Endolumenal colon occlusion device for transanal and transrectal surgery—a porcine feasibility study

Purpose

Although several studies have demonstrated the feasibility of transrectal natural orifice translumenal endoscopic surgery (NOTES), its clinical application has been hindered by concerns regarding potential infectious complications. The aim of this study was to evaluate the feasibility of a newly developed device for endolumenal colon occlusion (ColoShield) in an acute porcine model.

Methods

The principle of the ColoShield device is based on two balloons, with negative pressure in between. The ColoShield device and a gauze tamponade as a control group were evaluated in a non-survival study on 16 pigs. The efficacy of the occlusion system in establishing a leak-proof pneumorectum and in sealing the colon from proximal (watertight sealing) was tested by a standardized study course. Finally, the colon/rectum was explanted for macroscopic and microscopic examination.

Results

A 20-mmHg leak-proof pneumorectum over a period of 10 min could be achieved in seven of eight (87 %) animals with the ColoShield device and in none of eight (0 %) animals with gauze tamponade (p?<?0.001). In the watertight sealing test, mean intracolonic pressures of 23.5?±?18.1 (0–53) mmHg using the ColoShield device and 0?±?1.1 (0–3) mmHg using gauze tamponade (p?=?0.003) were documented proximal to the occlusion system before a leakage occurred. Macroscopic and histopathological examinations revealed no significant impairment of the colon specimen in either group.

Conclusions

ColoShield proved to be a safe and effective device for a reversible endolumenal colon occlusion. Further studies should evaluate its impact on procedural sterility during transrectal NOTES.     

Attitudes about the safety and efficacy of bariatric surgery among patients with type 2 diabetes and a body mass index of 30–40 kg/m2

BackgroundDespite increasing awareness within the medical community about the benefits of bariatric surgery for type 2 diabetes mellitus (T2DM), little is known about patients’ attitudes toward bariatric surgery as a treatment for T2DM. The objective of this study was to investigate the attitudes of individuals with T2DM and a body mass index of 30 to 40 kg/m² concerning bariatric surgery for the treatment of T2DM.MethodsPatients identified from the Pennsylvania Integrated Clinical and Administrative Research Database (PICARD) were surveyed about perceptions of the safety profile and efficacy of bariatric surgery as a treatment for obesity and T2DM and their willingness to be randomly assigned to receive a surgical procedure.ResultsA total of 130 individuals of 513 (25.3%) responded. Respondents had a median (interquartile range) age of 58.0 (range 51.0–63.0) years and self-reported body mass index of 32.9 (range 30.9–35.2) kg/m². Roughly half (66 of 130) were female. Overall, only 20.3% of respondents had positive views of bariatric surgery, with few reporting that it is a safe (14.3%) and effective (28.5%) treatment for T2DM. Less than 20% of respondents were willing to be randomly assigned to undergo a surgical procedure for the treatment of diabetes (16.1%) or obesity (17.5%).ConclusionsFew obese individuals with T2DM who responded to the survey had positive views about bariatric surgery. Patients’ concerns about the procedure’s safety profile and efficacy must be addressed to improve the acceptability of bariatric surgery as well as the feasibility of randomized, controlled trials of bariatric surgery for these individuals.     

Maximized song learning of juvenile male zebra finches following BDNF expression in the HVC

During song learning, vocal patterns are matched to an auditory memory acquired from a tutor, a process involving sensorimotor feedback. Song sensorimotor learning and song production of birds is controlled by a set of interconnected brain nuclei, the song control system. In male zebra finches, the beginning of the sensorimotor phase of song learning parallels an increase of the brain‐derived neurotrophic factor (BDNF) in just one part of the song control system, the forebrain nucleus HVC. We report here that transient BDNF‐mRNA upregulation in the HVC results in a maximized copying of song syllables. Each treated bird shows motor learning to an extent similar to that of the selected best learners among untreated zebra finches. Because this result was not found following BDNF overexpression in the target areas of HVC within the song system, HVC‐anchored mechanisms are limiting sensorimotor vocal learning.     

Scorpion venoms and associated toxins as anticancer agents: update on their application and mechanism of action

Cancer remains one of the deadliest non-infectious diseases of the 21^st century, causing millions of mortalities per year worldwide. Analyses of conventional treatments, such as radiotherapy and chemotherapy, have shown not only a lower therapeutic efficiency rate but also plethora of side-effects. Considering the desperate need to identify promising anticancer agents, researchers are in quest to design and develop new tumoricidal drugs from natural sources. Over the past few years, scorpion venoms have shown exemplary roles as pivotal anticancer agents. Scorpion venoms associated metabolites, particularly toxins demonstrated in vitro anticancer attributes against diversified cell lines by inhibiting the growth and progression of the cell cycle, inhibiting metastasis by blocking ion channels such as K⁺ and Cl⁻, and/or inducing apoptosis by intrinsic and extrinsic pathways. This review sheds light not only on in vitro anticancer properties of distinct scorpion venoms and their toxins, but also on their mechanism of action for designing and developing new therapeutic drugs in future.     

Deletion of integrin-linked kinase from skeletal muscles of mice resembles muscular dystrophy due to alpha 7 beta 1-integrin deficiency

Integrin-linked kinase (Ilk) is a serine/threonine kinase and an adaptor protein that links integrins to the actin cytoskeleton and to a number of signaling pathways involved in integrin action. We hypothesized that Ilk may act as an important effector of integrins in skeletal muscle, where these receptors provide a critical link between the sarcolemma and the extracellular matrix. Using the cre/lox system, we deleted Ilk from skeletal muscles of mice. The resulting mutants developed a progressive muscular dystrophy with multiple degenerating and regenerating muscle fibers, increased central nuclei, and endomysial fibrosis. These defects were widespread but were most severe near myofascial junctions where Ilk mutants showed displacement of focal adhesion-related proteins, including vinculin, paxillin, focal adhesion kinase, dystrophin, and the alpha 7 beta 1D-integrin subunits. Distal ends of mutant muscle fibers appeared irregular, and there was restructuring of the actin cytoskeleton. These findings resemble those seen in humans and mice lacking the alpha 7-integrin subunit and suggest that Ilk may act as a cytoplasmic effector of alpha 7 beta1-integrin in the pathogenesis of these deficiencies.     

Laterally closed tunnel technique with and without adjunctive photobiomodulation therapy for the management of isolated gingival recession—a randomized controlled assessor-blinded clinical trial

Lasers in Medical Science - The objective of this prospective randomized controlled single-center clinical trial was to prove the efficacy of adjunctive photobiomodulation in improving selected...     

Bone Microenvironment-Suppressed T Cells Increase Osteoclast Formation and Osteolytic Bone Metastases in Mice

Immunotherapies use components of the immune system, such as T cells, to fight cancer cells, and are changing cancer treatment, causing durable responses in some patients. Bone metastases are a debilitating complication in advanced breast and prostate cancer patients. Approved treatments fail to cure bone metastases or increase patient survival and it remains unclear whether immunotherapy could benefit patients. The bone microenvironment combines various immunosuppressive factors, and combined with T cell products could increase bone resorption fueling the vicious cycle of bone metastases. Using syngeneic mouse models, our study revealed that bone metastases from 4T1 breast cancer contain tumor-infiltrating lymphocyte (TILs) and their development is increased in normal mice compared to immunodeficient and T-cell depleted mice. This effect seemed caused by the TILs specifically in bone, because T-cell depletion increased 4T1 orthotopic tumors and did not affect bone metastases from RM-1 prostate cancer cells, which lack TILs. T cells increased osteoclast formation ex vivo and in vivo contributing to bone metastasis vicious cycle. This pro-osteoclastic effect is specific to unactivated T cells, because activated T cells, secreting interferon γ (IFNγ) and interleukin 4 (IL-4), actually suppressed osteoclastogenesis, which could benefit patients. However, non-activated T cells from bone metastases could not be activated in ex vivo cultures. 4T1 bone metastases were associated with an increase of functional polymorphonuclear and monocytic myeloid-derived suppressor cells (MDSCs), potent T-cell suppressors. Although effective in other models, sildenafil and zoledronic acid did not affect MDSCs in bone metastases. Seeking other therapeutic targets, we found that monocytic MDSCs are more potent suppressors than polymorphonuclear MDSCs, expressing programmed cell death receptor-1 ligand (PD-L1)⁺ in bone, which could trigger T-cell suppression because 70% express its receptor, programmed cell death receptor-1 (PD-1). Collectively, our findings identified a new mechanism by which suppressed T cells increase osteoclastogenesis and bone metastases. Our results also provide a rationale for using immunotherapy because T-cell activation would increase their anti-cancer and their anti-osteoclastic properties. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).