Burden of comorbidities: Osteoporotic vertebral fracture during non-small cell lung cancer - the BONE study.

INTRODUCTION: Immunotherapy and targeted therapy have extended life expectancy in non-small cell lung cancer (NSCLC) patients, shifting it into a chronic condition with comorbidities, including osteoporosis. This study aims to evaluate the prevalence and incidence of osteoporotic vertebral fracture (OPVF) during NSCLC follow-up, identify risk factors of OPVF, and determine the impact on overall survival (OS). METHODS: We performed a longitudinal single-center retrospective cohort study involving patients with histologically proven NSCLC of any stage. Chest-abdomen-pelvis computed tomography (CAP CT) at diagnosis and during follow-up were double-blind reviewed to determine OPVF site, count, type, time to incident OPVF, and trabecular volumetric bone density (TVBD). An institutional expert committee adjudicated discrepancies. Binary logistic regression was used to predict the occurrence of incident OPVF. OS was calculated using the Kaplan-Meier method. RESULTS: We included 289 patients with a median follow-up of 29.7 months. OPVF prevalence was 10.7% at inclusion and 23.2% at the end of follow-up. Cumulative incidence was 12.5%, with an incidence rate of 4 per 100 patient-years. Median time to incident OPVF was 13 months (IQR: 6.7-21.2). Seven of the 36 patients with incident OPVF received denosumab or bisphosphonates. In multivariable analysis, independent risk factors for incident OPVF were BMI < 19 kg/m2 (OR: 5.62, 95%CI 1.84-17.20, p = 0.002), lower TVBD (OR: 0.982 per HU, 95%CI 0.97-0.99, p = 0.001) and corticosteroid use (OR: 4.77, 95%CI: 1.76-12.89, p = 0.001). OPVF was not significantly associated with OS. CONCLUSIONS: Osteoporosis should be screened for in NSCLC patients. Thoracic oncologists must broaden the use of steroid-induced osteoporosis recommendations.

Non-overweight depressed patients who respond to antidepressant treatment have a higher risk of later metabolic syndrome: findings from the METADAP cohort.

BACKGROUND: Major depressive disorder (MDD) is a complex disorder with a significant public health burden. Depression remission is often associated with weight gain, a major risk factor for metabolic syndrome (MetS). The primary objective of our study was to assess prospectively the impact of response to antidepressant treatment on developing MetS in a sample of MDD patients with a current major depressive episode (MDE) and who are newly initiating their treatment. METHODS: In the 6-month prospective METADAP cohort, non-overweight patients, body mass index <25 kg/m2, with MDD and a current MDE were assessed for treatment response after 3 months of treatment, and incidence of MetS after 3 and 6 months of treatment. Outcome variables were MetS, number of MetS criteria, and each MetS criterion (high waist circumference, high blood pressure, high triglyceridemia, low high-density lipoprotein-cholesterolemia, and high fasting plasma glucose). RESULTS: In total, 98/169 patients (58%) responded to treatment after 3 months. A total of 2.7% (1/38) developed MetS out of which 12.7% (10/79) (p value < 0.001) had responded to treatment after 3 months. The fixed-effect regression models showed that those who responded to treatment after 3 months of follow-up had an 8.6 times higher odds of developing MetS (odds ratio = 8.58, 95% confidence interval 3.89-18.93, p value < 0.001). CONCLUSION: Compared to non-responders, non-overweight patients who responded to treatment after 3 months of antidepressant treatment had a significantly higher risk of developing MetS during the 6 months of treatment. Psychiatrists and nurses should closely monitor the metabolic profile of their patients, especially those who respond to treatment.

Effect of chronic unpredictable stress on the progression of experimental apical periodontitis in rats.

AIM: To establish an experimental model combining chronic stress and apical periodontitis by assessing the development of periapical lesions in rats in three different time points. METHODOLOGY: Forty-eight male Wistar rats were randomly assigned into two equal groups: Apical periodontitis (AP) and AP + Stress (AP + S). The animals of the AP group were not exposed to stressful conditions whereas the AP + S group were exposed to a variety of stressors on a daily basis until the end of the experiment. After three weeks of chronic unpredictable stress, apical periodontitis was induced in both groups by exposing the pulpal tissue of the mandibular first molar to the oral environment. Each group was further subdivided into three subgroups according to the euthanasia period: 14, 21 and 28 days after pulp exposure. The animals were weighed, and the blood was collected for corticosterone serum dosage by radioimmunoassay. The mandibles were removed and submitted to histopathological and microtomography analyses to assess the inflammatory response and the progression of periapical lesions. Comparisons between the AP and AP + S groups were performed using Student's t-test and Mann-Whitney U-test for parametric and nonparametric data, respectively. The one-way anova test followed by Tukey's test (parametric data) and Kruskal-Wallis followed by Dunn's test (nonparametric data) were used for comparisons between the three time points within the same group (P < 0.05). RESULTS: The AP + S group had a significantly lower average percentage of weight gain at 14 days and 21 days after AP induction (P < 0.05). Significantly higher levels of corticosterone were found in the AP + S group at 21 days (P < 0.05). The AP + S group had a significantly greater intensity and extension of inflammatory infiltrate with larger areas of bone loss compared to the AP groups at 21 days (P < 0.05). The volume of the periapical lesions in the AP + S group was significantly larger than that of the AP group 21 days following pulp exposure (P < 0.05). CONCLUSIONS: The chronic unpredictable stress model applied for 6 weeks exacerbated the inflammatory response and increased bone loss associated with AP, especially 21 days after its induction. This model appears to be suitable for investigating the bidirectional relationship between apical periodontitis and chronic stress.

Clinical influence of calcium hydroxide and N-acetylcysteine on the levels of resolvins E1 and D2 in apical periodontitis.

AIM: To investigate the presence of resolvins E1 (RvE1) and D2 (RvD2) in teeth with primary endodontic infections and apical periodontitis, and to assess the influence of calcium hydroxide medication [Ca(OH)2 ], in association with 2% chlorhexidine gel (2% CHX gel), and N-acetylcysteine (NAC) on the levels of RvE1 and RvD2 in periapical tissues. METHODOLOGY: Thirty-six single-rooted teeth with primary endodontic infections and apical periodontitis were selected and randomly divided into three groups according to the medication: [Ca(OH)2 ] + saline solution (SSL) [Ca(OH)2  + SSL group] (n = 12), Ca(OH)2  + 2% chlorhexidine gel [Ca(OH)2  + 2% CHX gel group] (n = 12) and NAC [NAC group] (n = 12). Samples were collected from the periapical interstitial fluid at two different sampling times: before (S1) and after 14 days of intracanal medications (S2). Resolvins were measured using the enzyme-linked immunosorbent assay. Data were analysed using paired t-test, Wilcoxon test and Kruskal-Wallis test, followed by Dunn's post hoc test; all statistical tests were performed at a significance level of 5%. RESULTS: RvE1 and RvD2 were detected in 100% of the samples (36/36) at S1 and S2. Ca(OH)2 medication did not increase the levels of RvE1 or RvD2 (both P > 0.05); however, NAC significantly increased the levels of RvE1 and RvD2 after 14 days of treatment (P < 0.05). CONCLUSIONS: RvE1 and RvD2 were detected in periapical tissues from teeth with root canal infections. Moreover, calcium hydroxide medication did not increase the levels of resolvins in apical periodontitis. In contrast, the use of NAC intracanal medication significantly increased the levels of RvE1 and RvD2 after 14 days of treatment.

Estimating the prevalence of autism spectrum disorder in Lebanon.

This cross-sectional survey examines the prevalence rate of Autism spectrum disorder (ASD) in 818 children (16-48 months) across all Lebanese regions. Screening was done using the revised form of the Modified-Checklist for Autism in Toddlers. Based on the total score of items failed, children were classified into 3 categories of ASD risk (low, moderate and high). Phone calls follow-up interviews and clinical assessments for diagnosis ascertainment were conducted. Given the caregivers' reluctance to participate, the prevalence rate was estimated between 49 and 513 per 10,000 with a male predominance. Our prevalence estimation, even under restrictive assumptions, is higher than elsewhere in the Arab region. Anti- stigma interventions adapted to the socio-cultural context are needed prior to future research in the field.

Bioremediation of PAH-contaminated shooting range soil using integrated approaches.

Serious contamination of polycyclic aromatic hydrocarbons (PAHs) occurs at outdoor shooting ranges due to the accumulation of clay target fragments containing coal tar or petroleum pitch. These contaminated sites are characterized with high-molecular-weight PAHs that are low in bioavailability and recalcitrant to bioremediation. We evaluated the effectiveness of different remediation strategies, used individually or in combinations, to decontaminate PAHs in a shooting range soil. The treatments included vegetation with bermudagrass [Cynodon dactylon (L.) Pers] or switchgrass [Panicum virgatum]), bioaugmentation of Mycobacterium vanbaalenii PYR-1, and addition of surfactants (Brij-35, rhamnolipid biosurfactant, or Brij-35/sodium dodecyl sulfate mixture). The initial total PAH concentration in the shooting range soil was 373 mg/kg and consisted of primarily high-molecular-weight PAHs (84%). Planting of bermudagrass and switchgrass resulted in 36% and 27% ∑16PAH reduction compared to the non-vegetated control, respectively. Bermudagrass enhanced soil dehydrogenase activity and both vegetation treatments also increased polyphenol oxidase activity. Bioaugmentation of M. vanbaalenii PYR-1 had a significant effect only on the dissipation of high-molecular-weight PAHs, leading to a 15% decrease (∑10PAH) compared to the control. In the non-vegetated soil, Brij-35/sodium dodecyl sulfate mixture increased PAH degradation compared to the no surfactant control. The increased PAH biodegradation in the vegetated and bioaugmented treatments improved lettuce [Lactuca sativa] seed germination, suggesting reduced toxicity in the treated soils. Phytoremediation using bermudagrass or switchgrass with bioaugmentation of M. vanbaalenii PYR-1 was an effective in situ remediation option for shooting range soils with heavy PAH contamination.

Direct etching at the nanoscale through nanoparticle-directed capillary condensation.

We report a method to locally deliver a chemical etchant at the nanoscale in the vapor phase by capillary condensation forming a meniscus at the nanoparticle/substrate interface. The process is simple, scalable and does not require functionalization of the nanoparticles. Furthermore, it does not rely on any specific chemical properties of the materials other than the solution being aqueous and the wettability properties of the surfaces involved, which should enable its application to other material and chemical combinations. In particular, in this work we demonstrate the proposed process by periodically pattering a SiO2 layer using a self-assembled monolayer of polystyrene particles exposed to HF vapors. The patterned SiO2 layer is then used as a mask to etch a pattern of inverted nanopyramids on Si. The silicon nanopatterning has been demonstrated for particles sizes ranging from 800 nm down to 100 nm, providing pyramids with a size down to 50 nm for 100 nm nanoparticles.

Reduction in myocardial strain is evident in adolescents and young adults with obesity and type 2 diabetes.

AIMS/HYPOTHESIS: Heart failure is a complication of type 2 diabetes (T2DM). Echocardiography can identify subclinical systolic dysfunction in adults with T2DM. We hypothesized that reduced systolic strain was present in youth with T2DM. METHODS: Global longitudinal strain (GLS) was measured in 151 subjects with T2DM matched to lean (L = 146), and obese (O = 162) subjects (23.0 ± 4.0 years, 35% male, 63% African American). Anthropometrics, BP, HR, labs, and echocardiograms were obtained. ANOVA was performed to compare differences among groups, and ANCOVA to determine if T2DM remained an independent predictor after corrections. RESULTS: BP, lipid levels, and metabolic control worsened and GLS was reduced from L to O to T2DM. BMI was lower in L than O or T2DM. Global longitudinal strain rate (GLSR) was lower and LVM/ht2.7 was higher in O and T2DM as compared to L (all P ≤ .05). Presence of T2DM was an independent determinant of GLS and GLSR adjusted for most CV risk factors, but lost significance when BMI was added to the model. GLS = -21.6-age*0.088 - male*1.8 + 0.12*BMI + 0.045*DBP + 0.058*HR - 0.023*HDL (R2 = 0.38, P ≤ .0001); GLSR = -1.20-male*0.093 + WHR*0.48 + DBP*0.0029 (R2 = 0.23, P ≤ .0001). CONCLUSION: Both adiposity and T2DM have a deleterious effect on systolic cardiac function. Treatment of obesity in youth is necessary for prevention of future heart failure.

Atopic dermatitis and the metabolic syndrome: a cross-sectional study of 116 816 patients.

BACKGROUND: Data regarding the association between atopic dermatitis (AD) and the metabolic syndrome are controversial. OBJECTIVE: To evaluate the prevalence of the metabolic syndrome and its components in a large group of patients with AD compared to a matched reference group. METHODS: A cross-sectional study of AD patients diagnosed by a dermatologist between 1998 and 2016, and a matched comparison group was performed. We analysed the association between AD and metabolic syndrome, its components and possible complications for the entire study population, adults (age > 18) and adults with moderate-to-severe AD. RESULTS: The study included 116 816 patients with AD and 116 812 comparison enrollees. AD in the entire group of patients and in the adult patients was associated with a higher prevalence of dyslipidaemia and a lower prevalence of diabetes and metabolic syndrome. Moderate and severe AD were associated, respectively, with higher prevalence rates of the metabolic syndrome (17.0% vs. 9.4%), its components (obesity: 22.2% vs. 18.6%; diabetes: 15.9% vs. 9.2%; hypertension 27.9% vs. 15.3%; dyslipidaemia 47.1% vs. 28.5%, all P values < 0.001) and cardiovascular morbidity (all P values < 0.001). Multivariate analysis demonstrated a significant overrepresentation of the metabolic syndrome in moderate-to-severe AD (P = 0.04). CONCLUSIONS: Severely affected patients with AD may have one or more undiagnosed components of metabolic syndrome.

Effect of maturation conditions on light and temperature requirements during seed germination of Citrullus colocynthis from the Arabian Desert.

Seed germination of Citrullus colocynthis, as in many other species of Cucurbitaceae, is inhibited by light, particularly at low temperatures. Germination response to light and temperature has been attributed to day length and temperature during seed maturation. This study assessed the effects of these factors on the germination response of C. colocynthis to temperature and light quality. Ripe fruits were collected from natural habitats during December and February and germinated at three temperatures (15/25, 20/30 and 25/35 °C) in five light treatments (dark, white light and Red:Far Red (R:FR) ratios of 0.30, 0.87 and 1.19). Additionally, unripe fruits were also collected from natural habitats and completed their maturation in growth chambers under different day lengths (6, 16 and 24 h of darkness) at 10/20 °C, and in darkness at both 10/20 °C and 25/35 °C. Mature seeds of the different treatments were germinated in the same five light treatments at 15/25 °C. Germination was significantly higher in the dark than that in any light treatment. Seeds matured at higher temperatures (i.e. seeds from the December collection and those matured at 25/35 °C) had significantly higher germination than those matured at lower temperatures (i.e. seeds from the February collection and those matured at 10/20 °C). Dark germination was significantly higher for the December collection than for the February collection. Seeds of the two collections germinated in the dark only at 15/25 °C. However, seeds matured in a growth chamber at 10/20 °C in darkness germinated at 15/25 °C in all light treatments, except for the R:FR ratio 0.30. Seeds of the different treatments failed to germinate in FR-rich light. This study demonstrates that both temperature and day length during seed maturation play significant roles in the germination response of C. colocynthis. Additionally, the dark requirement for germination is likely beneficial for species with the larger seeds, such as C. colocynthis, which produce bigger seedlings that are able to emerge from deep soils and are competitively superior under dense vegetation and resource-limited conditions.

Cri du Chat syndrome: Characteristics of 73 Brazilian patients.

BACKGROUND: Cri du Chat syndrome (CdCS) is a genetic syndrome caused by deletions in the short arm of chromosome 5. Although the main clinical features of CdCS are well known, the neurocognitive and behavioural characteristics of the phenotype are rarely described in detail in the literature. In this study, we analysed the main phenotypic features of CdCS from a parental perspective. METHOD: A questionnaire was sent to 700 Brazilian families that were registered in the Brazilian Association of CdCS. The questions involved specific domains of CdCS, such as pregnancy and birth conditions, recurrence of the disease in the family, current major health problems, and aspects of cognitive development. RESULTS: In total, 73 questionnaires were completed: 44 females and 29 males, ranging from 9.5 months old to 40 years old (mean = 13.8 years; median = 12 years). Most of the parents noticed the typical cat-like cry at birth (94.4%). The age at diagnosis of CdCS ranged from the time of birth to 180 months (mean = 14 months; median = 6 months), while one case was diagnosed during pregnancy. In all of the cases, the diagnosis of CdCS was made by G-banding karyotype analysis. In 66.2% of the cases, the parents underwent cytogenetic investigation. A total of 52.1% of the parents answered that they did not remember what the recurrence risk of CdCS was in their family. The main health problems that were reported were as follows: swallowing problems (80.3%), feeding problems (80.3%), congenital heart disease (31.5%), spine abnormalities (28.8%), and neurological symptoms (20.5%), including seizures (11%). The behavioural problems that were reported were as follows: aggressive behaviour, stereotypies, anxiety, phobias, and genital manipulation/masturbation. Neurodevelopmental delay was reported in all of the cases. Independent walking was achieved in 72.2% of the patients. Approximately 50% of the patients never presented expressive language, and most of the patients are dependent on others for their daily activities. CONCLUSIONS: The questionnaire was a pioneer initiative in the CdCS support group, and the answers used in this study can improve the health care assistance to these patients because they focus attention on the demands from a parental perspective. In addition, nearly half of the families stated that they did not remember information regarding recurrence risk, which reinforces the importance of genetic counselling follow-up and the need for the expansion of genetic services in Brazil.

Do Drains Contribute to Pancreatic Fistulae? Analysis of over 5000 Pancreatectomy Patients.

INTRODUCTION: Conflicting evidence exists from randomized controlled trials supporting both increased complications/fistulae and improved outcomes with drain placement after pancreatectomy. The objective was to determine drain practice patterns in the USA, and to identify if drain placement was associated with fistula formation. METHODS: Demographic, perioperative, and patient outcome data were captured from the most recent annual NSQIP pancreatic demonstration project database, including components of the fistula risk score. Significant variables in univariate analysis were entered into adjusted logistic regression models. RESULTS: Of 5013 pancreatectomy patients, 4343 (87%) underwent drain placement and 18% of patients experienced a pancreatic fistula. When controlled for other factors, drain placement was associated with ducts < 3 mm, soft glands, and blood transfusion within 72 h of surgery. Age, obesity, neoadjuvant radiation, preoperative INR level, and malignant histology lost significance in the adjusted model. Drained patients experienced higher readmission rates (17 vs. 14%; p < 0.05) and increased (20 vs. 8%; p < 0.01) pancreatic fistulae. Fistula was associated with obesity, no neoadjuvant chemotherapy, drain placement, < 3 mm duct diameter, soft gland, and longer operative times. Drain placement remained independently associated with fistula after both distal pancreatectomy (OR = 2.84 (1.70, 4.75); p < 0.01) and pancreatoduodenectomy (OR = 2.29 (1.28, 4.11); p < 0.01). CONCLUSIONS: Despite randomized controlled clinical trial data supporting no drain placement, drains are currently placed in the vast majority (87%) of pancreatectomy patients from > 100 institutions in the USA, particularly those with soft glands, small ducts, and perioperative blood transfusions. When these factors are controlled for, drain placement remains independently associated with fistulae after both distal and proximal pancreatectomy.

Analysis of an electrical impedance spectroscopy system in short-term digital dermoscopy imaging of melanocytic lesions.

BACKGROUND: Electrical impedance spectroscopy (EIS) is a noninvasive diagnostic technique that measures tissue impedance. OBJECTIVES: To evaluate the effect of adding an EIS measurement at baseline to suspicious melanocytic lesions undergoing routine short-term sequential digital dermoscopy imaging (SDDI). METHODS: Patients presented with suspicious melanocytic lesions that were eligible for short-term SDDI (with no clear feature of melanoma on dermoscopy). EIS measurement was performed at the first visit following dermoscopic photography. Normally, an EIS score of ≥ 4 is considered positive; however, this protocol investigated a higher cut-off in combination with SDDI. When the EIS score was ≥ 7 the lesion was excised immediately owing to the high risk of melanoma. Lesions with a score < 7 were monitored with standard SDDI over a 3-month period. RESULTS: From a total of 160 lesions analysed, 128 of 154 benign lesions received an EIS score of 0-6, giving a specificity of the EIS method for the diagnosis of melanoma of 83·1% [95% confidence interval (CI) 76·3-88·7]. Five of the six melanomas found in this study had an EIS score ≥ 7, with a sensitivity for melanoma diagnosis of 83·3% (95% CI 35·9-99·6). When EIS 0-6 lesions were subsequently followed up with SDDI, one additional melanoma was detected (EIS = 6) giving a sensitivity for the diagnosis of melanoma overall of 100% (95% CI 54·1-100; six of six malignant melanomas excised) and a specificity of 69·5% (95% CI 61·5-76·6; 107 of 154 benign lesions not excised). CONCLUSIONS: If utilizing a protocol where an EIS score ≤ 3 requires no SDDI and ≥ 7 requires immediate excision, it reduced the need for SDDI by 46·9% (n = 75/160; 95% CI 39·0-54·9).

Epigenetic suppression of neprilysin regulates breast cancer invasion.

In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT-PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer, and epigenetic suppression of neprilysin in invasive breast cancer cells enables invasion. Together, this implicates neprilysin as an important regulator of breast cancer invasion and clarifies its utility as a potential biomarker for invasive breast cancer.

Validation of the Arabic Rowland Universal Dementia Assessment Scale (A-RUDAS) in elderly with mild and moderate dementia.

OBJECTIVES: Validated screening tests for dementia in Arabic are lacking. Given the low levels of education among elderly in the Middle East and North Africa region, the commonly used screening instrument, the Mini Mental State Examination, is not best suited. Alternatively, the Rowland Universal Dementia Assessment Scale (RUDAS) was especially designed to minimize the effects of cultural learning and education. The aim of this study was to validate the RUDAS in the Arabic language (A-RUDAS), evaluate its ability to screen for mild and moderate dementia, and assess the effect of education, sex, age, depression, and recruitment site on its performance. METHODS: A-RUDAS was administered to 232 elderly aged ≥65 years recruited from the communities, community-based primary care clinics, and hospital-based specialist clinics. Of these, 136 had normal cognition, and 96 had dementia. Clinicians diagnosed dementia according to the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) criteria. Interviewers, blind to the cognitive status of participants, administered A-RUDAS. The psychometric properties of A-RUDAS were examined for three cutoffs. RESULTS: At the cutoff of ≤22, A-RUDAS exhibited good sensitivity (83%) and specificity (85%) with an area under the receiver operating characteristic curve of 83.95%. Adjusting for age, sex, education, depression, and recruitment site, A-RUDAS score demonstrated a high level of accuracy in screening for mild and moderate dementia against DSM-IV diagnosis. CONCLUSION: The A-RUDAS is proposed for dementia screening in clinical practice and in research in Arabic-speaking populations with an optimal cutoff of ≤22.