Oral shedding of herpesviruses in HIV-infected patients with varying degrees of immune status.
Herpesvirus shedding in the oral cavity was analyzed to determine if presence in the oral compartment correlates with systemic changes in HIV-associated immune deficiency as measured by CD4 cell counts, plasma HIV viral load and presence of AIDS-defining events. A5254 is a multicenter, cross-sectional, single-visit study to evaluate oral complications of HIV/AIDS and determine the association between clinical appearance, herpesvirus shedding, and immune status as ascertained by CD4 cell count and HIV viral load. In total, 307 HIV-infected individuals were evaluated and throat wash collected. Fisher's exact test and Kruskal-Wallis test were used to assess the association between presence of herpesviruses and the state of immunodeficiency as stratified by a combination of CD4 cell count and HIV viral load. Relationship between pathogens and HIV viral load in plasma was modeled by logistic regression. The presence of cytomegalovirus (CMV) and herpes simplex virus-1 in throat wash was associated with decreased CD4 cell counts. By contrast, Kaposi sarcoma-associated herpesvirus and Epstein-Barr virus were similarly detectable across all levels of CD4 cell counts. One unit increase in log10 (HIV viral load) was associated with 1.31 times higher odds of detecting CMV in throat wash when controlling for oral candidiasis, CD4 cell count, and sites (95% confidence interval 1.04-1.65, P = 0.02). Oral CMV shedding was significantly higher in highly immunocompromised HIV participants. Our finding supports the recommendations to start antiretroviral therapy independent of CD4 cell count as this may have the added benefit to lower the risk of herpesvirus transmission among persons infected with HIV and their partners.


Intraventricular injections of tachykinin NK3 receptor agonists suppress the intake of "salty" tastes by sodium deficient rats.
Intraventricular injections of the tachykinin NK3 receptor (NK3-R) agonist, senktide, suppress the ingestion of hypertonic (0.5 M) NaCl by decreasing the initial lick rate and accelerating the decay in lick rate in sodium deficient rats. The present experiment examined whether the effects of intraventricular injections of senktide on lick rate were selective for NaCl solution, or if the ability of NK3-R agonists to inhibit intake generalizes other sodium-containing solutions. The effects of lateral ventricular injections of isotonic saline or senktide (200 ng) on intake and lick rate of 0.5 M solutions of sodium chloride (NaCl), sodium acetate (Na acetate), sodium bicarbonate (Na bicarbonate), and monosodium glutamate (MSG) were measured in sodium deficient rats. Compared to saline injection, senktide injection had no effect on the lick rate or intake of Na bicarbonate. In contrast, intraventricular injection of senktide suppressed the intake of NaCl, Na acetate, and MSG compared to saline injection. Senktide injection accelerated the decay in lick rate for NaCl, Na acetate and MSG, but only suppressed the initial lick rate for NaCl and Na acetate. The results show that activation of NK3-R in sodium deficient rats suppresses the intake of tastes that are classified as "salty" tasting and that the decrease in intake reflects effects on the initial lick rate, the decay in lick rate, or both.


Toxicity of polyunsaturated fatty acid esters for human monocyte-macrophages: the anomalous behaviour of cholesteryl linolenate.
We have investigated the toxicity to human monocytemacrophages, and susceptibility to oxidation, of different individual dietary fatty acids in cholesterol esters and triglycerides, added to the cell cultures as coacervates with bovine serum albumin. Toxicity was assessed using release of radioactivity from cells preloaded with tritiated adenine. Lipid oxidation was measured by gas chromatography (GC). The triglycerides showed a direct relationship between toxicity and increasing unsaturation, which in turn correlated with increasing susceptibility to oxidation. Triolein (18:1; omega-9) and trilinolein (18:2; omega-6) were non-toxic. Trilinolenin (18:3; omega-3) was toxic only after prolonged incubation. Triarachidonin (20:4; omega-6), trieicosapentaenoin (20:5; omega-3) and tridocosahexaenoin (22:6; omega-3) were profoundly and rapidly toxic. There was a similar relationship between toxicity and increasing unsaturation for most of the cholesterol esters, but cholesteryl linolenate was apparently anomalous, being non-toxic in spite of possessing three double bonds and being extensively oxidised. Probucol and DL-alpha-tocopherol conferred protection against the toxicity of cholesteryl arachidonate and triarachidonin. The oxidation in these experiments was largely independent of the presence of cells. GC indicated that formation of 7-oxysterols might contribute to the toxicity of cholesteryl linoleate. The toxicity of triglycerides suggests that polyunsaturated fatty acid peroxidation products are also toxic. Possible mechanisms of cytotoxicity and relevance to atherosclerosis are discussed.


Efficient growth inhibition of ErbB2-overexpressing tumor cells by anti-ErbB2 ScFv-Fc-IL-2 fusion protein in vitro and in vivo.
To investigate the antitumor activities of an anti-ErbB2 scFv-Fc-interleukin 2 (IL-2) fusion protein (HFI) in vitro and in vivo. Fusion protein HFI was constructed. The efficacy of HFI in mediating tumor cell lysis was determined by colorimetric lactate dehydrogenase release assays. The antitumor activity of HFI was evaluated in tumor xenograft models. The fusion protein was folded as a homodimer formed by covalently linking Fc portions and it retained ErbB2 specificity and IL-2 biological activity. HFI mediated antibody-dependent cell-mediated cytotoxicity (ADCC) at low effector-to-target ratios in vitro and improved the therapeutic efficacy of IL-2 in experiments in vivo. The genetically-engineered anti-ErbB2 scFv-Fc-IL-2 fusion protein exhibited high efficiency both in mediating ADCC in vitro and significant antitumor activity in tumor xenograft models.


A Programmed DNA Marker Based on Bis(4-ethynyl-1,8-naphthalimide) and Three-Methane-Bridged Thiazole Orange.
Two large conjugated naphthalimide derivatives with or without three-methane-bridged thiazole orange (TO3; i.e., compounds 1 a and 2 a, respectively) were designed and synthesized. The fluorescence of the naphthalimide group in compound 1 a at λ=532 nm initially decreased and that for the TO3 group at λ=655 nm increased sequentially upon adding Salmon testes (St) DNA. In contrast, without the TO3 group, the fluorescence intensity of compound 2 a monotonously decreased in response to the addition of DNA. The non-monotonic change in the fluorescence for compound 1 a could be divided into two linear sections with two different wavelengths in the range of 0<Rb/1 a <1.2 and 1.2 <Rb/1 a <6.0 (Rb/1 a =[base pair]/[1 a]). Thus, compound 1 a can be regarded as a programmed responding molecule for DNA, which can semi-quantitatively determine the concentration of DNA over a large concentration range from the standard fluorescence curve of compound 1 a at different wavelengths when bound with DNA. Furthermore, the binding modes of compounds 1 a and 2 a with StDNA were studied by using CD spectroscopy and melting temperature (Tm ) testing. The results showed that compound 1 a interacts with StDNA through multi-interactions including weak intercalation, weak minor groove binding, and inter-dye interactions, whereas compound 2 a bound with DNA through simultaneous intercalation and minor groove binding.


Acceptor engineering of metallacycles with high phototoxicity indices for safe and effective photodynamic therapy.
Although metallacycle-based photosensitizers have attracted increasing attention in biomedicine, their clinical application has been hindered by their inherent dark toxicity and unsatisfactory phototherapeutic efficiency. Herein, we employ a π-expansion strategy for ruthenium acceptors to develop a series of Ru(ii) metallacycles (Ru1-Ru4), while simultaneously reducing dark toxicity and enhancing phototoxicity, thus obtaining a high phototoxicity index (PI). These metallacycles enable deep-tissue (∼7 mm) fluorescence imaging and reactive oxygen species (ROS) production and exhibit remarkable anti-tumor activity even under hypoxic conditions. Notably, Ru4 has the lowest dark toxicity, highest ROS generation ability and an optimal PI (∼146). Theoretical calculations verify that Ru4 exhibits the largest steric bulk and the lowest singlet-triplet energy gap (ΔE ST, 0.62 eV). In vivo studies confirm that Ru4 allows for effective and safe phototherapy against A549 tumors. This work thus is expected to open a new avenue for the design of high-performance metal-based photosensitizers for potential clinical applications.


Recent advances in the management of non-infectious posterior uveitis.
To review the current regimens and novel therapeutic modalities in various stages of research and development for the management of non-infectious posterior uveitis (NIPU). We performed a thorough review of current literature using PubMed, Google Scholar and Clinicaltrials.gov to identify the published literature about the available therapeutics and novel drugs/therapies in different stages of clinical trials. The current management regimen for non-infectious posterior uveitis includes corticosteroids, immunomodulatory therapies and anti-metabolites. However, NIPU requires long-term management for efficacious remission of the disease and to prevent disease relapse. Long-term safety issues associated with steroids have led to efforts to develop novel therapeutic agents including biological response modulators and immunosuppressants. The current therapeutic agents in various stages of development include calcineurin inhibitors, biologic response modifiers and a more a comprehensive modalities like ocular gene therapy as well as novel drug delivery mechanisms for higher bioavailability to the target tissues, with minimal systemic effects. Novel efficacious therapeutic modalities under development will help overcome the challenges associated with the traditional therapeutic agents.


Traumatic Facial Injuries Among Elderly Nursing Home Residents: Never Event or Frequent Occurrence?
As the nursing home population continues to increase, an understanding of preventable injuries becomes exceedingly important. Although other fall-related injuries have been characterized, little attention has been dedicated to facial trauma. To estimate the incidence of facial trauma among nursing home residents and detail mechanisms of injury, injury characteristics, and patient demographic data. The National Electronic Injury Surveillance System was used to calculate a weighted national incidence of facial trauma among individuals older than 60 years from a nationally representative collection of emergency departments from January 1, 2011, through December 31, 2015. Entries were screened for nursing home residents, and diagnosis, anatomical site, demographic data, and mechanism of injury were analyzed. There were 109 795 nursing home residents (median age, 84.1 years; interquartile range, 79-89 years; 71 466 women [65.1%]) who required emergency department care for facial trauma. Women sustained a greater proportion of injuries with increasing age. The most common injuries were lacerations (48 679 [44.3%]), other soft-tissue injuries (45 911 [41.8%]; avulsions, contusions, and hematomas), and fractures (13 814 [12.6%]). Nasal (9331 [67.5%]) and orbital (1144 [8.3%]) fractures were the most common sites. The most common injury causes were direct contact with structural housing elements or fixed items (62 604 [57.0%]) and transfer to and from bed (24 870 [22.6%]). Despite falls being considered a Centers for Medicare & Medicaid Services preventable never event in hospitals, our analysis in the nursing home setting found more than 100 000 facial injuries during 5 years, suggesting these underappreciated injuries contribute substantially to health care expenditures. Although structural elements facilitated the greatest number of falls, transfer to and from bed remains a significant mechanism, suggesting an area for intervention.


The endocrinologist as the focus in a multidisciplinary approach to management of erectile dysfunction.
To present an approach to the complete but cost-effective office evaluation and treatment of erectile dysfunction. The numerous medical, hormonal, and psychologic causes of erectile dysfunction are reviewed, and the various treatment strategies are outlined. Erectile dysfunction, which might also include libido and ejaculatory disturbances, is the most frequently encountered type of sexual dysfunction seen in office practice. Before 1960, the assessment of this disorder was dominated by psychiatrists; later, urologists assumed a role. More recently, physicians in internal medicine have become involved in the management of this problem. Diabetes mellitus, hypertension, and tobacco abuse are the three most common causes of erectile dysfunction in men older than 50 years of age. In addition to optimizing the management of diabetes, the endocrinologist can treat other endocrine problems associated with erectile dysfunction. A multidisciplinary approach to the evaluation and treatment of erectile dysfunction is logical, and the endocrinologist--because of an extensive background in internal medicine and expertise in hormonal diagnosis and treatment--should be the focal point of this diagnostic and therapeutic team.


[Description of Onchocerca dewittei n. sp. (Filarioidea), parasite of Sus scrofa, in Malaysia (author's transl)].
Onchocerca dewittei n. sp. was collected from a wild Boar at the metatarse level (tendons and subcutaneous connective tissue); it can be differentiated from other species by the female cuticle showing straight ridges which overlap in the lateral fields, and by its relatively thick microfilaria (length 228-247 mu and width 6-7 mu). This suidean Onchocerca displays some primitive characters such as straight ridges and persistency of ten pairs of caudal papillae in the male; but as a whole this species is undoubtedly more highly evolved than O. raillieti Bain, Müller and coll., 1976, a parasite of Equidae.


An algorithm for family screening for coeliac disease.
To assess the level of undiagnosed coeliac disease (CD) in relatives of patients affected by the condition. We collected blood from 914 relatives of probands. We screened these individuals by ELISA for IgA and IgG tTG antibodies, confirming any positive IgA tTG results with an IgA EMA and looked for evidence of IgA deficiency in those who were IgG tTG positive alone, and performed IgG1 EMA in these individuals. We undertook HLA typing where positive screening was found, and this confirmed a strong prevalence of HLA-DQ2 in the coeliac population. Follow-up small intestinal biopsy was undertaken in cases with positive serological screening, wherever possible. Use of this serological screening algorithm revealed a prevalence of undiagnosed CD in 5%-6% of first degree relatives of probands. Our data suggests that first degree relatives of individuals with CD should be screened for this condition.


[IL-25 derived from epithelial cells has the potential to promote airway remodeling in asthma].
To explore the role of interleukin-25(IL-25) in the pathogenesis of eosinophilic asthma (EA) and non-eosinophilic asthma (NEA) through detecting its expression in serum, induced sputum and bronchial epithelial mucosa of asthmatic patients. Serum and induced sputum were collected from 55 untreated asthmatic patients and 27 healthy control subjects. The asthmatic patients were divided into EA and NEA groups according to sputum eosinophils(EOS) percentage (3% as a dividing point). The level of IL-25 in serum and induced spntum was determined by ELISA; the expression of IL-25 in bronchial epithelium was quantified by immunohistochemistry in biopsied specimens from 10 cases of EA, 10 NEA and 10 controls. Basement membrane thickness as an important index of airway remodeling was detected by HE staining. Compared with healthy control subjects, the lung function was impaired in patients with EA and NEA. ELISA results showed that the levels of IL-25 in the serum and induced sputum of asthmatic patients were significantly higher than those in healthy subjects (P<0.05). But there were no statistic differences between EA and NEA patients (P>0.05). The immunohistochemical results indicated that the expression of IL-25 was higher in asthmatic bronchial epithelium than in control ones. HE staining showed that the basement membrane thickness increased in EA and NEA patients(P<0.05). Correlation analysis showed that the levels of IL-25 in serum and induced sputum were positively correlated with the average thickness of basement membrane in asthmatic patients. IL-25 secreted from epithelial cells has the potential to promote airway remodeling in asthma. EOS has nothing to do with the thickness of basement membrane, and it may not be necessary for airway remodeling in asthma.


Healing the Spirit: Exploring Sexualized Trauma and Recovery among Indigenous Men in Toronto.
Colonial policies in Canada have led to social disruption and intergenerational trauma across Indigenous nations, contributing to high rates of sexualized violence within many communities. While mental health and social science discourse has identified the harmful impacts of violence against Indigenous women in Canada, there continues to be a lack of focus on the unique mental health needs of Indigenous men in this regard. This article reviews the results of a nationally funded research study which looked at the mental health and healing needs of Indigenous men in Toronto who have experienced sexualized trauma. This study followed Indigenous protocols for research and was conducted in partnership with Anishnawbe Health Toronto, a culture-based community health center. The methodology utilized a narrative inquiry and interviewed six community men about their recovery journeys and ten community healers and counselors about recovery through a gendered lens. The results explore the discourses that contribute to the social construction of masculinity(ies) and the impacts of these social norms on help-seeking behaviors. These results inform culturally appropriate and gender-relevant mental health service provision for Indigenous male clients recovering from sexualized trauma.


Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons.
Leptin acts in the brain to prevent obesity. The underlying neurocircuitry responsible for this is poorly understood, in part because of incomplete knowledge regarding first-order, leptin-responsive neurons. To address this, we and others have been removing leptin receptors from candidate first-order neurons. While functionally relevant neurons have been identified, the observed effects have been small, suggesting that most first-order neurons remain unidentified. Here we take an alternative approach and test whether first-order neurons are inhibitory (GABAergic, VGAT⁺) or excitatory (glutamatergic, VGLUT2⁺). Remarkably, the vast majority of leptin's antiobesity effects are mediated by GABAergic neurons; glutamatergic neurons play only a minor role. Leptin, working directly on presynaptic GABAergic neurons, many of which appear not to express AgRP, reduces inhibitory tone to postsynaptic POMC neurons. As POMC neurons prevent obesity, their disinhibition by leptin action on presynaptic GABAergic neurons probably mediates, at least in part, leptin's antiobesity effects.


To be blamed or pitied? The effect of illness on social behavior, cytokine levels and feed intake in undocked boars.
Tail biting is detrimental to animal welfare and has negative consequences for producer economy. Poor health is one of the risk factors for tail biting. The first aim of this study was therefore to test for links between health status and behavior related to tail biting at the individual level. The second aim of this study was to test whether variation in cytokines was related to variation in social behavior. These small molecules produced upon immune activation are known to influence behavior both in the direction of withdrawal and increased aggression. This could potentially increase non-functional social behavior and thereby the risk of a tail biting outbreak. To investigate this, we collected behavioral data, health data, feeding data and blood samples from undocked boars at a test station farm in Norway. We compared groups with three different diagnoses: osteochondrosis diagnosed by computer tomography scanning (OCSAN), osteochondrosis diagnosed by clinical examination (OCCLIN) and respiratory tract disease (RESP), with healthy controls (CTR). We tested whether the diagnoses were associated with feeding and growth, social behavior and cytokine levels. We then tested whether there were correlations between cytokine levels and social behavior. We also provide raw data on cytokine levels in the extended sample (N=305) as there are few publications on cytokine levels measured in pigs living under commercial conditions. OCCLIN pigs visited the feeder less, and fed longer compared to CTR pigs. Pigs diagnosed with RESP showed a large drop in growth the first week after filming, which corresponds to the week they were likely to have been diagnosed with illness, and a tendency to compensatory increase in the week after that. Social behavior differed between experimental groups with OCSCAN pigs receiving more social behavior (both aggressive and non-aggressive) compared to CTR, and RESP pigs tending to perform more ear- and tail-biting than controls. There were no differences in absolute levels of cytokines between categories. However IL1-ra and IL-12 showed correlations with several behaviors that have been shown by others to be associated with current or future tail biting activity. To our knowledge, this is the first published study indicating a role for illness in non-functional social behavior in pigs and the first showing a correlation between cytokine levels and social behavior.


Do natural autoantibodies play an important role in the elimination of senescent or damaged red blood cells?
Natural autoantibodies (NAAbs) are an important constituent of circulating immunoglobins. Some demonstrate polyspecific reactivity and high idiotypic connectivity. For example, they are reactive with DNA and cytoskeleton protein; others exhibit restricted binding specificity. Among several hypotheses, we have explored the possibility that NAAbs constitute a physiologic system in the organism that participates in the elimination of dead tissues and cellular debris by opsonization and phagocytosis.


Laser ablation of silicon induced by a femtosecond optical vortex beam.
We investigate laser ablation of crystalline silicon induced by a femtosecond optical vortex beam, addressing how beam properties can be obtained by analyzing the ablation crater. The morphology of the surface structures formed in the annular crater surface allows direct visualization of the beam polarization, while analysis of the crater size provides beam spot parameters. We also determine the diverse threshold fluences for the formation of various complex microstructures generated within the annular laser spot on the silicon sample. Our analysis indicates an incubation behavior of the threshold fluence as a function of the number of laser pulses, independent of the optical vortex polarization, in weak focusing conditions.


Histopathological evaluation of urethroplasty with dorsal buccal mucosa: an experimental study in rabbits.
Buccal mucosa is a widely accepted tissue for urethroplasty. The exact healing and tissue integration process, mainly the histological characteristics of dorsal buccal mucosa graft urethroplasty when used dorsally to reconstruct the urethral plate has not previously been assessed, and thus we developed an experimental model to address this question. In 12 New Zealand rabbits (weight 2.5 kg) we surgically created a dorsal penile urethral defect. A buccal mucosa graft was sutured to the corpora and tunica albuginea, and the ventral urethra anastomosed to this new urethral plate. The animals were divided in three groups and sacrificed 1, 3 and 6 weeks after surgery (groups 1, 2 and 3). A retrograde urethrogram was obtained at autopsy in the last group and the penis analyzed histologically with hematoxylin-eosin and Masson's staining. The urethrograms showed no evidence of fistula or stricture. In group 1 the histopathological analysis showed submucosal lymph-mononuclear inflammatory edema, numerous eosinophils and squamous epithelium integrated into the adjacent urothelium. In group 2 there was no evidence of an inflammatory response but rather complete subepithelial hyaline healing, which was more marked in group 3. Healing of buccal mucosa grafts to reconstruct the urethral plate can be achieved by total integration of the squamous epithelium with the urothelium, maintaining the original histological properties of the graft with no fibrosis or retraction.


Percutaneous ethanol injection of unresectable medium-to-large-sized hepatomas using a multipronged needle: efficacy and safety.
Fine needles with an end hole or multiple side holes have traditionally been used for percutaneous ethanol injection (PEI) of hepatomas. This study retrospectively evaluates the safety and efficacy of PEI of unresectable medium-to-large (3.5-9 cm) hepatomas using a multipronged needle and with conscious sedation. Twelve patients, eight men and four women (age 51-77 years; mean: 69) received PEI for hepatomas, mostly subcapsular or exophytic in location with average tumor size of 5.6 cm (range: 3.5-9.0 cm). Patients were consciously sedated and an 18G retractable multipronged needle (Quadrafuse needle; Rex Medical, Philadelphia, PA) was used for injection under real-time ultrasound guidance. By varying the length of the prongs and rotating the needle, the alcohol was widely distributed within the tumor. The progress of ablation was monitored by contrast-enhanced ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) after each weekly injection and within a month after the final (third) injection and 3 months thereafter. An average total of 63 mL (range: 20-154 ml) of alcohol was injected per patient in an average of 2.3 sessions. Contrast-enhanced CT, ultrasound, or MRI was used to determine the degree of necrosis. Complete necrosis was noted in eight patients (67%), near-complete necrosis (90-99%) in two (16.7%), and partial success (50-89%) in two (16.7%). Follow-up in the first 9 months showed local recurrence in two patients and new lesions in another. There was no mortality. One patient developed renal failure, liver failure, and localized perforation of the stomach. He responded to medical treatment and surgery was not required for the perforation. One patient had severe postprocedural abdominal pain and fever, and another had transient hyperbilirubinemia; both recovered with conservative treatment. PEI with a multipronged needle is a new, safe, and efficacious method in treating medium-to-large-sized hepatocellular carcinoma under conscious sedation. Its survival benefits require further investigations.


CNF-Functionalization as Versatile Tool for Tuning Activity in Cellulose-Derived Product Hydrogenation.
Carbon nanofibers (CNFs) have been functionalized by introducing O, N, and P containing groups in order to investigate the effect of support functionalization in Ru catalysed hydroxymethyl furfural (HMF) and levulinic acid (LA) hydrogenation. In the case of HMF, despite the fact that no effect on selectivity was observed (all the catalysts produced selectively gamma-valerolactone (GVL)), the functionalization strongly affected the activity of the reaction. O-containing and N-containing supports presented a higher activity compared to the bare support. On the contrary, in HMF hydrogenation, functionalization of the support did not have a beneficial effect on the activity of a Ru-catalysed reaction with respect to bare support and only CNFs-O behaved similarly to bare CNFs. In fact, when CNFs-N or CNFs-P were used as the supports, a lower activity was observed, as well as a change in selectivity in which the production of ethers (from the reaction with the solvent) greatly increased.


First-principles study of substitutional magnesium and zinc in hydroxyapatite and octacalcium phosphate.
First-principles calculations are performed for Mg(2+) and Zn(2+) substitution in hydroxyapatite (HAp) and octacalcium phosphate (OCP), because the foreign ions are known to play an important role for bone formation. In order to study their possible location in the system of HAp in contact with the aqueous solution, OCP is considered as a structural model of the transition region between HAp and the solution. It is found that, when the foreign ions substitute for Ca sites, the surrounding oxygen ions undergo considerable inward relaxation, due to their smaller ionic sizes than Ca(2+), which results in the smaller coordination numbers with oxygen as compared with those of Ca in bulk HAp and OCP. From the calculated defect formation energies, it is likely that the substitutional foreign ions are quite difficult to dissolve into HAp whereas can be more easily incorporated in OCP. In particular, Zn(2+) can more favorably substitute for the specific Ca site of OCP, as compared to Mg(2+), which is attributed with covalent bond formation between Zn and the surrounding oxygen ions. It is thus considered that zinc may play its role to promote bone formation by being incorporated into the transition region between HAp and the surrounding solution.


Bronchoscopic monitoring after lung transplantation.
Despite advances in gene and immunological monitoring techniques that hold great promise for the future, fiberoptic bronchoscopy remains the gold standard to establish the presence or absence of acute pulmonary allograft rejection or infection after lung transplantation (LT). There is general agreement that clinically mandated transbronchial lung biopsies enhance diagnostic precision and have a satisfactory risk:benefit ratio in experienced hands. Surveillance transbronchial biopsies have a lower yield but may provide longitudinal insight into immunological events in the allograft, which can assist long-term management. Indeed, much of our knowledge about the significance of allograft histopathological events over time has been garnered from centers that perform routine surveillance procedures, and it is exactly the balance between individual and community benefit which underscores discussion about the value of invasive monitoring. Obliterative bronchiolitis (OB) is the most common cause of late chronic allograft dysfunction leading to death after LT. Significant OB is invariably associated with reduced graft function, denoted physiologically by the bronchiolitis obliterans syndrome (BOS). Importantly, not all BOS is due to OB; hence the move to develop an all embracing phraseology for late graft dysfunction, specifically "chronic lung allograft dysfunction" (CLAD). The major risk factor for BOS was once thought to be acute cellular rejection (ACR), but new data support an important role for lymphocytic bronchiolitis (LB) independent of so-called vascular acute rejection, albeit when diagnosed and treated. This review examines the role of fiberoptic bronchoscopy after LT as a surveillance tool versus a clinically mandated diagnostic procedure.


Designing a Mobile Health App for Patients With Dysphagia Following Head and Neck Cancer: A Qualitative Study.
Adherence to swallowing rehabilitation exercises is important to develop and maintain functional improvement, yet more than half of head and neck cancer (HNC) patients report having difficulty adhering to prescribed regimens. Health apps with game elements have been used in other health domains to motivate and engage patients. Understanding the factors that impact adherence may allow for more effective gamified solutions. The aim of our study was to (1) identify self-reported factors that influence adherence to conventional home therapy without a mobile device in HNC patients and (2) identify appealing biofeedback designs that could be used in a health app. A total of 10 (4 females) HNC patients (mean=60.1 years) with experience completing home-based rehabilitation programs were recruited. Thematic analysis of semi-structured interviews was used to answer the first objective. Convergent interviews were used to obtain reactions to biofeedback designs. Facilitators and barriers of adherence to home therapy were described through 6 themes: patient perceptions on outcomes and progress, clinical appointments, cancer treatment, rehabilitation program, personal factors, and connection. App visuals that provide feedback on performance during swallowing exercises should offer an immediate representation of effort relative to a goal. Simple, intuitive graphics were preferred over complex, abstract ones. Continued engagement with the app could be facilitated by tracking progress and by using visuals that build structures with each use. This is a detailed documentation of the initial steps in designing a health app for a specific patient group. Results revealed the importance of patient engagement in early stages of app development.


Nonvolatile memory properties of Pt nanoparticle-embedded TiO(2) nanocomposite multilayers via electrostatic layer-by-layer assembly.
It is demonstrated that notable resistive switching memory properties depending on voltage polarity (i.e. bipolar switching properties) can be obtained from the layer-by-layer (LbL) assembled multilayers based on transition metal oxides and metal nanoparticles. Cationic poly(allylamine hydrochloride) and anionic titania precursor layers were deposited alternately onto Pt-coated Si substrates using an electrostatic LbL assembly process. Anionic Pt nanoparticles (Pt(NP)) with about 5.8 nm diameter size were also inserted within the multilayers using the same interactions mentioned above. These multilayers were converted to Pt(NP)-embedded TiO(2) films by thermal annealing and the films were then coated with a top electrode. When external bias was applied to the devices, bipolar switching properties were observed at low operating voltages showing the high ON/OFF ratio (>10(4)) and the stable device performance. These phenomena were caused by the presence of Pt(NP) inserted within TMO films.


Instability of CHO chromosomes containing interstitial telomeric sequences originating from Chinese hamster chromosome 10.
We identified a marker chromosome in the CHO K1 cell line containing amplifications of interstitial telomeric sequences originating from Chinese hamster chromosome 10. Analysis of the progression of this chromosome in two subclones of CHO K1 revealed sensitivity of one amplicon to chromosome breakage, resulting in telomere function at the break site. In addition, two more marker chromosomes, both containing amplifications of interstitial telomeric sequences from chromosome 10, were formed during karyotypic evolution of the CHO K1 subclones. The presence of some of the marker chromosomes was also identified in the radiosensitive xrs 5 cell line derived from CHO K1. These results indicate instability of CHO K1 chromosomes containing interstitial telomeric sequences originating from Chinese hamster chromosome 10.


PCBs, PCDD/Fs, and organochlorine pesticides in farmed Atlantic salmon from Maine, eastern Canada, and Norway, and wild salmon from Alaska.
Farmed Atlantic salmon (Salmo salar) from Maine and eastern Canada, wild Alaskan Chinook salmon (Oncorhynchus tshawytscha), and organically farmed Norwegian salmon samples were analyzed for the presence of polychlorinated biphenyls (PCBs), dioxin-like PCBs, polychlorinated dibenzo-p-dioxins (PCDDs), dibenzo-p-furans (PCDFs), and chlorinated pesticides. PCDD and PCDF congeners were not detected in > 80% of the samples analyzed. Total PCB concentrations (7.2-29.5 ng/g, wet weight, ww) in the farmed salmon were significantly higher than those in the wild Alaskan Chinook samples (3.9-8.1 ng/g, ww). Concentrations of PCBs, WHO PCB TEQs, and chlorinated pesticides varied significantly by region. PCB and WHO PCB TEQ concentrations in farmed salmon from eastern Canada were lower than those reported in samples collected two years earlier, possibly reflecting recent industry efforts to lower contaminant concentrations in feed. Organically farmed Norwegian salmon had the highest concentrations of PCBs (mean: 27 ng/g, ww) and WHO PCB TEQs (2.85 pg/g,ww); their TEQ values are in the higher range of those reported in farmed salmon from around the world. Removal of skin from salmon fillets resulted in highly variable reductions of lipids and contaminants, and in some skin-off samples, contaminant levels were higher, suggesting that skin removal does not protect the consumer from health risks associated with consumption of farmed salmon.


Multiple in vivo liver biopsies using a freeze-clamping technique.
A multiple in vivo liver biopsy technique was developed to measure labile metabolites (creative phosphate [CP], ATP, lactate) without interfering with normal perfusion and metabolism. Anesthetized rats (n = 7) had a midline abdominal incision done to expose the liver. Four biopsies were taken across 20 min. Bleeding was controlled by a small, nontraumatic clamp proximal to the biopsy. Prefrozen dressing forceps grasped the liver and scissors cut the biopsy, which was frozen in liquid nitrogen. Bleeding was minimal and hemodynamic stability was preserved. This technique has few complications, bleeding is easily controlled, and it allows for large multiple biopsies, which give reliable metabolic data and can be consistently taught.


Modelling the influence of the sporulation temperature upon the bacterial spore heat resistance, application to heating process calculation.
Environmental conditions of sporulation influence bacterial heat resistance. For different Bacillus species a linear Bigelow type relationship between the logarithm of D values determined at constant heating temperature and the temperature of sporulation was observed. The absence of interaction between sporulation and heating temperatures allows the combination of this new relationship with the classical Bigelow model. The parameters zT and zT(spo) of this global model were fitted to different sets of data regarding different Bacillus species: B. cereus, B. subtilis, B. licheniformis, B. coagulans and B. stearothermophilus. The origin of raw products or food process conditions before a heat treatment can lead to warm temperature conditions of sporulation and to a dramatic increase of the heat resistance of the generated spores. In this case, provided that the temperature of sporulation can be assessed, this model can be easily implemented to rectify F values on account of possible increase of thermal resistance of spores and to ensure the sterilisation efficacy.


Photoluminescence Properties of Graphene Oxide in Non-Aqueous Solvents.
Detailed attention to the interaction between graphene oxide (GO) and various organic fluorophores has been documented in literature as a result of which the impact of GO on the photophysical properties of the fluorophores is well known to the scientific community. However, the photoluminescence (PL) properties of GO in polar aprotic solvents are yet to be established. In this article, the PL properties of GO in polar aprotic solvents using various spectroscopic techniques have been reported. n-π* transition due to the C=O bonds in the sp3 hybrid regions and π-π* transition due to C=C bonds in the sp2 hybrid are prominent in GO. The presence of quasi-molecules within sp2 -sp3 domains acts as PL centers located in the sp3 matrixes of GO are responsible for the PL properties. This study showcases the presence of multiple emissive states of GO in polar aprotic solvents and conveys the fact that the PL properties of GO are very much wavelength-dependent.


High-dose hydroxyurea plus G-CSF mobilize BCR-ABL-negative progenitor cells (CFC, LTC-IC) into the blood of newly diagnosed CML patients at any time of hematopoietic regeneration.
The objective of this study was to analyze the mobilization kinetics of normal (BCR-ABL(neg)) and malignant (BCR-ABL(pos)) progenitor cells using a new, low toxic, out-patient-based mobilization regimen for Philadelphia chromosome-positive (Ph(pos)) chronic myelogenous leukemia (CML) patients. High doses of hydroxyurea (HD-HU, 3.5 g/m(2) per day, orally for 7 days) followed by granulocyte colony-stimulating factor (G-CSF) (10 microg/kg subcutaneously) were administered to 11 newly diagnosed CML patients. Each apheresis product (n = 30) was individually analyzed for the number and genotype of mature colony-forming cells (CFC) and primitive long-term culture initiating cells (LTC-IC), respectively, by reverse transcription polymerase chain reaction (RT-PCR) of individual colonies. Sufficient numbers of CD34(+) cells/kg bodyweight (BW) could easily be obtained in all patients (median, 15 x 10(6)/kg BW per patient) with a median number of three aphereses performed per patient (range 2-4). Almost each apheresis itself (25/30) contained > or =2 x 10(6) CD34(+) cells/kg BW. All patients with low and intermediate Sokal risk indices (9/11) mobilized primarily BCR-ABL(neg) LTC-IC (median 92%, range 47-100) and CFC (median 89%, range 57-100). Moreover, the mean percentage of BCR-ABL(neg) CFC and LTC-IC in the various apheresis products in these patients did not change throughout the entire time of hematopoietic regeneration. The toxicity of the mobilization procedure was low. Side effects were mild erythema in 8/11 and oral mucositis in 3/11 patients. Overall, the low toxicity of this regimen, together with the fact that sufficient BCR-ABL(neg) progenitors can be collected throughout the entire period of hematopoietic regeneration, renders this mobilization regimen particularly attractive for the collection of BCR-ABL(neg) progenitors in early chronic phase of Ph(pos) CML.


Distributed Training for Multi-Layer Neural Networks by Consensus.
Over the past decade, there has been a growing interest in large-scale and privacy-concerned machine learning, especially in the situation where the data cannot be shared due to privacy protection or cannot be centralized due to computational limitations. Parallel computation has been proposed to circumvent these limitations, usually based on the master-slave and decentralized topologies, and the comparison study shows that a decentralized graph could avoid the possible communication jam on the central agent but incur extra communication cost. In this brief, a consensus algorithm is designed to allow all agents over the decentralized graph to converge to each other, and the distributed neural networks with enough consensus steps could have nearly the same performance as the centralized training model. Through the analysis of convergence, it is proved that all agents over an undirected graph could converge to the same optimal model even with only a single consensus step, and this can significantly reduce the communication cost. Simulation studies demonstrate that the proposed distributed training algorithm for multi-layer neural networks without data exchange could exhibit comparable or even better performance than the centralized training model.


Genetic variants of the vitamin D receptor gene alter risk of cutaneous melanoma.
Sunlight causes DNA damage but also induces production of vitamin D whose metabolite 1,25-(OH)2D3 has antiproliferative and pro-differentiative effects in both melanocytes and cutaneous melanoma (CM) cells mediated through the vitamin D receptor (VDR). We hypothesized that genetic polymorphisms of VDR are associated with risk of CM. In a hospital-based case-control study of 602 non-Hispanic white CM patients and 603 cancer-free control subjects frequency matched by age and sex, we genotyped two VDR polymorphisms (TaqI and FokI) and assessed their association with CM risk. We found that a significantly decreased risk was associated with VDR-TaqI Tt (adjusted odds ratio (OR), 0.70; 95% confidence interval (CI), 0.54-0.90) and Tt+tt (OR=0.70; 95% CI, 0.55-0.89) genotypes, compared with the VDR-TaqI TT genotype, whereas an increased risk was associated with VDR-FokI Ff genotype (OR=1.32; 95% CI, 1.03-1.68), and a borderline significantly increased risk was associated with Ff+ff (OR=1.26; 95% CI, 1.00-1.59) genotypes, compared with the VDR-FokI FF genotype. In conclusion, genetic variants (i.e., TaqI t protective allele and FokI f risk allele) in VDR may alter risk of CM.


Safety and Efficacy of Ceftaroline in Neonates With Staphylococcal Late-onset Sepsis: A Case Series Analysis.
Treatment of late-onset neonatal staphylococcal sepsis is sometimes challenging with feared side effects of vancomycin, increasing minimal inhibitory concentrations and questions about catheter management. In case of failure, ceftaroline was administered as a compassionate treatment in 16 infants (gestational age of less than 32 weeks and less than 28 postnatal days), whose first-line treatment failed. We report 11 successes and no severe adverse drug reactions. Larger data are required to confirm these encouraging results.


Leaders as attachment figures: leaders' attachment orientations predict leadership-related mental representations and followers' performance and mental health.
In 3 studies, the authors examined the contribution of leaders' attachment styles to their leadership motives and beliefs and to followers' outcomes. In Study 1, participants completed measures of attachment orientation, leadership motives, self-representations, and leadership style. Studies 2 and 3 were conducted within Israeli military units either during a leadership workshop or during intensive combat training. Israeli military officers and their soldiers (followers) reported on their attachment styles, and the soldiers reported on the officers' leadership qualities and on the soldiers' own performance and mental health. Leaders' attachment anxiety was associated with more self-serving leadership motives and with poorer leadership qualities in task-oriented situations. Leaders' attachment anxiety also predicted followers' poorer instrumental functioning. Leaders' attachment-related avoidance was negatively associated with prosocial motives to lead, with the failure to act as a security provider, and with followers' poorer socioemotional functioning and poorer long-range mental health. Results are discussed with respect to the value of attachment theory for the study of leadership.


Neuregulin-mediated ErbB3 signaling is required for formation of zebrafish dorsal root ganglion neurons.
Dorsal root ganglia (DRGs) arise from trunk neural crest cells that emerge from the dorsal neuroepithelium and coalesce into segmental streams that migrate ventrally along the developing somites. Proper formation of DRGs involves not only normal trunk neural crest migration, but also the ability of DRG progenitors to pause at a particular target location where they can receive DRG-promoting signals. In mammalian embryos, a receptor tyrosine kinase proto-oncogene, ErbB3, is required for proper trunk neural crest migration. Here, we show that in zebrafish mutants lacking ErbB3 function, neural crest cells do not pause at the location where DRGs normally form and DRG neurons are not generated. We also show that these mutants lack trunk neural crest-derived sympathetic neurons, but that cranial neural crest-derived enteric neurons appear normal. We isolated three genes encoding neuregulins, ErbB3 ligands, and show that two neuregulins function together in zebrafish trunk neural crest cell migration and in DRG formation. Together, our results suggest that ErbB3 signaling is required for normal migration of trunk, but not cranial, neural crest cells.


Characterization of Avian Influenza and Newcastle Disease Viruses from Poultry in Libya.
On March 2013, the Libyan poultry industry faced severe outbreaks due to mixed infections of APMV-1 (Newcastle disease) and low pathogenic avian influenza (AI) of the H9N2 subtype which were causing high mortality and great economic losses. APMV-1 and H9N2 were isolated and characterized. Genetic sequencing of the APMV-1/chicken/Libya/13VIR/ 7225-1/2013 isolate revealed the presence of a velogenic APMV-1 belonging to lineage 5 (GRRRQKR*F Lin.5) or genotype VII in class II, according to the nomenclature in use. Three AI viruses of the H9N2 subtype, namely A/avian/Libya/13VIR7225-2/2013, A/avian/Libya/13VIR7225-3/2013, and A/avian/Libya/13VIR7225-5/2013, were isolated and found to belong to the G1 lineage. Analysis of amino acid sequences showed that the analyzed H9N2 viruses contained the amino acid Leu at position 226 (H3 numbering) at the receptor binding site of the HA, responsible for human virus-like receptor specificity. On March 2014, an outbreak of highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype was diagnosed in a backyard poultry farm in an eastern region of Libya. The H5N1 isolate (A/chicken/Libya/14VIR2749-16/2014) was detected by real time RT-PCR (rRT-PCR). Genetic characterization of the HA gene revealed that the identified subtype was highly pathogenic, belonged to the 2.2.1 lineage, and clustered with recent Egyptian viruses. This study revealed the presence of a velogenic APMV-1 genotype and of two influenza subtypes, namely HPAI H5N1 and H9N2, which are of major interest for public and animal health. Considering these findings, more investigations must be undertaken to establish and implement adequate influenza surveillance programs; this would allow better study of the epidemiology of APMV-1 genotype VII in Libya and evaluation of the current vaccination strategies.


Prenatal diagnosis of the Dandy-Walker malformation associated with partial trisomy 12p and distal 15q deletion.
Dandy-Walker malformation (DWM) is characterized by complete or partial agenesis of the cerebellar vermis, cyatic dilatation of the forth ventricle, and enlarged posterior fossa. However, the mechanism is still not completely understood up to now. In this study, we reported a rare case that a foetus with DWM showed partial trisomy 12p and distal 15q deletion. Karyotype analysis and chromosomal microarray analysis (CMA) were not always concordant with each other, and it is suggested that they should be performed for prenatal genetic diagnosis together. DWM is a rare central nervous system malformation, reported in 1/25-30,000 live births, characterized by complete or partial agenesis of the cerebellar vermis, cyatic dilatation of the forth ventricle, and enlarged posterior fossa (Kumar et al. 2001; Klein et al. 2003; Agrawal et al. 2016). The neurological development of children with DWM may range from normal to severely retarded, and cause variable clinical feature. Although several efforts have been made to explore its pathogenesis, however, it is still not completely understood. During the past decade, some genetic loci, microdeletion or duplication have been reported to be associated with DWM, such as 9p trisomy, partial deletions of the long arm of chromosome 13, genes ZIC1 and ZIC4 (von Kaisenberg et al. 2000; McCormack et al. 2003; Grinberg et al. 2004). In the present study, we describe a prenatal diagnosis case that a foetus with DWM on ultrasound scanning accepted genetic testing, and it revealed a microduplication of 12p13.33p11.1 and microdeletion of 15q11.2 in 750K single nucleotide polymorphism (SNP) array, while it showed 46,XX,der(8)(8pter→8q24::12p10→12qter),i(12)(p10) in karyotyping.


Kidney Injury after Intravenous versus Intra-arterial Contrast Agent in Patients Suspected of Having Coronary Artery Disease: A Randomized Trial.
Background In the absence of randomized studies, it has been controversial whether the likelihood of acute kidney injury (AKI) differs between intravenous and intra-arterial contrast agent administration. Purpose To compare intravenous versus intra-arterial contrast agent administration in relationship to AKI and analyze the association between AKI and chronic kidney disease (defined as at least mildly decreased estimated glomerular filtration rates [eGFRs]). Materials and Methods This was a prospective study (ClinicalTrials.gov: NCT00844220) that involved randomizing participants with atypical chest pain and suspected coronary artery disease (CAD) between February 2009 and August 2015 to undergo coronary CT angiography with intravenous contrast agent administration or cardiac catheterization angiography with intra-arterial contrast agent administration. This prespecified secondary analysis compared AKI (serum creatinine increase of ≥ 25% or 0.5 mg/dL after 18-24 or 46-50 hours) determined by blinded investigators using absolute differences and relative risks, including two-sided 95% confidence intervals (CIs). Results A total of 320 participants (163 [50.9%] women; mean age, 60 years ± 11) were included. Baseline eGFR did not differ between the CT angiography group (84.3 mL/min/1.73 m2 ± 17.2) and the catheterization group (87.1 mL/min/1.73 m2 ± 16.7) (P = .14). AKI occurred in nine of 161 participants in the CT angiography group (5.6%; 95% CI: 3%, 10%) and in 21 of 159 participants in the catheterization group (13.2%; 95% CI: 9%,19%) (relative risk, 2.4; 95% CI: 1.1, 5.0; P = .02). Also in the subgroup of participants without obstructive CAD, in those not requiring coronary interventions, AKI was more common in the catheterization group (11.9%; 95% CI: 8%, 19%) than in the CT angiography group (4.3% [95% CI: 2%, 9%]; difference, 7.7% [95% CI: 1.3%, 14.1%]; relative risk, 2.8 [95% CI: 1.1, 7.0]; P = .02). Obstructive CAD (odds ratio [OR]: 2.7 [95% CI: 1.1, 6.6]; P = .02), femoral catheter access (OR: 2.5 [95% CI: 1.1, 5.6]; P = .04), and cine ventriculography were associated with AKI (OR: 2.3 [95% CI: 1.0, 4.9]; P = .03). In multivariable analysis, the presence of postcontrast AKI was associated with chronic kidney disease (hazard ratio: 12.4 [95% CI: 4.5, 34.6]; P < .01). Conclusion Acute kidney injury was more common after cardiac catheterization than after CT angiography in this prospective randomized study of patients suspected of having coronary artery disease. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Einstein and Newhouse in this issue.


Clinical outcomes in the presence and absence of keratinized mucosa in mandibular guided implant surgeries: a pilot study with a proposal for the modification of the technique.
To test the hypothesis of the outcome of complete arch flapless guided implant surgery mandibular rehabilitations in the presence or absence of a residual band of keratinized mucosa (KM) < 6 mm wide in the vestibular-lingual aspect, with and without a modification of the surgical protocol. Thirty-nine patients were included in this study (12 men and 27 women), with a mean age of 62.5 years (range, 42 to 79 years), divided into 3 groups of 13 patients according to the status of residual band of KM: group 1, KM < 6 mm rehabilitated through a modified guided surgical protocol with flap opening to preserve KM; group 2, KM ≥ 6 mm; and group 3, KM < 6 mm; patients from both groups 2 and 3 were rehabilitated through flapless guided implant surgery without modification of the protocol. Group 2 and 3 patients were age- and sex-matched with group 1. Outcome measures were clinical attachment loss (CAL) ≥ 2 mm after 1 year (backward conditional regression), incidence of dehiscences, dental plaque, bleeding, and implant infections. The level of significance chosen was 5%. Thirty-nine patients with 156 implants were followed for 1 year, and no dropouts occurred. Absence of a residual band of KM ≥ 6 mm in the vestibular-lingual aspect was significantly associated with CAL (odds ratio, 39.1; P = .036) and dehiscences (P = .003). Within the limitations of this study, the absence of a residual band of KM ≥ 6 mm wide in the vestibular-lingual aspect in patients rehabilitated in the complete edentulous mandible with flapless guided implant surgery may be associated with CAL and a higher incidence of dehiscences after 1 year of follow-up. This possible association needs to be confirmed in studies with stronger designs and longer follow-ups.


RENAL FUNCTION MARKERS FOR LONG-TERM CARDIOVASCULAR PREDICTION IN INDIVIDUALS AFTER MYOCARDIAL REVASCULARIZATION.
Goal - assessment of the renal dysfunction impact on the probability of cardiovascular complications development in the long-term period after myocardial revascularization. 90 patients with ischemic heart disease (IHD) and myocardial revascularization indications were involved in the study. All the patients underwent coronary angiography (CAG), by determining the method of myocardial revascularization (MR) - coronary artery bypass grafting or coronary artery stenting. Traditional risk factors and renal dysfunction markers (albuminuria in the range of 30-300 mg/L, β2-microglobulinuria) were revealed in all the patients examined. Renal risk factors were examined twice - before myocardial revascularization and 6.3±0.1 months after it. According to CAG results, the endophytic growth rate of atheromatous plaque was determined by the calculation method. Death or need for repeated myocardial revascularization in 5.8±0.05 years was considered the endpoint of the study. Of the 81 patients who continued to participate in the study, 10 patients died (12.3%), 4 patients underwent MR (4.9%). Statistical analysis of the data showed that increase in Al semi-quantitative value (χ-test - 4.25; p=0.04) has a significant effect on the probability of reaching the endpoint of the study. A significant effect on the studied prognosis of β2-microglobulin (β2-MG) (>0.05) could not be established. However, a direct linear relationship between β2-MG value in urine and VEG AB (r=0.41, p=0.0008) was established. Among all the traditional risk factors studied, a significant impact of the left ventricle myocardial hypertrophy indicators on the death risk or repeated MR [thickness of interventricular septum (χ-test - 4.03; p=0.04) and left ventricular posterior wall (χ-test - 7 49; p=0.006)] was established. According to the results of the study, implementation of the cardiorenal syndrome in the form of a predictive Al value and β2-MG determination in urine, was shown. An increased urinary albumin excretion in dynamics is a cardiovascular risk marker in the long-term period after MR. β2-MG indicator has a direct linear relationship with the atherosclerosis progression rate. Among all the traditional risk factors, the left ventricular hypertrophy indicators have a particular importance.


Drug Repositioning: A Unique Approach to Refurbish Drug Discovery.
For a decade, it has been observed that there is a remarkable decrease in the quantum of novel clinically approved drugs, in spite of modernization in the research and development process. We have highlighted repositioning of drugs as a methodology that has found new therapeutic implications for clinically approved drugs but with different indications. This can be considered as an upbringing strategy to deliver timely and cost-effective solutions, which still need exploration for getting over the shortage of novel drugs reaching the market. This review focuses on an activity-based drug repositioning approach, which is used to explore new uses of known drugs that are already approved for specific indications and are now being used for other indications on the basis that a single drug interacts with multiple targets. It also includes current research trends related to drug repositioning, which depends on strong knowledge of medicinal chemistry and involves elucidation of mechanisms of action and validation of novel targets. The review highlights the importance of computational tools and databases of various forms for drug repositioning purposes, which have enhanced the ability to pose reasonable and testable hypotheses. The critical nature of this aspect is obvious in cases where data gathered from in vitro, or animal models do not confirm in subsequent clinical trials. Hence, considering the positive outcomes of drug repositioning, it can be surmised that this approach can serve as a promising one that can develop into a robust drug discovery strategy.


Systematic review of the effectiveness of prehospital critical care following out-of-hospital cardiac arrest.
Improving survival after out-of-hospital cardiac arrest (OHCA) is a priority for modern emergency medical services (EMS) and prehospital research. Advanced life support (ALS) is now the standard of care in most EMS. In some EMS, prehospital critical care providers are also dispatched to attend OHCA. This systematic review presents the evidence for prehospital critical care for OHCA, when compared to standard ALS care. We searched the following electronic databases: PubMed, EmBASE, CINAHL Plus and AMED (via EBSCO), Cochrane Database of Systematic Reviews, DARE, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, NIHR Health Technology Assessment Database, Google Scholar and ClinicalTrials.gov. Search terms related to cardiac arrest and prehospital critical care. All studies that compared patient-centred outcomes between prehospital critical care and ALS for OHCA were included. The review identified six full text publications that matched the inclusion criteria, all of which are observational studies. Three studies showed no benefit from prehospital critical care but were underpowered with sample sizes of 1028-1851. The other three publications showed benefit from prehospital critical care delivered by physicians. However, an imbalance of prognostic factors and hospital treatment in these studies systematically favoured the prehospital critical care group. Current evidence to support prehospital critical care for OHCA is limited by the logistic difficulties of undertaking high quality research in this area. Further research needs an appropriate sample size with adjustments for confounding factors in observational research design.


Ethyl Caffeate Ameliorates Collagen-Induced Arthritis by Suppressing Th1 Immune Response.
The present study was designed to assess the antiarthritic potential of ECF in collagen-induced arthritis (CIA) and explore its underlying mechanism. Methods. In vitro, lymphocyte proliferation assay was measured by CCK-8 kit. In vivo, the therapeutic potential of ECF on CIA was investigated; surface marker, Treg cell, and intracellular cytokines (IL-17A and IFN-γ) were detected by flow cytometry. Th1 cell differentiation assay was performed, and mRNA expression in interferon-γ-related signaling was examined by q-PCR analysis. Results. In vitro, ECF markedly inhibited the proliferation of splenocytes in response to ConA and anti-CD3. In vivo, ECF treatment reduced the severity of CIA, inhibited IFN-γ and IL-6 secretion, and decreased the proportion of CD11b+Gr-1+ splenic neutrophil. Meanwhile, ECF treatment significantly inhibited the IFN-γ expression in CD4+T cell without obviously influencing the development of Th17 cells and T regulatory cells. In vitro, ECF suppressed the differentiation of naive CD4+ T cells into Th1. Furthermore, ECF intensely blocked the transcriptional expression in interferon-γ-related signaling, including IFN-γ, T-bet, STAT1, and STAT4. Conclusion. Our results indicated that ECF exerted antiarthritic potential in collagen-induced arthritis by suppressing Th1 immune response and interferon-γ-related signaling.


Team-based approach to identify cardiac toxicity in critically ill hematopoietic stem cell transplant recipients.
We observed pulmonary hypertension (PH), pericardial effusions, and left ventricular systolic dysfunction (LVSD) in multiple critically ill hematopoietic stem cell transplant (HSCT) recipients. We implemented routine structured echocardiography screening for HSCT recipients admitted to the pediatric intensive care unit (PICU) using a standardized multidisciplinary process. HSCT recipients admitted to the PICU with respiratory distress, hypoxia, shock, and complications related to transplant-associated thrombotic microangiopathy were screened on admission and every 1-2 weeks thereafter. Echocardiography findings requiring intervention and/or further screening included elevated right ventricular pressure, LVSD, and moderate to large pericardial effusions. All echocardiograms were compared to the patient's routine pretransplant echocardiogram. Seventy HSCT recipients required echocardiography screening over a 3-year period. Echo abnormalities requiring intervention and/or further screening were found in 35 (50%) patients. Twenty-four (34%) patients were noted to have elevated right ventricular pressure; 14 (20%) were at risk for PH, while 10 (14%) had PH. All patients with PH were treated with pulmonary vasodilators. LVSD was noted in 22 (31%) patients; 15/22 (68%) received inotropic support. Moderate to large pericardial effusions were present in nine (13%) patients, with six needing pericardial drain placement. Echocardiographic abnormalities are common in critically ill HSCT recipients. Utilization of echocardiogram screening may allow for early detection and timely intervention for cardiac complications in this high-risk cohort.


[Response of Plasmodium falciparum to quinine in a hospital environment in a chloroquine-resistant region. Bujumbura, Republic of Burundi].
Plasmodium falciparum's response to quinine (7.5 g of base in 5 days) was studied in vivo in 58 adult patients hospitalized in 1985--47% presented a pernicious malaria fever three deaths were registered during treatment, two of them attributed to late hospitalization, and the third patient was struck down by a sudden acute hepatitis. Three days after treatment started 89 of the patients did not present any asexual forms. At day 7, all patients responded favourably to the treatment. Parasitemia lowered very quickly whatever the route of administration had been. Quinine had no effect on production of gametocytes during the first four days. Clinical improvement is rapidly observed and the side effects of quinine disappeared when stopping the treatment. Despite the presence in the region of an important resistance of Plasmodium falciparum to chloroquine (80% specimens), one can conclude to a satisfying susceptibility of this parasite to quinine, provided posology and divided doses are respected.


Pickles and ice cream! Food cravings in pregnancy: hypotheses, preliminary evidence, and directions for future research.
Women in the United States experience an increase in food cravings at two specific times during their life, (1) perimenstrually and (2) prenatally. The prevalence of excess gestational weight gain (GWG) is a growing concern due to its association with adverse health outcomes in both mothers and children. To the extent that prenatal food cravings may be a determinant of energy intake in pregnancy, a better understanding of craving etiology could be crucial in addressing the issue of excessive GWG. This paper reviews the available literature to corroborate and/or dispute some of the most commonly accepted hypotheses regarding the causes of food cravings during pregnancy, including a role of (1) hormonal changes, (2) nutritional deficits, (3) pharmacologically active ingredients in the desired foods, and (4) cultural and psychosocial factors. An existing model of perimenstrual chocolate craving etiology serves to structure the discussion of these hypotheses. The main hypotheses discussed receive little support, with the notable exception of a postulated role of cultural and psychosocial factors. The presence of cravings during pregnancy is a common phenomenon across different cultures, but the types of foods desired and the adverse impact of cravings on health may be culture-specific. Various psychosocial factors appear to correlate with excess GWG, including the presence of restrained eating. Findings strongly suggest that more research be conducted in this area. We propose that future investigations fall into one of the four following categories: (1) validation of food craving and eating-related measures specifically in pregnant populations, (2) use of ecological momentary assessment to obtain real time data on cravings during pregnancy, (3) implementation of longitudinal studies to address causality between eating disorder symptoms, food cravings, and GWG, and (4) development of interventions to ensure proper prenatal nutrition and prevent excess GWG.


Oligomerization and origin DNA-binding activity of simian virus 40 large T antigen.
Simian virus 40 (SV40) large tumor antigen (T antigen) exists in multiple molecular forms, some of which are separable by zone velocity sedimentation of soluble extracts from infected monkey cells. Three subclasses of this antigen from SV40-infected monkey cells have been separated and characterized: the 5S, 7S, and 14S forms. Newly synthesized T antigen occurs primarily in the 5S form. Chemical cross-linking provided evidence that the 14S form is primarily a tetramer, whereas the 5S and 7S forms could not be cross-linked into oligomers. The DNA-binding properties of each subclass were investigated after immunopurification. The affinities of the three forms for SV40 DNA and for a synthetic 19-base-pair sequence from binding site I are very similar (equilibrium dissociation constant [KD], 0.3 to 0.4 nM). The specific activity of DNA binding was greatest for the 5S and 7S subclasses and least for the 14S subclass. Moreover, the specific activity of the 5S and 7S subclasses increased sharply at about 40 h after infection, whereas the activity of the 14S subclass was maintained at a constant low level throughout infection. A model relating oligomerization and DNA binding of T antigen in infected cells is presented.


Fanconi anemia: correlating central nervous system malformations and genetic complementation groups.
Congenital central nervous system abnormalities in children with Fanconi anemia are poorly characterized, especially with regard to specific genetic complementation groups. To characterize the impact of genetic complementation groups on central nervous system anatomy. Through chart review we identified 36 patients with Fanconi anemia with available brain MRIs at the University of Minnesota (average age, 11.3 years; range, 1-43 years; M:F=19:17), which we reviewed and compared to 19 age- and sex-matched controls (average age, 7.9 years; range, 2-18 years; M:F=9:10). Genotypic information was available for 27 patients (15 FA-A, 2 FA-C, 3 FA-G, and 7 FA-D1 [biallelic mutations in BRCA2 gene]). Of the 36 patients, 61% had at least one congenital central nervous system or skull base abnormality. These included hypoplastic clivus (n=12), hypoplastic adenohypophysis (n=11), platybasia (n=8), pontocerebellar hypoplasia (n=7), isolated pontine hypoplasia (n=4), isolated vermis hypoplasia (n=3), and ectopic neurohypophysis (n=6). Average pituitary volume was significantly less in patients with Fanconi anemia (P<0.0001) than in controls. Basal angle was significantly greater in Fanconi anemia patients (P=0.006), but the basal angle of those with FA-D1 was not significantly different from controls (P=0.239). Clivus length was less in the Fanconi anemia group (P=0.002), but significance was only observed in the FA-D1 subgroup (P<0.0001). Of the seven patients meeting criteria for pontocerebellar hypoplasia, six belonged to the FA-D1 group. Patients with Fanconi anemia have higher incidences of ectopic neurohypophysis, adenohypophysis hypoplasia, platybasia and other midline central nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations.


Measurement of cardiac output and tissue perfusion.
Recent technologic innovations have allowed a greater scope for cardiac output measurement in critically ill children. There is a move toward both less invasive and continuous methods, several of which also offer novel measures of preload. Many of the new methods are still undergoing preliminary evaluation in the pediatric population and will be summarized in this article.


Blueprint for a Palliative Advanced Practice Registered Nurse Fellowship.
Opportunities for advanced practice registered nurses (APRNs) to train for specialty palliative care practice are insufficient to meet workforce needs. Graduate nursing programs in the United States do not have uniform or required curricula in palliative and end-of-life care of the seriously ill. In clinical practice, APRNs acquire palliative care skills by a mix of on-the-job experience, self-study, and continuing education. While physician colleagues can pursue post-residency training in one of 156 accredited hospice and palliative medicine fellowships, there are fewer than a dozen fellowships for APRNs, each training between one and three nurse fellows for specialty palliative care practice. This disparity slows the pipeline of palliative nursing experts and leaders, taxes employers with significant training duties, and results in an APRN workforce without uniform training. There are grass roots initiatives-often by non-nursing educators-to adapt existing physician and interprofessional fellowships for nurse learners, both in palliative care and other specialties. While these efforts help meet staffing needs and promote interprofessionalism, these programs are built upon medical curricula and competencies rather than grounding from a nursing framework. Nursing fellowship directors may not have the same administrative support, protected nonclinical time, funding, or access to nursing mentors and faculty afforded to their medical counterparts. This article provides a blueprint for clinician educators from nursing or non-nursing disciplines, who want to develop or refine training programs for APRNs that adhere to palliative nursing standards and offer a curriculum integrated with supervised practice and mentorship.


des-Met carboxyl-terminally modified analogues of bombesin function as potent bombesin receptor antagonists, partial agonists, or agonists.
In the present study we examined the effect of carboxyl-terminal modifications of des-Met14-bombesin (Bn) on Bn receptor affinity in murine 3T3 cells, rat and guinea pig pancreatic acini, and the ability to initiate biologic responses by synthesizing 18 des-Met14-Bn(6-13) analogues. With guinea pig acini and 3T3 cells, affinity was affected by the chain length of the alkyl moiety (R) added to [D-Phe6]Bn(6-13)NH2R with relative potencies: propyl greater than ethyl greater than butyl = hexyl greater than heptyl greater than free amide, whereas in rat acini affinity was not increased by the chain length. In each cell system the affinity of the alkylamide was not increased by insertion of a phenyl group in the alkyl side chain, by making the analogue more neuromedin B-like or by addition of a reduced peptide bond. The affinity in each cell system was increased by additions of other electron releasing groups to the COOH-terminal carboxyl group such as [D-Phe6]Bn(6-13)ethyl or methyl ester, or hydrazide. In guinea pig pancreas and 3T3 cells, 12 analogues were antagonists, 1 a full and 5 partial agonists. In rat pancreas, 8 were antagonists, 5 full agonists, and 5 partial agonists. Potent antagonists in each cell system were the methyl and ethyl ester, hydrazide, and ethylamide analogues. In 3T3 cells or guinea pig pancreas, agonist activity of the alkylamide was critically dependent on the chain length, whereas with rat pancreatic Bn receptors any alkylamide longer than the ethylamide had agonist activity. In all three cell systems any alteration that made the alkylamide more neuromedin B-like caused agonist activity. These results demonstrate that the nature of the substitution on the carboxyl terminus of des-Met14-Bn analogues is critically important, not only for determining Bn receptor affinity, but also for determining the ability to initiate a biologic response. In contrast to previous studies, the present results demonstrate that the presence of the COOH-terminal amino acid in position 14 of Bn is not essential for initiating a biologic response. Several des-Met14-Bn analogues were potent partial agonists, whereas others such as the hydrazide or ethyl ester are very potent antagonists.


Study on work load and work-related musculoskeletal disorders amongst male jute mill workers of West Bengal, India.
Work-related problems, many of which could be prevented with proper ergonomic techniques are particularly common in developing countries. The aim of this study was to evaluate the work stress and the development of the work-related musculoskeletal disorders (WRMSDs) of workers employed in the jute mills of India. About 219 male workers engaged in different departments of three jute industries in 24-Parganas (North) and Hooghly districts of West Bengal, India volunteered for this study. Questionnaires along with direct observation of work postures were conducted. Physical parameters such as body weight, height; physiological parameters like heart rate response, blood pressure and psycho-physiological parameters such as perceived exertion rating were studied during different tasks performed by them. It was observed that the 'hacklers' are mostly stressed. Analyses of working postures (OWAS) suggested that their adopted awkward postures were very stressful. A large number of hacklers (92.5% suffer from intense pain in different body parts as compared to workers in other departments of the jute industries. Workers report that the pain even lasts many hours after work. Since most of the workers perform repetitive tasks, so both the workplace as well as the work-rest schedule must be reorganized.


Isolation and Functional Analysis of ZmLTP3, a Homologue to Arabidopsis LTP3.
Plant lipid transfer proteins (LTPs) are encoded by multigene families and play important roles in plant physiology. One full-length cDNA encoding an Arabidopsis LTP3 homologue was isolated from maize by RT-PCR and named as ZmLTP3. RT-PCR analysis indicated that the ZmLTP3 expression is induced by salicylic acid (SA), mannitol and salt. Furthermore, in different tissues the ZmLTP3 displayed different expression patterns, indicating that ZmLTP3 may play multiple roles in stress resistance. Over-expression of ZmLTP3 in wild-type Arabidopsis resulted in the increased salt tolerance. Under salt stress condition, compared to wild-type (WT) plants, transgenic Arabidopsis grew better, had higher seedling fresh (FW), dry weight (DW), seed yields, proline content and lower MDA content and relative electric conductivity level. Our results suggest that maize ZmLTP3 might encode a member of LTPs family and play roles in salt resistance.


Is Ghrelin Synthesized in the Central Nervous System?
Ghrelin is an octanoylated peptide that acts via its specific receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a), and regulates a vast variety of physiological functions. It is well established that ghrelin is predominantly synthesized by a distinct population of endocrine cells located within the gastric oxyntic mucosa. In addition, some studies have reported that ghrelin could also be synthesized in some brain regions, such as the hypothalamus. However, evidences of neuronal production of ghrelin have been inconsistent and, as a consequence, it is still as a matter of debate if ghrelin can be centrally produced. Here, we provide a comprehensive review and discussion of the data supporting, or not, the notion that the mammalian central nervous system can synthetize ghrelin. We conclude that no irrefutable and reproducible evidence exists supporting the notion that ghrelin is synthetized, at physiologically relevant levels, in the central nervous system of adult mammals.


Overview on research and development of computer-aided diagnostic schemes.
Computer-aided diagnosis (CAD) has become a practical clinical approach in diagnostic radiology, although at present only in the area of detection of breast cancer in mammograms. Current research efforts have been focused on detection and classification of images of many different types of lesions in a number of organs, obtained with various imaging modalities. It is likely that the present results of CAD are only at the tip of the iceberg. Although automated computer diagnosis is a concept based on computer algorithms only, CAD is a concept established by taking into account equally the roles of physicians and computers. The effect of CAD on differential diagnosis has already indicated that the performance level is high, and that CAD would be ready for clinical trials and commercialization efforts. The presentation of images similar to those of an unknown case may be useful as a supplemental tool for CAD in the differential diagnosis.


Cancer-related fatigue: can exercise physiology assist oncologists?
Most patients with cancer experience fatigue, a severe activity-limiting symptom with a multifactorial origin. To avoid cancer-related fatigue, patients are frequently advised to seek periods of rest and to reduce their amount of physical activity. This advice is reminiscent of that formerly given to patients with heart disease. However, such recommendations can paradoxically compound symptoms of fatigue, since sedentary habits induce muscle catabolism and thus cause a further decrease in functional capacity. By contrast, there is scientific evidence that an exercise programme of low to moderate intensity can substantially reduce cancer-related fatigue and improve the quality of life of these patients. Current knowledge, combined with findings soon to be published, could launch new opportunities for patients with cancer. In this new century, exercise physiology could soon prove to be very useful for oncologists.


Influence of Host Ecology and Behavior on Campylobacter jejuni Prevalence and Environmental Contamination Risk in a Synanthropic Wild Bird Species.
Campylobacter jejuni is a foodborne pathogen that often leads to human infections through the consumption of contaminated poultry. Wild birds may play a role in the transmission of C. jejuni by acting as reservoir hosts. Despite ample evidence that wild birds harbor C. jejuni, few studies have addressed the role of host ecology in transmission to domestic animals or humans. We tested the hypothesis that host social behavior and habitat play a major role in driving transmission risk. C. jejuni infection and host ecology were studied simultaneously in wild American crows (Corvus brachyrhynchos) in Davis, CA, over 3 years. We found that 178 of 337 samples tested were culture positive (53%), with infection varying by season and host age. Among adult crows, infection rates were highest during the winter, when migrants return and crows form large communal roosts. Nestlings had the highest risk of infection, and whole-genome sequencing supports the observation of direct transmission between nestlings. We deployed global positioning system (GPS) receivers to quantify habitat use by crows; space use was nonrandom, with crows preferentially occupying some habitats while avoiding others. This behavior drastically amplified the risk of environmental contamination from feces in specific locations. This study demonstrates that social behavior contributes to infection within species and that habitat use leads to a heterogeneous risk of cross-species transmission. Campylobacter jejuni is the most common cause of gastroenteritis in industrialized countries. Despite efforts to reduce the colonization of poultry flocks and eventual infection of humans, the incidence of human C. jejuni infection has remained high. Because wild birds can harbor strains of C. jejuni that eventually infect humans, there has long been speculation that wild birds might act as an important reservoir in the C. jejuni infection cycle. We simultaneously studied infection prevalence, social behavior, and movement ecology in wild American crows (Corvus brachyrhynchos). We found that social behavior contributed to patterns of infection and that movement behavior resulted in some areas having a high risk of transmission while others had a low risk. The incorporation of ecological data into studies of C. jejuni in wild birds has the potential to resolve when and how wild birds contribute to domestic animal and human C. jejuni infection, leading to better control of initial poultry contamination.


Outcomes of endovascular treatment for popliteal artery disease.
Background: Finding the appropriate endovascular revascularization strategy for patients with peripheral artery disease and a popliteal artery lesion remains particulary challenging. Data regarding predictors for a beneficial outcome are scarce. Patients and methods: All endovascular procedures of popliteal artery lesions (n=227) performed in 197 patients between February 2009 and May 2018 at our institution were retrospectively analyzed. Hemodynamically relevant restenosis represented the primary endpoint. Results: The overall technical success rate was 98% and yielded 99% for stenoses (n=145) and 97% for occlusions (n=82). In a median follow-up of 10 months, the overall rate of restenosis was 23%. After 1 and 2 years, the primary patency rates were 76% and 55% and the secondary patency rate was 100%, respectively. The estimated probability of restenosis was significantly higher in stented lesions (stent vs. no stent; 36.0% vs. 19.1%; p=0.030). Multivariate analysis identified stent implantation (hazard ratio: 2.4; overall P=0.010) and diabetes (hazard ratio 2.0; P=0.023) as significant predictors for the development of restenosis. Conclusions: Endovascular therapy for popliteal artery disease was associated with high technical success rates and accompanied with a promising mid-term outcome, particularly in lesions treated with balloon angioplasty alone.


Effects of repeated handling and air exposure on the immune response and the disease resistance of gibel carp (Carassius auratus gibelio) over winter.
High mortalities and suppressed immune functions of farmed fish over winter are the universal problems in aquaculture. It is necessary to improve the immune response and disease resistance in the overwintering fish. A recent study suggested that repeated handling increased innate immune mechanisms and disease resistance in Senegalese sole. Therefore, the present study evaluated the hypothesis that appropriate repeated handling could compromise the immune depression and increase the disease resistance in gibel carp over winter. The experiment was executed in field net cages (2 m × 2 m × 2 m) from Dec. 4, 2012 to Apr. 2, 2013. Three cages with 50 fish per cage were randomly designed as the control group and did not receive any interfere over winter. The other three cages received repeated handling with an air exposure for 5 min every week during the experiment. Fish were not fed over winter. At the end of the trial, fish were challenged with Aeromonas hydrophila at a dose of 1.5 × 10(8) CFU ml(-1). The results showed that no significant difference of final body weight was found between groups. The spleen and kidney somatic index increased in the control fish after bacterial challenge and showed a rising trend but not a statistical change in repeated handled fish. Plasma cortisol levels significantly increased in the control fish at 6 h post bacterial challenge and then declined. However, repeated handled fish did not show any significant change in plasma cortisol levels after challenge. The reduced inducement of heat shock protein 70 (HSP70) expressions by repeated handling was found in gibel carp post bacterial challenge. After overwintering, the repeated handled fish exhibited increased catalase (CAT) and superoxide dismutase (SOD) activities. Enhanced plasma CAT activities and reduced plasma malondialdehyde (MDA) contents were found in repeated handled fish over time against invading bacteria. Up-regulation of myeloid differentiation primary response gene 88 (MyD88) and interleukin 11 (IL11) was observed in repeated handled fish over time after bacterial challenge. The overexpression of IL11 was significantly reduced by repeated handling against invading bacteria compared to the control group. The present results implied that a MyD88-dependent signaling pathway was involved in the innate immune responses of gibel carp by repeated handling over winter against invading bacteria.


Catalytic DNA: a novel tool for gene suppression.
RNA, as an intermediate in the production of every gene encoded protein and the genetic material of many pathogenic viruses, presents an attractive target for both biological and therapeutic manipulation. Despite its extensive involvement in living systems, its chemical diversity based on four units is relatively low compared with protein. This provides the opportunity for a generic approach to targeting with specificity based on primary structure rather than complex higher order structures. This form of recognition occurs naturally in complementary nucleic acids, due to an ability to bind their single stranded target through Watson-Crick interactions. The most established nucleic acid based approach to gene suppression at the RNA level is through antisense oligodeoxynucleotides (ODNs). These compounds form heteroduplex with target RNA which are thought to either block its function or mediate its destruction by activation of RNase H. Alternatively, RNA can be targeted by catalytic RNA such as the hammerhead ribozyme. Ribozymes have the advantage of being equipped with their own RNA cleavage apparatus and are therefore independent of host nuclear protein activity. At present, the utility of ribozyme oligonucleotides is restricted by the relative difficulty synthesising active molecules with sufficient resistance to nuclease degradation. Recently the power of in vitro selection has been used to evolve catalytic DNA sequences with RNA cleavage specificity and activity rivalling the very best ribozymes, while maintaining the more robust chemistry of an ODN. These deoxyribozymes or DNAzymes have tremendous potential as gene suppression agents for both target validation and therapeutic applications. A number of studies evaluating the biological activity of these compounds have shown promising results. However, as with other oligonucleotide based strategies, future exploitation of this approach may depend on accessory technology to assist with the accessibility of a target which is folded by its own secondary structure and hidden within the intracellular compartment.


Ketamine inhibits proliferation of neural stem cell from neonatal rat hippocampus in vitro.
Ketamine is a widely used anesthetic in obstetric and pediatric anesthesia. In the developing brain, the widespread neuron apoptosis triggered by ketamine has been demonstrated. However, little is known about its effect on neural stem cells (NSCs) function. This study aimed to investigate the effect of ketamine on proliferation of NSCs from neonatal rat hippocampus. Neural stem cells were isolated from the hippocampus of Sprague-Dawley rats on postnatal day 3. In dose-response experiments, cultured neural stem cells (NSCs) were exposed to different concentrations of ketamine (0-1000 µM) for 24 hrs. The proliferative activity of NSCs was evaluated by 5-Bromo-2'-deoxyuridine (BrdU) incorporation assay. Apoptosis of neural stem cells were assessed using caspase-3 by western blot. The intracellular Ca(2+) concentration ([Ca(2+)]i) in NSCs was analyzed by flow cytometry. The activation of protein kinase C-α (PKCα) and the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) were measured by western blot analysis. Clinical relevant concentration of ketamine (10, 20 and 50 µM) did not markedly alter the proliferation of NSCs from neonatal rat hippocampus in vitro. However, ketamine (200, 500, 800 and 1000μM) significantly inhibited the proliferation of NSCs and did not affect the expression of caspase-3. Meanwhile, ketamine (200, 500, 800 and 1000μM) also markedly decreased [Ca(2+)]i as well as suppressed PKCα activation and ERK1/2 phosphorylation in NSCs. A combination of subthreshold concentrations of ketamine (100 μM) and Ca(2+) channel blocker verapamil (2.5 μM), PKCα inhibitor chelerythrine (2.5 μM) or ERK1/2 kinase inhibitor PD98059 (5 μM) significantly produced suprathreshold effects on PKCα activation, ERK1/2 phosphorylation and NSC proliferation. Ketamine inhibited proliferation of NSCs from neonatal rat hippocampus in vitro. Suppressing Ca(2+)-PKCα-ERK1/2 signaling pathway may be involved in this inhibitory effect of ketamine on NSCs proliferation.


Characterizing the effects of amplitude, frequency and limb position on vibration induced movement illusions: Implications in sensory-motor rehabilitation.
Strategic vibration of musculotendinous regions of a limb elicits illusionary sensations of movement. As a rehabilitation technique, this 'kinesthetic illusion' has demonstrated beneficial results for numerous sensory-motor disorders. However, literature shows little consistency in the vibration parameters or body positioning used, and their effects have yet to be comprehensively investigated. To characterize the effects of the vibration amplitude, frequency, and limb position on the kinesthetic illusion. Movement illusions were induced in 12 participants' biceps and triceps. The effect of amplitude (0.1 to 0.5 mm), frequency (70 to 110 Hz), and two limb positions were quantified on the strength of illusion (SOI), range of motion (ROM) and velocity. Amplitude significantly affected the illusionary SOI, ROM and velocity in the biceps and triceps (p< 0.05). Increasing amplitude resulted in an increase of all three output variables. Limb position showed an effect on illusionary velocity in the biceps as well as ROM and velocity in the triceps (p< 0.05). Frequency demonstrated no statistical effect. Amplitude demonstrated the most profound impact on the kinesthetic illusion in the experimental ranges tested. This work may help guide clinicians and researchers in selecting appropriate vibratory parameters and body positions to consistently elicit and manipulate the kinesthetic illusion.


Placebo response in pain, fatigue, and performance: Possible implications for neuromuscular disorders.
The placebo response in neuromuscular disorders is not well understood. The only available data regarding its underlying mechanisms are related to neuropathic pain. In this review, we describe the factors that contribute to improved outcomes in the placebo arm, with specific attention to pain and fatigue, as well as some of the most important psychobiological mechanisms that may explain such a response. This approach may also improve our insight into the symptomatology and therapeutic responses of other neuromuscular disorders. The fact that >90% of tested analgesics for neuropathic pain have failed in advanced phases of clinical trials should prompt a greater investment of effort and resources into understanding the mechanisms and impact of placebos in clinical research. Such an endeavor will help improve the design of clinical trials and will provide information that informs clinical neuromuscular practice. Muscle Nerve 56: 358-367, 2017.


The complete mitochondrial genome sequence of Trichiurus nanhaiensis (Perciformes: Trichiuridae).
The Naihai cutlassfish (Trichiurus nanhaiensis, Wang and Xu, 1992) is an important commercial fish species in South China Sea, while the taxonomy is still controversial. The 17,060 base pair mitochondrial genome sequence of T. nanhaiensis was determined, which shared the features with the other bony fishes for gene arrangement, nucleotide composition, and tRNA structures except for tRNA(pro) gene. The termination-associated sequence, central conserved sequence blocks (CSB-F, CSB-E, CSB-D), and conserved sequence blocks (CSB-1, CSB-2, CSB-3), as well as tandem repeats were detected in the control region. Phylogenetic analyses revealed that T. nanhaiensis together with T. lepturus, T. japonicus, and T. brevis formed a clade of Trichiurus based on the complete Cyt b genes and partial CO I genes; meanwhile, the closest relationship was established between T. nanhaiensis and T. lepturus.


Prevalence of geriatric diseases among parents of medical doctors in Lahore.
The burden of geriatric diseases has a significant impact upon the socio-cultural, socioeconomic and administration of health services. The study was carried out to identify a burden of geriatric conditions, magnitude of disease problems and involvements of body systems in the parents of medical doctors from Lahore. After taking the consent, interview based active disease surveillance/information was collected from a total of 137 medical doctors and their parents. They were interviewed about the health status of their parents and recorded in a pre-tested questionnaire. The prevalence of each system involved in each of the category of parents was compared by ANOVA at a significant alpha level of 0.05. Prevalence of cardiovascular diseases was the highest, (18.61%), followed by musculoskeletal (10.21%) and digestive system (9.12%). The ranking of other systems in descending order was 4.74%, 3.64% and 1.82% for the respiratory system, urogenital system, and ENT respectively due to single system involvement. A cumulative prevalence due to all diseases in terms of disease load/burden of diseases in both mothers and fathers was 53.28% due to single system involvement and 67.51% because of multiple system involvement. Fifty-three percent of the older population, who were above the age of 60, were sick due to the involvement of one body system and sixty eight percent had multiple body systems involvement.


[A clinical report of five cases of central nervous system miliary tuberculomas first diagnosed by neurologists].
To explore the clinical characteristics and imaging features of miliary tuberculomas in central nervous system(CNS). A total of 5 cases diagnosed with tuberculosis in CNS first diagnosed by neurologists in Navy General Hospital of PLA were enrolled in the study. All clinical and imaging data were collected and analyzed retrospectively. The main initial symptoms were fever and headache (4/5). Multiple diffused miliary lesions were shown by brain MRI, with maximum diameter ranged from 1-4 mm and ring-shape or nodular enhancement after gadolinium injection. As mycobacterium tuberculosis could seldomly be found in serum and cerebrospinal fluid, contrast MRI remains the effective method for detecting miliary tuberculomas in CNS.