Aniseed, Pimpinella anisum, as a source of new agrochemicals: phytochemistry and insights on insecticide and acaricide development

Pimpinella anisum L. (Apiaceae), known around the world as aniseed, is a widely cultivated crop, native of the sub-Mediterranean area. Its essential oil (EO) is exploitable in different fields such as food and beverages, pharmaceutics, cosmetics, and nutraceuticals. Regardless of the geographic origin, the EO exhibited consistent transanethole predominancy. Among the numerous biological properties exerted by aniseed EO, its antimicrobial, antifungal, insecticidal, and acaricidal effects have been extensively investigated for the formulation of biopesticides against larvae and adults of various pests and vectors. Hereafter, the published data on the insecticidal and acaricidal activity of aniseed EO and its major compounds on agricultural pests, stored-product pests, and arthropods of medical and veterinary interest is reviewed. For each study, the arthropod and the developmental stage on which the aniseed EO or the aniseed EO-based formulation were tested, the mode of action, the main constituents, and the exerted mortality, as well as the toxicity to non-target organisms and the possible sub-lethal effects are reported. The advantages of the possible use of aniseed EO as a biopesticide are analysed, as well as the current weaknesses and the critical points to be overcome to open the doors to the industrial utilization of Apiaceae EOs by the agrochemical industry

Laparoscopic simple prostatectomy vs bipolar plasma enucleation of the prostate in large benign prostatic hyperplasia. a two-center 3-year comparison

Purpose: To compare surgery outcomes and safety of button bipolar enucleation of the prostate vs laparoscopic simple prostatectomy in patients with large prostates (> 80 g) in a two-center cohort study. Methods: All patients with lower urinary tract symptoms due to benign prostatic enlargement (Prostate volume > 80 cc) undergoing button bipolar enucleation of the prostate (BTUEP) or laparoscopic simple prostatectomy (LSP) in two centers were enrolled. Data on clinical history, physical examination, urinary symptoms, uroflowmetry and prostate volume were collected at 0, 1, 3 6, 12, 24 and 36 months. Early and long-term complications were recorded. Results: Overall, 296 patients were enrolled. Out of them, 167/296 (56%) performed a LSP and 129/296 (44%) performed a BTUEP. In terms of efficacy both procedures showed durable results at three years with a reintervention rate of 8% in the LSP group and of 5% in the BTUEP group. In terms of safety, BTUEP and LSP presented similar safety profiles with a 9% of transfusion rate and no major complications. Conclusion: LSP and BTUEP are safe and effective in treating large-volume adenomas with durable results at three years when performed in experienced centers

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Natural history of KBG syndrome in a large European cohort

KBG syndrome (KBGS) is characterized by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential diagnosis. We aimed to better characterize natural history of KBGS. In the context of a European collaborative study, we collected the largest cohort of KBGS patients (49). A combined array- based Comparative Genomic Hybridization and next generation sequencing (NGS) approach investigated both genomic Copy Number Variants and SNVs. Intellectual disability (ID) (82%) ranged from mild to moderate with severe ID identified in two patients. Epilepsy was present in 26.5%. Short stature was consistent over time, while occipitofrontal circumference (median value: -0.88 SD at birth) normalized over years. Cerebral anomalies, were identified in 56% of patients and thus represented the second most relevant clinical feature reinforcing clinical suspicion in the paediatric age when short stature and vertebral/dental anomalies are vague. Macrodontia, oligodontia and dental agenesis (53%) were almost as frequent as skeletal anomalies, such as brachydactyly, short fifth finger, fifth finger clinodactyly, pectus excavatum/carinatum, delayed bone age. In 28.5% of individuals, prenatal ultrasound anomalies were reported. Except for three splicing variants, leading to a premature termination, variants were almost all frameshift. Our results, broadening the spectrum of KBGS phenotype progression, provide useful tools to facilitate differential diagnosis and improve clinical management. We suggest to consider a wider range of dental anomalies before excluding diagnosis and to perform a careful odontoiatric/ear-nose-throat (ENT) evaluation in order to look for even submucosal palate cleft given the high percentage of palate abnormalities. NGS approaches, following evidence of antenatal ultrasound anomalies, should include ANKRD11.</p

Human platelets express authentic CB₁ and CB₂ receptors

In the last decade, the neurovascular effects exerted by endocannabinoids (eCBs) have attracted growing interest, because they hold the promise to open new avenues of therapeutic intervention against major causes of death in Western society. Several actions of eCBs are mediated by type-1 (CB₁) or type-2 (CB₂) cannabinoid receptors, yet there is no clear evidence of the presence of these proteins in platelets. To demonstrate that CB₁ and CB₂ are expressed in human platelets, we analyzed their protein level by Western blotting and ELISA, visualized their cellular localization by confocal microscopy, and ascertained their functionality by binding assays. We found that CB₁, and to a lesser extent CB₂, are expressed in highly purified human platelets. Both receptor subtypes were predominantly localized inside the cell, thus explaining why they might remain undetected in preparations of plasma membranes. The identification of authentic CB₁ and CB₂ in human platelets supports the potential exploitation of selective agonists or antagonists of these receptors as novel therapeutics to combat neurovascular disorders. It seems remarkable that some of these substances have been already used in humans to treat disease states

Impairment of autophagy may represent the molecular mechanism behind the relationship between obesity and inflammation in patients with BPH and LUTS

BACKGROUND: Aim of this study was to evaluate the roles of inflammation and autophagy in obese patients with Benign prostatic Hyperplasia (BPH) and Lower Urinary Tract Symptoms (LUTS).METHODS: We analyzed 150 surgical specimens from patients underwent Transurethral Resection of the Prostate (TURP) for LUTS/BPH (Median age 70.3±8.1 years, Median BMI 25.7±4.0 kg/m2 and median PSA 6.0±5.4 ng/ml). All surgical specimens were investigated for the presence inflammatory infiltrates, according to the standardized classification of chronic prostatitis of the National Institute of Health. The Inflammatory Score (IS Score) was calculated. High IS score was defined as ≥7. Each sample was stained for anti-LC3B (cell signalling) and for anti-P62/SQSTM1 (MBL) according to manufacturer's suggestions and scored as follow: 0=No dots; 1=detectable dots in 5-25% of cells; 2=readily detectable dots in 25-75% of cells; 3=dots in &gt;75% of cells. High percentage of p62 or LC3B was defined as &gt;25%, whereas low percentage of p62 or LC3B was defined as &lt;25% of cells with dots.RESULTS: Overall 74/150 (49.3%) patients were overweight or obese (BMI &gt;25 kg/m2). Obese patients presented a higher inflammatory score. Obese/overweight patients presented a lower percentage of LC3B (58/74; 78.4%) and higher of p62 (49/74; 66.2%) compared to those of normal weight, which it means a deactivated autophagy (p&lt;0.05). At multivariate analysis LC3B (OR: 0.22; CI: 0.069-0.70; p=: 0.01) percentage and BMI (OR:1.118;CI: 1.001-1.250; p=: 0.04) were independent risk factors of prostatic inflammation (IS ≥ 7).CONCLUSIONS: Here we confirm the association between obesity and prostatic inflammatory infiltrates and present the first evidence of autophagy deregulation in obese patients with LUTS/BPH. Further studies should better investigate this relationship and provide new possible therapeutic targets

Adverse events related to radium-223 treatment: "real-life" data from the Eudra-Vigilance database

Background: The aim of our study was to analyze adverse events (AEs) associated with radium-223 using real life data from Eudra-Vigilance (EV) database. Methods: EV database is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European economic area (EEA). We recorded number of AEs for radium-223 per category and severity from 2013 to May 2019. We recorded AEs per age group (&lt;65 years old; between 65 and 85 years; &gt;85 years old) pooled relative risk (PRR) were used to compare groups. The number of individual cases identified in EV database was 4339. Results: According to the registry study the most frequent AEs in patients treated with radium-223 were hematological, general and gastrointestinal disorders and they were confirmed as the most frequent AEs in the EV database. In the EV database over 90% of the reported AEs were defined as serious and 8% were fatal. Older patients (&gt;85 years) treated with radium-223 were at increased risk of cardiac, infectious, and metabolism disorders when compared to younger patients (&lt;65). However, we have no information on the number of patients under treatment in the EV database. Conclusions: EV database highlights several AEs which are not reported in registry studies as well as different AEs profiles according to age. Clinicians should consider these data when treating patients with radium-223

Night shift workers refer higher urinary symptoms with an impairment quality of life. a single cohort study

BACKGROUND: Our aim is to assess the impact of night shift work (NSW) on urinary symptoms.METHODS: Between March 2018 and October 2018, we evaluated a group of National Health care system workers. Urinary symptoms and quality of life were measured by Overactive Bladder Questionnaire Short Form (OABq-sf). Clinical variables (i.e. age, smoking status, medical history) were collected and analyzed according to be NS workers (NSWs) -subjects working at least one time from 8pm to 8am- or traditional workers (TWs). Univariate and multivariate analysis was performed to identify predictive variables of worse OAB outcomes (OABq-sf &gt;30, OABq-SB≥ 12, OABq HRQL≥ 18).RESULTS: A total of 136 participants (68 males and 68 females) were included in the study. On OABq-sf, total score, symptoms bother (OABq-SB) and health related quality of life (OABq-HRQL) domains were significantly (p&lt;0.05) higher in NSWs group, respectively: 31 (IQR 26-35) Vs 19 (IQR 19-20); 11 (IQR 10-13) Vs 6 (IQR 6-7); 19 (IQR 16-22) Vs 13 (13-14). Finally, seven NSWs (10.6%) referred nocturia respect to only one (1%) TWs, (p=0.02). On multivariate analysis NSW was an independent predictor of OABq-sf&gt; 30 units (OR:30; CI: 9-111, p=0.001), OABq-SB ≥ 12 units (OR:16, CI:6-43 p=0.001) and OABq HRQL ≥ 18 units (OR:20, 6-70, p = 0,001).CONCLUSIONS: Night shift workers presented worst OAB score and poor QL when compared to similar traditional workers. Long-term data on NSWs patients are also needed to further clarify this relationship

Pressure effects on alpha-synuclein amyloid fibrils: An experimental investigation on their dissociation and reversible nature

\u3b1-synuclein amyloid fibrils are found in surviving neurons of Parkinson's disease affected patients, but the role they play in the disease development is still under debate. A growing number of evidences points to soluble oligomers as the major cytotoxic species, while insoluble fibrillar aggregates could even play a protection role. In this work, we investigate \u3b1-synuclein fibrils dissociation induced at high pressure by means of Small Angle X-ray Scattering and Fourier Transform Infrared Spectroscopy. Fibrils were produced from wild type \u3b1-synuclein and two familial mutants, A30P and A53T. Our results enlighten the different reversible nature of \u3b1-synuclein fibrils fragmentation at high pressure and suggest water excluded volumes presence in the fibrils core. Wild type and A30P species stabilized at high pressure are highly amyloidogenic and quickly re-associate into fibrils upon decompression, while A53T species shows a partial reversibility of the process likely due to the presence of an intermediate oligomeric state stabilized at high pressure. The amyloid fibrils dissociation process is here suggested to be associated to a negative activation volume, supporting the notion that \u3b1-synuclein fibrils are in a high-volume and high-compressibility state and hinting at the presence of a hydration-mediated activated state from which dissociation occurs