Effects of infant care posture and weight on static postural balance.

BACKGROUND: Studies investigating postural balance during various infant care postures have not been reported yet. OBJECTIVE: The aim of this study was to measure static postural balance when holding an infant dummy in-arms and carrying an infant dummy on back according to different infant dummy weights. METHODS: Sixteen healthy young subjects participated in a balance test. Infant dummies with weights of 4.6 kg (1-month) and 9.8 kg (12-month) were used in this study. All subjects were asked to naturally stand on a force platform in two infant care postures (holding an infant in-arms and carrying an infant on one's back). Center of pressure (COP) was measured from the force platform. Quantitative variables were derived from the COP. Two-way repeated measure analysis of variance (ANOVA) was performed to determine main effects of infant care postures, infant weight, and their interactions on COP variables. RESULTS: Back carrying a 12-month infant dummy had the greatest amplitude in all COP variables. Back carrying posture showed significantly greater mean distance and peak power, faster mean velocity, and wider COP area compared to holding posture (P< 0.05). There were significant weight effects of most COP variables mainly in AP direction (P< 0.01). CONCLUSIONS: Our results could contribute to the prevention of musculoskeletal diseases or prevention of fall due to various infant care activities by developing an assisting device to improve postural balance.

SARS-CoV-2 infection exacerbates the cellular pathology of Parkinson's disease in human dopaminergic neurons and a mouse model.

While an association between Parkinson's disease (PD) and viral infections has been recognized, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on PD progression remains unclear. Here, we demonstrate that SARS-CoV-2 infection heightens the risk of PD using human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons and a human angiotensin-converting enzyme 2 (hACE2) transgenic (Tg) mouse model. Our findings reveal that SARS-CoV-2 infection exacerbates PD susceptibility and cellular toxicity in DA neurons pre-treated with human preformed fibrils (hPFFs). Additionally, nasally delivered SARS-CoV-2 infects DA neurons in hACE2 Tg mice, aggravating the damage initiated by hPFFs. Mice infected with SARS-CoV-2 display persisting neuroinflammation even after the virus is no longer detectable in the brain. A comprehensive analysis suggests that the inflammatory response mediated by astrocytes and microglia could contribute to increased PD susceptibility associated with SARS-CoV-2. These findings advance our understanding of the potential long-term effects of SARS-CoV-2 infection on the progression of PD.

UBE2N is essential for maintenance of skin homeostasis and suppression of inflammation.

UBE2N, a Lys63-ubiquitin conjugating enzyme, plays critical roles in embryogenesis and immune system development and function. However, its roles in adult epithelial tissue homeostasis and pathogenesis are unclear. We generated conditional mouse models that deleted Ube2n in skin cells in a temporally and spatially controlled manner. We found that Ube2n-knockout (KO) in the adult skin keratinocytes induced a range of inflammatory skin defects characteristic of psoriatic and actinic keratosis. These included inflammation, epidermal and dermal thickening, parakeratosis, and increased immune cell infiltration, as well as signs of edema and blistering. Single cell transcriptomic analyses and RT-qPCR showed that Ube2n KO keratinocytes expressed elevated myeloid cell chemo-attractants such as Cxcl1 and Cxcl2 and decreased the homeostatic T lymphocyte chemo-attractant Ccl27a. Consistently, the infiltrating immune cells were predominantly myeloid-derived cells including neutrophils and M1-like macrophages that expressed high levels of inflammatory cytokines such as Il1ß and Il24. Pharmacological blockade of the IL-1 receptor associated kinases (IRAK1/4) alleviated inflammation, epidermal and dermal thickening, and immune infiltration of the Ube2n mutant skin. Together, these findings highlight a key role of keratinocyte-UBE2N in maintenance of epidermal homeostasis and skin immunity, and identify IRAK1/4 as potential therapeutic target for inflammatory skin disorders.

Value of Sonazoid-enhanced ultrasonography in characterizing indeterminate focal liver lesions on gadoxetic acid-enhanced liver MRI in patients without risk factors for hepatocellular carcinoma.

PURPOSE: To evaluate the added value of contrast-enhanced ultrasonography (CEUS) using Sonazoid in characterizing focal liver lesions (FLLs) with indeterminate findings on gadoxetic acid-enhanced liver MRI in patients without risk factors for hepatocellular carcinoma (HCC). METHODS: Patients who underwent CEUS using Sonazoid for characterizing indeterminate FLLs on gadoxetic acid-enhanced liver MRI were. The indeterminate FLLs were classified according to the degree of malignancy on a 5-point scale on MRI and combined MRI and CEUS. The final diagnosis was made either pathologically or based on more than one-year follow-up. The diagnostic performance was assessed using a receiver operating characteristic (ROC) curve analysis, and the net reclassification improvement (NRI) was calculated. RESULTS: A total of 97 patients (mean age, 49 years ± 16, 41 men, 80 benign and 17 malignant lesions) were included. When CEUS was added to MRI, the area under the ROC curve increased, but the difference was not statistically significant (0.87 [95% confidence interval {CI}, 0.77-0.98] for MRI vs 0.93 [95% CI, 0.87-0.99] for CEUS added to MRI, P = 0.296). The overall NRI was 0.473 (95% CI, 0.100-0.845; P = 0.013): 33.8% (27/80) of benign lesions and 41.2% (7/17) of malignant lesions were appropriately reclassified, whereas 10.0% (8/80) of benign lesions and 17.6% (3/17) of malignant lesions were incorrectly reclassified. CONCLUSIONS: Although performing CEUS with Sonazoid did not significantly improve the overall diagnostic performance in characterizing indeterminate FLLs on gadoxetic acid-enhanced liver MRI in patients without risk factors for HCC, it may increase radiologist's confidence in classifying FLLs.

Total Iodine Quantification and In Vitro Bioavailability Study in Abalone (Haliotis discus hannai) Using Inductively Coupled Plasma Mass Spectrometry.

The aim of this study is to determine the total iodine content in Korean abalone (Haliotis discus hannai) and to investigate the bioavailability of iodine using an in vitro method. This research paper focuses on total iodine quantification in abalone (Haliotis discus hannai) and its components (viscera and muscle) using inductively coupled plasma mass spectrometry (ICP-MS). Additionally, an in vitro bioavailability study explored iodine absorption potential. Abalone pretreatment involved both the European standard method (ES) and microwave-assisted extraction method (MAE). The limits of detection (LOD) were 0.11 ng/g for both ES and MAE, with a limit of quantification (LOQ) of 5.4 ng/g for MAE. Accuracy, assessed using a reference material (fish muscle, ERM-BB422), showed values of 1.5 ± 0.010 mg/kg for ES and 1.6 ± 0.066 mg/kg for MAE, within an acceptable range of 1.4 ± 0.42 mg/kg. Precision, evaluated using the Horwitz ratio (HorRat) with a reference material, was determined to be 0.45 for ES and 0.27 for MAE. Therefore, total iodine contents were estimated as 74 ± 2.2 µg/g for abalone viscera and 17 ± 0.77 µg/g for abalone muscle with ES, and 76 ± 1.0 µg/g for abalone viscera and 17 ± 0.51 µg/g for abalone muscle with MAE. Recovery tests demonstrated an acceptable range of 90-110%. In the in vitro bioavailability assessment, digestion efficiency yielded ranges of 42-50.2% for viscera and 67-115% for muscle. Absorption efficiency variations were determined as 37-43% for viscera and 48-75% for muscle.

Toxicity and speciation of inorganic arsenics and their adverse effects on in vivo endpoints and oxidative stress in the marine medaka Oryzias melastigma.

Here, we investigate the effects of acute and chronic exposure to arsenate (AsV) and arsenite (AsIII) in the marine medaka Oryzias melastigma. In vivo effects, biotransformation, and oxidative stress were studied in marine medaka exposed to the two inorganic arsenics for 4 or 28 days. An investigation of embryonic development revealed no effect on in vivo parameters, but the hatching rate increased in the group exposed to AsIII. Exposure to AsIII also caused the greatest accumulation of arsenic in medaka. For acute exposure, the ratio of AsV to AsIII was higher than that of chronic exposure, indicating that bioaccumulation of inorganic arsenic can induce oxidative stress. The largest increase in oxidative stress was observed following acute exposure to AsIII, but no significant degree of oxidative stress was induced by chronic exposure. During acute exposure to AsV, the increase in the enzymatic activity of glutathione-S-transferase (GST) was twice as high compared with exposure to AsIII, suggesting that GST plays an important role in the initial detoxification process. In addition, an RNA-seq-based ingenuity pathway analysis revealed that acute exposure to AsIII may be related to cell-cycle progression. A network analysis using differentially expressed genes also revealed a potential link between the generation of inflammatory cytokines and oxidative stress due to arsenic exposure.

Peripapillary microvasculature and retinal nerve fiber layer damage according to the severity of diabetic retinopathy.

PURPOSE: To identify damage to the inner retinal layer and microvasculature in the peripapillary area according to the severity of diabetic retinopathy (DR). METHODS: Patients were divided into four groups: control (group 1), type 2 diabetes (T2DM) without DR (group 2), mild to moderate nonproliferative DR (NPDR) (group 3), and severe NPDR (group 4). The peripapillary retinal nerve fiber layer (pRNFL) thickness and peripapillary vessel density (VD) were compared. Linear regression analysis was performed to identify factors associated with the DR severity. RESULTS: The average pRNFL thicknesses were 96.2 ± 7.1, 94.1 ± 9.6, 92.0 ± 9.9, and 90.3 ± 12.4 µm in groups 1, 2, 3, and 4, respectively (P = 0.003) (post hoc analyses: group 1 vs. group 2, P = 0.529; group 2 vs. group 3, P = 0.627; group 2 vs. group 4, P = 0.172; group 3 vs. group 4, P = 0.823). The VDs of the outer ring were 18.9 ± 0.6, 18.4 ± 0.8, 17.9 ± 1.1, and 17.3 ± 1.6 mm-1 in groups 1, 2, 3 and 4, respectively (P < 0.001) (all pairwise comparisons, P < 0.050). In multivariate analysis, the VD of the outer ring (B = - 0.35, P < 0.001) was significantly associated with the DR severity. CONCLUSIONS: The peripapillary microvasculature reflects retinal damage following DR progression better than the structure of the pRNFL.

Dual-Emissive Detection of ATP and Hypochlorite Ions for Monitoring Inflammation-Driven Liver Injury In Vitro and In Vivo.

Reactive oxygen species play a pivotal role in liver disease, contributing to severe liver damage and chronic inflammation. In liver injury driven by inflammation, adenosine-5'-triphosphate (ATP) and hypochlorite ion (ClO-) emerge as novel biomarkers, reflecting mitochondrial dysfunction and amplified oxidative stress, respectively. However, the dynamic fluctuations of ATP and ClO- in hepatocytes and mouse livers remain unclear, and multidetection techniques for these biomarkers are yet to be developed. This study presents RATP-NClO, a dual-channel fluorescent bioprobe capable of synchronously detecting ATP and ClO- ions. RATP-NClO exhibits excellent selectivity and sensitivity for ATP and ClO- ions, demonstrating a dual-channel fluorescence response in a murine hepatocyte cell line. Upon intravenous administration, RATP-NClO reveals synchronized ATP depletion and ClO- amplification in the livers of mice with experimental metabolic dysfunction-associated steatohepatitis (MASH). Through a comprehensive analysis of the principal mechanism of the developed bioprobe and the verification of its reliable detection ability in both in vitro and in vivo settings, we propose it as a unique tool for monitoring changes in intracellular ATP and ClO- level. These findings underscore its potential for practical image-based monitoring and functional phenotyping of MASH pathogenesis.

Association between maternal antidepressant use during pregnancy and the risk of autism spectrum disorder and attention deficit hyperactivity disorder in offspring.

Prenatal antidepressant exposure has been reported to be associated with adverse neurodevelopmental outcomes, yet studies considering confounding factors in Asian populations are lacking. This study utilized a nationwide data base in Taiwan, enrolling all liveborn children registered in the National Health Insurance system between 2004 and 2016. Subjects were divided into two groups: antidepressant-exposed (n = 55,707)) and antidepressant-unexposed group (n = 2,245,689). The effect of antidepressant exposure during different trimesters on autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) was examined. Sibling controls and parallel comparisons by paternal exposure status were treated as negative controls. Additional sensitivity analyses were conducted to examine the effects of antidepressant exposure before and after pregnancy. Prenatal antidepressant exposure was associated with increased risks of ASD and ADHD in population-wide and adjusted analysis. However when comparing antidepressant-exposed children with their unexposed siblings, no differences were found for ASD (Hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.76-1.42 in first trimester; HR: 0.96, 95% CI 0.62-1.50 in second trimester; HR: 0.69, 95% CI 0.32-1.48 in third trimester) and ADHD (HR: 0.98, 95%CI 0.84-1.15 in first trimester; HR: 0.91, 95% CI 0.73-1.14 in second trimester; HR: 0.79, 95% CI 0.54-1.16 in third trimester). Increased risks for ASD and ADHD were also noted in paternal control, before and after pregnancy analyses. These results imply that the association between prenatal antidepressant exposure and ASD and ADHD is not contributed to by an intrauterine medication effect but more likely to be accounted for by maternal depression, genetic, and potential environmental factors.

Remote optogenetic control of the enteric nervous system and brain-gut axis in freely-behaving mice enabled by a wireless, battery-free optoelectronic device.

Wireless activation of the enteric nervous system (ENS) in freely moving animals with implantable optogenetic devices offers a unique and exciting opportunity to selectively control gastrointestinal (GI) transit in vivo, including the gut-brain axis. Programmed delivery of light to targeted locations in the GI-tract, however, poses many challenges not encountered within the central nervous system (CNS). We report here the development of a fully implantable, battery-free wireless device specifically designed for optogenetic control of the GI-tract, capable of generating sufficient light over large areas to robustly activate the ENS, potently inducing colonic motility ex vivo and increased propulsion in vivo. Use in in vivo studies reveals unique stimulation patterns that increase expulsion of colonic content, likely mediated in part by activation of an extrinsic brain-gut motor pathway, via pelvic nerves. This technology overcomes major limitations of conventional wireless optogenetic hardware designed for the CNS, providing targeted control of specific neurochemical classes of neurons in the ENS and brain-gut axis, for direct modulation of GI-transit and associated behaviours in freely moving animals.

Hydrophobic residues in S1 modulate enzymatic function and voltage sensing in voltage-sensing phosphatase.

The voltage-sensing domain (VSD) is a four-helix modular protein domain that converts electrical signals into conformational changes, leading to open pores and active enzymes. In most voltage-sensing proteins, the VSDs do not interact with one another, and the S1-S3 helices are considered mainly scaffolding, except in the voltage-sensing phosphatase (VSP) and the proton channel (Hv). To investigate its contribution to VSP function, we mutated four hydrophobic amino acids in S1 to alanine (F127, I131, I134, and L137), individually or in combination. Most of these mutations shifted the voltage dependence of activity to higher voltages; however, not all substrate reactions were the same. The kinetics of enzymatic activity were also altered, with some mutations significantly slowing down dephosphorylation. The voltage dependence of VSD motions was consistently shifted to lower voltages and indicated a second voltage-dependent motion. Additionally, none of the mutations broke the VSP dimer, indicating that the S1 impact could stem from intra- and/or intersubunit interactions. Lastly, when the same mutations were introduced into a genetically encoded voltage indicator, they dramatically altered the optical readings, making some of the kinetics faster and shifting the voltage dependence. These results indicate that the S1 helix in VSP plays a critical role in tuning the enzyme's conformational response to membrane potential transients and influencing the function of the VSD.

An integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology.

Neurotechnologies and genetic tools for dissecting neural circuit functions have advanced rapidly over the past decade, although the development of complementary pharmacological method-ologies has comparatively lagged. Understanding the precise pharmacological mechanisms of neuroactive compounds is critical for advancing basic neurobiology and neuropharmacology, as well as for developing more effective treatments for neurological and neuropsychiatric disorders. However, integrating modern tools for assessing neural activity in large-scale neural networks with spatially localized drug delivery remains a major challenge. Here, we present a dual microfluidic-photometry platform that enables simultaneous intracranial drug delivery with neural dynamics monitoring in the rodent brain. The integrated platform combines a wireless, battery-free, miniaturized fluidic microsystem with optical probes, allowing for spatially and temporally specific drug delivery while recording activity-dependent fluorescence using genetically encoded calcium indicators (GECIs), neurotransmitter sensors GRAB NE and GRAB DA , and neuropeptide sensors. We demonstrate the performance this platform for investigating neuropharmacological mechanisms in vivo and characterize its efficacy in probing precise mechanistic actions of neuroactive compounds across several rapidly evolving neuroscience domains.

Tumour growth rate predicts overall survival in patients with recurrent WHO grade 4 glioma.

PURPOSE: Accurate prognostication may aid in the selection of patients who will benefit from surgery at recurrent WHO grade 4 glioma. This study aimed to evaluate the role of serial tumour volumetric measurements for prognostication at first tumour recurrence. METHODS: We retrospectively analyzed patients with histologically-diagnosed WHO grade 4 glioma at initial and at first tumour recurrence at a tertiary hospital between May 2000 and September 2018. We performed auto-segmentation using ITK-SNAP software, followed by manual adjustment to measure serial contrast-enhanced T1W (CE-T1W) and T2W lesional volume changes on all MRI images performed between initial resection and repeat surgery. RESULTS: Thirty patients met inclusion criteria; the median overall survival using Kaplan-Meier analysis from second surgery was 10.5 months. Seventeen (56.7%) patients received treatment post second surgery. Univariate cox regression analysis showed that greater rate of increase in lesional volume on CE-T1W (HR = 2.57; 95% CI [1.18, 5.57]; p = 0.02) in the last 2 MRI scans leading up to the second surgery was associated with a higher mortality likelihood. Patients with higher Karnofsky Performance Score (KPS) (HR = 0.97; 95% CI [0.95, 0.99]; p = 0.01) and who received further treatment following second surgery (HR = 0.43; 95% CI [0.19, 0.98]; p = 0.04) were shown to have a better survival. CONCLUSION: Higher rate of CE-T1W lesional growth on the last 2 MRI images prior to surgery at recurrence was associated with increase mortality risk. A larger prospective study is required to determine and validate the threshold to distinguish rapidly progressive tumour with poor prognosis.

Congenital central hypoventilation syndrome in korea: 20 years of clinical observation and evaluation of the ventilation strategy in a single center.

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder characterized by hypoventilation due to impaired breathing control by the central nervous system and other symptoms of autonomic dysfunction. Mutations in paired-like homeobox 2 B (PHOX2B) are responsible for most cases of CCHS. Patients with CCHS have various phenotypes and severities, making the diagnosis difficult. This study aimed to present a comprehensive single-center experience of patients with CCHS, including key clinical features, treatment strategies, and outcomes. A retrospective chart review was performed for patients diagnosed with CCHS between January 2001 and July 2023 at Seoul National University Children's Hospital. Finally, we selected 24 patients and collected their demographic data, genotypes, ventilation methods, and clinical features related to autonomic dysfunction. The relationship between the clinical manifestations and genotypes was also examined. All patients used home ventilators, and tracheostomy was performed in 87.5% of patients. Fifteen (62.5%) patients had constipation and nine (37.5%) were diagnosed with Hirschsprung disease. Arrhythmia, endocrine dysfunction, and subclinical hypothyroidism were present in nine (37.5%), six patients (25.0%), and two patients (16.7%), respectively. A significant number of patients exhibited neurodevelopmental delays (19 patients, 79.2%). There was a correlation between the phenotype and genotype of PHOX2B in patients with CCHS. (r = 0.71, p < 0.001).   Conclusion: There was a positive correlation between paired-like homeobox 2 B mutations (especially the number of GCN repeats in the polyalanine repeat mutations sequence) and clinical manifestations. This study also demonstrated how initial treatment for hypoventilation affects neurodevelopmental outcomes in patients with CCHS. What is Known: • Congenital central hypoventilation syndrome is a rare genetic disorder characterized by hypoventilation and dysfunction of autonomic nervous system. • The disease-defining gene of CCHS is PHOX2B gene - most of the cases have heterozygous PARMs and the number of GCN triplets varies among the patients(20/24 - 20/33). What is New: • We have noted in the Korean patients with CCHS that there is a correlation between genotype (number of GCN repeats) and severity of phenotype. • National support for rare diseases allowed for a prompter diagnosis of patients with CCHS in Korean population.

Ultrasound-triggered three dimensional hyaluronic acid hydrogel promotes in vitro and in vivo reprogramming into induced pluripotent stem cells.

Cellular reprogramming technologies have been developed with different physicochemical factors to improve the reprogramming efficiencies of induced pluripotent stem cells (iPSCs). Ultrasound is a clinically applied noncontact biophysical factor known for regulating various cellular behaviors but remains uninvestigated for cellular reprogramming. Here, we present a new reprogramming strategy using low-intensity ultrasound (LIUS) to improve cellular reprogramming of iPSCs in vitro and in vivo. Under 3D microenvironment conditions, increased LIUS stimulation shows enhanced cellular reprogramming of the iPSCs. The cellular reprogramming process facilitated by LIUS is accompanied by increased mesenchymal to epithelial transition and histone modification. LIUS stimulation transiently modulates the cytoskeletal rearrangement, along with increased membrane fluidity and mobility to increase HA/CD44 interactions. Furthermore, LIUS stimulation with HA hydrogel can be utilized in application of both human cells and in vivo environment, for enhanced reprogrammed cells into iPSCs. Thus, LIUS stimulation with a combinatorial 3D microenvironment system can improve cellular reprogramming in vitro and in vivo environments, which can be applied in various biomedical fields.

Assessing the suitability of artificial intelligence-based chatbots as counseling agents for brain tumor patients: A comprehensive survey analysis.

The internet, particularly social media, has become a popular resource for learning about health and investigating one's own health conditions. The development of AI chatbots has been fueled by the increasing availability of digital health data and advances in natural language processing techniques. While these chatbots are more accessible than before, they sometimes fail to provide accurate information. We used representative chatbots currently available (ChatGPT-3.5, Bing Chat, and Google Bard) to answer questions commonly asked by brain tumor patients. The simulated situations with questions were made and selected by the brain tumor committee. These questions are commonly asked by brain tumor patients. The goal of the study was introduced to each chatbot, the situation was explained, and questions were asked. All responses were collected without modification. The answers were shown to the committee members, and they were asked to judge the responses while blinded to the type of chatbot. There was no significant difference in accuracy and communication ability among the three groups (p=0.253, 0.090, respectively). For empathy, Bing Chat and Google Bard were superior to ChatGPT (p=0.004, 0.002, respectively). The purpose of this study was not to assess or verify the relative superiority of each chatbot. Instead, the aim was to identify the shortcomings and changes needed if AI chatbots are to be used for patient medical purposes. AI-based chatbots are a convenient way for patients and the general public to access medical information. Under such circumstances, medical professionals must ensure that the information provided to chatbot users is accurate and safe.

Single-cell transcriptome analysis reveals subtype-specific clonal evolution and microenvironmental changes in liver metastasis of pancreatic adenocarcinoma and their clinical implications.

BACKGROUND: Intratumoral heterogeneity (ITH) and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) play important roles in tumor evolution and patient outcomes. However, the precise characterization of diverse cell populations and their crosstalk associated with PDAC progression and metastasis is still challenging. METHODS: We performed single-cell RNA sequencing (scRNA-seq) of treatment-naïve primary PDAC samples with and without paired liver metastasis samples to understand the interplay between ITH and TME in the PDAC evolution and its clinical associations. RESULTS: scRNA-seq analysis revealed that even a small proportion (22%) of basal-like malignant ductal cells could lead to poor chemotherapy response and patient survival and that epithelial-mesenchymal transition programs were largely subtype-specific. The clonal homogeneity significantly increased with more prevalent and pronounced copy number gains of oncogenes, such as KRAS and ETV1, and losses of tumor suppressor genes, such as SMAD2 and MAP2K4, along PDAC progression and metastasis. Moreover, diverse immune cell populations, including naïve SELLhi regulatory T cells (Tregs) and activated TIGIThi Tregs, contributed to shaping immunosuppressive TMEs of PDAC through cellular interactions with malignant ductal cells in PDAC evolution. Importantly, the proportion of basal-like ductal cells negatively correlated with that of immunoreactive cell populations, such as cytotoxic T cells, but positively correlated with that of immunosuppressive cell populations, such as Tregs. CONCLUSION: We uncover that the proportion of basal-like subtype is a key determinant for chemotherapy response and patient outcome, and that PDAC clonally evolves with subtype-specific dosage changes of cancer-associated genes by forming immunosuppressive microenvironments in its progression and metastasis.

Evaluating micronized adipose tissue niche and artificial dermis grafts following nonmelanoma skin cancer excision: a pilot study.

BACKGROUND: Recently, micronized adipose tissue (MAT) grafts have shown promising results in wound healing, including diabetic ulcers. OBJECTIVE: To assess the possibility of using 3D printed MAT niche grafts in the management of skin and soft tissue defects resulting from non-melanoma skin cancer (NMSC) resections. MATERIALS AND METHODS: A retrospective feasibility study was conducted on patients with skin and soft tissue defects resulting from NMSC resections. Twenty-one patients were treated using either artificial dermis (n = 11) or MAT niche (n = 10) grafting. Healing time and POSAS scores were compared. The Mann-Whitney U test and the Pearson chi-square test were used in statistical analysis to compare between and within groups based on preoperative and postoperative measurements. RESULTS: Wounds in the MAT niche group reepithelialized significantly faster than those in the artificial dermis group (mean [SD] 39.2 [11.4] days vs 63.7 [34.8] days; P = .04). In the 21 scar parameters evaluated, the MAT niche group demonstrated significantly superior outcomes in only 2 parameters based on operator assessment scores: relief (mean [SD] 1.6 [0.7] vs 2.2 [0.6]; P = .047) and scar contracture (mean [SD] 1.3 [0.5] vs 2.5 [1.0]; P = .011). CONCLUSION: This study proves the feasibility of exploring the effects of MAT niche grafting following NMSC excision on healing time and specific parameters of scarring, including scar relief and scar contracture.

Development of new hormonal male contraception for the couple.

BACKGROUND: Current options for male contraception are limited to condoms, the withdrawal method, or a vasectomy. Studies indicate that men have expressed growing interest in bearing responsibility for family planning. OBJECTIVES: To review prior studies investigating the role of an androgen-only or androgen with progestin regimen for hormonal male contraception and to provide an update of a promising new hormonal agent, a transdermal gel. DISCUSSION: Thus far, there have been six studies conducted in couples evaluating the contraceptive efficacy of an androgen-only or androgen co-administered with a progestin regimen for hormonal male contraception. The only ongoing study is by the National Institute of Child Health and Human Development, in collaboration with the Population Council. They have developed a novel transdermal gel containing testosterone and segesterone acetate (Nestorone), a progestin. An ongoing phase II study enrolling more than 460 couples has shown great potential with respect to the product's efficacy, safety, reversibility, and acceptability. As this agent advances in development, a rapid at-home test for sperm concentration will provide couples with immediate feedback regarding their potential for pregnancy. CONCLUSION: There is promise for the first-of-its-kind hormonal male contraceptive, a transdermal gel, to achieve market approval for distribution in the United States and elsewhere. Its safety, efficacy, reversibility, and user-control are all appealing qualities that make it readily adoptable for clinical practice.

Melatonin alleviates myocardial dysfunction through inhibition of endothelial-to-mesenchymal transition via the NF-κB pathway.

Endothelial-to-mesenchymal transition (EndMT) is a complex biological process of cellular transdifferentiation by which endothelial cells (ECs) lose their characteristics and acquire mesenchymal properties, leading to cardiovascular remodeling and complications in the adult cardiovascular diseases environment. Melatonin is involved in numerous physiological and pathological processes, including aging, and has anti-inflammatory and antioxidant activities. This molecule is an effective therapeutic candidate for preventing oxidative stress, regulating endothelial function, and maintaining the EndMT balance to provide cardiovascular protection. Although recent studies have documented improved cardiac function by melatonin, the mechanism of action of melatonin on EndMT remains unclear. The present study investigated the effects of melatonin on induced EndMT by transforming growth factor-ß2/interleukin-1ß in both in vivo and in vitro models. The results revealed that melatonin reduced the migratory ability and reactive oxygen species levels of the cells and ameliorated mitochondrial dysfunction in vitro. Our findings indicate that melatonin prevents endothelial dysfunction and inhibits EndMT by activating related pathways, including nuclear factor kappa B and Smad. We also demonstrated that this molecule plays a crucial role in restoring cardiac function by regulating the EndMT process in the ischemic myocardial condition, both in vessel organoids and myocardial infarction (MI) animal models. In conclusion, melatonin is a promising agent that attenuates EC dysfunction and ameliorates cardiac damage compromising the EndMT process after MI.