Is 'oil pulling' a 'snake oil'? : a clinical trial

The traditional Ayurveda practice of ‘oil pulling’ has become a recent phenomenon and concerns about its efficacy have been raised. Objectives: (1) to determine awareness about the practice of ‘oil pulling’ among a group of young adults, and to determine variations in awareness with respect to socio-demographic factors, oral health behaviours (oral hygiene and dental attendance) and use of natural health products; (2) to determine the effectiveness of ‘oil pulling’ and conventional oral hygiene practice compared to the use of conventional oral hygiene practice alone in terms of oral hygiene and (3) to determine the effectiveness of ‘oil pulling’ and conventional oral hygiene practice compared to the use of conventional oral hygiene practice alone in terms of gingival health. Methods: Group members recruited seventy-four young adults to participate in a clinical trial over a two-month period comparing the effectiveness of (a) ‘oil pulling’ and conventional oral hygiene methods (toothbrush and toothpaste) versus (b) conventional oral hygiene methods alone. Oral hygiene was assessed using the Plaque Index - PI (Silness and Löe, 1964) and the proportion of sites with visible plaque (PVP). Gingival health was assessed using the Gingival Index – GI (Silness and Löe,1963) and the proportion of sites with gingival bleeding (PGB). Participants were block randomized in groups of four to a cross over clinical trial and assessments were conducted at one-month and two-months. Results: Approximately a quarter (28.4%, 21) of participants was aware of the practice of ‘oil pulling’. Awareness of the practice was associated with reported use of natural dental/oral health products (p0.05). There were observed significant differences in gingival health among both the test and control groups from baseline to one-month (p0.05). No significant differences were observed in oral health parameters from one-month to two-month among neither the test nor control groups (p>0.05). Conclusion: Awareness of the practice of ‘oil pulling’ is relatively common and is associated with use of natural dental/oral health products. Findings from the clinical trial failed to support the adjunct use of ‘oil pulling’ in addition to conventional oral hygiene practices.published_or_final_versio

Genome sequence and genetic linkage analysis of Shiitake mushroom _Lentinula edodes_

_Lentinula edodes_ (Shiitake/Xianggu) is an important cultivated mushroom. Understanding the genomics and functional genomics of _L. edodes_ allows us to improve its cultivation and quality. Genome sequence is a key to develop molecular genetic markers for breeding and genetic manipulation. We sequenced the genome of _L. edodes_ monokaryon L54A using Roche 454 and ABI SOLiD genome sequencing. Sequencing reads of about 1400Mb were de novo assembled into a 40.2 Mb genome sequence. We compiled the genome sequence into a searchable database with which we have been annotating the genes and analyzing the metabolic pathways. In addition, we have been using many molecular techniques to analyze genes differentially expressed during development. Gene ortholog groups of _L. edodes_ genome sequence compared across genomes of several fungi including mushrooms identified gene families unique to mushroom-forming fungi. We used a mapping population of haploid basidiospores of dikaryon L54 for genetic linkage analysis. High-quality variations such as single nucleotide polymorphisms, insertions, and deletions of the mapping population formed a high-density genetic linkage map. We compared the linkage map to the _L. edodes_ L54A genome sequence and located selected quantitative trait loci. The Shiitake community will benefit from these resources for genetic studies and breeding.
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Aberrant Transferrin and Ferritin Upregulation Elicits Iron Accumulation and Oxidative Inflammaging Causing Ferroptosis and Undermines Estradiol Biosynthesis in Aging Rat Ovaries by Upregulating NF-Κb-Activated Inducible Nitric Oxide Synthase: First Demonstration of an Intricate Mechanism

We report herein a novel mechanism, unraveled by proteomics and validated by in vitro and in vivo studies, of the aberrant aging-associated upregulation of ovarian transferrin and ferritin in rat ovaries. The ovarian mass and serum estradiol titer plummeted while the ovarian labile ferrous iron and total iron levels escalated with age in rats. Oxidative stress markers, such as nitrite/nitrate, 3-nitrotyrosine, and 4-hydroxy-2-nonenal, accumulated in the aging ovaries due to an aberrant upregulation of the ovarian transferrin, ferritin light/heavy chains, and iron regulatory protein 2(IRP2)-mediated transferrin receptor 1 (TfR1). Ferritin inhibited estradiol biosynthesis in ovarian granulosa cells in vitro via the upregulation of a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p65/p50-induced oxidative and inflammatory factor inducible nitric oxide synthase (iNOS). An in vivo study demonstrated how the age-associated activation of NF-κB induced the upregulation of iNOS and the tumor necrosis factor α (TNFα). The downregulation of the keap1-mediated nuclear factor erythroid 2-related factor 2 (Nrf2), that induced a decrease in glutathione peroxidase 4 (GPX4), was observed. The aberrant transferrin and ferritin upregulation triggered an iron accumulation via the upregulation of an IRP2-induced TfR1. This culminates in NF-κB-iNOS-mediated ovarian oxi-inflamm-aging and serum estradiol decrement in naturally aging rats. The iron accumulation and the effect on ferroptosis-related proteins including the GPX4, TfR1, Nrf2, Keap1, and ferritin heavy chain, as in testicular ferroptosis, indicated the triggering of ferroptosis. In young rats, an intraovarian injection of an adenovirus, which expressed iron regulatory proteins, upregulated the ovarian NF-κB/iNOS and downregulated the GPX4. These novel findings have contributed to a prompt translational research on the ovarian aging-associated iron metabolism and aging-associated ovarian diseases

Cigarette Smoking Accelerated Brain Aging and Induced Pre-Alzheimer-Like Neuropathology in Rats

Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD). To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD) rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP) processing by increasing the production of sAPPβ and accumulation of β–amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia

University Staff’s Perceptions of Community College Transfer Students’ Transition Experiences Within a “2+2” Pathway in an Asian Educational Context

Various countries have alternative pathway policies for 2-year community college graduates to articulate to 2-year university study, forming a “2+2” pathway. However, few studies have explored university staff members’ perceptions of this “2+2” transfer pathway and their understanding of transfer students’ (TSs) transition experiences. This descriptive qualitative study addressed this research gap. Forty-two academic and supporting staff participated in the focus group interviews. Specifically, the study explored the assets and challenges of the “2+2” pathway from the university staff perspective in Hong Kong. The articulation pathway and TSs are highly recognized for their prior learning, academic performances, and the value of the second chance. However, while the university staff were sympathetic to the challenges filling these transfer pathways, their offering of help was limited by government funding and policies restrictions. It is recommended that policies should be established at government and university levels to recognize and tackle TSs’ unique needs to alleviate their heavy workloads through better articulation between community college and university studies. Improving articulation will allow TSs time for social involvement in university life and thus enhance their mental well-being

Influência do regime alimentar sobre os parâmetros de crescimento de borregas merinas.

O presente trabalho teve por objetivo avaliar o efeito que três suplementos alimentares (alimento composto comercial (CP), farinha forrageira de milho (FM) e cladódios de Opuntia ficus-indica (OFI)) tiveram sobre os indicadores de crescimento de borregas de substituição de raça Merino Branco alimentadas com feno de consociação (F), como alimento forrageiro base em regime ad libitum controlado, assim como a ingestão de água. Os 24 animais selecionados foram organizados em grupos de 8 borregas cada um, homogéneos em relação ao peso vivo, à idade e ao ganho de peso médio diário do nascimento até ao início do ensaio. Cada grupo de 8 borregas foi organizado em quatro subgrupos de 2 borregas cada um e o controlo da ingestão alimentar foi feito para cada um destes subgrupos. Para cada tratamento avaliou-se os seguintes parâmetros de crescimento e de consumo de alimentos: peso vivo; ganho de peso diário; consumo de feno (MS); consumo de cada um dos suplementos alimentares (MS); consumo de MS/kg0,75; consumo de PB/kg0,75; consumo de EM/kg0,75; consumo de NDF/kg0,75; consumo de NFC/kg0,75; índice de conversão alimentar (kg MS/kg PVG); consumo de água; ingestão total de água. Durante os 63 dias de ensaio, verificou-se que as borregas submetidas ao regime alimentar CP+F (T1) apresentaram maior ingestão (p≤0,05) de MS, MS/kg PV0,75, C, NDF, ADF, PB, PB/kg PV0,75, GB, EM e H2O e menor ingestão (p≤0,05) de NFC e de NFC/kg PV0,75. No regime alimentar FM+F (T2), verificou-se maior ingestão (p≤0,05) de NFC/kg PV0,75 e menor ingestão (p≤0,05) de C. No regime alimentar OFI+FM+F (T3) as borregas ingeriram menos (p≤0,05) NDF, PB/kg PV0,75 e H2O. Não se encontraram diferenças estatísticas significativas entre os tratamentos T2 e T3 relativamente à ingestão média diária de MS, de EM, de PB, de NDF e de ADF (p≤0,05). O maior consumo de H2O foi apresentado no T1 (2,037 kg/dia) (p≤0,05), seguido das borregas do T2 (1,459 kg/dia). O menor consumo médio diário de H2O de bebida ocorreu nas borregas do T3 (0,277 kg/dia ±0,038) (p≤0,05), no entanto as borregas do T3 apresentaram o maior CTH2O (3,900 kg/dia) (p≤0,05). As borregas do T1 apresentaram GPD significativamente mais elevado (0,180 kg/dia ±0,009) (p≤0,05) do que as borregas do T2 e T3 (0,110 kg/dia ±0,020 e 0,131 kg/dia 0,006 respetivamente). No final do ensaio, as borregas do T3 alimentadas com OFI+FM+F apresentaram PV semelhante (29,5 kg; p≤0,05) às borregas do T2 alimentadas com FM+F (27,94 kg), porém inferiores (p≤0,05) às borregas do T1 alimentadas com CP+F (33,01 kg). Considera-se que a baixa concentração proteica dos 2 regimes alimentares OFI+FM+F (85,54 g PB/kg MS ±0,560) e FM+F (84,76 g PB/kg MS ±0,367) terá afetado o crescimento dos animais relativamente aos animais alimentados com CP+F (148,62 g PB/kg MS ±2,914).The objective of this study was to evaluate the effect of three feed supplements (commercial compound (CC), corn flour (CF) and Opuntia ficus-indica (OFI) cladodes) on the growth indicators of Merino Branco female lambs, fed as forage with hay (H) of association based on controlled ad libitum regime, as well water intake. The 24 animals selected were organized in groups of 8 lambs each, homogeneous in relation to live weight, age and average daily weight gain from birth until the beginning of the test. Each group of 8 lambs was organized in four subgroups of 2 lambs each and the food intake control was done for each of these subgroups. For each treatment the following growth and food consumption parameters were evaluated: live weight; daily weight gain; hay consumption (DM); consumption of each dietary supplements (DM); consumption of DM/kg0,75; consumption of CP/kg0,75; consumption of ME/kg0,75; consumption of NDF/kg0,75; consumption of NFC/kg0,75; feed conversion index (kg DM/kg DWG); water consumption; total water intake. During the 63 test days, it has been found that lambs submitted on the diet CC+H (T1) presented the highest intake (p≤0.05) of DM, DM/kg LW0,75, A, NDF, ADF, CP, CP/kg LW0,75, CF, ME and H2O, and the lowest intake (p≤0.05) of NFC and NFC/kg LW0,75. In the CF+H diet (T2), it was verified the highest intake (p≤0.05) of NFC/kg LW0,75 and the lowest intake (p≤0.05) of A. In the OFI+CF+H diet (T3) the lambs ingested less (p≤0.05) NDF, CP/kg LW0,75 and H2O. No statistically significant differences were found between treatments T2 and T3 in relation to the mean daily intake of DM, ME, CP, NDF and ADF (p≤0.05). The T1 showed the highest H2O intake (2.037 kg/day) (p≤0.05), followed by the lambs of T2 (1.459 kg/day). The lowest daily H2O intake occurred in the lambs of T3 (0.277 kg/day ±0.038) (p≤0.05), however the lambs of T3 showed the highest TH2OI (3.900 kg/day) (p≤0.05). The lambs of T1 presented significantly higher DWG (0.180 kg/day ±0.009) (p≤0.05) than lambs of T2 and T3 (0.110 kg/day ±0.020 and 0.131 kg/day 0.006 respectively). At the end of the test, the lambs fed with OFI+CF+H (T3) showed a LW similar (29.5 kg; p≤0.05) to the lambs fed with CF+H (T2) (27.94 kg) but lower (p≤0.05) than the animals fed with CC+H (T1) (33.01 kg). It was considered that the low protein concentration of the 2 feed treatments OFI+CF+H (85.54 g CP/kg DM ±0,560) and CF+H (84.76 g CP/kg DM ±0,367) will have affected the growth of the animals compared to animals feed with CC+H (148.62 g CP/kg DM ±2.914)

A Recombination Hotspot in a Schizophrenia-Associated Region of GABRB2

Background: Schizophrenia is a major disorder with complex genetic mechanisms. Earlier, population genetic studies revealed the occurrence of strong positive selection in the GABRB2 gene encoding the β2 subunit of GABAA receptors, within a segment of 3,551 bp harboring twenty-nine single nucleotide polymorphisms (SNPs) and containing schizophrenia-associated SNPs and haplotypes. Methodology/Principal Findings:In the present study, the possible occurrence of recombination in this 'S1-S29' segment was assessed. The occurrence of hotspot recombination was indicated by high resolution recombination rate estimation, haplotype diversity, abundance of rare haplotypes, recurrent mutations and torsos in haplotype networks, and experimental haplotyping of somatic and sperm DNA. The sub-segment distribution of relative recombination strength, measured by the ratio of haplotype diversity (Hd) over mutation rate (θ), was indicative of a human specific Alu-Yi6 insertion serving as a central recombining sequence facilitating homologous recombination. Local anomalous DNA conformation attributable to the Alu-Yi6 element, as suggested by enhanced DNase I sensitivity and obstruction to DNA sequencing, could be a contributing factor of the increased sequence diversity. Linkage disequilibrium (LD) analysis yielded prominent low LD points that supported ongoing recombination. LD contrast revealed significant dissimilarity between control and schizophrenic cohorts. Among the large array of inferred haplotypes, H26 and H73 were identified to be protective, and H19 and H81 risk-conferring, toward the development of schizophrenia. Conclusions/Significance: The co-occurrence of hotspot recombination and positive selection in the S1-S29 segment of GABRB2 has provided a plausible contribution to the molecular genetics mechanisms for schizophrenia. The present findings therefore suggest that genome regions characterized by the co-occurrence of positive selection and hotspot recombination, two interacting factors both affecting genetic diversity, merit close scrutiny with respect to the etiology of common complex disorders. © 2010 Ng et al

Alternative-Splicing in the Exon-10 Region of GABAA Receptor β2 Subunit Gene: Relationships between Novel Isoforms and Psychotic Disorders

BACKGROUND: Non-coding single nucleotide polymorphisms (SNPs) in GABRB2, the gene for beta(2)-subunit of gamma-aminobutyric acid type A (GABA(A)) receptor, have been associated with schizophrenia (SCZ) and quantitatively correlated to mRNA expression and alternative splicing. METHODS AND FINDINGS: Expression of the Exon 10 region of GABRB2 from minigene constructs revealed this region to be an "alternative splicing hotspot" that readily gave rise to differently spliced isoforms depending on intron sequences. This led to a search in human brain cDNA libraries, and the discovery of two novel isoforms, beta(2S1) and beta(2S2), bearing variations in the neighborhood of Exon-10. Quantitative real-time PCR analysis of postmortem brain samples showed increased beta(2S1) expression and decreased beta(2S2) expression in both SCZ and bipolar disorder (BPD) compared to controls. Disease-control differences were significantly correlated with SNP rs187269 in BPD males for both beta(2S1) and beta(2S2) expressions, and significantly correlated with SNPs rs2546620 and rs187269 in SCZ males for beta(2S2) expression. Moreover, site-directed mutagenesis indicated that Thr(365), a potential phosphorylation site in Exon-10, played a key role in determining the time profile of the ATP-dependent electrophysiological current run-down. CONCLUSION: This study therefore provided experimental evidence for the importance of non-coding sequences in the Exon-10 region in GABRB2 with respect to beta(2)-subunit splicing diversity and the etiologies of SCZ and BPD

Occurrence of Highly Conjugative IncX3 Epidemic Plasmid Carrying blaNDM in Enterobacteriaceae Isolates in Geographically Widespread Areas

The emergence of New Delhi metallo-β-lactamase (NDM) in common enterobacterial species is a major concern for healthcare. Early reports have revealed that the spread of NDM involved diverse and heterogeneous plasmids. Recently, the involvement of a rare, IncX3 subtype plasmid has been increasingly recognized. Here, we studied the prevalence of IncX plasmid subtypes in 198 carbapenem-resistant Enterobacteriaceae, originating from a territory-wide active surveillance in Hong Kong in 2016. The complete sequences and biological features of the blaNDM-carrying plasmids were investigated. A total of 62 NDM-type, 21 OXA-48 type, 14 IMP-type, 8 KPC-type, 4 IMI-type producers, and 89 non-carbapenemase-producers were tested for presence of IncX subtypes. IncX3 (n = 60) was the most common subtype, followed by IncX4 (n = 6) and IncX1 (n = 2). The prevalence of IncX3 subtype in isolates producing NDM, other carbapenemase types and non-carbapenemase producers were 75.8, 21.3, and 3.4%, respectively (P < 0.001). An IncX3 plasmid (size ∼50 kb) was confirmed to carry blaNDM in 47 isolates of different enterobacterial species. Thirteen IncX3 plasmids originating from six healthcare regions in Hong Kong were completely sequenced. The results showed that the IncX3 plasmids carrying blaNDM share a high degree of sequence identity with a previously reported plasmid, pNDM-HN380 (GenBank accession JX104760), over the backbone and genetic load regions. A blast search further revealed the occurrence of identical or nearly identical IncX3 plasmids carrying blaNDM in other part of China, Korea, Myanmar, India, Oman, Kuwait, Italy, and Canada. Two IncX3 carrying blaNDM were investigated further. Conjugation experiments demonstrated that the IncX3 plasmids could be efficiently transferred to multiple enterobacterial species at frequencies that are comparable or higher than the epidemic IncFII plasmid carrying blaCTX-M (pHK01). In addition, efficient transfer of the NDM plasmids occurred over a range of temperatures. In conclusion, this study demonstrated the important role played by IncX3 in the dissemination of NDM and the occurrence of pNDM-HN380-like plasmids in geographically widespread areas. The high mobility of IncX3 plasmid across different enterobacterial species highlights the ability of this plasmid replicon to be an important vehicle in worldwide dissemination of NDM

A systematic review of quality and consistency of clinical practice guidelines on the primary prevention of food allergy and atopic dermatitis

Background and aims: With an increasing number of Clinical Practice Guidelines (CPGs) addressing primary prevention of food allergy and atopic dermatitis, it is timely to undertake a comprehensive assessment of the quality and consistency of recommendations and evaluation of their implementability in different geographical settings. Methods: We systematically reviewed CPGs from 8 international databases and extensive website searches. Seven reviewers screened records in any language and then used the AGREE II and AGREE REX instruments to critically appraise CPGs published between January 2011 and April 2022. Results: Our search identified 2138 relevant articles, of which 30 CPGs were eventually included. Eight (27%) CPGs were shortlisted based on our predefined quality criteria of achieving scores \u3e70% in the “Scope and Purpose” and “Rigour of Development” domains of the AGREE II instrument. Among the shortlisted CPGs, scores on the “Applicability” domain were generally low, and only 3 CPGs rated highly in the “Implementability” domain of AGREE-REX, suggesting that the majority of CPGs fared poorly on global applicability. Recommendations on maternal diet and complementary feeding in infants were mostly consistent, but recommendations on use of hydrolysed formula and supplements varied considerably. Conclusion: The overall quality of a CPG for Food Allergy and Atopic Dermatitis prevention did not correlate well with its global applicability. It is imperative that CPG developers consider stakeholders’ preferences, local applicability, and adapt existing recommendations to each individual population and healthcare system to ensure successful implementation. There is a need for development of high-quality CPGs for allergy prevention outside of North America and Europe. PROSPERO registration number: CRD42021265689