Search

Objective: The objective of this paper is to analyse motivation factors for female entrepreneurship in Mexico. In the proposed article, the authors discuss the factors which compelled women to start their enterprises in Mexico. Research Design & Methods: Based on in-depth interviews with female entrepreneurs and entrepreneurship experts, the authors show which factors motivated women to start their own business in Mexico. Findings: The study proves that women in Mexico are motivated by a combination of push and pull factors, where the majority of the factors are pull factors. The findings of the study help to conclude that female entrepreneurship development is influenced by different factors including the entrepreneurs’ personal traits, social and economic factors. Due to their conservative traditional attitude, risk adverse tendency, and non-cooperation of family members, etc. women entrepreneurs are sometimes deterred to start a business in Mexico. Implications & Recommendations: It is necessary to raise the awareness of different factors that promote female entrepreneurship in Mexico. Governmental programmes which support female entrepreneurship, business incubators, and networking could be very helpful for women when starting their own business. Contribution & Value Added: The originality of this work lies in studying motivational factors for female entrepreneurship in Mexico. The Mexican society faces a big revolution towards female entrepreneurship. Based on the change of family structure and traditions, women nowadays are having more opportunities to develop as entrepreneurs.

Abstract Background Muscarinic-receptor antagonists and β-adrenoceptor agonists are used, alone or in combination, as first-line treatment for chronic obstructive pulmonary disease. Both drugs decrease airway smooth muscle tone by post-junctional mechanisms but they may have opposing effects on pre-junctional acetylcholine (ACh)-release. Methods We studied the effects of the muscarinic-receptor antagonist glycopyrronium (GLY), the β-adrenoceptor agonist indacaterol (IND) and their combination on electrically-induced ACh-release and contractile response in isolated bovine trachealis. Data were analyzed by paired t-test and analysis of variance for repeated or independent measures with Newmann-Keuls post-hoc test when appropriate. Results GLY 10−8 M decreased contractile response by 19 ± 6% (p = 0.010) without altering ACh-release. GLY 10−7 M and 10−6 M almost abolished contractile responses even if the ACh-release was increased by 27 ± 19% (p

Abstract Background Aedes aegypti (Diptera: Culicidae) is the main vector of the dengue virus globally. Dengue vector control is mainly based on reducing the vector population through interventions, which target potential breeding sites. However, in Tanzania, little is known about this vector’s habitat productivity and insecticide susceptibility status to support evidence-based implementation of control measures. The present study aimed at assessing the productivity and susceptibility status of A. aegypti mosquitoes to pyrethroid-based insecticides in Dar es Salaam, Tanzania. Methods An entomological assessment was conducted between January and July 2015 in six randomly selected wards in Dar es Salaam, Tanzania. Habitat productivity was determined by the number of female adult A. aegypti mosquitoes emerged per square metre. The susceptibility status of adult A. aegypti females after exposure to 0.05% deltamethrin, 0.75% permethrin and 0.05% lambda-cyhalothrin was evaluated using the standard WHO protocols. Mortality rates were recorded after 24 h exposure and the knockdown effect was recorded at the time points of 10, 15, 20, 30, 40, 50 and 60 min to calculate the median knockdown times (KDT50 and KDT95). Results The results suggest that disposed tyres had the highest productivity, while water storage tanks had the lowest productivity among the breeding habitats Of A. aegypti mosquitoes. All sites demonstrated reduced susceptibility to deltamethrin (0.05%) within 24 h post exposure, with mortalities ranging from 86.3 ± 1.9 (mean ± SD) to 96.8 ± 0.9 (mean ± SD). The lowest and highest susceptibilities were recorded in Mikocheni and Sinza wards, respectively. Similarly, all sites demonstrated reduced susceptibility permethrin (0.75%) ranging from 83.1 ± 2.1% (mean ± SD) to 96.2 ± 0.9% (mean ± SD), in Kipawa and Sinza, respectively. Relatively low mortality rates were observed in relation to lambda-cyhalothrin (0.05%) at all sites, ranging from 83.1 ± 0.7 (mean ± SD) to 86.3 ± 1.4 (mean ± SD). The median KDT50 for deltamethrin, permethrin and lambda-cyhalothrin were 24.9–30.3 min, 24.3–34.4 min and 26.7–32.8 min, respectively. The KDT95 were 55.2–90.9 min for deltamethrin, 54.3–94.6 min for permethrin and 64.5–69.2 min for lambda-cyhalothrin. Conclusions The productive habitats for A. aegypti mosquitoes found in Dar es Salaam were water storage containers, discarded tins and tyres. There was a reduced susceptibility of A. aegypti to and emergence of resistance against pyrethroid-based insecticides. The documented differences in the resistance profiles of A. aegypti mosquitoes warrants regular monitoring the pattern concerning resistance against pyrethroid-based insecticides and define dengue vector control strategies.

Aldose reductase (AR) is an enzyme devoted to cell detoxification and at the same time is strongly involved in the aetiology of secondary diabetic complications and the amplification of inflammatory phenomena. AR is subjected to intense inhibition studies and dimethyl sulfoxide (DMSO) is often present in the assay mixture to keep the inhibitors in solution. DMSO was revealed to act as a weak but well detectable AR differential inhibitor, acting as a competitive inhibitor of the L-idose reduction, as a mixed type of non-competitive inhibitor of HNE reduction and being inactive towards 3-glutathionyl-4-hydroxynonanal transformation. A kinetic model of DMSO action with respect to differently acting inhibitors was analysed. Three AR inhibitors, namely the flavonoids neohesperidin dihydrochalcone, rutin and phloretin, were used to evaluate the effects of DMSO on the inhibition studies on the reduction of L-idose and HNE.

Positive inotropic agents are fundamental in the treatment of heart failure; however, their arrhythmogenic liability and the increased myocardial oxygen demand strongly limit their therapeutic utility. Pursuing our study on cardiovascular activities of lupin alkaloid derivatives, several 2-(4-substituted-phenyl)-2-dehydrosparteines and 2-(4-substituted-phenyl)sparteines were prepared and tested for inotropic and chronotropic activities on isolated guinea pig atria. Four compounds (6b, 6e, 7b, and 7f) exhibited significant inotropism that, at the higher concentrations, was followed by negative inotropism or toxicity. Compound 7e (2-(4-tolyl)sparteine) exhibited a steep dose-depending inotropic activity up to the highest concentration tested (300 µM) with an Emax of 116.5 ± 3.4% of basal force, proving less potent but much more active in comparison to the highest concentrations tested of digoxin and milrinone having Emax of 87.5 ± 3.1% and 52.2 ± 1.1%, respectively. Finally, docking studies suggested that the relevant sparteine derivatives could target the sigma-1 receptor, whose involvement in cardiac activity is well documented.

Casein kinase 1 delta (CK1δ) has a tumor-promoting role in different cancers and it is genetically amplified in a portion of human epithelial ovarian cancer (EOC). CK1δ is involved in pleiotropic cellular functions such as cell proliferation, DNA damage, and migration. We specifically knocked down CK1δ by short hairpin RNA (shRNA) in human ovarian cancer cells and we performed proliferation, chemosensitivity, as well as in vitro and in vivo migration assays. CK1δ knocked-down cells displayed reduced proliferation capability both in vitro and in vivo. Nonetheless, these cells were sensitized to the first line chemotherapeutic agent carboplatin (CPT), and this observation could be associated to reduced expression levels of p21(Cip1/Waf1), involved in DNA damage response, and the anti-apoptotic X-linked inhibitor of apoptosis protein (XIAP). Moreover, CK1δ knocked-down cells were affected in their migratory and lung homing capability, even if in opposite ways, i.e., IGROV1, SKOV3 and MES-OV lost, while OVCAR3 gained motility potential. The results suggest CK1δ as a potential exploitable target for pharmacological EOC treatment, but they also advise further investigation of its role in cell migration.

The objective of this study is to investigate the “inversion approach” for flood defense optimization in an inundated area. This new methodology within this engineering field consists in defining a “safety criterion” (for instance, “the water level in a given location must be lower than a given value”) and the combined analysis of all the uncertain controlled parameters (i.e., flood defense geometry, location, etc.) that ensure the safety objective for all the possible combinations of uncontrolled parameters (i.e., the flow hydrograph parameters) representing the natural phenomenon is not exceeded. To estimate this safety set, a metamodeling approach will be used which significantly reduces the number of model evaluations required. This algorithm relies on a kriging surrogate built from a few model evaluations, sequentially enriched with new numerical model evaluations as long as the remaining uncertainty of the entire safety set remains too high. Also known as “Stepwise Uncertainty Reduction,” this algorithm is embedded in the “Funz” engine (https://github.com/Funz) tasked with bridging the numerical model and any design of experiments algorithm. We applied this algorithm to a real two-dimensional numerical model of the Garonne river (France), constructed using the open-source TELEMAC-2D model. We focused our attention mainly on the maximum water depth in a given area (the “safety criterion”) when considering the influence of a simplified flood defense during a flooding event. We consider the two safety control parameters describing the slab and dyke elevations of the flood defense system, to design against the full operating range of the river in terms of possible watershed flooding. For this application case, it appears that less than 200 simulations are needed to properly evaluate the restricted zone of the design parameters (the “safety zone”) where the safety criterion is always met. This provides highly valuable data for full risk-informed management of the area requiring protection.

Abstract A decreased lung diffusing capacity for carbon monoxide (DLCO) in systemic sclerosis (SSc) is considered to reflect losses of alveolar membrane diffusive conductance for CO (DMCO), due to interstitial lung disease, and/or pulmonary capillary blood volume (VC), due to vasculopathy. However, standard DLCO does not allow separate DMCO from VC. Lung diffusing capacity for nitric oxide (DLNO) is considered to be more sensitive to decrement of alveolar membrane diffusive conductance than DLCO. Standard DLCO and DLNO were compared in 96 SSc subjects with or without lung restriction. Data showed that DLNO was reduced in 22% of subjects with normal lung volumes and DLCO, whereas DLCO was normal in 30% of those with decreased DLNO. In 30 subjects with available computed tomography of the chest, both DLCO and DLNO were negatively correlated with the extent of pulmonary fibrosis. However, DLNO but not DLCO was always reduced in subjects with ≥ 5% fibrosis, and also decreased in some subjects with

We describe a patient affected by migraine with visual and somatosensory aura, whose symptoms were consistently attenuated by noninvasive peripheral vagal nerve stimulation (nVNS) in multiple prospectively recorded attacks. When compared with the current standard of care, nVNS significantly reduced the duration of visual aura in all the attacks ( n = 5) and prevented the somatosensory aura in three of the five attacks. The overall duration of nVNS-treated auras was 19.0 ± 4.2 min, significantly shorter than the duration of aura in attacks treated with standard of care (103.8 ± 10.3 min). This single-case study requires confirmation in a larger sample size, but we believe that this first report is suggestive of likely efficacy given the relatively high number of treated attacks and the consistent effect of nVNS.

Canine atopic dermatitis is a common skin problem involved dogs and cats, genetically predisposed, associated with the synthesis of IgE antibodies against environmental antigens. The disease is present in young animals (aged between 6 months and 3-4 years), most frequently in female than male clinical features. Pruritus and erythema are principal clinical signs. Non-dermatological forms characterized by rhinitis, cataracts, asthma, gastrointestinal symptoms and irregular estrous cycle. The Authors analyze the conditions enabling the redhibitory action in cases of dogs affected by atopic dermatitis and suggest new medico-legal perspectives concerning buying and selling to prevent disputes

Background: Early traumatic experiences and Stressful episodes appear to be associated to the development and perpetuation of chronic pain disorders and to dependence-related behaviors.Objective: The present study evaluated whether these factors can be predictors, together with psychiatric conditions, of the outcome of a detoxification treatment in patients suffering from chronic migraine and medication-overuse headache in a 2-month follow-up.Methods: Consecutive patients undergoing a detoxification program as therapy for treating chronic migraine and medication overuse headache at the Pavia Headache Center were analyzed. During this program, lasting about 1 week, all patients received the standard CARE in-patient withdrawal protocol, which consisted in discontinuing abruptly the overused drug(s) and receiving daily detoxification therapy. Data on childhood traumatic events and recent stressful ones were analyzed by means of the Childhood Trauma Questionnaire and Stressful life-events Questionnaire. Psychiatric conditions were evaluated using the Structured Clinical Interview for Diagnostic and Statistical Manual of mental disorders.Results: A total of 166 (80% females; mean age 44.7) patients completed the follow-up at 2 months after the detoxification program: of these 118 (71%) (78% females; mean age 44.7) stopped overuse and reverted to an episodic pattern of headache (Group A); 19 (11%) (89% females; mean age 41.3) kept overusing and maintained a chronic pattern of headache (Group B); and 29 (18%) (79% females; mean age 46.9) stopped overuse without any benefit on headache frequency (Group C). At the multivariate analyses, a higher number of early life emotional distress (Odds Ratio 11.096; p = 0.037) arose as a prognostic factor for the outcome in Group B, while major depression during life-time (Odds Ratio 3.703; p = 0.006) and higher number of severe stressful episodes in the past 10 years (Odds Ratio 1.679; p = 0.045) were prognostic factors for the outcome of Group C.Conclusions: Data suggest that early life traumas and stressful events have a negative impact on the outcome of the detoxification program in subjects overusing acute medication for headache. The history of emotional childhood traumas is associated to the failure to cease overuse, whereas recent very serious life events are associated to the persistence of headache chronicity.

Pleuroparenchymal fibroelastosis is characterized by upper lobes subpleural intra-alveolar fibrosis and elastosis with visceral pleural fibrosis, which may occur after allogenic haematopoietic stem-cell transplantation (HSCT). The longitudinal changes of lung function preceding this complication have not been described. We report the case of an adult woman undergoing allogeneic HSCT for Hodgkin's lymphoma. Pulmonary function tests evolved from normal, before transplantation, to a restrictive pattern with normal residual volume 3 months after transplantation, then to an obstructive pattern consistent with bronchiolitis obliterans 18 months after transplantation, and finally to a severe mixed pattern with preserved residual volume. Computed tomography showed the distinctive features of pleuroparenchymal fibroelastosis, confirmed by histology of specimen from apical resection after pneumothorax. This case report suggests that pleuroparenchymal fibroelastosis may occur after HSCT following bronchiolitis obliterans syndrome with a mixed (restrictive-obstructive) lung function pattern. Keywords: Haematopoietic stem-cell transplantation, Idiopathic pneumonia syndrome, Bronchiolitis obliterans syndrome, Pleuroparenchymal fibroelastosis, Lung restriction, Air trapping

Objective: Testosterone levels play a role in cardiac and vascular pathology. In the present study we investigated the prognostic significance of this hormone for cardiovascular outcome, in a 5-year follow-up. Materials and methods: Our cohort included 802 adult subjects, from 40 to 80 years. Patients were excluded if they had a past history of peripheral or coronary artery disease, and revascularization. A blood sample was drawn to valuate testosterone level, and we considered normal testosterone levels 300 ng/dl. FMD (flow mediated dilatation) of the brachial artery was assessed by measuring the increase of the brachial artery diameter during reactive hyperemia after transient forearm ischemia. B-mode longitudinal images of the brachial artery were obtained at the level of the antecubital fossa. The FMD was defined as the percentage change in the brachial artery diameter 60 s after releasing the ischemic cuff. Erectile dysfunction (ERD) was assessed by the International Index of Erectile Function-5 (IIEF-5) score questionnaire. We considered composite end points including the following major adverse cardiovascular events (MACEs) Results: Subjects with lower serum testosterone levels (n = 332) had higher prevalence of traditional cardiovascular risk factors, such as hypertension (p = 0.009), diabetes (p = 0.03), dyslipidemia (p < 0.0001), obesity (p = 0.002), and endothelial function score (p < 0.0001). AMI, death after AMI, major stroke and all clinical events were more frequent (p < 0.001) in patients with testosterone levels < 300 ng/dl. Further, by multiple logistic regression analysis we found that only dyslipidemia (p = 0,001), obesity (p = 0,007), testosterone < 300 ng/dl (p < 0,0001) and ED (p < 0,0001) were independent predictors of future events. Conclusions: A therapeutic intervention on testosterone may not only have a positive effect on the cardiovascular system but also an important role in preventing new cardiovascular events.

This work is divided into two parts. In the first one, the combinatorics of a new class of randomly generated objects, exhibiting the same properties as the distribution of prime numbers, is solved and the probability distribution of the combinatorial counterpart of the n-th prime number is derived together with an estimate of the prime-counting function π(x). A proposition equivalent to the Prime Number Theorem (PNT) is proved to hold, while the equivalent of the Riemann Hypothesis (RH) is proved to be false with probability 1 (w.p. 1) for this model. Many identities involving Stirling numbers of the second kind and harmonic numbers are found, some of which appear to be new. The second part is dedicated to generalizing the model to investigate the conditions enabling both PNT and RH. A model representing a general class of random integer sequences is found, for which RH holds w.p. 1. The prediction of the number of consecutive prime pairs as a function of the gap d, is derived from this class of models and the results are in agreement with empirical data for large gaps. A heuristic version of the model, directly related to the sequence of primes, is discussed, and new integral lower and upper bounds of π(x) are found.

Chelant agents are the mainstay of treatment in copper-associated hepatitis in humans, where D-penicillamine is the chelant agent of first choice. In veterinary medicine, the use of D-penicillamine has increased with the recent recognition of copper-associated hepatopathies that occur in several breeds of dogs. Although the different regulatory authorities in the world (United States Food and Drugs Administration—U.S. FDA, European Medicines Agency—EMEA, etc.) do not approve D-penicillamine for use in dogs, it has been used to treat copper-associated hepatitis in dogs since the 1970s, and is prescribed legally by veterinarians as an extra-label drug to treat this disease and alleviate suffering. The present study aims to: (a) address the pharmacological features; (b) outline the clinical scenario underlying the increased interest in D-penicillamine by overviewing the evolution of its main therapeutic goals in humans and dogs; and finally, (c) provide a discussion on its use and prescription in veterinary medicine from a regulatory perspective.

Sex-associated hormones such as testosterone have been demonstrated to modulate immune responses, which can result in different disease outcomes. The present study was aimed at evaluating the efficacy of a gonadotropin-releasing hormone GnRH agonist implant as deslorelin acetate in association with meglumine antimoniate plus allopurinol in dogs with canine leishmaniosis (CanL). Twenty-two dogs with CanL confirmed by clinical findings and laboratory tests were included in the study. Dogs were randomized into two groups. A control group (CTR, n = 12) was treated with meglumine antimoniate 50 mg/kg SC q 12 h for 28 days plus allopurinol at 10 mg/kg PO q 12 h for the whole study period (six months). An experimental group was treated with allopurinol and meglumine antimoniate, plus an implant of 4.7 mg deslorelin acetate (DES, n = 10). The animals were observed for three months, during which clinical evaluation, indirect fluorescent antibody test (IFAT) titre and testosterone assay were performed on time at day (D)0, 90 and 180. A significantly lower clinical score was recorded in DES than in CTR (p < 0.01) at D90 and D180 (p < 0.01). After 180 days of treatment (D180), a significant reduction of mean levels of IFAT was observed in the DES group (p = 0.03). A highly significant reduction of testosterone (p = 0.01) was observed in the DES group during the study. No statistical correlation between clinical scores, IFAT titres and testosterone within two groups was observed. Data suggested that the agonist of GnRH may be useful in the treatment of CanL.

The commercial release of the New Oral Anticoagulants (NOACs) has been the most significant change in anticoagulant therapy in recent years. The work aimed to evaluate the economic and health impact for the Local Health Agency Barletta-Andria-Trani (BT). Through the Regional Information System data about naïve patients on NOAC treatment and patients on anti-vitamin-k (VKA), treatments were extrapolated. We assessed therapeutic continuity, pharmaceutical expenditure, hospitalizations, and deaths in 2017 and 2018. Therapeutic continuity was similar in the two groups. The number and the average cost of hospitalizations for a patient treated with VKAs were almost constant, while those of patients treated with NOACs decreased. The treatment of adult-aged naïve patients with NOACs, compared to VKAs therapy, involves an increase in expenditure of about 100€ for a patient, but the reduced hospitalizations could generate, in the long term, saving for the Health System. Clinical data, according to the Real-World Data, confirmed the safety and effectiveness of these drugs. However, attention to the special population is necessary to improve the safety and effectiveness of NOACs. Innovative formulations for pediatric patients are being developed. The challenge for Health Systems is the appropriate use of available resources through health interventions with transversal competences.

Background: A patient decides to leave the hospital against medical advice. Is this an erratic eccentric behavior of the patient, or a gap in the quality of care provided by the hospital? With a significant and increasing prevalence of up to 1–2% of all hospital admissions, leaving against medical advice affects both the patient and the healthcare provider. We hereby explore this persistent problem in the healthcare system. We searched Medline and PubMed within the last 10 years, using the keywords “discharge against medical advice,” “DAMA,” “leave against medical advice,” and “AMA.” We retrospectively reviewed 49 articles in our project. Ishikawa fishbone root cause analysis (RCA) was employed to explore reasons for leaving against medical advice (AMA). This report presents the results of the RCA and highlights the consequences of discharge against medical advice (DAMA). In addition, the article explores preventive strategies, as well as interventions to ameliorate leaving AMA.

Through the years, inspiration from nature has taken the lead for technological development and improvement. This concept firmly applies to the design of the antennas, whose performances receive a relevant boost due to the implementation of bio-inspired geometries. In particular, this idea holds in the present scenario, where antennas working in the higher frequency range (5G and mm-wave), require wide bandwidth and high gain; nonetheless, ease of fabrication and rapid production still have their importance. To this aim, polymer-based 3D antennas, such as Dielectric Resonator Antennas (DRAs) have been considered as suitable for fulfilling antenna performance and fabrication requirements. Differently from numerous works related to planar-metal-based antenna development, bio-inspired DRAs for 5G and mm-wave applications are at their beginning. In this scenario, the present paper proposes the analysis and optimization of a bio-inspired Spiral shell DRA (SsDRA) implemented by means of Gielis’ superformula, with the goal of boosting the antenna bandwidth. The optimized SsDRA geometrical parameters were also determined and discussed based on its fabrication feasibility exploiting Additive Manufacturing technologies. The results proved that the SsDRA provides relevant bandwidth, about 2 GHz wide, and satisfactory gain (3.7 dBi and 5 dBi, respectively) at two different frequencies, 3.5 GHz and 5.5 GHz.

Background: The Zolfino bean is a variety of Phaseolus vulgaris, which is cultivated in a limited area of Tuscany, Italy, and is widely appreciated for its flavor and culinary uses. Objectives: A yellow Zolfino landrace cultivated in the Leccio-Reggello area was characterized and compared with three other varieties of Phaseolus vulgaris (i.e. the Borlotto, Cannellino, and Corona beans) in terms of its general features and potential as an antioxidant/anti-inflammatory agent. Design: The length, width, thickness, equatorial section surface, weight, volume, and seed coat section were measured in all the beans. The seed surface area was also estimated by an original empirical method. The ability of the different beans to interfere with the enzymes of the polyol pathway (that is, aldose reductase (AR) and sorbitol dehydrogenase) was tested using the supernatant after soaking the beans at room temperature and after thermal treatment, which simulated the bean-cooking process in a controlled fashion. Results: Concerning the general features, Zolfino was comparable with other beans, except Corona, in terms of surface–volume ratio, which possesses the lowest tegument thickness. Moreover, Zolfino appears the most effective in inhibiting AR activity. The inhibitory ability is unaffected by thermal treatment and appears to be associated with compound(s) present in the coat of the bean. Conclusions: The ability of Zolfino to inhibit AR, thus reducing the flux of glucose through the polyol pathway, highlights the features of Zolfino as a functional food, potentially useful in treating the dysfunctions linked to the hyperactivity of AR, such as diabetic complications or inflammatory responses.

Pyometra is considered the most common disease in intact bitches, being associated with potentially life-threatening disorders. Myocardial damage is a potentially life-threatening consequence of pyometra. The aim of this study was to describe the electrocardiographic patterns in bitches affected by closed cervix pyometra, to assess the clinical relevance of electrocardiographic changes with the occurrence of pyometra, and to relate their severity with laboratory and clinical findings. A total of 39 bitches with closed cervix pyometra and 10 healthy female dogs were included in this study. During the hospitalization, bitches underwent a complete physical examination. An electrocardiographic examination before the ovariohysterectomy was performed. Blood samples for biochemical and hematological analysis were also evaluated. Bitches suffering pyometra at least one arrhythmia 31/39 (79.4%), sinus tachycardia (22/39, 56.4%), ventricular premature complexes (9/39, 23%), increased amplitude of T wave (7/39, 17.9%), ST depression (4/39, 10.2%), second-degree atrioventricular block (2/39, 5.1%), increase of QT interval (2/39, 5.1%), sinus bradycardia (2/39, 5.1%), and first-degree atrioventricular block (1/39, 2.5%). Some bitches were also detected with low wave amplitude (17/39, 43.5%). Cardiac arrhythmias associated with canine pyometra are frequent events. These data suggest that arrhythmias may be the consequence of one or more factors that can occur during pyometra, such as myocardial damage, electrolyte/metabolic disorders, and/or sepsis.

Although inflammation is an important physiological response, it plays a prominent role in several diseases across the mammalian species. In horses, in particular, inflammation secondary to bacterial infection or translocation is one of the most frequent causes of morbidity and mortality. Research in new molecules with anti-inflammatory and immunomodulatory proprieties and safe use profile is constantly an active field; natural compounds are an important source of molecules with peculiar properties such as antioxidants, anti-inflammatory and immune modulating. Silibinin, a natural polyphenolic flavonoid, extracted from plant milk thistle, Silybum marianum, has been reported to have actions such as antioxidant immunomodulatory and anti-inflammatory. The aim of this study was to test the effect of silibinin on lipopolysaccharide (LPS)-induced inflammatory response in equine peripheral blood mononuclear cells (PBMCs). Our results showed the protective effect of silibinin 10 μM and 50 μM in equine PBMCs stimulated with LPS. Silibilinin was able to prevent the LPS induced increased levels of TNF-α, IL-1β, IL-6 and IL-8. The results from this study on LPS-stimulated equine PBMCs showed that silibinin could be a useful pharmacological approach in treatment or prevention of several inflammatory conditions in horse.

A 3-year-old Arabian mare underwent medical examinations due to the presence of abnormalities of the reproductive apparatus and stallion behavior (nervous temperament, aggressiveness, masculine attitude). During the clinical visit, an anovulvar distance shorter than normal was observed; moreover, vulvar lips were dorsally fused except for the lower neckline, showing a blind ending from which a penis-like structure protruded. The ultrasound examination revealed the presence of a cervix and corpus of a uterus, hypoplastic uterine horns, and small gonads with an echogenicity similar to a testis. Blood testosterone levels ranged from 0.4 to 0.6 ng/mL. Cytogenetic analysis showed a normal female karyotype (2n = 64,XX), while PCR amplification of SRY and ZFY genes revealed the absence of a Y chromosome. At necroscopic examination, internal genitalia arising from the genital ridge in the form of masculine type structures were found, while those deriving from the Mullerian ducts were of feminine type. In addition, an infundibular portion of the salpinx at the cranial pole of the gonads was found. This is the first case in equine species of DSD 2n = 64,XX SRY-negative, with the simultaneous presence of male (hypoplastic testicles, epididymal portions, and a penis-like structure) and female (cervix, horn and body of a hypoplastic uterus) genital structures.

Prostate cancer (PCa) has become the most common cancer among males in Europe and the USA. Adoptive immunotherapy appears a promising strategy to control the advanced stages of the disease by specifically targeting the tumor, in particular through chimeric antigen receptor T (CAR-T) cell therapy. Despite the advancements of CAR-T technology in the treatment of hematological malignancies, solid tumors still represent a challenge. To overcome current limits, other cellular effectors than T lymphocytes are under study as possible candidates for CAR-engineered cancer immunotherapy. A novel approach involves the NK-92 cell line, which mediates strong cytotoxic responses against a variety of tumor cells but has no effect on non-malignant healthy counterparts. Here, we report a novel therapeutic approach against PCa based on engineering of NK-92 cells with a CAR recognizing the human prostate-specific membrane antigen (PSMA), which is overexpressed in prostatic neoplastic cells. More importantly, the potential utility of NK-92/CAR cells to treat PCa has not yet been explored. Upon CAR transduction, NK-92/CAR cells acquired high and specific lytic activity against PSMA-expressing prostate cancer cells in vitro, and also underwent degranulation and produced high levels of IFN-γ in response to antigen recognition. Lethal irradiation of the effectors, a safety measure requested for the clinical application of retargeted NK-92 cells, fully abrogated replication but did not impact on phenotype and short-term functionality. PSMA-specific recognition and antitumor activity were retained in vivo, as adoptive transfer of irradiated NK-92/CAR cells in prostate cancer-bearing mice restrained tumor growth and improved survival. Anti-PSMA CAR-modified NK-92 cells represent a universal, off-the-shelf, renewable, and cost-effective product endowed with relevant potentialities as a therapeutic approach for PCa immunotherapy.

Pulmonic stenosis (PS) is a malformation of pulmonary valve, involving the right ventricular outflow tract or the pulmonary artery. German shepherd, Bulldog, Labrador retriever, Collie and Boxer are breeds predisposed. Clinical signs are aspecific and include stunting, exercise intolerance, dyspnoea, syncope and ascites. Often PS may determine audible cardiac murmur and when audible is a high frequency, crescendo-decrescendo murmur during systole, loudest over the left side of the thorax, near the sternal cardiac border. The veterinarian should be able to assess PS such as heart defects because they may be object of legal disputes. In this study, the Authors report some cases of PS in dogs to clarify whether or not it may be considered a redhibitory defect.

L'attenzione del mondo accademico sulla storia dell'Università italiana si sposta sempre più verso il periodo repubblicano. Concentrandosi sull'Emilia-Romagna e i suoi atenei, in comparazione con il contesto nazionale, si è analizzato l'andamento degli iscritti sia nel dato generale che relativo alle matricole, alla popolazione studentesca femminile, quella straniera, le iscrizioni ai singoli settori disciplinari e i docenti, utilizzando i dati degli Annuari di statistica dell'istruzione.

The emergence of resistance against artemisinin combination treatment is a major concern for malaria control. ACTs are recommended as the rescue treatment, however, there is limited evidence as to whether treatment and re-treatment with ACTs select for drug-resistant P. falciparum parasites. Thus, the purpose of the present study is to investigate the impact of (re-)treatment using artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) on the selection of P. falciparum multidrug resistance-1 (Pfmdr1) alleles in clinical settings.P. falciparum positive samples were collected from children aged 12-59 months in a clinical trial in DR Congo and Uganda. Pfmdr1 single nucleotide polymorphisms (SNPs) analysis at codons N86Y, Y184F, and D1246Y were performed at baseline and post-treatment with either AL or ASAQ as a rescue treatment using nested PCR followed by restriction fragment length polymorphism (RFLP) assays.The pre-treatment prevalence of Pfmdr1 N86 and D1246Y varied significantly between the sites, (p>0.001) and (p = 0.013), respectively. There was borderline significant directional selection for Pfmdr1 184F in recurrent malaria infections after treatment with AL in Uganda site (p = 0.05). Pfmdr1 NFD haplotype did not significantly change in post-treatment infections after re-treatment with either AL or ASAQ. Comparison between pre-treatment and post-treatment recurrences did not indicate directional selection of Pfmdr1 N86, D1246 alleles in the pre-RCT, RCT and post-RCT phases in both AL and ASAQ treatment arms. Pfmdr1 86Y was significantly associated with reduced risk of AL treatment failure (RR = 0.34, 95% CI:0.11-1.05, p = 0.04) while no evidence for D1246 allele (RR = 1.02; 95% CI: 0.42-2.47, p = 1.0). Survival estimates showed that the Pfmdr1 alleles had comparable mean-time to PCR-corrected recrudescence and new infections in both AL and ASAQ treatment arms.We found limited impact of (re-)treatment with AL or ASAQ on selection for Pfmdr1 variants and haplotypes associated with resistance to partner drugs. These findings further supplement the evidence use of same or alternative ACTs as a rescue therapy for recurrent P.falciparum infections. Continued monitoring of genetic signatures of resistance is warranted to timely inform malaria (re-)treatment policies and guidelines.

Hypoglycemia is a very common problem, mostly in frail, severely ill, older hospitalized patients. Hypoglycemia has been implicated in the development of adverse clinical outcomes, including an increased mortality. Fear of iatrogenic hypoglycemia remains an obstacle to adequate inpatient glycemic control. It may be considered as a marker of disease, rather than cause in itself of undesirable events. Several factors, such as treatment with exogenous insulin, mismatch between insulin administration and meal intake with the loss of normal counter regulatory responses, place patients with diabetes at higher risk for hypoglycemia than the ones without diabetes. In this review we discuss the causes and predictors of hypoglycemia in non-critically ill hospitalized patients and how to prevent them. Subcutaneous insulin with basal-bolus regimen rather than sliding scale and the use of analogues may minimize hypoglycemic events. In-patient glycemic management should be patient-centered, following the current guidelines, and aimed to prevent hypoglycemic events.

The use of monoclonal antibodies (mAb) for the diagnosis and treatment of malignancies is acquiring an increasing clinical importance, thanks to their specificity, efficacy and relative easiness of use. However, in the context of Epstein-Barr virus (EBV)-related malignancies, only cancers of B-cell origin can benefit from therapeutic mAb targeting specific B-cell lineage antigens. To overcome this limitation, we generated a new mAb specific for BARF1, an EBV-encoded protein with transforming and immune-modulating properties. BARF1 is expressed as a latent protein in nasopharyngeal (NPC) and gastric carcinoma (GC), and also in neoplastic B cells mainly upon lytic cycle induction, thus representing a potential target for all EBV-related malignancies. Considering that BARF1 is largely but not exclusively secreted, the BARF1 mAb was selected on the basis of its ability to bind a domain of the protein retained at the cell surface of tumor cells. In vitro, the newly generated mAb recognized the target molecule in its native conformation, and was highly effective in mediating both ADCC and CDC against BARF1-positive tumor cells. In vivo, biodistribution analysis in mice engrafted with BARF1-positive and -negative tumor cells confirmed its high specificity for the target. More importantly, the mAb disclosed a relevant antitumor potential in preclinical models of NPC and lymphoma, as evaluated in terms of both reduction of tumor masses and long-term survival. Taken together, these data not only confirm BARF1 as a promising target for immunotherapeutic interventions, but also pave the way for a successful translation of this new mAb to the clinical use.

Protecting the environment by improving the crop-system nitrogen (N) use efficiency (NUE) while maximising yield and quality is a primary challenge for modern agriculture, and understanding the processes that govern N fluxes in the plant-soil system is essential to improve NUE. An on-farm study was conducted over two fall-winter seasons to evaluate the NUE, agronomical and physiological response of romaine (var. longifolia, cv Manavert) and red oak-leaf (var. crispa, cv Aruba) lettuce (Lactuca sativa L.) to different N-rates (0, 60, 120, 180 kg ha–1 of N). Nitrogen rate influenced all tested parameters, including plant fresh and dry weight, N accumulation, leaf NO3– and dry matter content, NUE indices, N nutrition index (NNI), soil residual N and the estimated N losses at the end of the crop season. Fresh yield, dry weight and N-accumulation response to N rate were influenced by lettuce genotype. Manavert had higher N recovery, NUE, and lower leaf NO3– concentration than Aruba. Analysing the NNI overtime, 120 kg ha–1 of N assured an optimal N status in both Manavert and Aruba, while N deficiency and excess were observed at lower and higher N-rates, respectively. An empirical relationship was observed between NNI and leaf NO3– concentration, suggesting that leaf NO3– concentration may be used to predict NNI and thus the crop N status. The relationship between NNI and leaf NO3– concentration may be used to define optimal leaf NO3– concentration ranges for the rapid and site-specific assessment of the crop N status, and the dynamic adjustment of N-fertilisation, contributing to improve crop NUE, minimise N-losses, and optimise yield and quality of lettuce crops.

Summary: Background: Quinine or alternative artemisinin-based combination treatment (ACT) is the recommended rescue treatment for uncomplicated malaria. However, patients are often re-treated with the same ACT though it is unclear whether this is the most suitable approach. We assessed the efficacy and safety of re-treating malaria patients with uncomplicated failures with the same ACT used for the primary episode, compared with other rescue treatments. Methods: This was a bicentre, open-label, randomised, three-arm phase 3 trial done in Lisungi health centre in DR Congo, and Kazo health centre in Uganda in 2012–14. Children aged 12–60 months with recurrent malaria infection after treatment with the first-line ACT were randomly assigned to either re-treatment with the same first-line ACT, an alternative ACT, which were given for 3 days, or quinine-clindamycin (QnC), which was given for 5–7 days, following a 2:2:1 ratio. Randomisation was done by computer-generated randomisation list in a block design by country. The three treatment groups were assumed to have equivalent efficacy above 90%. Both the research team and parents or guardians were aware of treatment allocation. The primary outcome was the proportion of patients with an adequate clinical and parasitological response (ACPR) at day 28, in the per-protocol population. This trial was registered under the numbers NCT01374581 in ClinicalTrials.gov and PACTR201203000351114 in the Pan African Clinical Trials Registry. Findings: From May 22, 2012, to Jan 31, 2014, 571 children were included in the trial. 240 children were randomly assigned to the re-treatment ACT group, 233 to the alternative ACT group, and 98 to the QnC group. 500 children were assessed for the primary outcome. 71 others were not included because they did not complete the follow-up or PCR genotyping result was not conclusive. The ACPR response was similar in the three groups: 91·4% (95% CI 87·5–95·2) for the re-treatment ACT, 91·3% (95% CI 87·4–95·1) for the alternative ACT, and 89·5% (95% CI 83·0–96·0) for QnC. The estimates for rates of malaria recrudescence in the three treatment groups were similar (log-rank test: χ2=0·22, p=0·894). Artemether-lumefantrine was better tolerated than QnC (p=0·0005) and artesunate-amodiaquine (p

The formation of the adduct between the lipid peroxidation product 4-hydroxy-2-nonenal (HNE) and glutathione, which leads to the generation of 3-glutathionyl-4-hydroxynonane (GSHNE), is one of the main routes of HNE detoxification. The aldo-keto reductase AKR1B1 is involved in the reduction of the aldehydic group of both HNE and GSHNE. In the present study, the effect of chirality on the recognition by aldose reductase of HNE and GSHNE was evaluated. AKR1B1 discriminates very modestly between the two possible enantiomers of HNE as substrates. Conversely, a combined kinetic analysis of the glutathionyl adducts obtained starting from either 4R- or 4S-HNE and mass spectrometry analysis of GSHNE products obtained from racemic HNE revealed that AKR1B1 possesses a marked preference toward the 3S,4R-GSHNE diastereoisomer. Density functional theory and molecular modeling studies revealed that this diastereoisomer, besides having a higher tendency to be in an open aldehydic form (the one recognized by AKR1B1) in solution than other GSHNE diastereoisomers, is further stabilized in its open form by a specific interaction with the enzyme active site. The relevance of this stereospecificity to the final metabolic fate of GSHNE is discussed.

The strengthening of the bond between humans and animals has changed the landscape of the veterinary profession. This has, in turn, led the legal system to assess damages in veterinary malpractice and liability cases more carefully, paying attention to the possibility of using clinical practice guidelines (CPGs) to prove whether the defendant veterinarian contravened or not the standard of care. In this era of evidence-based veterinary medicine, CPGs are becoming an integral part of many aspects of veterinary practice, even if CPGs do not have the force of law and are situated halfway between ethical rules and legal requirements. Although guidelines have been used for several years, there seems to be a general lack of recognition of the medical and legal ramifications of CPGs for veterinarians. This creates ambiguity and inconsistency in the care that veterinary practitioners provide, compromises the care animals receive, and prevents the courts from assessing veterinarian competence in a systematic and rational way. On the basis of these considerations, this article discusses the legal implications of CPGs in veterinary medicine for dogs and cats and explores how the law may treat CPGs in the future. Redefining the CPGs should be a priority for veterinary profession. NOTE: The authors chose to use the terms “companion animal,” “pet,” and “small animal” interchangeably throughout this article, as all three are commonly in use and refer to the same animals (dogs and cats).

Segmental dilatation of the intestine (SDI) is an unusual condition presenting during the neonatal period, with symptoms of obstruction. Late diagnosed cases are also reported. The clinical polymorphism, and the lack of specificity of radiological investigations, make diagnosis difficult. Prenatal detection of abdominal cystic lesions or bowel dilatation has occasionally been reported to be associated with SDI. We herein report two cases of SDI, with a prenatal ultrasonographic suspicion of intestinal abnormality. In both infants, a dilatation of the ileum was found at surgery, without any evident site of obstruction or abnormal histology. SDI must be taken into consideration when a prenatal alert of possible bowel obstruction is not followed by postnatal clinical signs.

Perturbations during the cell DNA-Damage Response (DDR) can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs), small non-coding RNAs that act as post-transcriptional regulators of gene expression. The oncogenic miR-27a is over-expressed in several tumors and, in the present study, we investigated its interaction with ATM, the gene coding for the main kinase of DDR pathway. Experimental validation to confirm miR-27a as a direct regulator of ATM was performed by site-direct mutagenesis of the luciferase reporter vector containing the 3'UTR of ATM gene, and by miRNA oligonucleotide mimics. We then explored the functional miR-27a/ATM interaction under biological conditions, i.e., during the response of A549 cells to ionizing radiation (IR) exposure. To evaluate if miR-27a over-expression affects IR-induced DDR activation in A549 cells we determined cell survival, cell cycle progression and DNA double-strand break (DSB) repair. Our results show that up-regulation of miR-27a promotes cell proliferation of non-irradiated and irradiated cells. Moreover, increased expression of endogenous mature miR-27a in A549 cells affects DBS rejoining kinetics early after irradiation.

Background. Tanzania started a countrywide lymphatic filariasis elimination programme in 2000 adopting the mass drug administration (MDA) strategy. The drug used for the programme was the combination of ivermectin and albendazole. However, there is limited information on the current epidemiological trend of the infections, where MDA implementation is ongoing. The present study aimed at assessing the current status of Bancroftian filariasis infection rate and morbidity where MDA has been distributed and administered for over eight rounds. Methodology. The study was a cross-sectional descriptive study involving 272 individuals (>18 years) from endemic communities in Tanga region where MDA has been implemented. Clinical, sociodemographic, and circulating filarial antigen (CFA) test was undertaken using immune chromatographic card test according to the manufacturer’s instructions. Results. A total of 472 individuals were screened: 307/472 (65.1%) were males while 165/472 (34.9%) were females. The overall prevalence of CFA was 5.51%, that of hydrocoele was 73.2%, and that of lymphoedema was 16.0%. The prevalence of hydrocoele combined with lymphoedema was 5.5%. Conclusion. Our findings demonstrate a considerable reduction in filarial infection. However, there is clear evidence of ongoing transmission despite the 8 rounds of MDA. It is unlikely that the annual MDA would interrupt filarial transmission; therefore, additional strategies are needed to accelerate lymphatic filariasis control and elimination.

Wandering spleen and gastric volvulus are two rare entities that have been described in association with congenital diaphragmatic hernia. The diagnosis is difficult and any delay can result in ischemia and necrosis of both organs. We present a case of a 13-year-old girl, previously operated on for anterior diaphragmatic hernia and intrathoracic gastric volvulus, that presented to our service for a subdiaphragmatic gastric volvulus recurrence associated with a wandering spleen. In this report we reviewed the literature, analyzing the clinical presentation, diagnostic assessment, and treatment options of both conditions, in particular in the case associated with diaphragmatic hernia.

In the original article mentioned above, the name of the sixth author was wrongly mentioned as “Vincenzo Briganti” instead of “Vito Briganti”.

Inhaled β2-adrenoceptor (β2-AR) agonists are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptoms-relievers and, in combination with inhaled corticosteroids, as disease-controllers. In this article, we first review the basic mechanisms by which the β2-adrenergic system contributes to the control of airway smooth muscle tone. Then, we go on describing the structural characteristics of β2-AR and the molecular basis of G-protein-coupled receptor signaling and mechanisms of its desensitization/ dysfunction. In particular, phosphorylation mediated by protein kinase A and β-adrenergic receptor kinase are examined in detail. Finally, we discuss the pivotal role of inhaled β2-AR agonists in the treatment of asthma and the concerns about their safety that have been recently raised.

Climate change has been one of the most debated topics in the past few decades, but a number of challenges have hindered the development of robust policies and strategies by nations. At the same time, social media platforms—such as Instagram, Twitter, and Facebook—have given the opportunity for the general public to share opinions and engage with the issue of climate change like never before. This phenomenon is considered to be a new form of soft power which can provide input into the discussion and possibly affect the current international political mechanisms. The present paper aims to (1) define the forms and characteristics of social media as a soft power method, (2) analyze its influence on the awareness of societies, and (3) assess if increased public awareness could influence the official political and policy processes. In order to assess if social media has influence on people's relative awareness, we have focused on analyzing the links between a few highly visible climate change related events and the trends in people's searches on the Internet in connection to those events. The study finds that even though it is difficult to assess the effects of social media as a soft power tool with certainty, there are visible links between social media and changing public perceptions, with the possibility of public opinion influencing political decision-making. [ABSTRACT FROM AUTHOR]

Chlorproguanil-dapsone (CD) has been linked to hemolysis in symptomatic glucose-6-phosphate dehydrogenase deficient (G6PDd) children. Few studies have explored the effects of G6PD status on hemolysis in children treated with Intermittent Preventive Treatment in infants (IPTi) antimalarial regimens. We sought to examine the joint effects of G6PD status and IPTi antimalarial treatment on incidence of hemolysis in asymptomatic children treated with CD, sulfadoxine-pyrimethamine (SP), and mefloquine (MQ).A secondary analysis of data from a double-blind, placebo-controlled trial of IPTi was conducted. Hemoglobin (Hb) measurements were made at IPTi doses, regular follow-up and emergency visits. G6PD genotype was determined at 9 months looking for SNPs for the A- genotype at coding position 202. Multivariable linear and logistic regression models were used to examine hemolysis among children with valid G6PD genotyping results. Hemolysis was defined as the absolute change in Hb or as any post-dose Hb

Due to the liberalization and transformation of emerging markets economies, the attractiveness of these countries for foreign direct investors has been rising in the last decades. This paper explores foreign direct investment (FDI) location choice factors of German and Austrian companies in Brazilian regions. We perform a quantitative analysis, based on the Multinomial Nested Logit Model and supplement its findings by the qualitative analysis, based on the semi-structured experts’ interview. The analyses show that investor-nation specific agglomeration, industry specialization, workforce qualification and physical infrastructure were important FDI location choice factors for German and Austrian companies in Brazil. Suggestions for future research of the FDI location choice factors are discussed.

We have introduced a new hybrid fabrication method for lab-on-a-chip devices through the combination of femtosecond laser micromachining and removable insert micro-injection molding. This method is particularly suited for the fast prototyping of new devices, while maintaining a competitive low cost. To demonstrate the effectiveness of our approach, we designed, fabricated, and tested a completely integrated flow cytometer coupled to a portable media device. The system operation was tested with fluorescent plastic micro-bead solutions ranging from 100 beads/μL to 500 beads/μL. We demonstrated that this hybrid lab-on-a-chip fabrication technology is suitable for producing low-cost and portable biological microsystems and for effectively bridging the gap between new device concepts and their mass production.

Airway hyper-responsiveness (AHR) is a cardinal feature of asthma. Its absence has been considered useful in excluding asthma, whereas it may be present in other diseases such as atopic rhinitis and chronic obstructive pulmonary disease. AHR is often considered an epiphenomenon of airway inflammation. Actually, the response of airways to constrictor stimuli is modulated by a complex array of factors, some facilitating and others opposing airway narrowing. Thus, it has been suggested that AHR, and perhaps asthma, might be present even without or before the development of airway inflammation. We begin this review by highlighting some terminological and methodological issues concerning the measurement of AHR. Then we describe the neurohumoral mechanisms controlling airway tone. Finally, the pivotal role of airway smooth muscle and internal and external modulation of airway caliber in vivo are discussed in detail.