The hypoactive corpora cavernosa with degenerative erectile dysfunction: a new syndrome

BACKGROUND: In a group of 22 patients with erectile dysfunction, vasculogenic, neurogenic, endocrinologic or psychogenic investigations failed to find a cause for their erectile dysfunction. The electro-cavernosograms of these patients recorded a diminished activity. We investigated the hypothesis that diminished corpus cavernosum electromyography activity was the cause of erectile dysfunction in these patients. METHODS: The study comprised the above mentioned 22 patients (study group, 43.8 ± 5.9 SD years) and 15 healthy volunteers (control group, 41.8 ± 5.1 SD years). The electro-cavernosograms were recorded in the flaccid, erectile and detumescent phases by 2 electrodes inserted into the corpus cavernosum. RESULTS: The electro-cavernosogram of the healthy volunteers registered in the flaccid phase regular slow waves and random action potentials. The wave variables declined significantly in the erectile phase (p < 0.01). In the study group, the slow wave variables in the flaccid phase exhibited a significant decrease (p < 0.05) compared to the healthy volunteers, and the rhythm was irregular. Erection did not occur with sildenafil administration or intracavernosal papaverine injection, and penile implant was performed. Biopsy examination showed degenerated muscle fibers, and fragmented collagen and elastic fibers with areas of fibrosis. CONCLUSION: A novel concept of the cause of erectile dysfunction was presented. Corpora cavernosa showed degenerative changes on histopathologic examination and exhibited diminished electromyography activity. They did not respond to sildenafil administration or intracavernosal papaverine injection. Penile implants were the only treatment. The condition is given the name 'hypoactive corpus cavernosum'. The cause of corpus cavernosum degenerative changes needs further study

Needs assessment to strengthen capacity in water and sanitation research in Africa:experiences of the African SNOWS consortium

Despite its contribution to global disease burden, diarrhoeal disease is still a relatively neglected area for research funding, especially in low-income country settings. The SNOWS consortium (Scientists Networked for Outcomes from Water and Sanitation) is funded by the Wellcome Trust under an initiative to build the necessary research skills in Africa. This paper focuses on the research training needs of the consortium as identified during the first three years of the project

The burden and risks of pediatric pneumonia in Nigeria: A desk‐based review of existing literature and data

Background: Pneumonia is a leading killer of children under‐5 years, with a high burden in Nigeria. We aimed to quantify the regional burden and risks of pediatric pneumonia in Nigeria, and specifically the states of Lagos and Jigawa. / Methods: We conducted a scoping literature search for studies of pneumonia morbidity and mortality in under‐5 children in Nigeria from 10th December 2018 to 26th April 2019, searching: Cochrane, PubMed, and Web of Science. We included grey literature from stakeholders' websites and information shared by organizations working in Nigeria. We conducted multivariable logistic regression using the 2016 to 2017 Multiple Cluster Indicators Survey data set to explore factors associated with pneumonia. Descriptive analyses of datasets from 2010 to 2019 was done to estimate trends in mortality, morbidity, and vaccination coverage. / Results: We identified 25 relevant papers (10 from Jigawa, 8 from Lagos, and 14 national data). None included data on pneumonia or acute respiratory tract infection burden in the health system, inpatient case‐fatality rates, severity, or age‐specific pneumonia mortality rates at state level. Secondary data analysis found that no household or caregiver socioeconomic indicators were consistently associated with self‐reported symptoms of cough and/or difficulty breathing, and seasonality was inconsistently associated, dependant on region. / Conclusion: There is a clear evidence gap around the burden of pediatric pneumonia in Nigeria, and challenges with the interpretation of existing household survey data. Improved survey approaches are needed to understand the risks of pediatric pneumonia in Nigeria, alongside the need for investment in reliable routine data systems to provide data on the clinical pneumonia burden in Nigeria

Health system challenges for improved childhood pneumonia case management in Lagos and Jigawa, Nigeria

Background: Case fatality rates for childhood pneumonia in Nigeria remain high. There is a clear need for improved case management of pneumonia, through the sustainable implementation of the Integrated Management of Childhood Illnesses (IMCI) diagnostic and treatment algorithms. We explored barriers and opportunities for improved case management of childhood pneumonia in Lagos and Jigawa states, Nigeria. / Methods: A mixed‐method analysis was conducted to assess the current health system capacity to deliver quality care. This was done through audits of 16 facilities in Jigawa and 14 facilities in Lagos, questionnaires (n = 164) and 13 focus group discussions with providers. Field observations provided context for data analysis and triangulation. / Results: There were more private providers in Lagos (4/8 secondary facilities) and more government providers in Jigawa (4/8 primary, 3/3 secondary, and 1/1 tertiary facilities). Oxygen and pulse oximeters were available in two of three in Jigawa and six of eight in Lagos of the sampled secondary care facilities. None of the eight primary facilities surveyed in Jigawa had oxygen or pulse oximetry available while in Lagos two of three primary facilities had oxygen and one of three had pulse oximeters. Other IMCI and emergency equipment were also lacking including respiratory rate timers, particularly in Jigawa state. Health care providers scored poorly on knowledge of IMCI, though previous IMCI training was associated with better knowledge. Key enabling factors in delivering pediatric care highlighted by health care providers included accountability procedures and feedback loops, the provision of free medication for children, and philanthropic acts. Common barriers to provide care included the burden of out‐of‐pocket payments, challenges in effective communication with caregivers, delayed presentation, and lack of clear diagnosis, and case management guidelines. / Conclusion: There is an urgent need to improve how the prevention and treatment of pediatric pneumonia is directed in both Lagos and Jigawa. Priority areas for reducing pediatric pneumonia burden are training and mentoring of health care providers, community health education, and introduction of oximeters and oxygen supply

Proteomics: in pursuit of effective traumatic brain injury therapeutics

Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients

N-player quantum games in an EPR setting

The $N$-player quantum game is analyzed in the context of an Einstein-Podolsky-Rosen (EPR) experiment. In this setting, a player's strategies are not unitary transformations as in alternate quantum game-theoretic frameworks, but a classical choice between two directions along which spin or polarization measurements are made. The players' strategies thus remain identical to their strategies in the mixed-strategy version of the classical game. In the EPR setting the quantum game reduces itself to the corresponding classical game when the shared quantum state reaches zero entanglement. We find the relations for the probability distribution for $N$-qubit GHZ and W-type states, subject to general measurement directions, from which the expressions for the mixed Nash equilibrium and the payoffs are determined. Players' payoffs are then defined with linear functions so that common two-player games can be easily extended to the $N$-player case and permit analytic expressions for the Nash equilibrium. As a specific example, we solve the Prisoners' Dilemma game for general $N \ge 2$. We find a new property for the game that for an even number of players the payoffs at the Nash equilibrium are equal, whereas for an odd number of players the cooperating players receive higher payoffs.Comment: 26 pages, 2 figure

On the pathogenesis of penile venous leakage: role of the tunica albuginea

<p>Abstract</p> <p>Background</p> <p>Etiology of venogenic erectile dysfunction is not exactly known. Various pathologic processes were accused but none proved entirely satisfactory. These include presence of large venous channels draining corpora cavernosa, Peyronie's disease, diabetes and structural alterations in fibroblastic components of trabeculae and cavernous smooth muscles. We investigated hypothesis that tunica albuginea atrophy with a resulting subluxation and redundancy effects venous leakage during erection.</p> <p>Methods</p> <p>18 patients (mean age 33.6 ± 2.8 SD years) with venogenic erectile dysfunction and 17 volunteers for control (mean age 31.7 ± 2.2 SD years) were studied. Intracorporal pressure was recorded in all subjects; tunica albuginea biopsies were taken from 18 patients and 9 controls and stained with hematoxylin and eosin and Masson's trichrome stains.</p> <p>Results</p> <p>In flaccid phase intracorporal pressure recorded a mean of 11.8 ± 0.8 cm H₂O for control subjects and for patients of 5.2 ± 0.6 cm, while during induced erection recorded 98.4 ± 6.2 and 5.9 ± 0.7 cmH₂O, respectively. Microscopically, tunica albuginea of controls consisted of circularly-oriented collagen impregnated with elastic fibers. Tunica albuginea of patients showed degenerative and atrophic changes of collagen fibers; elastic fibers were scarce or absent.</p> <p>Conclusion</p> <p>Study has shown that during erection intracorporal pressure of patients with venogenic erectile dysfunction was significantly lower than that of controls. Tunica albuginea collagen fibers exhibited degenerative and atrophic changes which presumably lead to tunica albuginea subluxation and floppiness. These tunica albuginea changes seem to explain cause of lowered intracorporal pressure which apparently results from loss of tunica albuginea veno-occlusive mechanism. Causes of tunica albuginea atrophic changes and subluxation need to be studied.</p

Grb2 depletion under non-stimulated conditions inhibits PTEN, promotes Akt-induced tumor formation and contributes to poor prognosis in ovarian cancer

In the absence of extracellular stimulation the adaptor protein growth factor receptor-bound protein (Grb2) and the phospholipase Plcγ1 compete for the same binding site on fibroblast growth factor receptor 2 (FGFR2). Reducing cellular Grb2 results in upregulation of Plcγ1 and depletion of the phospholipid PI(4,5)P2. The functional consequences of this event on signaling pathways are unknown. We show that the decrease in PI(4,5)P2 level under non-stimulated conditions inhibits PTEN activity leading to the aberrant activation of the oncoprotein Akt. This results in excessive cell proliferation and tumor progression in a xenograft mouse model. As well as defining a novel mechanism of Akt phosphorylation with important therapeutic consequences, we also demonstrate that differential expression levels of FGFR2, Plcγ1 and Grb2 correlate with patient survival. Oncogenesis through fluctuation in the expression levels of these proteins negates extracellular stimulation or mutation and defines them as novel prognostic markers in ovarian cancer

Cocaine Is Low on the Value Ladder of Rats: Possible Evidence for Resilience to Addiction

International audienceBACKGROUND:Assessing the relative value of cocaine and how it changes with chronic drug use represents a long-standing goal in addiction research. Surprisingly, recent experiments in rats--by far the most frequently used animal model in this field--suggest that the value of cocaine is lower than previously thought.METHODOLOGY/PRINCIPAL FINDINGS:Here we report a series of choice experiments that better define the relative position of cocaine on the value ladder of rats (i.e., preference rank-ordering of different rewards). Rats were allowed to choose either taking cocaine or drinking water sweetened with saccharin--a nondrug alternative that is not biologically essential. By systematically varying the cost and concentration of sweet water, we found that cocaine is low on the value ladder of the large majority of rats, near the lowest concentrations of sweet water. In addition, a retrospective analysis of all experiments over the past 5 years revealed that no matter how heavy was past cocaine use most rats readily give up cocaine use in favor of the nondrug alternative. Only a minority, fewer than 15% at the heaviest level of past cocaine use, continued to take cocaine, even when hungry and offered a natural sugar that could relieve their need of calories.CONCLUSIONS/SIGNIFICANCE:This pattern of results (cocaine abstinence in most rats; cocaine preference in few rats) maps well onto the epidemiology of human cocaine addiction and suggests that only a minority of rats would be vulnerable to cocaine addiction while the large majority would be resilient despite extensive drug use. Resilience to drug addiction has long been suspected in humans but could not be firmly established, mostly because it is difficult to control retrospectively for differences in drug self-exposure and/or availability in human drug users. This conclusion has important implications for preclinical research on the neurobiology of cocaine addiction and for future medication development