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1.
Neural Regen Res ; 20(4): 1192-1206, 2025 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38989956

RESUMO

JOURNAL/nrgr/04.03/01300535-202504000-00033/figure1/v/2024-07-06T104127Z/r/image-tiff Behavioral recovery using (viable) peripheral nerve allografts to repair ablation-type (segmental-loss) peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration. Furthermore, such peripheral nerve allografts undergo immunological rejection by the host immune system. In contrast, peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks, reduced immune responses, and many axons do not undergo Wallerian degeneration. The relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this study. We hypothesized that polyethylene glycol might have some immune-protective effects, but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral recovery. We examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal fusion. Ablation-type sciatic nerve injuries in outbred Sprague-Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts, but peripheral nerve allografts were loose-sutured (loose-sutured polyethylene glycol) with an intentional gap of 1-2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host axons. Similar to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts, animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days postoperatively. Other morphological signs of rejection, such as collapsed Schwann cell basal lamina tubes, were absent in polyethylene glycol-fused peripheral nerve allografts but commonly observed in negative control and loose-sutured polyethylene glycol peripheral nerve allografts at 21 days postoperatively. Loose-sutured polyethylene glycol peripheral nerve allografts had more pro-inflammatory and less anti-inflammatory macrophages than negative control peripheral nerve allografts. While T cell counts were similarly high in loose-sutured-polyethylene glycol and negative control peripheral nerve allografts, loose-sutured polyethylene glycol peripheral nerve allografts expressed some cytokines/chemokines important for T cell activation at much lower levels at 14 days postoperatively. MHCI expression was elevated in loose-sutured polyethylene glycol peripheral nerve allografts, but MHCII expression was modestly lower compared to negative control at 21 days postoperatively. We conclude that, while polyethylene glycol per se reduces some immune responses of peripheral nerve allografts, successful polyethylene glycol-fusion repair of some axons is necessary to prevent Wallerian degeneration of those axons and immune rejection of peripheral nerve allografts, and produce recovery of sensory/motor functions and voluntary behaviors. Translation of polyethylene glycol-fusion technologies would produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation peripheral nerve injuries.

2.
Front Endocrinol (Lausanne) ; 15: 1417437, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39114287

RESUMO

Introduction: Using a non-human primate (NHP) model of maternal Western-style diet (mWSD) feeding during pregnancy and lactation, we previously reported altered offspring beta:alpha cell ratio in vivo and insulin hyper-secretion ex vivo. Mitochondria are known to maintain beta-cell function by producing ATP for insulin secretion. In response to nutrient stress, the mitochondrial network within beta cells undergoes morphological changes to maintain respiration and metabolic adaptability. Given that mitochondrial dynamics have also been associated with cellular fate transitions, we assessed whether mWSD exposure was associated with changes in markers of beta-cell maturity and/or mitochondrial morphology that might explain the offspring islet phenotype. Methods: We evaluated the expression of beta-cell identity/maturity markers (NKX6.1, MAFB, UCN3) via florescence microscopy in islets of Japanese macaque pre-adolescent (1 year old) and peri-adolescent (3-year-old) offspring born to dams fed either a control diet or WSD during pregnancy and lactation and weaned onto WSD. Mitochondrial morphology in NHP offspring beta cells was analyzed in 2D by transmission electron microscopy and in 3D using super resolution microscopy to deconvolve the beta-cell mitochondrial network. Results: There was no difference in the percent of beta cells expressing key maturity markers in NHP offspring from WSD-fed dams at 1 or 3 years of age; however, beta cells of WSD-exposed 3 year old offspring showed increased levels of NKX6.1 per beta cell at 3 years of age. Regardless of maternal diet, the beta-cell mitochondrial network was found to be primarily short and fragmented at both ages in NHP; overall mitochondrial volume increased with age. In utero and lactational exposure to maternal WSD consumption may increase mitochondrial fragmentation. Discussion: Despite mWSD consumption having clear developmental effects on offspring beta:alpha cell ratio and insulin secretory response to glucose, this does not appear to be mediated by changes to beta-cell maturity or the beta-cell mitochondrial network. In general, the more fragmented mitochondrial network in NHP beta cells suggests greater ability for metabolic flexibility.


Assuntos
Dieta Ocidental , Células Secretoras de Insulina , Fenômenos Fisiológicos da Nutrição Materna , Mitocôndrias , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/ultraestrutura , Gravidez , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Dieta Ocidental/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Masculino , Lactação
3.
Science ; 385(6709): 651-656, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39116250

RESUMO

The energetic disorder induced by fluctuating liquid environments acts in opposition to the precise control required for coherence-based sensing. Overcoming fluctuations requires a protected quantum subspace that only weakly interacts with the local environment. We report a ytterbium complex that exhibited an ultranarrow absorption linewidth in solution at room temperature with a full width at half maximum of 0.625 milli-electron volts. Using spectral hole burning, we measured an even narrower linewidth of 410 pico-electron volts at 77 kelvin. Narrow linewidths allowed low-field magnetic circular dichroism at room temperature, used to sense Earth-scale magnetic fields. These results demonstrated that ligand protection in lanthanide complexes could substantially diminish electronic state fluctuations. We have termed this system an "atomlike molecular sensor" (ALMS) and proposed approaches to improve its performance.

4.
Schizophr Bull Open ; 5(1): sgae016, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39144106

RESUMO

While continued cannabis use and misuse in individuals with schizophrenia is associated with a variety of negative outcomes, individuals with a history of use tend to show higher cognitive performance compared to non-users. While this is replicated in the literature, few studies have used task-based functional magnetic resonance imaging (fMRI) to evaluate whether the brain networks underpinning these cognitive features are similarly impacted. Forty-eight first-episode individuals with schizophrenia (FES) with a history of cannabis use (FES + CAN), 28 FES individuals with no history of cannabis use (FES-CAN), and 59 controls (CON) performed the AX-Continuous Performance Task during fMRI. FES+CAN showed higher cognitive control performance (d'-context) compared to FES-CAN (P < .05, ηp 2 = 0.053), and both FES+CAN (P < .05, ηp 2 = 0.049) and FES-CAN (P < .001, ηp 2 = 0.216) showed lower performance compared to CON. FES+CAN (P < .05, ηp 2 = 0.055) and CON (P < 0.05, ηp 2 = 0.058) showed higher dorsolateral prefrontal cortex (DLPFC) activation during the task compared to FES-CAN, while FES+CAN and CON were not significantly different. Within the FES+CAN group, the younger age of initiation of cannabis use was associated with lower IQ and lower global functioning. More frequent use was also associated with higher reality distortion symptoms at the time of the scan. These data are consistent with previous literature suggesting that individuals with schizophrenia and a history of cannabis use have higher cognitive control performance. For the first time, we also reveal that FES+CAN have higher DLPFC brain activity during cognitive control compared to FES-CAN. Several possible explanations for these findings are discussed.

5.
RSC Chem Biol ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39144403

RESUMO

The chemical logic associated with assembly of many bacterial terpenoids remains poorly understood. We focused our efforts on the early-stage biosynthesis of the phenalinolactone diterpenoids, demonstrating that the anti/anti/syn-perhydrophenanthrene core is constructed by sequential prenylation, epoxidation, and cyclization. The functions and timing of PlaT1-PlaT3 were assigned by comprehensive heterologous reconstitution. We illustrated that the UbiA prenyltransferase PlaT3 acts on geranylgeranyl diphosphate (GGPP) in the first step of phenalinolactone biosynthesis, prior to epoxidation by the flavin-dependent monooxygenase PlaT1 and cyclization by the type II terpene cyclase PlaT2. Finally, we isolated eight new-to-nature terpenoids, expanding the scope of the bacterial terpenome. The biosynthetic strategy employed in the assembly of the phenalinolactone core, with cyclization occurring after prenylation, is rare in bacteria and resembles fungal meroterpenoid biosynthesis. The findings presented here set the stage for future discovery, engineering, and enzymology efforts in bacterial meroterpenoids.

6.
Animals (Basel) ; 14(15)2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39123676

RESUMO

Free-ranging nilgai antelope (Boselaphus tragocamelus) are an understudied species, both on their native ranges of India, Pakistan, and Nepal and on their introduced ranges in southern Texas. Basic data related to population sizes, survival, reproduction, and recruitment are needed throughout their range to inform management and conservation decisions. We collected nilgai fetuses from 3 ranches in southern Texas, including East Foundation's El Sauz and Santa Rosa ranches, and the Norias Division of the King Ranch® from 2018-2021. We calculated the percentage of individuals that were pregnant in each of the sample years and overall. We determined monthly average, maximum, and minimum fetus length. Of 488 nilgai cows, we found 386 to be pregnant (79%) and 214 to be pregnant with twins (56%). We found nilgai cows as young as 1-year old to have fetuses and therefore to have reached sexual maturity. Sex ratios of fetuses during any sampling year did not differ. We found ample evidence supporting our hypothesis that nilgai are fecund on their introduced range of southern Texas. To prevent nilgai overpopulation and associated problems, harvest management strategies should be implemented, specifically on nilgai cows.

7.
Nat Commun ; 15(1): 7052, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39147740

RESUMO

The interplay of topology, magnetism, and correlations gives rise to intriguing phases of matter. In this study, through state-of-the-art angle-resolved photoemission spectroscopy, density functional theory, and dynamical mean-field theory calculations, we visualize a fourfold degenerate Dirac nodal line at the boundary of the bulk Brillouin zone in the antiferromagnet YMn2Ge2. We further demonstrate that this gapless, antiferromagnetic Dirac nodal line is enforced by the combination of magnetism, space-time inversion symmetry, and nonsymmorphic lattice symmetry. The corresponding drumhead surface states traverse the whole surface Brillouin zone. YMn2Ge2 thus serves as a platform to exhibit the interplay of multiple degenerate nodal physics and antiferromagnetism. Interestingly, the magnetic nodal line displays a d-orbital dependent renormalization along its trajectory in momentum space, thereby manifesting Hund's coupling. Our findings offer insights into the effect of electronic correlations on magnetic Dirac nodal lines, leading to an antiferromagnetic Hund nodal line.

8.
Immunity ; 57(8): 1893-1907.e6, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39096910

RESUMO

Naive CD4+ T cells in specific pathogen-free (SPF) mice are characterized by transcriptional heterogeneity and subpopulations distinguished by the expression of quiescence, the extracellular matrix (ECM) and cytoskeleton, type I interferon (IFN-I) response, memory-like, and T cell receptor (TCR) activation genes. We demonstrate that this constitutive heterogeneity, including the presence of the IFN-I response cluster, is commensal independent insofar as being identical in germ-free and SPF mice. By contrast, Nippostrongylus brasiliensis infection altered this constitutive heterogeneity. Naive T cell-intrinsic transcriptional changes acquired during helminth infection correlated with and accounted for decreased immunization response to an unrelated antigen. These compositional and functional changes were dependent variables of helminth infection, as they disappeared at the established time point of its clearance in mice. Collectively, our results indicate that the naive T cell pool is subject to dynamic transcriptional changes in response to certain environmental cues, which in turn permutes the magnitude of the immune response.


Assuntos
Linfócitos T CD4-Positivos , Nippostrongylus , Animais , Camundongos , Linfócitos T CD4-Positivos/imunologia , Nippostrongylus/imunologia , Infecções por Strongylida/imunologia , Infecções por Strongylida/parasitologia , Organismos Livres de Patógenos Específicos , Transcrição Gênica , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Helmintíase/imunologia , Interferon Tipo I/metabolismo , Interferon Tipo I/imunologia , Camundongos Endogâmicos C57BL , Ativação Linfocitária/imunologia
9.
BMC Health Serv Res ; 24(1): 924, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39135057

RESUMO

BACKGROUND: A longer duration of untreated psychosis (DUP) is associated with poorer treatment outcomes. Screening for psychosis spectrum disorders in the primary care setting could help support the earlier detection and treatment of individuals in need. However, the acceptability of screening for psychosis in this setting as part of routine care is currently unknown. METHODS: We conducted a qualitative interview study with providers and service users who participated in an early psychosis screening program conducted in an integrated behavioral health primary care (IBH-PC) setting. Interviews were recruited from one of eight WellSpace Federally Qualified Health Center IBH-PC clinics in the Sacramento, CA area. Transcripts of the recorded interviews were analyzed using thematic analysis. RESULTS: In total, 12 providers and eight service users participated in the interviews. Most service user and provider participants were supportive of psychosis screening in an IBH-PC setting, but not as part of the general practitioner consultation due to the brief, non-behavioral health nature of many of the appointments, and the expected low prevalence of psychosis in this population. The support of leadership, adequate training and support, staff turnover, and organizational changes were all seen to impact the successful implementation of the program. Different barriers and facilitators were considered important at each stage of the process from introducing the screening procedures to service users; to determining when, where, and how to screen; and how to effectively manage the referral and post-referral stages. CONCLUSIONS: Despite the additional challenges of screening in an IBH-PC setting relative to secondary mental health services, the process was considered acceptable and feasible to providers and service users. Services that plan to conduct psychosis screening in their clinics need to consider the challenges and their potential solutions to implementation at each stage of the screening process.


Assuntos
Programas de Rastreamento , Atenção Primária à Saúde , Transtornos Psicóticos , Pesquisa Qualitativa , Humanos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/terapia , Masculino , Feminino , Adulto , Programas de Rastreamento/métodos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Entrevistas como Assunto , Pessoa de Meia-Idade , Prestação Integrada de Cuidados de Saúde/organização & administração , Serviços de Saúde Mental/organização & administração , Atitude do Pessoal de Saúde
10.
Elife ; 132024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136687

RESUMO

Apicomplexan parasites balance proliferation, persistence, and spread in their metazoan hosts. AGC kinases, such as PKG, PKA, and the PDK1 ortholog SPARK, integrate environmental signals to toggle parasites between replicative and motile life stages. Recent studies have cataloged pathways downstream of apicomplexan PKG and PKA; however, less is known about the global integration of AGC kinase signaling cascades. Here, conditional genetics coupled to unbiased proteomics demonstrates that SPARK complexes with an elongin-like protein to regulate the stability of PKA and PKG in the model apicomplexan Toxoplasma gondii. Defects attributed to SPARK depletion develop after PKG and PKA are down-regulated. Parasites lacking SPARK differentiate into the chronic form of infection, which may arise from reduced activity of a coccidian-specific PKA ortholog. This work delineates the signaling topology of AGC kinases that together control transitions within the asexual cycle of this important family of parasites.


Assuntos
Proteínas de Protozoários , Toxoplasma , Toxoplasma/genética , Toxoplasma/enzimologia , Toxoplasma/fisiologia , Toxoplasma/crescimento & desenvolvimento , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Animais , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/genética , Transdução de Sinais , Reprodução Assexuada
11.
J Am Chem Soc ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39140852

RESUMO

Nature uses compact but functionalized biosynthetic fragments as building blocks to generate complex natural products. To leverage this strategy for the discovery of natural products with new scaffolds, we performed genome mining to identify biosynthetic gene clusters (BGCs) in fungi that embed genes that can synthesize targeted fragments. The three-enzyme pathway that biosynthesizes the strained dityrosine cyclophane in the herquline A pathway was used to identify a large number of potential BGCs that may use the cyclophane as a fragment. Characterization of a conserved BGC from fungal strains led to the isolation of octacyclin A, an octacyclic natural product with an unprecedented structure, including two hetero-[3.3.1]bicycles and a combination of fused, bridged, and macrocyclic rings. Biosynthetic steps leading to octacyclin A were fully elucidated using pathway reconstitution and enzymatic assays, unveiling intriguing chemical logic and new enzymatic reactions in building the octacyclic core. Our work demonstrates the potential utility of fragment-guided genome mining in expanding natural product chemical space.

12.
Biol Trace Elem Res ; 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080232

RESUMO

Two experiments were conducted to examine the impact of trace mineral (TM) source on in vitro and in vivo solubility characteristics. Experiment 1: Hydroxy TM (HTM) and sulfate TM (STM) sources of Cu, Mn, and Zn were incubated separately in water for 24 h. Immediately after mixing, initial pH of each solution was greater (P < 0.03) for HTM compared to STM for all elements. Final pH tended to be greater for Cu (P = 0.09) and Zn (P = 0.07) from HTM compared to STM. Water solubility of Cu, Mn, and Zn from STM was greater (P < 0.01) than HTM sources. Experiment 2: Eight steers fitted with rumen cannula were blocked by body weight and randomly assigned to treatments. Treatments consisted of 10 mg Cu, 40 mg Mn, and 60 mg Zn/kg DM from either STM or HTM sources. Steers were individually fed a cracked corn-corn silage-based diet. Treatments were top-dressed daily. Rumen contents were collected at 0, 2, and 4 h post-feeding on d 1 and 14. On d 15, strained ruminal fluid and particle-associated microorganisms were obtained. Zinc was more tightly bound (P = 0.01) to the digesta in HTM-supplemented steers compared to STM on d 14. These data indicate that TM source influences pH and solubility of Cu, Mn, and Zn in water and may affect rumen soluble Cu concentrations and binding strength of Zn to solid digesta.

13.
Nat Mater ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009656

RESUMO

A nematic phase breaks the point-group symmetry of the crystal lattice and is known to emerge in correlated materials. Here we report the observation of an intra-unit-cell nematic order and associated Fermi surface deformation in the kagome metal ScV6Sn6. Using scanning tunnelling microscopy and scanning tunnelling spectroscopy, we reveal a stripe-like nematic order breaking the crystal rotational symmetry within the kagome lattice itself. Moreover, we identify a set of Van Hove singularities adhering to the kagome-layer electrons, which appear along one direction of the Brillouin zone and are annihilated along other high-symmetry directions, revealing rotational symmetry breaking. Via detailed spectroscopic maps, we further observe an elliptical deformation of the Fermi surface, which provides direct evidence for an electronically mediated nematic order. Our work not only bridges the gap between electronic nematicity and kagome physics but also sheds light on the potential mechanism for realizing symmetry-broken phases in correlated electron systems.

14.
Neurosurgery ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041790

RESUMO

BACKGROUND AND OBJECTIVE: Ambulatory surgery centers (ASCs) are increasingly common venues for same-day neurosurgical procedures, allowing for cost-effective, high-quality patient care. We present the first and largest series of patients undergoing diagnostic cerebral angiography at an ASC to demonstrate the effectiveness, safety, and efficiency of outpatient endovascular care. METHODS: We retrospectively reviewed data for consecutive patients who underwent diagnostic cerebral angiography at our ASC between January 1, 2024, and May 29, 2024. Data collected included vascular access approach, procedural duration, turnover time, and periprocedural complications. Using a standardized 2-week postprocedural survey, patients were asked to provide comments and rate their subjective satisfaction from a 1 to 5 scale, with "5" being completely satisfied. All cases were performed with a physician team comprising 1 attending neuroendovascular neurosurgery and 1 neuroendovascular fellow present. Fentanyl and midazolam were administered for conscious sedation in all cases. RESULTS: Among the 67 patients included in this series, the mean procedural duration was 29.4 ± 8.6 minutes. The mean turnover time was 13.7 ± 3.6 minutes. Between transradial (46 of 67 [68.7%]) and transfemoral (21 of 67 [31.3%]) access site approaches, there were no statistically significant differences in mean procedural duration (29.4 ± 8.0 vs 29.2 ± 9.9 minutes, respectively; P = .72) or turnover time (14.0 ± 3.9 vs 12.9 ± 2.8 minutes, respectively; P = .4). No complications occurred periprocedurally or within the 2-week follow-up period. A total of 48 (71.6%) of 67 patients responded to the postprocedural survey, all of whom unanimously reported a score of "5." CONCLUSION: We found that diagnostic cerebral angiography performed at our ASC was safe and effective for patient care. In addition, all survey respondents (71.6% of those provided the survey) reported highest levels of satisfaction. The integration of neuroendovascular procedures into ASCs potentially offers a cost-effective and highly efficient option in an evolving economic landscape.

15.
Nat Mater ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060470

RESUMO

Helicity in solids often arises from the precise ordering of cooperative intra- and intermolecular interactions unique to natural, organic or molecular systems. This exclusivity limited the realization of helicity and its ensuing properties in dense inorganic solids. Here we report that Ga atoms in GaSeI, a representative III-VI-VII one-dimensional (1D) van der Waals crystal, manifest the rare Boerdijk-Coxeter helix motif. This motif is a non-repeating geometric pattern characterized by 1D face-sharing tetrahedra whose adjacent vertices are rotated by an irrational angle. Using InSeI and GaSeI, we show that the modularity of 1D van der Waals lattices accommodates the systematic twisting of a periodic tetrahelix with a 41 screw axis in InSeI to an infinitely extending Boerdijk-Coxeter helix in GaSeI. GaSeI crystals are non-centrosymmetric, optically active and exfoliable to a single chain. These results present a materials platform towards understanding the origin and physical manifestation of aperiodic helicity in low-dimensional solids.

16.
Brain Behav Immun ; 121: 280-290, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39032543

RESUMO

Converging data show that exposure to maternal immune activation (MIA) in utero alters brain development in animals and increases the risk of neurodevelopmental disorders in humans. A recently developed non-human primate MIA model affords opportunities for studies with uniquely strong translational relevance to human neurodevelopment. The current longitudinal study used 1H-MRS to investigate the developmental trajectory of prefrontal cortex metabolites in male rhesus monkey offspring of dams (n = 14) exposed to a modified form of the inflammatory viral mimic, polyinosinic:polycytidylic acid (Poly IC), in the late first trimester. Brain metabolites in these animals were compared to offspring of dams that received saline (n = 10) or no injection (n = 4). N-acetylaspartate (NAA), glutamate, creatine, choline, myo-inositol, taurine, and glutathione were estimated from PRESS and MEGA-PRESS acquisitions obtained at 6, 12, 24, 36, and 45 months of age. Prior investigations of this cohort reported reduced frontal cortical gray and white matter and subtle cognitive impairments in MIA offspring. We hypothesized that the MIA-induced neurodevelopmental changes would extend to abnormal brain metabolite levels, which would be associated with the observed cognitive impairments. Prefrontal NAA was significantly higher in the MIA offspring across all ages (p < 0.001) and was associated with better performance on the two cognitive measures most sensitive to impairment in the MIA animals (both p < 0.05). Myo-inositol was significantly lower across all ages in MIA offspring but was not associated with cognitive performance. Taurine was elevated in MIA offspring at 36 and 45 months. Glutathione did not differ between groups. MIA exposure in male non-human primates is associated with altered prefrontal cortex metabolites during childhood and adolescence. A positive association between elevated NAA and cognitive performance suggests the hypothesis that elevated NAA throughout these developmental stages reflects a protective or resilience-related process in MIA-exposed offspring. The potential relevance of these findings to human neurodevelopmental disorders is discussed.

17.
S D Med ; 77(1): 6-23, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38986144

RESUMO

In 2022, there was a decrease in births in the state with 111 fewer resident newborns than in the previous year. This represented a decrease of 1% of its white and 3.5% of its AIBO (American Indian, Black and Other) births. The 2022 birth rate per 1,000 population for the state (12.3) is higher than observed nationally (10.9) but matches its 2020 rate that was an historic low. Approximately 22% of all births in 2022 were AIBO and this percent of the state's entire birth cohort has decreased in the past several years. The American Indian contribution to the AIBO cohort has also decreased as its racial diversity has increased. The percent of births that are low birth weight has consistently been lower in South Dakota than nationally. An increase of 16 infant deaths in 2022 from 2021 and the decreased number of births led to an increase in the infant mortality rate (IMR = deaths in first year of life per 1,000 live births) from 6.3 to 7.8, but this 2022 IMR is not statistically significantly higher than its previous five-year mean. Further, the 2022 increase in the IMR was almost entirely among white infants with the post neonatal mortality rate (PNMR = deaths between 28 and 365 days of life) decreasing between these two years for AIBO infants. Nonetheless, the state's five year mean rates of death (2018-2022) are significantly higher for the AIBO than white infants for the neonatal (0-27 days) and post neonatal periods of the first year of life. Recently, however, the ratio of AIBO to white post neonatal mortality rate (PNMR) has decreased, but increased for the neonatal mortality rate (NMR). Infants in South Dakota are significantly more likely between 2018 and 2022 to die of congenital anomalies, sudden unexpected infant death (SUID), and accidents/homicides than in the United States in 2021. SUID remains the leading cause of post neonatal death and its risk may be decreased when babies are placed to sleep supine and alone in environments that are devoid of soft hazards.


Assuntos
Coeficiente de Natalidade , Mortalidade Infantil , South Dakota/epidemiologia , Humanos , Mortalidade Infantil/tendências , Recém-Nascido , Lactente , Coeficiente de Natalidade/tendências , Recém-Nascido de Baixo Peso , Indígenas Norte-Americanos/estatística & dados numéricos
18.
Conserv Physiol ; 12(1): coae045, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974502

RESUMO

In the age of global climate change, extreme climatic events are expected to increase in frequency and severity. Animals will be forced to cope with these novel stressors in their environment. Glucocorticoids (i.e. 'stress' hormones) facilitate an animal's ability to cope with their environment. To date, most studies involving glucocorticoids focus on the immediate physiological effects of an environmental stressor on an individual, few studies have investigated the long-term physiological impacts of such stressors. Here, we tested the hypothesis that previous exposure to an environmental stressor will impart lasting consequences to an individual's glucocorticoid levels. In semi-arid environments, variable rainfall drives forage availability for herbivores. Reduced seasonal precipitation can present an extreme environmental stressor potentially imparting long-term impacts on an individual's glucocorticoid levels. We examined the effects of rainfall and environmental characteristics (i.e. soil and vegetation attributes) during fawn-rearing (i.e. summer) on subsequent glucocorticoid levels of female white-tailed deer (Odocoileus virginianus) in autumn. We captured 124 adult (≥2.5-year-old) female deer via aerial net-gunning during autumn of 2015, 2016 and 2021 across four populations spanning a gradient of environmental characteristics and rainfall in the semi-arid environment of South Texas, USA. We found for every 1 cm decrease in summer rainfall, faecal glucocorticoid levels in autumn increased 6.9%, but only in lactating females. Glucocorticoid levels in non-lactating, female deer were relatively insensitive to environmental conditions. Our study demonstrates the long-lasting effects of environmental stressors on an individual's glucocorticoid levels. A better understanding of the long-term effects stressors impart on an individual's glucocorticoid levels will help to evaluate the totality of the cost of a stressor to an individual's welfare and predict the consequences of future climate scenarios.

19.
Schizophr Bull ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979781

RESUMO

BACKGROUND AND HYPOTHESIS: Identifying biomarkers that predict treatment response in early psychosis (EP) is a priority for psychiatry research. Previous work suggests that resting-state connectivity biomarkers may have promise as predictive measures, although prior results vary considerably in direction and magnitude. Here, we evaluated the relationship between intrinsic functional connectivity of the attention, default mode, and salience resting-state networks and 12-month clinical improvement in EP. STUDY DESIGN: Fifty-eight individuals with EP (less than 2 years from illness onset, 35 males, average age 20 years) had baseline and follow-up clinical data and were included in the final sample. Of these, 30 EPs showed greater than 20% improvement in Brief Psychiatric Rating Scale (BPRS) total score at follow-up and were classified as "Improvers." STUDY RESULTS: The overall logistic regression predicting Improver status was significant (χ2 = 23.66, Nagelkerke's R2 = 0.45, P < .001, with 85% concordance). Significant individual predictors of Improver status included higher default mode within-network connectivity, higher attention-default mode between-network connectivity, and higher attention-salience between-network connectivity. Including baseline BPRS as a predictor increased model significance and concordance to 92%, and the model was not significantly influenced by the dose of antipsychotic medication (chlorpromazine equivalents). Linear regression models predicting percent change in BPRS were also significant. CONCLUSIONS: Overall, these results suggest that resting-state functional magnetic resonance imaging connectivity may serve as a useful biomarker of clinical outcomes in recent-onset psychosis.

20.
J Strength Cond Res ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38968202

RESUMO

ABSTRACT: Dengel, DR, Studee, HR, Juckett, WT, Bosch, TA, Carbuhn, AF, Stanforth, PR, and Evanoff, NG. Muscle-to-bone ratio in NCAA division I collegiate football players by position. J Strength Cond Res XX(X): 000-000, 2024-The purpose of this study was to compare the muscle-to-bone ratio (MBR) in National Collegiate Athletic Association Division I football players (collegiate football players [CFP]) to healthy, age-matched controls. In addition, we examined MBR in CFP by position. A total of 553 CFP and 261 controls had their total and regional lean mass (LM), fat mass (FM), and bone mineral content (BMC) determined by dual x-ray absorptiometry (DXA). College football players were categorized by positions defined as offensive linemen (OL), defensive linemen (DL), tight end, linebacker (LB), running back (RB), punter or kicker, quarterback (QB), defensive back (DB), and wide receiver (WR). There were significant differences between CFP and controls for total LM (80.1 ± 10.0 vs. 56.9 ± 7.8 kg), FM (22.2 ± 12.5 vs. 15.2 ± 7.1 kg), and BMC (4.3 ± 0.5 vs. 3.1 ± 0.5 kg). Although there were significant differences in body composition between CFP and controls, there was no significant differences in total MBR between CFP and controls (18.6 ± 1.4 vs. 18.8 ± 1.7). Regionally, CFP had significantly lower trunk MBR than controls (26.7 ± 2.7 vs. 28.7 ± 4.2), but no difference was seen in leg or arm MBR. Positional differences in CFP were noted as total MBR being significantly higher in DL (19.0 ± 1.4) than in DB (18.1 ± 1.3), WR (18.1 ± 1.3), and LB (18.2 ± 1.3). OL had a significantly higher total MBR (19.2 ± 1.3) than DB (18.1 ± 1.3), LB (18.2 ± 1.3), QB (18.1 ± 1.0), and WR (18.1 ± 1.3). In addition, RB had significantly higher total MBR (18.8 ± 1.3) than DB (18.1 ± 1.3) and WR (18.1 ± 1.3). This study may provide athletes and training staff with normative values when evaluating total and regional MBR with DXA.

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