Long-term outcomes associated to video-assisted thoracic sympathotomy for palmar-axillar subtype of the hyperhidrosis.
Surgery for both palmar and axillar hyperhidrosis usually includes the interruption of the sympathetic chain in multiple levels. This study aimed to determine the long-term outcomes associated to video-assisted thoracic sympathotomy (VATS) of T2, T3 and T4 ganglia for these cases. Analysis of the outcomes obtained from 36 patients regarding the rate of resolution of the symptoms and the compensatory sweating (CS). All subjects were followed-up for 36 months. Good outcomes were observed in 98.6% for palmar and 60% for axillary hyperhidrosis (p=0.0423), respectively. Of the subjects, 86% reported some postoperative episode of CS, however only 45% (p=0.0031) still noticed it at the end of the follow-up period. VATS is effective for the excessive palmar sweating, whereas it is fully efficient for only two thirds of the cases sustaining associated axillar hyperhidrosis. CS is expected as a rule following the proposed operative protocol, however it is usually self-limited.


Bioluminescence Imaging to Detect Late Stage Infection of African Trypanosomiasis.
Human African trypanosomiasis (HAT) is a multi-stage disease that manifests in two stages; an early blood stage and a late stage when the parasite invades the central nervous system (CNS). In vivo study of the late stage has been limited as traditional methodologies require the removal of the brain to determine the presence of the parasites. Bioluminescence imaging is a non-invasive, highly sensitive form of optical imaging that enables the visualization of a luciferase-transfected pathogen in real-time. By using a transfected trypanosome strain that has the ability to produce late stage disease in mice we are able to study the kinetics of a CNS infection in a single animal throughout the course of infection, as well as observe the movement and dissemination of a systemic infection. Here we describe a robust protocol to study CNS infections using a bioluminescence model of African trypanosomiasis, providing real time non-invasive observations which can be further analyzed with optional downstream approaches.


Hypoxia: an alarm signal during intestinal inflammation.
Intestinal epithelial cells that line the mucosal surface of the gastrointestinal tract are positioned between an anaerobic lumen and a highly metabolic lamina propria. As a result of this unique anatomy, intestinal epithelial cells function within a steep physiologic oxygen gradient relative to other cell types. Furthermore, during active inflammatory disease such as IBD, metabolic shifts towards hypoxia are severe. Studies in vitro and in vivo have shown that the activation of hypoxia-inducible factor (HIF) serves as an alarm signal to promote the resolution of inflammation in various mouse models of disease. Amelioration of disease occurs, at least in part, through transcriptional upregulation of nonclassic epithelial barrier genes. There is much interest in harnessing hypoxia-inducible pathways, including stabilizing HIF directly or via inhibition of prolyl hydroxylase enzymes, for therapy of IBD. In this Review, we discuss the signaling pathways involved in the regulation of hypoxia and discuss how hypoxia may serve as an endogenous alarm signal for the presence of mucosal inflammatory disease. We also discuss the pros and cons of targeting these pathways to treat patients with IBD.


Effects of in vitro platelet activation on platelet derived nitric oxide production in healthy humans and in chronic myeloproliferative diseases with elevated platelet counts.
Intravascular EDRF-NO production is known to be impaired in some diseases, e.g., diabetes. This phenomenon may also contribute to the development of diabetic vascular disease. More recently the presence of NO synthase (ecNOS, iNOS) have been recognized in human platelets. Platelets produce NO only during activation, even though in minute amounts. This platelet derived NO seems to play an important physiological role, as it inhibits further platelet recruitment quite substantially. In the present report washed platelets isolated from healthy persons and patients with chronic myeloproliferative diseases (CMPD) were exposed to common and physiologically relevant activators (i.e., thrombin, collagen, epinephrine etc.). These tests were carried out in 20 healthy volunteers and 15 patients suffering from myeloproliferative disorders associated with thrombocytosis. As a consequence of pathological platelet function observed in CMPD, the in vitro platelet NO response is impaired in the patient group. One may assume, that reduced platelet NO response, at least in part, may contribute to platelet hyperfunction, angiopathy and thrombotic complications in some cases of CMPD.


Effect of doxycycline on pre-menstrual syndrome: a double-blind randomized clinical trial.
Thirty patients with well-defined symptoms of pre-menstrual syndrome were randomly treated with the antibiotic doxycycline or placebo. The antibiotic-treated group showed a highly significant reduction of symptoms. Subsequent antibiotic treatment of the original placebo group similarly diminished the symptoms in this group. A 6-month follow-up demonstrated that the improvement in symptom scores was permanent and independent from the presence of the antibiotic. Luteal phase endometrial biopsies showed a high incidence of out-of-phase endometrium. An unexpectedly high percentage of endometrial biopsy cultures yielded positive findings for mycoplasma, Chlamydia trachomatis and anaerobic bacteria. There were no characteristic hormonal changes in this study group. An infectious aetiology, possibly a sub-clinical endometrial or ovarian infection, behind certain cases of pre-menstrual syndrome is postulated.


Protein multiple sequence alignment.
Protein sequence alignment is the task of identifying evolutionarily or structurally related positions in a collection of amino acid sequences. Although the protein alignment problem has been studied for several decades, many recent studies have demonstrated considerable progress in improving the accuracy or scalability of multiple and pairwise alignment tools, or in expanding the scope of tasks handled by an alignment program. In this chapter, we review state-of-the-art protein sequence alignment and provide practical advice for users of alignment tools.


Spectral sensitivity of direction-selective ganglion cells in the fish retina.
In color matching experiments with extracellular recordings from axon terminals of ganglion cells in the tectum opticum of immobilized goldfish, direction-selective ganglion cells were shown to be color-blind. Their spectral sensitivity is determined by a high positive input from the long wavelength-sensitive cones and weak opponent input from other cone types.


A Bayesian finite mixture change-point model for assessing the risk of novice teenage drivers.
The driving risk during the initial period after licensure for novice teenage drivers is typically the highest but decreases rapidly right after. The change-point of driving risk is a critical parameter for evaluating teenage driving risk, which also varies substantially among drivers. This paper presents latent class recurrent-event change-point models for detecting the change-points. The proposed model is applied to the Naturalist Teenage Driving Study, which continuously recorded the driving data of 42 novice teenage drivers for 18 months using advanced in-vehicle instrumentation. We propose a hierarchical BFMM to estimate the change-points by clusters of drivers with similar risk profiles. The model is based on a non-homogeneous Poisson process with piecewise-constant intensity functions. Latent variables which identify the membership of the subjects are used to detect potential clusters among subjects. Application to the Naturalistic Teenage Driving Study identifies three distinct clusters with change-points at 52.30, 108.99 and 150.20 hours of driving after first licensure, respectively. The overall intensity rate and the pattern of change also differ substantially among clusters. The results of this research provide more insight in teenagers' driving behaviour and will be critical to improve young drivers' safety education and parent management programs, as well as provide crucial reference for the GDL regulations to encourage safer driving.


Diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy in clinical practice: A survey among Dutch neurologists.
The diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is often a challenge. The clinical presentation is diverse, accurate biomarkers are lacking, and the best strategy to initiate and maintain treatment is unclear. The aim of this study was to determine how neurologists diagnose and treat CIDP. We conducted a cross-sectional survey on diagnostic and treatment practices among Dutch neurologists involved in the clinical care of CIDP patients. Forty-four neurologists completed the survey (44/71; 62%). The respondents indicated to use the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 CIDP guideline for the diagnosis in 77% and for treatment in 50%. Only 57% of respondents indicated that the presence of demyelinating electrophysiological findings was mandatory to confirm the diagnosis of CIDP. Most neurologists used intravenous immunoglobulins (IVIg) as first choice treatment, but the indications to start, optimize, or withdraw IVIg, and the use of other immune-modulatory therapies varied. University-affiliated respondents used the EFNS/PNS 2010 diagnostic criteria, nerve imaging tools, and immunosuppressive drugs more often. Despite the existence of an international guideline, there is considerable variation among neurologists in the strategies employed to diagnose and treat CIDP. More specific recommendations regarding: (a) the minimal set of electrophysiological requirements to diagnose CIDP, (b) the possible added value of nerve imaging, especially in patients not meeting the electrodiagnostic criteria, (c) the most relevant serological examinations, and (d) the clear treatment advice, in the new EFNS/PNS guideline, would likely support its implementation in clinical practice.


Structural diversity of silver(I) 4,6-dipyridyl-2-aminopyrimidine complexes: effect of counteranions and ligand isomerism.
Using two ligands, 4,6-bis(2-pyridyl)-2-aminopyrimidine (L1) with two N,N'-chelating sites and 4-(2-pyridyl)-6-(4-pyridyl)-2-aminopyrimidine (L2) (as the isomer of L1) containing one chelating site and one bridging unit, a series of novel Ag(I) complexes varying from zero- to two-dimensions have been prepared and their crystal structures determined via single-crystal X-ray diffraction. The two ligands are employed for the first time in coordination chemistry. The structures of compounds 1-3 are directed by the counteranions adopted in the reaction system: The reaction of L1 with AgNO3 yielded a dimer [Ag2L12](NO3)2 (1). The reaction of L1 with AgCF3SO3 led to a one-dimension "V-shaped" chain {[AgL1](CF3SO3)}n (2). When AgSCN was used, a one-dimension ladder {[Ag2L1(SCN)2].H2O}n (3) was obtained. While ligand L2 reacted with AgNO3, a two-dimension {[Ag2(L2)2](NO3)2.H2O}n (4) was prepared with the help of an argentophilic interaction. Compounds 1-4 display room-temperature photoluminescence.


Carotid artery resection and replacement in patients with head and neck malignant tumors.
Tumor involvement of the carotid artery with head and neck cancers may be present either simultaneously with the primary lesion or more often appears at a later date following resection of the primary tumor. Management of the secondary tumor consists of its resection together with the involved carotid artery with or without carotid artery reconstruction. The Authors are convinced that the best chance for cure of patients with advanced head and neck squamous cell cancers involving the carotid artery is radical extirpation with ablative surgery in the form of en block resection of the primary lesion, the secondary tumor, and the involved carotid artery followed by immediate revascularization. This bold approach was carried out in two male patients, 48 and 61 years of age, followed by chemotherapy and radiation therapy in one and radiation therapy alone in the other, with excellent results. Dermal grafts were placed over the entire length of the arterialized veins to protect them from radiation injury. Based on this limited experience and excellent results, we recommend this one-stage surgical ablative procedure in well selected patients. However, cooperation between the ENT and vascular surgeons, strict adherence to the principles and techniques of vascular surgery, and coverage of the arterialized vein with a dermal graft is absolutely essential.


Association between endotoxin levels in dust from indoor swine housing environments and the immune responses of pigs.
Indoor animal husbandry environments are inevitably contaminated with endotoxins. Endotoxin exposure is associated with various inflammatory illnesses in animals. This cross-sectional study evaluated the relationship between the degree of endotoxin exposure and the cellular and humoral immune profiles of fattening pigs. Blood samples were taken from the jugular vein of 47 pigs from ten pig farms in Korea. Whole blood cell counts and plasma immunoglobulin (Ig) classes were determined. Peripheral-blood mononuclear cells were stimulated in vitro with concanavalin A for 48 h, and cytokines released into culture supernatants were measured. The barns in which the pigs lived were assessed for endotoxin levels in the total and respirable dust by using the limulus amebocyte lysate kinetic QCL method. Low and high endotoxin exposures were defined as ≤ 30 and > 30 EU/m³, respectively. Compared to pigs with low endotoxin exposure (n = 19), highly exposed pigs (n = 28) had higher circulating neutrophil and lymphocyte (particularly B cells) counts, IgG and IgE levels, interferon-gamma (IFNγ) and interleukin (IL)-4 productions, and lower IgA levels and tumor necrosis factor-alpha (TNFα) production. The IL-4, IFNγ, and TNFα levels significantly correlated with endotoxin level and/or pig age. Constant exposure of pigs to high levels of airborne endotoxins can lead to aberrant immune profiles.


Inspiratory obstruction.
Obstructing lesions of the trachea and larynx which cause a predominantly inspiratory obstruction can be satisfactorily diagnosed by measuring both F.I.V.(1) and F.E.V.(1). Chronic airways obstruction involving intrathoracic airways produces a much lower F.E.V.(1)/F.I.V.(1) percentage than normal, whereas obstruction to larynx and trachea causes a raised F.E.V.(1)/F.I.V.(1) percentage. If flow-volume measurements are not available the F.E.V.(1)/F.I.V.(1) percentage should provide a simple and useful method for diagnosis of upper airways obstruction.In one of the patients reported a predominantly inspiratory obstruction caused CO(2) retention. In patients with airways obstruction the correlation between Pco(2) and F.I.V.(1) was found to be the same as between Pco(2) and F.E.V.(1). This suggests that respiratory failure can be caused by either inspiratory or expiratory airways obstruction and that neither is of greater importance in producing CO(2) retention.


Effect of a SiO2 coating on the magnetic properties of Fe3O4 nanoparticles.
In this work the effect of a SiO2 coating on the magnetic properties of Fe3O4 nanoparticles obtained by the sol-gel method is analyzed. Two sets of samples were prepared: Fe3O4 nanoparticles and Fe3O4@SiO2 core-shell composites. The samples display the characteristic spinel structure associated with the magnetite Fe3O4 phase, with the majority of grain sizes around 5-10 nm. At room temperature the nanoparticles show the characteristic superparamagnetic behavior with mean blocking temperatures around 160 and 120 K for Fe3O4 and Fe3O4@SiO2, respectively. The main effect of the SiO2 coating is reflected in the temperature dependence of the high field magnetization (μ(0)H = 6 T), i.e. deviations from the Bloch law at low temperatures (T < 20 K). Such deviations, enhanced by the introduction of the SiO2 coating, are associated with the occurrence of surface spin disordered effects. The induction heating effects (magnetic hyperthermia) are analyzed under the application of an AC magnetic field. Maximum specific absorption rate (SAR) values around 1.5 W g(-1) were achieved for the Fe3O4 nanoparticles. A significant decrease (around 26%) is found in the SAR values of the SiO2 coated nanocomposite. The different heating response is analyzed in terms of the decrease of the effective nanoparticle magnetization in the Fe3O4@SiO2 core-shell composites at room temperature.


Use of the Adverse Outcome Pathway (AOP) framework to evaluate species concordance and human relevance of Dibutyl phthalate (DBP)-induced male reproductive toxicity.
Dibutyl phthalate (DBP) is a phthalate ester used as a plasticizer, and solvent. Studies using rats consistently report that DBP exposure disrupts normal development of the male reproductive system in part via inhibition of androgen synthesis. However, studies using xenograft models report that in human fetal testis DBP exposure is unlikely to impair testosterone synthesis. These results question the validity of the rat model for assessment of male reproductive effects caused by DBP. The Adverse Outcome Pathway (AOP) framework was used to evaluate the available evidence for DBP-induced toxicity to the male reproductive system. Three relevant biological elements were identified: 1) fetal rats are more sensitive than other rodents and human fetal xenografts to DBP-induced anti-androgenic effects, 2) DBP-induced androgen-independent adverse outcomes are conserved amongst different mammalian models and human fetal testis xenografts, and 3) DBP-induced anti-androgenic effects are conserved in different mammalian species when exposure occurs during postnatal life stages.


Modified Thoracoscopic Hepatectomy For Segment VIII: A Case Report.
Although previous studies have reported the use of total thoracoscopic hepatectomy (TH) for malignant liver tumors, it is technically impossible to perform intraoperative ultrasonography (IUSO) to exclude intrahepatic metastasis for the whole liver via a thoracic approach. Therefore, total TH may be inappropriate for these patients. We here report the first case of modified TH for a malignant liver tumor in China.The patient was a 26-year-old man with a 10-year HBV infection. Preoperative CT showed a 1.2 cm × 0.9 cm mass located in segment VIII. His alpha-fetal protein level was 444 ng/mL. Child-Pugh was Grade (A, 6), whereas an ICG-15 test yielded 2.7%. HCC was diagnosed preoperatively. The indications for TH were difficult tumor location, HCC, and a young patient with good resilience.The modified TH included 2 steps: (1) the patient was placed in a supine position. IUSO was used to locate the tumor in segment VIII and determine that intrahepatic metastasis had not occurred. The hepatoduodenal ligament was hanged over using a Pringle maneuver; (2) patient was then placed in the left-lateral position with single-lung ventilation. Three trocars were placed into the right thoracic cavity. The intra-thoracic space was observed using a regular 10-mm rigid scope. The diaphragm was transected and retracted. IUSO was used again to confirm the tumor location. Under the Pringle maneuver (once every 10 min), the superficial portion of the liver was transected by ultrasonic shears, whereas the deeper tissue was transected by LigaSure. Bipolar was used for hemostasis. The specimen was put into a retrieval bag and removed from the abdominal trocar. The diaphragm was repaired by running suturing. The operation time was 260 minutes and estimated blood loss was 30 mL. The patient was discharged on postoperative day 5 with normal liver function. No complications arose.Total TH may be inappropriate for malignant liver tumors due to the limitation of IUSO for the whole liver. The 2-step modified TH is technically feasible and suitable for malignant liver tumors located in segments VII or VIII.Video abstract: http://links.lww.com/MD/B6.


Yeast polysaccharide affects fusaric acid content in maize root rot.
Protective action of sulfoethyl glucan (SEG), a derivative of the cell wall glucan prepared from the baker's yeast Saccharomyces cerevisiae, was investigated in the maize seedlings infected by a plant pathogen Fusarium verticillioides (Sacc.). Several markers were assayed with the SEG addition and in the control experiments. Two evaluations were performed on the 7th and the 14th days. Addition of SEG led to the increased productivity parameters of the infected plants and maintained them at the level of non-infected plants during the 14 days of experiment. After seven days of cultivation, concentration of fusaric acid (=5-butylpyridine-2-carboxylic acid; FA) decreased in all infected plants cultivated in the presence of SEG when compared to that detected in the infected plants grown in the absence of SEG. After 14 days of cultivation, polysaccharide addition resulted in the reduction of FA concentration almost to 75% in comparison to the infected plants grown without polysaccharide addition. In the experiment, when exogenous FA was added to the growth medium, its concentration decreased up to 60% in the presence of SEG. Thus, it is feasible to assume that SEG binds and adsorbs FA, and, in this way, reduces its content and exerts protective action in plants against its toxic effect.


Population genetics of the filarial worm wuchereria bancrofti in a post-treatment region of Papua New Guinea: insights into diversity and life history.
Wuchereria bancrofti (Wb) is the primary causative agent of lymphatic filariasis (LF). Our studies of LF in Papua New Guinea (PNG) have shown that it is possible to reduce the prevalence of Wb in humans and mosquitoes through mass drug administration (MDA; diethylcarbamazine with/without ivermectin). While MDAs in the Dreikikir region through 1998 significantly reduced prevalence of Wb infection, parasites continue to be transmitted in the area. We sequenced the Wb mitochondrial Cytochrome Oxidase 1 (CO1) gene from 16 people infected with Wb. Patients were selected from 7 villages encompassing both high and moderate annual transmission potentials (ATP). We collected genetic data with the objectives to (i) document contemporary levels of genetic diversity and (ii) distinguish between populations of parasites and hosts across the study area. We discovered 109 unique haplotypes currently segregating in the Wb parasite population, with one common haplotype present in 15 out of 16 infections. We found that parasite diversity was similar among people residing within the same village and clustered within transmission zones. For example, in the high transmission area, diversity tended to be more similar between neighboring villages, while in the moderate transmission area, diversity tended to be less similar. In the Dreikikir region of PNG there are currently high levels of genetic diversity in populations of Wb. High levels of genetic diversity may complicate future MDAs in this region and the presence of dominant haplotypes will require adjustments to current elimination strategies.


Asymmetric synthesis of fluorinated cyclic beta-amino acid derivatives through cross metathesis.
The asymmetric synthesis of several fluorinated cis-2-aminocycloalkane carboxylic acids (cis-2-ACACs) with a cross metathesis (CM) reaction as the key step has been carried out, constituting the first time a metathesis protocol has been undertaken with fluorinated imidoyl chlorides. Subsequent chemoselective hydrogenation of the olefin moiety, Dieckmann condensation, and stereoselective reduction of the iminic double bond afforded the corresponding beta-amino esters with several ring sizes. The asymmetric version of the process was achieved by using (-)-8-phenylmenthol as a chiral auxiliary.


Back From the Brink: Alterations in B and T Cell Responses Modulate Recovery of Rainbow Trout From Chronic Immunopathological Tetracapsuloides bryosalmonae Infection.
Proliferative kidney disease (PKD) caused by the myxozoan parasite Tetracapsuloides bryosalmonae is one of the most serious infectious diseases negatively impacting farmed and wild salmonids throughout Europe and North America. PKD pathogenesis results in a massive B cell proliferation and dysregulation with aberrant immunoglobulin production and plasma cell differentiation along with a decrease in myeloid cells and inhibition of innate pathways. Despite the huge immunopathological reaction in the kidney during infection, under specific conditions, fish can survive and return to full fitness. Fish are unique in this ability to recover renal structure and functionality from extensive tissue damage in contrast to mammals. However, only limited knowledge exists regarding the host immune response coinciding with PKD recovery. Moreover, almost no studies of the immune response during disease recovery exist in fish. We utilized the rainbow trout-T. bryosalmonae system as an immunological model of disease recovery. Our results demonstrated that recovery is preceded by an intense immune response at the transcript level, decreasing parasite burden, and an increased degree of kidney inflammation. Later in the recovery phase, the immune response transpired with a significant decrease in lymphocytes and an increase in myeloid cells. These lymphocytes populations contained lower levels of B cells comparative to the control in the anterior and posterior kidney. Additionally, there was downregulation of several transcripts used as markers for plasma cells (blimp1, igt sec, igm sec, igd sec, and cd38) and T cell subsets (cd4, cd8α, cd8β, and tcrβ). The decrease in these T cell transcripts significantly correlated with decreasing parasite intensity. Alternatively, there was strong upregulation of pax-5 and igt mem. This suggests a change in B cell processes during the recovery phase relative to clinical PKD may be necessary for the host to re-establish homeostasis in terms of an arrest in the dominant antibody like response transitioning to a transcriptional profile associated with resting B cells. The knowledge generated here in combination with earlier studies illuminates the full power of analyzing the entire trajectory of disease from the normal healthy state to recovery enabling the measurement of an immune response to pinpoint a specific disease stage.


Differential cytokine production associated with distinct phases of murine graft-versus-host reaction.
Previous studies which demonstrated that cytokines such as interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are essential for the development of graft-versus-host reaction (GvHR) did not establish whether the individual cytokines were responsible for distinct features of the disease. In this report, we show that IFN-gamma production is associated with the early proliferative phase of the disease, whereas the late, destructive phase correlates with production of TNF-alpha. These studies may assist in the development of specific immunotherapies aimed at individual aspects of immunologically mediated disease.


[Studies on analytical method for 10 drugs of abuse in urine using HPLC].
A systematic determination method for 10 drugs of abuse, morphine, codeine, 6-monoacetylmorphine, heroin, levorphanol, pethidine, ethylmorphine, anadol, pentazocine and ethamivan, using high performance liquid chromatography is described. Separation of the 10 drugs was achieved on a 25 cm x 4.6 mm ID, 10 microns Zorbax C8 column, using methanol--0.05 mol.L-1 KH2PO4--diethyl amine (27:73:0.5, pH 4) as mobile phase. Codeine was used as the interal standard. Calibration graphs were linear over the concentration range of 10-200 micrograms.ml-1 and regression equations showed correlation coefficients of greater than 0.999. Precision (RSD) were found to be better than 3% for each compound. Precision and linearity of the method are satisfactory for clinical toxicological applications. The extraction procedure yielded cleaner extracts. The recovery rates from urine were all above 87% without interference. This method is rapid, sensitive and specific.


Difficult intubation in obese patients: incidence, risk factors, and complications in the operating theatre and in intensive care units.
Intubation procedure in obese patients is a challenging issue both in the intensive care unit (ICU) and in the operating theatre (OT). The objectives of the study were (i) to compare the incidence of difficult intubation and (ii) its related complications in obese patients admitted to ICU and OT. We conducted a multicentre prospective observational cohort study in ICU and OT in obese (BMI≥30 kg m(-2)) patients. The primary endpoint was the incidence of difficult intubation. Secondary endpoints were the risk factors for difficult intubation, the use of difficult airway management techniques, and severe life-threatening complications related to intubation (death, cardiac arrest, severe hypoxaemia, severe cardiovascular collapse). In cohorts of 1400 and 11 035 consecutive patients intubated in ICU and in the OT, 282 (20%) and 2103 (19%) were obese. In obese patients, the incidence of difficult intubation was twice more frequent in ICU than in the OT (16.3% vs 8.2%, P<0.01). In both cohorts, risk factors for difficult intubation were Mallampati score III/IV, obstructive sleep apnoea syndrome, and reduced mobility of cervical spine, while limited mouth opening, severe hypoxaemia, and coma appeared only in ICU. Specific difficult airway management techniques were used in 66 (36%) cases of difficult intubation in obese patients in the OT and in 10 (22%) cases in ICU (P=0.04). Severe life-threatening complications were significantly more frequent in ICU than in the OT (41.1% vs 1.9%, relative risk 21.6, 95% confidence interval 15.4-30.3, P<0.01). In obese patients, the incidence of difficult intubation was twice more frequent in ICU than in the OT and severe life-threatening complications related to intubation occurred 20-fold more often in ICU. Current controlled trials. Identifier: NCT01532063.


The impact of clergy-perpetrated sexual abuse: the role of gender, development, and posttraumatic stress.
The literature on clergy-perpetrated sexual abuse suggests that there are two modal populations of survivors: boys and adult women. We review what is known about trauma and post-traumatic stress disorder following sexual abuse and explore the different treatment needs for these two survivor groups. For children, clergy-perpetrated sexual abuse can catastrophically alter the trajectory of psychosocial, sexual, and spiritual development. Depending on the age at which abuse occurred, adult clients may present with clinical issues that are more appropriate for a younger developmental stage. Additionally, the symptoms of traumatic stress may be misunderstood when clients conceptualize their abuse as an "affair" or "consensual" relationship. We discuss empirically supported treatments for post-traumatic stress disorder and potential adaptations for the needs of clergy-perpetrated sexual abuse survivors.


Reconstitution of Fo of the sodium ion translocating ATP synthase of Propionigenium modestum from its heterologously expressed and purified subunits.
The atpB and atpF genes of Propionigenium modestum were cloned as His-tag fusion constructs and expressed in Escherichia coli. Both recombinant subunits a and b were purified via Ni(2+) chelate affinity chromatography. A functionally active Fo complex was reassembled in vitro from subunits a, b and c, and incorporated into liposomes. The F(o) liposomes catalysed (22)Na(+) uptake in response to an inside negative potassium diffusion potential, and the uptake was prevented by modification of the c subunits with N,N'-dicyclohexylcarbodiimide (DCCD). In the absence of a membrane potential the Fo complexes catalysed (22)Na(+)(out)/Na(+)(in)-exchange. After F(1) addition the F(1)F(o) complex was formed and the holoenzyme catalysed ATP synthesis, ATP dependent Na(+) pumping, and ATP hydrolysis, which was inhibited by DCCD. Functional F(o) hybrids were reconstituted with recombinant subunits a and b from P. modestum and c(11) from Ilyobacter tartaricus. These Fo hybrids had Na(+) translocation activities that were not distinguishable from that of P. modestum F(o).


Safety and efficacy of once-daily didanosine, tenofovir and nevirapine as a simplification antiretroviral approach.
To assess the efficacy and safety of a once-daily antiretroviral regimen in HAART-experienced subjects with long-lasting viral suppression. One-hundred-and-sixty-nine patients with chronically suppressed viral load (limit of detection <50 copies/ml) were recruited. Based on patient willingness to simplify treatment, 84 of them continued receiving their usual treatment (BID Group) and 85 switched to once-daily didanosine/tenofovir/nevirapine (QD Group) in a non-randomized fashion. At week 48, the proportion of patients with viral suppression in the QD and in the BID Group, respectively, was 97 vs 100% in the per-protocol analysis (P = 0.497), and 76 vs 86% for the intention-to-treat analysis (P = 0.176). Nevertheless, CD4 count decreased in the QD Group, with a mean decline of 95 cells/mm3 (95% CI: 45-145). Twelve subjects in the QD Group (14%) discontinued treatment due to adverse events, mainly nevirapine-related hepatitis (6%). No significant differences regarding the rate of acute pancreatitis or peripheral neuropathy were observed between both groups. A significant improvement in the lipid profile was only seen in the QD Group. High levels of adherence were observed in both groups during follow-up, as well as a good quality of life. At week 48, a reduction in effort to take medication (P < or = 0.001) and an increment in the satisfaction with the treatment (P < 0.001) was only seen in the QD group. No differences were observed in median nevirapine trough levels between patients on twice-daily nevirapine at baseline (4820 ng/ml) and subjects in the QD Group (6090 ng/ml, P = 0.30). Treatment simplification to a once-daily antiretroviral regimen based on didanosine, tenofovir and nevirapine may be a valid approach in HIV-infected subjects with long-lasting viral suppression. Combination of standard doses of didanosine and tenofovir may have contributed to the CD4 cell decline observed with this QD regimen.


Morningness and eveningness: the free cortisol rise after awakening in "early birds" and "night owls".
We investigated salivary cortisol profiles in the first hour after awakening in morning versus evening chronotypes. Chronotypes were defined by Horne and Ostberg's Owl-and-Lark-Questionnaire. In a sample of 112 healthy, day-active young men, we identified 9 morning and 29 evening chronotypes. Saliva samples were collected 0, 30, 45, and 60min after awakening on 2 consecutive days. Log-transformed cortisol levels were analyzed with General Linear Model procedures (GLMs) and awakening time and sleep duration were entered as covariates. On both days, a significant main effect of chronotype emerged (both p=0.02), and this effect could not be explained by differences in awakening time or sleep duration. The present data support the idea that morning relative to evening chronotypes might show higher cortisol levels in the first hour after awakening. In sum, individual chronotype should be acknowledged as one further possible source of interindividual variability in the cortisol rise after awakening.


Thermostability of the human respiratory syncytial virus fusion protein before and after activation: implications for the membrane-fusion mechanism.
Anchorless fusion (F) proteins () of human respiratory syncytial virus (RSV) are seen by electron microscopy as unaggregated cones when the proteolytic cleavage at two furin sites required for membrane-fusion activity is incomplete, but aggregate into rosettes of lollipop-shaped spikes following cleavage. To show that this aggregation occurred by interactions of the fusion peptide, a deletion mutant of lacking the first half of the fusion peptide was generated. This mutant remained unaggregated even after completion of cleavage, supporting the notion that aggregation of involved the fusion peptide. As exposure of the fusion peptide is a key event that occurs after activation of F proteins, the uncleaved and cleaved forms of may represent the pre- and post-active forms of RSV F protein. In an analysis of the structural differences between the two forms, their thermostability before and after proteolytic cleavage was examined. In contrast to other viral proteins involved in membrane fusion (e.g. influenza haemagglutinin), the pre-active (uncleaved) and post-active (cleaved) forms of were equally resistant to heat denaturation, assessed by spectrofluorimetry, circular dichroism or antibody binding. These results are interpreted in terms of the proposed structural changes associated with the process of membrane fusion mediated by RSV F protein.


Radiation therapy in chronic hidradenitis suppurativa: case report.
A 26-year-old female presented recurrent painful, carbuncles at both axillae for 10 years. It caused offensive odor and scar. Tissue diagnosis was chronic hidradenitis suppurativa. She was treated using antibiotics followed by multiple excisions with drainage but showed no improvement. Isotretinoin provided no benefit. She was socially isolated and experienced lower quality of life. Consequently, she was sent for radiation therapy. Computed tomography simulation was performed revealing an ulcer with deep chronic pus tracts at her axilla. Three-dimensional conformal radiation therapy was provided with 6 MV photon (7.5 Gy in 3 fractions) covering all ulcers and pus tracts. On the last day of radiation therapy, carbuncles and wounds at the left axilla exhibited much improvement without pus. Three months follow-up showed much improvement of the lesions. The skin was smoother without pus or odor. Radiation therapy was confirmed one treatment option for chronic hidradenitis suppurativa.


Faba bean (Vicia faba) inclusion in dairy cow diets: Effect on nutrient digestion, rumen fermentation, nitrogen utilization, methane production, and milk performance.
The objective of this study was to determine the effect of replacing on isonitrogenous and isoenergetic basis soybean meal (SBM) and corn grain with ground or rolled faba bean (FB; Vicia faba major var. Baie-Saint-Paul) in dairy cow diets (17% of diet dry matter) on nutrient digestion, rumen fermentation, N utilization, methane production, and milk performance. For this purpose, 9 lactating cows were used in a replicated 3 × 3 Latin square design (35-d period) and fed (ad libitum) a total mixed ration (forage:concentrate ratio = 59:41 on a dry matter basis). In the concentrate portion, SBM and corn grain (control diet) were completely and partially replaced, respectively, with either ground or rolled FB. Ruminal degradability (in sacco) of crude protein was higher for ground FB (79.4%) compared with SBM (53.3%) and rolled FB (53.2%). Including FB in the diet did not affect dry matter intake, milk production, and milk composition. Experimental treatment had no effect on total volatile fatty acid concentration, acetate-to-propionate ratio, and protozoa numbers. Compared with cows fed the control diet, ruminal NH3 concentration increased and tended to increase for cows fed ground FB and rolled FB, respectively; however, we found no difference in ruminal NH3 concentration between the 2 processed FB. Apparent total-tract digestibility of crude protein was similar between cows fed the control diet and cows fed rolled FB and tended to increase for cows fed ground FB compared with cows fed the control diet. Feeding rolled FB decreased CP digestibility compared with feeding ground FB. Urinary and manure (feces + urine) N excretion (g/d or as a proportion of N intake) were not affected by the inclusion of FB in the diet. Enteric CH4 production was similar among the experimental diets. Results from this study show that including FB (17% of dietary dry matter) at the expense of SBM and corn grain in the diet had no effect on milk production, N excretion, and enteric CH4 production of dairy cows.


Ventilatory effects of selective beta 1-(prenalterol) or beta 2-(salbutamol) adrenoceptor agonism in man.
We compared the ventilatory effects of prenalterol (beta 1-selective adrenoceptor agonist) with those of salbutamol (beta 2-selective adrenoceptor agonist) in 6 healthy volunteers. Two intravenous doses of prenalterol (1 mg/60 min, 2 mg/60 min) and of salbutamol (300 micrograms/60 min, 600 micrograms/60 min) were given in random order in 4 separate sessions of 60 minutes each. Pulmonary ventilation per minute (V'E) increased only on the high dose of salbutamol. Mouth occlusion pressure (P0.1) did not vary either on prenalterol or on salbutamol. Only the high dose of salbutamol induced (1) an increase in tidal volume (VT) without changes in respiratory rate (RR), (2) an increase in mean inspiratory flow (VT/Ti) without changes in the fraction of inspiratory time to total cycle duration (Ti/Ttot). During forced expiration, salbutamol elicited a small bronchodilating effect at the level of both large (FEV1, FEF25-75, FEF50) and small (FEV3, FEF75-85, FEF75) airways. Prenalterol induced a very small dilatation of the large airways, and a somewhat more pronounced effect at the level of the small airways. Neither the indexes of ventilatory pattern nor those of bronchial tone showed any statistical or biological differences between values on prenalterol and values on salbutamol. However, both the former and the latter indexes showed a trend to be higher on salbutamol than on prenalterol. Results suggest that salbutamol-induced increase in pulmonary ventilation per minute in subjects without bronchial obstruction is likely the result of a reduced bronchomotor tone at rest, leading to an increase in tidal volume because of the rise in the VT/Ti ratio.(ABSTRACT TRUNCATED AT 250 WORDS)


Risk of Severe COVID-19 Increased by Metabolic Dysfunction-associated Fatty Liver Disease: A Meta-analysis.
The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) in coronavirus disease-2019 (COVID-19) patients and whether it affects the outcomes of COVID-19 requires investigation. The aim was to determine the prevalence of MAFLD among COVID-19 patients and its influence on the outcomes of COVID-19 by meta-analysis. Our study protocol has been registered on PROSPERO (CRD42021242243). The studies published on PubMed, Embase, Cochrane Library, and Web of Science before March 11, 2021 were screened. The Newcastle-Ottawa scale (NOS) and Agency for Healthcare Research and Quality scale were used to assess the quality of the studies. Pooled analysis was conducted using the software RevMan version 5.3 and Stata version 15.0 SE. The stability of the results was assessed by sensitivity analysis. Publication bias was evaluated using funnel plots, Egger test, and trim-and-fill analysis. Seven studies covering 2141 COVID-19 patients were included. It was confirmed that MAFLD increased the risk of severe COVID-19 (odds ratios: 1.80, 95% confidence interval: 1.53-2.13, P<0.00001). No association was found between the presence of MAFLD and the occurrence of COVID-19 death. The pooled prevalence of MAFLD among COVID-19 patients was 36% (95% confidence interval: 0.23-0.49, P<0.00001). Sensitivity analysis confirmed that the initial results were stable. MAFLD can increase the incidence of severe COVID-19, but the correlation between MAFLD and COVID-19 death has not been confirmed. Further investigation is needed to explore the possible mechanism of this association. Since MAFLD is common among patients infected with SARS-CoV-2, more care should be given to COVID-19 patients with underlying MAFLD.


Ectopic cervical thymoma--the great mimic: a case report.
Ectopic cervical thymoma is a rare tumour that probably arises from thymic tissue trapped during the migration of the thymus into the anterior mediastinum from the third and fourth pharyngeal pouches. As it occurs in the region of the thyroid gland it mimics thyroid lesions and can cause confusion to the clinician, sonologist and cytologist. Misinterpretation of frozen sections can also occur if knowledge of this entity is not present. We are reporting a case of this rare entity in an elderly lady who presented with a neck mass that mimicked a thyroid lesion. Ectopic cervical thymoma should be considered in the list of differential diagnosis of neck masses in the elderly.


A biostatistical insight into the As(2)O(3) high dilution effects on the rate and variability of wheat seedling growth.
Most criticism of homeopathy concerns the lack of scientific bases and theoretical models. Fundamental research could make important contributions to our understanding of the mechanisms of action of homeopathic treatments. Plant-based bioassays are suitable for basic research -- lacking the placebo effect and ensuring large data samples for structured statistical analyses. The aim of this study was to reproduce a previous experiment on the effects of arsenic trioxide (As(2)O(3)) high dilutions on wheat seedling growth in order to verify whether the same significant results could be obtained working in a different place and with a different experimental team. A further goal was to investigate high dilution effects on variability. A structured experiment was performed blind over 9 weeks, using wheat seeds previously stressed with a sublethal dose of As(2)O(3). The seeds were then treated with either potentized As(2)O(3) (5x, 15x, 25x, 35x, 45x), potentized water (equivalent potencies) or diluted As(2)O(3) (10(-5), 10(-15), 10(-25), 10(-35), 10(-45)). The working variable was the stem length, measured after 4, 5, 6 and 7 days. Some potencies (As(2)O(3) 45x and H(2)O 45x) induced a relevant increase in seedling growth and/or a variability decrease. Diluted As(2)O(3) did not induce any significant results. Confirmation of a significant stimulating effect on seedling growth and a significant decrease of variability was obtained with ultra-high dilutions at the 45x potency. The model of wheat germination and growth has been confirmed to be a good tool for basic research in homeopathy.


Cell Migration and Cell Adhesion Assays to Investigate Leishmania-Host Cell Interaction.
Leishmania is an intracellular protozoan parasite that causes a broad spectrum of clinical manifestations, ranging from self-resolving localized cutaneous lesions to a highly fatal visceral form of the disease. An estimated 12 million people worldwide are currently infected, and another 350 million face risk of infection. It is known that host cells infected by Leishmania parasites, such as macrophages or dendritic cells, can migrate to different host tissues, yet how migration contributes to parasite dissemination and homing remains poorly understood. Therefore, assessing these parasites' ability to modulate host cell response, adhesion, and migration will shed light on mechanisms involved in disease dissemination and visceralization. Cellular migration is a complex process in which cells undergo polarization and protrusion, allowing them to migrate. This process, regulated by actin and tubulin-based microtubule dynamics, involves different factors, including the modulation of cellular adhesion to the substrate. Cellular adhesion and migration processes have been investigated using several models. Here, we describe a method to characterize the migratory aspects of host cells during Leishmania infection. This detailed protocol presents the differentiation and infection of dendritic cells, the analysis of host cell motility and migration, and the formation of adhesion complexes and actin dynamics. This in vitro protocol aims to further elucidate mechanisms involved in Leishmania dissemination within vertebrate host tissues and can also be modified and applied to other cell migration studies.


Continuous-wave cavity ring-down polarimetry.
We present a new cavity-based polarimetric scheme for highly sensitive and time-resolved measurements of birefringence and dichroism, linear and circular, that employs rapidly pulsed single-frequency continuous wave (CW) laser sources and extends current cavity-based spectropolarimetric techniques. We demonstrate how the use of a CW laser source allows for gains in spectral resolution, signal intensity, and data acquisition rate compared to traditional pulsed-based cavity ring-down polarimetry (CRDP). We discuss a particular CW-CRDP modality that is different from intensity-based cavity-enhanced polarimetric schemes as it relies on the determination of the polarization rotation frequency during a ring-down event generated by large intracavity polarization anisotropies. We present the principles of CW-CRDP and validate the applicability of this technique for the measurement of the non-resonant Faraday effect in solid SiO2 and CeF3 and gaseous butane. We give a general analysis of the fundamental sensitivity limits for CRDP techniques and show how the presented frequency-based methodology alleviates the requirement for high finesse cavities to achieve high polarimetric sensitivities and, thus, allows for the extension of cavity-based polarimetric schemes into different spectral regimes, but most importantly renders the CW-CRDP methodology particularly suitable for robust portable polarimetric instrumentations.


Spin-spin relaxation in experimental allergic encephalomyelitis. Analysis of CPMG data using a non-linear least squares method and linear inverse theory.
We have used the CPMG pulse sequence to measure proton T2 values and water content in spinal cord and brain samples from Hartley guinea pigs inoculated to produce experimental allergic encephalomyelitis (EAE). Relaxation data were fitted using minuit, a non-linear curve fitting routine. Three exponentials provided the best fit to spinal cord data (10 ms (13%), 76 ms (57%), 215 ms (30%)) and two exponentials for brain tissue (10 ms (4%), 92 ms (96%)). Least squares algorithms were also used to analyse the spinal cord data in terms of discrete and smooth distributions of relaxation times. The discrete least squares solutions consisted of three to five isolated spikes between 0.010 and 0.300 s. This type of solution was difficult to interpret in terms of water reservoirs. Smooth solutions consisted of two broad peaks, a small peak with a T2 near 0.010 s and a larger peak near 0.100 s. The integral ratio of the larger to the smaller peak was 7.092 +/- 1.782 for normal tissue, and increased to a maximum of 16 with increasing parenchymal cellular infiltration and demyelination. The short T2 peak has been assigned to water in the hydration layers of the myelin sheath. The width of the longer T2 peak was sensitive to tissue heterogeneity. The least squares and smooth distribution analysis models could be used to distinguish samples with extensive parenchymal infiltration from normal tissue, even though only a maximum of 60% of the tissue was affected.(ABSTRACT TRUNCATED AT 250 WORDS)


Short-chain fatty acids and total parenteral nutrition affect intestinal gene expression.
The supplementation of total parenteral nutrition (TPN) formulas with short-chain fatty acids (SCFAs) increases glucose uptake and the expression of glucose transporters in parenterally fed animals. Several signals may be involved in intestinal adaptation; however, increased messenger RNA (mRNA) levels for proglucagon and several early-response genes, including c-myc and c-fos, are seen in animals receiving SCFA-supplemented TPN. Although the effects of a mixture of SCFAs are well documented, the relative contribution of individual SCFAs is unknown. Butyrate is a preferred fuel of colonocytes, with documented effects on cellular proliferation and gene expression. Accordingly, this study was undertaken to determine the relative role of butyrate in initiating an adaptive response in nonresected rats receiving TPN. Animals received standard TPN for 66 hours, followed by 6 hours of either standard TPN, TPN supplemented with a mixture of SCFAs (acetate, propionate, and butyrate, 60 mmol/L total), or TPN supplemented with butyrate alone (9 mmol/L). An oral control group was fed an elemental diet, similar in macronutrient content to the TPN, so that all animals received the same amount of energy daily. SCFAs increased ileal glucose transporter 2 (GLUT2) mRNA expression compared with the orally fed group. SCFAs also increased proglucagon mRNA expression compared with the TPN group. No changes in Na+K(+)-adenosine triphosphatase or early-response gene expression were found in this study. In a rat model of TPN, the use of 9 mmol/L butyrate did not have the same effect on GLUT2 and proglucagon expression as a 60-mmol/L mixture of SCFAs. This suggests that the effect of a mixture of SCFAs on intestinal gene expression is not butyrate specific.


Regulation of mouse oocyte growth: probable nutritional role for intercellular communication between follicle cells and oocytes in oocyte growth.
Intercellular communication, as determined by two different assay procedures, was established in vitro between mouse oocytes free of adhering follicle cells and monolayers of either follicle or 3T3 cells. Both of these cell types are known to be able to form homologous gap junctions, and follicle cells naturally form heterologous gap junctions with oocytes in vivo. Monolayers of L cells that are communication deficient did not establish intercellular communication with oocytes as determined by the two different assays for intercellular communication. The diameter of oocytes cultured for 4 days in medium or on monolayers of L cells decreased markedly, 9.7 and 13.1 micron, respectively. In contrast, oocytes cultured for 4 days on follicle cell monolayers increased on the average about 4.7 micron in diameter. Oocytes cultured for 4 days on monolayers of 3T3 cells decreased slightly in diameter, i.e., 2.1 micron. Results from these experiments support a nutritional role for intercellular communication between follicle cells and oocytes in oocyte growth.


Magnetophoresis-integrated hydrodynamic filtration system for size- and surface marker-based two-dimensional cell sorting.
A simple microfluidic system has been presented to perform continuous two-parameter cell sorting based on size and surface markers. Immunomagnetic bead-conjugated cells are initially sorted based on size by utilizing the hydrodynamic filtration (HDF) scheme, introduced into individual separation lanes, and simultaneously focused onto one sidewall by the hydrodynamic effect. Cells are then subjected to magnetophoretic separation in the lateral direction, and finally they are individually recovered through multiple outlet branches. We successfully demonstrated the continuous sorting of JM (human lymphocyte cell line) cells using anti-CD4 immunomagnetic beads and confirmed that accurate size- and surface marker-based sorting was achieved. In addition, the sorting of cell mixtures was performed at purification ratios higher than 90%. The proposed system enables two-dimensional cell sorting without necessitating complicated setups and operations, and thus, it can be a useful tool for general biological experiments including cell-based disease diagnosis, stem cell engineering, and cellular physiological studies.


Hydrodynamic synchronization of nonlinear oscillators at low Reynolds number.
We introduce a generic model of a weakly nonlinear self-sustained oscillator as a simplified tool to study synchronization in a fluid at low Reynolds number. By averaging over the fast degrees of freedom, we examine the effect of hydrodynamic interactions on the slow dynamics of two oscillators and show that they can lead to synchronization. Furthermore, we find that synchronization is strongly enhanced when the oscillators are nonisochronous, which on the limit cycle means the oscillations have an amplitude-dependent frequency. Nonisochronity is determined by a nonlinear coupling α being nonzero. We find that its (α) sign determines if they synchronize in phase or antiphase. We then study an infinite array of oscillators in the long-wavelength limit, in the presence of noise. For α>0, hydrodynamic interactions can lead to a homogeneous synchronized state. Numerical simulations for a finite number of oscillators confirm this and, when α<0, show the propagation of waves, reminiscent of metachronal coordination.


Mental health training program for community mental health staff in Guangzhou, China: effects on knowledge of mental illness and stigma.
In order to reduce the huge treatment gap in mental health, WHO has called for integrating mental health into primary care. The purposes of this study are to provide a training course to improve the community mental health staff's knowledge of mental health and reduce stigma related to mental illness, as well as to evaluate the impact of this training on knowledge and stigma. The training intervention was a one day course for community mental health staff in Guangzhou, China. Evaluation questionnaires were given before and after the training session. Mental health knowledge was assessed using two vignettes. Stigma was evaluated by the Mental Illness: Clinicians' Attitudes Scale (MICA) and the Reported and Intended Behavior Scale (RIBS). A total of 99 community mental health staff from eight regions in Guangzhou, China were recruited for the study. The training course did not lead to a significant improvement of participants' levels of mental health knowledge. The mean score of MICA decreased from 47.92 ± 8.63 to 43.53 ± 9.61 after the training (t = 6.64, P < 0.001). As for the RIBS, the mean scores increased from (14.12 ± 3.90) to (15.38 ± 3.41) at post-test (t = -5.44, P < 0.001), indicating a significant improvement. The results from this study show that the training course is an effective way to improve community mental health staff's attitudes toward people with mental illness in the short term, as well as to lessen the social distance between staff and people with mental illness.


Human Rabies - Wyoming and Utah, 2015.
In September 2015, a Wyoming woman was admitted to a local hospital with a 5-day history of progressive weakness, ataxia, dysarthria, and dysphagia. Because of respiratory failure, she was transferred to a referral hospital in Utah, where she developed progressive encephalitis. On day 8 of hospitalization, the patient's family told clinicians they recalled that, 1 month before admission, the woman had found a bat on her neck upon waking, but had not sought medical care. The patient's husband subsequently had contacted county invasive species authorities about the incident, but he was not advised to seek health care for evaluation of his wife's risk for rabies. On October 2, CDC confirmed the patient was infected with a rabies virus variant that was enzootic to the silver-haired bat (Lasionycteris noctivagans). The patient died on October 3. Public understanding of rabies risk from bat contact needs to be improved; cooperation among public health and other agencies can aid in referring persons with possible bat exposure for assessment of rabies risk.


Organocatalytic C-H bond arylation of aldehydes to bis-heteroaryl ketones.
An organocatalytic aldehyde C-H bond arylation process for the synthesis of complex heteroaryl ketones has been developed. By exploiting the inherent electrophilicity of diaryliodonium salts, we have found that a commercial N-heterocyclic carbene catalyst promotes the union of heteroaryl aldehydes and these heteroaromatic electrophile equivalents in good yields. This straightforward catalytic protocol offers access to ketones bearing a diverse array of arene and heteroarene substituents that can subsequently be converted into molecules displaying structural motifs commonly found in medicinal agents.


Language play facilitates language learning: Optimizing the input for gender-like category induction.
Gender induction has been claimed to be virtually impossible unless nouns provide reliable semantic or phonological gender-relevant cues. However, learners might exploit syntactic cues, such as definite articles, to infer the gender of gender-unmarked nouns. In children's poems and songs, such syntactic cues are presented in a highly structured fashion. We assessed gender-like category induction in an artificial language that provided exclusively syntactic cues for its gender-like subclasses. We trained participants with structured or unstructured input presented in a prose, a rhyming, a melodic, or a rhyming and melodic fashion. Input structuring significantly facilitated gender-like category induction. Participants trained in the Rhyme-and-Melody mode significantly outperformed participants trained in the Prose mode, especially when the input was structured. The Rhyme-only and Melody-only modes yielded intermediate results. Thus, a highly structured rhyming and melodic input substantially facilitates gender-like category induction, making a case for the use of children's songs in language teaching.


Effect of liposomes containing sodium butyrate conjugated with anti-CD19 monoclonal antibody on in vitro and in vivo growth of malignant lymphoma.
A differentiation-inducer, sodium butyrate (SB), encapsulated in liposomes conjugated covalently to a monoclonal antibody directed to CD19 antigen, was successfully targeted to human lymphoma cell lines SKLY-18 and Ramos grown in vitro and in vivo in nude mice. Various control liposomes (lacking SB, lacking antibody, containing SB alone, or coupled to irrelevant antibody) were not effective targeters. Growth of tumor cells not expressing the relevant antigen was unaffected by the antibody-SB-liposome complex. Suppression of lymphoma growth in vivo was remarkable, and tumor regression was observed under certain conditions, although changes in morphology were not clearly observed. In view of the practical nonexistence of "tumor-specific" antigens, targeting of differentiation-inducers or growth modifiers, rather than cytotoxic drugs, to tumor cells, as exemplified in these experiments, may provide a useful approach for conversion of highly malignant to less malignant tumors, although the exact mechanism of the growth inhibitory effect on B-cell lymphoma of the anti-CD19 antibody-SB-liposome complex is unknown.


Selecting patients for epilepsy surgery: identifying a structural lesion.
One of the most important components of presurgical evaluation of patients with epilepsy is structural imaging, predominantly using magnetic resonance imaging. This study is now part of the basic assessment of patients with epilepsy and is as important as the electroencephalogram. Epilepsy protocol magnetic resonance imaging studies must be part of the overall assessment of the patient. To understand the basis of the epileptic disorder, interpretation of these investigations relies on knowledge of the clinical details and features of the seizures, the functional abnormality in the brain as shown on the electroencephalogram, and structural assessment of the brain with a magnetic resonance imaging study optimized for epilepsy. This review considers the essential elements of this issue and gives a broad overview of what imaging options are available for the investigation of the patient with epilepsy from the perspective of the practicing epileptologist.


Maternal effects in human cleft lip and palate.
To look for a persistent maternal effect of CL(P) and CP, 8,000 pedigrees were screened for half sibships, and data were pooled from 16 investigators. After excluding known genetic or cytogenetic diagnoses from the probands with facial clefts, a recurrence risk of .011 was obtained for CL(P) based upon 342 maternal half sibs. This was nearly identical to the risk of .014 based upon 210 paternal half sibs. CP proband frequencies of .004 for maternal half sibs and .009 for the paternal counterparts were also found. The lack of significant maternal effects in this data supports previously reported data from twin studies and from interracial crosses from Hawaii. The lack of maternal effect in human CL(P) and CP is in contrast to genetic data on clefting in mice.


Elimination of pharmaceuticals and personal care products in subsurface flow constructed wetlands.
Removal efficiency and elimination rates of 11 pharmaceuticals and personal care products (PPCPs)were measured in two subsurface horizontal flow constructed wetlands (SSFs) characterized by different water depths (i.e. 0.3 and 0.5 m) in a 2-year study. Dissolved and particulate phases of wastewater and gravel samples were collected and analyzed. The PPCP influent concentration ranged from 1 to 25 microg L(-1). The best removal efficiency was found in the shallower bed SSF due to its less negative redox potential. PPCPs were classified in four groups according to their removal behavior: (i) the efficiently removed (>80%) namely caffeine, salicylic acid, methyl dihydrojasmonate, and carboxy-ibuprofen, (ii) the moderately removed (50-80%) namely ibuprofren, hydroxy-ibuprofen, and naproxen, (iii) the recalcitrant to the elimination namely ketoprofen and diclofenac, and,finally, (iv) compounds that were eliminated by hydrophobic interactions namely polycyclic musks (i.e. galaxolide and tonalide). These compounds were removed more than 80% from the effluent but occurred at high concentrations (up to 824 microg kg(-1)) in the gravel bed. Accordingly, their elimination by sorption onto the organic matter retained is the predominant removal mechanism. Furthermore, the constructed wetland clogging appears to induce a negative effect in the PPCP degradation in the SSF evaluated. The PPCP elimination classified as efficiently and moderately removed through the shallow bed fitted to either zero- or a first-order areal kinetics. Finally, the apparent distribution coefficients between suspended solids (Kd'ss) or gravel bed (Kd'gb) and water were determined in the different sampling points of the wetland obtaining values comparable to the described previously for sewage sludge.


An irregularity in the transmembrane domain helix correlates with the rate of insulin receptor internalization.
Internalization of insulin and its receptor via receptor-mediated endocytosis is an important step in insulin-induced signal transduction. To investigate the structural determinants underlying the enhanced internalization rate observed for the insulin receptor transmembrane mutant Gly933-Pro934-->Ala-Ala (GP-->AA), we have designed and chemically synthesized two peptides, IR(TM)-GP and IR-(TM)-AA, corresponding respectively to the N-terminal portion of the wild-type and the mutant insulin receptor TM segment containing these sites. Conformational studies by circular dichroism (CD) spectroscopy on these two peptides in their monomeric states revealed that peptide IR(TM)-GP forms an irregular helix in the membrane-mimetic environments of sodium dodecyl sulfate (SDS) micelles with a possible "kink" in the helix imposed by its Gly-Pro sequence, while peptide IR(TM)-AA assumes largely classical alpha-helical structure under corresponding conditions. The helical pattern of peptide IR(TM)-AA was maintained at elevated temperatures, while the shape of the CD curve for peptide IR(TM)-GP was found to alter as a function of temperature. At higher concentrations, both peptides formed high molecular weight aggregates in SDS micelles, as demonstrated by SDS-PAGE gels, but peptide IR(TM)-AA was shown to aggregate more readily and more extensively than peptide IR(TM)-GP. Fluorescent dye-leakage experiments indicated that peptide IR(TM)-GP produces an enhanced disruption of the membrane bilayer in phosphatidylglycerol vesicles vs that induced by IR(TM)-AA.(ABSTRACT TRUNCATED AT 250 WORDS)


Total pelvic exenteration: effective palliation of perineal pain in patients with locally recurrent prostate cancer.
Locally recurrent prostate cancer can be a debilitating disease. Perineal pain associated with rectal involvement by prostate cancer is difficult to palliate by conventional methods. We describe a group of patients who had intractable perineal pain due to locally recurrent prostate cancer and underwent total pelvic exenteration for palliation. We retrospectively reviewed the data for men who underwent total pelvic exenteration with urinary and colonic diversion at our institution between October 1995 and October 2002 for the relief of perineal pain from prostate cancer. Patients were selected for consideration for surgical extirpation on the basis of the presence of biopsy proven recurrent prostate cancer and evidence of rectal invasion on sonography. All patients received radiation therapy and hormonal therapy and had intractable perineal or pelvic pain resistant to narcotics. A total of 14 men underwent total pelvic exenteration for palliation during the 7-year period evaluated. There were no perioperative deaths. There were 7 postoperative events, including pulmonary embolus in 2 patients, and ileus, wound infection, cholecystitis, stomal stenosis and pelvic abscess in 1 patient each. After exenteration all patients had significant relief of pain and 11 (79%) had complete relief of pain symptoms. For these 11 patients the average symptom-free period was 14.1 months (range 3 to 36). Seven patients eventually died of disease, with the median period from exenteration to death being 24 months. Total pelvic exenteration is effective therapy for palliation of perineal pain associated with locally recurrent prostate cancer and can also effectively palliate other local symptoms such as hematuria, ureteral obstruction, voiding dysfunction and rectal incontinence. This procedure can be performed with acceptable morbidity in a highly select group of patients.


Concentration of free thyroxin in serum of a patient with euthyroid hyperthyroxinemia secondary to increased thyroxin-binding prealbumin: results by various methods compared.
We used various kits to measure free thyroxin (T4) in serum from a patient with the very rare syndrome of euthyroid hyperthyroxinemia secondary to increased thyroxin-binding prealbumin in serum. This patient's free T4 by equilibrium dialysis was 13 ng/L (normal 9-21), whereas the free-T4 index was 18.6 (normal 5.5-11.5). Using six different commercial methods, the last three listed being T4-analog methods, we measured the serum free T4 in this patient. The mean +/- SD (and normal range) free-T4 concentrations (ng/L) measured were: GammaCoat, Two-Step, 19.2 +/- 4.5 (6.9-26.9); Liquisol, 17.8 +/- 3.0 (12.4-20.8); Immo Phase, Two-Step 26.8 +/- 0.3 (12.4-21.2); GammaCoat, Single-Step, 19.7 +/- 5.7 (10.3-21.0); Immo Phase, Single-Step, 27.7 +/- 0.9 (8.6-25.0); and Amerlex, 14.1 +/- 0.6 (5.3-14.1). In four patients with familial dysalbuminemic hyperthyroidism, in whom the serum T4 by equilibrium dialysis was normal, all three T4-analog methods gave results far exceeding normal (greater than 50 ng/L).


Development of a reliable multimedia, computer-based measure of clinical skills in bedside neurology.
This study reports the development of reliable multimedia, computer-based measures of bedside neurology skills. A consortium of neurologists and medical educators (1) identified bedside skills and (2) created a computer-based test. Test-item stems were multimedia clips of standardized patients. Options appeared as text. Sixty-one junior medical students responded to these items. The 77-item test yielded a reliability coefficient of 0.85. Subgroup item analysis resulted in reliability coefficients of 0.73 for the 20-question "pretest" (Test A) and 0.75 for the 20-question "posttest" (Test B). Two sets of test items were developed that can be used as outcome measures in studies that assess the effectiveness of educational interventions in bedside neurology.


Testing the cognitive-behavioural maintenance models across DSM-5 bulimic-type eating disorder diagnostic groups: a multi-centre study.
The original cognitive-behavioural (CB) model of bulimia nervosa, which provided the basis for the widely used CB therapy, proposed that specific dysfunctional cognitions and behaviours maintain the disorder. However, amongst treatment completers, only 40-50 % have a full and lasting response. The enhanced CB model (CB-E), upon which the enhanced version of the CB treatment was based, extended the original approach by including four additional maintenance factors. This study evaluated and compared both CB models in a large clinical treatment seeking sample (N = 679), applying both DSM-IV and DSM-5 criteria for bulimic-type eating disorders. Application of the DSM-5 criteria reduced the number of cases of DSM-IV bulimic-type eating disorders not otherwise specified to 29.6 %. Structural equation modelling analysis indicated that (a) although both models provided a good fit to the data, the CB-E model accounted for a greater proportion of variance in eating-disordered behaviours than the original one, (b) interpersonal problems, clinical perfectionism and low self-esteem were indirectly associated with dietary restraint through over-evaluation of shape and weight, (c) interpersonal problems and mood intolerance were directly linked to binge eating, whereas restraint only indirectly affected binge eating through mood intolerance, suggesting that factors other than restraint may play a more critical role in the maintenance of binge eating. In terms of strength of the associations, differences across DSM-5 bulimic-type eating disorder diagnostic groups were not observed. The results are discussed with reference to theory and research, including neurobiological findings and recent hypotheses.


Soybean soluble polysaccharide enhances absorption of soybean genistein in mice.
This study was designed to probe the promoting effects of soybean soluble polysaccharide (SSPS) on bioavailability of genistein in mice and the underlying molecular mechanism. Male Kunming mice (n=8) were administered intragastrically with either saline, SSPS (5mg/kgbw), genistein (100mg/kgbw), or SSPS (5 or 50mg/kgbw) together with genistein (100mg/kgbw) for consecutive 28days. UPLC-qTOF/MS analysis showed that co-administration of SSPS and genistein in mice caused significant elevation in the urinary levels of genistein and its metabolites (p<0.05). Furthermore, the fecal excretion of genistein was also enhanced by co-administration of SSPS. However, the feces level of dihydrogenistein, a characteristic metabolite of genistein degraded by gut microorganism, was dose-dependently decreased by the combined treatment of SSPS. Additionally, co-treatment of SSPS with genistein also decreased the small intestinal levels of uridinediphosphate-glucuronosyltransferase (UGT), sulfotransferase (SULT), P-glycoprotein (P-gp), multidrug resistance-associated protein-1 (MRP1), and multidrug resistance-associated protein-2 (MRP2) in mice. These findings suggest that the inhibition of SSPS against small intestinal first-pass metabolism of genistein is involved in the promoting effect of genistein bioavailability in mice.


Effects of administration of beta-carotene, ascorbic acid, persimmons, and pods on antioxidative ability in UV-irradiated ODS rats.
To evaluate the effects of supplementing diets with carotenoid and ascorbic acid (AsA) on the antioxidative ability of Osteogenic Disorder-Shionogi (ODS) rats, we added synthetic beta-carotene (betaC), AsA, and powders of persimmon (Ka) and pods (Po) containing betaC and AsA to the diet and obtained the following results. The urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration was low in the -betaC.AsA and +AsA groups but high in the +betaC.AsA, +Ka, and +Po groups. The thiobarbituric acid-reactive substances (TBARS) in both the liver and skin were higher in the -betaC.AsA group than in the +betaC.AsA group and were low in the +Ka and +Po groups. As antioxidant enzymes, glutathione peroxidase (GSH-Px) activity was high in the +betaC.AsA group, low in the -beta3C.AsA group in both the skin and liver, and also high in the + Ka and +Po group in the liver. Superoxide dismutase (SOD) activity was high in the -betaC.AsA group and low in the +betaC.AsA and +Ka groups in both the skin and liver. Catalase (CAT) activity in the liver was low in the -betaC.AsA, +AsA, and +betaC groups and high in the +betaC.AsA and +Po groups. These results confirmed that the administration of betaC, AsA, and persimmons and pods increases antioxidative ability in the skin and liver of ultraviolet-b(UV-B)-irradiated ODS rats.


[One hepatic echinococcosis patient complicated with systemic sclerosis].
This article reports one hepatic echinococcosis patient complicated with systemic sclerosis. His clinical manifestations were the progressive fibrosis of the skin, sour regurgitation, and belching. The blood examination showed that eosinophils was reduced, and antinuclear antibody (ANA) was positive at 1:100 in cytoplasm particle type. He was given prednisone acetate 25 mg, q. d., aspirin 100 mg, q. d., centella triterpenes cream 12 mg t. i. d., esomeprazole 40 mg q. d., and domperidone 10 mg t. i. d. After one week, the Rodnan skin score reduced from 27 to 17. The liver hydatid cyst resection was performed, and the follow-up showed that his clinical manifestations improved and the Rodnan skin score reduced further.


3-(2-Pyridyl)-[1,2,3]triazolo[1,5-a]pyridines. An experimental and theoretical (DFT) study of the ring-chain isomerization.
An experimental ((1)H NMR) and theoretical (DFT) study of the ring-chain-ring isomerization of 3-(2-pyridyl)-[1,2,3]triazolo[1,5-a]pyrid-7-yl derivatives (A) into 6-{[1,2,3]triazolo[1,5-a]pyrid-3-yl}-2-pyridyl derivatives (B) has been carried out. Based on the calculations, a mechanism of several steps will be proposed. The experimental results as well as the calculations lead to the conclusion that the A-B ratio depends on the electronic properties of the substituents.


Provision of antiretroviral therapy for HIV-positive TB patients--19 countries, sub-Saharan Africa, 2009-2013.
Considerable progress has been made in the provision of life-saving antiretroviral therapy (ART) for persons with human immunodeficiency virus (HIV) infection worldwide, resulting in an overall decrease in HIV incidence and acquired immunodeficiency syndrome (AIDS)-related mortality. In the strategic scale-up of HIV care and treatment programs, persons with HIV and tuberculosis (TB) are a priority population for receiving ART. TB is the leading cause of death among persons living with HIV in sub-Saharan Africa and remains a potential risk to the estimated 35 million persons living with HIV globally. Of the 9 million new cases of TB disease globally in 2013, an estimated 1.1 million (13%) were among persons living with HIV; of the 1.5 million deaths attributed to TB in 2013, a total of 360,000 (24%) were among persons living with HIV. ART reduces the incidence of HIV-associated TB disease, and early initiation of ART after the start of TB treatment reduces progression of HIV infection and death among HIV-positive TB patients. To assess the progress in scaling up ART provision among HIV-positive TB patients in 19 countries in sub-Saharan Africa with high TB and HIV burdens, TB and HIV data collected by the World Health Organization (WHO) were reviewed. The results found that the percentage of HIV-positive TB patients receiving ART increased from 37% in 2010 to 69% in 2013. However, many TB cases among persons who are HIV-positive go unreported, and only 38% of the estimated number of HIV-positive new TB patients received ART in 2013. Although progress has been made, the combination of TB and HIV continues to pose a threat to global health, particularly in sub-Saharan Africa.


Reporting measles case fatality due to complications from a tertiary care hospital of Kolkata, West Bengal 2011-2013.
Measles is affecting millions of people in the developing countries particularly in India with significant morbidity and responsible for thousands of death in spite of having a safe, effective, and cheap vaccine. Pulmonary complications account for 90% measles-related death. The objectives of this study were to describe age distribution, clinical features, complications, and clinical outcomes of measles cases in a referral infectious disease hospital of West Bengal. We conducted a retrospective descriptive study including 584 patients and collected information from record section on demographics, clinical features, complications, and clinical outcomes using data abstraction form. The mean age of 584 measles cases was 3.7 years (±1.2 years). The most common complication was pneumonia (149 cases) followed by diarrhea and encephalopathy. Very severe pneumonia occurred in 34 cases requiring intensive care out of which 13 patients died. The average duration of stay in the hospital was 5.7 days (±3.2 days). Surprisingly, 45 cases admitted to this hospital were <9 months of age with subsequent death in 5 cases. Substantial number of measles cases was seen in zero to <9 months of age group and fatality due to complication was more among them.


[Nursing care adapted to different types of stoma].
As soon as the patient leaves the operating theatre, in the recovery room, then in the surgical clinical unit, nurses carry out stoma care and monitor the possible occurrence of complications. Stoma therapists educate patients in caring for the stoma themselves, advise them in the choice of equipment and support them as they regain autonomy.


Postoperative pulmonary function in children. Comparison of scoliosis with peripheral surgery.
We measured lung volumes, forced expirograms, and arterial blood gases in 2 groups of elective pediatric surgical patients (mean age, 11.4 +/- SD 2.8; n = 11, 12 operations) the day prior to surgery (control) and between the first and eighth postoperative days. The patients were Group I: peripheral surgery (n = 6) and Group II: reconstructive surgery for scoliosis (n = 5). The preoperative lung volumes and forced expiratory volume in one second were within the predicted normal range in both groups, except for a reduction in total lung capacity (TLC) and vital capacity (VC) in Group II. The postoperative lung volumes in Group I were not significantly different from the preoperative volumes. In group II, on postoperative Days 2 and 3, the lung volumes as a percent of preoperative volumes (mean +/- SEM) were VC, 44 +/- 11; functional residual capacity (FRC), 81 +/- 6; residual volume, 124 +/- 10; TLC, 61 +/- 10. Although the mean FRC returned to the preoperative volume by postoperative Days 5 and 6, the VC and its components remained reduced on postoperative Days 5, 6, and 8. We conclude that postoperative lung volume abnormalities are related to the site and magnitude of surgery and associated phenomena, such as pain, and preoperative respiratory function abnormalities.


Similarities and differences between high-affinity binding sites for cocaine and imipramine in mouse cerebral cortex.
Previously we found close similarities between high-affinity binding sites for [3H]cocaine and those for [3H]imipramine in the mouse cerebral cortex in regard to their association with neuronal uptake of serotonin. In the present study we investigated whether the two ligands bind to the same site. The two ligands had the following high-affinity binding properties in common: localization in both synaptosomal and microsomal fractions; vulnerability to treatment with N-ethylmaleimide, trypsin, and phospholipase A2; and resistance to exposure to dithiothreitol. In contrast, cocaine binding in the cerebral cortex was more sensitive to heat inactivation than imipramine binding. In addition, the mechanism by which cocaine inhibited [3H]imipramine binding differed from that by which imipramine inhibited [3H]cocaine binding. These data suggest that the high-affinity binding sites for [3H]cocaine and [3H]imipramine in the cerebral cortex are distinct entities.


Enhancing Care for Hospitalized Patients With Parkinson's Disease: Development of a Formal Educational Program for Nursing Staff.
Although not generally a primary admission diagnosis, Parkinson's disease (PD) can be a significant comorbidity during hospitalization. Hospitalized individuals with PD can experience a variety of complications, such as confusion, pneumonia, and urinary infections. More than 20% of patients experience deterioration in symptoms and hospital stays are extended by an average of 4 days. Late, omitted, or inappropriate medications are frequent culprits leading to serious consequences, including falls and aspiration. To address an identified gap in staff knowledge about PD, a formal educational program was developed to review its etiology, symptoms, treatments, and unique considerations in care and medication administration. This 2-hour intervention comprises a knowledge pre-test, PowerPoint® presentation, two concise handouts for reference, discussion of an unfolding case study, and review of the Aware in Care kit. Nurses can play a key role in educating staff to reduce avoidable hospital-related complications and enhance outcomes for this vulnerable group. [Journal of Gerontological Nursing, 43(5), 18-22.].


Mechanisms governing inflammasome activation, assembly and pyroptosis induction.
Inflammasomes are multimeric protein complexes that regulate inflammatory responses and pyroptotic cell death to exert host defense against microbes. Intracellular pattern-recognition receptors such as nucleotide-binding domain and leucine-rich repeat receptors (NLRs) and absent in melanoma 2 like receptors (ALRs) assemble the inflammasome complexes in response to pathogens and danger or altered-self signals in the cell. Inflammasome sensors, in association with an adaptor protein-apoptosis-associated speck-like protein containing a caspase-activation and -recruitment domain (ASC)-activate inflammatory caspase-1 to enable the release of inflammatory cytokines and induce cell death, conferring host defense against pathogens. Beyond infectious diseases, the importance of inflammasomes is implicated in a variety of clinical conditions such as auto-inflammatory diseases, neuro-degeneration and metabolic disorders and the development of cancers. Understanding inflammasome activation and its molecular regulation can unveil therapeutic targets for controlling inflammasome-mediated disorders. In this review, we describe recent advances in inflammasome biology and discuss its activation, structural insights into inflammasome assembly and mechanisms for the execution of pyroptosis.


Pediatric sepsis screening in US hospitals.
Sepsis is a major cause of morbidity and mortality in children. While adverse outcomes can be reduced through prompt initiation of sepsis protocols including fluid resuscitation and antibiotics, provision of these therapies relies on clinician recognition of sepsis. Recognition is challenging in children because early signs of shock such as tachycardia and tachypnea have low specificity while hypotension often does not occur until late in the clinical course. This narrative review highlights the important context that has led to the rapid growth of pediatric sepsis screening in the United States. In this review, we (1) describe different screening tools used in US emergency department, inpatient, and intensive care unit settings; (2) highlight details of the design, implementation, and evaluation of specific tools; (3) review the available data on the process of integrating sepsis screening into an overall sepsis quality improvement program and on the effect of these screening tools on patient outcomes; (4) discuss potential harms of sepsis screening including alarm fatigue; and (5) highlight several future directions in sepsis screening, such as novel tools that incorporate artificial intelligence and machine learning methods to augment sepsis identification with the ultimate goal of precision-based approaches to sepsis recognition and treatment. IMPACT: This narrative review highlights the context that has led to the rapid growth of pediatric sepsis screening nationally. Screening tools used in US emergency department, inpatient, and intensive care unit settings are described in terms of their design, implementation, and clinical performance. Limitations and potential harms of these tools are highlighted, as well as future directions that may lead to a more precision-based approach to sepsis recognition and treatment.


Meta-analysis of single-port versus conventional laparoscopic cholecystectomy comparing body image and cosmesis.
The purpose of this study was to evaluate improvements in cosmetic results and postoperative morbidity for single-incision laparoscopic cholecystectomy (SILC) in comparison with multiport laparoscopic cholecystectomy (MLC). A literature search was undertaken for RCTs comparing SILC with MLC in adult patients with benign gallbladder disease. Primary outcomes were body image and cosmesis scores at different time points. Secondary outcomes included intraoperative and postoperative complications, postoperative pain and frequency of port-site hernia. Thirty-seven RCTs were included, with a total of 3051 patients. The body image score favoured SILC at all time points (short term: mean difference (MD) -2·09, P < 0·001; mid term: MD -1·33, P < 0·001), as did the cosmesis score (short term: MD 3·20, P < 0·001; mid term: MD 4·03, P < 0·001; long-term: MD 4·87, P = 0·05) and the wound satisfaction score (short term: MD 1·19, P = 0·03; mid term: MD 1·38, P < 0·001; long-term: MD 1·19, P = 0·02). Duration of operation was longer for SILC (MD 13·56 min; P < 0·001) and SILC required more additional ports (odds ratio (OR) 6·78; P < 0·001). Postoperative pain assessed by a visual analogue scale (VAS) was lower for SILC at 12 h after operation (MD in VAS score -0·80; P = 0·007). The incisional hernia rate was higher after SILC (OR 2·50, P = 0·03). All other outcomes were similar for both groups. SILC is associated with better outcomes in terms of cosmesis, body image and postoperative pain. The risk of incisional hernia is four times higher after SILC than after MLC.


Integrated Clinical, Molecular and Immunological Characterization of Pulmonary Sarcomatoid Carcinomas Reveals an Immune Escape Mechanism That May Influence Therapeutic Strategies.
Pulmonary sarcomatoid carcinoma (PSC) has highly aggressive biological behaviour and poor clinical outcomes, raising expectations for new therapeutic strategies. We characterized 179 PSC by immunohistochemistry, next-generation sequencing and in silico analysis using a deep learning algorithm with respect to clinical, immunological and molecular features. PSC was more common in men, older ages and smokers. Surgery was an independent factor (p < 0.01) of overall survival (OS). PD-L1 expression was detected in 82.1% of all patients. PSC patients displaying altered epitopes due to processing mutations showed another PD-L1-independent immune escape mechanism, which also significantly influenced OS (p < 0.02). The effect was also maintained when only advanced tumour stages were considered (p < 0.01). These patients also showed improved survival with a significant correlation for immunotherapy (p < 0.05) when few or no processing mutations were detected, although this should be interpreted with caution due to the small number of patients studied. Genomic alterations for which there are already approved drugs were present in 35.4% of patients. Met exon 14 skipping was found more frequently (13.7%) and EGFR mutations less frequently (1.7%) than in other NSCLC. In summary, in addition to the divergent genomic landscape of PSC, the specific immunological features of this prognostically poor subtype should be considered in therapy stratification.


Desensitization of the delta-opioid receptor correlates with its phosphorylation in SK-N-BE cells: involvement of a G protein-coupled receptor kinase.
Phosphorylation of G protein-coupled receptors is considered an important step during their desensitization. In SK-N-BE cells, recently presented as a pertinent model for the studies of the human delta-opioid receptor, pretreatment with the opioid agonist etorphine increased time-dependently the rate of phosphorylation of a 51-kDa membrane protein. Immunological characterization of this protein with an antibody, raised against the amino-terminal region of the cloned human delta-opioid receptor, revealed that it corresponded to the delta-opioid receptor. During prolonged treatment with etorphine, phosphorylation increased as early as 15 min to reach a maximum within 1 h. Phosphorylation and desensitization of adenylyl cyclase inhibition paralleled closely and okadaic acid inhibited the resensitization, a result strongly suggesting that phosphorylation of the delta-opioid receptor plays a prominent role in its rapid desensitization. The increase in phosphorylation of the delta-opioid receptor, as well as its desensitization, was not affected by H7, an inhibitor of protein kinase A and protein kinase C, but was drastically reduced by heparin or Zn2+, known to act as G protein-coupled receptor kinase (GRK) inhibitors. These results are the first to show, on endogenously expressed human delta-opioid receptor, that a close link exists between receptor phosphorylation and agonist-promoted desensitization and that desensitization involves a GRK.


The association of optimism and perceived discrimination with health care utilization in adults with sickle cell disease.
We evaluated the effect of perceived discrimination, optimism, and their interaction on health care utilization among African American adults with sickle cell disease (SCD). Measures of optimism and perceived discrimination were obtained in 49 African American SCD patients. Multiple regression analyses controlling for sex and age tested effects of optimism and perceived discrimination on the number of emergency department visits (ED) and number and duration of hospitalizations over the past year. A perceived discrimination-optimism interaction was associated with number of emergency departments visits (b = .29, p = .052), number of hospitalizations (b = .36, p = .019), and duration of hospitalizations (b = .30, p = .045) such that those with high perceived discrimination/high optimism had the greatest health care utilization. African American SCD patients with high perceived discrimination/high optimism had greater health care utilization than patients who reported either low perceived discrimination or low optimism. This study suggests that patient personality and coping styles should be considered when evaluating the effects of stress on SCD-related outcomes.


Perinatal mental health screening for women of refugee background: Addressing a major gap in pregnancy care.
Perinatal mental health disorders affect up to 20% of all women. Women of refugee background are likely to be at increased risk, yet little research has explored this. This study aimed to assess if women of refugee background are more likely to screen risk positive for depression and anxiety than non-refugee women, using the Edinburgh Postnatal Depression Scale (EPDS); and if screening in pregnancy using the EPDS enables better detection of depression and anxiety symptoms in women of refugee background than routine care. This implementation study was conducted at an antenatal clinic in Melbourne, Australia. Women of refugee and non-refugee backgrounds were screened for depression using English or translated versions of the EPDS and a psychosocial assessment on a digital platform. The psychosocial assessment records of 34 women of refugee background receiving routine care (no screening) were audited. Overall, 274 women completed the EPDS; 43% of refugee background. A similar proportion of women of refugee and non-refugee backgrounds had EPDS scores of ≥9 (39% vs. 40% p = 0.93). Women receiving the combined EPDS and psychosocial screening were more likely to receive a referral for further support than women receiving routine care (41% vs. 18%, p = 0.012). Similarly, high proportions of women of refugee and non-refugee backgrounds were at increased risk of experiencing a current depressive disorder in early pregnancy, suggesting pregnancy care systems should acknowledge and respond to the mental health needs of these women. Screening appeared to facilitate the identification and referral of women compared to routine care.


A practical approach to risk-benefit estimation in pediatric drug research.
One of the most difficult challenges in pediatric drug research is in exposing children to risk, often without a balanced chance of benefits. While the concept of risk is similar in adult research, the adult patient can decide for himself/herself on an acceptable level of risk, whereas children have to accept the decisions of their guardians. This paper attempts to put the complexities of estimating risk in pediatric drug research into their practical perspective, and to familiarize the reader with the way such processes are conducted in different parts of the world. Although there are regional differences, all authorities typically quantify risks of pediatric research in general, and drug research in particular, in three levels: those experienced in day-to-day life; risks slightly above this 'baseline' risk; and risks substantially above 'baseline risk'. Proportionally, the diligence of the ethics process depends on these levels, as well as on the potential benefits (or lack of) to the child involved in the research. Importantly, risk is context dependent, and a particular intervention may be effective or safe in one setting but not in another, based on local experience, staffing levels, and similar variabilities.


A technique to correct floppy eyelid syndrome.
In patients with floppy eyelid syndrome, surgical treatments aim to improve eyelid stability and position. The authors treated 3 cases of floppy eyelid syndrome using auricular conchal cartilage to reinforce the lax tarsus of the upper eyelid. The postoperative course was uncomplicated in all patients and the result was extremely satisfying, with resolution of ocular discomfort and conjunctivitis. There were no relapses.


When new employee orientation doesn't go as planned. "It is time for Plan B ... but, what is Plan B?".
Although organizations have standard orientation programs for newly hired registered nurses, there are times when orientees are unable to meet expectations. When this happens, it is important to implement a Plan B--a revised orientation program that includes individualized strategies and content--to meet the needs of the orientee who is not progressing. This article will identify factors that may predict the need for increased orientation time and strategies to assist the new employee to complete orientation successfully.