Comparison of nutrition screening tools and calf circumference in estimating the preoperative prevalence of malnutrition among patients with aerodigestive tract cancers-a prospective observational cohort study.

PURPOSE: There is paucity of data on the prevalence of malnutrition among cancer patients in India and a brief tool to identify the same would be an asset. Our aim was to evaluate two nutrition screening tools and calf circumference (CC) with the European Society for Clinical Nutrition and Metabolism (ESPEN) consensus guidelines for malnutrition among patients with head and neck (H&N) and gastrointestinal (GI) cancers. METHODS: Nutritional evaluation was performed preoperatively using Malnutrition Universal Screening Tool (MUST), Short Form of Mini Nutritional Assessment (MNA-SF), and calf circumference (CC) in 206 patients. The diagnostic accuracy of these tools was compared with the ESPEN criteria for malnutrition. Patients evaluated were grouped as normal or malnourished. The incidence of infection, antibiotic days, antibiotic escalation, and length of stay was compared among the groups. Clavien-Dindo score at discharge, 30-day readmission, and mortality were also examined. RESULTS: A total of 28.6% were malnourished as per ESPEN criteria and 25.2% had CC less than the cut-off. With respect to ESPEN criteria, MUST and MNA-SF had 100% sensitivity and negative predictive value. CC had the highest specificity and positive predictive value for the total population (91.16%, 75% respectively). The agreement between the tools was acceptable except in MNA-SF (MNA-SF-ESPEN κ = 0.228, MUST-ESPEN κ = 0.565, CC-ESPEN κ = 0.594). There was no difference in postoperative outcomes between the malnourished and normal. CONCLUSION: Thus, more than a quarter of patients with H&N and GI cancers are malnourished preoperatively. As the best agreement between the screening tools was for MUST-ESPEN and CC-ESPEN, either of them can be used to identify malnutrition at admission.

Gap junction protein Innexin2 modulates the period of free-running rhythms in Drosophila melanogaster.

A neuronal circuit of ∼150 neurons modulates rhythmic activity-rest behavior of Drosophila melanogaster. While it is known that coherent ∼24-hr rhythms in locomotion are brought about when 7 distinct neuronal clusters function as a network due to chemical communication amongst them, there are no reports of communication via electrical synapses made up of gap junctions. Here, we report that gap junction proteins, Innexins play crucial roles in determining the intrinsic period of activity-rest rhythms in flies. We show the presence of Innexin2 in the ventral lateral neurons, wherein RNAi-based knockdown of its expression slows down the speed of activity-rest rhythm along with alterations in the oscillation of a core-clock protein PERIOD and the output molecule pigment dispersing factor. Specifically disrupting the channel-forming ability of Innexin2 causes period lengthening, suggesting that Innexin2 may function as hemichannels or gap junctions in the clock circuit.

Waveform Plasticity under Entrainment to 12-h T-cycles in Drosophila melanogaster: Behavior, Neuronal Network, and Evolution.

A crucial property of circadian clocks is the ability to regulate the shape of an oscillation over its cycle length (waveform) appropriately, thus enhancing Darwinian fitness. Many studies over the past decade have revealed interesting ways in which the waveform of rodent behavior could be manipulated, one of which is that the activity bout bifurcates under environments that have 2 light/dark cycles within one 24-h day (LDLD). It has been observed that such unique, although unnatural, environments reveal acute changes in the circadian clock network. However, although adaptation of waveforms to different photoperiods is well studied, modulation of waveforms under LDLD has received relatively less attention in research on insect rhythms. Therefore, we undertook this study to ask the following questions: what is the extent of waveform plasticity that Drosophila melanogaster exhibits, and what are the neuronal underpinnings of such plasticity under LDLD? We found that the activity/rest rhythms of wild-type flies do not bifurcate under LDLD. Instead, they show similar but significantly different behavior from that under a long-day LD cycle. This behavior is accompanied by differences in the organization of the circadian neuronal network, which include changes in waveforms of a core clock component and an output molecule. In addition, to understand the functional significance of such variations in the waveform, we examined laboratory selected populations that exhibit divergent eclosion chronotypes (and therefore, waveforms). We found that populations selected for predominant eclosion in an evening window (late chronotypes) showed reduced amplitude plasticity and increased phase plasticity of activity/rest rhythms. This, we argue, is reflective of divergent evolution of circadian neuronal network organization in our laboratory selected flies.

The Familial α-Synuclein A53E Mutation Enhances Cell Death in Response to Environmental Toxins Due to a Larger Population of Oligomers.

Amyloid formation of α-synuclein (α-Syn) and its familial mutations are directly linked with Parkinson's disease (PD) pathogenesis. Recently, a new familial α-Syn mutation (A53E) was discovered, associated with an early onset aggressive form of PD, which delays α-Syn aggregation. When we overexpressed wild-type (WT) and A53E proteins in cells, showed neither toxicity nor aggregate formation, suggesting merely overexpression may not recapitulate the PD phenotype in cell models. We hypothesized that cells expressing the A53E mutant might possess enhanced susceptibility to PD-associated toxicants compared to that of the WT. When cells were treated with PD toxicants (dopamine and rotenone), cells expressing A53E showed more susceptibility to cell death along with compromised mitochondrial potential and an increased production of reactive oxygen species. The higher toxicity of A53E could be due to more oligomers being formed in cells as confirmed by a dot blot assay using amyloid specific OC and A11 antibody and using an  in vitro aggregation study. The cellular model presented here suggests that along with familial mutation, environmental and other cellular factors might play a crucial role in dictating PD pathogenesis.