebrospinal fluid drug levels after subcutaneous injection. A single injection of pegfilgrastim was shown to achieve stable levels of granulocyte colony-stimulating factor in both serum and cerebrospinal fluid with substantially higher levels compared to repetitive filgrastim injections. Leucocyte blood counts were only transiently increased after repeated injections. We demonstrated substantial dose-dependent long-term neuroprotection by pegfilgrastim in both young and aged mice, using bodyweight-adjusted doses that are applicable in clinical settings. Importantly, we found evidence for the functionally relevant preservation of nigrostriatal projections by pegfilgrastim in our model of Parkinson's disease, which resulted in improved motor performance. The more stable levels of pegylated neuroprotective proteins in serum and cerebrospinal fluid may represent a general advantage in the treatment of chronic neurodegenerative diseases and the resulting longer injection intervals are likely to improve patient compliance. In summary, we found that pegylation of a neuroprotective growth factor improved its pharmacokinetic profile over its non-modified counterpart in an in vivo model of Parkinson's disease. As the clinical safety profile of pegfilgrastim is already established, these data suggest that evaluation of pegfilgrastim in further Parkinson's disease models and ultimately clinical feasibility studies are warranted.


RRDetection: Respiration Rate Estimation Using Earbuds During Physical Activities.
In modern times, earbuds have become both popular and essential accessories for people to use with a wide range of devices in their everyday lives. Moreover, the respiration rate is a crucial vital sign that is sensitive to various pathological conditions. Many earbuds now come equipped with multiple sensing capabilities, including inertial and acoustic sensors. These sensors can be used by researchers to passively monitor users' vital signs, such as respiration rates. While current earbud-based breath rate estimation algorithms mostly focus on resting conditions, recent studies have demonstrated that respiration rates during physical activities can predict cardio-respiratory fitness for healthy individuals and pulmonary conditions for respiratory patients. To address this gap, we propose a novel algorithm called RRDetection that leverages the motion sensors in ordinary earbuds to detect respiration rates during light to moderate physical activities.


Linking learning methods to outcomes in public health leadership development.
The purpose of this research is to present evaluation findings from the National Public Health Leadership Institute (PHLI) regarding how the curriculum's learning methods work singly and together to produce outcomes for learners and their organizations. Six months after graduation from PHLI, four recent cohorts of PHLI graduates were asked to report overall reactions to PHLI by using an online survey. The survey consisted of quantitative questions about key leadership behaviors taught in the program and the usefulness of PHLI's five learning methods as well as qualitative questions about changes in understanding, skill, practices, and outcomes. The evaluation survey yielded a 66 percent response rate (n=133). PHLI's learning methods are interrelated and lead to such outcomes as changed leadership understanding, knowledge and skill development, increased confidence, increased self-awareness, leadership practice changes, and organizational results. The learning project was strongly associated with development of collaborations, whereas assessment tools and coaching were most often associated with increased self-awareness. These preliminary findings support the idea that particular learning methods are related to specific outcomes. However, graduates often integrate information and skills from multiple methods to achieve outcomes. Future research should investigate whether the associations identified in this evaluation are present in other leadership development programs. This is the first published evaluation that has attempted to link specific learning methods with outcomes for participants of a public health leadership development program.


[Carnosine: endogenous physiological corrector of antioxidative system activity].
The results of research of camosine as an antioxidative system corrector in conditions of oxidative stress caused by the action of damaging factors (y-rays, overcooling, hypobaric hypoxia, brain ischemia, neurotoxin impact) are summarized in the present review. The effects of carnosine are characterized not only at the level of the whole organism but also in "in vitro" models with use of a whole series of enzymatic systems. The results of the experiments conducted displayed the ability of carnosine to protect animals from oxidative stress based on the combination of direct antioxidative effects and a modulation of enzymes' activities which participate in controlling of reactive oxygen species level in tissues.


The Effects of Artemisinin on the Cytolytic Activity of Natural Killer (NK) Cells.
Artemisinin, a chemical compound used for the treatment of malaria, has been known to show anti-cancer activity. However, the effect of this chemical on natural killer (NK) cells, which are involved in tumor killing, remains unknown. Here, we demonstrate that artemisinin exerts a potent anti-cancer effect by activating NK cells. NK-92MI cells pre-treated with artemisinin were subjected to a cytotoxicity assay using K562 cells. The results showed that artemisinin significantly enhances the cytolytic activity of NK cells in a dose-dependent manner. Additionally, the artemisinin-enhanced cytotoxic effect of NK-92MI cells on tumor cells was accompanied by the stimulation of granule exocytosis, as evidenced by the detection of CD107a expression in NK cells. Moreover, this enhancement of cytotoxicity by artemisinin was also observed in human primary NK cells from peripheral blood. Our results suggest that artemisinin enhances human NK cell cytotoxicity and degranulation. This is the first evidence that artemisinin exerts antitumor activity by enhancing NK cytotoxicity. Therefore, these results provide a deeper understanding of the action of artemisinin and will contribute to the development and application of this class of compounds in cancer treatment strategies.


Traumatic brain injury: a review of pathophysiology and management.
To review current information regarding the pathophysiology associated with traumatic brain injury (TBI), and to outline appropriate patient assessment, diagnostic, and therapeutic options. TBI in veterinary patients can occur subsequent to trauma induced by motor vehicle accidents, falls, and crush injuries. Primary brain injury occurs at the time of initial impact as a result of direct mechanical damage. Secondary brain injury occurs in the minutes to days following the trauma as a result of systemic extracranial events and intracranial changes. The initial diagnosis is often made based on history and physical examination. Assessment should focus on the cardiovascular and respiratory systems followed by a complete neurologic examination. Advanced imaging may be indicated in a patient that fails to respond to appropriate medical therapy. Primary brain injury is beyond the control of the veterinarian. Therefore, treatment should focus on minimizing the incidence or impact of secondary brain injury. Because of a lack of prospective or retrospective clinical data, treatment recommendations for veterinary TBI patients are primarily based on human and experimental studies and personal experience. Therapeutic guidelines have been developed that center on maintaining adequate cerebral perfusion. Severe head trauma is associated with high mortality in humans and animals. However, dogs and cats have a remarkable ability to compensate for loss of cerebral tissue. It is therefore important not to reach hasty prognostic conclusions based on initial appearance. Many pets go on to have a functional outcome and recover from injury.


Safety assessment, whole genome sequence, and metabolome analysis of Streptococcus thermophilus CICC 20372 for bone cement fermentation.
Bone is a kind of meat processing by-product with high nutritional value but low in calorie, which is a typical food in China and parts of East Asian countries. Microbial fermentation by lactic acid bacteria showed remarkable advantages to increase the absorption of nutrients from bone cement by human body. Streptococcus thermophilus CICC 20372 is proven to be a good starter for bone cement fermentation. No genes encoding virulence traits or virulence factors were found in the genome of S. thermophilus CICC 20372 by a thorough genomic analysis. Its notable absence of antibiotic resistance further solidifies the safety. Furthermore, the genomic analysis identified four types of gene clusters responsible for the synthesis of antimicrobial metabolites. A comparative metabolomic analysis was performed by cultivating the strain in bone cement at 37 °C for 72 h, with the culture in de Man, Rogosa, and Sharpe (MRS) medium as control. Metabolome analysis results highlighted the upregulation of pathways involved in 2-oxocarboxylic acid metabolism, ATP-binding cassette (ABC) transporters, amino acid synthesis, and nucleotide metabolism during bone cement fermentation. S. thermophilus CICC 20372 produces several metabolites with health-promoting function during bone cement fermentation, including indole-3-lactic acid, which is demonstrated ameliorative effects on intestinal inflammation, tumor growth, and gut dysbiosis. In addition, lots of nucleotide and organic acids were accumulated at higher levels, which enriched the fermented bone cement with a variety of nutrients. Collectively, these features endow S. thermophilus CICC 20372 a great potential strain for bone food processing.


Induction of myofibrillogenesis in cardiac lethal mutant axolotl hearts rescued by RNA derived from normal endoderm.
A strain of axolotl, Ambystoma mexicanum, that carries the cardiac lethal or c gene presents an excellent model system in which to study inductive interactions during heart development. Embryos homozygous for gene c contain hearts that fail to beat and do not form sarcomeric myofibrils even though muscle proteins are present. Although they can survive for approximately three weeks, mutant embryos inevitably die due to lack of circulation. Embryonic axolotl hearts can be maintained easily in organ culture using only Holtfreter's solution as a culture medium. Mutant hearts can be induced to differentiate in vitro into functional cardiac muscle containing sarcomeric myofibrils by coculturing the mutant heart tube with anterior endoderm from a normal embryo. The induction of muscle differentiation can also be mediated through organ culture of mutant heart tubes in medium 'conditioned' by normal anterior endoderm. Ribonuclease was shown to abolish the ability of endoderm-conditioned medium to induce cardiac muscle differentiation. The addition of RNA extracted from normal early embryonic anterior endoderm to organ cultures of mutant hearts stimulated the differentiation of these tissues into contractile cardiac muscle containing well-organized sarcomeric myofibrils, while RNA extracted from early embryonic liver or neural tube did not induce either muscular contraction or myofibrillogenesis. Thus, RNA from anterior endoderm of normal embryos induces myofibrillogenesis and the development of contractile activity in mutant hearts, thereby correcting the genetic defect.


Kainic acid induces distinct types of epileptiform discharge with differential involvement of hippocampus and neocortex.
Systemic administration of kainic acid (KA), an excitatory amino acid agonist, provides a model of epilepsy due to increased neural excitation. We examined discharges using multi-channel EEG recording and spectral analysis in rats implanted with neocortical and hippocampal electrodes after intravenous infusion of KA (10 mg/kg), until and including the first convulsive seizure. Gamma activity (30-80 Hz) increased in hippocampus from 3-9 min after KA administration. Two types of preconvulsive bilateral rhythmic discharges were observed, both consisting of generalised high voltage sharp waves at low frequencies (<10 Hz) mixed with fast oscillations (<20 Hz): (1) generalised non-convulsive discharges (GNCD) occurred in all animals and (2) spike-wave discharges (SW), predominantly localised in neocortex, occurred in 45% of animals. Convulsive seizure evolved out of a GNCD. Spectral profiles of epileptiform discharges were characterised by an increase in power of low (<10 Hz) and high (beta and gamma range, 20-80 Hz) frequencies which were differently expressed in neocortex and hippocampus. Thus, in this model of convulsive epilepsy caused by increased excitation, there is an early increase in gamma activity, a process that might contribute to synchronisation, and two distinct types of bilateral discharges, hippocampal-neocortical (GNCD) and preferentially neocortical (SW). Neocortical, not hippocampal, changes in EEG power correlated with development of convulsive behaviours.


Comparative analysis of the pharmacology of GluR1 in complex with transmembrane AMPA receptor regulatory proteins gamma2, gamma3, gamma4, and gamma8.
AMPA receptors (AMPARs) mediate the majority of fast synaptic transmission in the CNS of vertebrates. They are believed to be associated with members of the transmembrane AMPA receptor regulatory protein (TARP) family. TARPs mediate the delivery of AMPA receptors to the plasma membrane and mediate their synaptic trafficking. Moreover, TARPs modulate essential electrophysiological properties of AMPA receptors. Here, we compare the influence of rat TARPs (gamma2, gamma3, gamma4, and gamma8) on pharmacological properties of rat GluR1(Q)flip. We show that agonist potencies are increased by all TARPs, but to individually different extents. On the other hand, all TARPs increase agonist potencies at the virtually non-desensitizing mutant GluR1-L479Y almost identically. Comparison of the influence of individual TARPs on relative agonist efficacies confirmed that the TARPs can be functionally subdivided into two subgroups, one consisting of gamma2 and gamma3 and one consisting of gamma4 and gamma8. Surprisingly, we found that TARPs convert certain AMPA receptor antagonists to agonists. The potency of one of these converted antagonists is dependent on the particular TARP. Moreover, TARPs (except gamma4) reduce the ion channel block by the synthetic Joro spider toxin analog 1-naphthylacetyl spermine (NASP). In addition, TARPs increase the permeability of the receptor to calcium, indicating that TARPs directly modulate important ion pore properties. In summary, the data presented herein will illustrate and help to understand the previously unexpected complexities of modulation of AMPA receptor pharmacological properties by TARPs.


A Questionnaire Survey of Current Rehabilitation Practices for Adults With Normal Hearing Sensitivity Who Experience Auditory Difficulties.
Purpose A questionnaire survey was conducted to collect information from clinical audiologists about rehabilitation options for adult patients who report significant auditory difficulties despite having normal or near-normal hearing sensitivity. This work aimed to provide more information about what audiologists are currently doing in the clinic to manage auditory difficulties in this patient population and their views on the efficacy of recommended rehabilitation methods. Method A questionnaire survey containing multiple-choice and open-ended questions was developed and disseminated online. Invitations to participate were delivered via e-mail listservs and through business cards provided at annual audiology conferences. All responses were anonymous at the time of data collection. Results Responses were collected from 209 participants. The majority of participants reported seeing at least one normal-hearing patient per month who reported significant communication difficulties. However, few respondents indicated that their location had specific protocols for the treatment of these patients. Counseling was reported as the most frequent rehabilitation method, but results revealed that audiologists across various work settings are also successfully starting to fit patients with mild-gain hearing aids. Responses indicated that patient compliance with computer-based auditory training methods was regarded as low, with patients generally preferring device-based rehabilitation options. Conclusions Results from this questionnaire survey strongly suggest that audiologists frequently see normal-hearing patients who report auditory difficulties, but that few clinicians are equipped with established protocols for diagnosis and management. While many feel that mild-gain hearing aids provide considerable benefit for these patients, very little research has been conducted to date to support the use of hearing aids or other rehabilitation options for this unique patient population. This study reveals the critical need for additional research to establish evidence-based practice guidelines that will empower clinicians to provide a high level of clinical care and effective rehabilitation strategies to these patients.


Lantibiotics, class I bacteriocins from the genus Bacillus.
Antimicrobial peptides exhibit high levels of antimicrobial activity against a broad range of spoilage and pathogenic microorganisms. Compared with bacteriocins produced by lactic acid bacteria, antimicrobial peptides from the genus Bacillus have been relatively less recognized despite their broad antimicrobial spectra. These peptides can be classified into two different groups based on whether they are ribosomally (bacteriocins) or nonribosomally (polymyxins and iturins) synthesized. Because of their broad spectra and high activity, antimicrobial peptides from Bacillus spp. may have great potential for applications in the food, agricultural, and pharmaceutical industries to prevent or control spoilage and pathogenic microorganisms. In this review, we introduce ribosomally synthesized antimicrobial peptides, the lantibiotic bacteriocins produced by members of Bacillus. In addition, the biosynthesis, genetic organization, mode of action, and regulation of subtilin, a well-investigated lantibiotic from Bacillus subtilis, are discussed.


Using realist synthesis to understand the mechanisms of interprofessional teamwork in health and social care.
Realist synthesis offers a novel and innovative way to interrogate the large literature on interprofessional teamwork in health and social care teams. This article introduces realist synthesis and its approach to identifying and testing the underpinning processes (or "mechanisms") that make an intervention work, the contexts that trigger those mechanisms and their subsequent outcomes. A realist synthesis of the evidence on interprofessional teamwork is described. Thirteen mechanisms were identified in the synthesis and findings for one mechanism, called "Support and value" are presented in this paper. The evidence for the other twelve mechanisms ("collaboration and coordination", "pooling of resources", "individual learning", "role blurring", "efficient, open and equitable communication", "tactical communication", "shared responsibility and influence", "team behavioural norms", "shared responsibility and influence", "critically reviewing performance and decisions", "generating and implementing new ideas" and "leadership") are reported in a further three papers in this series. The "support and value" mechanism referred to the ways in which team members supported one another, respected other's skills and abilities and valued each other's contributions. "Support and value" was present in some, but far from all, teams and a number of contexts that explained this variation were identified. The article concludes with a discussion of the challenges and benefits of undertaking this realist synthesis.


Predictors of variceal bleeding: an analysis of clinical, endoscopic, and haemodynamic variables, with special reference to intravariceal pressure.
To assist in the prediction of variceal bleeding we examined 12 clinical, endoscopic and haemodynamic variables in 126 patients with portal hypertension (72 bleeders and 54 non-bleeders). Multiple regression and discriminant analysis were utilised for 101 patients. Stepwise regression among the 12 variables explained only 54% of the variability existing between bleeders and non-bleeders. Six of the 12 variables accounted for 51% of the total bleeder/non-bleeder variability. A predicting equation was evolved [Yp = -0.60 + 0.19 X1 (colour of varices) + 0.16 X2 (cherry red spots) + 0.03 X3 (red wale, markings) + 0.01 X4 (haematocystic spots) + 0.15 X5 (Conn's grading of variceal size) + 0.03 X6 (intravariceal pressure)]. Of the six variables used, variceal size indicated 35%, and intravariceal pressure accounted for 12%, of the explained variability between bleeders and non-bleeders. The presence of the three red colour signs and the colour of the varices accounted for only 3% and 1% respectively of the total explained variation. Using the discriminant function analysis, we were able to correctly identify 85% of the bleeders and 81% of the non-bleeders. Additional studies are required to detect the variables responsible for the unexplained variability (46%) between bleeders and non-bleeders.


[Involutional peculiarities of digestion and resorption--deduction of preventive and therapeutic needs].
First indication of an age-related alteration of digestive tract can be proseed an age of fourty. In healthy elderly man functional capacity of nutritions is lowered. Normally the digestive capacity will be sufficient provided a reasonable nourishment. Usually the intestinal absorptive capacity tends to decrease in the elderly. But following delayed intestinal transit of nutritients absorption to a certain degree can occur sufficiently. Considering the nutrition of elderly people recommendations are given.


Nano-to-micro scale dynamics of P-selectin detachment from leukocyte interfaces. III. Numerical simulation of tethering under flow.
Transient capture of cells or model microspheres from flow over substrates sparsely coated with adhesive ligands has provided significant insight into the unbinding kinetics of leukocyte:endothelium adhesion complexes under external force. Whenever a cell is stopped by a point attachment, the full hydrodynamic load is applied to the adhesion site within an exceptionally short time-less than the reciprocal of the hydrodynamic shear rate (e.g., typically <0.01 s). The decay in numbers of cells or beads that remain attached to a surface has been used as a measure of the kinetics of molecular bond dissociation under constant force, revealing a modest increase in detachment rate at growing applied shear stresses. On the other hand, when detached under steady ramps of force with mechanical probes (e.g., the atomic force microscope and biomembrane force probe), P-selectin:PSGL-1 adhesion bonds break at rates that increase enormously under rising force, yielding 100-fold faster off rates at force levels comparable to high shear. The comparatively weak effect of force on tether survival in flow chamber experiments could be explained by a possible partition of the load amongst several bonds. However, a comprehensive understanding of the difference in kinetic behavior requires us to also inspect other factors affecting the dynamics of attachment-force buildup, such as the interfacial compliance of all linkages supporting the adhesion complex. Here, combining the mechanical properties of the leukocyte interface measured in probe tests with single-bond kinetics and the kinetics of cytoskeletal dissociation, we show that for the leukocyte adhesion complex P-selectin:PSGL-1, a detailed adhesive dynamics simulation accurately reproduces the tethering behavior of cells observed in flow chambers. Surprisingly, a mixture of 10% single bonds and 90% dimeric bonds is sufficient to fully match the data of the P-selectin:PSGL-1 experiments, with the calculated decay in fraction of attached cells still appearing exponential.


Changes in bile acid composition are correlated with reduced intestinal cholesterol uptake in intestine-specific WASH-deficient mice.
The Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex is a pentameric protein complex localized at endosomes, where it facilitates the transport of numerous receptors from endosomes toward the plasma membrane. Recent studies have shown that the WASH complex plays an essential role in cholesterol and glucose homeostasis in humans and mice. To investigate the physiological importance of intestinal WASH, we ablated the WASH component WASHC1 specifically in murine enterocytes. Male and female intestine-specific WASHC1-deficient mice (Washc1IKO) were challenged with either a standard chow diet or a high-cholesterol (1.25 %) diet (HCD). Washc1IKO mice fed a standard diet did not present any apparent phenotype, but when fed an HCD, their hepatic cholesterol levels were ~ 50 % lower compared to those observed in control mice. The intestinal cholesterol absorption was almost 2-fold decreased in Washc1IKO mice, which translated into increased fecal neutral sterol loss. The intestinal expression of cholesterogenic genes, such as Hmgcs1, Hmgcr, and Ldlr, was significantly higher in Washc1IKO mice than in control mice and correlated with increased whole-body de novo cholesterol synthesis, likely to compensate for impaired intestinal cholesterol absorption. Unexpectedly, the ratio of biliary 12α-/non-12α-hydroxylated bile acids (BAs) was decreased in Washc1IKO mice and reversing this reduced ratio by feeding the mice with the HCD supplemented with 0.5 % (w/w) sodium cholate normalized the improvement of hepatic cholesterol levels in Washc1IKO mice. Our data indicate that the intestinal WASH complex plays an important role in intestinal cholesterol absorption, likely by modulating biliary BA composition.


Guidelines and protocols for cardiovascular magnetic resonance in children and adults with congenital heart disease: SCMR expert consensus group on congenital heart disease.
Cardiovascular magnetic resonance (CMR) has taken on an increasingly important role in the diagnostic evaluation and pre-procedural planning for patients with congenital heart disease. This article provides guidelines for the performance of CMR in children and adults with congenital heart disease. The first portion addresses preparation for the examination and safety issues, the second describes the primary techniques used in an examination, and the third provides disease-specific protocols. Variations in practice are highlighted and expert consensus recommendations are provided. Indications and appropriate use criteria for CMR examination are not specifically addressed.


COVID-19 challenge for modern medicine.
Coronaviruses cause disease in animals and people around the world. Human coronaviruses (HCoV) are mainly known to cause infections of the upper and lower respiratory tract but the symptoms may also involve the nervous and digestive systems. Since the beginning of December 2019, there has been an epidemic of SARS-CoV-2, which was originally referred to as 2019-nCoV. The most common symptoms are fever and cough, fatigue, sputum production, dyspnea, myalgia, arthralgia or sore throat, headache, nausea, vomiting or diarrhea (30%). The best prevention is to avoid exposure. In addition, contact per-sons should be subjected to mandatory quarantine. COVID-19 patients should be treated in specialist centers. A significant number of patients with pneumonia require passive oxygen therapy. Non-invasive ventilation and high-flow nasal oxygen therapy can be applied in mild and moderate non-hypercapnia cases. A lung-saving ventilation strategy must be implemented in acute respiratory distress syndrome and mechanically ventilated patients. Extracorporeal membrane oxygenation is a highly specialized method, available only in selected centers and not applicable to a significant number of cases. Specific pharmacological treatment for COVID-19 is not currently available. Modern medicine is gearing up to fight the new coronavirus pandemic. The key is a holistic approach to the patient including, primar-ily, the use of personal protective equipment to reduce the risk of further virus transmission, as well as patient management, which consists in both quarantine and, in the absence of specific pharmacological therapy, symptomatic treatment.


Mealtimes on eating disorder wards: a two-study investigation.
This research had two aims. First, to assess the current mealtime practices within UK eating disorders units. Second, to investigate staff perspectives of these mealtimes, including their involvement and understanding of patients' experience. Study 1 involved a survey to assess mealtime protocols across 22 eating disorders units. In Study 2, sixteen semistructured interviews were conducted with staff at three eating disorders units. Between and within-unit variation exist regarding the implementation of mealtimes. Thematic analysis revealed that staff perceived their provision of mealtimes to be influenced by their own interpersonal difficulties created by the meals. Additionally, they perceived that these issues could be aided by forward planning, successful teamwork, and focused staff training. There is a need for specialized mealtime implementation training. Furthermore, research is required to evaluate current mealtime practices from patient perspectives and to determine the impact of modified mealtime approaches on treatment outcome.


Caveolae and Lipid Rafts in Endothelium: Valuable Organelles for Multiple Functions.
Caveolae are flask-shaped invaginations of the plasma membrane found in numerous cell types and are particularly abundant in endothelial cells and adipocytes. The lipid composition of caveolae largely matches that of lipid rafts microdomains that are particularly enriched in cholesterol, sphingomyelin, glycosphingolipids, and saturated fatty acids. Unlike lipid rafts, whose existence remains quite elusive in living cells, caveolae can be clearly distinguished by electron microscope. Despite their similar composition and the sharing of some functions, lipid rafts appear more heterogeneous in terms of size and are more dynamic than caveolae. Following the discovery of caveolin-1, the first molecular marker as well as the unique scaffolding protein of caveolae, we have witnessed a remarkable increase in studies aimed at investigating the role of these organelles in cell functions and human disease. The goal of this review is to discuss the most recent studies related to the role of caveolae and caveolins in endothelial cells. We first recapitulate the major embryological processes leading to the formation of the vascular tree. We next discuss the contribution of caveolins and cavins to membrane biogenesis and cell response to extracellular stimuli. We also address how caveolae and caveolins control endothelial cell metabolism, a central mechanism involved in migration proliferation and angiogenesis. Finally, as regards the emergency caused by COVID-19, we propose to study the caveolar platform as a potential target to block virus entry into endothelial cells.


Bilateral Vestibular Hypofunction in Quantitative Head Impulse Test: Clinical Characteristics in 23 Patients.
To explore clinical features of patients with bilateral vestibular hypofunction (BVH) verified in motorized head impulse test (MHIT). We examined clinical records of 23 adult patients (10 males and 13 females), whose gain of the vestibulo-ocular reflex in the MHIT was bilaterally lowered. Fifteen of 62 unilateral cochlear implant (CI) recipients routinely tested both pre- and postoperatively with the MHIT had BVH. Eight of 198 vestibular outpatients selected to the MHIT due to clinical causes had BVH. Clinical characteristics and a questionnaire regarding current sensations were analyzed. The mean gain±SD in the MHIT was 0.26±0.17 on the right and 0.26±0.14 on the left side. The mean gain in the CI recipients did not differ from that of vestibular outpatients (p>0.05). All outpatients with BVH suffered from oscillopsia, whereas only 46% of CI recipients experienced oscillopsia (p=0.048). Instability was more prominent (p=0.004) and quality of life further decreased (p=0.012) among vestibular outpatients compared with CI patients. Most common etiology for the BVH was meningitis. Other causes were either sudden or progressive loss of labyrinthine function, bilateral Meniére's disease, and ototoxicity. BVH is rare even in a specialized clinic. Vestibular outpatients were more disabled than CI recipients with the BVH.


Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects.
We analyzed candidate platelet function disorder genes in 13 index cases with a history of excessive bleeding in association with a significant reduction in dense granule secretion and impaired aggregation to a panel of platelet agonists. Five of the index cases also had mild thrombocytopenia. Heterozygous alterations in FLI1 and RUNX1, encoding Friend leukemia integration 1 and RUNT-related transcription factor 1, respectively, which have a fundamental role in megakaryocytopoeisis, were identified in 6 patients, 4 of whom had mild thrombocytopenia. Two FLI1 alterations predicting p.Arg337Trp and p.Tyr343Cys substitutions in the FLI1 DNA-binding domain abolished transcriptional activity of FLI1. A 4-bp deletion in FLI1, and 2 splicing alterations and a nonsense variation in RUNX1, which were predicted to cause haploinsufficiency of either FLI1 or RUNX1, were also identified. Our findings suggest that alterations in FLI1 and RUNX1 may be common in patients with platelet dense granule secretion defects and mild thrombocytopenia.


Reflectance calculations of anisotropic dielectric constants of graphene-like two-dimensional materials.
A new optical method for determining anisotropic dielectric constants of graphene-like two-dimensional materials on semiconductor or metal substrates is developed. The method is based on the surface differential reflectance measurements at three different incident angles. The inversion problem is resolved analytically in a long-wavelength approximation, where graphene is discussed within the framework of macroscopic electrodynamics as a uniaxially anisotropic film with the optical axis perpendicular to the film surface. The method is fast and has no need for the initial guesses of the desired parameters. It also offers an effective technique to get good start points for iterative numerical methods to improve the preliminary results. The method is unique in its simplicity and, therefore, important for graphene research.


Capillary electrophoresis for screening of adenylosuccinate lyase deficiency.
We report a new screening method for adenylosuccinate lyase (ASase) deficiency using capillary electrophoresis (CE). This enzyme defect causes secondary autism and psychomotor retardation in early childhood. In all body fluids of these patients, two succinylpurine metabolites can be found that are normally not detectable: succinyladenosine and succinylaminoimidazole carboxamide (SAICA) riboside. A Beckman P/ACE 2050 capillary electrophoresis system was used with a 47.1 cm capillary, 75 microns ID, and the P/ACE Beckman UV absorbance detector. Untreated urine, injected for 1 s, was separated in a pH 8.63 borate buffer at 20 kV. The two succinylpurines (migration times 13.36 and 13.60 min) were detected at 254 nm only in urine of patients with ASase deficiency but not in control samples.


Spine surgery in athletes with low back pain-considerations for management and treatment.
While degenerative lumbar spine conditions are common in the general population, there are unique considerations when diagnosed in high-level athletes. Genetic factors have been identified as a more significant contributor to the development of degenerative disc disease than occupational risks, however, some have postulated that the incessant training of young, competitive athletes may put them at a greater risk for accelerated disease. The evidence-based literature regarding lumbar disc herniation in elite athletes suggests that it is reasonable to expect excellent clinical outcomes and successful return-to-sport after either operative or non-operative treatment regardless of sport played. However, those athletes who require repetitive torque on their lumbar spines may have poorer long-term outcomes if surgical treatment is required for this condition. Painful spondylolysis in the athlete can often be treated successfully with non-operative treatment, however, if surgery is required, pars repair techniques provides a motion-sparing alternative that may lead to successful return to sport.


Retrospective memories of parental care and health from mid- to late life.
Perceptions of early caregiving experiences are hypothesized to be influential across the life span. However, previous research testing this hypothesis focuses primarily on young adults and use mostly cross-sectional designs. The current study examined associations between memories of early caregiving experiences and trajectories of depressive symptoms and physical health in 2 large samples of middle-aged and older adults. Sample 1 consisted of participants from the National Survey of Midlife Development in the United States (n = 7,108) followed for 18 years (from 1995/1996 until 2013/2014). Sample 2 consisted of participants from the Health and Retirement Study (n = 15,234) followed over a 6-year period. Memories of caregiver support before age 18 were retrospectively assessed in middle and older adulthood; associations between these memories and changes in self-rated health, chronic health conditions, and depressive symptoms over time were examined. Memories of higher parental affection in early childhood were associated with better self-rated health and lower depressive symptoms over intervals of approximately 6 and 18 years, in both samples; the results for chronic health conditions was more mixed. These associations persisted over time and were not moderated by time. Associations between perceptions of caregiver support and health persisted over time, underscoring the importance of memories of close relationships for health and depressive symptoms across the life span, even into late life. Findings are discussed in relation to models that link perceptions of early life experiences to later life outcomes. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Outer radius-wall thickness ratio, a postmortem quantitative histology in human coronary arteries.
Although the anatomy, histology and pathology of human coronary arteries have been studied extensively, little is known about the functional relationship between vessel radius and wall thickness. It is the purpose of this study to present detailed measurements and to describe this relationship covering the range from the feeding coronary artery to the arterioles. Human hearts of 10 adults less than 36 +/- 3 years old were investigated immediately postmortem. Ten cubic tissue blocks, measuring about 10 mm in length on each side, were dissected from the left ventricular wall. After fixation by immersion, 15-microm sections were prepared and outer and inner perimeters of 52 arterial segments were digitalized. Vessel radius and wall thickness were calculated and plotted to show their relationship over the whole range of vessel calibers. Outer vessel radii ranged from 100 to 3,000 microm and wall thickness from 80 to 800 microm. Plotting the outer vessel radius against the wall thickness, the data points were found to cluster around a straight line. A significant correlation between the two parameters was found (R2 = 0.79). This mathematical correlation and the good agreement of the presented results with data from other species indicate a common physiologic concept.


Test-and-treat in Los Angeles: a mathematical model of the effects of test-and-treat for the population of men who have sex with men in Los Angeles County.
There is evidence to suggest that antiretroviral therapy (ART) and testing for human immunodeficiency virus (HIV) reduce the probability of transmission of HIV. This has led health officials across the United States to take steps toward a test-and-treat policy. However, the extent of the benefits generated by test-and-treat is debatable, and there are concerns, such as increased multidrug resistance (MDR), that remain unaddressed. We developed a deterministic epidemiologic model to simulate the HIV/AIDS epidemic for men who have sex with men (MSM) in Los Angeles County (LAC). We calibrated the model to match the HIV surveillance data from LAC across a 10-year period, starting in 2000. We then modified our model to simulate the test-and-treat policy and compared epidemiologic outcomes under the test-and-treat scenario to the status quo scenario over the years 2012-2023. Outcome measures included new infections, deaths, new AIDS cases, and MDR. Relative to the status quo, the test-and-treat model resulted in a 34% reduction in new infections, 19% reduction in deaths, and 39% reduction in new AIDS cases by 2023. However, these results are counterbalanced by a near doubling of the prevalence of MDR (9.06% compared to 4.79%) in 2023. We also found that the effects of increasing testing and treatment were not complementary. Although test-and-treat generates substantial benefits, it will not eliminate the epidemic for MSM in LAC. Moreover, these benefits are counterbalanced by large increases in MDR.


Thrombin-stimulated effects on megakaryocytopoiesis and pulmonary-platelet interactions.
The effects of thrombin stimulation on megakaryocytopoiesis and pulmonary-platelet interactions were investigated before and after administration of the compound to 15 mongrel dogs. Each dog served as its own control. Thrombin was given to encourage the traffic of megakaryocytes into the lung and to study the thrombin-stimulated effects on megakaryocytopoiesis in the bone marrow. Our results showed that thrombin increased the numbers of bone marrow cells in general and megakaryocytes (MK) in particular. In addition, the maturation cycle of megakaryocytes was accelerated and the number of MK migrating into the central venous circulation was nearly doubled. Most of the circulating MK ultimately became sequestered in pulmonary capillaries, where platelets were shed into the arterial circulation. We conclude that thrombin has a major stimulatory effect on megakaryocytopoiesis in the bone marrow and that the lung plays an important role as a vascular filter and regulator of circulating platelet count.


Seroprevalence of Infections with Dengue, Rift Valley Fever and Chikungunya Viruses in Kenya, 2007.
Arthropod-borne viruses are a major constituent of emerging infectious diseases worldwide, but limited data are available on the prevalence, distribution, and risk factors for transmission in Kenya and East Africa. In this study, we used 1,091 HIV-negative blood specimens from the 2007 Kenya AIDS Indicator Survey (KAIS 2007) to test for the presence of IgG antibodies to dengue virus (DENV), chikungunya virus (CHIKV) and Rift Valley fever virus (RVFV).The KAIS 2007 was a national population-based survey conducted by the Government of Kenya to provide comprehensive information needed to address the HIV/AIDS epidemic. Antibody testing for arboviruses was performed on stored blood specimens from KAIS 2007 through a two-step sandwich IgG ELISA using either commercially available kits or CDC-developed assays. Out of the 1,091 samples tested, 210 (19.2%) were positive for IgG antibodies against at least one of the three arboviruses. DENV was the most common of the three viruses tested (12.5% positive), followed by RVFV and CHIKV (4.5% and 0.97%, respectively). For DENV and RVFV, the participant's province of residence was significantly associated (P≤.01) with seropositivity. Seroprevalence of DENV and RVFV increased with age, while there was no correlation between province of residence/age and seropositivity for CHIKV. Females had twelve times higher odds of exposure to CHIK as opposed to DENV and RVFV where both males and females had the same odds of exposure. Lack of education was significantly associated with a higher odds of previous infection with either DENV or RVFV (p <0.01). These data show that a number of people are at risk of arbovirus infections depending on their geographic location in Kenya and transmission of these pathogens is greater than previously appreciated. This poses a public health risk, especially for DENV.


Robust estimation of spatially variable noise fields.
Consideration of spatially variable noise fields is becoming increasingly necessary in MRI given recent innovations in artifact identification and statistically driven image processing. Fast imaging methods enable study of difficult anatomical targets and improve image quality but also increase the spatial variability in the noise field. Traditional analysis techniques have either assumed that the noise is constant across the field of view (or region of interest) or have relied on separate MRI acquisitions to measure the noise field. These methods are either inappropriate for many modern scanning protocols or are overly time-consuming for already lengthy scanning sessions. We propose a new, general framework for estimating spatially variable noise fields from related, but independent MR scans that we call noise field equivalent scans. These heuristic analyses enable robust noise field estimation in the presence of artifacts. Generalization of noise estimators based on uniform regions, difference images, and maximum likelihood are presented and compared with the estimators derived from the proposed framework. Simulations of diffusion tensor imaging and T(2)-relaxometry demonstrate a 10-fold reduction in mean squared error in noise field estimation, and these improvements are shown to be robust to artifact contamination. In vivo studies show that spatially variable noise fields can be readily estimated with typical data acquired at 1.5T.