COSMOS 2044. Experiment K-7-19. Pineal physiology in microgravity: Relation to rat gonadal function

It is now known that the pineal organ can interact with many endocrine and nonendocrine tissues in a regulatory fashion. Given its key role in the regulation of melatonin synthesis, its high concentration, and that its levels may persist longer than the more rapidly changing melatonin, it was felt that serotonin might give a more accurate assessment of the effects of microgravity on pineal function following recovery of animals from flight. Five-hydroxyindole acetic acid (5-HIAA), a major metabolite of serotonin metabolism, was also measured. One of the most interesting concomitants to spaceflight and exposure to microgravity has been the disturbing alteration in calcium metabolism and resulting skeletal effects. Given the link between exposure to microgravity and perturbation of calcium metabolism and the fact that the pineal is apparently one of the only soft tissues to calcify, pineal calcium content was examined following spaceflight

Diffusion Tensor Imaging in a Large Longitudinal Series of Patients With Cervical Spondylotic Myelopathy Correlated With Long-Term Functional Outcome

BACKGROUND Fractional anisotropy (FA) of the high cervical cord correlates with upper limb function in acute cervical cord injury. We investigated the correlation between preoperative FA at the level of maximal compression and functional recovery in a group of patients after decompressive surgery for cervical spondylotic myelopathy (CSM). OBJECTIVE To determine the usefulness of FA as a biomarker for severity of CSM and as a prognostic biomarker for improvement after surgery. METHODS Patients received diffusion tensor imaging (DTI) scans preoperatively. FA values of the whole cord cross-section at the level of maximal compression and upper cervical cord (C1-2) were calculated. Functional status was measured using the modified Japanese Orthopedic Association (mJOA) scale preoperatively and at follow-up up to 2 yr. Regression analysis between FA and mJOA was performed. DTI at C4-7 was obtained in controls. RESULTS Forty-four CSM patients enrolled prior to decompression were compared with 24 controls. FA at the level of maximal compression correlated positively with preoperative mJOA score. Preoperative FA correlated inversely with recovery throughout the postoperative period. This was statistically significant at 12 mo postoperation and nearly so at 6 and 24 mo. Patients with preoperative FA0.55. CONCLUSION In the largest longitudinal study of this kind, FA promises a valid biomarker for severity of CSM and postoperative improvement. FA is an objective measure of function and could provide a basis for prognosis. FA is particularly useful if preoperative values are less than 0.55

Sesame seed sensitization in a group of atopic Egyptian children

Background: There are no published data on the prevalence of sesame allergy/sensitization in Egypt. Objective: In this pilot study, we thought to estimate the frequency of sesame seed sensitization in a group of atopic Egyptian infants and children. Methods: We consecutively enrolled 90 patients with physician diagnosed allergic disease. The study measurements included clinical evaluation for the site and duration of allergy, history suggestive of sesame seed allergy, and family history of allergy, as well as skin prick testing (SPT) using a commercial sesame extract, and serum sesame specific IgE (SpIgE) estimation. Results: None of the studied patients reported symptoms suggestive of sesame seed allergy. Nevertheless, two children (2.2%) showed positive SPT response to sesame (wheal diameter ≥ 3 mm above the negative control). Only one of them had a wheal diameter which exceeded that of the histamine control. The serum sesame SpIgE exceeded 0.35 IU/ml in all subjects [range = 0.35 - 3.0 IU/ml; median (IQR) = 0.9 (0.6) IU/ml]. Serum sesame SpIgE was significantly increased in patients with history of recurrent urticaria (p=0.03). Conclusion: Sesame seed sensitization is not uncommon in atopic Egyptian children. It can be associated with any clinical form of allergy and the causal relationship needs meticulous evaluation. Wider scale population-based studies are needed to assess the prevalence of sesame allergy and its clinical correlates in our country.Keywords: Food allergy, sesame, atopic children

Cell cycle responses to Topoisomerase II inhibition: Molecular mechanisms and clinical implications.

DNA Topoisomerase IIA (Topo IIA) is an enzyme that alters the topological state of DNA and is essential for the separation of replicated sister chromatids and the integrity of cell division. Topo IIA dysfunction activates cell cycle checkpoints, resulting in arrest in either the G2-phase or metaphase of mitosis, ultimately triggering the abscission checkpoint if non-disjunction persists. These events, which directly or indirectly monitor the activity of Topo IIA, have become of major interest as many cancers have deficiencies in Topoisomerase checkpoints, leading to genome instability. Recent studies into how cells sense Topo IIA dysfunction and respond by regulating cell cycle progression demonstrate that the Topo IIA G2 checkpoint is distinct from the G2-DNA damage checkpoint. Likewise, in mitosis, the metaphase Topo IIA checkpoint is separate from the spindle assembly checkpoint. Here, we integrate mechanistic knowledge of Topo IIA checkpoints with the current understanding of how cells regulate progression through the cell cycle to accomplish faithful genome transmission and discuss the opportunities this offers for therapy

Synthesis and evaluation of designed PKC modulators for enhanced cancer immunotherapy.

Bryostatin 1 is a marine natural product under investigation for HIV/AIDS eradication, the treatment of neurological disorders, and enhanced CAR T/NK cell immunotherapy. Despite its promising activity, bryostatin 1 is neither evolved nor optimized for the treatment of human disease. Here we report the design, synthesis, and biological evaluation of several close-in analogs of bryostatin 1. Using a function-oriented synthesis approach, we synthesize a series of bryostatin analogs designed to maintain affinity for bryostatin's target protein kinase C (PKC) while enabling exploration of their divergent biological functions. Our late-stage diversification strategy provides efficient access to a library of bryostatin analogs, which per our design retain affinity for PKC but exhibit variable PKC translocation kinetics. We further demonstrate that select analogs potently increase cell surface expression of CD22, a promising CAR T cell target for the treatment of leukemias, highlighting the clinical potential of bryostatin analogs for enhancing targeted immunotherapies

Studies on Pseudomonas aeruginosa Infection in Hatcheries and Chicken

ΔΕΝ ΔΙΑΤΙΘΕΤΑΙ ΠΕΡΙΛΗΨΗThe aim of this work was to spot light on the presence of Pseudomonas aeruginosa (P. aeruginosa) strains in hatcheries and dead in shell embryos. A total of 406 samples representing 200 and 206 swabs from hatcheries environment and yolk sacs of dead in shell embryos were collected from Damietta governorate, Egypt. P. aeruginosa was isolated and identified. Some virulent genes (toxA, psIA and fliC) of P. aeruginosa were detected using polymerase chain reaction (PCR). The antimicrobial susceptibility of P. aeruginosa was tested in vitro. Day and 11 days old broiler chicks were challenged with P. aeruginosa to determine the pathogenicity of the isolated strains. The results showed that P. aeruginosa was recovered from 16 (8%) out of 200 hatcheries and from 17 (8.25%) out of 206 chicken embryos samples. Isolated strains of P. aeruginosa showed presence of toxA, psIA and fliC virulent genes. P. aeruginosa strains were sensitive (100%) to ciprofloxacin, levofloxacin and gentamycin but resistant (100%) to amoxycillin/clavulanic acid, doxycycline and erythromycin. The pathogenicity test of day and 11 days old chicks revealed that P. aeruginosa was highly pathogenic induced mortality rates of 72 and 40%, respectively. Septicaemia of internal organs, unabsorbed yolk sacs, pneumonia, greenish exudates in the abdominal cavity, liver necrosis and enteritis were the predominant lesions. Histopathological changes supported the previous lesions. In conclusion, P. aeruginosa is of great importance pathogen of embryos and newly hatched chicks based on presence of virulent genes as well as in vivo pathogenicity study; respectively

Regional variation in histopathology‐specific incidence of invasive cervical cancer among Peruvian women

ObjectiveTo evaluate patterns of cervical cancer incidence in Peru by examining variation in 2 common histopathologic types, squamous cell carcinoma (SCC) and adenocarcinoma (ADC), and analyzing trends over time.MethodsData on the incidence of invasive cervical cancer between 1984 and 2006 were obtained from 3 population‐based cancer registries in Peru: Lima, Trujillo, and Arequipa. For each registry, data quality assessment was performed, crude and age‐specific incidence was calculated, and time trends were analyzed.ResultsOverall and SCC incidence varied across registries but incidence of ADC did not. Overall and SCC incidence showed significant declines in Trujillo (P 0.05) over time. ADC incidence showed marginally significant increases among women aged 15–29 years in Trujillo (P = 0.10) and modest increases among young women in Lima (P > 0.05).ConclusionPopulation‐based cancer registries were an efficient source of data for evaluating the incidence of cervical cancer once data quality had been established. Geographic and temporal variations in cervical cancer burden were documented in Peru. The trends suggest that cervical ADC is increasing among young women in urban Peru, particularly in Trujillo. We recommend supplementing current Papanicolaou test screening with complementary methods of cervical cancer control, including human papillomavirus (HPV) vaccination and HPV DNA testing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135622/1/ijgo47.pd

Changing Patterns of lung, liver, and head and neck non-AIDS-defining cancers relative to HIV status in Tanzania between 2002-2014

Abstract Background Tanzania, like other low-income countries, has an increasing cancer burden that remains underestimated. Infection-associated malignancies, particularly HIV-infection, represent a great proportion of cancer burden in Tanzania and throughout Africa. Availability of HIV treatment and improved survival of HIV patients are suggested factors related to increasing prevalence of non-AIDS-defining cancers (NADCs). This study examined patterns of NADCs and proportions of HIV-positivity at the Ocean Road Cancer Institute (ORCI). Methods We reviewed logbooks of all ORCI patients diagnosed and/or treated for lung, liver, and head and neck cancers during 2002–2014. The number of total cancers diagnosed at ORCI during this period was used to calculate proportions of NADCs. We abstracted medical records to obtain demographic and clinical profiles and HIV status information for 1127 patients diagnosed or treated during 2010–2014. Trends in numbers and proportions of NADCs were analyzed using Joinpoint regression. Characteristics of NADC patients were analyzed using multinomial logistic regression. Results NADCs diagnosed at ORCI increased by 33.8% from 2002 to 2014 while the proportion of NADCs relative to all cancers significantly decreased from 6.8% in 2002 to 5.6% in 2014 (APC = -2.74%). Numbers and proportions of lung and liver cancers increased compared to all cancer diagnoses from 2002 to 2014. The number of head and neck cancers increased while decreasing proportionally compared to all cancer diagnoses from 2002 to 2014. Among patients with pathologically confirmed NADCs between 2010 and 2014, HIV prevalence showed a non-statistically significant decrease from 8.1 to 7.1% (APC = -3.77%). Conclusions Absolute numbers of lung, liver, and head and neck cancers increased at ORCI by 1/3 since 2002. Improving survivorship of HIV patients and varying immunodeficiency status may have contributed to the increasing number of NADCs. Total cancer diagnoses nearly doubled during this period, leading to a smaller relative proportion of NADCs diagnosed in 2014 compared to 2002. Late- stage diagnosis and short survival of NADCs included this study may explain possible underestimation and smaller increase in proportion of these particular NADCs compared to other NADCs studied in Tanzania. The slight decrease in proportion of HIV-positive NADC patients during 2010–2014 may suggest increasing patient longevity and more effective HIV management in Tanzania.http://deepblue.lib.umich.edu/bitstream/2027.42/134744/1/13027_2016_Article_106.pd

The changing pattern of ano-rectal cancer, squamous cell carcinoma of the eye, and Hodgkin’s lymphoma as non-AIDS-defining cancers, by HIV status, in Tanzania over 11 years (2002-2012): a retrospective case-report study

Abstract Background In Tanzania, 5.1% of adults aged 15-49 are infected with HIV. While rates of HIV-related malignancies have declined globally with antiretroviral therapy (ART), including Tanzania, rates of non-AIDS-defining cancers (NADCs) are believed to have increased. Therefore, we determined trends of three NADCs in Tanzania: ano-rectal cancer, squamous cell carcinoma of the eye, and Hodgkin’s lymphoma. Methods This study was conducted at the Ocean Road Cancer Institute (ORCI) in Dar es Salaam. All medical records of patients diagnosed with ano-rectal cancer, squamous cell carcinoma of the eye, and Hodgkin’s lymphoma between 2002 and 2012 were reviewed regarding HIV status, cancer clinical characteristics and management. Analysis was conducted to determine trends and proportions in these three NADCs and patient characteristics. Results We identified 980 NADCs. The relative proportion of these three NADCs at ORCI out of all cancers treated increased from 2.37% in 2002 to a peak of 4.34% in 2009. The prevalence of HIV in patients diagnosed with these NADCs also increased—from 6.67% in 2002 to 20.87% in 2010—and 85% of squamous cell carcinoma of the eye cancer patients with a reported HIV status were HIV-positive. Conclusions The frequency and proportions of these three NADCs in Tanzania have increased over the past 11 years, as has the prevalence of HIV positivity amongst these NADC patients. The current and possibly increasing burden of NADCs in Tanzania and other low- and middle-income countries with high HIV rates should be a focus for future cancer prevention and control and HIV therapy programs.http://deepblue.lib.umich.edu/bitstream/2027.42/111050/1/13027_2014_Article_524.pd