SAFE USE OF INTRA-OPERATIVE TOURNIQUETS IN A DISTRICT HOSPITAL IN THE UK-AN AUDIT STUDY IN ORTHOPAEDIC THEATRES AND REVIEW OF CURRENT LITERATURE.

The use of tourniquet is common in orthopaedic surgeries as it reduces blood loss, enhances visualization of the operating field, and leads to quicker procedures. However, the use of tourniquet has certain risks which can be avoided by following guidelines like British Orthopaedic Association Standards for Trauma (BOAST) guidelines for safe use of tourniquet. This audit study was done in a District general hospital to check the compliance of two trauma theatres with BOAST guidelines. The audit found that there was poor documentation of tourniquet details in the operation notes (10%). Regarding tourniquet time and pressure, the compliance in the two theatres was 95 % & 97.5 %. The recommendations of this audit were to use a template to improve documentation of tourniquet details in the operation notes and training of theatre staff on BOAST guidelines for safe use of tourniquet.

IMPORTANCE OF JOINT LINE RESTORATION IN TOTAL KNEE ARTHROPLASTY.

The restoration of the joint line is important for a good functional outcome after a Total Knee Arthroplasty(TKA). Knee joint biomechanics need to be restored as near normal as possible. Joint line elevation leads to anterior knee pain, decrease in range of motion, patella baja ,mid-flexion instability and impingement of patellar tendon. Joint line depression on the other hand leads to patella alta, risk of patellar subluxation and mid-flexion instability of the knee. Various studies have demonstrated various range of acceptable joint line variation but there is no clear acceptable range of joint line variation. More studies are required for establishing the acceptable range of joint line variation and standard practices should be established for arthroplasty surgeons for preventing variation of joint line.

Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment.

OBJECTIVES: Wnt pathway upregulation contributes to knee osteoarthritis (OA) through osteoblast differentiation, increased catabolic enzymes, and inflammation. The small-molecule Wnt pathway inhibitor, lorecivivint (SM04690), which previously demonstrated chondrogenesis and cartilage protection in an animal OA model, was evaluated to elucidate its mechanism of action. DESIGN: Biochemical assays measured kinase activity. Western blots measured protein phosphorylation in human mesenchymal stem cells (hMSCs), chondrocytes, and synovial fibroblasts. siRNA knockdown effects in hMSCs and BEAS-2B cells on Wnt pathway, chondrogenic genes, and LPS-induced inflammatory cytokines was measured by qPCR. In vivo anti-inflammation, pain, and function were evaluated following single intra-articular (IA) lorecivivint or vehicle injection in the monosodium iodoacetate (MIA)-induced rat OA model. RESULTS: Lorecivivint inhibited intranuclear kinases CDC-like kinase 2 (CLK2) and dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Lorecivivint inhibited CLK2-mediated phosphorylation of serine/arginine-rich (SR) splicing factors and DYRK1A-mediated phosphorylation of SIRT1 and FOXO1. siRNA knockdowns identified a role for CLK2 and DYRK1A in Wnt pathway modulation without affecting ß-catenin with CLK2 inhibition inducing early chondrogenesis and DYRK1A inhibition enhancing mature chondrocyte function. NF-κB and STAT3 inhibition by lorecivivint reduced inflammation. DYRK1A knockdown was sufficient for anti-inflammatory effects, while combined DYRK1A/CLK2 knockdown enhanced this effect. In the MIA model, lorecivivint inhibited production of inflammatory cytokines and cartilage degradative enzymes, resulting in increased joint cartilage, decreased pain, and improved weight-bearing function. CONCLUSIONS: Lorecivivint inhibition of CLK2 and DYRK1A suggested a novel mechanism for Wnt pathway inhibition, enhancing chondrogenesis, chondrocyte function, and anti-inflammation. Lorecivivint shows potential to modify structure and improve symptoms of knee OA.

A small-molecule inhibitor of the Wnt pathway (SM04690) as a potential disease modifying agent for the treatment of osteoarthritis of the knee.

OBJECTIVES: Osteoarthritis (OA) is a degenerative disease characterized by loss of cartilage and increased subchondral bone within synovial joints. Wnt signaling affects the pathogenesis of OA as this pathway modulates both the differentiation of osteoblasts and chondrocytes, and production of catabolic proteases. A novel small-molecule Wnt pathway inhibitor, SM04690, was evaluated in a series of in vitro and in vivo animal studies to determine its effects on chondrogenesis, cartilage protection and synovial-lined joint pathology. DESIGN: A high-throughput screen was performed using a cell-based reporter assay for Wnt pathway activity to develop a small molecule designated SM04690. Its properties were evaluated in bone-marrow-derived human mesenchymal stem cells (hMSCs) to assess chondrocyte differentiation and effects on cartilage catabolism by immunocytochemistry and gene expression, and glycosaminoglycan breakdown. In vivo effects of SM04690 on Wnt signaling, cartilage regeneration and protection were measured using biochemical and histopathological techniques in a rodent acute cruciate ligament tear and partial medial meniscectomy (ACLT + pMMx) OA model. RESULTS: SM04690 induced hMSC differentiation into mature, functional chondrocytes and decreased cartilage catabolic marker levels compared to vehicle. A single SM04690 intra-articular (IA) injection was efficacious in a rodent OA model, with increased cartilage thickness, evidence for cartilage regeneration, and protection from cartilage catabolism observed, resulting in significantly improved Osteoarthritis Research Society International (OARSI) histology scores and biomarkers, compared to vehicle. CONCLUSIONS: SM04690 induced chondrogenesis and appeared to inhibit joint destruction in a rat OA model, and is a candidate for a potential disease modifying therapy for OA.

Time-constrained mother and expanding market: emerging model of under-nutrition in India.

BACKGROUND: Persistent high levels of under-nutrition in India despite economic growth continue to challenge political leadership and policy makers at the highest level. The present inductive enquiry was conducted to map the perceptions of mothers and other key stakeholders, to identify emerging drivers of childhood under-nutrition. METHODS: We conducted a multi-centric qualitative investigation in six empowered action group states of India. The study sample included 509 in-depth interviews with mothers of undernourished and normal nourished children, policy makers, district level managers, implementer and facilitators. Sixty six focus group discussions and 72 non-formal interactions were conducted in two rounds with primary caretakers of undernourished children, Anganwadi Workers and Auxiliary Nurse Midwives. RESULTS: Based on the perceptions of the mothers and other key stakeholders, a model evolved inductively showing core themes as drivers of under-nutrition. The most forceful emerging themes were: multitasking, time constrained mother with dwindling family support; fragile food security or seasonal food paucity; child targeted market with wide availability and consumption of ready-to-eat market food items; rising non-food expenditure, in the context of rising food prices; inadequate and inappropriate feeding; delayed recognition of under-nutrition and delayed care seeking; and inadequate responsiveness of health care system and Integrated Child Development Services (ICDS). The study emphasized that the persistence of child malnutrition in India is also tied closely to the high workload and consequent time constraint of mothers who are increasingly pursuing income generating activities and enrolled in paid labour force, without robust institutional support for childcare. CONCLUSION: The emerging framework needs to be further tested through mixed and multiple method research approaches to quantify the contribution of time limitation of the mother on the current burden of child under-nutrition.

Role of chicken astrovirus as a causative agent of gout in commercial broilers in India.

Several outbreaks of gout were reported in commercial broilers in India during 2011 and 2012, causing up to 40% mortality in the birds. Gross and histopathological observations confirmed gout. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis from kidney samples of gout-affected birds indicated the presence of chicken astrovirus (CAstV) in 41.7% of cases and a mixed infection of CAstV and avian nephritis virus (ANV) in 36.4% of cases. CAstV isolated from gout-affected kidneys by inoculating embryonated specific pathogen free (SPF) eggs showed dwarfing in embryos and a cytopathic effect in chicken embryo kidney cells. Inoculation of 1-day-old SPF and broiler chicks with CAstVs caused gout and mortality between 4 and 10 days post inoculation. Virus isolation and qRT-PCR analysis showed the presence of only CAstV in inoculated chicks. Sequence analysis of capsid genes indicated a major group of Indian CAstVs that displayed 92.0 to 99.2% intergroup amino acid identity and 83.9 to 90.4% identity with subgroup Bi CAstVs of UK origin. We designated this group Indian Bi. Analysis of the partial polymerase amino acid sequences of our isolates indicated two groups of CAstVs (Indian 1 and 2) that displayed 90.2 to 95.5% amino acid identity between them. We thus report for the first time that, in addition to infectious bronchitis virus and ANV, CAstVs are a causative agent of gout.

Interdistrict variations in child health status and health services utilization: lessons for health sector priority setting and planning from a cross-sectional survey in rural India.

BACKGROUND: There are limited data on interdistrict variations in child health status and health services utilization within the states of India. We conducted this study to identify and understand district-wise variations in child morbidity, mortality, healthcare seeking, and the status of health facilities in India. METHODS: A cross-sectional population-based cluster survey was conducted from April to July 2007 in 16 districts of eight states in India. Two districts with similar demographic profile and health criteria were selected from each study state. RESULTS: A total of 216 794 households and 24 812 under-5 children were surveyed. There were wide interdistrict variations in the health status of children within the same state and between different states across India. Interdistrict difference of >5 points/1000 live-births was found for infant mortality rate and under-5 mortality rate in all eight study states, while in six out of eight states this difference was >10 points/1000 live-births. Four states had a difference of >10 points/1000 live-births between respective districts for neonatal mortality rate. The interdistrict differences were also noted in childhood morbidity and health-seeking behaviour. Analysis of proportion of health facilities conforming to Indian public health standards revealed that the difference was m10% for availability of vaccines in five states, emergency services in three, laboratory services and logistics in four each, and referral facility in three of the eight study states. CONCLUSION: This study underscores an important information gap in the country where planners seem to rely heavily on a few selected national-level databases that may not be adequate at the micro level. The current process of sporadic health surveys also appears inadequate and inappropriate. There is a need for district-specific data for planning, improving quality of service and generating demand for health service utilization to improve child survival in India. The findings of this study may prove useful for child health programme planning in India.

Anti-urolithiatic activity of Bryophyllum pinnatum Lam. hydroalcoholic extract in sodium oxalate-induced urolithiasis in rats.

BACKGROUND AND AIM: Despite advances in modern medicine, the development and growth of calculi continues to be a source of concern for mankind, as there is no effective treatment for kidney stones. In the present study we investigated antiurolithiatic activity of Bryophyllum pinnatum Lam against sodium oxalate (NaOx) induced urolithiasis in rats. EXPERIMENTAL PROCEDURE: In rats with renal calculi caused by sodium oxalate (NaOx, 70 mg/kg, i.p.); the antiurolithiatic action of Bryophyllum pinnatum hydroalcoholic extract (BPHE) was studied. BPHE was given every day orally at doses of 50, 200 mg/kg for 14 days to rats to examine activity against sodium oxalate (NaOx) mediated urolithiasis, with Cystone (500 mg/kg, p.o.) as a reference standard. The effect of the extract on urine oxalate, creatinine and phosphate retention and excretion in the kidney, as well as serum and biochemical analysis of kidney homogenate and histopathological examinations were studied. RESULTS AND CONCLUSION: Oral administration of BPHE at doses of 50,100, and 200 mg/kg to rats with sodium oxalate-mediated renal calculi showed dose-dependent substantial (P<0.05) antiurolithiatic potential, with notable reversal of NaOx-induced ion excretion and urinary CaOx concentration. These findings justify the traditional use of Bryophyllum pinnatum hydroalcoholic extract (BPHE) in the treatment of renal calculi.

COVID-19: a conundrum to decipher.

OBJECTIVE: Recent worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of respiratory coronavirus disease 2019 (COVID-19), is a current, ongoing life-threatening crisis, and international public health emergency. The early diagnosis and management of the disease remains a major challenge. In this review, we aim to summarize the updated epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus SARS-CoV-2. MATERIALS AND METHODS: A broad search of the literature was performed in "PubMed" "Medline" "Web of Science", "Google Scholar" and "World Health Organization-WHO" using the keywords "severe acute respiratory syndrome coronavirus", "2019-nCoV", "COVID-19, "SARS", "SARS-CoV-2" "Epidemiology" "Transmission" "Pathogenesis" "Clinical Characteristics". We reviewed and documented the information obtained from literature on epidemiology, pathogenesis and clinical appearances of SARS-CoV-2 infection. RESULTS: The global cases of COVID-19 as of April 2, 2020, have risen to more than 900,000 and morbidity has reached more than 47,000. The incidence rate for COVID-19 has been predicted to be higher than the previous outbreaks of other coronavirus family members, including those of SARS-CoV and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The main clinical presentation of SARS-CoV-2 infection ranges from asymptomatic stages to severe lower respiratory infection in the form of pneumonia. Most of the patients also presented with fever, cough, sore throat, headache, fatigue, myalgia and breathlessness. Individuals at higher risk for severe illness include elderly people and patients with a weakened immune system or that are suffering from an underlying chronic medical condition like hypertension, diabetes mellitus, cancer, respiratory illness or cardiovascular diseases. CONCLUSIONS: SARS-Cov-2 has emerged as a worldwide threat, currently affecting 170 countries and territories across the globe. There is still much to be understood regarding SARS-CoV-2 about its virology, epidemiology and clinical management strategies; this knowledge will be essential to both manage the current pandemic and to conceive comprehensive measures to prevent such outbreaks in the future.

Fixed-dose combination in management of type 2 diabetes mellitus: Expert opinion from an international panel.

Type 2 diabetes mellitus (T2DM) is a progressive disease with multifactorial etiology. The first-line therapy includes monotherapy (with metformin), which often fails to provide effective glycemic control, necessitating the addition of add-on therapy. In this regard, multiple single-dose agents formulated as a single-dose form called fixed-dose combinations (FDCs) have been evaluated for their safety, efficacy, and tolerability. The primary objective of this review is to develop practice-based expert group opinion on the current status and the causes of concern regarding the irrational use of FDCs, in Indian settings. After due discussions, the expert group analyzed the results from several clinical evidence in which various fixed combinations were used in T2DM management. The panel opined that FDCs (double or triple) improve patient adherence, reduce cost, and provide effective glycemic control and, thereby, play an important role in the management of T2DM. The expert group strongly recommended that the irrational metformin FDC's, banned by Indian government, should be stopped and could be achieved through active participation from the government, regulatory bodies, and health ministry, and through continuous education of primary care physicians and pharmacists. In T2DM management, FDCs play a crucial role in achieving glycemic targets effectively. However, understanding the difference between rational and irrational FDC combinations is necessary from the safety, efficacy, and tolerability perspective. In this regard, primary care physicians will have to use a multistep approach so that they can take informed decisions.

Unravelling the utility of modern sulfonylureas from cardiovascular outcome trials and landmark trials: expert opinion from an international panel.

AIM: The primary objective of this review is to develop practice-based expert group opinions on the cardiovascular (CV) safety and utility of modern sulfonylureas (SUs) in cardiovascular outcome trials (CVOTs). BACKGROUND: The United States Food and Drug Administration issued new guidance to the pharmaceutical industry in 2008 regarding the development of new antihyperglycemic drugs. The guidance expanded the scope for the approval of novel antihyperglycemic drugs by mandating CVOTs for safety. A few long-term CVOTs on dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors have been completed, while others are ongoing. SUs, which constitute one of the key antihyperglycemic agents used for the management of type 2 diabetes mellitus (T2DM), have been used as comparator agents in several CVOTs. However, the need for CVOTs on modern SUs remains debatable. In this context, a multinational group of endocrinologists convened for a meeting and discussed the need for CVOTs of modern SUs to evaluate their utility in the management of patients with T2DM. At the meeting, CVOTs of modern SUs conducted to date and the hypotheses derived from the results of these trials were discussed. REVIEW RESULTS: The expert group analyzed the key trials emphasizing the CV safety of modern SUs and also reviewed the results of various CVOTs in which modern SUs were used as comparators. Based on literature evidence and individual clinical insights, the expert group opined that modern SUs are cardiosafe and that since they have been used as comparators in other CVOTs, CVOTs of SUs are not required. CONCLUSION: Modern SUs can be considered a cardiosafe option for the management of patients with diabetes mellitus and CV disease; thus CVOTs among individuals with T2DM are not required.

A brief review of recent discoveries in human anatomy.

In the last few years, a cluster of anatomical discoveries has been reported which overturned the long existing dogmas about the structure and function of human body. First to come was the discovery that established the existence of a lymphatic system pertaining to the central nervous system (CNS). CNS was believed to be anatomically immune privileged owing to the absence of any lymphatics and presence of the blood-brain barrier around it, but latest research has established beyond any reasonable doubt that true lymphatic channels carry immune cells in meninges thus challenging the existing theory. Studies also supported the presence of a 'Glymphatic system' (created by the perivascular spaces lined with the leptomeninges and a sheath of glial cells) in the CNS draining interstitial metabolic waste from CNS. The second discovery unraveled the previously unknown parts of the human mesentery in adult and established that it is a continuous entity all along the intra-abdominal gut tube against the previous notion that it is fragmented in the adult humans. A very recently reported third discovery demonstrated a previously unknown tissue component-'interstitium'-a networked collagen bound fluid-filled space existent in a number of human organs. All these structures bear considerable applied importance towards the pathogenesis, prognostic and diagnostic investigations and management of human diseases. This article attempts to present a brief review of all three remarkable discoveries and emphasizes their applied importance within the realm of medical sciences.

Neurotransmitter precursor amino acids in the treatment of multi-infarct dementia and Alzheimer's disease.

Ten patients with severe dementia due to Alzheimer's disease (AD) or multi-infarct dementia (MID) or both, were treated with the precursor amino acids of the neurotransmitters serotonin and dopamine. The precursor amino acids (PAA) were given orally in a preparation that included tyrosine (4 gm daily) and 5-hydroxy-tryptophan (5-HTP) (800 mg daily), plus carbidopa (100 mg daily) as an aromatic amino-acid decarboxylase inhibitor. Diagnosis was established by an electroencephalogram, brain scan, computerized axial tomographic scan, and in one case by necropsy findings. Serial clinical evaluations and measurements of neuropsychologic function were performed. Levels of homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) were determined before and after administration of probenecid. Side effects of the PAA therapy were diarrhea, drowsiness, nausea, vomiting and agitation, all of which were controlled by reducing the dosage. One patient with MID and one with AD+MID showed clinical and psychologic improvement, but the others did not improve. Analysis of the cerebrospinal fluid for HVA and 5-HIAA before and after the probenecid test indicated some improvement in the metabolic turnover of these acid metabolites of serotonin and dopamine after administration of their precursor amino acids.

Indirect sympathomimetic agents and cerebral blood flow and metabolism.

The effects upon cerebral blood flow (CBF) and oxygen consumption (CMRO2) of the infusion into the internal carotid artery of tyramine and amphetamine were investigated in 24 anaesthetized baboons. The infusion of tyramine was without effect upon CBF and CMRO2 at normocapnia, even at concentrations which significantly raised arterial blood pressure. However, marked reductions in cerebral blood flow were noted at hypercapnia during the infusion of tyramine (2.5 X 10(-7) moles/kg/min). The infusion of amphetamine (7.5 X 10(-10) moles/kg/min) resulted in significant increases in CBF (32%) and CMRO2 (37%). However, an increased concentration of amphetamine (2.5 X 10(-7) moles/kg/min) significantly reduced CBF (22%) and CMRO2 (20%). It is suggested that amphetamine, by virtue of being able to cross the blood--brain barrier and interact with the cerebral monoamine systems, is able to influence cerebral blood flow by inducing changes in cerebral metabolism, and that the minimal reactivity of the cerebral circulation to the infusion of tyramine is the result of the inability of tyramine to cross the blood--brain barrier.

Differences in the time course of regional cerebral hemo-dynamics of gray and white matter during experimental hypertension.

Investigations concerned with the pathogenesis of hypertensive encephalopathy have reported two opposing changes in cerebral hemodynamics during induced hypertension: (1) vasospasm or vasoconstriction of the leptomeningeal arteries and (2) increase of cerebral blood flow which has been termed "breakthrough" of the cerebral autoregulation. To resolve this apparent conflict, continuous measurements of focal cerebral flow and oxygen availability were made in 17 baboons by the use of implanted platinum electrodes placed in both gray and white matter during induced hypertension. Autoregulation was initially well maintained in gray matter followed by "breakthrough" but the autoregulatory response was poorly maintained in the cerebral white matter. The vasoconstriction of the leptomeningeal arteries reported in earlier investigations from observations made through a skull window appears to be due to a marked autoregulatory response to hypertension rather than vasospasm. The autoregulatory response appears to be efficient in gray matter but relatively deficient in white matter.

Effect of acetylcholine on cerebral circulation.

Effects of intravertebral, intracarotid, and intravenous infusion of acetylcholine on cerebral blood flow (CBF) and metabolism was studied in 17 baboons anesthetized with pentobarbital. We measured CBF by the bilateral jugular venous outflow technique using two electromagnetic flowmeters. Effect of acetylcholine infusion on cerebral vascular response to hypercapnia was also assessed. Intravertebral infusion of acetylcholine (0.01 mg/kg/min) increased CBF by 27% and cerebral metabolic rate for oxygen by 19% and decreased cerebral vascular resistance by 25%. On intracarotid injection of acetylcholine, only an 8% increase in CBF was observed, and intravenous infusion produced no change in the parameters observed. Acetylcholine administered by any of the three routes did not enhance the CBF response to hypercapnia. Increase in CBF on intravertebral administration of acetylcholine is associated with an arousal effect and an increase in cerebral metabolism.

Central cholinergic control of cerebral blood flow in the baboon. Effect of cholinesterase inhibition with neostigmine on autoregulation and CO2 responsiveness.

Cerebral autoregulation and vastomotor responsiveness to carbon dioxide (CO2) were measured quantitatively by the use of the autoregulation index and chemical index, respectively, in normal baboons before and after intravertebral and intracarotid infusion of the anticholinesterase agent, neostigmine methylsufate (Prostigmin). Continuous measurements were made of cerebral blood flow (measured as bilateral internal jugular venous outflow), arterial and cerebral venous pO2 and pCO2, cerebral arteriovenous oxygen differences, and endotracheal CO2. The effect of intravertebral infusion of neostigmine (12.5 mug/kg body weight) was compared to intravertebral infusion of neostigmine (25 mug/kg body weight) for assessment of any specific action of the drug on a hypothetical cholinergic vasomotor center, presumed to be located in the territory of the vertebrobasilar supply. No significant or persistent changes in cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) followed either intravertebral or intracarotid infusion of neostigmine. Cerebral vascular resistance (CVR) and cerebral perfusion pressure (CPP), however, decreased significantly after intravertebral infusion. Cerebral autoregulatory vasoconstriction during increases of CCP was significantly reduced following both intravertebral and intracarotid infusion. Cerebral autoregulatory vasodilatation was not altered as CPP was lowered. Cerebral vasodilatory reactivity to CO2 inhalation was significantly enhanced following intravertebral neostigime but not following intracarotid neostigmine. Cerebral vasoconstrictive response to hyperventilation was not influenced by neostigmine. These results support the view that central cholinergic cerebrovascular influences exist, and are vasodilatory in nature.

Insulin resistance: a common factor in the triad of dyslipidemia, hypertension, and coronary artery disease?

In addition to the goal of controlling elevated blood pressure in patients with hypertension improving Dyslipidemia associated with insulin resistance may be an important element in preventing coronary artery disease. Antihypertensive treatment may differ based on the pathophysiology present. It appears that the evidence that supports the development of lipid abnormalities in patients who have insulin resistance is growing. In such patients the morbidity and mortality associated with coronary artery disease may be significantly decreased by selecting agents with favourable metabolic consequences.

Physiological classification of sleep-wake states: based on tri-vesicular (3V) model of the brain.

A new physiological classification of sleep-wake states, based on a novel Tri-Vesicular (3V) model of the brain is proposed. The 3V model consists of an interconnected network of three primal brain vesicles, namely, right and left Arch-Encephalon (Mesencephalon + Diencephalon + Telencephalon) and one DeuterEncephalon (Metencephalon + Myelencephalon). Nine sleep-wake states are defined on the basis of the central activational index (activation and/or inhibition of the 3 brain vesicles), and the level of global arousal. Four sleep states I-IV, four wake states I-IV, and one transitional sleep-wake state, are characterized. The four sleep states correspond with the four non-REM sleep stages, the transitional sleep-wake state correlates with REM sleep, and four wake states are defined in terms of minimal, low, moderate, and high, global behavioral arousal. Three sets of data in the form of polysomnographic and aerobic exercise studies in five adult subjects, and 30 days' data of self-monitored arousal and oro-nasal breathing patterns, are provided in support of this physiological classification of sleep-wake states and the 3V brain model.

Limbic autonomic arousal: its physiological classification and review of the literature.

The object of this article is to present a novel physiological classification of Limbic-Autonomic (LA) arousal on the basis of human physiological data, specifically the oro-nasal breathing patterns in man. It is proposed that the multidimensional LA arousal can be classified into five grades: Grade I: Non-nasal (NN) or oral breathing with bilateral nasal congestion, and nonactive behavior, Grade II: Left Nasal (LN) breathing and quiet behavior, Grade III: Right Nasal (RN) breathing and active behavior, Grade IV: Bilateral Nasal (BN) breathing and very active behavior, and Grade V: Oral and Bilateral Nasal (ON) breathing with maximal behavioral activation. The data from polygraphic electroencephalographic recordings from five healthy volunteers, before, during and after exercise are presented in support of this physiological classification of LA arousal. On the basis of Limbic-Autonomic asymmetry a novel concept of "Visceral Dominance" is also proposed.