Notes

Stomach microbiota as an growing restorative opportunity for the non-alcoholic fatty liver organ disease.
Participants were overwhelmingly positive about the Government's response and advised the Government to take the same approach in the future. This is a particularly reassuring finding from some of the most vulnerable New Zealanders.

An early and hard lockdown, the welfare state, compassion and clearly communicated leadership were keys to a successful lockdown for the low-income people in this study. Research of the experience of low-income people during pandemics is critical to ensuring inequities in pandemic impact are mitigated.
An early and hard lockdown, the welfare state, compassion and clearly communicated leadership were keys to a successful lockdown for the low-income people in this study. Research of the experience of low-income people during pandemics is critical to ensuring inequities in pandemic impact are mitigated.
Stress plays a key role in Parkinson's disease (PD) by acting on the dopaminergic system and worsening patients' motor function. The impact of New Zealand's strict lockdown measures to contain COVID-19 on perceived stress and PD motor symptoms remains unknown. Here we examined the relationship between perceived levels of stress, changes in physical activity levels and PD motor symptoms during lockdown.

During lockdown, 134 participants with PD and 49 controls completed a survey assessing perceived stress, self-reported changes in PD motor symptoms and physical activity duration and intensity prior to and during lockdown.

Perceived stress was higher in PD than controls, and in those reporting a worsening of tremor, balance/gait, dyskinesia and bradykinesia compared to those indicating no change during the COVID-19 lockdown. These effects were not modulated by physical activity.

Reducing stressors may be an important adjunct treatment strategy to improve motor function in PD.
Reducing stressors may be an important adjunct treatment strategy to improve motor function in PD.
We aim to quantify differences in clinical outcomes from COVID-19 infection in Aotearoa New Zealand by ethnicity and with a focus on risk of hospitalisation.

We used data on age, ethnicity, deprivation index, pre-existing health conditions and clinical outcomes on 1,829 COVID-19 cases reported in New Zealand. We used a logistic regression model to calculate odds ratios for the risk of hospitalisation by ethnicity. We also considered length of hospital stay and risk of fatality.

After controlling for age and pre-existing conditions, we found that Māori have 2.50 times greater odds of hospitalisation (95% CI 1.39-4.51) than non-Māori non-Pacific people. Pacific people have three times greater odds (95% CI 1.75-5.33).

Structural inequities and systemic racism in the healthcare system mean that Māori and Pacific communities face a much greater health burden from COVID-19. Older people and those with pre-existing health conditions are also at greater risk. This should inform future policy decisions including prioritising groups for vaccination.
Structural inequities and systemic racism in the healthcare system mean that Māori and Pacific communities face a much greater health burden from COVID-19. Older people and those with pre-existing health conditions are also at greater risk. This should inform future policy decisions including prioritising groups for vaccination.
To identify the extent of the provision of handwashing amenities in public toilets at the time of the COVID-19 pandemic, and also to make comparisons with a related pre-pandemic survey.

We collected data from 400 toilet facilities that were open to the public all those in three contiguous city council territories (228) and a further convenience sample of 172 around other parts of New Zealand. Comparisons were made with the data on the same facilities included in a 2012/2013 survey.

Of the toilets in this survey, 2.5% had no water for handwashing and 14.8% had no soap. There was COVID-19-related health messaging signage in 19.5% of toilets, with posters of the COVID-19 QR code used for contact tracing in 12.3%, and generic handwashing signage in 1.8%. selleckchem The handwashing water had 'no-touch' activation at 28.0% of toilets, and 18.5% of toilets had no-touch bowl flushing. Toilet bowl lids were not present at 32.8%, and 2.3% of toilets had damage that would impair their functionality (eg, broken toilet seats). This new survey found significantly increased provision of soap (risk ratio = 1.47; 95%CI 1.25 to 1.72), but no increased provision of water, at the 128 sites that had also been examined in the previous survey.

Although handwashing is probably a much less critical COVID-19 control intervention than reducing aerosol transmission, it should still be strongly supported. Yet this survey found multiple deficiencies with handwashing amenities at public toilets and only modest improvements since a previous survey.
Although handwashing is probably a much less critical COVID-19 control intervention than reducing aerosol transmission, it should still be strongly supported. Yet this survey found multiple deficiencies with handwashing amenities at public toilets and only modest improvements since a previous survey.In response to the COVID-19 pandemic, Aotearoa New Zealand adopted a clear 'elimination strategy', which has (up to June 2021) been very successful in both health and economic terms compared to other OECD countries. Nevertheless, the pandemic response has still been a very major shock to the New Zealand health system. This issue of the New Zealand Medical Journal has 14 new pandemic-related articles. Some of this work can help inform vaccination prioritisation decisions and inform preparations of primary and secondary care services and social services for any future raising of levels in the pandemic Alert Level system. Particularly strong themes are around the value (and challenges) of telehealth services, and also the need for responses throughout the health system to ensure health equity and support for the most vulnerable citizens.Chimeric antigen receptor (CAR) T cell immunotherapy involves the genetic modification of the patient's own T cells so that they specifically recognize and destroy tumour cells. Considerable clinical success has been achieved using this technique in patients with lymphoid malignancies, but clinical studies that investigated treating solid tumours using this emerging technology have been disappointing. A number of developments might be able to increase the efficacy of CAR T cell therapy for treatment of prostate cancer, including improved trafficking to the tumour, techniques to overcome the immunosuppressive tumour microenvironment, as well as methods to enhance CAR T cell persistence, specificity and safety. Furthermore, CAR T cell therapy has the potential to be combined with other treatment modalities, such as androgen deprivation therapy, radiotherapy or chemotherapy, and could be applied as focal CAR T cell therapy for prostate cancer.Preclinical and clinical data suggest that fibroblast growth factor 21 (FGF21) is anti-fibrotic, improves metabolic status and has potential to treat non-alcoholic steatohepatitis (NASH). We assessed the safety and efficacy of efruxifermin, a long-acting Fc-FGF21 fusion protein, for the treatment of NASH. BALANCED was a randomized, placebo-controlled study in patients with NASH conducted at 27 centers in the United States (ClinicalTrials.gov NCT03976401 ). Eighty patients, stratified by hepatic fat fraction (HFF) and fibrosis stage, were randomized using a centrally administered minimization algorithm 1111 to receive placebo (n = 21) or efruxifermin 28 mg (n = 19), efruxifermin 50 mg (n = 20) or efruxifermin 70 mg (n = 20) via weekly subcutaneous injection for 16 weeks. The primary endpoint-absolute change from baseline in HFF measured as magnetic resonance imaging-proton density fat fraction at week 12-was met. For the full analysis set, the least squares mean absolute changes (one-sided 97.5% confidence interval) from baseline in HFF were -12.3% (-infinity (-inf), -10.3), -13.4% (-inf, -11.4) and -14.1% (-inf, -12.1) in the 28-, 50- and 70-mg groups, respectively, versus 0.3% (-inf, 1.6) in the placebo group, with statistically significant differences between efruxifermin groups and placebo (P  less then  0.0001 each). Overall, 70 of 79 patients who received the study drug (89%) experienced at least one treatment-emergent adverse event (TEAE), with the majority grade 1-2 (64 (81%)), five (6%) grade 3 and one grade 4. The most commonly reported drug-related TEAEs were grade 1-2 gastrointestinal (36 (46%)). Treatment with efruxifermin significantly reduced HFF in patients with F1-F3 stage NASH, with an acceptable safety profile.Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical benefit across tumor types, but also a high rate of immune-related adverse events. Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we profiled the blood, tumor and gut microbiome of 77 patients with advanced melanoma treated with CICB, with a high rate of any ≥grade 3 immune-related adverse events (49%) with parallel studies in pre-clinical models. Tumor-associated immune and genomic biomarkers of response to CICB were similar to those identified for ICB monotherapy, and toxicity from CICB was associated with a more diverse peripheral T-cell repertoire. Profiling of gut microbiota demonstrated a significantly higher abundance of Bacteroides intestinalis in patients with toxicity, with upregulation of mucosal IL-1β in patient samples of colitis and in pre-clinical models. Together, these data offer potential new therapeutic angles for targeting toxicity to CICB.Clonal hematopoiesis (CH) in apparently healthy individuals is implicated in the development of hematological malignancies (HM) and cardiovascular diseases. Previous studies of CH analyzed either single-nucleotide variants and indels (SNVs/indels) or copy number alterations (CNAs), but not both. Here, using a combination of targeted sequencing of 23 CH-related genes and array-based CNA detection of blood-derived DNA, we have delineated the landscape of CH-related SNVs/indels and CNAs in 11,234 individuals without HM from the BioBank Japan cohort, including 672 individuals with subsequent HM development, and studied the effects of these somatic alterations on mortality from HM and cardiovascular disease, as well as on hematological and cardiovascular phenotypes. The total number of both types of CH-related lesions and their clone size positively correlated with blood count abnormalities and mortality from HM. CH-related SNVs/indels and CNAs exhibited statistically significant co-occurrence in the same individuals. In particular, co-occurrence of SNVs/indels and CNAs affecting DNMT3A, TET2, JAK2 and TP53 resulted in biallelic alterations of these genes and was associated with higher HM mortality. Co-occurrence of SNVs/indels and CNAs also modulated risks for cardiovascular mortality. These findings highlight the importance of detecting both SNVs/indels and CNAs in the evaluation of CH.Inhibitors of the PD-1-PD-L1 axis have been approved as therapy for many human cancers. In spite of the evidence for their widespread clinical activity, little is known about the immunological alterations that occur in human cancer tissue after PD-1 blockade. We developed and employed a patient-derived tumor fragment platform to dissect the early immunological response of human tumor tissue to ex vivo PD-1 blockade. We observed that the capacity of immune cells to be reactivated ex vivo was predictive of clinical response, and perturbation analyses identified tumor-resident T cells as a key component of this immunological response. In addition, through combined analysis of baseline properties and immune response capacity, we identified a new subgroup of infiltrated tumors that lacks the capacity to respond to PD-1 blockade. Finally, the baseline presence of tertiary lymphoid structures and their components correlated with the capacity of cancers to undergo intratumoral immune cell reactivation.
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