Exploring the role of anticipatory postural adjustment duration within APA2 subphase as a potential mediator between clinical disease severity and fall risk in Parkinson's disease.

Introduction: People with Parkinson's Disease (PD) often show reduced anticipatory postural adjustments (APAs) before voluntary steps, impacting their stability. The specific subphase within the APA stage contributing significantly to fall risk remains unclear. Methods: We analyzed center of pressure (CoP) trajectory parameters, including duration, length, and velocity, throughout gait initiation. This examination encompassed both the postural phase, referred to as anticipatory postural adjustment (APA) (APA1, APA2a, APA2b), and the subsequent locomotor phases (LOC). Participants were instructed to initiate a step and then stop (initiating a single step). Furthermore, we conducted assessments of clinical disease severity using the Unified Parkinson's Disease Rating Scale (UPDRS) and evaluated fall risk using Tinetti gait and balance scores during off-medication periods. Results: Freezing of gait (FOG) was observed in 18 out of 110 participants during the measurement of CoP trajectories. The Ramer-Douglas-Peucker algorithm successfully identified CoP displacement trajectories in 105 participants (95.5%), while the remaining 5 cases could not be identified due to FOG. Tinetti balance and gait score showed significant associations with levodopa equivalent daily dose, UPDRS total score, disease duration, duration (s) in APA2a (s) and LOC (s), length in APA1 (cm) and APA2b (cm), mediolateral velocity in APA1 (X) (cm/s), APA2a (X) (cm/s), APA2b (X) (cm/s) and LOC (X) (cm/s), and anterior-posterior velocity in APA2a (Z) (cm/s) and APA2b (Z) (cm/s). Multiple linear regression revealed that only duration (s) in APA2a and UPDRS total score was independently associated with Tinetti gait and balance score. Further mediation analysis showed that the duration (s) in APA2a served as a mediator between UPDRS total score and Tinetti balance and gait score (Sobel test, p = 0.047). Conclusion: APA2 subphase duration mediates the link between disease severity and fall risk in PD, suggesting that longer APA2a duration may indicate reduced control during gait initiation, thereby increasing fall risk.

Artificial Intelligence Application in Skull Bone Fracture with Segmentation Approach.

This study aims to evaluate an AI model designed to automatically classify skull fractures and visualize segmentation on emergent CT scans. The model's goal is to boost diagnostic accuracy, alleviate radiologists' workload, and hasten diagnosis, thereby enhancing patient outcomes. Unique to this research, both pediatric and post-operative patients were not excluded, and diagnostic durations were analyzed. Our testing dataset for the observer studies involved 671 patients, with a mean age of 58.88 years and fairly balanced gender representation. Model 1 of our AI algorithm, trained with 1499 fracture-positive cases, showed a sensitivity of 0.94 and specificity of 0.87, with a DICE score of 0.65. Implementing post-processing rules (specifically Rule B) improved the model's performance, resulting in a sensitivity of 0.94, specificity of 0.99, and a DICE score of 0.63. AI-assisted diagnosis resulted in significantly enhanced performance for all participants, with sensitivity almost doubling for junior radiology residents and other specialists. Additionally, diagnostic durations were significantly reduced (p < 0.01) with AI assistance across all participant categories. Our skull fracture detection model, employing a segmentation approach, demonstrated high performance, enhancing diagnostic accuracy and efficiency for radiologists and clinical physicians. This underlines the potential of AI integration in medical imaging analysis to improve patient care.

Variability in Inner Ear Morphology Among a Family With Pendred Syndrome Due to a SLC26A4 Gene Variant.

OBJECTIVES: Pendred syndrome, an autosomal recessive disorder, is often associated with pathogenic variants of the SLC26A4 gene that encodes the pendrin protein. Given its autosomal recessive inheritance, tracing the family history and screening siblings become crucial once a diagnosis of Pendred syndrome is confirmed. This case report aims to underscore the variability in inner ear morphology within a family diagnosed with Pendred syndrome, all carrying the same SLC26A4 gene mutation. METHODS: A chart review and a review of the literature. RESULTS: We present a family of 4, all of whom possess sensorineural hearing loss due to the same homozygous SLC26A4 variant c.919-2A>G. Intriguingly, clinical manifestations, especially inner ear deformities, displayed variability among family members. Notably, 1 family member exhibited a normal cochleovestibular structure morphology, which was rarely reported in the literature. CONCLUSIONS: This report highlights the significance of genetic testing and familial consultation when a proband exhibits typical Pendred syndrome symptoms. It also underscores that the inner ear morphology can exhibit variability among family members, even with the same homozygous SLC26A4 variant.

Addressing methodological concerns in omega-3 trial for bipolar disorder relapse prevention.

Our response addresses concerns raised about our pilot trial on omega-3 for bipolar disorder. We clarify randomization procedures, highlight the benefits of eicosapentaenoic-predominant formulations for a specific bipolar patients subgroup, and justify the use of Kaplan-Meier analysis despite limitations. We acknowledge analytical challenges due to strict inclusion criteria and encourage future research on specific bipolar subtypes and larger-scale trials for robust validation.

Multiscale brain age prediction reveals region-specific accelerated brain aging in Parkinson's disease.

Brain biological age, which measures the aging process in the brain using neuroimaging data, has been used to assess advanced brain aging in neurodegenerative diseases, including Parkinson disease (PD). However, assuming that whole brain degeneration is uniform may not be sufficient for assessing the complex neurodegenerative processes in PD. In this study we constructed a multiscale brain age prediction models based on structural MRI of 1240 healthy participants. To assess the brain aging patterns using the brain age prediction model, 93 PD patients and 91 healthy controls matching for sex and age were included. We found increased global and regional brain age in PD patients. The advanced aging regions were predominantly noted in the frontal and temporal cortices, limbic system, basal ganglia, thalamus, and cerebellum. Furthermore, region-level rather than global brain age in PD patients was associated with disease severity. Our multiscale brain age prediction model could aid in the development of objective image-based biomarkers to detect advanced brain aging in neurodegenerative diseases.

Salvage radiofrequency ablation followed by external beam radiotherapy for inoperable recurrent differentiated thyroid cancer.

PURPOSE: The treatment of recurrent thyroid cancer with critical organ invasion is challenging. The combination of radiofrequency ablation (RFA) and external beam radiation therapy (EBRT) has been proposed as an effective option. This study evaluates outcomes for inoperable residual/recurrent differentiated thyroid cancer (rDTC) patients treated with RFA followed by EBRT. MATERIALS AND METHODS: Patients with rDTC treated with RFA followed by EBRT were retrospectively studied. RFA was performed using a free-hand, 'moving-shot' technique under US or CT guidance. For lesions invading critical structures intolerant to 'en bloc' high-temperature RFA, limited-field EBRT using 6- or 10-MV photons was used for adjuvant treatment at a dose of 66 Gy in 33 daily fractions. Toxicities and outcomes were reviewed. RESULTS: Between April 2020 and January 2022, 11 patients with 14 rDTC lesions underwent RFA followed by EBRT. Five patients had metastatic lesions at rDTC diagnosis. With a median follow-up period of 33.7 months, all patients maintained locoregional control, while achieving a 2-year survival rate of 90.9%. This combined treatment achieved a volume reduction ratio of 92.1% ± 5.1%. The mean nadir thyroglobulin level in patients without initial distant metastases after treatment was 1.40 ± 0.81 ng/ml. Regarding treatment-related complications, one patient (9%) experienced temporary hoarseness after RFA, grade 2 radiation dermatitis occurred in 3 patients (27.2%), and grade 2 dysphagia was noted in 4 patients (36.4%). No grade 3 or greater toxicities occurred. CONCLUSIONS: Salvage RFA followed by EBRT is feasible, effective and safe for patients with rDTC.

A comparison of various insulin resistance indices and the possibility of hypertension in military adults: CHIEF study.

BACKGROUND: Insulin resistance is associated with the development of hypertension, whereas there were rare studies comparing various non-insulin based insulin resistance (NI-IR) indices for the possibility of hypertension among young and middle-aged adults. METHODS: This cross-sectional study included a total of 4,080 military personnel, aged 18-50 years, without antihypertensive medications therapy in 2014. All subjects received annual health examinations for blood pressure (BP) measurements. Stage I isolated diastolic hypertension (IDH) and isolated systolic hypertension (ISH) and combined hypertension were respectively defined as systolic BP (SBP) < 130 mmHg/diastolic BP (DBP) 80-89 mmHg, SBP 130-139 mmHg/DBP < 80 mmHg, and SBP 130-139 mmHg/DBP 80-89 mmHg. The cut-off values of stage II hypertension for SBP and DBP were 140-159 mmHg and 90-99 mmHg, respectively. Four NI-IR indices included the serum triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio, TyG index, Metabolic Score for IR (METS-IR) and ZJU index which were defined according to their specific formula. Multiple logistic regression analysis with adjustments for age, sex, anthropometrics, substance use, kidney function, serum uric acid, atherogenic cholesterols and physical activity was performed to determine the associations. RESULTS: There were 1,024 subjects with hypertension (25.1%) in which 739 were stage I hypertension, and 285 were stage II hypertension. For total hypertension, there were an association with TyG and METS-IR indices [odds ratios (ORs) and 95% confidence intervals: 1.432 (1.215-1.688) and 1.553 (1.040-2.321), respectively]. For hypertension subtypes, TyG index was positively associated with overall, stage I, and stage II ISH [ORs: 1.447 (1.149-1.823), 1.317 (1.029-1.687), and 2.011 (1.351-2.994), respectively], while TG/HDL-C, METS-IR and ZJU indices were merely associated with stage II ISH [ORs: 1.053 (1.006-1.103), 3.001 (1.171-7.696) and 1.009 (1.000-1.017), respectively]. In addition, TyG and METS-IR indices were positively associated with stage II IDH [ORs: 1.813 (1.207-2.721) and 2.85 (1.080-7.520), respectively], and TyG index was also associated with combined hypertension [OR: 1.425 (1.007-1.833)]. CONCLUSION: Among young and middle-aged adults, insulin resistance assessed by the four NI-IR indices was positively associated with stage II ISH, while only TyG index had a significant association for both stage II IDH and combined hypertension.

Prognostic factors and outcomes of invasive pulmonary aspergillosis, a retrospective hospital-based study.

Objective: Invasive pulmonary aspergillosis (IPA) affects immunocompromised hosts and is associated with higher risks of respiratory failure and mortality. However, the clinical outcomes of different IPA types have not been identified. Methods: Between September 2002 and May 2021, we retrospectively enrolled patients with IPA in Taichung Veterans General Hospital, Taiwan. Cases were classified as possible IPA, probable IPA, proven IPA, and putative IPA according to EORTC/MSGERC criteria and the AspICU algorithm. Risk factors of respiratory failure, kidney failure, and mortality were analyzed by logistic regression. A total of 3-year survival was assessed by the Kaplan-Meier method with log-rank test for post-hoc comparisons. Results: We included 125 IPA patients (50: possible IPA, 47: probable IPA, 11: proven IPA, and 17: putative IPA). Comorbidities of liver cirrhosis and solid organ malignancy were risk factors for respiratory failure; diabetes mellitus and post-liver or kidney transplantation were related to kidney failure. Higher galactomannan (GM) test optical density index (ODI) in either serum or bronchoalveolar lavage fluid was associated with dismal outcomes. Probable IPA and putative IPA had lower 3-year respiratory failure-free survival compared to possible IPA. Probable IPA and putative IPA exhibited lower 3-year renal failure-free survival in comparison to possible IPA and proven IPA. Putative IPA had the lowest 3-year overall survival rates among the four IPA groups. Conclusion: Patients with putative IPA had higher mortality rates than the possible, probable, or proven IPA groups. Therefore, a prompt diagnosis and timely treatment are warranted for patients with putative IPA.

Adult-onset congenital cholesteatoma in the hypotympanum initially presenting as Bell's palsy: A case report.

INTRODUCTION: Cholesteatoma is a rare disease characterized by the accumulation of keratinized squamous epithelial cells in the middle ear or mastoid cavity. Vertigo and facial palsy, which are rare complications, may indicate erosion into the semicircular canals or the fallopian canal. PATIENT CONCERNS: A 40-year-old woman presented to our clinic with progressive right-sided hearing loss over 5 years (primary concern). Approximately 10 years ago, the patient had developed acute right-sided facial weakness with no additional symptoms. A neurologist at another hospital had diagnosed her condition as Bell's palsy and treated it accordingly. DIAGNOSIS: Adult-onset congenital cholesteatoma in the hypotympanum. INTERVENTION: Combined endoscopic and microscopic removal of the cholesteatoma. OUTCOMES: Physical examination revealed slight improvement in right-sided peripheral facial palsy. LESSON: Routine eardrum examination is recommended for patients presenting with isolated peripheral facial palsy. If necessary, a patient should be referred to an otologist for further evaluation and treatment.

The Angiotensin II Receptor Neprilysin Inhibitor LCZ696 Inhibits the NLRP3 Inflammasome By Reducing Mitochondrial Dysfunction in Macrophages and Alleviates Dextran Sulfate Sodium-induced Colitis in a Mouse Model.

The intracellular sensor protein complex known as the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome plays a crucial role in regulating inflammatory diseases by overseeing the production of interleukin (IL)-1ß and IL-18. Targeting its abnormal activation with drugs holds significant promise for inflammation treatment. This study highlights LCZ696, an angiotensin receptor-neprilysin inhibitor, as an effective suppressor of NLRP3 inflammasome activation in macrophages stimulated by ATP, nigericin, and monosodium urate. LCZ696 also reduces caspase-11 and GSDMD activation, lactate dehydrogenase release, propidium iodide uptake, and the extracellular release of NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in ATP-activated macrophages, suggesting a potential mitigation of pyroptosis. Mechanistically, LCZ696 lowers mitochondrial reactive oxygen species and preserves mitochondrial integrity. Importantly, it does not significantly impact NLRP3, proIL-1ß, inducible nitric oxide synthase, cyclooxygenase-2 expression, or NF-κB activation in lipopolysaccharide-activated macrophages. LCZ696 partially inhibits the NLRP3 inflammasome through the induction of autophagy. In an in vivo context, LCZ696 alleviates NLRP3-associated colitis in a mouse model by reducing colonic expression of IL-1ß and tumor necrosis factor-α. Collectively, these findings suggest that LCZ696 holds significant promise as a therapeutic agent for ameliorating NLRP3 inflammasome activation in various inflammatory diseases, extending beyond its established use in hypertension and heart failure treatment.

The Best Strategy for the Black Hole Phenomenon between Intravascular Ultrasound and Optical Coherence Tomography.

The black hole (BH) phenomenon is an intraluminal restenotic lesion. It was identified by intravascular ultrasound (IVUS) and optical coherence tomography (OCT) after intracoronary brachytherapy and drug-eluting stent implantation. Despite the similarity in the mode of action of brachytherapy and drug-eluting stent implantation, the BH phenomenon appears to be uncommon after drug-eluting stent implantation. Specifically, the BH phenomenon is better identified by OCT than by IVUS. Herein, we present a case of in-stent restenosis with suspected BH phenomenon on IVUS and confirmed by OCT.

Evaluation of deep learning computer vision for water level measurements in rivers.

Image-based gauging stations offer the potential for substantial enhancement in the monitoring networks of river water levels. Nonetheless, the majority of camera gauges fall short in delivering reliable and precise measurements because of the fluctuating appearance of water in the rivers over the course of the year. In this study, we introduce a method for measuring water levels in rivers using both the traditional continuous image subtraction (CIS) approach and a SegNet neural network based on deep learning computer vision. The historical images collected from on-site investigations were employed to train three neural networks (SegNet, U-Net, and FCN) in order to evaluate their effectiveness, overall performance, and reliability. The research findings demonstrated that the SegNet neural network outperformed the CIS method in accurately measuring water levels. The root mean square error (RMSE) between the water level measurements obtained by the SegNet neural network and the gauge station's readings ranged from 0.013 m to 0.066 m, with a high correlation coefficient of 0.998. Furthermore, the study revealed that the performance of the SegNet neural network in analyzing water levels in rivers improved with the inclusion of a larger number of images, diverse image categories, and higher image resolutions in the training dataset. These promising results emphasize the potential of deep learning computer vision technology, particularly the SegNet neural network, to enhance water level measurement in rivers. Notably, the quality and diversity of the training dataset play a crucial role in optimizing the network's performance. Overall, the application of this advanced technology holds great promise for advancing water level monitoring and management in river systems.

Human transcriptome array analysis and diffusion tensor imaging in attention-deficit/hyperactivity disorder.

The mRNA markers identified using microarray assay and diffusion tensor magnetic resonance imaging (DTI) were applied to elucidate the pathophysiology of attention-deficit hyperactivity disorder (ADHD). First, we obtained total RNA from leukocytes from three children with ADHD and three healthy controls for analysis with microarray assays. Subsequently, we applied real-time quantitative polymerase chain reaction (qRT‒PCR) assays to validate the differential expression of 7 genes (COX7B, CYCS, TFAM, UTP14A, ZNF280C, IFT57 and NDUFB5) between 130 ADHD patients and 70 controls, and we built an ADHD prediction model based on the ΔCt values of aforementioned seven genes (AUROC = 0.98). Finally, in a validation group (28 patients with ADHD and 27 healthy controls), mRNA expression of the above seven genes also significantly differentiated ADHD patients from controls (AUROC value = 0.91). The DTI analysis showed increased fractional anisotropy (FA) of the forceps minor, superior corona radiata, posterior corona radiata and anterior corona radiata in ADHD patients. Moreover, the FA of the right superior corona radiata tract was positively correlated with ΔCt levels of the COX7B gene and the IFT57 gene. The results shed a new light on a genetic profile of ADHD that may help in deciphering the white matter microstructural features in disease pathogenesis.

Comparison of contraction-type and noncontraction-type lymphatic vessels in lymphaticovenous anastomosis for cancer-related unilateral lower limb lymphedema: a retrospective cohort propensity-score-matched outcome analysis.

BACKGROUND: Contraction-type lymphatic vessels (LV) are considered suboptimal for lymphaticovenous anastomosis (LVA). However, despite these pathological changes, their functionality and link to outcomes have not been fully elucidated. The aim of this study was to determine the impact on outcomes when contraction-type LVs were used for LVA compared to the noncontraction-type (normal + ectatic) counterpart for treating lower limb lymphedema. STUDY DESIGN: Eighty-three patients with gynecologic cancer-related unilateral lower-limb lymphedema who underwent LVA as their primary treatment were enrolled in this study. The study group included 20 patients who used only contraction-type LVs. An additional 63 patients (control group) received noncontraction-type LVs only. Patients with a history of LVA, liposuction, or excisional therapy were excluded. Patient characteristics, intraoperative findings, functional parameters, and pre-LVA and post-LVA volume changes were recorded and matched using propensity scores. The primary endpoint was the volume change at 6/12 months after LVA. RESULTS: After matching, 20 patients were included in each group. All parameters were matched, except that the study group still had a significantly inferior indocyanine green (ICG)-positive ratio, lymph flow-positive ratio, and washout-positive ratios ( P <0.001, P =0.003, and P <0.001, respectively) when compared to the control group after matching. However, at 1-year follow-up, the postoperative percentage volume reduction was comparable between the groups ( P= 0.619). CONCLUSION: The use of contraction-type LVs for LVA is encouraged when no other LVs are available.

Successful management of massive postpartum haemorrhage in a woman with acquired haemophilia A.

Postpartum haemorrhage (PPH) is an obstetric emergency and a leading cause of severe maternal morbidity and mortality. Timely and accurate diagnosis of the underlying cause of PPH is critical in achieving optimal care for the patient as any potential delays may result in severe morbidity and even mortality. We present a rare case of a patient presenting with PPH secondary to acquired haemophilia. This case highlights the importance of early diagnosis and multidisciplinary management in achieving optimal management of this complex condition.

Sub-volt high-speed silicon MOSCAP microring modulator driven by high-mobility conductive oxide.

Silicon microring modulator plays a critical role in energy-efficient optical interconnect and optical computing owing to its ultra-compact footprint and capability for on-chip wavelength-division multiplexing. However, existing silicon microring modulators usually require more than 2 V of driving voltage (Vpp), which is limited by both material properties and device structures. Here, we present a metal-oxide-semiconductor capacitor microring modulator through heterogeneous integration between silicon photonics and titanium-doped indium oxide, which is a high-mobility transparent conductive oxide (TCO) with a strong plasma dispersion effect. The device is co-fabricated by Intel's photonics fab and our in-house TCO patterning processes, which exhibits a high modulation efficiency of 117 pm/V and consequently can be driven by a very low Vpp of 0.8 V. At a 11 GHz modulation bandwidth where the modulator is limited by the RC bandwidth, we obtained 25 Gb/s clear eye diagrams with energy efficiency of 53 fJ/bit.

Association of Autonomic Symptom Burden with Sudden Sensorineural Hearing Loss.

OBJECTIVE: To investigate the autonomic symptom burden in patients with sudden sensorineural hearing loss (SSNHL) and its association with the severity and prognosis. STUDY DESIGN: Observational prospective study. SETTING: Tertiary academic medical center. METHODS: Patients diagnosed with SSNHL at a single medical center completed the COMPASS 31 questionnaire, which assesses dysautonomia across 6 domains with 31 questions. A total COMPASS 31 score was calculated by summing the scores from each weighted domain. The treatment outcome was evaluated by the percentage of recovery, calculated as the hearing gain in pure tone average (PTA) after treatment divided by the pretreatment PTA difference between the 2 ears. We defined poor recovery as a percentage of recovery <80%. RESULTS: A total of 63 SSNHL patients were included. The mean COMPASS 31 score was 23.4 (SD 14). Patients with poor recovery had significantly higher COMPASS 31 scores than those with good recovery (mean 26.4 [SD 14.4] vs 16.9 [SD 10.4]; 95% confidence interval [CI] 2-17). There was a negative association between COMPASS 31 score and both hearing gain (r = -.323, 95% CI -0.082 to -0.529) and percentage of recovery (r = -.365, 95% CI -0.129 to -0.562). Multivariate analyses of independent factors indicate that patients with higher COMPASS 31 scores had a greater risk for poor recovery (OR 1.06 [95% CI 1.003-1.117]). CONCLUSION: This study highlights the association between autonomic symptom burden and poor hearing outcomes in SSNHL patients. The findings underscore the importance of evaluating autonomic function during the treatment of SSNHL.

Diabetic Macular Edema Is Predictive of Renal Failure in Patients With Diabetes Mellitus and Chronic Kidney Disease.

CONTEXT: Chronic hyperglycemia in patients with diabetes mellitus (DM) causes retinal damage and leakage, resulting in vision loss. Although diabetic retinopathy (DR) and diabetic kidney disease (DKD) are usually correlated, the relationship between diabetic macular edema (DME) and DKD remains unknown. OBJECTIVE: To assess whether DME presence can predict renal failure in patients with DM and chronic kidney disease (CKD). METHODS: This retrospective cohort study used data from 120 healthcare organizations in the TriNetX network. Electronic medical records of approximately 90 million patients were reviewed. The study population was classified into DME and non-DME cohorts. Primary and secondary outcomes were new-onset end-stage renal disease (ESRD) and all-cause mortality, respectively. Covariate factors were incorporated to reduce confounding effects. RESULTS: Before matching, the DME cohort used more medication and had poorer renal function and blood sugar control than the non-DME cohort. Subsequently, the 2 groups were well-matched in demographics, socioeconomic status, lifestyle, comorbidities, and medication usage. The DME cohort had a significantly higher risk of ESRD, dialysis, and renal transplantation than the non-DME cohort. Subgroup analyses showed consistent results irrespective of follow-up duration, initial estimated glomerular filtration rate, or glycated hemoglobin levels. Additionally, the DME cohort had a lower risk of all-cause mortality than the non-DME cohort. CONCLUSION: Statistically significant 5-year increased risks of ESRD, dialysis, and renal transplantation were observed in patients with concurrent DME. Therefore, close monitoring and follow-up of the renal function in DM patients with DME are necessary and strongly recommended.