Technological disasters in Asia: Epidemiological profile from the year 2000 to 2021.

BACKGROUND: Technological disasters in Asia have significant public health and environmental implications, but there is limited epidemiological analysis of these events. This study aims to characterize the epidemiological profile of technological disasters in Asia from 2000 to 2021, focusing on morbidity and mortality trends. METHODS: A retrospective descriptive observational analysis was conducted using data from emergency events database (EM-DAT), DesInventar, NatCAt, and Sigma. The study categorized disasters into transport, industrial, and miscellaneous accidents. Statistical analyses were used to examine frequencies, trends, and correlations among the different disaster types. RESULTS: From 2000 to 2021, Asia experienced 2333 technological disasters, with transport accidents being the most frequent (55.77%), followed by industrial (26.10%) and miscellaneous accidents (18.13%). The overall trend showed a statistically significant decrease in the frequency of these disasters and in average mortality and injury rates. The study highlighted the varying impact of different disaster types, with industrial accidents causing the highest fatality and affected rates despite being less frequent than transport accidents. CONCLUSIONS: The study indicates a declining trend in the frequency and severity of technological disasters in Asia, reflecting improved safety measures and disaster management. However, the high impact of industrial accidents underscores the need for targeted prevention strategies.

Disposition kinetics and bioavailability of doxycycline after parenteral administrations in ewes.

Doxycycline is a tetracycline, which have been marketed in different species for treating infections caused by susceptible bacteria. There is limited information on the disposition kinetics of this drug in ewes and this antimicrobial may be useful against several sheep pathogens that are common causes of morbidity and economic loss. Therefore, the aim of this work was to establish the pharmacokinetics of doxycycline after intravenous (IV) and extravascular (subcutaneous (SC) and intramuscular (IM)) administrations in this species. A cross-over model was designed (n = 6). Doxycycline was dosed at 5 mg/kg for IV administration and 20 mg/kg for extravascular administrations. Non-compartmental pharmacokinetic methods were used to calculate plasma concentration-time data. The value of apparent volume of distribution (Vz) suggests a moderate distribution of this antibiotic in sheep, with a value of 0.84 L/kg. The maximum concentrations achieved after extravascular administrations (Cmax) were similar, with no significant differences between the two routes of administration (IM and SC). However, doxycycline absorption was slower after SC administration than after IM administration, taking twice as long to reach maximum plasma concentration (tmax). Bioavailabilities after extravascular routes of administration were low and after IM administration doxycycline caused lameness in all animals. Therefore, the SC administration showed a better profile with respect to pharmacokinetic properties and safety. Future studies on the susceptibility of isolated sheep pathogens to doxycycline are needed to establish appropriate dosing regimens.

Separation of oxygen from nitrogen using a graphdiyne membrane: a quantum-mechanical study.

Efficient separation of oxygen and nitrogen from air is a process of great importance for many industrial and medical applications. Two-dimensional (2D) membranes are very promising materials for separation of gases, as they offer enhanced mass transport due to their smallest atomic thickness. In this work, we examine the capacity of graphdiyne (GDY), a new 2D carbon allotrope with regular subnanometric pores, for separating oxygen (16O2) from nitrogen (14N2). A quantum-mechanical model has been applied to the calculation of the transmission probabilities and permeances of these molecules through GDY using force fields based on accurate electronic structure computations. It is found that the 16O2/14N2 selectivity (ratio of permeances) is quite high (e.g., about 106 and 102 at 100 and 300 K, respectively), indicating that GDY can be useful for separation of these species, even at room temperature. This is mainly due to the N2 transmission barrier (∼0.37 eV) which is considerably higher than the O2 one (∼0.25 eV). It is also found that molecular motions are quite confined inside the GDY pores and that, as a consequence, quantum effects (zero-point energy) are significant in the studied processes. Finally, we explore the possibility of 18O2/16O2 isotopologue separation due to these mass-dependent quantum effects, but it is found that the process is not practical since reasonable selectivities are concomitant with extremely small permeances.

Diagnostic Accuracy of Dermatoscopy Versus Microbiological Culture and Polymerase Chain Reaction in the Diagnosis of Onychomycosis: A Cross-Sectional Study.

BACKGROUND: Several clinical signs in dermatoscopy are very characteristic of onychomycosis and can be a quick complement for the diagnosis of onychomycosis. OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of dermatoscopy compared to microbiological culture and polymerase chain reaction (PCR), as well as the clinical signs associated with onychomycosis. METHODS: The clinical signs of 125 patients were assessed cross-sectionally using dermatoscopy, and a positive or negative result was assigned. A sample was then taken for PCR and microbiological culture. RESULTS: Of the 125 patients, 69.6% (87/125) had positive results when both laboratory tests were combined. When they were not combined, the prevalence was lower at 48% (60/125) with PCR and at 43.2% (54/125) with culture. Furthermore, 76.8% (96/125) were classified as positive with dermatoscopy with a sensitivity of 1, a specificity of 0.76, positive predictive value of 0.91 and negative predictive value of 1 (with 95% confidence intervals). Of the 96 dermatoscopy-positive samples, 36 were negative with PCR (p < 0.001), 42 were negative with culture (p < 0.001) and nine were negative when both tests were combined (p < 0.001). Clinical signs that were significantly associated with the presence of onychomycosis were subungual hyperkeratosis (dermatoscopy: p = 0.004, odds ratio (OR) = 2.438; PCR + microbiological culture: p = 0.004, OR = 3.221), subungual detritus (p = 0.033, OR = 3.01, only with dermatoscopy) and dermatophytoma (dermatoscopy: p = 0.049, OR = 3.02; PCR + microbiological culture: p = 0.022, OR = 2.40). CONCLUSIONS: The results suggest that dermatoscopy is a good tool for the diagnosis of onychomycosis but should be used as a complementary test or for screening patients to be sampled for laboratory testing. The combination of the three tests can lead to a reduction of false-positive and false-negative clinical and laboratory results. This allows for early diagnosis and specific treatment based on test results.

Comparison of CellRox green fluorescence upon thawing on in vitro Bos taurus and Bos indicus embryos cryopreserved by slow freezing or vitrification.

The aim of this study was to compare the levels of reactive oxygen species (ROS) in Bos taurus and Bos indicus in vitro embryos cryopreserved using either slow freezing or vitrification. Embryos were divided into four groups based on subspecies and freezing method: Bos indicus slow freezing (BiSF; n = 8), Bos indicus vitrification (BiVT; n = 10), Bos taurus slow freezing (BtSF; n = 9), and Bos taurus vitrification (BtVT; n = 6). After thawing, the embryos were incubated with CellRox Green and images were obtained using a confocal microscope. The fluorescence intensity of each cell was measured and expressed as arbitrary units of fluorescence (auf) and compared using a multiple regression and unpaired t-test with α = 0.05. Results showed that subspecies and the freezing method significantly affected auf (P < 0.001; R2 = 0.1213). Bos indicus embryos had higher auf than Bos taurus embryos, whether frozen by slow freezing (67.05 ± 23.18 vs 51.30 ± 16.84, P < 0.001) or vitrification (64.44 ± 23.32 vs 47.86 ± 17.53, P < 0.001). Slow freezing induced higher auf than vitrification in both Bos taurus (51.30 ± 16.84 vs 47.86 ± 17.53, P < 0.001) and Bos indicus (67.05 ± 23.18 vs 64.44 ± 23.32, P < 0.014). In conclusion, Bos taurus embryos had lower ROS levels when frozen using vitrification, while Bos indicus embryos had consistent ROS patterns regardless of the freezing method. However, Bos indicus embryos frozen by slow freezing tended to have a higher number of cells with elevated ROS levels.

Combined Treatment of Face-to-Face Physical Therapy and Telerehabilitation in Workers with Whiplash Syndrome.

Objective: Interventions through telerehabilitation have shown positive effects in various clinical conditions, facilitating the return to work of the working population. This study aimed to compare conventional, center-based physiotherapy versus an intervention combining home- and center-based treatment for whiplash syndrome in workers enrolled in a mutual insurance company, evaluating differences in the number of face-to-face sessions and the duration of sickness absence. The secondary aim was to assess the acceptability and usability of the telerehabilitation intervention. Methods: The study population (n = 387) comprised workers aged 16 to 65 years who required physiotherapy due to whiplash (ICD-9 847.0). The main outcome variable was the number of face-to-face sessions. The duration of sickness absence was also calculated. A survey was also conducted to determine patient acceptance and usability of the platform. The analyses were adjusted for sex, age, occupation, and the center where the physiotherapy treatment was administered. Results: The number of face-to-face physiotherapy sessions dropped significantly, from 9 to 7, due to the implementation of telerehabilitation. This decrease was not associated with a longer duration of sickness absence. The difference in the median duration of sickness absence between patients who had not undergone telerehabilitation and those who had undergone telerehabilitation was -1 [95% CI= (-6 to 2)]. Conclusion: Telerehabilitation reduces the number of face-to-face physiotherapy sessions needed, which can reduce the care burden in physiotherapy centers and avoid the need for patients to travel (with a corresponding reduction in transportation costs), without increasing the duration of sickness absence.

Regulation of synapse density by Pumilio RNA-binding proteins.

The formation, stabilization, and elimination of synapses are tightly regulated during neural development and into adulthood. Pumilio RNA-binding proteins regulate the translation and localization of many synaptic mRNAs and are developmentally downregulated in the brain. We found that simultaneous downregulation of Pumilio 1 and 2 increases both excitatory and inhibitory synapse density in primary hippocampal neurons and promotes synapse maturation. Loss of Pum1 and Pum2 in the mouse brain was associated with an increase in mRNAs involved in mitochondrial function and synaptic translation. These findings reveal a role for developmental Pumilio downregulation as a permissive step in the maturation of synapses and suggest that modulation of Pumilio levels is a cell-intrinsic mechanism by which neurons tune their capacity for synapse stabilization.

Atomoxetine on neurogenic orthostatic hypotension: a randomized, double-blind, placebo-controlled crossover trial.

PURPOSE: We previously reported that single doses of the norepinephrine transporter inhibitor, atomoxetine, increased standing blood pressure (BP) and ameliorated symptoms in patients with neurogenic orthostatic hypotension (nOH). We aimed to evaluate the effect of atomoxetine over four weeks in patients with nOH. METHODS: A randomized, double-blind, placebo-controlled crossover clinical trial between July 2016 and May 2021 was carried out with an initial open-label, single-dose phase (10 or 18 mg atomoxetine), followed by a 1-week wash-out, and a subsequent double-blind 4-week treatment sequence (period 1: atomoxetine followed by placebo) or vice versa (period 2). The trial included a 2-week wash-out period. The primary endpoint was symptoms of nOH as measured by the orthostatic hypotension questionnaire (OHQ) assessed at 2 weeks. RESULTS: A total of 68 patients were screened, 40 were randomized, and 37 completed the study. We found no differences in the OHQ composite score between atomoxetine and placebo at 2 weeks (-0.3 ± 1.7 versus -0.4 ± 1.5; P = 0.806) and 4 weeks (-0.6 ± 2.4 versus -0.5 ± 1.6; P = 0.251). There were no differences either in the OHSA scores at 2 weeks (3 ± 1.9 versus 4 ± 2.1; P = 0.062) and at 4 weeks (3 ± 2.2 versus 3 ± 2.0; P = 1.000) or in the OH daily activity scores (OHDAS) at 2 weeks (4 ± 3.0 versus 5 ± 3.1, P = 0.102) and 4 weeks (4 ± 3.0 versus 4 ± 2.7, P = 0.095). Atomoxetine was well-tolerated. CONCLUSIONS: While previous evidence suggested that acute doses of atomoxetine might be efficacious in treating nOH; results of this clinical trial indicated that it was not superior to placebo to ameliorate symptoms of nOH. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02316821.

Cantharidin (1%), podophyllin (5%), and salicylic acid (30%) formulation in recalcitrant plantar warts: Analysis of 48 patients.

A plantar wart is a benign hyperplasia that appears on the feet due to the human papillomavirus (HPV). One method used for the treatment of recalcitrant plantar warts, those lasting over 2 years or persisting after at least two treatment attempts, is the cantharidin (1%), podophyllin (5%), and salicylic acid (30%) formulation, also known as the CPS formulation. Although this method is in use, there are few studies on it. This study's objective was to ascertain its cure rate. For this retrospective observational study, we reviewed the medical records of patients treated with the CPS formulation at a podiatric clinic specializing in plantar wart treatment. Our sample size was 48 subjects. The CPS formulation had a cure rate of 62.5%. Out of the cured patients, 86.67% (26/30) required one or two applications. There was no observable correlation (p > 0.05) between wart resolution and virus biotype, evolution time, patient's morphological and clinical attributes, location, number of warts, or preceding treatments. The CPS formulation presents a relatively high efficacy rate for treating recalcitrant HPV plantar warts. Still, additional studies are necessary to evaluate its safety and efficiency.

New insights into the magnetism and magnetic structure of LuCrO3 perovskite.

A polycrystalline sample LuCrO3 has been characterized by neutron powder diffraction (NPD) and magnetization measurements. Its crystal structure has been Rietveld refined from NPD data in space group Pnma; this perovskite contains strongly tilted CrO6 octahedra with extremely bent Cr-O-Cr superexchange angles of ∼142°. The NPD data show that below Néel temperature (TN ≃ 131 K), the magnetic structure can be defined as an A-type antiferromagnetic arrangement of Cr3+ magnetic moments, aligned along the b axis, with a canting along the c axis. A noticeable magnetostrictive effect is observed in the unit-cell parameters and volume upon cooling down across TN. The AC magnetic susceptibility indicates the onset of magnetic ordering below 112.6 K; the magnetization isotherms below TN show a nonlinear behaviour that is associated with the described canting of the Cr3+ magnetic moments. From the Curie-Weiss law, the effective moment of the Cr3+ sublattice is found to be µeff = 3.55 µB (calculated 3.7 µB) while the ΘCW parameter yields a value of -155 K, indicating antiferromagnetic interactions. There is a conspicuous increase of TN upon the application of external pressure, which must be due to shortening of the Cr-O bond length under compression that increases the orbital overlap integral.

Luminescent Ln(III)-Metallopeptide Sensors for Monitoring Pseudomonas aeruginosa Elastase B Activity in Complex Biological Media.

The detection and monitoring of Pseudomonas aeruginosa and its virulence factors, such as the LasB protease, are crucial for managing bacterial infections. Traditional fluorescent sensors for this protease face limitations in bacterial cultures due to interference from pigments like pyoverdine secreted by this opportunistic pathogen. We report here a Ln(III)-metallopeptide that combines a DO3A-Ln(III) complex and a sensitizing unit via a short peptide sequence as a simple, tunable, and selective probe for detecting P. aeruginosa's LasB. The probe's luminescence switches off in the presence of P. aeruginosa's secretome due to LasB cleavage but remains stable in other bacterial environments, such as non-LasB-secreting P. aeruginosa strains or E. coli cultures. It also resists degradation by other proteases, like human leukocyte elastase and trypsin, and remains stable in the presence of bioanalytes related to P. aeruginosa infections, such as glutathione, H2O2, and pyocyanin, and in complex media like FBS. Importantly, time-gated experiments completely remove the background fluorescence of P. aeruginosa pigments, thus demonstrating the potential of the developed Ln(III)-metallopeptide for real-time monitoring of LasB activity in bacterial cultures.

Performance of an Autonomous Sanitary Sterilisation Ultraviolet Machine (ASSUM) on terminal disinfection of surgical theaters and rooms of an intensive-intermediate care unit.

Background: Ultraviolet- C (UV-C) light is effective for reducing environmental bioburden in hospitals, and the use of robots to deliver it may be advantageous. Aim: To evaluate the feasibility and clinical efficacy of an autonomous programmable UV-C robot in surgical and intensive care unit (ICU) rooms of a tertiary hospital. Method: During ten consecutive months, the device was used in six theatres where cardiac, colorectal and orthopaedic surgeries were performed, and in the rooms previously occupied by patients subjected to contact precautions of a 14-bed ICU. Surgical site infection (SSI) rates of procedures performed in the UV-cleaned theatres were compared with those of the previous year. Incidence in clinical samples of ICU-acquired multiple-drug resistant (MDR) microorganisms was compared with that of the same period of the previous year. An UV-C exposure study done by semi-quantitative dosimeters and a survey of the bioburden on surfaces were carried out. Findings: SSI rates in the pre- and post-intervention periods were 8.67% (80/922) and 7.5% (61/813), respectively (p=0.37). Incidence of target microorganisms in clinical samples remained unchanged (38.4 vs. 39.4 per 10,000 patient-days, p=0.94). All the dosimeters exposed to ≤1 meter received ≥500 mJ/cm2. The bacterial load on surfaces decreased after the intervention, particularly in ICU rooms (from 4.57±7.4 CFU to 0.27±0.8 CFU, p<0.0001). Conclusion: Deployment of an UV-C robot in surgical and ICU rooms is feasible, ensures adequate delivery of germicidal UV-C light and reduces the environmental bacterial burden. Rates of surgical site infections or acquisition of MDR in clinical samples of critically-ill patients remained unchanged.

Magnetism of metastable γ-Fe85Pd15 nanowire arrays across an unusually broad temperature range (5 K to 800 K).

Arrays of 50 nm diameter Fe85Pd15 cylindrical nanowires were electrochemically grown, crystallizing in a metastable γ-Fe(Pd) fcc A1 disordered solid solution. After performing a heating-cooling thermal cycle between 300 K and 1000 K, the γ-Fe(Pd) fcc metastable phase still predominates (97%), coexisting with a not-fully-identified minority phase. The thermal cycling induces a moderate increase in the crystallite size and a reduction of the lattice parameter although leading to a significant heating-cooling magnetic hysteresis. No further changes in temperature-dependent magnetization, M(T), are observed during subsequent cycling. The full-range (5 K to 800 K) saturation magnetization Ms(T) curve is quite accurately described by a phenomenological expression, which provides a Bloch-type contribution as T → 0 and undergoes the critical behavior near the Curie temperature TC. An upturn in Ms(T) is observed below 100 K which is described by a spin-glass-like second contribution, with freezing temperature Tf = (80 ± 2) K, and kBTf comparable to the exchange interactions in Fe-Pd systems. A Curie temperature of TC = 830 K, and a critical exponent value ß = 0.42 ± 0.05 are estimated. These regimes (below and above 100 K) are also observed in the magnetization process. The temperature dependence of coercivity between 100 K and 800 K is consistent with a nucleation/propagation remagnetization mechanism, with activation energy of (320 ± 20) kJ mol-1 and critical field for magnetization reversal of (65 ± 1) mT, at 0 K. The analysis of the effective magnetic anisotropy as a function of temperature allows us to conclude that it essentially arises from the balance between different magnetostatic contributions.

Climate change and antibiotic resistance: A scoping review.

This scoping review aimed to investigate the potential association between climate change and the rise of antibiotic resistance while also exploring the elements of climate change that may be involved. A scoping review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews, comprehensively searching scientific literature up to 31 January 2024. Multiple databases were utilized, including MEDLINE, Web of Science and SCOPUS. Various search strategies were employed, and selection criteria were established to include articles relevant to antibiotic resistance and climate change. The review included 30 selected articles published predominantly after 2019. Findings from these studies collectively suggest that rising temperatures associated with climate change can contribute to the proliferation of antibiotic resistance, affecting diverse ecosystems. This phenomenon is observed in soil, glaciers, rivers and clinical settings. Rising temperatures are associated with a rise in the prevalence of antibiotic resistance across various environments, raising concerns for global health. However, these studies provide valuable insights but do not establish a definitive causal link between environmental temperature and antibiotic resistance. The selective pressure exerted by antibiotics and their residues in ecosystems further complicates the issue.

Prevalence and impact of multidrug-resistant bacteria in solid cancer patients with bloodstream infection: a 25-year trend analysis.

The study aimed to describe the epidemiology of multidrug-resistant (MDR) bacteria among solid cancer (SC) patients with bloodstream infections (BSIs), evaluating inappropriate empiric antibiotic treatment (IEAT) use and mortality trends over a 25-year period. All BSI occurrences in adult SC patients at a university hospital were analyzed across five distinct five-year intervals. MDR bacteria were classified as extended-spectrum beta-lactamases (ESBL)-producing and/or Carbapenem-resistant Enterobacterales, non-fermenting Gram-negative bacilli (GNB) resistant to at least three antibiotic classes, methicillin-resistant Staphylococcus aureus (MRSA), and Vancomycin-resistant Enterococci. A multivariate regression model identified the risk factors for MDR BSI. Of 6,117 BSI episodes, Gram-negative bacilli (GNB) constituted 60.4% (3,695/6,117), being the most common are Escherichia coli with 26.8% (1,637/6,117), Klebsiella spp. with 12.4% (760/6,117), and Pseudomonas aeruginosa with 8.6% (525/6,117). MDR-GNB accounted for 644 episodes (84.8% of MDR or 644/759), predominantly ESBL-producing strains (71.1% or 540/759), which escalated significantly over time. IEAT was administered in 24.8% of episodes, mainly in MDR BSI, and was associated with higher mortality (22.9% vs. 14%, P < 0.001). Independent factors for MDR BSI were prior antibiotic use [odds ratio (OR) 2.93, confidence interval (CI) 2.34-3.67], BSI during antibiotic treatment (OR 1.46, CI 1.18-1.81), biliary (OR 1.84, CI 1.34-2.52) or urinary source (OR 1.86, CI 1.43-2.43), admission period (OR) 1.28, CI 1.18-1.38, and community-acquired infection (OR 0.57, CI 0.39-0.82). The study showed an increase in MDR-GNB among SC patients with BSI. A quarter received IEAT, which was linked to increased mortality. Improving risk assessment for MDR infections and the judicious prescription of empiric antibiotics are crucial for better outcomes. IMPORTANCE: Multidrug-resistant (MDR) bacteria pose a global public health threat as they are more challenging to treat, and they are on the rise. Solid cancer patients are often immunocompromised due to their disease and cancer treatments, making them more susceptible to infections. Understanding the changes and trends in bloodstream infections in solid cancer patients is crucial, to help physicians make informed decisions about appropriate antibiotic therapies, manage infections in this vulnerable population, and prevent infection. Solid cancer patients often require intensive and prolonged treatments, including surgery, chemotherapy, and radiation therapy. Infections can complicate these treatments, leading to treatment delays, increased healthcare costs, and poorer patient outcomes. Investigating new strategies to combat MDR infections and researching novel antibiotics in these patients is of paramount importance to avoid these negative impacts.

Early identification of the nosocomial spread of vancomycin-resistant Enterococcus faecium by Fourier-transform infrared spectroscopy and performance comparison with PFGE and WGS.

Early detection of disseminating vancomycin-resistant Enterococcus faecium (VREfm) in ICU wards is crucial for outbreak identification and the implementation of prompt infection control measures. Genotypic methods like pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) are costly and time-consuming, hindering rapid response due to batch dependency. Fourier-transform infrared spectroscopy (FT-IR) offers the potential for real-time outbreak detection and reliable strain typing. We utilized FT-IR to identify clonal VREfm dissemination and compared its performance to PFGE and WGS. Between February through October 2023, an unusually high number of VREfm were recovered at a tertiary hospital in Barcelona. Isolates were examined for antimicrobial susceptibility, carriage of vanA/vanB genes and clonality was also studied using FT-IR, PFGE, and WGS. Routine FT-IR inspections revealed recurring VREfm clustering during the outbreak's initial weeks. In total, 104 isolates were recovered from 75 patients and from multiple wards. However, only one isolate was recovered from an environmental sample, suggesting the absence of environmental reservoirs. An ST80 vancomycin-resistant (vanA) E. faecium strain was the main strain responsible for the outbreak, although a few additional VREfm strains were also identified, all belonging to CC17. PFGE and cgMLST (WGS) yielded identical clustering results to FT-IR, and WGS confirmed vanA/vanB gene carriage in all VREfm isolates. Infection control measures led to a rapid decline in VREfm isolates, with no isolates detected in November. FT-IR spectroscopy offers rapid turnaround times, sensitivity, and reproducibility, comparable to standard typing methods. It proved as an effective tool for monitoring VREfm dissemination and early outbreak detection.

Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study.

PURPOSE: To evaluate the efficacy and safety of the combination of olaparib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC) and germinal BRCA mutations (gBRCAm). METHODS: OPHELIA (NCT03931551) was a single-arm, open-label, phase 2 clinical trial. Patients aged ≥18 years diagnosed with HER2-positive ABC with germinal deleterious mutations in BRCA1 or BRCA2 who had received at least one prior systemic regimen for advanced disease were enrolled. Patients received olaparib plus trastuzumab until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was investigator-assessed clinical benefit rate for at least 24 weeks as per RECIST v.1.1. Key secondary endpoints included overall response rate (ORR) and safety profile. RESULTS: A total of 68 pre-treated HER2-positive ABC patients were screened. Due to slow accrual the trial was stopped after enrolling 5 patients instead of the planned sample size of 20. Four patients achieved clinical benefit (80.0 %, 95 % CI; 28.4-99.5, p < 0.001) and the primary endpoint was met. The ORR was 60.0 % (95 % CI; 14.7-94.7), including one complete response. Four (80.0 %) patients experienced at least one treatment-related treatment-emergent adverse event (TEAE). Most TEAEs were grade 1 or 2. There were no treatment-related deaths and no new safety signals were identified. CONCLUSIONS: This study suggests that the combination of olaparib plus trastuzumab may be effective and safe in pre-treated patients with HER2-positive gBRCAm ABC. This ABC patient population should be further studied and not be pre-emptively excluded from clinical trials of targeted therapy for BRCA1/2-driven cancers.

A new type of Class C ß-lactamases defined by PIB-1. A metal-dependent carbapenem-hydrolyzing ß-lactamase, from Pseudomonas aeruginosa: Structural and functional analysis.

Antibiotic resistance is one of most important health concerns nowadays, and ß-lactamases are the most important resistance determinants. These enzymes, based on their structural and functional characteristics, are grouped in four categories (A, B, C and D). We have solved the structure of PIB-1, a Pseudomonas aeruginosa chromosomally-encoded ß-lactamase, in its apo form and in complex with meropenem and zinc. These crystal structures show that it belongs to the Class C ß-lactamase group, although it shows notable differences, especially in the Ω- and P2-loops, which are important for the enzymatic activity. Functional analysis showed that PIB-1 is able to degrade carbapenems but not cephalosporins, the typical substrate of Class C ß-lactamases, and that its catalytic activity increases in the presence of metal ions, especially zinc. They do not bind to the active-site but they induce the formation of trimers that show an increased capacity for the degradation of the antibiotics, suggesting that this oligomer is more active than the other oligomeric species. While PIB-1 is structurally a Class C ß-lactamase, the low sequence conservation, substrate profile and its metal-dependence, prompts us to position this enzyme as the founder of a new group inside the Class C ß-lactamases. Consequently, its diversity might be wider than expected.

HBeeID: a molecular tool that identifies honey bee subspecies from different geographic populations.

BACKGROUND: Honey bees are the principal commercial pollinators. Along with other arthropods, they are increasingly under threat from anthropogenic factors such as the incursion of invasive honey bee subspecies, pathogens and parasites. Better tools are needed to identify bee subspecies. Genomic data for economic and ecologically important organisms is increasing, but in its basic form its practical application to address ecological problems is limited. RESULTS: We introduce HBeeID a means to identify honey bees. The tool utilizes a knowledge-based network and diagnostic SNPs identified by discriminant analysis of principle components and hierarchical agglomerative clustering. Tests of HBeeID showed that it identifies African, Americas-Africanized, Asian, and European honey bees with a high degree of certainty even when samples lack the full 272 SNPs of HBeeID. Its prediction capacity decreases with highly admixed samples. CONCLUSION: HBeeID is a high-resolution genomic, SNP based tool, that can be used to identify honey bees and screen species that are invasive. Its flexible design allows for future improvements via sample data additions from other localities.

Influence of Fractures and Dislocations in Severity of Rocker-Bottom Deformity in Patients with Charcot Foot.

The objective of this study was to identify bone fractures and joint dislocations that have greater association with the severity of arch collapse in patients with Charcot foot involving the midfoot.A retrospective study in 28 (N = 29 feet) patients who had Charcot foot deformity of the midfoot. The study included stage III of Eichenholtz classification, and Schon classification types I to III. Talar-first metatarsal and calcaneal pitch angles and cuboid height were used to evaluate the severity of the midfoot deformity in a weightbearing lateral radiograph. Two investigators evaluated the bone fracture and joint dislocation involved in weightbearing antero-posterior and lateral radiographs.There were 13 (46%) feet that showed pattern 1, 9 (31%) feet with pattern 2, and 7 (25%) feet with pattern 3 according to the Schon classification. One foot had a combination of patterns 1 and 2. Midfoot ulceration occurred in 64% (n = 19) of feet. In the multivariate analysis, plantarflexion of talar-first metatarsal angle was predicted by navicular-medial cuneiform dislocation (p = .007 [-20.620-3.683]), an increase of the negative calcaneal pitch angle by fragmentation of the cuboid (p = .003 [-15.568-3.626]), and increment of the negative cuboid height by navicular-medial cuneiform and medial cuneiform-first metatarsal dislocations (p = .040 [-12.779-0.317], p = .002 [-13.437-3.267], respectively).Bone fractures and dislocations in the sagittal plane seem to contribute to midfoot collapse, but navicular-medial cuneiform dislocation/non-union and cuboid fragmentation predict severe rocker-bottom deformity in cases of Charcot foot.