Depression State Correlates with Functional Recovery Following Elective Lumbar Spine Fusion.

OBJECTIVE: To determine how depression state impacts postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores and achievement of minimum clinically important difference (MCID) following lumbar fusion. Depression has been shown to negatively impact outcomes following numerous orthopedic surgeries. Situational and major clinical depression can differentially affect postoperative outcomes. METHODS: Adult patients undergoing elective 1-3 level lumbar fusion were reviewed. Patients with a formal diagnosis of major depression were classified as "clinically depressed" whereas patients with at least "mild" PROMIS Depression scores in the absence of formal depression diagnosis were deemed "situationally depressed." analysis of variance testing was used to assess differences within and between groups. Multivariate regression was used to identify features associated with the achievement of MCID. RESULTS: Two hundred patients were included. The average age was 65.9 ± 12.2 years. 75 patients (37.5%) were nondepressed, 66 patients (33.0%) were clinically depressed, and 59 patients (29.5%) were situationally depressed. Situationally depressed patients had worse preoperative physical function (PF) and pain interference (PI) scores and were more likely to have severe symptoms (P = 0.001, P = 0.001). All groups improved significantly from preoperative baseline scores. All groups met MCID PF at different rates, with highest proportion of situationally depressed reaching this metric (P = 0.03). Rates of achieving MCID PI were not significantly different between groups (P = 0.47). Situational depression was predictive of achieving MCID PF (P = 0.002) but not MCID PI. CONCLUSIONS: Our study investigated the relationship between depression and postoperative PROMIS scores and identified situationally depressed patients as having the worst preoperative impairment. Despite this, the situationally depressed cohort had the highest likelihood of achieving MCID PF, suggestive of a bidirectional relationship between lumbar degenerative disease and subclinical, situational depression. These findings may help guide preoperative counseling on expectations, and patient selection.

The Rowing Spine: A Review of Biomechanics, Injury, and Treatment.

OBJECTIVE: We aimed to describe spinal biomechanics and injury patterns in rowing. METHODS: In this systematic literature review, a Google and PubMed literature search was undertaken using keywords "rowing," "biomechanics," and "spine." RESULTS: Relevant articles were reviewed and synthesized to describe biomechanics, injury patterns, treatment options, and techniques for injury prevention. CONCLUSIONS: Rowing has increased in popularity throughout the United States. Up-to-date knowledge of rowing biomechanics and spinal injury patterns is necessary for prompt diagnosis and appropriate treatment of the injured rowing athlete.

Clinical Improvement After Lumbar Fusion: Using PROMIS to Assess Recovery Kinetics.

STUDY DESIGN: Retrospective review of a single institution cohort. OBJECTIVE: The goal of this study is to identify features that predict delayed achievement of minimum clinically important difference (MCID) following elective lumbar spine fusion using Patient-Reported Outcomes Measurement Information System (PROMIS) surveys. SUMMARY OF BACKGROUND DATA: Preoperative prediction of delayed recovery following lumbar spine fusion surgery is challenging. While many studies have examined factors impacting the achievement of MCID for patient-reported outcomes in similar cohorts, few studies have assessed predictors of early functional improvement. METHODS: We retrospectively reviewed patients undergoing elective one-level posterior lumbar fusion for degenerative pathology. Patients were subdivided into two groups based on achievement of MCID for each respective PROMIS domain either before six months ("early responders") or after six months ("late responders") following surgical intervention. Multivariable logistic regression analysis was used to determine features associated with odds of achieving distribution-based MCID before or after six months follow up. RESULTS: 147 patients were included. The average age was 64.3±13.0 years. At final follow-up, 57.1% of patients attained MCID for PI and 72.8% for PF. However, 42 patients (49.4%) reached MCID for PI by six months, compared to 44 patients (41.1%) for PF. Patients with severe symptoms had the highest probability of attaining MCID for PI (OR 10.3; P =0.001) and PF (OR 10.4; P =0.001) Preoperative PROMIS symptomology did not predict early achievement of MCID for PI or PF. Patients who received concomitant iliac crest autograft during their lumbar fusion had increased odds of achieving MCID for PI (OR 8.56; P =0.001) before six months. CONCLUSION: Our study demonstrated that the majority of patients achieved MCID following elective one-level lumbar spine fusion at long-term follow-up, although less than half achieved this clinical benchmark for each PROMIS metric by six months. We also found that preoperative impairment was not associated with when patients would achieve MCID. Further prospective investigations are warranted to characterize the trajectory of clinical improvement and identify the risk factors associated with poor outcomes more accurately.

Socioeconomic disadvantage is correlated with worse PROMIS outcomes following lumbar fusion.

BACKGROUND CONTEXT: Socioeconomic status (SES) has been associated with differential healthcare outcomes and may be proxied using the area-deprivation index (ADI). Few studies to date have investigated the role of ADI on patient-reported outcomes and clinically meaningful improvement following lumbar spine fusion surgery. PURPOSE: The purpose of this study is to investigate the role of SES on lumbar fusion outcomes using Patient-Reported Outcomes Measurement Information System (PROMIS) surveys. STUDY DESIGN/SETTING: Retrospective review of a single institution cohort. PATIENT SAMPLE: About 205 patients who underwent elective one-to-three level posterior lumbar spine fusion. OUTCOME MEASURES: Change in PROMIS scores and achievement of minimum clinically important difference (MCID). METHODS: Patients 18 years or older undergoing elective one-to-three level lumbar spine fusion secondary to spinal degeneration from January 2015 to September 2021 with minimum one year follow-up were reviewed. ADI was calculated using patient-supplied addresses and patients were grouped into quartiles. Higher ADI values represent worse deprivation. Minimum clinically important difference (MCID) thresholds were calculated using distribution-based methods. Analysis of variance testing was used to assess differences within and between the quartile cohorts. Multivariable regression was used to identify features associated with the achievement of MCID. RESULTS: About 205 patients met inclusion and exclusion criteria. The average age of our cohort was 66±12 years. The average time to final follow-up was 23±8 months (range 12-36 months). No differences were observed between preoperative baseline scores amongst the four quartiles. All ADI cohorts showed significant improvement for pain interference (PI) at final follow-up (p<.05), with patients who had the lowest socioeconomic status having the lowest absolute improvement from preoperative baseline physical function (PF) and PI (p=.01). Only those patients who were in the lowest socioeconomic quartile failed to significantly improve for PF at final follow-up (p=.19). There was a significant negative correlation between socioeconomic level and the absolute proportion of patients reaching MCID for PI (p=.04) and PF (p=.03). However, while ADI was a significant predictor of achieving MCID for PI (p=.02), it was nonsignificant for achieving MCID for PF. CONCLUSIONS: Our study investigated the influence of ADI on postoperative PROMIS scores and identified a negative correlation between ADI quartile and the proportion of patients reaching MCID. Patients in the worse ADI quartile had lower chances of reaching clinically meaningful improvement in PI. Policies focused on alleviating geographical deprivation may augment clinical outcomes following lumbar surgery.

Response to kisspeptin and gonadotropin-releasing hormone agonist administration in Holstein-Friesian dairy heifers with positive or negative genetic merit for fertility traits.

Previous research has identified that Holstein-Friesian dairy heifers with positive (POS) genetic merit for fertility traits (FertBV) reach puberty earlier than heifers with negative (NEG) FertBV. The hypothalamus-pituitary-gonadal (HPG) axis is functional in heifers before the onset of puberty, with increased LH release evident as heifers progress toward puberty. We investigated the functionality of the HPG axis in peripubertal Holstein-Friesian dairy heifers with divergent POS or NEG FertBV, hypothesizing that the earlier puberty onset of POS heifers is associated with earlier activation of the HPG axis than in NEG heifers. In experiment 1, we tested the dose responsiveness of POS heifers to an intravenous injection of either kisspeptin [Kiss; 2, 4, or 8 µg/kg of body weight (BW); n = 3 per dose] or a GnRH agonist (buserelin; 5, 10, or 20 ng/kg of BW; n = 3 per dose). The use of these 2 agonists investigates the status of the HPG axis in both the hypothalamus (Kiss) and pituitary (buserelin) glands. Doses of 4 µg/kg BW of Kiss and 10 ng/kg BW of buserelin produced submaximal LH responses and were used in experiment 2, in which previously unused POS (n = 22) and NEG (n = 18) FertBV heifers were challenged with both agonists at 10 and 12 mo of age in a partial crossover design. Heifers were randomly allocated to treatment groups, balanced for age and BW. The LH response to buserelin was greater in POS heifers than NEG heifers at 10 mo of age, with no difference in response at 12 mo. The FSH response to buserelin and the LH and FSH responses to Kiss did not differ between the POS and NEG heifers at either age. These results indicate an association between divergent genetic merit for fertility and the LH release to buserelin at 10 mo of age, supporting the hypothesis that gonadotropin responsiveness to a GnRH agonist is more advanced in POS heifers than in NEG heifers.

Distal Ventral Iliac Pathway for Spinopelvic Fixation: Technique Description and Case Series.

BACKGROUND: Pelvic fixation improves the stability of spinal instrumentation and can be used in high-grade degenerative disease, trauma, deformity, and destabilizing invasive pathologies, such as infection and tumor. Classic techniques for spinopelvic fixation include traditional iliac screws and S2-Alar-Iliac screws. We present a case series describing the distal ventral iliac pathway (DVIP) for spinopelvic fixation and discuss surgical indications and merits of this technique. We describe the use of the DVIP for spinopelvic fixation in the setting of degenerative and traumatic pathologies, compare this technique with existing approaches, and summarize literature to support this approach. METHODS: One hundred twenty-eight cases of DVIP screws were identified at 1 academic medical center, and 3 cases were chosen as representative examples for technique demonstration. RESULTS: Patient ages ranged from 19 to 81 (mean 62) years. Intraoperative and postoperative complications include 12 incidental durotomies, 3 suprafascial infections, and 2 compressive hematomas. There were 22 instances of hardware failure and 8 instances of pseudoarthrosis. Overall, 26 patients underwent revision surgery. Mean estimated blood loss, operative time, and time under fluoroscopy were 1959 mL, 386 minutes, and 3.19 minutes, respectively. CONCLUSIONS: The DVIP is both safe and effective as a treatment for patients with degenerative and traumatic lumbosacral pathology. Spinopelvic fixation provides improved soft tissue coverage and fewer hardware complications at minimum of 1 year follow up. This case series demonstrates a novel surgical technique for spinopelvic fixation in the setting of numerous spinal pathologies. LEVEL OF EVIDENCE: 4. CLINICAL RELEVANCE: This surgical technique is less technically challenging than current approaches, minimizes radiation exposure, and obviates the need for horizontal connector rods. In addition, in highly destabilizing pathologies, this technique also allows for multiple screw placement within the ilium, while maintaining the ability to connect to a single rod construct. This technique is safe, technically approachable, and broadly applicable to an array of spinopelvic pathologies.

Cement-Augmented and Dual-Headed Posterior Screw Reconstruction After Corpectomy for Metastatic Tumor Resection.

BACKGROUND: Metastatic spinal tumors have a well-documented deleterious effect on the overall strength of the bony spine. Surgical interventions must address not only removal of the tumor itself, but the integrity of reconstructive hardware constructs as well. METHODS: We present a series of 8 patients with metastatic spine tumors who were successfully treated with tumor resection and reconstruction of residual 3-column defect with cement-augmented fenestrated pedicle screws and dual-rod posterior stabilization. RESULTS: All patients demonstrated resolution of their presenting neurologic symptoms. CONCLUSIONS: This series supports the use of the aforementioned constructs in conjunction to provide added stability and reduce hardware failure when treating a diversity of spinal tumors.

C2 quad-screws facilitate 4-rod fixation across the cervico-thoracic junction.

BACKGROUND: Cervical spine deformity is a potentially devitalizing problem. Contemporary techniques for repair and reconstruction include fusion using rods of tapered diameter alone, or quadruple-rod constructs in which primary rods are joined to floating accessory rods by connectors. Here, we present how we utilized a quadruple-rod construct to perform five C2 to thoracic spine fusions. METHODS: Our hospital electronic medical record revealed five patients who underwent the four rod C2-thoracic spine fixation. Patients ranged in age from 14-years-old to 78-years-old. The mean operative time was 715.8 min (range 549-987 min), and average estimated blood loss was 878 cc (range 40-1800 cc). RESULTS: None of the five patients sustained any intraoperative complications, and none demonstrated progressive kyphotic deformity over the average follow-up interval of 8 months. CONCLUSION: We successfully treated five patients with degenerative or oncologic cervical pathology requiring fixation across the cervicothoracic junction utilizing a 4-rod C2-cervicothoracic fusion technique.

Laminopedicular Osteotomy for En-bloc Resection of Posterolateral Thoracic Osteoblastoma: Technical Note.

BACKGROUND: Osteoblastomas are a type of primary osseous neoplasm that exhibit a proclivity for the spine, primarily the posterior elements. While generally considered benign, some variants of osteoblastoma exhibit aggressive growth with lytic osseous destruction and soft tissue invasion, with some recurring after initial treatment. Given their proximity to vital structures and potential for rapid growth, these tumors are often managed with aggressive surgery, with en-bloc resection preferred. METHODS: Here we describe our osteotomy technique for resecting en bloc a posterolateral thoracic osteoblastoma causing rapidly progressive myelopathy in a 17-year-old male. RESULTS: Successful treatment of osteoblastoma in a 17-year-old male demonstrates the efficacy of our laminopedicular osteotomy technique in treating 1 instance of a rapidly presenting spinal tumor. CONCLUSIONS: This case bolsters the growing body of literature that favors the outcomes of a more conservative approach to en-bloc resection of spinal tumors.

Pseudotumor and Subsequent Implant Loosening as a Complication of Revision Total Hip Arthroplasty with Ceramic-on-Metal Bearing: A Case Report.

Pseudotumors are not uncommon complications after total hip arthroplasty (THA) and may occur due to differences in bearing surfaces of the head and the liner ranging from soft to hard articulation. The most common causes of pseudotumors are foreign-body reaction, hypersensitivity and wear debris. The spectrum of pseudotumor presentation following THA varies greatly-from completely asymptomatic to clear implant failure. We report a case of pseudo-tumor formation with acetabular cup aseptic loosening after revision ceramic-on-metal hip arthroplasty. The patient described herein underwent pseudotumor excision and re-revision complex arthroplasty using a trabecular metal shell and buttress with ceramic-on-polyethylene THA. Surgeons should be aware of the possibility of a pseudotumor when dealing with revisions to help prevent rapid progression of cup loosening and implant failure, and should intervene early to avoid complex arthroplasty procedures.

Osteoglycin, a novel coordinator of bone and glucose homeostasis.

OBJECTIVE: The skeleton, which is strongly controlled by endocrine factors, has recently been shown to also play an active endocrine role itself, specifically influencing energy metabolism. However, much less is known about this role. Therefore, we sought to identify novel endocrine factors involved in the regulation of both bone mass and whole-body glucose homeostasis. METHODS: We used transcriptomic and proteomic analysis of Y1 receptor deficient osteoblasts combined with the generation of a novel osteoglycin deficient mouse model and performed comprehensive in vivo phenotype profiling, combined with osteoglycin administration in wildtype mice and human studies. RESULTS: Here we identify a novel role for osteoglycin, a secreted proteoglycan, in coordinating bone accretion with changes in energy balance. Using an osteoglycin knockout mouse model, we show that at a whole body level, osteoglycin acts to suppress bone formation and modulate whole body energy supplies by altering glucose uptake through changes in insulin secretion and sensitivity, as well as by altering food intake through central signaling. Examining humans following gastric surgery as a model of negative energy balance, we show that osteoglycin is associated with BMI and lean mass as well as changes in weight, BMI, and glucose levels. CONCLUSIONS: Thus, we identify osteoglycin as a novel factor involved in the regulation of energy homeostasis and identify a role for it in facilitating the matching of bone acquisition to alterations in energy status.

Stimulation of growth hormone by kisspeptin antagonists in ewes.

Kisspeptin signalling is indispensable for fertility, stimulating gonadotropin-releasing hormone (GnRH) secretion and mediating gonadal steroid feedback on GnRH neurons. Moreover, kisspeptin neurons have been implicated in other non-reproductive neuroendocrine roles. Kisspeptin appears to also regulate growth hormone secretion but much of the data appear contradictory. We sought to clarify a potential role of kisspeptin in growth hormone (GH) regulation by examining the effect of kisspeptin antagonists on GH secretion in ewes under various physiological conditions. Our data show clear and robust increases in GH secretion following lateral ventricle or third ventricle infusion of kisspeptin antagonists p-234 and p-271 in either ovariectomized or anestrous ewes. Central infusion of kisspeptin-10 had no effect on GH secretion. To determine the level at which kisspeptin may influence GH secretion, we examined expression of the cognate kisspeptin receptor, GPR54, in pituitary cells and showed by immunocytochemistry that the majority of somatotropes express GPR54 while expression was largely negative in other pituitary cells. Overall, we have demonstrated that blocking kisspeptin signalling by antagonists stimulates GH secretion in ewes and that this is likely mediated by inhibiting endogenous kisspeptin activation of GPR54 expressed on somatotropes. The findings suggest that endogenous kisspeptin inhibits GH secretion through GPR54 expressed on somatotropes.

Central RANK signalling in NPY neurons alters bone mass in male mice.

RANKL signalling known to be important for the control of bone mass, has recently also been implicated in the brain to control thermoregulation, however, it is not known which neuronal pathways are involved and whether other aspects of energy homeostasis are also affected. Here we show that selective deletion of RANK from NPY neurons down-regulated NPY mRNA expression in the hypothalamus. While comprehensive phenotyping of germline-induced NPY neuron specific RANK deficient mice revealed no significant changes in physical or metabolic parameters, adult onset deletion of RANK from NPY neurons led to a significant increase in fat mass and a decrease in whole body bone mineral content and bone mineral density. Intriguingly, when these conditional knockout mice were placed on a high fat diet, body weight and fat mass did not differ to control mice. However, they were able to significantly increase their bone mass to match their increased body weight, an ability that was lacking in control mice. Taken together, results from this study demonstrate that RANK signalling in NPY neurons is involved in modulating NPY levels and through that matching bone mass to body weight.

Population-based analysis of ocular Chlamydia trachomatis in trachoma-endemic West African communities identifies genomic markers of disease severity.

BACKGROUND: Chlamydia trachomatis (Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. Ct strain-specific differences in clinical trachoma suggest that genetic polymorphisms in Ct may contribute to the observed variability in severity of clinical disease. METHODS: Using Ct whole genome sequences obtained directly from conjunctival swabs, we studied Ct genomic diversity and associations between Ct genetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea-Bissau, West Africa. RESULTS: All Ct sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion in trpA resulting in a truncated non-functional protein and the ocular tyrosine repeat regions present in tarP associated with ocular tissue localization. We have identified 21 Ct non-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs within pmpD (odds ratio, OR = 4.07, p* = 0.001) and tarP (OR = 0.34, p* = 0.009). Eight synonymous SNPs associated with disease severity were found in yjfH (rlmB) (OR = 0.13, p* = 0.037), CTA0273 (OR = 0.12, p* = 0.027), trmD (OR = 0.12, p* = 0.032), CTA0744 (OR = 0.12, p* = 0.041), glgA (OR = 0.10, p* = 0.026), alaS (OR = 0.10, p* = 0.032), pmpE (OR = 0.08, p* = 0.001) and the intergenic region CTA0744-CTA0745 (OR = 0.13, p* = 0.043). CONCLUSIONS: This study demonstrates the extent of genomic diversity within a naturally circulating population of ocular Ct and is the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocular Ct pathogenesis and disease transmission.

Alteration in the relationship between tanycytes and gonadotrophin-releasing hormone neurosecretory terminals following long-term metabolic manipulation in the sheep.

The activity of the hypothalamic-pituitary gonadal axis is influenced by energy reserves, such that an increase or a decrease in adiposity may perturb the secretion and action of gonadotrophin-releasing hormone (GnRH). This is considered to be a result of the signalling of hormones such as leptin, which act upon neuronal systems controlling GnRH secretion. Other work shows plasticity in the relationship between tanycytes and GnRH neurosecretory terminals in the median eminence across the oestrous cycle and we hypothesised that a similar plasticity may occur with altered metabolic status. We studied Lean, Normal and Fat ovariectomised ewes, which displayed differences in gonadotrophin status, and investigated the relationship between tanycytes and GnRH neuroterminals. Under both Lean and Fat conditions, an altered anatomical arrangement between these two elements was observed in the vicinity of the blood vessels of the primary plexus of the hypophysial portal blood system. These data suggest that such plasticity is an important determinant of the rate of secretion of GnRH in animals of differing metabolic status and that this also contributes to the relative hypogonadotrophic condition prevailing with metabolic extremes.

Effect of gonadotropin-inhibitory hormone on luteinizing hormone secretion in humans.

BACKGROUND: Gonadotropin-inhibitory hormone (GnIH, human homologue of RFRP-3) suppresses gonadotropin secretion in animal models, but its effects have not been studied in the human. OBJECTIVE: We tested the hypotheses that exogenous GnIH inhibits LH secretion (i) in postmenopausal women and (ii) in men concurrently administered exogenous kisspeptin. DESIGN: Following in vitro and in vivo preclinical studies to functionally characterize the GnIH peptide, a dose-finding study (human GnIH: 1·5-150 µg/kg/h, iv for 3 h) was undertaken, and 50 µg/kg/h selected for further evaluation. Five postmenopausal women were administered 50 µg/kg/h iv infusion for 3 h or vehicle on two separate days. Four men were administered kisspeptin-10 (0·3 µg/kg iv bolus) with simultaneous infusion of GnIH (50 µg/kg/h, iv for 3 h) or vehicle. PARTICIPANTS: Healthy postmenopausal women (mean age 58 ± 2 years, LH: 30·8 ± 2·9 IU/l, FSH: 78·7 ± 6·4 IU/l, oestradiol: <50 pmol/l) and men (39·8 ± 2·1 years, mean total testosterone 12·1 ± 1·8 nmol/l, LH 2·2 ± 0·2 IU/l). PRIMARY OUTCOME: Change in area under curve (AUC) of LH during GnIHvs vehicle. RESULTS: During GnIH administration in postmenopausal women, LH secretion decreased (ΔAUC: -9·9 ± 1·8 IU/3 h) vs vehicle (ΔAUC: -0·5 ± 1·7 IU/3 h; P = 0·02). Kisspeptin-10-stimulated LH responses in men were not affected by GnIH co-administration (60-min AUC of LH 6·2 ± 0·8 IU/h with kisspeptin-10 alone, 6·3 ± 1·0 IU/h, kisspeptin-10 with GnIH, P = 0·72). Exogenous GnIH was well tolerated, with no adverse events reported. CONCLUSIONS: Gonadotropin-inhibitory hormone decreased LH secretion in postmenopausal women in this first-in-human study. Kisspeptin-stimulated LH secretion in men was not inhibited during concomitant administration of GnIH.

Stress, cortisol, and obesity: a role for cortisol responsiveness in identifying individuals prone to obesity.

There is a strong inter-relationship between activation of the hypothalamo-pituitary-adrenal axis and energy homeostasis. Patients with abdominal obesity have elevated cortisol levels. Furthermore, stress and glucocorticoids act to control both food intake and energy expenditure. In particular, glucocorticoids are known to increase the consumption of foods enriched in fat and sugar. It is well-known that, in all species, the cortisol response to stress or adrenocorticotropin is highly variable. It has now emerged that cortisol responsiveness is an important determinant in the metabolic sequelae to stress. Sheep that are characterized as high-cortisol responders (HRs) have greater propensity to weight gain and obesity than low-cortisol responders (LRs). This difference in susceptibility to become obese is associated with a distinct metabolic, neuroendocrine, and behavioral phenotype. In women and ewes, HR individuals eat more in response to stress than LR. Furthermore, HR sheep have impaired melanocortin signaling and reduced skeletal muscle thermogenesis. High-cortisol responder sheep exhibit reactive coping strategies, whereas LRs exhibit proactive coping strategies. This complex set of traits leads to increased food intake and reduced energy expenditure in HR and thus, predisposition to obesity. We predict that cortisol responsiveness may be used as a marker to identify individuals who are at risk of weight gain and subsequent obesity.

New concepts of the central control of reproduction, integrating influence of stress, metabolic state, and season.

Gonadotropin releasing hormone is the primary driver of reproductive function and pulsatile GnRH secretion from the brain causes the synthesis and secretion of LH and FSH from the pituitary gland. Recent work has revealed that the secretion of GnRH is controlled at the level of the GnRH secretory terminals in the median eminence. At this level, projections of kisspeptin cells from the arcuate nucleus of the hypothalamus are seen to be closely associated with fibers and terminals of GnRH cells. Direct application of kisspeptin into the median eminence causes release of GnRH. The kisspeptin cells are activated at the time of a natural "pulse" secretion of GnRH, as reflected in the secretion of LH. This appears to be due to input to the kisspeptin cells from glutamatergic cells in the basal hypothalamus, indicating that more than 1 neural element is involved in the secretion of GnRH. Because the GnRH secretory terminals are outside the blood-brain barrier, factors such as kisspeptin may be administered systemically to cause GnRH secretion; this offers opportunities for manipulation of the reproductive axis using factors that do not cross the blood-brain barrier. In particular, kisspeptin or analogs of the same may be used to activate reproduction in the nonbreeding season of domestic animals. Another brain peptide that influences reproductive function is gonadotropin inhibitory hormone (GnIH). Work in sheep shows that this peptide acts on GnRH neuronal perikarya, but projections to the median eminence also allow secretion into the hypophysial portal blood and action of GnIH on pituitary gonadotropes. GnIH cells are upregulated in anestrus, and infusion of GnIH can block the ovulatory surge in GnRH and/or LH secretion. Metabolic status may also affect the secretion of reproduction, and this could involve action of gut peptides and leptin. Neuropeptide Y and Y-receptor ligands have a negative impact on reproduction, and Neuropeptide Y production is markedly increased in negative energy balance; this may be the cause of lowered GnRH and gonadotropin secretion in this state. There is a complex interaction between appetite-regulating peptide neurons and kisspeptin neurons that enables the former to regulate the latter both positively and negatively. In terms of how GnRH secretion is reduced during stress, recent data indicate that GnIH cells are integrally involved, with increased input to the GnRH cells. The secretion of GnIH into the portal blood is not increased during stress, so the negative effect is most likely effected at the level of GnRH neuronal cell bodies.

Expression of regulatory neuropeptides in the hypothalamus of red deer (Cervus elaphus) reveals anomalous relationships in the seasonal control of appetite and reproduction.

Red deer are seasonal with respect to reproduction and food intake, so we tested the hypothesis that their brains would show seasonal changes in numbers of cells containing hypothalamic neuropeptides that regulate these functions. We examined the brains of male and female deer in non-breeding and breeding seasons to quantify the production of kisspeptin, gonadotropin inhibitory hormone (GnIH), neuropeptide Y (NPY) and γ-melanocyte stimulating hormone (γ-MSH - an index of pro-opiomelanocortin production), using immunohistochemistry. These neuropeptides are likely to be involved in the regulation of reproductive function and appetite. During the annual breeding season there were more cells producing kisspeptin in the arcuate nucleus of the hypothalamus than during the non-breeding season in males and females whereas there was no seasonal difference in the expression of GnIH. There were more cells producing the appetite stimulating peptide, NPY, in the arcuate/median eminence regions of the hypothalamus of females during the non-breeding season whereas the levels of an appetite suppressing peptide, γ-MSH, were highest in the breeding season. Male deer brains exhibited the converse, with NPY cell numbers highest in the breeding season and γ-MSH levels highest in the non-breeding season. These results support a role for kisspeptin as an important stimulatory regulator of seasonal breeding in deer, as in other species, but suggest a lack of involvement of GnIH in the seasonality of reproduction in deer. In the case of appetite regulation, the pattern exhibited by females for NPY and γ-MSH was as expected for the breeding and non-breeding seasons, based on previous studies of these peptides in sheep and the seasonal cycle of appetite reported for various species of deer. An inverse result in male deer most probably reflects the response of appetite regulating cells to negative energy balance during the mating season. Differences between the sexes in the seasonal changes in appetite regulating peptide cells of the hypothalamus present an interesting model for future studies.

Chemically driven tetragonal-to-monoclinic polymorphic transformation in retrieved ZTA femoral heads from dual mobility hip implants.

Two short-term (two and nine months) retrieved zirconia-toughened alumina (ZTA) femoral heads and nine pristine femoral heads from the same manufacturer have been investigated with respect to their surface stability by means of confocal Raman spectroscopy. Quantitative estimations of monoclinic volume fraction have been carried out in both non-wear and main wear zones of the retrieved heads, which invariantly showed high volume fractions of monoclinic polymorph. In-depth (sub-surface) profiles, non-destructively collected in the main wear zones with the Raman probe in confocal configuration, indeed confirmed that polymorphic transformation was extended down to 100µm below the bearing surface of the femoral heads. Acceleration of tetragonal-to-monoclinic transformation rate leads to unexpectedly high fractions of monoclinic phase within very short-term in-vivo exposures. Phase transformation in-vivo is much more marked than what one could actually predict according to simply simulating a hydrothermal environment in-vitro and could not be simply ascribed to the mechanical stress fields generated during normal service at the bearing surface. Instead, the chemical consequences of metal contamination on the ZTA femoral head surface are shown to play the most detrimental role in phase destabilization.