Sarcopenia and the management of spinal disease in the elderly.

Sarcopenia, generally defined by the loss of skeletal mass and function, may disproportionately affect elderly individuals and heavily influence spinal disease. Muscle atrophy is associated with myriad clinical problems, including thoracic kyphosis, increased sagittal vertical axis (SVA), spinal implant failures, and postoperative complications. As such, the aim of this narrative review is to synthesize pertinent literature detailing the intersection between sarcopenia and the impact of sarcopenia on the management of spine disease. Specifically, we focus on the domains of etiology, diagnosis and assessment, impact on the cervical and lumbar spine, spinal augmentation procedures, neoplastic disease, whiplash injury, and recovery/prevention. A narrative review was conducted by searching the PubMed and Google Scholar databases from inception to July 12, 2024, for any cohort studies, systematic reviews, or randomized controlled trials. Case studies and conference abstracts were excluded. Diagnosis of sarcopenia relies on the assessment of muscle strength and quantity/quality. Strength may be assessed using clinical tools such as gait speed, timed up and go (TUG) test, or hand grip strength, whereas muscle quantity/quality may be assessed via computed tomography (CT scan), magnetic resonance imaging (MRI), and dual-energy X-ray absorptiometry (DXA scan). Sarcopenia has a generally negative impact on the clinical course of those undergoing cervical and lumbar surgery, and may be predictive of mortality in those with neoplastic spinal disease. In addition, severe acceleration-deceleration (whiplash) injuries may result in cervical extensor muscle atrophy. Intervention and recovery measures include nutrition or exercise therapy, although the evidence for nutritional intervention is lacking. Sarcopenia is a widely prevalent pathology in the advanced-age population, in which the diagnostic criteria, impact on spinal pathology, and recovery/prevention measures remain understudied. However, further understanding of this therapeutically challenging pathology is paramount, as surgical outcome may be heavily influenced by sarcopenia status.

Boosting NIR Laser Marking Efficiency of a Transparent Epoxy Using a Layered Double Hydroxide.

Efficient near-infrared (NIR) laser marking on transparent polymers like polypropylene, epoxy, and polyethylene has posed a big challenge due to their lack of absorption in the NIR. Currently, inorganic additives are used to improve NIR laser marking efficiency, but they come with issues such as toxicity, high loading requirement, adverse effects on color/opaqueness, and the need for low laser head speeds. Herein, we report a new strategy of incorporating a food-grade, Mg2Al-CO3 LDH as a boosting coadditive alongside the commercial NIR laser marking additive (Iriotech 8815) in an epoxy system. Our findings demonstrate that the incorporation of Mg2Al-CO3 LDH can significantly increase both the darkness and contrast of marking even at high laser head speed (5000 mm/s), while minimizing surface damage. Notably, by replacing 95% of Iriotech 8815 with Mg2Al-CO3 LDH, an epoxy plate can exhibit high transparency, while producing dark, sharply defined markings with excellent readable QR code markings at high laser speeds. This result offers a promising solution for enhancing high-speed NIR laser marking on transparent polymers with additional advantages of lower toxicity and cost and with minimal optical interference from high additive loadings.

IFNγ Production by Functionally Reprogrammed Tregs Promotes Antitumor Efficacy of OX40/CD137 Bispecific Agonist Therapy.

Regulatory T cells (Treg) are highly enriched within many tumors and suppress immune responses to cancer. There is intense interest in reprogramming Tregs to contribute to antitumor immunity. OX40 and CD137 are expressed highly on Tregs, activated and memory T cells, and NK cells. In this study, using a novel bispecific antibody targeting mouse OX40 and CD137 (FS120m), we show that OX40/CD137 bispecific agonism induces potent antitumor immunity partially dependent upon IFNγ production by functionally reprogrammed Tregs. Treatment of tumor-bearing animals with OX40/CD137 bispecific agonists reprograms Tregs into both fragile Foxp3+ IFNγ+ Tregs with decreased suppressive function and lineage-instable Foxp3- IFNγ+ ex-Tregs. Treg fragility is partially driven by IFNγ signaling, whereas Treg instability is associated with reduced IL2 responsiveness upon treatment with OX40/CD137 bispecific agonists. Importantly, conditional deletion of Ifng in Foxp3+ Tregs and their progeny partially reverses the antitumor efficacy of OX40/CD137 bispecific agonist therapy, revealing that reprogramming of Tregs into IFNγ-producing cells contributes to the anti-tumor efficacy of OX40/CD137 bispecific agonists. These findings provide insights into mechanisms by which bispecific agonist therapies targeting costimulatory receptors highly expressed by Tregs potentiate antitumor immunity in mouse models. SIGNIFICANCE: The bispecific antibody FS120, an immunotherapy currently being tested in the clinic, partially functions by inducing anti-tumor activity of Tregs, which results in tumor rejection.

Safety and efficacy of antibiotic-impregnated absorbable calcium sulfate beads (Stimulan) in cranioplasty.

Cranioplasty is a common neurosurgical procedure that follows hemicraniectomy in the setting of neoplasm resection or increased intracranial pressure. Although standardized practices aim at minimizing infection risk, infection of the surgical site has been reported in 6.6%-8.4% of patients. In this work, we document the novel use of synthetic dissolvable antibiotic-impregnated calcium sulfate beads (STIMULANⓇ Rapid Cure, Biocomposites Ltd, Wilmington, NC, USA) in five cases of cranioplasty at our institution. Four patients experienced wound healing as expected with no complications related to the use of Stimulan beads. One patient's clinical course was complicated by pseudomeningocele with superficial wound infection occurring 74 days following cranioplasty. Of note, this patient had suffered an avulsion injury and subgaleal hematoma of the scalp ipsilateral to the cranial incision, predisposing to infection due to incompetent scalp vasculature. No complications could be directly attributed to the use of STIMULANⓇ beads.

Clinical Research Primer for Medical Students: Overview and Illustrative Experiences.

Background The ability to participate in clinical scholarship is a foundational component of modern evidence-based medical practice, empowering improvement across essentially every aspect of clinical care. In tandem, the need for comprehensive exposure to clinical research has been identified as a critical component of medical student training and preparation for residency that is underserved by traditional undergraduate medical education models. The goal of the current work was to provide guidelines and recommendations to assist novice medical students in taking ownership of their research education. Methods The Clinical Research Primer was composed from pooled research documents compiled by the study authors and our institutional neurosurgery student research group. The Primer was then structured as the natural evolution of a research project from its inception through the submission process. Results We divided the foundational components of the Clinical Research Primer into seven domains, each representing a landmark in the development of a peer-reviewed study, and a set of skills critical for junior scholars to develop. These vital components included the following: pitching and designing clinical studies, developing a research workflow, navigating the Institutional Review Board, data collection and analysis, manuscript writing and editing, submission mechanics, and tracking research projects for career development. Conclusion We anticipate that the tools included in the Clinical Research Primer will increase student research productivity and preparedness for residency. Although our recommendations are informed by our experiences within neurosurgery, they have been written in a manner that should generalize to almost any field of clinical study.

The safety and efficacy of the Stryker OptaBlate™ Bone Tumor Ablation system for vertebral body metastases.

Background: Metastatic spinal lesions are a significant cause of morbidity and decreased quality of life in those with a high tumor burden. Despite treatment modalities such as medical therapy (e.g., chemotherapy, steroids), spinal augmentation procedures, and radiation therapy, many patients still experience refractory back pain due to neoplastic infiltration of the vertebral body and/or pathologic compression fractures. With the aim to address refractory pain in patients who have exhausted conventional treatment options, Stryker developed the OptablateTM Bone Tumor Ablation system (BTA; Stryker Corporation, Kalamazoo, MI), which delivers radiofrequency energy to pathologic vertebral body lesions. In this preliminary single-institution study, we characterize the use of the BTA system in 11 patients undergoing kyphoplasty for pathologic spinal lesions with the goal to demonstrate the impact of this novel technology on refractory pain in this challenging clinical setting. Methods: A single-center retrospective chart review was performed on all patients identified as those receiving tumor ablation/kyphoplasty for spinal neoplasms using the OptablateTM BTA system performed by a single surgeon at the University of Oklahoma Medical Center. Sex, age, primary lesion type, presenting symptomatology, spinal level, time of follow-up, and outcome were obtained from the electronic medical record (EMR). Results: Eleven patients (4 males, 7 females) with a mean age of 62 (range, 38-82) years had an average follow-up time of 6 months. Presenting symptoms attributed to spinal pathology included back pain (n = 11, 100%), pathologic fracture (n = 6, 55%), and lower extremity weakness (n = 3, 27%). A total of 20 lesions were ablated at 12 vertebral levels. Eight patients (73%) had improved pain. No complications were reported. Conclusion: This preliminary study documents the safety of the BTA system, in addition to its diverse use across many levels. The majority of patients reported improvement in their pain. Further study is required to fully characterize the use of the BTA system in those with neoplastic spinal pathology.

Evaluating osteoporosis and bone quality in the aging spine: modern considerations for surgical management in the geriatric population.

Surgical management paradigms of spinal pathologies in the aging population carry inherent substantial risks, with surgical complications being more prevalent among patients with osteoporosis compared to those with normal bone mineral density. In this narrative review, we aim to highlight important clinical understanding and considerations in perioperative evaluation and management of patients elected to undergo spinal surgery. Osteoporosis is a well-defined risk factor for mechanical complications following spinal surgery, and as such, perioperative optimization of bone health in the setting of surgery for geriatric patients remains a critical research area alongside intraoperative surgical augmentation techniques. Surgical techniques to circumvent challenges with instrumentation of poor bone mineral density have included augmentation of pedicle screw fixation, including segmental bicortical screw fixation techniques, cement augmentation with fenestrated screws, or use of expandable pedicle screws to improve bone-implant interface. Judicious selection of treatment modalities and subsequent perioperative optimization is paramount to minimize surgical complications. Contemporary guidelines and evolving paradigms in perioperative evaluation, optimization, and management of the aging spine include the advent of quantitatively evaluating computed tomography (CT) via assessment of the magnitude of Hounsfield units. Prescribing pharmacotherapeutic agents and monitoring bone health requires a multidisciplinary team approach, including endocrinologists and geriatricians to coordinate high-quality care for advanced-age patients who require surgical management of their spinal disorders.

Genetically Distinct Oligosarcoma Arising from Oligodendroglioma: Systematic Review & Illustrative Case Example.

BACKGROUND: Oligosarcoma is a rare central nervous system (CNS) neoplasm that may arise following oligodendroglioma resection, which demonstrates a unique genetic profile and aggressive clinical phenotype. We present a systematic review and illustrative case example emphasizing the clinical and prognostic features of this unusual and unfavorable neuro-oncologic disease. METHODS: Systematic literature review and illustrative case report. RESULTS: A 41-year-old man who had undergone 2 neurosurgical resections for a World Health Organization grade II oligodendroglioma (Ki-67 = 5-10%, 1p/19q codeleted, IDH2 mutated), without adjuvant chemoradiation, presented with seizures seven years after resection. An extra-axial mass was identified adjacent to the resection cavity, in which gross total resection was achieved. Pathology confirmed World Health Organization grade IV oligosarcoma (Ki-67 = 20%). Adjuvant chemoradiation was initiated, with disease control observed over 6 months of follow-up. Seven publications met inclusion criteria. Oligosarcoma has been confirmed in 36 lesions, arising in 35 patients; 5 were primary oligosarcoma, while 31 occurred in the setting of prior resected oligodendroglioma or oligoastrocytoma. Features shared by these lesions include regain of H3K27me3 expression, 1p/19q codeletion, homozygous deletion of CDKN2A/B, loss of 6q, loss of NF1 and YAP1, and attenuation of CpG island methylator. Median survival after oligosarcoma diagnosis was 1.3 years (range, 0-5.2; n = 35). CONCLUSIONS: Oligosarcoma is a prognostically unfavorable CNS neoplasm with characteristic imaging and pathologic features, and a strong association with previously resected oligodendroglioma. Aggressive treatment is recommended, including gross total resection and adjuvant chemoradiation. Further study is required to define optimal treatment protocol for this CNS malignancy.

Surgical management of spinal pathologies in the octogenarian: a narrative review.

Optimal management paradigms of spinal pathologies in the octogenarian population are controversial given the higher incidence of comorbidities with concern for poor prognosis and fear of increased complications associated with surgical management. In this narrative review, we aim to detail the complex clinical considerations when approaching odontoid screw fixation/instrumented fusion, spinal decompression, and spinal fusion in the octogenarian. Literature review was conducted via Google Scholar and PubMed databases, with literature selected based on statistical power and clinical relevance to the following pathologies/surgical techniques: odontoid fracture, surgical decompression, and surgical fusion in the octogenarian. The aforementioned pathologies were selected based on prevalence in the advanced-age population in which surgical screening techniques and management remain nonuniform. Preoperative evaluation of the octogenarian patient increasingly includes frailty, sarcopenia, and osteopenia/osteoporosis assessments. In cases of odontoid fracture, conservative management appears to provide beneficial clinical outcomes with lower rates of complication compared to surgery; however, rates of radiographic odontoid fusion are far lower in conservatively managed patients. Regarding surgical decompression and fusion, the presence of comorbidities may be more predictive of outcome rather than age status, with the advent of minimally invasive techniques providing safety and efficacy in the surgical management of this age cohort. Age status may be less pertinent than previously thought in the decision to pursue spinal surgery for odontoid fracture, spinal decompression, or spinal fusion; however, each of these procedures has respective risks and benefits that must be considered within the context of each patient's comorbidity profile.

Acquisition of suppressive function by conventional T cells limits antitumor immunity upon Treg depletion.

Regulatory T (Treg) cells contribute to immune homeostasis but suppress immune responses to cancer. Strategies to disrupt Treg cell-mediated cancer immunosuppression have been met with limited clinical success, but the underlying mechanisms for treatment failure are poorly understood. By modeling Treg cell-targeted immunotherapy in mice, we find that CD4+ Foxp3- conventional T (Tconv) cells acquire suppressive function upon depletion of Foxp3+ Treg cells, limiting therapeutic efficacy. Foxp3- Tconv cells within tumors adopt a Treg cell-like transcriptional profile upon ablation of Treg cells and acquire the ability to suppress T cell activation and proliferation ex vivo. Suppressive activity is enriched among CD4+ Tconv cells marked by expression of C-C motif receptor 8 (CCR8), which are found in mouse and human tumors. Upon Treg cell depletion, CCR8+ Tconv cells undergo systemic and intratumoral activation and expansion, and mediate IL-10-dependent suppression of antitumor immunity. Consequently, conditional deletion of Il10 within T cells augments antitumor immunity upon Treg cell depletion in mice, and antibody blockade of IL-10 signaling synergizes with Treg cell depletion to overcome treatment resistance. These findings reveal a secondary layer of immunosuppression by Tconv cells released upon therapeutic Treg cell depletion and suggest that broader consideration of suppressive function within the T cell lineage is required for development of effective Treg cell-targeted therapies.

BACH2 restricts NK cell maturation and function, limiting immunity to cancer metastasis.

Natural killer (NK) cells are critical to immune surveillance against infections and cancer. Their role in immune surveillance requires that NK cells are present within tissues in a quiescent state. Mechanisms by which NK cells remain quiescent in tissues are incompletely elucidated. The transcriptional repressor BACH2 plays a critical role within the adaptive immune system, but its function within innate lymphocytes has been unclear. Here, we show that BACH2 acts as an intrinsic negative regulator of NK cell maturation and function. BACH2 is expressed within developing and mature NK cells and promotes the maintenance of immature NK cells by restricting their maturation in the presence of weak stimulatory signals. Loss of BACH2 within NK cells results in accumulation of activated NK cells with unrestrained cytotoxic function within tissues, which mediate augmented immune surveillance to pulmonary cancer metastasis. These findings establish a critical function of BACH2 as a global negative regulator of innate cytotoxic function and tumor immune surveillance by NK cells.

Multidisciplinary neurocutaneous syndrome clinics: a systematic review and institutional experience.

OBJECTIVE: Neurocutaneous syndromes have variable multisystem involvement. The multiorgan involvement, potential pathologies, and various treatment options necessitate collaboration and open discussion to ensure optimal treatment in any given patient. These disorders provide quintessential examples of chronic medical conditions that require a lifelong, multidisciplinary approach. The objectives of this study were to 1) perform a systematic review, thoroughly assessing different multidisciplinary clinic layouts utilized in centers worldwide; and 2) characterize an institutional experience with the management of these conditions, focusing on the patient demographics, clinical presentation, complications, and therapeutic strategies seen in a patient population. METHODS: A systematic review of studies involving multidisciplinary clinics and their reported structure was performed according to PRISMA guidelines using the PubMed database. Then a retrospective chart review of patients enrolled in the Oklahoma Children's Hospital Neurocutaneous Syndromes Clinic was conducted. RESULTS: A search of the PubMed database yielded 251 unique results. Of these, 15 papers were included in the analysis, which identified 16 clinics that treated more than 2000 patients worldwide. The majority of these clinics treated patients with neurofibromatosis (13/16). The remaining clinics treated patients with von Hippel-Lindau syndrome (n = 1), tuberous sclerosis complex (n = 1), and multiple neurocutaneous syndromes (n = 1). The most commonly represented subspecialties in these clinics were genetics (15/16) and neurology (13/16). Five clinics (31%) solely saw pediatric patients, 10 clinics saw a combination of children and adults, and the final clinic had separate pediatric and adult clinics. The retrospective chart review of the Neurocutaneous Syndromes Clinic demonstrated that 164 patients were enrolled and seen in the clinic from April 2013 to December 2021. Diagnoses were made based on clinical findings or results of genetic testing; 115 (70%) had neurofibromatosis type 1, 9 (5.5%) had neurofibromatosis type 2, 35 (21%) had tuberous sclerosis complex, 2 (1%) had von Hippel-Lindau syndrome, 2 (1%) had Gorlin syndrome, and the remaining patient (0.6%) had Aarskog-Scott syndrome. Patient demographics, clinical presentation, complications, and therapeutic strategies are also discussed. CONCLUSIONS: To the best of the authors' knowledge, this is the first detailed description of a comprehensive pediatric neurocutaneous clinic in the US that serves patients with multiple syndromes. There is currently heterogeneity between described multidisciplinary clinic structures and practices. More detailed accounts of clinic compositions and practices along with patient data and outcomes are needed in order to establish the most comprehensive and efficient multidisciplinary approach for neurocutaneous syndromes.

Physical Forces in Glioblastoma Migration: A Systematic Review.

The invasive capabilities of glioblastoma (GBM) define the cancer's aggressiveness, treatment resistance, and overall mortality. The tumor microenvironment influences the molecular behavior of cells, both epigenetically and genetically. Current forces being studied include properties of the extracellular matrix (ECM), such as stiffness and "sensing" capabilities. There is currently limited data on the physical forces in GBM-both relating to how they influence their environment and how their environment influences them. This review outlines the advances that have been made in the field. It is our hope that further investigation of the physical forces involved in GBM will highlight new therapeutic options and increase patient survival. A search of the PubMed database was conducted through to 23 March 2022 with the following search terms: (glioblastoma) AND (physical forces OR pressure OR shear forces OR compression OR tension OR torsion) AND (migration OR invasion). Our review yielded 11 external/applied/mechanical forces and 2 tumor microenvironment (TME) forces that affect the ability of GBM to locally migrate and invade. Both external forces and forces within the tumor microenvironment have been implicated in GBM migration, invasion, and treatment resistance. We endorse further research in this area to target the physical forces affecting the migration and invasion of GBM.

The potential of volatile organic compound analysis in cervicovaginal mucus to predict estrus and ovulation in estrus-synchronized heifers.

Cervicovaginal mucus is a mixture of mucins, ions, salts, and water, the proportions of which change during the reproductive cycle. It is suspected that this mucus emits an important volatile signal indicative of the reproductive state of the female. The objective of this study was to identify volatile organic compounds (VOC) in bovine cervicovaginal mucus that are modulated during the estrous cycle and could potentially be used as biomarkers of estrus and ovulation. Cervicovaginal mucus was collected from crossbred beef heifers (n = 8), which were synchronized using an 8-d controlled internal drug release (CIDR) protocol and in which onset of estrus and time of ovulation were determined by visual observation and ultrasonography, respectively. Mucus samples were collected between 0 and 96 h after CIDR removal (estrus onset occurred at 49.1 ± 3.3 h after CIDR removal). A validation study was performed on an independent group of 15 heifers from which cervicovaginal mucus samples were collected every 8 h from 40 to 80 h after CIDR removal. The VOC in mucus were identified using gas chromatography-mass spectrometry and selected compounds were quantified using selected-ion flow-tube mass spectrometry. The presence of 47 VOC was detected in mucus samples by gas chromatography-mass spectrometry with those exhibiting highest abundance including 2-butanone, acetone, 2-pentanone, 4-methyl-2-pentanone, 1-(1-methylethoxy)-2-propanone, ethanol, 2-methyl-2-propanol, and 2-butanol. All VOC peaked between 24 to 47 h after the onset of estrus (ovulation occurred 26.6 ± 5.6 h after estrus onset). Two VOC, 2-pentanone and 4-methyl-2-pentanone, exhibited a significant increase at the onset of estrus, whereas concentration of 2-butanone increased significantly just after estrus onset, indicating that these VOC may be used as putative biomarkers of estrus. The results of our study may contribute to the development of a sensor device based on VOC to aid the detection of estrus and ovulation in cattle, with particular relevance for the dairy industry where the majority of females are bred by artificial insemination.

Roles of interferon-stimulated gene 15 protein in bovine embryo development.

Interferon (IFN)-stimulated gene 15 (ISG15) is one of several proteins induced by conceptus-derived Type I or II IFNs in the uterus, and is implicated as an important factor in determining uterine receptivity to embryos in ruminants. But little is known about the role the ISG15 gene or gene product plays during embryo development. In the present study, both the expression profile and function of ISG15 were investigated in early bovine embryos in vitro. ISG15 mRNA was detectable in Day 0, 2, 6 and 8 bovine embryos, but IFN-τ (IFNT) mRNA only appeared from Day 6. This means that embryonic expression of ISG15 on Days 0 and 2 was not induced by embryonic IFNT. However, ISG15 mRNA expression paralleled the expression of IFNT mRNA in Day 6 and 8 embryos. ISG15-lentivirus interference plasmid (ISG15i) was injected into 2-cell embryos to knockdown ISG15 expression. This resulted in decreases in the proportion of hatching blastocysts, the diameter of blastocysts and cell number per diameter of blastocysts compared with control embryos. In addition, ISG15i inhibited IFNT, Ets2 (E26 oncogene homolog 2) mRNA and connexion 43 protein expression in Day 8 blastocysts, whereas exogenous IFNT treatment (100ngmL-1, from Day 4 to Day 8) improved ISG15 mRNA and connexion 43 protein expression. In conclusion, it appears that ISG15 is involved in early bovine embryo development and that it regulates IFNT expression in the blastocyst.

Surveillance for hepatocellular carcinoma in a mixed-aetiology UK cohort with cirrhosis: does α-fetoprotein still have a role?

Mortality from hepatocellular carcinoma (HCC) in people with cirrhosis is increasing whereas mortality from other causes is declining. Surveillance appears to reduce mortality but the optimal strategy is uncertain. Current guidelines differ by recommending ultrasonography alone or with α-fetoprotein (αFP). Records in three UK hospitals were analysed from 2006 to 2011. Of 111 HCC cases identified, 24 (47.1%) of those eligible were under surveillance: 21 (87.5%) were under combined ultrasonography-αFP, 2 (8.3%) ultrasonography-only and 1 (4.2%) αFP-only surveillance. αFP was elevated in 19 (86.4%), and αFP alone triggered a confirmatory study in 11 (9.9%) overall and 7 (29.1%) under surveillance. Surveillance, but not αFP, correlated with smaller tumours. Survival did not differ significantly between groups. Given that αFP use is associated with identifying smaller HCCs and that several diagnoses would have been delayed without αFP in this real-life cohort, these data support ongoing αFP use. However, further work is necessary with regard to whether αFP translates into improved clinical outcome and overall cost effects. In our area, stopping αFP use would also represent a significant change in practice.

Effects of systemic progesterone during the early luteal phase on the availabilities of amino acids and glucose in the bovine uterine lumen.

The uterine histotroph provides essential nutrition to the developing conceptus during the preimplantation period of pregnancy. The objective of the present study was to examine the effects of cycle stage and progesterone (P4) concentrations in the blood on the recoverable quantities of amino acids and glucose in the histotroph during the preimplantaion period of conceptus development. Following oestrus, dairy heifers were assigned to low, control or high P4 groups (n=6 heifers per treatment and time point). The uterine horn ipsilateral to the corpus luteum was flushed on either Day 7 or Day 13. The present study quantified 24 amino acids and glucose in the uterine flushings using HPLC and fluorometry, respectively. Heifers in the low P4 group had lower plasma concentrations of P4 throughout the cycle, whereas heifers in the high group had higher plasma concentrations of P4 between Days 3 and 7 compared with the control group (P<0.05). Total recoverable neutral (Ser, Gln, Gly, Thr, Cit, ß-Ala, Tau, Ala, Tyr, Trp, Met, Val, Phe, Ile, Leu, Pro and Cys), acidic (Glu) and basic (His, Arg, Orn and Lys) amino acids were greater (P<0.05) on Day 13 than on Day 7. There was no significant difference in the amount of Asp or Asn between Day 7 and Day 13. The amount of amino acids recovered on Day 7 was similar across treatment groups. On Day 13, the amount of Asn, His and Thr was lower (P<0.05) in the low P4 heifers compared with the controls and/or high P4 heifers. Quantities of glucose were not altered by cycle stage or P4 treatment. In conclusion, the stage of oestrous cycle and P4 play important roles in modulating amino acids in the histotroph, a potentially critical factor for early embryonic and/or conceptus survival.

Molecular aspects of mucin biosynthesis and mucus formation in the bovine cervix during the periestrous period.

Mucus within the cervical canal represents a hormonally regulated barrier that reconciles the need to exclude the vaginal microflora from the uterus during progesterone dominance, while permitting sperm transport at estrus. Its characteristics change during the estrous cycle to facilitate these competing functional requirements. Hydrated mucin glycoproteins synthesized by the endocervical epithelium form the molecular scaffold of this mucus. This study uses the bovine cervix as a model to examine functional groups of genes related to mucin biosynthesis and mucus production over the periestrous period when functional changes in cervical barrier function are most prominent. Cervical tissue samples were collected from 30 estrus synchronized beef heifers. Animals were slaughtered in groups starting 12 h after the withdrawal of intravaginal progesterone releasing devices (controlled internal drug releases) until 7 days postonset of estrus (luteal phase). Subsequent groupings represented proestrus, early estrus, late estrus, metestrus, and finally the early luteal phase. Tissues were submitted to next generation RNA-seq transcriptome analysis. We identified 114 genes associated with biosynthesis and intracellular transport of mucins, and postsecretory modifications of cervical; 53 of these genes showed at least a twofold change in one or more experimental group in relation to onset of estrus, and the differences between groups were significant (P < 0.05). The majority of these genes showed the greatest alteration in their expression in the 48 h postestrus and luteal phase groups.

The postpartum endometrial inflammatory response: a normal physiological event with potential implications for bovine fertility.

After calving, the bovine endometrium undergoes marked morphological and functional changes that are necessary for subsequent re-breeding. Regulation and integration of these key events are largely uncharacterised. Here, endometrial swabs and biopsies were taken at 15, 30 and 60 days postpartum (DPP) from 13 healthy primiparous cows, 10 of which subsequently conceived, with a view to characterising innate and inflammatory gene expression profiles. Endometrial biopsies exhibited severe inflammation (>75 leukocytes per high-power field) at 15 DPP, which had begun to resolve by 30 DPP and had completely resolved by 60 DPP. The severe inflammation at 15 DPP coincided with uterine infection in all cows and a significant increase (P < 0.05) in the expression of all of 16 genes investigated, including CD45, IL8, IL6, IL1, TNF, TAP, SAA3 and HP at 15 DPP, relative to 60 DPP. All of these parameters had begun to return to normal physiological levels at 30 DPP. Systemically, serum protein concentrations of IL-8 were elevated at 15 DPP compared with 60 DPP (78 pgmL(-1)vs 48 pgmL(-1); P = 0.02). These results indicate that endometrial inflammation, leukocyte infiltration and increased expression of pro-inflammatory, antimicrobial and acute-phase protein genes are expected features of the postpartum period, critical to bacterial clearance and uterine involution.