Prevention and control of Zika fever as a mosquito-borne and sexually transmitted disease

The ongoing Zika virus (ZIKV) epidemic poses a major global public health emergency. It is known that ZIKV is spread by \textit{Aedes} mosquitoes, recent studies show that ZIKV can also be transmitted via sexual contact and cases of sexually transmitted ZIKV have been confirmed in the U.S., France, and Italy. How sexual transmission affects the spread and control of ZIKV infection is not well-understood. We presented a mathematical model to investigate the impact of mosquito-borne and sexual transmission on spread and control of ZIKV and used the model to fit the ZIKV data in Brazil, Colombia, and El Salvador. Based on the estimated parameter values, we calculated the median and confidence interval of the basic reproduction number R0=2.055 (95% CI: 0.523-6.300), in which the distribution of the percentage of contribution by sexual transmission is 3.044 (95% CI: 0.123-45.73). Our study indicates that R0 is most sensitive to the biting rate and mortality rate of mosquitoes while sexual transmission increases the risk of infection and epidemic size and prolongs the outbreak. In order to prevent and control the transmission of ZIKV, it must be treated as not only a mosquito-borne disease but also a sexually transmitted disease

Orbital and Spin Parameter Variations of Partial Eclipsing Low Mass X-ray Binary X 1822-371

We report our measurements for orbital and spin parameters of X 1822-371 using its X-ray partial eclipsing profile and pulsar timing from data collected by the Rossi X-ray Timing Explorer (RXTE). Four more X-ray eclipse times obtained by the RXTE 2011 observations were combined with historical records to trace evolution of orbital period. We found that a cubic ephemeris likely better describes evolution of the X-ray eclipse times during a time span of about 34 years with a marginal second order derivative of $ddot{P}_{orb}=(-1.05 pm 0.59) imes 10^{-19}$ s$^{-1}$. Using the pulse arrival time delay technique, the orbital and spin parameters were obtained from RXTE observations from 1998 to 2011. The detected pulse periods show that the neutron star in X 1822-371 is continuously spun-up with a rate of $dot{P}_{s}=(-2.6288 pm 0.0095) imes 10^{-12}$ s s$^{-1}$. Evolution of the epoch of the mean longitude $l=pi /2$ (i.e. $T_{pi / 2}$) gives an orbital period derivative value consistent with that obtained from the quadratic ephemeris evaluated by the X-ray eclipse but the detected $T_{pi / 2}$ values are significantly and systematically earlier than the corresponding expected X-ray eclipse times by $90 pm 11$ s. This deviation is probably caused by asymmetric X-ray emissions. We also attempted to constrain the mass and radius of the neutron star using the spin period change rate and concluded that the intrinsic luminosity of X 1822-371 is likely more than $10^{38}$ ergs s$^{-1}$.postprin

Optimal circulant modulation for submodule voltage ripple minimization with inherent balancing capability in modular multilevel dc-dc converters

The modularity of the modular multilevel dc-dc converters (MMDCs) makes it as a competitive candidate in medium voltage applications but brings the submodule (SM) voltage balancing issue. This paper proposes an optimal circulant modulation method for minimizing the SM voltage ripples with inherent balancing capability proven at the same time, which allows smaller SM capacitors and avoids the high-frequency communication for SM voltage balancing. Firstly, the optimal switching pattern is strictly derived providing a general method to theoretically minimize the SM capacitor voltage ripple. Then the switching matrix of the optimal circulant modulation is formulated by introducing the generalized-circulant matrix. It verifies the circularity and full-rank feature of the optimal switching matrix, which promises the uniformity of SM actions and the inherent balancing of SM voltages. Finally, full-scale simulations and down-scaled experiments are both provided with the isolated LLC -based MMDC model and prototype. The results show that the proposed optimal circulant modulation can reduce the SM capacitor voltage ripple by 37% compared with the existed method, and it also promises the inherent SM voltage balancing and the SM uniformity

Group-Based Parent Training Interventions for Parents of Children with Autism Spectrum Disorders: a Literature Review

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Parents of children with autism spectrum disorders should have access to interventions to help them understand and support their child. This literature review examines the existing evidence for group-based parent training interventions that support parents of children with autism. From the literature, core intervention processes and outcomes are identified and include parenting and parent behaviour, parent health, child behaviour and peer and social support. Results show a positive trend for intervention effectiveness, but findings are limited by low-quality studies and heterogeneity of intervention content, outcomes and outcome measurement. Future research should focus on specifying effective intervention ingredients and modes of delivery, consistent and reliable outcome measurement, and improving methodological rigour to build a more robust evidence base

XRCC2 R188H (rs3218536), XRCC3 T241M (rs861539) and R243H (rs77381814) single nucleotide polymorphisms in cervical cancer risk

Human Papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesions. Transformation may be induced by several mechanisms, including oncogene activation and genome instability. Individual differences in DNA damage recognition and repair have been hypothesized to influence cervical cancer risk. The aim of this study was to evaluate whether the double strand break gene polymorphisms XRCC2 R188H G>A (rs3218536), XRCC3 T241M C>T (rs861539) and R243H G>A (rs77381814) are associated to cervical cancer in Argentine women. A case control study consisting of 322 samples (205 cases and 117 controls) was carried out. HPV DNA detection was performed by PCR and genotyping of positive samples by EIA (enzyme immunoassay). XRCC2 and 3 polymorphisms were determined by pyrosequencing. The HPV-adjusted odds ratio (OR) of XRCC2 188 GG/AG genotypes was OR = 2.4 (CI = 1.1-4.9, p = 0.02) for cervical cancer. In contrast, there was no increased risk for cervical cancer with XRCC3 241 TT/CC genotypes (OR = 0.48; CI = 0.2-1; p = 0.1) or XRCC3 241 CT/CC (OR = 0.87; CI = 0.52-1.4; p = 0.6). Regarding XRCC3 R243H, the G allele was almost fixed in the population studied. In conclusion, although the sample size was modest, the present data indicate a statistical association between cervical cancer and XRCC2 R188H polymorphism. Future studies are needed to confirm these findings.Fil: Perez, Luis Orlando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Crivaro, Andrea Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Barbisan, Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Poleri, Lucía Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Golijow, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentin

A Rationale for Schistosomiasis Control in Elementary Schools of the Rainforest Zone of Pernambuco, Brazil

In 2001, a World Health Assembly resolution urged member states to ensure treatment against schistosomiasis and soil-transmitted helminthiasis in endemic areas with the goal of attaining a minimum target of at least 75% of all school-aged children by 2010. In the highly endemic Rainforest Zone of Pernambuco (ZMP), northeast Brazil, the Schistosomiasis Control Program has registered a cumulative coverage of only 20% of the population at risk, which jeopardizes the accomplishment of the minimum target for that area. Demographic and parasitological data from a representative municipality of the ZMP provide evidence that the current, community-based approach to control can be complemented with school-based actions. In the most troubled municipalities, individual diagnosis and treatment could be focused on school-aged children rather than whole populations without compromising the principles of the primary health care system. Local health and education teams should be encouraged to include school-based interventions to scale up coverage and achieve a rapid impact on infection

A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease

BACKGROUND: Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. METHODS: Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. RESULTS: A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. CONCLUSIONS: These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy. TRIAL REGISTRATION: ISRCTN Registry 48776874

Retargeted adenoviruses for radiation-guided gene delivery

The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment

Nuclear β-catenin expression is closely related to ulcerative growth of colorectal carcinoma

Although most colorectal cancer develops based on the adenoma–adenocarcinoma sequence, morphologically, colorectal cancer is not a homogeneous disease entity. Generally, there are two distinct morphological types: polypoid and ulcerative colorectal tumours. Previous studies have demonstrated that K-ras codon 12 mutations are preferentially associated with polypoid growth of colorectal cancer; however, little is known about the molecular mechanism that determines ulcerative growth of colorectal cancer. β-catenin complex plays a critical role both in tumorigenesis and morphogenesis. We examined the differential expression of β-catenin and its related factors among different types of colorectal cancer in order to determine any relationship with gross tumour morphology. Immunohistochemical staining of β-catenin, E-cadherin and MMP-7 was performed on 51 tumours, including 26 polypoid tumours and 25 ulcerative tumours. Protein truncation tests and single-strand conformational polymorphism for mutation of the adenomatous polyposis coli tumour suppressor gene, as well as single-strand conformational polymorphism for the mutation of β-catenin exon 3 were also done. Nuclear expression of β-catenin was observed in 18 out of 25 (72%) cases of ulcerative colorectal cancer and seven out of 26 (26.9%) cases of polypoid colorectal cancer. A significant relationship of nuclear β-catenin expression with ulcerative colorectal cancer was found (P<0.001). However, this finding was independent of adenomatous polyposis coli tumour suppressor gene mutation and E-cadherin expression. Together with previous data, we propose that different combinations of genetic alterations may underlie different morphological types of colorectal cancer. These findings should be taken into consideration whenever developing a new genetic diagnosis or therapy for colorectal cancer