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Decompression sickness (DCS) risk limits human undersea operations through tissue inert gas supersaturation and pathological bubble formation. Switching the inert breathing gas prior to decompression to a gas with lower diffusivity could allow faster and safer decompression. This principle was tested in 20 kg swine after a helium-oxygen (He/O2) dive using carbon tetrafluoride. Sedated swine breathed He/O2 79/21 at a pressure equivalent of 200 feet of seawater (714 kPa) in a hyperbaric chamber for 50 min until randomized to continuing He/O2 or switching to carbon tetrafluoride and oxygen (CF4/O2 79/21) for 10 min before decompression. The CF4/O2 group had reduced DCS with lower mortality, hypoxemia, pulmonary edema, venous gas emboli, gait disturbance, rash, and central nervous system hemorrhage. CF4/O2 has the potential to expand human exploration through enabling deeper dives, longer dives, and rapid decompression while maintaining safety.
Two new species of bogidiellid amphipods, Bogidiella isajii and B. painushima are described from an anchialine undersea cave in Minamidaito Island and freshwater flowing through a cave in Ishigaki Island, Ryukyu Islands. Bogidiella isajiisp. nov. differs from its congeners in the absence of an inner ramus on the pleopods, armature of uropods 1 and 2 rami, and shape of the telson. Bogidiella painushimasp. nov. is morphologically similar to B. aprutina and B. broodbakkeri, but differs from these two species in the shape of antennal sinus of the head, size of antenna 2 peduncular article 2 gland cone, armature of the accessory setal row of the mandible, shape of gnathopod 1 propodus and pereopod 7 coxa, and armature of the telson. Nucleotide sequences of the mitochondrial cytochrome c oxidase subunit I from paratypes of the two new species were determined for future studies.
Type 1 diabetes mellitus (T1DM) is a complex systemic condition that poses unique challenges for diagnosis and management in military environments, particularly on submarines where access to standard medical resources is limited. This case series examines three instances of a first diagnosis of T1DM among active duty male U.S. Navy submariners, highlighting the challenges of managing this condition in austere military environments. Case 1 involves a 27-yr-old experiencing gastrointestinal symptoms during deployment and found to have diabetic ketoacidosis (DKA) complicated by renal failure and pancreatitis. Case 2 features a 22-yr-old presenting with weakness and fatigue on board leading to a diagnosis of DKA and pancreatitis. In Case 3, a 20-yr-old initially treated for pilonidal disease later manifests classic T1DM symptoms, leading to delayed diagnosis despite increased access to care in port. These cases underscore the importance of early recognition and intervention, particularly in environments with limited medical resources. Delays in communication and access to higher echelons of care further compound the challenges of managing T1DM and DKA on submarines. To address these issues, the Naval Undersea Medical Institute has developed protocols to empower medical personnel in diagnosing and managing T1DM in such settings. By sharing these experiences, this report aims to improve awareness and preparedness for managing T1DM in submarines, ultimately enhancing the care provided to patients in austere military environments. Monroe DM, Earley JP. Diabetic ketoacidosis reported from U.S. Navy submarines, 2021-2024. Aerosp Med Hum Perform. 2026; 97(5):379-383.
North Atlantic minke whales (Balaenoptera acutorostrata acutorostrata) were acoustically detected and localized in real-time for 3.5 h off Jacksonville, Florida. During 1 h of this encounter, an individual was visually and acoustically tracked. Manual review of the recordings identified continuous low-frequency pulse trains (40-674 Hz). Not all pulse trains observed have been documented previously in the North Atlantic. Variation in frequency, duration, and the combination of known pulse trains were documented. The tracked whale also altered its calling behavior while the research vessel was present. These data provide insight into the acoustic behavior of minke whales in their winter habitat.
Prevena (3M KCI, US) is a new incisional negative pressure wound therapy system (iNPWT) for closed surgical incision management. The surgical management of pressure ulcers (PUs) remains challenging. A high rate of recurrence and overall complications have been reported. This study analysed the clinical efficacy of the iNPWT system in patients with PUs. In this retrospective study, patients with stage 3 or 4 PUs who were surgically managed by a single plastic surgeon specialising in PUs at Tri-Service General Hospital, Taiwan, between January 2011 and June 2022 were reviewed. The primary outcomes assessed were: wound healing complications; dressing change frequency; and length of hospital stay. Patients were divided into two groups: those receiving the iNPWT system (iNPWT group) and those not receiving the iNPWT system (non-iNPWT group). A total of 187 patients were included (n=161 non-iNPWT group; n=26 iNPWT group). The rate of poor outcomes (defined as partial dehiscence or inadequate wound healing that required a secondary debridement followed by primary closure or additional flap reconstruction) was 19.2% (n=5) in the iNPWT group compared to 31.1% (n=50) in the non-iNPWT group. A lower number of dressing changes was noted in the iNPWT group (p<0.001). Male sex and multiple debridement procedures (≥2 times) were significantly associated with poor outcomes, with odds ratios of 2.10 (p=0.032) and 3.72 (p=0.009), respectively. A higher albumin level (>3.0g/dl) was significantly associated with better outcomes (p=0.009). A lower poor outcome rate of wound healing was noted in the iNPWT group. Otherwise, the use of the iNPWT system reduced the number of dressing changes, which potentially reduces the caregiving burden and improves patient comfort. The Prevena system may be a more effective choice for patients with PUs after reconstruction.
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The qualification of additively manufactured (AM) components produced from engineering polymers poses unique challenges, particularly when evaluating mechanical properties according to ASTM D638. The application of high-performance thermoplastics, such as ULTEM™ 9085 and ULTEM™ 1010, frequently relies on manufacturer-provided datasheets for qualification. However, existing datasheets do not provide guidance specific to articles printed in the XY plane, which can be complicated by failures that initiate at microstructural anomalies rather than being driven by intrinsic material behavior. The objective of this study was to investigate the performance and qualification of ULTEM 9085™, examined according to ASTM D638, and pursue improvements through refined print parameters. A significant improvement in strength and conforming failures was achieved with modest adjustments to the print settings. For Type 1 samples printed with ±45° infill, gage section failures improved from only 5% to 100%, while samples with 0/90° infill achieved 80%. Correspondingly, the ultimate tensile strength increased from 49 ± 2 MPa to 61 ± 2 MPa and from 53 ± 3 MPa to 63 ± 6 MPa, respectively. These results underscore the critical role of process parameters, including contour overlap, in qualifying polymer AM materials, and their contribution to the performance and reliability of printed components.
Mitochondrial dysfunction resulting in mitochondrial DNA (mtDNA) leakage is one of the main triggers of immune responses in systemic lupus erythematosus (SLE). In contrast, mitochondrial RNA (mtRNA) leakage and its role in SLE remains poorly understood. Interferon-alpha (IFN-α) and immune complexes (ICs) are both pathogenic contributors to SLE. Following the detection of increased mtRNA in the serum of patients with SLE, we explored the mechanisms of mtRNA leakage. Exposure to IFN-α at 100 U/ml, a pathophysiological concentration detected in SLE patients with mild to moderate disease activity, resulted in mitochondrial permeability transition pore (mPTP) opening and voltage dependent anion channel 1 (VDAC1) oligomerization, leading to mtRNA leakage and downstream inflammatory pathway activation in bone marrow-derived macrophages (BMDMs) of mice. However, we did not observe the activation of BCL2 antagonist/killer 1 (BAK) and BAK/BCL2-associated X (BAX) (BAX/BAK) pores and mitophagy does not play roles in these effects. Overloaded mitochondrial calcium released from the endoplasmic reticulum is likely responsible for mitochondrial pore opening. Similar effects were observed with ICs treatment. Several commonly recognized events contributing to mitochondrial pore opening such as cell death, apoptosis and changes of mitochondrial membrane potential were not detected and a pan-caspase inhibitor Z-VAD-FMK could not block IFN-α and ICs-induced mtRNA release. Our studies demonstrated an unexpected phenomenon that a pathophysiological concentration of IFN-α and ICs can selectively induce mitochondrial pore opening leading to mtRNA release in primary macrophages.
BACKGROUND: Activation of the cannabinoid type 2 (CB2) receptor has been demonstrated to offer protective effects against various inflammatory conditions and tissue injuries across different organs. Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, has been increasingly recognized as a contributor to the severity of acute lung injury (ALI). However, the precise role of CB2 receptor activation in hyperoxia-induced acute lung injury (HALI) remains poorly defined. METHODS: This study investigated the effects of JWH133, a selective CB2 receptor agonist, using both in vivo animal models and in vitro cellular models exposed to hyperoxia conditions. Lung tissue and bronchoalveolar lavage fluid (BALF) were collected at the end of the experiments for analyses, and animal survival rates were recorded throughout the experimental period. Concurrently, mouse lung epithelial cells (MLE-12) were cultured under hyperoxia conditions. To specifically elucidate the role of GPX4, siRNA-mediated knockdown was employed in both animal and cellular models, providing a detailed assessment of its functional relevance. RESULTS: Treatment with JWH133 significantly improved survival rates, reduced pulmonary edema, and markedly decreased inflammatory cytokine levels, oxidative stress markers, and indicators of ferroptosis in hyperoxia-exposed models. Furthermore, JWH133 effectively inhibited NF-κB signaling and reduced cell death in lung tissues, accompanied by enhanced expression of glutathione peroxidase 4 (GPX4). Consistent with these in vivo findings, hyperoxia-exposed MLE-12 cells treated with JWH133 exhibited similar protective effects. Notably, the protective effects of JWH133 were negated when GPX4 expression was silenced using targeted siRNA in both animal and cellular models. CONCLUSION: Our findings suggest that JWH133 confers protection against HALI primarily by upregulating GPX4 expression, highlighting its potential as a promising therapeutic strategy for HALI.
This study aimed to clarify the scientific basis for deriving Tolerable Daily Intake (TDI) values in risk assessments conducted by the Food Safety Commission of Japan (FSCJ), with a particular focus on the types of studies used, uncertainty factors (UFs), and critical effect levels (No-Observed-Adverse-Effect Levels and Lowest-Observed-Adverse-Effect Levels). We reviewed 77 chemical risk assessment reports published by the FSCJ as of October 2022. Using a standardized data extraction template developed with reference to the ATSDR and IRIS formats, ten trained reviewers examined and coded relevant toxicological information. In total, 46 reports were included in the final analysis. Most TDI values (73.9%) were derived from animal studies and were typically accompanied by large UFs ranging from 100 to 1000. Human-based TDIs derived from human observational (15.2%) and human intervention (10.9%) studies accounted for a smaller proportion but were generally associated with higher TDI values and smaller UFs. The examination of the NOAEL and LOAEL distributions indicated that lower exposure thresholds were primarily based on human study, whereas higher thresholds predominantly relied on animal studies. The derivation of TDI in Japan relies predominantly on animal study. Enhancing the availability of high-quality human data and improving consistency in the application of UFs may strengthen the transparency and scientific validity of health-based guidance in the future.
The melatonin receptor 1 A (MTNR1A), a highly conserved G protein-coupled receptor (GPCR), mediates crucial physiological functions. Its structure features an N-terminus responsible for melatonin binding and a C-terminus that initiates downstream signaling pathways to modulate target gene expression. Given MTNR1A's ability to form homodimers or heterodimers with other GPCRs, its expression levels are critical for the precise control of cellular signaling. This review article provides a comprehensive update on MTNR1A, highlighting recent developments concerning its expression distribution, gene regulation, protein motifs, and mediated signaling pathways. We also discuss the clinical relevance of single-nucleotide polymorphisms (SNPs) associated with the MTNR1A receptor and the range of diseases linked to its dysfunction. Current understanding and future perspectives regarding gene regulation and the stimulation of MTNR1A expression are critically addressed. Furthermore, we investigate the role of MTNR1A genetic variants in idiopathic osteoporosis and the association between decreased MTNR1A expression and membranous nephropathy. The systemic involvement of MTNR1A downregulation in cancer, fetal growth restriction, type 2 diabetes, and Parkinson's and Alzheimer's diseases is further underlined by its established biological functions. In conclusion, targeting MTNR1A-related downregulation and developing specific agonists or modulators offer a promising avenue for advancement in therapeutic medicine.
The aim of this study was to evaluate the clinical efficacy of intravenous laser irradiation of blood (ILIB) therapy as an adjunct treatment for patients with ischemic stroke. Despite the diverse medical applications of ILIB, there was no strong evidence on the efficacy of ILIB for improving the clinical outcomes of ischemic stroke. A total of 22 patients with ischemic stroke were randomly assigned to either the ILIB or the control group. The ILIB group received intravenous laser therapy, whereas the control group received the same intervention but without the output power. The after outcome measures were assessed at baseline and at 3 days, 1 month, and 3 months post intervention: National Institute of Health Stroke Scale score, modified Rankin Scale score, Stroke Impact Scale (SIS) score, Fugl-Meyer assessment-Motor Function (FMA-MF) score, and 6-minute walking test (6-MWT) performance. In total, 10 and 12 participants were randomized to the ILIB and control groups, respectively. Compared with the control group, the ILIB group showed significantly better SIS scores at the 3-month follow-up (p = 0.019), significantly higher FMA-MF scores at the 3-day and 3-month follow-ups (p = 0.003 and p = 0.022), and significantly better 6-MWT performance at the 3-day follow-up (p = 0.018). ILIB therapy provided short-term improvements in functional outcomes, including SIS, FMA-MF scores, and 6-MWT, in patients with ischemic stroke.
Prostate cancer remains a major cause of cancer-related mortality, and new therapeutic strategies are needed for advanced disease. Niclosamide and related salicylanilide compounds have emerged as multitarget anticancer agents, but the molecular contexts associated with their activity remain incompletely understood. Here, we applied a phenotype-oriented integrative framework to characterize the molecular context and phenotypic activity of NSC828786, a niclosamide-like salicylanilide derivative. Cross-cohort transcriptomic analyses identified AMACR (alpha-methylacyl-CoA racemase) and HPN (hepsin) as consistently upregulated genes in independent prostate adenocarcinoma cohorts. NCI-60 profiling demonstrated broad-spectrum low-micromolar antiproliferative activity, including AR-negative prostate cancer and breast cancer cell lines spanning multiple receptor subtypes; however, quantitative ranking did not support preferential receptor subtype selectivity. CellMiner COMPARE analysis showed no significant correlation between baseline AMACR or HPN expression and NSC828786 sensitivity. Structure-based analyses supported computational compatibility of NSC828786 with predicted HPN- and AMACR-associated binding regions, while zebrafish assays showed no overt developmental abnormalities at concentrations ≤ 5 μM. These findings identify NSC828786 as a phenotypically active salicylanilide derivative and position HPN and AMACR as exploratory candidate molecular associations warranting further mechanistic and target engagement studies.
Sudden sensorineural hearing loss (SSNHL) is an otologic emergency with a highly variable clinical course. Hyperbaric oxygen therapy (HBOT) has been widely used as an adjunctive treatment; however, its efficacy and determinants of treatment response remain incompletely defined. The aim of this study was to evaluate hearing outcomes in patients receiving HBOT and to assess the association between treatmentrelated factors and audiometric recovery. This retrospective study included 65 patients with idiopathic SSNHL. Pure tone audiometry thresholds were evaluated at baseline, post-treatment, and long-term follow-up when available. Changes were analyzed with the Wilcoxon signed-rank and Friedman tests, and correlations with recovery were assessed using Spearman's analysis. Complete pre- and post-treatment data were available for 65 patients. A statistically significant improvement in hearing thresholds was observed, decreasing from 41.7 ± 21.9 dB at baseline to 31.9 ± 22.1 dB following HBOT (P < .001). Among 19 patients with long-term follow-up, hearing thresholds further improved to 25.9 ± 17.3 dB. A significant difference was observed between baseline and long-term measurements (P = 0.006), although the overall comparison did not reach statistical significance (P = .209). No significant correlations were identified between hearing improvement and the number of HBOT sessions (r = 0.11, P = .387) or treatment delay (r = -0.06, P = .658). Etiological factors observed in the study population included upper respiratory infection (n = 30), acoustic barotrauma (n = 2), trauma (n = 1), and cases with no identifiable cause (n = 32). When analyzed according to etiology, no statistically significant difference in hearing threshold improvement was observed between groups (Kruskal-Wallis test, P = .151). HBOT demonstrated a positive effect on hearing thresholds in patients with SSNHL, with the observed audiological improvements appearing to be sustained at long-term follow-up Cite this article as: Kuduban O, Özkan R. Shortand long-term hearing outcomes after hyperbaric oxygen therapy in idiopathic sudden sensorineural hearing loss. 2026, 58(4), 1486, doi: 10.5152/ eurasianjmed.2026.261486.
In 2026, the US Centers for Medicare & Medicaid Services implemented an update to the Physician Fee Schedule establishing a unified reimbursement rate for skin substitutes, also referred to as cellular, acellular and matrix-like products (CAMPs). This policy change introduced a fixed payment of [Formula: see text]127.14 per cm2, regardless of product type or regulatory classification. The aim of this work was to assess perceived impacts of the revised fee schedule that went into effect on 1 January 2026. The Wound and Hyperbaric Association conducted an online national survey of wound care practitioners and practices from 4 February 2026 to 14 April 2026. The Access Crisis Feedback Form consisted of 13 questions, including two open-ended items. Over the 69 days that the survey was open, 130 (~3%) responses were received from a comparative pool of 4551 National Provider Identifiers that had applied a CAMP in 2024. Collectively, respondents reported providing care to approximately 12,000 patients with wounds per week. Geographic representation included 36 of 50 (72%) states and Washington DC, and 8 of 12 (67%) Medicare Administrative Contractors. Most respondents (82%) practiced in non-facility settings; however, hospital-affiliated outpatient wound centres, and ambulatory surgery centres were also represented. The most severe concern identified was the 'Closure or planned closure of a wound care practice or service line', reported by just over 45% of responding settings. Only five (4%) respondents reported no significant impact, indicating that 96% perceived at least one operational impact following implementation of the revised payment policy. The most frequently cited concern (61%) was 'Authorisation delays for clinically eligible patients'. Analysis of the survey data suggests widespread impacts of the implemented CAMPs universal fee schedule across diverse wound care delivery settings in the US, including a substantial risk of service line closures. These findings raise concerns that a uniform CAMP product payment may not achieve site-of-care neutrality when hospital outpatient departments receive a separate application facility payment, while non-facility providers do not. Respondents reported that patients are already experiencing reduced access to advanced wound care, with associated complications such as: infection; sepsis; amputation; wound deterioration or enlargement; hospital readmission; the need for surgical debridement in the operating room setting; and flap- or graft-based salvage procedures. Responding wound care providers and practices, across diverse care settings and geographic regions, urge reevaluation of the current reimbursement framework to ensure the financial sustainability of wound care services, and to protect patient access and outcomes.
This paper extends prior work on an auditory inspired adaptive synchrony capture filterbank (SCFB) architecture for acoustic frequency tracking. The earlier SCFB architecture used a weighted sum of frequency discriminator loop (FDL) and a phased locked loop (PLL) to track frequency components precisely. The key improvements in this paper are the introduction of adaptive FDL and PLL weights and the incorporation of a place theory-based mechanism to preferentially activate fewer filters, resulting in enhanced biomimicry and computational efficiency. The effectiveness of these improvements is demonstrated using synthetic time-varying signals, simultaneously highlighting the algorithm's robust denoising capability under challenging noise conditions.
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults. Whilst glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for obesity management, their potential impact on AMD risk in individuals without diabetes remains unclear. This study aimed to evaluate the association between GLP-1RA initiation and the risk of incident AMD in obese adults without diabetes. We conducted a target trial emulation using the TriNetX global health research network (January 2014-June 2025). Eligible participants were adults aged ≥ 60 years with obesity but without diabetes mellitus. New users of GLP-1RAs were compared with new users of other weight-loss medications. Following 1:1 propensity score matching, Cox proportional hazards models estimated hazard ratios (HRs) for incident AMD over a maximum 7-year observation window (median follow-up: 1.11 years [IQR: 1.48] in the GLP-1RA group versus 2.56 years [IQR: 3.89] in the comparator group). In 157 880 matched patients (78 940 per group), GLP-1RA use was associated with a significantly lower risk of incident AMD (HR 0.82; 95% CI 0.68-0.98) compared with other weight-loss medications. Subtype analyses revealed reduced risk for unspecified AMD (HR 0.70; 95% CI 0.52-0.93) and a potential trend towards a lower risk of nonexudative AMD (HR 0.78; 95% CI 0.60-1.00; p = 0.050). Subgroup analyses suggested stronger effects in women and adults aged 60-69 years; all subgroup findings should be interpreted as exploratory. GLP-1RA use is associated with a reduced risk of incident AMD-statistically significant for unspecified AMD, with a potential trend towards a lower risk of nonexudative AMD-in obese adults without diabetes. Whether this reflects direct GLP-1RA neuroprotective mechanisms, greater weight-loss magnitude or both remains to be determined. Further mechanistic research and prospective clinical trials are warranted.
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Metacognitive awareness of decision quality is important for adaptive decision-making. One marker of decision quality is the strength of internal evidence accumulation. Increasing sensitivity to evidence accumulation thus offers a potential mechanism for improving metacognition. To test this hypothesis, we trained two groups of participants (n = 34 per group) to reproduce the motion direction of one of two sequentially presented dot-motion stimuli. Participants in the forced-choice group were instructed which stimulus to respond to, whereas those in the free-choice group chose which stimulus they responded to. This manipulation targeted the instrumental value of metacognitive awareness, as participants in the free-choice group could use metacognition to optimize their choices. Before and after training, participants completed a near-transfer motion-discrimination task and provided metacognitive judgments, allowing us to assess how training altered sensitivity to evidence accumulation. Evidence accumulation was measured using the centroparietal positivity (CPP) and the drift rate. Participants in both groups performed better and exhibited improved metacognition following training. Training increased sensitivity to the predecisional CPP in the free-choice group and to the postdecisional CPP in the forced-choice group. Moreover, training increased sensitivity to the drift rate in the free-choice group but not the forced-choice group. These results provide novel insights into the neurocognitive mechanisms underlying training-induced improvements in metacognition.NEW & NOTEWORTHY We tested whether a novel training paradigm could increase participants' sensitivity to internal signals of decision quality and improve their decision-making and metacognition. Participants' behavioral performance improved following training, and this was accompanied by increased strength of the relationship between the centro-parietal positivity, a neural correlate of evidence accumulation, and participants' metacognitive judgments. Our work demonstrates that training can increase sensitivity to internal signals of decision uncertainty.