Can N-Methyl-D-Aspartate Receptor Hypofunction in Schizophrenia Be Localized to an Individual Cell Type?

Hypofunction of N-methyl-D-aspartate glutamate receptors (NMDARs), whether caused by endogenous factors like auto-antibodies or mutations, or by pharmacological or genetic manipulations, produces a wide variety of deficits which overlap with—but do not precisely match—the symptom spectrum of schizophrenia. In order to understand how NMDAR hypofunction leads to different components of the syndrome, it is necessary to take into account which neuronal subtypes are particularly affected by it in terms of detrimental functional alterations. We provide a comprehensive overview detailing findings in rodent models with cell type–specific knockout of NMDARs. Regarding inhibitory cortical cells, an emerging model suggests that NMDAR hypofunction in parvalbumin (PV) positive interneurons is a potential risk factor for this disease. PV interneurons display a selective vulnerability resulting from a combination of genetic, cellular, and environmental factors that produce pathological multi-level positive feedback loops. Central to this are two antioxidant mechanisms—NMDAR activity and perineuronal nets—which are themselves impaired by oxidative stress, amplifying disinhibition. However, NMDAR hypofunction in excitatory pyramidal cells also produces a range of schizophrenia-related deficits, in particular maladaptive learning and memory recall. Furthermore, NMDAR blockade in the thalamus disturbs thalamocortical communication, and NMDAR ablation in dopaminergic neurons may provoke over-generalization in associative learning, which could relate to the positive symptom domain. Therefore, NMDAR hypofunction can produce schizophrenia-related effects through an action on various different circuits and cell types

Atmospheric Cold Plasma Inactivation of Salmonella and Escherichia coli on the Surface of Golden Delicious Apples

The contamination of fruits with human pathogens is a reoccurring concern in the fresh produce industry. Atmospheric cold plasma (ACP) is a potential alternate to customary approaches for non-thermal decontamination of foods. In this study, the efficacy of a dielectric barrier discharge ACP system against Salmonella (Salmonella Typhimurium, ATCC 13311; Salmonella Choleraesuis, ATCC 10708) and Escherichia coli (ATCC 25922, ATCC 11775) was explored. For each bacteria, a two-strain mixture at 8 log10 CFU/ml was spot inoculated on the surface of Golden Delicious apples, air dried, and exposed to ACP at a fixed distance of 35 mm, input power of 200 W for 30, 60, 120, 180, and 240 s. Bacterial inactivation was achieved in all treatment times with highest reduction of 5.3 log10 CFU/cm2 for Salmonella and 5.5 log10 CFU/cm2 for E. coli. Our results showed that reductions were interrelated to exposure time and ranged from 1.3 to 5.3 and 0.6 to 5.5 log10 CFU/cm2 for Salmonella and E. coli, respectively. Salmonella and E. coli significantly decreased (\u3e5.0 log) at 180 and 240 s as compared to 30, 60, and 120 s exposure. Microbial inactivation data was modeled by using Weibull distribution. These findings demonstrate the potential of ACP as a postharvest technology to effectively reduce pathogens on apples, with reference to Salmonella and E. coli

UV-C treatment on the safety of skim milk: Effect on microbial inactivation and cytotoxicity evaluation

The efficacy of UV-C irradiation as a nonthermal processing method for skim milk (SM) was investigated. SM inoculated with two surrogate viruses (MS2 and T1UV), and three bacteria (Escherichia coli ATCC 25922, Salmonella enterica serovar Typhimurium ATCC 13311, and Listeria monocytogenes ATCC 19115) was treated with Deanflow UV-C irradiation, a spiral reactor with the fluid pumped around a central low-pressure mercury UV lamp (40 W) emitting at 254 nm wave-length. A series of known UV doses (0–168.33 mJ·cm2) were delivered to the samples. The microbial loads of MS2, T1UV, E. coli, Salmonella, and Listeria were reduced by more than 5 log10. The inactivation kinetics of all microorganisms were best described by log linear models with a low RMSE and higher coefficient of determination (R2 \u3e 0.95). This study demonstrated that high levels of inactivation of pathogenic particles can be achieved in SM. Practical applications This scientific study provides evidence based data on the advantages of UV-C light in achieving microbial reduction in skim milk. The irradiated skim milk did not show any toxicity on mice liver and intestinal cells. UV-C irradiation is an efficient food preservation technology and offers opportunities for dairy and food processing industries to meet the growing demand from consumers for safer foods. This exploration would provide methodological evidence for commercialization of UV-C processing of milk and dairy based beverages

The feasibility of integrating alcohol risk-reduction counseling into existing VCT services in Kenya

This pretest-posttest separate-sample study with intervention and comparison groups documented the abilities and willingness of trained voluntary counseling and testing (VCT) service providers to integrate alcohol screening and risk reduction counseling into their routine service delivery. Pre-test (n=1073) and post-test data (n=1058) were collected from different clients exiting from 25 VCT centers. A 12-month intervention that required all VCT providers from the intervention groups to screen all VCT clients for their alcohol use and offer them brief risk reduction alcoholrelated counseling was implemented. At post-test, the intervention group clients (n=456) had better study outcomes than the comparison group clients (n=602). Intervention clients were more likely to report that their VCT service provider had: asked them about their alcohol use (83% vs. 41%:

Mesh inlay, mesh kit or native tissue repair for women having repeat anterior or posterior prolapse surgery: randomised controlled trial (PROSPECT)

Funding The project was funded by the National Institute for Health Research Health Technology Assessment Programme (Project Number 07/60/18). The Health Services Research Unit and the Health Economics Research Unit are funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. Acknowledgements The authors wish to thank the women who participated in the PROSPECT study. We also thank Margaret MacNeil for her secretarial support and data management; Dawn McRae and Lynda Constable for their trial management support; the programming team in CHaRT, led by Gladys McPherson; members of the Project Management Group for their ongoing advice and support of the study; and the staff at the recruitment sites who facilitated the recruitment, treatment and follow up of study participants.Peer reviewedPublisher PD

Microbial inactivation and cytotoxicity evaluation of UV irradiated coconut water in a novel continuous flow spiral reactor

A continuous-flow UV reactor operating at 254 nm wave-length was used to investigate inactivation of microorganisms including bacteriophage in coconut water, a highly opaque liquid food. UV-C inactivation kinetics of two surrogate viruses (MS2, T1UV) and three bacteria (E. coli ATCC 25922, Salmonella Typhimurium ATCC 13311, Listeria monocytogenes ATCC 19115) in buffer and coconut water were investigated (D10 values ranging from 2.82 to 4.54 mJ·cm− 2). A series of known UV-C doses were delivered to the samples. Inactivation levels of all organisms were linearly proportional to UV-C dose (r2 \u3e 0.97). At the highest dose of 30 mJ·cm− 2, the three pathogenic organisms were inactivated by \u3e 5 log10 (p \u3c 0.05). Results clearly demonstrated that UV-C irradiation effectively inactivated bacteriophage and pathogenic microbes in coconut water. The inactivation kinetics of microorganisms were best described by log linear model with a low root mean square error (RMSE) and high coefficient of determination (r2 \u3e 0.97). Models for predicting log reduction as a function of UV-C irradiation dose were found to be significant (p \u3c 0.05) with low RMSE and high r2. The irradiated coconut water showed no cytotoxic effects on normal human intestinal cells and normal mouse liver cells. Overall, these results indicated that UV-C treatment did not generate cytotoxic compounds in the coconut water. This study clearly demonstrated that high levels of inactivation of pathogens can be achieved in coconut water, and suggested potential method for UV-C treatment of other liquid foods. Industrial relevance This research paper provides scientific evidence of the potential benefits of UV-C irradiation in inactivating bacterial and viral surrogates at commercially relevant doses of 0–120 mJ·cm− 2. The irradiated coconut water showed no cytotoxic effects on normal intestinal and healthy mice liver cells. UV-C irradiation is an attractive food preservation technology and offers opportunities for horticultural and food processing industries to meet the growing demand from consumers for healthier and safe food products. This study would provide technical support for commercialization of UV-C treatment of beverages

The impact of scaling up cervical cancer screening and treatment services among women living with HIV in Kenya: a modelling study

Introduction: We aimed to quantify health outcomes and programmatic implications of scaling up cervical cancer (CC) screening and treatment options for women living with HIV in care aged 18–65 in Kenya. Methods: Mathematical model comparing from 2020 to 2040: (1) visual inspection with acetic acid (VIA) and cryotherapy (Cryo); (2) VIA and Cryo or loop excision electrical procedure (LEEP), as indicated; (3) human papillomavirus (HPV)-DNA testing and Cryo or LEEP; and (4) enhanced screening technologies (either same-day HPV-DNA testing or digitally enhanced VIA) and Cryo or LEEP. Outcomes measured were annual number of CC cases, deaths, screening and treatment interventions, and engaged in care (numbers screened, treated and cured) and five yearly age-standardised incidence. Results: All options will reduce CC cases and deaths compared with no scale-up. Options 1–3 will perform similarly, averting approximately 28 000 (33%) CC cases and 7700 (27%) deaths. That is, VIA screening would yield minimal losses to follow-up (LTFU). Conversely, LTFU associated with HPV-DNA testing will yield a lower care engagement, despite better diagnostic performance. In contrast, option 4 would maximise health outcomes, averting 43 200 (50%) CC cases and 11 800 (40%) deaths, given greater care engagement. Yearly rescreening with either option will impose a substantial burden on the health system, which could be reduced by spacing out frequency to three yearly without undermining health gains. Conclusions: Beyond the specific choice of technologies to scale up, efficiently using available options will drive programmatic success. Addressing practical constraints around diagnostics’ performance and LTFU will be key to effectively avert CC cases and deaths