Rationale and evidence for the incorporation of heparin to the diclofenac epolamine medicated plaster

The nonsteroidal anti-inflammatory drug (NSAID) diclofenac epolamine (DHEP) formulated as a topical patch has demonstrated efficacy and safety in the localized treatment of acute pain from minor strains, sprains, and contusions, and for epicondylitis and knee osteoarthritis. The glycosaminoglycan heparin enhances the activity of topical NSAIDs formulated as a medicated plaster, even in the absence of any significant release of heparin. Therefore, DHEP Plus, a new formulation of the DHEP medicated plaster containing a small amount of heparin sodium as excipient has been developed. Methods: We reviewed the pivotal and supportive studies of the clinical development program of the new patch and evaluated the role of heparin as an enhancer in the treatment of localized pain/inflammation of musculoskeletal structures, associated with post-traumatic and/or rheumatic conditions. Results: The data were consistent with the concept that heparin increased the clinical activity of the DHEP Plus medicated plaster versus the reference DHEP medicated plaster through improved bioavailability due to enhanced movement of diclofenac from the plaster. Both DHEP formulations have the same dissolution profile, indicating that heparin does not change the physical and chemical characteristics of the plaster. Permeation testing showed that heparin is not released from the DHEP Plus medicated plaster. Efficacy studies showed that the DHEP Plus medicated plaster was significantly more effective in reducing pain than the reference marketed DHEP medicated plaster. Conclusions: The benefit/risk assessment of DHEP Plus 180 mg medicated plaster is favorable, with a safety profile equal to placebo and improved efficacy over the reference marketed DHEP medicated plaster

Suitability of composting process for the disposal and valorization of brewer’s spent grain

The brewing industry is characterized by the large production of by-products. Following the fundamentals of a circular economy, several attempts to recycle brewers’ spent grain (BSG) have been investigated. However, little information is available on its use for composting. Consid-ering the main parameters required for optimal development of composting, the objective of the present review was to analyze the literature to determine whether the microbial and physicochemical characteristics of BSG make it suitable for direct composting. As the main factors in the composting process, we considered the BSG moisture content, total carbon, total nitrogen, C/N ratio, and pH. As described in the literature, the BSG moisture content, C/N ratio, and pH range from 70.6% to 81.3%, 7.1 to 26.5, and 3.8 to 6.9, respectively. This C/N ratio range is lower than the composting target range (20–30). Instead, the mean moisture content in the literature is higher than the 60% to 65% recommended for composting. Optimum pH for aerobic stabilization of compost ranges from 5.5 to 7.5, while the BSG pH in the literature is typically more acidic. Therefore, BSG is not suitable for direct composting. Addition of lignocellulosic bulking agents improves the reduction of moisture content during composting, while also optimizing the substrate properties, such as C/N ratio, air spaces, and pH, to positively affect the composting process. Moreover, livestock manure should be included as a starting material to promote the composting process. In this context, two hypothetical initial mixtures of BSG plus a lignocellulosic bulking agent and livestock manure are presented

Anti-Phospholipase A2 Receptor Antibodies in Membranous Nephropathy : from Bench to the Patient

Membranous Nephropathy (MN) is the leading cause of nephrotic syndrome in adults. Primary or idiopathic Membranous Nephropathy (iMN) has been considered as an organ-specific autoimmune disease with an unknown aetiology. By contrast, secondary membranous nephropathy has been described as the expression of a systemic autoimmune response to malignancy or bacterial/viral infections. In the majority of iMN cases, glomerular lesions are determined by autoantibodies against a podocyte membrane protein, the M-type of phospholipase A2 receptor 1 (PLA2R1). Several studies have suggested that the detection of anti-PLA2R1 in patients sera with nephrotic syndrome may be pathognomonic of iMN, thus obviating the need for a diagnostic renal biopsy and an extensive workup for underlying causes. Many authors inferred that the measurement of anti-PLA2R1 may change the diagnostic algorithm in patients with nephrotic syndrome and guide treatment decisions in patients with iMN. Measurement of anti-PLA2R1 antibodies is now possible through an easy to use, commercially available assay. The aim of this review is to describe the clinical relevance of anti-PLA2R1 assessment in patients with MN, and to extensively discuss the biotechnological methods available to measure them

Remote sensing reveals scale‐specific effects of forage crop mowing and landscape structure on a declining farmland bird

The effectiveness of agri-environment schemes (AESs), the largest conservation-related expenditure for farmland biodiversity conservation within the European Union, is often compromised by a limited spatial scale of implementation. We focused on multiannual forage crops, a surrogate habitat for grassland birds, to assess the scale-dependent effects of mowing timing and frequency on the local population size of an iconic species, the skylark (Alauda arvensis). While there is much evidence for a negative impact of in-field mowing activities on grassland birds, whether such effects occur also at broader spatial scales is largely unknown. We surveyed breeding skylarks in the Po Plain (northern Italy) to determine (1) the association between landscape composition/configuration and abundance and (2) how abundance is affected by forage crop mowing timing and frequency. We addressed both questions through scale optimisation, identifying the most influential spatial scales for each covariate. Forage crop mowing timing was assessed through a novel remote sensing algorithm based on high-resolution Sentinel-2 satellite images. We observed a strong scale dependence on the importance of different habitats in determining skylark abundance. Abundance increased with an increasing cover of forage crops locally (200 m) and of winter crops at a landscape scale (2600 m), suggesting that the species is favoured by heterogeneous agroecosystems. Locally (150–350 m), skylarks were more abundant when crops were aggregated, being negatively impacted by crop fragmentation caused by urbanization and by seminatural habitats. At the landscape scale (1150 m), the timing of mowing was consistent across years, with early-mown areas supporting fewer skylarks. This is probably because, over longer temporal scales, early-mown forage patches have limited or null productivity, eventually limiting local population size. Synthesis and applications. We provide a new perspective on the overarching influence of spatial scale in driving the abundance of a declining farmland bird species, supporting the urgency of designing landscape scale-effective AESs. This should be framed within the new EU Common Agricultural Policy reform and operated by farmer collectives, whereby management interventions should be monitored by state-of-the-art remote sensing techniques. These results suggest that implementing scale-optimized AESs could be crucial for effective farmland biodiversity conservatio

Habitat selection of the threatened northern lapwing (Vanellus vanellus) breeding in an intensive agroecosystem

Land use changes induced by agricultural intensification and wetland reclamation are negatively impacting farmland biodiversity. In this context, information on habitat selection of wildlife can be fundamental to developing effective conservation actions targeting biodiversity conservation, shedding light on fine-scale species-habitat relationships. We studied nesting and foraging habitat selection in a declining shorebird, the northern lapwing ( Vanellus vanellus ), in the intensive agroecosystem of the Po Plain, Italy. Out of 67 nests we found, 94% were in wetlands and summer crops, wetlands being the only habitat actively selected. The likelihood that a pair of lapwings nested in a cropland patch was inversely proportional to plant height and ground cover, which likely explains why summer crops were more favourable than winter and hay crops to the species nest settlement. Tracking data showed that GPS tagged lapwings ( n = 14) stayed close (207 ± 153 m) to their nests throughout the entire breeding period, and they selected the same habitat types for foraging as for nesting. Home ranges averged 56 ha (range = 3–161 ha), and were on average larger than previously reported from elsewhere, probably because the overall low quality of the habitat in the Po Plain. Home ranges of lapwings breeding in croplands were larger and significantly more cohesive than those of birds breeding in wetlands, suggesting a need to explore larger areas to find suitable foraging patches. The dual nesting and feeding strategy highlighted the crucial importance of both wetlands and, unexpectedly, summer crops for this species of conservation concern. To provide suitable habitat for breeding lapwings, restored wetlands must be well managed and attention should be given to intrafield heterogeneity, possibly increasing bare ground patches

SARS-COV-2 comorbidity network and outcome in hospitalized patients in Crema, Italy

We report onset, course, correlations with comorbidities, and diagnostic accuracy of nasopharyngeal swab in 539 individuals suspected to carry SARS-COV-2 admitted to the hospital of Crema, Italy. All individuals underwent clinical and laboratory exams, SARS-COV-2 reverse transcriptase-polymerase chain reaction on nasopharyngeal swab, and chest X-ray and/or computed tomography (CT). Data on onset, course, comorbidities, number of drugs including angiotensin converting enzyme (ACE) inhibitors and angiotensin-II-receptor antagonists (sartans), follow-up swab, pharmacological treatments, non-invasive respiratory support, ICU admission, and deaths were recorded. Among 411 SARS-COV-2 patients (67.7% males) median age was 70.8 years (range 5-99). Chest CT was performed in 317 (77.2%) and showed interstitial pneumonia in 304 (96%). Fatality rate was 17.5% (74% males), with 6.6% in 60-69 years old, 21.1% in 70-79 years old, 38.8% in 80-89 years old, and 83.3% above 90 years. No death occurred below 60 years. Non-invasive respiratory support rate was 27.2% and ICU admission 6.8%. Charlson comorbidity index and high Creactive protein at admission were significantly associated with death. Use of ACE inhibitors or sartans was not associated with outcomes. Among 128 swab negative patients at admission (63.3% males) median age was 67.7 years (range 1-98). Chest CT was performed in 87 (68%) and showed interstitial pneumonia in 76 (87.3%). Follow-up swab turned positive in 13 of 32 patients. Using chest CT at admission as gold standard on the entire study population of 539 patients, nasopharyngeal swab had 80% accuracy. Comorbidity network analysis revealed a more homogenous distribution 60-40 aged SARS-COV-2 patients across diseases and a crucial different interplay of diseases in the networks of deceased and survived patients. SARS-CoV-2 caused high mortality among patients older than 60 years and correlated with pre-existing multiorgan impairment. Copyright