Esophageal cancer mortality disparities between Black and White adults in the United States, 1999-2020: insights from CDC-WONDER.

BACKGROUND AND AIM: Esophageal cancer significantly contributes to US cancer mortality, with notable racial disparities. This study aims to provide updated esophageal cancer mortality trends among Black and White adults from 1999 to 2020. METHODS: CDC-WONDER was used to identify Black and White adults in the United States from 1999 to 2020. We calculated age-standardized mortality rates, absolute rate differences, and rate ratios to compare the mortality differences between these populations. RESULTS: From 1999 to 2020 in the United States, there were 303 267 esophageal cancer deaths, with significant racial disparities. The age-adjusted mortality rate for Black adults fell from 6.52 to 2.62 per 100 000, while for White adults, it declined from 4.19 to 3.97 per 100 000, narrowing the racial mortality gap. Gender-wise, the study showed a decrease in the mortality rate from 3.31 to 2.29 per 100 000 in Black women, but an increase from 1.52 to 1.99 per 100 000 in White women. Among young men, the rate dropped in Black men from 12.82 to 6.26 per 100 000 but rose in White men from 9.90 to 10.57 per 100 000. Regionally, Black adults in the Midwest and South initially had higher mortality rates than Whites, but this gap reduced over time. By 2020, Black men had lower mortality rates across all regions. CONCLUSIONS: Over the last two decades, age-adjusted esophageal cancer mortality decreased in Black adults but stabilized in White adults, reflecting distinct cancer trends and risk factors. The study highlights the importance of tailored public health strategies for healthcare access and risk factor management.

Measurement properties of the Foot Function Index (FFI) questionnaire: A systematic review.

OBJECTIVE: Large numbers of people are subject to alterations and pathologies in the foot. To quantify how these problems of foot function affect the quality of life, clinicians and researchers have developed measures such as the Foot Function Index (FFI). Our aim is to determine the methodological quality of the FFI including adaptations to other languages. DATA SOURCES: The studies considered in this review were extracted from the PubMed, Embase and CINAHL databases. The inclusion criteria were followed: (1) studies of patients with no previous foot or ankle pathology and aged over 18 years; (2) based on English-language patient-reported outcome measures that assess foot function; (3) the patient-reported outcome measures should present measurement properties based on COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) criteria. REVIEW METHODS: The systematic review was conducted following the COSMIN criteria to establish the methodological quality of the original FFI, together with its variants and adaptations. The last search was carried out in May 2024. RESULTS: Of the 1994 studies obtained in the preliminary search, 20 were eligible for inclusion in the final analysis. These results are the validations and cross-cultural adaptations to the following languages: the original FFI has cross-cultural adaptation in 13 languages and the FFI-Revised Short Form has been adapted and validated for use in 2 languages. CONCLUSION: In terms of methodological quality, the FFI-Revised Short Form questionnaire is a valuable instrument for evaluating ankle and foot function and could usefully be expanded to be available in more languages.

Constitutive Expression of Hif2α Confers Acute O2 Sensitivity to Carotid Body Glomus Cells.

Acute oxygen (O2) sensing and adaptation to hypoxia are essential for physiological homeostasis. The prototypical acute O2 sensing organ is the carotid body, which contains chemosensory glomus cells expressing O2-sensitive K+ channels. Inhibition of these channels during hypoxia leads to cell depolarization, transmitter release, and activation of afferent sensory fibers terminating in the brain stem respiratory and autonomic centers. Focusing on recent data, here we discuss the special sensitivity of glomus cell mitochondria to changes in O2 tension due to Hif2α-dependent expression of several atypical mitochondrial electron transport chain subunits and enzymes. These are responsible for an accelerated oxidative metabolism and the strict dependence of mitochondrial complex IV activity on O2 availability. We report that ablation of Epas1 (the gene coding Hif2α) causes a selective downregulation of the atypical mitochondrial genes and a strong inhibition of glomus cell acute responsiveness to hypoxia. Our observations indicate that Hif2α expression is required for the characteristic metabolic profile of glomus cells and provide a mechanistic explanation for the acute O2 regulation of breathing.

Cross-Cultural adaptation and validation of the Exercise-Induced Leg Pain questionnaire for Spanish speaking patients.

OBJECTIVES: To cross-culturally adapt and validate a Spanish version of the Exercise-Induced Leg Pain questionnaire. DESIGN: Clinical measurement study. PARTICIPANTS: The validity and reliability of the adapted version were assessed in four groups of 40 patients with exercise-induced leg pain, 40 physically active healthy individuals (control group), 40 athletes with other leg conditions and 40 athletes, military personnel and candidates with no history of injury (risk group). MAIN MEASURE: Exercise-Induced Leg Pain questionnaire. REFERENCE MEASURES: Spanish version of the Short-Form 36 and Schepsis postsurgical classification scale. RESULTS: In patients with exercise-induced leg pain, the mean age was 24.9 (± 6.7) years and the mean score of the questionnaire was 62.8 (± 10.9). The standard error of measurement and minimum detectable change threshold were 1.67 and 4.63 points, respectively. Excellent internal consistency (Cronbach's α = 0.942) and test-retest reliability (intraclass correlation coefficient = 0.995) were found. The exploratory and confirmatory factor analyses indicated that a one-factor solution explained 66.84% of the variance. For construct validity, 87.5% of the previously stated hypotheses were fulfilled between the total score of the questionnaire and Short-Form 36 dimensions. Concurrent validity, assessed by the Schepsis scale, was almost perfect (r = 0.92, p < 0.001). The predictive validity of the questionnaire was demonstrated using the receiving operating curve (area of 0.992; 95% CI: 0.983-1, p < 0.001). CONCLUSION: The Spanish version of the Exercise-Induced Leg Pain questionnaire resulted in a reliable and valid instrument to assess patients with exercise-induced leg pain.

Systematic Review of Patient-Reported Outcome Measures for Patients with Exercise-Induced Leg Pain.

Background and Objectives: To determine the most commonly used patient-reported outcome measures (PROMs) in exercise-induced leg pain (EILP) and to identify specific PROMs for EILP in order to evaluate their psychometric properties and methodological quality. Materials and Methods: A strategic search was performed in different databases to identify and extract the characteristics of studies based on the use of PROMs in patients with EILP. Specific PROMs were evaluated according to the Terwee et al. and COSMIN criteria. Results: Fifty-six studies were included in the review. The Medial Tibial Stress Syndrome Score (MTSSS), Lower Extremity Functional Scale (LEFS) and Exercise-Induced Leg Pain Questionnaire (EILP-Q) were identified as specific PROMs for EILP. The Visual Analog Scale (VAS) was the most widely used instrument in the assessment of EILP. The methodological quality assessment showed six positive values for the LEFS, four for the MTSSS and three for the EILP-Q for the eight psychometric properties analyzed according to the COSMIN criteria. The evaluation of the nine psychometric properties according to Terwee showed five positive values for the LEFS and MTSSS, and three for the EILP-Q. Conclusions: The overall methodological quality of the PROMs used was low. The VAS was the most widely used instrument in the assessment of EILP, and the LEFS was the highest quality PROM available for EILP, followed by the MTSSS and EILP-Q, respectively.

Perfluorooctanoic acid disrupts gap junction intercellular communication and induces reactive oxygen species formation and apoptosis in mouse ovaries.

Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acid family of compounds. Due to the presence of strong carbon-fluorine bonds, it is practically nonbiodegradable and highly persistent in the environment. PFOA has been detected in the follicular fluid of women, and positively associated with reduced fecundability and infertility. However, there are no reports concerning the experimental evaluation of PFOA on oocyte toxicity in mammals. The aim of the present study was to determine if PFOA is able to induce oxidative stress in fetal ovaries and cause apoptosis in oocytes in vitro. In addition, since inhibition of the gap junction intercellular communication (GJIC) by PFOA has been demonstrated in liver cells in vivo and in vitro, the effect of PFOA on the GJIC between the oocyte and its supportive cumulus cells was studied. Results show that PFOA induced oocyte apoptosis and necrosis in vitro (medium lethal concentration, LC50 = 112.8 µM), as evaluated with Annexin-V-Alexa 508 in combination with BOBO-1 staining. Reactive oxygen species (ROS) levels, as assessed by DCFH-DA, increased significantly in fetal ovaries exposed to » LC50 (28.2 µM, a noncytotoxic and relevant occupational exposure concentration) and LC50 PFOA ex vivo. This perfluorinated compound also caused the blockage of GJIC in cumulus cells-oocyte complexes (COCs) obtained from female mice exposed in vivo, as evaluated by calcein transfer from cumulus cells to the oocyte. The ability of PFOA of disrupting the GJIC in COCs, generating ROS in the fetal ovary and causing apoptosis and necrosis in mammal's oocytes, might account for the reported association between increasing maternal plasma concentrations of PFOA with reduced fertility in women.

Acute Achilles Tendon Ruptures: Efficacy of Conservative and Surgical (Percutaneous, Open) Treatment-A Randomized, Controlled, Clinical Trial.

There is controversy regarding the best treatment for acute ruptures of the Achilles tendon. Multiple treatments present good results in the short and long term, none being superior to the other if a protocol of rehabilitation with full early weightbearing rehabilitation is followed. The objective of this study was to provide evidence on the efficacy and safety of conservative or surgical (percutaneous or open) treatment for acute Achilles tendon rupture. A randomized, controlled, parallel-groups, pilot clinical trial was performed in patients aged ≥18 years who arrived at the emergency room of our center experiencing acute Achilles tendon rupture. Patients were randomized via a computer-generated list to receive 1 of 3 treatments (conservative, percutaneous surgery, or open surgery). All patients followed the same protocol of rehabilitation with early weightbearing. A responder (i.e., successful treatment) was defined as capable of standing heelrise mono- and bipodally for 3 seconds, having a pain score ≤2 (verbal numerical rating scale) after walking, and having returned to active previous life (sport) at 1-year follow-up. From 2014 to 2017, 34 consecutive patients (median age, 41 years [range 18 to 59]; 32 male [94%]) were included: 11 conservative treatment, 11 percutaneous surgery, and 12 open surgery. At 1-year follow-up, the proportion of responders was 100% (11/11, 95% confidence interval [CI] 74% to 100%), 82% (9/11, 95% CI 52% to 95%), and 83% (10/12, 95% CI 55% to 95%), respectively. There was no case of total rerupture. Similar efficacy was found for conservative, percutaneous, and open surgery treatments for acute Achilles tendon rupture at 1-year follow-up with an early weightbearing rehabilitation program.

Prediction of bilateral cerebral oxygen desaturations from a single sensor in adult cardiac surgery: A prospective observational study.

BACKGROUND: Monitoring regional cerebral oxygen saturation (rcSO2) with near-infrared spectroscopy is increasingly being performed in patients scheduled for cardiac surgery. It is sometimes difficult to monitor both frontal lobes due to anatomical or space compromises. However, it remains unclear whether the use of only one lateral or medial probe can provide adequate bilateral monitoring. OBJECTIVE: To evaluate the efficacy of using a single lateral or medial probe to detect substantial desaturations on both sides. DESIGN: A prospective observational study. SETTING: Tertiary university teaching hospital. PATIENTS: Seventeen adult patients undergoing elective cardiac surgery monitored with three near-infrared spectroscopy probes (two lateral and one medial) using an INVOS 5100C monitor. INTERVENTIONS: The value of rcSO2 was recorded up to 19 times during each procedure. Substantial desaturation was defined as an absolute rcSO2 value of 50% or less or a decrease of more than 20% compared with baseline values on spontaneous ventilation with 21% oxygen. MAIN OUTCOME MEASURES: The level of agreement between the three pairs of probes using the Bland-Altman method for repeated measures, and the grade of concordant and discordant results between the three pairs of probes by means of contingency tables and the κ coefficient. RESULTS: We obtained 244 records per probe. Greater agreement was observed between the two lateral probes (mean ±â€ŠSD of the differences between recordings was -0.9 ±â€Š5.5); mean difference between left and medial, and right and medial probes was 2.4 ±â€Š7.3 and 3.3 ±â€Š6.7, respectively. The rate of discordant results between the two lateral probes was 5.7%, κ coefficient of 0.6 with 95% confidence interval (95% CI 0.4 to 0.8), and between the left and medial, and right and medial of 8.2 and 7.4%, with κ coefficients of 0.57 (95% CI 0.38 to 0.76) and 0.5 (95% CI 0.29 to 0.71), respectively. CONCLUSION: In cardiac surgery patients in whom there is difficulty in accommodating two rcSO2 probes, a single lateral probe can effectively measure bilateral rcSO2 in specific scenarios.

Internal control for real-time polymerase chain reaction based on MS2 bacteriophage for RNA viruses diagnostics.

BACKGROUND: Real-time reverse transcription polymerase chain reaction (RT-PCR) is routinely used to detect viral infections. In Brazil, it is mandatory the use of nucleic acid tests to detect hepatitis C virus (HCV), hepatitis B virus and human immunodeficiency virus in blood banks because of the immunological window. The use of an internal control (IC) is necessary to differentiate the true negative results from those consequent from a failure in some step of the nucleic acid test. OBJECTIVES: The aim of this study was the construction of virus-modified particles, based on MS2 bacteriophage, to be used as IC for the diagnosis of RNA viruses. METHODS: The MS2 genome was cloned into the pET47b(+) plasmid, generating pET47b(+)-MS2. MS2-like particles were produced through the synthesis of MS2 RNA genome by T7 RNA polymerase. These particles were used as non-competitive IC in assays for RNA virus diagnostics. In addition, a competitive control for HCV diagnosis was developed by cloning a mutated HCV sequence into the MS2 replicase gene of pET47b(+)-MS2, which produces a non-propagating MS2 particle. The utility of MS2-like particles as IC was evaluated in a one-step format multiplex real-time RT-PCR for HCV detection. FINDINGS: We demonstrated that both competitive and non-competitive IC could be successfully used to monitor the HCV amplification performance, including the extraction, reverse transcription, amplification and detection steps, without compromising the detection of samples with low target concentrations. In conclusion, MS2-like particles generated by this strategy proved to be useful IC for RNA virus diagnosis, with advantage that they are produced by a low cost protocol. An attractive feature of this system is that it allows the construction of a multicontrol by the insertion of sequences from more than one pathogen, increasing its applicability for diagnosing different RNA viruses.

Cytoskeletal reorganization evoked by Rho-associated kinase- and protein kinase C-catalyzed phosphorylation of cofilin and heat shock protein 27, respectively, contributes to myogenic constriction of rat cerebral arteries.

Our understanding of the molecular events contributing to myogenic control of diameter in cerebral resistance arteries in response to changes in intravascular pressure, a fundamental mechanism regulating blood flow to the brain, is incomplete. Myosin light chain kinase and phosphatase activities are known to be increased and decreased, respectively, to augment phosphorylation of the 20-kDa regulatory light chain subunits (LC20) of myosin II, which permits cross-bridge cycling and force development. Here, we assessed the contribution of dynamic reorganization of the actin cytoskeleton and thin filament regulation to the myogenic response and serotonin-evoked constriction of pressurized rat middle cerebral arteries. Arterial diameter and the levels of phosphorylated LC(20), calponin, caldesmon, cofilin, and HSP27, as well as G-actin content, were determined. A decline in G-actin content was observed following pressurization from 10 mm Hg to between 40 and 120 mm Hg and in three conditions in which myogenic or agonist-evoked constriction occurred in the absence of a detectable change in LC20 phosphorylation. No changes in thin filament protein phosphorylation were evident. Pressurization reduced G-actin content and elevated the levels of cofilin and HSP27 phosphorylation. Inhibitors of Rho-associated kinase and PKC prevented the decline in G-actin; reduced cofilin and HSP27 phosphoprotein content, respectively; and blocked the myogenic response. Furthermore, phosphorylation modulators of HSP27 and cofilin induced significant changes in arterial diameter and G-actin content of myogenically active arteries. Taken together, our findings suggest that dynamic reorganization of the cytoskeleton involving increased actin polymerization in response to Rho-associated kinase and PKC signaling contributes significantly to force generation in myogenic constriction of cerebral resistance arteries.

Overexpression of BDNF and Full-Length TrkB Receptor Ameliorate Striatal Neural Survival in Huntington's Disease.

BACKGROUND: Several cellular mechanisms have been proposed to explain the pathogenesis of Huntington's disease (HD), including the lack of striatal brain-derived neurotrophic factor (BDNF). Thus, by preferentially binding to tropomyosin receptor kinase B (TrkB) receptor, BDNF is an important neurotrophin implicated in striatal neuronal survival. OBJECTIVE: To study the influence of BDNF and TrkB receptors in intracellular signaling pathways and caspase-3 activation in HD striatal cells. METHODS: HD mutant knockin and wild-type striatal cells were transduced with preproBDNF or full-length TrkB receptors to analyze BDNF processing, AKT and extracellular signal-regulated kinase (ERK) activation and the activity of caspase-3 in the absence or presence of staurosporine (STS). RESULTS: HD mutant cells transduced with preproBDNF-mCherry (mCh) expressed similar levels of pro- and mature BDNF compared to WT cells, but HD cells released lower levels of pro- and mature BDNF. Despite this, BDNF-mCh overexpression rescued decreased AKT phosphorylation and reduced the caspase-3 activation observed in HD cells. Activated ERK was also enhanced in HD BDNF-mCh/TrkB-eGFP receptor co-cultures. Of relevance, overexpression of TrkB-eGFP in HD cells decreased caspase-3 activation, and stimulation of TrkB-eGFP-transduced mutant cells with recombinant human BDNF reduced both basal and STS-induced caspase-3 activation. CONCLUSION: The results highlight the importance of BDNF-induced TrkB receptor signaling in rescuing HD-mediated apoptotic features in striatal cells.

Adult Hepatoblastoma and Concomitant Hepatitis B Infection.

We report a case of hepatoblastoma in a 26-year-old man with a background of type 2 diabetes mellitus and untreated hepatitis B, initially presenting with hematemesis and a recent diagnosis of hepatocellular carcinoma on computed tomography scan from a different hospital and recent referral to hospice. On presentation to our hospital, given atypical presentation for hepatocellular carcinoma, histological examination was made, revealing hepatoblastoma. Treatment included chemotherapy and management of hepatitis B, although complicated by chemotherapy-induced cytopenias and tumor progression, ultimately losing the patient to follow-up after 2 years.

Modifiable Risk Factors in Hispanic Adults With Gastric Cancer in the United States.

BACKGROUND: Hispanics make up 19% of the U.S. population and are experiencing rising rates of cancer, primarily due to an increase in infection-related cancers (gastric, hepatic, cervical) and advanced cancers secondary to delayed screening (colorectal, cervical, breast). There is an increased incidence of gastric cancer (associated with infection, obesity, alcohol, and tobacco use) in Hispanics, especially at a young age, highlighting the need to consider ethnicity as a risk factor. METHODS: This study utilized the 2016-2019 National Inpatient Sample database to examine all patients admitted with gastric cancer. Individuals were stratified by race, age, and comorbidities, including modifiable risk factors that are associated with gastric cancer. RESULTS: There were 5,785 (7.44%) patients aged 18-44, 28,370 (36.49%) aged 45-64, and 43,590 (56.07%) over 65 years of age. Notably, 34.3% of the youngest group were Hispanic, contrasted with 19.7% and 12.9% in the older groups, respectively. Younger Hispanic patients showed a higher prevalence of H. pylori infection (8.6%) compared with older Hispanics (3.6% in the middle age group and 2.1% in the oldest, p<0.01). There was a high prevalence of obesity, tobacco use, and gastric ulcers in this cohort. Other risk factors such as alcohol use and gastric polyps were present at a lesser prevalence. CONCLUSIONS: This study reveals that Hispanic patients tend to have a younger age of onset of gastric cancer, coupled with an increased incidence of H. pylori infection at a younger age. This finding underscores the potential benefit of H. pylori screening among asymptomatic young Hispanics with the aim of reducing gastric cancer morbidity and mortality in this population.

A pilot study to identify suitable MRI protocols for preoperative planning of total hip arthroplasty.

PURPOSE: The purpose of this study is to identify suitable MRI sequences and evaluate the feasibility and performance of MRI for total hip arthroplasty (THA) preoperative planning. METHOD: A multicentric pilot study was conducted to evaluate DP TSE and T1 GRE 3D sequences. High-resolution pelvis, hip, knee and ankle images were acquired. Protocols were optimised to enhance image quality (IQ) and reduce acquisition time to fit clinical practice. The final protocol was validated with 19 healthy volunteers with variable BMIs at 1.5 and 3 Tesla. Visual assessment was performed by five radiographers and radiologists using the ViewDEX software. Visual Grading Analysis (VGA), Intraclass Correlation Coefficient (ICC), Prevalence-adjusted and bias-adjusted kappa (PABAK) and Visual Grading Characteristics (VGC) were performed to analyse data. RESULTS: VGA scores indicated that the optimised 3D DP TSE and 3D T1 GRE sequences at 3 T, as well as 3D DP TSE sequence at 1.5 T offer adequate IQ and allow a correct visualisation of the anatomy. Overall ICC analysis was moderate to good reliability at 0.749 (95 % CI 0.69-0.79) and increased from good to excellent at 0.846 (95 % CI 0.72-0.91) for DP at 3 T. PABAK shows fair agreement at 0.25 (95 % CI 0.227-0.273). VGC analysis showed that 3D DP TSE sequences performed statistically better than 3D T1 GRE at 1.5 and 3 T (p-value ≤ 0.05). Furthermore, 3 T sequences showed a statistically better performance compared to 1.5 T (p-value ≤ 0.05). CONCLUSIONS: According to the results, 3D DP and T1 MRI sequences can be considered for preoperative planning for THA. Further research is required to emphasize the clinical validation of the results.

Kaposi's Varicelliform Eruption: A Potentially Life-Threatening Complication of Atopic Dermatitis.

Introduction: Kaposi's varicelliform eruption (KVE), also known as eczema herpeticum or eczema vaccinatum, is an acute dermatosis that affects patients with chronic dermatopathies. The diagnosis is primarily clinical and is characterised by the presence of a vesicular exanthema on physical examination. The exanthema subsequently evolves into crusted lesions with typical circular ulcerations in 'punched-out' areas on the skin affected by the underlying dermatopathy. Case description: We present the case of a 6-year-old patient who presented to the Paediatric Emergency department with skin lesions consistent with eczema herpeticum. The patient's management was initially outpatient; however, due to the slow progression of the condition, hospitalisation and intravenous antiviral treatment were initiated. Discussion: KVE affects patients with chronic dermatoses, especially atopic dermatitis. It is important to know the clinical presentation for an early suspicion. KVE is a medical emergency that requires prompt diagnosis and treatment. It can progress to secondary viraemia, which can be fatal in up to 10% of immunocompetent individuals and up to 50% of immunocompromised individuals. It is important to be aware of this condition and to start early treatment with antivirals, especially given the high prevalence of atopic dermatitis in our population. This condition is one of the most serious complications that can occur in these patients. LEARNING POINTS: To facilitate early suspicion and diagnosis, disseminate information about eczema vaccinatum.Emphasise the importance of initiating antiviral treatment early to prevent potential complications of eczema herpeticum.If left untreated, Kaposi's varicelliform eruption can result in up to a 10% mortality rate in immunocompetent individuals and a 50% mortality rate in those who are immunocompromised.

Hif1α-dependent mitochondrial acute O2 sensing and signaling to myocyte Ca2+ channels mediate arterial hypoxic vasodilation.

Vasodilation in response to low oxygen (O2) tension (hypoxic vasodilation) is an essential homeostatic response of systemic arteries that facilitates O2 supply to tissues according to demand. However, how blood vessels react to O2 deficiency is not well understood. A common belief is that arterial myocytes are O2-sensitive. Supporting this concept, it has been shown that the activity of myocyte L-type Ca2+channels, the main ion channels responsible for vascular contractility, is reversibly inhibited by hypoxia, although the underlying molecular mechanisms have remained elusive. Here, we show that genetic or pharmacological disruption of mitochondrial electron transport selectively abolishes O2 modulation of Ca2+ channels and hypoxic vasodilation. Mitochondria function as O2 sensors and effectors that signal myocyte Ca2+ channels due to constitutive Hif1α-mediated expression of specific electron transport subunit isoforms. These findings reveal the acute O2-sensing mechanisms of vascular cells and may guide new developments in vascular pharmacology.

Ca2+ sensitization due to myosin light chain phosphatase inhibition and cytoskeletal reorganization in the myogenic response of skeletal muscle resistance arteries.

Abstract The myogenic response of resistance arteries to intravascular pressure elevation is a fundamental physiological mechanism of crucial importance for blood pressure regulation and organ-specific control of blood flow. The importance of Ca(2+) entry via voltage-gated Ca(2+) channels leading to phosphorylation of the 20 kDa myosin regulatory light chains (LC20) in the myogenic response is well established. Recent studies, however, have suggested a role for Ca(2+) sensitization via activation of the RhoA/Rho-associated kinase (ROK) pathway in the myogenic response. The possibility that enhanced actin polymerization is also involved in myogenic vasoconstriction has been suggested. Here, we have used pressurized resistance arteries from rat gracilis and cremaster skeletal muscles to assess the contribution to myogenic constriction of Ca(2+) sensitization due to: (1) phosphorylation of the myosin targeting subunit of myosin light chain phosphatase (MYPT1) by ROK; (2) phosphorylation of the 17 kDa protein kinase C (PKC)-potentiated protein phosphatase 1 inhibitor protein (CPI-17) by PKC; and (3) dynamic reorganization of the actin cytoskeleton evoked by ROK and PKC. Arterial diameter, MYPT1, CPI-17 and LC20 phosphorylation, and G-actin content were determined at varied intraluminal pressures ± H1152, GF109203X or latrunculin B to suppress ROK, PKC and actin polymerization, respectively. The myogenic response was associated with an increase in MYPT1 and LC20 phosphorylation that was blocked by H1152. No change in phospho-CPI-17 content was detected although the PKC inhibitor, GF109203X, suppressed myogenic constriction. Basal LC20 phosphorylation at 10 mmHg was high at ∼40%, increased to a maximal level of ∼55% at 80 mmHg, and exhibited no additional change on further pressurization to 120 and 140 mmHg. Myogenic constriction at 80 mmHg was associated with a decline in G-actin content by ∼65% that was blocked by inhibition of ROK or PKC. Taken together, our findings indicate that two mechanisms of Ca(2+) sensitization (ROK-mediated phosphorylation of MYPT1-T855 with augmentation of LC20 phosphorylation, and a ROK- and PKC-evoked increase in actin polymerization) contribute to force generation in the myogenic response of skeletal muscle arterioles.

Postmortem computed tomography angiography vs. conventional autopsy: advantages and inconveniences of each method.

PURPOSE: Postmortem computed tomography angiography (PMCTA) was introduced into forensic investigations a few years ago. It provides reliable images that can be consulted at any time. Conventional autopsy remains the reference standard for defining the cause of death, but provides only limited possibility of a second examination. This study compares these two procedures and discusses findings that can be detected exclusively using each method. MATERIALS AND METHODS: This retrospective study compared radiological reports from PMCTA to reports from conventional autopsy for 50 forensic autopsy cases. Reported findings from autopsy and PMCTA were extracted and compared to each other. PMCTA was performed using a modified heart-lung machine and the oily contrast agent Angiofil® (Fumedica AG, Muri, Switzerland). RESULTS: PMCTA and conventional autopsy would have drawn similar conclusions regarding causes of death. Nearly 60 % of all findings were visualized with both techniques. PMCTA demonstrates a higher sensitivity for identifying skeletal and vascular lesions. However, vascular occlusions due to postmortem blood clots could be falsely assumed to be vascular lesions. In contrast, conventional autopsy does not detect all bone fractures or the exact source of bleeding. Conventional autopsy provides important information about organ morphology and remains the only way to diagnose a vital vascular occlusion with certitude. CONCLUSION: Overall, PMCTA and conventional autopsy provide comparable findings. However, each technique presents advantages and disadvantages for detecting specific findings. To correctly interpret findings and clearly define the indications for PMCTA, these differences must be understood.