Multidisciplinary Clinics in Neuromuscular Medicine.
Multidisciplinary care is comprehensive, coordinated clinical care across medical disciplines and allied health professions. Neuromuscular disorders, such as amyotrophic lateral sclerosis and muscular dystrophies, are often associated with disabling weakness and extramuscular symptoms and may benefit from care in a model that consolidates numerous clinic visits into a single more efficient multidisciplinary clinic visit. The goal of the neuromuscular multidisciplinary care model is to improve patient outcomes, patient satisfaction, quality of life, access to medications and equipment, and survival. Although the costs of running a multidisciplinary clinic are high, they are likely associated with cost savings from the patient's perspective. Several barriers to acceptance of multidisciplinary clinics include the distance needed to travel to the clinic and the duration of the clinic visit. Telehealth multidisciplinary clinic visits may address some of these concerns. Further study is needed to understand the value of multidisciplinary clinics and is a necessary step toward creating a sustainable model.


Kinetic analysis of ligand interaction with the gonococcal transferrin-iron acquisition system.
The transferrin iron acquisition system of Neisseria gonorrhoeae consists of two dissimilar transferrin binding proteins (Tbp) A and B. TbpA is a TonB dependent transporter while TbpB is a lipoprotein that makes iron acquisition from transferrin (Tf) more efficient. In an attempt to further define the individual roles of these receptors in the process of Tf-iron acquisition, the kinetics of the receptor proteins in regards to ligand association and dissociation were evaluated. Tf association with TbpB was rapid as compared to TbpA. Tf dissociation from the wild-type receptor occurred in a biphasic manner; an initial rapid release was followed by a slower dissociation over time. Both TbpA and TbpB demonstrated a two-phase release pattern; however, TbpA required both TonB and TbpB for efficient Tf dissociation from the cell surface. The roles of TbpA and TbpB in Tf dissociation were further examined, utilizing previously created HA fusion proteins. Using a Tf-utilization deficient TbpA-HA mutant, we concluded that the slower rate of ligand dissociation demonstrated by the wild-type transporter was a function of successful iron internalization. Insertion into the C-terminus of TbpB decreased the rate of Tf dissociation, while insertion into the N-terminus had no effect on this process. From these studies, we propose that TbpA and TbpB function synergistically during the process of Tf iron acquisition and that TbpB makes the process of Tf-iron acquisition more efficient at least in part by affecting association and dissociation of Tf from the cell surface.


Rapamycin-resistant and torin-sensitive mTOR signaling promotes the survival and proliferation of leukemic cells.
The serine/threonine kinase mTOR is essential for the phosphoinositide 3-kinases (PI3K) signaling pathway, and regulates the development and function of immune cells. Aberrant activation of mTOR signaling pathway is associated with many cancers including leukemia. Here, we report the contributions of mTOR signaling to growth of human leukemic cell lines and mouse T-cell acute leukemia (T-ALL) cells. Torin, an ATP-competitive mTOR inhibitor, was found to have both cytotoxic and cytostatic effects on U-937, THP-1, and RPMI-8226 cells, but not on Jurkat or K-562 cells. All cells were relatively resistant to rapamycin even with suppressed activity of mTOR complex 1. Growth of T-ALL cells induced by Notch1 was profoundly affected by torin partially due to increased expression of Bcl2l11 and Bbc3. Of note, activation of Akt or knockdown of FoxO1 mitigated the effect of mTOR inhibition on T-ALL cells. Our data provide insight on the effect of mTOR inhibitors on the survival and proliferation of leukemic cells, thus further improving our understanding on cell-context-dependent impacts of mTOR signaling.


The Neuroprotective Effect of α-Lipoic Acid and/or Metformin against the Behavioral and Neurochemical Changes Induced by Hypothyroidism in Rat.
The present study evaluates the neuroprotective effect of α-lipoic acid (ALA) and/or metformin (MET) on the behavioral and neurochemical changes induced by hypothyroidism. Rats were divided into control, rat model of hypothyroidism induced by propylthiouracil, and rat model of hypothyroidism treated with ALA, MET, or their combination. Behaviorally, hypothyroid rats revealed impaired memory and reduced motor activity as indicated from the novel object recognition test and open-field test, respectively. Hypothyroidism induced a significant increase in lipid peroxidation (malondialdehyde [MDA]) and a significant decrease in reduced glutathione (GSH) and nitric oxide (NO) in the cortex and hippocampus. These were associated with a significant increase in tumor necrosis factor-α (TNF-α) and a significant decrease in brain-derived neurotrophic factor (BDNF). Hypothyroidism decreased significantly the levels of serotonin (5-HT), norepinephrine (NE), and dopamine (DA) and reduced the activities of acetylcholinesterase (AchE) and Na+, K+-ATPase in the cortex and hippocampus. Treatment of hypothyroid rats with ALA and/or MET showed an improvement in memory function and motor activity. Moreover, ALA and/or MET prevented the increase in MDA and TNF-α, and the decline in GSH, NO, BDNF, 5-HT, NE, and DA. It also restored AchE and Na+, K+-ATPase activities in the studied brain regions. ALA and/or MET has a potential neuroprotective effect against the adverse behavioral and neurochemical changes induced by hypothyroidism in rats.


Synthesis and analytical use of 3-carboxypropionyl-alanyl-alanyl-valine-4-nitroanilide: a specific substrate for human leukocyte elastase.
A simple synthesis is described for 3-carboxypropionyl-Ala-Ala-Val-4-nitroanilide, a convenient and very specific substrate for human leukocyte elastase (Km = 1.0mM, kcat = 8.7 s-1). The substrate does not undergo appreciable spontaneous hydrolysis. It is not cleaved by trypsin or chymotrypsin and only rather slowly by porcine pancreatic elastase (Km = 9.1mM, kcat = 1.4 s-1).


Protonation structures of Cys-sulfinic and Cys-sulfenic acids in the photosensitive nitrile hydratase revealed by Fourier transform infrared spectroscopy.
Nitrile hydratase (NHase) from Rhodococcus N-771, which catalyzes hydration of nitriles to the corresponding amides, exhibits novel photosensitivity; in the dark, it is in the inactive form that binds an endogenous nitric oxide (NO) molecule at the non-heme iron center, and photodissociation of the NO activates the enzyme. NHase is also known to have a unique active site structure. Two cysteine ligands to the iron center, alphaCys112 and alphaCys114, are post-translationally modified to sulfinic acid (Cys-SO(2)H) and sulfenic acid (Cys-SOH), respectively, which are thought to play a crucial role in the catalytic reaction. Here, we have determined the protonation structures of these Cys-SO(2)H and Cys-SOH groups using Fourier transform infrared (FTIR) spectroscopy in combination with density functional theory (DFT) calculations. The light-induced FTIR difference spectrum of NHase between the dark inactive and light active forms exhibited two prominent signals at (1154-1148)/1126 and (1040-1034)/1019 cm(-1), which downshifted to 1141/1114 and 1026/1012 cm(-1), respectively, in the uniformly (34)S-labeled NHase. In addition, a minor signal at 915/908 cm(-1) also showed a considerable downshift upon (34)S labeling. These (34)S-sensitive signals were basically conserved in D(2)O buffer with only slight shifts. Vibrational frequencies of methanesulfenic acid (CH(3)SOH) and methanesulfinic acid (CH(3)SO(2)H), simple model compounds of Cys-SOH and Cys-SO(2)H, respectively, were calculated using the DFT method in both the protonated and deprotonated forms and in metal complexes. Comparison of the calculated frequencies and isotope shifts with the observed ones provided the assignment of the two major signals around 1140 and 1030 cm(-1) to the asymmetric and symmetric SO(2) stretching vibrations, respectively, of the S-bonded Cys-SO(2)(-) complex, and the assignment of the minor signal around 910 cm(-1) most likely to the SO stretch of the S-bonded Cys-SO(-) complex. These assignments and the small frequency shifts upon deuteration are consistent with the view that the deprotonated alphaCys112-SO(2)(-) and alphaCys114-SO(-) are hydrogen-bonded with the protons from betaArg56 and/or betaArg141, forming a reactive cavity at the interface of the alpha and beta subunits. There is further speculation that either of these groups is hydrogen bonded to a reactant water molecule, increasing its basicity to facilitate the nucleophilic attack on the nitrile substrate bound to the iron center.


[Surgical treatment of Parkinson's disease in Poland in the last century].
Surgery of Parkinson's disease started in the middle of the last century. At the same time this treatment was introduced in Poland. Choróbski removed Broadsman's area 4 through craniotomy. In 1961 Liszka in Kraków introduced the stereotactic procedures, thalamo- and pallidotomy. This type of surgery was soon introduced in two other neurosurgical centers. For the next several years treatment was mostly pharmacological. However, stereotactic treatment was used in patients poorly tolerating drugs. In the meantime first attempts were made at implantation of fetal substantia nigra, with good results. At the end of the century in several patients electrostimulators were implanted. In the last century all known methods of surgical treatment were applied in Poland.


Guided ion beam studies of the collision-induced dissociation of CuOH+(H2O)n (n = 1-4): comprehensive thermodynamic data for copper ion hydration.
Threshold collision-induced dissociation (TCID) using a guided ion beam tandem mass spectrometer is performed on CuOH(+)(H2O)n where n = 1-4. The primary dissociation pathway for the n = 2-4 reactants consists of loss of a single water molecule followed by the sequential loss of additional water molecules at higher collision energies. The n = 1 reactant departs from this trend by losing the OH ligand and the H2O ligand competitively. Loss of the OH ligand is thermodynamically favored, whereas H2O loss is the kinetically favored process, consistent with heterolytic cleavage of the dative bond. The data are analyzed using a statistical model after accounting for internal and kinetic energy distributions, multiple collisions, and kinetic shifts to obtain 0 K bond dissociation energies (BDEs). These are also converted using a rigid rotor/harmonic oscillator approximation to yield thermodynamic values at room temperature. Experimental BDEs are compared to theoretical BDEs determined at the B3LYP, cam-B3LYP, B3P86, M06, CCSD(T), and MP2(full) levels of theory with a 6-311+G(2d,2p) basis set using geometries and vibrational frequencies determined at the B3LYP/6-311+G(d,p) level. In addition, BDEs for the loss of OH from CuOH(+)(H2O)n where n = 0, 2-4 are derived using the experimental BDEs for dissociation of CuOH(+)(H2O)n and literature values for Cu(+)(H2O)n.


The National Tuberculosis Control Programme in Mozambique, 1985-1990.
The structure, manpower and tasks of the Tuberculosis Programme (ELAT) in Mozambique are explained. The activities are organised on three levels (ministerial, provincial and district). From 1985 to 1990 (1st half) 59,339 cases were detected. Of them, 32,978 were new smear-positive, 17,772 new smear-negative, 5,664 relapses and 2,425 extra-pulmonary cases. Results achieved by 3 regimens used by the Programme varied on average from 55% for the standard, 77% for the short-course and 72% for the retreatment regimen. The Programme is run by paramedical staff and no specific personnel exists in the districts. To upgrade the few personnel involved in the ELAT, supervision and training are considered as backbones of the Programme. The country suffers from a devastating war, which has aggravated the poor transport network, reduced accessibility to remote areas, hampered regular supervision and makes distribution of supplies irregular and very expensive, since drugs, reagents, forms and spare parts have to be sent by air or sea. In spite of all these terrible misfortunes, results achieved show that it is possible to diagnose and treat cases under such condition.


[Advances of research in ion channels in idiopathic epilepsy].
Epilepsy is a kind of brain dysfunction syndrome caused by so many reasons instead of a certain disease. Abnormal neuron discharge can cause epilepsy. Idiopathic epilepsy refers to epilepsy or epilepsy syndrome without any latent reasons but inherited trait. Idiopathic epilepsy is confirmed as an ion channelopathy at present. The first genemutation was found in idiopathic epilepsy in 1995, and a lot of genes coding either voltage-gated or ligand-gated ion channels have been found since then. In the present review, some new advances in research on ion channels dysfunction in idiopathic epilepsy are summarized.


Low bone mass in newly diagnosed multiple sclerosis and clinically isolated syndrome.
Osteoporosis is common in patients with multiple sclerosis (MS) with long-standing disease. Hypovitaminosis D is a candidate risk factor for MS, and vitamin D also mediates bone mineralization. If vitamin D exerts a major effect on MS risk, skeletal consequences of hypovitaminosis D could be apparent shortly after the onset of MS. In order to test this hypothesis, we assessed bone mineral density (BMD) at early stages of disease in patients with no or minor disability. A population-based case-control study was conducted on 99 consecutive and newly diagnosed patients with clinically isolated syndrome or MS, and on 159 age-, sex-, and ethnicity-matched controls. BMD was measured by dual-energy x-ray absorptiometry of the femoral neck, total hip, anterior-posterior lumbar spine, total body, and nondominant ultradistal radius. A total of 50.5% of the patients exhibited either osteopenia (-2.5 < T score < -1.0) or osteoporosis (T score ≤-2.5) in at least one skeletal site, compared to 37.1% of controls (p = 0.034). After adjusting for possible confounders, left femoral total hip T score and lumbar spine BMD and T score were significantly lower in patients than in controls (p = 0.023, 0.039, and 0.026, respectively). Low bone mass appears to occur early in MS. This is compatible with shared etiologic or pathogenic factors in MS and osteoporosis, and calls for an active approach to optimize bone health in early stages of MS.


[Epidemiological study of snoring--a questionnaire survey in factory workers].
There has been no epidemiological study of snoring in Japan, and we therefore performed a questionnaire survey (in about 7,000 adult men working at a steel-making factory at the time of the yearly health examination, and investigated the relationship between the severity of snoring and 17 items including age, obesity, family history of snoring, daytime hypersomnolence, hypertension, smoking, alcohol intake and traffic accidents. We classified all the subjects into three groups, no snoring, mild snoring, and severe snoring group. We defined severe snorers as persons who snored loudly in both inspiratory and expiratory phases and those who snored loudly with apnea. We found that aging, obesity, smoking and alcohol intake are risk factors for snoring. Compared with non-snorers, severe snorers were found to have a high incidence of family history of snoring, daytime hypersomnolence, and history of treatment of hypertension. No relationship was found between the severity of snoring and the occurrence of automobile accidents. The proportion of severe snorers over 40 years old with obesity, daytime hypersomnolence and morning headache was 0.25%, representing the group that may have obstructive sleep apnea syndrome. The probable incidence of sleep apnea syndrome in men may be considerably lower in Japan compared with that in either U.S.A. or Europe.


Attaching and effacing Escherichia coli isolated from dogs in Brazil: characteristics and serotypic relationship to human enteropathogenic E. coli (EPEC).
Escherichia coli isolates recovered from 182 fecal specimens from dogs up to five months old from the cities of São Paulo and Campinas, SP, Brazil, were examined by polymerase chain reaction (PCR) for several virulence factors and properties. The eae gene was found in 23 isolates of E. coli from 22 dogs, 19 of 146 (13%) from dogs with diarrhea and 3 of 36 (8.3%) from dogs with no diarrhea. Two different eae+ isolates were recovered from one dog with diarrhea. Isolates from two dogs with diarrhea harbored the bfpA gene, and none of the isolates possessed genes for enterotoxins, the EAF plasmid or Shiga toxins. PCR showed that, among the 23 isolates, eight were positive for beta intimin, six for gamma, two for, one for alpha, one for kappa, and five showed no amplification with any of the nine pairs of specific intimin primers used. PCR also showed that the LEE (locus of enterocyte effacement) was inserted in selC in four isolates, likely in pheU in seven isolates, and in undetermined sites in twelve isolates. Fifteen isolates adhered to HEp-2 cells and were fluorescence actin staining (FAS) positive. The predominant adherence pattern was the localized adherence-like (LAL) pattern. The eae-positive isolates belonged to a wide diversity of serotypes, including O111:H25, O119:H2 and O142:H6, which are serotypes that are common among human EPEC. These results confirmed the presence of EPEC in dogs (DEPEC) with and without diarrhea. The virulence factors found in these strains were similar to those in human EPEC, leading to the possibility that EPEC may move back and forth among human and canine populations.


Role of Na+/Ca2+ Exchangers in Therapy Resistance of Medulloblastoma Cells.
Alterations of cytosolic Ca2+-activity ([Ca2+]i) are decisive in the regulation of tumor cell proliferation, migration and survival. Transport processes participating in the regulation of [Ca2+]i include Ca2+ extrusion through K+-independent (NCX) and/or K+-dependent (NCKX) Na+/Ca2+-exchangers. The present study thus explored whether medulloblastoma cells express Na+/Ca2+-exchangers, whether expression differs between therapy sensitive D283 and therapy resistant UW228-3 medulloblastoma cells, and whether Na+/Ca2+-exchangers participate in the regulation of cell survival. In therapy sensitive D283 and therapy resistant UW228-3 medulloblastoma cells transcript levels were estimated by RT-PCR, protein abundance by Western blotting, cytosolic Ca2+-activity ([Ca2+]i) from Fura-2-fluorescence, Na+/ Ca2+-exchanger activity from the increase of [Ca2+]i (Δ[Ca2+]i) and from whole cell current (Ica) following abrupt replacement of Na+ containing (130 mM) and Ca2+ free by Na+ free and Ca2+ containing (2 mM) extracellular perfusate as well as cell death from PI -staining and annexin-V binding in flow cytometry. The transcript levels of NCX3, NCKX2, and NCKX5, protein abundance of NCX3, slope and peak of Δ[Ca2+]i as well as Ica were significantly lower in therapy sensitive D283 than in therapy resistant UW228-3 medulloblastoma cells. The Na+/Ca2+-exchanger inhibitor KB-R7943 (10 µM) significantly blunted Δ[Ca2+]i, and augmented the ionizing radiation-induced apoptosis but did not significantly modify clonogenicity of medulloblastoma cells. Apoptosis was further enhanced by NCX3 silencing. Na+/Ca2+-exchanger activity significantly counteracts apoptosis but does not significantly affect clonogenicity after radiation of medulloblastoma cells.


Adaptive root foraging strategies along a boreal-temperate forest gradient.
The tree root-mycorhizosphere plays a key role in resource uptake, but also in the adaptation of forests to changing environments. The adaptive foraging mechanisms of ectomycorrhizal (EcM) and fine roots of Picea abies, Pinus sylvestris and Betula pendula were evaluated along a gradient from temperate to subarctic boreal forest (38 sites between latitudes 48°N and 69°N) in Europe. Variables describing tree resource uptake structures and processes (absorptive fine root biomass and morphology, nitrogen (N) concentration in absorptive roots, extramatrical mycelium (EMM) biomass, community structure of root-associated EcM fungi, soil and rhizosphere bacteria) were used to analyse relationships between root system functional traits and climate, soil and stand characteristics. Absorptive fine root biomass per stand basal area increased significantly from temperate to boreal forests, coinciding with longer and thinner root tips with higher tissue density, smaller EMM biomass per root length and a shift in soil microbial community structure. The soil carbon (C) : N ratio was found to explain most of the variability in absorptive fine root and EMM biomass, root tissue density, N concentration and rhizosphere bacterial community structure. We suggest a concept of absorptive fine root foraging strategies involving both qualitative and quantitative changes in the root-mycorrhiza-bacteria continuum along climate and soil C : N gradients.


A narrative review of a type of pancreatitis worthy of attention: acute pancreatitis associated with pancreatic tumors-current problems and future thinking.
Our purpose is to explain the onset, diagnosis, and treatment of pancreatic tumor-associated pancreatitis (PTP), and inform clinicians about the management of PTP. It is hoped that clinicians can gain some experience and inspiration from this review, so that patients can obtain better treatment results. Acute pancreatitis (AP) is an inflammatory disease, and pancreatic tumors are one of the causes of pancreatitis. When pancreatic tumors and pancreatitis exist at the same time, and there is a "connection" between them, this type of pancreatitis is referred to as PTP. The manifestations of PTP can be as follows: (I) AP is the first symptom of pancreatic tumors; (II) pancreatitis is found in patients after pancreatic tumor diagnosis or during pancreatic tumor surgery. Because pancreatic tumors are not one of the most common causes of pancreatitis, PTP has not attracted the attention of researchers and clinicians, and there is no consistent and clear understanding of the diagnosis and treatment of PTP. From the online database PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Web of Science (https://webofknowledge.com/), we use specific retrieval strategies to retrieve relevant articles, and we review and discuss them. What we need to realize is that PTP is different from ordinary AP. It has its own characteristics in terms of diagnosis and treatment, which requires the attention of clinicians. More importantly, future research should design the best diagnosis and treatment algorithms for PTP.


Evaluation of paper gradient concentration strips for antifungal combination testing of Candida spp.
In vitro combination testing with broth microdilution chequerboard (CHEQ) method is widely used although it is time-consuming, cumbersome and difficult to apply in routine setting of clinical microbiology laboratory. A new gradient concentration paper strip method, the Liofilchem(®) MIC test strips (MTS), provides an alternative easy and fast method enabling the simultaneous diffusion of both drugs in combination. We therefore tested a polyene+azole and an azole+echinocandin combination against 18 Candida isolates with the CHEQ method based on EUCAST guidelines and the MTS method in research and routine settings. Fractional inhibitory concentration (FIC) indices were calculated after 24 and 48 h of incubation based on complete and prominent (FIC-2) growth inhibition endpoints. Reproducibility and agreement within 1 twofold dilution was assessed. The FICs of the two methods were correlated quantitatively with t-test and Pearson analysis and qualitatively with Chi-squared test. The reproducibility of the CHEQ and MTS method was 88-100% and their agreement was 80% with 62-77% of MTS FICs being higher than the corresponding CHEQ FICs. A statistically significant Pearson correlation (r = 0.86, P = 0.0003) and association (χ(2) = 17.05, df = 4, P = 0.002) was found between MTS FIC and CHEQ FIC-2 after 24 h. Categorical agreement was 63% with no very major or major errors. All MTS synergistic interactions were also synergistic with the CHEQ method.


Phytochemical study, an evaluation of the antioxidant potential and the antimicrobial activity of Inga semialata (Vell.) C. Mart. hydroalcohol extract.
Inga semialata (Vell.) C. Mart. belongs to the family Fabaceae. It is known for its therapeutic properties, highlighting its antimicrobial and antioxidant potential. The objective of the present work was to obtain crude extract leaves of Inga semialata, to identify and quantify active compounds, to evaluate the antioxidant potential of the crude extract in vitro, as well as to determine its antimicrobial activity. The crude extract was obtained by the maceration process. The identified and quantified of compounds present in the crude extract of Inga semialata was performed by high performance liquid chromatography. The evaluation of the antioxidant potential of the extract was realized by in vitro tests (DPPH, diacetate dichlorofluorescein test and nitric oxide test) and the evaluation of the antimicrobial activity was carried out using the minimum inhibitory concentration methodology.


Management of injuries of the eye and its adnexa.
The face plays the main role in interpersonal communication and in aesthetic perception. What is more, on account of the complex eyelid anatomy required to ensure the functioning of the eye, the treatment of periocular injuries requires a profound knowledge of anatomy and plastic reconstructive surgery, even if a loss of soft tissue is involved. Many methods for the reconstruction of eyelid defects have been described in the current literature. These methods must be guided by the site and extent of the defect on the one hand and by cosmetic requirements on the other to produce best results in terms of form and function. The treatment of injuries in the area of the eyelid involves some peculiarities that must be considered. The management of large defects in particular requires the cooperation of all head surgery disciplines.


Charons 36 to 40: multi enzyme, high capacity, recombination deficient replacement vectors with polylinkers and polystuffers.
New phage lambda based cloning vectors, Charons 36-40, have been constructed which allow cloning of large (up to 24 kb) DNA fragments with up to sixteen cloning enzymes. Several of these could not be used previously with lambda vectors. Clones produced with these vectors can be propagated under recombination deficient conditions. A novel polystuffer method has been developed that permits vector arms to be purified by simple precipitation and which allows reliable identification of clones that have reincorporated any part of the stuffer. Three of the vectors are available with amber mutations in essential genes.


Chronic myelogenous leukemia. Association with 45 XO Philadelphia chromosome karyotype and prolonged survival.
A 42-year-old man with chronic myelogenous leukemia for ten years was found to have a 45 XO Philadelphia chromosome karyotype in myeloid cells with normal 46 XY pattern in peripheral blood lymphocytes. This chromosome pattern has been postulated to be associated with delay in onset of blastic transformation. The prolonged survival of this patient, with only minimal initial chemotherapy and lack of symptoms for ten years, lends support to the concept that the missing Y chromosome may be associated with a favorable prognosis in Philadelphia chromosome-positive men with chronic myelogenous leukemia.


Progress and peril: examining antibiotic resistance and systemic contaminants.
As part of its ongoing mission to inform and support trustees and staff of health foundations and corporate giving programs, Grantmakers In Health (GIH), in conjunction with the Health and Environmental Funders Network (HEFN), held a day-long Issue Dialogue on two important environmental health issues: antibiotic resistance and systemic contaminants. Experts and advocates from many organizations came together to discuss concerns and opportunities, as well as current and potential roles for health philanthropy. This Issue Brief brings together key points from the day's discussion with factual information on environmental health drawn from a background paper prepared for the participants.


[Evaluation of a fully automated microbiology system, RAISUS to determine antimicrobial susceptibility for the isolates of Haemophilus influenzae].
A fully automated microbiology system, RAISUS (Nissui Pharmaceuticals Co., Ltd., Tokyo) was evaluated to determine antimicrobial susceptibility of the isolates of Haemophilus influenzae. The test procedures were fully automated from the inoculation of the test organism through the reading of growth-endpoint on the test plates. Also, Haemophilus Test Medium (HTM) broth supplemented with oxidation-reduction color dye, Redox, assures us of enough bacterial growth and of accurate interpretation of bacterial growth. In the evaluation, the RAISUS provided 99.2% (1,012 of 1,020 testings) agreement in MIC determinations, and 96.4% (983 of 1,020 testings) agreement in category interpretations when compared to the results obtained by the NCCLS M7-A6 and M100-S14 standards. Also, ampicillin (ABPC)-resistance in H. influenzae was characterized by the RAISUS through the addition of clavulanic acid (CVA) into the test broth. Sixteen beta-lactamase-positive isolates resulted in conversion to susceptible interpretation by addition of CVA, whereas the remaining 11 isolates did not. These unaffected isolates were presumptively identified as being beta-lactamase positive, ABPC/CVA-resistant (BLPACR). Of fifty-four beta-lactamase-negative isolates, twelve were regarded as being beta-lactamase negative, ampicillin-resistant (BLNAR) due to 4 microg/ml or greater MICs against ABPC and unaffected MICs by CVA. With the results obtained, it is concluded that the RAISUS can provide comparable determinations for the isolates of H. influenzae, in both MIC determinations and category interpretations, to the NCCLS standards, and is applicable to the routine testing in clinical laboratories.


[Determination of the level of spontaneous damage in human and mammalian cell DNA].
A technique for registration of spontaneous DNA lesions in intact mammalian cells is proposed. Arabinosid cytosine and hydroxyurea were shown to inhibit the repair of gaps spontaneously formed and accumulated in DNA leading to the formation of double-strand DNA breaks and cell death. The rate of spontaneous lesions was different in cells from different animal species and different tissues. A considerable increase in the level of spontaneous lesions was noted with ageing. It is concluded that the level of spontaneous DNA lesions is one of the fundamental biologically important characteristics of a cell.


The Use of Music Therapy During the Treatment of Cancer Patients: A Collection of Evidence.
Music therapy is one of the oldest forms of creative art therapy and has been shown to have effects in different clinical and therapeutic settings, such as schizophrenia, pain, cardiovascular parameters, and dementia. This article provides an overview of some of the recent findings in this field and also reports two single case vignettes that offer insight into day-to-day applications of clinical music therapy. For the collection of clinical studies of music therapy in oncology, the databases AMED, CAIRSS, EMBASE, MEDLINE, PsychINFO, and PSYNDEX were searched with the terms "Study OR Trial" AND "Music Therapy" AND "Cancer OR Oncolog$." Studies were analyzed with respect to their design, setting and interventions, indications, patients, and outcomes. In addition, two case vignettes present the application of music therapy for a child with leukemia and an adult patient with breast cancer. We found a total of 12 clinical studies conducted between 2001 and 2011 comprised of a total of 922 patients. Eight studies had a randomized controlled design, and four studies were conducted in the field of pediatric oncology. Studies reported heterogeneous results on short-term improvements in patients' mood and relaxation and reduced exhaustion and anxiety as well as in coping with the disease and cancer-related pain. Case descriptions showed similar effects in expressing emotions, opening up new goals, and turning the mind toward a healthy process and away form a disease-centered focus. The use of music therapy in the integrative treatment of cancer patients is a therapeutic option whose salutogenetic potential is shown in many case studies such as those presented here. Study results, however, did not draw a conclusive picture of the overall effect of music therapy. In addition to further clinical trials, the evidence mosaic should be complemented with qualitative studies, single case descriptions, and basic research.


Management of Spontaneous Hepatic Rupture on Top of HELLP Syndrome: Case Report and Review of the Literature.
We report the case of a patient with antepartum HELLP syndrome and simultaneous rupture of the right liver lobe. An emergency caesarean section was performed and the liver rupture was managed surgically via perihepatic packing. The mother and her child recovered well and were discharged 19 days after admission. We describe a case report and review the literature. Based on our own experience and the most common clinical presentations of such patients, we were able to establish an algorithm for managing such cases. An association between liver rupture and HELLP syndrome is rare but was previously described in several case reports. In pregnant women with HELLP syndrome and acute onset abdominal pain, a potential spontaneous hepatic rupture should be taken into consideration.


Single Mild Traumatic Brain Injury Induces Persistent Disruption of the Blood-Brain Barrier, Neuroinflammation and Cognitive Decline in Hypertensive Rats.
Traumatic brain injury (TBI) induces blood-brain barrier (BBB) disruption, which contributes to secondary injury of brain tissue and development of chronic cognitive decline. However, single mild (m)TBI, the most frequent form of brain trauma disrupts the BBB only transiently. We hypothesized, that co-morbid conditions exacerbate persistent BBB disruption after mTBI leading to long term cognitive dysfunction. Since hypertension is the most important cerebrovascular risk factor in populations prone to mild brain trauma, we induced mTBI in normotensive Wistar and spontaneously hypertensive rats (SHR) and we assessed BBB permeability, extravasation of blood-borne substances, neuroinflammation and cognitive function two weeks after trauma. We found that mTBI induced a significant BBB disruption two weeks after trauma in SHRs but not in normotensive Wistar rats, which was associated with a significant accumulation of fibrin and increased neuronal expression of inflammatory cytokines TNFα, IL-1β and IL-6 in the cortex and hippocampus. SHRs showed impaired learning and memory two weeks after mild TBI, whereas cognitive function of normotensive Wistar rats remained intact. Future studies should establish the mechanisms through which hypertension and mild TBI interact to promote persistent BBB disruption, neuroinflammation and cognitive decline to provide neuroprotection and improve cognitive function in patients with mTBI.


Titanates and Titanate-Metal Compounds in Biological Contexts.
Metal ions are notorious environmental contaminants, some causing toxicity at exquisitely low (ppm-level) concentrations. Yet, the redox properties of metal ions make them attractive candidates for bio-therapeutics. Titanates are insoluble particulate compounds of titanium and oxygen with crystalline surfaces that bind metal ions; these compounds offer a means to scavenge metal ions in environmental contexts or deliver them in therapeutic contexts while limiting systemic exposure and toxicity. In either application, the toxicological properties of titanates are crucial. To date, the accurate measurement of the in vitro toxicity of titanates has been complicated by their particulate nature, which interferes with many assays that are optical density (OD)-dependent, and at present, little to no in vivo titanate toxicity data exist. Compatibility data garnered thus far for native titanates in vitro are inconsistent and lacking in mechanistic understanding. These data suggest that native titanates have little toxicity toward several oral and skin bacteria species, but do suppress mammalian cell metabolism in a cells-pecific manner. Titanate compounds bind several types of metal ions, including some common environmental toxins, and enhance delivery to bacteria or cells. Substantial work remains to address the practical applicability of titanates. Nevertheless, titanates have promise to serve as novel vehicles for metal-based therapeutics or as a new class of metal scavengers for environmental applications.


Influences of Socio-Demographic Factors and Health Utilization Factors on Patient-Centered Provider Communication.
Patient-centered care has been documented as a measure of quality of health care and has been associated with positive health outcomes. However, the effect of health utilization on improving patient-centered communication has not been investigated. This study examined the effect of three important kinds of health utilization: routine check-up, frequency of provider visits in the last year, and quality of health care to patient-centered provider communication. Cross-sectional data from 3,608 respondents to Health Information National Trends Survey-Cycle 4 2014 were analyzed. Multiple regressions were used to examine the association of sociodemographic factors and health utilization to patient-centered provider communication. Results showed that adults above 50 years and women reported higher patient-centered provider communication. Hispanic and Asian versus White respondents reported poorer patient-centered provider communication. Respondents with routine checkups between 1 and 2 years, 2 and 5 years, 5 or more years and none were all negatively associated with patient-centered provider communication in comparison with routine checkup within 1 year. Respondents who didn't visit health provider within past year had poorer patient-centered provider communication when compared to those who visited once. Finally, higher quality of healthcare experience was associated with higher patient-centered provider communication. Thus, this study highlights that race and ethnicity, age, and gender are significant factors that influence patient-centered provider communication; and specifically higher quality of healthcare experience, one provider visit within past year, and annual routine checkup as measures of health utilization predicts improved patient-centered provider communication.


Stored electromagnetic energy and quality factor of radiating structures.
This paper deals with the old yet unsolved problem of defining and evaluating the stored electromagnetic energy-a quantity essential for calculating the quality factor, which reflects the intrinsic bandwidth of the considered electromagnetic system. A novel paradigm is proposed to determine the stored energy in the time domain leading to the method, which exhibits positive semi-definiteness and coordinate independence, i.e. two key properties actually not met by the contemporary approaches. The proposed technique is compared with an up-to-date frequency domain method that is extensively used in practice. Both concepts are discussed and compared on the basis of examples of varying complexity.


Long-term electrical stimulation of bed nucleus of stria terminalis for obsessive-compulsive disorder.
We previously reported that bilateral electrical stimulation in the anterior limb of the internal capsule/bed nucleus of the stria terminalis (IC/BST) effectively reduces symptoms in severe treatment-resistant obsessive-compulsive disorder (OCD) patients. Here we used a linear mixed model to investigate the evolution of symptomatic and functional status of our patients (n=24) and examined if baseline variables could predict this evolution. Data were collected during routine, clinical psychiatric visits. Our analysis showed a long-term, sustained effect of electrical stimulation in the IC/BST. After a fast initial decline of OCD symptoms, these symptoms remain relatively stable. In addition, we found a strong ON/OFF effect of stimulation (e.g., due to battery depletion). Our data also show that it is not the surgical procedure but rather the electrical stimulation that drives the improvement in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. The Beck Depression Inventory (BDI) at baseline was the only predictor significantly related to the evolution of the Y-BOCS. A higher BDI at baseline seemed to be related to a smaller decrease of the Y-BOCS over time. In conclusion, electrical stimulation in the IC/BST has a fast and sustained effect on OCD and comorbid symptoms and functional status of patients.


Mothers of Deaf Children in the 21st Century. Dynamic Positioning Between the Medical and Cultural-Linguistic Discourses.
Traditional research examining the communicational choices made by families with deaf children tends to emanate from the premise that families engage with either of the two grand discourses on deafness (i.e., the medical or cultural-linguistic perspective). This study investigated hearing mother's engagement with the educational options for their child from a dynamic, poststructural perspective. Three Flemish mothers were interviewed in-depth at the child's ages of 6, 9, 12, 18, and 24 months. The data were analyzed within a theoretical model that describes the positioning process of the mothers. This method yielded alternative explanations for former findings concerning mothers' decision-making processes, especially the difficulty of learning sign language as a second language in an effort to provide a bilingual-bicultural education, and highlighted the importance of having rich experiences. It further showed that a bilingual-bicultural position was scarcely available and poorly supported for these mothers. These findings are discussed in relation to recent international consensus statements on best practices in early intervention.


Technical-economic comparison of chemical precipitation and ion exchange processes for the removal of phosphorus from wastewater.
Chemical precipitation with the addition of ferric chloride is commonly used to remove phosphorus from wastewater. However, since its application also involves several disadvantages, alternative solutions are required. The present paper shows the results of a full-scale experimental work aimed at evaluating the efficiency of the ion exchange process using a polymeric anion exchange resin impregnated with aluminum ions in the removal of phosphorus from wastewater. The study compared the results obtained through this process with chemical precipitation, considering both technical and economic issues. At the same dosage of 6 L/hour and influent concentration (about 6 mg/L), total removal efficiency of 95% and 78% (including also that occurring in the mechanical and biological processes) was achieved by means of the anion exchange process and chemical precipitation, respectively. However, in the latter case, this value was insufficient to ensure consistent compliance with the limit of 2 mg/L Ptot set on the effluent; to achieve this goal, the ferric chloride dosage had to be raised to 12 L/hour, thus increasing the related costs. Furthermore, the anion exchange process generated a lower sludge production. Therefore, the ion exchange process represents a valid alternative to chemical precipitation for P removal from wastewater.


Nucleus accumbens deep brain stimulation improves depressive-like behaviors through BDNF-mediated alterations in brain functional connectivity of dopaminergic pathway.
Major depressive disorder (MDD), a common psychiatric condition, adversely affects patients' moods and quality of life. Despite the development of various treatments, many patients with MDD remain vulnerable and inadequately controlled. Since anhedonia is a feature of depression and there is evidence of leading to metabolic disorder, deep brain stimulation (DBS) to the nucleus accumbens (NAc) might be promising in modulating the dopaminergic pathway. To determine whether NAc-DBS alters glucose metabolism via mitochondrial alteration and neurogenesis and whether these changes increase neural plasticity that improves behavioral functions in a chronic social defeat stress (CSDS) mouse model. The Lab-designed MR-compatible neural probes were implanted in the bilateral NAc of C57BL/6 mice with and without CSDS, followed by DBS or sham stimulation. All animals underwent open-field and sucrose preference testing, and brain resting-state functional MRI analysis. Meanwhile, we checked the placement of neural probes in each mouse by T2 images. By confirming the placement location, mice with incorrect probe placement (the negative control group) showed no significant therapeutic effects in behavioral performance and functional connectivity (FC) after receiving electrical stimulation and were excluded from further analysis. Western blotting, seahorse metabolic analysis, and electron microscopy were further applied for the investigation of NAc-DBS. We found NAc-DBS restored emotional deficits in CSDS-subjected mice. Concurrent with behavioral amelioration, the CSDS DBS-on group exhibited enhanced FC in the dopaminergic pathway with increased expression of BDNF- and NeuN-positive cells increased dopamine D1 receptor, dopamine D2 receptors, and TH in the medial prefrontal cortex, NAc, ventral hippocampus, ventral tegmental area, and amygdala. Increased pAMPK/total AMPK and PGC-1α levels, functions of oxidative phosphorylation, and mitochondrial biogenesis were also observed after NAc-DBS treatment. Our findings demonstrate that NAc-DBS can promote BDNF expression, which alters FC and metabolic profile in the dopaminergic pathway, suggesting a potential strategy for ameliorating emotional processes in individuals with MDD.


When a Specialty Becomes "Women's Work": Trends in and Implications of Specialty Gender Segregation in Medicine.
The gender composition of physician specialties varies dramatically with some becoming increasingly female predominant while others remain overwhelmingly male. In their analysis of physician workforce data, the authors demonstrate that despite large increases in the number of female physicians over 4 decades, the degree of gender segregation between specialties has not declined. The authors describe lessons from the highly gender-segregated U.S. workforce as a whole to understand these demographic patterns in the physician workforce. Echoing U.S. workforce findings, women physicians are becoming overrepresented in certain specialties, and this appears to be associated with a relative decline in earnings for physicians in these specialties over time. The authors found a strong negative relationship between the proportion of female physicians in a specialty and its mean salary, with gender composition explaining 64% of the variation in salaries among the medical specialties.Female physicians face biases in the workplace and fall behind male peers in leadership attainment, academic advancement, and earnings. Tenacious gender stereotypes and the conflation of gender and status contribute to these biases and reinforce occupational gender segregation. The clustering of women in certain specialties means these specialties will be disproportionately affected by gender bias. Recognizing the consequences of gender demographics within physician specialties is important to maintain the strong and diverse physician workforce needed to support the health care needs of the populations who depend on these specialties for care.


Linking the Heart and the Head: Humanism and Professionalism in Medical Education and Practice.
This paper articulates a practical interpretive framework for understanding humanism in medicine through the lens of how it is taught and learned. Beginning with a search for key tensions and relevant insights in the literature on humanism in health professions education, we synthesized a conceptual model designed to foster reflection and action to realize humanistic principles in medical education and practice. The resulting model centers on the interaction between the heart and the head. The heart represents the emotive domains of empathy, compassion, and connectedness. The head represents the cognitive domains of knowledge, attitudes, and beliefs. The cognitive domains often are associated with professionalism, and the emotive domains with humanism, but it is the connection between the two that is vital to humanistic education and practice. The connection between the heart and the head is nurtured by critical reflection and conscious awareness. Four provinces of experience nurture humanism: (1) personal reflection, (2) action, (3) system support, and (4) collective reflection. These domains represent potential levers for developing humanism. Critical reflection and conscious awareness between the heart and head through personal reflection, individual and collective behavior, and supportive systems has potential to foster humanistic development toward healing and health.


Pancreatic neuroendocrine carcinoma with exocrine differentiation in a young cat.
A 35-mo-old spayed female mixed-breed cat with continuous vomiting, emaciation, and abdominal distention for 2 wk was presented to a private veterinary clinic for evaluation. At 71 d after the initial visit, the cat died with anemia, jaundice, and hypoalbuminemia, and was subjected to autopsy. Grossly, numerous firm masses, 0.5-2.5 cm diameter, were randomly located in the left lobe of the pancreas. Histologic examination revealed that the pancreatic mass consisted of 2 tumor cell types: mostly small round cells with a minority of epithelial cells. The small cells were arranged in nests of various sizes, which were separated by thin fibrous stroma, and had small, round, hyperchromatic nuclei, scant cytoplasm containing argyrophilic granules, and often formed rosettes. The epithelial cells formed luminal structures. Metastases were observed in the liver, greater omentum, and pancreatic, gastric, pulmonary, and mediastinal lymph nodes. Immunohistochemical examination revealed that the small cells were positive for vimentin, neuron-specific enolase, chromogranin A, cytokeratin (CK) AE1/AE3, and trypsin, whereas the epithelial cells were positive for AE1/AE3, trypsin, CK19, and nestin. Ultrastructurally, the small cells contained abundant electron-dense granules, ~200 nm diameter, whereas the epithelial cells had apical microvilli and numerous zymogen granules, ~300 nm diameter. These findings indicated that the tumor was a pancreatic neuroendocrine carcinoma with exocrine differentiation and systemic metastases.


Two new species of Heptapterus (Siluriformes: Heptapteridae) from the Uruguay River basin, Brazil.
As part of an ongoing taxonomic revision of the genus Heptapterus from the Laguna dos Patos and Uruguay River drainages and Atlantic coastal streams of southern Brazil and Uruguay, two new species closely related to Heptapterus mustelinus were identified. Both species are endemic to small tributaries of the Uruguay River. The two new species are distinguished from each other and from other species of Heptapterus by arrangement of cephalic and trunk laterosensory systems, number of vertebrae and number of dorsal, pectoral and anal-fin rays. Phylogenetic analyses of mitochondrial DNA (coI and cytb) sequence data further supports distinctiveness of the two new species.


Potent antimalarial febrifugine analogues against the plasmodium malaria parasite.
Although febrifugine (1) and isofebrifugine (2), alkaloids isolated from roots of the Dichroa febrifuga plant, show powerful antimalarial activity against Plasmodium falciparum, strong side effects such as the emetic effect have precluded their clinical use against malaria. However, their antimalarial potency makes them attractive substances as leads for developing new types of chemotherapeutic antimalarial drugs. Thus, we have evaluated the in vitro antimalarial activity of the analogues of febrifugine (1) and isofebrifugine (2). The activities of the analogues derived from Df-1 (3) and Df-2 (4), condensation products of 1 and 2 with acetone, respectively, were also obtained. The 3' '-keto derivative (7, EC(50) = 2.0 x 10(-8) M) of 1 was found to exhibit potential antimalarial activity with high selectivity against P. falciparum in vitro. The in vitro activities of the reduction product (8, EC(50) = 2.0 x 10(-8) M) of 1 at C-2' and its cyclic derivatives 9 and 10 (EC(50) = 3.7 x 10(-9) and 8.6 x 10(-9) M, respectively) were found to be strongly active and selective. Additionally, the Dess-Martin oxidation product of 3 was found to be strongly active with high selectivity against P. falciparum. A structure-activity relationship study (SAR) demonstrates that the essential role played by the 4-quinazolinone ring in the appearance of activity and the presence of a 1' '-amino group and C-2', C-3' ' O-functionalities are crucial in the activity of 1. For 7, 8, and 9, prepared as racemic forms, an in vivo study has also been conducted.


Effect of combination therapy with atenolol and the angiotensin-converting enzyme inhibitor benazepril.
The purpose of this study was to determine whether patients whose blood pressure failed to normalize while receiving monotherapy with atenolol would experience further blood pressure lowering by adding the angiotensin-converting enzyme (ACE) inhibitor benazepril hydrochloride to their treatment regimen. Seventy-four of the original 127 patients treated with atenolol met the criteria for entry into the 4-week, double-blind phase of the study, in which either benazepril 10 mg twice daily (increased after 1 week, if necessary, to 20 mg twice daily) or placebo was added to atenolol. At end point, 46% of the benazepril group had achieved an excellent or good response (ie, diastolic blood pressure [DBP] < 90 mm Hg or a decrease of > or = 10 mm Hg below the baseline) compared with 14% of the placebo group (P < 0.01). The mean fall in DBP at end point was -5.6 mm Hg in the benazepril group and -3.7 mm Hg in the placebo group. Because six patients in the benazepril group experienced an increase of blood pressure that offset the fall observed in the responders, the difference in DBP response between the benazepril group and the placebo group was not statistically significant. We conclude that adding benazepril to the regimen of patients whose blood pressure is inadequately controlled while receiving atenolol monotherapy can produce an additional decrease in blood pressure in almost half the patients.


Wave-particle energy exchange directly observed in a kinetic Alfvén-branch wave.
Alfvén waves are fundamental plasma wave modes that permeate the universe. At small kinetic scales, they provide a critical mechanism for the transfer of energy between electromagnetic fields and charged particles. These waves are important not only in planetary magnetospheres, heliospheres and astrophysical systems but also in laboratory plasma experiments and fusion reactors. Through measurement of charged particles and electromagnetic fields with NASA's Magnetospheric Multiscale (MMS) mission, we utilize Earth's magnetosphere as a plasma physics laboratory. Here we confirm the conservative energy exchange between the electromagnetic field fluctuations and the charged particles that comprise an undamped kinetic Alfvén wave. Electrons confined between adjacent wave peaks may have contributed to saturation of damping effects via nonlinear particle trapping. The investigation of these detailed wave dynamics has been unexplored territory in experimental plasma physics and is only recently enabled by high-resolution MMS observations.


Systemic conditions for performance of pharmacoepidemiologic studies in Slovenia.
In Slovenia, the national health insurance system covers almost the whole population. The average patient receives six to seven prescriptions per year with an average value of 15 USD per prescription. This paper presents the systemic conditions necessary for the performance of pharmacoepidemiologic studies. A recent study addressing the use of antiepileptic drugs is an example. The current law on Personal Data Protection, which is compliant with EU Directive 95/46/EC, prevents infringement of personal integrity resulting from inappropriate use of personal data or inappropriate management and use of databases containing personal data. Since July 2000, the Law on Health Care Related Databases has defined the databases and the ways data can be acquired, processed, transferred, and exchanged among persons authorized to perform health care services. When gathering additional data not currently contained in the health care-related databases defined by the law, written consent from participants is required, and study documentation must be submitted for approval to the national Medical Ethics Committee. The main legislation covering clinical and pharmacoepidemiologic research is the Medicinal Products and Medical Devices Act of 1999, together with its by-laws, which is also in accordance with EU Directives.


Pathogenetic and therapeutic considerations of carotid-cavernous sinus fistulas.
Carotid-cavernous sinus fistula (CCF) is a syndrome in which arteriovenous shunts exist between the carotid artery and the cavernous sinus. These shunts vary widely in pathogenesis, angiogram, haemodynamics and treatment. Several systems of classification in terms of either haemodynamics, aetiology and/or pathogenesis have been reported, but they are not comprehensive. A more comprehensive and simpler nomenclature of classification is now required. Fifty seven cases of CCFs were analyzed and were classified according to their pathogenesis, angiography and treatment modalities. There were 11 traumatic CCFs with direct shunts (T-D group), and 2 traumatic CCFs with indirect shunts (T-I group). Spontaneous CCFs were divided into three groups. There were 37 spontaneous CCFs caused by dural arteriovenous shunts that were naturally classified as being indirect shunts (SD-I group). There were 5 spontaneous CCFs caused by suspected connective tissue disorders, such as fibromuscular dysplasia, Ehlers-Danlos syndrome etc.; these had direct shunts. Care was needed to avoid dissection of the artery or complications due to the fragility of connective tissue (SC-D group). There were 2 spontaneous CCFs caused by the rupture of an inflaclinoid aneurysm without any background of connective tissue disorder; these had direct shunts (SA-D group). By this system of grouping and use of abbreviations, each case of CCF can be clearly delineated in terms of its pathogenesis and selection for appropriate treatment.


Periprocedural unfractionated heparin bolus during endovascular treatment in acute ischemic stroke does more harm than good.
Unfractionated heparin (UFH) bolus is occasionally administered during endovascular treatment (EVT) to reduce thrombotic complications in acute ischemic stroke patients. However, the MR CLEAN-MED trial showed an increase in symptomatic intracranial hemorrhages (sICH) and a non-significant shift towards worse functional outcome with UFH administration. We aimed to analyze the impact of periprocedural UFH bolus in a real-world setting in anterior (ACS) and posterior circulation stroke (PCS) patients. We analyzed data from the German Stroke Registry-Endovascular Treatment using propensity score matching. Primary outcome was the modified Rankin Scale at 3 months, and secondary outcome measures included mortality, angiographic outcomes, post-EVT National Institute of Health Stroke Scale scores and ICH at 24 hours. Among 13,082 patients, 7948 with ACS (UFH bolus use in 15%) and 841 with PCS (UFH bolus use in 16.3%) were included in the propensity score matching analysis. Applying MR CLEAN-MED study criteria, UFH bolus was associated with worse functional outcomes (odds ratio [OR] 1.44; 95% CI 1.06-1.96). Analyzing all ACS and PCS patients, UFH bolus did not provide any net benefit. In ACS patients treated with intravenous thrombolysis (IVT), UFH bolus use was associated with worse functional outcomes (OR 2.40; 95% CI 1.34 to 5.06). Our findings show transferability of the MR CLEAN-MED results into a real-world setting, confirming a negative effect of periprocedural UFH on functional outcome in this subgroup of patients. Considering all ACS and PCS patients, periprocedural UFH did not provide a net benefit and appears to be harmful, particularly in IVT-treated patients.


[Bilateral laparoscopic nephrectomy for renal cancer].
To report the case of a patient with a bilateral synchronic renal tumor who underwent a laparoscopic surgical approach. 57-year-old caucasian male with history of end stage renal disease and secondary hypertension, type II diabetes Mellitus, proteinuria of 2.83 g/24 hours, chronic smoker, and allergic to iodinated contrast who underwent right nephrectomy and simultaneous left laparoscopic transperitoneal nephroureterectomy for a bilateral renal tumor. Operative time was 4 hours; NG tube was inserted; estimated blood loss was 200 ml and no transfusions were required. Oral intake was re-established after two days. No intraoperative complications occurred; metabolic acidosis appearing in the intermediate postoperative period was corrected with intravenous sodium bicarbonate. Hospital stay was 9 days. Bilateral laparoscopic nephrectomy is an effective therapeutic option in the management of patients with bilateral malignant renal diseases, which ensures surgical radicality, and diminishes morbidity, hospital stay and recovery time.


The development of the conception of socioeconomic mobility in children from Mexico and Spain.
The authors studied the developmental stages of children's understanding of upward socioeconomic mobility. They interviewed one hundred 6- to 14-year-old participants from Mexico and Spain and asked them about sources of wealth and factors related to socioeconomic mobility. Categorical analyses of the responses showed few age-related changes but noted some cross-national differences. A different analysis designed to identify levels of understanding showed a significant association between age and type of explanation of socioeconomic mobility. Overall, cross-national comparisons yielded similarities in children's developmental trends, and only slight differences were found with regard to cultural background. The present results contrast with those of studies conducted from the perspective of the social representation theory.


Clinical features of tuberous sclerosis cases.
Tuberous sclerosis (TS) is an autosomal dominant, multisystemic and neurocutaneous disease with high spontaneous mutation rate, and it mostly involves the skin, brain, kidneys, heart and the eyes. This study included 35 patients diagnosed with tuberous sclerosis and aged 6 months to 17 years, with a mean age of 6.5+/-4.8 years. The most frequently observed manifestations were those of the skin (97.1%) and of the central nervous system (seizures 94.2%, mental retardation 51.4%), followed by renal (32.2%), cardiac (25.8%) and ocular (22.5%) manifestations. Among cutaneous manifestations, hypomelanotic macules (94.3%), facial angiofibromas (40%), shagreen spots (20%), fibrous plaques on the forehead (5.7%) and ungula fibromas (5.7%) were observed. Tonic seizures (37.1%) and infantile spasms (21.2%) accounted for majority of seizures. Neurophysiological development was normal in 25.6% of cases, retarded in 51.4% and borderline in 23%. Thirty-four patients had typical pathological findings on magnetic resonance imaging (MRI). In conclusion, the earliest and most frequent complaint is seizure in cases with TS. Careful investigation for hypomelanotic macules and other skin manifestations typical for TS in cases presenting with convulsion makes early diagnosis possible and obviates unnecessary investigations.


Increased prevalence of unprovoked seizures in patients with a 22q11.2 deletion.
Many neurologic abnormalities have been identified in patients with a deletion of chromosome region 22q11.2, including recurrent, apparently unprovoked seizures. We reviewed the database of patients with a 22q11.2 deletion at the Children's Hospital of Philadelphia to assess the prevalence of idiopathic epilepsy in this population. The records of 383 patients with a confirmed 22q11.2 deletion were reviewed for documentation of seizures; precipitating events such as hypocalcemia, fever, and recent surgery; MRI and EEG findings (to aid in seizure classification); and potential risk factors for epilepsy. Of 348 patients with adequately detailed histories, 27 patients had apparently unprovoked seizures (7% of the total population). A disproportionate number of these patients met criteria for generalized epilepsy. Cardiac disease and prematurity were not risk factors for the development of unprovoked seizures in this population. The prevalence of unprovoked seizures in individuals meeting criteria for epilepsy in patients with a 22q11.2 deletion evaluated at our institution is much greater than in the general population. The association with generalized epilepsy suggests that this increased risk is a primary manifestation of the genetic syndrome, not a secondary result of the other manifestations of 22q11.2 deletions. These results suggest that diagnostic screening for the 22q11.2 deletion syndrome should be considered in patients with epilepsy and other signs suggestive of this interstitial deletion syndrome, and have implications for the identification of potential genetic loci for idiopathic epilepsy.


Three functional subdomains of the Escherichia coli FtsQ protein are involved in its interaction with the other division proteins.
FtsQ, an essential protein for the Escherichia coli divisome assembly, is able to interact with various division proteins, namely FtsI, FtsL, FtsN, FtsB and FtsW. In this paper, the FtsQ domains involved in these interactions were identified by two-hybrid assays and co-immunoprecipitations. Progressive deletions of the ftsQ gene suggested that the FtsQ self-interaction and its interactions with the other proteins are localized in three periplasmic subdomains: (i) residues 50-135 constitute one of the sites involved in FtsQ, FtsI and FtsN interaction, and this site is also responsible for FtsW interaction; (ii) the FtsB interaction is localized between residues 136 and 202; and (iii) the FtsL interaction is localized at the very C-terminal extremity. In this third region, the interaction site for FtsK and also the second site for FtsQ, FtsI, FtsN interactions are located. As far as FtsW is concerned, this protein interacts with the fragment of the FtsQ periplasmic domain that spans residues 67-75. In addition, two protein subdomains, one constituted by residues 1-135 and the other from 136 to the end, are both able to complement an ftsQ null mutant. Finally, the unexpected finding that an E. coli ftsQ null mutant can be complemented, at least transiently, by the Streptococcus pneumoniae divIB/ftsQ gene product suggests a new strategy for investigating the biological significance of protein-protein interactions.


Sinularin Induces Apoptosis through Mitochondria Dysfunction and Inactivation of the pI3K/Akt/mTOR Pathway in Gastric Carcinoma Cells.
Sinularin is an active compound isolated from the cultured soft coral Sinularia flexibilis. In this study, we investigated the effects of sinularin on two human gastric cancer cell lines, AGS and NCI-N87. Our results demonstrated that sinularin suppressed the proliferation of gastric cancer cells in a dose-dependent manner and induced apoptosis. In addition, the loss of mitochondrial membrane potential, the release of cytochrome C, the activation of Bax, Bad and caspase-3/9, and the suppression of p-Bad, Bcl-xL and Bcl-2 were observed in the cells treated with sinularin. This finding suggests that sinularin-induced apoptosis is associated with mitochondria-mediated apoptosis and occurs through caspase-dependent pathways. Furthermore, sinularin inhibited the phosphoinositol 3-kinase/Akt/mechanistic target of the rapamycin signaling pathway. Taken together, our results show that sinularin-induced apoptosis is mediated by activation of the caspase cascade and mitochondrial dysfunction. Our findings suggest that sinularin merits further evaluation as a chemotherapeutic agent for human gastric cancer.


Immune Checkpoint Inhibitor-Related Myositis: From Biology to Bedside.
: Immune checkpoint inhibitor (ICI)-related inflammatory diseases, including polymyositis (PM) and dermatomyositis (DM), in patients suffering from neoplastic disorders represent a medical challenge. The treatment of these conditions has taken on new urgency due to the successful and broad development of cancer-directed immunological-based therapeutic strategies. While primary and secondary PM/DM phenotypes have been pathophysiologically characterized, a rational, stepwise approach to the treatment of patients with ICI-related disease is lacking. In the absence of high-quality evidence to guide clinical judgment, the available data must be critically assessed. In this literature review, we examine partially neglected immunological and clinical findings to obtain insights into the biological profiles of ICI-related PM/DM and potential treatment options. We show that differential diagnosis is essential to stratifying patients according to prognosis and therapeutic impact. Finally, we provide a comprehensive assessment of druggable targets and suggest a stepwise patient-oriented approach for the treatment of ICI-related PM/DM.


[Hip rotation degrees, intoeing problem, and sitting habits in nursery school children: an analysis of 1,134 cases].
We investigated hip rotation degrees, frequency of intoeing problems, and sitting habits in nursery school children and the relationship between these parameters. The study included 1,134 children (612 boys, 522 girls), aged between three to six years, attending 26 nursery schools in the central area of Afyon. First, informed consent was obtained from the parents and a questionnaire was administered about demographic data and sitting habits of the children. Then, the children were examined in lower underwear. Foot progression angles were determined and progression to midline during walking was evaluated as intoeing. Internal and external rotation degrees of the hips were measured using a goniometer in prone and supine positions. In girls, internal rotation of the hip was nearly 13 degrees greater in the prone position, and 9 degrees greater in the supine position compared to those of the boys. Intoeing was detected in 67 children (5.9%), 76.1% being bilateral. The girl-to-boy ratio was 2.4/1. Intoeing problem originated from the femur in 74.6%, and from the tibia in 25.4%. Compared to normal children, intoeing was associated with a greater internal rotation and a smaller external rotation of the hip. Overall, 36.7% had a crossed-leg sitting habit, and 63.3% had a television sitting habit. The latter was more frequent in intoeing children (p=0.001). Although hip rotation degrees in our study were similar to those reported in the literature, higher hip internal rotation degrees were found especially in girls. Television sitting which is a frequently preferred position among nursery school children was significantly prevalent in intoeing children.


Checklist of the cestode parasites of wild birds of Argentina.
An annotated checklist of the cestode parasites of Argentinean wild birds is presented, as the result of a compilation of parasitological papers published between 1900 and April 2021. This review provides data on hosts, geographical distribution, sites of infection, location of material deposited in helminthological collections, references and taxonomic comments. A host/parasite list is also provided. During this period, 38 papers were published that gather information about 34 cestode nominal species and 11 taxa identified at generic level, belonging to three orders, ten families and 35 genera. The highest number of cestode taxa was recorded in the family Hymenolepididae, with 12 nominal species and two taxa identified at generic level, followed by Dilepididae, with eight nominal species and three taxa identified at generic level. Of the 1042 species of birds reported in Argentina, only 29 (2.8%) were reported as hosts of adult cestodes. The families of birds with the highest number of reported taxa were Laridae and Anatidae, with 20 and 14 taxa, respectively.


FGFR3 is a negative regulator of the expansion of pancreatic epithelial cells.
Fibroblast growth factors (FGFs) and their receptors (FGFRs) are key signaling molecules for pancreas development. Although FGFR3 is a crucial developmental gene, acting as a negative regulator of bone formation, its participation remains unexplored in pancreatic organogenesis. We found that FGFR3 was expressed in the epithelia in both mouse embryonic and adult regenerating pancreata but was absent in normal adult islets. In FGFR3 knockout mice, we observed an increase in the proliferation of epithelial cells in neonates, leading to a marked increase in islet areas in adults. In vitro studies showed that FGF9 is a very potent ligand for FGFR3 and activates extracellular signal-related kinases (ERKs) in pancreatic cell lines. Moreover, FGFR3 blockade or FGFR3 deficiency led to increased proliferation of pancreatic epithelial cells in vivo. This was accompanied by an increase in the proportion of potential islet progenitor cells. Thus, our results show that FGFR3 signaling inhibits the expansion of the immature pancreatic epithelium. Consequently, this study suggests that FGFR3 participates in regulating pancreatic growth during the emergence of mature islet cells.


Ikaros Zinc Finger Transcription Factors: Regulators of Cytokine Signaling Pathways and CD4+ T Helper Cell Differentiation.
CD4+ T helper cells are capable of differentiating into a number of effector subsets that perform diverse functions during adaptive immune responses. The differentiation of each of these subsets is governed, in large part, by environmental cytokine signals and the subsequent activation of downstream, cell-intrinsic transcription factor networks. Ikaros zinc finger (IkZF) transcription factors are known regulators of immune cell development, including that of CD4+ T cell subsets. Over the past decade, members of the IkZF family have also been implicated in the differentiation and function of individual T helper cell subsets, including T helper 1 (TH1), TH2, TH17, T follicular (TFH), and T regulatory (TREG) cells. Now, an increasing body of literature suggests that the distinct cell-specific cytokine environments responsible for the development of each subset result in differential expression of IkZF factors across T helper populations. Intriguingly, recent studies suggest that IkZF members influence T helper subset differentiation in a feed-forward fashion through the regulation of these same cytokine-signaling pathways. Here, we review the increasingly prominent role for IkZF transcription factors in the differentiation of effector CD4+ T helper cell subsets.


Recombinant Lipase from Gibberella zeae Exhibits Broad Substrate Specificity: A Comparative Study on Emulsified and Monomolecular Substrate.
Using the classical emulsified system and the monomolecular film technique, the substrate specificity of recombinant Gibberella zeae lipase (rGZEL) that originates from Gibberella zeae was characterized in detail. Under the emulsified reaction system, both phospholipase and glycolipid hydrolytic activities were observed, except for the predominant lipase activity. The optimum conditions for different activity exhibition were also determined. Compared with its lipase activity, a little higher ratio of glycolipid hydrolytic activity (0.06) than phospholipase activity (0.02) was found. rGZEL preferred medium chain-length triglycerides, while lower activity was found for the longer-chain triglyceride. Using the monomolecular film technique, we found that the preference order of rGZEL to different phospholipids was 1,2-diacyl-sn-glycero-3-phospho-l-serine (PS) > 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (PG) > 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) > l-α-phosphatidylinositol (PI) > cardiolipin (CL) > 3-sn-phosphatidic acid sodium salt (PA) > l-α-phosphatidylethanolamine (PE), while no hydrolytic activity was detected for sphingomyelin (SM). Moreover, rGZEL showed higher galactolipase activity on 1,2-distearoyimonoglactosylglyceride (MGDG). A kinetic study on the stereo- and regioselectivity of rGZEL was also performed by using three pairs of pseudodiglyceride enantiomers (DDGs). rGZEL presented higher preference for distal DDG enantiomers than adjacent ester groups, however, no hydrolytic activity to the sn-2 position of diglyceride analogs was found. Furthermore, rGZEL preferred the R configuration of DDG enantiomers. Molecular docking results were in concordance with in vitro tests.


Reinnervation of allografted pancreatic islets in the rat liver.
Rat pancreatic islets were allografted in the liver and were studied morphologically in order to evaluate possible reinnervation. Islets isolated from rat pancreas were allotransplanted in the liver of streptozocin-induced diabetic rats via the portal vein. Electron microscopy revealed nerve endings with synaptic vesicles in the transplanted islets 100 days after transplantation, whereas axons in the islets appeared to degenerate several hours after isolation and prior to transplantation. These findings suggest that the nerve endings observed in the transplanted islets regenerate from nerves that innervate the recipient's liver. The tissue specimens were also investigated immunohistochemically using antityrosine hydroxylase antibody, and histochemically by the modified Karnovsky and Roots' method for visualizing acetylcholinesterase. Some nerve endings in the transplanted islets reacted positively to antityrosine hydroxylase antibody. Acetylcholinesterase was visualized in other nerves. These results indicate that norepinephrine- and acetylcholinesterase-containing nerves may reinnervate the transplanted islets.


Association between constipation and major depression in adult Americans: evidence from NHANES 2005-2010.
Current studies on the association between constipation and depression is still insufficient. In this study, we investigated the detailed association between constipation and major depression among American adults. In this cross-sectional study, 12,352 adults aged 20 and older were selected from the National Health and Nutrition Examination Survey 2005-2010 for the sample. Constipation was defined as fewer than three defecation frequencies per week. For the assessment of major depression, the validated Patient Health Questionnaire-9 was used. Adjusted odds ratios (ORs) were calculated using multivariate logistic regression models. A subgroup analysis was carried out to ensure that the results were stable. Of the 12,352 participants, 430 reported constipation, with a prevalence of 3.5%. Depression was reported in 1030 cases, indicating a prevalence rate of 8.3%. Patients with constipation were significantly more likely to have major depression (20.9%) than those without it (7.9%, p < 0.001). After adjusting for age, sex, race/ethnicity, marital status, education level, body mass index, vigorous physical activity, alcohol consumption, smoking status, poverty income ratio, diabetes, selective serotonin reuptake inhibitor use, liver disease, heart disease, pulmonary disease, hypertension, arthritis, cancer, dietary fiber intake, moisture intake, total fat intake, carbohydrates intake, and protein intake, constipation is significantly associated with major depression (OR: 2.20, 95%CI: 1.68-2.87, p < 0.001). Subgroup analyses by age, sex, dietary intake, risk behaviors, and common complications showed no statistically significant interactions (p > 0.05). In conclusion, this study showed that constipation were significantly associated with depression. When treating patients with constipation, it is necessary for clinicians to screen and evaluate depression, and provide timely and effective intervention for patients with depression to avoid further deterioration of the condition.


Objective measures of sleep in fibromyalgia syndrome: Relationship to clinical, psychiatric, and immunological variables.
We aimed to investigate the changes in the objective and subjective sleep variables during painful episodes of fibromyalgia and post-episode period, and to evaluate the impact of the sleep variables on the current clinical, psychological, and immunologic parameters. Thirty-one consecutive patients who were referred to the Erenköy Physical Therapy and Rehabilitation Polyclinic with a diagnosis of fibromyalgia were evaluated before and in the sixth week of the acute pain treatment. The sleep variables were measured by polysomnography, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale. The clinical and psychiatric assessment of patients was performed by using Fibromyalgia Impact Questionnaire; Patient Health Questionnaire-Somatic, Anxiety, and Depressive Symptoms; and Visual Analog Scale. Serum pro-inflammatory molecules were measured to evaluate the immunological status. The pain treatment significantly affected subjective sleep variables, psychiatric variables, clinical variables, and IL-6 levels. The subjective sleep parameters, clinical and psychiatric variables, and IL-6 levels were improved with pain treatment in fibromyalgia. The objective sleep variables, IL-1 and TNF-alpha levels were not significantly improved with the pain treatment, and they were not related to clinical presentation of patients with fibromyalgia. Subjective variability of sleep contributes to the clinical presentation, suggesting that the objective structure is trait-specific with IL-1 and TNF-alpha.


Screening of furanocoumarin derivatives in citrus fruits by enzyme-linked immunosorbent assay.
This paper reports a sensitive and specific enzyme-linked immunosorbent assay for screening of furanocoumarin derivatives as cytochrome P450 3A4 inhibitors in citrus fruits. Anti-6',7'-dihydroxybergamottin antibody was obtained by immunizing rabbits with 6',7'-dihydroxybergamottin conjugated with bovine serum albumin using the N-succinimidyl ester method. An enzyme marker was similarly prepared by coupling 6',7'-dihydroxybergamottin with beta-D-galactosidase. The enzyme-linked immunosorbent assay is capable of detecting as little as 800 pg/ml of 6',7'-dihydroxybergamottin and 4 ng/ml of bergamottin. Cross-reactivity data showed that the antibody well recognizes both the furanocoumarin and 6,7-dihydroxy-3,7-dimethyloct-2-enyloxy moieties of the 6',7'-dihydroxybergamottin, and is thus specific to the structure of furanocoumarin derivatives containing geranyloxy side chain as the cytochrome P450 3A4 inhibitors in grapefruit juice. The antibody was, therefore, used for screening a large number of citrus fruits for furanocoumarin derivatives such as 6',7'-dihydroxybergamottin. Fifteen citrus fruits were examined and significant reactivity was observed in 8 of these: red pummelo, sweetie, melogold, banpeiyu pummelo, hassaku, sour orange, lime and natsudaidai. This enzyme-linked immunosorbent assay may be a powerful tool for screening for furanocoumarin derivatives as cytochrome P450 3A4 inhibitors in grapefruit juice.


Deep-Ultraviolet Nonlinear-Optical Material K3Sr3Li2Al4B6O20F: Addressing the Structural Instability Problem in KBe2BO3F2.
A beryllium-free deep-ultraviolet (DUV) nonlinear-optical (NLO) material, K3Sr3Al4Li2B6O20F, has been synthesized and characterized. Unlike KBe2BO3F2 (KBBF), the reported NLO material does not require the use of toxic BeO in the synthesis, and through the judicious selection of cations, strong interlayer interactions are observed that facilitate the crystal growth. K3Sr3Al4Li2B6O20F exhibits second-harmonic generation (SHG) at both 1064 and 532 nm with efficiencies of 1.7KH2PO4 and 0.3β-BaB2O4 and has an absorption edge of 190 nm. Because of the strong interlayer interactions, we were able to grow well-faceted large crystals, 8 × 8 × 5 mm3, through a top-seeded-solution-growth technique. With these crystals, we determined a birefringence of 0.0574 at 1064 nm and a type I phase-matching SHG limit of 224 nm.


[Considerations on the surgical treatment of hallux valgus].
The authors, after showing a critical analysis of the most interesting operations for correction of valgus big toe in the history of orthopaedics, show the technique they followed, as well as the results obtained, in a specimen chosen among the patients treated with such method.


Vowel reduction across tasks for male speakers of American English.
This study examined acoustic variation of vowels within speakers across speech tasks. The overarching goal of the study was to understand within-speaker variation as one index of the range of normal speech motor behavior for American English vowels. Ten male speakers of American English performed four speech tasks including citation form sentence reading with a clear-speech style (clear-speech), citation form sentence reading (citation), passage reading (reading), and conversational speech (conversation). Eight monophthong vowels in a variety of consonant contexts were studied. Clear-speech was operationally defined as the reference point for describing variation. Acoustic measures associated with the conventions of vowel targets were obtained and examined. These included temporal midpoint formant frequencies for the first three formants (F1, F2, and F3) and the derived Euclidean distances in the F1-F2 and F2-F3 planes. Results indicated that reduction toward the center of the F1-F2 and F2-F3 planes increased in magnitude across the tasks in the order of clear-speech, citation, reading, and conversation. The cross-task variation was comparable for all speakers despite fine-grained individual differences. The characteristics of systematic within-speaker acoustic variation across tasks have potential implications for the understanding of the mechanisms of speech motor control and motor speech disorders.


Measuring the Ultrafast Correlation Dynamics between the Q x and Q y Bands in Chlorophyll Molecules.
We use two-dimensional electronic spectroscopy to measure the ultrafast correlation dynamics between the Q x and Q y transitions in chlorophyll molecules. We derive a variation to the center line slope method to quantify the frequency fluctuation cross-correlation function, C xy( Tw). Compared with the frequency fluctuation correlation function of the Q y transition, we observe that there is only a minimal correlation between the Q x and Q y transition, even at the ultrashort timescale of ∼100 fs, which then decays to zero in a time scale of ∼2 ps.


Cannabinoids modulate spontaneous synaptic activity in retinal ganglion cells.
The endocannabinoid (ECB) system has been found throughout the central nervous system and modulates cell excitability in various forms of short-term plasticity. ECBs and their receptors have also been localized to all retinal cells, and cannabinoid receptor activation has been shown to alter voltage-dependent conductances in several different retinal cell types, suggesting a possible role for cannabinoids in retinal processing. Their effects on synaptic transmission in the mammalian retina, however, have not been previously investigated. Here, we show that exogenous cannabinoids alter spontaneous synaptic transmission onto retinal ganglion cells (RGCs). Using whole-cell voltage-clamp recordings in whole-mount retinas, we measured spontaneous postsynaptic currents (SPSCs) in RGCs in adult and young (P14-P21) mice. We found that the addition of an exogenous cannabinoid agonist, WIN55212-2 (5 μM), caused a significant reversible reduction in the frequency of SPSCs. This change, however, did not alter the kinetics of the SPSCs, indicating a presynaptic locus of action. Using blockers to isolate inhibitory or excitatory currents, we found that cannabinoids significantly reduced the release probability of both GABA and glutamate, respectively. While the addition of cannabinoids reduced the frequency of both GABAergic and glutamatergic SPSCs in both young and adult mice, we found that the largest effect was on GABA-mediated currents in young mice. These results suggest that the ECB system may potentially be involved in the modulation of signal transmission in the retina. Furthermore, they suggest that it might play a role in the developmental maturation of synaptic circuits, and that exogenous cannabinoids are likely able to disrupt retinal processing and consequently alter vision.


Importance of target calorie intake in hospitalized patients.
To evaluate the feasibility and clinical outcome of a nutritional algorithm based on target calorie intake commenced as enteral nutrition (EN) alone or in combination with supplemental parenteral nutrition (SPN) among hospitalized patients. In total, 301 hospitalized patients who were provided with nutritional support, including EN (n=125) or EN+SPN (n=176), due to various medical conditions during their hospitalization were included in this study conducted at Antalya Training and Research Hospital. All the patients were evaluated during their hospitalization under nutritional support until discharge or in-hospital death. Data on the length of stay (LOS) and serum pre-albumin and C-reactive protein (CRP) levels and records for feeding days considering nutritional risk screening (NRS) 2002 scores were collected. Overall, 85.7% of patients achieved the target calorie intake within a median of 4.0 days, while discharge and in-hospital death rates were 58.1% and 41.9%, respectively. Of the 5719 feeding days recorded during follow-up, 1076 (18.8%) days were associated with failure to achieve the target calorie intake with hemodynamic instability (33.3%), procurement problems (33.3%), and oral reluctance (23.0%). Our findings emphasize the role of keeping the intake closer to the target calorie intake and immediate use of SPN whenever full EN fails to achieve the target calorie intake for improving the adequacy of clinical nutrition in the early phase of critical illness. The EN and EN+SPN groups were found to be similar in terms of rates of target achievement, mortality, and discharge, while a lower mortality rate and improved nutritional status were evident in achievers than in non-achievers of the target calorie intake regardless of the type of nutrition.


Apical hypertrophic cardiomyopathy with unusual features in a Greek woman.
We present a Mediterranean female patient with abnormal electrocardiographic findings and a history of shortness of breath during excessive effort (NYHA I) in whom apical hypertrophic cardiomyopathy with unusual features was detected by echocardiography and magnetic resonance imaging. There was a single fused apical hypertrophic papillary muscle and akinesia of the left ventricular apical segment. Abnormal left ventricular filling was also detected by Doppler echocardiography.


Genome-wide characterization and expression profiling of HD-Zip gene family related to abiotic stress in cassava.
Homeodomain-leucine zipper (HD-Zip) gene family plays important roles in various abiotic stresses and hormone signaling in plants. However, no information is currently available regarding this family in cassava (Manihot esculenta), an important drought-tolerant crop in tropical and sub-tropical areas. Here, 57 HD-Zip genes (MeHDZ01-57) were identified in the cassava genome, and they were classified into four subfamilies based on phylogenetic analysis, which was further supported by their gene structure and conserved motif characteristics. Of which five gene pairs were involved in segmental duplication but none for tandem duplication, suggesting that segmental duplication was the main cause for the expansion of MeHDZ gene family in cassava. Global expression profiles revealed that MeHDZ genes were constitutively expressed, or not expressed, or tissue-specific expressed in examined tissues in both cultivated and wild subspecies. Transcriptomic analysis of three genotypes showed that most of MeHDZ genes responded differently to drought and polyethylene glycol treatments. Subsequently, quantitative RT-PCR analysis revealed comprehensive responses of twelve selected MeHDZ genes to various stimuli including cold, salt, and ABA treatments. These findings will increase our understanding of HD-Zip gene family involved in abiotic stresses and signaling transduction, and will provide a solid base for further functional characterization of MeHDZ genes in cassava.


Development of a high magnetic field assisted pulsed laser deposition system.
A high magnetic field assisted pulsed laser deposition (HMF-PLD) system has been developed to in situ grow thin films in a high magnetic field up to 10 T. In this system, a specially designed PLD cylindrical vacuum chamber is horizontally located in the bore configuration of a superconducting magnet with a bore diameter of 200 mm. To adjust the focused pulsed laser into the target in such a narrow PLD vacuum chamber, an ingeniously built-in laser leading-in chamber is employed, including a laser mirror with a reflection angle of 65° and a damage threshold up to 3.4 J/cm(2). A laser alignment system consisting of a built-in video-unit leading-in chamber and a low-energy alignment laser is applied to monitor and align the pulsed laser propagation in the PLD vacuum chamber. We have grown La0.7Sr0.3MnO3 (LSMO) thin films on (LaAlO3)0.3(Sr2AlTaO6)0.7 (001) [LSAT (001)] substrates by HMF-PLD. The results show that the nanostructures of the LSMO films can be tuned from an epitaxially continuous film structure without field to a vertically aligned nanorod structure with an applied high magnetic field above 5 T, and the dimension size of the nanorods can be tuned by the strength of the magnetic field. The associated magnetic anisotropy is found to be highly dependent on the nanorod structures. We show how the HMF-PLD provides an effective route toward tuning the nanostructures and the physical properties of functional thin films, giving it an important role in development of nanodevices and their application.


Maternal serum homocysteine and uterine artery Doppler as predictors of preeclampsia and poor placentation.
The aim of this study was to evaluate the role of maternal serum total Homocysteine (tHcy) and uterine artery (Ut-A) Doppler as predictors of preeclampsia (PE), intrauterine growth restriction (IUGR), and other complications related to poor placentation. A prospective cohort study was conducted on 500 women with spontaneous pregnancies. tHcy was measured at 15-19 weeks, and then, Ut-A Doppler was performed at 18-22 weeks of pregnancy. 453 pregnant women completed the follow-up of the study. The tHcy and Ut-A resistance index were significantly higher in women who developed PE, IUGR, and other complications when compared to controls (tHcy: 7.033 ± 2.744, 6.321 ± 3.645, and 6.602 ± 2.469 vs 4.701 ± 2.082 μmol/L, respectively, p value <0.001 and Ut-A resistance index: 0.587 ± 0.072, 0.587 ± 0.053, and 0.597 ± 0.069 vs 0.524 ± 0.025, respectively, p value <0.001). The use of both tHcy assessment and Ut-A Doppler improved the sensitivity of prediction of PE relative to the use of each one alone (85.2 relative to 73.33 and 60%, respectively). The use of elevated homocysteine and uterine artery Doppler screening are valuable in prediction of preeclampsia, IUGR, and poor placentation disorders. CLINCALTRIAL. NCT02854501.


Bacterial Sensing and Biofilm Monitoring for Infection Diagnostics.
Recent insights into the rapidly emerging field of bacterial sensing and biofilm monitoring for infection diagnostics are discussed as well as recent key developments and emerging technologies in the field. Electrochemical sensing of bacteria and bacterial biofilm via synthetic, natural, and engineered recognition, as well as direct redox-sensing approaches via algorithm-based optical sensing, and tailor-made optotracing technology are discussed. These technologies are highlighted to answer the very critical question: "how can fast and accurate bacterial sensing and biofilm monitoring be achieved? Following on from that: "how can these different sensing concepts be translated for use in infection diagnostics? A central obstacle to this transformation is the absence of direct and fast analysis methods that provide high-throughput results and bio-interfaces that can control and regulate the means of communication between biological and electronic systems. Here, the overall progress made to date in building such translational efforts at the level of an individual bacterial cell to a bacterial community is discussed.