Identification of NDM-1 in a Putatively Novel Acinetobacter Species (“NB14”) Closely Related to Acinetobacter pittii

In this study, we describe the molecular characterization of a plasmid-located bla_NDM-1 harbored by an Acinetobacter clinical isolate recovered from a patient in Turkey that putatively constitutes a novel Acinetobacter species, as shown by its distinct ARDRA (amplified 16S ribosomal DNA restriction analysis) profile and molecular sequencing techniques. bla_NDM-1 was carried by a conjugative plasmid widespread among non-baumannii Acinetobacter isolates, suggesting its potential for dissemination before reaching more clinically relevant Acinetobacter species.     

Amoxicillin for acute lower respiratory tract infection in primary care: subgroup analysis of potential high-risk groups

Background

Antibiotics are of limited overall clinical benefit for uncomplicated lower respiratory tract infection (LRTI) but there is uncertainty about their effectiveness for patients with features associated with higher levels of antibiotic prescribing.

Aim

To estimate the benefits and harms of antibiotics for acute LRTI among those producing coloured sputum, smokers, those with fever or prior comorbidities, and longer duration of prior illness.

Design and setting

Secondary analysis of a randomised controlled trial of antibiotic placebo for acute LRTI in primary care.

Method

Two thousand and sixty-one adults with acute LRTI, where pneumonia was not suspected clinically, were given amoxicillin or matching placebo. The duration of symptoms, rated moderately bad or worse (primary outcome), symptom severity on days 2–4 (0–6 scale), and the development of new or worsening symptoms were analysed in pre-specified subgroups of interest. Evidence of differential treatment effectiveness was assessed in prespecified subgroups by interaction terms.

Results

No subgroups were identified that were significantly more likely to benefit from antibiotics in terms of symptom duration or the development of new or worsening symptoms. Those with a history of significant comorbidities experienced a significantly greater reduction in symptom severity between days 2 and 4 (interaction term −0.28, P = 0.003; estimated effect of antibiotics among those with a past history −0.28 [95% confidence interval = −0.44 to −0.11], P = 0.001), equivalent to three people in 10 rating symptoms as a slight rather than a moderately bad problem. For subgroups not specified in advance antibiotics provided a modest reduction in symptom severity for non-smokers and for those with short prior illness duration (<7 days), and a modest reduction in symptom duration for those with short prior illness duration.

Conclusion

There is no clear evidence of clinically meaningful benefit from antibiotics in the studied high-risk groups of patients presenting in general practice with uncomplicated LRTIs where prescribing is highest. Any possible benefit must be balanced against the side-effects and longer-term effects on antibiotic resistance.     

Rejection of unfair offers in the ultimatum game is no evidence of strong reciprocity

The strong reciprocity model of the evolution of human cooperation has gained some acceptance, partly on the basis of support from experimental findings. The observation that unfair offers in the ultimatum game are frequently rejected constitutes an important piece of the experimental evidence for strong reciprocity. In the present study, we have challenged the idea that the rejection response in the ultimatum game provides evidence of the assumption held by strong reciprocity theorists that negative reciprocity observed in the ultimatum game is inseparably related to positive reciprocity as the two sides of a preference for fairness. The prediction of an inseparable relationship between positive and negative reciprocity was rejected on the basis of the results of a series of experiments that we conducted using the ultimatum game, the dictator game, the trust game, and the prisoner’s dilemma game. We did not find any correlation between the participants’ tendencies to reject unfair offers in the ultimatum game and their tendencies to exhibit various prosocial behaviors in the other games, including their inclinations to positively reciprocate in the trust game. The participants’ responses to postexperimental questions add support to the view that the rejection of unfair offers in the ultimatum game is a tacit strategy for avoiding the imposition of an inferior status.     

Merkel Cell Carcinoma: 30-Year Experience from a Single Institution

Background

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy. Few single-institution series have been reported.

Methods

Review of MCC patients treated at our institution between 1980 and 2010. Patient, tumor, and treatment variables were analyzed to determine MCC-specific outcomes.

Results

We identified 161 patients with MCC. There was a 2.5-fold increase in cases over the last decade. Median length of follow-up was 36 months. Stage at diagnosis was I in 35 %, II in 21 %, IIIa in 12 %, IIIb in 23 %, and IV in 9 %. The 5-year MCC-specific survival rates were 87, 63, 42, and 0 % for stages I, II, III, and IV, respectively. Death from the disease occurred in 10 % of patients with T1 and in 50 % with larger lesions. One-third of patients presented with nodal disease. Sentinel lymph node biopsy (SLNB) identified micrometastases in 9 out of 27 (33 %) early-stage patients. Recurrence developed in 56 % of SLNB-positive and 39 % of SLNB-negative patients. Half of patients recurred after a median time of 9 months. Proportions of first recurrence location were distant (52 %), nodal (27 %), and local (21 %). Adjuvant treatments did not improve recurrence or survival rates. One-third of patients died of the disease.

Conclusions

SLNB identifies micrometastasis in one-third of early-stage patients. Negative SLNB may predict for improved but not necessarily favorable outcome. Initial tumor size and clinical nodal disease predict for poor outcome. High recurrence rates warrant the development of more effective adjuvant therapies, and better markers of recurrence and treatment response for MCC are needed.     

Effects of the compounds resveratrol,rutin, quercetin,and quercetin nanoemulsion on oxaliplatin-induced hepatotoxicity and neurotoxicity in mice

Oxaliplatin (OXA) is a platinum compound widely used in the treatment of some solid tumors, especially colorectal cancer. Despite its usefulness, oxaliplatin-associated neurotoxicity represents the main dose-limiting factor of this drug, and until now, there is no suitable treatment. Chemotherapy with oxaliplatin also increases the rate of developing hepatic damages with inflammatory activity, termed chemotherapy-associated steatohepatitis (CASH). In the present study, we aimed to compare the effects of a series of antioxidant compounds on simultaneous development of oxaliplatin-induced hepato- and neurotoxicity in mice. Mice BALB/c were treated with oxaliplatin for 6 weeks, 10 mg/kg, intraperitoneally, resulting in mechanical allodynia and hepatic steatosis. We administered the following antioxidant compounds—rutin (RT) (20 mg/kg), resveratrol (RVS) (100 mg/kg), quercetin (QT) (20 mg/kg), and quercetin nanoemulsion (NQT) (20 mg/kg)—daily by gavage to BALB/c, and N-acetylcysteine (NAC) was used as positive control. Treatments with RSV, RUT, or NQT were able to prevent mechanical allodynia when compared to the OXA group, and this effect was associated with decreased c-Fos immunopositivity in the lumbar spinal cord. Regarding the effects on steatohepatitis, RVS, QT, and NQT almost completely reversed the mean liver weight increase induced by OXA. In accordance with these previous data, histological evaluation indicated attenuation of all features of hepatic steatosis evaluated in RSV, RUT, QT, and NQT groups. These compounds were able to reduce the immunopositivity for the apoptosis marker caspase-3. On the other hand, only QT and NQT treatments were able to reduce neutrophil migration measured by myeloperoxidase (MPO) activity. These results suggest that the compounds tested, RSV, RUT, QT, and NQT, would be useful for the clinical treatment of neuro- and hepatoxicity induced by oxaliplatin.