The effects of surgery on plasma/serum vitamin C concentrations: a systematic review and meta-analysis.

Vitamin C (ascorbic acid) is a water-soluble vitamin with an array of biological functions. A number of proposed factors contribute to the vitamin's plasma bioavailability and ability to exert optimal functionality. The aim of this review was to systematically assess plasma vitamin C levels post-surgery compared with pre-surgery/the magnitude and time frame of potential changes in concentration. We searched the PUBMED, SCOPUS, SciSearch and the Cochrane Library databases between 1970 and April 2020 for relevant research papers. Prospective studies, control groups and true placebo groups derived from controlled trials that reported means and standard deviations of plasma vitamin C concentrations pre- and postoperatively were included into the meta-analysis. Data were grouped into short-term (≤7 d) and long-term (>7 d) postoperative follow-up. Twenty-three of thirty-one studies involving 642 patients included in the systematic review were suitable for meta-analysis. Pooled data from the meta-analysis revealed a mean depletion of plasma vitamin C concentration of -17·99 µmol/l (39 % depletion) (CI -22·81, -13·17) (trial arms = 25, n 565, P < 0·001) during the first postoperative week and -18·80 µmol/l (21 % depletion) (CI -25·04, -12·56) (trial arms = 6, n 166, P < 0·001) 2-3 months postoperatively. Subgroup analyses revealed that these depletions occurred following different types of surgery; however, high heterogeneity was observed amongst trials assessing concentration change during the first postoperative week. Overall, our results warrant larger, long-term investigations of changes in postoperative plasma vitamin C concentrations and their potential effects on clinical symptomology.

Memory T helper cells identify patients with nickel, cobalt, and chromium metal allergy.

BACKGROUND: Patch testing is the gold standard for identifying culprit allergens in allergic contact dermatitis; however, it is laborious and positive reactions are difficult to quantitate. Development of complementary in vitro tests is, therefore, of great importance. OBJECTIVES: This study aimed to improve the in vitro lymphocyte proliferation test (LPT) to detect allergic responses to nickel (Ni), cobalt (Co), and chromium (Cr). METHODS: Twenty-one metal allergic patients with a positive patch test to Ni (n=16), Co (n=8), and Cr (n=3) and 13 controls were included. All were tested by a flow cytometric LPT. RESULTS: Metal-reactive cells were identified as T helper (Th) cells with high expression of the memory marker CD45RO. Skin-homing (cutaneous lymphocyte-associated antigen positive [CLA+]) Ni-reactive memory Th (Thmem hi ) cells identified individuals with a positive patch test for Ni with 100% sensitivity (95% confidence interval [CI] 81%-100%) and 92% specificity (95% CI 67%-100%). Moreover, Co-specific Thmem hi cells expressing CCR6 identified patients with a positive patch test for Co with 63% sensitivity (95% CI 31%-86%) and 100% specificity (95% CI 77%-100%). In Cr allergic individuals, Cr-reactive Thmem hi cells tended to increased CLA and CCR6 expression. CONCLUSION: Metal-reactive Th cells with high expression of CD45RO and coexpression of CLA and CCR6 improved the LPT, making it an attractive supplement to the patch test.

FuGeF: A Resource Bound Secure Forwarding Protocol for Wireless Sensor Networks.

Resource bound security solutions have facilitated the mitigation of spatio-temporal attacks by altering protocol semantics to provide minimal security while maintaining an acceptable level of performance. The Dynamic Window Secured Implicit Geographic Forwarding (DWSIGF) routing protocol for Wireless Sensor Network (WSN) has been proposed to achieve a minimal selection of malicious nodes by introducing a dynamic collection window period to the protocol's semantics. However, its selection scheme suffers substantial packet losses due to the utilization of a single distance based parameter for node selection. In this paper, we propose a Fuzzy-based Geographic Forwarding protocol (FuGeF) to minimize packet loss, while maintaining performance. The FuGeF utilizes a new form of dynamism and introduces three selection parameters: remaining energy, connectivity cost, and progressive distance, as well as a Fuzzy Logic System (FLS) for node selection. These introduced mechanisms ensure the appropriate selection of a non-malicious node. Extensive simulation experiments have been conducted to evaluate the performance of the proposed FuGeF protocol as compared to DWSIGF variants. The simulation results show that the proposed FuGeF outperforms the two DWSIGF variants (DWSIGF-P and DWSIGF-R) in terms of packet delivery.

The effects of multivitamin supplementation on mood and general well-being in healthy young adults. A laboratory and at-home mobile phone assessment.

Previous research has suggested that multivitamin (MV) supplementation may be associated with beneficial effects for mood and general well-being, although treatment durations have typically been less than 90 days, samples have often been restricted to males only and acute effects have not been adequately differentiated from chronic effects. In the current study a MV supplement containing high levels of B-vitamins was administered daily to 138 healthy young adult participants between the ages of 20 and 50 years over a 16-week period. Chronic mood measures (GHQ-28, POMS, Chalder fatigue, PILL, Bond-Lader and custom visual analogue scales) were administered pre-dose at baseline, 8- and 16-weeks. Changes in Bond-Lader and VAS in response to a multi-tasking framework (MTF) were also assessed at 8- and 16-weeks. For a subset of participants, at-home mobile-phone assessments of mood were assessed on a weekly basis using Bond-Lader and VAS. No significant treatment effects were found for any chronic laboratory mood measures. In response to the MTF, a significant treatment x time interaction was found for STAI-S, with a trend towards a greater increase in stress ratings for male participants in the MV group at 16 weeks. However, this finding may have been attributable to a larger proportion of students in the male MV group. In contrast, at-home mobile-phone assessments, where assessments were conducted post-dose, revealed significantly reduced stress, physical fatigue and anxiety in the MV group in comparison to placebo across a number of time points. Further research using both acute and chronic dosing regimens are required in order to properly differentiate these effects.

Homology-based annotation yields 1,042 new candidate genes in the Drosophila melanogaster genome.

The approach to annotating a genome critically affects the number and accuracy of genes identified in the genome sequence. Genome annotation based on stringent gene identification is prone to underestimate the complement of genes encoded in a genome. In contrast, over-prediction of putative genes followed by exhaustive computational sequence, motif and structural homology search will find rarely expressed, possibly unique, new genes at the risk of including non-functional genes. We developed a two-stage approach that combines the merits of stringent genome annotation with the benefits of over-prediction. First we identify plausible genes regardless of matches with EST, cDNA or protein sequences from the organism (stage 1). In the second stage, proteins predicted from the plausible genes are compared at the protein level with EST, cDNA and protein sequences, and protein structures from other organisms (stage 2). Remote but biologically meaningful protein sequence or structure homologies provide supporting evidence for genuine genes. The method, applied to the Drosophila melanogaster genome, validated 1,042 novel candidate genes after filtering 19,410 plausible genes, of which 12,124 matched the original 13,601 annotated genes. This annotation strategy is applicable to genomes of all organisms, including human.

Structural genomics: beyond the human genome project.

With access to whole genome sequences for various organisms and imminent completion of the Human Genome Project, the entire process of discovery in molecular and cellular biology is poised to change. Massively parallel measurement strategies promise to revolutionize how we study and ultimately understand the complex biochemical circuitry responsible for controlling normal development, physiologic homeostasis and disease processes. This information explosion is also providing the foundation for an important new initiative in structural biology. We are about to embark on a program of high-throughput X-ray crystallography aimed at developing a comprehensive mechanistic understanding of normal and abnormal human and microbial physiology at the molecular level. We present the rationale for creation of a structural genomics initiative, recount the efforts of ongoing structural genomics pilot studies, and detail the lofty goals, technical challenges and pitfalls facing structural biologists.

Strategic protein target analysis for developing drugs to stop dental caries.

Dental caries is the most common disease to cause irreversible damage in humans. Several therapeutic agents are available to treat or prevent dental caries, but none besides fluoride has significantly influenced the disease burden globally. Etiologic mechanisms of the mutans group streptococci and specific Lactobacillus species have been characterized to various degrees of detail, from identification of physiologic processes to specific proteins. Here, we analyze the entire Streptococcus mutans proteome for potential drug targets by investigating their uniqueness with respect to non-cariogenic dental plaque bacteria, quality of protein structure models, and the likelihood of finding a drug for the active site. Our results suggest specific targets for rational drug discovery, including 15 known virulence factors, 16 proteins for which crystallographic structures are available, and 84 previously uncharacterized proteins, with various levels of similarity to homologs in dental plaque bacteria. This analysis provides a map to streamline the process of clinical development of effective multispecies pharmacologic interventions for dental caries.

Ageist Communication Experienced by Middle-Aged and Older Canadians.

Ageism has been well-documented in the United States, but ageism experiences in Canada remain less well-known. To address this gap, in the current research middle-aged and older Canadians completed a conversational interview in which they described their ageism experiences. Their descriptions were coded for life domain, perpetrator, and type of ageist communication. The most common domain in which ageist communication occurred was the public sphere, with perpetrators most often being strangers. Ageist communication most often involved age-based social or physical assumptions about the participant. In combination, these findings detail how ageism manifests in the everyday lives of Canadians and contribute to understanding the nuances of the expression of ageism in North America.

Impact of COVID-19 pandemic on cancer care: A cross-sectional study of Egyptian patients' perspectives and concerns.

BACKGROUND: Worldwide, COVID-19 greatly reduced healthcare accessibility and utilization by non-COVID patients including cancer. This study aimed to quantify and characterize cancer care adjustments experienced by cancer patients/survivors; and to explore their concerns, beliefs, and knowledge regarding COVID-19. METHODS: A cross-sectional study was conducted using a questionnaire distributed through social media patients' groups (June-December 2020). Questionnaire included basic information, care adjustments (in "care provision" and in "treatment plan"), and patients' concerns, beliefs, and knowledge. Data description and analysis were done. RESULTS: Out of 300 participants, there were 68.0% on-treatment and 32.0% in follow-up stage. Care adjustments were reported by 29.7%; mostly in care provision (27.3%) rather than treatment plan (4.9%). Adjustments were less likely to occur when healthcare facility was in governorate other than that of residence (OR:0.53, 95%CI:0.30-0.96, P = 0.037) and more likely with long-standing diagnosis (≥12 months) compared with recent (<3 months) (adjusted-OR:4.13, 95%CI:1.19-14.34, P = 0.026). Lower proportion of on-treatment patients used remote consultation than patients in follow-up [4.4% versus 17.7%, P < 0.001]. Patients were concerned about fulfilling their care visits more than the probable COVID-19 infection (72.3%). It was uncommon to feel that the risk of COVID-19 infection is higher in care places than in the community (27.3%) or to feel safe with remote consultations (34.3%). However, patients increased their infection control practice (64.0%) and the majority were aware of their increased susceptibility to complications (86.0%). Somewhat, they were also concerned about the care quality (57.3%). Many had adequate access to COVID-19 information (69.0%) and their main sources were the Ministry of Health webpage and ordinary media (radio/TV). CONCLUSION: Cancer patients were primarily concerned about fulfilling their planned care and COVID-19 infection was less appreciated. POLICY SUMMARY: Launching of a policy for enhancement of telemedicine experience through more patients' engagement-as essential stakeholders-may be required. To heighten pandemic resilience for cancer care in Egypt, more investment in establishing specialized end-to-end cancer care facilities that ensure continuity of care may be justified.

Dysregulated expression of suppressor loop of circadian rhythm genes in colorectal cancer pathogenesis.

BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease and activation of WNT and TGFß mediated oncogenic pathways is frequently observed in this pathology. However, to date, limited reports have been published addressing the association of circadian clock with CRC pathogenesis and stratification. The current study aims at assessing the expression of important circadian markers, PER2, PER3 and NR1D1, in independent CRC cohorts and their associations with CRC-related pathways. METHODS: Gene expression analysis was performed using available GEO (GSE39582) and TCGA datasets. Quantitative real time polymerase chain reaction was used to quantify the expression levels of PER2, PER3 and NRID1 in FFPE (formalin fixed paraffin embedded) CRC tissue samples. Furthermore, enrichment of circadian markers in WNT and TGFß pathways-activated tumors was assessed. RESULTS: Statistically significant downregulation of PER3 was found in tumor versus control samples in GEO (P<0.0001) and TCGA colon and rectal adenocarcinoma datasets (P<0.05). Analysis of GEO dataset revealed a statistically significant upregulation of PER2 (P<0.01), and NR1D1 in colon adenocarcinoma, which was confirmed by qRT-PCR in CRC tumor samples versus controls in FFPE validation cohort. Higher expression of NR1D1 was associated with poor prognosis in colon adenocarcinoma. Contrastingly, PER3 was significantly downregulated in tumors (P<0.001) compared to controls and was associated with high-grade CRC tumors versus low-grade tumors. Tumors with WNT pathway activation had significantly low PER3 and slightly upregulated PER2 (<0.0001) expression. Interestingly, differential expression of PER3 and NR1D1 was significantly correlated with TGFß1-expressing tumors (P<0.0001). Moreover, MYC- amplified tumors exhibited decreased PER3 levels. CONCLUSIONS: Thus, low PER3 expression in CRC and poor survival of patients with NR1D1-high tumors reveal that genes in the suppressor loop of circadian rhythm are dysregulated in CRC, hence pointing out to the importance of dissecting the circadian pathway in cancer.

Fate of two mast cell tryptases in V3 mastocytosis and normal BALB/c mice undergoing passive systemic anaphylaxis: prolonged retention of exocytosed mMCP-6 in connective tissues, and rapid accumulation of enzymatically active mMCP-7 in the blood.

The mouse mast cell protease granule tryptases designated mMCP-6 and mMCP-7 are encoded by highly homologous genes that reside on chromosome 17. Because these proteases are released when mast cells are activated, we sought a basis for distinctive functions by examining their fates in mice undergoing passive systemic anaphylaxis. 10 min-1 h after antigen (Ag) was administered to immunoglobulin (Ig)E-sensitized mice, numerous protease/proteoglycan macromolecular complexes appeared in the extracellular matrix adjacent to most tongue and heart mast cells of normal BALB/c mice and most spleen and liver mast cells of V3 mastocytosis mice. These complexes could be intensively stained by anti-mMCP-6 Ig but not by anti-mMCP-7 Ig. Shortly after Ag challenge of V3 mastocytosis mice, large amounts of properly folded, enzymatically active mMCP-7 were detected in the plasma. This plasma-localized tryptase was approximately 150 kD in its multimeric state and approximately 32 kD in its monomeric state, possessed an NH2 terminus identical to that of mature mMCP-7, and was not covalently bound to any protease inhibitor. Comparative protein modeling and electrostatic calculations disclosed that mMCP-6 contains a prominent Lys/Arg-rich domain on its surface, distant from the active site. The absence of this domain in mMCP-7 provides an explanation for its selective dissociation from the exocytosed macromolecular complex. The retention of exocytosed mMCP-6 in the extracellular matrix around activated tissue mast cells suggests a local action. In contrast, the rapid dissipation of mMCP-7 from granule cores and its inability to be inactivated by circulating protease inhibitors suggests that this tryptase cleaves proteins located at more distal sites.

Challenges at the frontiers of structural biology.

Knowledge of the three-dimensional structures of proteins is the key to unlocking the full potential of genomic information. There are two distinct directions along which cutting-edge research in structural biology is currently moving towards this goal. On the one hand, tightly focused long-term research in individual laboratories is leading to the determination of the structures of macromolecular assemblies of ever-increasing size and complexity. On the other hand, large consortia of structural biologists, inspired by the pace of genome sequencing, are developing strategies to determine new protein structures rapidly, so that it will soon be possible to predict reasonably accurate structures for most protein domains. We anticipate that a small number of complex systems, studied in depth, will provide insights across the field of biology with the aid of genome-based comparative structural analysis.

Protein structure prediction and structural genomics.

Genome sequencing projects are producing linear amino acid sequences, but full understanding of the biological role of these proteins will require knowledge of their structure and function. Although experimental structure determination methods are providing high-resolution structure information about a subset of the proteins, computational structure prediction methods will provide valuable information for the large fraction of sequences whose structures will not be determined experimentally. The first class of protein structure prediction methods, including threading and comparative modeling, rely on detectable similarity spanning most of the modeled sequence and at least one known structure. The second class of methods, de novo or ab initio methods, predict the structure from sequence alone, without relying on similarity at the fold level between the modeled sequence and any of the known structures. In this Viewpoint, we begin by describing the essential features of the methods, the accuracy of the models, and their application to the prediction and understanding of protein function, both for single proteins and on the scale of whole genomes. We then discuss the important role that protein structure prediction methods play in the growing worldwide effort in structural genomics.

Understanding protein folding via free-energy surfaces from theory and experiment.

The ability of protein molecules to fold into their highly structured functional states is one of the most remarkable evolutionary achievements of biology. In recent years, our understanding of the way in which this complex self-assembly process takes place has increased dramatically. Much of the reason for this advance has been the development of energy surfaces (landscapes), which allow the folding reaction to be described and visualized in a meaningful manner. Analysis of these surfaces, derived from the constructive interplay between theory and experiment, has led to the development of a unified mechanism for folding and a recognition of the underlying factors that control the rates and products of the folding process.

Mycotoxin concentrations in rice from three climatic locations in Africa as affected by grain quality, production site, and storage duration.

Information on the mycotoxin contamination of rice in Africa is limited although the risk of contamination is high. In this study, domestic milled rice processed by actors using suboptimal methods was purchased and total fumonisin (FUM), zearalenone, and aflatoxin concentrations determined at 0, 90, and 180 days after storage. Three different climatic locations, Cotonou (Benin) in the Guinea savanna, Yaoundé (Cameroon) in the Tropical forest, and N'diaye (Senegal) in the Sahel, were selected as storage sites. Subsets of the samples collected from Glazoue (Benin), Ndop (Cameroon), and Dagana (Senegal) were stored in plastic woven bags under room conditions in the respective sites with or without calcium oxide (burnt scallop shell-BSS, 0.1% w/w) treatment. Multivariance analysis showed that FUM concentration was positively influenced by the duration of storage only while zearalenone concentration was negatively influenced by relative humidity and head rice but positively by impurities. Zearalenone concentration was also influenced by sample collection/storage location, processing type, and duration of storage. Aflatoxin concentration was influenced negatively by storage room temperature and head rice but positively by impurities and chalky grains. In addition, aflatoxin concentration was influenced by collection/storage location and processing type. BSS treatment followed by storage for 6 months had no effect on the concentration of the three assessed mycotoxins. Strategies to reduce the risk of mycotoxin contamination in study sites will include the improvement of physical rice quality through better pre- and postharvest practices and proper packaging of both treated rice and untreated rice in hermetic systems before marketing and storage.

lynx1, an endogenous toxin-like modulator of nicotinic acetylcholine receptors in the mammalian CNS.

Elapid snake venom neurotoxins exert their effects through high-affinity interactions with specific neurotransmitter receptors. A novel murine gene, lynx1, is highly expressed in the brain and contains the cysteine-rich motif characteristic of this class of neurotoxins. Primary sequence and gene structure analyses reveal an evolutionary relationship between lynx1 and the Ly-6/neurotoxin gene family. lynx1 is expressed in large projection neurons in the hippocampus, cortex, and cerebellum. In cerebellar neurons, lynx1 protein is localized to a specific subdomain including the soma and proximal dendrites. lynx1 binding to brain sections correlates with the distribution of nAChRs, and application of lynx1 to Xenopus oocytes expressing nAChRs results in an increase in acetylcholine-evoked macroscopic currents. These results identify lynx1 as a novel protein modulator for nAChRs in vitro, which could have important implications in the regulation of cholinergic function in vivo.

Appropriate parboiling steaming time at atmospheric pressure and variety to produce rice with weak digestive properties.

Consumers with diabetes mellitus have shown interest in products with low postprandial glucose. To produce rice for this group of consumers, the effect of parboiling steaming time (0, 5, 15, 25, 35, and 45 min) and variety (NERICA1, NERICA7, WITA4, and IR841) on resistant, damaged starch fractions and glycemic response in rats was investigated. Resistant and damaged starch fractions were influenced by variety and steaming time but this was not the case for glycemic index. Nonparboiled NERICA7 and NERICA7 steamed for 25 min recorded the highest (10.07%) and lowest (2.49%) resistant starch fraction, respectively. Resistant starch correlated negatively with protein and sodium and positively with lipids. Damaged starch was high for WITA4 steamed for 45 min (26.80%) and low for nonparboiled NERICA1 (6.59%). Damaged starch correlated positively with lipid content and negatively with ash and total starch content. NERICA7 steamed for 35 min recorded the lowest postprandial glucose level 30 min after feeding (0.16 g/L), while WITA4 steamed for 15, 25, and 35 min and nonparboiled NERICA7 recorded higher levels (0.76, 0.91, 0.84, and 0.76 g/L, respectively). NERICA7 steamed for 35 min recorded both low glycemic and weak digestive properties because the glycemic index was lowest 120 min and increased steadily up to 180 min after feeding. We conclude that the digestive properties of rice depend both on the intrinsic properties of the variety and the parboiling steaming time.

Physicochemical and nutritional properties of rice as affected by parboiling steaming time at atmospheric pressure and variety.

To elucidate the effect of different parboiling steaming time on the physicochemical and nutritional quality of rice, four varieties, NERICA1, NERICA7, IR841, and WITA4, were soaked at the same initial temperature (85°C) and steamed for 5, 15, 25, 35, and 45 min. NERICA7 steamed for 25 min recorded the highest head rice yield (71.9%). Nonparboiled IR841 recorded the shortest cooking time (17.0 min), while NERICA1 steamed for 35 min recorded the longest cooking time (26.1 min). NERICA1 steamed for 45 min was the hardest (63.2 N), while nonparboiled IR841 was the softest (28.7 N). NERICA7 recorded higher peak and final viscosities across all steaming times compared to the other varieties. NERICA7 steamed for 35 and 45 min recorded the lowest total starch (77.3%) and the highest protein (13.2%) content, respectively. NERICA7 steamed for 25 and 45 min recorded the highest phosphorus (0.166%), magnesium (572 mg/kg), and potassium (2290 mg/kg) content, respectively. We conclude that, depending on desired physicochemical and nutritional properties, specific varieties and steaming times can be selected to achieve those outcomes.

Advances in comparative protein-structure modelling.

Comparative modelling of protein 3D structure can now be applied with reasonable accuracy to ten times more protein sequences than the number of experimentally determined protein structures. A protein sequence that has at least 40% identity to a known structure can be modelled automatically with an accuracy approaching that of a low resolution X-ray structure or a medium resolution NMR structure. Currently, the errors in comparative models include mistakes in the packing of sidechains, in the conformation and shifts of the core segments and loops, and, most importantly, in an incorrect alignment of the modelled sequence with related known structures. Nevertheless, the number of applications in which comparative modelling has been proven to be useful has grown rapidly.