Cross-immunization against respiratory coronaviruses may protect children from SARS-CoV2: more than a simple hypothesis?

In January 2020, a new coronavirus was identified as responsible for a pandemic acute respiratory syndrome. The virus demonstrated a high infectious capability and not-neglectable mortality in humans. However, similarly to previous SARS and MERS, the new disease COVID-19 caused by SARS-CoV-2 seemed to relatively spare children and younger adults. Some hypotheses have been proposed to explain the phenomenon, including lower ACE2 expression in children, cross-immunization from measles/rubella/mumps and BCG-vaccination, as well as the integrity of respiratory mucosa. Herein, we hypothesize that an additional mechanism might contribute to children\u2019s relative protection from SARS-CoV-2, the cross-immunization conferred by previous exposures to other common respiratory coronaviruses. To support our hypothesis, we show a statistically significant similarity in genomic and protein sequences, including epitopes for B- and T-cell immunity, of SARS-CoV-2 and the other beta coronaviruses. Since these coronaviruses are highly diffused across pediatric populations, cross-reactive immunity might reasonably induce an at least partial protection from SARS-CoV-2 in children

Cost of care and antibiotic prescribing attitudes for community-acquired complicated intra-abdominal infections in Italy: a retrospective study.

INTRODUCTION: Complicated intra-abdominal infections (cIAIs) are a common cause of morbidity worldwide, and in spite of improvements in patient care, therapeutic failure still occurs, impacting in-hospital resource consumption. This study aimed to assess the costs associated with the treatment of community-acquired cIAIs, from the Italian National Health Service perspective. METHODS: This retrospective study analyzed the charts of patients who were discharged from four Italian university hospitals between January 1 and December 31, 2009 with a primary diagnosis of community-acquired cIAIs. Patient characteristics, diagnosis, surgical procedure, antibiotic therapy, and length of hospital stay were all recorded and the cost of total hospital care was estimated. Costs were calculated in Euros at 2009 values. RESULTS: The records of 260 patients (mean age 48.9 years; 57% males) were analyzed. The average cost of care for a patient hospitalized due to cIAI was €4385 (95% CI 3650–5120), with an average daily cost of €419 (95% CI 378–440). Antibiotic therapy represented just under half (44.3%) of hospitalization costs. The strongest predictor of the increase in hospital costs was clinical failure: patients who clinically failed received an average of 8.2 additional days of antibiotic therapy and spent 11 more days in hospital compared with patients who responded to first-line therapy (both p < 0.05 vs. patients who were successfully treated). Furthermore, they incurred €5592 in additional hospitalization costs (2.88 times the cost associated with clinical success) with 53% (€2973) of the additional costs attributable to antibiotic therapy. Overall, antibiotic appropriateness rate was 78.8% (n = 205), and was significantly higher in patients receiving combination therapy compared with those treated with monotherapy (97.3% vs. 64.6%). CONCLUSION: The results of this study suggest that hospitals need to be aware of the clinical and economic consequences of antibiotic therapy of cIAIs and to reduce overall resource use and costs by improving the rate of success with appropriate initial empiric therapy

Oxidative DNA damage bypass in Arabidopsis thaliana requires DNA polymerase λ and proliferating cell nuclear antigen 2

The oxidized base 7,8-oxoguanine (8-oxo-G) is the most common DNA lesion generated by reactive oxygen species. This lesion is highly mutagenic due to the frequent misincorporation of A opposite 8-oxo-G during DNA replication. In mammalian cells, the DNA polymerase (pol) family X enzyme DNA pol l catalyzes the correct incorporation of C opposite 8-oxo-G, together with the auxiliary factor proliferating cell nuclear antigen (PCNA). Here, we show that Arabidopsis thaliana DNA pol l, the only member of the X family in plants, is as efficient in performing error-free translesion synthesis past 8-oxo-G as its mammalian homolog. Arabidopsis, in contrast with animal cells, possesses two genes for PCNA. Using in vitro and in vivo approaches, we observed that PCNA2, but not PCNA1, physically interacts with DNA pol l, enhancing its fidelity and efficiency in translesion synthesis. The levels of DNA pol l in transgenic plantlets characterized by overexpression or silencing of Arabidopsis POLL correlate with the ability of cell extracts to perform error-free translesion synthesis. The important role of DNA pol l is corroborated by the observation that the promoter of POLL is activated by UV and that both overexpressing and silenced plants show altered growth phenotypes

Arabidopsis Topless-related 1 mitigates physiological damage and growth penalties of induced immunity

Transcriptional corepressors of the Topless (TPL) family regulate plant hormone and immunity signaling. The lack of a genome-wide profile of their chromatin associations limits understanding of the TPL family roles in transcriptional regulation. Chromatin immunoprecipitation with sequencing (ChIP-Seq) was performed on Arabidopsis thaliana lines expressing GFP-tagged Topless-related 1 (TPR1-GFP) with and without constitutive immunity via Enhanced Disease Susceptibility 1 (EDS1). RNA-Seq profiling of the TPR1-GFP lines and pathogen-infected tpl/tpr mutants, combined with measuring immunity, growth, and physiological parameters was employed to investigate TPL/TPR roles in immunity and defense homeostasis. TPR1 was enriched at promoter regions of c. 1400 genes and c. 10% of the detected binding required EDS1 immunity signaling. In a tpr1 tpl tpr4 (t3) mutant, resistance to bacteria was slightly compromised, and defense-related transcriptional reprogramming was weakly reduced or enhanced, respectively, at early (< 1 h) and late 24 h stages of bacterial infection. The t3 plants challenged with bacteria or pathogen-associated molecular pattern nlp24 displayed photosystem II dysfunctions. Also, t3 plants were hypersensitive to phytocytokine pep1 at the level of root growth inhibition. Transgenic expression of TPR1 rescued these t3 physiological defects. We propose that TPR1 and TPL family proteins function in Arabidopsis to reduce detrimental effects associated with activated transcriptional immunity

Aetiology of pneumonia following isolated closed head injury

AbstractPatients undergoing mechanical ventilation (MV) after an isolated closed head injury (ICHI) have often been found to develop hospital-acquired pneumonia (HAP) well before subjects who require MV for different reasons. In a prospective study of patients receiving MV after an ICHI, 38 subjects (out of 65 with clinically suspected HAP) had a bacteriological diagnosis established on the basis of correspondence between cultures made from bronchoalveolar lavage and protected specimen brush (with quantitative thresholds of 104 and 103 cfu ml−1, respectively). Patients were separated according to the time of onset of HAP, with 20 subjects who developed HAP within 4 days of the start of MV (early onset pneumonia, EOP) and 18 subjects who developed HAP after the fourth day (late onset pneumonia, LOP). In those who had LOP, an expected spectrum of organisms was found, with Gram-negatives (especially Pseudomonas sp.) accounting for the majority of isolates. However, in EOP cases, Gram-positive bacteria (especially Staphylococcus sp. and Streptococcus pneumoniae) were found to largely predominate (P = 0·0000026). This confirms the high incidence of staphylococcal pneumonia in neurosurgery patients, and also provides evidence that the vast majority of such staphylococcal pneumonia are EOP. Unlike most previous reports, the microbiological findings from the present study suggest that a cut-off point of 4 days successfully distinguishes between EOP and LOP. Since these two clinical entities differ significantly in terms of pathogenesis and aetiology, preventive measures and therapeutical protocols have to be tailored accordingly

Prolonged hospitalisation for immigrants and high risk patients with positive smear pulmonary tuberculosis.

Background and objective. Tuberculosis (TB) occurring in immigrants and resistance to drugs are major problems for TB control in Western countries. Directly observed therapy (DOT) reduces disease transmission, but this approach may have poor results among illegal immigrants. Our aim was to evaluate a prolonged hospitalisation programme to improve early outcome of TB treatment in high risk patients. Methods. All the consecutive adult patients with sputum smear-positive pulmonary TB admitted to 2 Italian referral TB Centres were evaluated. Hospital-based DOT was provided to high risk patients up-to smear conversion. Demographic, microbiological and clinical conditions, as potential factors associated with confirmed smear conversion at 60 and 90 days of anti-tuberculous therapy were evaluated. Results. 122 patients were studied, 45.9% of them were immigrants (20% illegal) from high-prevalence TB countries. HIV testing was negative in all cases. Twelve patients had M. tuberculosis resistant to ≥ 1 first-line anti-tuberculous agents. The rate of defaulting from TB treatment was 7.3%. Sputum smear became negative in 84.4% cases after 60 days and 93.3% cases after 90 days. At such time, smear conversion rates were similar among different high risk subgroups such as illegal immigrants (95.9%), legal foreign-born (92.5%) and Italian persons (94.8%). Persistent sputum smear positivity was independently correlated with the extent of pulmonary lesions at 60 (p&lt;0.0001) and 90 days (p=0.038) of hospital-based DOT. Conclusions. These findings suggest that prolonged hospitalisation for illegal immigrants and high risk TB patients, may positively influence the early outcome of TB treatment despite of drug resistance and legal status

Predicting candidemia in internal medicine departments: are we chasing the Holy Grail?

Candidemia is a challenging clinical condition with high rates of morbidity and mortality.1 Key requirements for its prompt management include early identification and timely initiation of appropriate systemic antifungal therapy, consistently reported as a major determinant of survival. However, the diagnosis of candidemia can be challenging and is often delayed as there are no specific clinical signs, blood cultures have low sensitivity, and detection of fungal blood cultures takes a long time. In addition, there is evidence that a significant percentage of such infections occurs in patients admitted to internal medicine departments. This is not particularly surprising given the advanced age of many inpatients at internal medicine departments and multiple complex comorbidities. Moreover, related therapies and healthcare system contacts often involve the use of central venous catheters and other indwelling devices, potentially entailing high risk of candidemia.2 Therefore, optimization of the diagnostic and therapeutic approach is an important and still unfulfilled need for the management of candidemia in internal medicine department