SUMMARY Parkinson’s disease (PD) has been attributed to a combination of genetic and non-genetic factors. We studied a set of monozygotic twins harboring the heterozygous glucocerebrosidase mutation (GBA N370S) but clinically discordant for PD. We applied induced pluripotent stem (iPS) cell technology for PD disease modeling using the twins’ fibroblasts to evaluate and dissect the genetic and non-genetic contributions. Utilizing fluorescence-activated cell sorting, we obtained a homogenous population of ‘footprint-free’ iPS cell-derived midbrain dopaminergic (mDA) neurons. The mDA neurons from both twins had ~ 50% GBA enzymatic activity, ~ 3-fold elevated α-synuclein protein levels, and a reduced capacity to synthesize and release dopamine. Interestingly, the affected twin’s neurons showed an even lower dopamine level, increased monoamine oxidase B (MAO-B) expression, and impaired intrinsic network activity. Overexpression of wild-type GBA and treatment of MAO-B inhibitors normalized α-synuclein and dopamine levels, suggesting a combination therapy for the affected twin.

Induced pluripotent stem cells (iPSCs) are an essential tool for modeling how causal genetic variants impact cellular function in disease, as well as an emerging source of tissue for regenerative medicine. The preparation of somatic cells, their reprogramming and the subsequent verification of iPSC pluripotency are laborious, manual processes limiting the scale and reproducibility of this technology. Here we describe a modular, robotic platform for iPSC reprogramming enabling automated, high-throughput conversion of skin biopsies into iPSCs and differentiated cells with minimal manual intervention. We demonstrate that automated reprogramming and the pooled selection of polyclonal pluripotent cells results in high-quality, stable iPSCs. These lines display less line-to-line variation than either manually produced lines or lines produced through automation followed by single-colony subcloning. The robotic platform we describe will enable the application of iPSCs to population-scale biomedical problems including the study of complex genetic diseases and the development of personalized medicines.

Pancreaticopleural fistula is a rare diagnosis requiring a high index of clinical suspicion due to the predominant manifestation of thoracic symptoms. The current literature suggests that confirmation of elevated pleural fluid amylase is the most important diagnostic test. Magnetic resonance cholangiopancreatography is the recommended imaging modality to visualise the fistula, as it is superior to both computed tomography and endoscopic retrograde cholangiopancreatography (ERCP) in delineating the tract within the pancreatic region. It is also less invasive than ERCP. While a trial of medical regimen has traditionally been the first-line treatment, failure would result in higher rates of complications. Hence, it is suggested that management strategies be planned based on pancreatic ductal imaging, with patients having poor chances of spontaneous closure undergoing either endoscopic or surgical intervention. We also briefly describe a case of pancreaticopleural fistula in a patient who was treated using a modified Puestow procedure after failed endoscopic treatment.

There was no statistically significant difference in postoperative pain, pain site and analgesia requirement; however, patients who underwent SILC returned to their normal activity 1.8 days earlier than the LC patients. Larger RCTs are needed to compare postoperative outcomes between SILC and LC.

• MRE is superior to DWI for differentiating benign and malignant focal liver lesions. • Benign lesions with large fibrous components may have higher stiffness with MRE. • Cholangiocarcinomas tend to have higher stiffness than hepatocellular carcinomas. • Hepatocellular adenomas tend to have lower stiffness than focal nodular hyperplasia. • MRE is superior to conventional MRI in differentiating benign and malignant liver lesions.

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SILC has improved short-term pain outcomes compared to LC and is not inferior in both short-term and long-term pain outcomes. The operating time is longer, but remains feasible in routine surgical practice.

Laparoscopic drainage of cryptogenic liver abscesses should be considered as an option for drainage of liver abscess.