Meal frequency and timing in health and disease

Although major research efforts have focused on how specific components of foodstuffs affect health, relatively little is known about a more fundamental aspect of diet, the frequency and circadian timing of meals, and potential benefits of intermittent periods with no or very low energy intakes. The most common eating pattern in modern societies, three meals plus snacks every day, is abnormal from an evolutionary perspective. Emerging findings from studies of animal models and human subjects suggest that intermittent energy restriction periods of as little as 16 h can improve health indicators and counteract disease processes. The mechanisms involve a metabolic shift to fat metabolism and ketone production, and stimulation of adaptive cellular stress responses that prevent and repair molecular damage. As data on the optimal frequency and timing of meals crystalizes, it will be critical to develop strategies to incorporate those eating patterns into health care policy and practice, and the lifestyles of the population.     

PROTEIN DISULFIDE ISOMERASE LIKE 5-1 is a susceptibility factor to plant viruses

Protein disulfide isomerases (PDIs) catalyze the correct folding of proteins and prevent the aggregation of unfolded or partially folded precursors. Whereas suppression of members of the PDI gene family can delay replication of several human and animal viruses (e.g., HIV), their role in interactions with plant viruses is largely unknown. Here, using a positional cloning strategy we identified variants of PROTEIN DISULFIDE ISOMERASE LIKE 5–1 (HvPDIL5-1) as the cause of naturally occurring resistance to multiple strains of Bymoviruses. The role of wild-type HvPDIL5-1 in conferring susceptibility was confirmed by targeting induced local lesions in genomes for induced mutant alleles, transgene-induced complementation, and allelism tests using different natural resistance alleles. The geographical distribution of natural genetic variants of HvPDIL5-1 revealed the origin of resistance conferring alleles in domesticated barley in Eastern Asia. Higher sequence diversity was correlated with areas with increased pathogen diversity suggesting adaptive selection for bymovirus resistance. HvPDIL5-1 homologs are highly conserved across species of the plant and animal kingdoms implying that orthologs of HvPDIL5-1 or other closely related members of the PDI gene family may be potential susceptibility factors to viruses in other eukaryotic species.Infectious diseases caused by plant viruses threaten agricultural productivity and reduce globally attainable agricultural production by about 3% (1). In specific pathosystems, plant viruses can result in the loss of the entire crop. For example, the devastation of cassava production by cassava mosaic geminiviruses (CMGs) in Uganda during the 1990s led to widespread food shortages and famine-related deaths (2). Unfortunately protecting plants against viruses (especially soil-borne viruses) by using agrochemicals to control virus vectors is seldom efficient from economic or ecological perspectives. Therefore, crop protection based on naturally occurring virus resistance is key to minimizing losses and achieving sustainable crop yields.Positive-strand RNA viruses represent the largest group of plant viruses (3). They cause a very high proportion of the important infectious virus diseases in agriculture (4, 5). Such plant viruses carry a reduced genome that encodes a limited set of functional proteins (4–10 viral proteins)—insufficient to complete the entire virus replication and proliferation cycle (6). Instead, over evolutionary time, viruses recruited host factors to perform the infectious life cycle (7). This dependence on host factors establishes a possibility that plants can evolve escape, tolerance, or resistance mechanisms to ameliorate the consequences of viral infection. The absence of essential host factors could interfere with the infection process or restrict proliferation (8) leading to either mono- or polygenic recessive resistance (5). Prominent examples of such susceptibility factors that are conserved in multiple plant–virus systems are the EUKARYOTIC TRANSLATION INITIATION FACTORS (EIF)4E, iso4E, 4G, and iso4G (9). Translation initiation factors may interact directly with viral RNA where they catalyze the initiation of translation of viral polyproteins (10, 11). In addition, to establish replication and assembly complexes during infection, viruses typically create membrane-bound environments, referred to as “virus factories” (12). There, cellular chaperones such as HSP70 and DNAJ-like proteins likely contribute to the correct folding and translocation of substrates (12, 13). However, only a few such host factors are known (7, 9, 14).Barley yellow mosaic virus disease caused by barley yellow mosaic virus (BaYMV) and barley mild mosaic virus (BaMMV) (both belong to Bymoviruses) seriously threatens winter barley production in Europe and East Asia (4). Infection leads to yellow discoloration and stunted growth and may result in yield loss of up to 50% (15). Soil-borne transmission via the plasmodiophorid Polymyxa graminis prohibits plant protection by chemical measures, and breeding for resistant cultivars is therefore the only practicable way to prevent yield loss. The naturally occurring recessive resistance locus rym11 confers complete broad-spectrum resistance to all known European isolates of BaMMV and BaYMV (16–19). In the present study, we used a positional cloning strategy to identify the gene underlying rym11-based resistance. We show that it is a susceptibility factor belonging to a gene family of PROTEIN DISULFIDE ISOMERASES (PDIs), and is highly conserved across eukaryotic species. We observe a strong correlation between natural allelic variation and geographic distribution, suggesting that both the origin and subsequent adaptive selection for rym11-based resistance in winter barley occurred in East Asia.     

Screening for Bronchoscopic Lung Volume Reduction: Reasons for Not Receiving Interventional Treatment

Background

Evidence for bronchoscopic lung volume reduction (BLVR) is based on phase 2 studies and small randomized controlled trials with in- and exclusion criteria defining a therapeutic window and contraindications. Little is known about the applicability in routine clinical practice.

Aim

Which percentage of patients with severe emphysema referred to a specialized treatment center for BLVR is ultimately suitable for interventional bronchoscopic treatment? What is the relevance of the different contraindications?

Methods

Retrospective evaluation of emphysema patients referred to Asklepios Fachkliniken Munich-Gauting for BLVR between January 2014 and June 2015.

Results

138 patients were referred for evaluation of BLVR. 38 patients (27.5%) underwent BLVR procedures (valves n = 18; coils n = 18; thermal vapor ablation n = 2). 100 patients (72.5%) were deemed not eligible for BLVR based on the following contraindications: 34% emphysema morphology and emphysema-related findings (severe homogeneous emphysema, extensive pleuropulmonary adhesions, postinflammatory scaring with natural volume reduction, giant bullae), 16% active smoking; 9% pulmonary function not within indication range; 8% unexpected CT findings (nodules, cancer, interstitial disease); 8% chronic ventilatory failure; 8% patient refused BLVR; 5% relevant comorbidity; 5% frequent exacerbations, 3% preserved quality of life, 4% other.

Conclusion

BLVR is a therapeutic option for highly selected patients. In our cohort, one in four could be treated. These data highlight the limitations of BLVR under real-life conditions.

     

Post-operative delay in return of function following guided growth tension plating and use of corrective physical therapy

Purpose

Guided growth has long been used to treat growth deformities, but the Eight-Plate^® system has recently become more widely used by pediatric orthopaedists. Because the current literature lacks evaluation of functional status in the immediate post-operative period, we investigated functional status following use of the Eight-Plate^® system.

Methods

We evaluated post-operative delay in return of function following treatment with the Eight-Plate^® system at two weeks after surgery. Fifty-one consecutive patients with a growth deformity were treated with the Eight-Plate^® system. Patients were comprised of 32 male and 19 female patients with an average age of 11 years (range 2–17.9 years).

Results

Among study participants, 19 patients (37.3 %) had post-operative delay of function. The rate of delayed function for patients 10 years of age or younger and 11 years of age or older was respectively 11.8 and 50 % (P = 0.002). Six of the 19 patients were treated with four or more plates, of which five patients (83.3 %) developed delayed return of function. The rate of delayed function in patients with at least one femoral plate compared to no femoral plate was respectively 45 and 9.1 % (P = 0.006). Bilateral operations were associated with a 66.7 % rate of delayed function compared to 25 % with unilateral operations (P = 0.004). When patients with delay of function were treated with physical therapy, 12 of 13 patients (92.3 %) had complete resolution of their symptoms.

Conclusion

Statistical significance demonstrated that patients at the greatest risk were 11 years of age or older, with four or more plates, with femoral plates, or with bilateral operations. Patients with delayed function were readily corrected by physical therapy.     

Geographic Residency Status and Census Tract Socioeconomic Status as Determinants of Colorectal Cancer Outcomes

Objectives. We examined the impact of geographic residency status and census tract (CT)-level socioeconomic status (SES) on colorectal cancer (CRC) outcomes.Methods. This was a retrospective cohort study of patients diagnosed with CRC in Georgia for the years 2000 through 2007. Study outcomes were late-stage disease at diagnosis, receipt of treatment, and survival.Results. For colon cancer, residents of lower-middle-SES and low-SES census tracts had decreased odds of receiving surgery. Rural, lower-middle-SES, and low-SES residents had decreased odds of receiving chemotherapy. For patients with rectal cancer, suburban residents had increased odds of receiving radiotherapy, but low SES resulted in decreased odds of surgery. For survival, rural residents experienced a partially adjusted 14% (hazard ratio [HR] = 1.14; 95% confidence interval [CI] = 1.07, 1.22) increased risk of death following diagnosis of CRC that was somewhat explained by treatment differences and completely explained by CT-level SES. Lower-middle- and low-SES participants had an adjusted increased risk of death following diagnosis for CRC (lower-middle: HR = 1.16; 95% CI = 1.10, 1.22; low: HR = 1.24; 95% CI = 1.16, 1.32).Conclusions. Future efforts should focus on developing interventions and policies that target rural residents and lower SES areas to eliminate disparities in CRC-related outcomes.For men and women in the United States, colorectal cancer (CRC) ranks third in incidence and mortality among cancers, with an estimated 142 820 new cases and 50 830 deaths in 2013.1 Reflecting the US population distribution according to geography2 and evidence of similar incidence rates3,4 for rural residents, approximately 20% of incident CRC cases are expected to occur in rural populations. Although CRC incidence is equivalent for rural and urban residents, CRC mortality is higher in rural populations,5 and the causes of rural versus urban disparities in CRC mortality are not well understood. Compared with their suburban and urban counterparts, rural citizens are more likely to be older, live in poverty, have less education, lack health insurance, and have no regular health care provider.6–9 These facets of rural living pose challenges to accessing health promotional messages and high-quality primary care, not to mention treatment of cancer.10,11Those of lower socioeconomic status (SES) have worse health-related outcomes than their more affluent counterparts, and SES often has a gradient effect on health.12 A challenge in studying the association between rurality and health is being able to disentangle the confounding effect of SES associated with geographic residency.13 As we previously demonstrated for a sample of urban and rural residents of Georgia with CRC, rural residence was associated with an increased risk of death following diagnosis.14 A limitation of that study was an inability to account for SES differences between urban and rural populations. If adjustment for SES explains the poorer survival that is associated with rural residence, this explanation provides an opportunity to investigate mediators of the SES effect as potential avenues for intervention.15 Identification of these mediating factors will facilitate the development of focused interventions with the goal of eliminating rural CRC-related disparities.16,17Building on our previous work,14 we evaluated the independent and combined effects of rurality and area-level SES on CRC outcomes. In our previous study, (1) we were unable to evaluate the independent and potential confounding effect of SES on rurality,2 (2) our study population was a sample of the Georgia CRC population, and (3) residents were classified as urban or rural at the county level, which may have resulted in misclassification. In the present study, the exposures of interest were geographic residency status (rural, suburban, or urban) and area-level SES, both at the census tract (CT) level. In addition, the study population represents the entire state of Georgia rather than a sample. The primary study outcome was overall survival. Secondarily, we wanted to evaluate the effect of SES and geography adjusted for SES on the odds of late-stage disease at diagnosis and receipt of first-course treatment.The findings of this study are meant to bring importance to a highly relevant area of public health research: disparities related to rural versus urban cancer outcomes, and specifically to rural CRC outcomes. As a result, interventions may be designed and policies developed to address the difficulties of accessing and providing high-quality cancer care in rural areas of the United States.11 It is through the combination of applying what is learned from epidemiological findings to community-level interventions and policymaking that the elimination of health disparities will occur.18     

Schizosaccharomyces pombe: A novel transport vehicle of functional DNA and mRNA into mammalian antigen-presenting cells

Vaccine vehicles based on recombinant yeasts have become promising candidates for the induction of cellular immune responses. In this study, we investigated the capacity of the fission yeast Sz. pombe for the delivery of functional nucleic acids into murine and human antigen-presenting cells. We demonstrate that Sz. pombe cells effectively induce maturation of human dendritic cells (DC), an important prerequisite for T-cell activation. Further, recombinant fission yeast efficiently delivers functional DNA and mRNA into murine macrophages and human DC resulting in the expression of the model antigen eGFP in these cells. Thus, Sz. pombe suggests itself as a promising candidate for a novel live vaccine.