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1.
Clin Case Rep ; 12(6): e8985, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38836109

RESUMEN

We present a case of Cronkhite-Canada syndrome in a patient with decompensated cirrhosis who had successful induction of remission with nutritional supplementation alone. We propose that early institution of high-protein, high-energy enteral supplementation should be offered to all patients, especially those with compelling contraindications to immunosuppression.

2.
Transl Anim Sci ; 8: txae082, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38840693

RESUMEN

The objective was to determine the effects of ad libitum-fed roughage-based diets or limit-fed high-energy diets on growth performance, behavior, health, and digestion in newly received growing cattle and subsequent implications on feedlot growth performance and carcass characteristics. In experiment 1, 409 crossbred heifers (initial body weight [BW] = 279 ±â€…24 kg) in 32 pens were used in a randomized block design. Heifers were fed one of two dietary treatments: a total mixed ration with 0.99 Mcal net energy for gain (NEg)/kg dry matter (DM) fed ad libitum (0.99AL) or 1.32 Mcal NEg/kg DM limit-fed at 85% of intake of heifers fed 0.99AL (1.32LF85%). Both diets contained 40% DM as a branded wet corn gluten feed. In experiment 2, 370 crossbred heifers (initial BW = 225 ±â€…20 kg) were used in a randomized block design and were fed a diet formulated to contain 0.99 Mcal of NEg/kg DM for ad libitum intake or a diet formulated to contain 1.32 Mcal of NEg/kg DM and fed at 2.2% of BW daily (DM basis; 1.32LF2.2). For experiments 1 and 2, treatment integrity was maintained through the finishing phase where cattle were fed a common diet. Cattle were sorted by BW into heavy and light groups prior to finishing, with light cattle fed longer than heavy cattle to reach similar harvest BW. In experiment 3, eight ruminally cannulated heifers (average BW = 305 ±â€…23 kg) were used in a 2-period cross-over design and fed treatments from experiment 1 to assess digestibility and ruminal fermentation characteristics. Gain:feed was 47% and 35% greater (P < 0.01) in experiments 1 and 2, respectively, for limit-fed heifers compared with 0.99AL heifers. Rumination time was greater (P < 0.01) for 0.99AL compared with limit-fed treatments in experiments 1 and 2. Activity was greater (P < 0.01) for 1.32LF2.2 than for 0.99AL in experiment 2. In experiment 1, more (P = 0.03) carcasses from light-sort heifers than carcasses from heavy-sort heifers had livers with large, active abscesses. In experiment 2, finishing phase morbidity was greater (P < 0.01) for 1.32LF2.2 than for 0.99AL. Light-sort groups had fewer (P < 0.01) edible livers than heavy-sort groups, suggesting that greater number of days on feed may increase the risk of liver abscess prevalence and condemnation. In experiment 3, apparent total-tract DM and organic matter digestibilities were greater (P < 0.01) for 1.32LF85% than for 0.99AL. Overall, dietary treatments during the growing phase had little carryover effect on feedlot growth performance, carcass characteristics, or liver abscesses prevalence at harvest.

3.
Front Cell Neurosci ; 18: 1386352, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38841202

RESUMEN

Oligodendrocyte-lineage cells are central nervous system (CNS) glia that perform multiple functions including the selective myelination of some but not all axons. During myelination, synaptic vesicle release from axons promotes sheath stabilization and growth on a subset of neuron subtypes. In comparison, it is unknown if pre-myelinating oligodendrocyte process extensions selectively interact with specific neural circuits or axon subtypes, and whether the formation and stabilization of these neuron-glia interactions involves synaptic vesicle release. In this study, we used fluorescent reporters in the larval zebrafish model to track pre-myelinating oligodendrocyte process extensions interacting with spinal axons utilizing in vivo imaging. Monitoring motile oligodendrocyte processes and their interactions with individually labeled axons revealed that synaptic vesicle release regulates the behavior of subsets of process extensions. Specifically, blocking synaptic vesicle release decreased the longevity of oligodendrocyte process extensions interacting with reticulospinal axons. Furthermore, blocking synaptic vesicle release increased the frequency that new interactions formed and retracted. In contrast, tracking the movements of all process extensions of singly-labeled oligodendrocytes revealed that synaptic vesicle release does not regulate overall process motility or exploratory behavior. Blocking synaptic vesicle release influenced the density of oligodendrocyte process extensions interacting with reticulospinal and serotonergic axons, but not commissural interneuron or dopaminergic axons. Taken together, these data indicate that alterations to synaptic vesicle release cause changes to oligodendrocyte-axon interactions that are neuron subtype specific.

4.
J Hypertens ; 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38860390

RESUMEN

OBJECTIVES: Average values for self-measured blood pressure (SMBP) more accurately reflect a patient's risk of cardiovascular disease than do office measurements. Oftentimes, however, patients provide lists of individual home blood pressure (BP) measurements, and average values cannot be computed within the time constraints of a clinic visit. In contrast, the home BP load - defined as the proportion of BP values greater than a partition value (e.g., 130 mmHg) - can be easily calculated. We examined the utility of the BP load in predicting the mean SMBP and confirming elevated SMBP. METHODS: Four hundred twenty untreated adults at least 30 years of age acquired SMBP data twice in the morning and twice in the evening over 10 days. The 'true' SMBP was defined as the mean of these 40 determinations. RESULTS: Using all 10 days of BP data and a systolic BP threshold of 130 mmHg, the average SMBP associated with a home BP load of 0.50 was 130 mmHg, with a 95% prediction interval of 126-133 mmHg. True systolic SMBP was approximately 6 mmHg lower and higher at home BP loads of 0.25 and 0.75, respectively. There was a 90% probability that the true systolic SMBP was greater than 130 mmHg if the systolic home BP load was at least 0.60. Corresponding values for 3 days and 1 day of SMBP were at least 0.68 and at least 0.84, respectively. CONCLUSION: Our analysis demonstrates that the home BP load can be used to estimate the average BP acquired on home monitoring and confirm elevated SMBP.

5.
medRxiv ; 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38853946

RESUMEN

Greater perceived physical fatigability and lower skeletal muscle energetics are predictors of mobility decline. Characterizing associations between muscle energetics and perceived fatigability may provide insight into potential targets to prevent mobility decline. We examined associations of in vivo (maximal ATP production, ATPmax) and ex vivo (maximal carbohydrate supported oxidative phosphorylation [max OXPHOS] and maximal fatty acid supported OXPHOS [max FAO OXPHOS]) measures of mitochondrial energetics with two measures of perceived physical fatigability, Pittsburgh Fatigability Scale (PFS, 0-50, higher=greater) and Rating of Perceived Exertion (RPE Fatigability, 6-20, higher=greater) after a slow treadmill walk. Participants from the Study of Muscle, Mobility and Aging (N=873) were 76.3±5.0 years old, 59.2% women, and 85.3% White. Higher muscle energetics (both in vivo and ex vivo ) were associated with lower perceived physical fatigability, all p<0.03. When stratified by sex, higher ATPmax was associated with lower PFS Physical for men only; higher max OXPHOS and max FAO OXPHOS were associated with lower RPE fatigability for both sexes. Higher skeletal muscle energetics were associated with 40-55% lower odds of being in the most (PFS≥25, RPE Fatigability≥12) vs least (PFS 0-4, RPE Fatigability 6-7) severe fatigability strata, all p<0.03. Being a woman was associated with 2-3 times higher odds of being in the most severe fatigability strata when controlling for ATPmax but not the in vivo measures (p<0.05). Better mitochondrial energetics were linked to lower fatigability and less severe fatigability in older adults. Findings imply that improving skeletal muscle energetics may mitigate perceived physical fatigability and prolong healthy aging.

6.
medRxiv ; 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38826359

RESUMEN

COVID-19 disproportionately affected minorities, while research barriers to engage underserved communities persist. Serological studies reveal infection and vaccination histories within these communities, however lack of consensus on downstream evaluation methods impede meta-analyses and dampen the broader public health impact. To reveal the impact of COVID-19 and vaccine uptake among diverse communities and to develop rigorous serological downstream evaluation methods, we engaged racial and ethnic minorities in Massachusetts in a cross-sectional study (April - July 2022), screened blood and saliva for SARS-CoV-2 and human endemic coronavirus (hCoV) antibodies by bead-based multiplex assay and point-of-care (POC) test and developed across-plate normalization and classification boundary methods for optimal qualitative serological assessments. Among 290 participants, 91.4 % reported receiving at least one dose of a COVID-19 vaccine, while 41.7 % reported past SARS-CoV-2 infections, which was confirmed by POC- and multiplex-based saliva and blood IgG seroprevalences. We found significant differences in antigen-specific IgA and IgG antibody outcomes and indication of cross-reactivity with hCoV OC43. Finally, 26.5 % of participants reported lingering COVID-19 symptoms, mostly middle-aged Latinas. Hence, prolonged COVID-19 symptoms were common among our underserved population and require public health attention, despite high COVID-19 vaccine uptake. Saliva served as a less-invasive sample-type for IgG-based serosurveys and hCoV cross-reactivity needed to be evaluated for reliable SARS-CoV-2 serosurvey results. Using the developed rigorous downstream qualitative serological assessment methods will help standardize serosurvey outcomes and meta-analyses for future serosurveys beyond SARS-CoV-2.

7.
J Chem Phys ; 160(21)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38828818

RESUMEN

Here, we report the frequency-dependent spectrum of ice Ih in the range of 0.2-2 THz. We confirm the presence of a feature that blue-shifts from around 1.55-1.65 THz with a decreasing temperature from 260 to 160 K. There is also a change in the trend of the refractive index of ice corresponding to a dispersion, which is also around 1.6 THz. The features are reproduced in data acquired with three commercial terahertz time-domain spectrometers. Computer-simulated spectra assign the feature to lattice translations perpendicular to the 110 and 1̄10 planes of the ice Ih crystal. The feature's existence should be recognized in the terahertz measurements of frozen aqueous solution samples to avoid false interpretations.

8.
Spine J ; 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38838854

RESUMEN

BACKGROUND CONTEXT: With the goal of improving patient outcomes, the Integrated Spine Center at UT Southwestern Medical Center implemented an Enhanced Recovery After Surgery (ERAS) protocol which includes pre- and post-surgery guidelines. Numerous studies have shown benefit of implementation of ERAS protocols to standardize peri-operative care in line with best practices; however, the literature on complication rates, LOS, and readmissions shows mixed results. PURPOSE: The goal of this study was to investigate the impact of the ERAS protocol implementation on complication rates in the perioperative period, as well as hospital and ICU length of stay and hospital re-admission rates. STUDY DESIGN/SETTING: A retrospective cohort study was performed on all patients who underwent spine surgery between September 2016 and September 2021 at a single institution. Patients who met inclusion criteria were divided into non-ERAS and ERAS groups, and comparative statistics were used to evaluate ERAS protocol effectiveness. PATIENT SAMPLE: All patients who underwent spine surgery at UT Southwestern between September 2016 and September 2021 were evaluated for inclusion in the study. The patient sample was further refined to include only complex patient cases which were able to receive the full ERAS protocol (non-emergent admissions). OUTCOME MEASURES: Presence of absence of post-operative complications including surgical site infection, AKI, DVT, MI, sepsis, pneumonia, PE, stroke, shock, and other complications were compared between groups, as were hospital and ICU length of stay, and 7, 30, and 90 day readmissions. Self-reported or functional measures were not used in outcome evaluation. METHODS: A database of patient and surgery characteristics was built using an EMR query tool with spot checks performed by the authors. Control and treatment groups were matched for gender, age, BMI, ASA score, and surgery type. Total number of complication rates was compared between ERAS and non-ERAS groups, and comparative statistics were used to determine significance. RESULTS: Significant differences between ERAS versus non-ERAS groups were found in rates of UTI (6.8% vs. 3.1%, respectively; P=0.031), constipation (20.6% vs. 11.4%, respectively; P=0.001), and any complications (31.4% vs. 19.4%, respectively; P<0.001). There was no significant difference in the rates of other complications, in length of hospital or ICU stay, or readmissions at 7, 30, and 90 days. CONCLUSIONS: Implementation of the ERAS protocol did not decrease complication rates or length of stay, and ERAS patients had significantly higher rates of UTI, constipation, and any complications. There may have been confounding factors due to the impact of COVID-19 on delivery of care, as well as misalignment between ERAS goals and outcome measures.

9.
J Drugs Dermatol ; 23(6): e144-e148, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38834228

RESUMEN

Bullous pemphigoid is often difficult to treat with the limited therapies available. Here, we describe clinical outcomes among 30 adults with bullous pemphigoid patients treated with dupilumab. We performed a multicenter, retrospective case series between March 2020 to August 2022. Patients received a loading dose of dupilumab 600 mg, followed by 300 mg maintenance dose with varying administration frequency tailored to individual patient response. All patients experienced at least some improvement in blister formation and pruritus, with 23 (76.7%) of patients demonstrating either complete clearance of blistering or marked response. Complete clearance of pruritus or marked response was noted in 25 (83.3%) of patients. Eight patients were effectively maintained solely on dupilumab. One (3.3%) patient reported an injection site reaction. Thirty patients represent a small sample, however, to our knowledge, this is the second largest group of BP treated with dupilumab. Furthermore, we provide an understandable framework for clinicians outside of academics to follow and assess treatment responses in their BP patients treated with dupilumab. Dupilumab should be considered as a therapeutic option in patients with bullous pemphigoid given its ability to induce sustained blistering and pruritus response in both typical and refractory cases while maintaining a favorable safety profile. J Drugs Dermatol. 2024;23(6):e144-e148. doi:10.36849/JDD.8258e.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Penfigoide Ampolloso , Prurito , Humanos , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/diagnóstico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Estudios Retrospectivos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Anciano de 80 o más Años , Prurito/tratamiento farmacológico , Prurito/etiología , Prurito/diagnóstico , Adulto , Reacción en el Punto de Inyección/etiología , Reacción en el Punto de Inyección/diagnóstico
10.
Vet Surg ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38841876

RESUMEN

OBJECTIVE: To determine the influence of arthroscopy and injection volume on post-procedure intra-articular (IA) injection extravasation. STUDY DESIGN: Ex vivo prospective study. SAMPLE POPULATION: A total of 40 paired canine cadaver forelimbs. METHODS: After radiographs and computed tomography (CT) scans with three-dimensional (3D) digital bone model reconstructions, elbows were randomly assigned to the arthroscopy or control group and randomly assigned to receive an IA injection of 2 or 4 mL of contrast. Elbow arthroscopy was performed on assigned specimens, followed by IA injections of contrast in all elbows, and imaging was repeated. 3D digital model volumes were compared. Images were interpreted and scored for extravasation by a radiologist unaware of treatment and volume assignments. RESULTS: Based on CT images and regardless of treatment group, IA injections of 4 mL resulted in a mean extravasation score of 2.25 (SD 0.97) versus 1.55 (SD 1.05) (p = .02) for 2 mL IA injections. The change in 3D model volumes after IA injections was a mean of 13.2 cm3 (SD 5.85) after 4 mL injections, compared to 6.97 cm3 (SD 6.28) (p = .003) after 2 mL injections. On radiographic evaluation, but not CT, the mean extravasation scores were 2.45 (SD 1.15) for the arthroscopy group and 1.25 (SD 0.79) for the control group (p < .001). CONCLUSION: A larger volume of IA injection resulted in higher CT extravasation scores and larger 3D volumes regardless of arthroscopic treatment. CLINICAL SIGNIFICANCE: IA injections performed immediately after arthroscopy resulted in 50% or less extravasation, especially with a smaller IA injection volume.

11.
Artículo en Inglés | MEDLINE | ID: mdl-38842034

RESUMEN

OBJECTIVE: Initiating postoperative radiotherapy (PORT) within 6 weeks of surgery for head and neck squamous cell carcinoma (HNSCC) is included in the National Comprehensive Cancer Network Clincal Practice Guidelines and is a Commission on Cancer quality metric. Factors associated with delays in starting PORT have not been systematically described nor synthesized. DATA SOURCES: PubMed, Scopus, and CINAHL. REVIEW METHODS: We included studies describing demographic characteristics, clinical factors, or social determinants of health associated with PORT delay (>6 weeks) in patients with HNSCC treated in the United States after 2003. Meta-analysis of odds ratios (ORs) was performed on nonoverlapping datasets. RESULTS: Of 716 unique abstracts reviewed, 21 studies were included in the systematic review and 15 in the meta-analysis. Study sample size ranged from 19 to 60,776 patients. In the meta-analysis, factors associated with PORT delay included black race (OR, 1.46, 95% confidence interval [CI]: 1.28-1.67), Hispanic ethnicity (OR, 1.37, 95% CI, 1.17-1.60), Medicaid or no health insurance (OR, 2.01, 95% CI, 1.90-2.13), lower income (OR, 1.38, 95% CI, 1.20-1.59), postoperative admission >7 days (OR, 2.92, 95% CI, 2.31-3.67), and 30-day hospital readmission (OR, 1.37, 95% CI, 1.29-1.47). CONCLUSION: Patients at greatest risk for a delay in initiating guideline-adherent PORT include those who are from minoritized communities, of lower socioeconomic status, and experience postoperative challenges. These findings provide the foundational evidence needed to deliver targeted interventions to enhance equity and quality in HNSCC care delivery.

12.
Elife ; 132024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38847388

RESUMEN

Facultative parthenogenesis (FP) has historically been regarded as rare in vertebrates, but in recent years incidences have been reported in a growing list of fish, reptile, and bird species. Despite the increasing interest in the phenomenon, the underlying mechanism and evolutionary implications have remained unclear. A common finding across many incidences of FP is either a high degree of homozygosity at microsatellite loci or low levels of heterozygosity detected in next-generation sequencing data. This has led to the proposal that second polar body fusion following the meiotic divisions restores diploidy and thereby mimics fertilization. Here, we show that FP occurring in the gonochoristic Aspidoscelis species A. marmoratus and A. arizonae results in genome-wide homozygosity, an observation inconsistent with polar body fusion as the underlying mechanism of restoration. Instead, a high-quality reference genome for A. marmoratus and analysis of whole-genome sequencing from multiple FP and control animals reveals that a post-meiotic mechanism gives rise to homozygous animals from haploid, unfertilized oocytes. Contrary to the widely held belief that females need to be isolated from males to undergo FP, females housed with conspecific and heterospecific males produced unfertilized eggs that underwent spontaneous development. In addition, offspring arising from both fertilized eggs and parthenogenetic development were observed to arise from a single clutch. Strikingly, our data support a mechanism for facultative parthenogenesis that removes all heterozygosity in a single generation. Complete homozygosity exposes the genetic load and explains the high rate of congenital malformations and embryonic mortality associated with FP in many species. Conversely, for animals that develop normally, FP could potentially exert strong purifying selection as all lethal recessive alleles are purged in a single generation.


Asunto(s)
Lagartos , Partenogénesis , Animales , Partenogénesis/genética , Femenino , Lagartos/genética , Masculino , Meiosis/genética , Homocigoto
15.
Molecules ; 29(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38893345

RESUMEN

Among brain tumors, glioblastoma (GBM) is very challenging to treat as chemotherapeutic drugs can only penetrate the brain to a limited extent due to the blood-brain barrier (BBB). Nanoparticles can be an attractive solution for the treatment of GBM as they can transport drugs across the BBB into the tumor. In this study, normal and GBM organoids comprising six brain cell types were developed and applied to study the uptake, BBB penetration, distribution, and efficacy of fluorescent, ultrasmall gold nanoparticles (AuTio-Dox-AF647s) conjugated with doxorubicin (Dox) and AlexaFluor-647-cadaverine (AF647) by confocal laser scanning microscopy (CLSM), using a mixture of dissolved doxorubicin and fluorescent AF647 molecules as a control. It was shown that the nanoparticles could easily penetrate the BBB and were found in normal and GBM organoids, while the dissolved Dox and AF647 molecules alone were unable to penetrate the BBB. Flow cytometry showed a reduction in glioblastoma cells after treatment with AuTio-Dox nanoparticles, as well as a higher uptake of these nanoparticles by GBM cells in the GBM model compared to astrocytes in the normal cell organoids. In summary, our results show that ultrasmall gold nanoparticles can serve as suitable carriers for the delivery of drugs into organoids to study BBB function.


Asunto(s)
Barrera Hematoencefálica , Doxorrubicina , Glioblastoma , Oro , Nanopartículas del Metal , Organoides , Doxorrubicina/farmacología , Doxorrubicina/química , Doxorrubicina/farmacocinética , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patología , Nanopartículas del Metal/química , Oro/química , Humanos , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Organoides/efectos de los fármacos , Organoides/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral
16.
Adv Virus Res ; 119: 63-110, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38897709

RESUMEN

The surfaces of cells and enveloped viruses alike are coated in carbohydrates that play multifarious roles in infection and immunity. Organisms across all kingdoms of life make use of a diverse set of monosaccharide subunits, glycosidic linkages, and branching patterns to encode information within glycans. Accordingly, sugar-patterning enzymes and glycan binding proteins play integral roles in cell and organismal biology, ranging from glycoprotein quality control within the endoplasmic reticulum to lymphocyte migration, coagulation, inflammation, and tissue homeostasis. Unsurprisingly, genes involved in generating and recognizing oligosaccharide patterns are playgrounds for evolutionary conflicts that abound in cross-species interactions, exemplified by the myriad plant lectins that function as toxins. In vertebrates, glycans bearing acidic nine-carbon sugars called sialic acids are key regulators of immune responses. Various bacterial and fungal pathogens adorn their cells in sialic acids that either mimic their hosts' or are stolen from them. Yet, how viruses commandeer host sugar-patterning enzymes to thwart immune responses remains poorly studied. Here, we review examples of viruses that interact with sialic acid-binding immunoglobulin-like lectins (Siglecs), a family of immune cell receptors that regulate toll-like receptor signaling and govern glycoimmune checkpoints, while highlighting knowledge gaps that merit investigation. Efforts to illuminate how viruses leverage glycan-dependent checkpoints may translate into new clinical treatments that uncloak viral antigens and infected cell surfaces by removing or masking immunosuppressive sialoglycans, or by inhibiting viral gene products that induce their biosynthesis. Such approaches may hold the potential to unleash the immune system to clear long intractable chronic viral infections.


Asunto(s)
Glicocálix , Virus , Glicocálix/metabolismo , Humanos , Animales , Virus/inmunología , Virus/metabolismo , Polisacáridos/metabolismo , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico/metabolismo , Virosis/inmunología , Virosis/metabolismo , Virosis/virología , Interacciones Huésped-Patógeno/inmunología
17.
Trends Plant Sci ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38897884

RESUMEN

The Green Revolution transformed agriculture with high-yielding, stress-resistant varieties. However, the urgent need for more sustainable agricultural development presents new challenges: increasing crop yield, improving nutritional quality, and enhancing resource-use efficiency. Soil plays a vital role in crop-production systems and ecosystem services, providing water, nutrients, and physical anchorage for crop growth. Despite advancements in plant and soil sciences, our understanding of belowground plant-soil interactions, which impact both crop performance and soil health, remains limited. Here, we argue that a lack of understanding of these plant-soil interactions hinders sustainable crop production. We propose that targeted engineering of crops and soils can provide a fresh approach to achieve higher yields, more efficient sustainable crop production, and improved soil health.

18.
Int J Surg ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38869970

RESUMEN

INTRODUCTION: Despite advanced infection control practices including preoperative antibiotic prophylaxis, surgical site infection (SSI) remains a challenge. This study aimed to test whether local administration of a novel prolonged-release Doxycycline-Polymer-Lipid Encapsulation matriX (D-PLEX) before wound closure, concomitantly with standard of care (SOC), reduces the incidence of incisional SSI after elective abdominal colorectal surgery. MATERIALS AND METHODS: This was a phase 3 randomized, controlled, double-blind, multinational study (SHIELD 1) between June 2020 to June 2022. Patients with at least one abdominal incision length >10 cm were randomized 1:1 to the investigational arm (D-PLEX+SOC) or control (SOC) arm . The primary outcome was a composite of incisional SSI, incisional reintervention, and all-cause mortality. RESULTS: A total of 974 patients were analyzed, of whom 579 (59.4%) were male. The mean age (±SD) was 64.2±13.0 years. The primary outcome occurred in 9.3% of D-PLEX patients versus 12.1% (SOC) (risk difference estimate [RDE], -2.8%; 95% CI [-6.7%, 1.0%], P=0.1520). In a pre-specified analysis by incision length, a reduction in the primary outcome was observed in the >20 cm subpopulation: 8% (D-PLEX) versus 17.5% (SOC) (RDE, -9.4%; 95% CI [-15.5%, -3.2%], P=0.0032). In the >10 to ≤20 cm subgroup, no reduction was observed: 9.9% versus 7.9% (RDE, 2.0%; 95% CI [-2.8%, 6.7%], P=0.4133). Exploratory post-hoc analyses of patients with increased SSI risk (≥1 patient-specific comorbidity) indicated a reduction in the incidence of the primary outcome: 9.0% (D-PLEX) versus 13.7% (SOC) (RDE, -4.8%; 95% CI [-9.5%, -0.1%], P=0.0472). The D-PLEX safety profile was good (no difference in treatment-emergent adverse events between the groups). CONCLUSIONS: The SHIELD-1 study did not meet its primary outcome of reduced incisional SSI, incisional reinterventions, or all-cause mortality. Pre-specified and post-hoc analyses suggested that D-PLEX may reduce the incidence of the primary outcome event in patients with increased SSI risk, including lengthy incisions.

19.
Neurology ; 103(1): e209496, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38870464

RESUMEN

BACKGROUND AND OBJECTIVES: Prolonged compound muscle action potential (CMAP) duration and preferential loss of myosin are considered the diagnostic hallmarks of critical illness myopathy (CIM); however, their correlation and prognostic values have not been studied. We aimed to investigate the correlation between CMAP duration and myosin loss and their effect on mortality by comparing between patients with CIM with and without myosin loss. METHODS: We searched the Mayo Clinic Electromyography Laboratory databases (1986-2021) for patients diagnosed with CIM on the basis of prolonged distal CMAP durations (>15 msec in fibular motor nerve studies recording over the tibialis anterior or >8 msec in other motor nerves) and needle EMG findings compatible with myopathy. Electrodiagnostic studies were generally performed within 24 hours after weakness became noticeable. We included only patients who underwent muscle biopsy. Clinical, electrophysiologic, and myopathologic data were reviewed. We conducted myosin/actin ratio analysis when muscle tissue was available. We used the Fisher exact test for categorical data comparisons and the Mann-Whitney 2-tailed test for continuous data. We applied the Kaplan-Meier technique to analyze survival rates. RESULTS: Twenty patients (13 female patients) were identified [median age at diagnosis of 62.5 years (range: 19-80 years)]. The median onset of weakness was 24 days (range: 1-128) from the first day of intensive care unit admission. Muscle biopsy showed myosin loss in 14 patients, 9 of whom had >50% of myofibers affected (high grade). Type 2 fiber atrophy was observed in 19 patients, 13 of whom also had myosin loss. Patients with myosin loss had higher frequency of steroid exposure (14 vs 3; p = 0.004); higher median number of necrotic fibers per low-power field (2.5 vs 1, p = 0.04); and longer median CMAP duration (msec) of fibular (13.4 vs 8.75, p = 0.02), tibial (10 vs 7.8, p = 0.01), and ulnar (11.1 vs 7.95, p = 0.002) nerves compared with those without. Only patients with high-grade myosin loss had reduced myosin/actin ratios (<1.7). Ten patients died during median follow-up of 3 months. The mortality rate was similar between patients with and without myosin loss. Patients with high-grade myosin loss had a lower overall survival rate than those with low-grade or no myosin loss, but this was not statistically significant (p = 0.05). DISCUSSION: Myosin loss occurred in 70% of the patients with CIM with prolonged CMAP duration. Longer CMAP duration predicts myosin-loss pathology. The extent of myosin loss marginally correlates with the mortality rate. Our findings highlight the potential prognostic values of CMAP duration and myosin loss severity in predicting disease outcome.


Asunto(s)
Potenciales de Acción , Enfermedad Crítica , Electromiografía , Músculo Esquelético , Enfermedades Musculares , Miosinas , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Potenciales de Acción/fisiología , Pronóstico , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Enfermedades Musculares/patología , Enfermedades Musculares/fisiopatología , Enfermedades Musculares/metabolismo , Miosinas/metabolismo , Adulto , Estudios Retrospectivos , Anciano de 80 o más Años
20.
Artículo en Inglés | MEDLINE | ID: mdl-38871179

RESUMEN

INTRODUCTION: The risk of complications associated with transvenous ICDs make the subcutaneous implantable cardiac defibrillator (S-ICD) a valuable alternative in patients with adult congenital heart disease (ACHD). However, higher S-ICD ineligibility and higher inappropriate shock rates-mostly caused by T wave oversensing (TWO)- are observed in this population. We report a novel application of deep learning methods to screen patients for S-ICD eligibility over a longer period than conventional screening. METHODS: Adult patients with ACHD and a control group of normal subjects were fitted with a 24-h Holters to record their S-ICD vectors. Their T:R ratio was analysed utilising phase space reconstruction matrices and a deep learning-based model to provide an in-depth description of the T: R variation plot for each vector. T: R variation was compared statistically using t-test. RESULTS: 13 patients (age 37.4 ± 7.89 years, 61.5 % male, 6 ACHD and 7 control subjects) were enrolled. A significant difference was observed in the mean and median T: R values between the two groups (p < 0.001). There was also a significant difference in the standard deviation of T: R between both groups (p = 0.04). CONCLUSIONS: T:R ratio, a main determinant for S-ICD eligibility, is significantly higher with more tendency to fluctuate in ACHD patients when compared to a population with normal hearts. We hypothesise that our novel model could be used to select S-ICD eligible patients by better characterisation of T:R ratio, reducing the risk of TWO and inappropriate shocks in the ACHD patient cohort.

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