Chronomics: circadian and circaseptan timing of radiotherapy, drugs, calories, perhaps nutriceuticals and beyond

We suggest a putative benefit from timing nutriceuticals (substances that are both nutrients and pharmaceuticals) such as antioxidants for preventive or curative health care, based on the proven merits of timing nutrients, drugs, and other treatments, as documented, i.a., in India. The necessity of timing melatonin, a major antioxidant, is noted. A protocol to extend the scope of chronoradiotherapy awaits testing. Imaging in time by mapping rhythms and broader time structures, chronomes, for earliest diagnoses, for example detection of vascular disease risk, is recommended. The study of rhythms and broader chronomes leads to a dynamic functional genomics, guided by imaging in time of free radicals and antioxidants, amongst many other variables.     

Brain activations during motor imagery of locomotor-related tasks: a PET study

Positron emission tomography (PET) was used to study the involvement of supraspinal structures in human locomotion. Six right-handed adults were scanned in four conditions while imagining locomotor-related tasks in the first person perspective: Standing (S), Initiating gait (IG), Walking (W) and Walking with obstacles (WO). When these conditions were compared to a rest (control) condition to identify the neural structures involved in the imagination of locomotor-related tasks, the results revealed a common pattern of activations, which included the dorsal premotor cortex and precuneus bilaterally, the left dorsolateral prefrontal cortex, the left inferior parietal lobule, and the right posterior cingulate cortex. Additional areas involving the pre-supplementary motor area (pre-SMA), the precentral gyrus, were activated during conditions that required the imagery of locomotor movements. Further subtractions between the different locomotor conditions were then carried out to determine the cerebral regions associated with the simulation of increasingly complex locomotor functions. These analyses revealed increases in rCBF activity in the left cuneus and left caudate when the W condition was compared to the IG condition, suggesting that the basal ganglia plays a role in locomotor movements that are automatic in nature. Finally, subtraction of the W from the WO condition yielded increases in activity in the precuneus bilaterally, the left SMA, the right parietal inferior cortex and the left parahippocampal gyrus. Altogether, the present findings suggest that higher brain centers become progressively engaged when demands of locomotor tasks require increasing cognitive and sensory information processing.     

Are Particulate Matter Exposures Associated with Risk of Type 2 Diabetes?

Background

Although studies have found that diabetes mellitus (DM) modifies the impact of exposures from air pollution on cardiovascular outcomes, information is limited regarding DM as an air pollution-associated outcome.

Objectives

Using two prospective cohorts, the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS), we investigated the relationship of incident type 2 DM with exposures to particulate matter (PM) <2.5 μm (PM_2.5), PM <10 μm (PM₁₀), and PM between 2.5 and 10 μm in aerodynamic diameter (PM_10–2.5) in the previous 12 months and the distance to roadways.

Methods

Cases were reported and confirmed through biennial and supplemental questionnaires of diagnosis and treatment information. During follow-up from 1989 to 2002, questionnaires provided information on time-varying covariates and updated addresses. Addresses were geocoded and used to assign air pollution exposures from spatiotemporal statistical models.

Results

Among participants living in metropolitan areas of the northeastern and midwestern United States, there were 3,784 incident cases of DM in the NHS, and 688 cases in the HPFS. Pooled results from random effects meta-analysis of cohort-specific models adjusted for body mass index and other known risk factors produced hazard ratios (HRs) for incident DM with interquartile range (IQR) increases in average PM during the 12 months before diagnosis of 1.03 [95% confidence interval (CI), 0.96–1.10] for PM_2.5, 1.04 (95% CI, 0.99–1.09) for PM₁₀, and 1.04 (95% CI, 0.99–1.09) for PM_10–2.5. Among women, the fully adjusted HR for living < 50 m versus ≥ 200 m from a roadway was 1.14 (95% CI, 1.03–1.27).

Conclusions

Overall, results did not provide strong evidence of an association between exposure to PM in the previous 12 months and incident DM; however, an association with distance to road (a proxy marker of exposure to traffic-related pollution) was shown among women.     

Non-Asthmatic Patients Show Increased Exhaled Nitric Oxide Concentrations

OBJECTIVE:

Evaluate whether exhaled nitric oxide may serve as a marker of intraoperative bronchospasm.

INTRODUCTION:

Intraoperative bronchospasm remains a challenging event during anesthesia. Previous studies in asthmatic patients suggest that exhaled nitric oxide may represent a noninvasive measure of airway inflammation.

METHODS:

A total of 146,358 anesthesia information forms, which were received during the period from 1999 to 2004, were reviewed. Bronchospasm was registered on 863 forms. From those, three groups were identified: 9 non-asthmatic patients (Bronchospasm group), 12 asthmatics (Asthma group) and 10 subjects with no previous airway disease or symptoms (Control group). All subjects were submitted to exhaled nitric oxide measurements (parts/billion), spirometry and the induced sputum test. The data was compared by ANOVA followed by the Tukey test and Kruskal-Wallis followed by Dunn’s test.

RESULTS:

The normal lung function test results for the Bronchospasm group were different from those of the asthma group (p <0.05). The median percentage of eosinophils in induced sputum was higher for the Asthma [2.46 (0.45–6.83)] compared with either the Bronchospasm [0.55 (0–1.26)] or the Control group [0.0 (0)] (p <0.05); exhaled nitric oxide followed a similar pattern for the Asthma [81.55 (57.6–86.85)], Bronchospasm [46.2 (42.0–62.6] and Control group [18.7 (16.0–24.7)] (p< 0.05).

CONCLUSIONS:

Non-asthmatic patients with intraoperative bronchospasm detected during anesthesia and endotracheal intubation showed increased expired nitric oxide.     

Interleukin 28B-related polymorphisms: A pathway for understanding hepatitis C virus infection?

AIM:To analyze the role of rs12979860 and rs8099917polymorphisms in hepatitis C virus(HCV)genotype 1infection of Brazilians.METHODS:A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C(CHC)who had completed a 48-wk regimen of pegylated-interferonα-2a or-2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and199 healthy blood donors(controls)from a single site between January 2010 and January 2012.Data on the patients’response to treatment was collected.Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin(IL)28B gene fragment encompassing the single nucleotide polymorphisms(SNPs)rs12979860(C/T)and rs8099917(T/G)was carried out for 79 of the CHC patients and 199 of the controls.Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients.RESULTS:SNP rs12979860 genotyping was successful in 99.5%of the controls and 97.2%of the CHC patients,whereas the SNP rs8099917 genotyping was successful in 95.5%of the controls and 100%of the CHC patients.The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups,with significantly higher genotype frequencies of CC and TT in the controls(P=0.037 and 0.046,respectively)and of TT and GG in the CHC patients(P=0.0009and 0.0001,respectively).Analysis of the CHC patients who achieved sustained virological response(SVR)to treatment(n=55)indicated that the rs12979860 C allele and CC genotype were predictors of SVR(P=0.02).No significant correlation was found between rs8099917 genotypes and treatment response,but carriers of the T allele showed significantly higher rates of SVR(P=0.02).Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917(P=0.07).CONCLUSION:The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCVinfected individuals may indicate a potential pro     

Periodontitis as a manifestation of chronic benign neutropenia

BACKGROUND: A subcategory of chronic neutropenia is chronic benign neutropenia, which is characterized by a prolonged non-cyclic neutropenia as the sole abnormality, with no underlying disease to which the neutropenia can be attributed. Chronic neutropenia is defined as a low absolute neutrophil count for >6 months. In this presentation, periodontitis seems to be the sole manifestation of a juvenile patient with chronic benign neutropenia. A 7-year-old white male presented with periodontitis of the primary dentition and early tooth loss. His medical and dental history was otherwise unremarkable. Suspecting some systemic illness as the underlying cause, the patient was referred for a medical consultation and a series of blood tests. METHODS: Blood analyses included a complete blood count (CBC), sequential multiple analyzer 24 (SMA 24), glycated hemoglobin levels, and screening for anti-white blood cell antibodies. Blood levels of calcium, vitamin D, dihydroxyvitamin-D, phosphorus, and alkaline phosphatase were also measured. Liver function tests were performed. RESULTS: Following analysis of recent and previous blood test results, a diagnosis of chronic benign neutropenia was assigned. The patient's periodontal condition was treated with scaling and root planing, oral hygiene instruction, and antimicrobial mouthrinses. Three-month recall visits were recommended as a follow-up protocol. CONCLUSIONS: This case represents the importance of diagnosing periodontal disease as a possible indicator of underlying systemic disease. When a patient presents with an unusual, generalized form of periodontal disease, screening for systemic disorders is required, as the oral condition may be the first or only manifestation of a systemic abnormality. This case also illustrates the reason for the change in classification of such a condition to periodontitis as a manifestation of systemic disease. This condition was previously classified as prepubertal periodontitis, a disease diagnosis that focused on the patient's age at the onset of the disease rather than the etiology.     

Respiratory symptoms and intensity of occupational dust exposure

Objectives: Occupational exposure to dusts may result in chronic respiratory symptoms. Methods: To investigate the utility of obtaining a history of occupational exposure to dust in US veterans, a respiratory health survey was conducted between 1988 and 1992 in a community-based cohort of US veterans in southeastern Massachusetts that were eligible for Veterans Affairs (VA) healthcare benefits but were not regular users. A mail questionnaire was used to obtain a history of cough, phlegm, and wheeze, work in a dusty job, and duration, type, and intensity of dust exposure. Information on cigarette use and other possible confounders was obtained. Results: In 2,617 white men, after the data had been adjusted for cigarette smoking, age, distance to the nearest major roadway, and chronic respiratory disease, the relative odds of chronic cough, chronic phlegm, and persistent wheeze attributable to occupational dust exposure was increased twofold. Risk also increased, based on exposure intensity. For heavy dust exposure the OR was 1.98 (95% CI 1.39–2.81) for chronic cough, 2.82 (95% CI 2.03–3.93) for chronic phlegm, and 2.70 (95% CI 1.95–3.75) for persistent wheeze. Conclusions: After active cigarette smoking and other possible confounders had been considered, it was found that dust exposure was related to respiratory symptoms in US veterans and that the greatest risk was attributable to heavy intensity exposure.Presented in abstract form at the 1994 annual meeting of the American Thoracic Society.