Peptide-based opioid ligands are important candidates for the development of novel, safer, and more effective analgesics to treat pain. To develop peptide-based safer analgesics, we synthesized a mixture-based cyclic pentapeptide library containing a total of 24,624 pentapeptides and screened the mixture-based library samples using a 55 °C warm-water tail-withdrawal assay. Using this phenotypic screening approach, we deconvoluted the mixture-based samples to identify a novel cyclic peptide Tyr-[D-Lys-Dap(Ant)-Thr-Gly] (CycloAnt), which produced dose- and time-dependent antinociception with an ED50 (and 95% confidence interval) of 0.70 (0.52-0.97) mg/kg i.p. mediated by the mu-opioid receptor (MOR). Additionally, higher doses (≥ 3 mg/kg, i.p.) of CycloAnt antagonized delta-opioid receptors (DOR) at least 3 hours. Pharmacological characterization of CycloAnt showed the cyclic peptide did not reduce breathing rate in mice at doses up to 15 times the analgesic ED50 value, and dramatically less hyperlocomotion than the MOR agonist, morphine. While chronic administration of CycloAnt resulted in antinociceptive tolerance, it was without opioid-induced hyperalgesia and significantly reduced signs of naloxone-precipitated withdrawal suggestive of reduced physical dependence as compared to morphine. Collectively, the results suggest this dual MOR/DOR multifunctional ligand is an excellent lead for the development of peptide-based safer analgesics.

Different notions of entropy can be identified in different communities: (i) the thermodynamic sense, (ii) the information sense, (iii) the statistical sense, (iv) the disorder sense, and (v) the homogeneity sense. Especially the “disorder sense” and the “homogeneity sense” relate to and require the notion of space and time. One of the few prominent examples relating entropy to geometry and to space is the Bekenstein-Hawking entropy of a Black Hole. Although being developed for the description of a physics object—a black hole—having a mass, a momentum, a temperature, a charge etc. absolutely no information about these attributes of this object can eventually be found in the final formula. In contrast, the Bekenstein-Hawking entropy in its dimensionless form is a positive quantity only comprising geometric attributes like an area A—which is the area of the event horizon of the black hole-, a length L_P—which is the Planck length - and a factor ¼. A purely geometric approach towards this formula will be presented. The approach is based on a continuous 3D extension of the Heaviside function, with this extension drawing on the phase-field concept of diffuse interfaces. Entropy enters into the local, statistical description of contrast respectively gradient distributions in the transition region of the extended Heaviside function definition. The structure of the Bekenstein-Hawking formula eventually is derived for a geometric sphere based on mere geometric-statistic considerations.

As SARS-CoV-2 continues to spread among human populations, genetic changes occur and accumulate in the circulating virus. Some of these genetic changes have caused amino acid mutations, including deletions, which may have potential impact on critical SARS-CoV-2 countermeasures, including vaccines, therapeutics, and diagnostics. Considerable efforts have been made to categorize the amino acid mutations of the angiotensin-converting enzyme 2 (ACE2) receptor binding domain (RBD) of the spike (S) protein along with certain mutations in other regions within the S protein as specific variants in an attempt to study the relationship between these mutations and the biological behavior of the virus. However, the currently used whole genome sequencing surveillance technologies can test only a small fraction of the positive specimens with high viral loads and often generate uncertainties in nucleic acid sequencing that needs additional verification for precision determination of mutations. This article introduces a generic protocol to routinely sequence a 437-bp nested RT-PCR cDNA amplicon of the ACE2 RBD and a 490-bp nested RT-PCR cDNA amplicon of the N-terminal domain (NTD) of the S gene for detection of the amino acid mutations needed for accurate determination of all variants of concern and variants of interest according to the definitions published by the U.S. Centers for Disease Control and Prevention. This protocol was able to amplify both nucleic acid targets into cDNA amplicons to be used as templates for Sanger sequencing on all 16 clinical specimens that were positive for SARS-CoV-2.

A method for calibrating models of agricultural production and resource use presented by Howitt [1] for policy analysis is proposed to leverage multidisciplinary agricultural research at the National Center for Alluvial Aquifer Research (NCAAR). An illustrative example for Sunflower County, MS is presented to show how plot-level research can be extended to draw systemic region or basin wide implications. A hypothetical improvement in yields for dryland soybean varieties is incorporated to the model and shown to have a positive impact on aquifer outcomes and producer profits. The example illustrates that a change in one practice-crop combination can have system-wide impacts as evidenced by the change in acreages for all crops and practices.

Like all RNA viruses, SARS-CoV-2 shows high mutation rate, which has led to the emergence of new variants. Among them, Gamma and Delta developed at the turn of 2020-2021 in Amazonas and India, two ecoregions characterized by hot-humid weather, very similar to that of the summer season due to climate change in Italy, the first Western country to have been hit hard by COVID-19 and to experience lockdown restrictions in a democratic framework of 58,85 million people. Methods: during the state of national health emergency and the Draghi government, the Civil Defense Department daily released the aggregate data coming from the Ministry of Health, the Higher Institute of Health, the Independent Provinces and the Italian Regions, in order to inform about the pandemic situation in Italy. Among these data there were the number of deaths, hospitalizations in intensive care units (ICU), non-ICU patients, contagions, and performed swabs. By means of a team effort, we have collected and elaborated all these data, comparing COVID-19 pandemic in Italy during the summers 2020 (following the nationwide lockdown), 2021 and 2022. Results: from summer 2020 (before mass vaccination) to summers 2021 (after primary mass vaccination) and 2022 (after booster mass vaccination) all pandemic trend indicators have showed a sharp worsening in Italy. COVID-19 deaths increased by ≈298% and ≈834%, ICU hospitalizations by ≈386% and ≈310%, non-ICU hospitalizations by ≈224% and ≈600%, contagions by ≈627% and ≈6.850% (i.e. ≈68,50 times), swabs by ≈354% and ≈370%, and the mean positivity rate passed from ≈1% to ≈2% and ≈20%, respectively. Conclusions: SARS-CoV-2 can be transmitted in any climate, including areas with hot and humid weather, and the emergence of variants adapted to hot-humid climate may result in summer COVID-19 outbreaks, even in neither tropical nor subtropical countries. Although COVID-19 vaccines can confer cross-protection against newly emerging variants, this cross-immunity is obviously not absolute but limited, also taking into account that vaccine protection wanes considerably after 6 months. It follows that a subject vaccinated at the beginning of winter will not be completely covered in the height of summer, without forgetting the unvaccinated. As a final remark, the long nationwide lockdown made it possible to flatten SARS-CoV-2 circulation and, therefore, its negative impact on Italy during summer 2020.

In August 4 2011, United Nations Environmental Program (UNEP) submitted an unprecedented, scientific, groundbreaking Environmental Assessment Report (EAR) of Ogoniland, to the Nigerian government. This was the outcome of a 14–month intensive evaluation of the extent of pollution. It was intended that UNEP’s recommendations would be implemented to restore the devastated environment, on the one hand, and on the other, counteract the numerous environmental health issues that have for decades, plagued Ogoniland. However, five years post EAR, and, despite the seriousness of the situation, no significant resolution has occurred, both on the part of the government, and on the part of Shell Petroleum Development Company (SPDC) or Shell. To date, millions of Niger Delta residents, particularly those living in the oil-bearing communities, continue to suffer severe consequences. Although, the assessment was conducted in Ogoniland, other communities in the Niger Delta are also affected. This article explores prevailing issues, using Ogoniland (a microcosm of the Niger Delta) as an example. A multidisciplinary approach for sustainable mitigation of environmental health risks in the Niger Delta is paramount, and Environmental Management tools offer valuable strategies. Adopting UNEP’s recommendations for addressing environmental health problems requires implementing the Environmental Management/Environmental Management System (EM/EMS) model.