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1.
Clin Case Rep ; 12(8): e9100, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39091616

RESUMEN

Key Clinical Message: Posterior Reversible Encephalopathy Syndrome, typically characterized by parieto-occipital vasogenic edema, can present atypically, as a bilateral symmetrical vasogenic edema in the basal ganglia, featuring the called "lentiform fork sign." Prompt recognition of such variations is crucial for accurate diagnosis and tailored management, highlighting the complexity of this syndrome's manifestations. Abstract: Posterior Reversible Encephalopathy Syndrome (PRES) manifests as transient neurological symptoms and cerebral edema, commonly associated with immunosuppressive drugs (ISDs) in transplant recipients. ISDs can lead to endothelial dysfunction and compromise the blood-brain barrier. Typically, PRES exhibits identifiable MRI patterns, often demonstrating vasogenic edema in the bilateral parieto-occipital white matter. Identifying unique presentations, such as the recently observed "lentiform fork sign," commonly seen in uremic encephalopathy, emphasizes this syndrome's broad spectrum manifestations. A 19-year-old male, who underwent bilateral lung and liver transplantation, experienced a bilateral tonic-clonic seizure of unknown onset 47 days post-surgery. MRI findings revealed an unconventional PRES pattern, featuring the "lentiform fork sign" as bilateral symmetrical vasogenic edema in the basal ganglia, surrounded by a hyperintense rim outlining the lentiform nucleus bilaterally. Subsequent management, including ISD modification and magnesium supplementation, resulted in clinical and neuroimaging resolution. An almost complete clinical and radiological resolution was achieved after 14 days. The occurrence of PRES in transplant recipients highlights the intricate interplay among ISDs, physiological factors, and cerebrovascular dynamics, potentially involving direct neurovascular endothelial toxicity and disruption of the blood-brain barrier. Neuroimaging plays a pivotal role in diagnosis. The distinctive "lentiform fork sign" was observed in this patient despite the absence of typical metabolic disturbances. Management strategies usually involve reducing hypertension, discontinuing ISDs, correcting electrolyte imbalances, and initiating antiseizure drugs if necessary. Identifying the presence of the "lentiform fork sign" alongside typical PRES edema in a patient lacking renal failure emphasizes that this manifestation is not solely indicative of uremic encephalopathy. Instead, it might represent the final common pathway resulting from alterations in the blood-brain barrier integrity within the deep white matter. Understanding such atypical imaging manifestations could significantly aid earlier and more precise diagnosis, influencing appropriate management decisions.

2.
Vet Parasitol Reg Stud Reports ; 53: 101060, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39025553

RESUMEN

Snakes of the genus Bothrops inhabit tropical forests in Central and South America and are important for the biomedical and pharmaceutical industries because of the chemical properties of their venom. They serve as either definitive or intermediate hosts for many parasitic helminths. The Marajó Island (Brazil) is the natural habitat of venomous snakes, Bothrops atrox and Bothrops marajoensis, which are often found around rural and peri-urban areas and are known to bite humans. Samples of helminths parasitizing the oral cavity, subcutaneous tissues, coelomic cavity, and intestine of four B. atrox from Marajó Island (Pará-Brazil) were collected. The specimens studied were taxonomically classified as trematodes of the species Stycholecitha serpentis, nematodes of the genera Eustrongylides and Camallanus and cystacanths of an acanthocephalan of the genus Centrorhynchus. The aims of the present study were: to record helminths found in B. atrox from the Marajó Island; to discuss their role as definitive, intermediate, or paratenic hosts; and to compile a list of helminths that have been recorded in snakes of the genus Bothrops of the Neotropical region.


Asunto(s)
Bothrops , Helmintiasis Animal , Animales , Bothrops/parasitología , Brasil/epidemiología , Helmintiasis Animal/parasitología , Helmintiasis Animal/epidemiología , Masculino , Helmintos/clasificación , Helmintos/aislamiento & purificación , Femenino , Bothrops atrox
3.
Microbiol Res ; 287: 127840, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39032267

RESUMEN

Rhodosporidium toruloides has emerged as an excellent option for microbial lipid production due to its ability to accumulate up to 70 % of lipids per cell dry weight, consume multiple substrates such as glucose and xylose, and tolerate toxic compounds. Despite the potential of Rhodosporidium toruloides for high lipid yields, achieving these remains is a significant hurdle. A comprehensive review is essential to thoroughly evaluate the advancements in processes and technologies to enhance lipid production in R. toruloides. The review covers various strategies for enhancing lipid production like co-culture, adaptive evolution, carbon flux analysis, as well as different modes of fermentation. This review will help researchers to better understand the recent developments in technologies for sustainable and scalable lipid production from R. toruloides and simultaneously emphasize the need for developing an efficient and sustainable bioprocess.

4.
Biochim Biophys Acta Proteins Proteom ; 1872(5): 141034, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39009203

RESUMEN

The HSPA5 protein (BiP/Grp78) serves as a pivotal chaperone in maintaining cellular protein quality control. As a member of the human HSP70 family, HSPA5 comprises two distinct domains: a nucleotide-binding domain (NBD) and a peptide-binding domain (PBD). In this study, we investigated the interdomain interactions of HSPA5, aiming to elucidate how these domains regulate its function as a chaperone. Our findings revealed that HSPA5-FL, HSPA5-T, and HSPA5-N exhibit varying affinities for ATP and ADP, with a noticeable dependency on Mg2+ for optimal interactions. Interestingly, in ADP assays, the presence of the metal ion seems to enhance NBD binding only for HSPA5-FL and HSPA5-T. Moreover, while the truncation of the C-terminus does not significantly impact the thermal stability of HSPA5, experiments involving MgATP underscore its essential role in mediating interactions and nucleotide hydrolysis. Thermal stability assays further suggested that the NBD-PBD interface enhances the stability of the NBD, more pronounced for HSPA5 than for the orthologous HSPA1A, and prevents self-aggregation through interdomain coupling. Enzymatic analyses indicated that the presence of PBD enhances NBD ATPase activity and augments its nucleotide affinity. Notably, the intrinsic chaperone activity of the PBD is dependent on the presence of the NBD, potentially due to the propensity of the PBD for self-oligomerization. Collectively, our data highlight the pivotal role of allosteric mechanisms in modulating thermal stability, nucleotide interaction, and ATPase activity of HSPA5, underscoring its significance in protein quality control within cellular environments.


Asunto(s)
Adenosina Trifosfato , Chaperón BiP del Retículo Endoplásmico , Proteínas de Choque Térmico , Estabilidad Proteica , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/metabolismo , Humanos , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/química , Adenosina Difosfato/metabolismo , Adenosina Difosfato/química , Unión Proteica , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP70 de Choque Térmico/química , Dominios Proteicos , Magnesio/metabolismo , Magnesio/química
5.
Mol Biol Evol ; 41(7)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958167

RESUMEN

Admixture between populations and species is common in nature. Since the influx of new genetic material might be either facilitated or hindered by selection, variation in mixture proportions along the genome is expected in organisms undergoing recombination. Various graph-based models have been developed to better understand these evolutionary dynamics of population splits and mixtures. However, current models assume a single mixture rate for the entire genome and do not explicitly account for linkage. Here, we introduce TreeSwirl, a novel method for inferring branch lengths and locus-specific mixture proportions by using genome-wide allele frequency data, assuming that the admixture graph is known or has been inferred. TreeSwirl builds upon TreeMix that uses Gaussian processes to estimate the presence of gene flow between diverged populations. However, in contrast to TreeMix, our model infers locus-specific mixture proportions employing a hidden Markov model that accounts for linkage. Through simulated data, we demonstrate that TreeSwirl can accurately estimate locus-specific mixture proportions and handle complex demographic scenarios. It also outperforms related D- and f-statistics in terms of accuracy and sensitivity to detect introgressed loci.


Asunto(s)
Frecuencia de los Genes , Modelos Genéticos , Genética de Población/métodos , Cadenas de Markov , Flujo Génico , Genoma , Simulación por Computador , Ligamiento Genético
6.
Infect Dis Clin North Am ; 38(3): 581-598, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38971672

RESUMEN

The authors examine the HIV epidemic in the Southern United States, emphasizing its severe impact on minority and young populations. The authors highlight challenges including limited health care access, systemic racism influencing social determinants of health, and lesbian, gay, bisexual, transgender, and queer+ stigma. The South faces a critical human immunodeficiency virus (HIV) workforce shortage, especially in rural areas, and struggles with coexisting syndemics like other sexually transmitted infections and substance-use disorders. The authors describe comprehensive strategies such as Medicaid expansion, workforce enhancement, stigma reduction, and policy reforms to improve HIV prevention and treatment, emphasizing the need for a multifaceted approach to improve health outcomes for those living with HIV in the South.


Asunto(s)
Epidemias , Infecciones por VIH , Estigma Social , Humanos , Infecciones por VIH/epidemiología , Estados Unidos/epidemiología , Accesibilidad a los Servicios de Salud , Minorías Sexuales y de Género , Femenino , Masculino
8.
J Vis Exp ; (207)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38856212

RESUMEN

Retinal pigment epithelial cells (RPE) are critical for the proper function of the retina. RPE dysfunction is involved in the pathogenesis of important retinal diseases, such as age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy. We present a streamlined approach for the isolation of RPE from murine adult eyes. In contrast to previously reported methods, this approach enables the isolation and culture of highly pure RPE from adult mice. This simple and fast method does not require extensive technical skill and is achievable with basic scientific tools and reagents. Primary RPE are isolated from C57BL/6 background mice aged 3- to 14-weeks by enucleation of the eye followed by the removal of the anterior segment. Enzymatic trypsinization and centrifugation are used to dissociate and isolate the RPE from the eyecup. In conclusion, this approach offers a quick and effective protocol for the utilization of RPE in the study of retinal function and disease.


Asunto(s)
Ratones Endogámicos C57BL , Epitelio Pigmentado de la Retina , Animales , Ratones , Epitelio Pigmentado de la Retina/citología , Técnicas Citológicas/métodos , Técnicas de Cultivo de Célula/métodos , Células Epiteliales/citología
9.
Chemosphere ; 361: 142490, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38821131

RESUMEN

Aromatic hydrocarbons like benzene, toluene, xylene, and ethylbenzene (BTEX) can escape into the environment from oil and gas operations and manufacturing industries posing significant health risks to humans and wildlife. Unlike conventional clean-up methods used, biological approaches such as bioremediation can provide a more energy and labour-efficient and environmentally friendly option for sensitive areas such as nature reserves and cities, protecting biodiversity and public health. BTEX contamination is often concentrated in the subsurface of these locations where oxygen is rapidly depleted, and biodegradation relies on anaerobic processes. Thus, it is critical to understand the anaerobic biodegradation characteristics as it has not been explored to a major extent. This review presents novel insights into the degradation mechanisms under anaerobic conditions and presents a detailed description and interconnection between them. BTEX degradation can follow four activation mechanisms: hydroxylation, carboxylation, methylation, and fumarate addition. Hydroxylation is one of the mechanisms that explains the transformation of benzene into phenol, toluene into benzyl alcohol or p-cresol, and ethylbenzene into 1-phenylethanol. Carboxylation to benzoate is thought to be the primary mechanism of degradation for benzene. Despite being poorly understood, benzene methylation has been also reported. Moreover, fumarate addition is the most widely reported mechanism, present in toluene, ethylbenzene, and xylene degradation. Further research efforts are required to better elucidate new and current alternative catabolic pathways. Likewise, a comprehensive analysis of the enzymes involved as well as the development of advance tools such as omic tools can reveal bottlenecks degradation steps and create more effective on-site strategies to address BTEX pollution.


Asunto(s)
Derivados del Benceno , Benceno , Biodegradación Ambiental , Tolueno , Xilenos , Anaerobiosis , Derivados del Benceno/metabolismo , Benceno/metabolismo , Tolueno/metabolismo , Xilenos/metabolismo , Contaminantes Ambientales/metabolismo , Hidrocarburos Aromáticos/metabolismo
10.
An Acad Bras Cienc ; 96(1): e20220822, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38808808

RESUMEN

Multirotors Aerial Vehicles are special class of Unmanned Aerial Vehicles with many practical applications. The growing demand for this class of aircraft requires tools that speed up their development. Simulated environments have gained increasing importance, as they facilitate testing and prototyping solutions, where virtual environments allow real-time interaction with simulated models, with similar behavior to real systems. More recently, the use of Augmented Reality has allowed an increasing experience of immersion and integration between the virtual world and a real scenario. This work proposes the use of Augmented Reality technology and a simulated model of a multirotor to create an interactive flight environment, aiming to improve the user experience in the analysis of simulated models. For this purpose, a smartphone was adopted as a hardware platform, a game engine is used as a basis for the development of the Augmented Reality application, that represents a numerical simulation of the flight dynamics and the control system of a multirotor, and a game controller is adopted for user interaction. The resulting system demonstrates that Augmented Reality is a viable technology that can be used to increase the possibilities of evaluating simulated systems.


Asunto(s)
Aeronaves , Realidad Aumentada , Aeronaves/instrumentación , Simulación por Computador , Humanos , Interfaz Usuario-Computador , Realidad Virtual
11.
Reprod Domest Anim ; 59(5): e14582, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38715452

RESUMEN

Crossbred cattle are commonly used for milk production in the tropics, combining the potential benefits of pure breeds with the heterosis effects of the offspring. However, no comprehensive assessment of lifetime productivity for crossbred versus purebred cattle in low-altitude tropical environments has been carried out. The present study compares the lifetime productivity of purebred Holstein (HO, n = 17,269), Gyr (GY4, n = 435), and Brahman (BR4, n = 622) with crossbreds Gyr × Holstein (GY × HO, n = 5521) and Brahman×Holstein (BR × HO, n = 5429) cows from dairy farms located in low and medium altitude tropical regions in Costa Rica. The production traits of interest were age at first calving (AFC), days open (DO), milk production per lactation (TMP), lactation length (LLEN), age at culling (ACUL), and number of lactations (NLAC). Estimates of heterosis were also calculated. The AFC for GY × HO crosses (33-34 months) was not significantly different (p > .05) from HO (33.8 months). For BR × HO crosses, a significant (p < .05) decrease in AFC (BR3HO1 35.6 months, BR2HO2 34.5 months, and BR1H03 33.3 months) was observed as the fraction of HO breed increased. Estimates of heterosis for AFC were favourable for both crosses, of a magnitude close to 3%. The DO for F1 crosses (GY2HO2 94 days; BR2HO2 96 days) was significantly (p < .05) lower than HO (123 days). Estimates of heterosis for DO were also favourable and above 15% for both crosses. The TMP and LLEN were higher for HO (TMP = 5003 kg; LLEN = 324 days) compared with GY × HO (TMP = 4428 to 4773 kg; LLEN = 298 to 312 days) and BR × HO (TMP = 3950 to 4761 kg; LLEN = 273 to 313 days) crosses. Heterosis for TMP was favourable but low for both crosses, with a magnitude below 3.0%. The NLAC for HO (4.6 lactations) was significantly (p < .05) lower than F1 (GY2HO2, 5.8 lactations; BR2HO2, 5.4 lactations). Heterosis for NLAC was above 6.0% for both crosses. Overall, estimates of lifetime income over feed costs per cow on average were USD 2637 (30.3%) and USD 734 (8.4%) higher in F1 GY × HO and BR × HO, respectively, compared to HO. In conclusion, crossbred animals, specifically those with Gyr and Brahman genetics, extend the productive lifespan, increasing economic returns.


Asunto(s)
Vigor Híbrido , Lactancia , Leche , Clima Tropical , Animales , Bovinos/genética , Bovinos/fisiología , Lactancia/genética , Lactancia/fisiología , Femenino , Costa Rica , Cruzamiento , Hibridación Genética , Altitud , Cruzamientos Genéticos
12.
Nat Genet ; 56(5): 792-808, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38637617

RESUMEN

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.


Asunto(s)
Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/genética , Población Blanca/genética , Neurobiología , Sitios Genéticos
13.
Arch. argent. pediatr ; 122(2): e202310146, abr. 2024. ilus
Artículo en Inglés, Español | LILACS, BINACIS | ID: biblio-1537953

RESUMEN

Los tumores de músculo liso que no pueden ser clasificados según su histología como leiomiomas o leiomiosarcomas se denominan tumores de músculo liso de comportamiento maligno incierto. La localización nasal de estos tumores es muy infrecuente y la extensión adecuada de la cirugía para tratar estas neoplasias no está bien definida. Se describe el caso clínico de una adolescente de 16 años, que consultó por padecer un tumor de aspecto vascular en la cavidad nasal derecha y que fue tratada con éxito mediante cirugía intranasal. El diagnóstico histológico fue tumor de músculo liso de comportamiento maligno incierto. Por la rareza de estas neoplasias, su infrecuente localización nasal y la falta de evidencia que soporte cuál debe ser la extensión de la cirugía, es relevante la descripción y discusión del caso clínico.


Smooth muscle tumors that cannot be histologically classified as leiomyomas or leiomyosarcomas are defined as smooth muscle tumors of uncertain malignant potential. The location of these tumors in the nose is very rare, and the appropriate surgical extent to manage these neoplasms has not been adequately defined. Here we describe the case of a 16-year-old female adolescent who consulted due to a vascular-like tumor in the right nasal cavity who was successfully treated with intranasal surgery. The histological diagnosis was smooth muscle tumor of uncertain malignant potential. Given that these neoplasms are rare, the uncommon location in the nose, and the lack of evidence indicating the extent of surgery, it is relevant to describe and discuss this clinical case.


Asunto(s)
Humanos , Femenino , Adolescente , Tumor de Músculo Liso/cirugía , Tumor de Músculo Liso/diagnóstico , Tumor de Músculo Liso/patología , Leiomioma/patología , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/patología
14.
Matern Child Nutr ; 20(3): e13635, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38433606

RESUMEN

Small and nutritionally at-risk infants aged under 6 months (<6 months) are at high risk of death, but important evidence gaps exist on how to best identify them. We aimed to determine associations between anthropometric deficits and mortality among infants <6 months admitted to inpatient therapeutic care. A secondary analysis of 2002-2008 data included 5034 infants aged <6 months from 12 countries. We estimated the prevalence, concurrence, and severity of wasted, stunted, and underweight, as stand-alone indicators, and using the Composite Index of Anthropometric Failure (CIAF), which combines these indicators into six subgroups of single and multiple anthropometric deficits and into one combined indicator called CIAF. We used logistic regression to examine the association of different anthropometric deficits with in-programme mortality. Among 3692 infants aged <6 months with complete data, 3539 (95.8%) were underweight, 3058 (82.8%) were wasted, 2875 (77.8%) were stunted and 3575 (96.8%) had CIAF. Infants with multiple anthropometric deficits were presented with significantly lower anthropometric indices, that is, they were more severely wasted, stunted and underweight. A total of 141 infants died during inpatient therapeutic care. Among these, severely wasted (116) and severely underweight (138) infants had higher odds of mortality than normal infants (odds ratio [OR] = 2.1, 95% confidence interval [CI]: 1.2-2.7, p = 0.009, and OR = 3.3, 95% CI: 0.8-13.6, p = 0.09, respectively). Boys had higher odds of inpatient mortality than girls (OR = 1.40, 95% CI: 1.02-1.92, p = 0.03). Mortality was only observed in infants <6 months presenting multiple anthropometric deficits, although their odds of mortality were not significant, for example, OR = 2.4, 95% CI: 0.5-10.0, p = 0.21 for stunted, wasted and underweight infants <6 months. In conclusion, multiple anthropometric deficits (CIAF) is common among infants <6 months and may be reported in nutrition care programmes and surveys. Both weight-for-length/height z-score and weight-for-age z-score were found to be useful indicators for programme admission and in-programme prognosis. Future work needs to explore which better accounts for admission bias. Boys appear to be most at-risk of dying while receiving malnutrition therapeutic care. Programmes should ensure that all infants receive timely, evidence-based, effective care.


Asunto(s)
Delgadez , Humanos , Lactante , Masculino , Femenino , Delgadez/mortalidad , Delgadez/epidemiología , Antropometría , Trastornos de la Nutrición del Lactante/mortalidad , Trastornos de la Nutrición del Lactante/epidemiología , Trastornos de la Nutrición del Lactante/terapia , Factores de Riesgo , Recién Nacido , Prevalencia , Mortalidad Infantil , Modelos Logísticos , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/mortalidad , Estado Nutricional , Hospitalización/estadística & datos numéricos
15.
Open Respir Arch ; 6(2): 100302, 2024.
Artículo en Español | MEDLINE | ID: mdl-38444983

RESUMEN

Introduction: COPD is the third cause of death globally and in Argentina COPD has a prevalence of 14.5%, but the management of patients in real life is unknown. The objectives of this work were: a) To know the opinions of pulmonologists in Argentina who manage patients with COPD in different aspects of daily practice. b) Compare our findings with specialists from Spain and c) Consider our results to plan future directives in the management of COPD in our country. Material and methods: 89 pulmonologists from Argentina, experts in COPD, participated in a Delphi consensus, who responded to a survey with five domains. a) Adherence to treatment, b) Control of COPD, c) Treatable features, d) Inhalation devices and e) Accessibility to therapeutic resources. Results: After two rounds of questions, total consensus was achieved in 77.6% of the statements and discriminating by domain: Treatment adherence: 5/9 (55.5%). COPD control: 10/14 (71.4%). Treatable traits: 6/6 (100%). Inhalation devices: 10/14 (71.4%) and Accessibility to treatment: 6/6 (100%). In most of the affirmations, the results were similar to those obtained by Spanish pulmonologists. Conclusions: Pulmonologists from Argentina manage COPD patients in a similar way and with minimal differences with our Spanish colleagues. It became evident that, in daily practice, there are factors that negatively impact access to the indicated treatments. Our work could serve as a starting point to improve this situation.

16.
Health Sci Rep ; 7(3): e1965, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38524774

RESUMEN

Background and Aim: Until the May 2022 Monkeypox (MPXV) outbreak, which spread rapidly to many non-endemic countries, the virus was considered a viral zoonosis limited to some African countries. The Andalusian circuit of genomic surveillance was rapidly applied to characterize the MPXV outbreak in the South of Spain. Methods: Whole genome sequencing was used to obtain the genomic profiles of samples collected across the south of Spain, representative of all the provinces of Andalusia. Phylogenetic analysis was used to study the relationship of the isolates and the available sequences of the 2022 outbreak. Results: Whole genome sequencing of a total of 160 MPXV viruses from the different provinces that reported cases were obtained. Interestingly, we report the sequences of MPXV viruses obtained from two patients who died. While one of the isolates bore no noteworthy mutations that explain a potential heightened virulence, in another patient the second consecutive genome sequence, performed after the administration of tecovirimat, uncovered a mutation within the A0A7H0DN30 gene, known to be a prime target for tecovirimat in its Vaccinia counterpart. In general, a low number of mutations were observed in the sequences reported, which were very similar to the reference of the 2022 outbreak (OX044336), as expected from a DNA virus. The samples likely correspond to several introductions of the circulating MPXV viruses from the last outbreak. The virus sequenced from one of the two patients that died presented a mutation in a gene that bears potential connections to drug resistance. This mutation was absent in the initial sequencing before treatment.

17.
Cells ; 13(5)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38474393

RESUMEN

CD40 induces pro-inflammatory responses in endothelial and Müller cells and is required for the development of diabetic retinopathy (DR). CD40 is upregulated in these cells in patients with DR. CD40 upregulation is a central feature of CD40-driven inflammatory disorders. What drives CD40 upregulation in the diabetic retina remains unknown. We examined the role of advanced glycation end products (AGEs) in CD40 upregulation in endothelial cells and Müller cells. Human endothelial cells and Müller cells were incubated with unmodified or methylglyoxal (MGO)-modified fibronectin. CD40 expression was assessed by flow cytometry. The expression of ICAM-1 and CCL2 was examined by flow cytometry or ELISA after stimulation with CD154 (CD40 ligand). The expression of carboxymethyl lysine (CML), fibronectin, and laminin as well as CD40 in endothelial and Müller cells from patients with DR was examined by confocal microscopy. Fibronectin modified by MGO upregulated CD40 in endothelial and Müller cells. CD40 upregulation was functionally relevant. MGO-modified fibronectin enhanced CD154-driven upregulation of ICAM-1 and CCL2 in endothelial and Müller cells. Increased CD40 expression in endothelial and Müller cells from patients with DR was associated with increased CML expression in fibronectin and laminin. These findings identify AGEs as inducers of CD40 upregulation in endothelial and Müller cells and enhancers of CD40-dependent pro-inflammatory responses. CD40 upregulation in these cells is associated with higher CML expression in fibronectin and laminin in patients with DR. This study revealed that CD40 and AGEs, two important drivers of DR, are interconnected.


Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Humanos , Retinopatía Diabética/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Fibronectinas/metabolismo , Células Ependimogliales/metabolismo , Células Endoteliales/metabolismo , Óxido de Magnesio/metabolismo , Retina/metabolismo , Antígenos CD40/metabolismo , Ligando de CD40/metabolismo , Laminina/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Diabetes Mellitus/metabolismo
18.
Cureus ; 16(2): e54108, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38487146

RESUMEN

Introduction Ventilator-associated pneumonia (VAP) is the most common infectious complication related to admission to an Intensive Treatment Unit (ITU). Ventilator-associated lower respiratory tract infection (VA-LRTI) is a broader diagnosis than VAP. By disregarding radiological criteria, it will include both VAP and ventilator-associated tracheobronchitis. This study, conducted in the setting of a Portuguese ITU, aims to study the incidence, microbiology and clinical outcome of VA-LRTI and its association with COVID-19. Methods A retrospective cohort study included patients admitted to a Portuguese ITU who underwent invasive mechanical ventilation (IMV) for over 48 hours between 01/01/2021 and 31/12/2021. The Hospitals in Europe Link for Infection Control through Surveillance (HELICS) criteria were applied, disregarding the radiological criteria, for the diagnosis of VA-LRTI. Results The group of patients with COVID-19 had 46.38 episodes of VA-LRTI/1000 days of ventilation, while patients without COVID-19 had 16.35 episodes/1000 days of ventilation (RR 2.78, p < 0.001). Of the 85 microorganisms isolated, 82% were gram-negative microorganisms, with species of the genus Klebsiella being the most prevalent (22.4%). There was a lower prevalence of beta-lactam-resistant organisms in patients with COVID-19 (RR 0.35, p = 0.031). The development of VA-LRTI is associated with longer times of IMV (difference in medians 10 days, p < 0.001), but with no significant differences in mortality (RR 1.21, p = 0.14). Discussion Patients with COVID-19 seem more predisposed to developing VA-LRTI, possibly due to intrinsic characteristics of the disease. Although no increase in mortality has been demonstrated, VA-LRTI can entail important costs related to morbidity, antibiotic pressure and economic costs that must be considered.

19.
Dig Surg ; 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38412841

RESUMEN

Radical gastrectomy is associated with significant functional complications. In appropriate patients may be amenable to less invasive resection aimed at preserving the vagal trunks. The aim of this systematic review and meta-analysis is to assess the functional consequences and oncological safety of vagal sparing gastrectomy (VSG) compared to conventional non-vagal sparing gastrectomy (CG). A systematic review of four databases was undertaken for studies published between 1/11990 and 15/122021, comparing patients who underwent VSG to CG. We meta-analysed the following outcomes: operative time, blood loss, nodal yield, days to flatus, body weight changes, as well as the incidence of post-operative cholelithiasis, diarrhoea, delayed gastric emptying, and dumping syndrome. Thirty studies were included in the meta-analysis with a selection of studies qualitatively analysed. VSG was associated with a lower rate of cholelithiasis (OR 0.25, 95% CI 0.15-0.41, p<0.010) and early dumping syndrome (OR 0.42, 95% CI 0.21 - 0.86; p=0.02), less blood loss (MD -51 ml, 95% CI -89.11 to -12.81 ml, p=0.009), less long term weight loss (MD 2.03%, 95% CI 0.31-3.76%, p=0.02) and a faster time to flatus (MD -0.42 days, 95% CI -0.48 - 0.36, p<0.001). There was no significant difference in nodal harvest, overall survival, and all other endpoints. VSG significantly reduces the incidence of post-operative cholelithiasis and dumping syndrome, decreases weight loss and facilitates an earlier return of gut motility. Although technically more challenging, VSG should be considered for prophylactic surgery.

20.
Glob Health Action ; 17(1): 2297513, 2024 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-38323339

RESUMEN

Diabetes is estimated to affect between 3.3% and 8.3% of adults in Ghana, and prevalence is expected to rise. The lack of cost-effective diabetes prevention programmes designed specifically for the Ghanaian population warrants urgent attention. The Contextual Awareness, Response and Evaluation (CARE): Diabetes Project in Ghana is a mixed methods study that aims to understand diabetes in the Ga Mashie area of Accra, identify opportunities for community-based intervention and inform future diabetes prevention and control strategies. This paper presents the study design for the quantitative survey within the CARE project. This survey will take place in the densely populated Ga Mashie area of Accra, Ghana. A household survey will be conducted using simple random sampling to select households from 80 enumeration areas identified in the 2021 Ghana Population and Housing Census. Trained enumerators will interview and collect data from permanent residents aged ≥ 25 years. Pregnant women and those who have given birth in the last six months will be excluded. Data analysis will use a combination of descriptive and inferential statistics, and all analyses will account for the cluster sampling design. Analyses will describe the prevalence of diabetes, other morbidities, and associated risk factors and identify the relationship between diabetes and physical, social, and behavioural parameters. This survey will generate evidence on drivers and consequences of diabetes and facilitate efforts to prevent and control diabetes and other NCDs in urban Ghana, with relevance for other low-income communities.


Asunto(s)
Diabetes Mellitus , Enfermedades no Transmisibles , Embarazo , Adulto , Humanos , Femenino , Ghana/epidemiología , Prevalencia , Diabetes Mellitus/epidemiología , Factores de Riesgo
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