Distribution of epidemic clonal genetic markers among Listeria monocytogenes 4b isolates.

Recent genome sequencing of isolates of Listeria monocytogenes serotype 4b implicated in some major outbreaks of foodborne listeriosis has revealed unique genetic markers in these isolates. The isolates were grouped into two distinct epidemic clones, ECI and ECII. In the present study, selected ECI- and ECII-specific genetic markers were detected in 16 and 15 of 89 L. monocytogenes 4b isolates, respectively. The ECI markers were found in 6 of 34 clinical isolates, 9 of 50 food isolates, and 1 of 5 environmental isolates, and the ECII markers were detected in 7 of 34 clinical isolates, 7 of 50 food isolates, and 1 of 5 environmental isolates. Hence, of the isolates with the epidemic clonal genetic markers, 38% (13 of 34) were of clinical origin, 32% (16 of 50) were of food origin, and 40% (2 of 5) were of environmental origin. The predominance of the epidemic clonal markers among the clinical and environmental isolates supports the hypothesis that these markers are correlated with the pathogenic potential of strains and with their environmental persistence. Several isolates had only one epidemic clonal marker, either the ECI-specific marker 133 or the ECII-specific marker 4bSF18. Pulsed-field gel electrophoresis analysis revealed higher genomic diversity among the strains with ECII-like characteristics than among those strains carrying the ECI-specific genetic markers

Clostridium botulinum spores and toxin in mascarpone cheese and other milk products

A total of 1,017 mascarpone cheese samples, collected at retail, were analyzed for Clostridium botulinum spores and toxin, aerobic mesophilic spore counts, as well as pH, a(w) (water activity), and Eh (oxidation-reduction potential). In addition 260 samples from other dairy products were also analyzed for spores and botulinum toxin. Experiments were carried out on naturally and artificially contaminated mascarpone to investigate the influence of different temperature conditions on toxin production by C. botulinum. Three hundred and thirty-one samples (32.5%) of mascarpone were positive for botulinal spores, and 7 (0.8%) of the 878 samples produced at the plant involved in an outbreak of foodborne botulism also contained toxin type A. The chemical-physical parameters (pH, a(w), Eh) of all samples were compatible with C. botulinum growth and toxinogenesis. Of the other milk products, 2.7% were positive for C. botulinum spores. Growth and toxin formation occurred in naturally and experimentally contaminated mascarpone samples after 3 and 4 days of incubation at 28 degrees C, respectively

A homogeneous treatment for non-DIPG diffuse midline glioma

Introduction: The H3K27M-mutant diffuse midline glioma (DMG) was first included in the World Health Organization (WHO) Classification of central nervous system (CNS) tumors in 2016, and confirmed in its fifth edition. The biological behavior and dismal prognosis of this tumor resemble diffuse intrinsic pontine gliomas (DIPG). Homogeneously-treated series are rarely reported. Methods: From 2016 onwards, we treated patients with DMG with radiotherapy and concomitant/adjuvant nimotuzumab/vinorelbine, plus re-irradiation at relapse, as already done for DIPG. Results: We treated nine patients, seven females, with a median age at diagnosis of 13 years. Tumor sites were: thalamic in five cases, pontocerebellar in two, pineal in one, and paratrigonal with nodular/leptomeningeal dissemination in one. Three patients were biopsied, and six had partial tumor resections. Central pathological review was always performed. The median time to local progression was 12.7 months, and the median overall survival was 17.8 months. Six patients died of tumor progression, one of cerebral bleeding at progression. Two were alive, one in continuous remission, the other after relapsing, at 38.6 and 46.3 months after diagnosis. Progression-free survival was 33.3% at one year. Overall survival was 88.9%, 33.3% and 22.2% at 1, 2 and 3 years, respectively. Conclusions: This is a small series of homogeneously-treated DMG patients. The results obtained are comparable with those of DIPG patients. Given the phenotypically- and molecularly-defined setting of DMG and severe outcome in this orphan population, they should be treated and included in registries and protocols of DIPG

Secreting Germ Cell Tumors of the Central Nervous System: A Long-Term Follow-up Experience

Simple Summary Nongerminomatous germ cell tumors of the central nervous system are rare tumours. Differently from germinomas, they have a severe prognosis above all when presenting with high alfafetoprotein levels. We report the results of a combined chemo- and radiotherapy approach in 28 patients affected by this disease with craniospinal irradiation and a boost tailored on the response to pre-radiant chemotherapy. Metastatic patients and high-risk disease are discussed as well. The 5 years overall survival and event-free survival were both 81% while at 10 years they were 81% and 76% respectively. Our series, even if small, concerns nongerminomatous germ cell tumors only (whereas in some papers they are mixed with pure germinomas), furthermore our patients had a very long follow-up (over 11 years) with encouraging survival data for localized and metastatic disease. Improving survival while trying to contain/avoid the long-term sequelae of chemotherapy and radiotherapy are the main goals of future studies. Introduction: Due to the rarity of nongerminomatous germ cell tumors (NGGCT) with non-standard treatment as yet, we report retrospectively our 30 year experience with chemotherapy followed by craniospinal irradiation (CSI), plus a boost of whole ventricular irradiation (WVI)/tumor bed (TB), tailored to pre-radiation chemotherapy response. Methods: Between 1988 and 2016, 28 patients received four cycles of PEB (cisplatin/etoposide/bleomycin), then CSI, and two further PEB cycles. Between 1988 and1994, CSI was 25.5 Gy for patients in complete remission (CR), 30 Gy if in partial remission (PR) or metastatic, with a boost to TB up to 45-54 Gy. In the period of 1995-2010, the boost included WVI and any extra-ventricular tumor sites up to 45 Gy. After 2010, CSI was reduced to 25.5 Gy for all non-metastatic patients, and a boost was given only to TB up to 40.5/45.5 Gy, depending on patients' CR/PR status. After 2003, patients with alfafetoprotein (alpha FP) > 1000 ng/mL received intensified treatment, also including autologous stem cell transplantation. Results: Among 28 patients (23 males; median age 12 years, 6 metastatic), 25 responded to PEB, and three progressed (PD) after one to four cycles; 26 received radiotherapy obtaining 13 CR, 7 PR and 5 stable disease (SD), 1 PD; 6 (21%) died (5 for disease, 1 for pneumonia while in CR). Five-year overall survival (OS) and progression-free survival (PFS) were both 81%; 10 year OS and PFS 81% and 76%, respectively (median follow-up 11 years). Conclusions: Survival for children with NGGCT, independently from disease extent, was encouraging. Further studies should elucidate which patients could benefit from reduced volume and dose irradiation

Selective Amine Recognition Driven by Host\u2013Guest Proton Transfer and Salt Bridge Formation

The stepwise synthesis of ionizable p-tert-butylcalix[5]arenes 1a\ub7H and 1b\ub7H, featuring a fixed cone cavity endowed with a carboxyl moiety at the narrow rim, is described. Single-crystal X-ray analyses have shown that in the solid state 1a\ub7H and 1b\ub7H adopt a cone-out conformation with the carboxylic OH group pointing in, toward the bottom of the aromatic cavity, as a result of a three- or two-center hydrogen-bonding pattern between the carboxyl group and the phenolic oxygen atom(s). The affinity of amines for calix[5]arene derivatives 1a\ub7H and 1b\ub7H was probed by 1H NMR spectroscopy and single-crystal X-ray diffraction studies. These carboxylcalix[5]arenes are shown to selectively recognize linear primary amines - over branched, secondary, and tertiary amines - by a two-step process involving a proton transfer from the carboxyl to the amino group to provide the corresponding alkylammonium ion, followed by binding of the latter inside the cavity of the ionized calixarene. Proton transfer occurs only with linear primary amines, that is, when the best size and shape fit between host and substrate is achieved, while the other amines remain in their noncompeting unprotonated form. The role of the solvent in the ionization/complexation process is discussed. Structural studies on the n-BuNH2 complexes with 1a\ub7H and 1b\ub7H provide evidence that binding of the in situ formed n-BuNH3 + substrate to the cavity of the ionized macrocycle is ultimately secured, in the case of 1a\ub7H, by the formation of an unprecedented salt-bridge interaction

Probing the Inner Space of Salt-Bridged Calix[5]arene Capsules

A combined DOSY and XRD study indicates that a carboxylcalix[5]arene receptor is able to encapsulate alpha,omega-diamines of appropriate length by means of a proton-transfer-mediated recognition process followed by salt-bridge-assisted bis-endo-complexation

Hydrogen bond-assisted solid-state formation of a salt-bridged calix[5]arene pseudo-dimer

Co-crystallization of a carboxylcalix[5]arene in the presence of n-butylamine afforded the corresponding host\u2013guest carboxylate\u2013butylammonium salt-bridged complex as a result of a proton transfer process assisted by a second non-ionized calixarene molecule. The crystals isolated consist of a supramolecular pseudo-dimer in which a host\u2013guest inclusion complex is connected to a formally neutral receptor molecule \u2013 hosting a solvent molecule in the aromatic cavity \u2013 via a strong negative charge-assisted H-bond between the carboxyl/carboxylate substituents present at the narrow rim of the two interacting calixarene molecules

Acute Kidney Injury with SARS-CoV-2 Infection in Pediatric Patients Receiving High-Dose Methotrexate Chemotherapy: A Report of Three Cases

Background. Methotrexate is renally excreted. HDMTX (high dose-methotrexate)-induced acute kidney injury (AKI) is a non-oliguric decrease in glomerular filtration rate (GFR) heralded by an acute rise in serum creatinine. Moreover, AKI is also a frequent complication of COVID-19. Among our patients treated with HDMTX, some of these developed AKI during SARS-CoV-2 infection. Therefore, we wondered whether our patients’ kidney failure might have been triggered by their underlying SARS-CoV-2 positivity. Methods. Data were collected from the database at the Pediatric Oncology Unit of the Istituto Nazionale dei Tumori in Milan (Italy) regarding patients who matched the following selective criteria: (a) treatment with HDMTX during the pandemic period; (b) SARS-CoV-2 infection during the treatment; (c) development of AKI during HDMTX treatment and SARS-CoV-2 infection. Results. From March 2020 to March 2022, a total of 23 patients were treated with HDMTX; 3 patients were treated with HDMTX during SARS-CoV-2 infection and all 3 developed AKI. Conclusions. Clinical manifestations associated with this virus are many, so we are not yet able to lower our guard and rule out this infection as a cause of clinical manifestations with any certainty

Encapsulation of biogenic polyamines by carboxylcalix[5]arenes: when solid-state design beats recognition in solution

The biogenic tetraamines, spermine and norspermine, are efficiently encapsulated in the solid state by two molecules of carboxylcalix[5]arene, by means of a highly regioselective proton-transfer followed by bis-endo-cavity inclusion, providing overall-neutral complexes with a 70\u201372% packing coefficient, despite the modest affinity shown in solution

\u3b1,\u3c9-Alkanediyldiammonium dications sealed within calix[5]arene capsules with a hydrophobic bayonet-mount fastening

A combined XRD and 1H NMR study revealed that two molecules of tetrakis-(tert-butyloxycarbonylmethoxy)-calix[5]arene carboxylic acid are able to efficiently encapsulate \u3b1,\u3c9-diaminoalkanes of suitable length as a result of proton-transfer-mediated recognition. In the case of 1,10-diaminodecane and 1,11-diaminoundecane, rim-to-rim attractive van der Waals interactions drive the formation of capsular complexes with a packing coefficient close to 70%. The two calixarene bowls in these capsules are seen in an eclipsed conformation. On the other hand, when the longer 1,12-diaminododecane guest is used, a quasi-capsular complex is formed in which the capsule seal is lost and the two calixarenes are arranged in a staggered conformation as a result of a reciprocal rotation of the two facing macrocyclic cavities. A comparison with similar capsular complexes confirms that a hydrophobic 'bayonet-mount' fastening is mandatory for the encapsulation of suitably sized guests