Unveiling the Brazilian kefir microbiome: discovery of a novel Lactobacillus kefiranofaciens (LkefirU) genome and in silico prospection of bioactive peptides with potential anti-Alzheimer properties.

BACKGROUND: Kefir is a complex microbial community that plays a critical role in the fermentation and production of bioactive peptides, and has health-improving properties. The composition of kefir can vary by geographic localization and weather, and this paper focuses on a Brazilian sample and continues previous work that has successful anti-Alzheimer properties. In this study, we employed shotgun metagenomics and peptidomics approaches to characterize Brazilian kefir further. RESULTS: We successfully assembled the novel genome of Lactobacillus kefiranofaciens (LkefirU) and conducted a comprehensive pangenome analysis to compare it with other strains. Furthermore, we performed a peptidome analysis, revealing the presence of bioactive peptides encrypted by L. kefiranofaciens in the Brazilian kefir sample, and utilized in silico prospecting and molecular docking techniques to identify potential anti-Alzheimer peptides, targeting ß-amyloid (fibril and plaque), BACE, and acetylcholinesterase. Through this analysis, we identified two peptides that show promise as compounds with anti-Alzheimer properties. CONCLUSIONS: These findings not only provide insights into the genome of L. kefiranofaciens but also serve as a promising prototype for the development of novel anti-Alzheimer compounds derived from Brazilian kefir.

Focal point technology: Controlling treatment depth and pattern of skin injury by a novel highly focused laser.

BACKGROUND: Selective photothermolysis has limitations in efficacy and safety for dermal targets. We describe a novel concept using scanned focused laser microbeams for precise control of dermal depth and pattern of injury, using a 1550 nm laser that generates an array of conical thermal zones while minimizing injury to the epidermis. OBJECTIVE: To characterize the conical thermal zones in vivo and determine safe starting parameters to transition to a second phase to explore potential clinical indications. METHODS: A focused toroidal (ring) laser beam was delivered through a cold sapphire window, sparing epidermal injury in a central zone. Pulse energy, lesion depth, density, and energy delivery were titrated in ex vivo human skin and subsequently on the backs of 21 human subjects. RESULTS: Histology showed microscale patterns of thermal injury, which varied predictably with laser parameters. Time-course healing through histology and skin surface imaging demonstrated the ability of the device to deliver high energies without sequelae. LIMITATIONS: Clinical data are currently being collected to further explore the safety and efficacy of the device. CONCLUSION: The 1550 nm laser with focal point technology enables precise control of lesion depth while simultaneously sparing a large portion of the epidermis, lowering the risk of adverse effects.

Diverse decarbonization pathways under near cost-optimal futures.

Energy system optimization models offer insights into energy and emissions futures through least-cost optimization. However, real-world energy systems often deviate from deterministic scenarios, necessitating rigorous uncertainty exploration in macro-energy system modeling. This study uses modeling techniques to generate diverse near cost-optimal net-zero CO2 pathways for the United States' energy system. Our findings reveal consistent trends across these pathways, including rapid expansion of solar and wind power generation, substantial petroleum use reductions, near elimination of coal combustion, and increased end-use electrification. We also observe varying deployment levels for natural gas, hydrogen, direct air capture of CO2, and synthetic fuels. Notably, carbon-captured coal and synthetic fuels exhibit high adoption rates but only in select decarbonization pathways. By analyzing technology adoption correlations, we uncover interconnected technologies. These results demonstrate that diverse pathways for decarbonization exist at comparable system-level costs and provide insights into technology portfolios that enable near cost-optimal net-zero CO2 futures.

Live birth and maternity outcome in childhood and adolescent cancer survivors under 18 years at diagnosis: a 40-year population-based cohort study.

BACKGROUND: Survival from childhood and adolescent cancer has increased, but the chance of a livebirth in female survivors under 18 years at diagnosis may be reduced. METHODS: We performed a national population-based analysis, including all female cancer survivors diagnosed in Scotland before the age of 18 years between 1981 and 2012. Scottish Cancer Registry records were linked to Scottish maternity records. Females from the exposed group with no pregnancies before cancer diagnosis (n = 2118) were compared with three general population controls matched for age and year of diagnosis. FINDINGS: The cumulative incidence of a livebirth for all diagnoses was reduced to 37% (95% CI 33-40%) for cancer survivors at 30 years of age vs 58% (57-60%) for controls. The deficit varying by diagnosis: for lymphoid leukaemia, the cumulative incidence at 30 years was 29% (23-36%) vs 57% (52-61%) for controls with similar deficits in CNS tumours and retinoblastoma. There was a steady improvement in the chance of livebirth in those diagnosed more recently. INTERPRETATION: We have shown a reduced chance of livebirth in female survivors of cancer diagnosed before age 18. The deficit is present for all diagnoses.

A practical device to produce consistent, controlled cryoinjury on the skin.

It has long been known that sensitivity to cold-induced damage can vary greatly between different cell types, with lethal temperatures reportedly ranging from -2 °C for canine osteocytes, to -70 °C for mammary adenocarcinomas. This suggests that, for certain applications, "therapeutic windows" may exist wherein the cryosurgery temperature could be controlled to specifically target more cold-sensitive cell types, while sparing less sensitive cells. However, this potential selectivity has not been developed into practical clinical treatments, in part because of a lack of available investigative tools that can provide consistent, reproducible cooling within the desired temperature range. Here we describe an experimental cryosurgery tool that allows user control over the three key cryosurgery parameters - temperature, pressure, and duration. The tool is composed of inexpensive components that are generally accessible in most laboratory settings, and could be a practical investigative tool for developing and optimizing novel topical cryosurgery approaches.

Effect of hyaluronic acid-stabilized silver nanoparticles on lettuce (Lactuca sativa L.) seed germination.

Nanotechnology has brought significant advancements to agriculture through the development of engineered nanomaterials (ENPs). Silver nanoparticles (AgNPs) capped with polysaccharides have been applied in agricultural diagnostics, crop pest management, and seed priming. Hyaluronic acid (HA), a natural polysaccharide with bactericidal properties, has been considered a growth regulator for plant tissues and an inducer of systemic resistance against plant diseases. Additionally, HA has been employed as a stabilizing agent for AgNPs. This study investigated the synthesis and effects of hyaluronic acid-stabilized silver nanoparticles (HA-AgNPs) as a seed priming agent on lettuce (Lactuca sativa L.) seed germination. HA-AgNPs were characterized using several techniques, exhibiting spherical morphology and good colloidal stability. Germination assays conducted with 0.1, 0.04, and 0.02 g/L of HA-AgNPs showed a concentration-dependent reduction in seed germination. Conversely, lower concentrations of HA-AgNPs significantly increased germination rates, survival, tolerance indices, and seed water absorption compared to silver ions (Ag+). SEM/EDS indicated more significant potential for HA-AgNPs internalization compared to Ag+. Therefore, these findings are innovative and open new avenues for understanding the impact of Ag+ and HA-AgNPs on seed germination.

Successful Extracorporeal Cardiopulmonary Resuscitation Despite Aortic Occlusion.

We present the case of a 62-year-old man with severe coronary artery disease who presented to the hospital in refractory ventricular fibrillation cardiac arrest. He showed signs of life despite prolonged resuscitation. We thus decided to initiate extracorporeal cardiopulmonary resuscitation (ECPR). The patient had a known total occlusion of his infrarenal aorta that had been surgically bypassed with a bifemoral-axillary graft. We successfully initiated ECPR via the surgical graft, establishing blood flow to the central circulation through the axillary artery in a peripheral configuration while ensuring blood flow to the left leg via the femoral-femoral graft. The patient was extubated neurologically intact the following day and subsequently underwent coronary artery bypass graft surgery while on extracorporeal membrane oxygenation (ECMO) support. He was subsequently weaned off inotropic support and decannulated from ECMO. He was discharged home neurologically intact and independent in his activities of daily living. This case demonstrates that cannulation for ECPR via a surgical vascular graft is possible and that a total occlusion of the infrarenal aorta in the presence of a surgical bypass is not an absolute contraindication to ECMO.

Attentional Focus Strategies Can Improve Performance of Postural Control in Runners.

Attentional focus strategies, especially external focus, are associated with improvements in mechanisms of postural control. This can be important in reducing sports injuries in practices such as running, which has seen an increase in adherence. However, the impacts of these strategies on postural control in runners are unclear. This study aimed to investigate the effects of internal and external focus strategies on postural control performance with different bases of support tasks in runners. A total of 19 young adults (18-38 years old) were divided into a running group (n = 9) and a control group (n = 10). Posturography tests were performed on stable and unstable surfaces, under control, and internal and external focus conditions. The distance, mean velocity, and total velocity of the center of pressure were analyzed (p ≤ .05). There was a reduction in oscillation under external focus compared to internal and control conditions, as well as under internal focus compared to the control condition. A Group × Surface × Focus interaction for the variables distance and mean velocity in the mediolateral direction was found only for the control group. However, no significant effects were found between groups for postural control performance. Attentional focus strategies were able to reduce postural sway, with external focus condition being the most effective. Practitioners can benefit from these strategies to increase postural control performance to help reduce the number of injuries and improve sports performance. It is speculated that the effects of attentional control strategies on postural control may differ depending on the specific adaptations of each sport.

Structural and molecular characteristics of weight-bearing volar skin can be reconstituted by micro skin tissue column grafting.

For patients with lower limb amputations, prostheses are immensely helpful for mobility and the ability to perform job-related or recreational activities. However, the skin covering the amputation stump is typically transposed from adjacent areas of the leg and lacks the weight-bearing capacity that is only found in the specialized skin covering the palms and soles (a.k.a. volar skin). As a result, the skin tissue in direct contact with the prosthesis frequently breaks down, leading to the development of painful sores and other complications that limit, and often preclude, the use of prostheses. Transplanting volar skin onto amputation stumps could be a solution to these problems, but traditional skin transplantation techniques cause substantial morbidity at the donor site, such as pain and scarring, which are especially problematic for volar skin given the critical functional importance of the volar skin areas. We previously developed the technology to collect and engraft full-thickness skin tissue while avoiding long-term donor site morbidity, by harvesting the skin in the form of small (~0.5 mm diameter) cores that we termed "micro skin tissue columns" (MSTCs), so that each donor wound is small enough to heal quickly and without clinically appreciable scarring or other long-term abnormalities. The goal of this study was to establish whether a similar approach could be used to confer the structural and molecular characteristics of volar skin ectopically to other skin areas. In a human-to-mouse xenograft model, we show the long-term persistence of various human plantar MSTC-derived cell types in the murine recipient. Then in an autologous porcine model, we harvested MSTCs from the bottom of the foot and transplanted them onto excision wounds on the animals' trunks. The healing processes at both the donor and graft sites were monitored over 8 weeks, and tissue samples were taken to verify volar-specific characteristics by histology and immunohistochemistry. The volar donor sites were well-tolerated, healed rapidly, and showed no signs of scarring or any other long-term defects. The graft sites were able to maintain volar-specific histologic features and expression of characteristics protein markers, up to the 8-week duration of this study. These results suggest that MSTC grafting could be a practical approach to obtain autologous donor volar skin tissue, confer volar skin characteristics ectopically to nonvolar skin areas, improve the load-bearing capacity of amputation stump skin, and ultimately enhance mobility and quality-of-life for lower limb amputees.

Lower Microscopy Sensitivity with Decreasing Malaria Prevalence in the Urban Amazon Region, Brazil, 2018-2021.

Malaria is increasingly diagnosed in urban centers across the Amazon Basin. In this study, we combined repeated prevalence surveys over a 4-year period of a household-based random sample of 2,774 persons with parasite genotyping to investigate the epidemiology of malaria in Mâncio Lima, the main urban transmission hotspot in Amazonian Brazil. We found that most malarial infections were asymptomatic and undetected by point-of-care microscopy. Our findings indicate that as malaria transmission decreases, the detection threshold of microscopy rises, resulting in more missed infections despite similar parasite densities estimated by molecular methods. We identified genetically highly diverse populations of Plasmodium vivax and P. falciparum in the region; occasional shared lineages between urban and rural residents suggest cross-boundary propagation. The prevalence of low-density and asymptomatic infections poses a significant challenge for routine surveillance and the effectiveness of malaria control and elimination strategies in urbanized areas with readily accessible laboratory facilities.

Analysis of culture and RNA isolation methods for precision-cut liver slices from cirrhotic rats.

Precision-cut liver slices (PCLS) are increasingly used as a model to investigate anti-fibrotic therapies. However, many studies use PCLS from healthy animals treated with pro-fibrotic stimuli in culture, which reflects only the early stages of fibrosis. The effects of different culture conditions on PCLS from cirrhotic animals has not been well characterized and there is no consensus on optimal methods. In this study, we report a method for the collection and culture of cirrhotic PCLS and compare the effect of common culture conditions on viability, function, and gene expression. Additionally, we compared three methods of RNA isolation and identified a protocol with high yield and purity. We observed significantly increased albumin production when cultured with insulin-transferrin-selenium and dexamethasone, and when incubated on a rocking platform. Culturing with insulin-transferrin-selenium and dexamethasone maintained gene expression closer to the levels in fresh slices. However, despite stable viability and function up to 4 days, we found significant changes in expression of key genes by day 2. Interestingly, we also observed that cirrhotic PCLS maintain viability in culture longer than slices from healthy animals. Due to the influence of matrix stiffness on fibrosis and hepatocellular function, it is important to evaluate prospective anti-fibrotic therapies in a platform that preserves tissue biomechanics. PCLS from cirrhotic animals represent a promising tool for the development of treatments for chronic liver disease.

Blue Light Compromises Bacterial ß-Lactamases Activity to Overcome ß-Lactam Resistance.

OBJECTIVE: In this study, we evaluated the effectiveness of antimicrobial blue light (aBL; 410 nm wavelength) against ß-lactamase-carrying bacteria and the effect of aBL on the activity of ß-lactamases. METHODS: Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae strains carrying ß-lactamases as well as a purified ß-lactamase enzymes were studied. ß-lactamase activity was assessed using a chromogenic cephalosporin hydrolysis assay. Additionally, we evaluated the role of porphyrins in the photoreaction, as well as protein degradation by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Finally, we investigated the bactericidal effect of combined aBL-ceftazidime exposure against a metallo-ß-lactamase expressing P. aeruginosa strain. RESULTS: Our study demonstrated that aBL effectively killed ß-lactamase-producing bacteria and reduced ß-lactamase activity. After an aBL exposure of 1.52 J/cm2, a 50% reduction in enzymatic activity was observed in P. aeruginosa. Additionally, we found a 40% decrease in the photoreaction activity of porphyrins following an aBL exposure of 64.8 J/cm2. We also revealed that aBL reduced ß-lactamase activity via protein degradation (after 136.4 J/cm2). Additionally, aBL markedly improved the bactericidal effect of ceftazidime (by >4-log10) in the metallo-ß-lactamase P. aeruginosa strain. CONCLUSION: Our results provide evidence that aBL compromises bacterial ß-lactamase activity, offering a potential approach to overcome ß-lactam resistance in bacteria.

Rhizospheric Bacteria of Cover Legumes from Acidic Soils Are Capable of Solubilizing Different Inorganic Phosphates.

Due to its adsorption with aluminum and iron hydroxides, phosphorus viability is low in acidic soils; thus, the aim of this study was to isolate and identify bacteria from the rhizosphere of four legumes growing in acidic soils of the Cumbaza Sub-basin, San Martín, Peru, as well as to characterize their ability to solubilize aluminum phosphate and iron phosphate. The isolation process was conducted on TSA medium and the isolates were classified based on their origin and morphocolonial characteristics, with the bacillary shape being the most frequent, followed by cocci. To assess the solubilization of aluminum and iron phosphates, the liquid medium GELP was employed. Sixteen strains were selected, among which three stood out for their effectiveness in solubilizing AlPO4 (Sfcv-098-02, 22.65 mg L-1; Sfc-093-04, 26.50 mg L-1; and Sfcv-041-01-2, 55.98 mg L-1) and one for its ability to solubilize FePO4 (Sfcr-043-02, 32.61 mg L-1). These four strains were molecularly characterized, being identified as Enterobacter sp., Pseudomonas sp., and Staphylococcus sp. Additionally, a decrease in pH was observed in the reactions, with values ranging from 5.23 to 3.29, which enhanced the phosphate of solubilization. This suggests that the selected bacteria could be used to improve phosphorus availability in agricultural soils.

CYP2C19 Genotype Is Associated With Adverse Cardiovascular Outcomes in Black Patients Treated With Clopidogrel Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear. METHODS AND RESULTS: Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P<0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel-treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person-years; adjusted hazard ratio, 2.00 [95% CI, 1.20-3.33], P=0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups. CONCLUSIONS: Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real-world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.

Endogenous androgens, coronary atheroma and remodeling in women with suspected ischemic heart disease: A report from the Women's Ischemia Syndrome Evaluation (WISE) study.

Background: Women have smaller coronary size than men independent of body surface area. Female to male heart transplantation demonstrates coronary lumen enlargement. Purpose: To investigate relationships between endogenous androgens and coronary luminal size in women with suspected ischemic heart disease (IHD). Methods: We analyzed 69 women with available androgen levels. Results: Group mean age was 54 ± 10 years with 64 % post-menopausal. Lumen cross-sectional area (CSA) and external elastic membrane (EEM) CSA positively correlated with free testosterone (FT) (r = 0.29, p = 0.049; r = 0.29, p = 0.01), respectively, and negatively correlated with SHBG (r = -0.26, p = 0.03; r = -0.29, p = 0.02), respectively. Atheroma CSA positively correlated with FT (r = 0.24. p = 0.05). These correlations became non-significant after adjusting for waist circumference. Conclusions: In women with suspected ischemic heart disease, endogenous androgens, coronary atheroma and luminal size are related, and may be moderated by waist circumference.

Myoclonus improvement after seizures in progressive myoclonic epilepsy type 7: a case report.

BACKGROUND: Progressive Myoclonic Epilepsy (PME) is a group of rare diseases that are difficult to differentiate from one another based on phenotypical characteristics. CASE REPORT: We report a case of PME type 7 due to a pathogenic variant in KCNC1 with myoclonus improvement after epileptic seizures. DISCUSSION: Myoclonus improvement after seizures may be a clue to the diagnosis of Progressive Myoclonic Epilepsy type 7.

Relationships of emerging biomarkers of cancer cachexia with quality of life, appetite, and cachexia.

PURPOSE: Quality of life (QoL), appetite, cachexia, and biomarkers [albumin, hemoglobin (Hb), neutrophils, lymphocytes, platelets, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), interleukin 8 (IL-8), C-X-C motif chemokine ligand 5 (CXCL5) and citrullinated histoneH3 (H3Cit)] were compared for 40 cases with advanced cancer and 40 healthy controls. Baseline differences and significant relationships were explored for biomarkers with QoL, appetite, and cachexia. METHODS: In a prospective case-control, age and sex matched study, the European Organisation for the Research and Treatment of Cancer Quality of Life-C30 questionnaire (EORTC-QLQ-C30) for QoL, the Functional Assessment of Anorexia and Cachexia Therapy assessment (FAACT A/CS-12) for appetite, and a five-factor cachexia assessment tool for cachexia assessment were performed. Routine hematological measurements and blood chemistry analyses together with ELISA procedures and a Multiplex® bead array platform, were used for biomarker analysis. Descriptive statistics and regression analyses were undertaken. P < 0.05 defined statistical significance. RESULTS: Global health status (QL-G), functional scales (QL-FS), and symptom scales (QL-SS) differed for cases and controls (p < 0.01). In cases, differences were observed for QL-G (p < 0.01), QL-FS (p < 0.01), and QL-SS (p = 0.01) compared to standardized references values. FAACT A/CS-12 scores differed significantly between cases and controls (p < 0.01) and 30% of cases scored "poor" appetites. Cachexia was present in 60% of cases. Albumin, lymphocytes, platelets, Hb, platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), CRP, TNFα, all at p < 0.01, neutrophil to lymphocyte ratio (NLR) (p = 0.02), IL-6 (p < 0.04), and IL-8 (p = 0.02) differed significantly between cases and controls. No difference was found for CXCL5 or H3Cit. Albumin NLR, Hb, PLR, SII, TNFα, IL-8, and CRP showed significant relationships with all aspects of QoL. QL-FS was significantly related to CXCL5 (p = 0.04), significant relationships with FAACT A/CS-12 included: NLR (p = 0.002), Hb (p < 0.001), and PLR (p < 0.01). NLR, PLR, SII, TNFα, IL-6, IL-8, and CRP correlated positively to cachexia and albumin while Hb and lymphocyte count correlated negatively to cachexia. CONCLUSION: CXCL5 and H3Cit were not reliable biomarkers for cancer cachexia, nor significantly related to QoL, appetite or cachexia. Albumin, NLR, Hb, PLR, SII, TNFα, IL-8, and CRP were reliable indicators of QoL, appetite, and cachexia. Future research should include other novel biomarkers namely growth differentiation factor-15 (GDF-15), fibroblast growth factor 21 (FGF-21), fractakline, interferon gamma (IFN-y), IL-16, macrophage colony stimulating factor (M-CSF), and macrophage procoagulant-inducing factor (MPIF).

Improvements in fermentation and nutritive quality of elephant grass [Cenchrus purpureus (Schumach.) Morrone] silages: a review.

Elephant grass [Pennisetum purpureum Schumach. syn. Cenchrus purpureus (Schumach.) Morrone], also known as Napier grass and King grass, includes varieties Taiwán, Gigante, Merkerón, Maralfalfa, and others. The grass achieves high biomass production in tropical-subtropical, temperate, and arid areas. The high-water concentration of elephant grass suggests that ensiling could offer an alternative way to preserve the nutritional quality of the grass during storage, however, some considerations should be addressed because of the particularities of the grass. Ensiling elephant grass may produce adequate fermentation but could suffer effluent losses and subsequent losses of nutrients due to leaching. To improve fermentation and nutrient characteristics of elephant grass silages, several studies were conducted with the inclusion of additives. Lactic acid bacteria inocula have reduced pH and increased crude protein content of elephant grass silage, but aerobic stability of silages could be affected by the bacterial inoculation. There is limited information, however, on the potential of different silage inoculants to reduce growth of spoilage microorganisms during the aerobic phase of silage prepared with elephant grass. Exogenous fibrolytic enzymes also may improve elephant grass silage quality by enhancing microbial fiber-degradation with subsequent increase in lactic acid and its associated pH reduction. Another study approach to improve fermentation and nutritional quality of elephant grass silages involved the addition of different feeds at ensiling, including conventional feeds such corn, wheat, rice bran, and molasses or alternative feeds such as different dehydrated by-products obtained from the food industries of juice and jelly. In the manuscript, the presented scientific information shows the great potential of the different manipulations to improve the quality of elephant grass silages and with possible enhance of the economic profit and sustainability of livestock farming in the tropical areas.