Anthropometric indices of Gambian children after one or three annual rounds of mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin, carried out for the control of blinding trachoma, has been linked to reduced mortality in children. While the mechanism behind this reduction is unclear, it may be due, in part, to improved nutritional status via a potential reduction in the community burden of infectious disease. To determine whether MDA with azithromycin improves anthropometric indices at the community level, we measured the heights and weights of children aged 1 to 4 years in communities where one (single MDA arm) or three annual rounds (annual MDA arm) of azithromycin had been distributed. METHODS: Data collection took place three years after treatment in the single MDA arm and one year after the final round of treatment in the annual MDA arm. Mean height-for-age, weight-for-age and weight-for-height z scores were compared between treatment arms. RESULTS: No significant differences in mean height-for-age, weight-for-age or weight-for-height z scores were found between the annual MDA and single MDA arms, nor was there a significant reduction in prevalence of stunting, wasting or underweight between arms. CONCLUSIONS: Our data do not provide evidence that community MDA with azithromycin improved anthropometric outcomes of children in The Gambia. This may suggest reductions in mortality associated with azithromycin MDA are due to a mechanism other than improved nutritional status

Program Design Considerations for Leadership Training for Dental and Dental Hygiene Students

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153631/1/jddj002203372012762tb05246x.pd

Значение пластики лоскутом на временной питающей ножке в замещении раневых дефектов

РАНЫ И ТРАВМЫ /ХИРКОЖИ ТРАНСПЛАНТАЦИЯПЕРЕСАДКА КОЖИДЕРМАТОПЛАСТИКАЛОСКУТЫХИРУРГИЧЕСКИЕ ЛОСКУТЫХИРУРГИЧЕСКИЕ ОПЕРАЦИИ ВОССТАНОВИТЕЛЬНЫЕ /МЕТОДЫИТАЛЬЯНСКАЯ ПЛАСТИКАПЛАСТИКА ИТАЛЬЯНСКАЯРАНЕВЫЕ ПОКРЫТИЯЦель. Провести комплексный анализ возможностей, технических особенностей и недостатков методики пластики ран перемещенным из отдаленных областей сложносоставным кожным лоскутом на временной питающей ножке при закрытии раневых дефектов конечностей. Материал и методы. В исследование включено 14 пациентов с раневыми дефектами конечностей различного происхождения, которым на восстановительном этапе лечения применен метод пластики перемещенным из отдаленных областей сложносоставным кожным лоскутом на временной питающей ножке. Раневые дефекты имели различное происхождение (глубокие отморожения, хронический остеомиелит, нейротрофические нарушения), локализацию и площадь. Показанием к данному виду полнослойной пластики служила необходимость закрытия раны в функционально значимой зоне и невозможность применения других, более простых методов кожной пластики. Результаты. Положительный ближайший результат лечения получен во всех 14 случаях перемещения полнослойных кожных лоскутов из отдаленных частей тела. В 3 случаях в раннем послеоперационном периоде отмечено развитие осложнений (критический перегиб ножки лоскута, подлоскутная гематома, краевой некроз лоскута), не повлиявших существенно на ближайший результат операции. Отдаленные результаты лечения оценены у 8 пациентов в сроки от 1 до 22 лет после операции. Ключевым моментом, определяющим отдаленный результат лечения, стала комплаентность пациента в условиях денервации лоскута и закрытия ран в функционально значимых областях. В двух случаях у пациентов, не соблюдающих рекомендации, произошел некроз лоскута в зоне опорной поверхности стопы. В остальных наблюдениях получен стойкий положительный результат. Заключение. Пластика ран перемещенным из отдаленных областей сложносоставным кожным лоскутом является эффективным методом реконструкции в функционально значимых областях в условиях ограниченных пластических резервов окружающей кожи. Денервация таких лоскутов предъявляет дополнительные требования к пациентам в плане соблюдения рекомендаций. Успех операции в отдаленные сроки во многом определяется комплаентностью пациента.Objective. Comprehensive analysis of opportunities, technical features and disadvantages of wound plasty with distant pedicled flap closing wound defects of the limbs was performed. Methods. The study included 14 patients with limb wounds of different origin, who were treated using distant pedicled flaps grafting. Wounds were of different origin (deep frostbites, chronic osteomyelitis, neurotrophic disorders), diverse localization and perimeter. The indication for this type of full-layer plastics was the need to treat the wound in a functionally significant zone and the impossibility of using other, less complex methods of skin grafting. Results. A positive immediate result of treatment was obtained in all 14 cases of distant flaps grafting. The development of complications (critical bend of the pedicle of the flap, sub-flap hematoma, the flap’s edge necrosis) was registered in 3 cases in the early postoperative period, those complications did not significantly affect the immediate outcome of the operation. Long-term outcomes of treatment were evaluated in 8 patients in terms from 1 to 22 years after the operation. The key point determining the long-term treatment outcome was the patient’s compliance in the conditions of denervation of the flap and closure of wounds in functionally important areas. A flap necrosis in the plantar area occurred in two cases in patients, who did not follow the recommendations. In the remaining observations a stable positive result was obtained. Conclusions. The distant pedicled flaps grafting is an effective method of reconstruction in functionally important areas under the conditions of limited plastic reserves of the surrounding skin. Denervation of such flaps exposes additional requirements to patients in terms of compliance with recommendations. The success of the operation in the long term period is largely determined by the patient’s compliance

Neddylation inhibition upregulates PD‐L1 expression and enhances the efficacy of immune checkpoint blockade in glioblastoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149569/1/ijc32379_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149569/2/ijc32379-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149569/3/ijc32379.pd

The HyVac4 Subunit Vaccine Efficiently Boosts BCG-Primed Anti-Mycobacterial Protective Immunity

BACKGROUND: The current vaccine against tuberculosis (TB), BCG, has failed to control TB worldwide and the protective efficacy is moreover limited to 10-15 years. A vaccine that could efficiently boost a BCG-induced immune response and thus prolong protective immunity would therefore have a significant impact on the global TB-burden. METHODS/FINDINGS: In the present study we show that the fusion protein HyVac4 (H4), consisting of the mycobacterial antigens Ag85B and TB10.4, given in the adjuvant IC31® or DDA/MPL effectively boosted and prolonged immunity induced by BCG, leading to improved protection against infection with virulent M. tuberculosis (M.tb). Increased protection correlated with an increased percentage of TB10.4 specific IFNγ/TNFα/IL-2 or TNFα/IL-2 producing CD4 T cells at the site of infection. Moreover, this vaccine strategy did not compromise the use of ESAT-6 as an accurate correlate of disease development/vaccine efficacy. Indeed both CD4 and CD8 ESAT-6 specific T cells showed significant correlation with bacterial levels. CONCLUSIONS/SIGNIFICANCE: H4-IC31® can efficiently boost BCG-primed immunity leading to an increased protective anti-M.tb immune response dominated by IFNγ/TNFα/IL-2 or TNFα/IL2 producing CD4 T cells. H4 in the CD4 T cell inducing adjuvant IC31® is presently in clinical trials

Regulation of Mycobacterium tuberculosis-Dependent HIV-1 Transcription Reveals a New Role for NFAT5 in the Toll-Like Receptor Pathway

Tuberculosis (TB) disease in HIV co-infected patients contributes to increased mortality by activating innate and adaptive immune signaling cascades that stimulate HIV-1 replication, leading to an increase in viral load. Here, we demonstrate that silencing of the expression of the transcription factor nuclear factor of activated T cells 5 (NFAT5) by RNA interference (RNAi) inhibits Mycobacterium tuberculosis (MTb)-stimulated HIV-1 replication in co-infected macrophages. We show that NFAT5 gene and protein expression are strongly induced by MTb, which is a Toll-like receptor (TLR) ligand, and that an intact NFAT5 binding site in the viral promoter of R5-tropic HIV-1 subtype B and subtype C molecular clones is required for efficent induction of HIV-1 replication by MTb. Furthermore, silencing by RNAi of key components of the TLR pathway in human monocytes, including the downstream signaling molecules MyD88, IRAK1, and TRAF6, significantly inhibits MTb-induced NFAT5 gene expression. Thus, the innate immune response to MTb infection induces NFAT5 gene and protein expression, and NFAT5 plays a crucial role in MTb regulation of HIV-1 replication via a direct interaction with the viral promoter. These findings also demonstrate a general role for NFAT5 in TLR- and MTb-mediated control of gene expression

An Integrative Design Framework for New Service Development

Service innovation is focused on customer value creation. At its core, customer-centric service innovation in an increasingly digital world is technology-enabled, human-centered, and process-oriented. This requires a cross-disciplinary, holistic approach to new service design and development (NSD). This paper proposes a new service strategy-aligned integrative design framework for NSD. It correlates the underlying theories and principles of disparate but interrelated aspects of service design thinking: service strategy, concept, design, experience and architecture into a coherent framework for NSD, consistent with the service brand value. Application of the framework to NSD is envisioned to be iterative and holistic, accentuated on continuous organizational and customer learning. The preliminary framework's efficacy is illustrated using a simplified telecom case example. © Springer International Publishing Switzerland 2014

Molecular mechanisms of EGF signaling-dependent regulation of pipe, a gene crucial for dorsoventral axis formation in Drosophila

During Drosophila oogenesis the expression of the sulfotransferase Pipe in ventral follicle cells is crucial for dorsoventral axis formation. Pipe modifies proteins that are incorporated in the ventral eggshell and activate Toll signaling which in turn initiates embryonic dorsoventral patterning. Ventral pipe expression is the result of an oocyte-derived EGF signal which down-regulates pipe in dorsal follicle cells. The analysis of mutant follicle cell clones reveals that none of the transcription factors known to act downstream of EGF signaling in Drosophila is required or sufficient for pipe regulation. However, the pipe cis-regulatory region harbors a 31-bp element which is essential for pipe repression, and ovarian extracts contain a protein that binds this element. Thus, EGF signaling does not act by down-regulating an activator of pipe as previously suggested but rather by activating a repressor. Surprisingly, this repressor acts independent of the common co-repressors Groucho or CtBP