Innovation in wastewater near-source tracking for rapid identification of COVID-19 in schools [Comment]

COVID-19 is one of the biggest global public health challenges of the century with almost 42 million cases and more than a million deaths to date. Until a COVID-19 vaccine or effective pharmaceutical intervention is developed, alternative tools for the rapid identification, containment, and mitigation of the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of paramount importance for managing community transmission. Within this context, school closure has been one of the strategies implemented to reduce spread at local and national levels. [...

Evaluating equality in prescribing Novel Oral Anticoagulants (NOACs) in England: the protocol of a Bayesian small area analysis

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting about 1.6% of the population in England. Novel oral anticoagulants (NOACs) are approved AF treatments that reduce stroke risk. In this study, we estimate the equality in individual NOAC prescriptions with high spatial resolution in Clinical Commissioning Groups (CCGs) across England from 2014 to 2019. Methods A Bayesian spatio-temporal model will be used to estimate and predict the individual NOAC prescription trend on ‘prescription data’ as an indicator of health services utilisation, using a small area analysis methodology. The main dataset in this study is the “Practice Level Prescribing in England,” which contains four individual NOACs prescribed by all registered GP practices in England. We will use the defined daily dose (DDD) equivalent methodology, as recommended by the World Health Organization (WHO), to compare across space and time. Four licensed NOACs datasets will be summed per 1,000 patients at the CCG-level over time. We will also adjust for CCG-level covariates, such as demographic data, Multiple Deprivation Index, and rural-urban classification. We aim to employ the extended BYM2 model (space-time model) using the RStan package. Discussion This study suggests a new statistical modelling approach to link prescription and socioeconomic data to model pharmacoepidemiologic data. Quantifying space and time differences will allow for the evaluation of inequalities in the prescription of NOACs. The methodology will help develop geographically targeted public health interventions, campaigns, audits, or guidelines to improve areas of low prescription. This approach can be used for other medications, especially those used for chronic diseases that must be monitored over time

The active second-generation proteasome inhibitor oprozomib reverts the oxaliplatin-induced neuropathy symptoms

Oxaliplatin-induced neuropathy (OXAIN) is a major adverse effect of this antineoplastic drug, widely used in the treatment of colorectal cancer. Although its molecular mechanisms remain poorly understood, recent evidence suggest that maladaptive neuroplasticity and oxidative stress may participate to the development of this neuropathy. Given the role played on protein remodeling by ubiquitin–proteasome system (UPS) in response to oxidative stress and in neuropathic pain, we investigated whether oxaliplatin might cause alterations in the UPS-mediated degradation pathway, in order to identify new pharmacological tools useful in OXAIN. In a rat model of OXAIN (2.4 mg kg−1 i.p., daily for 10 days), a significant increase in chymotrypsin-(β5) like activity of the constitutive proteasome 26S was observed in the thalamus (TH) and somatosensory cortex (SSCx). In addition, the selective up-regulation of β5 and LMP7 (β5i) subunit gene expression was assessed in the SSCx. Furthermore, this study revealed that oprozomib, a selective β5 subunit proteasome inhibitor, is able to normalize the spinal prodynorphin gene expression upregulation induced by oxaliplatin, as well as to revert mechanical allodynia and thermal hyperalgesia observed in oxaliplatin-treated rats. These results underline the relevant role of UPS in the OXAIN and suggest new pharmacological targets to counteract this severe adverse effect. This preclinical study reveals the involvement of the proteasome in the oxaliplatin-induced neuropathy and adds useful information to better understand the molecular mechanism underlying this pain condition. Moreover, although further evidence is required, these findings suggest that oprozomib could be a therapeutic option to counteract chemotherapy-induced neuropathy

Oral platelet gel supernatant plus supportive medical treatment versus supportive medical treatment in the management of radiation-induced oral mucositis: a matched explorative active control trial by propensity analysis

OBJECTIVES:: In this active control trial, the rate of radio-induced WHO grade 3/4 oral mucositis and the change in quality of life, assessed by OMWQ-HN, were measured in subjects with head and neck cancer treated by platelet gel supernatant (PGS) and supportive medical treatment versus subjects treated by supportive medical treatment alone. MATERIALS AND METHODS:: Eighty patients with nonmetastatic head and neck cancer underwent curative or adjuvant radiotherapy. All patients underwent supportive medical treatment and/or PGS at the beginning and during radiotherapy. Sixteen patients received PGS in association with supportive medical treatment. To obtain 2 groups virtually randomized for important clinical characteristics subjects were matched, by propensity analysis, with a group of subjects (64 patients) treated with supportive medical treatment alone. RESULTS:: Subjects treated with standard supportive treatment experienced significant higher WHO grade 3/4 toxicity (55%; 35/64) than subjects treated by PGS (13%; 3/16). The reduced toxicity found in PGS group paralleled with the evidence that they developed later symptoms with respect to controls. The Cox proportional hazard model indicated that patients treated with standard supportive medical treatment experienced 2.7-fold increase (hazard ratio=2.7; 95% confidence interval, 1.3-5.7) in the occurrence of WHO grade 3/4 toxicity. PGS group significantly experienced higher quality of life than control groups as measured by OMWQ-HN. A significant decrease in the opioid analgesics usage was found in the PGS group. CONCLUSIONS:: These preliminary data should be interpreted with caution and could serve as a framework around which to design future trials

Effect of Tomato Peel Extract Grown under Drought Stress Condition in a Sarcopenia Model

Tomatoes and their derivates represent an important source of natural biologically active components. The present study aims to investigate the protective effect of tomato peel extracts, grown in normal (RED-Ctr) or in drought stress (RED-Ds) conditions, on an experimental model of sarcopenia. The phenolic profile and total polyphenols content (TPC) of RED-Ctr and RED-Ds were determined by Ultra High-Performance Liquid Chromatography (UHPLC) analyses coupled to electrospray ionization high-resolution mass spectrometry (ESI-HR-MS). Human skeletal muscle myoblasts (HSMM) were differentiated in myotubes, and sarcopenia was induced by dexametha- sone (DEXA) treatment. Differentiation and sarcopenia were evaluated by both real-time PCR and immunofluorescent techniques. Data show that myosin heavy chain 2 (MYH2), troponin T (TNNT1), and miogenin (MYOG) were expressed in differentiated myotubes. 5 μg Gallic Acid Equivalent (GAE/mL) of TPC from RED-Ds extract significantly reduced muscle atrophy induced by DEXA. Moreover, Forkhead BoxO1 (FOXO1) expression, involved in cell atrophy, was significantly decreased by RED-Ds extract. The protective effect of tomato peel extracts depended on their qualitative polyphenolic composition, resulting effectively in the in vitro model of sarcopenia

Synergic stimulation of serotonin 5-HT1A receptor and α2-adrenoceptors for neuropathic pain relief: Preclinical effects of 2-substituted imidazoline derivatives

Neuropathic pain affects millions of people causing disability and impairing quality of life. Commonly used analgesics are generally characterized by limited therapeutic outcomes. The serotonin 5-HT1A receptor and the α2 adrenergic receptors are involved in central nociceptive mechanisms with a pivotal role in the inhibitory descending pain pathway. Since their stimulation may modulate the nervous signaling altered by neuropathies, the purpose of the present research is the study of the combined activation of 5-HT1A and α2 receptors by rationally designed imidazoline ligands ((S)-(-)-1 and 2-5) in a rat model of neuropathic pain (chronic constriction injury - CCI). On day 14 after nerve damage, the acute administration per os (p.o.) of low doses of (S)-(-)-1 (0.1-1mg/kg) was able to significantly increase the pain threshold to mechanical noxious stimuli for more than 1h. (S)-(-)-1 efficacy was confirmed by the decrease of spontaneous pain evaluated as hind limb weight bearing alterations. The clinically-used compound gabapentin (100mg/kg p.o.) induced a pain relieving effect similar to (S)-(-)-1 administered at 100 fold lower dose. In the same model, the selected analogues, compounds 2-5 (1mg/kg p.o.) were effective 30min after administration. In particular, 5 fully reverted the CCI-induced hypersensitivity. The pain relieving activity of 5 was significantly prevented by the selective 5-HT1A receptor antagonist WAY 100635 (1mg/kg intraperitoneally, i.p.) and, at a lesser extent, by the α2 antagonist yohimbine (3mg/kg i.p.). A novel pharmacodynamic approach to the treatment of neuropathic pain is presented