Background: With the epidemic of COVID-19, the health care workers (HCWs) require proper respiratory personal protective equipment (rPPE) against viral respiratory infectious diseases. However, there is little published evidence comparing their efficacy. Therefore, we conducted a network meta-analysis (NMA) to compare the efficacy of rPPEs and the wearing manner preventing from the viral respiratory infectious diseases (VRID). Methods: This NMA protocol was registered in PROSPERO (CRD42020179489). PubMed, the Cochrane Library, Web of Science, and EMBASE were searched by computer to collect cluster randomized control trials of comparing the effectiveness of rPPEs and wearing manner in preventing HCWs from VRID. The primary outcome was the incidence of laboratory-confirmed viral respiratory infection. The secondary outcome was the incidence of CRI. The Bayesian NMA was conducted to use the control group as the comparison group. Incidence of the VRID and CRI were reported as network odds ratio (network OR) and 95% credibility interval (CrI). Results: Six studies encompassed 11,828 HCWs and seven interventions were included. In terms of the incidence of laboratory-confirmed viral respiratory infection, the continuous wearing of N95 respirator (network OR, 0.48; 95% CrI 0.27 to 0.86; SUCRA score, 85.4) showed more effective than the control group. In terms of the incidence of CRI, there are no interventions that showed more effective than the control group. Conclusion: There are significant differences in preventive efficacy among current rPPEs. Our result suggests that continuous wearing of N95 respirator can serve as the best preventive rPPE for HCWs from the VRID.

Adult granulosa cell tumor is predominant form of granulosa cell tumor, typically diagnosed after the age of 40 years. We report a case of a 16-year-old girl with an AGCT who presented with raised testosterone levels. After fertility sparing surgery, patient was commenced on combined oral contraceptives (COCs) due to the menstrual cycle irregularities. Subsequently, patient’s father developed pulmonary embolism caused by venous thromboembolism. Hematologic evaluation in our patient, revealed decreased protein S levels. Nevertheless, COCs were continued for up to the six months. Since menstrual cycles irregularities reoccurred, we are starting with progesterone-only oral contraceptives at present time.

INTRODUCTION: The SARS-CoV-2 coronavirus pandemic has caused more than fifteen million infections worldwide. Our aim is to investigate the differentiating characteristics in asthmatic patients with SARS-CoV-2 infection in the community of Castilla la Mancha. METHODS: We used the Savana® software and its algorithm based on Big Data and artificial intelligence, performed a retrospective search of the diagnoses of COVID 19 and asthma in the digitized medical records with positive RT-PCR results for SARS-CoV-2, and analysed the demographic characteristics, comorbidities, hospitalization data and deaths. RESULTS: 6,310 patients with positive RT-PCR for SARS-CoV-2 were selected, of which 577 had a diagnosis of asthma with a prevalence of 9.14%. The mean age in SARS-CoV-2 (SC2) was 59 ±19 years of age and in SARS-CoV2-asthma (SC2-A) 55 ±20 years of age. SC2 included 2983 (41%) men and 3327 (59%) women, while SC2-A included 198 (31%) men and 379 (69%) women. High blood pressure (BP) was the most common comorbidity in both groups (51%). 2,164 SC2 (34.2%) and 131 SC2-A (22.7%) required hospitalization with an asthma prevalence of 6.05%. 250 SC2 (3.96%) and 21 SC2-A (3.64%) died. CONCLUSION: The prevalence of asthma in our SARS-CoV-2 positive RT-PCR population was 9.14% and 6.05% in hospitalized patients. HBP is the most frequent comorbidity in both groups, and smoking is the only one with significant differences, more frequent in asthmatics. Mortality is lower in patients with asthma

Drug hypersensitivity reactions (DHRs) represent a global threat to healthcare systems due to their incidence, with a significant increase over last years1. DHR figures are overestimated in the general population since less than 40% of cases initially labelled as allergic can be confirmed as such when evaluated in an allergy unit2. Achieving an accurate diagnosis is complex and time consuming; besides, tests must be tailored to specific clinical manifestations and underlying mechanisms and will depend on the culprit drugs. Diagnosis often requires performing drug provocation tests (DPTs), which are especially problematic for severe reactions, making management of these patients challenging and expensive for the health care system.Clinically, DHRs are classified into immediate and non-immediate, based on the time interval between drug exposure and onset of the symptoms3. The most severe immediate reaction is anaphylaxis. This issue of the journal has been dedicated o drug hypersensitivity, which is becoming a major public health issue during the last decade, especially with the introduction of biologicals to medicine. Bilo et al. 4 evaluated the anaphylaxis mortality rate in Italy from 2004 to 2016 and found an average mortality rate for definite anaphylaxis (ICD-10 code) of 0.51 per million population per year, mostly due to the use of medications (73.7%), although in 98% of the cases culprit drugs were not identified. Regarding non-immediate reactions, one of the most challenging diagnoses is drug reaction with eosinophilia and systemic symptoms (DRESS), which is sometimes difficult, at an early stage, due to overlapping clinical symptoms with maculopapular exanthema (MPE). Pedruzzi et al. 5 identified 7 microRNAs (miRNAs) that correctly classified DRESS or MPE patients and were associated with keratinocyte differentiation/skin inflammation, type I IFN pathway viral replication, ATP-binding cassette transporters, and T lymphocyte polarisation, being all of them potential biomarkers. Non-immunologically mediated adverse reactions, such as attention-deficit/hyperactivity disorder (ADHD) are reported by Fuhrmannet al. 6 in association with systemic H1-antihistamines administration in school-age children, especially the 1st generation agents.The mechanism underlying DHR and the reason why patients treated with the same drug develop a tolerance response or an immediate or non-immediate DHR is not completely understood (Figure 1). Therefore, the prediction of who may experience a DHR, and if so, in what form, remains clinically obscure for most drugs. Goh SJR et al. 7 elegantly analyse this complexity, using non-immediate reactions to penicillins as a model. They focus on the understanding of the role of nature of the lesional T cells, the characterisation of drug-responsive T cells isolated from patient blood, and the potential mechanisms by which penicillins enter the antigen-processing and presentation pathway to stimulate these deleterious responses.Regarding specific drugs involved in allergy, betalactam antibiotics (BL) are the most frequent culprit, being many reactions mediated by IgE. This type of reaction varies among patients, with some reacting only to one BL and others to several of them; it tends to change over time and differs between European countries, depending on BL consumption. Nowadays, amoxicillin (AX), alone or in combination with the β-lactamase inhibitor clavulanic acid (CLV), is the most often prescribed BL worldwide (Figure 2) and the most common elicitor of reactions in both children and adults. It is unclear why patients after the administration of AX-CLV develop selective hypersensitivity to AX, while tolerating CLV and vice-versa. Ariza et al. 8 generated drug-specific T-cell clones from AX- or CLV-selective immediate hypersensitivity patients and found that both AX- and CLV-specific clones were generated irrespective of whether AX or CLV was the culprit, although a higher secretion of Th2 cytokines (IL-13 and IL-5) was detected when clones were activated with the culprit BL compared with clones stimulated with the tolerated BL, in which higher secretion of Th1 cytokines (IFN-γ) was observed. Regarding selective non-immediate reactions to CLV, Copaescu A et al. 9 report on a cohort of patients with a history of non-immediate reaction to CLV, who demonstrated a delayed intradermal skin test response to CLV, 17% were allergic to both CLV and ampicillin, and 83% were selective reactors with good tolerance to AX. IFN-γ release enzyme-linked immunospot (ELISpot) was performed giving a sensitivity of 33%. Other drugs such as sulphonamides, either antibiotic or non-antibiotics are important triggers of non-immediate DHRs. Vilchez-Sanchez et al. 10 showed that lymphocyte transformation tests (LTT) can help avoid the performance of DPT with a sensitivity of 75%, a specificity of 100%, and negative and positive predictive values of 72.7% and 100%, respectively.There has been a great expansion in the use of biological agents (mainly monoclonal antibodies (mAbs)), and they have greatly improved the treatment landscape of hemato-oncologic, autoimmune, inflammatory and rheumatologic diseases. In parallel, the incidence rate of reported DHRs associated with these products has increased considerably within the last years, ranging from mild to life-threatening. Yang BC et al. 11 recommend risk stratification as the first step for managing patients with DHRs to these drugs. In cases with negative skin test and mild reactions, DPT is an option, and in moderate or severe reactions, desensitisation becomes the preferred approach. In cases with positive skin test, desensitisation is the recommended course of action, especially when there is no alternative medication. Desensitisation is also widely used in the management of immediate hypersensitivity reactions to chemotherapy agents, such as platinums. There is suspicion about the presence of a longer memory of tolerance in subsequent desensitisation protocols partially resembling the regulatory tolerance mechanisms induced by allergen immunotherapy. Tüzer et al. 12 demonstrate the possible role of IL-10 in desensitisation with platinums, as they found a dynamic change in serum IL-10 levels observed as an increase during desensitisation and a decrease in between the protocols.Finally, a wide spectrum of drugs has been considered for treatment of coronavirus disease 2019 (COVID-19) and all of them can potentially induce DHRs. Gelincik A et al .13 reviewed DHRs in COVID-19 times to these drugs, with knowledge mainly coming from previous clinical experience in patients not infected with COVID-19. As in other viral infections, skin symptoms, including exanthemas, may appear during the evolution of the disease, leading to differential diagnosis with DHRs. Whether COVID-19 can aggravate T–cell mediated DHRs reactions as some viruses is at present unknown.We can conclude that new drugs are continuously introduced into the markets and confirmed as inducers of hypersensitivity reactions. We still do not completely understand the mechanisms underlying many of these reactions and further studies for improving diagnostic and management are needed even in classic and well-studied drugs as BLs.Abbreviations: AX: Amoxicillin; CLV: Clavulanic acid; COVID-19: Coronavirus disease 2019; DHR: Drug hypersensitivity reactions; DPT: Drug provocation tests; DRESS: Drug reaction with eosinophilia and systemic symptoms; ELISpot: enzyme-linked immunospot; LTT: Lymphocyte transformation tests; MPE: Maculopapular exanthema.

A valid measurement of the SARS-CoV-2 incubation period is needed for case definitions and for adapting appropriate isolation measures but is challenging in an emergency context. The objective was to systematically review recent literature of reported estimates of the distribution of incubation period of SARS-CoV-2 for describing the distribution and its variability and dispersion through meta-analysis. A systematic review search was carried out up to July 1st 2020 of all identified references available reporting the SARS-CoV-2 incubation. Individual mean and standard deviation were used to produce the pooled estimate. Heterogeneity was also assessed using I2 statistics and sources of heterogeneity were explored using a meta-regression. The main outcome was the SARS-CoV-2 incubation period defined as the time from exposure to onset of clinical illness. In total, 43 studies were eligible, including 12 (27.9%) cohorts and 31 (72.1%) case reports and series. The pooled estimate of the mean incubation period across the studies was 6.24 days, 95% CI [5.80;6.69] ranging from 2.33 to 17.60 days. Shorter incubation periods were reported in cohorts compared to case series (p<0.01) and among studies with high proportions of males (p<0.05). The mean incubation period will help for identification times of exposure but determinants of its variations/range might be explored for potential links with clinical outcome or early pathogenic steps. The impact of individuals with extreme values of incubation on the outbreak dynamic should be evaluated taking account for the basic reproductive number. A real time of meta-analysis, called the InCoVid Lyon, is proposed.

Reports of children with cancer and COVID-19 from U.S.A and Europe had informed most patients presented with mild disease. Experience from upper and lower middle-income countries is needed to corroborate these findings. This report describes the experience with cancer patients in a tertiary care level hospital, in Mexico City. Of 24 symptomatic patients, 14 had a positive RT-PCR test. Eight required low-flow supplemental oxygen. None required critical care. One patient died due to pulmonary hemorrhage. Even though the infection seems to have an uncomplicated clinical course, it is necessary to ensure that all seeking medical attention do so safely.

Pull-in effect always occurs in a micro-electromechanical system, and its pull-in analysis is essential for the normal operation. This paper aims at studying the environment effect on the pull-in instability, especially the nano/micro particles in air. A fractal model is established using a fractal derivative, and the pull-in instability can be converted into a novel state of pull-in stability when the fractal dimension tends to be very small.

The aim of this paper is to construct a numerical scheme for solving a class of bilateral free boundaries problem. First, using a shape functional and some regularization terms, an optimal control problem is formulated, in addition, we prove its solution existence's. The first optimality conditions and the shape gradient are computed. the proposed numerical scheme is a genetic algorithm guided conjugate gradient combined with the finite element method, at each mesh regeneration, we perform a mesh refinement in order to avoid any domain singularities. Some numerical examples are shown to demonstrate the validity of the theoretical results, and to prove the robustness of the proposed scheme.

Background: There is a known female predominance in immunological conditions. Gender differences have also been demonstrated in perioperative hypersensitivity. The aim of this study was to investigate gender differences in the incidence of perioperative allergic reactions in Norway from 1997 to 2017. Methods: Spontaneous reports on allergic reactions during anesthesia were collected, and information about demographic, clinical and laboratory findings were recorded. Results: Women account for 66% of reported cases, and gender difference was most pronounced in fertile women (ages 14 to 51), where 74% of reports were from women. After withdrawal of the only pholcodine containing cough syrup on the market in 2007, the female predominance fell from 72 to 60% in all age groups. We found no differences in severity of the reaction or in laboratory findings between men and women. Conclusions: Women are at increased risk of suffering perioperative hypersensitivity reactions. The gender difference was less pronounced after the withdrawal of pholcodine.

Background: HSCT related complications and disease relapse are major obstacles in successful transplantation. Addition of ATG has shown to reduce rejection and Graft Vs Host Disease (GVHD) incidence significantly. Procedure: Here we report single center retrospective analysis for relative efficacy of rabbit and equine ATG during conditioning of pediatric patients who underwent HSCT. Results: Rabbit or Equine ATG were used as a part of conditioning regimen in 117 pediatric patients. Equine ATG group was labeled as group-1 and rabbit ATG as group-2. Both groups were analyzed for transplant related complications and outcome. In thalassemia, outcomes were comparable except Group-1 had more cases of proven bacterial infection (p=0.07) and veno-occlusive disease (p=0.03). In SAA, Group-1 had early neutrophil and platelet engraftment with less number of proven bacterial infections. Acute GVHD, chronic GVHD, median chimerism at day+30 and day+90 and overall survival (OS) was comparable in two groups, both in thalassemia and SAA patients. Analysis of 7 hematological malignancy cases and 10 immunodeficiency disorders also showed similar results. Conclusion: In conclusion, effectiveness of rabbit and horse ATG were similar in thalassemia, primary immunodeficiency patients and hematological malignancy while in SAA equine ATG use was associated with early neutrophil engraftment but OS in both groups were comparable.

We show global well-posedness and scattering for the defocusing, energy-subcritical Hartree equation \begin{equation*} iu_t + \Delta u =F(u), (t,x)\in\mathbb{R}\times\mathbb{R}^5 \end{equation*} where $F(u)= \big( V* |u|^2 \big) u$, $V(x)=|x|^{-\gamma}$, $3< \gamma< 4$, and initial data $u_0(x)$ is radial in almost sharp Sobolev space $ H^{s}\left(\R^5\right)$ for $s>s_c=\gamma/2-1$. Main difficulty is the lack of the conservation law. The main stategy is to use I-method together with the radial Sobolev inequality, the interaction Morawetz estimate, long-time Strichartz estimate and local smoothing effect to control the energy transfer of the solution and obtain the increment estimate of the modified energy $E(Iu)(t)$.

The Pearson type family densities are among the most important classes of distributions that play a key role in the directional statistics. Their particular structures make them suitable candidates to analysis data on non-Euclidean space, such as sphere. To model data scattered asymmetrically on such spaces, the researchers confined themselves to extend particular distributions from the class of the Pearson type family densities. Those specific distributions are symmetric in nature but their extended versions are usually heavy tailed. In this paper, we introduce some alternative probability density functions in the class of Pearson type distributions on the sphere having the spherical Student’s $t$, Fisher and Chi-square densities as the subfamilies. Via investigating various theoretical properties of this new subclass, we show that it is inheritably asymmetric. To further evaluating this subclass, some simulation studies are conducted. Also, modeling of two real-life data using the proposed densities and then comparing their fitting consequences with those resulted from invoking other common spherical distributions are considered.

In this article, Haar wavelet collocation technique is adapted to acquire the approximate solution of fractional KdV, Burgers' and KdV-Burgers' equations. The fractional order derivatives involved are described using the Caputo definition. In the proposed technique, the given nonlinear fractional differential equation is discretized with the help of Haar wavelet and reduced to the nonlinear system of equations, which are solved with Newton's or Broyden's method. The proposed method is semi-analytic as it involves exact integration of Caputo derivative. The proposed technique is widely applicable and robust. The technique is tested upon many test problems. The results are computed and presented in the form of maximum absolute errors which shows the accuracy, efficiency and simple applicability of the proposed method.

Objective: To investigate the clinical significance of specific IgE-staphylococcal enterotoxin in CRS. Design: Retrospective analysis of patients who were positive for specific IgE-staphylococcal enterotoxin B. Setting: Tertiary rhinology clinic. Participants: A total of 965 patients who were positive for specific IgE-staphylococcal enterotoxin B from December 2016 to December 2017 Main outcome measures: We retrospectively reviewed the records of 965 patients who were positive for specific IgE-staphylococcal enterotoxin B from December 2016 to December 2017. Patient demographics, titre specific IgE to staphylococcal enterotoxin B (IgE-SEB) levels, MAST, serologic test, and medical records were reviewed. Results: IgE-SEB (KU/L) was higher in CRS patients than Non-CRS patients (0.13±0.37 vs 0.08±0.22, respectively; p-value: 0.044), and the IgE-SEB (+, ≥0.35) rate was also higher (10.06% vs 4.46%, respectively; p-value: 0.030). IgE-SEB (KU/L) was higher in the CRS group than in the fungal sinusitis group (0.13±0.37 vs 0.03±0.05, respectively; p-value: <0.001), and the IgE-SEB (+, ≥0.35) rate was also higher (10.06% vs 0 %, respectively; p-value: 0.015). Between the CRSsNP (chronic rhinosinusitis without nasal polyps) and CRSwNP (chronic rhinosinusitis with nasal polyps) groups, there were no differences in IgE-SEB (KU/L) or IgE-SEB (+) rates. As the values of IgE-SEB(KU/L) and the IgE-SEB (+,>0.1) rate increased, the CRS severity also increased. Conclusions: IgE-SEB showed a positive correlation with CRS severity but not with postoperative recurrence or nasal polyps. Further studies are needed to obtain clear evidence that IgE-SEB can be considered as an independent CRS endotype.

It is widely recognized that multi-year drought can induce changes in catchment hydrological behaviors. However, at present, our understanding about multi-year, drought-induced changes in catchment hydrological behaviors and its driving factors at the process level is still very limited. This study proposed a new approach using a data assimilation technique with a process-based hydrological model to detect multi-year drought-induced changes in catchment hydrological behaviors and to identify driving factors for the changes in an unimpaired Australian catchment (Wee Jasper) which experienced prolonged drought from 1997 to 2009. Modelling experiments demonstrated that the multi-year drought caused a significant change in the catchment rainfall-runoff relationship, indicated by significant step changes in the estimated time-variant hydrological parameters SC (indicating catchment active water storage capacity) and C (reflecting catchment evapotranspiration dynamics), whose average values increased 23.4% and 10.2%, respectively, due to drought. The change in the rainfall-runoff relationship identified by the data assimilation method is consistent with that arrived at by a statistical examination. The proposed method provides insights about the drivers of the changes in the rainfall-runoff relationship at the processes level. Declining groundwater and deep soil moisture depleted by persistent evapotranspiration of deep-rooted woody vegetation during drought are the main driving factors for the catchment behaviors change in the Wee Jasper catchment. The new method proposed in this study was found to be an effective technique for detecting both the change of hydrological behaviors induced by prolonged drought and its driving factors at the process level.

Background: Although asthmatic patients with chest tightness as their only presenting symptom (chest tightness variant asthma, CTVA) have clinical characteristics of eosinophilic airway inflammation similar to those of classic asthma (CA), the response of CTVA to treatment regimens used for CA is unclear. Objective: The response of 76 CTVA patients to standard asthma treatments with inhaled corticosteroids with long-acting beta-agonists was explored. Methods: The study was a multicenter, prospective, real-life study conducted in 16 centers in China. The primary efficacy endpoint was the changes in 5-point asthma control questionnaire (ACQ-5) score before and after treatment. Results: After 52 weeks of treatment with therapy regimens used for CA, the ACQ-5 scores decreased markedly from 1.38±0.91 (first administration) to 0.74±0.75 (26 weeks), and 0.71±0.78 (52 weeks) (P<0.01), and the mean decrease for ACQ-5 between 52 weeks and first administration was 0.674(95%CI 0.447-0.9, P<0.001), while the asthma quality of life questionnaire (AQLQ) scores increased from 5.77±0.75 (first administration) to 6.23±0.59 (26 weeks) and 6.20±0.58 (52 weeks) (P<0.01), and the mean increase for AQLQ between 52 weeks and first administration was 0.441(95%CI 0.258-0.625, P<0.001). Diurnal variation in peak expiratory flow (PEF) decreased from 18.4%±9.78(first administration) to 9.32%±5.33 (52 weeks) (P<0.01), and the provocation dose that caused a 20% fall in the FEV1 (PD20-FEV1) was significantly improved after one year of treatment. Conclusion: CTVA patients showed a good clinical response to anti-asthma treatments, and the treatment effects may be related to the severity of CTVA.

Introduction: Lung cancer is the most important cause of cancer related deaths across the world. The aim of the study is to find key genes and enriched pathways associated with lung cancer using bioinformatics and statistical techniques, hence providing potential targets for the identification and treatment of the cancer. Methods: Differentially expressed genes (DEGs) data of 54674 genes based on stage, tumor and status of the lung cancer was taken from 66 patients of African American (AAs) origin. 2392 DEGs were found based on stage, 13502 DEGs were found based on tumor, 2927 DEGs were found based on status having p value (p<0.05). Results: Total 33 common DEGs were found from stage, tumor and status of lung cancer patients. Gene ontology (GO) and KEGG pathway enrichment analysis is performed and 49 significant pathways were obtained, out of which 10 pathways were found that were exclusively involved in lung cancer development. Protein-protein interaction (PPI) network analysis found 69 nodes and 324 edges and identified 10 hub genes based on their highest degrees. Additionally, module analysis of PPI found that ‘Viral carcinogenesis’, ‘pathways in cancer’, ‘notch signaling pathway’, ‘AMPK signaling pathways’ had close association with lung cancer. Conclusion: it is seen that these identified DEGs do not directly participate in growth of lung cancer but regulate other genes which play important role in growth of lung cancer. The key genes and enriched pathways identified can thus help in better identification and prediction of lung cancer.

Chemotherapeutic drugs suffer from non-specific binding, undesired toxicity, and poor blood circulation which contribute to poor therapeutic efficacy. In this study, antibody-drug nanoparticles (ADNs) are engineered by synthesizing pure anti-cancer drug nanorods (NRs) in the core of nanoparticles with a therapeutic monoclonal antibody, Trastuzumab on the surface of the NRs for specific targeting and synergistic treatments of breast cancer cells. The ADNs were designed by first synthesizing ~95 nm diameter × ~500 nm long paclitaxel (PTX) NRs using the nanoprecipitation method. The surface of PTXNRs was functionalized at 2 OH nucleophilic site using carbonyldiimidazole and conjugated to TTZ through the lysine residue interaction forming PTXNR-TTZ conjugates (ADNs). The size, shape, and surface charge of ADNs were characterized using scanning electron microscopy (SEM), SEM, and zeta potential, respectively. Using fluorophore labeling and response surface analysis, the percentage conjugation efficiency was found >95% with a PTX to TTZ mass ratio of 4 (molar ratio  682). In vitro therapeutic efficiency of PTXNR-TTZ was evaluated in human epidermal growth factor receptor 2 (HER2) positive BT-474 and HER2 negative MDA-MB-231 breast cancer cells using MTT assay. PTXNR-TTZ inhibited >80% of BT-474 cells at a higher efficiency than individual PTX and TTZ treatments alone after 72 h. A combination index analysis indicated a synergistic combination of PTXNR-TTZ compared with the doses of single drug treatment. The molecular mechanisms of PTXNR-TTZ were investigated using cell cycle and Western blot analyses. The cell cycle analysis showed PTXNR-TTZ arrested >80% of BT-474 breast cancer cells in the G2/M phase, while >70% of untreated cells were found in the G0/G1 phase indicating that G2/M arrest induced apoptosis. A similar percentage of G2/M arrested cells were found to induce caspase-dependent apoptosis in PTXNR-TTZ treated BT-474 cells as revealed using Western blot analysis. PTXNR-TTZ treated BT-474 cells showed ~1.3, 1.4, and 1.6-fold higher expressions of cleaved caspase-9, cytochrome C, and cleaved caspase-3, respectively than untreated cells, indicating up-regulation of caspase-dependent activation of apoptotic pathways. The PTXNR-TTZ ADN represents a novel nanoparticle design that holds promise for targeted and efficient anti-cancer therapy by selective targeting and cancer cell death via apoptosis and mitotic cell cycle arrest.

Social life and isolation pose a complex suite of challenges to organisms prompting significant changes in neural state. However, plasticity in how brains respond to social challenges remains largely unexplored. The fire ants Solenopsis invicta provide an ideal scenario for examining this. Fire ant queens may found colonies individually or in groups of up to 30 queens. Here, we artificially manipulated availability of nesting sites to test how the brain responds to social vs. solitary colony founding at two key timepoints, and to group size. The difference between group and single founding queens involves only 1 gene when behaviour is still plastic and queens can switch from one modality to another, while hundreds of genes are involved once behaviours are more canalized. Furthermore, we show that large groups lead to greater changes in gene expression than small groups, perhaps due to higher cognitive demands of a more complex social environment.

Antheraea proylei J, is an economically important silkworm of North Eastern region of India reared for the production of the tasar silk. The silkworm is often exposed to various microbial diseases caused by bacteria and viruses. The disease causes significant damage to larvae and elicit pupal mortality, thus posing a serious threat to the linked economic activities. The gut microbiome of silkworms play an important role, in nutrient acquisition and immunity. In this study, we have reported molecular characterization and histopathological assessment of gut associated bacteria of healthy and diseased tasar silkworms. As compared to healthy silkworms, diseased infected silk glands shows loss of turbidity, secretory layer not distinguishable to tunica propria and lumen distorted. Both secretory and absorptive cells were found to be hypertrophied. Body fat becomes vacuolated and soft when compared to the healthy silkworms. Bacterial profile of healthy and diseased silkworm respectively was identified by 16S rRNA gene sequencing and analysis. Bacillus toyonensis and Bacillus thuringiensis were commonly found in healthy larvae whereas Bacillus aryabhattai and Bacillus megaterium were found in diseased larvae. The family Bacillus of phylum Firmicutes was dominant in both healthy and diseased silkworms. To the best of our knowledge, this is the first attempt to study A. proylei midgut microbiota from a biodiversity hotspot in North Eastern India. The present study might be helpful in disease prognosis and further comprehensive analysis on midgut microflora may lead towards the development of effective strategies for management of these economic silkworms.

In a polymorphic species, stable differences in resource use are expected among ecotypes, and homogeneity in resource use is predicted within an ecotype. Yet, using a broad resource spectrum has been identified as a strategy for fishes living in unproductive northern environments, where food is patchily distributed and ephemeral. We investigated whether individual specialization of trophic resources occurred within the generalist piscivore ecotype of lake trout from Great Bear Lake, Canada, reflective of a form of diversity. Four distinct dietary patterns of resource use within the lake trout ecotype were detected from fatty acid composition, with some variation linked to spatial patterns within Great Bear Lake. Feeding habits of different groups within the ecotype were not associated with detectable morphological or genetic differentiation, suggesting that behavioral plasticity caused the trophic differences. A low level of genetic differentiation was detected between exceptionally large-sized individuals and other individuals. Investigating a geologically young system that displays high levels of intraspecific diversity and focusing on individual variation in diet suggested that individual trophic specialization can occur within an ecotype. The characterization of niche use among individuals, as done in this study, is necessary to understand the role that individual variation can play at the beginning of differentiation processes.

INTRODUCTION Bone presents continuous remodeling and a generous regenerative capacity compared to other tissues. Lifelong bone remodeling is responsible for skeletal development, responses to mechanical stimuli, and maintaining mineral homeostasis. Intrinsic regeneration capacity guarantees bone integrity as an injury repair process. Moderate-sized bone defects repair without the need for a graft. However, complex clinical conditions are requiring a considerable amount of bone, in which natural bone regeneration capacity is not sufficient to establish functional tissue recovery. In the case of significant bone defects created by trauma, infection, skeletal disorders, or in the treatment of tumor excision, the regeneration process becomes compromised [1].Strategies may be necessary to guide or accelerate the process, increasing bone quantity or quality [2]. There is intense research in bone bioengineering, seeking to overcome the limitations observed in non-healing defects and alternative methods to autologous bone grafts, in order to produce bone substitutes with the same properties of this gold standard [3]. Osteoconduction is the process of perivascular tissue, precursor, and osteoprogenitor cell ingrowth, from the bony bed into implanted frameworks. Osteoinduction is the induction of undifferentiated mesenchymal stem cells into osteoprogenitor cells, also at ectopic sites [4]. The combination of three-dimensional biocompatible frameworks with cells and growth factors may stimulate osteogenesis and osteoinduction, enhance the osteogenic capacity of transplanted and endogenous cells and thus, ensure better healing [5].Calvarial “non-healing” defects are useful in the preclinical study of bone repair to analyze strategies of tissue engineering in intramembranous bone formation. Some advantages of this defect are the orthotopic non-load bearing site, its reproducibility, mechanical stability, and the limited baseline healing plateau, above which the effect of cell/scaffold implant on osteogenesis is noticeable [6-9]. The application of membranes is indicated for Guided Bone Regeneration (GBR), to isolate the bone defect from other tissues, and for bone reconstruction [10]. Commercially available collagen membranes are widely used in in vivo studies, associated with ceramic implant material [11], demineralized bone matrix [3], growth factors [12], and cells [13]. The membranes covering bone defects in calvaria provided stability for ceramic tricalcium phosphate (TCP) inserted into the defect, resulting in higher bone amount and better mechanical properties [11]. The association of ceramic and membrane with bone marrow mesenchymal stem cells have been demonstrated to favor earlier bone deposition [13]. Calvarial “non-healing” defects are effective in the preclinical study of bone repair to analyze strategies of tissue engineering in intramembranous bone formation. Some advantages of this defect is the orthotopic non-load bearing site, its reproducibility, mechanical stability, and the limited baseline healing plateau, above which the effect of cell/scaffold implant on osteogenesis is noticeable [6-10].Commercially available collagen membranes are widely used in in vivo studies, associated with ceramic implant material [11], demineralized bone matrix [3], growth factors [12] and cells [13]. The membranes covering bone defects in calvaria provided stability for TCP inserted into the defect, resulting in higher bone amount and better mechanical properties [11]. The association of ceramic and membrane with bone marrow mesenchymal stem cells has been demonstrated to favor earlier bone deposition [13].Tissues that are mainly available in maternity hospitals, and often discarded, can be a reliable source of allogenous cells and collagenous matrix for bone tissue engineering applications. Importantly, umbilical cord mesenchymal stem cells have been shown to stimulate vascularization and bone formation in vivo [14, 15]. In addition, amniotic membranes are known to be a source of stem cells and collagenous scaffold [16, 17]. Mesenchymal stem cells from amniotic membranes can stimulate osteogenic and angiogenic differentiation of various cell sources, including, adipose-derived stem cells [18]. Moreover, amniotic membranes present great potential in clinical application [19], tissue engineering [17], and the removal of the epithelial cell layer minimizes the risks of adverse immunological responses [20, 21].Amniotic membrane association with stem cells from bone marrow [22] and adipose tissue [23, 24] demonstrated that Decellularized Human Amniotic Membrane (DAM) is an excellent cell-carrier in tissue regeneration applications. Bone and periodontal tissue engineering studies have demonstrated that DAM can provide a preferential environment for osteogenic differentiation of dental apical papilla cells, increase the expression of osteogenic marker genes, and deposition of mineralized matrix in vitro [25]. Periodontal ligament stem cells transfer onto DAM [26], and ASCs cultured on DAM [27] have been shown to stimulate periodontal regeneration in vivo . Interestingly, double-layered cell transfer technique on DAM allowed transplantation of periodontal ligaments stem cells and osteoblasts, and enhanced bone formation in calvaria when compared to single-cell type transplantation [28]. The application of amniotic membrane in calvarial defects has been found to promote more significant bone regeneration compared to defect without graft, but less than the association with ceramic material (HA) and osteoinductive factor Bone morphogenetic protein (BMP) [29]. Interestingly, DAM associated with ASCs were also used successfully in a calvarial defect in rabbits [24].Studies using multipotent ASCs, since their first reports [30, 31] have demonstrated their potential as a significant source of adult stem cells in regenerative medicine. Some significant advantages of ASCs in bone engineering compared to Bone Marrow Stem Cells are the facility in harvesting, higher cellular yield, and proliferation capacity [32]. The application of the patient autologous cells from fat, transferred in order to enrich and accelerate the bone regeneration process was reported, in cranioplasties associated with TCP [33], in maxillary defect associated with titanium, TCP, BMP [34], and graft [35].Earlier studies investigating calvarial defects without cell expansion from the adipose tissue have used various materials, including fragmented adipose tissue [36, 37], Stromal Vascular Fraction (SVF) associated with polylactide (PLA), demineralized bone matrix (DBM) [38], and hypertrophic cartilage [39]. After isolation, ASCs were investigated as perivascular cells associated with poly(lactic-co-glycolic acid) (PLGA)/ hydroxyapatite (HA) composites [9, 40], stem cells associated with PLGA [41], stem cells associated with PLGA/HA composites [40, 42-48], stem cells associated with Whitlockite [49], with acellular collagen dermal matrix [50], with HA/TCP bioceramics and hydrogel [51], silicate bioceramic [52], and duck-beak bioceramic [53].Investigations on ASCs participation in calvarial bone defect repair have reported the occurrence of significant cell migration to the lesion site after intravenous cell administration [42], and paracrine effect of ASCs on in vitro and in vivo osteoblastic cell differentiation [47]. There was a significantly higher stimulation in cell association of immediately prepared defects, compared to cell graft with established bone defects [46]. There is considerable evidence indicating that ASCs cells may contribute to periodontal regeneration [54]. Our results demonstrated enhanced in vivobone regeneration by undifferentiated adipose-derived stromal cells loaded onto a decellularized human amniotic membrane.

Mesenchymal stem cells (MSCs) can be derived from several human and animal sources. According to this systematic review, the immortalization of these cells, by viral or gene transfer techniques (plasmid) and non-viral methods, are useful to ensure the reproducibility of the experiments and the prospect of using these cells in clinical studies. The resultant immortalized MSCs cells must undergo through different validation assays in order to prove their safety and phenotypic and genotypic stability; these assays include flow cytometry for specific MSC markers, trilineage differentiation, RT-PCR and qRT-PCR expression analysis for pluripotency genes, karyotype and telomere length and in vivo tumorigenicity assays.

This study aimed to differentiate human mesenchymal stem cells (hMSCs) from the human umbilical cord in cholinergic-like cells using a natural matrix. The isolation of hMSCs from Wharton's jelly (WJ) was carried out using "explant" and mononuclear cells by density gradient. hMSCs were plated in a natural functional biopolymer matrix for the production of neurospheres. Neural precursor cells were subjected to a standard cholinergic differentiation protocol. Dissociated neurospheres, neural precursor cells, and cholinergic-like cells were characterized by immunocytochemistry. The RT-PCR was performed. hMSCs were CD73+, CD90+, CD105+, CD34- and CD45- and demonstrated the trilineage differentiation. Neurospheres and their isolated cells were nestin-positive, and also expressed NESTIN, MAP2, ßIII-TUBULIN, GFAP genes. Neural precursor cells that were differentiated in cholinergic-like cells expressed ßIII-TUBULIN protein and choline acetyltransferase enzyme. hMSCs on the natural matrix were capable of differentiating hMSC into neurospheres, obtaining neural precursor cells without growth factors or gene transfection before cholinergic differentiation.