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2.
Orthop J Sports Med ; 12(6): 23259671241252813, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38845610

ABSTRACT

Background: Most healthcare providers utilize magnetic resonance imaging (MRI) to assist in diagnosing and treating osteochondritis dissecans (OCD) of the capitellum. However, consensus on imaging features that portend clinically relevant information in the care of these lesions has not been determined. Purpose: To conduct a survey on the MRI features of a capitellar OCD that are salient for clinical decision-making using a classic Delphi protocol. Study Design: A consensus statement. Methods: Invitations to participate were sent to 33 healthcare providers identified as capitellar OCD experts. A classic 3-round survey method was used to gather agreement and consensus on the level of importance for clinical decision-making on 33 MRI features. A concise list of features that guide decision-making on the stability of an OCD lesion and the ability of an OCD lesion to heal with nonoperative care was also identified. Agreement and consensus were determined a priori as ≥66%. Results: Of the 33 identified experts, 20 agreed to participate, and 17 (52%) completed all 3 rounds. Of the 33 MRI features evaluated, 17 reached agreement as important for clinical decision-making by the experts. Consensus was reached for a concise list of MRI features that were significant to decision-making (94%), suggestive of a stable lesion (100%), had the potential to heal with nonoperative treatment (94%), were suggestive of an unstable lesion (100%), and had low potential to heal with nonoperative treatment (88%). Conclusion: This 3-round Delphi process produced consensus on clinically relevant MRI features that contribute to clinical decision-making for capitellar OCD. The results of this study will be used as the basis for an interrater reliability assessment of the identified salient features, creating the foundation for developing a reliable MRI assessment tool rooted in clinical experiences. The development of a standardized assessment of capitellar OCD is intended to improve clinical practice and patient outcomes.

3.
Sci Adv ; 10(23): eadm7273, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38848365

ABSTRACT

By analyzing 15,000 samples from 348 mammalian species, we derive DNA methylation (DNAm) predictors of maximum life span (R = 0.89), gestation time (R = 0.96), and age at sexual maturity (R = 0.85). Our maximum life-span predictor indicates a potential innate longevity advantage for females over males in 17 mammalian species including humans. The DNAm maximum life-span predictions are not affected by caloric restriction or partial reprogramming. Genetic disruptions in the somatotropic axis such as growth hormone receptors have an impact on DNAm maximum life span only in select tissues. Cancer mortality rates show no correlation with our epigenetic estimates of life-history traits. The DNAm maximum life-span predictor does not detect variation in life span between individuals of the same species, such as between the breeds of dogs. Maximum life span is determined in part by an epigenetic signature that is an intrinsic species property and is distinct from the signatures that relate to individual mortality risk.


Subject(s)
DNA Methylation , Epigenesis, Genetic , Longevity , Mammals , Animals , Longevity/genetics , Mammals/genetics , Female , Humans , Male , Life History Traits , Species Specificity
4.
Int J Oral Maxillofac Implants ; 0(0): 1-15, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38941171

ABSTRACT

PURPOSE: To investigate residual debris within internal features of new "as received" dental implants. MATERIALS AND METHODS: A total of 15 new dental implants representing various dental implant brands were obtained in sealed containers from the manufacturers. Batch numbers and implant types were documented. In a controlled setting, implants were carefully unpacked, and their internal aspects were visually examined. Further analysis involved light microscopy imaging to document and photograph any foreign material. The internal aspect of the implants were sampled with both an endodontic paper cone and a fine bristle brush swab. These were inserted into the implant, rotated three times, then removed and examined under a microscope at 30x magnification. Post sampling some of the brushes/swabs were washed with alcohol to remove debris that could be further examined under magnification. RESULTS: Inspection of the implants without magnification revealed no visible foreign materials. However, under light microscopy (x10 and x30), all 15 implants exhibited small black particles at various internal sites, including connections, threads, and deep within screw channels. Swabs evaluated at magnification detected what appeared to be metal particles in all 15 implants, ranging from distinct metal shards to smaller particles. CONCLUSION: This study suggests that implant manufacturers have not effectively removed all machining debris from within implant bodies, potentially producing prosthetic and clinical complications.

5.
Front Microbiol ; 15: 1365681, 2024.
Article in English | MEDLINE | ID: mdl-38803380

ABSTRACT

Introduction: Medicinal plants, rich in phytochemicals like phenolic acids, flavonoids, and tannins, offer potential benefits in enhancing productivity, quality, and animal health. Amla fruit (Phyllanthus emblica) is one such plant with promising attributes. This study aimed to investigate the impact of fresh Amla fruit (FAF) supplementation on ruminal microbial composition and its correlation with rumen fermentation in lactating dairy cows. Methods: The study employed a repeated crossover design involving eight ruminally cannulated mid-lactation Holstein dairy cows. Animals received varying levels of fresh Amla fruit supplementation (0, 200, 400, and 600 g/d). Results: When 400 g/d of FAF was added to the diet, there was a significant increase in the relative abundance of Firmicutes (p = 0.02). However, at 200 g/d, the relative abundance of ruminal Bacteroidota was higher than the 0 and 400 g/d FAF supplementation (p < 0.01). LEfSe analysis identified distinct taxa, such as Clostridia vadinBB60 in the 200 g/d group, Oscillospiraceae in the 400 g/d group, and Elusimicrobium in the 600 g/d group. Notably, the random forest species abundance statistics identified Oscillospiraceae V9D2013 as a biomarker related to milk yield. Oscillospiraceae, Bacilli RF39, norank_f Prevotellaceae, and Bifidobacterium were positively correlated with ruminal total VFA and molar proportion of propionate, while Rikenellaceae RC9 gut group and Clostridia vadinBB60 were negatively correlated. Discussion: FAF supplementation affects the abundance of beneficial microbes in a dose-dependent manner, which can improve milk yield, efficiency, rumen health, desirable fatty acids, and animal health.

6.
Ann Vasc Surg ; 106: 426-437, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38815915

ABSTRACT

BACKGROUND: Aortoiliac occlusive disease (AIOD) has traditionally been treated with aortobifemoral bypass (ABF). Unibody endograft (UBE) for AIOD, however, has been increasingly utilized in selected patients. We report outcomes of patients undergoing ABF or UBE for AIOD. METHODS: Patients (2016-2021) undergoing elective ABF or UBE with a unibody device for AIOD were identified at an academic institution. Chi-square and Kaplan-Meier analysis were used to evaluate outcomes by group. RESULTS: One hundred thirty-one patients undergoing UBE or ABF were screened, with 82 included. Twenty-one patients underwent UBE (25.6%) and 61 (74.4%) underwent ABF. UBE patients were older (63.8 vs. 58.2 years; P = 0.01), with a higher prevalence of diabetes (52.4 vs. 19.7%; P = 0.004). Significant differences were seen between UBE and ABF including a shorter surgery length (214 vs. 360 min; P = 0.0001), less blood loss (300 vs. 620 mls; P = 0.001), larger minimum aortic diameter (14.6 vs. 12.6; P = 0.0006), larger common iliac artery (9.5 vs. 7.9; P = 0.005) and lower postoperative ankle-brachial index (0.8 vs. 0.9; P = 0.04). There were no differences in TASC C/D iliac lesions in the UBE than ABF group (66.6% vs. 63.9%; P < 0.82) or Trans-Atlantic Inter-Society Consensus classification femoropopliteal lesions. Unadjusted analysis revealed no significant differences between UBE and ABF for 30-day mortality (0 vs. 1.6%; P = 1), stroke (0 vs. 3.3%; P = 1), or major adverse cardiac events (4.8 vs. 4.9%; P = 1). There were no significant differences in mid-term surgical outcomes over a mean follow-up period of 23.7 months between UBE and ABF groups; specifically endovascular (0 vs. 8.2%; P = 0.3) or open/hybrid reintervention (9.5 vs. 14.8%; P = 0.7) with similar limb occlusion (4.8 vs. 27.8; P = 0.12). Kaplan-Meier estimated primary, primary-assisted, and secondary patency at 36 months were similar with 94%, 100%, and 94% for UBE and 86%, 95%, and 86% for ABF, respectively. Estimated survival at 36 months was 95% for UBE and 97% for ABF (P = 0.8). CONCLUSIONS: Equivalent outcomes were seen between AIOD treated with UBE or ABF in similar patient populations. Mid-term outcomes such as reintervention and patency are similar for UBE and ABF. We still recommend ABF over UBE as a primary modality of treatment in surgically fit patients with greater complexity aortoiliac lesions and with smaller arterial diameters, especially women.

7.
Microorganisms ; 12(5)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38792689

ABSTRACT

In recent years, there has been an exponential increase in the number of papers that have investigated the microbiome of animals and humans [...].

8.
Animals (Basel) ; 14(10)2024 May 17.
Article in English | MEDLINE | ID: mdl-38791705

ABSTRACT

There is growing concern about the potential adverse health effects of phthalates (PAEs) on human health and the environment due to their extensive use as plasticizers and additives in commercial and consumer products. In this study, we assessed PAE concentrations in serum samples from aquarium-based delphinids (Tursiops truncatus, n = 36; Orcinus orca, n = 42) from California, Florida, and Texas, USA. To better understand the physiological effects of phthalates on delphinids, we also explored potential correlations between phthalates and the biomarkers aldosterone, cortisol, corticosterone, hydrogen peroxide, and malondialdehyde while accounting for sex, age, and reproductive stage. All PAEs were detected in at least one of the individuals. ΣPAE ranges were 5.995-2743 ng·mL-1 in bottlenose dolphins and 5.372-88,675 ng·mL-1 in killer whales. Both species displayed higher mean concentrations of DEP and DEHP. PAEs were detected in newborn delphinids, indicating transference via placenta and/or lactation. Linear mixed model results indicated significant correlations between aldosterone, month, location, status, and ΣPAEs in killer whales, suggesting that aldosterone concentrations are likely affected by the cumulative effects of these variables. This study expands on the knowledge of delphinid physiological responses to PAEs and may influence management and conservation decisions on contamination discharge regulations near these species.

9.
J Pediatr Orthop ; 44(6): 373-378, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38606635

ABSTRACT

BACKGROUND: Increasing strength through weightlifting has become a core component of competitive sports training, recreational exercise programs, and school physical education classes. Although many health benefits exist, there is concern for injury, especially with improper supervision and accelerated progression of training loads. Though organizations have advocated safe training practices, trends in the national health burden of injuries, specifically fractures, associated with weightlifting in the adolescent population have not been investigated. METHODS: The National Electronic Injury Surveillance System database was queried between 2002 and 2021 for patients aged 11 to 21 years presenting to US Emergency Departments with weight lifting-related injuries. The narrative component of each case identified was analyzed to include only patients noted to be using weightlifting equipment or free weights at the time of injury. Estimates and analyses were performed with 95% CIs. RESULTS: Although there has been some variability in weight lifting-related injuries, the incidence remained roughly constant over the 20 years ( R2 =0.0364). 14,497 cases were identified, reflecting a national estimate of 540,986 total injuries and an annual estimate of 27,049 injuries. Most injuries occurred among 15-to-18-year olds (44.1%±1.6%) and 19-to-21-year olds (38.3%±2.0%). The most common injuries were sprain/strain (36.7%±1.3%), contusion/abrasion (15.7%±0.7%), and fracture (9.9%±0.3%). There were 53,813 estimated fractures, giving an annual incidence of 2,691 fractures. As a portion of all injuries, the number of fractures decreased significantly as patients got older, accounting for 26.8%±3.3% at age 11 and only 8.3%±0.9% at age 21 ( R2 =0.6626). Fingers (37.1%±1.8%) and toes (27.9%±1.4%) were the most fractured body parts. Overall, fractures mainly occurred either at school (25.3%±2.0%) or places of recreation (24.7%±2.2%). CONCLUSIONS: Despite the guidelines to improve safety, the national health burden of weight lifting-related injuries among adolescents has remained constant over the past 20 years. Given that most of the fractures occur in the distal extremities, such as toes and fingers, at school and places of recreation, there may be an opportunity to promote safer weightlifting practices and the development of weightlifting equipment with in-built safety mechanisms, especially at gyms and schools. LEVEL OF EVIDENCE: Level III-prognostic.


Subject(s)
Fractures, Bone , Weight Lifting , Humans , Adolescent , Weight Lifting/injuries , Weight Lifting/statistics & numerical data , Female , Male , Child , Fractures, Bone/epidemiology , Fractures, Bone/etiology , United States/epidemiology , Young Adult , Incidence , Athletic Injuries/epidemiology , Databases, Factual
10.
Pract Radiat Oncol ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38636586

ABSTRACT

Although standardization has been shown to improve patient safety and improve the efficiency of workflows, implementation of standards can take considerable effort and requires the engagement of all clinical stakeholders. Engaging team members includes increasing awareness of the proposed benefit of the standard, a clear implementation plan, monitoring for improvements, and open communication to support successful implementation. The benefits of standardization often focus on large institutions to improve research endeavors, yet all clinics can benefit from standardization to increase quality and implement more efficient or automated workflow. The benefits of nomenclature standardization for all team members and institution sizes, including success stories, are discussed with practical implementation guides to facilitate the adoption of standardized nomenclature in radiation oncology.

11.
J Oral Implantol ; 50(1): 39-44, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38579111

ABSTRACT

Ingestion or aspiration of dental implant screwdrivers or implant components is potentially life-threatening. There are no reports on the frequency at which dentists drop these devices within the mouth or which components are most problematic. There are few reports on what protective measures clinicians take, where risks exist, and how this problem is managed. A 9-part questionnaire was provided to dentists. Data collected included clinicians' roles, implant surgeons, restorative clinicians, or both-the frequency of dropping implant screwdrivers or components, items considered most problematic. Patient protection and management were also requested. Finally, questions related to how much of a problem clinicians considered this to be and if further solutions and a standardized management protocol should be developed. One hundred twelve dentists voluntarily completed the survey. Of the dentists, 54% restored, 37% restored and surgically placed, and 9% solely placed implants. Twenty-nine percent claimed never to drop components, with 56% dropping an instrument less than 10% of the time. Less than half would suggest patients seek medical advice if a screwdriver or component was accidentally dropped intraorally and was not recovered. Thirty percent never tied floss tethers to screwdrivers, and a similar percentage reported they only sometimes did so. Throat pack protection was reported 51% of the time. Ninety percent considered dropping components an issue, with screwdrivers most problematic. Aspiration or ingestion of implant screwdrivers and components is problematic, with dentists varying their use of protection devices. There is a need to standardize and implement patient protection procedures and management and develop methods to reduce the risk of these potentially life-threatening issues.


Subject(s)
Dental Implants , Humans , Surveys and Questionnaires , Dentists
12.
Sleep Adv ; 5(1): zpae008, 2024.
Article in English | MEDLINE | ID: mdl-38425454

ABSTRACT

Study Objectives: This study analyzed fatigue and its management in US Naval Surface Force warships, focusing on understanding current practices and barriers, and examining the influence of organizational and individual factors on managing chronic fatigue. Furthermore, this study explored the impact of organizational and individual factors on fatigue management. Methods: As part of a larger study, 154 naval officers (mean ±â€…standard deviation; 31.5 ±â€…7.0 years; 8.8 ±â€…6.8 years of service; 125 male, and 29 female) completed a fatigue survey. The survey addressed (1) self-reported fatigue, (2) fatigue observed in others, (3) fatigue monitoring strategies, (4) fatigue mitigation strategies, and (5) barriers to fatigue mitigation. Logistic and ordinal regressions were performed to examine the effect of individual (i.e. sleep quality and years in military service) and organizational (i.e. ship-class) factors on fatigue outcomes. Results: Fatigue was frequently experienced and observed by 23% and 54% of officers, respectively. Of note, officers often monitored fatigue reactively (i.e. 65% observed others nodding off and 55% observed behavioral impairments). Still, officers did not frequently implement fatigue mitigation strategies, citing few operationally feasible mitigation strategies (62.3%), being too busy (61.7%), and not having clear thresholds for action (48.7%). Fatigue management varies across organizational factors, which must be considered when further developing fatigue management strategies. Conclusions: Fatigue remains a critical concern aboard surface force ships and it may be better addressed through development of objective sleep and fatigue monitoring tools that could inform leadership decision-making.

13.
Microorganisms ; 12(3)2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38543587

ABSTRACT

The catabolic activity of the ruminal microbial community of cattle enables the conversion of low-quality feedstuffs into meat and milk. The rate at which this conversion occurs is termed feed efficiency, which is of crucial importance given that feed expenses account for up to 70% of the cost of animal production. The present study assessed the relationship between cattle feed efficiency and the composition of their ruminal microbial communities during the feedlot finishing period. Angus steers (n = 65) were fed a feedlot finishing diet for 82 days and their growth performance metrics were evaluated. These included the dry matter intake (DMI), average daily gain (ADG), and residual feed intake (RFI). Steers were rank-ordered based upon their RFI, and the five lowest RFI (most efficient) and five highest RFI (least efficient) steers were selected for evaluations. Ruminal fluid samples were collected on days 0 and 82 of the finishing period. Volatile fatty acids (VFA) were quantified, and microbial DNA was extracted and the 16S rRNA gene was sequenced. The results showed that the ADG was not different (p = 0.82) between efficiency groups during the 82-day feedlot period; however, the efficient steers had lower (p = 0.03) DMI and RFI (p = 0.003). Less-efficient (high RFI) steers developed higher (p = 0.01) ruminal Methanobrevibacter relative abundances (p = 0.01) and tended (p = 0.09) to have more Methanosphaera. In high-efficiency steers (low RFI), the relative abundances of Ruminococcaceae increased (p = 0.04) over the 82-day period. The molar proportions of VFA were not different between the two efficiency groups, but some changes in the concentration of specific VFA were observed over time. The results indicated that the ruminal microbial populations of the less-efficient steers contained a greater relative abundance of methanogens compared to the high-efficiency steers during the feedlot phase, likely resulting in more energetic waste in the form or methane and less dietary energy being harvested by the less-efficient animals.

14.
J Clin Transl Sci ; 8(1): e48, 2024.
Article in English | MEDLINE | ID: mdl-38510694

ABSTRACT

Background: Assessing perceptions of the COVID-19 vaccines is essential for understanding vaccine hesitancy and for improving uptake during public health emergencies. In the complicated landscape of COVID-19 vaccine mandates and rampant misinformation, many individuals faced challenges during vaccination decision-making. The purpose of our mixed methods study is to elucidate factors affecting vaccine decision-making and to highlight the discourse surrounding the COVID-19 vaccines in diverse and underserved communities. Methods: This mixed methods study was conducted in Arizona, Florida, Minnesota, and Wisconsin between March and November 2021, combining a cross-sectional survey (n = 3593) and focus groups (n = 47). Results: The groups least likely to report receiving a vaccination were non-Hispanic Whites, Indigenous people, males, and those with moderate socioeconomic status (SES). Those indicating high and low SES reported similar vaccination uptake. Focus group data highlighted resistance to mandates, distrust, misinformation, and concerns about the rapid development surrounding the COVID-19 vaccines. Psychological reactance theory posits that strongly persuasive messaging and social pressure can be perceived as a threat to freedom, encouraging an individual to take action to restore that freedom. Conclusion: Our findings indicate that a subsection of participants felt pressured to get the vaccine, which led to weaker intentions to vaccinate. These results suggest that vaccine rollout strategies should be reevaluated to improve and facilitate informed decision-making.

15.
Nat Commun ; 15(1): 1942, 2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38431634

ABSTRACT

Arl1 is an Arf-like (Arl) GTP-binding protein that interacts with the guanine nucleotide exchange factor Gea2 to recruit the golgin Imh1 to the Golgi. The Arl1-Gea2 complex also binds and activates the phosphatidylserine flippase Drs2 and these functions may be related, although the underlying molecular mechanism is unclear. Here we report high-resolution cryo-EM structures of the full-length Gea2 and the Arl1-Gea2 complex. Gea2 is a large protein with 1459 residues and is composed of six domains (DCB, HUS, SEC7, HDS1-3). We show that Gea2 assembles a stable dimer via an extensive interface involving hydrophobic and electrostatic interactions in the DCB and HUS region. Contrary to the previous report on a Gea2 homolog in which Arl1 binds to the dimerization surface of the DCB domain, implying a disrupted dimer upon Arl1 binding, we find that Arl1 binds to the outside surface of the Gea2 DCB domain, leaving the Gea2 dimer intact. The interaction between Arl1 and Gea2 involves the classic FWY aromatic residue triad as well as two Arl1-specific residues. We show that key mutations that disrupt the Arl1-Gea2 interaction abrogate Imh1 Golgi association. This work clarifies the Arl1-Gea2 interaction and improves our understanding of molecular events in the membrane trafficking.


Subject(s)
ADP-Ribosylation Factors , Membrane Proteins , Golgi Matrix Proteins/metabolism , Membrane Proteins/metabolism , ADP-Ribosylation Factors/genetics , ADP-Ribosylation Factors/metabolism , Protein Structure, Tertiary , Golgi Apparatus/metabolism
16.
Front Cell Dev Biol ; 12: 1310593, 2024.
Article in English | MEDLINE | ID: mdl-38415274

ABSTRACT

Over 8% of couples worldwide are affected by infertility and nearly half of these cases are due to male-specific issues where the underlying cause is often unknown. Therefore, discovery of new genetic factors contributing to male-specific infertility in model organisms can enhance our understanding of the etiology of this disorder. Here we show that murine ATP10A, a phospholipid flippase, is highly expressed in male reproductive organs, specifically the testes and vas deferens. Therefore, we tested the influence of ATP10A on reproduction by examining fertility of Atp10A knockout mice. Our findings reveal that Atp10A deficiency leads to male-specific infertility, but does not perturb fertility in the females. The Atp10A deficient male mice exhibit smaller testes, reduced sperm count (oligozoospermia) and lower sperm motility (asthenozoospermia). Additionally, Atp10A deficient mice display testes and vas deferens histopathological abnormalities, as well as altered total and relative amounts of hormones associated with the hypothalamic-pituitary-gonadal axis. Surprisingly, circulating testosterone is elevated 2-fold in the Atp10A knockout mice while luteinizing hormone, follicle stimulating hormone, and inhibin B levels were not significantly different from WT littermates. The knockout mice also exhibit elevated levels of gonadotropin receptors and alterations to ERK, p38 MAPK, Akt, and cPLA2-dependent signaling in the testes. Atp10A was knocked out in the C57BL/6J background, which also carries an inactivating nonsense mutation in the closely related lipid flippase, Atp10D. We have corrected the Atp10D nonsense mutation using CRISPR/Cas9 and determined that loss of Atp10A alone is sufficient to cause infertility in male mice. Collectively, these findings highlight the critical role of ATP10A in male fertility in mice and provide valuable insights into the underlying molecular mechanisms.

17.
BMC Ecol Evol ; 24(1): 25, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38378475

ABSTRACT

BACKGROUND: Human-commensal species often display deep ancestral genetic structure within their native range and founder-effects and/or evidence of multiple introductions and admixture in newly established areas. We investigated the phylogeography of Eutropis multifasciata, an abundant human-commensal scincid lizard that occurs across Southeast Asia, to determine the extent of its native range and to assess the sources and signatures of human introduction outside of the native range. We sequenced over 350 samples of E. multifasciata for the mitochondrial ND2 gene and reanalyzed a previous RADseq population genetic dataset in a phylogenetic framework. RESULTS: Nuclear and mitochondrial trees are concordant and show that E. multifasciata has retained high levels of genetic structure across Southeast Asia despite being frequently moved by humans. Lineage boundaries in the native range roughly correspond to several major biogeographic barriers, including Wallace's Line and the Isthmus of Kra. Islands at the outer fringe of the range show evidence of founder-effects and multiple introductions. CONCLUSIONS: Most of enormous range of E. multifasciata across Southeast Asia is native and it only displays signs of human-introduction or recent expansion along the eastern and northern fringe of its range. There were at least three events of human-introductions to Taiwan and offshore islands, and several oceanic islands in eastern Indonesia show a similar pattern. In Myanmar and Hainan, there is a founder-effect consistent with post-warming expansion after the last glacial maxima or human introduction.


Subject(s)
Lizards , Animals , Humans , Phylogeny , Lizards/genetics , Asia, Southeastern , Phylogeography , Indonesia
18.
Biochim Biophys Acta Mol Cell Res ; 1871(4): 119700, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38382846

ABSTRACT

Type IV P-type ATPases (P4-ATPases) are a family of transmembrane enzymes that translocate lipid substrates from the outer to the inner leaflet of biological membranes and thus create an asymmetrical distribution of lipids within membranes. On the cellular level, this asymmetry is essential for maintaining the integrity and functionality of biological membranes, creating platforms for signaling events and facilitating vesicular trafficking. On the organismal level, this asymmetry has been shown to be important in maintaining blood homeostasis, liver metabolism, neural development, and the immune response. Indeed, dysregulation of P4-ATPases has been linked to several diseases; including anemia, cholestasis, neurological disease, and several cancers. This review will discuss the evolutionary transition of P4-ATPases from cation pumps to lipid flippases, the new lipid substrates that have been discovered, the significant advances that have been achieved in recent years regarding the structural mechanisms underlying the recognition and flipping of specific lipids across biological membranes, and the consequences of P4-ATPase dysfunction on cellular and physiological functions. Additionally, we emphasize the requirement for additional research to comprehensively understand the involvement of flippases in cellular physiology and disease and to explore their potential as targets for therapeutics in treating a variety of illnesses. The discussion in this review will primarily focus on the budding yeast, C. elegans, and mammalian P4-ATPases.


Subject(s)
Adenosine Triphosphatases , Caenorhabditis elegans , Animals , Adenosine Triphosphatases/metabolism , Caenorhabditis elegans/metabolism , Cell Membrane/genetics , Cell Membrane/metabolism , Lipids , Mammals/metabolism
19.
Science ; 383(6680): eadf2341, 2024 01 19.
Article in English | MEDLINE | ID: mdl-38236959

ABSTRACT

Liquid biopsies enable early detection and monitoring of diseases such as cancer, but their sensitivity remains limited by the scarcity of analytes such as cell-free DNA (cfDNA) in blood. Improvements to sensitivity have primarily relied on enhancing sequencing technology ex vivo. We sought to transiently augment the level of circulating tumor DNA (ctDNA) in a blood draw by attenuating its clearance in vivo. We report two intravenous priming agents given 1 to 2 hours before a blood draw to recover more ctDNA. Our priming agents consist of nanoparticles that act on the cells responsible for cfDNA clearance and DNA-binding antibodies that protect cfDNA. In tumor-bearing mice, they greatly increase the recovery of ctDNA and improve the sensitivity for detecting small tumors.


Subject(s)
Cell-Free Nucleic Acids , Neoplasms , Animals , Mice , Biomarkers, Tumor/blood , Cell-Free Nucleic Acids/blood , Circulating Tumor DNA/blood , Liquid Biopsy , Mutation , Neoplasms/blood , Neoplasms/diagnosis , Humans , Female , Mice, Inbred BALB C , Sensitivity and Specificity
20.
Life (Basel) ; 14(1)2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38255720

ABSTRACT

Polar bears (Ursus maritimus) face a number of challenges that threaten the survival of the species. Captive breeding represents one essential facet of species conservation, but aspects of the polar bear's reproductive physiology, such as follicle maturation, coitus-induced ovulation, and pseudopregnancy, are poorly characterized and present challenges for enhancing natural reproductive success and the application of advanced reproductive techniques. Due to the absence of a reliable transrectal or transabdominal ultrasound method for ovarian examination in the species, the ovaries of two adult female polar bears were examined laparoscopically to evaluate the feasibility of surgical access to the ovaries, oviduct, and uterus. The minimally invasive procedure was easily and rapidly performed in both bears and all procedures. Direct visual assessment of the ovary was possible after dissection of a fatty bursal sac, which completely enclosed the ovaries. In the second bear, laparoscopic manipulation of the ovary to draw it closer to the body wall enabled transcutaneous ultrasound. Laparoscopy may be a valuable tool to aid in the application of advanced reproductive technologies in polar bears.

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