Abstract Objectives The main challenge in treating bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the absence of an effective established treatment. We aimed to compare different ...potentially preventive treatments for BRONJ after dental extractions in zoledronic acid (ZA)-treated animals. We studied the local application of different combinations of adipose-derived stem cells (ASCs) with or without previous stimulation with bone morphogenetic protein 2 (BMP-2) and platelet-rich plasma (PRP) in rats. Material and methods Fifty-six male Wistar rats were treated with ZA for 9 weeks. Dental extractions were performed in the eighth week, and the animals were divided into 4 groups. In group 1 (n = 14), alveolar coverage with mucoperiosteal flap was performed. In group 2 (n = 14), PRP was applied over the sockets and covered with the flap. In group 3 (n = 15), allogeneic ASCs with PRP were applied and covered with the flap. In group 4 (n = 13), animals were treated with ASCs cultured with BMP-2, PRP, and flap coverage. Histologic, fluorescence, and radiologic studies of the maxillae were performed. Results ASC-treated animals showed lower frequency of osteonecrosis (14% vs 50%, p = 0.007) and greater bone turnover ( p = 0.024) and osteoclast count ( p = 0.045) than those not receiving the ASC treatment. Conclusions In this high-risk model, ASC-based treatments seem to prevent BRONJ more effectively than mucosal flap with or without PRP. The combination of ASCs and PRP appears to be synergistic, and the addition of BMP-2 could further improve the results.
The Dalitz plot analysis technique is used to study the resonant substructures of B−→D+π−π− decays in a data sample corresponding to 3.0 fb−1 of pp collision data recorded by the LHCb experiment ...during 2011 and 2012. A model-independent analysis of the angular moments demonstrates the presence of resonances with spins 1, 2 and 3 at high D+π− mass. The data are fitted with an amplitude model composed of a quasi-model-independent function to describe the D+π− S wave together with virtual contributions from the D*(2007)0 and B*0 states, and components corresponding to the D2*(2460)0, D1*(2680)0, D3*(2760)0 and D2*(3000)0 resonances. The masses and widths of these resonances are determined together with the branching fractions for their production in B−→D+π−π− decays. The D+π− S wave has phase motion consistent with that expected due to the presence of the D0*(2400)0 state. These results constitute the first observations of the D3*(2760)0 and D2*(3000)0 resonances, with significances of 10σ and 6.6σ, respectively.
A
bstract
A combination of measurements sensitive to the CKM angle γ from LHCb is performed. The inputs are from analyses of time-integrated
B
+
→
DK
+
,
B
0
→
DK
∗0
,
B
0
→
DK
+
π
−
and
B
+
→
DK
+
π
...+
π
−
tree-level decays. In addition, results from a time-dependent analysis of
B
s
0
→
D
s
∓
K
±
decays are included. The combination yields
γ
= (72. 2
− 7.3
+ 6.8
)
°
, where the uncertainty includes systematic effects. The 95.5% confidence level interval is determined to be γ ∈ 55
.
9
,
85
.
2°. A second combination is investigated, also including measurements from
B
+
→
D
π
+
and
B
+
→
D
π
+
π
−
π
+
decays, which yields compatible results.
Chronic kidney disease (CKD) remains a major epidemiological, clinical, and biomedical challenge. During CKD, renal tubular epithelial cells (TECs) present a persistent inflammatory and profibrotic ...response. Fatty acid oxidation (FAO), the main source of energy for TECs, is reduced in kidney fibrosis and contributes to its pathogenesis. To determine whether gain of function in FAO (FAO-GOF) could protect from fibrosis, we generated a conditional transgenic mouse model with overexpression of the fatty acid shuttling enzyme carnitine palmitoyl-transferase 1A (CPT1A) in TECs. Cptla-knockin (CPT1A-KI) mice subjected to 3 models of renal fibrosis (unilateral ureteral obstruction, folic acid nephropathy FAN, and adenine-induced nephrotoxicity) exhibited decreased expression of fibrotic markers, a blunted proinflammatory response, and reduced epithelial cell damage and macrophage influx. Protection from fibrosis was also observed when Cpt1a overexpression was induced after FAN. FAO-GOF restored oxidative metabolism and mitochondrial number and enhanced bioenergetics, increasing palmitate oxidation and ATP levels, changes that were also recapitulated in TECs exposed to profibrotic stimuli. Studies in patients showed decreased CPT1 levels and increased accumulation of short- and middlechain acylcarnitines, reflecting impaired FAO in human CKD. We propose that strategies based on FAO-GOF may constitute powerful alternatives to combat fibrosis inherent to CKD.
Tetracycline resistance (Tet
) has been evidenced as a good phenotypic marker for detection of livestock-associated methicillin-resistant
(LA-MRSA) isolates of the clonal complex CC398. The aim of ...this study was to characterise a collection of 95 Tet
-MRSA isolates, not belonging to the lineage CC398, that were obtained in a previous multicentre study, to detect other MRSA clonal complexes that could be associated with this phenotypic Tet
marker. The Tet
-MRSA isolates were recovered from 20 Spanish hospitals during 2016 and they were characterised to determine their antimicrobial resistance and virulence phenotypes/genotypes as well as the presence of the immune evasion cluster (IEC). A high proportion of isolates belonging to the CC1 lineage (46%) were observed, as well as to the CC5, CC8 and CC45 lineages (11% each one). Thirty-two different
-types were identified, being predominantly CC1-t127 (40%) and CC45-t1081 (11%). The IEC system (with the gene
as marker) was present in 73% of isolates and 16% produced the Panton Valentine leucocidin (PVL). A high proportion of MRSA-CC1 isolates were
-negative (38.6%) and 52.9% of them were
-negative. A multidrug resistance (MDR) phenotype was identified in 86% of MRSA isolates. The knowledge of other Tet
-MRSA genetic lineages, in addition to CC398, is highly relevant, since most of them were MDR and some of them presented important virulence factors. Strains potentially associated with livestock (as the subpopulation CC1-t127-
-negative) or with humans (as the CC45 lineage or the subpopulation CC1-
-positive) have been found in this study. The use of tetracycline-resistance for detection, not only of CC398 but also of other LA-MRSA lineages should be tracked in the future.
Abstract
Background
The impact of method of anastomosis and minimally invasive surgical technique on surgical and clinical outcomes after right hemicolectomy is uncertain. The aim of the MIRCAST ...study was to compare intracorporeal and extracorporeal anastomosis (ICA and ECA respectively), each using either a laparoscopic approach or robot-assisted surgery during right hemicolectomies for benign or malignant tumours.
Methods
This was an international, multicentre, prospective, observational, monitored, non-randomized, parallel, four-cohort study (laparoscopic ECA; laparoscopic ICA; robot-assisted ECA; robot-assisted ICA). High-volume surgeons (at least 30 minimally invasive right colectomy procedures/year) from 59 hospitals across 12 European countries treated patients over a 3-year interval The primary composite endpoint was 30-day success, defined by two measures of efficacy—absence of surgical wound infection and of any major complication within the first 30 days after surgery. Secondary outcomes were: overall complications, conversion rate, duration of operation, and number of lymph nodes harvested. Propensity score analysis was used for comparison of ICA with ECA, and robot-assisted surgery with laparoscopy.
Results
Some 1320 patients were included in an intention-to-treat analysis (laparoscopic ECA, 555; laparoscopic ICA, 356; robot-assisted ECA, 88; robot-assisted ICA, 321). No differences in the co-primary endpoint at 30 days after surgery were observed between cohorts (7.2 and 7.6 per cent in ECA and ICA groups respectively; 7.8 and 6.6 per cent in laparoscopic and robot-assisted groups). Lower overall complication rates were observed after ICA, specifically less ileus, and nausea and vomiting after robot-assisted procedures.
Conclusion
No difference in the composite outcome of surgical wound infections and severe postoperative complications was found between intracorporeal versus extracorporeal anastomosis or laparoscopy versus robot-assisted surgery.
The objective of the MIRCAST study was to compare intracorporeal and extracorporeal anastomoses, each using either a laparoscopic approach or robot-assisted surgery. No difference in the composite outcome of surgical wound infections and severe postoperative complications was found between intracorporeal versus extracorporeal anastomosis or laparoscopy versus robot-assisted surgery. The lower overall complication rates after intracorporeal anastomosis should be of interest when determining the surgical technique during hemicolectomy for neoplasms of the right colon.
The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over the first 20 min in adult patients treated with methoxyflurane versus standard analgesic treatment ...in Spain. This the first randomized, active-controlled, multicenter trial of methoxyflurane in the emergency setting in Europe.
This was a randomized, controlled study that enrolled adult patients with acute moderate to severe (score ≥4 on the 11-point Numeric Rating Scale) trauma-associated pain in 14 Spanish emergency departments. Patients were randomized 1:1 to methoxyflurane (up to 2×3 mL) or standard analgesic treatment. Coprimary endpoints were the change from baseline in Numeric Rating Scale pain intensity score during the first 20 minutes of treatment and time to first pain relief.
Three hundred five patients were randomized (methoxyflurane 156; standard analgesic treatment 149). Most patients in the standard analgesic treatment group (70%) received intravenous first-step analgesics and 9.4% of patients were treated with opioids. Mean decrease from baseline in Numeric Rating Scale pain intensity score was greater for methoxyflurane than standard analgesic treatment at all points, with a significant treatment difference overall up to 20 minutes (repeated-measures model 2.47 versus 1.39; treatment difference 1.00; 95% confidence interval 0.84 to 1.32). Median time to first pain relief was significantly shorter for methoxyflurane than standard analgesic treatment (3 versus 10 minutes). Methoxyflurane achieved better patient and clinician ratings for pain control and comfort of treatment than standard analgesic treatment and exceeded patient and clinician expectations of treatment in, respectively, 77% and 72% of cases compared with 38% and 19% for standard analgesic treatment.
These results support consideration of methoxyflurane as a nonnarcotic, easy-to-administer, rapid-acting, first-line alternative to currently available analgesic treatments for trauma pain.
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