Ceftazidime-avibactam resistance in Klebsiella pneumoniae sequence type 37: a decade of persistence and concealed evolution

The first reports of carbapenem-resistant Enterobacterales in our hospital date back to 2006. In that period, few ertapenem-resistant but meropenem-susceptible Klebsiella pneumoniae isolates belonging to sequence type (ST) 37 were retrieved from clinical samples. These strains produced the CTX-M-15 extended spectrum β-lactamase, OmpK35 was depleted due to a nonsense mutation, and a novel OmpK36 variant was identified. Yet, starting from 2010, Klebsiella pneumoniae carbapenemase (KPC)-producing ST512 isolates started prevailing and ST37 vanished from sight. Since 2018 the clinical use of the combination of ceftazidime-avibactam (CZA) has been introduced in clinical practice for the treatment of bacteria producing serine-β-lactamases, but KPC-producing, CZA-resistant K. pneumoniae are emerging. In 2021, four CZA-resistant ST37 isolates producing KPC variants were isolated from the same number of patients. blaKPC gene cloning in Escherichia coli was used to define the role of those KPC variants on CZA resistance, and whole genome sequencing was performed on these isolates and on three ST37 historical isolates from 2011. CZA resistance was due to mutations in the blaKPC genes carried on related pKpQIL-type plasmids, and three variants of the KPC enzyme have been identified in the four ST37 strains. The four ST37 isolates were closely related to each other and to the historical isolates, suggesting that ST37 survived without notice in our hospital for 10 years, waiting to re-emerge as a CZA-resistant K. pneumoniae clone. The ancestor of these contemporary isolates derives from ST37 wild-type porin strains, with no other mutations in chromosomal genes involved in conferring antibiotic resistance (parC, gyrA, ramR, mgrB, pmrB)

Genome-based retrospective analysis of a Providencia stuartii outbreak in Rome, Italy. Broad spectrum IncC plasmids spread the NDM carbapenemase within the hospital

Providencia stuartii is a member of the Morganellaceae family, notorious for its intrinsic resistance to several antibiotics, including last-resort drugs such as colistin and tigecycline. Between February and March 2022, a four-patient outbreak sustained by P. stuartii occurred in a hospital in Rome. Phenotypic analyses defined these strains as eXtensively Drug-Resistant (XDR). Wholegenome sequencing was performed on the representative P. stuartii strains and resulted in fully closed genomes and plasmids. The genomes were highly related phylogenetically and encoded various virulence factors, including fimbrial clusters. The XDR phenotype was primarily driven by the presence of the (NDM)-N-bla- 1 metallo- beta-lactamase alongside the rmtC 16S rRNA methyltransferase, conferring resistance to most beta-lactams and every aminoglycoside, respectively. These genes were found on an IncC plasmid that was highly related to an NDM-IncC plasmid retrieved from a ST15 Klebsiella pneumoniae strain circulating in the same hospital two years earlier. Given its ability to acquire resistance plasmids and its intrinsic resistance mechanisms, P. stuartii is a formidable pathogen. The emergence of XDR P. stuartii strains poses a significant public health threat. It is essential to monitor the spread of these strains and develop new strategies for their control and treatment

An Alternative Synthesis of 3′,4′-Diaminoflavones to Evaluate Their Antioxidant Ability and Cell Apoptosis of Zebrafish Larvae

[[abstract]]We described herein a concise synthesis of 3′,4′-diaminoflavone 10. This new, three-step synthetic approach is more efficient than the conventional seven-step synthetic method. The route is shortened significantly by introducing the amino moieties early and eliminating the need for nitro group reduction. The other two analogues, 5,7-dihydroxy-3′,4′-diaminoflavone 11 and 5,7-dimethoxy-3′,4′-diaminoflavone 12, were also synthesized similarly. The above three compounds, along with flavone, were evaluated for their antioxidant and UVB-protection abilities on zebrafish larvae. The data showed that compound 10 exhibited the best result, with −102.3% of ROS-scavenging rate.[[journaltype]]國外[[incitationindex]]SCI[[ispeerreviewed]]Y[[booktype]]電子版[[booktype]]紙本[[countrycodes]]CH

Emotional dysregulation, temperament and lifetime suicidal ideation among youths with mood disorders

Background: Psychopathological dimensions contributing to suicidal ideation in young age are poorly understood. We aimed to investigate the involvement of emotional dysregulation and temperament in suicide risk in a sample of accurately selected young patients with mood disorders and a matched sample of healthy controls (HC). Methods: We assessed 50 young patients (aged 14–25 years) with DSM-5 bipolar or depressive disorders for clinical and psychopathological characteristics and 82 age and sex, educational level, and smoking habits-matched HC. Emotional dysregulation and temperament were assessed using the Difficulties in Emotion Regulation Scale (DERS) and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A-39), respectively. We tested their associations with suicidal ideation, using standard univariate/bivariate methods, preceded by overall multivariate analysis. Results: In the group of patients, 24 (48%) reported lifetime suicide ideation (LSI). Patients with LSI scored higher on emotional dysregulation (p < 0.001) and cyclothymic (p < 0.001), irritable (p = 0.01), and hyperthymic temperaments (p = 0.003) than HC. Patients with LSI specifically presented with more emotional dysregulation (p < 0.001) and cyclothymic temperament (p = 0.001), than patients without LSI (N = 26). Conclusions: Tempera-mental features, in particular cyclothymic temperament, and emotion dysregulation may represent independent factors for increased vulnerability to lifetime suicidal ideation in young adults with mood disorders

Tutela dei lavoratori nel cambio di appalto

L'elaborato si concentra sulla nozione di cambio di appalto e le modalità con cui si distingue dal trasferimento, passando in rassegna anche le soluzioni proposte dalla contrattazione collettiva, rispetto alle problematiche giuslavoristiche definite da tale fenomeno economico. in seguito vengono analizzati gli stessi profili, ma nella disciplina degli appalti pubblici, per poi trattare in maniera specifica elementi e punti comuni, quali i licenziamenti e elementi strettamente contrattuali della tutela dei lavoratori