Practice guidelines to reduce testing in the hospital.
To reduce testing among hospitalized patients using practice guidelines for any of 14 medical problems. Comparison of test use before and after implementation of guidelines. The guidelines were developed by consensus panels of self-selected participating physicians. Non-participating physicians were monitored during the same periods. In addition, the two groups of physicians were evaluated similarly for their management of three medical problems for which guidelines were not developed. Acute care hospital. 1,638 hospitalized patients and their 79 physicians. Implementation of practice guidelines for the care of hospitalized patients. Geometric mean charges expressed in inflation-adjusted dollars were used as measures of test use. For the intervention group, laboratory tests decreased by 20.6%, x-rays by 42.3%, and EKGs by 34.2%. All the decreases were significant (p = 0.001). The non-participating physicians who were higher test users during both years of the study also achieved significant (p less than 0.05) but smaller reductions during the intervention year: 13.9% for laboratory tests, 30.3% for x-rays, and 21.8% for EKGs, perhaps because the same residents were involved in the care of both groups of patients. For the non-guideline diagnoses, the participating physicians achieved reductions of 11.1% for laboratory tests and 19.2% for x-rays, and a 3.5% increase in EKGs. Two-way analyses of variance that took into account the reductions in testing achieved by non-participants, or by participants with non-guideline diagnoses, revealed no significant reduction in testing attributable directly to the guidelines except for EKGs. Follow up of the participating physicians during the six months after the end of the intervention revealed that testing remained at the lower level achieved while the guidelines were in use. Outcome of care, as measured by deaths in the hospital, deaths within 90 days of discharge, and readmissions within 90 days of discharge, was not affected by the use of the guidelines. 1) A large group of physicians could be recruited in a hospital to establish practice guidelines by group consensus. 2) These self-selected physicians were willing to use the guidelines (or allow the housestaff to use them) while caring for their patients. 3) Participating physicians were able to achieve substantial and significant reductions in testing without any demonstrable adverse effect on quality of care as measured by deaths and readmissions, and without any demonstrable shifting of resources from the inpatient to the outpatient setting of care. 4) The reductions in testing, whether caused by the guidelines or not, persisted for at least six months beyond the end of the period of implementation.


Cutaneous injury by topical T-2 toxin: involvement of microvessels and mast cells.
Topical applications of various doses of T-2 toxin to rats led to delayed skin reactions. Following a dose-dependent latent period of 12-24 hr, there appeared vascular dilation, stasis, edema and mononuclear cell infiltration, with many degranulating mast cells. These signs were earliest and strongest in the subcutis. Epidermal necrosis occurred 1-2 days later and was probably caused secondarily by ischemia, due to microcirculatory failure. Ultrastructurally, endothelial cells of small vessels were the earliest sites of change. While intercellular junctions remained closed and pinocytosis decreased, the cytoplasm contained many ribosomes, vacuoles, and abnormal mitochondria. Another early effect of topical T-2 toxin was an increase in number and degranulation of mast cells, especially in the subcutis. The resemblance of the skin injury to that produced by irradiation is noted.


New multilayer coating using quaternary ammonium chitosan and κ-carrageenan in capillary electrophoresis: application in fast analysis of betaine and methionine.
The aim of this study was to develop a new multilayer coating with crosslinked quaternary ammonium chitosan (hydroxypropyltrimethyl ammonium chloride chitosan; HACC) and κ-carrageenan for use in capillary electrophoresis. A new semi-permanent multilayer coating was formed using the procedure developed and the method does not require the presence of polymers in the background electrolyte (BGE). The new capillary multilayer coating showed a cathodic electroosmotic flow (EOF) of around 30×10(-9) m(2) V(-1) s(-1) which is pH-independent in the range of pH 2 to 10. The enhanced EOF at low pH obtained contributed significantly to the development of a fast method of separation. The multilayer coating was then applied in the development of a fast separation method to determine betaine and methionine in pharmaceutical formulations by capillary zone electrophoresis (CZE). The BGE used to determine the betaine and methionine concentrations was composed of 10 mmol L(-1) tris(hydroxymethyl) aminomethane, 40 mmol L(-1) phosphoric acid and 10% (v/v) ethanol, at pH 2.1. A fused-silica capillary of 32 cm (50 µm ID×375 µm OD) was used in the experiments and samples and standards were analyzed employing the short-end injection procedure (8.5 cm effective length). The instrumental analysis time of the optimized method was 1.53 min (approx. 39 runs per hour). The validation of the proposed method for the determination of betaine and methionine showed good linearity (R(2)>0.999), adequate limit of detection (LOD <8 mg L(-1)) for the concentration in the samples and inter-day precision values lower than 3.5% (peak area and time migration). The results for the quantification of the amino acids in the samples determined by the CZE-UV method developed were statistically equal to those obtained with the comparative LC-MS/MS method according to the paired t-test with a confidence level of 95%.


Efficacy of a portable interface pressure sensor for robotic surgery in preventing compartment syndrome.
This study determines whether the use of a portable interface pressure sensor (Palm Q) for robotic surgery could prevent compartment syndrome. In the present single center, non-trial observational study, patients diagnosed with gynecological diseases between April 2015 and August 2020 treated with laparoscopic or robotic surgery were enrolled. We assessed 256 cases involving surgery performed in the lithotomy position with an operative time >4 h. The Palm Q device was placed preoperatively on both sides of the patients' lower legs. The pressure was measured every 30 min preoperatively and intraoperatively and adjusted to ≤30 mmHg. If the pressure reached ≥30 mmHg, the operation was stopped, the patient was repositioned, the leg position was released, the pressure was reduced to ≤30 mmHg, and the procedure was resumed. We compared the maximum creatine kinase levels of the Palm Q and non-Palm Q groups. We also analyzed the correlation between the patients' symptoms postoperatively (shoulder and leg pain) and compartment syndrome. Our data showed that immediate postoperative creatine kinase levels predict compartment syndrome. Propensity score matching of the 256 enrolled patients resulted in 92 cases (46 per group), balanced for age, body mass index, and lifestyle disease. Creatine kinase levels differed significantly between the Palm Q and non-Palm Q groups (p = 0.041). None of the patients in the Palm Q group experienced well-leg compartment syndrome complications. Palm Q can potentially help to prevent perioperative compartment syndrome.


Latino parents' accounts of attention deficit hyperactivity disorder.
Although researchers have conducted a vast amount of research about attention deficit hyperactivity disorder (ADHD), few have addressed how Latino families experience ADHD. (a) finding out about ADHD, (b) taking on a biomedical meaning, (c) living between two cultures, (d) caring for a child with ADHD, and (e) looking toward the future with ADHD. Although some of the circumstances encountered by Latino parents resemble those typically found in the literature about ADHD and families, their experience is rendered inordinately complex by multiple overlapping sociocultural, linguistic, and parental circumstances.


Thermal characteristics and cadmium binding behavior of EC-ELP fusion polypeptides.
Elastin-like polypeptides (ELPs) are stimulus-responsive protein-based biopolymers that exhibit phase transition behavior. By joining them to synthetic phytochelatin (EC), EC-ELP fusion proteins with temperature sensitivity and metal-binding functionality were generated to remove heavy metal ions biologically. Three different EC domains (EC10, EC20, EC30) were incorporated into the ELP, and the EC-ELP fusion proteins were expressed in E. coli. Their thermal properties and metal binding abilities were then investigated according to the EC length. In addition, the feasibility of reusing EC-ELPs and the cadmium ion binding affinity of reused EC-ELPs were explored.


Biomarker-assisted diagnosis of ovarian, cervical and pulmonary small cell carcinomas: the role of TTF-1, WT-1 and HPV analysis.
Small cell carcinoma of the ovary, hypercalcaemic-type (SCCOH) is morphologically similar to small cell carcinomas from other sites. The aims of this study were to (i) determine if a biomarker panel would distinguish small cell carcinomas of the ovary, cervix (SCCCx) and lung (SCCLu) and (ii) potentially determine the histogenesis of SCCOH. Nine ovarian small cell carcinomas (seven hypercalcaemic type; two pulmonary type), eight SCCCx and 22 SCCLu were immunostained for thyroid transcription factor (TTF)-1, WT-1, p16, cKIT and OCT3/4; a subset of cases were tested for human papillomavirus (HPV). WT-1 was diffusely positive in 6/7 SSCOH versus two of 33 other small cell carcinomas (P <or= 0.001). TTF-1 was diffusely positive in 20/22 SCCLu and 1/8 SCCCx, and negative in all SCCOH. p16 and cKIT demonstrated variable patterns of immunoreactivity in all cases. HPV was identified in 5/6 SCCCx; SCCOH and SCCLu were negative for HPV. Combined staining with WT-1 and TTF-1 will distinguish SCCOH from SCCLu and SCCCx with a sensitivity of 86% and specificity of 97%. HPV is specific for tumours of cervical origin, but p16 immunohistochemistry is not useful for this purpose. The presence of diffuse WT-1 supports a Müllerian origin for SCCOH, whereas the absence of cKIT and OCT3/4 argues against a germ cell origin.


Properties of white matter tract diffusivity in children with developmental dyslexia and comorbid attention deficit/hyperactivity disorder.
Developmental dyslexia (DD) and attention deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders. Individuals with DD or ADHD have both been shown to have deficits in white matter tracts associated with reading and attentional control networks. However, white matter diffusivity in individuals comorbid with both DD and ADHD (DD + ADHD) has not been specifically explored. Participants were 3rd and 4th graders (age range = 7 to 11 years; SD = 0.69) from three diagnostic groups ((DD (n = 40), DD + ADHD (n = 22), and typical developing (TD) (n = 20)). Behavioral measures of reading and attention alongside measures of white matter diffusivity were collected for all participants. DD + ADHD and TD groups differed in mean fractional anisotropy (FA) for the left and right Superior Longitudinal Fasciculus (SLF)-Parietal Terminations and SLF-Temporal Terminations. Mean FA for the DD group across these SLF tracts fell between the lower DD + ADHD and higher TD averages. No differences in mean diffusivity nor significant brain-behavior relations were found. Findings suggest that WM diffusivity in the SLF increases along a continuum across DD + ADHD, DD, and TD.


Deep Brain Stimulation Modulates Multiple Abnormal Resting-State Network Connectivity in Patients With Parkinson's Disease.
Deep brain stimulation (DBS) improves motor and non-motor symptoms in patients with Parkinson's disease (PD). Researchers mainly investigated the motor networks to reveal DBS mechanisms, with few studies extending to other networks. This study aimed to investigate multi-network modulation patterns using DBS in patients with PD. Twenty-four patients with PD underwent 1.5 T functional MRI (fMRI) scans in both DBS-on and DBS-off states, with twenty-seven age-matched healthy controls (HCs). Default mode, sensorimotor, salience, and left and right frontoparietal networks were identified by using the independent component analysis. Power spectra and functional connectivity of these networks were calculated. In addition, multiregional connectivity was established from 15 selected regions extracted from the abovementioned networks. Comparisons were made among groups. Finally, correlation analyses were performed between the connectivity changes and symptom improvements. Compared with HCs, PD-off showed abnormal power spectra and functional connectivity both within and among these networks. Some of the abovementioned abnormalities could be corrected by DBS, including increasing the power spectra in the sensorimotor network and modulating the parts of the ipsilateral functional connectivity in different regions centered in the frontoparietal network. Moreover, the DBS-induced functional connectivity changes were correlated with motor and depression improvements in patients with PD. DBS modulated the abnormalities in multi-networks. The functional connectivity alterations were associated with motor and psychiatric improvements in PD. This study lays the foundation for large-scale brain network research on multi-network DBS modulation.


Functional maturation of growth hormone cells in the anterior pituitary gland of the fetus.
Recent studies have disclosed the molecular mechanisms responsible for the phenotype determination of the anterior pituitary cell types. However, as far as growth hormone (GH) cells are concerned, particular extra-cellular cues are required for the initiation of GH and GH-releasing hormone (GHRH)-receptor gene production in addition to the expression of the cell type specific transcription factor, pit-1. The glucocorticoids play a principal role in the functional maturation of nascent GH cells in the fetal pituitary glands in rodents, inducing GH and GHRH-receptor gene expression, and establish the GH secretory system regulated by the brain in late gestation. Research supporting this role for glucocorticoid in the development of GH cells is discussed.


[Study on effect of fushenkeli on expression of TAK1 in human renal tubular epithelial cells and its possible mechanism].
To investigate the effects of fushenkeli on the expression of TAK1 in the proliferation of the renal tubular epithelial cells induced by TGF-beta1 and its possible mechanism. Human renal tubular epithelial (HK-2) cells were divided into five groups:blank control group, TGF-beta1 group (5 microg x L(-1)), intervention group 1 (5 microg x L(-1) of TGF-beta1 + 100 mg x L(-1) of fushenkeli), intervention group 2 (5 microg x L(-1) of TGF-beta1 + 500 mg x L(-1) of fushenkeli) and intervention group 3 (5 microg x L(-1) of TGF-beta1 + 1 g x L(-1) of fushenkeli). HK-2 proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay. Type IV collagen in the supernatants of the cultured HK-2 was detected by ELISA at 12, 24, 48 hours respectively. The protein and mRNA expressions of TAK1 was measured by Western blot and real-time quantitative PCR. 1) The cell proliferation and the expression of type IV collagen were increased compared with the control group (P<0.05, P<0.01), but they were decreased in intervention group. 2) The expressions of protein and mRNA of TAK1 in TGF-beta1 group were upregulating significantly compared with control group (P<0.01), but they were downregulating in intervention group, especially in intervention group 3. Fushenkeli could inhibits TAK1 expression induced by TGF-beta1 in the proliferation of HK-2 cell.


Radiofrequency Ablation of the Stellate Ganglion for Management of Acute Digital Ischemia: A Case Report.
The authors present a report of a pulsed radiofrequency ablation of the stellate ganglion performed on a patient with microemboli to the hand from a thrombosed abandoned arteriovenous fistula. The patient was initially managed using vasodilators and anticoagulation. However, the patient's skin mottling, pain, and decreased strength persisted. Ablation of the stellate ganglia increased perfusion to his hand and likely prevented amputation that has lasted for approximately 1 year. While radiofrequency ablation is more commonly used for pain syndromes, this is an example of its use in the treatment and potential treatment of acute ischemia.


Safety of dronedarone in routine clinical care.
The aim of this study was to examine mortality and liver disease among patients exposed to dronedarone. There has been concern about the safety of dronedarone, especially for patients with heart failure and permanent atrial fibrillation (AF). There have also been suspicions about liver toxicity. All 174,995 patients with a diagnosis of AF during 2010 to 2012 were identified in the Swedish Patient Register. Of these, 4,856 patients had received dronedarone according to the Swedish Drug Register, and 170,139 patients who had not were used as a control population. Mean follow-up was 1.6 years, with a minimal follow-up of 6 months. Patients prescribed dronedarone were younger (age 65.5 years vs. 75.7 years, p < 0.0001) and healthier than control patients. The annual mortality rate among patients who received dronedarone was 1.3% compared with 14.0% in the control population. There were no sudden cardiac deaths and no deaths related to liver failure among patients who received treatment with dronedarone. After propensity score matching and adjustment for cofactors, patients who received dronedarone had lower mortality than other AF patients (hazard ratio [HR]: 0.41; 95% confidence interval [CI]: 0.33 to 0.51). Dronedarone patients with heart failure had lower mortality than other heart failure patients (HR: 0.40; 95% CI: 0.30 to 0.53). They also had lower mortality than expected from the general population (standardized mortality ratio: 0.67; 95% CI: 0.55 to 0.78), which indicates the selection of low-risk patients. The risk of liver disease was not increased (HR: 0.57; 95% CI: 0.34 to 0.92). Dronedarone, as prescribed to AF patients in Sweden, has not exposed patients to increased risks of death or liver disease.


Bulbar and Limb Myorhythmia with "Smooch Sign": A Distinctive Movement Disorder in an Adult Patient with Reversible Anti-NMDA Receptor Encephalitis Associated with an Ovarian Teratoma.
Anti-N-Methyl-D-Aspartate receptor encephalitis is a recently described entity (Dalmau et al. 2007, 2008) that may present with a variety of complex movements in addition to other features (Kleinig et al. 2008). The purpose of our presentation of such a patient is twofold: (1) to characterize these complex oculo-oro-linguo-masticatory and limb movements with "smooch sign" as myorhythmia, based on a combined clinical and electrophysiological analysis (Masucci et al. 1984); and (2) to document possibly characteristic EEG evolution in the course of observation in our institution for three weeks from diffuse slowing to evolving rhythmic delta activity, which may represent a pattern of electrographic seizure activity.


Finite element modeling of the human cervical spinal cord and its applications: A systematic review.
Finite element modeling (FEM) is an established tool to analyze the biomechanics of complex systems. Advances in computational techniques have led to the increasing use of spinal cord FEMs to study cervical spinal cord pathology. There is considerable variability in the creation of cervical spinal cord FEMs and to date there has been no systematic review of the technique. The aim of this study was to review the uses, techniques, limitations, and applications of FEMs of the human cervical spinal cord. A literature search was performed through PubMed and Scopus using the words finite element analysis, spinal cord, and biomechanics. Studies were selected based on the following inclusion criteria: (1) use of human spinal cord modeling at the cervical level; (2) model the cervical spinal cord with or without the osteoligamentous spine; and (3) the study should describe an application of the spinal cord FEM. Our search resulted in 369 total publications, 49 underwent reviews of the abstract and full text, and 23 were included in the study. Spinal cord FEMs are used to study spinal cord injury and trauma, pathologic processes, and spine surgery. Considerable variation exists in the derivation of spinal cord geometries, mathematical models, and material properties. Less than 50% of the FEMs incorporate the dura mater, cerebrospinal fluid, nerve roots, and denticulate ligaments. Von Mises stress, and strain of the spinal cord are the most common outputs studied. FEM offers the opportunity for dynamic simulation, but this has been used in only four studies. Spinal cord FEM provides unique insight into the stress and strain of the cervical spinal cord in various pathological conditions and allows for the simulation of surgical procedures. Standardization of modeling parameters, anatomical structures and inclusion of patient-specific data are necessary to improve the clinical translation.


A systematic laboratory approach for the identification of drugs in presumably poisoned (overdosed) patients.
A systematic approach for evaluating the abuse of drugs in patients presenting to the hospital emergency room is presented from the laboratory point of view. This comprehensive screen involves qualitative colorimetric tests, ultraviolet (UV) spectrophotometry, thin layer chromatography (TLC), gas chromatography (GC), and gas chromatography - mass spectrometry (GC-MS). Laboratories with varying resources can adopt the screen presented. Thirty-two cases were evaluated with the methodology; these included tricyclic antidepressants, benzodiazepines, phencyclidine, methaqualone, and barbiturates. Increasing misuse of drugs requires that the clinical laboratory have a systematic approach to identify and confirm the presence of these drugs in emergency room patients.


A simple, semiselective medium for anaerobic isolation of anginosus group streptococci from patients with chronic lung disease.
The anaerobic isolation of anginosus group streptococci (AGS) from respiratory specimens containing diverse microbiota using a semiselective blood agar medium incorporating nalidixic acid and sulfamethazine (NAS) is described. AGS were detected in 60% of tested sputa from patients with cystic fibrosis, chronic obstructive pulmonary disease, and bronchiectasis. This demonstrates NAS to be a diagnostic tool for detecting AGS within the complex microbial communities associated with chronic lung disorders.


Cutaneous manifestations of NAXD deficiency - A case report.
Metabolism is a tightly regulated sequence of events, supported by key reactions between enzymes and enzyme-specific substrates. These reactions have the potential to produce metabolic side products that can have deleterious effects to further key metabolic reactions. The nicotinamide repair system consists of two partner enzymes, NAD(P)HX epimerase (NAXE) and NAD(P)HX dehydratase (NAXD). These enzymes regulate the levels of metabolic side products. Here we present a case of an 11-month old child who presented to our paediatric department with pyrexia, lethargy and multiple cutaneous lesions on the background of NAXD deficiency, a lethal neurometabolic disorder of early childhood. Despite early intervention with intravenous antibiotics, the patient failed to improve and subsequently passed away. The skin lesions were thought to be a consequence of systemic disease rather than a propagator of infection. Clinicians should be aware of this incredibly rare metabolic disease, its potential to cause widespread systemic dysfunction and the developing avenues for management.


Intra-operative electrocochleography to monitor cochlear potentials during acoustic neuroma excision.
Intra-operative electrocochleography (ECochG) was used in an attempt to monitor the action potential of the cochlear nerve during acoustic neuroma surgery in 14 patients with useful pre-operative hearing. Five patients had ECochG potentials preserved and yet only three could hear when tested audiometrically later. Of those losing the potentials intra-operatively all were subsequently deaf and the pattern of waveform loss allowed determination of the probable cause of hearing loss. Complete excision of the tumour was achieved in each case regardless of the ultimate effect on the AP as it was not felt justified to risk subsequent recurrence. In common with other studies one of the best prognostic factors for these preservation of hearing was found to be the size of the tumour.


Chronic musculoskeletal pain and functional status in juvenile rheumatoid arthritis: an empirical model.
An empirical model is proposed and tested on variables hypothesized to influence functional status in 23 children with juvenile rheumatoid arthritis experiencing chronic musculoskeletal pain. Child psychological adjustment, family psychosocial environment, chronic musculoskeletal pain, and disease activity were entered into multiple regression analyses to statistically predict 4 functional status criterion variables: activities of daily living (ADL), activities involvement, school functioning, and social functioning. Predictor variable relationships were found for all 4 functional status criterion variables, suggesting initial support for this empirical model of functional status in children with juvenile rheumatoid arthritis experiencing chronic musculoskeletal pain.


Executive Function Brain Network Activation Predicts Driving Hazard Detection in ADHD.
Drivers with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are at increased risk of experiencing driving difficulties. An important aspect of driving safety and skill involves hazard detection. This functional magnetic resonance imaging study examined the neural responses associated with driving hazard detection in drivers with ASD, ADHD, and typically developing (TD) drivers. Forty participants (12 ASD, 15 ADHD, 13 TD) ages 16-30 years completed a driving simulator task in which they encountered social and nonsocial hazards; reaction time (RT) for responding to hazards was measured. Participants then completed a similar hazard detection task in the MRI scanner so that neural response to hazards could be measured. Activation of regions of interest considered part of the executive function (EF) and theory of mind (ToM) networks were examined and related to driving simulator behavior. Results showed that stronger activation of the EF network during social hazard processing, including the bilateral dorsolateral prefrontal cortex and posterior parietal cortex, was associated with faster RT to social hazards among drivers with ADHD, but not among drivers with ASD. This provides the first evidence of a relationship between EF network brain activation and driving skills in ADHD and suggests that alterations in this network may underlie driving behavior. In comparison, the current study did not observe a relationship between ToM network activation and RT to social hazards in any group. This study lays the groundwork for relating neural activation to driving behavior among individuals with NDDs.


pH dependence of the reaction rate of His 48 with p-bromophenacyl bromide and of the binding constant to Ca2+ of the monomeric forms of intact and alpha-NH2 modified phospholipases A2 from Trimeresurus flavoviridis.
The phospholipase A2 of Trimeresurus flavoviridis was found to show monomer-dimer equilibria. Under conditions where the enzyme exists predominantly in the monomeric form, the chemical reaction rate of p-bromophenacyl bromide (BPB) with the catalytic group, His 48, was studied at 25 degrees C and ionic strength 0.2 by measuring the residual enzymic activity using a fluorescent substrate, 1,2-bis[4-(1-pyreno)butanoyl]-sn-glycero-3-phosphorylcholine (diPBPC). The pH-dependence curve of the reaction rate for the intact enzyme was practically the same as that for the modified enzyme, in which the N-terminal alpha-NH2 group had been selectively converted into an alpha-keto group. The pH-dependence curves were monophasic (sigmoidal) with a midpoint at pH 7.53, which corresponds to the pKa value of His 48. The pH dependences of the binding constants of Ca2+ to the intact and the alpha-NH2 modified enzymes were also studied at 25 degrees C and ionic strength 0.2 by measuring the changes in the tryptophyl fluorescence and/or aromatic CD spectra. The pH-dependence data for the modified enzyme were interpreted in terms of participation of Asp 49 (pKa 5.40) and His 48 (pKa 7.53), assuming that the protonation of Asp 49 competes with the Ca2+ binding. The pH-dependence data for the intact enzyme were similarly interpreted in terms of participation of the alpha-NH2 group (pKa 9.40) in addition to that of Asp 49 (pKa 5.40) and His 48 (pKa 7.53).(ABSTRACT TRUNCATED AT 250 WORDS)


Probity: a protein identification algorithm with accurate assignment of the statistical significance of the results.
An algorithm for protein identification based on mass spectrometric proteolytic peptide mapping and genome database searching is presented. The algorithm ranks database proteins based on direct calculation of the probability of random matching and assigns the statistical significance to each result. We investigate the performance of the algorithm by simulation and show that the algorithm responds to random data in the desired manner and that the statistical significance computed indicates the risk that a particular identification result is false.


Group feeding as a strategy for exploiting food resources in the burnet moth Pryeria sinica.
Pryeria sinica (Zygaenidae) larvae feed on young and growing leaves of Euonymus japonicus in groups. The larvae often defoliate their host plant. Hence, the larvae are occasionally subject to serious shortage in food resources. We hypothesize that larval aggregation is an adaptation for the economical utilization of limited food resources. To test this hypothesis, the patterns of resource utilization were studied on larvae settled on shoots of host plant in various group sizes. The amount of food resources in a shoot was affected by the following three factors; (1) shoot growth, (2) food consumption of larvae, and (3) inhibition of growth or degeneration of shoot by larval activity on it. These factors were measured and the efficiency in resource utilization was compared among groups of varied sizes. The loss in resources caused by the third factor was found to be decreased with group size, i.e., the larger the group size, the larvae utilized the food resources more economically. The advantages of group feeding in survival and reproduction of this species were discussed using a simple graphical model.


Warping of cross sections in the torsion of long bones with internal fracture fixation plates.
Torsion of noncircular beams results in warping of each cross section. When noncircular cross sections are constrained to remain plane, the resulting shear stress distribution is different from what Saint Venant torsion (with warping) would predict. This has practical implications to the stress analysis of plated long bones subjected to torsional loadings. Analyses in which warping is not allowed predict incorrect stress fields in the plate and bone and overpredict the amount of stress shielding associated with fracture plate fixation.


From functional pulmonary atresia to right ventricular restriction. Long term follow up of Uhl's anomaly.
We report a 14 year old boy who presented as a neonate with functional pulmonary atresia due to Uhl's disease with emphasis on the later detection of restrictive right ventricular physiology.


A qualitative exploration of alternative strategies for building community health partnerships: collaboration- versus issue-oriented approaches.
Broad-based community partnerships are seen as an effective way of addressing many community health issues, but the partnership approach has had relatively limited success in producing measurable improvements in long-term health outcomes. One potential reason, among many, for this lack of success is a mismatch between the goals of the partnership and its structure/membership. This article reports on an exploratory empirical analysis relating the structure of partnerships to the types of issues they address. A qualitative analysis of 34 "successful" community health partnerships, produced two relatively clear patterns relating partnership goals to structure/membership: (1) "collaboration-oriented" partnerships that included substantial resident involvement and focused on broader determinants of health with interventions aimed at producing immediate, concrete community improvements; and (2) "issue-oriented" partnerships that focused on a single, typically health-related issue with multilevel interventions that included a focus on higher-level systems and policy change. Issue-oriented partnerships tended to have larger organizations governing the partnership with resident input obtained in other ways. The implication of these results, if confirmed by further research, is that funders and organizers of community health partnerships may need to pay closer attention to the alignment between the membership/structure of a community partnership and its goals, particularly with respect to the involvement of community residents.


Hemophilus influenzae epididymo-orchitis.
Epididymo-orchitis is an unusual cause of acute scrotal swelling in early childhood. We report the coexistence of otitis media and epididymo-orchitis owing to Hemophilus influenzae, type b in 2 children.


Th17 pathway signatures in a large Indian cohort of Guillain Barré syndrome.
The etiopathogenesis of Guillain Barré Syndrome (GBS) is inadequately understood. The role of immuno-inflammatory Th17 pathway was examined in GBS patients by genetic, gene expression and biochemical studies. Genotyping of G197A single nucleotide polymorphism within IL17 gene was carried out by PCR-RFLP method in 220 GBS patients. Quantification of gene expression of STAT3 and RORC and estimation of plasma level of IL-17A were carried out in a subset of patients. Significantly increased STAT3 gene expression in lymphocytes and plasma IL-17A levels were observed in GBS patients. This study adds new dimension and reinforces important implications of Th17 pathway in GBS.


Atraumatic splenic rupture precipitated by splenic vein thrombosis.
We present the case of a 59-year-old man with atraumatic splenic rupture because of splenic vein thrombosis who was successfully treated with splenic artery embolization.


[Early recognition of hypoxic lesions in the cerebellum using Lie staining (HBFP staining)].
Using the Purkinje cells of the cerebellum from 42 rapidly and 28 slowly dying patients, we tried to find a correlation between the premortal hypoxie in brain and the result of HBFP staining. We found four different stages of staining and discuss here the causes of staining and false results.


Homogeneous photoelectrochemical biosensor for sensitive detection of omethoate via ALP-mediated pesticide assay and Bi2S3@Bi2Sn2O7 heterojunction as photoactive material.
A simple homogeneous photoelectrochemical (PEC) sensing platform based on an alkaline phosphatase (ALP)-mediated pesticide assay was established for the sensitive detection of omethoate (OM). The Bi2S3@Bi2Sn2O7 heterojunction was used as a photoactive material to provide stable background photocurrent signals. The inhibition of OM on ALP and PEC determination was carried out in the homogeneous system. In the absence of OM, dephosphorylation of L-ascorbic acid 2-phosphate trisodium salt (AAP) was catalyzed by ALP to produce the enzyme-catalyzed product (L-ascorbic acid, AA). AA, as an electron donor, could capture photogenerated holes on the Bi2S3@Bi2Sn2O7 heterojunction, thus inhibiting the recombination of electron holes to achieve an increase of the photocurrent signal. When the OM was introduced, the enzyme activity of ALP was reduced due to the organophosphorus pesticides (OPs)-based enzyme inhibition, and the AA produced by catalytic hydrolysis was also reduced, thus reducing the photocurrent signal. Compared with the traditional PEC sensor for OPs, this homogeneous PEC sensor avoided immobilization procedures, covalent labeling, separation, and the steric hindrance effect caused by immobilized biomolecules, which achieved high recognition efficiency and caused a reduction in analysis time. Additionally, an ALP-mediated pesticide assay for the determination of OPs with a simplified experimental process further improved the stability and reproducibility of the PEC sensor. The PEC sensor showed high sensitivity to the target OM within a dynamic range of 0.05 ~ 500 ng mL-1, and the detection limit was 0.0146 ng mL-1. Additionally, the PEC biosensing system showed good selectivity and anti-interference ability, and exhibited a satisfactory result in spinach and mustard samples. A homogeneous PEC biosensor based on ALP inhibition strategy was constructed for OM detection in vegetable samples via Bi2S3@Bi2Sn2O7 heterojunction as the photoactive substrate material.


The kitchen as therapy: qualitative assessment of an integrative cuisine workshop for patients undergoing chemotherapy.
Patients undergoing chemotherapy frequently suffer from gastrointestinal (GI) symptoms and functional difficulties in preparing and eating meals. We conducted a qualitative assessment of an integrative cuisine workshop program designed for patients receiving chemotherapy, examining the effects of the program on patient-reported GI symptoms and nutritional challenges. Patients were referred to a complementary/integrative medicine (CIM)-trained physician for consultation, followed by a patient-tailored treatment program. Patients with GI-related symptoms and nutritional concerns were offered a two-session integrative cuisine workshop program. The effects of the workshops were examined using inductive and deductive qualitative research methodologies. Patient narratives, as recorded in the Measure Yourself Concerns and Wellbeing (MYCAW) study tool, and electronic medical files were analyzed. Of 125 patients referred to the integrative cuisine program, 86 participated in at least one workshop. Participants and non-participants had similar demographic and disease-related characteristics, as well as quality-of-life (QOL)-related concerns. Inductive analysis suggested that participation in the workshops was helpful in developing social relationships, providing emotional support, and enhancing spirituality and nutritional awareness. Implementing the recommended changes at home led to improved QOL-related outcomes. The predominant themes derived from deductive analysis were the implementation of dietary changes and improved gastrointestinal and emotional issues. Chemotherapy-treated patients participating in an integrative cuisine workshop program showed improved QOL outcomes, specifically GI and emotional-related symptoms, and a reduction in nutritional and functional concerns. Increased knowledge and awareness of nutrition and supplement use ultimately resulted in implementation of the CIM recommendations by patients at home.


Anesthesia for pediatric orthotopic liver transplantation.
The anesthetic management of 68 liver transplantations in 50 pediatric patients is described. The surgical technique is briefly reviewed. The selection of an anesthetic technique was not as important as management of numerous intra-operative problems. Citrate intoxication secondary to massive blood transfusion in the hypothermic anhepatic patient is a major problem, as are coagulation deficiencies. Hyperkalemic cardiac arrest, also a significant hazard, produced the only intraoperative death.


Rhamnoarabinosyl and rhamnoarabinoarabinosyl side chains as structural features of coffee arabinogalactans.
The hot water soluble green coffee arabinogalactans, representing nearly 7% of total coffee bean arabinogalactans, were characterized by (1)H and (13)C NMR and, after partial acid hydrolysis, by ESI-MS/MS. Data obtained showed that these are highly branched type II arabinogalactans covalently linked to proteins (AGP), with a protein moiety containing 10% of 4-hydroxyproline residues. They possess a beta-(1-->3)-Galp/beta-(1-->3,6)-Galp ratio of 0.80, with a sugars composition of Rha:Ara:Gal of 0.25:1.0:1.5, and containing 2mol% of glucuronic acid residues. Beyond the occurrence of single alpha-L-Araf residues and [alpha-L-Araf-(1-->5)-alpha-L-Araf-(1-->] disaccharide residues as side chains, these AGPs contain unusual side chains at O-3 position of the beta-(1-->6)-linked galactopyranosyl residues composed by [alpha-L-Rhap-(1-->5)-alpha-L-Araf-(1-->] and [alpha-L-Rhap-(1-->5)-alpha-L-Araf-(1-->5)-alpha-L-Araf-(1-->] oligosaccharides. Rhamnoarabinosyl and rhamnoarabinoarabinosyl side chains are reported for the first time as structural features of plant arabinogalactan-proteins.


In vitro model systems permitting the analysis of the differentiation of mammalian progenitor cells either into neurons or into glial cells.
The peripheral nervous system, including both neurons and Schwann cells, is derived almost entirely from the neural crest. We described here the use of the migratory properties of mouse neural crest cells and chemically defined conditions to differentiate them in vitro into neuronal derivatives.


Two mechanisms necessary for the stable inheritance of plasmid RP4.
Plasmid RP4 is stably maintained in strains of Escherichia coli and other Gram-negative bacteria. Inactivation of the plasmid primase gene (pri) or removal of the PstIC fragment gave RP4 derivatives that are slightly unstably maintained in E. coli. Removal of the Tn 1 multimer resolution system (res and tnpR) did not lead to any detectable plasmid loss. Removal of all three of these regions, however, gave rise to pNJ5000 which is lost at high frequency. We have dissected the mechanisms causing this phenomenon. In contrast to RP4, pNJ5000 accumulates significantly as plasmid multimers in a Rec+ host; in a recA host, multimers are not seen and the plasmid is stably maintained. Multimers therefore appear to form by recA-mediated homologous recombination and cause plasmid instability, perhaps by interfering with partition. We demonstrate a mechanism provided by the PstIC fragment which acts on multimers analogously to the Tn1/3 resolution system on plasmid cointegrates, being effective only when cloned in cis. The loss of pri, on the other hand, can be complemented in trans. Our results are consistent with the view that primase prevents multimers forming (rather than resolving them once formed), perhaps by binding specifically to single-stranded regions of the plasmid and preventing homologous pairing.


Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity.
HIV-1 Nef enhances virion infectivity by counteracting host restriction factor SERINC5; however, the impact of natural Nef polymorphisms on this function is largely unknown. We characterize SERINC5 downregulation activity of 91 primary HIV-1 subtype B nef alleles, including isolates from 45 elite controllers and 46 chronic progressors. Controller-derived Nef clones display lower ability to downregulate SERINC5 (median 80% activity) compared with progressor-derived clones (median 96% activity) (p = 0.0005). We identify 18 Nef polymorphisms associated with differential function, including two CTL escape mutations that contribute to lower SERINC5 downregulation: K94E, driven by HLA-B∗08, and H116N, driven by the protective allele HLA-B∗57. HIV-1 strains encoding Nef K94E and/or H116N display lower infectivity and replication capacity in the presence of SERINC5. Our results demonstrate that natural polymorphisms in HIV-1 Nef can impair its ability to internalize SERINC5, indicating that variation in this recently described function may contribute to differences in viral pathogenesis.


Ru-Catalyzed Chemo- and Enantioselective Hydrogenation of 2,4-Pentadien-1-ones: Synthesis of Chiral 2,4-Pentadien-1-ols.
The asymmetric hydrogenation of 2,4-pentadien-1-ones has been achieved by using trans-RuCl2[(R)-XylylSunPhos][(R)-Daipen] as a catalyst under basic conditions. This hydrogenation demonstrated exclusive C1-carbonyl selectivity, and thus the conjugated 2,4-diene motifs remained untouched, which provides a synthetically useful method for various chiral 2,4-pentadien-1-ols.


Estrogenic activity of bis(4-hydroxyphenyl)methanes with cyclic hydrophobic structure.
Monoalkylated bis(4-hydroxyphenyl)methanes (e.g., 1) are reported to show weak binding affinity for estrogen receptor (ER). We hypothesized that introduction of appropriately located hydrophobic substituents in these compounds would increase the binding affinity. Indeed, we found that bis(4-hydroxyphenyl)methane bearing a 3,3-dimethylcyclohexyl group (7) shows potent ERα binding affinity, comparable to that of estradiol. Bulkier substituents could be introduced at the 3,3-position without decreasing the affinity. However, the position of the substituents was critical: the 4,4-dimethylcyclohexyl derivative (2) showed very weak binding affinity. The compounds with high ER-binding affinity showed predominantly agonistic activity, together with weak antagonistic activity at high concentration, in cell proliferation assay with human breast cancer cell line MCF-7. Further structure-function studies of these compounds and their derivatives might lead to the development of more selective and potent estrogen receptor modulators.


[Esterase spectrum in the hepatocytes and Kupffer cells of regenerating liver].
The esterase spectra of hepatocytes and Kupffer's cells from the regenerating rat liver were studied following partial hepatectomy. The starch-gen electrophoresis method was used. The relative number of Kupffer's cells, per cent of phagocytising Kupffer's cells, as well as mitotic rate of hepatocytes were determined. Hepatocyte esterase spectra from the intact liver consisted of six, whereas that of Kupffer's cells--of five zones of the enzyme activity. A "simplification" of hepatocyte esterase spectra could be seen 2 1/2 hours after partial hepatectomy. Additional activity bands appeared in 9 hours; these could be identified for a period of up to 24 hours after the operation. The initiar esterase spectrum was regained within 48 hours. The same tendency was observed in Kupffer's cells, but no full restoration of the enzyme spectra was observed 72 hours after partial hepatectomy.


scFates: a scalable python package for advanced pseudotime and bifurcation analysis from single-cell data.
scFates provides an extensive toolset for the analysis of dynamic trajectories comprising tree learning, feature association testing, branch differential expression and with a focus on cell biasing and fate splits at the level of bifurcations. It is meant to be fully integrated into the scanpy ecosystem for seamless analysis of trajectories from single-cell data of various modalities (e.g. RNA and ATAC). scFates is released as open-source software under the BSD 3-Clause 'New' License and is available from the Python Package Index at https://pypi.org/project/scFates/. The source code is available on GitHub at https://github.com/LouisFaure/scFates/. Code reproduction and tutorials on published datasets are available on GitHub at https://github.com/LouisFaure/scFates_notebooks. Supplementary data are available at Bioinformatics online.


A pH-responsive cell-penetrating peptide-modified liposomes with active recognizing of integrin αvβ3 for the treatment of melanoma.
The use of pH-responsive cell-penetrating peptides (CPPs) is an attractive strategy for drug delivery in vivo, however, they still could not actively target to the desired sites. Here, we designed a pH-responsive CPP (TR) with the ability of active targeting to integrin αvβ3, which was a tandem peptide consisted of active targeting ligand peptide (c(RGDfK)) and pH-responsive CPP (TH). The targeting efficiency of TR with integrin was evaluated by molecular simulation and docking studies. The affinity assays of TR peptide modified liposomes (TR-Lip) at pH7.4 and pH6.5 demonstrated adequately the pH-responsive binding efficacy of TR-Lip with integrin αvβ3. The cellular uptake of CFPE-labeled TR-Lip on integrin αvβ3-overexpressing B16F10 cells was 41.67-, 30.67-, and 11.90-fold higher than that of CFPE-labeled PEG-, RGD-, and TH-modified liposomes at pH6.5, respectively, suggesting that TR-Lip could not only actively target to αvβ3-overexpressing cells compared to TH-Lip, but also significantly increased cellular uptake compared to RGD-Lip. At the concentration of 20μg/mL paclitaxel (PTX), the killing activity of PTX-loaded TR-Lip (PTX-TR-Lip) against B16F10 cells was 1.80-, 1.45-, 1.30-, 1.15-time higher than that of PTX-loaded PEG-, RGD-, TH-modified liposomes and free PTX at pH6.5, respectively. In vivo imaging displayed the maximum accumulation of DiD-labeled TR-Lip at tumor sites compared to the other groups. Tumor inhibition rate of B16F10 tumor-bearing mice treated with PTX-TR-Lip was 85.04%, relative to that of PBS. In B16F10 tumor-bearing mice, PTX-TR-Lip showed significantly higher survival rate compared with the other groups. Collectively, all the results in vitro and in vivo suggested that TR-Lip would be a potential delivery system for PTX to treat integrin αvβ3-overexpressing tumor-bearing mice.


Vascular homografts for vessel substitution in skeletal and soft tissue sarcomas of the limbs.
Large vessel involvement by skeletal and soft tissue sarcomas of the extremities does not change the modern limb sparing surgery for those neoplasms. An arterial and, if the vein is open, a venous bypass should always be offered to any patient young or old, with high or low grade sarcoma, because preserving the limb permits quicker rehabilitation, which is particularly useful in the case of a short life expectancy. In 650 cases of skeletal sarcomas, 10 arterial (1.5%) and four venous bypasses were done, all with autologous veins but one in PTFE; we had no problems except a silent arterial occlusion. Of 1000 patients with soft tissue sarcomas, 32 (3%) had vessel involvement permitting limb sparing surgery. The arterial bypass, which is the limb-saving operation, was performed 16 times with a PTFE with one early occlusion and four cases of prosthesis infection, with two amputations despite redo operation with an autologous vein. The more recent 16 cases were, therefore, always done with biological vessel substitution--autologous vein or tissue bank vessel--with only one infection that healed without operation and one case of homograft rupture followed by amputation. Since 1999 in all 13 resected cases with an open vein, we did the arterial and the venous bypass (twice PTFE, six autologous vein, and five bank vessel) with the aim of avoiding postoperative venous hypertension, but only four of the venous bypasses remained open. Venous bypasses are a harmless, but still experimental, procedure.


Trends in clinical profile and medical treatments of atrial fibrillation patients over the last 10 years.
We sought to define trends in AF prevalence and its medical management using recent data based on data from two cross-sectional studies performed in a European country in 1999 and 2009. CARDIOTENS 1999 and CARDIOTENS 2009 were two observational, cross-sectional, multicenter studies. Patients were recruited in from primary care and cardiology outpatient clinics. A total of 32 051 and 25 137 subjects were analyzed in the two studies, 1540 and 1524 of them, respectively, diagnosed with AF. Over the course of the study period there was an increase in the prevalence of AF (from 4.8% to 6.1%), mainly due to the higher prevalence of AF in patients aged over 70 years (24.7% vs. 37.1%). Furthermore, patients with AF had a higher prevalence of hypertension (64.9% vs. 87.0%), diabetes (19.0% vs. 37.4%), heart failure (30.8% vs. 34.8%), coronary artery disease (23.0% vs. 25.8%) and previous stroke (1.5% vs. 8.9%). An overall increase in prescription of antithrombotic/antiplatelet therapy was observed (33.0% vs. 62.7% and 31.0% vs. 38.2% respectively); the difference observed in 1999 between prescription of oral anticoagulation by general practitioners and cardiologists was not seen in the later study. Differences in prescription of angiotensin-converting enzyme inhibitors (28.0% vs. 40.7%), angiotensin receptor blockers (10.0% vs. 40.0%), beta-blockers (14.0% vs. 41.5%) and calcium channel blockers (21.0% vs. 34.9%) were also identified. The number of patients with AF and a higher risk for thromboembolic events increased over the last 10 years. More aggressive antithrombotic treatment has been observed, especially in older patients.


Urinary excretion of deuterated metabolites in patients with tyrosinemia type I after oral loading with deuterated L-tyrosine.
1. The metabolic fate of orally given deuterated L-tyrosine, 50 mg/kg body weight, was investigated in seven patients with tyrosinemia type I in order to obtain evidence that the primary defect is at the level of fumarylacetoacetase. 2. The absence of fumarylacetoacetase could be proved in liver biopsy specimens obtained from four patients. 3. All patients excreted deuterated succinylacetoacetate and deuterated succinylacetone was detected in six out of seven. The total amount of these compounds was rather low; maximal 8.3% of the dose. The peak of the excretion occurred 3-6 h after loading, indicating an endogenous formation of the metabolites. 4. All patients excreted deuterated 4-hydroxyphenyl acids, probably reflecting secondary 4-hydroxyphenylpyruvate dioxygenase deficiency connected with liver damage. 5. No evidence for other secondary routes of tyrosine metabolism was found.


Dispositions and tissue residue of zearalenone and its metabolites α-zearalenol and β-zearalenol in broilers.
Zearalenone (ZEA) is a secondary fungal metabolite produced mainly by a Fusarium graminearum. To clarify the toxicokinetics, and residues of ZEA and its major metabolites α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL) in chickens, ZEA was then administered intravenously (iv) or orally (po) to broiler chickens at a dosage of 1.2 mg/kg body weight. The concentrations of ZEA, α-ZOL and β-ZOL in the plasma and various tissues were quantified using LC-MS/MS. The plasma concentrations of ZEA were measurable up to 2 h after iv and po administration, and the concentrations of α-ZOL and β-ZOL were detected up to 4 h after both types of administration. A two-compartment model was developed to describe the toxicokinetic of ZEA in broilers. The values of t1/2β and Vd were 1.36 ± 0.29 h and 6.40 ± 0.89 l/kg, respectively. The absolute oral bioavailability was 29.66 ± 5.6%. ZEA, α-ZOL and β-ZOL were measurable in the vital organs after po administration. These results suggest that ZEA is absorbed from the gastrointestinal tract and it has ability to penetrate into the various tissues of broiler chickens.


HistoCheck. Evaluating structural and functional MHC similarities.
The HistoCheck webtool provides clinicians and researchers with a way of visualizing and understanding the structural differences among related major histocompatibility complex (MHC) molecules. In the clinical setting, human leukocyte antigen (HLA) matching of hematopoietic stem cell donors and recipients is essential to minimize "graft versus host disease" (GvHD). Because exact HLA matching is often not possible, it is important to understand which alleles present the same structures (HLA-peptide complexes) to the T-cell receptor (TCR) despite having different amino acid sequences. HistoCheck provides a summary of amino acid mismatches, positions, and functions as well as 3-dimensional (3D) visualizations. In this chapter, we describe how HistoCheck is used and offer advice in interpreting the query results.


Trastuzumab-induced cardiotoxicity in elderly women with HER-2-positive breast cancer: a meta-analysis of real-world data.
We conducted a meta-analysis to assess the overall risk of cardiac toxicity associated with trastuzumab treatment in elderly breast cancer patients. We searched databases from PubMed, EMBASE and Cochrane Central Registry of Controlled Trials to identify relevant studies. Statistical analyses were conducted to calculate the incidence rate, overall hazard ratio (HR) and 95% CIs using a fixed effects model. A total of 116,342 and 360 elderly patients from five cohort studies and two randomized clinical trials (RCTs) were included for analysis. The pooled incidences of symptomatic congestive heart failure (CHF) and CHF/HF/CM were 6.4% (95% CI 4.1% - 9.4) and 16.4% (95% CI 16.19% - 16.61) in patients with median age of 67.5 years from two RCTs and in patients with median age of 67.5 (60 - 75), 71 (66 - 80+), 74.5 (65 - 89), 75 (66 - 81+) and 79.5 (60 - 99) from five cohort studies, respectively. Trastuzumab was significantly correlated with an increased risk of defined cardiac toxicities in five cohort studies (HR = 1.89, 95% CI 1.72 - 2.07, p < 0.00001) and two RCTs (HR = 3.00, 95% CI 1.71, 5.26, p < 0.00001). Sub-group analysis showed that the anthracycline-based chemotherapy increased the risk of CHF/HF and CM in patients among five cohort studies (HR = 2.16, 95% CI: 1.8 - 1.87, p < 0.00001). Trastuzumab is likely associated with an increased risk of cardiac toxicity in elderly patients with HER-2-positive breast cancer. Carefully monitoring cardiac function in elderly patients receiving trastuzumab, particularly with concurrent use of anthracycline, is warranted.


The Blalock-Taussig shunt in the first two years of life: a safe and effective procedure.
Many surgeons have been reluctant to perform Blalock shunts in patients who are in infancy or early childhood (less than 24 months old) and have done instead direct aortopulmonary anastomoses. Recently, others have advocated complete repair of tetralogy of Fallot in early infancy because of the high mortality of direct aortopulmonary shunts. We believe the Blalock-Taussig anastomosis is a safe and effective palliative procedure for all infants with inadequate pulmonary blood flow regardless of size. During the past nine years, 24 babies less than 2 years old who were followed had construction of Blalock-Taussig anastomosis for inadequate pulmonary blood flow. There were no operative deaths and no shunt-related late deaths. Of the 24 babies, 12 were less than 12 months old. Eighteen of the 24 had tetralogy of Fallot. The remaining 6 had a variety of lesions with inadequate pulmonary blood flow. The mean weight of the entire group was 7.3 +/- 1.6 kg. Of those infants less than 12 months old, the mean weight was 6.8 +/- 2.0 kg. More than 6 months following construction of the shunt, 2 babies died from sepsis unrelated to cardiovascular status. All infants had adequate but not excessive pulmonary blood flow after shunting. There were no late shunt failures.


Biological activity of oxadiazole and thiadiazole derivatives.
The 5-membered oxadiazole and thiadiazole scaffolds are the most privileged and well-known heterocycles, being a common and essential feature of a variety of natural products and medicinal agents. These scaffolds take up the center position and are the core structural components of numerous drugs that belong to different categories. These include antimicrobial, anti-tubercular, anti-inflammatory, analgesic, antiepileptic, antiviral, and anticancer agents. In this review, we mostly talk about the isomers 1,2,4-oxadiazole and 1,3,4-thiadiazole because they have important pharmacological properties. This is partly because they are chemical and heat resistant, unlike other isomers, and they can be used as bio-isosteric replacements in drug design. We are reviewing the structural modifications of different oxadiazole and thiadiazole derivatives, more specifically, the anti-tubercular and anticancer pharmacological activities reported over the last 5 years, as we have undertaken this as a core area of research. This review article desires to do a thorough study and analysis of the recent progress made in the important biological isomers 1,2,4-oxadiazole and 1,3,4-thiadiazol. This will be a great place to start for future research. KEY POINTS: • Five-membered heterocyclic compound chemistry and biological activity recent survey. • Synthesis and pharmacological evolution of 1,2,4-oxadiazole and 1,3,4-thiadiazole are discussed in detail. • The value and significance of heterocyclic compounds in the field of drug designing are highlighted.


Ethanediol monoester hydrolysis by monoacylglycerol lipase of rat liver microsomes.
The hydrolysis of long-chain monoester of ethanediol by rat,liver subcellular fractions was investigated in order to define the carboxylic acid ester hydrolase involved and to localize the enzymic activity. We found that with 1-O-hexadecanoyl [U-14C]ethanediol as substrate, hydrolytic activity was foremost associated with the rough microsomal fraction. The pH optimum occurred at 8.5. The apparent Km and V values were 6.5 . 10(-4) M and 13 mumol/h per mg microsomal protein, respectively. Enzymic activity was inhibited by p-chloromercuribenzoate and by diisopropylfluorophosphate, whereas NaF was less effective and CaCl2 did not affect apparent activity. Amongst a number of carboxylic acid esters tested as substrate, only long-chain 1-acyl and 2-acyl glycerols inhibited acyl diol hydrolysis competitively (Ki approximately 0.9 mM). It was concluded that long-chain monoesters of ethanediol are hydrolyzed by the monoacyl glycerol lipase system associated with the rat liver microsomal fraction. Because diol monoester is also utilized by the cholinephosphotransferase system of liver to form highly lytic acyl diol phosphocholines, efficient diol monoester hydrolysis by monoglyceride lipase may be a significant step in regulating acyl diol phosphocholine levels in biological systems.


Usage of sewage effluent in irrigation of some woody tree seedlings. Part 3: Swietenia mahagoni (L.) Jacq.
A pot experiment was investigated to study the effect of sewage irrigation treatments (primary and secondary effluents) compared with tap water on the growth and chemical constituents of mahogany seedlings (Swietenia mahagoni (L.) Jacq.) as well as soil chemical properties. The experiment was conducted at a greenhouse in the nursery of Timber Trees Research Department of Sabahia, Horticultural Research Station in Alexandria, Egypt, from June 2003 to December 2004 for three irrigation periods (6, 12 and 18 months). The sewage effluent waters were taken from oxidation ponds located in New Borg EL-Arab city and used directly for irrigation. The primary effluent treatment was superior than other treatments in improving the growth parameters (plant height, stem diameter, leaf area, leaves number, fresh and dry weights of leaves, shoots and roots and shoot/root ratio) and showed the highest concentration and total uptake of N, P, K, Cd, Ni, Pb and Fe in plant parts, followed by secondary effluent then tap water. The data revealed that soil salinity in terms of electrical conductivity of saturated paste (EC), CaCO3%, organic matter% and soluble anions and cations were influenced significantly by primary or secondary effluent treatment. The data also showed that the use of sewage effluent for irrigation increased N, P, K and DTPA-extractable-heavy metals (Cd, Cu, Ni, Pb, Fe, Mn and Zn). The effects of sewage effluent on growth parameters and elements content in plant parts and treated soil were more pronounced as water treatments were used for long period. The results suggested that the use of sewage effluent in irrigating mahogany trees grown on calcareous sandy loam soil was an important agriculture practice for improving soil properties, increasing fuel and timber production, and is an economic and safe way to dispose wastewaters.


Transient hemodynamic dysfunction after myocardial revascularization. Temperature dependence.
We studied hemodynamics and the effects of right atrial pacing (110 beats/min) following complete myocardial revascularization and hypothermic multidose potassium crystalloid cardioplegia in 12 patients with a normal preoperative left ventricular ejection fraction (LVEF). Measurements were made immediately preoperatively, postoperatively at specified temperatures during the rewarming period (90 degrees F, 94 degrees F, and 98 degrees F), and at 24 hours. No patient had a perioperative myocardial infarction. At 90 degrees F, hemodynamics were characterized by significant decreases in cardiac index, stroke volume index, and left ventricular stroke work index (LVSW) and an increase in systemic vascular resistance index (SVRI) compared to preoperative values (p less than 0.05). Right atrial pacing significantly increased cardiac index preoperatively and 24 hours postoperatively, but not during the rewarming period. Over the entire rewarming period (90 degrees F to 98 degrees F), each of the following variables correlated with temperature: cardiac index (r = 0.71 in sinus rhythm and r = 0.66 with right atrial pacing); stroke volume index (r = 0.33 and 0.66); SVRI (r = -0.80 and -0.64); LVSW (r = 0.37 and 0.73); and heart rate in sinus rhythm (r = 0.51). During the rewarming period, there was an inverse relationship between cardiac index and SVRI (r = -0.87). In conclusion, after myocardial revascularization: (1) transient hemodynamic dysfunction occurs during the rewarming period (90 degrees F to 98 degrees F); (2) this dysfunction is temperature-dependent; and (3) right atrial pacing at 110 beats/min does not improve hemodynamic function during the rewarming period. Temperature must be considered in the evaluation of left ventricular and hemodynamic function following myocardial revascularization.


Rethinking rurality: using hospital referral regions to investigate rural-urban health outcomes.
Rural residents in the United States face disproportionately poorer health outcomes compared to urban residents. This study aims to establish a continuous rural-urban measure for the 306 hospital referral regions (HRRs) in the U.S. and to investigate the relationship between the proportion of rural population served in each HRR and health outcomes, healthcare spending and utilization, and access to and quality of primary care. Cross-sectional analysis using data from The Dartmouth Atlas and the U.S. Census. The sample is limited to fee-for-service Medicare beneficiaries aged 65-99 years and living during 2015. The primary outcomes were measured at the HRR-level: mortality rates, Medicare reimbursements, percent Medicare enrollees who have at least one visit to a primary care physician, diabetic hemoglobin A1c testing rates, and mammography rates. We calculate a population-weighted rural proportion and population-weighted area deprivation index (ADI) for each HRR by aggregating zip-code level data. The most rural quartile of HRRs had significantly greater mean mortality rate of 4.50%, compared to 3.95% in most urban quartile of HRRs (p < 0.001). Increasing rural proportion was associated with decreasing price-adjusted Medicare reimbursements. In the multivariate, linear regression model, increasing area deprivation (ADI) was associated with increasing rates of mortality and greater utilization. Disparities in rural mortality are driven by sociodemographic disadvantage, rather than the quality of care provided at hospitals serving rural areas. After accounting for sociodemographic disadvantage, rural areas achieve similar quality of primary care in measured domains at an overall lower cost.


Electronic health records and patient safety: what lessons can Canada learn from the experience of others?
It is recognized that the Electronic Health Record (EHR) has significant potential to improve patient safety in Canada. However, the scientific evidence connecting EHRs to improvements in patient safety is incomplete. Additionally, international experience has demonstrated that EHRs trigger profound cultural and organizational changes in healthcare delivery. Consequently, Canada has a unique opportunity to learn from these experiences.


Use of 'small but smart' libraries to enhance the enantioselectivity of an esterase from Bacillus stearothermophilus towards tetrahydrofuran-3-yl acetate.
Two libraries of simultaneous double mutations in the active site region of an esterase from Bacillus stearothermophilus were constructed to improve the enantioselectivity in the hydrolysis of tetrahydrofuran-3-yl acetate. As screening of large mutant libraries is hampered by the necessity for GC/MS analysis, mutant libraries were designed according to a 'small but smart' concept. The design of focused libraries was based on data derived from a structural alignment of 3317 amino acid sequences of α/β-hydrolase fold enzymes with the bioinformatic tool 3DM. In this way, the number of mutants to be screened was substantially reduced as compared with a standard site-saturation mutagenesis approach. Whereas the wild-type esterase showed only poor enantioselectivity (E = 4.3) in the hydrolysis of (S)-tetrahydrofuran-3-yl acetate, the best variants obtained with this approach showed increased E-values of up to 10.4. Furthermore, some variants with inverted enantiopreference were found.


Purification, properties and induction of a specific benzoate-4-hydroxylase from Aspergillus niger (UBC 814).
An inducible benzoate-4-hydroxylase has been partially purified from crude extracts of the mycelial felts of Aspergillus niger. This enzyme catalyzes the transformation of benzoate to p-hydroxybenzoate with equimolar consumption of NADPH and O2. It requires tetrahydropteridine as a prosthetic group. The optimum activity was found at pH 6.2 with a Km value at 30 degrees C of 1.6-10-minus 4 for NADPH and 1.3-10-minus 4 M for benzoate. Fe-2+ (iron) is required for the enzyme activity. The enzyme is stabilized by the inclusion of benzoate, EDTA and glutathione in the extracting buffer. The enzyme is specific for benzoate as substrate. Sulfhydryl groups(s) are essential for enzyme activity as indicated by p-chloromercuri-benzoate and N-ethylmaleimide inactivation. Benzoate-4-hydroxylase activity is decreased in the mycelial felts of Aspergillus niger grown in the presence of higher concentrations of benzoate. Maximum activity of the enzyme was observed at 36 h after inoculation.


Cranial chondrosarcomas. Report of four cases and review of the literature.
Four cases of chondrosarcoma of the skull are presented. The clinical and radiographic features and differential diagnosis are discussed. The previous literature is reviewed and all cases tabulated. Computed tomography and angiography are important radiologic tools in suggesting the correct diagnosis prior to operation. Stippled, finely speckled, or amorphous calcification or bony erosion on radiographic studies and an avascular mass angiographically may suggest the diagnosis.


Lipid droplets in the adrenal cortex of the rat. Preservation after tannic acid-paraformaldehyde-glutaraldehyde fixation and extraction during staining.
Adrenocortical tissue from the rat was fixed in glutaraldehyde-paraformaldehyde-tannic acid with or without potassium pyroantimonate. An electron opacity was observed in lipid droplets from unstained sections of tissue with or without antimonate in the fixative and is most likely attributable to inclusion of tannic acid in the fixative. The opacity was largely removed after staining with uranyl acetate in absolute methanol followed by lead citrate. Removal of the opacity is attributable to staining in lead citrate, not uranyl acetate, because highly basic solution without lead also removes the density. An electron-opaque rim is present at the interface of lipid droplet and cytoplasm, although no distinct membranous structure is observable. The rim may correspond to myelin-like structures seen sometimes in lipid droplets from adrenocortical cells fixed by routine procedures employing pre-fixation with glutaraldehyde and post-fixation with osmium tetroxide. Results of this study point to the conclusion that ultrathin sections should be examined unstained in the validation of a new regime for processing tissues in electron microscopy.


The use of dissimilar progressives in the management of presbyopia.
The management of anisophoria with bifocal spectacle correction has always presented a challenging refractive problem. Historically, practitioners have used dissimilar bifocal segments or bicentric grinding to neutralize induced vertical imbalance. We present a method of reducing anisophoria at near point with dissimilar progressive multifocals. By incorporating different progressive designs, anisophoria can be minimized to a tolerable level, based on the dioptric power of lens and progressive lens design.


Relations of insulin sensitivity to longitudinal blood pressure tracking: variations with baseline age, body mass index, and blood pressure.
The relations of insulin sensitivity (IS) to hypertension incidence may vary according to baseline age, body mass index (BMI), and blood pressure (BP). We investigated the relations of IS (insulin sensitivity index, ISI(0,120)) to 4-year incidence of hypertension and BP progression in 1933 nonhypertensive Framingham Study participants (median age, 51 years; 56% women). Analyses were stratified by age (less than versus greater than or equal to median), BMI (<25 [normal], 25 to <30 [overweight], > or =30 kg/m2 [obese]), and BP category (systolic BP> or =130 or diastolic BP> or =85, "high normal" per the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High BP [JNC-VI] versus BP<130/85 mm Hg). On follow-up, 41% of participants had BP progression (> or =1 BP stage increase) and 18% had development of hypertension (systolic BP> or =140 or diastolic BP> or =90 mm Hg or antihypertensive medication use). In younger (<51 years) people with normal BMI and baseline BP<130/85 mm Hg, the second-to-fourth ISI(0,120) quartiles were associated with lower multivariable-adjusted odds for hypertension incidence (0.27; 95% CI, 0.09 to 0.83; P<0.05) and BP progression (0.37; 95% CI, 0.18 to 0.77; P<0.01) relative to the lowest (most insulin resistant) quartile. IS was not related to BP progression or hypertension incidence in older individuals, in obese participants, or in people with BP> or =130/85 mm Hg. In our large community-based sample, reduced IS predicted BP tracking principally in younger people with normal BMI and BP<130/85 mm Hg. Effect modification by age, BMI, and baseline BP may explain variation in the results of prior clinical investigations relating IS to hypertension incidence.


The metencephalic floor plate of chick embryos expresses two secretory glycoproteins homologous with the two glycoproteins secreted by the subcommissural organ.
The nature and the function of the compounds secreted by the floor plate (FP) of the metencephalon are little known. The FP cells of the hindbrain react with antibodies (AFRU) against the glycoproteins secreted by the subcommissural organ (SCO). One of the these proteins, RF-Gly I, is a 540-kDa core glycosylated protein. The aims of the present investigation were to identify by immunoblot the AFRU-immunoreactive compound secreted by the FP of chick embryos, to establish temporal and regional patterns of this secretory activity, and to obtain information about the fate of these compounds. It was established that the SCO and FP of chick embryos secrete two AFRU-immunoreactive compounds of 540 and 230 kDa. The two compounds secreted by the FP have been designated as FP-Gly I and FP-Gly II. The expression of these proteins was circumscribed to the metencephalic FP, and occurred from HH 29 to HH 36. Within the FP cells, FP-Gly I and FP-Gly II were confined to the supranuclear and apical regions, which under the electron microscope displayed numerous cisternae of the rough endoplasmic reticulum and granules. Aggregates of AFRU-immunoreactive material appeared on the free surface of the FP. The possibility that FP-Gly I and FP-Gly II are released into the ventricle to reach distant targets is discussed.


Synthesis of novel coumarin appended bis(formylpyrazole) derivatives: Studies on their antimicrobial and antioxidant activities.
A series of novel coumarin pyrazole hybrids of biological interest were synthesized from the hydrazones, carbazones and thiocarbazones via Vilsmeier Haack formylation reaction. These intermediates and formyl pyrazoles were evaluated for antimicrobial and antioxidant activities. Among the series, compounds 6g and 6h showed excellent antimicrobial activity against different bacterial and fungal strains and compounds 7g, 7h were found to be potent antioxidant agents in both DPPH and hydroxyl radical scavenging assays. Further, detailed quantitative structure-activity relationship (QSAR) analysis indicated the molecular parameters that contribute to increased potency of inhibition. The above findings would further encourage our understanding in employing coumarin pyrazole hybrids as potential antibiotic agents for treating infections caused by pathogenic microbes and fungi. Further, it also paves the way for exploration of these compounds as potential therapeutic agents to treat conditions arising because of excessive oxidative damage.


Complementation of the Fo c subunit of Escherichia coli with that of Streptococcus mutans and properties of the hybrid FoF1 ATP synthase.
The c subunit of Streptococcus mutans ATP synthase (FoF1) is functionally exchangeable with that of Escherichia coli, since E. coli with a hybrid FoF1 is able to grow on minimum succinate medium through oxidative phosphorylation. E. coli F1 bound to the hybrid Fo with the S. mutans c subunit showed N,N'-dicyclohexylcarbodiimide-sensitive ATPase activity similar to that of E. coli FoF1. Thus, the S. mutans c subunit assembled into a functional Fo together with the E. coli a and b subunits, forming a normal F1 binding site. Although the H(+) pathway should be functional, as was suggested by the growth on minimum succinate medium, ATP-driven H(+) transport could not be detected with inverted membrane vesicles in vitro. This observation is partly explained by the presence of an acidic residue (Glu-20) in the first transmembrane helix of the S. mutans c subunit, since the site-directed mutant carrying Gln-20 partly recovered the ATP-driven H(+) transport. Since S. mutans is recognized to be a primary etiological agent of human dental caries and is one cause of bacterial endocarditis, our system that expresses hybrid Fo with the S. mutans c subunit would be helpful to find antibiotics and chemicals specifically directed to S. mutans.


[Plastic surgery in preparing lower extremity stumps for prosthesis].
The experience with 113 dermatoplastic operations on lower extremities is described. The invalids with lower extremity stumps have obtained an opportunity to use modern prostheses.


Crosstalk between Rab GTPases and cell junctions.
For the past several years, studies from other laboratories, as well as ours, have begun to unravel the mechanism of germ cell movement in the testis by using several in vitro and in vivo models of tight and adherens junction assembly and disassembly, two cellular phenomena that confer cell movement. However, for cell movement to be fully appreciated, the importance of "intracellular" cell movements, such as those involving actin and microtubule filaments, must be better understood. Recent research on Rab GTPases has shown that members of this superfamily function in the trafficking of vesicles containing cargo to distinct subcellular sites such as the plasma membrane while utilizing actin and microtubule filaments as tracks. In this mini-review, we provide an overview of Rab GTPase structure, function, and regulation, while placing added emphasis on the role of Rabs in cell junction dynamics in the testis.


Geomimetic Hydrothermal Synthesis of Polyimide-Based Covalent Organic Frameworks.
Despite its abundance, water is not widely used as a medium for organic reactions. However, under geothermal conditions, water exhibits unique physicochemical properties, such as viscosity and a dielectric constant, and the ionic product become similar to those of common organic solvents. We have synthesized highly crystalline polyimide-based covalent organic frameworks (PICs) under geomimetic hydrothermal conditions. By exploiting triphenylene-2,3,6,7,10,11-hexacarboxylic acid in combination with various aromatic diamines, PICs with various pore dimensions and crystallinities were synthesized. XRD, FT-IR, and DFT calculations revealed that the solubility of the oligomeric intermediates under hydrothermal conditions affected the stacking structures of the crystalline PICs. Furthermore, the synthesized PICs demonstrate promising potential as an anode material in lithium-ion batteries owing to its unique redox-active properties and high surface area.


(Z)-Ethyl 2-(2,4-dimethyl-benzyl-idene)-7-methyl-3-oxo-5-phenyl-3,5-dihydro-2H-thia-zolo[3,2-a]pyrimidine-6-carboxyl-ate.
In the title compound, C(25)H(24)N(2)O(3)S, the dihedral angles between the thia-zole ring and the phenyl and substituted benzene rings are 84.91 (11) and 11.58 (10)°, respectively. The dihydro-pyrimidine ring adopts a flattened boat conformation. The olefinic double bond is in a Z configuration.


Role of hepatitis B virus infection in alcoholic patients.
The aim of this study was to determine the incidence of HBV markers in patients with alcoholic liver disease and to compare the results with those of patients with non-alcoholic liver disease and control subjects. We tried to determine whether the association between alcohol intake and HBV infection increases the risk of developing severe liver disease. The results showed an increased incidence of HBsAg in alcoholic patients when compared with controls as well as an increased incidence of severe chronic liver disease in HBV-positive groups when compared with HBV-negative groups. We conclude that HBV infection is an important additional risk factor for the development of severe liver disease in alcoholic patients.


Brain abscess as a cause of infant hydrocephalus. Case report.
The authors report on a case of hydrocephalus caused by brain abscess in a four-months-old girl. After repeated punctures and antibiotics administration extirpation of abscess was necessary. The child recovered with only slight neurological deficit.


Reduced D2-mediated signaling activity and trans-synaptic upregulation of D1 and D2 dopamine receptors in mice overexpressing the dopamine transporter.
The dopamine transporter (DAT) regulates the temporal and spatial actions of dopamine by reuptaking this neurotransmitter into the presynaptic neurons. We recently generated transgenic mice overexpressing DAT (DAT-tg) that have a 3-fold increase in DAT protein levels which results in a 40% reduction of the extracellular DA concentration in the striatum. The aim of this study was to examine the effect of this reduction in dopaminergic tone on postsynaptic responses mediated by dopamine receptors. We report here that DAT-tg mice have increased levels of striatal D1 (30%) and D2 (approximately 60%) dopamine receptors with D1 receptor signaling components not significantly altered, as evidenced by unaffected basal or stimulated levels of phospho-GluR1 (Ser845) and phospho-ERK2. However, the novel D2 mediated Akt signaling is markedly altered in DAT-tg animals. In particular, there is a 300% increase in the basal levels of phospho-Akt in the striatum of DAT-tg, reflecting the reduced extracellular dopamine tone in these animals. This increase in basal pAkt levels can be pharmacologically recapitulated by partial dopamine depletion in WT mice treated with the selective tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (alpha-MPT). Behaviorally, DAT-tg animals demonstrate an augmented synergistic interaction between up-regulated D1 and D2 receptors, which results in increased climbing behavior in transgenic mice after stimulation with either apomorphine or a co-administration of selective D1 and D2 receptor agonists. In sum, our study reveals that hypodopaminegia caused by up-regulation of DAT results in significant alterations at postsynaptic receptor function with most notable dysregulation at the level of D2 receptor signaling.


Pulmonary epithelial-mesenchymal interactions: beyond organogenesis.
Epithelial-mesenchymal interactions are important regulators of lung growth and organogenesis, but later functional maturation of the fetal lung is though to be primarily under hormonal control. Recent evidence, however, suggests that hormonal effects on pulmonary cellular and biochemical maturation continue to involve intercellular interactions. Communication between cells may have wider importance than has hitherto been appreciated. It should be noted that in addition to organogenesis and biochemical development, mature lung requires an extensive capillary network in close proximity to areas of gas exchange. Recent attempts to isolate and culture pumonary endothelium may be expected to provide new insights into this neglected aspect of lung maturation. The possibility of hormonal or intercellular mediation of the differentiation of airway epithelium might also merit investigation.


One-stage closure of isolated cleft palate with the Veau-Wardill-Kilner V to Y pushback procedure or the Cronin modification. III. Comparison of lateral craniofacial morphology.
The craniofacial morphology of 116 consecutive patients with isolated cleft palate was studied by means of lateral cephalograms at 17 to 20 years of age. One-stage hard- and soft-palate closure had been carried out at the mean age of 1.8 years by using the Veau-Wardill-Kilner or the Cronin mucoperiosteal palatal V-Y pushback technique. In the Veau-Wardill-Kilner group the cranial base was longer, the cranial base angle was larger, and the mandible longer and its ramus higher but less backward rotated. The patients with originally the most extensive clefts showed the most marked deviations in craniofacial morphology at adult age.


Long-term treatment with different calcium- and calmodulin-antagonists induces changes in rat brain alpha-adrenoceptors.
1. The binding characteristics (Bmax and Kd) of the alpha-adrenoceptor radioligand [3H] WB4101 in crude membrane fraction (fraction P2) from cerebral cortex were studied after 13-day oral treatment of male Wistar rats with the Ca(2+)-antagonists nifedipine (20 mg/kg), verapamil (50 mg/kg), flunarizine (10 mg/kg) and with the calmodulin-antagonist trifluoperazine (TFP) (3 mg/kg). 2. A significant reduction of the binding sites (Bmax) for [3H] WB4101 was established after the three Ca(2+)-antagonists as well as after TFP treatment. 3. Different changes in the affinity constant (Kd) of brain adrenoceptors were observed depending on the type of the Ca2+ or CaM-antagonist used: nifedipine did not change the Kd value, verapamil and TFP decreased whereas flunarizine increased the Kd value. 4. Relationships between Ca ions and alpha-adrenoceptor functions are suggested.


Formulary Policies a Battleground In HHS Proposal on Nondiscrimination: Are Tiering and Cost Sharing Civil Rights Issues?
The Department of Health and Human Services' proposed rule on Section 1557 of the Patient Protection and Affordable Care Act bans discrimination in health care. How the rule would affect formularies and P&T committees has prompted varying concerns.


Recruitment outcomes, challenges and lessons learned: the Healthy Communities Study.
The Healthy Communities Study (HCS) was a national study of community programs and policies that aimed to address childhood obesity; it necessitated recruitment of a large sample of children from communities throughout the United States. The HCS aimed to complete visits with an average of 45 children and 12 key informants from at least 120 communities, diverse with respect to region of the country, urbanicity, socioeconomic status, race, ethnicity and intensity of community programs and policies that aim to address childhood obesity. Purchased address lists were utilized to select households for recruitment during Wave 1 of the study, and recruitment of families through schools was employed for Wave 2. The HCS successfully obtained approval from 149 school districts and 478 schools in 130 communities, recruited 5138 families, and interviewed 1421 key informants to allow for characterization of overall intensity of obesity prevention/treatment efforts in each community. Lessons learned are presented. Future studies should plan for inclusion of the following in development of recruitment strategies: literature review, formative research, pilot testing, and ongoing monitoring and adjustment.


Characterization of haemagglutinin-esterase protein (HE) of murine corona virus DVIM by monoclonal antibodies.
We analyzed the characteristics of seven monoclonal antibodies (mAbs) raised against purified HE (hemagglutinin-esterase) glycoprotein of the murine coronavirus DVIM (diarrhea virus of infant mice). Immunocrossreaction of these mAbs with JHM and/or MHV-S suggest that antigenic epitopes of HE of DVIM are similar to those of JHM and/or MHV-S. Four mAbs (1b4, 3a28, 4c19, 10b7), designated as group A mAbs, strongly inhibited both HA and AE activities. On the other hand, three mAbs (5a3, 6a6, 13a4), referred to as group B, had a comparatively weak HA inhibition activity. These results indicate that the antigenic epitopes of this glycoprotein can be classified into at least two groups and that the functional sites of HA and AE activities are similar but not identical. Neutralizing activity was shown in group A mAbs exclusively, suggesting that the ratio of HA and/or AE activities may play important roles in the cell fusion activity of DVIM-infected cells.


A predictive mechanical model for evaluating vertebral fracture probability in lumbar spine under different osteoporotic drug therapies.
Osteoporotic vertebral fractures represent a major cause of disability, loss of quality of life and even mortality among the elderly population. Decisions on drug therapy are based on the assessment of risk factors for fracture from bone mineral density (BMD) measurements. A previously developed model, based on the Damage and Fracture Mechanics, was applied for the evaluation of the mechanical magnitudes involved in the fracture process from clinical BMD measurements. BMD evolution in untreated patients and in patients with seven different treatments was analyzed from clinical studies in order to compare the variation in the risk of fracture. The predictive model was applied in a finite element simulation of the whole lumbar spine, obtaining detailed maps of damage and fracture probability, identifying high-risk local zones at vertebral body. For every vertebra, strontium ranelate exhibits the highest decrease, whereas minimum decrease is achieved with oral ibandronate. All the treatments manifest similar trends for every vertebra. Conversely, for the natural BMD evolution, as bone stiffness decreases, the mechanical damage and fracture probability show a significant increase (as it occurs in the natural history of BMD). Vertebral walls and external areas of vertebral end plates are the zones at greatest risk, in coincidence with the typical locations of osteoporotic fractures, characterized by a vertebral crushing due to the collapse of vertebral walls. This methodology could be applied for an individual patient, in order to obtain the trends corresponding to different treatments, in identifying at-risk individuals in early stages of osteoporosis and might be helpful for treatment decisions.


Physical growth and nutritional status of Garhwali girls.
The present study was conducted to evaluate physical growth and nutritional status of 214 school-going girls ranging in age from 5 to 12 years of rural area in Pauri Garhwal district of Uttaranchal. Physical growth was evaluated using eleven standard anthropometric measurements viz., height, body weight, sitting height, biepicondylar humerus, bicondylar femur, head circumference, chest circumference, upper arm circumference, biceps skinfold, triceps skinfold and subscapular skinfold. To assess the nutritional status, weight deficit for age, height deficit for age, upper arm circumference deficit for age and triceps skinfold deficit for age have been calculated using NCHS standards. It has been observed that the well nourished Indian girls and American girls show better performance in physical growth parameters as compared to the Garhwali girls at all ages. The Garhwali girls were found to be comparable with rural Indian girls in their growth status. Grade-I and Grade-II malnutrition was prevalent among the Garhwali girls, however, Grade-III malnutrition was found to be present in only a few girls. This average to poor nutritional status of the present Garhwali girls may be attributed to low dietary intake, low-middle socio-economic background, uneducated or partially educated parents, large family size, gender discrimination etc.


Organotin compounds in surface and pore waters of Ganga Plain in the Kanpur-Unnao industrial region, India.
Organotin compounds (OTCs) belong to those chemicals most toxic to the aquatic organisms which are deliberately introduced into the aquatic system through anthropogenic activities. Various species of organotin compounds were detected in surface and pore waters of the Ganga Plain in Kanpur-Unnao industrial region in pre-and post-Monsoon periods of 1995. The extraction of these compounds was performed using a method of direct aqueous phase in situ ethylation with sodium tetraethylborate (NaBEt4). After extraction into hexane, they were detected by GC-MIP-AED. The water of this area is contaminated with dimethyltin (DMT), monobutyltin (MBT), dibutyltin (DBT) and tributyltin (TBT) compounds. Concentrations of these compounds in surface water of the pre-Monsoon period of 1995 range from 2.1 to 70.1 ng Sn/l for MBT, 1.7-101.1 for DBT and 2.9-19.8 for TBT, whereas in pore water; 9.7-23.5 ng Sn/l for MBT, 11.2-18.0 for DBT and 8.7-32.6 for TBT. However, in the post-Monsoon period of 1995, surface water shows considerable decrease in concentrations: DMT below detection-1.8 ng Sn/l, DBT 3.0-5.4, TBT 3.1-3.6 and MBT is below detection. This study is a preliminary documentation of water pollution by OTCs in the Kanpur-Unnao region of the Ganga Plain and suggests the necessity of further detailed OTCs studies in other regions of the Ganga Plain.


Age and type of crossed aphasia in dextrals due to stroke.
Thirty-nine cases (37 from the literature and 2 personal) of crossed aphasia in dextrals due to stroke were reviewed concerning age, sex, and type of aphasia. Results showed that Broca's aphasics are younger than the remaining group, males predominate, and several types of aphasia have been described similarly to the aphasias due to left-hemisphere lesions in dextrals.


Cutaneous T cell Lymphoma: an Update on Pathogenesis and Systemic Therapy.
Mycosis fungoides (MF) and its leukemic variant, Sézary syndrome (SS), are malignancies of skin-homing T cells that comprise the majority of cutaneous T cell lymphomas (CTCL). Treatment of CTCL is limited and can be approached by skin-directed therapy or systemic therapy. Recent investigations into the pathogenesis of MF and SS have broadened the therapeutic targets; here, we review emerging concepts in the pathogenesis of MF and SS as well as novel and traditional systemic therapies for MF and SS. These include histone deacetylase inhibitors (vorinostat, romidepsin, panobinostat, and belinostat), monoclonal antibodies (alemtuzumab, brentuximab vedotin, and mogamulizumab) and single-agent cytotoxic chemotherapeutic agents (e.g., pralatrexate, doxorubicin, bendamustine, and forodesine), as well as multi-agent chemotherapy regimens.


Discrete arcs of increased fundus autofluorescence in retinal dystrophies and functional correlate on microperimetry.
To describe the occurrence of discrete arcs of increased fundus autofluorescence (FAF) associated with various retinal dystrophies and to assess their functional significance by fundus-controlled microperimetry. Seven patients, three with pigmented paravenous retinochoroidal atrophy (PPRCA), one with sector retinitis pigmentosa (RP), one with typical RP, and two with macular dystrophy were assessed by retinal imaging including FAF imaging. Serial images were obtained within a review period of 6 and 10 years in a patient with PPRCA and macular dystrophy, respectively. Fundus-controlled microperimetry was performed in eight eyes of five patients to determine light increment sensitivity. A discrete arched line of increased FAF was observed without obvious correlate on fundus biomicroscopy. The orientation of this line differed from ring shape in RP and macular dystrophy, a semi-circle structure in sector RP to crescent shape with tiplike extensions towards branching retinal veins in PPRCA. Longitudinal investigation revealed slight migration of the arc in PPRCA and peripheral extension of the ring diameter in macular dystrophy. Microperimetry revealed that the arc of increased FAF sharply delineated areas of severely impaired retinal sensitivity. The findings indicate that arcs of increased FAF in PPRCA and other retinal dystrophies demarcate areas of impaired retinal function and may migrate over time. FAF imaging may therefore reveal the exact extent of neurosensory dysfunction that may exceed the dimensions anticipated by conventional examinations.


Transient cessation of female rat sexual cycle after electrolytic damage of locus coeruleus.
In order to evaluate the possible participation of the locus coeruleus (LC) in the regulation of estrous cyclicity, bilateral LC electrolytic lesions were made in intact female rats. Vaginal smears were sampled daily and the estrous cyclicity was established. LC lesions resulted in a transient loss of cyclicity characterized by a sustained diestrous period. The delay in recovery was dependent on the percentage of LC destroyed. The cyclicity of sham operated rats and of nonoperated rats showed no change. Results are discussed within the context of the LC as a generalized influencing system.