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Informed consent and shared decision making (SDM) are crucial portions of preoperative patient management. Informed consent is a standard for surgery from both a legal and ethical standpoint, involving disclosure of potential risks of a procedure and ensuring patient understanding of these risks. SDM is a process in which a clinician and patients decide between two or more treatment plans, taking into account the patient's goals and values. SDM is a particularly important aspect of patient-centered care when two or more treatment options exist or in situations where an indicated treatment may not align with the patient's long-term goals. This article details aspects of and issues surrounding informed consent and SDM.

Glaucoma is a multifactorial progressive optic neuropathy characterized by the loss of retinal ganglion cells leading to irreversible blindness. It is the leading cause of global irreversible blindness and is currently affecting over 70 million people. Elevated intraocular pressure (IOP) is considered the only modifiable risk factor and is a target of numerous treatment modalities. Researchers have assigned this elevation of IOP to accumulation of extracellular matrix (ECM) components in the aqueous humor (AH) outflow pathway. The major drainage structure for AH outflow is the trabecular meshwork (TM). The ECM of the TM is important in regulating IOP in both normal and glaucomatous eyes. In this work, we have studied the role of exogeneous glycosaminoglycans (GAGs), glucocorticoids, and culture conditions on the expression of the ECM gene and proteins by human TM (hTM) cells cultured on biomaterial scaffolds. Gene and protein expression levels of elastin, laminin, and matrix metalloproteinase-2 (MMP-2) were evaluated using quantitative PCR and immunohistochemistry. Pressure gradient changes in cell-laden scaffolds in perfusion cultures were also monitored. Our findings show that GAGs and dexamethasone play an influencing role in hTM ECM turnover at both transcriptional and translational levels by altering expression levels of elastin, laminin, and MMP-2. Understanding the role of exogeneous factors on hTM cell behavior is helpful in gaining insights on glaucoma pathogenesis and ultimately pivotal in development of novel therapeutics against the disease.

Very low carbohydrate/ketogenic diets (VLC/KDs) are popular but their role in managing pre-diabetes and type 2 diabetes (T2D) is uncertain. This study uses a systematic review and meta-analysis of randomized controlled trials to estimate the effect of these diets in this population.A systematic review identified randomized controlled trials of at least 6 months duration comparing efficacy and safety of VLC/KDs (≤50 g carbohydrate or ≤10% total energy from carbohydrate per day) with a control diet (carbohydrate above the VLC/KD threshold) in adults with pre-diabetes or T2D. The primary outcome variable was glycated haemoglobin (HbA1c) after 12 months. The meta-analysis method was inverse variance weighting of mean values for continuous variables.Key word searches identified 2290 studies; 2221 were not in scope. A full text review of 69 studies identified eight meeting inclusion criteria; in total, it involved 606 participants. Six studies reported HbA1c (%) at 12 months; four as change from baseline with a fixed effects estimate (95% confidence interval): VLC/KD minus control of 0.01% (-0.22 to 0.25), p = .91; and two as change from baseline: -0.65% (-0.99; -0.31) [-7.1 mmol/mol (-10.8; -3.4)], p .001. Serum triglycerides were lower with VLC/KD versus control: -0.28 mmol/L (-0.44 to -0.11), p .001. High-density lipoprotein was higher with an estimate of 0.04 mmol/L (0.01 to 0.08), p = .03, in the five studies reporting 12-month summary data.A VLC/KD may cause reductions in HbA1c and triglycerides in those with pre-diabetes or T2D but evidence of an advantage over other strategies is limited. More well-designed studies are required to provide certain evidence.

There is increasing evidence that adherence to a Mediterranean dietary pattern reduces the incidence of diet-related diseases. To date, the habitual dietary intake of New Zealand (NZ) adults has not been examined in relation to its alignment with a Mediterranean-style dietary pattern. This study aimed to define the habitual dietary patterns, nutrient intakes, and adherence to the Mediterranean Diet in a sample of 1012 NZ adults (86% female, mean age 48 ± 16 years) who had their diabetes risk defined by the Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK). Dietary intakes were collected using a validated semi-quantitative NZ food frequency questionnaire, and dietary patterns were identified using principal component analysis. Reported intakes from the FFQ were used in conjunction with the Mediterranean-Style Dietary Pattern Score (MSDPS) to determine adherence to a Mediterranean dietary pattern. Mixed linear models were used to analyze the association between dietary patterns and MSDPS with demographics, health factors, and nutrient intakes. Two distinct dietary patterns were identified: Discretionary (positive loadings on processed meat, meat/poultry, fast food, sweet drinks, and sugar, sweets, and baked good) and Guideline (positive loadings on vegetables, eggs/beans, and fruits). Adherence to dietary patterns and diet quality was associated with age and ethnicity. Dietary patterns were also associated with sex. Adherence to a Mediterranean dietary pattern defined by the MSDPS was low, indicating that a significant shift in food choices will be required if the Mediterranean Diet is to be adopted in the NZ population.

Medulloblastoma and central nervous system primitive neuroectodermal tumors (CNS-PNET) are aggressive, poorly differentiated brain tumors with limited effective therapies. Using Sleeping Beauty (SB) transposon mutagenesis, we identified novel genetic drivers of medulloblastoma and CNS-PNET. Cross-species gene expression analyses classified SB-driven tumors into distinct medulloblastoma and CNS-PNET subgroups, indicating they resemble human Sonic hedgehog and group 3 and 4 medulloblastoma and CNS neuroblastoma with FOXR2 activation. This represents the first genetically induced mouse model of CNS-PNET and a rare model of group 3 and 4 medulloblastoma. We identified several putative proto-oncogenes including Arhgap36, Megf10, and Foxr2. Genetic manipulation of these genes demonstrated a robust impact on tumorigenesis in vitro and in vivo. We also determined that FOXR2 interacts with N-MYC, increases C-MYC protein stability, and activates FAK/SRC signaling. Altogether, our study identified several promising therapeutic targets in medulloblastoma and CNS-PNET.Significance:A transposon-induced mouse model identifies several novel genetic drivers and potential therapeutic targets in medulloblastoma and CNS-PNET.

Figure S4. Shows ARHGAP36 expression in mouse and human neural tissue. Figure S5. Shows characterization of ARHGAP36 and Megf10 in C17.2 cells Figures S6-S7 show mechanistic analysis of FOXR2 in C17.2 and HSC1L cells

Characterization of SB-induced medulloblastomas and CNS-PNETs.

Diabetic foot ulcers (DFUs) are a devastating ailment for many diabetic patients with increasing prevalence and morbidity. The complex pathophysiology of DFU wound environments has made finding effective treatments difficult. Standard wound care treatments have limited efficacy in healing these types of chronic wounds. Topical biomaterial gels have been developed to implement novel treatment approaches to improve therapeutic effects and are advantageous due to their ease of application, tunability, and ability to improve therapeutic release characteristics. Here, we provide an updated, comprehensive review of novel topical biomaterial gels developed for treating chronic DFUs. This review will examine preclinical data for topical gel treatments in diabetic animal models and clinical applications, focusing on gels with protein/peptides, drug, cellular, herbal/antioxidant, and nano/microparticle approaches. Statement of Significance : By 2050, 1 in 3 Americans will develop diabetes, and up to 34% of diabetic patients will develop a diabetic foot ulcer (DFU) in their lifetime. Current treatments for DFUs include debridement, infection control, maintaining a moist wound environment, and pressure offloading. Despite these interventions, a large number of DFUs fail to heal and are associated with a cost that exceeds $31 billion annually. Biomaterials have been developed to help target specific impairments associated with DFU with the goal to improve healing. A summary of these approaches is needed to help better understand the current state of the research.. This review summarizes recent research and advances in topical biomaterials treatments for DFUs.

Glaucoma is the leading cause of irreversible blindness in the world, currently impacting 80 million people. Patients suffering from primary open-angle glaucoma experience aqueous humor accumulatio...

Hydrogels are three-dimensional networks of hydrophilic polymers that have garnered significant attention as wound-healing materials. Many synthetic hydrogels are fabricated using a radical polymerization approach that requires an initiator molecule that is often photo- or thermosensitive. Initiator-free hydrogels are an emerging area of research that focuses on hydrogel fabrication that occurs in the absence of an initiator or cross-linker molecule, making these hydrogels highly relevant in tissue engineering and regenerative medicine due to their excellent cytocompatibility and ease of scale-up. Here we present on the development of initiator-free zwitterionic hydrogels that photopolymerize without any initiator or cross-linker while under cytocompatible conditions. The hydrogels exhibit a wide range of mechanical characteristics that are dependent on their polymer composition. They resist nonspecific protein adsorption and exhibit a sustained release of proteins and small molecules. Additionally, these self-initiated hydrogels significantly mitigate inflammatory macrophage activation in vitro. Overall, the development of self-initiated photopolymerized zwitterionic hydrogels offers significant progress in the fields of biomaterials and materials science.

BACKGROUND The prevalence of hyperprolactinaemia in women presenting for infertility investigation has been found to be up to 17%, and many of these women are asymptomatic. Prolactin levels may be elevated by stress, including phlebotomy and not be of clinical significance. A cannulated prolactin study may be a useful way to discriminate this. AIM To determine the utility of a cannulated prolactin series in women presenting with infertility who have a raised prolactin measurement at referral for first fertility consultation. MATERIALS AND METHODS All women referred to two fertility centres had a prolactin level measured prior to first appointment over a two-year period. If the level remained elevated on the second measure after macroprolactin precipitation, women were referred for a cannulated prolactin series. If the prolactin concentration fell within the reference range during the series then the result was regarded as normal. RESULTS Forty-four (2.7%) of 1660 women seen for a first specialist appointment had persistently raised prolactin concentrations after two samples and were referred for a cannulated series. The proportion of women whose prolactin was found to be normal during the cannulated prolactin series was 61% (95% CI 47-74%). Even in patients with a referral prolactin of greater than 1000 mU/L, 45% had a normal two-hour cannulated series. CONCLUSION A high proportion (61%) of women with raised prolactin at time of referral for first specialist appointment had a normal prolactin after a two-hour cannulated series. A cannulated prolactin study can avoid unnecessary further investigations in these women.

In light of the worsening opioid epidemic and nationwide parenteral opioid shortage, our institution created an enhanced recovery after surgery (ERAS) protocol. Our objective was to evaluate our initial experience transitioning to ERAS in cardiac surgery. An institutional cardiac ERAS protocol was implemented in April 2018, consisting of opioid-sparing analgesia, liberalization of fasting and activity restrictions, and goal-directed standardization of perioperative care. Clinical outcomes, opioid administration, and pain scores of patients undergoing nonemergent cardiac surgery were reviewed from March 2017 to July 2018. Patients were propensity score matched into pre-ERAS and transition-to-ERAS (t-ERAS) cohorts and compared by univariate analysis. Of 467 patients, 236 patients were well-matched (118 per cohort). The transition to ERAS resulted in a 79% reduction in morphine equivalents through postoperative day 1 (359.3 mg pre-ERAS vs 75.4 mg ERAS, P0.0001). Despite less opioid utilization, t-ERAS patients reported lower pain scores (median 4.88 vs 4.14, P = 0.011). There was no difference in mortality (2% vs 0%, P = 0.498) or postoperative complications including initial hours ventilated (5.3 vs 5.2 hours, P = 0.380), prolonged ventilation (9.3% vs 6.8%, P = 0.473), renal failure (3.4% vs 2.5%, P = 0.701), and ICU length of stay (58.3 vs 70.4 hours, P = 0.272). The transition to cardiac ERAS resulted in significantly reduced opioid administration and improved patient pain scores while maintaining excellent outcomes. Well-supported, multidisciplinary teams of cardiac surgeons, anesthesiologists, and intensivists can dramatically reduce opioid use without sacrificing pain control or excellent clinical outcomes.

Dental cavities are the most prevalent, preventable disease worldwide providing a need for robust treatment options to restore both the form and function of decaying teeth. Here is a presentation of a possible regenerative pulp capping agent that can serve to restore tooth function while regenerating healthy dentin tissue over a long period of time. To achieve this goal a material needs to crosslink quickly, be structurally rigid, and support the proliferation and differentiation of stem cells contained within the dental pulp. In this study, calcium phosphate nanoparticles were embedded in polymer hydrogels of carboxymethyl-chitosan and a diglycidyl ether. The particle size, surface, and mechanical properties of these materials were characterized. These composites have moduli up to 3 MPa, support the culture of dental pulp stem cells more than 3 weeks and exhibit osteogenic potential even without osteogenic media. These composites demonstrate a promising potential as the next generation of pulp capping materials.

The growth plate is a complex cartilage structure in long bones that mediates growth in children. When injured, the formation of a "bony bar" can occur which impedes normal growth and can cause angular deformities or growth arrest. Current treatments for growth plate injuries are limited and result in poor patient outcomes, necessitating research toward novel treatments that can prevent bony bar formation and stimulate cartilage regeneration. This study investigates alginate-chitosan polyelectrolyte complex (PEC) hydrogels as an injectable biomaterial system to prevent bony bar formation. Biomaterial properties including stiffness and degradation are quantified, and the effect that material properties have on mesenchymal stem cell (MSC) fate is quantified in vitro. Specifically, this study aims to elucidate the effectiveness of biomaterial-based control over the differentiation behavior of MSCs toward osteogenic or chondrogenic lineages using biochemical metabolite assays and quantitative real time PCR. Further, the PEC hydrogels are employed in a rat growth plate injury model to determine their effectiveness in preventing bony bar formation in vivo. Results indicate that hydrogel composition and material properties affect the differentiation tendency of MSCs in vitro, and the PEC hydrogels show promise as an injectable biomaterial for growth plate injuries.

To investigate the relationship of metabolic syndrome severity score (MetSSS) with glucose regulatory and cardiovascular disease (CVD) status in Aotearoa New Zealand.MetSSS and MetSSS component coefficients were calculated for participants from the cross-sectional Workforce Diabetes Study (WDS) (n = 5,806) and Diabetes, Heart and Health Survey (DHAH) (n = 4,010) and compared by ethnicity (European, Māori, Pacific and Asian), glucose regulatory status [impaired fasting glucose, impaired glucose tolerance and type 2 diabetes) and history of cardiovascular disease.MetSSS positively associated with impaired glucose regulatory status and history of cardiovascular disease for all ethnic groups. Ethnicity significantly affected different coefficients of the MetSSS components, however all ethnicities had an approximately normal MetSSS distribution, with Māori and Pacific curves being right-shifted compared to European. While the MetSSS thresholds that capture 80% of participant with type 2 diabetes (T2D) were higher for Māori and Pacific, the difference in MetSSS between those participants with and without type 2 diabetes within an ethnicity group was similar across ethnicities.MetSSS may have utility as a tool to quantify an individual's cardiometabolic disease risk within the multi-ethnic population of Aotearoa New Zealand, however ethnic-specific categories for disease risk are likely to be required.