Delayed subaponeurotic fluid collection (DSFC): systematic review and case report.

PURPOSE: DSFC (delayed subaponeurotic fluid collection) is a benign pathology associated with the first weeks of life and scarcely described in the literature. Normally characterized by a lack of trauma and/or cranial fracture, it is associated with a history of instrumental delivery and the use of fetal electrodes. Taking it in consideration in the differential diagnosis of neonatal scalp swelling becomes important. The objective of this work is to expand knowledge on this entity: history, clinical characteristics, diagnosis, and treatment. METHODS: This article describes a new clinical case and conducts a systematic review according to the PRISMA criteria. RESULTS: Sixty-seven cases are included, they are summarized in a table. CONCLUSIONS: DSFC appears generally 15-16 weeks after birth. The diagnosis is mainly clinical, based on a history of instrumental birth, labor dystocia, or trauma, and with compatible symptoms and evolution. It may be supported by complementary tests such as ultrasound and or CT of the skull in doubtful cases. The treatment of choice is only conservative, and all cases resolve spontaneously and completely after an average of 4 weeks.

The Contribution of Declines in Blood Lead Levels to Reductions in Blood Pressure Levels: Longitudinal Evidence in the Strong Heart Family Study.

BACKGROUND: Chronic lead exposure is associated with both subclinical and clinical cardiovascular disease. We evaluated whether declines in blood lead were associated with changes in systolic and diastolic blood pressure in adult American Indian participants from the SHFS (Strong Heart Family Study). METHODS AND RESULTS: Lead in whole blood was measured in 285 SHFS participants in 1997 to 1999 and 2006 to 2009. Blood pressure and measures of cardiac geometry and function were obtained in 2001 to 2003 and 2006 to 2009. We used generalized estimating equations to evaluate the association of declines in blood lead with changes in blood pressure; cardiac function and geometry measures were considered secondary. Mean blood lead was 2.04 µg/dL at baseline. After ≈10 years, mean decline in blood lead was 0.67 µg/dL. In fully adjusted models, the mean difference in systolic blood pressure comparing the highest to lowest tertile of decline (>0.91 versus <0.27 µg/dL) in blood lead was -7.08 mm Hg (95% CI, -13.16 to -1.00). A significant nonlinear association between declines in blood lead and declines in systolic blood pressure was detected, with significant linear associations where blood lead decline was 0.1 µg/dL or higher. Declines in blood lead were nonsignificantly associated with declines in diastolic blood pressure and significantly associated with declines in interventricular septum thickness. CONCLUSIONS: Declines in blood lead levels in American Indian adults, even when small (0.1-1.0 µg/dL), were associated with reductions in systolic blood pressure. These findings suggest the need to further study the cardiovascular impacts of reducing lead exposures and the importance of lead exposure prevention.

Co-Culturing Microalgae with Roseobacter Clade Bacteria as a Strategy for Vibrionaceae Control in Microalgae-Enriched Artemia.

Bacterial communities associated with fish larvae are highly influenced by the microbiota of live prey used as feed (rotifers or Artemia), generally dominated by bacterial strains with a low degree of specialization and high growth rates, (e.g., Vibrionaceae), which can be detrimental to larvae. Co-cultivation of microalgae used in the enrichment of Artemia (e.g., Phaeodactylum tricornutum, or Chlorella minutissima) with Vibrio-antagonistic probiotics belonging to the Roseobacter clade bacteria (e.g., Phaeobacter spp. or Ruegeria spp.) was studied. The introduction of the probiotics did not affect microalgae growth or significantly modify the composition of bacterial communities associated with both microalgae, as revealed by DGGE analysis. The inoculation of P. tricornutum with Ruegeria ALR6 allowed the maintenance of the probiotic in the scale-up of the microalgae cultures, both in axenic and non-axenic conditions. Using Ruegeria-inoculated P. tricornutum cultures in the enrichment of Artemia reduced the total Vibrionaceae count in Artemia by 2 Log units, therefore preventing the introduction of opportunistic or pathogenic bacteria to fish larvae fed with them.

Utilidad de la monitorización neurofisiológica intraoperatoria como valor pronóstico de la parálisis facial posquirúrgica en schwannomas vestibulares / Utility of the intraoperative neurophysiological monitoring as a prognostic value of postoperative facial paresis in vestibular schwannomas

Antecedentes y objetivo La monitorización neurofisiológica intraoperatoria permite predecir la situación funcional del nervio facial tras la cirugía de schwannoma vestibular. Dada la gran variabilidad de los protocolos neurofisiológicos utilizados para ello, el objetivo del presente estudio es determinar la capacidad pronóstica del protocolo neurofisiológico usado en nuestro servicio. Material y métodos Se realizó un análisis estadístico de los datos de monitorización neurofisiológica recogidos en los pacientes intervenidos entre marzo de 2009 y julio de 2021 en el Servicio de Neurocirugía de Salamanca según su situación funcional, tanto en el período posquirúrgico inmediato como al año de la cirugía. Resultados Se analizó a 51 pacientes de entre 46 y 63 años (mediana: 54). Al estudiar el valor umbral de la intensidad de estimulación del nervio facial y la variación de los potenciales motores evocados córtico-bulbares, se hallaron diferencias significativas (p=0,043 y p=0,011, respectivamente) entre los pacientes con buena y mala situación clínica tras la cirugía. El valor umbral de intensidad más discriminativo fue 0,35mA (sensibilidad: 85%; especificidad: 48%). No se halló relación estadística en el grupo de estudio al año de la cirugía. Conclusiones El protocolo de monitorización intraoperatoria utilizado nos permite predecir la situación clínica de los pacientes en el período posquirúrgico inmediato y mejorar la información al paciente y sus familiares tras la intervención. No podemos, en cambio, utilizar estos parámetros para la predicción de la situación funcional al año de la cirugía ni para la toma de decisiones clínicas al respecto (AU)

Background and objective Intraoperative neurophysiological monitoring allows us to predict the functional status of the facial nerve after vestibular schwannoma surgery. Due to the great variability of the neurophysiological protocols used for it, the goal of this study is to determine the prognostic ability of our neurophysiological protocol. Material and methods We have performed a statistical analysis of the neurophysiological monitoring data collected from patients operated between March 2009 and July 2021 at the Neurosurgery Service of Salamanca according to their functional status, both in the immediate post-surgical period and one year after surgery. Results A number of 51 patients between 46 and 63 years old (median: 54) were analyzed. We have found significant differences studying the threshold value of the stimulation intensity of the facial nerve and the variation of the Cortico-bulbar Evoked Motor Potentials (P=0.043 and P=0.011, respectively) between the patients with good and bad clinical situation after surgery. The most discriminating intensity threshold value was 0.35mA (Sensitivity: 85%; Specificity: 48%). No statistical relationship was found in the study group one year after surgery. Conclusions Our intraoperative monitoring protocol allows us to predict the clinical situation of patients in the immediate postoperative period and improve information for the patient and her relatives after surgery. We cannot, however, use these parameters to predict the functional situation one year after surgery and make clinical decisions in this regard (AU)

Drug-induced liver injury associated to red yeast rice.

Hepatotoxicity is defined as a liver injury induced by a drug or a non-pharmacological agent like herbal medications or dietary supplements. Red yeast rice is rich in monacolin K, which has the same chemical structure as lovastatin, reason why it has been used for the management of hiperlipidemia. A 62 years old woman presented to the emergency service with 38.5ºC fever, coluric orine and loss of weight in the previous 3 weeks. The patient was taking RYR since the week before to the initial symptoms. Mixed hepatocellular and cholestatic acute hepatitis was diagnosed. Autoimmune liver serology resulted positive. Total DILI RECAM Score was 8 (highly probable DILI). Conservative treatment with exclusion of RYR was decided and during follow-up bilirubin and transaminases gradually dropped off. It has been reported a few cases of hepatitis associated to the use of RYR, promoted by a toxic or immunogenic metabolite. Cross-reactions may justify positive autoantibodies so hepatotoxicity should not be discard as a diagnose.

Slope until reaching the plateau: a new predictor of valve response obtained by lumbar infusion test for idiopathic normal pressure hydrocephalus.

BACKGROUND: Diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is based on clinical, radiological, and hydrodynamic data of cerebrospinal fluid (CSF) obtained by invasive methods such as lumbar infusion test, which is used to determine the resistance to CSF outflow (Rout). However, Rout has limitations, and its value as predictor of valve response is questioned. Other variables can be obtained by lumbar infusion test, such as the time to reach the plateau (TRP) and the slope until reaching the plateau (SRP). The objectives were to determine if SRP could be a predictor of response to ventriculoperitoneal shunt (VPS) and what variable (Rout versus SRP) would have greater predictive value. METHOD: Patients with probable iNPH who underwent a lumbar infusion test and were indicated for a VPS were retrospectively studied. Two groups were established, responders and non-responders. Rout, TRP (period between the start of infusion until reaching the plateau measured in seconds) and SRP ((plateau pressure-opening pressure)/TRP) were obtained. For Rout and SRP, the receiver operating curves (ROC) with its areas under the curve (AUC) were calculated. RESULTS: One hundred ten patients were included, being 86 responders (78.20%). Shunt responders had a significantly greater Rout (17.02 (14.45-20.23) versus 13.34 (12.10-16.28) mmHg/ml/min, p = 0.002) and SRP (0.049 (0.043-0.054) versus 0.031 (0.026-0.036) mmHg/sec, p < 0.001) and smaller TRP (641.28 (584.83-697.73) versus 777.65 (654.03-901.27) sec, p = 0.028) than non-responders. The AUC for SRP was greater than the AUC for Rout (0.763 (95 % CI 0.655-0.871, p < 0.001) versus 0.673 (95 % CI 0.595-0.801, p = 0.008), respectively), but the differences were not significant (p = 0.180). CONCLUSIONS: SRP could be considered predictor of response to VPS, and its accuracy tends to be better than Rout. So, this variable may be a useful tool to select shunt candidates among patients with probable iNPH.

Dynamic Changes in Non-Invasive Markers of Liver Fibrosis Are Predictors of Liver Events after SVR in HCV Patients.

Objectives: The course of progressive liver damage after achieving sustained virological response (SVR) with direct-acting antivirals (DAAs) remains undetermined. We aimed to determine risk factors associated with the development of liver-related events (LREs) after SVR, focusing on the utility of non-invasive markers. Methods: An observational, retrospective study that included patients with advanced chronic liver disease (ACLD) caused by hepatitis C virus (HCV), who achieved SVR with DAAs between 2014 and 2017. Patients were followed-up until December 2020. LREs were defined as the development of portal hypertension decompensation and the occurrence of hepatocellular carcinoma (HCC). Serological markers of fibrosis were calculated before treatment and one and two years after SVR. Results: The study included 321 patients, with a median follow-up of 48 months. LREs occurred in 13.7% of patients (10% portal hypertension decompensation and 3.7% HCC). Child-Pugh [HR 4.13 (CI 95% 1.74; 9.81)], baseline FIB-4 [HR 1.12 (CI 95% 1.03; 1.21)], FIB-4 one year post-SVR [HR 1.31 (CI 95% 1.15; 1.48)] and FIB-4 two years post-SVR [HR 1.42 (CI 95% 1.23; 1.64)] were associated with portal hypertension decompensation. Older age, genotype 3, diabetes mellitus and FIB-4 before and after SVR were associated with the development of HCC. FIB-4 cut-off values one and two years post-SVR to predict portal hypertension decompensation were 2.03 and 2.21, respectively, and to predict HCC were 2.42 and 2.70, respectively. Conclusions: HCV patients with ACLD remain at risk of developing liver complications after having achieved SVR. FIB-4 evaluation before and after SVR may help to predict this risk, selecting patients who will benefit from surveillance.

Surgical treatment for recurrent cholangiocarcinoma: a single-center series.

Purpose: The present study aims to assess the results obtained after surgical treatment of cholangiocarcinoma (CC) recurrences. Methods: We carried out a single-center retrospective study, including all patients with recurrence of CC. The primary outcome was patient survival after surgical treatment compared with chemotherapy or best supportive care. A multivariate analysis of variables affecting mortality after CC recurrence was performed. Results: Eighteen patients were indicated surgery to treat CC recurrence. Severe postoperative complication rate was 27.8% with a 30-day mortality rate of 16.7%. Median survival after surgery was 15 months (range 0-50) with 1- and 3-year patient survival rates of 55.6% and 16.6%, respectively. Patient survival after surgery or CHT alone, was significantly better than receiving supportive care (p< 0.001). We found no significant difference in survival when comparing CHT alone and surgical treatment (p=0.113). Time to recurrence of <1 year, adjuvant CHT after resection of the primary tumor and undergoing surgery or CHT alone versus best supportive care were independent factors affecting mortality after CC recurrence in the multivariate analysis. Conclusion: Surgery or CHT alone improved patient survival after CC recurrence compared to best supportive care. Surgical treatment did not improve patient survival compared to CHT alone.

Tissue-specific chromatin-binding patterns of Caenorhabditis elegans heterochromatin proteins HPL-1 and HPL-2 reveal differential roles in the regulation of gene expression.

Heterochromatin is characterized by an enrichment of repetitive elements and low gene density and is often maintained in a repressed state across cell division and differentiation. The silencing is mainly regulated by repressive histone marks such as H3K9 and H3K27 methylated forms and the heterochromatin protein 1 (HP1) family. Here, we analyzed in a tissue-specific manner the binding profile of the two HP1 homologs in Caenorhabditis elegans, HPL-1 and HPL-2, at the L4 developmental stage. We identified the genome-wide binding profile of intestinal and hypodermal HPL-2 and intestinal HPL-1 and compared them with heterochromatin marks and other features. HPL-2 associated preferentially to the distal arms of autosomes and correlated positively with the methylated forms of H3K9 and H3K27. HPL-1 was also enriched in regions containing H3K9me3 and H3K27me3 but exhibited a more even distribution between autosome arms and centers. HPL-2 showed a differential tissue-specific enrichment for repetitive elements conversely with HPL-1, which exhibited a poor association. Finally, we found a significant intersection of genomic regions bound by the BLMP-1/PRDM1 transcription factor and intestinal HPL-1, suggesting a corepressive role during cell differentiation. Our study uncovers both shared and singular properties of conserved HP1 proteins, providing information about genomic binding preferences in relation to their role as heterochromatic markers.

Urinary cystatin C and N-acetyl-beta-D-glucosaminidase (NAG) as early biomarkers for renal disease in dogs with leishmaniosis.

Canine leishmaniasis (CanL) is a disease caused by Leishmania infantum that can vary from a subclinical infection to a severe disease. Dogs affected with CanL present varying degrees of renal dysfunction. Unfortunately, traditional biomarkers such as urea and creatinine detect renal damage in advanced stages of the disease, so more accurate biomarkers are needed. Hence, we aimed to study how urinary cystatin C (CysC) and N-acetyl-beta-D-glucosaminidase (NAG), behave in dogs with CanL at different stages of the disease. Eighty-six CanL infected dogs were classified according to LeishVet stages: LI (16 dogs), LIIa (12 dogs), LIIb (12 dogs), LIII (16 dogs) and LIV (30 dogs); as a control, 17 healthy dogs were studied. Blood samples were collected for complete haematological and biochemistry analysis including plasma cystatin C. Urine analysis included urine specific gravity (USG), urine protein to creatinine ratio (UPC), CysC and NAG expressed as a ratio with creatinine uCysCc (µg/g) and uNAGc (IU/g). The haematological, biochemical and urinary analysis coincided with the LeishVet guidelines. The statistical study of the uCysCc ratio and the uNAGc, showed significant increase when compared against control starting from group LI (p < 0.05). Interestingly, when the cut-off values were calculated using the ROC curve, uCysCc (258.85 µg/g) and uNAGc (2.25 IU/g) 75 % of the dogs included in LI groups surpassed the threshold. Hence our study indicates that uCysCc and uNAGc, could help to detect early renal damage in CanL affected dogs.

[Utility of the intraoperative neurophysiological monitoring as a prognostic value of postoperative facial paresis in vestibular schwannomas]. / Utilidad de la monitorización neurofisiológica intraoperatoria como valor pronóstico de la parálisis facial posquirúrgica en schwannomas vestibulares.

BACKGROUND AND OBJECTIVE: Intraoperative neurophysiological monitoring allows us to predict the functional status of the facial nerve after vestibular schwannoma surgery. Due to the great variability of the neurophysiological protocols used for it, the goal of this study is to determine the prognostic ability of our neurophysiological protocol. MATERIAL AND METHODS: We have performed a statistical analysis of the neurophysiological monitoring data collected from patients operated between March 2009 and July 2021 at the Neurosurgery Service of Salamanca according to their functional status, both in the immediate post-surgical period and one year after surgery. RESULTS: A number of 51 patients between 46 and 63 years old (median: 54) were analyzed. We have found significant differences studying the threshold value of the stimulation intensity of the facial nerve and the variation of the Cortico-bulbar Evoked Motor Potentials (P=0.043 and P=0.011, respectively) between the patients with good and bad clinical situation after surgery. The most discriminating intensity threshold value was 0.35mA (Sensitivity: 85%; Specificity: 48%). No statistical relationship was found in the study group one year after surgery. CONCLUSIONS: Our intraoperative monitoring protocol allows us to predict the clinical situation of patients in the immediate postoperative period and improve information for the patient and her relatives after surgery. We cannot, however, use these parameters to predict the functional situation one year after surgery and make clinical decisions in this regard.

Clinical, Histopathologic and Genetic Features of Rhabdoid Meningiomas.

Rhabdoid meningiomas (RM) shows heterogeneous histological findings, and a wide variety of chromosomal copy number alterations (CNA) are associated with an unpredictable course of the disease. In this study, we analyzed a series of 305 RM samples from patients previously reported in the literature and 33 samples from 23 patients studied in our laboratory. Monosomy 22-involving the minimal but most common recurrent region loss of the 22q11.23 chromosomal region was the most observed chromosomal alteration, followed by losses of chromosomes 14, 1, 6, and 19, polysomies of chromosomes 17, 1q, and 20, and gains of 13q14.2, 10p13, and 21q21.2 chromosomal regions. Based on their CNA profile, RM could be classified into two genetic subgroups with distinct clinicopathologic features characterized by the presence of (1) chromosomal losses only and (2) combined losses and gains of several chromosomes. The latter displays a higher frequency of WHO grade 3 tumors and poorer clinical outcomes.

[The influence of cisnormative discourses on the physical and psycho-emotional care of trans youth in Mexico]. / Influencias de los discursos cisnormativos en el cuidado físico y psicoemocional de jóvenes trans de México.

Cisnormativity in the health field has involved the pathologization of identities that do not align with gender binaries. The aim of this study was to analyze the scope and influence of cisnormative discourses on the care and health of trans youth. Semi-structured interviews were carried out between March 2021 and May 2022, and results were analyzed from a social constructivist approach. Five young trans people between 20 and 29 years old participated in the study (2 trans women and 3 trans men). Results showed that aspects of cisnormative gender discourse were evident in their narratives; however, at the same time they generated alternative narratives, where psycho-emotional and bodily care led them to position themselves outside of common tropes such as dysphoria and "the wrong body". We conclude that this study contributes to dismantling the medical view of trans people by showing how they adopt self-care practices by mobilizing their own resources. Furthermore, it reflects the importance of building dialogues with trans people that will allow more and better care strategies to be generated.

La cisnormatividad en el ámbito de la salud ha implicado la patologización de identidades que no se identifican con los criterios de la lógica binaria del género. El objetivo de este estudio fue analizar el alcance y la influencia que los discursos cisnormativos tienen en el cuidado y la salud de las y los jóvenes trans. Entre marzo de 2021 y mayo de 2022, se llevaron a cabo entrevistas semiestructuradas que se analizaron a la luz de la perspectiva socioconstruccionista. Participaron cinco jóvenes trans (dos mujeres trans y tres varones trans), de entre los 20 y 29 años. Los resultados mostraron la incorporación en sus relatos de aspectos del discurso cisnormativo del género; no obstante, a la par generan narrativas alternativas, en las que el cuidado psicoemocional y del cuerpo les lleva a posicionarse lejos de tropos narrativos como la disforia y "el cuerpo equivocado". Concluimos que este trabajo contribuye a desmantelar la visión médica de las personas trans, mostrando cómo a través de sus recursos, adoptan prácticas de autocuidado. Asimismo, refleja la importancia de construir diálogos con las personas trans que permitan generar más y mejores estrategias de atención.

Renoportal Anastomosis and Its Complications: A Complex Case Report.

BACKGROUND: Renoportal anastomosis (RPA) is an effective technique in cases of complex portal vein thrombosis with the presence of a splenorenal shunt. The objective of this report is to describe the possible complications related to RPA. CASE REPORT: A 50-year-old man with alcohol-related and hepatitis C-related cirrhosis and 2 hepatocellular carcinomas underwent liver transplant. He presented a portal vein thrombosis Yerdel IV, a splenorenal shunt, and another shunt between the inferior mesenteric vein (IMV) and the perirectal plexus. During surgery, the flow of the left renal vein was 891 mL/min, and this rose to 1050 mL/min after IMV clamping. RPA was made through iliac vein graft interposition, and the IMV was ligated. Portal flow was 832 mL/min but drastically decreased because of mesenteric root compression. After finishing the liver transplant, a renoiliac graft percutaneous transhepatic stent was put in place. The patient presented graft dysfunction and acute kidney injury. On postoperative day +18, a second stent was put in place because of a thrombosis in the splenomesenteric confluence. The patient subsequently presented partial distal rethrombosis and a pancreaticoduodenal arteriovenous fistula, which required several embolizations. The patient developed ascites, recurrent gastrointestinal bleeding, and persistent bacterial peritonitis. Finally, a modified Sugiura procedure (without splenectomy) was performed, achieving a portal flow of 1800 mL/min. However, the patient developed sepsis and multiorgan failure, and died on postoperative day +70. CONCLUSIONS: Despite long-term patient and graft survival within accepted limits after LT, RPA is a challenging technique not exempt from complications.

Nonsplenorenal Spontaneous Portosystemic Shunts in Liver Transplant Attitude and Outcomes: A Single-Center Series.

BACKGROUND: Management of nonsplenorenal spontaneous portosystemic shunts (NSRSPSS) in liver transplant (LT) is controversial. Reports on the influence of its ligation suggest improvements in morbidity and survival. METHODS: Retrospective study of a single-center series. The objective was to analyze the outcomes and post-LT survival after the closure of NSRSPSS. RESULTS: Between January 2005 and April 2021 a total of 23 patients with NSRSPSS underwent LT. The shunt was superior mesenteric vein-vena cava in 12 (52.2%), inferior mesenteric vein-vena cava in 6 (26.1%), through the left gastric vein in 4 (17.4%), and portocava in 1 (4.3%). Seven patients presented portal vein thrombosis, with thrombectomy being performed in 5. Moreover, 21 patients had portoportal anastomosis, 1 patient required portal reconstruction at the splenomesenteric confluence, and 1 had a coronary-portal anastomosis. The NSRSPSS was closed in 22 cases (95.7%). The mean (SD) portal flow before and after the closure of NSRSPSS was 1395 (572) mL/min and 1773 (583) mL/min (104.4 [47.9] mL/min/100 g and 127.9 [4.9] mL/min/100 g, respectively). Six patients (26.1%) presented primary graft dysfunction, 13 (56.5%) acute kidney injury, and 9 (39%) ascites. Three arterial stenoses (13%), 2 biliary stenoses (8.6%), and 1 intrahepatic portal thrombosis (4.3%) occurred. Median intensive care unit and hospital stay was 5 days (range, 3-8 days) and 15 days (range, 13-21 days). After a mean follow-up of 5.18 (3.2) years, all patients except 1 are alive. CONCLUSIONS: The closure of the NSRSPSS during LT can optimize portal flow, with potential influence in morbidity and survival rates.

Blood cadmium, lead, manganese, mercury, and selenium levels in American Indian populations: The Strong Heart Study.

BACKGROUND: Many American Indian (AI) communities are in areas affected by environmental contamination, such as toxic metals. However, studies assessing exposures in AI communities are limited. We measured blood metals in AI communities to assess historical exposure and identify participant characteristics associated with these levels in the Strong Heart Study (SHS) cohort. METHOD: Archived blood specimens collected from participants (n = 2014, all participants were 50 years of age and older) in Arizona, Oklahoma, and North and South Dakota during SHS Phase-III (1998-1999) were analyzed for cadmium, lead, manganese, mercury, and selenium using inductively coupled plasma triple quadrupole mass spectrometry. We conducted descriptive analyses for the entire cohort and stratified by selected subgroups, including selected demographics, health behaviors, income, waist circumference, and body mass index. Bivariate associations were conducted to examine associations between blood metal levels and selected socio-demographic and behavioral covariates. Finally, multivariate regression models were used to assess the best model fit that predicted blood metal levels. FINDINGS: All elements were detected in 100% of study participants, with the exception of mercury (detected in 73% of participants). The SHS population had higher levels of blood cadmium and manganese than the general U.S. population 50 years and older. The median blood mercury in the SHS cohort was at about 30% of the U.S. reference population, potentially due to low fish consumption. Participants in North Dakota and South Dakota had the highest blood cadmium, lead, manganese, and selenium, and the lowest total mercury levels, even after adjusting for covariates. In addition, each of the blood metals was associated with selected demographic, behavioral, income, and/or weight-related factors in multivariate models. These findings will help guide the tribes to develop education, outreach, and strategies to reduce harmful exposures and increase beneficial nutrient intake in these AI communities.

Metabolism of 3-Chlorobiphenyl (PCB 2) in a Human-Relevant Cell Line: Evidence of Dechlorinated Metabolites.

Lower chlorinated polychlorinated biphenyls (LC-PCBs) and their metabolites make up a class of environmental pollutants implicated in a range of adverse outcomes in humans; however, the metabolism of LC-PCBs in human models has received little attention. Here we characterize the metabolism of PCB 2 (3-chlorobiphenyl), an environmentally relevant LC-PCB congener, in HepG2 cells with in silico prediction and nontarget high-resolution mass spectrometry. Twenty PCB 2 metabolites belonging to 13 metabolite classes, including five dechlorinated metabolite classes, were identified in the cell culture media from HepG2 cells exposed for 24 h to 10 µM or 3.6 nM PCB 2. The PCB 2 metabolite profiles differed from the monochlorinated metabolite profiles identified in samples from an earlier study with PCB 11 (3,3'-dichlorobiphenyl) under identical experimental conditions. A dechlorinated dihydroxylated metabolite was also detected in human liver microsomal incubations with monohydroxylated PCB 2 metabolites but not PCB 2. These findings demonstrate that the metabolism of LC-PCBs in human-relevant models involves the formation of dechlorination products. In addition, untargeted metabolomic analyses revealed an altered bile acid biosynthesis in HepG2 cells. Our results indicate the need to study the disposition and toxicity of complex PCB 2 metabolites, including novel dechlorinated metabolites, in human-relevant models.

Current status and future directions for a neurotoxicity hazard assessment framework that integrates in silico approaches.

Neurotoxicology is the study of adverse effects on the structure or function of the developing or mature adult nervous system following exposure to chemical, biological, or physical agents. The development of more informative alternative methods to assess developmental (DNT) and adult (NT) neurotoxicity induced by xenobiotics is critically needed. The use of such alternative methods including in silico approaches that predict DNT or NT from chemical structure (e.g., statistical-based and expert rule-based systems) is ideally based on a comprehensive understanding of the relevant biological mechanisms. This paper discusses known mechanisms alongside the current state of the art in DNT/NT testing. In silico approaches available today that support the assessment of neurotoxicity based on knowledge of chemical structure are reviewed, and a conceptual framework for the integration of in silico methods with experimental information is presented. Establishing this framework is essential for the development of protocols, namely standardized approaches, to ensure that assessments of NT and DNT based on chemical structures are generated in a transparent, consistent, and defendable manner.

Analysis of Nuclear Pore Complexes in Caenorhabditis elegans by Live Imaging and Functional Genomics.

Nuclear pore complexes (NPCs) are essential to communication of macromolecules between the cell nucleus and the surrounding cytoplasm. RNA synthesized in the nucleus is exported through NPCs to function in the cytoplasm, whereas transcription factors and other proteins are selectively and actively imported. In addition, many NPC constituents, known as nuclear pore proteins (nucleoporins or nups), also play critical roles in other processes, such as genome organization, gene expression, and kinetochore function. Thanks to its genetic amenability and transparent body, the nematode Caenorhabditis elegans is an attractive model to study NPC dynamics. We provide here an overview of available genome engineered strains and FLP/Frt-based tools to study tissue-specific functions of individual nucleoporins. We also present protocols for live imaging of fluorescently tagged nucleoporins in intact tissues of embryos, larvae, and adult and for analysis of interactions between nucleoporins and chromatin by DamID.