Ischemic conditioning by short periods of reperfusion attenuates renal ischemia/reperfusion induced apoptosis and autophagy in the rat

Prolonged ischemia amplified iscehemia/reperfusion (IR) induced renal apoptosis and autophagy. We hypothesize that ischemic conditioning (IC) by a briefly intermittent reperfusion during a prolonged ischemic phase may ameliorate IR induced renal dysfunction. We evaluated the antioxidant/oxidant mechanism, autophagy and apoptosis in the uninephrectomized Wistar rats subjected to sham control, 4 stages of 15-min IC (I15 × 4), 2 stages of 30-min IC (I30 × 2), and total 60-min ischema (I60) in the kidney followed by 4 or 24 hours of reperfusion. By use of ATP assay, monitoring O2-. amounts, autophagy and apoptosis analysis of rat kidneys, I60 followed by 4 hours of reperfusion decreased renal ATP and enhanced reactive oxygen species (ROS) level and proapoptotic and autophagic mechanisms, including enhanced Bax/Bcl-2 ratio, cytochrome C release, active caspase 3, poly-(ADP-ribose)-polymerase (PARP) degradation fragments, microtubule-associated protein light chain 3 (LC3) and Beclin-1 expression and subsequently tubular apoptosis and autophagy associated with elevated blood urea nitrogen and creatinine level. I30 × 2, not I15 × 4 decreased ROS production and cytochrome C release, increased Manganese superoxide dismutase (MnSOD), Copper-Zn superoxide dismutase (CuZnSOD) and catalase expression and provided a more efficient protection than I60 against IR induced tubular apoptosis and autophagy and blood urea nitrogen and creatinine level. We conclude that 60-min renal ischemia enhanced renal tubular oxidative stress, proapoptosis and autophagy in the rat kidneys. Two stages of 30-min ischemia with 3-min reperfusion significantly preserved renal ATP content, increased antioxidant defense mechanisms and decreased ischemia/reperfusion enhanced renal tubular oxidative stress, cytosolic cytochrome C release, proapoptosis and autophagy in rat kidneys

Design of Novel S-Shaped Quad-Band Antenna for MedRadio/WMTS/ISM Implantable Biotelemetry Applications

A novel S-shaped quad-band planar inverted-F antenna (PIFA) is proposed for implantable biotelemetry in the Medical Device Radiocommunications Service (MedRadio) band (401–406 MHz), Wireless Medical Telemetry Service (WMTS) band (1427–1432 MHz), and industrial, scientific, and medical (ISM) bands (433-434 MHz and 2.4–2.4835 GHz). The proposed antenna reveals compact dimension of 254 mm3 (10×10×2.45 mm3) and is composed of three substrates and a superstrate, which are constructed from an S-shaped radiator (layer 1) and two twin radiators of spiral structures (layer 2 and layer 3). The optimal antenna characteristics were measured in the ground pork skin, and the measured bandwidths are 150 MHz for the MedRadio and ISM bands (433 MHz), 52 MHz for the WMTS band, and 102 MHz for the ISM band (2.4 GHz), respectively. The characteristics of proposed antenna are enough to support the applications of implantable body area networks (BAN) for biotelemetry and can completely cover main available frequency bands of BAN for biotelemetry below 3 GHz

Mutations in the PKM2 exon-10 region are associated with reduced allostery and increased nuclear translocation.

PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2's activity through allosteric modulation and post-translational modifications. Furthermore, PKM2 can partner with KDM8, an oncogenic demethylase and enter the nucleus to serve as a HIF1α co-activator. Yet, the mechanistic basis of the exon-10 region in allosteric regulation and nuclear translocation remains unclear. Here, we determined the crystal structures and kinetic coupling constants of exon-10 tumor-related mutants (H391Y and R399E), showing altered structural plasticity and reduced allostery. Immunoprecipitation analysis revealed increased interaction with KDM8 for H391Y, R399E, and G415R. We also found a higher degree of HIF1α-mediated transactivation activity, particularly in the presence of KDM8. Furthermore, overexpression of PKM2 mutants significantly elevated cell growth and migration. Together, PKM2 exon-10 mutations lead to structure-allostery alterations and increased nuclear functions mediated by KDM8 in breast cancer cells. Targeting the PKM2-KDM8 complex may provide a potential therapeutic intervention

Macrophage activation increases the invasive properties of hepatoma cells by destabilization of the adherens junction

AbstractTumor-associated macrophages play an important role in tumor progression, but whether they exert a tumor-progressive effect remains controversial. Here, we demonstrated that activated macrophage-conditioned medium (AMCM) obtained from RAW macrophages (RAW/AMCM) induced epithelial-mesenchymal transition (EMT) and stimulated the migratory and invasive activities of HepG2 cells, whereas control conditioned media had no effect. Epithelial-cadherin (E-cadherin) and β-catenin staining patterns were altered at the adherens junctions by RAW/AMCM treatment, with an approximately 50% decrease in E-cadherin and β-catenin in the cell membrane. Importantly, levels of β-catenin-associated E-cadherin were also decreased. Following RAW/AMCM treatment, enhanced activation of c-Src was seen prior to increased tyrosine phosphorylation of β-catenin, and this led to the destabilization of adherens junctions. Pretreatment of HepG2 cells with the Src kinase inhibitor, PP2, completely abolished the effects of RAW/AMCM on the EMT, migration, invasion, and expression and association of E-cadherin and β-catenin. AMCMs obtained from human THP-1 monocytes and mouse peritoneal macrophages also caused disassembly of the adherens junctions and migration of HepG2 cells. Furthermore, inhibition of the epidermal growth factor receptor (EGFR) with gefitinib partially prevented the downregulation of E-cadherin and β-catenin at the adherens junctions and migration behavior induced by RAW/AMCM. Our results suggest that activated macrophages have a tumor-progressive effect on HepG2 cells which involves the c-Src- and EGFR-dependent signaling cascades

A large-scale survey of genetic copy number variations among Han Chinese residing in Taiwan

<p>Abstract</p> <p>Background</p> <p>Copy number variations (CNVs) have recently been recognized as important structural variations in the human genome. CNVs can affect gene expression and thus may contribute to phenotypic differences. The copy number inferring tool (CNIT) is an effective hidden Markov model-based algorithm for estimating allele-specific copy number and predicting chromosomal alterations from single nucleotide polymorphism microarrays. The CNIT algorithm, which was constructed using data from 270 HapMap multi-ethnic individuals, was applied to identify CNVs from 300 unrelated Han Chinese individuals in Taiwan.</p> <p>Results</p> <p>Using stringent selection criteria, 230 regions with variable copy numbers were identified in the Han Chinese population; 133 (57.83%) had been reported previously, 64 displayed greater than 1% CNV allele frequency. The average size of the CNV regions was 322 kb (ranging from 1.48 kb to 5.68 Mb) and covered a total of 2.47% of the human genome. A total of 196 of the CNV regions were simple deletions and 27 were simple amplifications. There were 449 genes and 5 microRNAs within these CNV regions; some of these genes are known to be associated with diseases.</p> <p>Conclusion</p> <p>The identified CNVs are characteristic of the Han Chinese population and should be considered when genetic studies are conducted. The CNV distribution in the human genome is still poorly characterized, and there is much diversity among different ethnic populations.</p

Interval between Intra-Arterial Infusion Chemotherapy and Surgery for Locally Advanced Oral Squamous Cell Carcinoma: Impacts on Effectiveness of Chemotherapy and on Overall Survival

Background. The interval between intra-arterial infusion chemotherapy (IAIC) and surgery was investigated in terms of its effects on survival in patients with locally advanced oral squamous cell carcinoma (OSCC). Methods. This retrospective study analyzed 126 patients who had completed treatment modalities for stage IV OSCC. All patients were followed up for 3 years. Kaplan-Meier and Cox regression methods were used to determine how survival was affected by general factors, primary tumor volume, TNM stage, and duration of neoadjuvant chemotherapy. Results. In 126 patients treated for locally advanced OSCC by preoperative induction IAIC using methotrexate, multivariate analysis of relevant prognostic factors showed that an IAIC duration longer than 90 days was significantly associated with poor prognosis (hazard ratio, 1.77; P=0.0259). Conclusions. Duration of IAIC is a critical factor in the effectiveness of multimodal treatment for locally advanced OSCC. Limiting the induction course to 90 days improves overall survival

A importância do tratamento das síndromes dolorosas no traumatismo cranioencefálico

Segundo o modelo do National Center for Medical Rehabilitation Research, a doença crônica (como o traumatismo cranioencefálico) deve ser observada por meio de 5 eixos – a fisiopatologia, a deficiência observável (a hemiparesia), a limitação funcional (incapacidade para tarefa especifica), incapacidade para realização de atividades de vida diária, e limitação social. Levando em conta que tais aspectos sejam interrelacionados, a abordagem interdisciplinar é o método de escolha da prática da Medicina de Reabilitação. O objetivo do presente relato é confirmar a interferência da dor na reabilitação do traumatismo cranioencefálico (TCE), cuja importância muitas vezes é minimizada, apesar de crescentes estudos acerca da etiopatogenia e tratamento da dor no TCE. Foi realizado acompanhamento de uma paciente vítima de TCE na Divisão de Medicina Física do Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo em 2002, para quem diversas modalidades analgésicas foram propostas, além da aplicação de questionário funcional e sobre qualidade de vida, com melhora observada em todas as medidas. É necessária análise crítica dos instrumentos de medida de saúde, na medida em que neles se observa alta capacidade para detecção de habilidades motoras e baixa eficiência em detectar melhora da funcionalidade devido aos ganhos nos campos psicoafetivos e sociais, que são diretamente relacionado à experiência dolorosaAccording to National Center for Medical Rehabilitation Research cronic disease model, there are 5 main axes to be on focus during treatment – pathophysiology, impairment, functional limitation, disability and societal limitations. Traumatic brain injury (TBI) is a condition in which patient faces all such problems. Due to great extension of life threaten, interdisciplinary approach is recommended approach. This case report aims to demonstrate the relevance of pain experienced by a TBI survivor and its level of interference during her rehabilitation. She has been treated by Division of Physical Medicine at the Institute of Orthopedics and Traumatology at the University of São Paulo during 2002 who has been submitted to several analgesic procedures. Her follow-up was demonstrated by means of quality of life and functional surveys, with significant improvement of measures. Although recent studies have been focused on pain characteristics in TBI, pain has been neglected among clinical practitioners. Critic analysis is necessary during scales interpretation because a global improvement may be due to psychossocial enhancement which is sometimes directly related to chronic pain

Association between the neutrophil-to-lymphocyte ratio and cognitive impairment: a meta-analysis of observational studies

BackgroundSystemic inflammation is one of the underlying mechanisms of cognitive impairment. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a systemic inflammation indicator. This meta-analysis aimed to evaluate the association between high NLR and cognitive impairment (CI) risk.MethodA comprehensive systematic search was conducted to identify eligible studies published until May 30, 2023. The reference group comprised patients with the lowest NLR level, whereas the exposure group comprised those with the highest NLR level. The main outcome was to examine the relationship between NLR and CI risk. The secondary outcome included the association between patient characteristics or comorbidities and CI risk.ResultsThis meta-analysis included 11 studies published between 2018 and 2023, involving 10,357 patients. Patients with CI had a higher NLR than those without (mean difference=0.35, 95% confidence interval [CI]: 0.26–0.44, p &lt; 00001, I2 = 86%). Consistently, pooled results revealed an association between high NLR and CI risk (odds ratio [OR]=2.53, 95% CI:1.67–3.82, p&lt;0.0001, I2 = 84%). Furthermore, aging (mean difference =4.31 years, 95% CI:2.83–5.8, p &lt; 0.00001, I2 = 92%), diabetes (OR=1.59, 95% CI:1.35–1.88, p &lt; 0.00001, I2 = 66%), and hypertension (OR=1.36, 95% CI:1.19–1.57, p &lt; 0.00001, I2 = 0%) were significant risk factors for CI. However, no significant associations were observed between CI and male gender (OR = 0.84, 95% CI:0.64–1.11, p = 0.22, I2 = 81%), body mass index (mean = −0.32 kg/m2, 95% CI: −0.82, 0.18, p = 0.2, I2 = 82%), alcohol consumption (OR = 1.11, 95% CI:0.95−1.3, p = 1.35, I2 = 0%), and smoking (OR = 0.99, 95% CI:0.87–1.13, p = 0.86, I2 = 0%). Meta-regression found that diabetes and hypertension, but not age, significantly moderated the association between NLR and CI.ConclusionThis meta-analysis showed a significant association between high NLR and increased CI risk. Moreover, meta-regression identified diabetes and hypertension, but not age, as significant moderating factors in the relationship between NLR and CI. To validate and strengthen these findings, further large-scale studies are required.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023430384, identifier CRD42023430384

Spatial modelling and mapping of teen birth rates in Taiwan in the period 1995-2010

Geographical variations in teen birth rates (TBR) still persist despite controlling for contextual factors. The aim of this research was to identify spatial patterns of TBR in Taiwan and to examine spatial relationships among different contextual factors. Using townships as the unit of analysis (N=359), this research used social and demographic variables for the years 1995, 2000, 2005 and 2010 and conducted spatial modelling of TBR. Geographical maps of TBR were presented, and Local Indicator of Spatial Autocorrelations was used to identify TBR clustering. Comparisons were made between ordinary least-squares models and spatial lag models, in which township-level TBRs were regressed on other township-level contextual characteristics. Our study found that townships with a high TBR were mostly in eastern, central and some southern regions of Taiwan, while townships with a low TBR were in the vicinity of metropolitan areas. The significant spatial lag indicated that townships would have a higher expected prevalence rate if adjacent townships have had higher rates. Results also indicated that the percentage of aborigines and the percentage of college-educated people were consistently associated with TBR over the years. Interventions aimed at reducing TBR in Taiwan should consider the presence of spatial correlations and should incorporate neighbouring townships

Implementation of the CMOS MEMS Condenser Microphone with Corrugated Metal Diaphragm and Silicon Back-Plate

This study reports a CMOS-MEMS condenser microphone implemented using the standard thin film stacking of 0.35 μm UMC CMOS 3.3/5.0 V logic process, and followed by post-CMOS micromachining steps without introducing any special materials. The corrugated diaphragm for the microphone is designed and implemented using the metal layer to reduce the influence of thin film residual stresses. Moreover, a silicon substrate is employed to increase the stiffness of the back-plate. Measurements show the sensitivity of microphone is −42 ± 3 dBV/Pa at 1 kHz (the reference sound-level is 94 dB) under 6 V pumping voltage, the frequency response is 100 Hz–10 kHz, and the S/N ratio >55 dB. It also has low power consumption of less than 200 μA, and low distortion of less than 1% (referred to 100 dB)