The effects of the environment on the mood and behaviour is in the focus of current brain research. All of us certainly have personal observations within this topic, like how much children love places with numerous colourful toys, or that people usually feel better in a bright and picturesque milieu compared to dark and dull places.
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Radiation Research, Volume 188, Issue 3, Page 369-371, September 2017.
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Motor planning, imagery or execution is associated with event-related desynchronization (ERD) of mu rhythm oscillations (8-13 Hz) recordable over sensorimotor areas using electroencephalography (EEG). It was s...
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Minimally invasive lumbar spinal stenosis procedures have uncertain long-term value.
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In quantitative genetics, the average effect at a single locus can be estimated by an additive (A) model, or additive plus dominance (AD) model. In the presence of dominance, the AD-model is expected to be more accurate, because the A-model falsely assumes that residuals are independent and identically distributed. Our objective was to investigate accuracy of an estimated average effect (α ) in the presence of dominance, using either a single locus A-model or AD-model. Estimation was based on a finite sample from a large population in Hardy-Weinberg equilibrium (HWE), and root mean squared error of α was calculated for several broad sense heritabilities, sample sizes, and sizes of the dominance effect. Results show that with the A-model, both sampling deviations of genotype frequencies from HWE frequencies and sampling deviations of allele frequencies contributed to the error. With the AD-model, only sampling deviations of allele frequencies contributed to the error, provided that all three genotype classes were sampled. In the presence of dominance, the root mean squared error of α with the AD-model was always smaller than with the A-model, even when the heritability was smaller than one. Remarkably, in the absence of dominance, there was no disadvantage of fitting dominance. In conclusion, the AD-model yields more accurate estimates of average effects from a finite sample, because it is more robust against sampling deviations from HWE frequencies than the A-model. Genetic models that include dominance, therefore, yield higher accuracies of estimated average effects than purely additive models when dominance is present.
There is vast evidence that supports the importance of obesity in the pathogenesis and progression of cardiovascular disease. Rapid weight loss induced by laparoscopic Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (LAGB) has proven beneficial. The aim of this study is to evaluate laparoscopic sleeve gastrectomy (LSG) as an alternative treatment modality and its impact on the Framingham-BMI 10-year risk score.
We retrospectively reviewed all patients that underwent bariatric surgery at our institution between 2010 and 2014. Patients who met the criteria for calculating the Framingham BMI 10-year risk score were included. Data collected included baseline demographics, perioperative parameters such as tobacco use, diagnosis of diabetes, treatment for hypertension, BMI and postoperative outcomes at 3 and 12 months.
From our 1129 bariatric patients, 358 (31.7%) met criteria for the Framingham BMI 10-year risk score calculation. LSG was the most prevalent surgery 61.45% (N = 220) followed by LRYGB 22.06% (N = 79). Females composed 69% (N = 248) of our population. The average age for females was 52.3 ± 10.8 years and for males 54.07 ± 11.2 years. The initial Framingham 10-year score risk was significantly higher in males compared with females (36.16% ± 22.3 vs. 16.97% ± 15.6 (p < 0.001)). After 12-month follow-up, the absolute risk reduction in males was 11.58% (p < 0.001) and 6.17% in females (p < 0.001). The preoperative heart age was high in females and males (69.23 ± 15.72 years and 73.55 ± 13.55 years, respectively (p = 0.012)), and after 12 months it was reduced 7.19 years in females (p < 0.001) and 7.04 years in males (p < 0.001). The percentage of estimated BMI loss at 1 year was 64.43% in females and 60.69% in males.
Sleeve gastrectomy has demonstrated to be an effective method of treatment for obesity. Our results suggest that rapid weight loss after LSG has a positive impact in the reduction of the 10-year cardiovascular disease risk. Further prospective studies may be needed to better assess these findings.
A multicenter, retrospective, cohort study was conducted in the Netherlands. The aim was to evaluate whether surgical volume of laparoscopic hysterectomies (LHs) performed by proven skilled gynecologists had an impact on the conversion rate from laparoscopy to laparotomy.
In 14 hospitals, all LHs performed by 19 proven skilled gynecologists between 2007 and 2010 were included in the analysis. Surgical volume, conversion rate and type of conversion (reactive or strategic) were retrospectively assessed. To estimate the impact of surgical volume on the conversion rate, logistic regressions were performed. These regressions were adjusted for patient's age, Body Mass Index (BMI), ASA classification, previous abdominal surgery and the indication (malignant versus benign) for the LH.
During the study period, 19 proven skilled gynecologists performed a total of 1051 LHs. Forty percent of the gynecologists performed over 20 LHs per year (median 17.3, range 5.4–49.5). Conversion to laparotomy occurred in 5.0% of all LHs (53 of 1051); 38 (3.6%) were strategic and 15 (1.4%) were reactive conversions. Performing over 20 LHs per year was significantly associated with a lower overall conversion rate (ORadjusted 0.43, 95% CI 0.24–0.77), a lower strategic conversion rate (ORadjusted 0.32, 95% CI 0.16–0.65), but not with a lower reactive conversion rate (ORadjusted 0.96, 95% CI 0.33–2.79).
A higher annual surgical volume of LHs by proven skilled gynecologists is inversely related to the conversion rate to laparotomy, and results in a lower strategic conversion rate.
Bilateral axillo-breast approach robotic thyroidectomy (BABA RT) is an excellent surgical method, being oncologically safe and with anatomic views similar to those of open surgery. BABA RT, however, requires training and a learning curve for proficiency. We evaluated the educational effectiveness of a surgical training model for BABA RT, comparing objective BABA scores with scores on the da Vinci Skills Simulator (dVSS).
Medical students, surgical residents, and surgical fellows performed structured tasks with the BABA training model and dVSS under the same conditions. All tasks were videotaped. BABA scores were compared with dVSS scores and with objective evaluation scores (GEARS and OSATS).
Eight medical students, ten surgical residents, and eight surgical fellows participated in this study. The educational effect of BABA training improved from one to two (p < 0.001), two to three (p = 0.003), and one to three (p < 0.001) procedures. Statistically significant differences were found when students were compared with residents (p = 0.025) and fellows (p < 0.001) in the BABA training model, and between students and fellows (p = 0.004) in dVSS. BABA scores showed similar distribution patterns in the three groups to GEARS and OSATS scores (p < 0.001 each).
The BABA training model is an excellent educational tool for surgical residents and surgical fellows to learn and practice BABA RT. Assessment by BABA score yielded objective results comparable to those of traditional scoring methodologies.
According to many Societies' guidelines, patients presenting with clinical T4 colorectal cancer should conventionally be approached by a laparotomy. Results of emerging series are questioning this attitude.
We retrospectively analysed the oncologic outcomes of 147 patients operated on between June 2008 and September 2015 for histologically proven pT4 colon cancers. All patients were treated with curative intent, either by a laparoscopic or open "en bloc" resection.
Median operative time, blood loss and hospital length of stay were significantly reduced in the laparoscopic group. Postoperative surgical complication rate and 30-day mortality did not significantly differ between the two groups ( p = 0.09 and p = 0.99, respectively). R1 resection rate and lymph nodes harvest, as well, did not remarkably differ when comparing the two groups. In the laparoscopic group, conversion rate was 19%. Long-term outcomes were not affected in patients who had undergone conversion. Five-year overall survival and disease-free survival did not significantly differ between the two groups (44.6% and 40.3% vs. 39.4% and 38.9%). Locally advanced stages (IIIB–IIIC) and R1 resections were detected as independent prognostic factors for overall survival.
Laparoscopic approach might be safe and acceptable for locally advanced colon cancer and does not jeopardize the oncologic results. Conversion to open surgery should be a part of a strategy as it does not seem to adversely affect perioperative and long-term outcomes. We consider laparoscopy, in expert hands, the last diagnostic tool and the first therapeutic approach for well-selected locally advanced colon cancers. Larger prospective studies are needed to widely assess this issue.
Although perforated marginal ulcers (pMU) following Roux-en-Y Gastric Bypass (RYGB) represent a surgical emergency, the epidemiology and outcome of this condition is not well understood. The purpose of this study was to evaluate incidence of pMU following RYGB and assess the natural history of this complication.
The SPARCS administrative database was used to identify patients undergoing RYGB between 2005 and 2010. With the use of a unique identifier, we followed patients up to 2014 for subsequent admission and re-intervention (repair or revision) for perforated MU. Groups were compared using Chi square tests with exact p values based on Monte Carlo simulation, t test with unequal variances, and the Wilcoxon rank-sum test when appropriate.
We identified 35,080 RYGB patients; 292 patients (0.83%) developed pMU 937 (443–1546) days following RYGB [Median (Q1–Q3)]. Among these 292 patients, tobacco use was present in one-third of patients. Repair of the perforation was performed in 115 patients, while anastomotic revision was reported in 64. Patients who underwent revision were more likely to have respiratory complications. Hospital length of stay was significantly longer for patients managed with RYGB revision (Median, Q1–Q3:7, 5–14, vs 6, 4–7, days, p = 0.001). Recurrence of marginal ulcer was common after either intervention (26.09% for repair and 29.69% for revision, p = 0.726).
Following RYGB, the incidence of pMU is small. Anastomotic revision for pMU is associated with prolonged length of stay compared to repair alone. Importantly, recurrence after intervention of pMU is common, suggesting possible value of a routine surveillance program for patients following pMU.
Bariatric surgery has been shown to lead to significant improvement in glucose homeostasis, resulting in greater rates of type 2 diabetes mellitus (T2DM) remission. While there is substantial evidence of the benefits of bariatric/metabolic surgery in obese diabetic patients on oral therapy (O-T2D), more evidence is necessary in the case of insulin-treated type 2 diabetes (I-T2D) patients and the selection of surgical procedure.
Analysis of the Ontario Bariatric Registry data was performed, comparing outcomes of Roux-en-Y-gastric bypass (RYGB) and sleeve gastrectomy (SG) on insulin-treated versus non-insulin-treated T2DM patients. We compared weight loss, medication use and remission rates during a 3-year follow up.
A total of 3668 diabetic Bariatric Registry patients underwent surgery from Jan 2010 to Feb 2017, across 7 Bariatric Centers of Excellence in Ontario. Of these 2872 were O-T2D and 1187 were I-T2D. Weight loss was similar between the two groups at 3 years; with mean %WL of 30.1% for the insulin group vs. 28.3% non-insulin (p = 0.0673). At 3 years, 11.3% of the non-insulin and 59.6% of the insulin-dependent group were using anti-diabetic medication (p < 0.0001). Among insulin-dependent patients, RYGB showed greater reduction in insulin use with 26.5 and 40% compared to SG at 3 years. O-T2D patients experienced more complete diabetes remission, with 66.5 vs. 18.5% (p < 0.0001) at 3 years. Complete remission for I-T2D patients was higher in the RYGB group than SG (p < 0.0001) at years 1 and 2 (8.5 vs. 5.4% and 24.4 vs. 21.1%). The same trend was found regardless of insulin use; complete remission higher for RYGB at 1 and 2 years [50.7 vs. 39.8% (p < 0.0001), and 54.6 vs. 49.1% (p < 0.0001)].
While both RYGB and SG procedures provide effective treatment for I-T2D patients in terms of weight loss and diabetes, incidence of complete remission for insulin-dependent patients is higher with RYGB in earlier years.
Transrectal natural orifice specimen extraction (NOSE) avoids abdominal organ retrieval during laparoscopic procedures and may reduce surgical trauma. However, this has not been proven clinically and transrectal peritoneal contamination is feared to cause infectious complications. This experimental study was designed to evaluate inflammatory response and peritoneal contamination after transrectal NOSE versus mini-laparotomy.
24 German Landrace pigs underwent transrectal NOSE (N = 12) or mini-laparotomy (N = 12) for standardized extraction of water-instilled balloon. Blood samples were taken for analysis of leucocytes, CRP, IL-6, IL-10, and TNFα at 6, 12, 24, 48, 72 h as well as 7 and 14 days postoperatively. After 14 days laparoscopy was performed to inspect the abdomen and for microbiological swab sampling.
Leucocytes were higher in the NOSE group at 72 h (19.3 ± 3.9/nl vs. 15.8 ± 4.2/nl, p = 0.046). IL-6 was lower in the NOSE group at day 7 (165 ± 100/nl vs. 306 ± 70/nl, p = 0.030). No difference was found comparing inflammatory parameters at all other time points. No difference was found regarding peritoneal contamination, which was 58.3% (7/12) in the NOSE group and 41.7% (5/12) in the MiniLap group (p = 0.414).
The results suggest a pronounced acute inflammatory response after transrectal NOSE compared to mini-laparotomy, while late cytokine response seems to be less after transrectal NOSE, which may reflect less intense wound healing process. Using standardized rectal decontamination and endolumenal colon occlusion transrectal NOSE seems to be safe and comparable to mini-laparotomy with regard to peritoneal contamination. Clinical evidence is needed now to weight transrectal NOSE against mini-laparotomy during laparoscopic surgery.
Submucosal tunneling endoscopic resection (STER) has been proved to be effective and safe for esophageal submucosal tumors (SMTs) originating from the muscularis propria (MP) layer. This study was aimed to further evaluate the effectiveness, safety, and influencing factors especially the types of mucosal incision of STER in a larger population.
A total of 89 patients undergoing STER with esophageal SMTs were retrospectively enrolled in this study from May 2012 to November 2016. Clinicopathological, endoscopic, and adverse events (AEs) data were collected and analyzed. Different incision methods were compared to evaluate the optimum incision method.
There were 27 females and 62 males with mean age of 46.5 ± 10.3 years. The medium size of the tumors was 16.0 mm (ranging 10.0–60.0 mm). Inverted T incisions were made in 29 (32.6%) patients, transverse incisions in 12 (13.5%) while longitudinal incisions in 48 (53.9%). En bloc resection was achieved in 70 (78.7%) patients. The residual rate was 1.1% (1/89), and no recurrence was noted even after piecemeal resection. The rate of AEs was 21.3% (19/89), and all of the AEs were cured without intervention or treated conservatively without the need for surgery. The en bloc resection rate was comparable among the three incision groups (P = 0.868); however, the incidence of AEs in the inverted T incision was lower than that in the longitudinal incision (P = 0.003). Fewer clips were used in the inverted T incision group than in the transverse incision group (P = 0.003).
Although STER failed to achieve en bloc resection in 21.3% patients, it was still an effective therapy owing to low residual rate and no recurrence rate after piecemeal resection. STER was safe with no severe AEs; however, minor AEs were common. Inverted T incision seems to be the optimum entry point.
Robotic-assisted procedures were frequently found to have similar outcomes and indications to their laparoscopic counterparts, yet significant variation existed in the acceptance of robotic-assisted technology between surgical specialties and procedures. We performed a retrospective cohort study investigating factors associated with the adoption of robotic assistance across the United States from 2008 to 2013.
Using the Nationwide Inpatient Sample database, patient- and hospital-level variables were examined for differential distribution between robotic-assisted and conventional laparoscopic procedures. Multilevel logistic regression models were constructed to identify independent factors associated with robotic adoption. Furthermore, cases were stratified by procedure and specialty before being ranked according to proportion of robotic-assistance adoption. Correlation was examined between robotic-assistance adoption and relative outcome in comparison with conventional laparoscopic procedures.
The national robotic case volume doubled over the five-year period while a gradual decline in laparoscopic case volume was observed, resulting in an increase in the proportion of procedures performed with robotic assistance from 6.8 to 17%. Patients receiving robotic procedures were more likely to be younger, males, white, privately insured, more affluent, and with less comorbidities. These differences have been decreasing over the study period. The three specialties with the highest proportion of robotic-assisted laparoscopic procedures were urology (34.1%), gynecology (11.0%), and endocrine surgery (9.4%). However, no significant association existed between the frequency of robotic-assistance usage and relative outcome statistics such as mortality, charge, or length of stay.
The variation in robotic-assistance adoption between specialties and procedures could not be attributable to clinical outcomes alone. Cultural readiness toward adopting new technology within specialty and target anatomic areas appear to be major determining factors influencing its adoption.
Safety and efficacy of laparoscopy surgery in locally Advanced Gastric Cancers (AGC) have not been proven by randomized control trials. Therefore, standard of care for AGC is still open surgery. Here, we are presenting a 64-year-old female with proximal gastric adenocarcinoma (close to cardio-oesophageal junction) adherent to tail of pancreas, who underwent D2 total gastrectomy en-mass distal pancreatectomy and splenectomy.
Five ports are entered into the peritoneal cavity (Three 10–12 mm and two 5 mm ports). Another 5 mm stab incision is made in the epigastrium for Nathanson Liver retractor. Standard D2 Gastrectomy was performed with en-mass removal of the spleen and body and tail of the pancreas. Roux-en-Y oesophago-jejunostomy (Hand sewn) and Jejuno-Jejunostomy reconstruction were performed laparoscopically. Hereby, we present a video of the above procedure.
Total Operating time was 235 min. Post-operatively the patient was able to mobilize independently. Total Parenteral Nutrition (TPN) was started and continued until post-operative day (POD) 7 once gastrografin test and blue dye test both showed no anastomotic leak. Patient started on oral feeding and was discharged home well on POD 9. Histology showed poorly differentiated adenocarcinoma with pT3N3b (17 nodes out of 62 positive).
Although laparoscopic D2 gastrectomy and en-mass distal pancreatectomy and splenectomy are feasible and safe in advanced gastric carcinoma, its oncological value has yet to be determined.
The volume-regulated anion channel (VRAC) is formed by heteromers of LRRC8 proteins containing the essential LRRC8A subunit and at least one among the LRRC8B-E subunits. Reactive oxygen species (ROS) play physiological and pathophysiological roles and VRAC channels are highly ROS sensitive. However, it is unclear if ROS act directly on the channels or on molecules involved in the activation pathway. We used fluorescently tagged LRRC8 proteins that yield large constitutive currents to test direct effects of oxidation. We found that 8A/8E heteromers are dramatically potentiated (more than 10-fold) by oxidation of intracellular cysteine residues by chloramine-T or tert-butyl hydroperoxide. Oxidation was, however, not necessary for hypotonicity induced activation. In contrast, 8A/8C and 8A/8D heteromers were strongly inhibited by oxidation. Endogenous VRAC currents in Jurkat T lymphocytes were similarly inhibited by oxidation, in agreement with the finding that LRRC8C and LRRC8D subunits were more abundantly expressed than LRRC8E in Jurkat cells. Our results show that LRRC8 channels are directly modulated by oxidation in a subunit dependent manner.
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The paramedics pushed the child with cardiac problems on a gurney for two blocks to the hospital
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The inverse correlation between circulating adiponectin concentration and hypertension or cardiac hypertrophy is still controversial. In addition to circulating adiponectin, adiponectin is also bound to tissues such as the heart and skeletal muscle. In this study, we investigated the relationship of serum adiponectin and heart-bound adiponectin to hypertension and cardiac hypertrophy. Four types of hypertensive rats presenting different blood pressure levels were used at different ages: normotensive Wistar-Kyoto rats (WKY); two sub-strains (strains C and B2, having low and high blood pressure, respectively) of spontaneously hypertensive rats (SHR); and stroke-prone SHR (SHRSP). Blood pressure, heart/body weight ratio, serum adiponectin, and heart-bound adiponectin were determined. Histopathological analysis of the heart was carried out to evaluate the relationship with heart-bound adiponectin. Serum adiponectin concentration did not inversely correlate with blood pressure or heart/body weight ratio. In contrast, heart-bound adiponectin levels were significantly lower in SHRSP than in other strains at respective ages. This resulted from a decrease in T-cadherin expression, which induced adiponectin binding to tissues. No significant difference in heart-bound adiponectin among WKY and SHR (C and B2) was detected, indicating that heart-bound adiponectin is not related to hypertension. In addition, differences in heart-bound adiponectin did not affect AMP-activated protein kinase in the traditional adiponectin activation cascade. Histopathological analysis revealed that heart-bound adiponectin inversely correlated with cardiomyocyte hypertrophy and left ventricular wall thickness, and partially with cardiac fibrosis. These results suggest that the decreased level of heart-bound adiponectin in SHRSP is more related to their cardiac hypertrophy than circulating adiponectin.
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Manipulating the work of breathing (WOB) during near-maximal exercise influences leg blood flow, but the effects on respiratory muscle blood flow are equivocal. We sought to simultaneously assess leg and respiratory muscle blood flow during intense exercise while manipulating WOB. We hypothesized that: (i) increasing the WOB would increase respiratory muscle blood flow and decrease leg blood flow, and (ii) decreasing the WOB would decrease respiratory muscle blood flow and increase leg blood flow. Eight healthy subjects (n = 5 m, n = 3 W) performed a maximal cycle test (Day 1) and a series of constant-load exercise trials at 90% of peak work rate (Day 2). On Day 2, WOB was assessed with oesophageal balloon catheters and was: increased (via resistors), decreased (via proportional assist ventilation), or unchanged (control) during the trials. Blood flow was assessed using near-infrared spectroscopy optodes placed over quadriceps and the sternocleidomastoid muscles, coupled with a venous indocyanine green dye injection. Changes in WOB were significantly and positively related to changes in respiratory muscle blood flow (r = 0.73), whereby increasing the WOB increased blood flow. Conversely, changes in WOB were inversely related to changes in locomotor blood flow (r = 0.57), whereby decreasing the WOB increased locomotor blood flow. Oxygen uptake was not different during the control and resistor trials (3.8 ± 0.9 vs. 3.7 ± 0.8 l min−1, P > 0.05), but was lower on the PAV trial (3.4 ± 0.7 l min−1, P < 0.05) compared to control. Our findings support the concept that respiratory muscle work significantly influences the distribution of blood flow to both respiratory and locomotor muscles.
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Oxygen uptake (VO2) and exercise tolerance in rats classified by myocardial infarction (MI) size are underexplored. The aim of this study was to evaluate VO2/carbon dioxide production (VCO2) and exercise tolerance in rats that have undergone MI. Fourteen weeks after MI or sham surgery, rats underwent an integrated approach to left ventricular function and VO2/VCO2, exercise tolerance and skeletal muscle weight evaluation. Based on MI size determination, rats were assigned to sham operated controls (Sham, n = 12), small myocardial infarction (SMI, n = 8), and large myocardial infarction (LMI, n = 5) groups. LMI rats showed lower systolic (ejection fraction and fractional shortening) and diastolic (E/A ratio) left ventricular function compared with SMI. VO2max (∼24%, P < 0.05), VO2reserve (∼30%, P < 0.05), time to exhaustion (∼36%, P < 0.05) and maximal velocity (∼30%, P < 0.05) was lower in LMI compared with sham operated controls, with no difference between SMI rats and sham operated controls. VCO2max and respiratory exchange ratio (RER) showed no significant difference between MI rats and sham operated control rats. LMI rats demonstrated lower gastrocnemius weight (∼12%, P < 0.05) and soleus weight (∼19%, P = 0.07) compared with sham operated control rats. Significant correlations between MI size, left ventricular end-diastolic pressure, right ventricle hypertrophy, pulmonary congestion, ejection fraction, and fractional shortening with VO2max and run distance were observed. O2 uptake and exercise intolerance are MI size dependent.
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The effects of meditation on arterial and tissue oxygenation are unknown and difficult to assess because respiration is often altered, directly or indirectly, during meditation practice. Thus, changes in respiration may affect cardiovascular responses independently from meditation. In this study, we aim to isolate the specific effect of meditation on arterial and tissue oxygenation and other cardiorespiratory indexes while systematically controlling for the role of respiration. Furthermore, we aim to clarify to what extent prior expertise in meditation practice is needed to observe reliable changes. Eighty participants, half with and half without prior meditation experience, were tested while pacing breathing at predetermined rates, in the presence or absence of mantra meditation instructions, and in a body scan meditation that did not involve controlled breathing. Continuous recordings were acquired for arterial and brain oxygenation, respiratory excursion, electrocardiogram, skin vasomotion, and blood pressure. In both groups, meditation acutely decreased arterial and cerebral oxygen saturation, reduced chemoreflex sensitivity, and prolonged the RR interval, independently of respiration. Conversely, slow breathing improved heart rate variability, independently of concurrent meditation. In addition to the immediate effects of meditation, the individuals with long-term practice of meditation had overall higher arterial and cerebral oxygen saturation, overall lower blood pressure, and slower baseline respiration. Meditation acutely lowers arterial and tissue oxygenation. A repeated exposure to this condition may lead to long-term adaptation and, through increased ventilatory efficiency and improved gas exchanges, to an increase in baseline oxygenation. Meditation induces favorable changes in cardiovascular and respiratory end points of clinical interest.
Disorders of brain formation can occur from pathogenic variants in various alpha and beta tubulin genes. Heterozygous pathogenic variants in the beta tubulin isotype A gene, TUBB2A, have been recently implicated in brain malformations, seizures, and developmental delay. Limited information is known regarding the phenotypic spectrum associated with pathogenic variants in this gene given the rarity of the condition. We report the sixth individual with a de novo heterozygous TUBB2A pathogenic variant, who presented with a severe neurological phenotype along with unique features of arthrogryposis multiplex congenita, optic nerve hypoplasia, dysmorphic facial features, and vocal cord paralysis, thereby expanding the gene-related phenotype.
Publication date: Available online 24 August 2017
Source:Mutation Research/Reviews in Mutation Research
Author(s): Q. Shi, R.W.L. Godschalk, F.J.Van Schooten
Exposure to benzo[a]pyrene (B[a]P) is known to play a role in lung carcinogenesis and the underlying processes can be modified by the presence of inflammation. The inflammatory process can for instance enhance the concentration of reactive metabolites that bind to DNA and may also diminish DNA repair. Additionally, during the inflammatory process mediators are released that create a microenvironment which is suitable for further stimulation of cancer development. Various transcriptional pathways are activated by inflammation, including pathways that are mediated via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), signal transducer and activator of transcription 3 (STAT-3), and hypoxia-inducible factor-1 (HIF-1). Crosstalk between these pathways and the aryl hydrocarbon receptor (AhR) occurs at multiple levels and thereby boosts B[a]P induced carcinogenesis. This review focuses on inflammatory mediators, including cytokines, chemokines and extracellular enzymes that modulate molecular events in B[a]P induced cancers.
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