Intracardiac Echocardiography for Point-of-Care Guided Left Ventricular Assist Device Implantation: Surgical Implications for COVID-19.

Data from animal models is now available to initiate assessment of human safety and feasibility of wide-angle three-dimensional intracardiac echocardiography (3D ICE) to guide point-of-care implantation of percutaneous left ventricular assist devices in critical care settings. Assessment of these combined new technologies could be best achieved within a surgical institution with pre-existing expertise in separate utilization of ICE and Impella.

Association of osteoarthritis and pain with Alzheimer's Diseases and Related Dementias among older adults in the United States.

BACKGROUND: Emerging evidence suggests that Pain Interference (PI) and certain chronic pain conditions, including Osteoarthritis (OA) may be associated with risk for Alzheimer's disease and Related Dementias (ADRD). However, research exploring the relation of OA and PI to ADRD remains sparse. OBJECTIVE: To assess the association of OA and PI to ADRD using cross-sectional data from a representative sample of USA adults aged ≥65 years. DESIGN: Retrospective cross-sectional. STUDY SAMPLE: Older adults (age ≥ 65 years) drawn from the Medical Expenditure Panel Survey (MEPS, 2009-2015). METHODS: OA was identified using both medical conditions files and participant responses to arthritis-specific queries. ADRD was ascertained using the medical conditions files. PI was defined as reported frequent PI with normal activities (PIA). OA and PIA were categorized as a composite variable: 1) OA with PIA; 2) OA without PIA; 3) No OA with PIA; and 4) No OA and no PIA (reference group). Adjusted associations of OA and PIA to ADRD were assessed using logistic regression and adjusted for biological, demographic, socio-economic, lifestyle, and health conditions. RESULTS: Overall, 27.1% had OA, of whom 47.6 % reported PIA vs 31.1% of those without OA; 2.8% had diagnosed ADRD. Adults with PIA either with or without OA had significantly higher odds of ADRD relative to those without OA or PIA (Adjusted odd ratios (AOR's) = 1.37, 95%CI - 1.01, 1.86 (p = 0.04) and 1.44, 95%CI - 1.13, 1.82 (p = 0.003), respectively). CONCLUSION: PIA in both the presence and absence of OA remained significantly and positively associated with ADRD after adjustment for multiple confounders.

Decreasing the blood flow of non-compressible intra-abdominal organs with non-invasive transcutaneous electrical stimulation.

Non-invasive neuromodulation of non-compressible internal organs has significant potential for internal organ bleeding and blood-shift in aero/space medicine. The present study aims to investigate the potential influences of the non-invasive transcutaneous electrical nerve stimulation (TENS) on multiple non-compressible internal organs' blood flow. Porcine animal model (n = 8) was randomized for a total of 48 neuromodulation sessions with two different TENS stimulation frequencies (80 Hz, 10 Hz) and a placebo stimulation. A combination of two different electrode configurations (Abdominal-only or Abdominal and hind limb) were also performed. Intraarterial blood flow measurements were taken during pre and post-stimulation periods at the left renal artery, common hepatic artery, and left coronary artery. Intracranial, and extracranial arterial blood flows were also assessed with digital subtraction angiography. TENS with abdominal-only electrode configurations at 10 Hz demonstrated significant reductions in average peak blood flow velocity (APV) of the common hepatic artery (p = 0.0233) and renal arteries (p = 0.0493). Arterial pressures (p = 0.0221) were also significantly lower when renal APV was reduced. The outcome of the present study emphasises the potential use of TENS in decreasing the blood flow of non-compressible internal organs when the correct combination of electrodes configuration and frequency is used.

A Preclinical Trial Protocol Using an Ovine Model to Assess Scaffold Implant Biomaterials for Repair of Critical-Sized Mandibular Defects.

The present work describes a preclinical trial (in silico, in vivo and in vitro) protocol to assess the biomechanical performance and osteogenic capability of 3D-printed polymeric scaffolds implants used to repair partial defects in a sheep mandible. The protocol spans multiple steps of the medical device development pipeline, including initial concept design of the scaffold implant, digital twin in silico finite element modeling, manufacturing of the device prototype, in vivo device implantation, and in vitro laboratory mechanical testing. First, a patient-specific one-body scaffold implant used for reconstructing a critical-sized defect along the lower border of the sheep mandible ramus was designed using on computed-tomographic (CT) imagery and computer-aided design software. Next, the biomechanical performance of the implant was predicted numerically by simulating physiological load conditions in a digital twin in silico finite element model of the sheep mandible. This allowed for possible redesigning of the implant prior to commencing in vivo experimentation. Then, two types of polymeric biomaterials were used to manufacture the mandibular scaffold implants: poly ether ether ketone (PEEK) and poly ether ketone (PEK) printed with fused deposition modeling (FDM) and selective laser sintering (SLS), respectively. Then, after being implanted for 13 weeks in vivo, the implant and surrounding bone tissue was harvested and microCT scanned to visualize and quantify neo-tissue formation in the porous space of the scaffold. Finally, the implant and local bone tissue was assessed by in vitro laboratory mechanical testing to quantify the osteointegration. The protocol consists of six component procedures: (i) scaffold design and finite element analysis to predict its biomechanical response, (ii) scaffold fabrication with FDM and SLS 3D printing, (iii) surface treatment of the scaffold with plasma immersion ion implantation (PIII) techniques, (iv) ovine mandibular implantation, (v) postoperative sheep recovery, euthanasia, and harvesting of the scaffold and surrounding host bone, microCT scanning, and (vi) in vitro laboratory mechanical tests of the harvested scaffolds. The results of microCT imagery and 3-point mechanical bend testing demonstrate that PIII-SLS-PEK is a promising biomaterial for the manufacturing of scaffold implants to enhance the bone-scaffold contact and bone ingrowth in porous scaffold implants. MicroCT images of the harvested implant and surrounding bone tissue showed encouraging new bone growth at the scaffold-bone interface and inside the porous network of the lattice structure of the SLS-PEK scaffolds.

A Comparison of In Vivo Bone Tissue Generation Using Calcium Phosphate Bone Substitutes in a Novel 3D Printed Four-Chamber Periosteal Bioreactor.

Autologous bone replacement remains the preferred treatment for segmental defects of the mandible; however, it cannot replicate complex facial geometry and causes donor site morbidity. Bone tissue engineering has the potential to overcome these limitations. Various commercially available calcium phosphate-based bone substitutes (Novabone®, BioOss®, and Zengro®) are commonly used in dentistry for small bone defects around teeth and implants. However, their role in ectopic bone formation, which can later be applied as vascularized graft in a bone defect, is yet to be explored. Here, we compare the above-mentioned bone substitutes with autologous bone with the aim of selecting one for future studies of segmental mandibular repair. Six female sheep, aged 7-8 years, were implanted with 40 mm long four-chambered polyether ether ketone (PEEK) bioreactors prepared using additive manufacturing followed by plasma immersion ion implantation (PIII) to improve hydrophilicity and bioactivity. Each bioreactor was wrapped with vascularized scapular periosteum and the chambers were filled with autologous bone graft, Novabone®, BioOss®, and Zengro®, respectively. The bioreactors were implanted within a subscapular muscle pocket for either 8 weeks (two sheep), 10 weeks (two sheep), or 12 weeks (two sheep), after which they were removed and assessed by microCT and routine histology. Moderate bone formation was observed in autologous bone grafts, while low bone formation was observed in the BioOss® and Zengro® chambers. No bone formation was observed in the Novabone® chambers. Although the BioOss® and Zengro® chambers contained relatively small amounts of bone, endochondral ossification and retained hydroxyapatite suggest their potential in new bone formation in an ectopic site if a consistent supply of progenitor cells and/or growth factors can be ensured over a longer duration.

Ex Vivo Preservation of Ovine Periosteum Using a Perfusion Bioreactor System.

Periosteum is a highly vascularized membrane lining the surface of bones. It plays essential roles in bone repair following injury and reconstruction following invasive surgeries. To broaden the use of periosteum, including for augmenting in vitro bone engineering and/or in vivo bone repair, we have developed an ex vivo perfusion bioreactor system to maintain the cellular viability and metabolism of surgically resected periosteal flaps. Each specimen was placed in a 3D printed bioreactor connected to a peristaltic pump designed for the optimal flow rates of tissue perfusate. Nutrients and oxygen were perfused via the periosteal arteries to mimic physiological conditions. Biochemical assays and histological staining indicate component cell viability after perfusion for almost 4 weeks. Our work provides the proof-of-concept of ex vivo periosteum perfusion for long-term tissue preservation, paving the way for innovative bone engineering approaches that use autotransplanted periosteum to enhance in vivo bone repair.

The effects of meditation on perceived stress and related indices of psychological status and sympathetic activation in persons with Alzheimer's disease and their caregivers: a pilot study.

Objective. To investigate the effects of an 8-week meditation program on perceived stress, sleep, mood, and related outcomes in adults with cognitive impairment and their caregivers. Methods. Community-dwelling adults with a diagnosis of mild cognitive impairment or early-stage Alzheimer's disease, together with their live-in caregivers, were enrolled in the study. After a brief training, participants were asked to meditate for 11 minutes, twice daily for 8 weeks. Major outcomes included measures of perceived stress (Perceived Stress Scale), sleep (General Sleep Disturbance Scale), mood (Profile of Mood States), memory functioning (Memory Functioning Questionnaire), and blood pressure. Participants were assessed pre- and post-intervention. Results. Ten participants (5 of 6 dyads) completed the study. Treatment effects did not vary by participant status; analyses were thus pooled across participants. Adherence was good (meditation sessions completed/week: X = 11.4 ± 1.1). Participants demonstrated improvement in all major outcomes, including perceived stress (P < 0.001), mood (overall, P = 0.07; depression, P = 0.01), sleep (P < 0.04), retrospective memory function (P = 0.04), and blood pressure (systolic, P = 0.004; diastolic, P = 0.065). Conclusions. Findings of this exploratory trial suggest that an 8-week meditation program may offer an acceptable and effective intervention for reducing perceived stress and improving certain domains of sleep, mood, and memory in adults with cognitive impairment and their caregivers.

Analogue Mean Systemic Filling Pressure: a New Volume Management Approach During Percutaneous Left Ventricular Assist Device Therapy.

The absence of an accepted gold standard to estimate volume status is an obstacle for optimal management of left ventricular assist devices (LVADs). The applicability of the analogue mean systemic filling pressure (Pmsa) as a surrogate of the mean circulatory pressure to estimate volume status for patients with LVADs has not been investigated. Variability of flows generated by the Impella CP, a temporary LVAD, should have no physiological impact on fluid status. This translational interventional ovine study demonstrated that Pmsa did not change with variable circulatory flows induced by a continuous flow LVAD (the average dynamic increase in Pmsa of 0.20 ± 0.95 mmHg from zero to maximal Impella flow was not significant (p = 0.68)), confirming applicability of the human Pmsa equation for an ovine LVAD model. The study opens new directions for future translational and human investigations of fluid management using Pmsa for patients with temporary LVADs.

Splitting the anterior mitral leaflet impairs left ventricular function in an ovine model.

OBJECTIVES: During mitral valve replacement, the anterior mitral leaflet is usually resected or modified. Anterior leaflet splitting seems the least disruptive modification. Reattachment of the modified leaflet to the annulus reduces the annulopapillary distance. The goal of this study was to quantify the acute effects on left ventricular function of splitting the anterior mitral leaflet and shortening the annulopapillary distance. METHODS: In 6 adult sheep, a wire was placed around the anterior leaflet and exteriorized through the left ventricular wall to enable splitting the leaflet in the beating heart. Releasable snares to reduce annulopapillary distance were likewise positioned and exteriorized. A mechanical mitral prosthesis was inserted to prevent mitral incompetence during external manipulations of the native valve. Instantaneous changes in left ventricular function were recorded before and after shortening the annulopapillary distance, then before and after splitting the anterior leaflet. RESULTS: After splitting the anterior leaflet, preload recruitable stroke work, stroke work, stroke volume, cardiac output, left ventricular end systolic pressure and mean pressure were significantly decreased by 26%, 23%, 12%, 9%, 15% and 11%, respectively. Shortening the annulopapillary distance was associated with significant decreases in the end systolic pressure volume relationship, preload recruitable stroke work, stroke work and left ventricular end systolic pressure by 67%, 33%, 15% and 13%, respectively. Shortening the annulopapillary distance after splitting the leaflet had no significant effect. CONCLUSIONS: Splitting the anterior mitral leaflet acutely impaired left ventricular contractility and haemodynamics in an ovine model. Shortening the annulopapillary distance after leaflet splitting did not further impair left ventricular function.

Comparison of two doses of ketamine for induction of anaesthesia in ponies undergoing field castration.

BACKGROUND: Ketamine-based total intravenous anaesthesia techniques are commonly used in equine practice for ponies requiring short procedures such as castration in field conditions. When a longer duration of recumbency than provided by the initial dose of anaesthetic agents is required, administration of supplementary 'top-up' doses of anaesthetic agents is required. Ideally, a single dose of anaesthetic agents would reliably achieve a longer duration of action whilst maintaining adequate anaesthetic, surgical and recovery qualities. AIM: This prospective, randomised and blinded study aimed to compare the UK-licensed induction dose of ketamine with an increased dose in ponies undergoing castration in field conditions. The hypothesis was that an increased dose would produce a longer duration of action without negatively affecting qualities of anaesthesia, surgical conditions and recovery. METHODS: Ponies were randomly allocated to receive ketamine at either 2.2 mg kg-1 (K2.2) or 3 mg kg-1 (K3) combined with diazepam 20 µg kg-1 following pre-anaesthetic medication with romifidine and butorphanol. Quality of anaesthesia, surgery and recovery were scored using simple descriptive scales (SDS) and timings of key events recorded. Top-up doses of ketamine 0.5 mg kg-1 were administered if anaesthesia was inadequate during surgery. Time of top-up doses and total ketamine doses were recorded. Data were analysed using Student t-tests or the Mann-Whitney U test (p < 0.05). RESULTS: Thirty-six ponies completed the study. Six ponies enrolled were excluded due to cryptorchidism or surgical complications that required deviation from the anaesthetic protocol. There were no differences in timing of events recorded, number of ponies requiring top-up ketamine, timing and frequency of top-ups or total ketamine dose. Scores for anaesthetic and recovery qualities, and surgical conditions were similar between groups. CONCLUSION: Both induction doses of ketamine provided a similar duration of action and provided conditions suitable to anaesthetise ponies undergoing castration.

Incorporating the anterior mitral leaflet to the annulus impairs left ventricular function in an ovine model.

Objectives: Transcatheter mitral valve prostheses are designed to capture the anterior leaflet and surgical techniques designed to fully preserve the subvalvular apparatus at prosthetic valve insertion both serve to shorten the anterior mitral leaflet height, thus effectively incorporating it into the anterior annulus. This study quantifies the acute effects of incorporating the anterior mitral leaflet into the annulus on left ventricular function. Methods: Fourteen adult sheep (weight, 48.7 ± 6.2 kg) underwent a mechanical mitral valve insertion on normothermic beating-heart cardiopulmonary bypass, with full retention of the native mitral valve but with placement of exteriorized releasable snares around the anterior mitral leaflet. Continuous measurements of left ventricular mechano-energetics were recorded throughout, alternating incorporating and releasing of the anterior mitral leaflet to the mitral annulus. Echocardiography confirmed the incorporation into the annulus and release. Results: The independent indices of left ventricular contractility (ie, end systolic pressure volume relationship and preload recruitable stroke work) were both significantly impaired when the anterior mitral leaflet was incorporated to the annulus and restored after release, as were the hemodynamic parameters: cardiac output, stroke volume, stroke work, and left ventricular pressure decreased by 15%, 17%, 23%, and 11%, respectively. Echocardiography demonstrated increased sphericity of the left ventricle during anterior mitral leaflet incorporation. Conclusions: Incorporating the anterior mitral leaflet to the anterior annulus adversely affected left ventricular contractility, caused distortion of the left ventricle in the form of increased sphericity, and impaired hemodynamic parameters in normal ovine hearts.

Bioprosthetic interstrut distance subtending the preserved anterior mitral leaflet mitigates left ventricular outflow tract obstruction.

Background: The anterior mitral leaflet (AML) contributes to left ventricular (LV) function but is normally excised at the time of a bioprosthetic valve insertion. This study aimed to investigate methods of safely retaining the AML at the time of mitral valve replacement. Methods: Five adult sheep (57 ± 3.8 kg) each underwent 3 insertions of a bioprosthetic mitral valve (asymmetric interstrut sectors) alternating the wide and narrow interstrut distance under the AML. Each insertion was performed on normothermic beating-heart cardiopulmonary bypass, with full retention of the native valve. After each valve insertion, continuous measurements of LV and aortic pressures were recorded with echocardiographic assessment of mitral valve function. If LV outflow tract obstruction (LVOTO) was not seen on the resumption of normal cardiac output, a bolus of adrenaline was given to precipitate it. Results: Thirteen of 15 valve insertions resulted in LVOTO caused by systolic anterior motion (SAM), independent of valve orientation. The wide interstrut distance subtending the AML was associated with a greater requirement for inotropic stress to precipitate an obstruction and was associated with late systolic rather than holosystolic obstruction. Conclusions: The predisposition to and nature of LVOTO due to SAM were associated with the bioprosthetic valve interstrut distance subtending the fully retained AML and may explain the survival differences in such patients. This model represents an effective method for research into prevention of LVOTO following mitral valve replacement with preservation of the native valve.

Implantation of Impella CP left ventricular assist device under the guidance of three-dimensional intracardiac echocardiography.

Impella CP is a percutaneously inserted left ventricular assist device indicated for temporary mechanical cardiac support during high risk percutaneous coronary interventions and for cardiogenic shock. The potential application of Impella has become particularly relevant during the current COVID-19 pandemic, for patients with acute severe heart failure complicating viral illness. Standard implantation of the Impella CP is performed under fluoroscopic guidance. Positioning of the Impella CP can be confirmed with transthoracic or transoesophageal echocardiography. We describe an alternative approach to guide intracardiac implantation of the Impella CP using two-dimensional and three-dimensional intracardiac echocardiography. This new technique can be useful in selected groups of patients when fluoroscopy, transthoracic and transoesophageal echocardiography is deemed inapplicable or limited for epidemiological or clinical reasons. Intracardiac three-dimensional echocardiography is a feasible alternative to the traditional techniques for implantation of an Impella CP device but careful consideration must be given to the potential limitations and complications of this technique.

Comparison of dynamic changes in stressed intravascular volume, mean systemic filling pressure and cardiovascular compliance: Pilot investigation and study protocol.

The mean systemic filling pressure (MSFP) represents an interaction between intravascular volume and global cardiovascular compliance (GCC). Intravascular volume expansion using fluid resuscitation is the most frequent intervention in intensive care and emergency medicine for patients in shock and with haemodynamic compromise. The relationship between dynamic changes in MSFP, GCC and left ventricular compliance is unknown. We conducted prospective interventional pilot study following euthanasia in post cardiotomy adult sheep, investigating the relationships between changes in MSFP induced by rapid intravascular filling with fluids, global cardiovascular compliance and left ventricular compliance. This pilot investigation suggested a robust correlation between a gradual increase in the intravascular stressed volume from 0 to 40 ml/kg and the MSFP r = 0.708 95% CI 0.435 to 0.862, making feasible future prospective interventional studies. Based on the statistical modelling from the pilot results, we expect to identify a strong correlation of 0.71 ± 0.1 (95% CI) between the MSFP and the stressed intravascular volume in a future study.

CDX2 promotes anchorage-independent growth by transcriptional repression of IGFBP-3.

CDX2 is a Drosophila caudal-related homeobox transcription factor that is important for the establishment and maintenance of intestinal epithelial cells. We have reported that CDX2 promotes tumorigenicity in a subset of human colorectal cancer cell lines. Here, we present evidence that CDX2 negatively regulates the well-documented growth inhibitor insulin-like growth factor binding protein-3 (IGFBP-3). Specifically, CDX2 binds to the IGFBP-3 gene promoter and can repress IGFBP-3 transcription, protein expression and secretion. Furthermore, inhibition of IGFBP-3 partially rescues the decreased anchorage-independent growth phenotype observed in CDX2 knockout cells. These data demonstrate for the first time that (1) CDX2 can function as a transcriptional repressor, and (2) one mechanism by which CDX2 promotes anchorage-independent growth is by transcriptional repression of IGFBP-3.

Bcl-2 has a cell cycle inhibitory function separable from its enhancement of cell survival.

Myeloid maturation appears to require exit from the cell cycle and leads to activation of apoptosis in the differentiated cells. The level of Bcl-2, which is known to promote cell survival, is shown here to influence both these critical steps. Bcl-2 function during myelomonocytic differentiation was investigated by introducing a deregulated bcl-2 gene into HL60 promyelocytic leukemia cells, which can be induced to exit the cell cycle and differentiate into granulocytes or monocytes. Deregulated Bcl-2 expression did not itself promote differentiation but extended the lifespan of mature cells elicited by granulocytic or monocytic inducers. Unexpectedly, in response to induction, Bcl-2 overexpression markedly potentiated and hastened cell cycle withdrawal into G(0). Enhanced survival cannot account for the elevated numbers of G(0) cells, because they arose under induction conditions that did not kill control cells. Since the cell cycle status and growth of uninduced cells was not affected by Bcl-2-overexpression, its cell cycle inhibitory activity must require an induction signal. While cell cycle withdrawal may be necessary for maturation, it was not sufficient, implicating a requirement for specific differentiative signals. These results identify, for the first time, a function for the bcl-2 proto-oncogene that is separable from its enhancement of cell survival.

Retroviral transduction of enriched hematopoietic stem cells allows lifelong Bcl-2 expression in multiple lineages but does not perturb hematopoiesis.

Transduction of hematopoietic stem cells with a novel retrovirus has allowed long-term expression of human Bcl-2 in multiple hematopoietic lineages. Thy-1.2lo Sca-1+ H-2Khi stem cells enriched from the bone marrow of 5-fluorouracil-treated (Ly5-2) mice were infected with the bcl-2 retrovirus and injected into (Ly5-1) irradiated recipients. Analysis at 5 months indicated that reconstitution of hematopoiesis occurred predominantly from donor-derived (Ly5-2+) stem cells and that, in half the mice (18 of 35), most blood cells derived from virally transduced stem cells. The level of Bcl-2 expression achieved with the retroviral vector approached that of a well-characterized transgenic vector and could be sustained for life in several blood cell lineages. In the 25 mice assessed at 10 months, human Bcl-2 was readily detectable in 62+/-22% of Ly5-2+ peripheral blood leukocytes. More detailed analysis of a cohort killed between 14 and 20 months established that human Bcl-2 protein could be detected in B and T lymphocytes, granulocytes, macrophages, and some immature erythroid cells. Furthermore, hematopoietic stem cells from the bone marrow of these mice maintained Bcl-2 expression in hematopoietic tissues of secondary recipients for at least another 19 months. These data provide clear evidence for efficient infection of primitive hematopoietic stem cells and for maintenance of proviral expression for over 2.5 years, the lifespan of mice. The level of exogenous Bcl-2 was sufficient to enhance survival of B and T lymphoid cells, granulocytes, and myeloid colony-forming cells cultured under suboptimal conditions, but hematopoiesis in the mice was not notably perturbed.

Relative glucose tolerance and subsequent development of hypertension in pregnancy.

OBJECTIVE: To test the hypothesis that relative carbohydrate tolerance, an indicator of insulin resistance, predicts subsequent risk for hypertension of pregnancy among previously normoglycemic, normotensive women. METHODS: We conducted a nested case-control study in women enrolled at a large Colorado urban health maintenance organization. Subjects were previously healthy pregnant women who tested abnormal on their initial 50-g glucose screens and subsequently completed 3-hour, 100-g oral glucose tolerance tests. Cases were 54 previously normotensive women who subsequently developed hypertension and controls were 51 subjects with normotensive pregnancies, matched to cases on parity. Subjects diagnosed with gestational diabetes (17 cases, six controls) were excluded from the main analyses. RESULTS: Among the 82 normoglycemic women (45 controls, 37 cases, 13 preeclampsia, 24 gestational hypertension), mean post-load glucose levels and total glucose area under the curve were significantly higher in cases than in controls (P < or =.04) and were positively correlated with peak mean arterial pressure. After adjustment for potential confounders, 2-hour post-load glucose levels remained strongly related to risk for hypertension (adjusted odds ratios = 1.48; 95% confidence interval 1.13, 1.92, per 10 mg/dL increase) and to peak mean arterial blood pressure (r =.23, P =.04), as did total glucose area under the curve (P < or =.04). Cases were also more likely to have had one abnormal glucose tolerance test (28% versus 5%, P =.004). Stratifying analyses by case severity (preeclampsia and gestational hypertension) yielded similar results. Among all subjects, more cases than controls were also diagnosed with gestational diabetes (31% versus 12%, P =.008). CONCLUSION: These findings are consistent with the hypothesis that insulin resistance precedes the clinical onset of hypertension in pregnancy, and may be important in the etiology of hypertension.

Functions of a proprioceptive sense organ in freely moving insects: characteristics of reflexes elicited by stimulation of the locust metathoracic femoral chordotonal organ.

(1) The metathoracic femoral chordotonal organ is an identified joint angle receptor of the locust hindleg. In order to assess and quantify the functions of this sense organ in the control of posture, mechanical stimuli were applied to the main ligament of the receptor in freely standing locusts. These stimuli produced an afferent discharge that mimicked a sudden small (10-15 degree) change in the angle of the femoro-tibial joint of the hindleg. The reflex effects that resulted from afferent stimulation were monitored myographically in the tibial extensor and flexor muscles. The angle of the femoro-tibial joint at the onset of sensory stimulation was also recorded by still photography. (2) As previously reported, stimulation of the chordotonal organ in freely standing animals produced resistance reflexes in tibial muscles that opposed the apparent joint movement. However, we also found that, at certain joint angles, a different mode of reflex response was elicited in which motoneurons to the tibial flexor muscle fired in response to apparent movements in any direction. (3) In this study, characteristics of resistance reflexes in the tibial extensor muscle were analyzed quantitatively, as that muscle is innervated by only one slow excitatory motoneuron. The gain of the resistance reflex (ratio of the firing frequency during afferent stimulation versus the rate of activity prior to the stimulus) was quite high in all preparations, and represent a greater than two-fold increase in motoneuron frequency (mean 2.11 +/- 0.54 S.D.). The reflex gain was also highest at the lowest initial rates of motoneuron activity (circa 5 Hz) and declined for higher firing frequencies (maximum 35 Hz).(ABSTRACT TRUNCATED AT 250 WORDS)