Dose-adapted post-transplant cyclophosphamide for HLA-haploidentical transplantation in Fanconi anemia.

We developed a haploidentical transplantation protocol with post-transplant cyclophosphamide (CY) for in vivo T-cell depletion (TCD) using a novel adapted-dosing schedule (25 mg/kg on days +3 and +4) for Fanconi anemia (FA). With median follow-up of 3 years (range, 37 days to 6.2 years), all six patients engrafted. Two patients with multiple pre-transplant comorbidities died, one from sepsis and one from sepsis with associated chronic GVHD. Four patients without preexisting comorbidities and early transplant referrals are alive with 100% donor chimerism and excellent performance status. We conclude that adjusted-dosing post-transplant CY is effective in in vivo TCD to promote full donor engraftment in patients with FA

3D-QSAR studija afiniteta vezanja na receptor za (R,S)-2-amino-3-(3-hidroksi-5-metilizoksazol-4-il)-propansku kiselinu

An approach for binding affinity evaluation is suggested and exemplified using a set of triazolo [1,5-a] quinoxaline for the (R,S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)-propionic acid (AMPA) receptor. Biological activity toward the AMPA receptor (expressed as -log IC5O) was taken as a dependent variable for building Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) models. The resulting models show the ways of increasing the binding affinity to the AMPA receptor as a potential target for epilepsy. The statistically significant results show that the cross-validated r2CV value (0.766) for the CoMFA model is greater than (0.758) for the CoMSIA model. The non-cross validated run giving the coefficient of determination r2 values of 0.944 and 0.919 for CoMFA and CoMSIA, respectively, provided good correlation between the observed and computed affinities of the training set compounds. The resulting CoMFA and CoMSIA models indicate that steric, electrostatic, hydrophobic (lipophilic), hydrogen bond donor and acceptor substituents play a significant role in increasing the binding affinity and selectivity of the compounds toward the AMPA receptor.U radu je vrednovan afinitet vezanja serije triazolo[1,5-a]kinoksalina na receptor za (R,S)-2-amino-3-(3-hidroksi-5-metilizoksazol-4-il)-propansku kiselinu (AMPA). Djelovanje na AMPA receptor (izraženo kao log IC5O) uzeta je kao zavisna varijabla u modelima usporedne analize molekulskih polja (Comparative Molecular Field Analysis, CoMFA) i usporedne analize molekulske sličnosti (Comparative Molecular Similarity Indices Analysis, CoMSIA). Ti modeli pokazuju kako povećati afinitet vezanja na AMPA receptor, što može biti korisno u terapiji epilepsije. Statistički značajni rezultati ukazuju da je križno validirana r2CV vrijednost za CoMFA model (0,766) veća nego za CoMSIA model (0,758). Koeficijenti r2 za CoMFA model (0,944) i CoMSIA (0,919) ukazuju na dobru korelaciju između izračunatih i eksperimentalno određanih afiniteta vezanja proučavane serije spojeva. Prema oba modela za povećanje afiniteta vezanja i selektivnost spojeva za AMPA receptor značajna su sterička, elektrostatska, hidrofobna (lipofilni) svojstva, te sposobnost stvaranja vodikovih veza

PHARMACOGNOSTICAL AND PHYTO-CHEMICAL EVALUATION OF PIPPALYADI YOGA: A POLYHERBAL FORMULATION

Pippalyadi Yoga is Churna Kalpana described by Acharya Chakrapani in Vandhyatva (infertility). Ovulatory dysfunction is the prime cause of Infertility among the world, Pippalyadi Yoga is useful in patients especially having Anovulation which is known as Abeejatva in Ayurveda. So a new pharmaceutical preparation Pippalyadi Yoga in the form of Churna (powder) was tried to standardize which is economical in terms of time and machinery usage. Pharmacognostical and phyto-chemical observations revealed the specific characters of all active constituents used in the preparation. The present work was carried out to standardize the finished product of Pippalyadi Yoga to confirm its identity, quality and purity. The presence of stone cells, oil globules, olio resin cells, parenchymatous cells, oval & beaker shaped starch grains, pollen grains were the characteristic features observed in the microscopy of the prepared drug. Phyto-chemical analysis showed Loss on drying 10.07 % w/w, ash value 6.55 %w/w, water soluble extract 14 % w/w, methanol soluble 13.40 % w/w, particle consistency above 60 mesh 4.10 % w/w, between 60-85 mesh 9.20 % w/w, between 85-120 mesh 13.30 % w/w & below 120 mesh 73.37 % w/w & pH 5.0. HPTLC of Pippalyadi Yoga is the preliminary quantitative analysis which shows 8 prominent spots at Rf. 0.09, 0.61, 0.67, 0.74, 0.80, 0.86, 0.91, 1.00 in UV 254 nm and 7 prominent spots at Rf. 0.06, 0.17, 0.63, 0.67, 0.75, 0.82, 0.88 in UV 366 nm. Pippalyadi Yoga, a polyherbal formulation of 4 ingredients was prepared and HPTLC finger print profile was developed and it can be considered pharmacopial standard of Pippalyadi Yoga

Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth

Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations

Systematic literature review of prediction techniques to identify work skillset

A mismatch of skillsets is a main cause to the unemployment in Malaysia. It is a situation where the level and work skillset that are available do not match the market demands and the individual does not know how to identify the skills that they have. To deal with this problem, prediction techniques is used to assist in identifying work-appropriate skills for individual. Thus, a systematic literature review (SLR) on predicting work skillsets using prediction techniques is proposed. The aim of this study is to give an overview on the prediction techniques that have been used to predict work skillset and the accuracy of the techniques. We use SLR to identify 383 prediction techniques studies for identifying skills published from 2014 to 2019. As a result, 9 studies report adequate information and methodology according to our criteria and apply. From the studies, classification techniques are used for predicting work skillset. The algorithms used is Random Forest with precision is 99%. From this study, a future study will be conducted by developing a prediction model to help identifying appropriate work skillsets to meet current needs and identifying the levels of skills they have. The significant of this study is the researchers are able to understand deeply about the prediction techniques used to identify work skillset and the accuracy of the techniques used

Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms' tumor: a CIBMTR retrospective analysis.

Despite the marked improvement in the overall survival (OS) for patients diagnosed with Wilms' tumor (WT), the outcomes for those who experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and were reported to the Center for International Blood and Marrow Transplantation Research. The 5-year estimates for event-free survival (EFS) and OS were 36% (95% confidence interval (CI); 29-43%) and 45% (95 CI; 38-51%), respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. As attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus HDT followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. As disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy

Maternal outcomes in subsequent delivery after previous obstetric anal sphincter injury (OASI): a multi-centre retrospective cohort study.

INTRODUCTION AND HYPOTHESIS: Women with a history of obstetric anal sphincter injury (OASI) are at increased risk of recurrence (rOASI) at subsequent delivery; however, evidence regarding the factors influencing this risk is limited. Furthermore, little is known about what factors influence the decision to alternatively deliver by elective caesarean section (ELLSCS). METHODS: Retrospective univariate and multivariate logistic regression analysis of prospectively collected data from four NHS electronic maternity databases including primiparous women sustaining OASIS during a singleton, term, cephalic, vaginal delivery between 2004 and 2015, who had a subsequent delivery. RESULTS: Two thousand two hundred seventy-two women met the criteria; 10.2% delivering vaginally had a repeat OASI and 59.4% had a second-degree tear. Women having an ELLSCS were more likely to be Caucasian, older, have previously had an operative vaginal delivery (OVD) and have a more severe degree of OASI. Positive predictors for rOASI were increased birth weight and maternal age at both index and subsequent deliveries, a more severe degree of initial OASI and Asian ethnicity. The overall mediolateral episiotomy (MLE) rate was 15.6%; 77.2% of those who had an episiotomy sustained no spontaneous perineal trauma. Only 4.4% of women with a rOASI had an MLE, whilst the MLE rate was 16.9% in those without a recurrence (p  4 kg increased the risk 2.5 fold. CONCLUSIONS: Women with previous OASIS are at an increased risk of recurrence. A more liberal use of MLE during subsequent vaginal delivery could significantly reduce the risk of recurrence