Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer.

Breast cancer remains as a significant cause of morbidity and mortality in women. Ultrastructural and biochemical evidence from breast biopsy tissue and cancer cells shows mitochondrial abnormalities that are incompatible with energy production through oxidative phosphorylation (OxPhos). Consequently, breast cancer, like most cancers, will become more reliant on substrate level phosphorylation (fermentation) than on oxidative phosphorylation (OxPhos) for growth consistent with the mitochondrial metabolic theory of cancer. Glucose and glutamine are the prime fermentable fuels that underlie therapy resistance and drive breast cancer growth through substrate level phosphorylation (SLP) in both the cytoplasm (Warburg effect) and the mitochondria (Q-effect), respectively. Emerging evidence indicates that ketogenic metabolic therapy (KMT) can reduce glucose availability to tumor cells while simultaneously elevating ketone bodies, a non-fermentable metabolic fuel. It is suggested that KMT would be most effective when used together with glutamine targeting. Information is reviewed for suggesting how KMT could reduce systemic inflammation and target tumor cells without causing damage to normal cells. Implementation of KMT in the clinic could improve progression free and overall survival for patients with breast cancer.

Clinically-Orientated Anatomy: Five exemplars to portray the concept

It has become almost a truism that, as for many biomedical sciences courses, gross anatomy tuition for healthcare curricula (including medicine and dentistry) should be integrated with clinical components to improve vocational relevance. Nevertheless, many fundamental questions remain to be answered relating to the content to be taught, who teaches the discipline, how the students react, and whether the students are prepared to integrate the clinical and biomedical components. We additionally need evidence of how the delivery of clinical content is influenced by technical developments such as medical imaging. This article documents some examples, or case scenarios, showing how interactions between professional anatomists and clinicians can be fostered, as well as providing illustrations of different teaching styles. From a review of the literature, as well as from our own experiences, we conclude that, for many branches of medicine, it is essential to have access to human bodies for both anatomical and clinical education and training and that postgraduate anatomical teaching remains important for a variety of specialities. We therefore support the notion that a close relationship between professional anatomists and surgeons can reinforce core anatomical knowledge by deepening the understanding of its clinical importance. Paradoxically, however, there is evidence that medical students do not believe that the teachers of anatomy should necessarily be clinically qualified. Furthermore, while students appreciate the value of using clinical examples, scenarios or case histories in anatomy teaching, they remain ambivalent about their use in assessments or examinations. This article also emphasises that anatomy is important both as a scientific and a clinical, translational discipline and argues that the discipline is crucial for appreciation of the human body, not just in disease, but also in health

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The Peptide Network between Tetanus Toxin and Human Proteins Associated with Epilepsy.

Sequence matching analyses show that Clostridium tetani neurotoxin shares numerous pentapeptides (68, including multiple occurrences) with 42 human proteins that, when altered, have been associated with epilepsy. Such a peptide sharing is higher than expected, nonstochastic, and involves tetanus toxin-derived epitopes that have been validated as immunopositive in the human host. Of note, an unexpected high level of peptide matching is found in mitogen-activated protein kinase 10 (MK10), a protein selectively expressed in hippocampal areas. On the whole, the data indicate a potential for cross-reactivity between the neurotoxin and specific epilepsy-associated proteins and may help evaluate the potential risk for epilepsy following immune responses induced by tetanus infection. Moreover, this study may contribute to clarifying the etiopathogenesis of the different types of epilepsy.

Ovarian cancer: designing effective vaccines and specific diagnostic tools.

AIM: Notwithstanding a renewed interest in the application of immunotherapy as an alternative to chemotherapy and radiotherapy for the treatment of ovarian cancer (OC), and in spite of the available knowledge about ovarian tumor-associated-antigens, the search for a vaccine against OC remains a scientific and clinical challenge. Likewise, immunodiagnostics can detect only a late stage of the disease. Thus, the development of new therapeutic and diagnostic options is highly desirable. METHODS: Based on the low-similarity hypothesis, which supports the concept that immunogenicity is preferentially associated to sequences with no/low-similarity to the host proteome, and using Protein Information Resource peptide match program, we searched the ovarian tumor antigen CA125 for amino acid sequences unique to CA125 and absent in the remaining human proteins. RESULTS & CONCLUSION: We identified a set of 159 pentapeptides unique to CA125 that might be used to design specific and effective immunological tools for diagnosis and treatment of OC.

Human papillomavirus (HPV) vaccines as an option for preventing cervical malignancies: (how) effective and safe?

We carried out a systematic review of HPV vaccine pre- and post-licensure trials to assess the evidence of their effectiveness and safety. We find that HPV vaccine clinical trials design, and data interpretation of both efficacy and safety outcomes, were largely inadequate. Additionally, we note evidence of selective reporting of results from clinical trials (i.e., exclusion of vaccine efficacy figures related to study subgroups in which efficacy might be lower or even negative from peer-reviewed publications). Given this, the widespread optimism regarding HPV vaccines long-term benefits appears to rest on a number of unproven assumptions (or such which are at odd with factual evidence) and significant misinterpretation of available data. For example, the claim that HPV vaccination will result in approximately 70% reduction of cervical cancers is made despite the fact that the clinical trials data have not demonstrated to date that the vaccines have actually prevented a single case of cervical cancer (let alone cervical cancer death), nor that the current overly optimistic surrogate marker-based extrapolations are justified. Likewise, the notion that HPV vaccines have an impressive safety profile is only supported by highly flawed design of safety trials and is contrary to accumulating evidence from vaccine safety surveillance databases and case reports which continue to link HPV vaccination to serious adverse outcomes (including death and permanent disabilities). We thus conclude that further reduction of cervical cancers might be best achieved by optimizing cervical screening (which carries no such risks) and targeting other factors of the disease rather than by the reliance on vaccines with questionable efficacy and safety profiles.

Transobturator surgery for female stress incontinence: a comparative anatomical study of outside-in vs inside-out techniques.

OBJECTIVE To assess the specific risks of injury to neural and vascular structures inherent in two approaches to transobturator surgery for inserting a suburethral sling, i.e. the outside-in (standard technique) and inside-out approaches. MATERIALS AND METHODS The study comprised seven cadavers, providing 14 obturator regions. Five specimens had a tape inserted outside-in on one side, and inside-out on the other; of the remaining two cadavers, one had an inside-out tape and one an outside-in tape, bilaterally. After tape insertion, the cadavers were dissected. Particular attention was paid to the distances between the tape and the deep external pudendal vessels, and between the tape and the posterior branch of the obturator nerve. RESULTS With the inside-out technique, the safety margins were reduced, and the external pudendal vessels and the posterior branch of the obturator nerve were at greater risk of injury. CONCLUSION The two techniques are not equivalent, with a lower risk of injury to vascular and nerve structures with the outside-in technique.

Nuclear medicine imaging technique in the erectile dysfunction evaluation: a mini-review

Functional imaging with positron emission tomography and single photon emission computed tomography is capable of visualizing subtle changes in physiological function in vivo. Erectile dysfunction(ED) diminishes quality of life for affected men and their partners. Identification of neural substrates may provide information regarding the pathophysiology of types of sexual dysfunction originating in the brain. The aim of this work is to verify the approaches of the nuclear medicine techniques in the evaluation of the erectile function/disfunction. A search using the words ED and nuclear medicine, ED and scintigraphy, ED and spect and ED and pet was done in the PubMed. The number of citations in each subject was determined. Neuroimaging techniques offer insight into brain regions involved in sexual arousal and inhibition. To tackle problems such as hyposexual disorders or ED caused by brain disorders, it is crucial to understand how the human brain controls sexual arousal and penile erection.

Imagens functionais, como o positron emission tomography e o single photon emission computed tomography são capazes de identificar súbitas alterações fisiológicas in vivo. A disfunção erétil diminui a qualidade de vida do casal. A identificação de substratos neurais pode esclarecer a fisiopatologia dos diferentes tipos de disfunções sexuais originadas no cérebro. O objetivo deste trabalho é verificar a abordagem das técnicas da medicina nuclear na avaliação da função/disfunção erétil. Uma pesquisa utilizando as palavras disfunção erétil e medicina nuclear, disfunção erétil e cintigrafia, disfunção erétil e SPECT e disfunção erétil e PET foi realizada no PubMed. O número de citações em cada palavra estudada foi determinado. Técnicas de neuroimagem permitem a avaliação das regiões cerebrais durante o estímulo ou inibição sexual. Para resolver alterações como disfunções hipossexuais ou disfunção erétil causada por alterações cerebrais, é crucial entender como o cérebro controla o estímulo sexual e a ereção peniana.

[Laparoscopic treatment of genital prolapse]. / Traitement laparoscopique des prolapsus génitaux.

Progresses performed in laparoscopic surgery during the last ten years offer the possibility to do complex and difficult gynaecologic operations by laparoscopy, specially surgical treatment of genital prolapse, with interesting results. We report the main laparoscopic techniques to treat genital prolapse. It is clear that most of the laparoscopic procedures are the same than the classical operations performed by laparotomy. The main techniques that we report treat completely the pelvic organ prolapse (POP), without any vaginal scar, avoiding the risks of the dyspareunia in the sexually active patients.

[Sacral staged reflexes to localize the pudendal compression: an anatomical validation of the concept]. / Les réflexes sacrés etagés dans l'etude de la névralgie pudendalte: validation anatomique.

Pudendal neuropathy is common. The diagnosis is clinical and the confirmation is electrophysiological. Distal pudendal nerve latencies have been used but they are unspecific and do not allow to localize the site of compression. A preliminary electrophysiological study has suggested separate innervations of the anterior and the posterior anal sphincter quadrants, so diverging from what main anatomy textbooks teach. By detailed dissections of pudendal nerve region we can confirm a dichotomy in the innervation of the two quadrants. Therefore, it seems feasible, by using the differences of staged sacral reflexes, to better localize the compressive neuropathy, with a stimulation of the clitoris and by recording latencies of different muscles.