One Year Facing COVID. Systematic Evaluation of Risk Factors Associated With Mental Distress Among Hospital Workers in Italy.

Introduction: Italy was the first Western country affected by the COVID-19 pandemic that still constitutes a severe challenge for healthcare workers (HCWs), with a deep impact on their mental health. Several studies confirmed that a considerable proportion of HCW developed adverse psychological impairment (PsI). To focus on preventive and rehabilitation measures, it is fundamental to identify individual and occupational risk factors. We systematically assessed possible PsI among all employees in a large university hospital in Italy, using validated psychometric scales in the context of occupational health surveillance. Methods: In the period of July 2020 to July 2021, we enrolled 990 HCWs. For each subject, the psychological wellbeing was screened in two steps. The first-level questionnaire collected gender, age, occupational role, personal and occupational COVID-19 exposure, general psychological discomfort (GHQ-12), post-traumatic stress symptoms (IES-R), and anxiety (GAD-7). Workers showing PsI (i.e., test scores above the cutoff in at least one among GHQ-12, IES-R, and GAD-7) have been further investigated by the second-level questionnaire (psycho-diagnostic) composed by PHQ-9, DES-II, and SCL-90 scales. If the second-level showed clinically relevant symptoms, then we offered individual specialist treatment (third level). Results: Three hundred sixteen workers (32%) presented signs of PsI at the first-level screening questionnaire. Women, nurses, and subjects engaged in the COVID-19 area and with an infected family member showed significantly higher PsI risk. PsI prevalence was strongly associated with the pandemic trend in the region but sensibly decreased after January 2021, when almost all workers received the vaccination. A proportion of subjects with PsI presented clinically relevant symptoms (second-level screening) on PHQ-9 (35%), DES (20%), and SCL-90 (28%). These symptoms were associated neither to direct working experience with patients with COVID-19 nor to COVID-19 experience in the family and seemed not to be influenced by the pandemic waves or workers vaccination. Conclusions: The evaluation of psychological wellbeing of all hospital workers, directly or indirectly exposed to pandemic consequences, constitutes a unique condition to detect individual, occupational, and non-occupational risk factors for PsI in situations of high stress and/or disasters, as well as variables associated with symptom chronicization.

COVID-19: What happened to the healthcare workers of a research and teaching hospital in Milan, Italy?

The paper wants to present the data of infection of the Health Care Workers of a research and teaching hospital in Milan, Italy. The majority (2554, 55.9%) of 4572 HCWs were tested for SARS-CoV-2 and 8.8% were found positive. Most of the tested workers were women, but we found higher relative frequency of positivity for men, even after adjustment for age, working area, and occupation. The higher frequency of positive tests in the medicine area is probably explained by the higher concentration in that area of COVID-19 patients. Conversely, the low frequency of positive HCWs in intensive care units is  probably explained by the diffuse and continuous use of PPD. Our results show that HCWs in a research and teaching hospital in the most hit Region in Italy had a similar pattern of infection as all other HCWs all over the world. The problem of SARS-CoV-2 infections among the hospital personnel HCWs should remind us  the concerns about hospital acquired infections both for patients and HCWs.

The "FraMo" System: A New Mini-Invasive Technique in the Treatment of Proximal Humerus Fractures.

Fractures of the proximal humerus are relatively common injuries in adults accounting for 5% of fractures. Nowadays the most common technique used is open reduction internal fixation with LCP plates. The risks associated with open reduction internal fixation had led us to develop and apply a "hybrid" system, which is based on external fixation and closed surgery principles. This system is capable of stabilize up to 4 fragment fractures on different planes while conferring a strong enough fixation to maintain fracture reduction while allowing the patient to perform passive and active movement since the first day following the surgery. Our study group started on November 2009 until December 2015 and consisted of 118 patients with a mean age of 68.84±10.52 years for females (76) and 65.62±12.56 for males (44). Patients were classified according to the AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma association) Classification. In a few patients we performed mini lateral accesses to allow reduction of the humeral head and greater tuberosity. Shoulder mobilization was initiated from the first day following surgery. The external fixator was removed at 5 weeks with successive check-ups at 3, 6, and 12 months. The majority of type B and type C1 fractures had almost a complete functional recovery. Patients also, especially in the elderly, reported a good quality of life without pain during any range of motion. Our group of patients, after removal of the apparatus at 5 weeks following the surgery, had a mean articular range of motion with active abduction of 90 degrees and about 100 degrees with passive abduction. Postoperative CS scores at 12 months follow-up was 75,47±8.02. In addition there was also significant (P<0.05) improvement between preoperative and postoperative visual analog scale measurements (in cm), 7.67±2.70 and 1.71±2.08, respectively. This technique has shown good functional results with reduced surgical risks and complications that are typical of open reduction surgical fixation of proximal humerus fractures, is quick in execution and minimally invasive. Given the very good results of the study of this new external fixation technique has shown to be a viable option for the treatment of proximal humerus fractures.

Synthesis of diverse ß-quaternary ketones via palladium-catalyzed asymmetric conjugate addition of arylboronic acids to cyclic enones.

The development and optimization of a palladium-catalyzed asymmetric conjugate addition of arylboronic acids to cyclic enone conjugate acceptors is described. These reactions employ air-stable and readily-available reagents in an operationally simple and robust transformation that yields ß-quaternary ketones in high yields and enantioselectivities. Notably, the reaction itself is highly tolerant of atmospheric oxygen and moisture and therefore does not require the use of dry or deoxygenated solvents, specially purified reagents, or an inert atmosphere. The ring size and ß-substituent of the enone are highly variable, and a wide variety of ß-quaternary ketones can be synthesized. More recently, the use of NH4PF6 has further expanded the substrate scope to include heteroatom-containing arylboronic acids and ß-acyl enone substrates.

Evolution of a unified, stereodivergent approach to the synthesis of communesin F and perophoramidine.

Expedient synthetic approaches to the highly functionalized polycyclic alkaloids communesin F and perophoramidine are described using a unified approach featuring a key decarboxylative allylic alkylation to access a crucial and highly congested 3,3-disubstituted oxindole. Described are two distinct, stereoselective alkylations that produce structures in divergent diastereomeric series possessing the critical vicinal all-carbon quaternary centers needed for each synthesis. Synthetic studies toward these challenging core structures have revealed a number of unanticipated modes of reactivity inherent to these complex alkaloid scaffolds. Additionally, several novel and interesting intermediates en route to the target natural products, such as an intriguing propellane hexacyclic oxindole encountered in the communesin F sequence, are disclosed. Indeed, such unanticipated structures may prove to be convenient strategic intermediates in future syntheses.

A diastereodivergent synthetic strategy for the syntheses of communesin F and perophoramidine.

An efficient, unified, and stereodivergent approach toward communesin F and perophoramidine was examined. The C(3) all-carbon quaternary center of an oxindole was smoothly constructed by base-promoted indolone-malonate alkylation chemistry. The complementary relative stereochemistry of the crucial vicinal quaternary centers found in communesin F and perophoramidine was selectively installed by substrate-controlled decarboxylative allylic alkylations.

Mechanism and enantioselectivity in palladium-catalyzed conjugate addition of arylboronic acids to ß-substituted cyclic enones: insights from computation and experiment.

Enantioselective conjugate additions of arylboronic acids to ß-substituted cyclic enones have been previously reported from our laboratories. Air- and moisture-tolerant conditions were achieved with a catalyst derived in situ from palladium(II) trifluoroacetate and the chiral ligand (S)-t-BuPyOx. We now report a combined experimental and computational investigation on the mechanism, the nature of the active catalyst, the origins of the enantioselectivity, and the stereoelectronic effects of the ligand and the substrates of this transformation. Enantioselectivity is controlled primarily by steric repulsions between the t-Bu group of the chiral ligand and the α-methylene hydrogens of the enone substrate in the enantiodetermining carbopalladation step. Computations indicate that the reaction occurs via formation of a cationic arylpalladium(II) species, and subsequent carbopalladation of the enone olefin forms the key carbon-carbon bond. Studies of nonlinear effects and stoichiometric and catalytic reactions of isolated (PyOx)Pd(Ph)I complexes show that a monomeric arylpalladium-ligand complex is the active species in the selectivity-determining step. The addition of water and ammonium hexafluorophosphate synergistically increases the rate of the reaction, corroborating the hypothesis that a cationic palladium species is involved in the reaction pathway. These additives also allow the reaction to be performed at 40 °C and facilitate an expanded substrate scope.

Palladium-catalyzed asymmetric conjugate addition of arylboronic acids to heterocyclic acceptors.

Flava Flavanone: Asymmetric conjugate additions to chromones and 4-quinolones are reported utilizing a single catalyst system formed in situ from Pd(OCOCF(3))(2) and (S)-tBuPyOX. Notably, these reactions are performed in wet solvent under ambient atmosphere, and employ readily available arylboronic acids as the nucleophile, thus providing ready access to these asymmetric heterocycles (see scheme).

Palladium-catalyzed asymmetric conjugate addition of arylboronic acids to five-, six-, and seven-membered ß-substituted cyclic enones: enantioselective construction of all-carbon quaternary stereocenters.

The first enantioselective Pd-catalyzed construction of all-carbon quaternary stereocenters via 1,4-addition of arylboronic acids to ß-substituted cyclic enones is reported. Reaction of a wide range of arylboronic acids and cyclic enones using a catalyst prepared from Pd(OCOCF(3))(2) and a chiral pyridinooxazoline ligand yields enantioenriched products bearing benzylic stereocenters. Notably, this transformation is tolerant to air and moisture, providing a practical and operationally simple method of synthesizing enantioenriched all-carbon quaternary stereocenters.

C2-symmetric chiral disulfoxide ligands in rhodium-catalyzed 1,4-addition: from ligand synthesis to the enantioselection pathway.

A family of chiral C(2)-symmetric disulfoxide ligands possessing biaryl atropisomeric backbones has been synthesized by using the Andersen methodology. Complete characterization includes X-ray crystallographic studies of all ligands and some of their rhodium complexes. Their synthesis, optical purity, electronic properties, and catalytic behavior in the prototypical rhodium-catalyzed 1,4-addition of phenylboronic acid to 2-cyclohexen-1-one are presented through an in depth study of this ligand class. Density functional theory calculations on the step of the catalytic cycle that determines the enantioselectivity are presented and reinforce the first hypothetical explanations for the high levels of asymmetric induction observed.

Efficient ring-closing metathesis of alkenyl bromides: the importance of protecting the catalyst during the olefin approach.

We present the first productive ring-closing metathesis reaction that leads to the construction of cyclic alkenyl bromides. Efficient catalysis employing commercially available Grubbs II catalyst is possible through appropriate modification of the starting bromoalkene moiety.

Highly chemo- and enantioselective synthesis of 3-allyl-3-aryl oxindoles via the direct palladium-catalyzed alpha-arylation of amides.

A new NHC x Pd-catalyzed asymmetric alpha-arylation of amides is reported that gives direct access to synthetically valuable, allylated oxindoles with quaternary carbon centers. The reaction is made possible by the introduction of a new chiral NHC ligand. The palladium complexes derived therefrom combine excellent reactivity with high chemo- and enantioselectivity for the title transformation.

Improving Grubbs' II type ruthenium catalysts by appropriately modifying the N-heterocyclic carbene ligand.

The introduction of N-heterocyclic carbene ligands that incorporate correctly substituted naphthyl side chains leads to increased activity and stability in second generation ruthenium metathesis catalysts.

Impact of NHC ligand conformation and solvent concentration on the ruthenium-catalyzed ring-closing metathesis reaction.

Two saturated N-heterocyclic carbene ligands with substituted naphthyl side chains were used for the preparation of Blechert-type ruthenium metathesis precatalysts. The resulting conformers of the complexes were separated and unambiguously assigned by X-ray diffraction studies. All new complexes were compared in terms of activity to the original, SIMes-derived Blechert catalyst and were shown to be superior. A study on the impact of solvent concentration in RCM reactions using the most active of these new catalysts ultimately led to the ring closing of a variety of substrates at very low catalyst loadings.

Unprecedented selectivity via electronic substrate recognition in the 1,4-addition to cyclic olefins using a chiral disulfoxide rhodium catalyst.

From zero to hero? Sulfoxides are generally not considered useful ligand entities in asymmetric metal catalysis. However, a chiral disulfoxide as a chelating ligand in the rhodium-catalyzed 1,4-addition of aryl boronic acids to cyclic, alpha,beta-unsaturated ketones and esters gives impressive catalytic results, thus opening the door to future applications of this new chiral ligand class.

Matching the chirality of monodentate N-heterocyclic carbene ligands: a case study on well-defined palladium complexes for the asymmetric alpha-arylation of amides.

N-Heterocyclic carbene ligands derived from C(2)-symmetric diamines with naphthyl side chains are introduced as chiral monodentate ligands, and their palladium complexes (NHC)Pd(cin)Cl are prepared. These compounds exist as a mixture of diastereomers, and the palladium complexes can be successfully separated and their absolute stereochemistry assigned. When used in the asymmetric intramolecular alpha-arylation of amides, oxindoles with quaternary carbon centers can be obtained in high yield and selectivity when correctly matching the chirality of the NHC complexes.

Identification and characterization of a new family of catalytically highly active imidazolin-2-ylidenes.

A new class of easily accessible and stable imidazolin-2-ylidenes has been synthesized where the side chains are comprised of substituted naphthyl units. Introduction of the naphthyl groups generates C 2 -symmetric ( rac) and C s- symmetric ( meso) atropisomers, and interconversion between the isomers is studied in detail both experimentally and computationally. Complete characterization of the carbenes includes rare examples of crystallographically characterized saturated NHC structures. Steric properties of the ligands and an investigation of their stability are also presented. In catalysis, the new ligands show versatility comparable to the most widely used NHCs IMes/SIMes or IPr/SIPr. Excellent catalytic results are obtained when either the NHC salts (ring-opening alkylation of epoxides), NHC-modified palladium compounds (C-C and C-N cross-couplings), or NHC-ruthenium complexes (ring-closing metathesis, RCM) are employed. In several cases, this new ligand family provides catalytic systems of higher reactivity than that observed with previously reported NHC compounds.