Impact of overweight and obesity on US renal cell carcinoma incidence trends (1995-2018)

In the United States, renal cell carcinoma (RCC) incidence and the prevalence of obesity, an established risk factor for RCC, have been increasing for several decades. RCC is more common among older individuals. We sought to quantify the contribution of excess adiposity to the rising incidence of RCC among individuals 60 years or older. National Institutes of Health-American Association of Retired Persons Diet and Health Study data (n = 453 859 participants, enrolled in 1995-1996, age at enrollment 50-71 years) were used to estimate multivariable-adjusted hazard ratios (HRs) for RCC across body mass index categories and HRs associated with smoking. Population attributable fractions (PAFs) were calculated using estimated HRs and annual overweight/obesity prevalence from the National Health Interview Survey (1985-2008). PAF estimates were combined with RCC incidence from Surveillance, Epidemiology and End Results-13 to calculate annual percent changes in RCC incidence attributable (and unrelated) to overweight/obesity. We found that between 1995 and 2018, among individuals aged 60 years and older, PAF for overweight/obesity increased from 18% to 29% for all RCCs. In comparison, the PAF for smoking declined from 12% to 9%. RCC incidence increased 1.8% per year (95% confidence interval [CI] 1.5%-2.1%) overall, while RCC incidence attributable to overweight/obesity increased 3.8% per year (95%CI 3.5%-4.2%) and RCC incidence unrelated to overweight/obesity increased 1.2% per year (95% CI 0.9%-1.4%). In conclusion, overweight/obesity appears to have contributed importantly to the rising incidence of RCC in the United States since the mid-1990s. Public health interventions focused on reducing overweight and obesity could help substantially in curbing this trend.     

Komplikationen bei skleranahtfixierter Kunstlinsenimplantation

Die Sklerafixation einer Kunstlinse ist bei insuffizientem Kapselapparat eine häufig gewählte Versorgung. Als nachteilig gilt das potenzielle Komplikationsprofil. Analyse des postoperativen Komplikationsprofils. In dieser monozentrischen, retrospektiven Analyse einer konsekutiven Fallserie von Patienten mit standardisierter, skleranahtfixierter Kunstlinsenimplantation (2007 bis 2017) wurden die dokumentierten Komplikationen in „dauerhaft visusbedrohend“ (Endophthalmitis, Aderhautblutung, Ablatio retinae) und „klinisch relevant, aber nicht dauerhaft visusbedrohend“ (z. B. Blutungen, Hypotonie) kategorisiert. Zudem wurde der Zeitpunkt der erstmaligen Dokumentation der Komplikationen erfasst und in 3 Zeiträume eingeordnet (0 bis 3, 4 bis 30 und ≥31 Tage). Vorliegend handelt es sich um das bislang größte publizierte Patientenkollektiv einer Studie mit Skleranahtfixierung einer Hinterkammerlinse (HKL). Es wurden 338 Augen von 338 Patienten in die Studie eingeschlossen (Frauen: 47 %), die mediane Nachbeobachtungszeit betrug 60 Tage (min.: 1 Tag, max.: 5833 Tage). In 68 % der Fälle wurden Komplikationen dokumentiert. „Dauerhaft visusbedrohende Komplikationen“ traten bei 3 % (n = 10) der Patienten auf. Als „klinisch relevante Komplikationen“ wurden ermittelt: okuläre Hypotension auf Werte ≤10 mm Hg (n = 119; 35 %), entrundete Pupille (n = 93; 28 %), Hyphäma, Iris- oder Glaskörperblutungen (n = 34; 10 %), Sekundärglaukom (n = 32; 9 %) und Iris-Capture (n = 17; 5 %); 41 % der Komplikationen traten innerhalb der ersten 3 Tage und 70 % innerhalb der ersten 30 Tage auf. Zu Revisionsoperationen kam es bei 4,5 % (n = 15) der Patienten. Obwohl bei ca. zwei Dritteln aller Eingriffe Komplikationen auftraten, war die Zahl der dauerhaft visusbedrohenden Komplikationen gering. Die Sklerafixation der Kunstlinse ist weiterhin ein vertretbarer Eingriff.     

The role of BDNF methylation and Val66Met in amygdala reactivity during emotion processing

Epigenetic alterations of the brain‐derived neurotrophic factor (BDNF) gene have been associated with psychiatric disorders in humans and with differences in amygdala BDNF mRNA levels in rodents. This human study aimed to investigate the relationship between the functional BDNF‐Val⁶⁶Met polymorphism, its surrounding DNA methylation in BDNF exon IX, amygdala reactivity to emotional faces, and personality traits. Healthy controls (HC, n = 189) underwent functional MRI during an emotional face‐matching task. Harm avoidance, novelty seeking and reward dependence were measured using the Tridimensional Personality Questionnaire (TPQ). Individual BDNF methylation profiles were ascertained and associated with several BDNF single nucleotide polymorphisms surrounding the BDNF‐Val⁶⁶Met, amygdala reactivity, novelty seeking and harm avoidance. Higher BDNF methylation was associated with higher amygdala reactivity (x = 34, y = 0, z = ?26, t₍₁₆₆₎ = 3.00, TFCE = 42.39, p_(FWE) = .045), whereby the BDNF‐Val⁶⁶Met genotype per se did not show any significant association with brain function. Furthermore, novelty seeking was negatively associated with BDNF methylation (r = ?.19, p = .015) and amygdala reactivity (r = ?.17, p = .028), while harm avoidance showed a trend for a positive association with BDNF methylation (r = .14, p = .066). The study provides first insights into the relationship among BDNF methylation, BDNF genotype, amygdala reactivity and personality traits in humans, highlighting the multidimensional relations among genetics, epigenetics, and neuronal functions. The present study suggests a possible involvement of epigenetic BDNF modifications in psychiatric disorders and related brain functions, whereby high BDNF methylation might reduce BDNF mRNA expression and upregulate amygdala reactivity.     

Autonomic Dysfunction in Parkinson’s Disease

Recognition of the importance of nonmotor dysfunction as a component of Parkinson’s disease has exploded over the past three decades. Autonomic dysfunction is a frequent and particularly important nonmotor feature because of the broad clinical spectrum it covers. Cardiovascular, gastrointestinal, urinary, sexual, and thermoregulatory abnormalities all can appear in the setting of Parkinson’s disease. Cardiovascular dysfunction is characterized most prominently by orthostatic hypotension. Gastrointestinal dysfunction can involve virtually all levels of the gastrointestinal tract. Urinary dysfunction can entail either too frequent voiding or difficulty voiding. Sexual dysfunction is frequent and frustrating for both patient and partner. Alterations in sweating and body temperature are not widely recognized but often are present. Autonomic dysfunction can significantly and deleteriously impact quality of life for individuals with Parkinson’s disease. Because effective treatment for many aspects of autonomic dysfunction is available, it is vitally important that assessment of autonomic dysfunction be a regular component of the neurologic history and exam and that appropriate treatment be initiated and maintained.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00897-4) contains supplementary material, which is available to authorized users.Key Words: Autonomic, gastrointestinal, orthostatic hypotension, urinary, erectile dysfunction, thermoregulatory     

A genome wide association study identifies new genes potentially associated with eyelid sagging

Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10^‐10) and rs4746957 (P = 1.06 × 10^‐8), were significantly associated with eyelid sagging severity. The rs16927253‐T and rs4746957‐A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity.