Paradigm Shift in the Management of Rectal Cancer

Surgery for rectal cancer in the pre-Total Mesorectal Excision (TME) era was associated with high local recurrence rates. The widespread adoption of the TME technique together with the addition of neoadjuvant oncological therapies have reduced local failure rates and improved survival for patients with rectal cancer. Advances in our knowledge, better understanding of tumour biology and refinement in minimal access techniques and equipment have significantly changed the management of rectal cancer. This paper reviews these changes and proposes a paradigm shift in how rectal cancer management is conceptualised and treated, such that the treatment of rectal cancer is separated into early tumours (potentially suitable for local excison), TME tumours (optimally managed by TME) and beyond TME tumours (optimally managed by multivisceral resection outside the TME plane).     

Application of Mechanistic Models for Process Design and Development of Biologic Drug Products

Modeling approaches play a valuable role at various stages of development and life-cycle management of biopharmaceutical products. In Quality-by-Design (QbD) paradigm, quality needs to be designed into the product rather than merely confirming it through end product testing; this requires in-depth understanding of the product quality and impact of manufacturing process on product quality (Group IEW 2005, 2008, 2009). Modeling strategies in support of QbD paradigm for biologics are particularly important because of the costs involved in the development of biologic products (Group CBW 2009; Fissore and Antonello (Qual Des Biopharm Drug Prod Dev 18:565–93, 2015)). This mini-review focuses on the application of mechanistic models in the development of biologic drug products as ready-to-use solutions or lyophilized drug products. The choice of the modeling approach is dependent on the specific processes involved in the unit operation as well as intent of application of modeling. The application of models to unit operations in biologics drug product processing such as mixing (compounding), membrane transfer (ultrafiltration/diafiltration), freeze-thaw, and lyophilization, to characterize the quality risks, define the design space, provide input to control strategy, and build robustness in the process will be discussed.     

Masking of electrocardiographic features of right ventricular infarction by true posterior left ventricular infarction

An echocardiographically documented case of right ventricular infarction is reported. Electrocardiographic diagnosis was masked by concomitant true posterior left ventricular infarction. This case highlights an important limitation of electrocardiography in diagnosing right ventricular infarction.     

Contribution of neuropsychiatric symptoms in Parkinson’s disease to different domains of caregiver burden

Journal of Neurology - Caregiver burden is high among caregivers of PD patients (CPD). Neuropsychiatric symptoms are leading contributors to CPD burden, but whether different symptoms...     

Microbial Diversity and Characteristics of Kombucha as Revealed by Metagenomic and Physicochemical Analysis

Kombucha is a fermented tea made from a Symbiotic Culture of Bacteria and Yeast (SCOBY) with a long history of use as a health tonic. It is likely that most health benefits come from the tea and fermentation metabolites from specific microbial communities. Despite its growing importance as a functional health drink, the microbial ecosystem present in kombucha has not been fully documented. To characterize the microbial composition and biochemical properties of ‘The Good Brew’ original base kombucha, we used metagenomics amplicon (16S rRNA and ITS) sequencing to identify the microbial communities at the taxonomic level. We identified 34 genera with 200 microbial species yet described in kombucha. The dominance of organic acid producing microorganisms Acetobacter, Komagataeibacter and Starmerella are healthy for the human gut and their glucose metabolising activities have a putative role in preventing conditions such as diabetes and obesity. Kombucha contains high protein (3.31 µg/mL), high phenolic content (290.4 mg/100 mL) and low sugars (glucose: 1.87 g/L; sucrose 1.11 g/L; fructose: 0.05 g/L) as compared to green tea. The broad microbial diversity with proven health benefits for the human gut suggests kombucha is a powerful probiotic. These findings are important to improve the commercial value of kombucha and uncover the immense prospects for health benefits.     

Nanoformulations as a strategy to overcome the delivery limitations of cannabinoids

Medical cannabis has received significant interest in recent years due to its promising benefits in the management of pain, anxiety, depression and neurological and movement disorders. Specifically, the major phytocannabinoids derived from the cannabis plant such as (−) trans-Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), have been shown to be responsible for the pharmacological and therapeutic properties. Recently, these phytocannabinoids have also attracted special attention in cancer treatment due to their well-known palliative benefits in chemotherapy-induced nausea, vomiting, pain and loss of appetite along with their anticancer activities. Despite the enormous pharmacological benefits, the low aqueous solubility, high instability (susceptibility to extensive first pass metabolism) and poor systemic bioavailability restrict their utilization at clinical perspective. Therefore, drug delivery strategies based on nanotechnology are emerging to improve pharmacokinetic profile and bioavailability of cannabinoids as well as enhance their targeted delivery. Here, we critically review the nano-formulation systems engineered for overcoming the delivery limitations of native phytocannabinoids including polymeric and lipid-based nanoparticles (lipid nano capsules (LNCs), nanostructured lipid carriers (NLCs), nanoemulsions (NE) and self-emulsifying drug delivery systems (SEDDS)), ethosomes and cyclodextrins as well as their therapeutic applications.