Genetic effects of chronic treatment with cathinone in mice

The mutagenicity of (—)-cathinone has been evaluated inthe germ cells of male albino mice using a dominant lethal test.An aqueous solution of cathinone was administered orally atdoses of 5, 20 or 40 mg/kg body wt, respectively to three differentgroups of male mice for a period of six weeks. After treatment,each male was allowed to mate with two different groups of threefemales each, on two consecutive weeks. These females were necropsiedon the 17th day after mating. The number of implants in eachfemale and the ratio of live and dead embryos was determined.The results of this study showed that treatment of male miceover a period of 6 weeks produced a dose-dependent reductionin fertility with total sterility at a dose of 40 mg/kg bodywt. Cathinone also induced dose-dependent post-implantationloss during the first week following treatment. However, nodominant lethality was detected during the second week of mating.     

Reiter's syndrome following intravesical BCG immunotherapy

A 71 year old woman developed conjunctivitis, asymmetrical oligoarthritis, and cystitis (Reiter's syndrome) secondary to intravesical BCG treatment for transitional cell carcinoma of the bladder. She received oral prednisolone, izoniazid, and pyridoxine and made a full recovery. Increasing use of BCG as immunotherapy will lead to an increase in the incidence of BCG associated reactive arthritis. Prompt recognition and early diagnosis will facilitate treatment and recovery.     

Association of dry eye disease with smoking: A systematic review and meta-analysis

There is conflicting evidence for the association between smoking and dry eye disease (DED). We conducted a meta-analysis to determine the true relationship between smoking and DED. A systematic literature search was performed using electronic databases, including PubMed, Embase and Cochrane Library, till August 2021 to identify observational studies with data on smoking as risk factor of DED. Quality assessment of the included studies was conducted using Joanna Briggs Institute (JBI) critical appraisal checklists. The random-effects model was used to calculate the pooled odds ratio (OR). Heterogeneity was evaluated by Cochrane Q and I² index; in addition, subgroup, sensitivity, and meta-regression analyses were performed. Publication bias was assessed using funnel plot and Egger’s regression test. A total of 22 studies (4 cohort and 18 cross-sectional studies) with 160,217 subjects met the inclusion criteria and were included in this meta-analysis. There is no statistically significant relationship between current smokers (OR_adjusted = 1.14; 95% CI: 0.95–1.36; P = 0.15; I² = 84%) and former smokers (OR_adjusted = 1.06; 95% CI: 0.93–1.20; P = 0.38; I² = 26.7%) for the risk of DED. The results remained consistent across various subgroups. No risk of publication bias was detected by funnel plot and Eggers’s test (P > 0.05). No source of heterogeneity was observed in the meta-regression analysis. Our meta-analysis suggest current or former smoking may not be involved in the risk of dry eye disease. Further studies to understand the mechanism of interaction between current smokers and formers smokers with DED are recommended.     

Effect of a low-dose endotoxin pretreatment on the gastric mucosal damage induced by aspirin, phenylbutazone and reserpine in rats

The effect of endotoxin pretreatment (1 mg/kg body weight, i.p., once daily for 2 days) on the gastric mucosal damage induced by aspirin, phenylbutazone and reserpine has been studied in albino rats. When given alone, endotoxin did not produce any visibly discernible gastric lesions. It produced a significant augmentation of the gastric lesions produced by phenylbutazone and reserpine but did not significantly alter the ulcerogenicity of aspirin. The involvement of endogenous histamine formation and its release following phenylbutazone and reserpine administration and also in response to endotoxin pretreatment may be responsible for the exacerbation of gastric lesions induced by these drugs. Recent reports indicate the involvement of endorphins and platelet activating factor (PAF) in the ulcerogenic activity of endotoxin when used in high doses and their role in the potentiation of phenylbutazone- and reserpine-induced gastric lesions has to be worked out.     

Metabolic and pharmacological profiling of Penicillium claviforme by a combination of experimental and bioinformatic approaches

BackgroundPenicillium produces a wide range of structurally diverse metabolites with significant pharmacological impacts in medicine and agriculture. For the first time, a complete metabolome of Penicillium claviforme (P. claviforme) (FBP-DNA-1205) was studied alongside pharmacological research in this study.MethodsThe metabolic profile of P. claviforme fermented on Potato Dextrose Broth (PDB) was investigated in this work. The complete metabolomics studies of fungus were performed using GC-MS and LC-MS-QTOF techniques. An in vitro model was utilised to study the cytotoxic and antioxidant activities, while an in vivo model was employed to investigate the antinociceptive and acute toxicity activities. Molecular Operating Environment (MOE) software was used for molecular docking analysis.ResultsGC-MS study showed the presence of alkanes, fatty acids, esters, azo and alcoholic compounds. Maculosin, obtain, phalluside, quinoline, 4,4’-diaminostilbene, funaltrexamine, amobarbital, and fraxetin were among the secondary metabolites identified using the LC-MS-QTOF technique. The n-hexane fraction of P. claviforme displayed significant cytotoxic activity in vitro, with an LD50 value of 92.22 µgml⁻¹. The antinociceptive effects in vivo were dose-dependent significantly (p < .001). Interestingly, during the 72 h of investigation, no acute toxicity was demonstrated. In addition, a docking study of tentatively identified metabolites against the inflammatory enzyme (COX-2) supported the antinociceptive effect in an in silico model.ConclusionMetabolic profile of P. claviforme shows the presence of biologically relevant compounds in ethyl acetate extract. In addition, P. claviforme exhibits substantial antioxidant and cytotoxic activities in an in vitro model as well as antinociceptive activity in an in vivo model. The antinociceptive action is also supported by a molecular docking study. This research has opened up new possibilities in the disciplines of mycology, agriculture, and pharmaceutics.

Key messages

• The first time explored complete metabolome through GC-MS and LC-MS-QTOF.
• Both in vivo & in vitro pharmacological investigation of P. claviforme.
• In silico molecular docking of LC-MS-QTOF metabolites.

     

Improved Shear Strength Prediction Model of Steel Fiber Reinforced Concrete Beams by Adopting Gene Expression Programming

In this study, an artificial intelligence tool called gene expression programming (GEP) has been successfully applied to develop an empirical model that can predict the shear strength of steel fiber reinforced concrete beams. The proposed genetic model incorporates all the influencing parameters such as the geometric properties of the beam, the concrete compressive strength, the shear span-to-depth ratio, and the mechanical and material properties of steel fiber. Existing empirical models ignore the tensile strength of steel fibers, which exercise a strong influence on the crack propagation of concrete matrix, thereby affecting the beam shear strength. To overcome this limitation, an improved and robust empirical model is proposed herein that incorporates the fiber tensile strength along with the other influencing factors. For this purpose, an extensive experimental database subjected to four-point loading is constructed comprising results of 488 tests drawn from the literature. The data are divided based on different shapes (hooked or straight fiber) and the tensile strength of steel fiber. The empirical model is developed using this experimental database and statistically compared with previously established empirical equations. This comparison indicates that the proposed model shows significant improvement in predicting the shear strength of steel fiber reinforced concrete beams, thus substantiating the important role of fiber tensile strength.     

The Effect of Dentifrice on Micro-Hardness,Surface Gloss,and Micro-Roughness of Nano Filled Conventional and Bulk-Fill Polymer Composite—A Micro Indentation and Profilometric Study

The aim of the present study was to evaluate the effect of brushing with two whitening dentifrices (Colgate Optic White (COW) and Colgate Optic White Charcoal (COC)) on surface gloss, micro-roughness, and micro-hardness of nanostructured hybrid conventional (Z350) and bulk-fill (Tetric N Ceram bulk-fill) polymer composite. In total, 96 disk samples using two nano-hybrid composite polymers (Z350 and Tetric N Ceram Bulk-fill) were prepared. All specimens were exposed to two different dentifrices (COW and COC), resulting in four main subgroups in the study. Specimens were assessed for surface gloss, micro-roughness (Ra), and micro-hardness using standardized methodology. Means and standard deviations of properties compared using paired t-test, one-way and two-way ANOVA, and post hoc test. The presence of dentifrices did not show any significant difference in micro-hardness values of Z350 (p > 0.05), whereas micro-hardness of bulk-fill composite significantly reduced on dentifrices exposure (p ≤ 0.05). Bulk-fill polymer composite showed significant reduction in gloss after dentifrice exposure (p < 0.05), however, Z350 showed no significant loss of gloss due to dentifrices (p > 0.05). A significant increase in Ra was observed for both resin materials after exposure to dentifrices (COC and COW). Conventional resin composite (Z350) showed comparable surface hardness and gloss before and after dentifrice exposure, however, micro-roughness increased significantly due to dentifrice exposure. Bulk-fill resin (Tetric N Ceram) showed significant loss of micro-hardness and gloss and increase in micro-roughness on dentifrice exposure. Conventional nano-hybrid composite polymer showed better durability in resisting loss of surface properties compared to bulk-fill resin polymer in the present experiment.     

Aggregation induced emission based fluorenes as dual-channel fluorescent probes for rapid detection of cyanide: applications of smartphones and logic gates

Rational modification of molecular structure by incorporating electron donating groups can play a potential role for designing aggregation induced emission (AIE) active fluorescent probes. Based on this principle, fluorescent probes (1a–c) were synthesized, and they displayed excellent aggregation induced emission (AIE) behavior in a H₂O/DMF (4 : 1, v/v) mixture due to restrictions in intramolecular charge transfer (ICT). As a comparison, probe 1d was synthesized by installing an electron withdrawing (–NO₂) group that surprisingly quenched the aggregation behaviour. Additionally, AIE active probes 1a–c displayed a highly sensitive dual channel (fluorometric and colorimetric) response towards rapid detection of CN⁻, which is an active toxic material. Probes 1a–c showed selectively enhanced fluorescence emission behavior towards CN⁻ with detection limits of 1.34 ppb, 1.38 ppb, and 1.54 ppb, respectively. The sensing mechanism involves Michael type adduct formation due to the nucleophilic addition reaction of cyanide with probes and was confirmed through ¹H NMR titration experiments. In contrast, probe 1d containing an electron withdrawing moiety showed insensitivity towards CN⁻. Therefore, this study provides the efficient strategy to induce AIE character in fluorescent probes and expands the mechanistic approach toward the sensing of toxic CN⁻.

Rational modification of molecular structure by incorporating electron donating groups can play a potential role for designing aggregation induced emission (AIE) active fluorescent probes.     

Changes in the prevalence of comorbidity of mental and physical disorders in Singapore between 2010 and 2016

INTRODUCTIONFew studies have examined the changes in the prevalence of comorbidity of mental and physical disorders in recent years. The present study sought to examine whether the prevalence of comorbidity of mental and physical disorders in Singapore showed any changes between 2010 and 2016.METHODSWe extracted data from two repeated nationally representative cross-sectional surveys conducted among resident adults aged ≥ 18 years in Singapore. Significant changes were tested using pooled multinomial logistic regression analyses.RESULTSThe prevalence of comorbid mental and physical disorders increased significantly from 5.8% in 2010 to 6.7% in 2016. Among those with physical disorders, there were significant increases over time in the prevalence of comorbid generalised anxiety disorder (GAD) (0.1% vs. 0.4%) and obsessive-compulsive disorder (OCD) (1.4% vs. 3.9%) in diabetes mellitus, and alcohol dependence in cardiovascular disorders (0.1% vs. 1.3%). Among those with mental disorders, there were significant increases over time in the prevalence of comorbid diabetes mellitus in OCD (4.1% vs. 10.9%), cancer in major depressive disorder (0.4% vs. 2.4%), and cardiovascular disorders in GAD (0.4% vs. 6.7%) and alcohol dependence (0.9% vs. 11.8%). Significant changes in the overall prevalence of comorbid mental and physical disorders were also observed across age group, education and employment status.CONCLUSIONThe prevalence of comorbid mental and physical disorders increased significantly over time. This finding supports the need for more appropriate clinical management with better integration between mental health and general medical care professionals across all aspects of the healthcare system to treat this comorbidity in Singapore.