Adequate Dietary Intake and Vitamin D Supplementation: A Study of Their Relative Importance in Determining Serum Vitamin D and Ferritin Concentrations during Pregnancy.

Vitamin D is essential for human health. However, it is not clear if vitamin D supplementation is necessary for all pregnant women. This study examines the relative importance of dietary patterns and vitamin D supplementation frequency in determining serum 25-hydroxyvitamin D (25(OH)D) and ferritin concentrations among pregnant women in Hong Kong, China. A total of 572 healthy women were recruited from antenatal clinics at 25-35 weeks pregnant. Participants completed an electronic version of the food frequency questionnaire and a web questionnaire on supplement use. Their blood samples were tested for serum 25(OH)D and ferritin. The associations of dietary patterns and vitamin D supplementation frequency with serum 25(OH)D and ferritin concentrations were analyzed using moderated hierarchical regression. Two dietary patterns were identified. The adequate dietary intake was characterized by the high probability of meeting recommended daily food group servings, whereas the inadequate dietary intake was characterized by inadequate consumption of vegetables, fruits, meat, fish, and eggs, or alternatives. The association between adequate dietary intake and serum ferritin concentrations was independent of vitamin D supplementation frequency (ß = 0.05, p = 0.035), but dietary patterns interacted with vitamin D supplementation frequency to determine serum 25(OH)D concentrations (ß = -13.22, p = 0.014). The current study presents evidence on the relative importance of dietary patterns and vitamin D supplementation in maintaining sufficient vitamin D and iron in pregnancy. Antenatal nutrition counselling services should be provided to pregnant women who show signs of inadequate dietary intake.

Regional anesthesia techniques for cardiac surgery: where are we?

PURPOSE OF REVIEW: Inadequate pain relief after cardiac surgery results in decreased patient experience and satisfaction, increased opioid consumption with its associated adverse consequences, and reduced efficiency metrics. To mitigate this, regional analgesic techniques are an increasingly important part of the perioperative cardiac anesthesia care plan. The purpose of this review is to compare current regional anesthesia techniques, and the relative evidence supporting their efficacy and safety in cardiac surgery. RECENT FINDINGS: Numerous novel plane blocks have been developed in recent years, with evidence of improved pain control after cardiac surgery. SUMMARY: The current data supports the use of a variety of different regional anesthesia techniques to reduce acute pain after cardiac surgery. However, future randomized trials are needed to quantify and compare the efficacy and safety of different regional techniques for pain control after cardiac surgery.

Vitamin D concentrations during pregnancy and in cord blood: a systematic review and meta-analysis.

CONTEXT: Effect size estimates for the association between vitamin D concentrations in maternal blood during pregnancy and in cord blood vary widely across studies, but no meta-analysis has been conducted to ascertain this association. OBJECTIVE: The aim of this systematic review was to estimate the pooled effect size for the association between circulating 25-hydroxyvitamin D (25[OH]D) concentrations, a marker of vitamin D status, in maternal blood during pregnancy and in cord blood. DATA SOURCES: The PubMed, Embase, and Web of Science databases were searched from their inception to February 2021. DATA EXTRACTION: Following the application of prespecified inclusion and exclusion criteria, 94 articles were eligible for full-text review, which was conducted by 2 authors independently. A third author was consulted when necessary and consensus reached. In total, 26 articles, which comprised 30 studies and 6212 mother-infant dyads, were included. Methodological quality was assessed using a modified version of the Joanna Briggs Institute's Critical Appraisal Checklist for Studies Reporting Prevalence Data. Correlation coefficient (r) values for the association between maternal serum 25(OH)D concentrations during pregnancy and in cord blood were extracted. DATA ANALYSIS: The r values were pooled using random-effects meta-analyses. Sensitivity and subgroup analyses were performed to investigate sources of heterogeneity. The pooled r for all studies was 0.72 (95%CI, 0.64-0.79), indicating high heterogeneity (I2 = 95%, P < 0.01). After influential and outlier studies were removed, the pooled r for 9 studies was 0.70 (95%CI, 0.66-0.74), which resulted in a substantial reduction in heterogeneity (I2 = 41%, P=0.10). CONCLUSION: The findings support a positive and large correlation between maternal vitamin D concentrations during pregnancy and vitamin D concentrations in cord blood. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42021273348.

An Assessment of Risk Factors for Insufficient Levels of Vitamin D during Early Infancy.

Recent evidence suggests that breastfeeding may increase the risk of vitamin D deficiency in offspring. However, it is unclear whether increased risk results from breastfeeding alone, or whether it is associated together with other risk factors. This study surveyed 208 infant-mother dyads recruited by stratified random sampling in different districts of Hong Kong. Mothers were asked to complete a questionnaire on their demographics, history of risk behavior, and feeding practices. Peripheral blood samples were collected from infants to determine their vitamin D status. Among all infant participants, 70 were vitamin D insufficient or deficient. Being breastfed, being a girl, having a multiparous mother, and the use of sun cream were found to be the strongest risk factors for vitamin D insufficiency during infancy (all p < 0.05), after mutual adjustment. The cumulative risk model displayed a dose-response pattern between the number of risk factors and the risk of vitamin D insufficiency during this period. Our findings indicate the risk profile of infants with insufficient vitamin D. Guidelines and recommendations on healthy diet and lifestyle should be provided to mothers during the early stage of pregnancy to increase the likelihood of adequate levels of vitamin D in their offspring.

Aromatherapy for Procedural Anxiety in Pain Management and Interventional Spine Procedures: A Randomized Trial.

OBJECTIVE: The aim of this study was to evaluate a nonsedating agent, lavender aromatherapy, to reduce anxiety before interventional spinal procedures. DESIGN: In this prospective, single-blind study performed at a tertiary care center for an academic institution, 144 patients undergoing spinal procedures (epidural steroid injection, medial branch block, or radiofrequency ablation) were randomized into two groups of 72 patients. The experimental group was exposed to a tablet formulation of lavender aromatherapy, while the control group was exposed to tablets devoid of any scent. The exposure duration for each group was 5 mins. The primary outcome measurement was patients' anxiety state before the spinal procedure using the six-item State-Trait Anxiety Inventory. Secondary outcomes quantified the rate of vasovagal events and aborted procedures because of patient intolerance. RESULTS: Compared with the control group, the posttreatment anxiety score of those exposed to lavender aromatherapy revealed a statistically significant difference as measured by the six-item State-Trait Anxiety Inventory (12.15 ± 2.67 and 10.67 ± 2.81, P < 0.05). Within group, the experimental group's anxiety level decreased from 12.26 ± 2.75 to 10.67 ± 2.81 (P < 0.05). There were two vasovagal episodes and one aborted procedure in the control group, whereas there was one vasovagal episode and no aborted procedures in the aromatherapy group. CONCLUSIONS: Lavender-based aromatherapy is effective in reducing preprocedural anxiety before interventional spine procedures for pain management.

Epigallocatechin Gallate Induces Hepatic Stellate Cell Senescence and Attenuates Development of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly morbid condition with lack of effective treatment options. HCC arises from chronically inflamed and damaged liver tissue; therefore, chemoprevention may be a useful strategy to reduce HCC incidence. Several reports suggest that epigallocatechin gallate (EGCG), extracted from green tea, can suppress liver inflammation and fibrosis in animal models, but its role in HCC chemoprevention is not well established. In this study, male Wistar rats were injected with diethylnitrosamine at 50 mg/kg for 18 weeks to induce cirrhosis and HCC, and EGCG was given in drinking water at a concentration of 0.02%. Clinically achievable dosing of EGCG was well-tolerated in diethylnitrosamine-injured rats and was associated with improved serum liver markers including alanine transaminase, aspartate transaminase, and total bilirubin, and reduced HCC tumor formation. Transcriptomic analysis of diethylnitrosamine-injured hepatic tissue was notable for increased expression of genes associated with the Hoshida high risk HCC gene signature, which was prevented with EGCG treatment. EGCG treatment also inhibited fibrosis progression, which was associated with inactivation of hepatic stellate cells and induction of the senescence-associated secretory phenotype. In conclusion, EGCG administered at clinically safe doses exhibited both chemopreventive and antifibrotic effects in a rat diethylnitrosamine liver injury model.

Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy.

Tumor-treating fields (TTFields) are alternating electric fields in a specific frequency range (100-300 kHz) delivered to the human body through transducer arrays. In this study, we evaluated whether TTFields-mediated cell death can elicit antitumoral immunity and hence would be effectively combined with anti-PD-1 therapy. We demonstrate that in TTFields-treated cancer cells, damage-associated molecular patterns including high-mobility group B1 and adenosine triphosphate are released and calreticulin is exposed on the cell surface. Moreover, we show that TTFields treatment promotes the engulfment of cancer cells by dendritic cells (DCs) and DCs maturation in vitro, as well as recruitment of immune cells in vivo. Additionally, our study demonstrates that the combination of TTFields with anti-PD-1 therapy results in a significant decline of tumor volume and increase in the percentage of tumor-infiltrating leukocytes in two tumor models. In orthotopic lung tumors, these infiltrating leukocytes, specifically macrophages and DCs, showed elevated expression of PD-L1. Compatibly, cytotoxic T-cells isolated from these tumors demonstrated increased production of IFN-γ. In colon cancer tumors, T-cells infiltration was significantly increased following long treatment duration with TTFields plus anti-PD-1. Collectively, our results suggest that TTFields therapy can induce anticancer immune response. Furthermore, we demonstrate robust efficacy of concomitant application of TTFields and anti-PD-1 therapy. These data suggest that integrating TTFields with anti-PD-1 therapy may further enhance antitumor immunity, hence achieve better tumor control.

Regeneration of Diabetic Foot Ulcers Based on Therapy with Red LED Light and a Natural Latex Biomembrane.

This study analyzes the effects of the Rapha® system, which employs red light therapy (RLT) and a natural latex biomembrane in the healing of neuropathic ulcers associated with the diabetic foot. We conducted a randomized, controlled, blinded clinical trial with 15 participants that were divided into three groups (GI, GII and GIII): (i) Rapha® system application by the participant and a health professional at home, with clinical status evaluation every 2 weeks at the hospital (GI); (ii) standard protocol used in Brazil, performed by a health professional at the hospital (GII; control); and (iii) the Rapha® system applied by the participant at home and clinical status evaluation every 2 weeks at the hospital (GIII). We used image processing techniques on photographic recordings of the lesions, and several statistical tests were used to analyze the data, allowing for the comparison of the average results for all groups. The average healing rates of GI, GII, and GIII were 77.0, 51.4, and 80%, respectively. The granulation tissue evaluation indicated a higher efficacy in the tissue repair of lesions treated with the Rapha® system. In conclusion, the Rapha® system proved to be an effective healing system, even when self-applied at the patient's home.

AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields).

Tumor Treating Fields (TTFields), an approved treatment modality for glioblastoma, are delivered via non-invasive application of low-intensity, intermediate-frequency, alternating electric fields. TTFields application leads to abnormal mitosis, aneuploidy, and increased cell granularity, which are often associated with enhancement of autophagy. In this work, we evaluated whether TTFields effected the regulation of autophagy in glioma cells. We found that autophagy is upregulated in glioma cells treated with TTFields as demonstrated by immunoblot analysis of the lipidated microtubule-associated protein light chain 3 (LC3-II). Fluorescence and transmission electron microscopy demonstrated the presence of LC3 puncta and typical autophagosome-like structures in TTFields-treated cells. Utilizing time-lapse microscopy, we found that the significant increase in the formation of LC3 puncta was specific to cells that divided during TTFields application. Evaluation of selected cell stress parameters revealed an increase in the expression of the endoplasmic reticulum (ER) stress marker GRP78 and decreased intracellular ATP levels, both of which are indicative of increased proteotoxic stress. Pathway analysis demonstrated that TTFields-induced upregulation of autophagy is dependent on AMP-activated protein kinase (AMPK) activation. Depletion of AMPK or autophagy-related protein 7 (ATG7) inhibited the upregulation of autophagy in response to TTFields, as well as sensitized cells to the treatment, suggesting that cancer cells utilize autophagy as a resistance mechanism to TTFields. Combining TTFields with the autophagy inhibitor chloroquine (CQ) resulted in a significant dose-dependent reduction in cell growth compared with either TTFields or CQ alone. These results suggest that dividing cells upregulate autophagy in response to aneuploidy and ER stress induced by TTFields, and that AMPK serves as a key regulator of this process.

In vitro anthelmintic and cytotoxic activities of extracts of Persea willdenovii Kosterm (Lauraceae).

This study describes the effects of extracts and fractions of Persea willdenovii leaves against goat gastrointestinal nematodes and their cytotoxicity on Vero cells. The in vitro ovicidal and larvicidal activities of the crude ethanolic, hexane, ethyl acetate (EAE), butanolic and residual hydroethanolic extracts were assessed through the inhibition of egg hatching and larval motility assays. The most active extract (EAE) was then fractionated by chromatography in an open column containing silica gel, to furnish six fractions (Fr1-Fr6), which were also tested. The cytotoxicity of active extracts and fractions was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and trypan blue exclusion assay. The EAE and two fractions (Fr1 and Fr2) showed inhibitory activity in the egg hatching of gastrointestinal nematodes of goats in a concentration-dependent manner. The effective concentrations for 50% inhibition (EC50) of egg hatching were 2.3, 0.12 and 2.94 mg/ml for EAE, Fr1 and Fr2, respectively. All extracts and fractions were not effective in inhibiting 50% of motility of infective larvae. EAE and Fr2 had IC50 values (50% inhibitory concentration) of 4.95 and 2.66 mg/ml, respectively. Fr1 showed a slight cytotoxic effect (cellular inviability <30%) only after 48 h of treatment (MTT test). Gas chromatography-mass spectrometry (GC-MS) analysis showed the presence of six fatty acid ethyl esters, a fatty acid methyl ester and a long-chain ketone in the most active fraction. These constituents identified in P. willdenovii can be related to the high ovicidal activity and relatively non-toxic effect of the extracts.

Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells.

BACKGROUND: Tumor Treating Fields (TTFields) are an anti-neoplastic treatment modality delivered via application of alternating electric fields using insulated transducer arrays placed directly on the skin in the region surrounding the tumor. A Phase 3 clinical trial has demonstrated the effectiveness of continuous TTFields application in patients with glioblastoma during maintenance treatment with Temozolomide. The goal of this study was to evaluate the efficacy of combining TTFields with radiation treatment (RT) in glioma cells. We also examined the effect of TTFields transducer arrays on RT distribution in a phantom model and the impact on rat skin toxicity. METHODS: The efficacy of TTFields application after induction of DNA damage by RT or bleomycin was tested in U-118 MG and LN-18 glioma cells. The alkaline comet assay was used to measure repair of DNA lesions. Repair of DNA double strand breaks (DSBs) were assessed by analyzing γH2AX or Rad51 foci. DNA damage and repair signaled by the activation pattern of phospho-ATM (pS1981) and phospho-DNA-PKcs (pS2056) was evaluated by immunoblotting. The absorption of the RT energy by transducer arrays was measured by applying RT through arrays placed on a solid-state phantom. Skin toxicities were tested in rats irradiated daily through the arrays with 2Gy (total dose of 20Gy). RESULTS: TTFields synergistically enhanced the efficacy of RT in glioma cells. Application of TTFields to irradiated cells impaired repair of irradiation- or chemically-induced DNA damage, possibly by blocking homologous recombination repair. Transducer arrays presence caused a minor reduction in RT intensity at 20 mm and 60 mm below the arrays, but led to a significant increase in RT dosage at the phantom surface jeopardizing the "skin sparing effect". Nevertheless, transducer arrays placed on the rat skin during RT did not lead to additional skin reactions. CONCLUSIONS: Administration of TTFields after RT increases glioma cells treatment efficacy possibly by inhibition of DNA damage repair. These preclinical results support the application of TTFields therapy immediately after RT as a viable regimen to enhance RT outcome. Phantom measurements and animal models imply that it may be possible to leave the transducer arrays in place during RT without increasing skin toxicities.

A novel approach in the treatment of acute whiplash syndrome: Ultrasound-guided needle percutaneous electrolysis. A randomized controlled trial.

INTRODUCTION: Whiplash associated disorders are currently a common musculoskeletal problem. Besides the high incidence in western countries, the costs derived from prolonged treatment and medicolegal compensation, make this entity a challenging problem for clinicians and insurance companies. To date, no conservative treatment has shown clear superiority in the management of acute cases. HYPOTHESIS: Percutaneous needle electrolysis (PNE) is an effective approach for the treatment of Quebec type II acute whiplash syndrome (AWS). PNE consists in the application of brief galvanic currents into a damaged structure, producing a local controlled inflammatory response, with subsequent tissular healing enhancement. MATERIALS AND METHODS: One hundred AWS patients were randomized into: (a) standard physiotherapy intervention for AWS; (b) a standardized PNE protocol for AWS. Both groups were assessed for treatment outcome at the 5th week mark. RESULTS: Both groups showed a statistically significant improvement according to the Northwick Park Neck Questionnaire, visual analogic scale and pressure pain threshold. The improvement was similar in both groups, except for the pain pressure threshold, with a 56.6% reduction vs. 44.4% reduction in favour of the PNE group (P=0.035). In addition, the physio group consumed a mean treatment time of 20hours, while the PNE intervention averaged less than 1 hour in total. DISCUSSION: PNE can be considered as an effective treatment option for AWS. Importantly, the technique is highly cost-effective, with limited equipment required and a notable treatment time reduction, compared to more comprehensive physiotherapy protocols. TYPE OF STUDY: Randomized controlled trial. LEVEL OF PROOF: 1b.

Flexible nanofilms coated with aligned piezoelectric microfibers preserve the contractility of cardiomyocytes.

The use of engineered cardiac tissue for high-throughput drug screening/toxicology assessment remains largely unexplored. Here we propose a scaffold that mimics aspects of cardiac extracellular matrix while preserving the contractility of cardiomyocytes. The scaffold is based on a poly(caprolactone) (PCL) nanofilm with magnetic properties (MNF, standing for magnetic nanofilm) coated with a layer of piezoelectric (PIEZO) microfibers of poly(vinylidene fluoride-trifluoroethylene) (MNF+PIEZO). The nanofilm creates a flexible support for cell contraction and the aligned PIEZO microfibers deposited on top of the nanofilm creates conditions for cell alignment and electrical stimulation of the seeded cells. Our results indicate that MNF+PIEZO scaffold promotes rat and human cardiac cell attachment and alignment, maintains the ratio of cell populations overtime, promotes cell-cell communication and metabolic maturation, and preserves cardiomyocyte (CM) contractility for at least 12 days. The engineered cardiac construct showed high toxicity against doxorubicin, a cardiotoxic molecule, and responded to compounds that modulate CM contraction such as epinephrine, propranolol and heptanol.

Determining the Optimal Inhibitory Frequency for Cancerous Cells Using Tumor Treating Fields (TTFields).

Tumor Treating Fields (TTFields) are an effective treatment modality delivered via the continuous, noninvasive application of low-intensity (1-3 V/cm), alternating electric fields in the frequency range of several hundred kHz. The study of TTFields in tissue culture is carried out using the TTFields in vitro application system, which allows for the application of electric fields of varying frequencies and intensities to ceramic Petri dishes with a high dielectric constant (Ɛ > 5,000). Cancerous cell lines plated on coverslips at the bottom of the ceramic Petri dishes are subjected to TTFields delivered in two orthogonal directions at various frequencies to facilitate treatment outcome tests, such as cell counts and clonogenic assays. The results presented in this report demonstrate that the optimal frequency of the TTFields with respect to both cell counts and clonogenic assays is 200 kHz for both ovarian and glioma cells.

Examining the Cervical Screening Behaviour of Women Aged 50 or above and Its Predicting Factors: A Population-Based Survey.

Under-screening may increase the risk of cervical cancer in middle-aged women. This study aimed to investigate cervical cancer screening behaviour and its predictors among women aged 50 years or above. A population-based sample of 959 women was recruited by telephone from domestic households in Hong Kong, using random methods, and a structured questionnaire developed to survey participants. Multivariable logistic regressions were performed to examine the factors independently associated with cervical screening behaviour. Nearly half the sample (48%) had never had a cervical smear test. Multivariable analyses showed that age, educational level, marital status, family history of cancer, smoking status, use of complementary therapy, recommendation from health professionals, and believing that regular visits to a doctor or a Chinese herbalist were good for their health were predictors of cervical screening behaviour. Misconceptions concerned with menopause may reduce women's perceived susceptibility to cervical cancer, especially if they are 50 or above, and exert a negative effect on their screening behaviour. Healthcare professionals should actively approach these high-risk groups-older unmarried women, smokers, those less educated and who are generally not much concerned with their health.

Revisión sistemática del tratamiento de fisioterapia en el reimplante de extremidad superior / Systematic review of the physiotherapy treatment in the replantation of upper extremity

Objetivo: Describir las técnicas de fisioterapia implementadas en el tratamiento posquirúrgico de reimplante de extremidad superior y evaluar los resultados funcionales. Estrategia de búsqueda y selección de estudios: Revisión sistemática de las bases de datos Pubmed, Web of Science, Scopus y Cochrane Library desde el 1 de enero de 1990 hasta el 30 de junio de 2015. Dos revisores independientes han examinado, analizado y evaluado los resultados. Se han incluido estudios originales de pacientes con reimplante del miembro superior en los que se describiera y analizara el tratamiento de fisioterapia y los resultados obtenidos. Síntesis de resultados: Se han obtenido 6 publicaciones, todas estudios de casos, sobre 6 reimplantes de antebrazo-mano y uno de todos los dígitos de ambas manos. Las intervenciones planteadas en el postoperatorio inmediato han sido la colocación de ortesis, el control del estado del reimplante, los ejercicios respiratorios, la educación sanitaria, el drenaje del edema, y la movilización controlada del miembro implantado y del resto de la extremidad. En la fase ambulatoria se ha propuesto continuar con la movilización pasiva, asistida y activa controlada; drenaje del edema; masaje de la cicatriz; electroterapia; trabajo de la sensibilidad y reeducación de las actividades de la vida diaria. Hallamos variabilidad en el inicio del tratamiento de fisioterapia y sus técnicas, especialmente en la movilización articular. Conclusiones: Se advierte de la escasez de referencias al tratamiento de fisioterapia en las publicaciones biomédicas, a pesar de ser una parte indispensable y vital para el éxito del reimplante

Objective: Describing the techniques of physiotherapy implemented in post-surgical treatment of upper extremity replantation and evaluate the functional results. Search strategy and article selection: Systematic review of Pubmed, Web of Science, Scopus and Cochrane Library from 1st January 1990 to 30th June 2015. Two independent reviewers have examined, analyzed and evaluated the results. It has included original studies of patients with upper limb replantation, in which is described and analyzed physiotherapy treatment and outcomes. Summary of results: Six publications have been obtained, all of them case studies, about 6 replantations of forearm-hand and one of all digits of both hands. The interventions in immediate postoperative period have been the placement of orthosis, state inspection of the replantation, breathing exercises, health education, drainage of edema, and controlled mobilization of the replanted member and the rest of the limb. In ambulatory phase it has been proposed to continue the passive, assisted and active controlled mobilization; drainage of edema; scar massage; electrotherapy; sensory reeducation and retraining of the activities of daily living. Presence of variability at the start of physical therapy and its techniques, especially in joint mobilization. Conclusions: The study warns of the paucity of references to physical therapy in the biomedical literature, despite being indispensable and vital to successful of the replantation

Vascular disease modeling using induced pluripotent stem cells: Focus in Hutchinson-Gilford Progeria Syndrome.

Induced pluripotent stem cells (iPSCs) represent today an invaluable tool to create disease cell models for modeling and drug screening. Several lines of iPSCs have been generated in the last 7 years that changed the paradigm for studying diseases and the discovery of new drugs to treat them. In this article we focus our attention to vascular diseases in particular Hutchinson-Gilford Progeria Syndrome (HGPS), a devastating premature aging disease caused by a mutation in the lamin A gene. In general, patients die because of myocardial infarction or stroke. Because the patients are fragile the isolation of a particular type of cells is very difficult. Therefore in the last 5 years, researchers have used cells derived from iPSCs to model aspects of the HGPS and to screen libraries of chemicals to retard or treat the disease.

Chemical characterization and spatial distribution of PAHs and heavy hydrocarbons in rural sites of Campania Region, South Italy.

In this paper, the behaviour and distribution patterns of heavy hydrocarbons and several polycyclic aromatic hydrocarbon (PAH) priority pollutants, as listed by the US Environmental Protection Agency, were evaluated in 891 soil samples. The samples were collected in three expected polluted rural sites in Campania (southern Italy) as part of the LIFE11 ECOREMED project, funded by the European Commission, to test innovative agriculture-based soil restoration techniques. These sites have been selected because they have been used for the temporary storage of urban and building waste (Teverola), subject to illicit dumping of unknown material (Trentola-Ducenta), or suspected to be polluted by metals due to agricultural practices (Giugliano). Chemical analysis of soil samples allowed the baseline pollution levels to be determined prior to any intervention. It was found that these areas can be considered contaminated for residential use, in accordance with Italian environmental law (Law Decree 152/2006). Statistical analysis applied to the data proved that average mean concentrations of heavy hydrocarbons could be as high as 140 mg/kg of dry soil with peaks of 700 mg/kg of dry soil, for the Trentola-Ducenta site; the median concentration of analytical results for hydrocarbon (HC) concentration for the Trentola-Ducenta and Giugliano sites was 63 and 73.4 mg/kg dry soil, respectively; for Teverola, the median level was 35 mg/kg dry soil. Some PAHs (usually benzo(a)pyrene) also exceeded the maximum allowed level in all sites. From the principal component analysis applied to PAH concentrations, it emerged that pollutants can be supposed to derive from a single source for the three sites. Diagnostic ratios calculated to determine possible PAH sources suggest petroleum combustion or disposal practice. Our sampling protocol also showed large dishomogeneity in soil pollutant spatial distribution, even at a scale as small as 3.3 m, indicating that variability could emerge at very short spatial scales.

The role of stimulus complexity, spectral overlap, and pitch for gap-detection thresholds in young and old listeners.

Thresholds for detecting a gap between two complex tones were determined for young listeners with normal hearing and old listeners with mild age-related hearing loss. The leading tonal marker was always a 20-ms, 250-Hz complex tone with energy at 250, 500, 750, and 1000 Hz. The lagging marker, also tonal, could differ from the leading marker with respect to fundamental frequency (f0), the presence versus absence of energy at f0, and the degree to which it overlapped spectrally with the leading marker. All stimuli were presented with steeper (1 ms) and less steep (4 ms) envelope rise and fall times. F0 differences, decreases in the degree of spectral overlap between the markers, and shallower envelope shape all contributed to increases in gap-detection thresholds. Age differences for gap detection of complex sounds were generally small and constant when gap-detection thresholds were measured on a log scale. When comparing the results for complex sounds to thresholds obtained for pure-tones in a previous study by Heinrich and Schneider [(2006). J. Acoust. Soc. Am. 119, 2316-2326], thresholds increased in an orderly fashion from markers with identical (within-channel) pure tones to different (between-channel) pure tones to complex sounds. This pattern of results was true for listeners of both ages although younger listeners had smaller thresholds overall.

Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide. Common treatment modalities for NSCLC include surgery, radiotherapy, chemotherapy, and, in recent years, the clinical management paradigm has evolved with the advent of targeted therapies. Despite such advances, the impact of systemic therapies for advanced disease remains modest, and as such, the prognosis for patients with NSCLC remains poor. Standard modalities are not without their respective toxicities and there is a clear need to improve both efficacy and safety for current management approaches. Tumor-treating fields (TTFields) are low-intensity, intermediate-frequency alternating electric fields that disrupt proper spindle microtubule arrangement, thereby leading to mitotic arrest and ultimately to cell death. We evaluated the effects of combining TTFields with standard chemotherapeutic agents on several NSCLC cell lines, both in vitro and in vivo. Frequency titration curves demonstrated that the inhibitory effects of TTFields were maximal at 150 kHz for all NSCLC cell lines tested, and that the addition of TTFields to chemotherapy resulted in enhanced treatment efficacy across all cell lines. We investigated the response of Lewis lung carcinoma and KLN205 squamous cell carcinoma in mice treated with TTFields in combination with pemetrexed, cisplatin, or paclitaxel and compared these to the efficacy observed in mice exposed only to the single agents. Combining TTFields with these therapeutic agents enhanced treatment efficacy in comparison with the respective single agents and control groups in all animal models. Together, these findings suggest that combining TTFields therapy with chemotherapy may provide an additive efficacy benefit in the management of NSCLC.