Bunch microclimate influence amino acids and phenolic profiles of Pinot noir grape berries.

Introduction: The increase of temperature due to climate change at different phenological stages of grapevine has already been demonstrated to affect accumulation of primary and secondary metabolites in grape berries. This has a significant implication for Pinot noir especially in New Zealand context as these compounds can have direct and indirect effects on wine quality. Methods: This study investigates how varying bunch microclimate through changes in temperature applied at veraison stage can affect: fresh weight, total soluble solids, the accumulation of anthocyanins, total phenolics and amino acids of the grape berries. This was studied over two growing seasons (2018/19 and 2019/20) with Pinot noir vines being grown at two different temperatures in controlled environment (CE) chambers. The vines were exposed to 800 µmol/m2/s irradiance with diurnal changes in day (22°C or 30°C) and night (15°C) temperatures. This experimental set up enabled us to determine the accumulation of these metabolite at harvest (both seasons) and throughout berry development (second season). Results and discussion: The results showed that berry weight was not influenced by temperature increase. The total soluble solids (TSS) were significantly increased at 30°C, however, this was not at the expense of berry weight (i.e., water loss). Anthocyanin content was reduced at higher temperature in the first season but there was no change in phenolic content in response to temperature treatments in either season. The concentrations of total amino acids at harvest increased in response to the higher temperature in the second season only. In addition, in the time course analysis of the second season, the accumulation of amino acids was increased at mid-ripening and ripening stage with the increased temperature. Significant qualitative changes in amino acid composition specifically the α-ketoglutarate family (i.e., glutamine, arginine, and proline) were found between the two temperatures. Significance: This study is the first to provide detailed analysis and quantification of individual amino acids and phenolics in Pinot noir in response to changes in temperature applied at veraison which could aid to develop adaptation strategies for viticulture in the future.

Projected Wine Grape Cultivar Shifts Due to Climate Change in New Zealand.

Climate change has already been affecting the regional suitability of grapevines with significant advances in phenology being observed globally in the last few decades. This has significant implications for New Zealand, where the wine industry represents a major share of the horticultural industry revenue. We modeled key crop phenological stages to better understand temporal and spatial shifts in three important regions of New Zealand (Marlborough, Hawke's Bay, Central Otago) for three dominant cultivars (Merlot, Pinot noir, and Sauvignon blanc) and one potential new and later ripening cultivar (Grenache). Simulations show an overall advance in flowering, véraison, and sugar ripeness by mid-century with more pronounced advance by the end of the century. Results show the magnitude of changes depends on the combination of greenhouse gas emission pathway, grape cultivar, and region. By mid-century, in the Marlborough region for instance, the four cultivars would flower 3 to 7 days earlier and reach sugar ripeness 7 to 15 days earlier depending on the greenhouse gas emission pathway. For growers to maintain the same timing of key phenological stages would require shifting planting of cultivars to more Southern parts of the country or implement adaptation strategies. Results also show the compression of time between flowering and véraison for all three dominant cultivars is due to a proportionally greater advance in véraison, particularly for Merlot in the Hawke's Bay and Pinot noir in Central Otago. Cross-regional analysis also raises the likelihood of the different regional cultivars ripening within a smaller window of time, complicating harvesting schedules across the country. However, considering New Zealand primarily accommodates cool climate viticulture cultivars, our results suggest that late ripening cultivars or extended ripening window in cooler regions may be advantageous in the face of climate change. These insights can inform New Zealand winegrowers with climate change adaptation options for their cultivar choices.

Drug delivery device for the inner ear: ultra-sharp fully metallic microneedles.

Drug delivery into the inner ear is a significant challenge due to its inaccessibility as a fluid-filled cavity within the temporal bone of the skull. The round window membrane (RWM) is the only delivery portal from the middle ear to the inner ear that does not require perforation of bone. Recent advances in microneedle fabrication enable the RWM to be perforated safely with polymeric microneedles as a means to enhance the rate of drug delivery from the middle ear to the inner ear. However, the polymeric material is not biocompatible and also lacks the strength of other materials. Herein we describe the design and development of gold-coated metallic microneedles suitable for RWM perforation. When developing microneedle technology for drug delivery, we considered three important general attributes: (1) high strength and ductility material, (2) high accuracy and precision of fabrication, and (3) broad design freedom. We developed a hybrid additive manufacturing method using two-photon lithography and electrochemical deposition to fabricate ultra-sharp gold-coated copper microneedles with these attributes. We refer to the microneedle fabrication methodology as two-photon templated electrodeposition (2PTE). We demonstrate the use of these microneedles by inducing a perforation with a minimal degree of trauma in a guinea pig RWM while the microneedle itself remains undamaged. Thus, this microneedle has the potential literally of opening the RWM for enhanced drug delivery into the inner ear. Finally, the 2PTE methodology can be applied to many different classes of microneedles for other drug delivery purposes as well the fabrication of small scale structures and devices for non-medical applications. Graphical Abstract Fully metallic ultra-sharp microneedle mounted at end of a 24-gauge stainless steel blunt syringe needle tip: (left) Size of microneedle shown relative to date stamp on U.S. one-cent coin; (right) Perforation through guinea pig round window membrane introduced with microneedle.

Diversity buffers winegrowing regions from climate change losses.

Agrobiodiversity-the variation within agricultural plants, animals, and practices-is often suggested as a way to mitigate the negative impacts of climate change on crops [S. A. Wood et al., Trends Ecol. Evol. 30, 531-539 (2015)]. Recently, increasing research and attention has focused on exploiting the intraspecific genetic variation within a crop [Hajjar et al., Agric. Ecosyst. Environ. 123, 261-270 (2008)], despite few relevant tests of how this diversity modifies agricultural forecasts. Here, we quantify how intraspecific diversity, via cultivars, changes global projections of growing areas. We focus on a crop that spans diverse climates, has the necessary records, and is clearly impacted by climate change: winegrapes (predominantly Vitis vinifera subspecies vinifera). We draw on long-term French records to extrapolate globally for 11 cultivars (varieties) with high diversity in a key trait for climate change adaptation-phenology. We compared scenarios where growers shift to more climatically suitable cultivars as the climate warms or do not change cultivars. We find that cultivar diversity more than halved projected losses of current winegrowing areas under a 2 °C warming scenario, decreasing areas lost from 56 to 24%. These benefits are more muted at higher warming scenarios, reducing areas lost by a third at 4 °C (85% versus 58%). Our results support the potential of in situ shifting of cultivars to adapt agriculture to climate change-including in major winegrowing regions-as long as efforts to avoid higher warming scenarios are successful.

Adhering to Radiographic Clinical Practice Guidelines for Distal Radial Fracture Management Is Associated with Improved Outcomes and Lower Costs.

BACKGROUND: The American Academy of Orthopaedic Surgeons Clinical Practice Guideline on the Treatment of Distal Radius Fractures has not been evaluated in clinical practice. We hypothesized that adhering to the distal radial fracture radiographic clinical practice guideline (CPG) improves outcomes and reduces costs. METHODS: We reviewed 266 patients with distal radial fractures treated at 1 institution. Based on CPG radiographic parameters (Recommendation 3), care was rated as "appropriate" or "inappropriate." QuickDASH (an abbreviated version of the Disabilities of the Arm, Shoulder and Hand [DASH] questionnaire) scores were collected. The direct costs of distal radial fracture care were determined. Descriptive statistics and nonparametric tests were used to evaluate demographic characteristics and outcomes across groups. QuickDASH scores, grouped by postoperative time interval, were analyzed using linear mixed effect models to predict outcome trends. RESULTS: In this study, 145 patients in the operative treatment group and 121 patients in the nonoperative treatment group were included. Of the 145 patients in the operative treatment group, 6 underwent an inappropriate surgical procedure, limiting any analyses of that group. Of the 121 patients in the nonoperative treatment group, 68 were treated inappropriately. For the patients in the nonoperative treatment group, appropriate care provided a significant outcome benefit by 1 year; the median QuickDASH score was 10.1 points for the appropriate treatment group and 19.5 points for the inappropriate treatment group (p = 0.05). The total direct costs for inappropriate nonoperative treatment were, on average, 60% higher than appropriate nonoperative treatment. In predictive models, patients with appropriate care in the operative treatment group and the nonoperative treatment group had better outcomes than patients with inappropriate nonoperative treatment at all time points after 29 days. CONCLUSIONS: When nonoperative distal radial fracture management was aligned with radiographic CPG criteria, patients in our cohort had improved patient-reported outcomes with lower costs. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Correlation of Soft Tissue Swelling and Timing to Surgery With Acute Wound Complications for Operatively Treated Ankle and Other Lower Extremity Fractures.

BACKGROUND: Considerable debate exists regarding how soft-tissue edema should influence timing of surgery for ankle and other lower extremity fractures. Assessment of swelling is subjective, and timing varies among surgeons. However, timing of surgery is one of the few modifiable factors in fracture care. Ultrasonography can objectively measure swelling and help determine optimal timing. The purposes of this study were to determine whether objective measures of swelling, timing to surgery, and patient-specific risk factors correlated with wound complications and to try to create a prediction model for postoperative wound complications based on identified modifiable and nonmodifiable risk factors. METHODS: Patients with closed ankle and other lower extremity fractures requiring surgery with an uninjured, contralateral extremity were included. Demographic information and sonographic measurements on both lower extremities were obtained pre-operatively. Subjects were followed for 3 months and wound complications were documented. A predictive algorithm of independent risk factors was constructed, determining wound complication risk. Given that patients with ankle fractures made up the majority of the study cohort (75/93 or 80%), a separate statistical analysis was performed on this group. A total of 93 subjects completed the study, with 75/93 sustaining ankle fractures. RESULTS: Overall wound complication rate was 18.3%. Timing to surgery showed no correlation with wound complications. A heel-pad edema index >1.4 was independently associated with wound complications. Subgroup analysis of ankle fractures demonstrated a 3.4× increase in wound complications with a heel-pad edema index >1.4. Tobacco history and BMI >25 were independent predictors of wound complications. An algorithm was established based on heel-pad edema index, BMI >25, and tobacco history. Patients with none of the 3 factors had a 3% probability of a wound complication. Patients with 1/3, 2/3 and 3/3 factors had a 12-36%, 60-86% and 96% probability of a wound complication, respectively. CONCLUSIONS: Timing to surgery had no correlation with wound complications. Heel-pad edema index >1.4, BMI >25, and tobacco-use correlated with wound complications. When separately analyzing the cohort that sustained ankle fractures, the heel-pad edema index of >1.4 was still demonstrated to be predictive of wound complications corresponding to a 3.4× increase in wound complication rates (11.1% vs 37.5%). Risk of wound complications significantly increased with each factor. In patients with increased BMI and/or tobacco use, resolution of heel edema may significantly reduce wound complications in lower extremity trauma. LEVEL OF EVIDENCE: Level II, prognostic, prospective cohort study.

Outcomes and indications for early hand therapy after multiple concomitant elective hand procedures.

STUDY DESIGN: Retrospective comparative study. INTRODUCTION: Trigger finger and carpal tunnel surgery are common, but not without complications including pain and edema, which are treated with hand therapy (HT). There are limited data for the outcomes of multiple trigger finger releases (MTFRs) or combined trigger finger and carpal tunnel surgery and the subsequent need for HT. PURPOSE OF THE STUDY: Based on our hypothesis that patients with more than 1 procedure may benefit from an early HT visit, we performed this study to compare the frequency of HT orders after single trigger finger releases (STFRs) and MTFRs and determine the reasoning for variation in the rate of HT orders after releases. METHODS: Subjects receiving either an STFR or an MTFR were identified. Patient-reported outcomes were recorded preoperatively and 2 weeks postoperatively. RESULTS: One hundred fifty-nine eligible subjects were identified; 33 MTFRs and 126 STFRs. MTFR subjects were prescribed postoperation HT at a higher rate compared with STFR subjects (66.7% vs 34.1%; P < .001). Of the HT subjects, MTFR subjects received prescriptions for edema management at a significantly higher rate compared with STFR subjects (P = .02). DISCUSSION: Patients with soft tissue dissection, edema, and stiffness would most likely benefit from HT services. It is important to identify these at-risk subpopulations to potentially alter their postoperative trajectories and improve outcomes. CONCLUSIONS: Higher rates of referral to HT occur when there are multiple concomitant hand procedures. This suggests surgeons triage HT services based on need. Policies that disallow postoperative therapy will have a greater impact on patients with these indications.

Trends and birth outcomes in adolescent refugees and migrants on the Thailand-Myanmar border, 1986-2016: an observational study.

Background: Currently there are more adolescents (10-19 years old) and young adults (20-24 years old) than ever. Reproductive health among this age group is often overlooked, although it can have a profound impact on the future. This is especially the case in conflict zones and refugee settings, where there is a heightened need for reproductive health care, and where both the resources and possibility for data collation are usually limited. Methods: Here we report on pregnancies, birth outcomes and risk factors for repeat pregnancies among adolescent and young adult refugees and migrants from antenatal clinics on the Thailand-Myanmar border across a 30 year time span. Results: Pregnancy and fertility rates were persistently high. Compared with 20-24-year-olds, 15-19-year-olds who reported being unable to read had 2.35 (CI: 1.97 - 2.81) times the odds for repeat pregnancy (gravidity >2). In primigravidae, the proportion of small for gestational age (SGA) and preterm births (PTB), and neonatal deaths (NND) decreased with increasing maternal age (all p <0.001). After adjustment, this association retained significance for PTB (cut-off point, ≤18 years) but not for SGA and NND. Conclusions: There is considerable room for improvement in adolescent pregnancy rates in these border populations, and educational opportunities may play a key role in effective interventions.

Comparison of Direct Perioperative Costs in Treatment of Unstable Distal Radial Fractures: Open Reduction and Internal Fixation Versus Closed Reduction and Percutaneous Pinning.

BACKGROUND: As the United States transitions to value-based insurance, bundled payments, and capitated models, it is paramount to understand health-care costs and resource utilization. The financial implications of open reduction and internal fixation (ORIF) with a volar locking plate for management of unstable distal radial fractures have not been established. We aimed to elucidate cost differences between ORIF and closed reduction and percutaneous pinning (CRPP). Our hypothesis was that ORIF has greater direct perioperative costs than CRPP but that the costs equilibrate over time. METHODS: We reviewed financial data for 40 patients prospectively enrolled and randomized to undergo CRPP or ORIF for treatment of a closed, displaced, unstable distal radial fracture. Clinical and functional outcomes, hospital-associated direct perioperative costs, postoperative care and therapy costs, and costs for additional procedures were compared. Cost data were stratified into perioperative, 90-day, and 1-year periods, and were reported utilizing cost ratios (CRs) relative to the CRPP cohort. Statistical analysis was performed with chi-square and independent-samples t tests with an alpha level of <0.05. RESULTS: Seventeen patients underwent CRPP and 23 underwent ORIF with a volar plate. Patients who underwent ORIF incurred greater 90-day (CR = 2.03/1.0, p < 0.001) and 1-year (CR = 1.60/1.0, p < 0.001) direct costs than those who underwent CRPP. The differential was greatest in the immediate perioperative period and gradually decreased over time. Operating room fees (CR = 1.7/1.0, p < 0.001), operating room implants, anesthesia (CR = 1.8/1.0, p < 0.001), and total perioperative costs (CR = 2.7/1.0, p < 0.001) were significantly greater in the ORIF cohort. Rehabilitation and cast technician costs were comparable (CR = 0.9/1.0 [ORIF/CRPP], p = 0.69). At 1 year, the CR for all costs of decreased to 1.6/1.0 (ORIF/CRPP, p < 0.001). Compared with the CRPP cohort, the ORIF cohort demonstrated significantly better functional outcomes at 6, 9, and 12 weeks and similar outcomes at 1 year. CONCLUSIONS: ORIF for a displaced, unstable distal radial fracture incurred greater direct costs than CRPP. Although implant costs for ORIF provided the greatest cost differential, additional procedures and higher clinic costs in the CRPP cohort narrowed the 90-day and 1-year cost gaps. LEVEL OF EVIDENCE: Economic Level II. See Instructions for Authors for a complete description of levels of evidence.

Bone Material Strength Index as Measured by Impact Microindentation in Postmenopausal Women With Distal Radius and Hip Fractures.

We tested whether cortical bone tissue properties assessed by in vivo impact microindentation would distinguish postmenopausal women with recent distal radius (DRF) or hip fracture (HF) from nonfracture controls (CONT). We enrolled postmenopausal women with recent DRF (n = 57), HF (n = 41), or CONT (n = 93), and used impact microindentation to assess bone material strength index (BMSi) at the anterior surface of the mid-tibia diaphysis. Areal bone mineral density (aBMD) (g/cm2 ) of the femoral neck (FN), total hip (TH), and lumbar spine (LS) were measured by dual-energy X-ray absorptiometry (DXA). HF and DRF subjects had significantly lower BMD than CONT at all sites (-5.6% to -8.2%, p < 0.001 for all). BMSi was 4% lower in DRF compared to CONT (74.36 ± 8.77 versus 77.41 ± 8.79, p = 0.04). BMSi was similarly lower in HF versus CONT, but the difference did not reach statistical significance (74.62 ± 8.47 versus 77.41 ± 8.79, p = 0.09). Lower BMSi was associated with increased risk of DRF (unadjusted OR, 1.43; 95% CI, 1.02 to 2.00, per SD decrease, p = 0.04), and remained statistically significant after adjustment for age, age and BMI, and age, BMI, and FN BMD (OR = 1.48 to 1.55). Lower BMSi tended to be associated with HF, but only reached borderline significance (unadjusted OR = 1.39; 95% CI, 0.96 to 2.01, p = 0.08). These results provide strong rationale for future investigations aimed at assessing whether BMSi can predict fracture in prospective studies and improve identification of women at risk for fragility fractures. © 2017 American Society for Bone and Mineral Research.

Empirical lessons regarding contraception in a protracted refugee setting: A descriptive study from Maela camp on the Thai-Myanmar border 1996 - 2015.

Conflict settings and refugee camps can be chaotic places, with large and rapid population movements, exacerbated public health problems, and ad hoc health services. Reproductive health care that includes family planning is of heightened importance in such settings, however, funding and resources tend to be constrained and geared towards acute health services such as trauma management and infectious disease containment. Here we report on the complexities and challenges of providing family planning in a post-emergency refugee setting, using the example of the largest refugee camp on the Thai-Myanmar border, in existence now for over 30 years. Data from 2009 demonstrates an upward trend in uptake of all contraceptives, especially long acting reversible contraception (LARC) and permanent methods (e.g. sterilization) over time. Increased uptake occurred during periods of time when there were boosts in funding or when barriers to access were alleviated. For example a surgeon fluent in local languages is correlated with increased uptake of tubal ligation in females. These data indicate that funding directed toward contraceptives in this refugee setting led to increases in contraceptives use. However, contraceptive uptake estimates depend on the baseline population which is difficult to measure in this setting. As far as we are aware, this is the longest reported review of family planning services for a refugee camp setting to date. The lessons learned from this setting may be valuable given the current global refugee crisis.

Lexical use in emotional autobiographical narratives of persons with schizophrenia and healthy controls.

Language dysfunction has long been described in schizophrenia and most studies have focused on characteristics of structure and form. This project focuses on the content of language based on autobiographical narratives of five basic emotions. In persons with schizophrenia and healthy controls, we employed a comprehensive automated analysis of lexical use and we identified specific words and semantically or functionally related words derived from dictionaries that occurred significantly more often in narratives of either group. Patients employed a similar number of words but differed in lower expressivity and complexity, more self-reference and more repetitions. We developed a classification method for predicting subject status and tested its accuracy in a leave-one-subject-out evaluation procedure. We identified a set of 18 features that achieved 65.7% accuracy in predicting clinical status based on single emotion narratives, and 74.4% accuracy based on all five narratives. Subject clinical status could be determined automatically more accurately based on narratives related to anger or happiness experiences and there were a larger number of lexical differences between the two groups for these emotions compared to other emotions.

Evaluator agreement in placement recommendations for insanity acquittees.

Research has examined differences between psychologists and psychiatrists in opinions on trial competency and criminal responsibility, but there is little research on such differences in risk assessment. This study examined the impact of disciplinary affiliation on opinions regarding whether new insanity acquittees should be hospitalized or released, and the risk factors given the most weight by each discipline. There was no significant difference between disciplines in the frequency of recommendations for hospitalization versus release. However, the concordance rate at the individual case level was only moderate when controlling for chance, which raises questions about the reliability and validity of forensic risk assessments in real-world settings. A number of variables emerged as significant in the decision-making of each discipline, with some differences noted.

Roles of superoxide and myeloperoxidase in ascorbate oxidation in stimulated neutrophils and H2O2-treated HL60 cells.

Ascorbate is present at high concentrations in neutrophils and becomes oxidized when the cells are stimulated. We have investigated the mechanism of oxidation by studying cultured HL60 cells and isolated neutrophils. Addition of H(2)O(2) to ascorbate-loaded HL60 cells resulted in substantial oxidation of intracellular ascorbate. Oxidation was myeloperoxidase-dependent, but not attributable to hypochlorous acid, and can be explained by myeloperoxidase (MPO) exhibiting direct ascorbate peroxidase activity. When neutrophils were stimulated with phorbol myristate acetate, about 40% of their intracellular ascorbate was oxidized over 20 min. Ascorbate loss required NADPH oxidase activity but in contrast to the HL60 cells did not involve myeloperoxidase. It did not occur when exogenous H(2)O(2) was added, was not inhibited by myeloperoxidase inhibitors, and was the same for normal and myeloperoxidase-deficient cells. Neutrophil ascorbate loss was enhanced when endogenous superoxide dismutase was inhibited by cyanide or diethyldithiocarbamate and appears to be due to oxidation by superoxide. We propose that in HL60 cells, MPO-dependent ascorbate oxidation occurs because cellular ascorbate can access newly synthesized MPO before it becomes packaged in granules: a mechanism not possible in neutrophils. In neutrophils, we estimate that ascorbate is capable of competing with superoxide dismutase for a small fraction of the superoxide they generate and propose that the superoxide responsible is likely to come from previously identified sites of intracellular NADPH oxidase activity. We speculate that ascorbate might protect the neutrophil against intracellular effects of superoxide generated at these sites.

Ascorbate interacts with reduced glutathione to scavenge phenoxyl radicals in HL60 cells.

We have compared the abilities of ascorbate and reduced glutathione (GSH) to act as intracellular free radical scavengers and protect cells against radical-mediated lipid peroxidation. Phenoxyl radicals were generated in HL60 cells, through the action of their myeloperoxidase, by adding H2O2 and phenol. Normally cultured cells, which contain no ascorbate; cells that had been preloaded with ascorbate; and those that had been depleted of GSH with buthionine sulfoximine were investigated. Generation of phenoxyl radicals resulted in the oxidation of ascorbate and GSH. Ascorbate loss was much greater in the absence of GSH, and adding glucose gave GSH-dependent protection against ascorbate loss. Ascorbate, or glucose metabolism, had little effect on the GSH loss. Glutathionyl radical formation was detected by spin trapping with DMPO in cells lacking ascorbate, and the signal was suppressed by ascorbate loading. Addition of phenol plus H2O2 to the cells caused lipid peroxidation, as measured with C11-BODIPY. Peroxidation was greatest in cells that lacked both ascorbate and GSH. Either scavenger alone gave substantial inhibition but optimal protection was seen with both present. These results indicate that GSH and ascorbate can each act as an intracellular radical scavenger and protect against lipid peroxidation. With both present, ascorbate is preferred and acts as the ultimate radical sink for phenoxyl or glutathionyl radicals. However, GSH is still consumed by metabolically recycling dehydroascorbate. Thus, recycling scavenging by ascorbate does not spare GSH, but it does enable the two antioxidants to provide more protection against lipid peroxidation than either alone.