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1.
Resusc Plus ; 19: 100678, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38912530

RESUMO

Background: Helicopter emergency medical services (HEMS) play a fundamental role in prehospital care. However, the impact of HEMS on survival of patients with out-of-hospital cardiac arrest (OHCA) is widely unknown. Therefore, the purpose of this study was to assess demographics, treatment, and outcome of patients with OHCA attended by physician-staffed helicopters. Methods: Retrospective cohort study enrolling OHCA patients treated by HEMS during a ten-year period (2010-2019) in Austria. Patients were identified using electronic mission records of 13 HEMS bases run by the Austrian Automobile, Motorcycle and Touring Club (OEAMTC), and subsequently matched with the national register of deaths to determine 30-day and one-year survival rates. Results are reported according to the 2015 Utstein Style. Multivariable logistic regression analysis was used to identify factors associated with patient outcome. Results: In total, 9344 presumed OHCA missions were identified. Cardiopulmonary resuscitation was attempted or continued by HEMS in 3889 cases. Approximately 32.2% of patients achieved return of spontaneous circulation (ROSC) and 22.5% sustained ROSC until arrival at the emergency department. Thirty-day and one-year survival rates were 14.0% and 12.4% respectively. HEMS response time, on-scene time, age, pathogenesis, arrest location, witness-status, first monitored rhythm, bystander automated external defibrillator (AED) use, airway type and administration of adrenaline were independent predictors of 30-day survival. Conclusions: This study provides an extensive insight into the management of OHCA in an almost nationwide HEMS sample. Thirty-day and one-year survival rates are high, indicating high-quality care and systematic selection of patients with favorable prognosis.

2.
Cell ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38889727

RESUMO

How evolution at the cellular level potentiates macroevolutionary change is central to understanding biological diversification. The >66,000 rove beetle species (Staphylinidae) form the largest metazoan family. Combining genomic and cell type transcriptomic insights spanning the largest clade, Aleocharinae, we retrace evolution of two cell types comprising a defensive gland-a putative catalyst behind staphylinid megadiversity. We identify molecular evolutionary steps leading to benzoquinone production by one cell type via a mechanism convergent with plant toxin release systems, and synthesis by the second cell type of a solvent that weaponizes the total secretion. This cooperative system has been conserved since the Early Cretaceous as Aleocharinae radiated into tens of thousands of lineages. Reprogramming each cell type yielded biochemical novelties enabling ecological specialization-most dramatically in symbionts that infiltrate social insect colonies via host-manipulating secretions. Our findings uncover cell type evolutionary processes underlying the origin and evolvability of a beetle chemical innovation.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38842969

RESUMO

BACKGROUND: Women respond more favorably to biventricular pacing (BIVP) than men. Sex differences in atrioventricular and interventricular conduction have been described in BIVP studies. Left bundle branch area pacing (LBBAP) offers advantages due to direct capture of the conduction system. We hypothesized that men could respond better to LBBAP than BIVP. OBJECTIVES: This study aims to describe the sex differences in response to LBBAP vs BIVP as the initial cardiac resynchronization therapy (CRT). METHODS: In this multicenter prospective registry, we included patients with left ventricular ejection fraction ≤35% and left bundle branch block or a left ventricular ejection fraction ≤40% with an expected right ventricular pacing exceeding 40% undergoing initial CRT with LBBAP or BIVP. The composite primary outcome was heart failure-related hospitalization and all-cause mortality. The primary safety outcome included all procedure-related complications. RESULTS: There was no significant difference in the primary outcome when comparing men and women receiving LBBAP (P = 0.46), whereas the primary outcome was less frequent in women in the BIVP group than men treated with BIVP (P = 0.03). The primary outcome occurred less frequently in men undergoing LBBAP (29.9%) compared to those treated with BIVP (46.5%) (P = 0.004). In women, the incidence of the primary endpoint was 24.14% in the LBBAP group and 36.2% in the BIVP group; however, this difference was not statistically significant (P = 0.23). Complication rates remained consistent across all groups. CONCLUSIONS: Men and women undergoing LBBAP for CRT had similar clinical outcomes. Men undergoing LBBAP showed a lower risk of heart failure-related hospitalizations and all-cause mortality compared to men undergoing BIVP, whereas there was no difference between LBBAP and BIVP in women.

4.
Cureus ; 16(5): e59943, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38854230

RESUMO

Hibernomas, rare benign tumors originating from brown adipose tissue, pose diagnostic challenges due to their infrequent occurrence and slow growth. We present a case of a 38-year-old woman with a progressively enlarging mass in her right lateral chest wall, initially stable in size but growing during pregnancy and causing pain and functional impairment. Radiological evaluation, including x-ray and MRI, provided inconclusive results, necessitating a biopsy for a definitive diagnosis. Ultrasound-guided needle aspiration biopsy revealed typical histopathological features consistent with hibernoma. A subsequent total surgical excision with negative margins was performed. The patient achieved complete recovery without recurrence during two years of follow-up. This case underscores the importance of considering hibernoma in the differential diagnosis of adipose tissue tumors, particularly in atypical clinical presentations. Moreover, it highlights the challenges in diagnosing and managing hibernomas and emphasizes the role of MRI and biopsy in achieving accurate diagnosis and optimal treatment outcomes. Continued reporting of such cases is crucial for increasing awareness and improving the management of this rare tumor.

5.
PLoS One ; 19(6): e0305106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38848391

RESUMO

Extreme weather events across coastal environments are expected to increase in frequency under predicted climate change scenarios. These events can impact coastal recreational fisheries and their supporting ecosystems by influencing the productivity of fish stocks or altering behaviours and decision-making among fishers. Using off-site telephone/diary survey data on estuarine and oceanic recreational fishing activity in eastern Australia, we analyse interannual and geographic variability in bream (Acanthopagrus spp) and snapper (Chrysophrys auratus) catch, total effort and total catch per unit effort (CPUE) through a period (2013/2014, 2017/2018 and 2019/2020) that encompassed severe drought, bushfires and flooding. Interacting spatial and temporal differences were detected for bream and may reflect spatial variation in the intensity and extent of some of the extreme weather events. The catch of snapper did not change temporally, providing little evidence that this species' catch may be influenced by the extreme weather events. Independent bioregional and temporal effects on effort were detected, while CPUE only showed significant bioregional differences. Although adverse conditions created by the extreme weather events may have dissuaded fisher participation and impacted effort, we propose that the observed temporal patterns in effort reflect the early influence of socio-economic changes brought on by the COVID-19 pandemic on coastal recreational fishing, over and above the impacts of extreme weather events. This study demonstrates how interrelated ecological, social and economic factors can shape coastal recreational fisheries and facilitates development of management strategies to address future threats to the sector.


Assuntos
COVID-19 , Clima Extremo , Pesqueiros , Animais , COVID-19/epidemiologia , Austrália , Recreação , Ecossistema , Análise Espaço-Temporal , Mudança Climática , Peixes/fisiologia , Humanos , SARS-CoV-2/isolamento & purificação
6.
Evolution ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753474

RESUMO

Hybrid zones are dynamic systems where natural selection, sexual selection, and other evolutionary forces can act on reshuffled combinations of distinct genomes. The movement of hybrid zones, individual traits, or both are of particular interest for understanding the interplay between selective processes. In a hybrid zone involving two lek-breeding birds, secondary sexual plumage traits of Manacus vitellinus, including bright yellow collar and olive belly color, have introgressed asymmetrically ~50 km across the genomic center of the zone into populations more genetically similar to Manacus candei. Males with yellow collars are preferred by females and are more aggressive than parental M. candei, suggesting that sexual selection was responsible for the introgression of male traits. We assessed the spatial and temporal dynamics of this hybrid zone using historical (1989 - 1994) and contemporary (2017 - 2020) transect samples to survey both morphological and genetic variation. Genome-wide SNP data and several male phenotypic traits show that the genomic center of the zone has remained spatially stable, whereas the olive belly color of male M. vitellinus has continued to introgress over this time period. Our data suggest that sexual selection can continue to shape phenotypes dynamically, independent of a stable genomic transition between species.

7.
Small ; : e2308072, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698574

RESUMO

Tunnel junctions comprising self-assembled monolayers (SAMs) from liquid crystal-inspired molecules show a pronounced hysteretic current-voltage response, due to electric field-driven dipole reorientation in the SAM. This renders these junctions attractive device candidates for emerging technologies such as in-memory and neuromorphic computing. Here, the novel molecular design, device fabrication, and characterization of such resistive switching devices with a largely improved performance, compared to the previously published work are reported. Those former devices suffer from a stochastic switching behavior limiting reliability, as well as from critically small read-out currents. The present progress is based on replacing Al/AlOx with TiN as a new electrode material and as a key point, on redesigning the active molecular material making up the SAM: a previously present, flexible aliphatic moiety has been replaced by a rigid aromatic linker, thereby introducing a molecular "ratchet". This restricts the possible molecular conformations to only two major states of opposite polarity. The above measures have resulted in an increase of the current density by five orders of magnitude as well as in an ON/OFF conductance ratio which is more than ten times higher than the individual scattering ranges of the high and low resistance states.

8.
ACS Cent Sci ; 10(5): 1094-1104, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38799669

RESUMO

In this study, an innovative approach is presented in the field of engineered plant living materials (EPLMs), leveraging a sophisticated interplay between synthetic biology and engineering. We detail a 3D bioprinting technique for the precise spatial patterning and genetic transformation of the tobacco BY-2 cell line within custom-engineered granular hydrogel scaffolds. Our methodology involves the integration of biocompatible hydrogel microparticles (HMPs) primed for 3D bioprinting with Agrobacterium tumefaciens capable of plant cell transfection, serving as the backbone for the simultaneous growth and transformation of tobacco BY-2 cells. This system facilitates the concurrent growth and genetic modification of tobacco BY-2 cells within our specially designed scaffolds. These scaffolds enable the cells to develop into predefined patterns while remaining conducive to the uptake of exogenous DNA. We showcase the versatility of this technology by fabricating EPLMs with unique structural and functional properties, exemplified by EPLMs exhibiting distinct pigmentation patterns. These patterns are achieved through the integration of the betalain biosynthetic pathway into tobacco BY-2 cells. Overall, our study represents a groundbreaking shift in the convergence of materials science and plant synthetic biology, offering promising avenues for the evolution of sustainable, adaptive, and responsive living material systems.

9.
Nature ; 629(8014): 1055-1061, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38778099

RESUMO

Cement production causes 7.5% of global anthropogenic CO2 emissions, arising from limestone decarbonation and fossil-fuel combustion1-3. Current decarbonation strategies include substituting Portland clinker with supplementary materials, but these mainly arise in emitting processes, developing alternative binders but none yet promises scale, or adopting carbon capture and storage that still releases some emissions4-8. However, used cement is potentially an abundant, decarbonated feedstock. Here we show that recovered cement paste can be reclinkered if used as a partial substitute for the lime-dolomite flux used in steel recycling nowadays. The resulting slag can meet existing specifications for Portland clinker and can be blended effectively with calcined clay and limestone. The process is sensitive to the silica content of the recovered cement paste, and silica and alumina that may come from the scrap, but this can be adjusted easily. We show that the proposed process may be economically competitive, and if powered by emissions-free electricity, can lead to zero emissions cement while also reducing the emissions of steel recycling by reducing lime flux requirements. The global supply of scrap steel for recycling may treble by 2050, and it is likely that more slag can be made per unit of steel recycled. With material efficiency in construction9,10, future global cement requirements could be met by this route.

10.
Nucleic Acids Res ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783119

RESUMO

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research.

11.
Am J Physiol Regul Integr Comp Physiol ; 326(6): R599-R608, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38682242

RESUMO

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with orthostatic intolerance (OI) is characterized by neurocognitive deficits perhaps related to upright hypocapnia and loss of cerebral autoregulation (CA). We performed N-back neurocognition testing and calculated the phase synchronization index (PhSI) between arterial pressure (AP) and cerebral blood velocity (CBV) as a time-dependent measurement of cerebral autoregulation in 11 control (mean age = 24.1 yr) and 15 patients with ME/CFS (mean age = 21.8 yr). All patients with ME/CFS had postural tachycardia syndrome (POTS). A 10-min 60° head-up tilt (HUT) significantly increased heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, P < 0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, P < 0.05) and decreased end-tidal CO2 (ETCO2; 33.9 ± 1.1 vs. 42.8 ± 1.2 Torr, P < 0.05) in ME/CFS versus control. In ME/CFS, HUT significantly decreased CBV compared with control (-22.5% vs. -8.7%, P < 0.005). To mitigate the orthostatic CBV reduction, we administered supplemental CO2, phenylephrine, and acetazolamide and performed N-back testing supine and during HUT. Only phenylephrine corrected the orthostatic decrease in neurocognition by reverting % correct n = 4 N-back during HUT in ME/CFS similar to control (ME/CFS = 38.5 ± 5.5 vs. ME/CFS + PE= 65.6 ± 5.7 vs. Control 56.9 ± 7.5). HUT in ME/CFS resulted in increased PhSI values indicating decreased CA. Although CO2 and acetazolamide had no effect on PhSI in ME/CFS, phenylephrine caused a significant reduction in PhSI (ME/CFS = 0.80 ± 0.03 vs. ME/CFS + PE= 0.69 ± 0.04, P < 0.05) and improved cerebral autoregulation. Thus, PE improved neurocognitive function in patients with ME/CFS, perhaps related to improved neurovascular coupling, cerebral autoregulation, and maintenance of CBV.NEW & NOTEWORTHY We evaluated cognitive function before and after CO2, acetazolamide, and phenylephrine, which mitigate orthostatic reductions in cerebral blood velocity. Neither CO2 nor acetazolamide affected N-back testing (% correct answers) during an orthostatic challenge. Only phenylephrine improved upright N-back performance in ME/CFS, as it both blocked hyperventilation and increased CO2 significantly compared with those untreated. And only phenylephrine resulted in improved PSI values in both ME/CFS and control while upright, suggesting improved cerebral autoregulation.


Assuntos
Pressão Sanguínea , Circulação Cerebrovascular , Intolerância Ortostática , Fenilefrina , Humanos , Circulação Cerebrovascular/efeitos dos fármacos , Fenilefrina/farmacologia , Feminino , Masculino , Intolerância Ortostática/fisiopatologia , Adulto , Adulto Jovem , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Síndrome de Fadiga Crônica/fisiopatologia , Síndrome de Fadiga Crônica/tratamento farmacológico , Teste da Mesa Inclinada , Cognição/efeitos dos fármacos , Homeostase , Estudos de Casos e Controles , Frequência Cardíaca/efeitos dos fármacos , Pressão Arterial/efeitos dos fármacos , Síndrome da Taquicardia Postural Ortostática/fisiopatologia , Síndrome da Taquicardia Postural Ortostática/tratamento farmacológico
12.
Clin Nucl Med ; 49(6): 500-504, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38661379

RESUMO

PURPOSE: The latest iteration of GPT4 (generative pretrained transformer) is a large multimodal model that can integrate both text and image input, but its performance with medical images has not been systematically evaluated. We studied whether ChatGPT with GPT-4V(ision) can recognize images from common nuclear medicine examinations and interpret them. PATIENTS AND METHODS: Fifteen representative images (scintigraphy, 11; PET, 4) were submitted to ChatGPT with GPT-4V(ision), both in its Default and "Advanced Data Analysis (beta)" version. ChatGPT was asked to name the type of examination and tracer, explain the findings and whether there are abnormalities. ChatGPT should also mark anatomical structures or pathological findings. The appropriateness of the responses was rated by 3 nuclear medicine physicians. RESULTS: The Default version identified the examination and the tracer correctly in the majority of the 15 cases (60% or 53%) and gave an "appropriate" description of the findings or abnormalities in 47% or 33% of cases, respectively. The Default version cannot manipulate images. "Advanced Data Analysis (beta)" failed in all tasks in >90% of cases. A "major" or "incompatible" inconsistency between 3 trials of the same prompt was observed in 73% (Default version) or 87% of cases ("Advanced Data Analysis (beta)" version). CONCLUSIONS: Although GPT-4V(ision) demonstrates preliminary capabilities in analyzing nuclear medicine images, it exhibits significant limitations, particularly in its reliability (ie, correctness, predictability, and consistency).


Assuntos
Medicina Nuclear , Humanos , Interpretação de Imagem Assistida por Computador/métodos
13.
Artigo em Inglês | MEDLINE | ID: mdl-38596606

RESUMO

Objectives: To identify predictors of coronary artery bypass graft surgery (CABG) requirement as a revascularization method in in real-world non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients. Materials and methods: . An individual pre-specified analysis of patients with NSTE-ACS was performed from two prospective Argentine registries between 2017 and 2022. We analyzed the difference in baseline characteristics between patients who required CABG and those who did not require this intervention. Then, a logistic regression analysis was performed to determine independent predictors in patients who received CABG as a method of revascularization. Results: A total of 1848 patients with a median age of 54.8 (interquartile range [IQR]: 53.7-56) years and an ejection fraction of 42.1% (IQR: 41.2-43.1) were included. A total of 233 patients required CABG (12.6%). Baseline characteristics between the two groups were similar, except in patients requiring CABG, who were younger (51.5 vs. 55.7 years; p=0.010), more frequently diabetic (38.2% vs. 25.7%; p=0.001) and male (90.1% vs. 73.7%; p=0.001). In addition, they had, to a lesser extent, previous cardiac surgery (2.1% vs. 11.2%; p=0.011). After multivariable analysis, the following were independently associated with CABG: age (Odds Ratio [OR]: 0.99, 95% confidence interval [CI]: 0.98-0.99; p=0.008), male sex (OR: 3.08, 95% CI: 1.87-5.1; p=0.001), history of previous CABG (OR: 0.14, 95% CI: 0.05-0.30; p=0.001) and diabetes (OR: 1.84, 95% CI: 1.31- 2.57; p=0.001). Conclusions: In this analysis of two NSTEACS registries, younger age, male sex, a diagnosis of diabetes and the absence of previous surgery were independent predictors of the requirement for inpatient CABG.

14.
Vascular ; : 17085381241247881, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630458

RESUMO

OBJECTIVES: Coronary artery disease (CAD) and abdominal aortic aneurysm (AAA) are common arterial pathologies that might occur simultaneously; however, there is not enough evidence about the optimal strategy for patients with concomitant indications of coronary artery bypass grafting (CABG) and open repair of the AAA (AAOR). This study aims to present the outcomes in low and moderate cardiac surgical risk patients who underwent one-stage or two-stage elective CABG and AAOR in a middle-income country. METHODS: An observational, retrospective case series study was conducted. Patients who had low and moderate cardiac surgical risk (less than 8% mortality risk on the STS score) and had the concomitant indication for CABG and AAOR between December 2005 and August 2021 were included. Patients were assigned to one of three strategies: Group 1 underwent one-stage surgery for CABG and AAOR, Group 2 underwent two-stage surgery within the same in-patient stay, and Group 3 underwent two-stage surgery in a new in-patient stay within 6 months. RESULTS: Twenty seven, patients with simultaneous requirements of CABG and AAOR were identified, with a mean age of 69.5 ± 6.1 years and 92.6% were male. The most common comorbidities were hypertension at 77.8% and dyslipidemia at 55.6%. The average mortality risk calculated by the STS score was 2.09% ± 1.53%. In Group 1 (n = 9), 1/9 had in-hospital mortality and no reinterventions were needed. In Group 2 (n = 10), 1/10 had in-hospital mortality, and the most common postoperative complication was acute kidney injury 2/10. Furthermore, 2/10 required a reintervention. In Group 3 (n = 8), no in-hospital mortality was present, however, complications such as sepsis, atrial fibrillation, and acute kidney injury occurred in 2/8 patients each, and 2/8 required a reintervention. CONCLUSION: Patients with CAD and AAA that need a concomitant surgical correction with CABG and an AAOR are uncommon in contemporary practice, given the advances in endovascular therapy. When indicated, one-stage surgery can be performed in patients with low cardiac surgical risk, proper patient selection plays a fundamental role and might be performed in experienced centers. However, two-staged surgeries at the same or different inpatient stay may be considered for asymptomatic AAA with close monitoring during the postoperative period. These findings can hold significance for addressing sociodemographic barriers in low and middle-income countries. More robust and extensive studies are needed to make clear comparisons between the different strategies.

15.
Plant Cell Environ ; 47(7): 2597-2613, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38549236

RESUMO

Plant leaves contain multiple cell types which achieve distinct characteristics whilst still coordinating development within the leaf. The bundle sheath possesses larger individual cells and lower chloroplast content than the adjacent mesophyll, but how this morphology is achieved remains unknown. To identify regulatory mechanisms determining bundle sheath cell morphology we tested the effects of perturbing environmental (light) and endogenous signals (hormones) during leaf development of Oryza sativa (rice). Total chloroplast area in bundle sheath cells was found to increase with cell size as in the mesophyll but did not maintain a 'set-point' relationship, with the longest bundle sheath cells demonstrating the lowest chloroplast content. Application of exogenous cytokinin and gibberellin significantly altered the relationship between cell size and chloroplast biosynthesis in the bundle sheath, increasing chloroplast content of the longest cells. Delayed exposure to light reduced the mean length of bundle sheath cells but increased corresponding leaf length, whereas premature light reduced final leaf length but did not affect bundle sheath cells. This suggests that the plant hormones cytokinin and gibberellin are regulators of the bundle sheath cell-chloroplast relationship and that final bundle sheath length may potentially be affected by light-mediated control of exit from the cell cycle.


Assuntos
Cloroplastos , Citocininas , Giberelinas , Luz , Oryza , Reguladores de Crescimento de Plantas , Folhas de Planta , Oryza/crescimento & desenvolvimento , Oryza/efeitos da radiação , Oryza/citologia , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/efeitos da radiação , Citocininas/metabolismo , Citocininas/farmacologia , Giberelinas/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Cloroplastos/metabolismo , Forma Celular/efeitos da radiação , Fatores de Tempo , Tamanho Celular/efeitos da radiação
16.
Microbiol Spectr ; 12(5): e0322123, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38526142

RESUMO

The emergence of antibiotic-resistant bacteria (ARB) has necessitated the development of alternative therapies to deal with this global threat. Bacteriophages (viruses that target bacteria) that kill ARB are one such alternative. Although phages have been used clinically for decades with inconsistent results, a number of recent advances in phage selection, propagation, and purification have enabled a reevaluation of their utility in contemporary clinical medicine. In most phage therapy cases, phages are administered in combination with antibiotics to ensure that patients receive the standard-of-care treatment. Some phages may work cooperatively with antibiotics to eradicate ARB, as often determined using non-standardized broth assays. We sought to develop a solid media-based assay to assess cooperativity between antibiotics and phages to offer a standardized platform for such testing. We modeled the interactions that occur between antibiotics and phages on solid medium to measure additive, antagonistic, and synergistic interactions. We then tested the method using different bacterial isolates and identified a number of isolates where synergistic interactions were identified. These interactions were not dependent on the specific organism, phage family, or antibiotic used. A priori susceptibility to the antibiotic or the specific phage were not requirements to observe synergistic interactions. Our data also confirm the potential for the restoration of vancomycin to treat vancomycin-resistant Enterococcus (VRE) when used in combination with phages. Solid media assays for the detection of cooperative interactions between antibiotics and phages can be an accessible technique adopted by clinical laboratories to evaluate antibiotic and phage choices in phage therapy.IMPORTANCEBacteriophages have become an important alternative treatment for individuals with life-threatening antibiotic-resistant bacteria (ARB) infections. Because antibiotics represent the standard-of-care for treatment of ARB, antibiotics and phages often are delivered together without evidence that they work cooperatively. Testing for cooperativity can be difficult due to the equipment necessary and a lack of standardized means for performing the testing in liquid medium. We developed an assay using solid medium to identify interactions between antibiotics and phages for gram-positive and gram-negative bacteria. We modeled the interactions between antibiotics and phages on solid medium, and then tested multiple replicates of vancomycin-resistant Enterococcus (VRE) and Stenotrophomonas in the assay. For each organism, we identified synergy between different phage and antibiotic combinations. The development of this solid media assay for assessing synergy between phages and antibiotics will better inform the use of these combinations in the treatment of ARB infections.


Assuntos
Antibacterianos , Bacteriófagos , Terapia por Fagos , Bacteriófagos/fisiologia , Bacteriófagos/isolamento & purificação , Antibacterianos/farmacologia , Terapia por Fagos/métodos , Humanos , Meios de Cultura/química , Testes de Sensibilidade Microbiana/métodos , Bactérias/virologia , Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana
17.
Knee Surg Sports Traumatol Arthrosc ; 32(5): 1308-1316, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38504506

RESUMO

PURPOSE: The aim of this study was to analyse the functional outcome and the conversion rate to total knee arthroplasty (TKA) after surgically treated tibial plateau fractures (TPF). METHODS: All patients undergoing surgical treatment of TPF at a single institution between January 2003 and December 2019 were retrospectively reviewed. The Knee injury and Osteoarthritis Outcome Score (KOOS) and Tegner activity scale (TAS) were collected. The conversion rate to TKA was examined 2, 5, 7 and 10 years after surgical treatment of TPF. RESULTS: Ninety-four patients, with a mean follow-up of 110.6 months (±60.0), were included in the functional outcome assessment. Mean KOOS scores were 75.4 for symptoms, 80.6 for pain, 84.3 for activities of daily living (ADL), 59.5 for sports and 61.3 for QOL. All subscales were significantly lower on the injured side compared with the contralateral leg. Lower KOOS was observed in patients with hardware removal and Schatzker type 5 and 6 injuries. Median TAS was postinjury (4) significantly lower than preinjury (5) (p < 0.001). The conversion rate to TKA was 6.3%, 10.9%, 11.7% and 12.2% after 2,5,7 and 10 years of follow-up, respectively. Patients undergoing TKA were older than patients with no conversion to TKA (2 years follow-up 53.8 vs. 64.5 years, p = 0.026). CONCLUSION: TPFs decrease the function of the knee when compared with the contralateral side and to the preoperative condition. Bicondylar fractures are associated with worse functional outcomes. A conversion rate to TKA of 12.2% was found at 10 years follow-up. LEVEL OF EVIDENCE: Level III.


Assuntos
Artroplastia do Joelho , Fraturas da Tíbia , Humanos , Feminino , Masculino , Fraturas da Tíbia/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Atividades Cotidianas , Adulto , Resultado do Tratamento , Recuperação de Função Fisiológica , Fraturas do Planalto Tibial
18.
Biotechnol J ; 19(3): e2300725, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38479989

RESUMO

Microalgae are considered to be a promising group of organisms for fuel production, waste processing, pharmaceutical applications, and as a source of food components. Unicellular algae are worth being considered because of their capacity to produce comparatively large amounts of lipids, proteins, and vitamins while requiring little room for growth. They can also grow on waste and fix CO2 and nitrogen compounds. However, production costs limit the industrial use of microalgae to the most profitable applications including micronutrient production and fish farming. Therefore, novel microalgae based technologies require an increase of the production efficiencies or values. Here we review the recent studies focused on getting strains with novel characteristics or cultivating techniques that improve production's robustness or efficiency and categorize these findings according to the fundamental factors that determine microalgae growth. Improvements of light and nutrient delivery, as well as other aspects of photobioreactor design, have shown the highest average increase in productivity. Other methods, such as an improvement of phosphorus or CO2 fixation and temperature adaptation have been found to be less effective. Furthermore, interactions with particular bacteria may promote the growth of microalgae, although bacterial and grazer contaminations must be managed to avoid culture failure. The competitiveness of the algal products will increase if these discoveries are applied to industrial settings.


Assuntos
Microalgas , Águas Residuárias , Microalgas/metabolismo , Dióxido de Carbono/metabolismo , Nitrogênio/metabolismo , Tecnologia , Biomassa
19.
Cureus ; 16(2): e54046, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38481923

RESUMO

Squamous cell carcinoma (SCC) is the most common tumor of the hand with a high tendency for local recurrence and a low rate of metastasis. Herein, we present an interesting case of SCC of the thumb of the right hand in a 68-year-old patient with one recurrence, treated with surgical excision and following radiotherapy. Five years postoperative, there are no clinical and imaging data for local recurrence, as well as the presence of metastases. We also make a brief review of the current literature on this neoplasia.

20.
Cells ; 13(6)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38534379

RESUMO

Disulfiram (DSF), an anti-alcoholism medicine, exerts treatment effects in patients suffering from persistent Borreliosis and also exhibits anti-cancer effects through its copper chelating derivatives and induction of oxidative stress in mitochondria. Since chronic/persistent borreliosis is characterized by increased amounts of pro-inflammatory macrophages, this study investigated opsonin-independent phagocytosis, migration, and surface marker expression of in vivo activated and in vitro cultured human monocyte-derived phagocytes (macrophages and dendritic cells) with and without DSF treatment. Phagocytosis of non-opsonized Dynabeads® M-450 and migration of macrophages and dendritic cells were monitored using live cell analyzer Juli™ Br for 24 h, imaging every 3.5 min. To simultaneously monitor phagocyte function, results were analyzed by a newly developed software based on the differential phase contrast images of cells before and after ingestion of Dynabeads. DSF decreased the phagocytic capacities exhibited by in vitro enriched and long-lived phagocytes. Although no chemotactic gradient was applied to the test system, vigorous spontaneous migration was observed. We therefore set up an algorithm to monitor and quantify both phagocytosis and migration simultaneously. DSF not only reduced phagocytosis in a majority of these long-lived phagocytes but also impaired their migration. Despite these selective effects by DSF, we found that DSF reduced the expression densities of surface antigens CD45 and CD14 in all of our long-lived phagocytes. In cells with a high metabolic activity and high mitochondrial contents, DSF led to cell death corresponding to mitochondrial oxidative stress, whereas metabolically inactive phagocytes survived our DSF treatment protocol. In conclusion, DSF affects the viability of metabolically active phagocytes by inducing mitochondrial stress and secondly attenuates phagocytosis and migration in some long-lived phagocytes.


Assuntos
Dissulfiram , Proteínas Opsonizantes , Humanos , Dissulfiram/farmacologia , Fagocitose , Fagócitos , Macrófagos
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