Impact of therapeutic choices on outcome of osteomyelitis caused by MRSA

Fifty-four patients with chronic osteomyelitis sustained by methicillin-resistant staphylococcus were treated with daptomycin, linezolid, or teicoplanin and observed over time. Median time to CRP normalization was 7 weeks for daptomycin, 8 weeks for linezolid, and 12 weeks for teicoplanin (X2 =14.1; p < 0.001). Cure rate (intention to treat analysis) was 83% for the cases receiving teicoplanin, 77% for those receiving linezolid and 92% for those receiving daptomycin. We conclude that daptomycin and linezolid have to be considered at least equivalent to teicoplanin for the treatment of MRSA osteomyelitis

Pea PSII-LHCII supercomplexes form pairs by making connections across the stromal gap

In higher plant thylakoids, the heterogeneous distribution of photosynthetic protein complexes is a determinant for the formation of grana, stacks of membrane discs that are densely populated with Photosystem II (PSII) and its light harvesting complex (LHCII). PSII associates with LHCII to form the PSII-LHCII supercomplex, a crucial component for solar energy conversion. Here, we report a biochemical, structural and functional characterization of pairs of PSII-LHCII supercomplexes, which were isolated under physiologically-relevant cation concentrations. Using single-particle cryo-electron microscopy, we determined the three-dimensional structure of paired C2S2M PSII-LHCII supercomplexes at 14 angstrom resolution. The two supercomplexes interact on their stromal sides through a specific overlap between apposing LHCII trimers and via physical connections that span the stromal gap, one of which is likely formed by interactions between the N-terminal loops of two Lhcb4 monomeric LHCII subunits. Fast chlorophyll fluorescence induction analysis showed that paired PSII-LHCII supercomplexes are energetically coupled. Molecular dynamics simulations revealed that additional flexible physical connections may form between the apposing LHCII trimers of paired PSII-LHCII supercomplexes in appressed thylakoid membranes. Our findings provide new insights into how interactions between pairs of PSII-LHCII supercomplexes can link adjacent thylakoids to mediate the stacking of grana membranes

In the lycophyte Selaginella martensii is the "extra-qT" related to energy spillover? Insights into photoprotection in ancestral vascular plants

Lycophytes are early diverging vascular plants, representing a minor group as compared to the dominating euphyllophytes, mostly angiosperms. Having maximally developed in a CO2-rich atmosphere, extant lycophytes are characterized by a low carbon fixing capacity, which is compensated by a marked ability to induce the non-photochemical quenching of chlorophyll fluorescence (NPQ). Different kinetic components contribute to NPQ, in particular the fast relaxing high-energy quenching qE, the middle relaxing qT, and the slowly relaxing qI. Unlike angiosperms, lycophytes enhance the qT component under high light, originating from an "extra-qT". In this research, we analyze whether in Selaginella martensii the extra-qT can reflect a photosystem (PS) I-based quenching mechanism activated upon saturation of qE capacity. From comparative analyses of fluorescence quenching parameters, carbon fixation, in vivo low- and room-temperature fluorescence spectroscopy, and thylakoid protein phosphorylation, it is proposed that the extra-qT is not mechanistically separate from the ordinary qT. The results suggest a relationship between qT and photoprotective energy spillover to PSI, which is activated upon sensing the excitation energy pressure inside PSII and is possibly facilitated by phosphorylation of Lhcb6, a minor antenna protein of PSII. Energy spillover emphasizes 77K fluorescence emission from PSI core (F714) and becomes more relevant at irradiance levels corresponding to the CO2-limited, potentially photoinhibiting phase of photosynthesis. At the highest irradiances, when Lhcb6 phosphorylation potential has been saturated, the major LHCII increases in turn its phosphorylation level, probably leading to the full exploitation of PSI as a safe excitation sink. It is suggested that the low photosynthetic capacity of lycophytes could allow an easier experimental access to the use of PSI as a safe excitation quencher for PSII, a debated, emerging issue about thylakoid photoprotection in angiosperms.</p

Isolation of novel PSII-LHCII megacomplexes from pea plants characterized by a combination of proteomics and electron microscopy

This work was supported by the Italian Ministry of Education, University and Research, “Futuro in Ricerca 2013” program RBFR1334SB to CP

Adverse Events Associated with BNT162b2 and AZD1222 Vaccines in the Real World: Surveillance Report in a Single Italian Vaccine Center

Aim: Despite huge efforts in developing specific drugs, vaccination represents the only effective strategy against COVID-19. Efficacy and safety of the COVID-19 vaccines were established during clinical trials. Nonetheless, it is very important to perform continuous surveillance. This observational study aimed to report potential Adverse Events Following Immunization (AEFI) following the first dose of two different COVID-19 vaccines, BNT162b2 and AZD1222. Methods and Results: Subjects who underwent vaccination at the vaccine center of the University Hospital of Salerno, Italy, were interviewed using an ad hoc questionnaire. AZD-vac group (n = 175) who received AZD1222 had a higher number of AEFI than the BNT-vac group (n = 1613) who received BNT162b2 (83% vs. 42%). The most frequent AEFI associated with AZD1222 and BNT162b2 were fever and pain at the injection site, respectively. The AZD-vac group used drugs to contrast AEFI more frequently than the BNT-vac group. In the BNT-vac group, there was a higher incidence of AEFI in women than in men (26.2% vs. 15.8%, p = 0.01), while no gender-related difference was observed in the AZD-vac group. Conclusions: AZD1222 and BNT162b2 vaccines show a good safety profile. Based on our results and literature data, there are no reasons to justify the reluctance that persists towards immunization

One-step isolation and biochemical characterization of a highlyactive plant PSII monomeric core

We describe a one-step detergent solubilization protocol for isolating a highly active form of Photosystem II (PSII) from Pisum sativum L. Detailed characterization of the preparation showed that the complex was a monomer having no light harvesting proteins attached. This core reaction centre complex had, however, a range of low molecular mass intrinsic proteins as well as the chlorophyll binding proteins CP43 and CP47 and the reaction centre proteins D1 and D2. Of particular note was the presence of a stoichiometric level of PsbW, a low molecular weight protein not present in PSII of cyanobacteria. Despite the high oxygen evolution rate, the core complex did not retain the PsbQ extrinsic protein although there was close to a full complement of PsbO and PsbR and partial level of PsbP. However, reconstitution of PsbP and PsbPQ was possible. The presence of PsbP in absence of LHCII and other chlorophyll a/b binding proteins confirms that LHCII proteins are not a strict requirement for the assembly of this extrinsic polypeptide to the PSII core in contrast with the conclusion of Caffarri et al. (2009)

Variations of the UNC13D gene in patients with autoimmune lymphoproliferative syndrome.

Autoimmune lymphoproliferative syndrome (ALPS) is caused by genetic defects decreasing Fas function and is characterized by lymphadenopathy/splenomegaly and expansion of CD4/CD8 double-negative T cells. This latter expansion is absent in the ALPS variant named Dianzani Autoimmune/lymphoproliferative Disease (DALD). In addition to the causative mutations, the genetic background influences ALPS and DALD development. We previously suggested a disease-modifying role for the perforin gene involved in familial hemophagocytic lymphohistiocytosis (FHL). The UNC13D gene codes for Munc13-4, which is involved in perforin secretion and FHL development, and thus, another candidate for a disease-modifying role in ALPS and DALD. In this work, we sequenced UNC13D in 21 ALPS and 20 DALD patients and compared these results with sequences obtained from 61 healthy subjects and 38 multiple sclerosis (MS) patients. We detected four rare missense variations in three heterozygous ALPS patients carrying p.Cys112Ser, p.Val781Ile, and a haplotype comprising both p.Ile848Leu and p.Ala995Pro. Transfection of the mutant cDNAs into HMC-1 cells showed that they decreased granule exocytosis, compared to the wild-type construct. An additional rare missense variation, p.Pro271Ser, was detected in a healthy subject, but this variation did not decrease Munc13-4 function. These data suggest that rare loss-of-function variations of UND13D are risk factors for ALPS development

Hot topics in necrotising skin and soft tissue infections

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Pediatric Visceral Leishmaniasis in Albania: A Retrospective Analysis of 1,210 Consecutive Hospitalized Patients (1995–2009)

Albania is a developing country that is rapidly improving in social, economic and sanitary conditions. The health care system in still in progress and the impact of some infectious diseases remains poorly understood. In particular, little information is available on incidence, clinical features and response to treatment of visceral leishmaniasis (VL) in childhood. We performed a retrospective analysis of data recorded from 1995 to 2009 at the national pediatric reference hospital of Tirana where any child suspected for VL is referred for specific diagnosis and treatment. Epidemiology, clinical features and management of the disease were considered. The main findings can be summarized as follows: i) The incidence of the disease in Albanian children (25/100,000 in the age group 0–6 years) is much higher than in developed Mediterranean countries endemic for VL; ii) The disease is associated with poor sanitary conditions as suggested by the high rate of severe clinical features and frequency of co-morbidities; iii) The cheapest drug available for Mediterranean VL treatment (meglumine antimoniate) is highly effective (99% full cure rate) and well tolerated. Limitations were identified in the low standard laboratory diagnostic capability and unsatisfactory medical surveillance in less urbanized areas. An improvement is warranted of a disease-specific surveillance system in Albania