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OBJECTIVES: Death certificate data are used to estimate state and national incidence of traumatic brain injury (TBI)-related deaths. This study evaluated the accuracy of this estimate in Oklahoma and examined the case characteristics of those persons who experienced a TBI-related death but whose death certificate did not reflect a TBI. METHODS: Data from Oklahoma's vital statistics multiple-cause-of-death database and from the Oklahoma Injury Surveillance System database were analyzed for TBI deaths that occurred during 2002. Cases were defined using the Centers for Disease Control and Prevention (CDC) ICD-10 code case definition. In multivariate analysis using a logistic regression model, we examined the association of case characteristics and the absence of a death certificate for persons who experienced a TBI-related death. RESULTS: Overall, sensitivity of death certificate-based surveillance was 78%. The majority (62%) of missed cases were due to listing 'multiple trauma' as the cause of death. Death certificate surveillance was more likely to miss TBI-related deaths among traffic crashes, falls, and persons aged > or = 65 years. After adding missed cases to cases captured by death certificate surveillance, traffic crashes surpassed firearm fatalities as the leading external cause of TBI-related death. CONCLUSIONS: Death certificate surveillance underestimated TBI-related death in Oklahoma and might lead to national underreporting. More accurate and detailed completion of death certificates would result in better estimates of the burden of TBI-related death. Educational efforts to improve death certificate completion could substantially increase the accuracy of mortality statistics. [ABSTRACT FROM AUTHOR]

Introduction and Importance: Prostatic utricle cyst (PUC) is an anatomic anomaly resulting from a vestigial remnant of the Müllerian duct in the posterior urethra. Proper diagnosis is crucial, as its presentation can vary widely and can present with infertility. The aim of this article is to present a rare case of a large prostatic utricle cyst as a cause of primary infertility, surgically managed with robotic excision followed by microdissection testicular sperm extraction to achieve fertility., Case Presentation: This is a case report of a 29-year-old male presenting with recurrent epididymo-orchitis and primary infertility. Imaging confirmed the presence of an enlarged PUC and was further managed as a case of obstructive azoospermia. Robotic surgery was done owing to its innovative approach in ensuring precise movements, improved anatomical visualization, and finer dissection into the deep pelvic cavity. Successful conception of a healthy offspring was achieved through one attempt of in vitro fertilization., Clinical Discussion: Large symptomatic prostatic utricle cysts are managed surgically, whether open, endoscopic, laparoscopic, or robotic. Robotic-assisted laparoscopic excision of prostatic utricle cysts offers many advantages in terms of surgical field exposure, highly improved surgical dexterity and precision, fewer intraoperative complications, and postoperative outcomes. Testicular sperm extraction after surgery is recommended in such cases if fertility is desired., Conclusion: Robotic excision with microdissection testicular sperm extraction for sperm cryopreservation for future fertility is a feasible and promising option for the treatment of large symptomatic prostatic utricle cysts., Competing Interests: Declaration of competing interest The authors hereby declare that they have no affiliations with or involvement in any organization or entity in the subject matter or materials discussed in this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: It has previously been demonstrated that Thrombelastography(TEG) angle may be associated with recurrence and survival in pancreas cancer in a cohort of patients operated on at the University of Colorado in 2016-2017. Now approaching 10 years of follow-up, we revisit these associations and strengthen these claims with multivariate analysis., Methods: Retrospective chart review was performed. Statistical analysis was conducted using STATA. Receiver operating characteristic(ROC) curves identified the performance of angle for predicting recurrence&survival. Unadjusted and adjusted cox regression models were used to identify significant predictors of these outcomes., Results: 47 patients were included with median follow-up of 29.6 months. ROC curves for angle predicting recurrence and survival identified a cutoff of 44.5°. KM curves demonstrated that patients above the cutoff were more likely to recur(90%vs46 ​%,p ​= ​0.001) and less likely to survive(16%vs56 ​%,p ​= ​0.001). Angle remained significant on multivariate analyses (HR recurrence:3.64[1.32-10.25],HR survival:3.80[1.38-10.46])., Conclusions: TEG angle is independently associated with disease recurrence and overall survival in pancreas cancer. This may be identifying virulent tumor biology, but further studies are required. A prospective study is underway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of interest: None declared.

T cells have emerged as sex-dependent orchestrators of pain chronification but the sexually dimorphic mechanisms by which T cells control pain sensitivity is not resolved. Here, we demonstrate an influence of regulatory T cells (Tregs) on pain processing that is distinct from their canonical functions of immune regulation and tissue repair. Specifically, meningeal Tregs (mTregs) express the endogenous opioid, enkephalin, and mTreg-derived enkephalin exerts an antinociceptive action through a presynaptic opioid receptor signaling mechanism that is dispensable for immunosuppression. We demonstrate that mTregs are both necessary and sufficient to suppress mechanical pain sensitivity in female, but not male, mice, with this modulation reliant on sex hormones. These results uncover a fundamental sex-specific, and immunologically-derived endogenous opioid circuit for nociceptive regulation with critical implications for pain biology., Competing Interests: Disclosures: Authors have no conflicts of interests to declare.

Background: Assessment of individual tumor biology and response to systemic therapy in pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge. The significance of anthropometric (body composition) changes during chemotherapy as a surrogate for tumor biology in the setting of localized PDAC is unknown., Methods: A retrospective, single-institution analysis of patients with PDAC who received neoadjuvant therapy (NAT) and pancreatectomy from 2017 to 2021 was performed. Radiologic anthropometric analysis used artificial intelligence-driven software to segment and compute total and sub-compartment muscle area, adipose tissue area, and attenuation values at the level of the L3 vertebra. Kaplan-Meier survival estimates, log-rank tests, and multivariable Cox regression models were used in survival analyses., Results: The inclusion criteria were met by 138 patients. Although decreases in muscle and adipose tissue areas during NAT were predominant, a subset of patients experienced an increase in these compartments. Increases in muscle greater than 5% (hazard ratio [HR], 0.352; 95% confidence interval [CI] 0.135-0.918; p = 0.033) and increases in adipose tissue greater than 15% (HR, 0.375; 95% CI 0.144-0.978; p = 0.045), were significantly associated with improved survival, whereas loss of visceral fat greater than 15% was detrimental (HR 1.853; CI 1.099-3.124; p = 0.021). No significant associations with single time-point anthropometrics were observed. Gains in total muscle and adipose mass were associated with improved pathologic response to systemic therapy and less advanced pathologic tumor stage., Conclusions: Dynamic anthropometric analysis during NAT for PDAC is a stronger prognostic indicator than measurements taken at a single point in time. Repeated anthropometric analysis during preoperative chemotherapy may serve as a biomarker for individual tumor biology and response to therapy., (© 2024. Society of Surgical Oncology.)

Plant proteins are increasingly being used in the food industry due to their sustainability. They can be isolated from food industry waste and converted into value-added ingredients, promoting a more circular economy. In this study, ultrasound-assisted alkaline extraction (UAAE) was optimized to maximize the extraction yield and purity of protein ingredients from grapeseeds. Grapeseed protein was extracted using UAAE under different pH (9-11), temperature (20-50 °C), sonication time (15-45 min), and solid/solvent ratio (10-20 mL/g) conditions. The structural and functional attributes of grapeseed protein and its major fractions (albumins and glutelins) were investigated and compared. The albumin fractions had higher solubilities, emulsifying properties, and in vitro digestibilities but lower fluid binding capacities and thermal stability than the UAAE and glutelin fraction. These findings have the potential to boost our understanding of the structural and functional characteristics of grapeseed proteins, thereby increasing their potential applications in the food and other industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

This study examined the equity implications of high-deductible health plans within the context of racial and ethnic wealth disparities. Using restricted data from the Medical Expenditure Panel Survey, we evaluated the net worth (in 2011-18) and financial assets (in 2011-16) of families with private insurance and those in high-deductible health plans with and without an associated health savings account. Our results represent, to our knowledge, the first estimates of racial and ethnic wealth disparities within these populations. Results show that White households consistently held significantly more wealth than did Black and Hispanic households across income levels. In the lowest income quartile, White privately insured families had more than 350 percent more in financial assets than their Black counterparts. Low-income Black and Hispanic families with high-deductible health plans but no savings accounts had median financial assets ($2,200 and $2,000, respectively) that were well below the average family coverage deductible. Study findings highlight the role of systemic racial wealth disparities, beyond that of income, to establish a unique pathway whereby high deductibles can exacerbate health care inequities.

Background: Accurate assessment of the pulmonary valve can dictate clinical management of patients with right ventricular outflow tract (RVOT) anomalies. Comparisons with available normal reference values are essential for accurate evaluation. The aim of the study was to generate normative data for the pulmonary valve annulus and sino-tubular (ST) junction using CT measurements derived from a heterogeneous pediatric population and create z-scores useful for clinical practice., Methods: Patients without heart disease who underwent cardiac CT between April 2014 and February 2021 ​at Children's Hospital Colorado were included. Minimum and maximum diameter (mm) and cross-sectional area (mm 2 ) for the pulmonary valve annulus and ST junction were measured. Previously validated models were used to normalize the measurements and calculate z-scores. Each measurement was plotted against BSA, and z-score distributions were used as reference lines., Results: Three-hundred-sixty-seven healthy patients with a mean age of 8.8 years (1-21), 56% male, and BSA of 1.1 ​m 2 (0.4-2.1) were analyzed. The Haycock formula was used to present data as predicted values for a given BSA and within equations relating each measurement to BSA. Predicted values and z-score boundaries for all measurements are graphically re-presented., Conclusions: CT-derived normative data for the pulmonary valve annulus and ST junction is reported from a heterogenous cohort of healthy children., Competing Interests: Declaration of competing interest All authors declare that they have received no grants, contracts, other forms of financial supports or relationships with the industry relevant to this paper., (Published by Elsevier Inc.)

Introduction: Next-generation DNA sequencing (NGS) technologies have increased the sensitivity for detecting the bacterial presence and have been used in other areas of orthopaedics to better understand the native microbiome of various joints. This study uses NGS to determine whether (1) a unique microbiome exists in human ankle tissues, (2) if components of the ankle microbiome affect patient outcomes, and (3) whether microbes found on the skin are a normal part of the ankle microbiome., Methods: A prospective study recruited 32 patients undergoing total ankle arthroplasty (n = 23) or ankle arthrodesis (n = 9) via direct anterior approach between November 2020 and October 2021. During surgery, five layers of the ankle were swabbed: skin (n = 32), retinaculum (n = 31), tibialis anterior tendon (n = 31), joint capsule (n = 31), and distal tibia (n = 32). These swabs (N = 157) were sent to MicroGen Diagnostics (Lubbock) for NGS. Demographics, medical comorbidities, surgical indication, postoperative complications, readmission, and revision surgery rates were collected from patient records., Results: The mean age was 60.7 (range, 19 to 85) years, and the mean follow-up duration was 10.2 (range, 4.8 to 20.6) months. Of 157 swabs sent for NGS, 19 (12.1%) indicated that bacteria were present (positive), whereas the remaining 138 (87.9%) had no bacteria present (negative). The most common organisms were Cutibacterium acnes in eight ankles (25.0%) and Staphylococcus epidermidis in two ankles (6.25%). Most bacteria were found in the retinaculum (29.6%). Complications, nonunions, infections, 90-day readmission, and revision surgery rates did not differ by NGS profile., Discussion: This study found that C acnes and S epidermidis were the most common bacteria in the ankle microbiome, with C acnes being present in 25% of ankles. Complication rates did not differ between patients with or without positive bacterial DNA remnants. Thus, we concluded that a unique ankle microbiome is present in some patients, which is unique from that of the skin of the ankle., Level of Evidence: Level II, Prospective cohort study., (Copyright © 2023 by the American Academy of Orthopaedic Surgeons.)

Competing Interests: The authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The franciscana dolphin is a small, vulnerable species often caught in artisanal gillnets. This study aims to provide a comprehensive assessment of their acoustic capabilities by using advanced equipment to collect a large dataset of wideband, continuous recordings. We examined the detailed acoustic signals of franciscana dolphins, comparing the sounds from rehabilitated dolphins in captivity with those of wild dolphins near fishing nets. Significant differences in acoustic characteristics were found between neonates and older dolphins, with juvenile and wild dolphins showing similar features. For the first time, repetition patterns in click production were identified, highlighting the importance of understanding the context of these sounds in regards to feeding and communication. This study emphasizes the need for detecting neonates for species protection and suggests the potential for developing acoustic classifiers specific to different age groups. Our findings offer valuable insights for conservation efforts and the development of protection strategies for franciscana dolphins.

Background: A significantly lower rate of non-small cell lung cancer (NSCLC) screening, greater health care avoidance, and changes to oncologic recommendations were some consequences of the Coronavirus disease 2019 (COVID-19) pandemic affecting the medical environment. We sought to determine how the health care environment during the COVID-19 pandemic affected the oncologic treatment of patients diagnosed with non-small cell lung cancer (NSCLC)., Methods: This was a retrospective cohort study evaluating patients with NSCLC in the National Cancer Database (2019-2020). Patients were divided into prepandemic (2019) and pandemic (2020) cohorts, and patient, oncologic, and treatment variables were compared. Multivariable logistic regression was performed to control for the impact of demographic characteristics on oncologic variables and the impact of oncologic variables on treatment variables., Results: The study population comprised 250,791 patients, including 114,533 patients (45.7%) in the pandemic cohort. There were 15% fewer new NSCLC diagnoses during the pandemic compared with prepandemic. Patients diagnosed during the pandemic had more advanced clinical TNM stage on presentation (P < .0001) and were more likely to have tumors in overlapping lobes or in a main bronchus (P = .0002). They were less likely to receive cancer treatment (P < .0001) and to undergo primary resection (P < .0001) and more likely to receive adjuvant systemic therapy (P = .004) and a combination of palliative treatment regimens (P < .0001). After risk adjustment, all these differences remained statistically significant (P < .05)., Conclusions: The COVID-19 pandemic was associated with increased clinical stage at presentation for patients with NSCLC, which impacted subsequent treatment strategies. However, treatment differed minimally when controlling for cancer stage. Future studies will examine the impact of these differences on overall survival and cancer-free survival., Competing Interests: Conflict of Interest Statement E.A.D. reports honoraria from Astra Zeneca. R.A.M. reports consulting fees from Medtronic (payments made to institution). The other authors have no conflicts of interest to report. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

The objective was to assess differences in productive and reproductive performance, and survival associated with vaginal discharge characteristics and fever in postpartum dairy cows located in western and southern states of the United States. This retrospective cohort study included data from 3 experiments conducted in 9 dairies. Vaginal discharge was evaluated twice within 12 DIM and scored on a 5-point scale. The highest vaginal discharge score observed for each cow was used to allocate them into 1 of 5 possible groups (VD group) as follows: VD 1 and 2 (VD 1/2; n = 1,174) = clear mucus or lochia with or without flecks of pus; VD 3 (n = 1,802) = mucopurulent with <50% pus; VD 4 (n = 1,643) = mucopurulent with ≥50% of pus or nonfetid reddish-brownish mucus, n = 1,643; VD 5 = fetid, watery, and reddish-brownish, n = 1,800. All VD 5 cows received treatment according to each herd's protocol. Rectal temperature was assessed in a subset of VD 5 cows, and subsequently divided into fever (rectal temperature ≥39.5°C; n = 334) and no fever (n = 558) groups. A smaller proportion of cows with VD 5 (67.6%) resumed ovarian cyclicity compared with VD 1/2 (76.2%) and VD 4 (72.9%) cows; however, a similar proportion of VD 5 and VD 3 (72.6%) cows resumed ovarian cyclicity. A smaller proportion of VD 5 (85.8%) cows received at least one AI compared with VD 1/2 (91.5%), VD 3 (91.0%), or VD 4 (91.6%) cows. Although we did not detect differences in pregnancy at first AI according to VD, fewer cows with VD 5 (64.4%) were pregnant at 300 DIM than cows with VD 1/2 (76.5%), VD 3 (76.2%), or VD 4 (74.7%). Hazard of pregnancy by 300 DIM was smaller for VD 5 compared with VD 1/2, VD 3, or VD 4 cows. A greater proportion of VD 5 cows were removed from the herd within 300 DIM compared with other VD groups. Milk production was 760 kg lower within 300 DIM for VD 5 compared with VD 2, VD 3, and VD 4, whereas VD 2, VD 3, and VD 4 had similar milk production. We did not detect an association between fever at diagnosis of VD 5 and reproductive performance or milk production. A greater proportion of VD 5 cows without fever were removed from the herd by 300 DIM compared with VD 5 cows with fever. Differences in productive and reproductive performance, and removal of the herd were restricted to fetid, watery, and reddish-brownish vaginal discharge, which was independent of fever., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Across mammalian species, new mothers undergo considerable behavioral changes to nurture their offspring and meet the caloric demands of milk production 1-5 . While many neural circuits underlying feeding and parenting behaviors are well characterized 6-9 , it is unclear how these different circuits interact and adapt during lactation. Here, we characterized the transcriptomic changes in the arcuate nucleus (ARC) and the medial preoptic area (MPOA) of the mouse hypothalamus in response to lactation and hunger. Furthermore, we showed that heightened appetite in lactating mice was accompanied by increased activity of hunger-promoting agouti-related peptide (AgRP) neurons in the ARC. To assess the strength of hunger versus maternal drives, we designed a conflict assay where female mice chose between a food source or a chamber containing pups and nesting material. Although food-deprived lactating mothers prioritized parenting over feeding, hunger reduced the duration and disrupted the sequences of parenting behaviors in both lactating and virgin females. We discovered that ARC AgRP neurons directly inhibit bombesin receptor subtype-3 (BRS3) neurons in the MPOA, a population that governs both parenting and satiety. Selective activation of this ARC AgRP to MPOA BRS3 circuit shifted behaviors from parenting to food-seeking. Thus, hypothalamic networks are modulated by physiological states and work antagonistically during the prioritization of competing motivated behaviors.

Background: Glioblastoma (GBM), is the most fatal form of brain cancer, with a high tendency for recurrence despite combined treatments including surgery, radiotherapy, and chemotherapy with temozolomide. The C-X-C chemokine receptor 4 (CXCR4) plays an important role in tumour radioresistance and recurrence, and is considered as an interesting GBM target. TRT holds untapped potential for GBM treatment, with CXCR4-TRT being a promising strategy for recurrent GBM treatment. Our study focuses on the preclinical assessment of different 177 Lu-labelled CXCR4-targeting peptides, CTCE-9908, DV1-K-DV3, and POL3026 for GBM treatment and exploring some of the radiobiological mechanisms underlying these therapies., Results: All three DOTA-conjugated peptides could be radiolabelled with 177 Lu with > 95% radiochemical yield. Binding studies show high specific binding of [ 177 Lu]Lu-DOTA-POL3026 to U87-CXCR4 + cells, with 42% of the added activity binding to the membrane at 1 nM, and 6.5% internalised into the cells. In the presence of the heterologous CXCR4 blocking agent, AMD11070, membrane binding was reduced by 95%, a result confirmed by quantitative in vitro autoradiography of orthotopic GBM xenograft sections. An activity-dependent decrease in cell viability was observed for [ 177 Lu]Lu-DOTA-DV1-K-DV3 and [ 177 Lu]Lu-DOTA-POL3026, along with a slight increase in the induction of apoptotic markers. Additionally, the expression of γH2AX increased in a time-and activity-dependent manner. Ex vivo biodistribution studies with [ 177 Lu]Lu-DOTA-POL3026 show uptake in the tumour reaching a SUV of 1.9 at 24 h post-injection, with higher uptake in the kidneys, lungs, spleen, and liver. Dosimetry estimations show an absorbed dose of 0.93 Gy/MBq in the tumour. A blocking study with AMD11070 showed a 38% reduction in tumour uptake, with no significant reduction observed in µSPECT imaging. Although no brain uptake was observed in the ex vivo biodistribution study, autoradiography on U87-CXCR4 + tumour inoculated mouse brain slices shows non-specific binding in the brain, next to high specific binding to the tumour., Conclusions: In conclusion, we compared different 177 Lu-radiolabelled CXCR4-targeting peptides for their binding potential in GBM, and demonstrated their varied cytotoxic action against GBM cells in vitro, with POL3026 being the most promising, causing considerable DNA damage. Though the peptide's systemic biodistribution remains to be improved, our data demonstrate the potential of [ 177 Lu]Lu-DOTA-POL3026 for CXCR4-TRT in the context of GBM., (© 2024. The Author(s).)

Background: The diagnosis of primary aldosteronism (PA) is comprehensive, which includes case-detection testing, case confirmation followed by subtype classification. In certain instances, such as in the setting of spontaneous hypokalemia, suppressed renin activity (PRA) plus plasma aldosterone concentration (PAC) of > 15 ng/dL, one may not proceed with confirmatory tests. However, the quality of evidence behind this approach is very low. This study sought to evaluate the proposed "simplified confirmatory pathway" that can spare confirmatory testing for primary aldosteronism by evaluating the diagnostic performances of the various pre-specified PAC thresholds in combination with findings of suppressed renin and spontaneous hypokalemia., Methods: This is a multi-center, retrospective diagnostic accuracy cohort-selected cross-sectional study. A total of 133 participants aged 18 years and above underwent saline infusion test between January 2010 to March 2024. The outcome measures comprise of the diagnostic performances of the different index test combinations (baseline PAC, baseline PRA and presence of spontaneous hypokalemia): sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy. Data analysis was performed using SPSS 29.0.1.0 & MedCalc 20.218., Results: Of the 133 patients who underwent saline infusion test, 88 (66.17%) were diagnosed with PA. A PAC of > 25 ng/dL plus PRA < 1.0 ng/dL/hr with spontaneous hypokalemia showed the highest specificity at 100% (95% CI 90.51%, 100.00%) and positive predictive value at 100% (85.18 - 100.00%). The minimum acceptable combination criteria were determined to be a PAC of > 20 ng/dL plus PRA < 0.6 ng/dL/hr, and presence of spontaneous hypokalemia. It has high specificity (94.59%; 95% CI 81.81%, 99.34%), positive predictive value (93.55%, 95% CI 78.49%, 98.29%), and moderate positive likelihood ratio (LR+) (6.39, 95% CI 1.61, 25.38) CONCLUSION: A hypertensive patient with spontaneous hypokalemia and screening findings of PAC > 20 ng/dL and suppressed PRA of < 0.6 ng/ml/hr, may be classified as "overt primary aldosteronism confirmed" and may not need to proceed with dynamic confirmatory testing., Protocol Registration Number: SRCTN34186253., (© 2024. The Author(s).)

Drugs of abuse cause changes in the prefrontal cortex (PFC) and associated regions that impair inhibitory control over drug-seeking. Breaking the contingencies between drug-associated cues and the delivery of the reward during extinction learning reduces relapse. Vagus nerve stimulation (VNS) has previously been shown to enhance extinction learning and reduce drug-seeking. Here we determined the effects of VNS-mediated release of brain-derived neurotrophic factor (BDNF) on extinction and cue-induced reinstatement in male rats trained to self-administer cocaine. Pairing 10 d of extinction training with VNS facilitated extinction and reduced drug-seeking behavior during reinstatement. Rats that received a single extinction session with VNS showed elevated BDNF levels in the medial PFC as determined via an enzyme-linked immunosorbent assay. Systemic blockade of tropomyosin receptor kinase B (TrkB) receptors during extinction, via the TrkB antagonist ANA-12, decreased the effects of VNS on extinction and reinstatement. Whole-cell recordings in brain slices showed that cocaine self-administration induced alterations in the ratio of AMPA and NMDA receptor-mediated currents in Layer 5 pyramidal neurons of the infralimbic cortex (IL). Pairing extinction with VNS reversed cocaine-induced changes in glutamatergic transmission by enhancing AMPAR currents, and this effect was blocked by ANA-12. Our study suggests that VNS consolidates the extinction of drug-seeking behavior by reversing drug-induced changes in synaptic AMPA receptors in the IL, and this effect is abolished by blocking TrkB receptors during extinction, highlighting a potential mechanism for the therapeutic effects of VNS in addiction., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking., Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy., Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months., Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection., Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively., Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89)., Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.

Polysialic acid (polySia) is a linear polymer of α2,8-linked sialic acid residues that is of fundamental biological interest due to its pivotal roles in the regulation of the nervous, immune, and reproductive systems in healthy human adults. PolySia is also dysregulated in several chronic diseases, including cancers and mental health disorders. However, the mechanisms underpinning polySia biology in health and disease remain largely unknown. The polySia-specific hydrolase, endoneuraminidase NF (EndoN), and the catalytically inactive polySia lectin EndoNDM, have been extensively used for studying polySia. However, EndoN is heat stable and remains associated with cells after washing. When studying polySia in systems with multiple polysialylated species, the residual EndoN that cannot be removed confounds data interpretation. We developed a strategy for site-specific immobilization of EndoN on streptavidin-coated magnetic beads. We showed that immobilizing EndoN allows for effective removal of the enzyme from samples, while retaining hydrolase activity. We used the same strategy to immobilize the polySia lectin EndoNDM, which enabled the enrichment of polysialylated proteins from complex mixtures such as serum for their identification via mass spectrometry. We used this methodology to identify a novel polysialylated protein, QSOX2, which is secreted from the breast cancer cell line MCF-7. This method of site-specific immobilization can be utilized for other enzymes and lectins to yield insight into glycobiology., (© The Author(s) 2024. Published by Oxford University Press.)

Non-alcoholic fatty liver disease (NAFLD) is a substantial contributor to liver-related morbidity worldwide, and yet, there are no standard, universal pharmacologic therapies approved for this indication. The aim of this systematic review and meta-analysis is to evaluate the effectiveness of SGLT-2 inhibitors in improving hepatic steatosis and hepatic fibrosis in patients with NAFLD. An extensive electronic database search was done to identify studies published from inception until December 2023, without any language restrictions. All randomized controlled trials (RCT) that evaluated the use of SGLT-2 inhibitors for patients with NAFLD, regardless of diabetes mellitus status, were included. The Cochrane Risk of Bias 2.0 tool was used to assess the risk of bias of each study included. Evidence from all studies were synthesized as mean differences for continuous data, and as risk ratio for dichotomous outcomes. An inverse variance or Mantel-Haenszel test was used in conjunction with a random-effects meta-analysis model, where necessary. 18 eligible RCTs involving 1330 participants were analyzed, all of which had risk of bias ranging from low to some concerns. Significant difference in means was observed for controlled attenuation parameter (6 trials, n = 372; MD: - 10.59 dB/m, 95% CI [- 18.25, - 2.92], p = 0.007, I 2  = 0%); L/S ratio (3 trials, n = 163; MD: 0.11, 95% CI [0.01, 0.21], p = 0.04, I 2  = 78%); LSM (7 trials, n = 447; MD: - 0.67 kPa, 95% CI [- 1.19, - 0.16], p = 0.010, I 2  = 69%); MRI-PDFF (5 trials, n = 330; MD: - 2.61%, 95% CI [- 5.05, - 0.17], p = 0.04, I 2  = 78%), and FIB-4 index (10 trials, n = 648; MD: - 0.12, 95% CI [- 0.21, - 0.04], p = 0.005, I 2  = 16%) after SGLT-2 inhibitor treatment as compared to controls. In conclusion, the use of SGLT-2 inhibitors may lead to slight improvement of hepatic steatosis and/or fibrosis as compared to controls in patients with NAFLD and Type 2 diabetes mellitus based on imaging and histopathology biomarkers with low to moderate certainty of evidence., (© 2024. The Author(s).)

Olive leaf, as an important by-product of olive farming, is generated from the pruning and harvesting of olive trees and represents >10 % of the total olive weight. The present study was conducted to evaluate the composition, functional and structural characterizations, as well as the in vitro digestibility of olive leaf proteins isolated from ultrasonic-assisted extraction, comparing to classical and industrial techniques. The ultrasound-assisted extraction of olive leaf protein was optimized by the simultaneous maximization of the yield and purity of protein using a Box-Behnken design (BBD) of response surface methodology (RSM). The results indicated that the optimal extraction conditions were as follows: pH of 10.99, temperature of 40.48 °C, sonication time of 47.25 min, and solvent/solid ratio of 24.08 mL/g. Under these conditions, the extraction yield and protein content were 11.67 and 51.2 %, respectively, which were significantly higher than those obtained by the conventional techniques. Regarding the functionality of protein, extraction technique had significant impacts on the structural and functional properties of proteins. In general, ultrasound assisted extraction had higher solubility, and better foaming and thermal properties and in vitro digestibility but lower emulsifying stability and fluid binding capacity compared to conventional ones. Ultrasound-assisted alkaline extraction has great potential to produce edible olive leaf protein with modified functional properties that can be used for various aims in the food applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The projected global population is expected to reach around 9.7 billion by 2050, indicating a greater demand for proteins in the human diet. Cereal bran proteins (CBPs) have been identified as high-quality proteins, with potential applications in both the food and pharmaceutical industries. In 2020, global cereal grain production was 2.1 billion metric tonnes, including wheat, rice, corn, millet, barley, and oats. Cereal bran, obtained through milling, made up 10-20% of total cereal grain production, varying by grain type and milling degree. In this article, the molecular composition and nutritional value of CBPs are summarized, and recent advances in their extraction and purification are discussed. The functional properties of CBPs are then reviewed, including their solubility, binding, emulsifying, foaming, gelling, and thermal properties. Finally, current challenges to the application of CBPs in foods are highlighted, such as the presence of antinutritional factors, low digestibility, and allergenicity, as well as potential strategies to improve the nutritional and functional properties by overcoming these challenges. CBPs exhibit nutritional and functional attributes that are similar to those of other widely used plant-based protein sources. Thus, CBPs have considerable potential for use as ingredients in food, pharmaceutical, and other products.

Background: Chronic infection with HBV is responsible for >50% of all hepatocellular cancer cases globally and disproportionately affects sub-Saharan African (sSA) countries. Migration from these countries to Europe has increased substantially in recent years, posing unique challenges to health systems. The aim of this study was to carry out a community-based intervention to increase HBV screening, vaccination, and linkage to care among sSA migrants in Catalonia, Spain., Methods: This was a prospective cohort study. Participants ≥18 years were offered community-based HBV screening between 20/11/20 and 21/01/22. Rapid HBV testing and blood sample collection utilizing plasma separation cards were carried out and linkage to care was offered to all participants. HBV vaccination and post-test counseling were performed at a second visit in the community. The main outcome was the odds of those with current HBV infection being successfully linked to hepatology. Rates of completing the care cascade of this model were analyzed., Results: In the present study, 444 people undergo screening, with 50.6% of participants showing evidence of past or current HBV infection, including an HBsAg prevalence of 9.2%. Migrants with current HBV infection exhibit 5.2 times higher odds of successful linkage to care compared to those in need of post-test counseling or vaccination. The study achieves a successful linkage to care rate of 72% for all participants, with specialist appointments arranged within 15.5 days., Conclusions: This community-based HBV screening program provides evidence of a successful model for identifying and providing care, including vaccination, to west African migrants at high risk of HBV infection who may otherwise not engage in care., (© 2023. The Author(s).)

Model validation of a well-known class of solid polymer electrolyte (SPE) is utilized to predict the ionic structure and ion dynamics of alternative alkali metal ions, leading to advancements in Na-, K-, and Cs-based SPEs for solid-state alkali metal batteries. A comprehensive study based on molecular dynamics (MD) is conducted to simulate ion coordination and the ion transport properties of poly(ethylene oxide) (PEO) with lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt across various LiTFSI concentrations. Through validation of the MD simulation results with experimental techniques, we gain a deeper understanding of the ionic structure and dynamics in the PEO/LiTFSI system. This computational approach is then extended to predict ion coordination and transport properties of alternative alkali metal ions. The ionic structure in PEO/LiTFSI is significantly influenced by the LiTFSI concentration, resulting in different lithium-ion transport mechanisms for highly concentrated or diluted systems. Substituting lithium with sodium, potassium, and cesium reveals a weaker cation-PEO coordination for the larger cesium-ion. However, sodium-ion based SPEs exhibit the highest cation transport number, indicating the crucial interplay between salt dissociation and cation-PEO coordination for achieving optimal performance in alkali metal SPEs.

Competing Interests: The authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Tuberculosis (TB) remains a global health problem and is the second leading cause of death from a single infectious agent, behind the novel coronavirus disease of 2019. Children are amongst the most vulnerable groups affected by TB, and imaging manifestations are different in children when compared to adults. TB primarily involves the lungs and mediastinal lymph nodes. Clinical history, physical examination, laboratory examinations and various medical imaging tools are combined to establish the diagnosis. Even though chest radiography is the accepted initial radiological imaging modality for the evaluation of children with TB, this paper, the first of two parts, aims to discuss the advantages and limitations of the various medical imaging modalities and to provide recommendations on which is most appropriate for the initial diagnosis and assessment of possible complications of pulmonary TB in children. Practical, evidence-based imaging algorithms are also presented., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite advances in diagnosis and treatment in recent years, tuberculosis (TB) remains a global health concern. Children are amongst the most vulnerable groups affected by this disease. Although TB primarily involves the lungs and mediastinal lymph nodes, it can affect virtually any organ system of the body. Along with clinical history combined with physical examination and laboratory tests, various medical imaging tools help establish the diagnosis. Medical imaging tests are also helpful for follow-up during therapy, to assess complications and exclude other underlying pathologies. This article aims to discuss the utility, strengths and limitations of medical imaging tools in the evaluation of suspected extrathoracic TB in the pediatric population. Imaging recommendations for the diagnosis will be presented along with practical and evidence-based imaging algorithms to serve as a guide for both radiologists and clinicians., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Uncontrolled hypertension is a significant problem in many parts of Asia. Effective management is essential to reduce the burden of hypertension. Home blood pressure monitoring (HBPM) is a promising tool that can aid in the diagnosis and management of hypertension. Experts from 11 countries/regions in Asia conceptualized a large-scale survey to examine the current realities of HBPM. A cross-sectional survey was conducted among health care professionals from China, India, Indonesia, Japan, Malaysia, the Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam between November 2019 and June 2021. Physicians' responses were summarized using descriptive statistics. A total of 7945 physicians participated in the survey. Among all respondents, 50.3% and 33.5% viewed HBPM as highly recognized by physicians and patients in their country/region, respectively. Lack of understanding of HBPM and concern with the accuracy and reliability of HBPM devices were identified as key barriers to HBPM recognition. Nearly all physicians (95.9%) reported recommending HBPM to their patients; however, they reported less than 50% of their patients measured home blood pressure (HBP). Among physicians who recommended HBPM, only 22.4% and 54.1% cited HBP diagnostic threshold values and timing of taking antihypertensive drugs that were consistent with available guidelines, respectively. The survey reveals that the recognition of HBPM as a valuable tool to diagnose and manage hypertension is suboptimal in most parts of Asia. Despite high recommendation of HBPM to hypertensive patients by physicians, there are considerable discrepancies between guidelines recommendations and practice realities. The recognition of HBPM as a valuable tool for the diagnosis and management of hypertension is suboptimal among both physicians and patients in Asia. A clear and consistent guidance for proper HBPM practice and use of validated and calibrated HBP monitors are among the top priorities to support the integration of HBPM into daily patient care. HBPM: home blood pressure monitoring, HBP: home blood pressure., (© 2023. The Author(s).)

The accumulation and aggregation of the microtubule-associated protein tau (tau) into intracellular neuronal tangles are a hallmark of a range of progressive neurodegenerative tauopathies, including Alzheimer's disease (AD), frontotemporal dementia, Pick's disease, and progressive supranuclear palsy. The aberrant phosphorylation of tau is associated with tau aggregates in AD. Members of the heat shock protein 70 kDa (Hsp70) family of chaperones bind directly to tau and modulate tau clearance and aggregation. Small molecules that inhibit the Hsp70 family of chaperones have been shown to reduce the accumulation of tau, including phosphorylated tau. Here, eight analogs of the rhodacyanine inhibitor, JG-98, were synthesized and evaluated. Like JG-98, many of the compounds inhibited ATPase activity of the cytosolic heat shock cognate 70 protein (Hsc70) and reduced total, aggregated, and phosphorylated tau accumulation in cultured cells. Three compounds, representing divergent c log P values, were evaluated for in vivo blood-brain barrier penetration and tau reduction in an ex vivo brain slice model. AL69, the compound with the lowest c log P and the lowest membrane retention in a parallel artificial membrane permeability assay (PAMPA), reduced phosphorylated tau accumulation. Our results suggest that benzothiazole substitutions of JG-98 that increase hydrophilicity may increase the efficacy of these Hsp70 inhibitors to reduce phosphorylated tau.

Bullous pemphigoid (BP) is characterized by deposition of immunoglobulins and complement along the epidermal basement membrane (BM). In humans, there is a lack of functional studies targeting the complement system (CS). This study investigates activation of all complement pathways in BP skin biopsies. Moreover, pharmacological inhibition at different levels of the CS was investigated using anti-complement compounds in a complement fixation BP assay. In this retrospective study, 21 frozen biopsies from BP patients were stained by direct immunofluorescence for C1q, MBL, ficolin-2, C4d, properdin, C3c and C5b-9. Sera from 10 patients were analysed in a complement fixation assay in the presence of C1 inhibitor, anti-factor B monoclonal antibody (mAb), anti-C3 mAb and anti-C5 mAb and compared with dexamethasone. The two readouts were the quantity of complement deposited along the BM and the release of sC5b-9 in the supernatant. Our results show classical and alternative complement pathway activation in BP skin biopsies, but could not demonstrate significant lectin pathway activation. In contrast to dexamethasone, complement deposition along the BM could be selectively inhibited by anti-C1 and anti- factor B. More downstream, selective intervention at the level of C3 and C5 could effectively reduce complement deposition along the BM and the release of sC5b-9 in the supernatant. This study shows that selective intervention in either the classical, alternative or terminal pathway prevented deposition of complement along the BM in an in vitro BP model. The results of our study greatly encourage the clinical development of complement inhibitors for the treatment of BP., (© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

The optical properties of periodic metallic nanoparticle lattices have found many exciting applications. Indium is an emerging plasmonic material that offers to extend the plasmonic applications given by gold and silver from the visible to the ultraviolet spectral range, with applications in imaging, sensing, and lasing. Due to the high vapor pressure/low melting temperature of indium, nanofabrication of ordered metallic nanoparticles is nontrivial. In this work, we show the potential of selective area electrochemical deposition to generate large-area lattices of In pillars for plasmonic applications. We study the optical response of the In lattices by means of angle-dependent extinction measurements demonstrating strong plasmonic surface lattice resonances and a good agreement with numerical simulations. The results open avenues toward high-quality lattices of plasmonic indium nanoparticles and can be extended to other promising plasmonic materials that can be electrochemically grown., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The left ventricular summit (LVS) is the area in the highest portion of the left ventricular epicardium, bounded by the left coronary arteries and the coronary venous circulation, and can be surrounded by thick epicardial fat that may preclude epicardial ablation. Ablation of LVS ventricular arrhythmias (VA) can be achieved from adjacent structures with good success rates. The long-term freedom from LVS VA recurrence remains variable. This article reviews the spatial and anatomic relationship of the structures surrounding the LVS, which provide vantage points for ablation, and the acute and long-term outcomes of different ablation approaches in LVS VA ablation., Competing Interests: Disclosure F.P. Chung: Speaker honorarium from Abbott Medical, Biosense Webster, and Boston Scientific., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Solid organ transplantation (SOT) recipients are known to carry an increased risk of malignancy because of long-term immunosuppression. However, the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN) in this population remains unclear. We performed a systematic review by searching PubMed, Embase, Scopus, and Google Scholar. All studies containing IPMNs in solid organ transplantation recipients were screened. We included 11 studies in our final analysis, totaling 274 patients with IPMNs of the 8213 SOT recipients. The prevalence from 8 studies was 4.7% (95% CI 2.4%-7.7%) in a random-effects model with median study periods of 24 to 220 months. The median rate for all progressions from 10 studies was 20% (range, 0%-88%) within 13 to 41 months of the median follow-up time. By utilizing the results of 3 case-control studies, the relative risk from a random-effects model for progression (worrisome features and high-risk stigmata) of IPMNs was 0.39 (95% CI 0.12-1.31). No adenocarcinoma derived from IPMN was reported in the included studies. Overall, this study indicates that the progression of pretransplant IPMN does not increase drastically compared with the general nontransplant population. However, considering the limited literature, further studies are required for confirmation., (Copyright © 2022 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

The advent of Li-metal batteries has seen progress toward studies focused on the chemical modification of solid polymer electrolytes, involving tuning either polymer or Li salt properties to enhance the overall cell performance. This study encompasses chemically modifying simultaneously both polymer matrix and lithium salt by assessing ion coordination environments, ion transport mechanisms, and molecular speciation. First, commercially used lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt is taken as a reference, where F atoms become partially substituted by one or two H atoms in the -CF 3 moieties of LiTFSI. These substitutions lead to the formation of lithium(difluoromethanesulfonyl)(trifluoromethanesulfonyl)imide (LiDFTFSI) and lithium bis(difluoromethanesulfonyl)imide (LiDFSI) salts. Both lithium salts promote anion immobilization and increase the lithium transference number. Second, we show that exchanging archetypal poly(ethylene oxide) (PEO) with poly(ε-caprolactone) (PCL) significantly changes charge carrier speciation. Studying the ionic structures of these polymer/Li salt combinations (LiTFSI, LiDFTFSI or LiDFSI with PEO or PCL) by combining molecular dynamics simulations and a range of experimental techniques, we provide atomistic insights to understand the solvation structure and synergistic effects that impact macroscopic properties, such as Li + conductivity and transference number., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Dengue is one of the most important vector-borne diseases worldwide and is a significant public health problem in the tropics. Mosquito control continues to be the primary approach to reducing the disease burden and spread of dengue virus (DENV). Aside from the traditional larviciding and adulticiding interventions, autodissemination using pyriproxyfen-treated (AD-PPF) ovitraps is one of the promising methods to complement existing vector control strategies. Our paper assessed the efficacy of AD-PPF in reducing DENV infections in two barangays in Parañaque City. Using saliva samples from the participants from both the control and intervention sites, we collected the seroprevalence data for three months in each of the two years. Spatial analysis was conducted to determine hotspot areas and identify DENV infection distributions across the trial periods. The results showed that the intervention site was identified as having a clustering of DENV infections in Month 0 of Year 1 and shifted to a random dispersion of dengue cases at the end of Month 3 in Year 2. The disappearance of the clustering of the intervention site translates to a decrease in the cases of DENV infection relative to the control site. Furthermore, we also identified that DENV transmission occurred at a small-scale level that did not go beyond 86 m. In conclusion, AD-PPF is suggested to be an effective strategy and may be used as an additional vector control approach, albeit based on this short-term implementation.

Medicaid provides virtually no-cost coverage to millions of low-income Americans. This study examines whether its beneficiaries realize similar health care access as their counterparts with private insurance. We draw on the 2014-2017 Medical Expenditure Panel Survey and control for observable confounding factors across coverage types by estimating and applying entropy weights. Medicaid beneficiaries were moderately more likely to report a usual source of care (74.5% vs 68.1%, p&lt;.01) and approximately equally as likely to report a checkup in the past year as the privately insured (43.5% vs 44.5%, p>.1), each significantly more likely than the uninsured. Medicaid beneficiaries had significantly more prescription fills (12.6 vs 8.2) and emergency-care visits (.26 vs .15) annually than the privately-insured on average, with similar numbers of physician visits. On balance, we did not find evidence that Medicaid was associated with diminished access or utilization relative to private insurance, while both had more access than the uninsured.

Although structural allograft has been previously described as acceptable practice for reconstructive foot and ankle surgery, results for an allograft bone wedge in Lapidus arthrodesis are unknown. Additionally, there is no consensus on the superiority of a single fixation construct in Lapidus cases. Our objective was (1) to report union rates for Lapidus arthrodesis with and without the use of an allograft bone wedge and (2) to determine if fixation construct impacts rates of union when using structural allograft. A review was performed for Lapidus cases with fixation constructs of 2 crossed compression screws (CS) and a medial locking plate with single transarticular screw (MPS), both with and without use of an allograft bone wedge. Inclusion required a CT scan to evaluate bony union. There was no significant difference in union rates (p = .41) between the use (90%) and the nonuse (97%) of an allograft bone wedge. Union rates were significantly different (p = .04) when comparing CS fixation (85%) and MPS fixation (98%). The comparative results between the fixation constructs highlight the importance of compression across the arthrodesis site as part of a robust fixation construct. Our findings demonstrate that the use of an allograft bone wedge in Lapidus arthrodesis may mitigate complications due to metatarsal shortening while providing satisfactory rates of union., (Copyright © 2022 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Tauopathies, such as Alzheimer's disease, are characterized by the misfolding and progressive accumulation of the microtubule associated protein tau. Chaperones, tasked with maintaining protein homeostasis, can become imbalanced with age and contribute to the progression of neurodegenerative disease. Cyclophilins are a promising pool of underinvestigated chaperones with peptidyl-prolyl isomerase activity that may play protective roles in regulating tau aggregation. Using a Thioflavin T fluorescence-based assay to monitor in vitro tau aggregation, all eight cyclophilins, which include PPIA to PPIH prevent tau aggregation, with PPIB, PPIC, PPID, and PPIH showing the greatest inhibition. The low thermal stability of PPID and the strong heparin binding of PPIB undermines the simplistic interpretation of reduced tau aggregation. In a cellular model of tau accumulation, all cyclophilins, except PPID and PPIH, reduce insoluble tau. PPIB, PPIC, PPIE, and PPIF also reduce soluble tau levels with PPIC exclusively protecting cells from tau seeding. Overall, this study demonstrates cyclophilins prevent tau fibril formation and many reduce cellular insoluble tau accumulation with PPIC having the greatest potential as a molecular tool to mitigate tau seeding and accumulation., (© 2022 The Protein Society.)

Dengue is a viral mosquito-borne disease that rapidly spreads in tropical and subtropical countries, including the Philippines. One of its most distinguishing characteristics is the ability of the Dengue Virus (DENV) to easily surpass the innate responses of the body, thus activating B cells of the adaptive immunity to produce virus-specific antibodies. Moreover, Dengvaxia ® is the only licensed vaccine for DENV, but recent studies showed that seronegative individuals become prone to increased disease severity and hospitalization. Owing to this limitation of the dengue vaccine, this study determined and compared consensus and unique B cell epitopes among each DENV (1-4) Philippine isolate to identify potential areas of interest for future vaccine studies and therapeutic developments. An in silico-based epitope prediction of forty (40) DENV 1-4 strains, each serotype represented by ten (10) sequences from The National Center for Biotechnology Information (NCBI), was conducted using Kolaskar and Tongaonkar antigenicity, Emini surface accessibility, and Parker hydrophilicity prediction in Immune Epitope Database (IEDB). Results showed that five (5) epitopes were consensus for DENV-1 with no detected unique epitope, one (1) consensus epitope for DENV-2 with two (2) unique epitopes, one (1) consensus epitope for DENV-3 plus two (2) unique epitopes, and two (2) consensus epitopes and one (1) unique epitope for DENV-4. The findings of this study would contribute to determining potential vaccine and diagnostic marker candidates for further research studies and immunological applications against DENV (1-4) Philippine isolates.

Introduction: Socks are of fundamental importance in reducing friction and in controlling the temperature and humidity of the foot, thus preventing the appearance of blisters. However, the influence of sock fibres (synthetic vs. natural) on blistering during long-distance hiking has received little research attention., Aims: This study evaluates the influence of sock fibres on the appearance of foot blisters in hikers., Method: The sample consisted of 203 male and female hikers, mean age 35.8 ± 14.5 years, from 22 countries. All were interviewed and assessed at shelters on the French route of the Camino de Santiago (Spain). Sociodemographic and clinical data were obtained for each hiker; other study data included the number of blisters on the foot, whether the socks were wet at the end of the day, the model of sock used and the nature of its constituent fibres., Results: Among the hikers interviewed, 68.5% presented foot blisters. 74.2% used socks with predominantly synthetic fibres, compared to 25.9% whose socks were mainly composed of natural fibres. On average, they had walked 253.7 km. Hiking in wet socks was associated with a 1.94 times greater risk of experiencing foot blisters (95% CI 1.04-3.61) (p = 0.035). Multivariate analysis showed that the proportion of natural/synthetic fibres in the composition of the sock was not related to the presence of blisters., Conclusions: The use of wet socks heightens the risk of foot blisters in hikers, but the composition of the sock is not associated with blistering. We recommend hikers change their socks in long stages to maintain feet dry and so avoiding the appereance of blisters., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)