Culture filtrate of Cryptococcus neoformans var. gattii (CneF) as a novel anti-inflammatory compound in the treatment of experimental septic arthritis

We examined the efficacy of the culture filtrate of Cryptococcus neoformans var. gattii (CneF) as a novel anti-inflammatory compound in experimental septic arthritis. Haematogenously infectious arthritis was induced in rats by a single intravenous injection of 109 CFU Staphylococcus aureus producing toxic shock syndrome toxin-1. CneF solution at two different doses (36 and 72 mg/kg, based on carbohydrate concentration) was administered intraperitoneally 2 h before bacterial inoculation in the prevention groups and simultaneously with the appearance of clinical signs in the therapeutic groups. CneF administration was continued at regular 48-h intervals for 10 injections. The results of clinical evaluation showed that CneF-treated rats were significantly protected from disease development compared with nontreated controls. This finding correlated with the results of histological and radiological assessments of the involved joints. Synovial hypertrophy, inflammatory cell infiltration, pannus formation and cartilage/bone destruction were found to be significantly decreased in the prevention and therapeutic groups compared with arthritic controls. The data suggest that CneF may have therapeutic potential in the treatment of septic arthritis.     

The Relationship between Anthropometric Indices and Breast Cancer in Central Iran

Background: Anthropometric indices have a debatable relationship with breast cancer (BC) among different ethnicity. In the current study, we have evaluated the relationship between anthropometric indices and BC in Iranian participants.

Methods: Between 2012 and 2014, a total of 7,805 women were enrolled from different mammography centers in Isfahan province, Iran. For each participant, a detailed questionnaire was filled out and anthropometric indices were measured by trained technicians. We used logistic regression models to estimate odds ratios (OR) and 95% confidence interval (CI) for BC risk associated with anthropometry measurements, stratified on menopausal status.

Results: In the postmenopausal group, weight ≥68 kg compared to weight <61.75 kg was associated with decreased risk of BC (OR = 0.78; 95% CI: 0.63–0.97). Postmenopausal women with Waist-Hip Ratio (WHR) ≥ 0.85 compared to WHR < 0.77 were at increased risk of BC (OR = 1.36; 95% CI: 1.07–1.73). Both premenopausal and postmenopausal women had a decreased risk of BC with higher Obesity Index (OI) and Relative Weight.

Conclusion: Ethnicity appears to play an important role in the discrepancies between results of different studies about the correlation of anthropometric features with BC.     

Endogenous sex steroids in premenopausal women and risk of breast cancer: the ORDET cohort

Introduction

Previous studies showed that higher testosterone levels are associated with greater risk of breast cancer in premenopausal women, but the literature is scant and inconsistent.

Methods

In a prospective nested case-control study of 104 premenopausal women with incident breast cancer and 225 matched controls, all characterized by regular menstrual cycles throughout their lifetime, we measured the concentration of estradiol, total and free testosterone (FT), progesterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in blood samples collected on days 20 through 24 of their cycles.

Results

In logistic regression models, the multivariate odds ratios (ORs) of invasive breast cancer for women in the highest tertile of circulating FT compared with the lowest was 2.43 (95% confidence interval (95% CI), 1.15 to 5.10; P_trend = 0.03), whereas for total testosterone, the association had the same direction but was not statistically significant (OR, 1.27; 95% CI, 0.62 to 2.61; P_trend = 0.51). Endogenous progesterone was not statistically associated with breast cancer (OR, 1.16; 95% CI, 0.60 to 2.27; P_trend = 0.75), nor were the other considered hormones.

Conclusions

Consistent with previous prospective studies in premenopausal women and our own earlier investigation, we observed that higher levels of FT are positively associated with breast cancer risk in women with regular menstrual cycles throughout their lifetimes. No evidence of risk was found associated with the other endogenous sex steroids.     

Free-radical-scavenging principles from Phlomis caucasica

Seven free-radical-scavenging phenolic compounds including five flavonoids, rutin (1), chrysoeriol 7-O-rutinoside (2), kaempferol 3-O-glucoside (3), chrysoeriol 7-O-glucoside (4) and naringenin (5), and two phenylethanoid glycosides, forsythoside B (6) and acteoside (7) were isolated from the methanol extract of the aerial parts of the Iranian medicinal plant Phlomis caucasica by reversed-phase preparative high-performance liquid chromatography (HPLC), and the structures of these compounds were elucidated by spectroscopic means. The free-radical-scavenging properties of 1–7 were assessed by 2,2-diphenyl-1-picryl hydrazyl (DPPH) assay. Among these compounds, forsythoside B (6) and acteoside (7) were found to be the most potent antioxidants with the RC₅₀ values of 4.97 and 4.27 μg/ml, respectively.     

Saffron and its derivatives,crocin, crocetin and safranal: a patent review

Introduction: Saffron and its main components have traditionally been used as pharmaceutical agents. Current experimental research projects have also exhibited their applications in a wide spectrum of disorder treatments.

Area covered: This review covers the demonstrated findings and patents on therapeutic/pharmaceutical properties of saffron and related derivatives, since 2000 to bold their outstanding merit on human health. An extensive literature review was performed in USP Patent, Patentscope, Espacenet and Google Patent in the field of CNS, cardiovascular, urogenital, dermatological and inflammatory disorders.

Expert opinion: The growing body of patents showed the value of saffron and the respective crucial components alone or in combination with the other raw materials, herbal extracts, to apply in various therapeutic/pharmaceutical areas. They could be engaged as an adjuvant treatment in phototherapy, cancer, cardiovascular and neurodegenerative diseases and hypoxia-induced dangerous conditions. However, the application of these components in the clinic has been limited to very few drugs yet. This might be due poor clinical trials data. According the human trend toward the use of plant-derived compounds instead of medicines derived from chemical substances, special attention must be focused to link the worth of saffron, herbal medicine of third millennium, from basic sciences to patients’ bed.     

Hepatitis C prevalence and elimination planning in Pakistan,a bottom-up approach accounting for provincial variation

In Pakistan, substantial changes to hepatitis C virus (HCV) programming and treatment have occurred since the 2008 nationwide serosurvey estimated a 4.8% anti-HCV prevalence. In the absence of an updated national study, this analysis uses provincial data to estimate a national prevalence and the interventions needed to achieve elimination. Using a Delphi process, epidemiologic HCV data for the four provinces of Pakistan (accounting for 97% of the population) were reviewed with 21 subject-matter experts in Pakistan. Province-level estimates were inputted into a mathematical model to estimate the national HCV disease burden in the absence of intervention (Base), and if the World Health Organization (WHO) elimination targets are achieved by 2030 (80% reduction in new infections, 90% diagnosis coverage, 80% treatment coverage, and 65% reduction in mortality: WHO Elimination). An estimated 9,746,000 (7,573,000–10,006,000) Pakistanis were living with viraemic HCV as of January 1, 2021; a viraemic prevalence of 4.3% (3.3–4.4). WHO Elimination would require an annual average of 18.8 million screens, 1.1 million treatments, and 46,700 new infections prevented anually between 2022 and 2030. Elimination would reduce total infections by 7,045,000, save 152,000 lives and prevent 104,000 incident cases of hepatocellular carcinoma from 2015 to 2030. Blood surveys, programmatic data, and expert panel input uncovered more HCV infections and lower treatment numbers in the provinces than estimated using national extrapolations, demonstrating the benefits of a bottom-up approach. Screening and treatment must increase 20 times and 5 times, respectively, to curb the HCV epidemic in Pakistan and achieve elimination by 2030.     

Antibodies as epidemiological markers of genetically modified crop exposure: detection of Cry1Ab-specific IgG

There has been an increasing concern with the safety of genetically modified (GM) crops. An important modification of GM crops is the expression of Bacillus thuringiensis (Bt) protein, Cry1Ab. Animal exposure to Cry1Ab indicates that the protein is safe, but that it is immunogenic. Whether Cry1Ab is a human immunogen and whether antibody response to this protein can serve as a marker of high exposure to GM crops is unknown. Here we develop an enzyme-linked immunosorbent assay to detect the presence of Cry1Ab-specific IgG in ～100 individuals living in each of three countries that have varied exposure to GM crops (Papua New Guinea (PNG), low exposure; Kenya, moderate exposure; and the USA, high exposure). Cry1Ab-specific IgG antibodies were detected in individuals living in each region (8%, the USA; 3%, PNG; and 2%, Kenya). Thus, individuals develop anti-Cry1Ab antibodies at a frequency that roughly correlates with the exposure to GM crops expressing this protein.     

Non-invasive Model-Based Assessment of Passive Left-Ventricular Myocardial Stiffness in Healthy Subjects and in Patients with Non-ischemic Dilated Cardiomyopathy

Patient-specific modelling has emerged as a tool for studying heart function, demonstrating the potential to provide non-invasive estimates of tissue passive stiffness. However, reliable use of model-derived stiffness requires sufficient model accuracy and unique estimation of model parameters. In this paper we present personalised models of cardiac mechanics, focusing on improving model accuracy, while ensuring unique parametrisation. The influence of principal model uncertainties on accuracy and parameter identifiability was systematically assessed in a group of patients with dilated cardiomyopathy (\(n=3\)) and healthy volunteers (\(n=5\)). For all cases, we examined three circumferentially symmetric fibre distributions and two epicardial boundary conditions. Our results demonstrated the ability of data-derived boundary conditions to improve model accuracy and highlighted the influence of the assumed fibre distribution on both model fidelity and stiffness estimates. The model personalisation pipeline—based strictly on non-invasive data—produced unique parameter estimates and satisfactory model errors for all cases, supporting the selected model assumptions. The thorough analysis performed enabled the comparison of passive parameters between volunteers and dilated cardiomyopathy patients, illustrating elevated stiffness in diseased hearts.     

Aging and Engaging: A Pilot Randomized Controlled Trial of an Online Conversational Skills Coach for Older Adults

ObjectiveCommunication difficulties negatively impact relationship quality and are associated with social isolation and loneliness in later life. There is a need for accessible communication interventions offered outside specialty mental health settings.DesignPilot randomized controlled trial.SettingAssessments in the laboratory and intervention completed in-home.ParticipantsTwenty adults age 60 and older from the community and a geriatric psychiatry clinic.InterventionA web-based communication coach that provides automated feedback on eye contact, facial expressivity, speaking volume, and negative content (Aging and Engaging Program, AEP), delivered with minimal assistance in the home (eight brief sessions over 4–6 weeks) or control (education and videos on communication).MeasurementsSystem Usability Scale and Social Skills Performance Assessment, an observer-rated assessment of social communication elicited through standardized role-plays.ResultsNinety percent of participants completed all AEP sessions and the System Usability Scale score of 68 was above the cut-off for acceptable usability. Participants randomized to AEP demonstrated statistically and clinically significant improvement in eye contact and facial expressivity.ConclusionThe AEP is acceptable and feasible for older adults with communication difficulties to complete at home and may improve eye contact and facial expressivity, warranting a larger RCT to confirm efficacy and explore potential applications to other populations, including individuals with autism and social anxiety.     

Detection of SARS-coronavirus-2 in the central nervous system of patients with severe acute respiratory syndrome and seizures

Journal of NeuroVirology - This study was designed to evaluate whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can directly target the central nervous system (CNS). We present...