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1.
Dev Cell ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38776925

RESUMO

During neural tube (NT) development, the notochord induces an organizer, the floorplate, which secretes Sonic Hedgehog (SHH) to pattern neural progenitors. Conversely, NT organoids (NTOs) from embryonic stem cells (ESCs) spontaneously form floorplates without the notochord, demonstrating that stem cells can self-organize without embryonic inducers. Here, we investigated floorplate self-organization in clonal mouse NTOs. Expression of the floorplate marker FOXA2 was initially spatially scattered before resolving into multiple clusters, which underwent competition and sorting, resulting in a stable "winning" floorplate. We identified that BMP signaling governed long-range cluster competition. FOXA2+ clusters expressed BMP4, suppressing FOXA2 in receiving cells while simultaneously expressing the BMP-inhibitor NOGGIN, promoting cluster persistence. Noggin mutation perturbed floorplate formation in NTOs and in the NT in vivo at mid/hindbrain regions, demonstrating how the floorplate can form autonomously without the notochord. Identifying the pathways governing organizer self-organization is critical for harnessing the developmental plasticity of stem cells in tissue engineering.

2.
Endocr Relat Cancer ; 31(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38713182

RESUMO

The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.


Assuntos
Acromegalia , Hormônio do Crescimento Humano , Tumores Neuroendócrinos , Prolactina , Somatostatina , Humanos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Masculino , Feminino , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Pessoa de Meia-Idade , Adulto , Prolactina/sangue , Prolactina/metabolismo , Estudos Retrospectivos , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/metabolismo , Acromegalia/tratamento farmacológico , Acromegalia/metabolismo , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/metabolismo , Idoso , Adulto Jovem
3.
Eur J Endocrinol ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771697

RESUMO

OBJECTIVE: To compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin co-secreting PA (GH&PRL-PA). DESIGN: Retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least six months of first-line medical treatment. METHODS: Baseline characteristics, first-line medical treatment strategies, and outcomes were analysed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality. RESULTS: Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs. 51.9 ± 12.7 years; p < 0.01) and harboring more frequently macroadenomas (89.7% vs. 72.1%, p = 0.03). First generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs. 15.2%; p < 0.01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs. 55.1%, p = 0.04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline. CONCLUSION: In GH&PRL-PA the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first line medical treatment in combination with fgSRLs in these subgroups of patients.

4.
Acta Neurochir (Wien) ; 166(1): 197, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683412

RESUMO

OBJECT: One of the critical steps for the success of intraventricular neuroendoscopic procedures is the entry into the third ventricle and passage of the endoscopy system through the foramen of Monro (FM). A diameter larger than that of the instrument used is considered a prerequisite for safely performing the technique, as damage to this structure can lead to alterations in the fornix and vascular structures. When the foramen diameter is narrow and there is no obstruction/stenosis, the role of foraminoplasty in reducing the risk of complications has not been adequately assessed in the literature. METHODS: A review of endoscopic procedures conducted at our center since 2018 was undertaken. Cases in which preoperative imaging indicated a FM diameter < 6 mm and foraminoplasty technique was applied were examined to determine the technical and functional success of the procedure. The technical success was determined by completing the neuroendoscopic procedure with the absence of macroscopic lesions in the various structures comprising the foramen and without complications in the follow-up imaging tests. Functional success was defined as the absence of cognitive/memory alterations during the 3-month postoperative follow-up. Additionally, a review of the various forms of foraminoplasty described in the literature is conducted. RESULTS: In our cohort, six patients were identified with a preoperative FM diameter < 6 mm without obstruction or stenosis. Foraminoplasty was planned for these cases to facilitate various intraventricular neuroendoscopic procedures. In all instances, the technique was successfully performed without causing macroscopic damage to the structures comprising the foramen. Follow-up visits included various cognitive tests to assess potential sequelae related to microscopic damage to the fornix. None of the patients exhibited anomalies. CONCLUSION: Foraminoplasty in patients with a narrow FM without signs of stenosis/obstruction is a useful technique to reduce the risk of complications during the passage of the endoscopy system through this structure, enabling the safe performance of neuroendoscopic procedures.


Assuntos
Neuroendoscopia , Terceiro Ventrículo , Humanos , Neuroendoscopia/métodos , Masculino , Feminino , Terceiro Ventrículo/cirurgia , Terceiro Ventrículo/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Hidrocefalia/cirurgia , Hidrocefalia/diagnóstico por imagem , Adolescente , Adulto Jovem , Criança , Estudos Retrospectivos , Resultado do Tratamento , Idoso
5.
World Neurosurg ; 187: 19-28, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583569

RESUMO

BACKGROUND: Ventriculoscopic neuronavigation has been described in several articles. However, there are different ventriculoscopes and navigation systems. Due to these different combinations, it is difficult to find detailed neuronavigation protocols. We describe, step-by-step, a simple method to navigate both the trajectory until reaching the ventricular system, as well as the intraventricular work. METHODS: We use a rigid ventriculoscope (LOTTA, KarlStorz) with an electromagnetic stylet (S8-StealthSystem, Medtronic). The protocol is based on a modified or 3-dimensionally printed trocar for navigating the extraventricular step and on a modified pediatric nasogastric tube for the intraventricular navigation. RESULTS: This protocol can be set up in less than 10 minutes. The extraventricular part is navigated by introducing the electromagnetic stylet inside the modified or 3-dimensionally printed trocar. Intraventricular navigation is done by combining a modified pediatric nasogastric tube with the electromagnetic stylet inside the endoscope's working channel. The most critical point is to obtain a blunt-bloodless ventriculostomy while achieving perfect alignment of all targeted structures via pure straight trajectories. CONCLUSIONS: This protocol is easy-to-set-up, avoids head rigid-fixation and bulky optical-based attachments to the ventriculoscope, and allows continuous navigation of both parts of the surgery. Since we have implemented this protocol, we have noticed a significant enhancement in both simple and complex ventriculoscopic procedures because the surgery is dramatically simplified.

6.
Drug Resist Updat ; 75: 101087, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38678745

RESUMO

In recent years, new evidence has shown that the SOS response plays an important role in the response to antimicrobials, with involvement in the generation of clinical resistance. Here we evaluate the impact of heterogeneous expression of the SOS response in clinical isolates of Escherichia coli on response to the fluoroquinolone, ciprofloxacin. In silico analysis of whole genome sequencing data showed remarkable sequence conservation of the SOS response regulators, RecA and LexA. Despite the genetic homogeneity, our results revealed a marked differential heterogeneity in SOS response activation, both at population and single-cell level, among clinical isolates of E. coli in the presence of subinhibitory concentrations of ciprofloxacin. Four main stages of SOS response activation were identified and correlated with cell filamentation. Interestingly, there was a correlation between clinical isolates with higher expression of the SOS response and further progression to resistance. This heterogeneity in response to DNA damage repair (mediated by the SOS response) and induced by antimicrobial agents could be a new factor with implications for bacterial evolution and survival contributing to the generation of antimicrobial resistance.

7.
Front Microbiol ; 15: 1379534, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659986

RESUMO

Introduction/objective: Suppression of the SOS response in combination with drugs damaging DNA has been proposed as a potential target to tackle antimicrobial resistance. The SOS response is the pathway used to repair bacterial DNA damage induced by antimicrobials such as quinolones. The extent of lexA-regulated protein expression and other associated systems under pressure of agents that damage bacterial DNA in clinical isolates remains unclear. The aim of this study was to assess the impact of this strategy consisting on suppression of the SOS response in combination with quinolones on the proteome profile of Escherichia coli clinical strains. Materials and methods: Five clinical isolates of E. coli carrying different chromosomally- and/or plasmid-mediated quinolone resistance mechanisms with different phenotypes were selected, with E. coli ATCC 25922 as control strain. In addition, from each clinical isolate and control, a second strain was created, in which the SOS response was suppressed by deletion of the recA gene. Bacterial inocula from all 12 strains were then exposed to 1xMIC ciprofloxacin treatment (relative to the wild-type phenotype for each isogenic pair) for 1 h. Cell pellets were collected, and proteins were digested into peptides using trypsin. Protein identification and label-free quantification were done by liquid chromatography-mass spectrometry (LC-MS) in order to identify proteins that were differentially expressed upon deletion of recA in each strain. Data analysis and statistical analysis were performed using the MaxQuant and Perseus software. Results: The proteins with the lowest expression levels were: RecA (as control), AphA, CysP, DinG, DinI, GarL, PriS, PsuG, PsuK, RpsQ, UgpB and YebG; those with the highest expression levels were: Hpf, IbpB, TufB and RpmH. Most of these expression alterations were strain-dependent and involved DNA repair processes and nucleotide, protein and carbohydrate metabolism, and transport. In isolates with suppressed SOS response, the number of underexpressed proteins was higher than overexpressed proteins. Conclusion: High genomic and proteomic variability was observed among clinical isolates and was not associated with a specific resistant phenotype. This study provides an interesting approach to identify new potential targets to combat antimicrobial resistance.

8.
J Fungi (Basel) ; 10(3)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38535195

RESUMO

Kodamaea ohmeri is an environmental yeast considered a rare emerging pathogen. In clinical settings, the correct identification of this yeast is relevant because some isolates are associated with resistance to antifungals. There is a lack of available data regarding the geographical distribution, virulence, and drug resistance profile of K. ohmeri. To contribute to the knowledge of this yeast, this study aimed to describe in depth three isolates of K. ohmeri associated with fungemia in Honduras. The identification of the isolates was carried out by sequencing the ribosomal ITS region. In addition, the susceptibility profile to antifungals was determined, and some properties associated with virulence were evaluated (exoenzyme production, biofilm formation, cell adhesion, and invasion). The isolates showed strong protease, phospholipase, and hemolysin activity, in addition to being biofilm producers. Adherence and invasion capacity were evident in the HeLa and Raw 264.7 cell lines, respectively. This study expands the understanding of the underlying biological traits associated with virulence in K. ohmeri, and it is the first report of the detection and identification of K. ohmeri in Honduras as a cause of human infection.

9.
Animals (Basel) ; 14(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38539928

RESUMO

Bergmann's and Allen's rules are two classic ecogeographic rules concerning the physiological mechanisms employed by endotherm vertebrates for heat conservation in cold environments, which correlate with adaptive morphological changes. Thus, larger body sizes (Bergmann's rule) and shorter appendages and limbs (Allen's rule) are expected in mammals inhabiting cold environments (higher latitudes). Both rules may also apply to elevational gradients, due to the decrease in external temperature as elevation increases. In this study, we evaluated whether these patterns were true in two coexisting sigmodontine rodents across an elevational gradient in central Chile. We analyzed whether the size of the skull, body, and appendages of Abrothrix olivacea (n = 70) and Phyllotis darwini (n = 58) correlated with elevation, as predicted by these rules in a range between 154 and 2560 m. Our data revealed weak support for the Bergmann and Allen predictions. Moreover, we observed opposite patterns when expectations of Bergmann's rules were evaluated, whereas Allen's rule just fitted for ear size in both rodent species. Our results suggest that morphological changes (cranial, body, and appendage sizes) may play a minor role in the thermoregulation of these two species at high elevations, although behavioral strategies could be more critical. Other ecological and environmental variables could explain the morphological trends observed in our study. These hypotheses should be assessed in future studies to consider the relative contribution of morphology, behavior, and physiological mechanisms to the thermal adaptation of these two rodent species at high elevations.

10.
J Phys Condens Matter ; 36(32)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38478995

RESUMO

We present a theoretical investigation of the Goös-Hanchen shift (GHS) experienced by acoustic and optical vibrational modes reflected and transmitted from the surfaces of a semiconductor thin film sandwiched between two semi-infinite media. Our study focuses on the impact of the incident angle on the GHS, considering the coupling between longitudinal and transverse modes. For acoustic vibrations, our findings reveal that the GHS can reach magnitudes up to seven times larger than the thickness of the thin film and up to 20 times larger than the incident wavelength. Besides, it is shown that this significant amplification of the GHS highlights the strong influence of the incident angle and the frequency of the modes involved. In the case of optical vibrations, we observe even more pronounced GHS values, exceeding 30 times the incident wavelength. This demonstrates the potential of GHS in acoustical systems, which opens up possibilities for applications in the design of acoustic devices.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38436926

RESUMO

PURPOSE: To evaluate differences in clinical presentation and in surgical outcomes between growth hormone-secreting pituitary adenomas (GH-PAs) and GH and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). METHODS: Multicenter retrospective study of 604 patients with acromegaly submitted to pituitary surgery. Patients were classified into two groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal and IHC for GH and PRL was positive or PRL levels were >100ng/and PRL IHC was not available (n=130) and b) GH-PAs who did not meet the previously mentioned criteria (n=474). RESULTS: GH&PRL-PAs represented 21.5% (n=130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P<0.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs. 77.4%, P=0.001) and tended to be more invasive (33.6% vs. 24.7%, P=0.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (OR 2.8, 95% CI 1.83-4.38). IGF-1 upper limit of normality (ULN) levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [IQR 1.73-3.29] vs. 2.7 [IQR 1.91-3.67], P=0.023). There were no differences in the immediate (41.1% vs 43.3%, P=0.659) or long-term post-surgical acromegaly biochemical cure rate (53.5% vs. 53.1%, P=0.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs. 2.4%, P=0.011) in GH&PRL-PAs patients. CONCLUSIONS: GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.

14.
Toxins (Basel) ; 16(2)2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38393182

RESUMO

Snakebite accident treatment requires the administration of antivenoms that provide efficacy and effectiveness against several snake venoms of the same genus or family. The low number of immunogenic components in venom mixtures that allow the production of antivenoms consequently gives them partial neutralization and a suboptimal pharmacological response. This study evaluates the immunorecognition and neutralizing efficacy of the polyvalent anticoral antivenom from the Instituto Nacional de Salud (INS) of Colombia against the heterologous endemic venoms of Micrurus medemi, and M. sangilensis, and M. helleri by assessing immunoreactivity through affinity chromatography, ELISA, Western blot, and neutralization capability. Immunorecognition towards the venoms of M. medemi and M. sangilensis showed values of 62% and 68% of the protein composition according to the immunoaffinity matrix, respectively. The analysis by Western blot depicted the highest recognition patterns for M. medemi, followed by M. sangilensis, and finally by M. helleri. These findings suggest that the venom compositions are closely related and exhibit similar recognition by the antivenom. According to enzyme immunoassays, M. helleri requires a higher amount of antivenom to achieve recognition than the others. Besides reinforcing the evaluation of INS antivenom capability, this work recommends the use of M. helleri in the production of Colombian antisera.


Assuntos
Antivenenos , Cobras Corais , Animais , Cobras Corais/metabolismo , Colômbia , Venenos Elapídicos/química , Venenos de Serpentes/química
15.
J Antimicrob Chemother ; 79(3): 641-647, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305703

RESUMO

BACKGROUND: BaeS/BaeR is a two-component system of Escherichia coli that controls the expression of porins and efflux pumps. Its role in beta-lactam resistance is limited. OBJECTIVES: To study the role of baeS/baeR two-component system in temocillin resistance in E. coli. METHODS: E. coli strain BW25113 and single-gene deletion mutants related to two-component systems were collected from the KEIO collection. Double-gen deletion mutants were generated. Temocillin-resistant mutant frequencies were determined at 32 mg/L. E. coli BW25113 mutants were selected by selective pressure from serial passages. Biological costs were analysed by growth curves. Genomes of the generated mutants were sequenced. The expression level of the mdtA, mdtB, mdtC, acrD and tolC in the ΔbaeS mutant was determined by RT-PCR (with/without temocillin exposure). RESULTS: The frequency of temocillin mutants ranged from 2.12 × 10-8 to 4.51 × 10-8 in single-porin mutants. No mutants were recovered from E. coli BW25113 (>10-9). Selection of temocillin-resistant variants by serial passage yielded mutants up to 128 mg/L. Mutations were found in the baeS gene. Temocillin MICs ranged from 4 to 32 mg/L (highest MICs for ΔbaeS and ΔompR). The efflux pumps mdtA, mdtB, mdtC and acrD pumps were overexpressed 3-10-fold in the presence of temocillin in ΔbaeS compared to control. CONCLUSIONS: Mutations in the sensor histidine kinase, baeS, may be involved in temocillin resistance through the expression of the efflux pumps mdtABC and acrD. In addition, the low mutation rate may be a good predictor of temocillin activity.


Assuntos
Cadaverina/análogos & derivados , Proteínas de Escherichia coli , Escherichia coli , Penicilinas , Escherichia coli/genética , Transporte Biológico , Transativadores , Proteínas de Escherichia coli/genética
16.
J Ultrasound ; 27(1): 191-197, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38308121

RESUMO

PURPOSE: Surgery of deep-seated brain tumors can be challenging. Several methods have been described to facilitate transcortical approaches, including ultrasound-assisted resection. Ultrasound-guided placement of a standard ventricular catheter is a widely reported technique and has been used to approach these lesions via the transcortical route. We describe how we usually perform this useful technique to assist and enhance the transcortical resection of some deep-seated brain tumors. METHODS: Standard electromagnetic frameless navigation (S8 Neuronavigation System, Medtronic, Minneapolis, USA) was employed to focus the craniotomy and to plan the trajectory of the ventricular catheter. After dural opening, an ultrasound device (Arietta 850, Hitachi-Aloka Medical, Tokyo, Japan) was used for intraoperative ultrasound (IOUS) assessment. A ventricular catheter was placed from the cortex to the lateral wall of the tumor under direct real-time IOUS visualization to guide the further transcortical dissection. RESULTS: Transcortical transcatheter ultrasound-assisted technique involved minimal time and infrastructure requirements. There were no major technical difficulties during its use, providing confidence and improving subcortical white matter dissection by guiding the route to the tumor. CONCLUSIONS: Recent improvement of IOUS image-quality devices offers several attractive options for real-time navigation. The combination of conventional neuronavigation systems with real-time IOUS assessment during the intradural step provides a higher degree of control by improving the execution of the surgery. We hope this description may be a useful tool for some selected cases and contribute to the further enhancement and improvement of this widely used technique.


Assuntos
Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Ultrassonografia
17.
J Antimicrob Chemother ; 79(4): 784-789, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38334407

RESUMO

BACKGROUND: Temocillin is an old antimicrobial that is resistant to hydrolysis by ESBLs but has variable activity against carbapenemase-producing Enterobacteriaceae. The current EUCAST susceptibility breakpoints for Enterobacterales are set at ≤16 mg/L (susceptible with increased exposure) based on a dose of 2 g q8h, but there is limited information on the efficacy of this dose against temocillin-susceptible carbapenemase-producing Klebsiella pneumoniae isolates. OBJECTIVES: To evaluate the efficacy of this dose using a hollow-fibre infection model (HFIM) against six KPC-2-producing clinical isolates of K. pneumoniae. METHODS: The isolates were characterized by WGS and temocillin susceptibility was determined using standard and high inoculum temocillin. Mutant frequencies were estimated and temocillin activity was tested in time-kill assays and in the HFIM. At standard conditions, three of the isolates were classified as susceptible (MIC ≤ 16 mg/L) and three as resistant (MIC > 16 mg/L). The HFIM was performed over 3 days to mimic human-like pharmacokinetics of 2 g q8h. Bacterial counts were performed by plating on Mueller-Hinton agar (MHA) and MHA containing 64 mg/L temocillin to detect resistant subpopulations. RESULTS: All isolates showed a reduction in bacterial population of at least 3 log cfu/mL within the first 8 h of simulated treatment in the hollow-fibre assay. Regrowth was observed for the three resistant isolates and one of the susceptible ones. The MIC value for these isolates was higher by at least two dilutions compared with their initial values. CONCLUSIONS: These data suggest that an optimized pharmacokinetic regimen may be of clinical interest for the treatment of KPC-2-producing K. pneumoniae susceptible to temocillin. These data showed activity of temocillin against KPC-2-producing K. pneumoniae susceptible to temocillin; however, a dose of 2g q8h administered over 30 min may be inadequate to prevent the emergence of resistant variants.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Penicilinas , Humanos , Antibacterianos/uso terapêutico , Klebsiella pneumoniae , beta-Lactamases/genética , Testes de Sensibilidade Microbiana , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Proteínas de Bactérias/genética
18.
Proc Natl Acad Sci U S A ; 121(6): e2305944121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38252845

RESUMO

Protected areas are of paramount relevance to conserving wildlife and ecosystem contributions to people. Yet, their conservation success is increasingly threatened by human activities including habitat loss, climate change, pollution, and species overexploitation. Thus, understanding the underlying and proximate drivers of anthropogenic threats is urgently needed to improve protected areas' effectiveness, especially in the biodiversity-rich tropics. We addressed this issue by analyzing expert-provided data on long-term biodiversity change (last three decades) over 14 biosphere reserves from the Mesoamerican Biodiversity Hotspot. Using multivariate analyses and structural equation modeling, we tested the influence of major socioeconomic drivers (demographic, economic, and political factors), spatial indicators of human activities (agriculture expansion and road extension), and forest landscape modifications (forest loss and isolation) as drivers of biodiversity change. We uncovered a significant proliferation of disturbance-tolerant guilds and the loss or decline of disturbance-sensitive guilds within reserves causing a "winner and loser" species replacement over time. Guild change was directly related to forest spatial changes promoted by the expansion of agriculture and roads within reserves. High human population density and low nonfarming occupation were identified as the main underlying drivers of biodiversity change. Our findings suggest that to mitigate anthropogenic threats to biodiversity within biosphere reserves, fostering human population well-being via sustainable, nonfarming livelihood opportunities around reserves is imperative.


Assuntos
Biodiversidade , Ecossistema , Humanos , Animais , Agricultura , Animais Selvagens , Mudança Climática
19.
Oper Neurosurg (Hagerstown) ; 26(2): 188-195, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37815208

RESUMO

BACKGROUND AND OBJECTIVES: One of the key aspects in the surgical technique of endoscopic third ventriculostomy (ETV) is the perforation of the floor of the third ventricle because of the high risk of injuring vital structures located in that region. According to the standard technique, this perforation should be performed in the midline halfway between mammillary bodies and the infundibular recess to avoid damage to the structures. This can be performed without excessive complications when the diameter of the prepontine cistern is wide. However, in situations where the diameter is reduced (defined in the literature as having a prepontine interval [PPI] ≤1 mm), the probability of complications increases exponentially.In this article, we propose using dorsum sellae as a key point to safely perform ETV in patients with a decreased PPI, guiding the trajectory and its marking using neuronavigation. METHODS: A review was conducted on the latest 100 ETV procedures performed by our team in the past 5 years. The measurement of the PPI was conducted using archived preoperative MRI imaging studies, specifically between the dorsum sellae and the basilar artery. In cases where the PPI was ≤1 mm and, therefore, the use of the dorsum sellae was applied as a reference point, the technical results and procedural functions were documented. RESULTS: In the cohort, 7 patients with a PPI ≤1 mm were identified. In all 7 cases, fenestration of the tuber cinereum was successfully performed without causing vascular damage or associated complications. ETV was successful in 6 patients, with only one experiencing ETV failure necessitating the placement of a ventriculoperitoneal shunt. CONCLUSION: The utilization of the dorsum sellae as a reference point to perform ETV in reduced PPI constitutes a safe alternative to the classical technique.


Assuntos
Terceiro Ventrículo , Ventriculostomia , Humanos , Ventriculostomia/métodos , Terceiro Ventrículo/diagnóstico por imagem , Terceiro Ventrículo/cirurgia , Espaço Subaracnóideo/cirurgia , Imageamento por Ressonância Magnética , Sela Túrcica/cirurgia
20.
J Clin Nurs ; 33(1): 357-367, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36919674

RESUMO

AIM AND OBJECTIVES: To evaluate changes in compassion fatigue (CF), burnout (BO), compassion satisfaction (CS) and fear of COVID-19 among Spanish nurses by comparing two assessment points: before and after the COVID-19 vaccination campaign. BACKGROUND: The COVID-19 pandemic has produced a great impact in healthcare worker's professional quality of life, especially among nurses. CF, BO and fear of COVID-19 decisively affect the care provided by nurses and put them at risk for mental health problems, so longitudinal studies are essential. DESIGN: A repeated cross-sectional design was carried out with a time-lapse of 12 months. METHODS: A total of 439 registered nurses in December 2020 and 410 in December 2021 participated in this study through an online survey. Data were collected using the Professional Quality of Life Questionnaire and the Fear of COVID-19 Scale. Occupational and sociodemographic variables were also analysed. This article adheres to the STROBE guidelines for the reporting of observational studies. RESULTS: The fear of COVID-19 has not been reduced among nurses. The levels of BO remain stable and continue to be high in half of the professionals. CF has been reduced with a small effect size (d = 0.30), while CS has also decreased (d = 0.30). Positive correlations were found in both assessment points between fear of COVID-19 and BO (r = .44, p ≤ .001; r = .41, p ≤ .001) and also between fear of COVID and CF (r = .57, p ≤ .001; r = .50, p ≤ .001). Negative correlations between fear and CS were also found (r = - .16, p = .001; r = - .22, p ≤ .001). RELEVANCE TO CLINICAL PRACTICE: Programmes to reduce fear of COVID-19, BO and CF are needed to improve mental health and to prevent psychological distress among nurses, as well as to increase CS and preserve the productivity and quality of nursing care. PATIENT OR PUBLIC CONTRIBUTION: The nurses collaborated by participating in the present study anonymously and disinterestedly.


Assuntos
Esgotamento Profissional , COVID-19 , Fadiga de Compaixão , Enfermeiras e Enfermeiros , Humanos , Estudos Transversais , Qualidade de Vida , Pandemias , Vacinas contra COVID-19 , COVID-19/epidemiologia , Esgotamento Profissional/psicologia , Fadiga de Compaixão/epidemiologia , Fadiga de Compaixão/psicologia , Inquéritos e Questionários , Empatia , Medo , Satisfação no Emprego
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