Notes

The outcome associated with Narrow-band Image around the Pre- and also Intra- surgical Assessments associated with Neoplastic and also Preneoplastic Laryngeal Skin lesions. A planned out Evaluate.
Hip and knee osteoarthritis (OA) affect a large and growing proportion of the population. Treatment options are typically conservative making self-management a priority. Using trained peers to support individuals with OA has potential to improve self-management.

To explore the process of engaging and training volunteers to become peer mentors; and to qualitatively evaluate the feasibility, acceptability and value of being a peer mentor to support others' self-management of OA.

A qualitative evaluation of a peer mentorship support intervention reporting the processes of recruitment and training; and semi-structured interviews conducted with nine active peer mentors. Transcribed interviews were coded and analysed using framework analysis.

It was possible to recruit, train and retain volunteers with OA to become peer mentors. The peer mentors benefitted from their training and felt equipped to deliver the intervention. They enjoyed social elements of the mentorship intervention and gained satisfaction thral to peer mentors' sustained engagement with the intervention.
Training volunteers with OA to become peer mentors was feasible and acceptable. Peer mentors perceived their support benefitted others with OA. They positively rated their experience of providing mentorship support.IMPLICATIONS FOR REHABILITATIONThis study demonstrates that it is possible to recruit, train and engage older volunteers to become peer mentors for people with osteoarthritis.Training should highlight the significance of employing key self-management techniques such as goal-setting.Peer mentors acknowledged that they benefitted from training and delivering the mentorship intervention, and this impacted positively on their own osteoarthritis self-management.Careful consideration of matching mentors and mentees appears to enhance the success of mentorship support.Recognising the impact of mentorship support on mentees' self-management is central to peer mentors' sustained engagement with the intervention.
To quantify employment stability of individuals with traumatic brain injury (TBI) who received comprehensive vocational rehabilitation (VR) using different measures to identify difficulties experienced and factors associated with employment stability.

72 individuals with predominantly moderate-severe TBI were interviewed. Neuropsychological assessment scores were collected. Three employment stability measures were used number of post-injury employers, duration with employer and average weekly hours. Descriptive and predictive analyses were performed.

90.2% remained employed at time of interview (Mean = 4.83 years post-injury). However, participants worked significantly fewer hours, 63.9% had changed roles or employers at least once and only 51% achieved their pre-injury level of responsibility. 61% reported a high level of employer support. Self-reported difficulties included physical sequelae, memory problems and fatigue. Post-injury testing found impaired memory (34.4%) and processing speed (49.2%). Ae employer and the employee in adjusting to these.VR should be individualised to support the impact of the unique cognitive and physical limitations experienced by each individual with TBI, based on the needs and employment demands of each workplace.
To characterise the assessments and treatments that comprise "usual care" for stroke patients with somatosensory loss, and whether usual care has changed over time.

Comparison of cross-sectional, observational data from (1) Stroke Foundation National Audit of Acute (2007-2019) and Rehabilitation (2010-2018) Stroke Services and (2) the SENSe Implement multi-site knowledge translation study with occupational therapists and physiotherapists (
 = 115). Descriptive statistics, random effects logistic regression, and content analysis were used.

Acute hospitals (
 = 172) contributed 24 996 cases across audits from 2007 to 2019 (median patient age 76 years, 54% male). Rehabilitation services (
 = 134) contributed organisational survey data from 2010 to 2014, with 7165 cases (median 76 years, 55% male) across 2016-2018 clinical audits (
 = 127 services). Somatoensory assessment protocol use increased from 53% (2007) to 86% (2019) (odds ratio 11.4, 95% CI 5.0-25.6). Reported use of sensory-specific retrainingining to benefit patients.
Sensory assessment protocol use has increased over time while sensory-specific training has remained stable. Sensory rehabilitation in the context of everyday activities is a common treatment approach. Clinical trial registration number ACTRN12615000933550IMPLICATIONS FOR REHABILITATIONOnly a small proportion of upper limb assessments conducted with stroke patients focus specifically on sensation; increased use of standardised upper limb assessments for sensory loss is needed.Stroke patients assessed as having upper limb sensory loss frequently do not receive treatment for their deficits.Therapists typically use everyday activities to treat upper limb sensory loss and may require upskilling in sensory-specific retraining to benefit patients.Chronic limb-threatening ischemia (CLTI) is associated with a short-term risk of limb loss. Multidisciplinary teams are often involved in CLTI treatment; however, in Asian countries, multidisciplinary teams that include podiatrists specializing in foot wounds and vascular surgeons who can perform distal bypass surgery are lacking. We investigated predictive factors for limb salvage and foot ulcer recurrence in patients with CLTI treated by a Japanese single-center intensive multidisciplinary team over 6 years. We retrospectively investigated 84 patients with CLTI and foot ulcers who had undergone revascularization and wound treatment between October 2013 and December 2019. Following postrevascularization treatment, including undertaking minor amputations, the healing rate was 77.8%, and the average wound healing time was 75 ± 68 days. To achieve adequate blood supply, 17.7% of patients were treated using a combination of endovascular revascularization and bypass surgeries. Thirty-three (44%) patients had wound recurrence and there was wound recurrence within 6 months in 58.9% of these patients. Multivariate logistic regression analysis showed that postrevascularization skin perfusion pressure was significantly associated with wound healing (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.033-1.243, P = .0078). Diabetes mellitus (OR 9.72, 95% CI 1.855-50.937, P = .0071), and heart disease (OR 3.51, 95% CI 1.052-11.693, P = .0411) were significantly associated with wound recurrence (P  less then  .05). Treatment within a single-center intensive multidisciplinary team resulted in good patient outcomes. Our study indicates that the revascularization endpoint of CLTI treatment should be marked by attainment of adequate blood supply and wound healing. The timing of revascularization and debridement is of utmost importance for the successful treatment of CLTI wounds.
The potential of multi-walled carbon nanotubes (MWCNTs) in inducing airway hyperresponsiveness (AHR) was investigated in human airways.

Human isolated bronchi were exposed to MWCNTs and the contractility to electrical field stimulation (EFS) was measured. Neuronal acetylcholine (ACh) and cyclic adenosine monophosphate (cAMP) were quantified. Some tissues were desensitized by consecutive administrations of capsaicin.

MWCNTs (100ng/ml - 100µg/ml) induced AHR (overall contractile tone vs. negative control +83.43±11.13%, P <0.01). The potency was significantly (P<0.05) greater when airways were stimulated at low frequency (EFS
) then at medium-to-high frequencies (EFS
and EFS
) (delta potency +2.13±0.74 and +2.40±0.65 logarithms, respectively). In capsaicin-desensitized airways, the AHR to MWCNTs 100ng/ml was abolished. MWCNTs increased the release of ACh, an effect prevented by capsaicin-desensitization (-90.17±18.59%, P <0.05). MWCNTs did not alter the level of cAMP.

MWCNTs administered at low concentrations elicit AHR in human airways by activating sensory C-fibers and, in turn, increasing the release of neuronal ACh. Our results suggest that work is required to understand the impact of MWCNTs in patients at risk of AHR, such as those suffering from chronic obstructive respiratory disorders.
MWCNTs administered at low concentrations elicit AHR in human airways by activating sensory C-fibers and, in turn, increasing the release of neuronal ACh. Our results suggest that work is required to understand the impact of MWCNTs in patients at risk of AHR, such as those suffering from chronic obstructive respiratory disorders.
The purpose of this study was to check whether the impact of abnormal vaginal colonization on perinatal outcomes would be different in patients with preterm labor (PTL) and premature membrane rupture (PPROM). We also sought to determine the concordance rate of microorganisms isolated from the maternal vagina and neonatal blood in cases of early-onset neonatal sepsis (EONS) in PTL and PPROM.

This retrospective study included 996 singleton pregnancies who were admitted to the high risk care unit of our institution due to PTL (
 = 519) or PPROM (
 = 477) and underwent vaginal culture examination at admission between January 2005 and April 2019. Abnormal vaginal colonization was defined upon isolation of aerobic microorganisms. The maternal baseline characteristics, delivery, and neonatal outcomes were compared according to the presence or absence of abnormal vaginal flora, both in PTL and PPROM.

The rate of abnormal vaginal colonization in PTL and PPROM was 17.0 and 21.4%, respectively. Both in PTL and Pk factor for EONS.
Our data showed that maternal vaginal colonization in PPROM, but not in PTL, is an independent risk factor for EONS.
Neuroimaging findings suggest that older adults with subjective memory decline (SMD) demonstrate some neurodegenerative brain changes and have high risk of developing dementia, but relatively little is known about the effectiveness of interventions for SMD. This study aimed to examine the effects of cognitive training on resting-state brain activity in SMD.

This study employed the amplitude of low frequency fluctuations (ALFF) and resting state functional connectivity (rs-FC) analyses. After baseline evaluations, participants were randomly allocated to the intervention and control group to receive a four-week cognitive training and lectures on health and aging, respectively. All participants were scanned before and after training with an interval of about three months.

(1) Participants in the intervention group showed significant improvements on the Associative Learning Test (ALT) and the Digit Span Forward task compared to the control group; (2) ALFF in the occipital lobe for the control group increased significantly, while that for the intervention group remained the same; ALFF changes were negatively correlated with ALT performance in the control group; (3) The mean value of rs-FC for the intervention group decreased, while that for the control group showed a trend of increase; rs-FC changes were also negatively correlated with ALT performance in the control group.

Resting-state brain activities in occipital region increased with aging. The cognitive training could counteract this brain function changes associated with aging or even reverse the changes. These findings provide new insights into the understanding of brain plasticity in posterior areas in SMD.

ChiCTR-IOR-15006165 in the Chinese Clinical Trial Registry.
ChiCTR-IOR-15006165 in the Chinese Clinical Trial Registry.
To analyse the cumulative incidence of any failure (AF), prostate cancer-specific failure (PCSF), any death (AD), prostate cancer-specific death (PCSD), and local control in 2387 men with prostate cancer (PC), consecutively treated with combined high-dose-rate brachytherapy (HDRBT) and external beam radiotherapy (EBRT) from 1998 to 2010.

A retrospective, single-institution study of men with localised PC. The mean age was 66 years and 54.7% had high-risk PC according to the Cambridge prognostic group (CPG) classification. The treatment was delivered as EBRT (2 Gy × 25) and HDRBT (10 Gy × 2) with combined androgen blockade (CAB). The median follow-up was 10.2 years.

The cumulative incidence of PCSD at 10 years was 5% [CI 95% 0.04-0.06]. The 10 years PCSD per risk group were low (L) 0.4%, intermediate favourable (IF) 1%, intermediate unfavourable (IU) 4.3%, high-risk favourable (HF) 5.8%, and high-risk unfavourable (HU) 13.9%. The PCSF rate at 10 years was 16.5% [CI 95% 0.15-0.18]. The PCSF per risk group at 10 years were L 2.5%, IF 5.5%, IU 15.9%, HF 15.6%, and HU 38.99%. PCSF occurred in 399 men, of whom 15% were found to have local failure. The estimated frequency of local failure in the entire cohort was 1.2%.

HDRBT combined with EBRT is an effective treatment with long-term overall survival and excellent local control for patients with PC. The low rate of local recurrence among men with relapse suggests that these patients were micro metastasised at time of treatment, which calls for improved methods to detect disseminated disease.
HDRBT combined with EBRT is an effective treatment with long-term overall survival and excellent local control for patients with PC. The low rate of local recurrence among men with relapse suggests that these patients were micro metastasised at time of treatment, which calls for improved methods to detect disseminated disease.Spatial suppression of a salient colour distractor is achievable via statistical learning. Distractor suppression attenuates unwanted capture, but at the same time target selection at the most likely distractor location is impaired. This result corroborates the idea that the distractor salience is attenuated via inhibitory signals applied to the corresponding location in the priority map. What is less clear, however, is whether lingering impairment in target selection when the distractor is removed are due to the proactive strategic maintenance of the suppressive signal at the previous most likely distractor location or result from the fact that suppression has induced plastic changes in the priority map, probably changing input weights. Here we provide evidence that supports the latter possibility, as we found that impairment in target selection persisted even when the singleton distractor in the training phase became the target of search in a subsequent test phase. This manipulation rules out the possibility that the observed impairments at the previous most likely distractor location were caused by a signal suppression maintained at this location. Rather, the results reveal that the inhibitory signals cause long-lasting changes in the priority map, which affect future computation of the target salience at the same location, and therefore the efficiency of attentional selection.
The effects of task-specific and voluntary exercise in upright positions for pusher behavior remain unclear. In this report, we aimed to describe the effects of dynamic supported standing training using a modified standing frame to correct the alignment in a patient with severe pusher behavior.

A 76-year-old man with cardioembolic ischemic stroke demonstrated pusher behavior. The patient underwent 3days of dynamic supported standing training using a modified standing frame. The Scale for Contraversive Pushing, the Burke Lateropulsion Scale, and the Trunk Control Test were used to assess changes.

Immediate improvements in sitting balance were observed after the intervention, and the effects persisted to 8days later.

Dynamic supported standing training using a modified standing frame may improve pusher behavior with short-term training. The collapsed posture of the patient in the present case was corrected using the modified standing frame. This neutral standing position could have a positive effect on motor learning with respect to holding one's posture.
Dynamic supported standing training using a modified standing frame may improve pusher behavior with short-term training. The collapsed posture of the patient in the present case was corrected using the modified standing frame. This neutral standing position could have a positive effect on motor learning with respect to holding one's posture.Acute myeloid leukemia (AML) is a highly malignant blood cancer disease, with dismal prognosis. The theory that cancer cells utilize metabolism to their growth advantage was postulated almost hundred years ago. However, only recently have been able to take advantage of this Achilles heel of malignant cell growth. Current observations suggest a crucial role for various metabolic pathways in AML, and special in leukemia stem cells, believed to be responsible for re-initiation of the leukemic clone, and hence relapse of this devastating disease. In the present article we discuss the features for metabolism in AML based on recent research, and special emphasizing the potential of pharmacological inhibiting metabolism as new treatment approaches.Spectroscopic signatures of cased high-explosive charge denotations are examined using emission spectroscopy with sub nanometer resolution. Eleven distinct case materials are investigated for atomic features of their major alloying elements. Molecular features of case material combustion products are also investigated for five case materials. Emission is monitored within the 275-425 nm range for atomic features and in the 310-755 nm range for molecular features. Major alloying elements with concentrations greater than 5% are generally detected through atomic emission. Al, Cu, Fe, Mg, Cr, Mn, Pb, and Ni are all detected in concentrations less than 5%. Undetected elements include Zn, Nb, Ta, and V. Molecular emission from aluminum monoxide, titanium monoxide, and CN is measured for aluminum alloy, titanium alloy, and carbon fiber cases, respectively.
Dapivirine (DPV), formulated as vaginal ring, demonstrated HIV risk reduction. MTN-026 explored DPV, formulated as rectal gel, for safety, pharmacokinetics, and acceptability.

HIV-uninfected men and women aged 18-45 years were enrolled at United States and Thailand sites and randomized 21 to receive DPV 0.05% or placebo gel via rectal applicator. A single dose phase was followed by 7 observed daily doses. Plasma, and fluid and tissue from both rectum and cervix were collected at baseline and after the final dose over 72 hours for pharmacokinetics, ex-vivo HIV-1 biopsy challenge, histology, and flow cytometry.

28 participants were randomized; 2 terminated early; 9 were female and 19 male; 12 were white, 11 Asian, 4 black and 1 other race/ethnicity. Mean age was 28.5 and 34.2 years in the DPV and placebo arms, respectively. Thirty adverse events occurred (all Grade 1 or 2, except one unrelated Grade 3) without study arm differences. DPV rectal tissue concentrations (median [interquartile range]) 0.5-1 and 2 hours after a single dose were 256 ng/gm (below limit of quantitation [BLQ], 666) and BLQ (BLQ, 600), respectively, then BLQ (BLQ, BLQ) from 24-72 hours; concentrations following multiple doses were similar. The largest median DPV plasma concentrations were 0.33 ng/mL (0.15, 0.48) after one dose and 0.40 (0.33, 0.49) after seven doses.

The DPV rectal gel was acceptable and without safety concerns. While DPV plasma concentrations were similar to the vaginal ring, rectal tissue concentrations were well below vaginal ring tissue concentrations, suggesting need for reformulation.
The DPV rectal gel was acceptable and without safety concerns. While DPV plasma concentrations were similar to the vaginal ring, rectal tissue concentrations were well below vaginal ring tissue concentrations, suggesting need for reformulation.Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disease caused by recessive mutations in the TYMP gene, which encodes the enzyme thymidine phosphorylase. In this study, the efficient integration of a TYMP transgene into introns of the Tymp and Alb loci of hepatocytes in a murine model of MNGIE was achieved by the coordinated delivery and activity of CRISPR/Cas9 and a TYMP cDNA. CRISPR/Cas9 was delivered either as mRNA using lipid or polymeric nanoparticles (LNP or PNP, respectively) or in an AAV2/8 viral vector; the latter was also used to package the TYMP cDNA. Insertion of the cDNA template downstream of the Tymp and Alb promoters ensured transgene expression. The best in vivo results were obtained using LNP carrying the CRISPR/Cas9 mRNAs. Treated mice showed a consistent long-term (1 year) reduction in plasma nucleoside (thymidine and deoxyuridine) levels that correlated with the presence of TYMP mRNA and functional enzyme in liver cells. In mice with an edited Alb locus, the transgene produced a hybrid Alb-hTP protein that was secreted, with supra-physiological levels of TP activity detected in the plasma. Equivalent results were obtained in mice edited at the Tymp locus. Finally, some degree of gene editing was found in animals treated only with AAV vectors containing the DNA templates, in the absence of nucleases, although there was no impact on plasma nucleoside levels. Overall, these results demonstrate the feasibility of liver-directed genome editing in the long-term correction of MNGIE, with several advantages over other methods.Alzheimer's disease (AD) is a progressive neurodegenerative disorder, for which blocking the early steps of extracellular misfolded amyloid-β (Aβ) aggregation is a promising therapeutic approach. However, the pathological features of AD progression include the accumulation of intracellular tau protein, membrane-catalyzed cell death and the abnormal deposition of Aβ. Here, we focus on anti-amyloid breaker peptides derived from the Aβ sequence and non-Aβ-based peptides containing both natural and modified amino acids. Critical aspects of the breaker peptides include N-methylation, conformational restriction through cyclization, incorporation of unnatural amino acid, fluorinated molecules, polymeric nanoparticles and PEGylation. This review confers a general idea of such breaker peptides with in vitro and in vivo studies, which may advance our understanding of AD pathology and develop an effective treatment strategy against AD.Camellia sinensis (tea) seeds have been identified as potential sources of nutraceutical compounds. In this study, caffeine and theaflavanoside IV were annotated as the most abundant phytochemicals in the seed shells of C. sinensis. Both compound displayed potent inhibitions against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 37.9 ± 3.5 and 8.7 ± 1.1 µM, respectively. In the kinetic study, caffeine inhibited PTP1B with mixed type I mode, which prefers to bind to free enzyme. Theaflavanoside IV showed competitive and reversible simple slow-binding inhibition [k3 = 0.1 µM-1·min-1, k4 = 0.002 min-1, Kiapp = 0.0002 µM]. This is the first report on PTP1B-inhibitory activity of these compounds and their action mechanisms. These results suggest their potential in the development of antidiabetic agents.Juncus effusus L. (J. effusus) is a Traditional Chinese Medicine (TCM) that has long been used for dealing with gynaecological disorders, such as relieving insomnia, preventing tinnitus, reducing edema with diuretic effect. In our course of evidence-based medical research focused on this herb, one new phenanthrene, Junfusol B (2), together with seventeen known compounds were isolated and identified. All the structures of these compounds were elucidated by spectroscopic methods. The absolute stereochemistry of compounds 1 and 2 was further determined by comparing their calculated and experimental Electronic Circular Dichroism (ECD) spectra and optical rotation (OR) values. The isolates were evaluated for their estrogenic and anti-inflammatory activities which were considered as relevant etiological factors of insomnia, tinnitus and edema in the ancient TCM theory. The results revealed that most of the obtained phenanthrenes in this work were found exerting agonistic effects on estrogen receptor. This is the first report to declare the exact estrogen-regulating potential among this type of compounds from J. effusus. Moreover, phenanthrenes 3 - 7 exhibited significant inhibitions on superoxide anion generation and elastase release in fMLP/CB-induced human neutrophilic inflammation model. J. effusus may be developed as a complementary agent utilized in menopausal multiple syndromes.Five new glycosides including mimenghuasu A and B (1-2), isolinarin (3), cyclocitralosides A and B (4-5), along with forty-seven known compounds were isolated from the flower buds of Buddleja officinalis. These structures were elucidated by extensive spectroscopic analysis (UV, IR, 1 D, 2 D NMR, and MS spectra). The anti-inflammatory activities of the isolated compounds were determined by enzyme-linked immunosorbent assay (ELISA) on the expression of TNF-α (LPS-activated RAW264.7 cells) and MTT experiment on LPS-induced HUVECs proliferation effects. Good suppressive effects on the expression of TNF-α were shown by 4 and 5 with IC50 values of 19.35 and 22.10 μM, respectively, compared to positive control indomethacin (IC50 16.40 μM). In addition to this, some isolated compounds exhibited excellent antioxidant activities including compounds 16, 18, 29, 39, and 47 (IC50 μM 82.59, 72.94, 33.65, 46.67, and 20.81, respectively) with almost the same or stronger potency with reference to vitamin C as positive control (IC50 81.83 μM).This research investigates antiviral potential of extracted honeybee products against COVID-19 main protease (Mpro) by computational methods. The crystal structure of COVID-19 Mpro was obtained from the protein data bank. Six synthetic drugs with antiviral properties were used as control samples in order to compare the results with those of natural ligands. The six honeybee components, namely 3,4,5-Tricaffeoylquinic acid, Kaempferol-3-O-glucoside, (E)-2'-Geranyl-3',4',7-Trihydroxyflavanone, 6-Cinnamylchrysin, (+)-Pinoresinol, and (24E)-3-Oxo-27,28-dihydroxycycloart-24-en-26-oic acid, have represented the lowest binding energies of -9.0, -8.5, -8.2, -7.8, -7.7, -7.3 and -6.7 Kcal/mol, respectively. These natural inhibitors were then picked for further investigations on their pharmacokinetic features. Also a 150 ns of Molecular dynamics simulations were carried out in order to evaluate their effects on protein structure and dynamics. The 3, 4, 5-Tricaffeoylquinic acid is hopefully proposed for COVID-19 Mpro inhibition if further in vitro, in vivo, and clinical trial studies will approve its effectiveness against COVID-19.The present study demonstrates the pharmacological tendency of Sideroxylon mascatense leaves extracts, fractions and sub-fractions using thin layer chromatography, column chromatography, and phytochemical (phenolics, flavonoids) and biological assays (free radical scavenging, antioxidative, antimicrobial, enzyme inhibition). The results disclosed that fractionation practice accumulated the active phytochemicals in few fractions and finally leads to the isolation of active compounds. The structural elucidation was carried out using spectroscopic 1D (1H, 13C) 2D NMR and spectrometric techniques. The n-hexane fraction led to isolation of lupeol. From the CHCl3 and EtOAc fractions, two compounds were isolated, hentriacontanol, and lupeol, respectively. The isolated compounds were also characterized for biological activities. This study concludes that bioactivity guided isolation can be performed for isolation of active constituents from S. mascatense which can be further explored for drug development.A new indole diketopiperazine alkaloid, named penilline D (1), together with five known indole alkaloid analogues (2-5, 11), two meroterpenoids (6 and 12), and four butenolide derivatives (7-10), were isolated from the Antarctic fungus Penicillium sp. SCSIO 05705. Extensive spectroscopic analysis and electronic circular dichroism (ECD) calculation were used to elucidate the structure of penilline D (1), including its absolute configuration. All isolated compounds (1-12) were evaluated for their cytotoxic, antibacterial and enzyme inhibitory activities against acetylcholinesterase (AChE) and pancreatic lipase (PL). Among them, compound 5 exhibited moderate in vitro cytotoxic activity against the 143B cell line with IC50 value of 12.64 ± 0.78 μM. Compound 6 showed strong inhibitory activity against AChE with IC50 value of 0.36 nM (IC50 18.7 nM for Tacrine), while compounds 6 and 11 showed weak PL enzyme inhibitory activity. Furthermore, an in silico molecular docking study was also performed between 6 and AChE.Phytochemical investigation of the whole plants of Lycopodiella cernua resulted in the isolation and identification of three new compounds (1-3), namely lycocernuaside E (1), lycernuic ketone F (2), and lycernuic B (3) and 12 known ones (4-15). Their chemical structures were established based on 1 D/2D NMR spectroscopic and HR-ESI-MS data analyses. Compounds 5, 12, and 13 displayed NO inhibitory effects in LPS-stimulated BV2 cells, with IC50 values of 21.2 ± 1.1, 28.5 ± 1.4, and 21.9 ± 1.1 µM, respectively. In addition, cytotoxic activity of the isolated compounds against MCF7 (breast carcinoma), HepG2 (hepatocarcinoma), and SK-Mel2 (melanoma) cancer cell lines were also reported.Fourteen sesquiterpene lactones were isolated from the whole plant of Carpesium abrotanoides L. Their structures were determined on the basis of comprehensive spectroscopic data analysis. All compounds were screened for their cytotoxic activity, and compound 6 showed the strongest activity (IC50 2.73 - 7.21 µM) against five human cancer cell lines, including A549, HepG2, HCT116, MDA-MB-231, and CNE2. Compound 6 was further investigated. Compound 6 effectively induced G2/M cell cycle arrest and ROS accumulation in a dose-dependent manner, which further led to apoptosis in cancer cells. Interestingly, compounds 1 and 6 could also activate protective autophagy, which was reported for the first time in sesquiterpene isolated from Carpesium abrotanoides. In addition, compounds 1 and 6 could induce lysosomal biogenesis by 173.2% and 163.7%, respectively. In sum, sesquiterpene lactones from Carpesium abrotanoides could induce apoptosis and protective autophagy in cancer cells, which provide a serial of compounds with potential clinical applications.Cholinesterase (ChE) inhibitors are currently the main drugs used to treat the cognitive symptoms of Alzheimer's disease (AD). Dual cholinesterase inhibitors, that is, compounds capable of inhibiting both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), are considered a new potential approach for the long-term treatment of patients with AD. We evaluated the ethyl acetate extract of Phomopsis sp., grown in liquid medium malt extract and potato dextrose (PDB), an endophyte isolated from the Brazilian medicinal plant Hancornia speciosa. The anticholinesterase (AChE) and butyrylcholinesterase (BuChE) activities were evaluated. The extracts exhibited dual action against AChE and BuChE. The compounds isolated from these extracts, nectriapyrone (1) and tryptophol (2), showed inhibitory action on BuChE (IC50 = 29.05 and 34.15 μM respectively), being selective towards BuChE. The discovery of selective BuChE inhibitors is extremely important for the development of drugs that can be used in the treatment of patients diagnosed with AD.Sixteen compounds (1-16) were isolated from Impatiens chapaensis. Chemical structures were determined by spectroscopic analyses and comparisons with previously published data. This report is the first to identify compounds 1, 5-7, 10, 12-14, and 16 from the genus Impatiens. Seven chosen isolates (5, 7, 10, 11, 12, 15, and 16) were submitted for α-glucosidase inhibition assays with acarbose as the positive control (IC50 = 227.14 ± 13.71 µM). Flavonoid 5 exhibited a significant inhibitory effect (IC50 = 101.00 ± 9.01 µM).Two new polyisoprenylated benzophenones, planchoniones A (1) and B (2), together with two known benzophenones (3, 4) and six known xanthones (5-10), were isolated from an ethyl acetate extract of the pericarp of Garcinia planchonii Pierre. Their structures were established using spectroscopic methods, mainly 1D and 2D NMR. The four benzophenones were evaluated for their cytotoxicity against MCF-7 human breast cancer cells, and showed almost no activity. Meanwhile, compounds 5-10 were investigated for their inhibitory effects towards α-glucosidase, and γ-mangostin (5) exhibited the most remarkable effect with IC50 value of 15.3 ± 0.9 µM (compared with acarbose, IC50 = 224.9 ± 3.6 µM).A new highly oxygenated cycloheptane derivative crustane (1), along with fourteen known compounds (2-15) were isolated from Penicillium crustosum JT-8. The structure of compound 1 was determined by extensive spectroscopic data, DP4+ probability analyses and dimolybdenum CD method. Compound 1 exhibited moderate antibacterial activity against Staphylococcus aureus with MIC of 4.0 μg/mL.We aimed to evaluate the chemical, antioxidant, cytotoxic, and antifungal activities of hydroalcoholic extracts of native plants from Southern Brazil Schinus terebinthifolia (SCH), Persicaria hydropiperoides (PER), Eugenia uniflora (EUG) and Equisetum hyemale (EQU). Ethyl gallate, quercetin, and quinic acid were prevalent compounds identified by LC-MS. For total phenolic/flavonoid contents and the antioxidant potential against ABTS/DPPH radicals, the ascending order was EQU 75%) at concentrations up to 12.5 mg/mL (MTT assay). By M38-A2/M27-A3 (CLSI) against 68 clinical isolates of animals and strains of Malassezia pachydermatis, Sporothrix brasiliensis, Microsporum canis, Microsporum gypseum and Trichophyton mentagrophytes, all extracts (MIC/MFC ≤3.13-100 mg/mL) were active, except EUG. SCH inhibited and killed S. brasiliensis (MIC/MFC50/90 3.12-12.5 mg/mL) and dermatophytes (MIC/MFC 6.25-25 mg/mL) resistant to ketoconazole and itraconazole. These findings support the promising use of the selected plant extracts as antifungal agents.The present study focuses on the polar constituents and biological effects of the methanol extract and the infusion of wild Sideritis sipylea Boiss. from Samos island (Greece), as well as on the nutritional and mineral contents of this plant. The total phenolic content and antioxidant activity were examined. In addition, the anti-acetylcholinesterase property was evaluated, revealing strictly lower results than the control, galanthamine. Furthermore, the nutritional value of the plant is reported herein for the first time, revealing a promising source of protein. To the best of our knowledge, this study is the first work on the infusion of this species and the nutritional value of the plant.Three previously unreported quinolinone alkaloids melicodenines J-L (1-3) and six known compounds (4-9), were isolated from the leaves of Melicope denhamii (Seem) T.G. Hartley. The structures of three quinolinone alkaloids were identified based on HRESIMS and NMR spectra. Compounds 1-9 were assayed in three cancer cells (MCF-7, HeLa, and P-388). Compounds 1 and 5 showed high cytotoxic activity against HeLa cells with IC50 values of 1.8 and 0.8 µM, respectively.A new muurolane-type sesquiterpene, a new flavone arabinofuranoside derivative, and other five known flavone arabinofuranoside derivatives were isolated from the leaves of Fissistigma bicolor (Annonaceae family). Their chemical structures were determined to be (1S,6R,7S)-muurola-4,10(14)-diene-15-ol (1), quercetin 3-O-β-D-apiofuranosyl-(1→2)-α-L-arabinofuranoside (2), quercetin 3-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinofuranoside (3), quercetin 3-O-α-L-arabinofuranoside (4), kaempferol 3-O-β-D-apiofuranosyl-(1→2)-α-L-arabinofuranoside (5), kaempferol 3-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinofuranoside (6), and kaempferol 3-O-α-L-arabinofuranoside (7) by analyses of HR-ESI-MS and NMR spectral data. Compounds 4 and 7 containing monosaccharide, arabinofuranoside, potentially inhibited NO productions in LPS activated RAW264.7 cells (IC50 13.4 ± 0.5 and 12.6 ± 0.4 µM) in compared to disaccharide derivatives (IC50 ranging from 58.9 ± 3.3 to 65.6 ± 3.8 µM).The hydro-distillation essential oil was obtained from the leaf, stem, and flower of Blumea paniculata (Willd.) M.R.Almeida (Asteraceae) and analysed using gas chromatography equipped with a flame ionisation detector (GC-FID) and gas chromatography coupled with mass spectrometry (GC-MS). Fifty-eight, sixty-nine and, fifty-seven constituents were identified from leaf oil (LO), stem oil (SO) and flower oil (FO), representing 95.8%, 96.3% and 95.1% of the total oil constituents, respectively. The major constituents were identified as germacrene D (39.6-48.1%), α-humulene (4.9-8.9%), β-caryophyllene (4.8-7.7%), and α-cadinol (2.9-6.8%) from different parts of the plant B. paniculata. The oils were found to be rich in sesquiterpenoid-type constituents.A new icetexane diterpenoid, 11, 12, 20α-trihydroxyl-7β-methoxyicetexa-8, 11, 13-triene-19, 10-lactone [Phyllane A (1)], and a new abietane diterpenoid, 7β, 20-epoxy-3β, 17-acetoxy-abieta-8, 11, 13-teriene-11, 12-diol [phyllane B (2)], along with two known compounds (3 and 4) were isolated from the methanol (MeOH) extract of twigs and leaves of the folk medicinal Isodon phyllopodus. Their structures were determined by spectroscopic analyses including 2 D NMR spectral data, and further confirmed by X-ray single crystal diffraction. Moreover, the compounds were evaluated for their cytotoxicity and anti-HIV activities, and phyllane A showed anti-HIV activity with an IC50 value of 15.7 μM, but phyllane B was found to be cytotoxic to the A549 host cells with a CC50 value of 108.5 μM.Three new naphthoquinones, 5,6,7-trimethoxydunnione (1), 6,7-dimethoxy-α-dunnione (2), and 5,6,7-trimethoxydunniol (3) were isolated from the tubers of Sinningia mauroana Chautems, together with eleven known compounds 5-hydroxy-6,7-dimethoxy-α-dunnione (4), 6-hydroxy-7-methoxy-α-dunnione (5), 7-hydroxy-6-methoxy-α-dunnione (6), cedrol (7), tectoquinone (8), plantainoside A (9), calceolarioside A (10), calceolarioside B (11), sanangoside (12), allo-calceolarioside A (13), and conandroside (14). The known compounds 4, 7-9 and 11-13 are being reported for the first time in this species. Hexane, ethyl acetate and ethanol extracts were tested for antioxidant activity by the ORAC-FL method, and the antioxidant capacity was measured as trolox equivalent (TE). The ethyl acetate (8808 µg TE g-1) and ethanol (7911 µg TE g-1) extracts showed high antioxidant capacity, while the hexane extract displayed weak antioxidant capacity (860 µg TE g-1).The present study has tentatively elucidated the structure of two acylated polyoxypregnane glycosides from Caralluma quadrangula (Forssk.) N.E.Br. (CQ). The analyses were performed using an electrospray-ionization quadrupole time-of-flight (ESI-Q-TOF) mass spectrometer in positive ionization modes to explore fragmentation pathways. The used ionization mode provided consistent and/or complementary information for most of the pregnane glycosides, their fragmentation sequences, and their aglycones. Presumably, this is due to higher efficiency, sensitivity, and better selectivity of the mass spectrometry-based method. The present experimental and theoretical report deals with the characteristic fragmentation behaviors of two acylated polyoxypregnane glycosides CQ1 and CQ2 from the aerial parts of C. quadrangular. A DFT Study was performed to elucidate the position of ikemoyl, and benzoyl residues in compounds CQ1 and CQ2, respectively.Two new sclerotioramines (1 and 2) and a new natural product of sclerotioramine analog (3), together with seven known compounds have been isolated from the mangrove endophytic fungus Penicillium sclerotiorin SCNU-F0040. Their structures were identified based on the 1 D, 2 D NMR and HRESIM spectra. The absolute configurations of new compounds were deduced by specific rotation data and electronic circular dichroism spectra. All the isolated new compounds were tested on anti-diabetes activity by using a-glucosidase inhibition assay and anti-inflammatory activity by using cyclooxygenase inhibition assay, respectively. Compounds 1 and 2 have a-glucosidase inhibition activity with IC50 values of 102.3 and 217.5 μM. Compound 2 shows a moderate cyclooxygenase-2 inhibitory activity with an IC50 value of 47.8 μM.A new ingol diterpenoid, namely 3-de-O-acetyleuphornan R (1), along with two known analogues, euphornans E (2) and N (3) were isolated from the seeds of Euphorbia marginata Pursh. The structure of 1 was elucidated by extensive 1H NMR, 13C NMR, HSQC, HMBC, and 1H-1H COSY, and HR-MS spectroscopic analyses.Smoking is a public health concern, and even though smoking cessation methods exist, nicotine replacement therapy (NRT) is often ineffective. Smoking behavior is related to the nicotine metabolizing enzyme (NME) P450 2A6 (mouse 2A5) polymorphisms. Accordingly, fast metabolizers are nicotine dependent, and have low quitting rates compared to slow metabolizers. In this study we examined the ability of Ginkgo biloba L (GB) and its constituents to inhibit the NME, using mouse liver microsomes containing the 2A5 enzyme. Our results indicate that GB can inhibit 2A5 (25% inhibition at 5%v/v), with the flavonoids quercetin, isorhamnetin, and kaempferol being responsible for this inhibition (23.5%, 10.7%, 25.2% inhibition at 60 ng/μL, respectively). Importantly, the flavonoids inhibited 2A5 via mechanism based inhibition (for quercetin 30 ng/μl inhibition increased from 20.8% to 26.9% within 15 minutes). Our results suggest that GB if consumed on a regular basis can help NRT enhancement particularly in fast nicotine metabolizers.A new cyclopentenone derivative, 4-hydroxyhypocrenone A, and a new naturally-occurring wickerol derivative, 8-acetoxywickerol A, as well as two known compounds, hypocrenone A and wickerol B, were purified from Trichoderma atroviride A-YMD-9-4, an endophytic fungus isolated from the marine red alga Gracilaria verrucosa. The structures and relative configurations of two new isolates were established by a combination of 1 D/2D NMR, IR, and mass spectroscopic methods, and the absolute configuration of 1 was assigned on the basis of ECD data analyzed by quantum chemical calculations. Compounds 1 and 2 exhibited weak inhibition of one or two marine phytoplankton species.
This study synthesized evidence regarding the prevalence of post-traumatic stress disorder (PTSD) in the United States (US).

A systematic literature review (SLR) identified recently published (2015-2019) observational studies of PTSD prevalence in the US
the MEDLINE, EMBASE, and PsycINFO databases. Eligible studies' most recent data were collected no earlier than 2013. Data elements extracted included study design, sample size, location, data source/year(s), study population(s), traumatic event type, prevalance estimates with corresponding look-back periods, and clinical metrics.

Data from 38 identified articles were categorized by population, diagnostic criteria, and lookback period. Among civilians, point prevalence ranged from 8.0% to 56.7%, 1-year prevalence from 2.3% to 9.1%, and lifetime prevalence from 3.4% to 26.9%. In military populations, point prevalence ranged from 1.2% to 87.5%, 1-year prevalence from 6.7% to 50.2%, and lifetime prevalence from 7.7% to 17.0%. Within these ranges, severalay allow for a better detection and management of PTSD.
To investigate the role of clinical parameters and immunohistochemical (IHC) biomarkers in their feasibility to predict the effect of neo-adjuvant chemotherapy (NAC) in patients with muscle-invasive urothelial bladder cancer (MIBC).

The first 76 consecutive patients with MIBC treated with NAC and radical cystectomy in two University hospitals in Finland between 2008 and 2013 were chosen for this study. After excluding patients with non-urothelial cancer, less than two cycles of chemotherapy, no tissue material for IHC analysis or non-muscle-invasive bladder cancer in re-review, 59 patients were included in the final analysis. A tissue microarray block was constructed from the transurethral resection samples and IHC stainings of Ki-67, p53, Her-2 and EGFR were made. The correlations between histological features in transurethral resection samples and immune-histochemical stainings were calculated. The associations of clinicopathological parameters and IHC stainings with NAC response were evaluated. Factorsissue are warranted to improve the selection of patients for neo-adjuvant chemotherapy.'Digital Mega-Studies' are entirely or extensively digitised, longitudinal, population-scale initiatives, collecting, storing, and making available individual-level research data of different types and from multiple sources, shaped by technological developments and unforeseeable risks over time. The Australian 'Gen V' project exemplifies this new research paradigm. In 2019, we undertook a multidisciplinary, multi-stakeholder process to map Digital Mega-Studies' key characteristics, legal and governance challenges and likely solutions. We conducted large and small group processes within a one-day symposium and directed online synthesis and group prioritisation over subsequent weeks. We present our methods (including elicitation, affinity mapping and prioritisation processes) and findings, proposing six priority governance principles across three areas-data, participation, trust-to support future high-quality, large-scale digital research in health.
Hydrogen sulfide (H
S) is an endogenous signaling molecule, regulating numerous physiological functions from vasorelaxation to neuromodulation. Iron is a well-known bioactive metal ion, being the central component of hemoglobin for oxygen transportation and participating in biomolecule degradation, redox balance, and enzymatic actions. The interplay between H
S and iron metabolisms and functions impact significantly on the fate and wellness of different types of cells. Recent advances Iron level in vivo affects the production of H
S via non-enzymatic reactions. On the other hand, H
S quenches excessive iron inside the cells and regulates the redox status of iron.

Abnormal metabolisms of both iron and H
S are associated with various conditions and diseases like iron overload, anemia, oxidative stress, cardiovascular and neurodegenerative diseases. The molecular mechanisms for the interactions of H
S and iron are unsettled yet. Here we review signaling links of the production, metabolism and their resn-rich cells and tissues to the others in which H2S and iron interaction has not received due attention.
It is unknown whether antiretroviral drugs (ARVs) in women living with HIV (WLHIV) are associated with mitochondrial toxicity and altered fat oxidation and branched-chain amino acid metabolism in the placenta and fetus.

Immediately after delivery, we froze placental biopsies from 20 WLHIV and 20 matched uninfected women. We analyzed global biochemical profiles using high performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We used t-tests, principle component analysis, hierarchical clustering, and random forest analysis (RFA) in our analysis.

Twelve WLHIV were on protease inhibitors, 6 on non-nucleoside reverse inhibitors, and 2 on integrase strand inhibitors with optimized backbone. Mean birthweight of HIV exposed neonates was significantly lower than unexposed neonates (3075g vs 3498g, p=0.01) at similar gestational age. RFA identified 30 of 702 analytes that differentiated the placental profiles of WLHIV from uninfected women with 72.5% predictive accuracy. Placental profiles of NNRTI-treated WLHIV exhibited lower levels of amino acids, including essential and branched-chain amino acids, and some medium chain acylcarnitines.

Placental metabolism may be altered in WLHIV, possibly associated with ARVs exposure. The lower birth weight among neonates of WLHIV suggest the need for further studies considering potential deleterious effects of altered placenta metabolism on fetal growth and development.
Placental metabolism may be altered in WLHIV, possibly associated with ARVs exposure. The lower birth weight among neonates of WLHIV suggest the need for further studies considering potential deleterious effects of altered placenta metabolism on fetal growth and development.Upper airway conductance, the ratio of inspiratory airflow to inspiratory effort, quantifies the degree of airway obstruction in hypopneas observed in sleep apnea. We evaluated the ratio of ventilation to non-invasive ventilatory drive as a surrogate of conductance. Further, we developed and tested a refinement of non-invasive drive to incorporate the interactions of inspiratory flow, pressure, and drive in order to better estimate conductance. Hypopneas were compiled from existing polysomnography studies with esophageal catheterization in 18 patients with known or suspected sleep apnea, totaling 1517 hypopneas during NREM sleep. For each hypopnea, reference-standard conductance was calculated as the ratio of peak inspiratory flow to esophageal pressure change during inspiration. Ventilatory drive was calculated using the algorithm developed by Terrill et al and then mathematically modified according to the presence or absence of flow limitation in order to non-invasively estimate esophageal pressure. The ratio of ventilation to ventilatory drive and the ratio of peak inspiratory flow to estimated esophageal pressure were each compared to the reference standard for all hypopneas and for median values from individual patients. Hypopnea ventilationdrive ratios were of limited correlation with the reference standard (R2 = 0.17, individual hypopneas; R2 = 0.03, median patient values). Modification of drive to estimated pressure yielded estimated conductance, which strongly correlated with reference standard conductance (R2 = 0.49, individual hypopneas; R2 = 0.77, median patient values-). We conclude that the severity of airway obstruction during hypopneas may be estimated from non-invasive drive by accounting for mechanical effects of flow on pressure.The aim was to investigate if acute recombinant human erythropoietin (rHuEPO) injection had an effect on mitochondrial function and if exercise would have an additive effect. Furthermore to investigate if in-vitro incubation with rHuEPO had an effect on muscle mitochondrial respiratory capacity. Eight healthy young men were recruited for this double blinded randomized placebo controlled crossover study. rHuEPO (400 IU/kg body weight) or saline injection was given intravenously, before an acute bout of exercise. Resting metabolic rate and fat oxidation were measured. Biopsies were obtained at baseline, 120 min after injection and right after the acute exercise bout. Mitochondrial function (mitochondrial respiration and H2O2 emission) was measured in permeabilized skeletal muscle using high-resolution respirometry and fluorometry. Specifik gene expression and enzyme activity were measured. Skeletal muscle mitochondrial respiratory capacity was measured with and without incubation with rHuEPO. Fat oxidation at rest increased after rHuEPO injection, but no difference was found in fat oxidation during exercise.
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