Journal of Medical Hypotheses and Ideas最新文献

Caesarean rate has been increasing year by year in China and other countries in the world. In fact, caesarean section is associated with increased risk of maternal mortality and serious foetal pulmonary morbidity. To reduce caesarean rate, obstetricians in physician-based birth units get used to take early intervention for any delay in labour progress that could cause dystocia. However, standard obstetric care enhanced by obstetric power has not consistently been shown to reduce rate of caesarean delivery. Other than physician-based model, midwife-led model of care is aiming to promote normal birth by use of midwives’ skills as well as continuous support rather than augmentation of labour through excessive medical treatment. Midwife-led care model is novel to worldwide birth units where standard obstetric care still dominates. It has made some headway in efforts to reduce caesarean rate. The fact that standard obstetric care of childbirth have not consistently reduced rate of caesarean delivery encourages us for creating the hypotheses that midwife-led care model satisfying puerpera with care and support could minimise unnecessary obstetric intervention and facilitate vaginal birth, and finally reduces caesarean rate. This hypothesis, if confirmed, might have the potential to be disseminated elsewhere in the world, where most women still take standard obstetric care. Moreover, it has political implications for the national health-care policymaking.

The anticancer activity demonstrated by genetically attenuated invasive Shigella flexneri contradicts the long-held understanding of bacterial infection-mediated anticancer activity (BIMAc), as a ‘by-stander effect’ caused by an immune response against any invading pathogen as a reason for tumour regression. Similarly, the selective tumouricidal effect by Salmonella A1 auxotrophic mutant in nude mice is another observation where the current theory fails. Considering these flaws, we set to re-examine the mechanisms behind BIMAc independent of immune response, on the basis of molecular understanding about the initial colonisation of gut epithelium by S. flexneri and its production of cell-cycle-inhibiting proteins called cyclomodulins. During infection, S. flexneri injects OspE effector protein into the gut epithelium. The resulting interaction of OspE with ILK prevents epithelial cell exfoliation and facilitates the pathogen’s colonisation of the gut. This interaction is also shown to enhance membrane retention of ILK in these infected cells. Correspondingly, another study reports the indispensable role of ILK in survival of cancer cells with supernumerary centrosomes by localising it to the centrosomes and clustering them into a bipolar spindle. Knockdown of ILK in these cells leads to apoptosis due to multipolar mitosis. From these cumulative facts we hypothesised that enhanced membrane retention of ILK in Shigella-infected cancer cells prevents localisation of ILK to centrosomes and provokes multipolar mitosis and therefore cell death in cancer subpopulations with supernumerary centrosomes. This interaction may also be metastasis suppressive, because of its inhibitory effect on the focal adhesion turnover of gut epithelium, which is quintessential for any form of cell migration. Apart from these, Shigella also encodes potent cell-cycle-inhibiting effector molecules such as cyclomodulins. The additive action of these cyclomodulins along with the OspE–ILK interaction may be considered as the reason behind the anticancer activity mediated by Shigella infection.

Autism is a neurodevelopment disorder. Its aetiology and pathophysiology are not clearly known. However, mitochondria may play a significant role at least in some cases of autism. There is no therapeutic approach for autism. Moreover, there are only few Food and Drug Administration (FDA)-approved medications for autism. Therefore, providing novel therapeutic approaches are highly required. Oxidative stress is suggested as an important factor in the aetiology of autism. Already some interventions targeting oxidative stress in autism are suggested.

This article reviews evidence about the possible role of gold nanoparticles and lipoic acid (LA) as anti-inflammatory agents. It mentions some evidence about the possible role of oxidative stress. Then, the role of gold nanoparticles and LA for the management of autism is discussed.

According to the above-mentioned evidence, it is hypothesised that gold nanoparticles and LA may reduce neuro-inflammation in autism.

Controlled experimental studies are needed to test whether gold nanoparticles plus LA enhance antioxidative stress system leading to the improvement of autism clinical symptoms.

Reconstruction of the extrahepatic bile duct following bile duct injury or defect is one of the most common challenges for hepatobiliary surgeons. There are currently a number of surgical strategies such as biliary-enteric anastomosis, end-to-end anastomosis and autologous tissue substitute. However, sphincter of Oddi dysfunction as well as biliary stricture may occur after surgical anastomosis. Also, insufficient tissue quantity remains a problem associated with the application of tissue substitute. Therefore, considerable attention has been attracted to explore a new replacement material of the bile duct for biliary reconstruction. The human umbilical cord (HUC) is abundant in resource and is convenient to collect, including two arteries and one vein, whose diameters are close to that of the common bile duct. In order to reduce immunogenicity (foreign-body reaction), cells and major histocompatibility complex (MHC) antigens can be removed from the HUC and the remaining tissue (extracellular matrix, ECM) can be used as a scaffold. The HUC provides a rich source of mesenchymal stem cells (MSCs). A current study has demonstrated that MSCs are able to differentiate into biliary epithelial cells in vivo and in vitro with low immunogenicity, which can be used as seed cells. The HUC might be a promising composite material of a scaffold (ECM) and seed cells (biliary epithelial cells), for bile duct replacement in situ without removal of sphincter of Oddi, or biliary stricture. In addition, the patients’ own umbilical cord without any foreign-body reaction can be directly banked for possible future use in bile duct reconstruction. Therefore, we hypothesise that the HUC may be a novel substitute for reconstruction of the extrahepatic bile duct.