Nocturnal hypoglycemia is associated with next day cognitive performance in adults with type 1 diabetes: Pilot data from the GluCog study.

OBJECTIVE:  Individuals with type 1 diabetes (T1D) have increased risk for cognitive dysfunction and high rates of sleep disturbance. Despite associations between glycemia and cognitive performance using cross-sectional and experimental methods few studies have evaluated this relationship in a naturalistic setting, or the impact of nocturnal versus daytime hypoglycemia. Ecological Momentary Assessment (EMA) may provide insight into the dynamic associations between cognition, affective, and physiological states. The current study couples EMA data with continuous glucose monitoring (CGM) to examine the within-person impact of nocturnal glycemia on next day cognitive performance in adults with T1D. Due to high rates of sleep disturbance and emotional distress in people with T1D, the potential impacts of sleep characteristics and negative affect were also evaluated. METHODS:  This pilot study utilized EMA in 18 adults with T1D to examine the impact of glycemic excursions, measured using CGM, on cognitive performance, measured via mobile cognitive assessment using the TestMyBrain platform. Multilevel modeling was used to test the within-person effects of nocturnal hypoglycemia and hyperglycemia on next day cognition. RESULTS:  Results indicated that increases in nocturnal hypoglycemia were associated with slower next day processing speed. This association was not significantly attenuated by negative affect, sleepiness, or sleep quality. CONCLUSIONS:  These results, while preliminary due to small sample size, showcase the power of intensive longitudinal designs using ambulatory cognitive assessment to uncover novel determinants of cognitive fluctuation in real world settings, an approach that may be utilized in other populations. Findings suggest reducing nocturnal hypoglycemia may improve cognition in adults with T1D.

Predation of the endangered Ae'o (Hawaiian Stilt) by a native raptor, the Pueo (Hawaiian Short-eared Owl) on the island of O'ahu, Hawai'i, USA.

While the impact of introduced predators is a widely acknowledged issue and key component of conservation considerations for endemic waterbird populations in the Hawaiian Islands, the impact of native predators on endemic, endangered waterbirds is not as frequently discussed or factored into recovery models. The Pueo (Hawaiian Short-eared Owl; Asio flammeus sandwichensis) is a subspecies of Short-eared Owl endemic to the Hawaiian Islands and is State-listed as Endangered on the island of O'ahu. The Ae'o (Hawaiian Stilt; Himantopus mexicanus knudensi) is a subspecies of the Black-necked Stilt endemic to Hawai'i and is federally listed as Endangered throughout its range. A variety of non-native predators are confirmed to consume Ae'o eggs, chicks, and adults, including invasive mammals (e.g., feral cats), birds (e.g., Barn Owls), and amphibians (e.g., bullfrogs). While predation by native predators was suspected, there are no cases documented in the literature to date describing Pueo preying upon Ae'o. Here, we describe four events that provide evidence of Pueo predating Ae'o during the 2019-2021 breeding seasons in a wetland area on the island of O'ahu: (1) confirmed Pueo predating an Ae'o chick, (2) a suspected predation attempt of a Pueo chasing adult Ae'o, and (3) two suspected predation events based on (a) 10 adult-sized Ae'o carcasses and remains found near an active Pueo nest and (b) game camera photos of Pueo visiting two Ae'o nests. To our knowledge, these novel observations are the first published accounts of predator-prey interactions between these two subspecies.

Confidence score: a data-driven measure for inclusive systematic reviews considering unpublished preprints.

OBJECTIVES: COVID-19, since its emergence in December 2019, has globally impacted research. Over 360 000 COVID-19-related manuscripts have been published on PubMed and preprint servers like medRxiv and bioRxiv, with preprints comprising about 15% of all manuscripts. Yet, the role and impact of preprints on COVID-19 research and evidence synthesis remain uncertain. MATERIALS AND METHODS: We propose a novel data-driven method for assigning weights to individual preprints in systematic reviews and meta-analyses. This weight termed the "confidence score" is obtained using the survival cure model, also known as the survival mixture model, which takes into account the time elapsed between posting and publication of a preprint, as well as metadata such as the number of first 2-week citations, sample size, and study type. RESULTS: Using 146 preprints on COVID-19 therapeutics posted from the beginning of the pandemic through April 30, 2021, we validated the confidence scores, showing an area under the curve of 0.95 (95% CI, 0.92-0.98). Through a use case on the effectiveness of hydroxychloroquine, we demonstrated how these scores can be incorporated practically into meta-analyses to properly weigh preprints. DISCUSSION: It is important to note that our method does not aim to replace existing measures of study quality but rather serves as a supplementary measure that overcomes some limitations of current approaches. CONCLUSION: Our proposed confidence score has the potential to improve systematic reviews of evidence related to COVID-19 and other clinical conditions by providing a data-driven approach to including unpublished manuscripts.

Incidence of Loss of Reduction After Open Reduction Internal Fixation of Metacarpal Shaft Fractures.

BACKGROUND: This study compared the incidence of loss of reduction (LOR) between metacarpal fractures fixed with screws alone and those fixed with plates and screws. Secondary aims included identifying patient or fracture characteristics associated with increased risk of LOR. METHODS: We retrospectively reviewed 138 metacarpal fractures in 106 patients treated with open reduction internal fixation with screws (60 fractures) or plates and screws (78 fractures) with a mean radiographic follow-up of 50 days for evidence of LOR. We compared the incidence of LOR between the screw and plate groups using a χ2 test. We performed logistic regression analysis to determine whether patient age, sex, metacarpal location (index, long, ring, small), the presence of multiple metacarpal fractures, or fracture pattern were associated with increased incidence of LOR. RESULTS: Loss of reduction occurred in 19 (13.8%) of 138 fractures, with no statistically significant difference between lag screw (7 of 60, 11.6%) and plate fixation (12 of 78, 15.4%). Neither fracture pattern nor the presence of multiple metacarpal fractures was associated with an increased incidence of LOR, but patients experienced a 7% increase in the risk of LOR for each additional year of age. Loss of reduction occurred most frequently in index metacarpal fractures (4 of 12, 33%), although this did not reach statistical significance. CONCLUSIONS: We found no difference in LOR incidence between lag screw fixation and plate fixation. The overall incidence of LOR was higher in this study than previously reported and increased with increasing patient age.

Outcomes of Abbreviated MRI (Ab-MRI) for Women of any Breast Cancer Risk and Breast Density in a Community Academic Setting.

BACKGROUND: Abbreviated magnetic resonance imaging (Ab-MRI) has been evaluated for elevated breast cancer risk or dense breasts but has not been evaluated across all risk profiles. METHODS: Patients selected underwent Ab-MRI from February 2020 to September 2021. Women were older than aged 30 years, up to date with screening mammography, and paid $299 cash. RESULTS: A total of 93 patients were identified with a mean age of 52 years; 92.5% were Caucasian, 0% black, and 97.9% were from high socioeconomic status. Mean Gail score was 14.2, and 83.3% had a lifetime risk of breast cancer <20%. Reasons for Ab-MRI: dense breasts (36.6%); family history (24.7%); palpable mass (12.9%). Providers ordering: OBGYN (49.5%); breast surgeon (39.1%); primary care (6.6%). Thirteen biopsies (14%) detected one breast cancer. 31.1% had a change in follow-up screening: 58.6% 6-month MRI, 20.7% 6-month mammogram, and 10.3% 6-month ultrasound. Negative predictive value was 100% (95% confidence interval [CI]: 95-100%, p < 0.0001). Sensitivity was 100% (95% CI: 2.5-100%, p < 0.0001), and specificity was 87% (95% CI: 78.3-93.1%, p < 0.0001) compared with 77.6% and 98.8% for mammography. Only one cancer was detected: cost of $27,807 plus cost of 13 MRI or ultrasound (US)-guided biopsies and additional follow-up imaging. Historically 20% of abnormalities detected on full MRI are malignant; however, 7.7% of ab-MRI abnormalities were malignant CONCLUSIONS: One third of women were recommended a change in follow-up, which predominantly included a 6-month MRI. Ab-MRI may introduce average risk women to unnecessary follow-up and increased biopsies with a lower cancer detection rate. Ab-MRI should be evaluated closely before implementation.

Role of Depression in Total Knee Arthroplasty: A Retrospective Analysis of Perioperative Outcomes in Patients in the United States.

We evaluate the patient demographics, perioperative outcomes, in-hospital complications, and assess recent national trends in clinically depressed and non-depressed patients undergoing primary total knee arthroplasty (TKA). Using the National Hospital Discharge Survey from 2001 and 2010, patients undergoing primary TKA in the United States were identified based upon the diagnosis of depression. Differences in gender, patient-demographics, comorbidities, complications, length of stay, and discharge disposition were analyzed. A total of 32,761 TKA patients were identified, consisting of 1,880 patients with a diagnosis of depression and 30,881 patients without. The depression group had an average age significantly younger than the non-depression cohort (p < 0.01). The depression group contained a significantly greater percentage of females when compared to the non-depression group. The non-depression group had a significantly greater percentage of African-Americans (p < 0.01), and a significantly smaller percentage of Caucasians (p < 0.01). Our findings contribute to the literature on the role of depression on perioperative outcomes of TKA. (Journal of Surgical Orthopaedic Advances 30(1):007-009, 2021).

Prevalence of depressive symptoms and associated factors in an urban, ophthalmic population.

OBJECTIVE: To determine the prevalence of depressive symptoms in an adult ophthalmic patient population and to delineate correlates. DESIGN: Cross-sectional study. PARTICIPANTS: Adult patients (⩾18 years) were approached in general and sub-specialty cornea, retina, and glaucoma ophthalmic clinics. A total of 367 patients from the four clinics were enrolled. METHODS: Depressive symptoms were assessed using the Patient Health Questionnaire-9. A cut-off score of ⩾10 was used to indicate clinically significant depressive symptoms. Patient Health Questionnaire-9 scores were used to evaluate bivariate relationships between depressive symptoms and distance visual acuity, ocular diagnosis, diabetes status, smoking status, demographic information, and medications. RESULTS: The majority of patients were female (52.9%) and Caucasian (48.6%). The mean age was 52.0 years (standard deviation: 16.7). Clinically significant depressive symptoms were present in 19.9% of patients overall; this rate varied slightly by clinic. Patients with low vision and blindness (visual acuity worse than 20/60) were more likely to have depressive symptoms (odds ratio = 2.82; 95% confidence interval: 1.90-4.21). Smoking and diabetes were also associated with depressive symptoms (odds ratio = 3.11 (2.66-3.64) and 3.42 (1.90-6.16), respectively). CONCLUSION: In a sample of urban ophthalmic adult patients, depressive symptoms were highly associated with low vision, smoking, and diabetes. This information can be used to target interventions to those at greatest risk of depressive symptoms.

Minimally Invasive Distal Pancreatectomy Is Associated with Decreased Postoperative Neutrophil to Lymphocyte Ratio.

Purpose: The neutrophil-to-lymphocyte ratio (NLR) is a marker of inflammation that has been investigated as a prognostic factor in many diseases. We hypothesized that NLR would be lower in patients undergoing minimally invasive distal pancreatectomy (MIDP). Methods: Using a prospective database, we identified patients who underwent open or minimally invasive (laparoscopic/robotic) distal pancreatectomy and splenectomy from 2006 to 2018. Patients were grouped according to their type of surgery and matched by age, gender, and benign or malignant pathology. The NLR was calculated from a complete blood count with differential on the second postoperative day. Statistical calculations were performed in Stata (v13.0). Results: A total of 106 patients were included, with 53 MIDP and 53 open cases. MIDP was associated with a significantly lower postoperative NLR than open surgery (13.3 vs. 17.2, p = 0.01). NLR did not vary significantly between patients who developed complications and those who did not (15.4 vs. 15.3, p = 0.95). Patients undergoing MIDP had decreased length of postoperative hospital stay (4 days vs. 5 days, p = 0.003). Multivariable linear regression failed to find a significant decrease in NLR with the use of laparoscopy (p = 0.14) when accounting for age, body mass index, surgical blood loss, pathology, and operative time as covariates. Conclusion: The NLR is significantly decreased when performing MIDP versus open distal pancreatectomy, but correlation with clinical outcomes has yet to be proven.

Transitioning to the Direct Anterior Approach in Total Hip Arthroplasty: Is It Safe in the Current Health Care Climate?

BACKGROUND: The direct anterior approach for total hip arthroplasty has recently gained interest for its quicker short-term recovery despite concerns about increased complications and operative time, especially during the steep learning curve period. The primary goal of this study was to determine if the transition from a posterior approach to a direct anterior approach for total hip arthroplasty can be achieved without harming patient safety. METHODS: This is a retrospective cohort single-surgeon study of consecutive primary total hip arthroplasties performed over a transition period from posterior to direct anterior (DA) approach. RESULTS: A total of 412 patients (211 anterior, 201 posterior) were included with no significant demographic differences between cohorts. There were no significant differences between the DA and posterior group in 30-day readmission rates (2.84% vs 2.49%, P = .823), 90-day readmission rates (4.27 vs 5.97, P = .432), complication rate (6.16% vs 3.48%, P = .206), or revision rate (1.90% vs 2.99%, P = .535). The DA group had a significantly lower percentage of cases outside the goal abduction angle range (35°-50°) than the posterior group (9.52%, n = 20 vs 19.6%, n = 39, P < .01). The number of cases outside the goal leg length discrepancy range (±10 mm) was not significantly different (P = .846) between the DA (12.9%) and posterior (13.6%) groups. CONCLUSION: This single-surgeon study demonstrates that the DA approach can be transitioned to safely with no significant increase in complications or readmissions over a high-volume experienced surgeon's first 200 cases. Furthermore, our results endorse the consistency of the DA approach during the learning curve period in regard to component positioning compared to posterior approach.

Gender Role in Total Knee Arthroplasty: A Retrospective Analysis of Perioperative Outcomes in US Patients.

BACKGROUND: Women present later than men for total knee arthroplasty (TKA) with more severe osteoarthritic disease but achieve comparable functional improvement and implant survival and also lower rates of revision. Despite these findings, there is significant underutilization of the procedure for women compared to men. METHODS: We conducted a retrospective study to address the lack of information in the literature concerning the immediate and short-term perioperative outcomes between genders. The National Hospital Discharge Survey was evaluated between 2001 and 2010 for men and women undergoing primary TKA in the United States. Differences in gender, patient demographics, comorbidities, complications, length of stay, and discharge disposition were analyzed and identified. RESULTS: The growth in TKA was 145% for men and 131% for women over the 10-year period. Women presented with significantly higher rates of obesity, morbid obesity, postoperative transfusion rate, and length of stay. In contrast, men showed a greater proportion of diabetes, postoperative wound infections, and increased mortality rates. Males were also more likely to be discharged to home, whereas females were more likely to be discharged to rehabilitation facilities. CONCLUSION: Our findings provide important insight into the perioperative outcomes that may be influencing gender disparity in TKA.

The non-genomic rapid acidification in peripheral T cells by progesterone depends on intracellular calcium increase and not on Na+/H+-exchange inhibition.

Progesterone is an endogenous immunomodulator that is able to suppress T cell activation during pregnancy. An increased intracellular free calcium concentration ([Ca(2+)](i)), acidification, and an inhibition of Na(+)/H(+)-exchange 1 (NHE1) are associated with this progesterone rapid non-genomic response that involves plasma membrane sites. Such acidification, when induced by phytohemagglutinin, is calcium dependent in PKC down-regulated T cells. We investigated the relationship between this rapid response involving the [Ca(2+)](i) increase and various membrane progesterone receptors (mPRs). In addition, we explored whether the induction of acidification in T cells by progesterone is a direct result of the [Ca(2+)](i) increase. The results show that the intracellular calcium elevation caused by progesterone is inhibited by SKF96365, U73122, and 2-APB, but not by pertussis toxin or U73343. The elevation is enhanced by the protein tyrosine kinase inhibitor staurosporine and the protein kinase C inhibitors Ro318220 and Go6983. These findings suggest that progesterone does not stimulate the [Ca(2+)](i) increase via the Gi coupled mPR(α). Furthermore, progesterone-induced acidification was found to be dependent on Ca(2+) entry and blocked by the inorganic channel blocker, Ni(2+). However, BAPTA, an intracellular calcium chelator, was found to prevent progesterone-induced acidification but not the inhibition of NHE1. This implies that acidification by progesterone is a direct result of the [Ca(2+)](i) increase and does not directly involve NHE1. Taken together, further investigations are needed to explore whether one or more mPRs or PGRMC1 are involved in bringing about the T cell rapid response that results in the [Ca(2+)](i) increase and inhibition of NHE1.

Non-genomic rapid inhibition of Na+/H+-exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids.

Glucocorticoids (GCs) have been employed as immunosuppressive agents for many years. However, it is still unclear how GCs instantly uncouple T cells from acute stressful inflammatory. In terms of time scale, the genomic activity of the classic GC receptor cannot fulfill this role under crisis; but a rapid non-genomic response can. In a previous study, intracellular acidification was found to be due to a rapid non-genomic inhibition of Na(+)/H(+)-exchange 1 (NHE1) and this event led to the immunosuppression of T cell proliferation by progesterone. The aim of this study was to examine whether there is a rapid acidification response caused by an inhibition of NHE1 activity and to explore the differential non-genomic effect on immunosuppression of hydrocortisone and dexamethasone. The IC(50) values for NHE1-dependent pH(i) recovery by hydrocortisone and dexamethasone are 250 and 1 nM, respectively. Co-stimulation of GCs with phytohemagglutinin (PHA) is able to inhibit PHA-induced IL-2 secretion, IL-4 secretion, and T-cell proliferation. Furthermore, apoptosis in PHA-activated T cells is not induced by hydrocortisone but by dexamethasone. The mechanism of immunosuppression on proliferation by dexamethasone was found to be different of hydrocortisone and seems to involve cytotoxicity against T cells. Moreover, apoptosis induced by dexamethasone and impermeable dexamethasone-bovine serum albumin suggests that the apoptotic immunosuppression occurs through both the plasma membrane and cytoplasmic sites. The rapid inhibitory responses triggered by GCs would seem to release T cells instantly when an acute stress-related response is needed. Nonetheless, the apoptotic immunosuppression by dexamethasone is attributable to its severe cytotoxicity.

Multi-layer plastic/glass microfluidic systems containing electrical and mechanical functionality.

This paper describes an approach for fabricating multi-layer microfluidic systems from a combination of glass and plastic materials. Methods and characterization results for the microfabrication technologies underlying the process flow are presented. The approach is used to fabricate and characterize multi-layer plastic/glass microfluidic systems containing electrical and mechanical functionality. Hot embossing, heat staking of plastics, injection molding, microstenciling of electrodes, and stereolithography were combined with conventional MEMS fabrication techniques to realize the multi-layer systems. The approach enabled the integration of multiple plastic/glass materials into a single monolithic system, provided a solution for the integration of electrical functionality throughout the system, provided a mechanism for the inclusion of microactuators such as micropumps/valves, and provided an interconnect technology for interfacing fluids and electrical components between the micro system and the macro world.