Interleukin-10 overexpression in macrophages suppresses atherosclerosis in hyperlipidemic mice.
In atherogenesis, macrophage foam cell formation is modulated by pathways involving both the uptake and efflux of cholesterol. We recently showed that interleukin-10 (IL-10) modulates lipid metabolism by enhancing both uptake and efflux of cholesterol in macrophages. However, the mechanistic details of these properties in vivo have been unclear. Thus, the purpose of this study was to determine whether expression of IL-10 in macrophages would alter susceptibility to atherosclerosis and whether IL-10 exerts its antiatherosclerotic properties by modulating lipid metabolism in macrophages. We utilized a macrophage-specific retroviral vector that allows long-term in vivo expression of IL-10 in macrophages through transplantation of retrovirally transduced bone marrow cells (BMCs). IL-10 expressed by macrophages derived from transduced BMCs inhibited atherosclerosis in LDLR(-/-) mice by reducing cholesteryl ester accumulation in atherosclerotic sites. Experiments with primary macrophages indicated that macrophage source of IL-10 stimulated both the uptake (by up-regulating scavenger receptors) and efflux of cholesterol (by activating the PPARgamma-LXR-ABCA1/ABCG1 pathway), thereby reducing inflammation and apoptosis in atherosclerosis. These findings indicate that BMC-transduced macrophage IL-10 production can act as a strong antiatherogenic agent, and they highlight a novel antiatherosclerotic therapy using a simple, yet effective, stem cell transduction system that facilitates long-term expression of IL-10 in macrophages.


Large Infarct Volume Post Thrombectomy: Characteristics, Outcomes, and Predictors.
Despite increasing interest in endovascular therapy (EVT) for large-core strokes, little is known about the predictors of good outcome in these patients. The aim of this study was to analyze patients with large-core strokes post-EVT and to define the predictors of favorable outcome in this population. A retrospective analysis of prospectively collected data on anterior circulation strokes undergoing EVT between January 2015 and February 2018 was performed. Patients with good baseline functional status who underwent EVT for occlusion of an anterior circulation artery and achieved successful recanalization (modified Treatment in Cerebral Ischemia score ≥2b) but had large follow-up infarct volume (FIV ≥70 cm3) were included in the study. Demographic characteristics, clinical and radiologic data, treatment and postprocedural outcomes were extracted and analyzed. The primary outcome was 90-day modified Rankin Scale (mRS) score, stratified by favorable (mRS 0-3) versus unfavorable (mRS 4-6). Of 355 patients meeting inclusion criteria, 85 (24%) had large FIV on follow-up imaging after EVT and constituted the study cohort. No patients achieved mRS score 0-2 at hospital discharge; 32% had 90-day mRS score 0-3. On multivariate logistic regression analysis, lower FIV (OR, -0.96 [0.95-0.99]; P = 0.007), male sex (OR, -1.29 [1.07-12.3]; P = 0.026), and intravenous tissue plasminogen activator use (OR, 3.6 [2.01-8.9]; P = 0.003) were independent predictors of favorable outcome. Independent predictors of mortality on multivariate analysis were higher FIV (OR, -1.01 [1.007-1.02]; P = 0.001) and female sex (OR, 4.08 [1.25-13.3]; P = 0.02). For patients with large-core strokes (≥70 cm3) after EVT, approximately one third have favorable outcome at 90 days. Independent predictors of favorable 90-day outcomes include male sex, intravenous tissue plasminogen activator use, and lower FIV.


Pediatric Ganglions of the Hand and Wrist: A Review of Current Literature.
The etiology, epidemiology, and treatment outcomes of ganglions in children have not been studied in depth. Most research has mainly focused on adults with this condition, with some research suggesting differing epidemiology and outcomes in the pediatric population. This review focuses on the existing literature on pediatric ganglions of the hand and wrist, highlighting 17 studies focused on prevalence and treatment outcomes. Within the pediatric population, epidemiology and outcomes differ depending on patient age. In children aged <10 years, cysts present on the volar aspect of the wrist and are generally amenable to observation, with spontaneous regression. For patients aged >10 years, ganglions resemble those in the adult population and present on the dorsal aspect of the wrist. Open surgical excision demonstrates a relatively low recurrence rate with minimal complications and is currently recommended for treatment.


Novel expression system for combined vaccine production in Edwardsiella tarda ghost and cadaver cells.
To develop combined vaccine systems, we have generated Edwardsiella tarda ghosts (ETG) displaying a foreign protein on the outer membrane and also Ed. tarda cadaver (ETC) expressing a heterologous protein in the cytoplasm. Green fluorescent protein (GFP) was used as a model foreign protein. A constitutive promoter (EtPR C28-1) cloned newly from Ed. tarda was used as a promoter for the expression of foreign protein. Comparison of the strength of the new promoter with a commercially available constitutive promoter (P(HCE)) showed higher expression levels of the novel expression system. The N-terminal domain of ice nucleation protein (InaN), an outer membrane protein of Pseudomonas syringae, was used as an anchor motif for surface display of GFP. By transformation of Ed. tarda with the constructed vectors, GFP was successfully expressed on the surface of ETG and in the cytoplasm of ETC. When compared to P(HCE) driven expression, approximately more than 2 times of GFP was expressed on ETG and in ETC by EtPR C28-1 promoter when judged by fluorescent spectrophotometry. Furthermore, significantly higher expression of GFP on the surface of ETG by EtPR C28-1 than by P(HCE) was demonstrated by serum agglutination assay. These results suggest that the newly cloned Ed. tarda constitutive promoter is capable to express foreign proteins not only on the surface of Ed. tarda ghosts but also in the cytoplasm of Ed. tarda cadavers, and can be used as an efficient promoter for the expression of heterologous antigens of the ETG and ETC-based combined vaccines.


Supraglottic stenosis in infants and children. A preliminary report.
To describe a condition identified in the pediatric population that narrows the supraglottic larynx. This condition has been termed supraglottic stenosis/collapse. To discuss common factors present in these children and to examine potential causes of this specific condition. Retrospective review of patients with supraglottic stenosis/collapse from October 1985 to June 1993. Academic tertiary care children's hospital. Seventeen patients aged 7 months to 14 years underwent laryngoscopy and bronchoscopy for evaluation or follow-up of upper airway obstruction or respiratory failure and were found to have supraglottic stenosis/ collapse. Each patient's records were reviewed for the average age at the time of diagnosis, history of prematurity, evidence of gastroesophageal reflux, history of long-term intubation, and any associated medical problems. In addition, patients were compared based on previous airway surgery (tracheostomy, laryngotracheal reconstruction, or anterior cricoid split). Chronic upper airway obstruction was identified in 17 patients caused by supraglottic stenosis/ collapse. All patients (100%) had undergone tracheostomy prior to the recognition of supraglottic stenosis/ collapse. Fifty-nine percent of the patients had undergone laryngotracheal reconstruction, and 53% had a history of gastroesophageal reflux. Supraglottic stenosis/collapse is a distinct entity that may be related to prior laryngeal or tracheal surgery. This diagnosis should be considered when evaluating and treating patients with chronic upper airway obstruction following laryngeal and/or tracheal surgery.


Individual fumonisin exposure and sphingoid base levels in rural populations consuming maize in South Africa.
Low and high oesophageal cancer incidence areas of the former Transkei region of South Africa have been associated with corresponding low and high levels of fumonisin contaminated home-grown maize. This is the first study in South Africa assessing fumonisin B (FB) mycotoxin exposure by quantifying individual maize consumption with weighed food records and FB levels from maize in each participant's household and concurrently evaluating sphinganine (Sa), sphingosine (So) and Sa/So ratios in plasma and urine of these participants as possible biomarkers of FB exposure. The high consumption of maize in Bizana (n=36) and Centane (n=30) of 0.41+/-0.21 and 0.39+/-0.19 kg/day, respectively, confirms the reliance on maize as the dietary staple. Mean total FB (FB(1)+FB(2)+FB(3)) levels in home-grown maize were 0.495+0.880 and 0.665+0.660 mg/kg in Bizana and Centane, respectively. Mean fumonisin exposure based on individual consumption was 3.9+/-7.3 and 4.1+/-7.6 microg/kg body weight/day, respectively, for Bizana and Centane. The mean combined sphinganine/sphingosine ratios in Bizana and Centane were similar and ranged from 0.10-0.55 in plasma (n=41) and urine (n=62). There was no association between sphingoid base levels and/or Sa/So ratios in the plasma and urine and individual fumonisin exposure, negating the sphingoid bases as potential biomarkers of fumonisin exposure in humans.


Association between blood lead levels and hyperlipidemiais: Results from the NHANES (1999-2018).
Research on the association between blood lead (Pb) and lipid biomarkers have yielded inconsistent results, and epidemiological studies on blood Pb levels and hyperlipidemia are scarce. The present study aimed to examine the association between blood Pb levels and hyperlipidemia in adults from the National Health and Nutrition Examination Survey (NHANES). A total of 43,196 participants in the NHANES from 1999 to 2018 were included in the final analysis. Hyperlipidemia was determined based on the National Cholesterol Education Program guidelines. Blood Pb levels were assessed using inductively-coupled plasma mass spectrometry. Weighted multivariable logistic regression analysis and subgroup analysis were conducted to determine the correlation between blood Pb levels and hyperlipidemia. In the multivariable logistic regression model, high blood Pb levels were significantly associated with hyperlipidemia after adjusting for confounders (OR 1.41; 95%CI: 1.18-1.67). Furthermore, elevated blood Pb levels were associated with an increased risk of hyperlipidemia across the four quartile (Q) groups (Q1: OR 1.00; Q2: OR 1.16 [95%CI: 1.04-1.29]; Q3: OR 1.39 [95%CI: 1.21-1.59]; and Q4: OR 1.33 [95%CI: 1.15-1.54]; P for trend <0.05). Significant moderating effects were found in the subgroup analysis stratified by age, education, hypertension, and diabetes (P < 0.05). In sensitivity analysis, the ORs for hyperlipidemia across the quartiles of blood Pb levels were 1.00, 1.17 (95%CI: 1.05-1.30), 1.42 (95%CI: 1.24-1.62), and 1.38 (95%CI: 1.19-1.60) for Q1, Q2, Q3, and Q4, respectively (P for trend <0.001) after removing adults with arteriosclerotic cardiovascular disease, and the ORs were 1.00, 1.13 (95%CI: 1.01-1.25), 1.38 (95%CI: 1.21-1.56), and 1.32 (95%CI: 1.16-1.52) for Q1, Q2, Q3, and Q4, respectively (P for trend <0.001) after including pregnant women. The current study showed a positive association between blood lead levels and hyperlipidemia.


Discovery of potent 4-aminoquinoline hydrazone inhibitors of NRH:quinoneoxidoreductase-2 (NQO2).
(NRH):quinone oxidoreductase 2 (NQO2) is associated with various processes involved in cancer initiation and progression probably via the production of ROS during quinone metabolism. Thus, there is a need to develop inhibitors of NQO2 that are active in vitro and in vivo. As part of a strategy to achieve this we have used the 4-aminoquinoline backbone as a starting point and synthesized 21 novel analogues. The syntheses utilised p-anisidine with Meldrum's acid and trimethyl orthoacetate or trimethyl orthobenzoate to give the 4-hydrazin-quinoline scaffold, which was derivatised with aldehydes or acid chlorides to give hydrazone or hydrazide analogues, respectively. The hydrazones were the most potent inhibitors of NQO2 in cell free systems, some with low nano-molar IC50 values. Structure-activity analysis highlighted the importance of a small substituent at the 2-position of the 4-aminoquinoline ring, to reduce steric hindrance and improve engagement of the scaffold within the NQO2 active site. Cytotoxicity and NQO2-inhibitory activity in vitro was evaluated using ovarian cancer SKOV-3 and TOV-112 cells (expressing high and low levels of NQO2, respectively). Generally, the hydrazones were more toxic than hydrazide analogues and further, toxicity is unrelated to cellular NQO2 activity. Pharmacological inhibition of NQO2 in cells was measured using the toxicity of CB1954 as a surrogate end-point. Both the hydrazone and hydrazide derivatives are functionally active as inhibitors of NQO2 in the cells, but at different inhibitory potency levels. In particular, 4-((2-(6-methoxy-2-methylquinolin-4-yl)hydrazono)methyl)phenol has the greatest potency of any compound yet evaluated (53 nM), which is 50-fold lower than its toxicity IC50. This compound and some of its analogues could serve as useful pharmacological probes to determine the functional role of NQO2 in cancer development and response to therapy.


Prospective Study of Muscle Injuries in Three Consecutive Seasons of the Brazilian Football Championship.
Objective To perform a prospective evaluation of muscle injuries that occurred during the matches of series A and B of the Brazilian Men's Football Championship from 2016 to 2018. Prospective A prospective-cohort study with data collection regarding muscle injuries that occurred during the official matches of the first and second divisions of the Brazilian Men's Soccer Championship in the 2016, 2017 and 2018 seasons. Results The total number of muscle injuries was of 577 throughout the 3 seasons, with a gradual and annual reduction in the incidence of injuries (219 injuries in 2016, 195 in 2017, and 163 in 2018), with a statistically significant difference between the 2016 and 2018 seasons. Muscle injuries represented approximately 35% of the total lesions. The incidence of muscle injuries was of 7.66 per 1,000 hours of play. During the 3 seasons (2016 to 2018), the most common injury was of the hamstring muscle (41.1%, 40.5%, and 33.7% respectively). Wingers were the most affected players, and the most common injury severity scale was moderate (8 to 28 days). The moment of the match with the highest incidence of injuries was in the period between 61 and 75 minutes, with an index of 19.9%, with no statistical difference in relation to the other periods of the match. Conclusion There was an incidence of muscle injuries of 7.7 /1,000 h, and they occurred predominantly in home games, in defenders (wingers and centre-backs), with an average age of 28 years, mainly involving the hamstring muscles, with a moderate mean time of absence (8 to 28 days).


Perception of oral and maxillofacial surgeons, orthodontists and laypersons in relation to the harmony of the smile.
Harmony is one of the main objectives in surgical and orthodontic treatment and this harmony must be present in the smile, as well as in the face. The aim of the present study was to assess the perceptions of professionals and laypersons in relation to the harmony of the smile of patients with or without vertical maxillary alterations. Sixty observers (oral and maxillofacial surgeons, orthodontists and laypersons) reported the degree of harmony of six smiles using an objective questionnaire and the participants indicated if there was a need for corrective surgery or not. The classification of observers was recorded on a Likert scale from 1 to 5. Mixed regression was used to determine differences between the three groups. Statistically significant differences were found only for the harmony of the smile between the oral and maxillofacial surgeons and laypersons, with laypersons being more critical when assessing the smile. There was no statistical difference between the other groups for the harmony of the smile or the indication of corrective surgery. The patterns of greater or lesser harmony determined by observers during the smile were similar to those found in the literature as the ideal standard in relation to vertical maxillary positioning. Laypersons had a tendency to be more critical in relation to facial harmony than surgeons, although no statistical differences were found in the other groups in relation to the harmony of the smile or indication for the corrective surgery. In addition, the patterns of greater or lesser harmony of the smile determined by the participants were similar to those found in the literature as the ideal standard in relation to vertical maxillary positioning. Overall, the present study demonstrates that adequate interaction between surgeons, orthodontists and laypersons is essential in order to achieve facial harmony with orthodontic and/or surgical treatment. Opinion of specialists and laypersons about the smile in relation to the vertical positioning of the maxilla.


Crystallographic and Theoretical Exploration of Weak Hydrogen Bonds in Arylmethyl N'-(adamantan-1-yl)piperidine-1-carbothioimidates and Molecular Docking Analysis.
Crystal structures of two potential chemotherapeutic agents, namely 4-nitrobenzyl N'-(adamantan-1-yl)piperidine-1-carbothioimidate 1 and 4-bromobenzyl N'-(adamantan-1-yl)piperidine-1-carbothioimidate 2, have been analyzed in detail. X-ray analysis reveals that the molecular conformations of these compounds are strikingly different. These two structures are compared with two of their closely related structures. In the related structures, morpholine replaces piperidine. Based on the Hirshfeld surface analysis and two-dimensional (2D) fingerprint plots, we describe the effects of piperidine/morpholine and Br/NO2 groups on the intermolecular interactions. An analysis of the CLP-PIXEL energy provides insight into the energetics of the dimers observed in the title compounds and their related structures. Compound 1 stabilizes with bifurcated C-H···S, C-H···O, and O(lp)···C(π) interactions, whereas compound 2 stabilizes with C-H···N, C-H···Br, and C-H···C interactions. The energy frameworks for the crystal structures of the title compounds reveal differences. The atoms-in-molecules (AIM) analysis was performed to confirm the intermolecular interactions found in the crystal structures of 1 and 2. Additionally, docking analysis suggests that the title compounds bind at the active site of human sphingosine kinase 1, a well-known cancer target.


1,2-Dihydro-9H-carbazole-4(3H)-thione.
The crystal structure of the title compound, C(12)H(11)NS, features parallel chains of alternating N-H⋯S hydrogen-bonded mirror-image conformers along [10[Formula: see text]]. The mol-ecular conformation is that of an envelope, with all of the framework atoms except one close to a mean plane (rms deviation 0.054 Å); one C atom of the cyclo-hexene-thione ring forms the envelope flap, which makes a dihedral angle of 48.6 (1)° with the rest of the mol-ecule. There is a π-π* inter-action between pairs of enanti-omers in adjacent chains; the distance between parallel planes is 3.466 (1) Å.


Is technetium-99m dimercaptosuccinic acid renal scintigraphy available for predicting vesicoureteral reflux in children with first febrile urinary tract infection under the age of 24 months?
Vesicoureteral reflux (VUR) is a common complication after urinary tract infection (UTI) and can lead to irreversible renal scar. Voiding cystourethrogram is the most reliable technology to detect VUR and its severity, but it is restricted in children's examinations for various shortcomings. This study aimed to evaluate and compare the efficiency of Tc-99m DMSA renal scintigraphy and conventional ultrasonography (USG) in predicting VUR with the gold standard of cystourethrogram results. This retrospective study consisted of 285 first febrile UTI children under the age of 24 months who completed inflammatory indicator examinations, USG, Tc-99m DMSA renal scintigraphy and underwent cystourethrography after controlling infection with prophylactic antibiotics. The efficiency of Tc-99m DMSA renal scintigraphy and USG in predicting VUR was calculated and compared. Abnormal USG (40.23% vs. 21.72%, P = 0.001) and Tc-99m DMSA renal scintigraphy results (87.36% vs. 71.72%, P = 0.004) were more common in VUR children. The sensitivity of USG in predicting VUR was only 40.23%, whereas the sensitivity and negative predictive value of Tc-99m DMSA renal scintigraphy reached 87.63 and 83.58%, respectively. Tc-99m DMSA renal scintigraphy had a higher efficacy than USG in predicting high-grade reflux kidneys (73.87% vs. 33.33%; P < 0.001), but there was no significant difference in predicting low-grade reflux kidneys ( P = 0.703). Tc-99m DMSA renal scintigraphy had a significant higher efficiency in predicting VUR (a common cause of renal scarring, detected on DMSA) in first febrile urinary tract infection children under the age of 24 months as compared with USG, especially in high-grade reflux.


The cocaine analog WIN 35,428 binds to two sites in fresh rat caudate-putamen: significance of assay procedures.
Binding of the potent cocaine analog [3H]WIN 35,428 (2 beta-carbomethoxy-3 beta-(4-fluoro-phenyl)-tropane) was examined in membrane homogenates prepared from fresh rat caudate-putamen. The number of rinses of the membranes following incubation with the ligand was varied. After one wash, only a single binding site was evident. With an increasing number of washes, however, two binding sites were observed. Additional rinses, up to a total of four, led to a decrease in the number of low affinity binding sites, with no change in the number of high affinity sites. These results suggest that the methodology used in these binding assays may be important for interpretation of the results.


Food sovereignty and sustainability mid-pandemic: how Michigan's experience of Covid-19 highlights chasms in the food system.
This paper offers observations on people's lived experience of the food system in Michigan during the early Covid-19 pandemic as an initial critical foray into the everyday pandemic food world. The Covid-19 crisis illuminates a myriad of adaptive food behaviors, as people struggle to address their destabilized lives, including the casual acknowledgement of the pandemic, then anxiety of the unknown, the subsequent new dependency, and the possible emergence of a new normal. The pandemic makes the injustices inherent in the food system apparent across communities, demonstrating that food injustice destabilizes all members of the food system, regardless of their social location. The challenges of eating in a pandemic also reinforce the importance of building a sustainable food system; the challenges of food sovereignty and food sustainability are inextricably linked, and the pandemic lays this bare.


Synthesis, anti-inflammatory and antimicrobial evaluation of novel 1-acetyl-3,5-diaryl-4,5-dihydro (1H) pyrazole derivatives bearing urea, thiourea and sulfonamide moieties.
A series of novel 1-acetyl-3-(3,4-dimethoxypheny)-5-(4-(3-(arylureido/arylthioureido/arylsulfonamido) phenyl)-4,5-dihydropyrazole derivatives of biological interest have been prepared by sequential cyclization of 1-(4-nitrophenyl)-3-(3,4-dimethoxyphenyl)-pro-2-ene-1 with hydrazine hydrate, reduction followed by reaction of resulting amine with different arylisocyanates or arylisothiocyanates or arylsulfonyl chlorides. All the synthesized compounds (1-32) have been screened for their pro-inflammatory cytokines (TNF-α and IL-6) and antimicrobial activity (antibacterial and antifungal). Biological evaluation study showed, the compounds 4, 5, 9, 11, 14 and 16 found to have promising anti-inflammatory activity (up to 61-85% TNF-α and 76-93% IL-6 inhibitory activity) at concentration of 10 μM with reference to standard dexamethasone (76% TNF-α and 86% IL-6 inhibitory activity at 1 μM). Compounds 24, 26, 27, 28 and 29 exhibited promising antimicrobial activity at MIC values ranging from 70 to 10 μg/mL against all the selected pathogenic bacteria and fungi.


[Stereotactic radiotherapy for prostate cancer].
Stereotactic radiotherapy is a new option in the treatment of prostate cancer. However, only retrospective series and a few prospective phase II trials are available at this moment, including a few thousands of patients with a short follow-up. Most of the protocols delivered 33 to 38 Gy in four or five fractions. Acute toxicity seems to be similar to the one observed after conventional radiotherapy. Late toxicity is less evaluable because of the short follow-up: the rate of radiation-induced proctitis seems low in the published series. Urinary toxicities are not properly evaluated: some series reported a high incidence of urinary complications grade or higher. Most of the patients belong to the D'Amico's favourable group: biochemical controls are equivalent to those observed after conventional irradiation, but the follow-up is often shorter than 5 years and no definitive conclusion could be made about the efficiency of the technique. Data for the intermediate and high risk groups are not mature. In conclusion, stereotactic radiotherapy could strongly modified the management of prostate cancer: some phase III trials have started to confirm the good results reported in preliminary series.


Urinary and air phthalate concentrations and self-reported use of personal care products among minority pregnant women in New York city.
Diethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) are used extensively in personal care products, including fragrances (DEP) and nail polish (DnBP). Between May 2003 and July 2006, we gathered questionnaire data on the use of seven product categories (deodorant, perfume, hair spray, hair gel, nail polish/polish remover, liquid soap/body wash, and lotion/mist) over 48 h during the third trimester of pregnancy from 186 inner-city women. A 48-h personal air sample was collected and analyzed for DEP and DnBP; a maternal spot urine sample was collected and analyzed for their monoester metabolites, monoethyl phthalate (MEP) and mono-n-butyl phthalate (MnBP), respectively. In all, 97% of air samples and 84% of urine samples were collected within ±2 days of the questionnaire. During the 48 h, 41% of women reported perfume use and 10% reported nail polish/polish remover use. In adjusted analyses, no association was seen between nail product use and air DnBP or urine MnBP concentrations. Women reporting perfume use had 2.3 times higher (95% CI 1.6, 3.3) urinary MEP concentrations. Personal air DEP increased by 7% for each 25% increase in a composite indicator of the six other product categories (P<0.05), but was not associated with perfume use. Air DEP was correlated with urine MEP concentrations only among non-perfume users (r=0.51, P<0.001). Results suggest that perfume use is a significant source of DEP exposure.


Tongue movements in patients with skeletal Class III malocclusions evaluated with real-time balanced turbo field echo cine magnetic resonance imaging.
The aim of this study was to evaluate the position and movements of the tongue in patients with skeletal Class III malocclusion. Sixty-six patients (31 male, 35 female) with Class III malocclusion were divided into 3 groups according to cephalometric analysis. The first group comprised 23 patients (13 male, 10 female) with mandibular prognathism, the second group comprised 21 patients (9 male, 12 female) with maxillary retrognathism, and the third group comprised 22 patients (9 male, 13 female) with both maxillary retrognathism and mandibular prognathism. Twenty-two skeletal Class I patients (10 male, 12 female) were also included as the control group. Dentofacial morphology affects the position and the movements of the tongue during deglutition. Contact of the anterior portion of the tongue with the rugae area of the hard palate decreased in the Class III malocclusion groups. The posterior portion of the dorsal tongue was positioned more inferiorly, and the root of the tongue was positioned more inferiorly and anteriorly in patients with Class III malocclusion than in the control group. The tip of the tongue was also in a more anterior position in the Class III groups. When the deglutition stages were evaluated, we observed that the manner of bolus transfer was different in patients with skeletal Class III malocclusion than in those with skeletal Class I malocclusion. Tongue posture is affected by dentofacial structures, and adaptive changes occur in the tip, dorsum, and root of the tongue. Deglutitive tongue movements in patients with skeletal Class III malocclusion are also different from those with skeletal Class I malocclusion.


Genome structure of the Lactobacillus temperate phage phi g1e: the whole genome sequence and the putative promoter/repressor system.
The complete genome sequence of a Lactobacillus temperate phage phi g1e was established. The double-stranded DNA is composed of 42,259 bp, and encodes for sixty-two possible open reading frames (ORF) as well as several potential regulatory sequences. Based on comparative analysis with other related proteins of the Lactobacillus and Lactococcus phages as well as the Escherichia coli phages (such as lambda), functions were putatively assigned to several phi g1e ORFs: cng and cpg (encoding for repressors), hel (helicase), ntp (NTPase), and several ORFs (e.g., minor capsid proteins). An about 1000-bp DNA region of phi g1e containing cpg and cng was inferred to function as a promoter/repressor system for the phi g1e lysogenic and lytic pathway.


Understanding older adults' functioning and health-seeking behaviour during the COVID-19 pandemic in Ghana: A descriptive qualitative study.
Little research has been conducted to explore the functional status of community-dwelling older adults in sub-Saharan Africa, including Ghana, especially during the COVID-19 pandemic. This study investigated the functional status and the health-seeking behaviour of older adults during the COVID-19 pandemic in Ghana. Utilising a descriptive qualitative approach, semi-structured interviews were used to collect data from 12 eligible older adults from southern Ghana. With the use of NVivo (v12), descriptive and focused coding techniques were employed to analyse the data. The following five themes were identified after the data analysis: (a) older adults' health status during COVID-19 pandemic, (b) feeling limited, (c) feeling of unhappiness for being inactive, (d) striving to be active and (e) seeking healthcare during COVID-19 pandemic. This study revealed the unique health and social-related needs of Ghanaian older adults during the COVID-19 pandemic. This study's findings draw attention to the urgent need for the state to devise practical health and social-related initiatives to support older adults during and after the COVID-19 pandemic.


Evaluation of self-oxidation and selectivity of iron-based reductant in anaerobic pentachlorophenol contaminated soil.
Soil contamination due to chlorinated organics prompts an important environmental problem; however, the iron-based reduction materials and complicated ground environment are the main barriers to implementation and promotion of in situ soil remediation. Therefore, this study aims to evaluate the reductants zero-valent iron (ZVI) and its activated carbon composite (AC-ZVI) in terms of their self-oxidation and selectivity in soil experiments. The results indicated that saturated moisture conditions were beneficial for degradation due to the dispersal of the pollutants from soil particles. Particularly, increasing the water/soil ratio to the over-saturated state would decrease the selectivity of ZVI and AC-ZVI. Meanwhile, increasing the reductant loading decreased the selectivity of ZVI and AC-ZVI, whereas the high initial concentration increased the selectivity of AC-ZVI. In addition, the self-oxidation of ZVI (3.0 ×10-3 h-1) is 4.2 times higher than that of AC-ZVI (0.7 ×10-3 h-1), and the selectivity of AC-ZVI (48%) is 6.9 times higher than that of ZVI (7%), which confirmed that AC-ZVI is a superior iron-based amendment in saturated moisture conditions. Therefore, this study provides a reliable and feasible evaluation method for in situ remediation process, and deepens the understanding of the effects of moisture contents.


Does transient increase in axial length during accommodation attenuate with age?
The aim was to profile transient accommodative axial length changes from early adulthood to advanced presbyopia and to determine whether any differences exist between the responses of myopic and emmetropic individuals. Ocular biometry was measured by the LenStar biometer (Haag-Streit, Switzerland) in response to zero, 3.00 and 4.50 D accommodative stimuli in 35 emmetropes and 37 myopes, aged 18 to 60 years. All results were corrected to reduce errors arising from the increase in crystalline lens thickness with accommodation. Accommodative responses were measured sequentially by the WAM 5500 Auto Ref/Keratometer (Grand Seiko, Hiroshima, Japan). Axial length increased significantly with accommodation (p < 0.001), with a mean corrected increase in axial length of 2 ± 18 µm and 8 ± 16 µm observed at 3.00 and 4.50 D, respectively. The magnitude of accommodative change in axial length was not dependent on refractive error classification (p = 0.959); however, a significant reduction in the magnitude and variance of axial length change was evident after 43 to 44 years of age (p < 0.002). The negative association between transient increase in axial length and age, in combination with reduced variance of data after age 43 to 44 years, is consistent with a significant increase in posterior ocular rigidity, which may be influential in the development of presbyopia.


Engineering cytokine therapeutics.
Cytokines have pivotal roles in immunity, making them attractive as therapeutics for a variety of immune-related disorders. However, the widespread clinical use of cytokines has been limited by their short blood half-lives and severe side effects caused by low specificity and unfavourable biodistribution. Innovations in bioengineering have aided in advancing our knowledge of cytokine biology and yielded new technologies for cytokine engineering. In this Review, we discuss how the development of bioanalytical methods, such as sequencing and high-resolution imaging combined with genetic techniques, have facilitated a better understanding of cytokine biology. We then present an overview of therapeutics arising from cytokine re-engineering, targeting and delivery, mRNA therapeutics and cell therapy. We also highlight the application of these strategies to adjust the immunological imbalance in different immune-mediated disorders, including cancer, infection and autoimmune diseases. Finally, we look ahead to the hurdles that must be overcome before cytokine therapeutics can live up to their full potential.


Hemoglobin Absorption Spectral Imaging (H.A.S.I.): a novel optical staining technique for microlaryngoscopy.
Optical image enhancement techniques are widely used in endoscopy to improve the visualization of blood vessels for diagnostic and therapeutic purposes. These techniques are monitor-based and therefore not available for direct microscopy. In this study, a novel optical microscope filter, Hemoglobin absorption spectral imaging (H.A.S.I.) was tested for use in microlaryngoscopy. A novel dichroic filter was designed to improve contrast in small blood vessels by highlighting transmission in the spectrum range of hemoglobin absorption maxima. A surgical microscope equipped with the novel H.A.S.I. filter was installed in one operating room in our institution. 68 consecutive patients referred to our ENT department for endoscopy were examined using white light and the novel H.A.S.I. filter during microlaryngoscopy. Surgeons described the blood vessels of the vocal cords using a classification chart and assessed for suspected malignancy using both white light and H.A.S.I. 77 consecutive microlaryngoscopies were performed on 68 patients. 142 vocal cords were visualized in microlaryngoscopy and the blood vessels classified according to the chart. With white light, 152 blood vessel characteristics were documented and 157 with H.A.S.I. Notably, pathologies like benign horizontal blood vessel changes, leukoplakia, and vertical blood vessel changes like dots and loops were seen more frequently with H.A.S.I. Finally, seven lesions were treated by transoral laser microsurgery (TLM) with H.A.S.I. to test the practicability of the method for microlaryngoscopic laser surgery. This is the first study describing H.A.S.I. as an optical staining method for microlaryngoscopy. In our experience, the method was practical and improved the evaluation of vocal cord blood vessels. In some cases, the use of H.A.S.I. led to a change in diagnosis and treatment. Also, H.A.S.I. was found to be helpful in microlaryngeal laser surgery for demarcating resection margins. This is, to our knowledge, the first optical staining method integrated into a surgical microscope and can be conveniently used during microlaryngeal laser surgery and does not require further equipment.


Purification and identification of dipeptidyl peptidase (DPP) IV inhibitory peptides from the macroalga Palmaria palmata.
Dipeptidyl peptidase (DPP)-IV inhibitory peptides were purified and identified from an aqueous Palmaria palmata protein extract hydrolysed with Corolase PP. The hydrolysate was fractionated by solid phase extraction (SPE) using a C18 matrix followed by semi-preparative reverse phase-high performance liquid chromatography (SP RP-HPLC). IC50 values of 1.47 ± 0.09, 0.54 ± 0.03 and 0.36 ± 0.03 mg/ml were obtained for the hydrolysate, the 25%--acetonitrile (ACN) SPE fraction and the most active SP RP-HPLC peptide fraction (SP RP-HPLC 25_F28), respectively. Thirteen peptide sequences were identified following UPLC-ESI MS/MS analysis of SP RP-HPLC 25_F28. Three novel DPP-IV inhibitory peptides, Ile-Leu-Ala-Pro, Leu-Leu-Ala-Pro and Met-Ala-Gly-Val-Asp-His-Ile, with IC50 values in the range 43-159 μM were identified. The results indicate that P. palmata derived peptides may have potential as functional food ingredients in the prevention and management of type 2 diabetes.


Influence of pre-analytical factors on α-galactosidase A, arylsulfatase B and α-glucosidase activities measured on dried blood spots on filter paper.
To analyze the effect of blood collection and storage conditions on activity of α-galactosidase A, arylsulfatase B and α-glucosidase. Blood was collected in EDTA, heparin, or direct spotting on filter paper and stored at different temperatures (-20, 4, 25 and 37°C) and storage times (3, 10, 17 and 180 days). The influence of filter paper size was also assessed (3.0 and 1.2mm). No statistically significant difference was observed between the three collection methods. α-Glucosidase A activity significantly decreased after the 10th day, while arylsulfatase B activity only differed significantly after the 180th day, and α-galactosidase A activity remained constant throughout this storage time. Excellent correlation coefficients were observed for the two filter paper sizes used. Both paper sizes may be employed. Filter paper specimens should be transported under refrigeration as soon as possible after blood collection.


The Bio-PIN: a concept to improve biobanking.
A new biobanking method is proposed, wherein samples and associated data would be deposited anonymously and labelled using a PIN code that is produced on the basis of personal biological characteristics, such as single nucleotide polymorphisms. The code would be the 'Bio-PIN' to uniquely distinguish the sample depositors, plus their samples and data. This method could help to diminish several long-discussed ethical, legal and societal problems in biobanking regarding privacy, informed consent, autonomy, data security and public trust.


Anthocyanin as a therapeutic in Alzheimer's disease: A systematic review of preclinical evidences.
The aim of this systematic review is to ponder the possible mechanism of action of anthocyanin in Alzheimer's disease (AD), to prompt the development of anthocyanin-based dietary supplementation or therapeutic intervention for AD and to explore the natural sources of anthocyanins. Electronic bibliographic databases such as PubMed, ScienceDirect, Proquest, DOAJ, Scopus, and Google Scholar were searched for preclinical studies probing the efficacy of anthocyanin on AD. The search strategy included no time limit, but was restricted to English. The review protocol is registered on PROSPERO, registration no. CRD42021272972. The systematic review followed the PICO approach for inclusion of reports. All the reports were appraised for risk of bias using the SYRCLE's RoB tool. Bibliographic details of the article, animal strain/weight/age, induction model, anthocyanin source, type of anthocyanin, dose, route of administration, duration, and the outcome measures were extracted from 12 retrieved reports explicitly. The implication of food-based anthocyanin in acute and long-term cognition and Aβ mediated neurodegeneration appears alluring. Majority of the studies comprehended in this review had moderate methodological quality. Efficacy of anthocyanin in alleviating oxidative stress, reactive astrogliosis, cholinergic dysfunction, apoptosis, synaptotoxicity, neuroinflammation, tau hyperphosphorylation, dysregulated membrane potential, neuronal extracellular calcium, dysfunctional amyloidogenic pathway, and cognitive deficits in various rodent models of AD is manifested compositely in 12 studies.


Perspectives from law enforcement officers who respond to overdose calls for service and administer naloxone.
Many law enforcement agencies across the United States equip their officers with the life-saving drug naloxone to reverse the effects of an opioid overdose. Although officers can be effectively trained to administer naloxone, and hundreds of law enforcement agencies carry naloxone to reverse overdoses, little is known about what happens on scene during an overdose call for service from an officer's perspective, including what officers perceive their duties and responsibilities to be as the incident evolves. The qualitative study examined officers' experiences with overdose response, their perceived roles, and what happens on scene before, during, and after an overdose incident. In-person interviews were conducted with 17 officers in four diverse law enforcement agencies in the United States between January and May 2020. Following an overdose, the officers described that overdose victims are required to go to a hospital or they are taken to jail. Officers also described their duties on scene during and after naloxone administration, including searching the belongings of the person who overdosed and seizing any drug paraphernalia. These findings point to a pressing need for rethinking standard operating procedures for law enforcement in these situations so that the intentions of Good Samaritan Laws are upheld and people get the assistance they need without being deterred from asking for future help.


Chemical composition, antibacterial activity and related mechanism of valonia and shell from Quercus variabilis Blume (Fagaceae) against Salmonella paratyphi a and Staphylococcus aureus.
Plant secondary metabolites and phytochemicals that exhibit strong bioactivities have potential to be developed as safe and efficient natural antimicrobials against food contamination and addressing antimicrobial resistance caused by the overuse of chemical synthetic preservative. In this study, the chemical composition, antibacterial activities and related mechanism of the extracts of the valonia and the shell of Quercus variabilis Blume were studied to determine its potential as a safe and efficient natural antimicrobial. The phenolic compositions of valonia and shell extracts were determined by folin-ciocalteau colourimetric method, sodium borohydride/chloranil-based assay and the aluminium chloride method and then further identified by the reverse-phase HPLC analysis. The antibacterial activities of valonia and shell extracts were evaluated by the agar disk diffusion method and agar dilution method. The related antibacterial mechanism was explored successively by the membrane of pathogens effect, phosphorous metabolism, whole-cell proteins and the microbial morphology under scanning electron microscopy. The n-butanol fraction and water fraction of valonia along with n-butanol fraction of the shell contains enrich phenolics including ellagic acid, theophylline, caffeic acid and tannin acid. The n-butanol fraction and ethanol crude extracts of valonia exhibited strong antibacterial activities against Salmonella paratyphi A (S. paratyphi A) and Staphylococcus aureus (S. aureus) with the DIZ values ranged from 10.89 ± 0.12 to 15.92 ± 0.44, which were greater than that of the Punica granatum (DIZ: 10.22 ± 0.18 and 10.30 ± 0.21). The MIC values of the n-butanol fraction and ethanol crude extracts of valonia against S. paratyphi A and S. aureus were 1.25 mg/ml and 0.625 mg/ml. The related antibacterial mechanism of n-butanol fraction and ethanol crude extracts of valonia may be attributed to their strong impact on membrane permeability and cellular metabolism. Those extracts exhibited strong antibacterial activity according to inhibit the synthesis of bacterial proteins and seriously change morphological structure of bacterial cells. The n-butanol fraction and ethanol crude extracts of valonia had reasonably good antibacterial activities against S. paratyphi A and S. aureus. This study suggests possible application of valonia and shell as natural antimicrobials or preservatives for food and medical application.


Magnetic resonance imaging of pediatric liver tumors.
Liver tumors in children can be benign or malignant. Although several clinical factors are important in the evaluation of these lesions, MRI is particularly important for lesion characterization and tumor staging. In children, use of a hepatobiliary contrast agent is recommended to evaluate a known or suspected liver lesion. In this review, we discuss the most common benign and malignant pediatric liver tumors, including vascular tumors, mesenchymal hamartoma, focal nodular hyperplasia, hepatocellular adenoma, hepatoblastoma, hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, undifferentiated embryonal sarcoma and metastases, with emphasis on relevant clinical information and imaging appearance at MRI using hepatobiliary agents.


Limited reversibility of transmembrane proton transfer assisting transmembrane electron transfer in a dihaem-containing succinate:quinone oxidoreductase.
Membrane protein complexes can support both the generation and utilisation of a transmembrane electrochemical proton potential (Deltap), either by supporting transmembrane electron transfer coupled to protolytic reactions on opposite sides of the membrane or by supporting transmembrane proton transfer. The first mechanism has been unequivocally demonstrated to be operational for Deltap-dependent catalysis of succinate oxidation by quinone in the case of the dihaem-containing succinate:menaquinone reductase (SQR) from the Gram-positive bacterium Bacillus licheniformis. This is physiologically relevant in that it allows the transmembrane potential Deltap to drive the endergonic oxidation of succinate by menaquinone by the dihaem-containing SQR of Gram-positive bacteria. In the case of a related but different respiratory membrane protein complex, the dihaem-containing quinol:fumarate reductase (QFR) of the epsilon-proteobacterium Wolinella succinogenes, evidence has been obtained that both mechanisms are combined, so as to facilitate transmembrane electron transfer by proton transfer via a both novel and essential compensatory transmembrane proton transfer pathway ("E-pathway"). Although the reduction of fumarate by menaquinol is exergonic, it is obviously not exergonic enough to support the generation of a Deltap. This compensatory "E-pathway" appears to be required by all dihaem-containing QFR enzymes and results in the overall reaction being electroneutral. However, here we show that the reverse reaction, the oxidation of succinate by quinone, as catalysed by W. succinogenes QFR, is not electroneutral. The implications for transmembrane proton transfer via the E-pathway are discussed.


Is multidisciplinary care of heart failure cost-beneficial when combined with optimal medical care?
Multidisciplinary care (MDC) of heart failure (HF) can significantly reduce rates of unplanned hospitalisation, the major cost component of HF care. This prospective, randomised, controlled study examines the cost-benefits of MDC of HF in the setting of optimal medical care. 98 NYHA class IV HF patients (mean age 70.8+/-10.5 years) were randomised to MDC (n=51) or routine care (RC; n=47) of HF. A direct intervention cost was calculated from contact time (scheduled and unscheduled) spent by the MDC team. Unplanned hospitalisation costs for HF were calculated at a daily rate of 242. Outcomes were determined in monetary terms, i.e. the cost of the service per hospitalisation prevented and net costs/savings at 3 months. The direct intervention cost of the MDC team was 5860, with an average cost per patient of 113 (95% Cl: 97-128). At 3 months, there were a total of 12 unplanned HF readmissions in the RC group (25.5% rate, 195 days) compared to 2 in the MDC group (3.9% rate, 17 days). The number needed to treat to prevent one hospitalisation for HF was 6 over 3 months. The cost of the service per hospitalisation prevented was 586. The intervention produced a net cost saving of 37,216 for 51 patients treated over 3 months. Sensitivity analyses using 50% variation in costs and lower relative risk reductions confirmed the cost-benefits of the intervention. MDC of HF remains cost-beneficial when combined with optimal, medical care. The significant clinical and cost-benefits suggest that this intensive approach to MDC and medical management should become the standard of care for HF.


Hydrophilic interaction liquid chromatography method for eremomycin determination in pre-clinical study.
A complex of hydrophilic interaction liquid chromatography (HILIC) methods for simple and efficient determination of eremomycin (ERM) as an active pharmaceutical ingredient (API) of a novel drug is proposed for preclinical study, which includes the dissolution test and pharmacokinetic study on the animals. A home-made HILIC silica-based stationary phase (SP) containing diol functionalities and positively charged nitrogen atoms in its structure was synthesized for this research and applied for the first time for performing the first step of preclinical study (dissolution test) of the novel ERM-containing drug. HILIC method developed using novel home-made SP allowed us to avoid any interferences from polyethylene glycol (PEG) contained in the drug matrix thus providing a unique advantage of the proposed approach over RP HPLC. The home-made SP demonstrated better chromatographic performance as compared to the tested commercially available columns with various functionalities. Different retention behaviour and mechanisms with various electrostatic impact were demonstrated for two glycopeptide antibiotics, namely, ERM and its analogue vancomycin (VAN), on the home-made SP. For the second step of the preclinical study HILIC-MS/MS method for ERM determination in rabbit plasma was developed and validated in accordance with the EMA requirements and successfully applied to the preclinical study on rabbits after intravenous and intraperitoneal drug administration. The results of dissolution test and pharmacokinetic study revealed similar in vitro solubility of ERM and VAN and low ERM bioavailability, which proved the potential safety and efficiency of the novel drug.


Partial characterisation of the high and low molecular weight forms of P388D1-derived interleukin 1.
The murine macrophage-derived cell line P388D1 secretes the lymphokine interleukin 1 (IL-1) when stimulated by a variety of agents. When stimulated by bacterial lipopolysaccharide (LPS) the cells release IL-1 in both high and low molecular weight (m.w.) forms. The proportion of high m.w. IL-1 is reduced when IL-1-containing supernatants are concentrated by ammonium sulfate precipitation subsequent to hollow-fiber filtration. The high m.w. form can be converted to the low m.w. form by proteolysis, reduction and alkylation, or chromatography in a dissociating solvent. The low m.w. form remains as such, even when reconcentrated in fetal calf serum-containing medium. The high m.w. form thus likely consists of a complex between low m.w. IL-1 and another protein secreted by the P388D1 cell line.


Radioactivity Reduction of 2-Deoxy-2-[18F] Fluoro-D-Glucose by Milk and Ursodeoxycholic Acid in Preclinical Study.
2-Deoxy-2-[18F] fluoro-d-glucose positron emission tomography (18F-FDG-PET) is a less-invasive and widely used diagnostic tool for detection of malignant tumors. However, prolonged retention of 18F-FDG in the body increases radiation exposure. This study evaluated the effect of oral administration of milk and ursodeoxycholic acid (UDCA) in terms of reducing radiation exposure by 18F-FDG. 18F-FDG radioactivity was measured using a digital γ counter in the whole body and in various organs of rats after oral administration of milk and milk plus UDCA (milk + UDCA). Western blotting was performed to measure the expression levels of G6Pase, HK 2, CREB, FoxO1, and PGC-1α in the brain, liver, small intestine, and large intestine to assess the mechanism underlying the reduction in radiation exposure from 18F-FDG by oral administration of milk and UDCA. We found a significant reduction in 18F-FDG radioactivity in the whole body and in the brain, liver, and small and large intestines. Expression of G6Pase was significantly increased in the above-mentioned organs in the milk and milk + UDCA groups. Expression of HK 2 was significantly decreased in the brain and small intestine in the milk and milk + UDCA groups. CREB, FoxO1, and PGC-1α expression levels in the brain, liver, and small intestine were increased in the milk and milk + UDCA groups. However, expression of PGC-1α in the large intestine in the milk and milk + UDCA groups was significantly decreased compared with that in the control group. The present study demonstrated that administration of milk and UDCA increased G6Pase expression levels and 18F-FDG release from the tissue. These results suggest milk and UDCA could be used to reduce radiation exposure from 18F-FDG after image acquisition. The mechanisms underpinning this phenomenon should be explored in a human study.


High serum magnesium is associated with lower risk of hepatocellular carcinoma among patients with nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is a major contributor to the rising incidence of hepatocellular carcinoma (HCC). Magnesium is a major cation in cellular activities. Epidemiological data on magnesium level and its relation to HCC are sparse. This study aimed to examine the associations between serum levels of magnesium and the risk of HCC among patients with NAFLD. A total of 26,053 patients with NAFLD were identified in the University of Pittsburgh Medical Center Electronic Health Records from 2004 through 2018. After an average of 5.15 years of follow-up, 395 patients developed HCC after the first measurement of serum magnesium. Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% CIs of HCC incidence associated with quartile levels of serum magnesium after adjustment for age, sex, race, body mass index, diuretics use, history of type 2 diabetes, history of hypertension, history of hyperlipidemia, and tobacco smoking. Patients with NAFLD who developed HCC had a significantly lower mean (± standard deviation) serum magnesium (0.769 ± 0.131 mmol/L) than those who remained free of HCC (0.789 ± 0.125 mmol/L; p = .003). Compared with the lowest quartile, the HRs (95% CIs) of HCC second, third, and fourth quartiles of serum magnesium were 0.87 (0.67-1.12), 0.77 (0.57-1.04), and 0.73 (0.56-0.96), respectively, after adjustment for multiple potential confounders (P trend = .02). This finding suggests higher levels of serum magnesium were significantly associated with decreased risk of HCC among patients with NAFLD.


Individual subject laryngeal dimensions of multiple mammalian species for biomechanical models.
This report provides a detailed knowledge base of individual subject laryngeal cartilage dimensions across multiple species to assist researchers in creating subject-specific biomechanical laryngeal models. The raw data from previous laryngeal cartilage studies were grouped by species (for human, canine, and ovine) and by cartilage (arytenoid, thyroid, and cricoid) by means of a previously reported labeling scheme. No animals were sacrificed specifically for the present study. More than 1,500 measurements from 37 subjects are presented in 15 tables. No comparisons of the average measures were attempted, as they were done in previous studies. By means of a database of individual subject dimensions, a laryngeal model could be designed and tested to morph from one subject to the next, predicting subject-specific results of laryngeal function. Eventually, this would lead to modeling patient-specific laryngeal disorders and the prediction of therapeutic outcomes. An electronic downloadable version of the database is made available to assist in this effort.


Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer.
The interaction between cancer cells and microenvironment has a critical role in tumor development and progression. Although microRNAs regulate all the major biological mechanisms, their influence on tumor microenvironment is largely unexplored. Here, we investigate the role of microRNAs in the tumor-supportive capacity of stromal cells. We demonstrated that miR-15 and miR-16 are downregulated in fibroblasts surrounding the prostate tumors of the majority of 23 patients analyzed. Such downregulation of miR-15 and miR-16 in cancer-associated fibroblasts (CAFs) promoted tumor growth and progression through the reduced post-transcriptional repression of Fgf-2 and its receptor Fgfr1, which act on both stromal and tumor cells to enhance cancer cell survival, proliferation and migration. Moreover, reconstitution of miR-15 and miR-16 impaired considerably the tumor-supportive capability of stromal cells in vitro and in vivo. Our data suggest a molecular circuitry in which miR-15 and miR-16 and their correlated targets cooperate to promote tumor expansion and invasiveness through the concurrent activity on stromal and cancer cells, thus providing further support to the development of therapies aimed at reconstituting miR-15 and miR-16 in advanced prostate cancer.


Pulmonary diffusing capacity measured by NO/CO transfer in Tunisian boys.
The diffusing capacity, which measures gas-exchange, uses reference values based on data from American or European studies. There are currently no reference values of pulmonary diffusing capacity (TL) and its components, such as the conductance of the membrane (Dm) and capillary lung volume (Vc) for healthy North African children. We determined the prediction equations-reference values for TL, Dm, Vc and the alveolar volume (VA) in healthy Tunisian boys. Values of Vc, Dm, TL, and VA were measured by the NO/CO transfer method, using a single breath maneuver in 118 Tunisian boys (8-14 years old) at rest. We performed linear regression analysis of the pulmonary parameters and independent variables, such as height, weight, and age. The reference equations for pulmonary diffusing capacity for carbon monoxide (TLCO ) was 0.201 × weight (kg) + 8.979; for TLNO was 0.76 × height (cm)-24.383; for Dm was 0.388 × height (cm)- 12.555 and for VA was 0.34 × height (cm)-3.951. Vc increased significantly with weight (P < .05) but not with age (P > .05). References norms for TLCO and TL for nitric oxide and its components in young Tunisian boys are similar to data from other countries. The prediction equations we developed can be extended to clinical practice in Tunisia and can be considered for use in neighboring North African countries.


Association of the functional polymorphism in the catechol-O-methyltransferase gene with schizophrenia in the three ethnic groups of the Malaysian population.
The catechol-O-methyltransferase (COMT) gene is a candidate gene for schizophrenia as its encoded enzyme is involved in the metabolic inactivation of dopamine and noradrenaline. Several molecular genetic studies thus far have demonstrated that the COMT functional polymorphism of Val158Met is susceptible with schizophrenia. Hence, the present study aims to determine this genetic association of this SNP in the three major ethnic groups of the Malaysian population. A total of 317 patients (79 Malays, 154 Chinese and 84 Indians) meeting DSM-IV criteria for schizophrenia and 417 healthy subjects (160 Malays, 164 Chinese and 93 Indians) were recruited. A PCR-RFLP method was used to determine the genotypes and alleles present. We found a significant association of genotypes within the total pooled samples, as well as in the female subgroup, with a higher frequency of heterozygotes in schizophrenia subjects. However, there were no significant differences in allele and genotype frequency between the schizophrenic patients and normal controls in all three ethnic groups. Our current findings suggest that the Val158Met polymorphism has a weak association with schizophrenia in the Malaysian population and does not play a major role in conferring susceptibility to the schizophrenia in any of the three major local ethnicities.


One-year durability of anti-spike IgG to SARS-CoV-2: Preliminary data from the anticrown prospective observational study one year durability of COVID-19 anti-spike IgG.
Data are presented of 368/503 post-COVID-19 outpatients followed within the AntiCROWN Cohort who have a one-year control and a baseline assessment of anti-S1/S2 antibodies, detected with the The LIAISON® SARS-CoV-2 S1/S2 IgG solution by DiaSorin. Loss of response occurred in 4 subjects having a baseline level below 50 AU/mL.


Distinct Mucoinflammatory Phenotype and the Immunomodulatory Long Noncoding Transcripts Associated with SARS-CoV-2 Airway Infection.
Respiratory epithelial cells are the primary target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the 3D human airway tissue model to evaluate innate epithelial cell responses to SARS-CoV-2 infection. A SARS-CoV-2 clinical isolate productively infected the 3D-airway model with a time-dependent increase in viral load (VL) and concurrent upregulation of airway immunomodulatory factors ( IL-6, ICAM-1 , and SCGB1A1 ) and respiratory mucins ( MUC5AC, MUC5B, MUC2 , and MUC4) , and differential modulation of select long noncoding RNAs (lncRNAs i.e., LASI, TOSL, NEAT1 , and MALAT1 ). Next, we examined these immunomodulators in the COVID-19 patient nasopharyngeal swab samples collected from subjects with high- or low-VLs (∼100-fold difference). As compared to low-VL, high-VL patients had prominent mucoinflammatory signature with elevated expression of IL-6, ICAM-1, SCGB1A1, SPDEF, MUC5AC, MUC5B , and MUC4 . Interestingly, LASI, TOSL , and NEAT1 lncRNA expressions were also markedly elevated in high-VL patients with no change in MALAT1 expression. In addition, dual-staining of LASI and SARS-CoV-2 nucleocapsid N1 RNA showed predominantly nuclear/perinuclear localization at 24 hpi in 3D-airway model as well as in high-VL COVID-19 patient nasopharyngeal cells, which exhibited high MUC5AC immunopositivity. Collectively, these findings suggest SARS-CoV-2 induced lncRNAs may play a role in acute mucoinflammatory response observed in symptomatic COVID-19 patients.


The acute and sub-chronic effects of levocetirizine, cetirizine, loratadine, promethazine and placebo on cognitive function, psychomotor performance, and weal and flare.
To compare the central and peripheral H1 inhibitory effects of acute and sub-chronic doses of levocetirizine (L-CTZ), cetirizine (CTZ), loratadine (LOR) and promethazine (PRM) versus placebo, using a battery of psychomotor and cognitive tests together with measures of the weal and flare reaction. PRM was included in the study as a positive internal control to validate the sensitivity of the psychometric test battery to the CNS effects of the various treatments. Twenty healthy volunteers (18-50 years) received L-CTZ 5mg, CTZ 10 mg, LOR 10 mg, PRM 30 mg and placebo once daily for four days in a five-way, double-blind, crossover study. For each treatment condition, subjects were assessed using a psychometric test system and a pinprick weal and flare response to 100 mg/ml histamine solution at baseline and at 1, 2, 3 ,4, 6, 8, 10 and 122 hours post-dose on days 1 and 4. The psychometrics comprised critical flicker fusion (CFF), choice reaction time (CRT), a continuous tracking task (CTT) and subjective rating scales for sedation (LARS). On days 2 and 3, subjects took their medication at pre-designated times while out of the unit. The verum (PRM) established the sensitivity of the test battery: a significant overall reduction in CFF thresholds on both days 1 and 4 (p < 0.05); an overall significant increase (impairment) in recognition, motor and total reaction times on day 1 (p < 0.05); a significant impairment of both the tracking accuracy and reaction time aspects of the CTT task on day 1 (p < 0.005) and significantly higher ratings of subjective sedation on day 1 (p < 0.05). L-CTZ, CTZ and LOR were not distinguishable from placebo in any of the objective and subjective tests at any time point on either day 1 or day 4. With regards to the peripheral inhibitory effects, L-CTZ inhibited both the weal and flare reaction, with maximum inhibition (almost 100%) occurring within two hours of drug ingestion. CTZ also showed evidence of potent peripheral inhibition of histamine, whereas PRM, and especially LOR, showed only a weak weal and flare reaction which had completely attenuated at day 4. In a study where the psychometric assessments were shown to be sensitive to impairment, L-CTZ 5 mg was found following both initial and repeated doses, but also to be demonstrably free from disruptive and sedative effects on objective measures of psychomotor and cognitive function. Similarly, CTZ showed evidence of pronounced antihistaminic activity and significantly reduced weal and flare scores after both acute and repeated doses, again without evidence of cognitive or psychomotor impairment. LOR also was non-sedative but the antihistaminic reaction was demonstrably weak.


Effects of Corrective Exercises on Posture, Pain, and Muscle Activation of Patients With Chronic Neck Pain Exposed to Anterior-Posterior Perturbation.
This study aimed to evaluate the effects of corrective exercises on posture, pain, and muscle activation of patients with chronic neck pain exposed to anterior-posterior perturbation. A total of 32 women (37.76 ± 3.83 years) with chronic, nonspecific neck pain were randomized into corrective exercise and control groups. The experimental group underwent a corrective exercise program for 8 weeks, 30 min/d, 3 days per week. The control group received active self-exercise instructions. Neck pain, forward head and protracted shoulder posture, and timing of superficial neck muscle activation were evaluated using the visual analog scale, photogrammetry, and electromyogram, respectively, before and then 48 hours after the 8-week program for both the experimental and control groups. All measurements at pretest and posttest were taken by a blinded assessor. Significant alterations were observed in cervical angle (P = .003, effect size = 0.329), shoulder angle (P = .008, effect size = 0.457), neck pain and disability (P = .009, effect size = 0.645), movement control (P = .038, effect size = 0.353), activation onset of the upper trapezius (P = .015, effect size = 0.746), the sternocleidomastoid (P = .018, effect size = 0.879) and cervical erector spinae (P = .031, effect size = 0.765), and the root mean square of the upper trapezius (P = .033, effect size = 0.742), the sternocleidomastoid (P = .041, effect size = 0.587), and the cervical erector spinae (P = .024, effect size = 0.832) in the intervention group from pre- to posttest (P < .05). Positive and significant alterations have been observed in the forward head and protracted shoulder posture, the timing of superficial neck muscle activation, neck pain, and disability in female patients with chronic neck pain exposed to anterior-posterior perturbation after performing an 8-week corrective exercise program.


Novel mutations in the SOX10 gene in the first two Chinese cases of type IV Waardenburg syndrome.
We analyzed the clinical features and family-related gene mutations for the first two Chinese cases of type IV Waardenburg syndrome (WS4). Two families were analyzed in this study. The analysis included a medical history, clinical analysis, a hearing test and a physical examination. In addition, the EDNRB, EDN3 and SOX10 genes were sequenced in order to identify the pathogenic mutation responsible for the WS4 observed in these patients. The two WS4 cases presented with high phenotypic variability. Two novel heterozygous mutations (c.254G>A and c.698-2A>T) in the SOX10 gene were detected. The mutations identified in the patients were not found in unaffected family members or in 200 unrelated control subjects. This is the first report of WS4 in Chinese patients. In addition, two novel mutations in SOX10 gene have been identified.


Serendipity meets precision: the integration of structure-based drug design and combinatorial chemistry for efficient drug discovery.
Structure-based drug design uses three-dimensional visualization of drug candidates bound to a target receptor to direct structural modifications that increase potency. This widely used approach is limited by the difficulty of accurately predicting drug-binding affinities from three-dimensional structures. The integration of structure-based drug design with combinatorial chemistry can overcome this limitation by providing an empirical understanding of drug-binding energies. This integration allows compound synthesis and evaluation in parallel, and also helps assure that the compounds produced have properties consistent with good bioavailability and safety.


A national advanced training program for laparoscopic radical gastrectomy has a positive impact on surgical trainees: A before and after study (ATP-LRG-1).
Due to the high technical requirements of laparoscopic radical gastrectomy (LRG), establishing an effective training system to promote clinical technology and operation specifications is necessary. We aimed to evaluate the effect of a national advanced training program for LRG (ATP-LRG). The contents of the training include the following: 1) detailed technique descriptions; 2) prevention and solving of intraoperative complications; 3) live surgery performance; 4) theory and practice of clinical research; 5) comments on trainees' videos; and 6) questions, answers, and discussions. This retrospective before and after study surveyed 875 trainees from January 2015 to October 2020. Endpoints were general surgical skills (GSS), laparoscopic gastrectomy acceptance (LGA), and clinical research possibilities (CRP). The analysis took place in December 2021. The response rate was 70.5% (617/875). ATP-LRG reportedly had a positive impact on the LRG practice of 99.5% (614/617) of trainees. Their GSS (before vs. after: 16.5 ± 3.7 vs. 20.3 ± 3.1, P < 0.001), LGA (4.2 ± 0.9 vs. 4.6 ± 0.7, P < 0.001), and CRP (2.6 ± 1.2 vs. 3.2 ± 1.1, P < 0.001) significantly improved. The improvement in GSS for those with professional titles of associate chief surgeons and below was significantly higher than that for chief surgeons (4.0 ± 3.0 vs 3.3 ± 2.4, P = 0.017), while those of LGA and CRP were not. The annual number of operations before training was negatively correlated with improvement in GSS (P < 0.001, Pearson's correlation coefficient: 0.14). Multivariate logistic regression showed that those with professional titles of associate chief surgeons and below (odds ratio [OR]: 1.719, 95% confidence interval [CI]: 1.038-2.846, P = 0.035), and with annual number of operations before training being <60, (OR: 5.257, 95% CI: 2.573-10.742, P < 0.001) were most prone to high-GSS improvement. The nationwide ATP-LRG facilitates the improvement of trainees' GSS, LGA, and CRP levels. Surgeons with lower professional titles and fewer performed operations are most likely to improve their GSS through training.


Spinal Cord Injury Clinical Classification Systems: What Is Available and a Proposed Alternative.
Spinal cord injury (SCI) remains a challenging disease in terms of surgical decision-making and improving neurologic outcome. As we have now entered a new era founded on routine "big data" capture, more advanced and meaningful yet simplified SCI classification systems and outcome measurement tools would be helpful to determine the efficacy of potential therapeutics in future clinical trials and registries. The proposed classification herein focuses on gross sensorimotor, sacral function below the injured level via an easy-to-use scoring system yielding grades 1 to 4 of injury severity. Such an optimized SCI scoring system would enhance real-time analytics and offer superior outcomes modeling.


Stereoselective separation of omeprazole and 5-hydroxy-omeprazole using dried plasma spots and a heart-cutting 2D-LC approach for accurate CYP2C19 phenotyping.
Omeprazole (OME) is a widely used gastric proton pump inhibitor, marketed as a racemic mixture comprising (S)- and (R)-enantiomers, with distinct pharmacokinetic profiles. OME is primarily metabolized by the cytochrome P450 enzymes 2C19 (CYP2C19) and 3A4 (CYP3A4). OME is a conventional probe for CYP2C19 phenotyping. Accurate measurement of these enantiomers and their metabolites is essential for pharmacokinetic studies. This article presents a sensitive and accurate two-dimensional liquid chromatography-mass spectrometry (LC-MS/MS) method for the simultaneous quantification of OME enantiomers and its hydroxylated metabolite (5-hydroxyomeprazole) in human plasma. The method involves an online extraction using an achiral Discovery HS C18 trapping column for purification (20 × 2.1 mm ID, 5μm particle size, Supelco) and subsequent forward flush elution onto a chlorinated phenylcarbamate cellulose-based chiral column (150x2mm ID, 3 μm particle size, Lux Cellulose-4, Phenomenex). The assay was fully validated and met international validation criteria for accuracy, precision, and stability and ensured high selectivity and sensitivity within a short runtime (<8 min). Application of this method to clinical samples demonstrated its utility in studying OME enantiomer pharmacokinetics, particularly its potential for phenotyping the activity of the CYP2C19 isoenzyme. This robust analytical approach offers a valuable tool for clinicians and researchers studying OME's pharmacokinetics, providing insights into its metabolism and potential implications for personalized medicine.


β1-Adrenoceptor antibody-induced increase in soluble CD40 ligand release in chronic periodontitis patients: role of prostaglandin E(2).
In this paper, we demonstrate that circulating antibodies from chronic periodontitis patients reacting with atrial β(1)-adrenoceptors (β(1)-ARs) act as an inducer of soluble CD40 ligand (sCD40L) release and prostaglandin E(2) (PGE(2)) generation. By enzyme-linked immunosorbent assay using β(1) synthetic peptide (with an amino acid sequence identical to the second loop of human myocardial β(1)-ARs) as a coating antigen, we demonstrated reactivity against the second extracellular loop on human myocardial β(1)-ARs. This autoantibody present in the serum of chronic periodontitis patients was significantly correlated with the release of sCD40L and PGE(2). The release of sCD40L was blunted by atenolol, SP600125 and β(1) synthetic peptide, and PGE(2) generation was inhibited by DuP 697 and slightly by FR122049. The effects of the antibody incubated with isolated rat atria upregulated sCD40L release with an increase of PGE(2) production and c-Jun N-terminal kinase phosphorylation. These results indicate that in chronic periodontitis patients, there is a positive association between sCD40L release and PGE(2) generation via the action of β(1)-AR antibodies.


[Role of ultrasound in microcrystalline arthritis].
Ultrasound is a new imaging technique that allows accurately visualize normal and pathological musculoskeletal structures and provide real-time information on the vascular flow. There are a number of ultrasound elemental lesions that alone or in combination are characteristics of gout and chondrocalcinosis. Gout ultrasound is proving to be valid in the diagnosis and monitoring of disease, both in acute as in the chronic and even in asymptomatic hyperuricemia and it is probably the most reliable technique for assessing the size and reduction of tophy. In chondrocalcinosis ultrasound is also proving a superior diagnostic value to other imaging techniques and possibly in the future may be used to monitoring treatment response.


Regeneration of the replication-associated proteins tandem direct repeat recognition nucleotide sequence at the origin of DNA replication of porcine circovirus type 1.
Four copies of a hexanucleotide (H) sequence are located to the right of the palindrome at the origin of DNA replication of the porcine circovirus type 1 (PCV1) genome. These sequences are organized in two direct tandems, the proximal H1/H2 and the distal H3/H4 repeats, and they have been shown to be binding sites for the essential Rep and Rep' proteins. Previous work demonstrated that infectious PCV1 virion can accommodate a variable number of H sequences at the origin of DNA replication. In this work, mutational analysis was conducted to elucidate the critical core element within the hexanucleotide with respect to self-DNA replication and progeny virus synthesis. It was found that while a single H sequence abutting the palindrome is sufficient for PCV1 viability, a tandem repeat arrangement is the more stable and thus preferred configuration. Within the H sequence, selected nucleotides at specific positions are critical for Rep-associated protein recognition and for viral DNA replication.


A comparison of conventional and retrospective measures of change in symptoms after elective surgery.
Measuring change is fundamental to evaluations, health services research and quality management. To date, the Gold-Standard is the prospective assessment of pre- to postoperative change. However, this is not always possible (e.g. in emergencies). Instead a retrospective approach to the measurement of change is one alternative of potential validity. In this study, the Gold-Standard 'conventional' method was compared with two variations of the retrospective approach: a perceived-change design (model A) and a design that featured observed follow-up minus baseline recall (model B). In a prospective longitudinal observational study of 185 hernia patients and 130 laparoscopic cholecystectomy patients (T0: 7-8 days pre-operative; T1: 14 days post-operative and T2: 6 months post-operative) changes in symptoms (Hernia: 9 Items, Cholecystectomy: 8 Items) were assessed at the three time points by patients and the conventional method was compared to the two alternatives. Comparisons were made regarding the percentage of missing values per questionnaire item, correlation between conventional and retrospective measurements, and the degree to which retrospective measures either over- or underestimated changes and time-dependent effects. Single item missing values in model A were more frequent than in model B (e.g. Hernia repair at T1: model A: 23.5%, model B: 7.9%. In all items and at both postoperative points of measurement, correlation of change between the conventional method and model B was higher than between the conventional method and model A. For both models A and B, correlation with the change calculated with the conventional method was higher at T1 than at T2. Compared to the conventional model both models A and B also overestimated symptom-change (i.e. improvement) with similar frequency, but the overestimation was higher in model A than in model B. In both models, overestimation was lower at T1 than at T2 and lower after hernia repair than after cholecystectomy. The retrospective method of measuring change was associated with a larger improvement in symptoms than was the conventional method. Retrospective assessment of change results in a more optimistic evaluation of improvement by patients than does the conventional method (at least for hernia repair and laparoscopic cholecystectomy).


Subcutaneous panniculitis-like T-cell lymphoma in a young girl presenting with periorbital edema and fever: A case report.
Subcutaneous panniculitis-like T-cell lymphoma is a rare and highly malignant extra-nodal lymphoma. It has a wide range of clinical presentations (such as periorbital swelling as in our case) and should be considered in the differential diagnosis of systemic lupus erythematosus, especially in children.


Spontaneously Arising Tumours and Tumour-like Lesions of the Cervix and Uterus in 83 Pet Guinea Pigs (Cavia porcellus).
Tumours and tumour-like lesions are rare findings in the genital system of guinea pigs. The aim of the present study was to characterize nodular lesions in the cervix and uterus of guinea pigs submitted for histopathological diagnosis. Samples from 83 pet animals were investigated. Cases included 64 surgically excised masses including complete uteri (n = 37), parts from uteri containing masses (n = 8), complete masses (n = 12) or samples from masses (n = 7) and 19 complete necropsy examinations. In 55 of the cases, only solitary changes were observed; in 28 cases two or more lesions were diagnosed. Histopathological diagnoses included polyps in the vagina, cervix or uterus (n = 8), hyperplastic lesions of the endocervix (n = 10) and seven adenomas and two adenocarcinomas of the endocervix. Endometrial alterations included single small glandular cysts (n = 3), nodular glandular-cystic hyperplasia (n = 8), adenoma (n = 20) and adenocarcinoma (n = 3). Four placentas, 10 focal decidualizations and six deciduomas were found. Furthermore, 18 leiomyomas and nine leiomyosarcomas were diagnosed. Uterine malignant mixed Müllerian tumours were observed in seven cases. Overall, benign lesions outnumbered malignant tumours in the female genital tract of pet guinea pigs. Therefore, surgical excision or ovariohysterectomy should be recommended as therapy.


Intercellular adhesion molecule-1 (ICAM-1) polymorphism is associated with diabetic retinopathy in Type 2 diabetes mellitus.
Leucocyte adhesion to the diabetic retinal vasculature has been implicated in the pathogenesis of diabetic retinopathy. We evaluated the relationship between genetic polymorphisms in leucocyte and endothelial cell adhesion molecules and diabetic retinopathy in Type 2 diabetes mellitus. We determined ICAM-1, platelet endothelial cell adhesion molecule-1 (PECAM-1), and leucocyte endothelial adhesion molecule-1 (LECAM-1) genotypes in 81 patients with and 50 without diabetic retinopathy. The frequency of ICAM-1 469KK genotype and K allele were significantly higher in the patients with diabetic retinopathy than in those without retinopathy (genotype 42% vs. 20%, chi2 = 6.70, P = 0.035; allele 66% vs. 50%, chi2 = 6.49, P = 0.011). With regard to the PECAM-1 V125L and LECAM-1 P213S polymorphisms, there were no significant associations between the distribution of genotypes or allele frequencies and the presence of diabetic retinopathy. Independent of other risk factors, the ICAM-1 469KK genotype was associated with a 3.51-fold increased risk for retinopathy. These data suggest that the ICAM-1 469KK genotype could be a genetic risk factor for retinopathy in Type 2 diabetes mellitus.


Immunocytochemical characterization of olfactory ensheathing cells in fish.
In the olfactory system of vertebrates, neurogenesis occurs throughout life. The regenerating activities of the olfactory receptor neurons are connected to particular glial cells in the olfactory pathway: the olfactory ensheathing cells. A considerable number of studies are available in literature regarding mammalian olfactory ensheathing cells; this is due to their potential role in cell-based therapy for spinal cord injury repair. But very little is known about these cells in non-mammalian vertebrates. In this study we examined the immunocytochemical characteristics of the olfactory ensheathing cells in fish, which provide a good model for the study of glial cells in the olfactory pathway of non-mammalian vertebrates. Paraffin sections from decalcified heads of Poecilia reticulata (microsmatic fish) and Carassius auratus (macrosmatic fish) were processed to immunocytochemically detect ensheathing cell markers used in research on mammals: GFAP, S100, NCAM, PSA-NCAM, vimentin, p75NTR and galectin-1. GFAP, S100 and NCAM were clearly detected in both fish, though the intracranial tract of the primary olfactory pathway of Carassius appears more S100 stained than the extracranial tract. P75NTR staining is more evident in Poecilia, PSA-NCAM positivity in Carassius. A slight vimentin immunostaining was detected only in Carassius. No galectin-1 staining appeared in the olfactory pathways of either fish. This study shows that some markers for mammalian olfactory ensheathing cells also stain the olfactory pathway in fish. Immunocytochemical staining differs in the two fish under examination, even along the various tracts of the olfactory pathway in the same species.


Scoring systems for the evaluation of adnexal masses nature: current knowledge and clinical applications.
Adnexal masses are a common finding in women, with 20% of them developing at least one pelvic mass during their lifetime. There are more than 30 different subtypes of adnexal tumours, with multiple different subcategories, and the correct characterisation of the pelvic masses is of paramount importance to guide the correct management. On that basis, different algorithms and scoring systems have been developed to guide the clinical assessment. The first scoring system implemented into the clinical practice was the Risk of Malignancy Index, which combines ultrasound evaluation, menopausal status, and serum CA-125 levels. Today, current guidelines regarding female patients with adnexal masses include the application of International Ovarian Tumours Analysis simple rules, logistic regression model 1 (LR1) and LR2, OVERA, cancer ovarii non-invasive assessment of treating strategy, and assessment of Different Neoplasias in the adnexa. In this scenario, the choice of the scoring system for the discrimination between benign and malignant ovarian tumours can be complex when approaching patients with adnexal masses. This review aims to summarise the available evidence regarding the different scoring systems to provide a complete overview of the topic.


Predictors of relapse in patients with medication overuse headache in Shanghai: A retrospective study with a 6-month follow-up.
Medication overuse headache (MOH) has a high relapse rate and disease heterogeneity. This study aimed to determine the predictors of MOH relapse in patients through a 6-month follow-up in Shanghai. In this retrospective study, patients diagnosed with MOH from June 2016 to June 2017 were recruited and followed up for 6 months after withdrawal treatment in Renji Hospital in Shanghai. Patients' information was obtained using headache questionnaires. Follow-up was conducted via telephone interview. Patients were divided into relapse group and no-relapse group according to the outcomes after 6 months. This study enrolled 124 outpatients with MOH at baseline. 102 patients completed the follow up and were analysis finally. Demographics and clinical characteristics were compared between the relapse (n = 39, 38.24%) and no-relapse (n = 63, 61.76%) group. Binary logistic regression analysis was performed, and two variables emerged as significant predictors of relapse before withdrawal; the headache frequency (day/month) was higher in the relapse group than in the no-relapse group [odds ratio (OR) 1.107, p = 0.008]. Furthermore, patients administered analgesics of ≥ 2 units per headache day had a higher risk of relapse [odds ratio (OR) 2.791, p = 0.038]. Headache frequency and analgesics units per headache day before withdrawal may be independent predictors of MOH relapse. Therefore, early identification of high-risk groups and enhancing patients' management could contribute to improving the prognosis of MOH.


Familial and sporadic pancreatic cancer share the same molecular pathogenesis.
Pancreatic ductal adenocarcinoma (PDAC) is nearly uniformly lethal, with a median overall survival in 2014 of only 6 months. The genetic progression of sporadic PDAC (SPC) is well established, with common somatic alterations in KRAS, p16/CDKN2A, TP53, and SMAD4/DPC4. Up to 10 % of all PDAC cases occur in families with two or more affected first-degree relatives (familial pancreatic cancer, FPC), but these cases do not appear to present at an obviously earlier age of onset. This is unusual because most familial cancer syndrome patients present at a substantially younger age than that of corresponding sporadic cases. Here we collated the reported age of onset for FPC and SPC from the literature. We then used an integrated approach including whole exomic sequencing, whole genome sequencing, RNA sequencing, and high density SNP microarrays to study a cohort of FPC cell lines and corresponding germline samples. We show that the four major SPC driver genes are also consistently altered in FPC and that each of the four detection strategies was able to detect the mutations in these genes, with one exception. We conclude that FPC undergoes a similar somatic molecular pathogenesis as SPC, and that the same gene targets can be used for early detection and minimal residual disease testing in FPC patients.


Triggered release of proteins from emulsan-alginate beads.
Emulsan/alginate beads were studied for protein adsorption and stability in the context of controlled release. The beads, 400 +/- 80 microm diameter with approximately 10% emulsan content, offer unusual opportunities for delivery of proteins due to the natural ability of emulsan to bind proteins, coupled with the selective biological activation features of this complex lipoheteropolysaccharide. The binding capacity of azo-bovine serum albumin by the emulsan/alginate beads was 0.637 +/- 0.004 vs. 0.170 +/- 0.007 microg/mg for beads formed from alginate alone. In additional protein adsorption experiments, the lipase and subtilisin maintained activity when adsorbed to the emulsan/alginate beads albeit with lower specific activity when compared to the enzyme free in solution. However, the half life of the adsorbed enzyme was significantly higher than the free forms. To explore functional utility of this system, two types of triggered release were studied in the context of these bead systems. First, azo-BSA as a model protein was physically bound to emulsan/alginate beads and then selectively released by triggering with subtilisin, a serine protease, which cleaves the azo dye, sulfanilic acid, from the bound protein. In absence of subtilisin no triggered release was observed. Second, azo-BSA as a prodrug model, was adsorbed to the emulsan/alginate beads and then release of the dye was demonstrated by lipase treatment which cleaves the fatty acid esters from the emulsan structure to release the bound protein. The results establish the versatility and utility of emulsan-based beads for protein binding and triggered release.


Strongyloides stercoralis Hyperinfection Syndrome as a Cause of Fatal Gastrointestinal Hemorrhage.
Strongyloides stercoralis is a small intestinal nematode that is widespread in regions with poor sanitation. We present a 57-year-old man from Colombia who was undergoing corticosteroid therapy for a meningioma who presented after neurosurgery with abdominal pain and a profound gastrointestinal (GI) bleed. The patient underwent an esophagogastroduodenoscopy (EGD), an attempted embolization, and an exploratory laparotomy to remove the necrosed duodenum. His pathology examination revealed Strongyloides infection of the duodenum, and he died of profound blood loss. This rare diagnosis displays the importance of screening patients at a high risk of Strongyloides infection before starting glucocorticoid therapy.


Long-term trends in smoking prevalence and its socioeconomic inequalities in Korea, 1992-2016.
The aim of this study was to investigate long-term trends in smoking prevalence and its socioeconomic inequalities in Korea. Data were collected from 10 rounds of the Social Survey of Statistics Korea between 1992 and 2016. A total of 524,866 men and women aged 19 or over were analyzed. Age-adjusted smoking prevalence was calculated according to three major socioeconomic position indicators: education, occupational class, and income. The prevalence difference, prevalence ratio, slope index of inequality (SII), and relative index of inequality (RII) were calculated to examine the magnitude of inequality in smoking. Smoking prevalence among men decreased from 71.7% in 1992 to 39.7% in 2016, while smoking prevalence among women decreased from 6.5% in 1992 to 3.3% in 2016. Socioeconomic inequalities in smoking prevalence according to the three socioeconomic position indicators were found in both men and women throughout the study period. In general, absolute and relative socioeconomic inequalities in smoking, measured by prevalence difference and prevalence ratio for education and occupational class, widened during the study period among Korean men and women. In men, the SII for income increased from 7.6% in 1999 to 10.8% in 2016 and the RII for income also increased from 1.11 in 1999 to 1.31 in 2016. In women, the SII for income increased from 0.1% in 1999 to 2.4% in 2016 and the RII for income increased from 1.39 in 1999 to 2.25 in 2016. Pro-rich socioeconomic inequalities in smoking prevalence were found in men and women. Socioeconomic inequalities in smoking have increased in parallel with the implementation of tobacco control policies. Tobacco control policies should be developed to decrease socioeconomic inequalities in cigarette use in Korea.


Target population for the screening of human papillomavirus (HPV) and anal carcinoma precursor lesions - Results from a pilot study in HIV-infected males with sexual risk factors.
Ninety-five percent of precursor lesions -high-grade squamous intraepithelial lesions (HSIL) and anal intraepithelial neoplasms (AIN)- and their progression to squamous anal cancer (AC) are induced by high-risk HPV (HR-HPV) serotypes 16 and 18. Their incidence is higher particularly in HIV-infected male patients who have sex with other males (HIV-MSM) (144/100,000/patients/year).


miR-185-5p response to usnic acid suppresses proliferation and regulating apoptosis in breast cancer cell by targeting Bcl2.
Breast cancer is the most common cancer types among women. Recent researches have focused on determining the efficiency of alternative molecules and miRNAs in breast cancer treatment. The aim of this study was to determine the effect of usnic acid response-miR-185-5p on proliferation in the breast cancer cell and to determine its relationship with apoptosis pathway. The cell proliferation and cell apoptosis rate were significantly increased following the ectopic expression of miR-185-5p in BT-474 cells. Furthermore, the results of cell cycle assay performed by flow cytometry revealed that the transfection with miR-185-5p induced G1/S phase arrest. The apoptosis-related genes expression analysis was performed by qRT-PCR and the direct target of miR-185-5p in BT-474 cells was identified by western blot and luciferase reporter assay. Our data showed that miR-185-5p can cause significant changes in apoptosis-related genes expression levels, suggesting that cell proliferation was suppressed by miR-185-5p via inducing apoptosis in breast cancer cells. According to western blot results, miR-185-5p lead to decrease BCL2 protein level in BT-474 cells and direct target of miR-185-5p was identified as BCL by luciferase reporter assay. This study revealed that miR-185-5p may be an effective agent in the treatment of breast cancer.