Syllable processing is organized in discrete subregions of the human superior temporal gyrus.

Modular organization at approximately 1 mm scale could be fundamental to cortical processing, but its presence in human association cortex is unknown. Using custom-built, high-density electrode arrays placed on the cortical surface of 7 patients undergoing awake craniotomy for tumor excision, we investigated receptive speech processing in the left (dominant) human posterior superior temporal gyrus. Responses to consonant-vowel syllables and noise-vocoded controls recorded with 1,024 channel micro-grids at 200 µm pitch demonstrated roughly circular domains approximately 1.7 mm in diameter, with sharp boundaries observed in 128 channel linear arrays at 50 µm pitch, possibly consistent with a columnar organization. Peak latencies to syllables in different modules were bimodally distributed centered at 252 and 386 ms. Adjacent modules were sharply delineated from each other by their distinct time courses and stimulus selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.

Co-occurrence between key HAB species and particle-attached bacteria and substrate specificity of attached bacteria in the coastal ecosystem.

The ecological dynamics of particle-attached bacteria (PAB) were observed through changes in the core phytoplankton phycosphere, and were associated with the dynamics of free-living bacteria (FLB) using metabarcoding and microscopic analyses over 210 days (with weekly sampling intervals) in the Jangmok coastal ecosystem, South Korea. Cluster analysis and non-metric multidimensional scaling classified the phytoplankton community into six groups comprising core phytoplankton species, including the harmful algal species Akashiwo sanguinea (dinoflagellate) in late autumn, Teleaulax amphioxeia (cryptomonads) in early winter and spring, Skeletonema marinoi-dohrnii complex (diatom) in winter, Pseudo-nitzschia delicatissima (diatom) in early spring, and diatom complexes such as Chaetoceros curvisetus and Leptocylindrus danicus in late spring. We identified 59 and 32 indicators in PAB and FLB, respectively, which rapidly changed with the succession of the six core phytoplankton species. The characteristics of PAB were mainly divided into "Random encounters" or "Attraction of motivation by chemotaxis." When Akashiwo sanguinea bloomed, bacteria of the genera Kordiimonas and Polaribacter, which are commonly observed in PAB and FLB, indicated "Random encounter" characteristics. In addition, Sedimenticola of PAB was uniquely presented in Akashiwo sanguinea, exhibiting characteristics of "Attraction of motivation by chemotaxis." In contrast, FLB followed the strategy of "Random encounters" because it was not affected by specific habitats and energy sources. Thus, many common bacteria were PAB and FLB, thereby dictating the bacteria's strategy of "Random encounters." "Attraction of motivation by chemotaxis" has characteristics of the species-specific interactions between PAB and specific harmful algal species, and is potentially influenced by organic matter of core phytoplankton cell surface and/or EPS released from phytoplankton.

Mechanical influence of facet tropism in patients with chronic discogenic pain disorder.

Aims: The presence of facet tropism has been correlated with an elevated susceptibility to lumbar disc pathology. Our objective was to evaluate the impact of facet tropism on chronic lumbosacral discogenic pain through the analysis of clinical data and finite element modelling (FEM). Methods: Retrospective analysis was conducted on clinical data, with a specific focus on the spinal units displaying facet tropism, utilizing FEM analysis for motion simulation. We studied 318 intervertebral levels in 156 patients who had undergone provocation discography. Significant predictors of clinical findings were identified by univariate and multivariate analyses. Loading conditions were applied in FEM simulations to mimic biomechanical effects on intervertebral discs, focusing on maximal displacement and intradiscal pressures, gauged through alterations in disc morphology and physical stress. Results: A total of 144 discs were categorized as 'positive' and 174 discs as 'negative' by the results of provocation discography. The presence of defined facet tropism (OR 3.451, 95% CI 1.944 to 6.126) and higher Adams classification (OR 2.172, 95% CI 1.523 to 3.097) were important predictive parameters for discography-'positive' discs. FEM simulations showcased uneven stress distribution and significant disc displacement in tropism-affected discs, where loading exacerbated stress on facets with greater angles. During varied positions, notably increased stress and displacement were observed in discs with tropism compared to those with normal facet structure. Conclusion: Our findings indicate that facet tropism can contribute to disc herniation and changes in intradiscal pressure, potentially exacerbating disc degeneration due to altered force distribution and increased mechanical stress.

Characterizing fluvial impact on the biochemical composition of particulate organic matter in the Laptev Sea and Western East Siberian Sea during the late summer of 2018.

The Laptev Sea (LS) and Western East Siberian Sea (W-ESS) are paradigmatic examples of seas dominated by terrestrial organic matter, attributed to substantial Siberian River discharges and coastal erosion. The influx of terrestrial organic matter significantly alters the biochemical composition of particulate organic matter (POM) in these Arctic coastal regions, potentially reducing the nutritional quality available to higher trophic levels. This study investigated the origin and qualitative characteristics of POM in the LS and W-ESS during the late summer of 2018 by analyzing elemental ratios (C/N ratio), stable carbon isotopes (δ13C), and biochemical compositions (biomolecular and amino acid (AA) compositions). The conspicuously depleted δ13C values (mean ± standard deviation (SD) = -30.2 ± 0.5 ‰) and alongside elevated molar C/N ratios (mean ± SD = 18.1 ± 6.2) suggest that terrestrial organic matter is the predominant source of POM in the study area. Although carbohydrates (CHO) were the dominant biomolecules, their prevalence was higher in the river-influenced W-ESS region (67.7 ± 6.6 %) than in the LS region (58.6 ± 13.9 %; p < 0.05). Furthermore, the CHO composition was closely associated with freshwater content and river fraction, suggesting that the heightened contribution of CHO may stem from terrestrial organic matter delivered by river inputs. Lower concentrations of particulate hydrolyzable AA (PAA) and carbon and nitrogen normalized yields of AAs (AA-POC% and AA-PON%) along with reduced contribution of glycine suggested a substantial contribution of terrestrial POM to both LS and W-ESS POM. Overall, this study provides valuable insights into the terrestrial influence on POM composition in Arctic marine ecosystems, emphasizing the need for continued monitoring of the consequences of terrestrial carbon inputs in the changing Arctic environment.

Comparison of Midterm Outcomes between All-Inside Arthroscopic and Open Modified Broström Procedures as Treatment for Chronic Ankle Instability.

Background: Although the all-inside arthroscopic modified Broström operation (AMBO) and open modified Broström operation (OMBO) for chronic lateral ankle instability (CLAI) showed favorable outcomes up to 1-year short-term follow-up, concerns about the long-term stability of AMBO are still present. Therefore, we aimed to compare midterm outcomes between the 2 methods by extending the observation period. Methods: Fifty-four patients undergoing ankle surgery between August 2013 and July 2017 were included in the AMBO (n = 37) and OMBO (n = 17) groups. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale and a visual analog scale (VAS) were used to evaluate the clinical outcomes. Anterior drawer test and talar tilt angle were used to evaluate the radiological outcomes. The mean follow-up duration was 59.69 months. Results: The 2 groups both showed improved clinical and radiological results statistically. In addition, they did not differ in age, sex, or preoperative AOFAS ankle-hindfoot scale score, VAS score, anterior drawer test, or talar tilt angle. No significant difference in the final follow-up postoperative clinical scores or radiological outcomes was observed. Conclusions: AMBO and OMBO as treatments for CLAI did not yield differing clinical or radiological outcomes at a mean follow-up time point of 59.69 months.

Suppressing anti-citrullinated protein antibody-induced osteoclastogenesis in rheumatoid arthritis using anti-CD64 and PAD-2 inhibitors.

OBJECTIVES: To evaluate the role of Fcγ receptors (FcγR) and peptidyl arginine deiminase (PAD) in anti-citrullinated protein antibody (ACPA)-induced fibroblast-like synoviocytes (FLSs)-mediated osteoclastogenesis in patients with rheumatoid arthritis (RA). METHODS: FLSs and peripheral blood mononuclear cells were collected from patients with RA. We stimulated RA-FLS with ACPA (100 ng/ml) with and without anti-cluster of differentiation (CD)32a/CD64 (FcγRIIA/FcγRI) antibody and PAD-2/4 inhibitors. Flow cytometry and enzyme-linked immunosorbent assay were also performed. CD14+ monocytes were cultured with receptor activator of nuclear factor kappa beta (RANKL) and macrophage colony-stimulating factor, and ACPA-stimulated RA-FLSs were added. These cells were cultured for 14 days, and osteoclastogenesis was quantified using tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: ACPA increased RANKL+ and tumour necrotic factor-alpha (TNF-α+) FLS, which decreased dose-dependently by adding 5 and 10 ug/mL anti-CD64 antibody rather than anti-CD32a antibody. In PAD inhibitor experiments, the proportion of RANKL+ and TNF-α+ FLS decreased in 50 µM condition containing PAD-2 inhibitor rather than PAD-4 inhibitor. The co-culture of ACPA-stimulated RA-FLSs and osteoclast precursors increased the TRAP+ multinucleated osteoclast count, which was decreased by anti-CD64 antibody and PAD2 inhibitor. CONCLUSIONS: The present study showed that ACPA increased RANKL and pro-inflammatory cytokine expression in RA-FLSs, and ACPA-activated RA-FLSs could augment osteoclastogenesis. These processes were inhibited by treatment with anti-CD64 antibody and PAD-2 inhibitors. These results show that CD64 and PAD-2-induced pathways may be involved in ACPA-induced FLS activation and osteoclastogenesis in patients with RA. Therefore, regulating the CD64 and PAD-2 pathways may improve RA treatment.

Risk factors for interstitial lung disease in rheumatoid arthritis: a cohort study from the KOBIO registry.

Background: Interstitial lung disease (ILD) is a critical extra-articular manifestation of rheumatoid arthritis (RA). However, little is known about the risk factors of RA-ILD. Objectives: Here, we examined the effect of demographic, clinical, therapeutic, and environmental factors on the incidence of ILD in RA patients using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. Design: We used data from the KOBIO registry, a multi-center, prospective, observational cohort that included RA patients in South Korea. Methods: RA patients who used biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) or conventional synthetic (cs)DMARDs, and were enrolled in the KOBIO registry, were examined. Demographic, clinical, and radiographic characteristics, as well as medications, were recorded at baseline and annually thereafter. Kaplan-Meier curves and the log-rank test were used to compare the incidence of ILD between RA patients taking different b/tsDMARDs. Hazard ratios (HRs) were calculated by Cox regression analyses. Results: In total, 2492 patients (1967 in the b/tsDMARDs group and 525 in the csDMARDs group) were analyzed. The b/tsDMARDs group showed longer disease duration, higher erythrocyte sedimentation rate/C-reactive protein, and higher disease activity score-28 (DAS28) than the csDMARDs group. The incidence of ILD was significantly higher in those taking tumor necrosis factor inhibitors and abatacept than in those taking csDMARDs (log ranked p < 0.001). Multivariate Cox regression analysis identified older age (HR = 1.057, p = 0.001), male sex (HR = 2.824, p = 0.007), time-averaged DAS28 (HR = 2.241, p < 0.001), and rheumatoid factor titer (HR = 1.009, p = 0.007) as having a significantly increased HR for ILD occurrence. Conclusion: ILD is a rare but critical extra-articular symptom of RA patients. Therefore, RA patients with the above risk factors should be monitored carefully for ILD development.

Interleukin-18 binding protein regulates mast cell activation and mast cell induced osteoclastogenesis of rheumatoid arthritis.

OBJECTIVES: Mast cell activation induces pathological responses, including increased osteoclastogenesis in rheumatoid arthritis (RA). Interleukin (IL)-18 binding protein (IL-18BP) has anti-inflammatory effects. In this study, we evaluated the effect of IL-18BP on mast cell activation and mast cell induced osteoclastogenesis. METHODS: Mast cells were activated by IL-33 (100 ng/mL) and cultured with IL-18BP (10, 50, and 100 ng/mL). The proliferation, apoptosis, and necroptosis of mast cells were measured using flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of mast cell enzymes, matrix metalloproteinase (MMP), soluble RANKL (sRANKL), and pro-inflammatory cytokines in the culture media. Monocytes from patients with RA patients (n=5) were cultured with activated mast cells with various concentrations of IL-18BP. TRAP+ multinucleated osteoclasts, bone resorption area, and osteoclast differentiation-related genes were measured. RESULTS: Proliferation of tryptase+chymase+c-kit+FcεR1+ mast cells was suppressed following incubation with IL-18BP (10, 50, and 100 ng/mL). RNA expression levels of tryptase and chymase were reduced by 100 ng/mL IL-18BP. Additionally, the levels of MMP-3/9, IL-17A, IL-6, TNF-α, and sRANKL were significantly inhibited by 100 ng/mL IL-18BP. Annexin V+ and annexin V-PI+ mast cells were reduced following incubation with 100 ng/mL IL-18BP. The addition of IL-33 significantly stimulated mast cell and increased TRAP+ multinucleated cells and bone resorption area, and these effects were suppressed by IL-18BP. The osteoclast-related genes (TRAP, ATP6v0d2, RANK, and cathepsin K) expression were suppressed by IL-18BP. CONCLUSIONS: IL-18BP suppressed mast cell activation and mast cell induced osteoclastogenesis. This suggests a potential anti-arthritic role for IL-18BP in patients with RA.

Inhibitory effects of compounds isolated from Geranium wilfordii on IL-4 production and ß-hexosaminidase release in RBL-2H3 cells.

This study aimed to investigate the anti-allergic activity of compounds isolated from Geranium wilfordii Maxim. and to suggest potential therapeutic agents for allergies. Nine compounds were isolated from an ethanolic G. wilfordii extract using chromatographic methods and identified chemically and by spectroscopic analysis. These compounds were identified using reported literature data as brevifolin carboxylic acid (1), chlorogenic acid (2), corilagin (3), ellagic acid (4), geraniol (5), kaempferol 3-O-dirhamnoside (6), kaempferol 3-O-neohesperidoside (7), protocatechuic acid (8), and gallic acid (9). All nine identified compounds were assessed for including IL-4 mRNA expression and ß-hexosaminidase release in RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA. IL-4 gene expression assay showed that corilagin (3) potently inhibited IL-4 production, and ß-hexosaminidase release assay showed that protocatechuic acid (8) markedly reduced histamine release. The study shows that of the nine compounds isolated from G. wilfordii, corilagin (3), and protocatechuic acid (8) are potential treatments for allergy-related diseases.

Seasonal patterns and bloom dynamics of phytoplankton based on satellite-derived chlorophyll-a in the eastern yellow sea.

Satellite-derived chlorophyll-a concentration (Chl-a) is essential for assessing environmental conditions, yet its application in the optically complex waters of the eastern Yellow Sea (EYS) is challenged. This study refines the Chl-a algorithm for the EYS employing a switching approach based on normalized water-leaving radiance at 555 nm wavelength according to turbidity conditions to investigate phytoplankton bloom patterns in the EYS. The refined Chl-a algorithm (EYS algorithm) outperforms prior algorithms, exhibiting a strong alignment with in situ Chl-a. Employing the EYS algorithm, seasonal and bloom patterns of Chl-a are detailed for the offshore and nearshore EYS areas. Distinct seasonal Chl-a patterns and factors influencing bloom initiation differed between the areas, and the peak Chl-a during the bloom period from 2018 to 2020 was significantly lower than the average year in both areas. Specifically, bimodal and unimodal peak patterns in Chl-a were observed in the offshore and nearshore areas, respectively. By investigating the relationships between environmental factors and bloom parameters, we identified that major controlling factors governing bloom initiation were mixed layer depth (MLD) and suspended particulate matter (SPM) in the offshore and nearshore areas, respectively. Additionally, this study proposed that the recent decrease in the peak Chl-a might be caused by rapid environmental changes such as the warming trend of sea surface temperature (SST) and the limitation of nutrients. For example, external forcing, phytoplankton growth, and nutrient dynamics can change due to increased SST and limitation of nutrients, which can lead to a decrease in Chl-a. This study contributes to understanding phytoplankton dynamics in the EYS, highlighting the importance of region-specific considerations in comprehending Chl-a patterns and bloom dynamics.

Palsy of Both the Tibial Nerve and Common Peroneal Nerve Caused by a Ganglion Cyst in the Popliteal Area.

A ganglion cyst is a benign mass consisting of high-viscosity mucinous fluid. It can originate from the sheath of a tendon, peripheral nerve, or joint capsule. Compressive neuropathy caused by a ganglion cyst is rarely reported, with the majority of documented cases involving peroneal nerve palsy. To date, cases demonstrating both peroneal and tibial nerve palsies resulting from a ganglion cyst forming on a branch of the sciatic nerve have not been reported. In this paper, we present the case of a 74-year-old man visiting an outpatient clinic complaining of left-sided foot drop and sensory loss in the lower extremity, a lack of strength in his left leg, and a decrease in sensation in the leg for the past month without any history of trauma. Ankle dorsiflexion and great toe extension strength on the left side were Grade I. Ankle plantar flexion and great toe flexion were Grade II. We suspected peroneal and tibial nerve palsy and performed a screening ultrasound, which is inexpensive and rapid. In the operative field, several cysts were discovered, originating at the site where the sciatic nerve splits into peroneal and tibial nerves. After successful surgical decompression and a series of rehabilitation procedures, the patient's neurological symptoms improved. There was no recurrence.

All-Inside Arthroscopic and Open Techniques of the Modified Broström Procedure for the Treatment of Lateral Ankle Instability: Comparison of the Times to Return to Play.

Background and Objectives: Lateral ankle injuries are commonly encountered injuries, and the open modified Broström operation (OMBO) is the primary treatment option. Recently, an arthroscopic modification of the Broström operation (AMBO) was developed; many studies have shown that there are no significant differences in clinical and radiological outcomes between the two surgical methods. However, no studies have been conducted comparing the two surgical methods in terms of return to play (RTP) time. This study assesses the time to RTP and the functional clinical outcomes. Materials and Methods: Sixty patients were enrolled from January 2012 to July 2014. They were segregated into two cohorts: the AMBO group comprised 30 patients, while the OMBO group comprised another 30 patients. Each participant underwent standardized treatment and rehabilitation regimens and RTP time was measured using seven questions that explored the times to return of painless walking, running, jumping, squatting, climbing stairs, and rising up on the heels and toes. We compared the time intervals from the onset of instability to the date of surgery. Clinical outcomes were evaluated before the surgery, 6 weeks after surgery, and 6 months after surgery. The assessments included the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, the pain visual analog scale (VAS) score, subjective satisfaction with rehabilitation, and activity level. Results: In terms of RTP, AMBO was associated with a shorter interval to walking without pain (7.07 ± 2.96 weeks) relative to OMBO (11.03 ± 8.58 weeks). No disparities were observed in the time to return to play (RTP) between OMBO and AMBO. While there were no discrepancies in the 6-month postoperative AOFAS or VAS scores, the 6-week postoperative VAS score was notably lower in the AMBO group compared to the OMBO group. AMBO provided a faster RTP in terms of two of the seven questions in a group exhibiting high-level physical activity. The rate of subjective satisfaction with rehabilitation was higher for AMBO than for OMBO. Conclusions: Aside from walking, the duration to return to play and the clinical outcomes were similar between AMBO and OMBO treatments for lateral ankle instability. AMBO is a good treatment option and should be carefully considered for athletes with lateral ankle instability. AMBO demonstrated positive outcomes in a group with higher activity levels compared to others, particularly in terms of time to RTP, subjective satisfaction, and postoperative pain.

Ameliorative effects of Wikstroemia trichotoma 95% EtOH extract on a mouse model of DNCB-induced atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Wikstroemia has been extensively utilized in traditional Chinese medicine (TCM) for the management of conditions such as coughs, edema, arthritis, and bronchitis. Studies have indicated that the crude extracts of Wikstroemia exhibit anti-inflammatory, anti-allergy, anti-aging, skin psoriasis, anti-cancer, and antiviral properties. In addition, these extracts are known to contain bioactive substances, including flavonoids, coumarins, and lignans. However, few studies have investigated the anti-inflammatory or anti-allergic activities of Wikstroemia trichotoma (Thunb.) Makino against atopic dermatitis (AD). AIM OF THE STUDY: The study aimed to explore the potential of a 95% ethanol extract of W. trichotoma (WTE) on the dysfunction of skin barrier and immune system, which are primary symptoms of AD, in 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice and phorbol 12-myristate 13-acetate (PMA)/ionomycin or immunoglobulin E (IgE) + 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulated rat basophilic leukemia cell line (RBL-2H3). Furthermore, we sought to identify the chemical contents of WTE using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA). MATERIALS AND METHODS: An in vitro study was conducted using RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA to assess the inhibitory effects of WTE on mast cell degranulation and interleukin-4 (IL-4) mRNA expression levels. For the in vivo study, AD was induced in SKH-1 hairless mice by applying 1% DNCB to the dorsal skin daily for 7 days. Subsequently, 0.1% DNCB solution was applied on alternate days, and mice were orally administered WTE (at 30 or 100 mg/kg/day) dissolved in 0.5% carboxymethyl cellulose (CMC) daily for 2 weeks. Transepidermal water loss (TEWL), skin hydration, skin pH, and total serum IgE levels were measured. RESULTS: In DNCB-stimulated SKH-1 hairless mice, WTE administration significantly improved AD symptoms and ameliorated dorsal skin inflammation. Oral administration of WTE led to a significant decrease in skin thickness, infiltration of mast cells, and level of total serum IgE, thus restoring skin barrier function in the DNCB-induced skin lesions. In addition, WTE inhibited ß-hexosaminidase release and reduced IL-4 mRNA levels in RBL-2H3 cells. Chemical profile analysis of WTE confirmed the presence of three phenolic compounds, viz. chlorogenic acid, miconioside B, and matteucinol-7-O-ß-apiofuranosyl (1 â†’ 6)-ß-glucopyranoside. CONCLUSIONS: WTE ameliorates AD symptoms by modulating in the skin barrier and immune system dysfunction. This suggests that W. trichotoma extract may offer therapeutic benefits for managing AD.

Risk of disease flare in spondyloarthritis patients after tapering tumor necrosis factor inhibitors: A meta-analysis and literature review.

BACKGROUND: Tumor necrosis factor inhibitors (TNFis) have shown dramatic benefit in patients with spondyloarthritis (SpA). Tapering of TNFi medication may be considered in patients with sustained low disease activity because continued use of TNFis at standard doses may increase the risk of side effects including infections and impose an economic burden. However, the optimal TNFi tapering strategy for SpA patients with inactive disease has not been established. In the present study, we investigated whether tapering TNFi doses is associated with similar risk of disease flare to maintaining SpA patients on TNFis at the standard dosage. METHODS: The MEDLINE, Embase, and Cochrane databases were systemically searched to retrieve randomized control trials (RCTs) and observational studies published prior to August 2023, that compared disease flare in SpA (including axial SpA [axSpA], psoriatic arthritis [PsA], and SpA with IBD) patients who received standard TNFi doses and those who received a tapered dose of TNFi. Odds ratios (ORs) and 95% confidence intervals (CIs) were directly retrieved or calculated, and meta-analyses were performed. Bias was assessed using funnel plots with Begg and Mazumdar rank correlation / Egger's regression method. RESULTS: Among 2,237 SpA patients in the 12 studies (9 RCTs and 3 observational studies) retrieved, 1,301 received the standard TNFi dose, while 936 SpA patients underwent TNFi tapering. Of these, 216 (16.6%) standard-dose TNFi and 217 (23.2%) TNF-tapering patients experienced disease flares. The pooled OR for disease flare in TNFi-tapering patients was 1.601 (95% CI 1.276 - 2.008) compared with the standard-dose patients. The funnel plot showed no publication bias. CONCLUSIONS: The strategy of TNFi tapering was associated with a significantly increased risk of disease flare compared to maintaining SpA patients at the standard TNF dose. Further studies are needed to determine which patients can safely undergo tapering of TNFi and to develop safe tapering strategies.

Factors Influencing Wound Healing in Diabetic Foot Patients.

Background and objectives: Diabetic foot stands out as one of the most consequential and devastating complications of diabetes. Many factors, including VIPS (Vascular management, Infection management, Pressure relief, and Source of healing), influence the prognosis and treatment of diabetic foot patients. There are many studies on VIPS, but relatively few studies on "sources of healing". Nutrients that affect wound healing are known, but objective data in diabetic foot patients are insufficient. We hypothesized that "sources of healing" would have many effects on wound healing. The purpose of this study is to know the affecting factors related to the source of healing for diabetic foot patients. Materials and Methods: A retrospective review identified 46 consecutive patients who were admitted for diabetic foot management from July 2019 to April 2021 at our department. Several laboratory tests were performed for influencing factor evaluation. We checked serum levels of total protein, albumin, vitamin B, iron, zinc, magnesium, copper, Hb, HbA1c, HDL cholesterol, and LDL cholesterol. These values of diabetic foot patients were compared with normal values. Patients were divided into two groups based on wound healing rate, age, length of hospital stay, and sex, and the test values between the groups were compared. Results: Levels of albumin (37%) and Hb (89%) were low in the diabetic foot patients. As for trace elements, levels of iron (97%) and zinc (95%) were low in the patients, but levels of magnesium and copper were usually normal or high. There were no differences in demographic characteristics based on wound healing rate. However, when compared to normal adult values, diabetic foot patients in our data exhibited significantly lower levels of hemoglobin, total protein, albumin, iron, zinc, copper, and HDL cholesterol. When compared based on age and length of hospital stay, hemoglobin levels were significantly lower in both the older age group and the group with longer hospital stays. Conclusions: Serum levels of albumin, Hb, iron, and zinc were very low in most diabetic foot patients. These low values may have a negative relationship with wound healing. Nutrient replacements are necessary for wound healing in diabetic foot patients.

Hippo-YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass.

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.

Real-world effectiveness of a single conventional disease-modifying anti-rheumatic drug (cDMARD) plus an anti-TNF agent versus multiple cDMARDs in rheumatoid arthritis: a prospective observational study.

Objective: The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea. Methods: At the treating physicians' discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months. Results: Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs -0.18, -0.38, and -0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus anti-TNF therapy than with multiple cDMARDs (BGD -0.18, -0.19, and -0.19 points, respectively; all p≤0.024). Conclusion: In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.

Costotransverse joint ankylosis and their association with syndesmophyte progression in patients with radiographic axial spondyloarthritis.

Background: Abnormal new bone formation can occur not only in the vertebral body but also can occur in facet, costovertebral, and costotransverse joints in radiographic axial spondyloarthritis (r-axSpA) patients. Little is known about the association between syndesmophyte progression and paravertebral joint ankylosis in r-axSpA. Objectives: Costotransverse joint ankylosis in r-axSpA patients was measured. Furthermore, the association between syndesmophyte progression for 2 years assessed by computed tomography syndesmophyte score (CTSS) and facet, costovertebral, and costotransverse joints ankylosis were evaluated. Design: Single-center, prospective, cohort study. Methods: Whole spine CT images taken at baseline and 2-year follow-up were used to calculate the CTSS of the vertebral body. In addition, ankylosis of the facet/costovertebral/costotransverse joints was scored. CTSS (range, 0-552) and facet joint ankylosis (range, 0-46) were assessed at 23 vertebral units. Costovertebral joints at T1-T12 (range, 0-48) and costotransverse joints at T1-T10 (range, 0-20) were also assessed by independent two readers. Intraclass correlation coefficients (ICC) were calculated to determine inter-reader reliability. Odds ratios (OR) were calculated to identify the associations between syndesmophyte progression and the baseline status of facet, costovertebral, and costotransverse joints. Results: In all, 50 patients with r-axSpA were included. Readers 1 and 2 identified C7-T3 (facet joints), T5-T7 and T12 (costovertebral joints), and T8-T9 (costotransverse joints), as common sites of ankylosis at baseline and at 2-year follow-up. The ICCs for the facet, costovertebral, and costotransverse joints at baseline were 0.876, 0.952, and 0.753, respectively. OR of baseline costovertebral and costotransverse joint ankylosis for predicting syndesmophyte progression of the vertebral body was 4.644 [95% confidence interval (CI), 2.295-9.398] and 1.524 (95% CI, 1.036-2.244), respectively. Conclusion: Costotransverse joint ankylosis in r-axSpA patients can be measured semi-quantitatively on whole spine CT, and ankylosis of the costotransverse and costovertebral joints predicts the progression of syndesmophytes.Trial registration: Not applicable.

Cutaneous Calcified Mass of Foot in Pseudohypoparathyoidism: Case Report.

Soft tissue calcifications frequently appear on imaging studies, representing a prevalent but non-specific discovery, varying from a local reaction without clear cause to suggesting an underlying systemic condition. Because calcifications like these can arise from various causes, an accurate differential diagnosis is crucial. Differential diagnosis entails a methodical assessment of the patient, encompassing clinical presentation, medical history, radiological and pathological findings, and other pertinent factors. Through scrutiny of the patient's medical and trauma history, we can refine potential causes of calcification to vascular, metabolic, autoimmune, neoplastic, or traumatic origins. Furthermore, routine laboratory assessments, including serum levels of calcium, phosphorus, ionized calcium, vitamin D metabolites, and parathyroid hormone (PTH), aid in identifying metabolic etiologies. We describe a rare occurrence of osteoma cutis in a 15-year-old female patient with a history of pseudohypoparathyroidism (PHP) and Albright's hereditary osteodystrophy (AHO). The patient presented with a painful mass on the lateral side of her left foot. The diagnosis was based on medical history, laboratory tests, and imaging, leading to an excisional biopsy and complete pain relief post-surgery. Understanding such rare occurrences and related conditions is crucial for accurate diagnosis and management.