Smart Sensing Chairs for Sitting Posture Detection, Classification, and Monitoring: A Comprehensive Review.

Incorrect sitting posture, characterized by asymmetrical or uneven positioning of the body, often leads to spinal misalignment and muscle tone imbalance. The prolonged maintenance of such postures can adversely impact well-being and contribute to the development of spinal deformities and musculoskeletal disorders. In response, smart sensing chairs equipped with cutting-edge sensor technologies have been introduced as a viable solution for the real-time detection, classification, and monitoring of sitting postures, aiming to mitigate the risk of musculoskeletal disorders and promote overall health. This comprehensive literature review evaluates the current body of research on smart sensing chairs, with a specific focus on the strategies used for posture detection and classification and the effectiveness of different sensor technologies. A meticulous search across MDPI, IEEE, Google Scholar, Scopus, and PubMed databases yielded 39 pertinent studies that utilized non-invasive methods for posture monitoring. The analysis revealed that Force Sensing Resistors (FSRs) are the predominant sensors utilized for posture detection, whereas Convolutional Neural Networks (CNNs) and Artificial Neural Networks (ANNs) are the leading machine learning models for posture classification. However, it was observed that CNNs and ANNs do not outperform traditional statistical models in terms of classification accuracy due to the constrained size and lack of diversity within training datasets. These datasets often fail to comprehensively represent the array of human body shapes and musculoskeletal configurations. Moreover, this review identifies a significant gap in the evaluation of user feedback mechanisms, essential for alerting users to their sitting posture and facilitating corrective adjustments.

Efficacy and tolerability of oral morphine versus oxycodone/acetaminophen for analgesia in the emergency department.

OBJECTIVE: Oxycodone/acetaminophen is one of the most commonly prescribed medications for pain management in the emergency department (ED) despite its high abuse liability. Our objective was to determine whether oral immediate-release morphine is as effective and well tolerated as oral oxycodone/acetaminophen for pain relief in stable ED patients. DESIGN: This is a prospective comparative study in which stable adult patients with acute painful conditions who had either oral morphine (15 or 30 mg) or oxycodone/acetaminophen (5/325 mg or 10/650 mg) ordered for them at the discretion of a triage physician were recruited. SETTING: This study took place in an urban, academic ED from 2016 to 2019. PARTICIPANTS: Seventy-three percent of the subjects were between the ages of 18 and 59, 57 percent were female, and 85 percent were African American. Most presented with abdominal, extremity, or back pain. Patient characteristics were similar between treatment groups. INTERVENTIONS: Of the 364 enrolled patients, 182 were given oral morphine and 182 were given oxycodone/acetaminophen at the discretion of the triage provider. They were asked to rate their pain score prior to receiving analgesia and at 60 and 90 minutes after administration. MAIN OUTCOME MEASURES: We examined pain scores, adverse effects, overall satisfaction, willingness to accept the same treatment again, and the need for additional analgesia. RESULTS: There was no difference in satisfaction reported by patients who received morphine versus oxycodone/acetaminophen: 15.9 percent vs 16.5 percent were very satisfied, 31.9 percent vs 26.4 percent were somewhat satisfied, and 23.6 percent vs 22.5 percent were not satisfied, p = 0.56. Secondary outcomes also showed no significant difference: net change in pain score -2 vs -2 at 60 and 90 minutes, p = 0.91 and p = 0.72, respectively; adverse effects 20.9 percent vs 19.2 percent, p = 0.69; need for further analgesia 9.3 percent vs 7.1 percent, p = 0.44; willingness to accept analgesic again 73.1 percent vs 78.6 percent, p = 0.22. CONCLUSIONS: Oral morphine is a feasible alternative to oxycodone/acetaminophen for analgesia in the ED.

Water-Resistant Surface Modification of Hydrophobic Polymers with Water-Soluble Surfactant Additives.

Water-soluble nonionic surfactant, pentaethylene glycol monododecyl ether, C12E5, spontaneously blooms to the surface of spin-cast hydrophobic polyisoprenes, generating hydrophilic surfaces. This system provides a simple model for hydrophilic chemical modification of rubbery polymers that demonstrates surprisingly rich, complex, and unexpected behaviour. The vertical depth profiles were quantified using neutron reflectometry (NR) using a novel procedure to account for undulations in the film thickness. Surface properties were characterized using contact angle analysis and atomic force microscopy (AFM). Despite the low surface tension of the toluene solvent used in film preparation and the low surface energy of the polyisoprene (PI) matrix, NR depth profiles revealed clear evidence of surfactant segregation. This surface layer was typically thicker than a monolayer, but incomplete, yet was remarkably stable with respect to dissolution, even when exposed to hundreds of thousands of times the volume of water required to dissolve all the surfactant on the surface. Despite the apparent resistance to removal from the surface, water exposure does alter the subsequent wettability of the surface, with a hydrophilic-to-hydrophobic transition occurring after rinsing. Complementary AFM images of these C12E5/cis-PI films showed unexpected strand-like features on the surface of the film, which we attribute to a non-uniform lateral distribution of some of the surfactant. This surface structure becomes more evident after rinsing, and it appears that there are two distinct populations of surfactant on the PI film surface. We conclude that some of the bloomed surfactant exists as layers, which are relatively inert with respect to rinsing or surface modification, and some is laterally inhomogeneous. This latter population is primarily responsible for surface wetting behaviour but is not detected by specular NR.

The rising cost of commonly used emergency department medications (2006-15).

OBJECTIVE: We determine how aggregate costs have changed for commonly used emergency department (ED) medications, and assess drivers of cost increases. METHODS: Using the National Hospital Ambulatory Medical Care Survey (NHAMCS), we identified the top 150 ED medications administered and prescribed at discharge in 2015. We used average wholesale prices (AWP) for each year from 2006 to 15 from the Red Book (Truven Health Analytics Inc.). Average wholesale price per patient (AWPP) was calculated by dividing AWP by drug uses. This was then multiplied by the total drug administrations or prescriptions to estimate the total cost in a given the year. All prices were converted to 2015 dollars. RESULTS: Aggregate costs of drugs administered in the ED increased from $688.7 million in 2006 to $882.4 million in 2015. For discharge prescriptions, aggregate costs increased from $2.031 billion in 2006 to $4.572 billion in 2015. AWPP for drugs administered in the ED in 2015 was 14.5% higher than in 2006 and 24.3% higher at discharge. The largest absolute increase in AWPP for drugs administered was for glucagon, which increased from $111 in 2006 to $235 in 2015. The largest AWPP increase at discharge was for epinephrine auto-injector, which increased from $124 in 2006 and to $481 in 2015. CONCLUSION: Over the course of the study period, the aggregate costs of the most common medications administered in the ED increased by 28% while the costs of medications prescribed at discharge increased 125%.

3D posture visualisation from body shape measurements using physics simulation, to ascertain the orientation of the pelvis and femurs in a seated position.

BACKGROUND AND OBJECTIVE: The paper presents a novel technique for the visualisation and measurement of anthropometric features from patients with severe musculoskeletal conditions. During a routine postural assessment, healthcare professionals use anthropometric measurements to infer internal musculoskeletal configuration and inform the prescription of Custom Contoured Seating systems tailored to individual needs. Current assessment procedures are not only time consuming but also do not readily facilitate the communication of musculoskeletal configuration between healthcare professionals nor the quantitative comparison of changes over time. There are many techniques measuring musculoskeletal configurations such as MRI, CT or X-ray. However, most are very resource intensive and do not readily lend themselves to widespread use in, for example, community based services. Due to the low volume of patient data and hence small datasets modern machine learning techniques are also not feasible and a bespoke solution is required. METHODS: The technique outlined in this paper uses physics simulation to visualise the orientation of the pelvis and femurs when seated in a custom contoured cushion. The input to the algorithm is a body shape measurement and the output is a visualised pelvis and femurs. The algorithm was tested by also outputting a multi-label classification of posture (specific to the pelvis and femurs). RESULTS: The physics simulation has a classification accuracy of 72.9% when labelling all 9 features of the model; when considering 6 features (excluding rotations about the x-axis) the accuracy is increased to 92.8%. CONCLUSIONS: This study has shown that a mechanical shape sensor can be used to capture the unsupported seated posture of an individual during a clinic. The results have demonstrated the potential of the physics simulation to be used for anthropometric feature extraction from body shape measurements leading to a better posture visualization. Capturing and visualising the seated posture in this way should enable clinicians to more easily compare the effects of clinical interventions over time and document postural changes. Overall, the algorithm performed well, however, in order to fully evaluate its clinical benefit, it needs to be tested in the future using data from patients with severe musculoskeletal conditions and complex body shapes.

Pulse Oximetry Is Unreliable in Patients on Veno-Venous Extracorporeal Membrane Oxygenation Caused by Unrecognized Carboxyhemoglobinemia.

Continuous bedside pulse oximetry (SpO2) is universally used to monitor oxygenation for patients supported on veno-venous extracorporeal membrane oxygenation (VV-ECMO). Yet, elevated carboxyhemoglobin (COHb), a known event in VV-ECMO, diminishes the reliability of SpO2. This retrospective cohort study aims to assess the accuracy of SpO2 compared with oxyhemoglobin (SaO2) and quantify COHb levels by co-oximetry in the VV-ECMO population. Forty patients on VV_ECMO from 2012 to 2017 underwent 1,119 simultaneous SaO2 and SpO2 measurements. Most patients were male (60%) with average age of 46 years. SpO2 overestimated SaO2 values by 2.35% at time of cannulation and 0.0061% for each additional hour on VV-ECMO (p < 0.0001). Twenty-nine (72.5%) patients developed elevated COHb (>3% of hemoglobin saturation) at least once during VV-ECMO support and 602 (40.2%) arterial blood gases yielded elevated COHb levels. Mean duration for ECMO with elevated COHb was 244 hours compared with 98 hours in patients without (p < 0.0048). Patients who developed COHb were younger (mean age 40 vs. 55 years, p < 0.024) and had single-site double-lumen cannulation (odds ratio = 4.5, p = 0.23). At time of cannulation, mean COHb was 2.18% and increased by 0.0054% for each additional hour (p < 0.0001). For every 1% increase in COHb, SaO2 decreased by 1.1% (p < 0.0001). During VV-ECMO, SpO2 often overestimates SaO2 by substantial margins. This is attributable to rising COHb levels proportional to duration on VV-ECMO. In this population where adequate oxygen delivery is often marginal, clinicians should be wary of the reliability of continuous pulse oximetry to assess oxygenation.

Hemophilia and von Willebrand Disease: A Review of Emergency Department Management.

BACKGROUND: Hemophilia and von Willebrand disease (VWD) are the most common congenital coagulation factor deficiencies. Patients with these disorders who experience bleeding complications are often initially managed in the emergency department (ED). OBJECTIVE OF THE REVIEW: This review will focus on the emergency department management of patients with these disorders and provide an update on current treatment options. DISCUSSION: The mainstay of management is initial stabilization, control of bleeding when possible, and administration of specific factors. Early coordination of care with hematology is critical. CONCLUSIONS: Emergency medicine providers must have an understanding of the pathophysiology, clinical presentation, and management strategies in order to optimally care for these complex patients.

The ED-SED Study: A Multicenter, Prospective Cohort Study of Practice Patterns and Clinical Outcomes Associated With Emergency Department SEDation for Mechanically Ventilated Patients.

OBJECTIVES: To characterize emergency department sedation practices in mechanically ventilated patients, and test the hypothesis that deep sedation in the emergency department is associated with worse outcomes. DESIGN: Multicenter, prospective cohort study. SETTING: The emergency department and ICUs of 15 medical centers. PATIENTS: Mechanically ventilated adult emergency department patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All data involving sedation (medications, monitoring) were recorded. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Sedation-Agitation Scale of 2 or 1. A total of 324 patients were studied. Emergency department deep sedation was observed in 171 patients (52.8%), and was associated with a higher frequency of deep sedation in the ICU on day 1 (53.8% vs 20.3%; p < 0.001) and day 2 (33.3% vs 16.9%; p = 0.001), when compared to light sedation. Mean (SD) ventilator-free days were 18.1 (10.8) in the emergency department deep sedation group compared to 20.0 (9.8) in the light sedation group (mean difference, 1.9; 95% CI, -0.40 to 4.13). Similar results according to emergency department sedation depth existed for ICU-free days (mean difference, 1.6; 95% CI, -0.54 to 3.83) and hospital-free days (mean difference, 2.3; 95% CI, 0.26-4.32). Mortality was 21.1% in the deep sedation group and 17.0% in the light sedation group (between-group difference, 4.1%; odds ratio, 1.30; 0.74-2.28). The occurrence rate of acute brain dysfunction (delirium and coma) was 68.4% in the deep sedation group and 55.6% in the light sedation group (between-group difference, 12.8%; odds ratio, 1.73; 1.10-2.73). CONCLUSIONS: Early deep sedation in the emergency department is common, carries over into the ICU, and may be associated with worse outcomes. Sedation practice in the emergency department and its association with clinical outcomes is in need of further investigation.

A method for the analysis of sugars in biological systems using reductive amination in combination with hydrophilic interaction chromatography and high resolution mass spectrometry.

Separation of sugar isomers extracted from biological samples is challenging because of their natural occurrence as alpha and beta anomers and, in the case of hexoses, in their pyranose and furanose forms. A reductive amination method was developed for the tagging of sugars with the aim of it becoming part of a metabolomics work flow. The best separation of the common hexoses (glucose, fructose, mannose and galactose) was achieved when 2H5-aniline was used as the tagging reagent in combination with separation on a ZICHILIC column. The method was used to tag a range of sugars including pentoses and uronic acids. The method was simple to perform and was able to improve both the separation of sugars and their response to electrospray ionisation. The method was applied to the profiling of sugars in urine where a number of hexose and pentose isomers could be observed. It was also applied to the quantification of sugars in post-mortem brain samples from three control samples and three samples from individuals who had suffered from bipolar disorder.

Impact of the single point of access referral system to reduce waiting times and improve clinical outcomes in an assistive technology service.

The introduction of a single point referral system that prioritises clients depending on case complexity and overcomes the need for re-admittance to a waiting list via a review system has been shown to significantly reduce maximum waiting times for a Posture and Mobility (Special Seating) Service from 102.0 ± 24.33 weeks to 19.2 ± 8.57 weeks (p = 0.015). Using this service model linear regression revealed a statistically significant improvement in the performance outcome of prescribed seating solutions with shorter Episode of Care completion times (p = 0.023). In addition, the number of Episodes of Care completed per annum was significantly related to the Episode of Care completion time (p = 0.019). In conclusion, it is recommended that it may be advantageous to apply this service model to other assistive technology services in order to reduce waiting times and to improve clinical outcomes.

Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1.

The treatment of Human African trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important; pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp., has been identified as a candidate target, and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from Trypanosoma brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. Eight compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus, although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development.

Communication between the zinc and tetrahydrobiopterin binding sites in nitric oxide synthase.

The nitric oxide synthase (NOS) dimer is stabilized by a Zn(2+) ion coordinated to four symmetry-related Cys residues exactly along the dimer 2-fold axis. Each of the two essential tetrahydrobiopterin (H4B) molecules in the dimer interacts directly with the heme, and each H4B molecule is ~15 Å from the Zn(2+). We have determined the crystal structures of the bovine endothelial NOS dimer oxygenase domain bound to three different pterin analogues, which reveal an intimate structural communication between the H4B and Zn(2+) sites. The binding of one of these compounds, 6-acetyl-2-amino-7,7-dimethyl-7,8-dihydro-4(3H)-pteridinone (1), to the pterin site and Zn(2+) binding are mutually exclusive. Compound 1 both directly and indirectly disrupts hydrogen bonding between key residues in the Zn(2+) binding motif, resulting in destabilization of the dimer and a complete disruption of the Zn(2+) site. Addition of excess Zn(2+) stabilizes the Zn(2+) site at the expense of weakened binding of 1. The unique structural features of 1 that disrupt the dimer interface are extra methyl groups that extend into the dimer interface and force a slight opening of the dimer, thus resulting in disruption of the Zn(2+) site. These results illustrate a very delicate balance of forces and structure at the dimer interface that must be maintained to properly form the Zn(2+), pterin, and substrate binding sites.

Rule-based algorithm for the classification of sitting postures in the sagittal plane from the Cardiff Body Match measurement system.

The purpose of this paper is to present the design and implementation of a novel rule-based algorithm for the classification of sitting postures in the sagittal plane. The research focused on individuals with severe musculoskeletal problems and, thus, specific requirements for posture and pressure management. Clients' body shapes were captured using the Cardiff Body Match system developed by the Rehabilitation Engineering Unit, Cardiff and Vale University Health Board. The algorithm consists of four main steps: the first step is the symmetry line detection, the second step involves the mathematical analysis of the curvature of the backrest profile, the third step is the sitting posture classification and the fourth step is the extraction of the geometric parameters from the curve. The results show the classification system was successful in identifying four types of curves characterizing sitting postures using local derivatives as curve descriptors with an overall accuracy of 93.9%.

Pelvis feature extraction and classification of Cardiff body match rig base measurements for input into a knowledge-based system.

The purpose of this paper is to determine whether it is possible to use an automated measurement tool to clinically classify clients who are wheelchair users with severe musculoskeletal deformities, replacing the current process which relies upon clinical engineers with advanced knowledge and skills. Clients' body shapes were captured using the Cardiff Body Match (CBM) Rig developed by the Rehabilitation Engineering Unit (REU) at Rookwood Hospital in Cardiff. A bespoke feature extraction algorithm was developed that estimates the position of external landmarks on clients' pelvises so that useful measurements can be obtained. The outputs of the feature extraction algorithms were compared to CBM measurements where the positions of the client's pelvis landmarks were known. The results show that using the extracted features facilitated classification. Qualitative analysis showed that the estimated positions of the landmark points were close enough to their actual positions to be useful to clinicians undertaking clinical assessments.

Tetrahydrobiopterin analogues with NO-dependent pulmonary vasodilator properties.

Reduced NO levels due to the deficiency of tetrahydrobiopterin (BH(4)) contribute to impaired vasodilation in pulmonary hypertension. Due to the chemically unstable nature of BH(4), it was hypothesised that oxidatively stable analogues of BH(4) would be able to support NO synthesis to improve endothelial dysfunction in pulmonary hypertension. Two analogues of BH(4), namely 6-hydroxymethyl pterin (HMP) and 6-acetyl-7,7-dimethyl-7,8-dihydropterin (ADDP), were evaluated for vasodilator activity on precontracted rat pulmonary artery rings. ADDP was administered to pulmonary hypertensive rats, followed by measurement of pulmonary vascular resistance in perfused lungs and eNOS expression by immunohistochemistry. ADDP and HMP caused significant relaxation in vitro in rat pulmonary arteries depleted of BH(4) with a maximum relaxation at 0.3µM (both P<0.05). Vasodilator activity of ADDP and HMP was completely abolished following preincubation with the NO synthase inhibitor, L-NAME. ADDP and HMP did not alter relaxation induced by carbachol or spermine NONOate. BH(4) itself did not produce relaxation. In rats receiving ADDP 14.1mg/kg/day, pulmonary vasodilation induced by calcium ionophore A23187 was augmented and eNOS immunoreactivity was increased. In conclusion, ADDP and HMP are two analogues of BH(4), which can act as oxidatively stable alternatives to BH(4) in causing NO-mediated vasorelaxation. Chronic treatment with ADDP resulted in improvement of NO-mediated pulmonary artery dilation and enhanced expression of eNOS in the pulmonary vascular endothelium. Chemically stable analogues of BH(4) may be able to limit endothelial dysfunction in the pulmonary vasculature.

Structure-based design of pteridine reductase inhibitors targeting African sleeping sickness and the leishmaniases.

Pteridine reductase (PTR1) is a target for drug development against Trypanosoma and Leishmania species, parasites that cause serious tropical diseases and for which therapies are inadequate. We adopted a structure-based approach to the design of novel PTR1 inhibitors based on three molecular scaffolds. A series of compounds, most newly synthesized, were identified as inhibitors with PTR1-species specific properties explained by structural differences between the T. brucei and L. major enzymes. The most potent inhibitors target T. brucei PTR1, and two compounds displayed antiparasite activity against the bloodstream form of the parasite. PTR1 contributes to antifolate drug resistance by providing a molecular bypass of dihydrofolate reductase (DHFR) inhibition. Therefore, combining PTR1 and DHFR inhibitors might improve therapeutic efficacy. We tested two new compounds with known DHFR inhibitors. A synergistic effect was observed for one particular combination highlighting the potential of such an approach for treatment of African sleeping sickness.

Modification of chiral dimethyl tartrate through transesterification: immobilization on POSS and enantioselectivity reversal in sharpless asymmetric epoxidation.

Modification of dimethyl tartrate has been investigated through transesterification with aminoalcohols to provide reactive functionalities for the covalent bonding of chiral tartrate to polyhedral oligomeric silsesquioxanes. The transesterification of dimethyl tartrate has been widely studied using different catalytic systems and reaction conditions. Through the proper selection of both the catalytic system and the reaction conditions, it is possible to achieve monosubstituted or bis-substituted tartrate derivatives as sole products. All the intermediate chiral tartrate-derived ligands were successfully used in the homogeneous enantioselective epoxidation of allylic alcohols providing moderate enantiomeric excess over the products. Attached amine groups have been used to support the modified tartrate ligands on to a haloaryl-functionalized silsesquioxane moiety. This final chiral tartrate ligand displays reverse enantioselectivity in the asymmetric epoxidation of allylic alcohols with regard to the starting dimethyl tartrate ligand, both molecules having the same chiral sign. However, the POSS-containing ligand can be easily recovered in almost quantitative yield and reused in asymmetric epoxidation reactions. In addition, recovered silsesquioxane-pendant ligand, though displaying decreasing catalytic activity in recycling epoxidation tests, showed very stable enantioselective behavior.

Diversity oriented syntheses of fused pyrimidines designed as potential antifolates.

Diversity oriented syntheses of some furo[2,3-d]pyrimidines and pyrrolo[2,3-d]pyrimidines related to folate, guanine, and diaminopyrimidine-containing drugs have been developed for the preparation of potential anti-infective and anticancer compounds. Amide couplings and Suzuki couplings on the basic heterocyclic templates were used, in the latter case yields being especially high using aromatic trifluoroborates as the coupling partner. A new ring synthesis of 6-aryl-substituted deazaguanines bearing 2-alkylthio groups has been developed using Michael addition of substituted nitrostyrenes. Diversity at C-2 has been introduced by oxidation and substitution with a range of amino nucleophiles. The chemical reactivity of these pyrrolopyrimidines with respect to both electrophilic substitution in ring synthesis and nucleophilic substitution for diversity is discussed. Several compounds were found to inhibit pteridine reductases from the protozoan parasites Trypanosoma brucei and Leishmania major at the micromolar level and to inhibit the growth of Trypanosma brucei brucei in cell culture at higher concentrations. From these results, significant structural features required for inhibition of this important drug target enzyme have been identified.

6-Acetyl-7,7-dimethyl-5,6,7,8-tetrahydropterin is an activator of nitric oxide synthases.

6-Acetyl-7,7-dimethyl-7,8-dihydropterin 3 has been shown to be able to substitute for the natural cofactor of nitric oxide synthases, tetrahydrobiopterin 1, in cells and tissues that contain active nitric oxide synthases (NOSs). In both macrophages, which produce iNOS, and endothelial cells, which produce eNOS, in which tetrahydrobiopterin biosynthesis has been blocked by inhibition of GTP cyclohydrolase 1, dihydropterin 3 restored production of nitric oxide by these cells. In tissues, 3 caused relaxation in preconstricted rat aortic rings, again in which tetrahydrobiopterin biosynthesis had been inhibited, an effect that was blocked by the NOS inhibitor, L-NAME. However, dihydropterin 3 was not itself an active cofactor in purified NOS (nNOS) preparations free of tetrahydrobiopterin suggesting that intracellular reduction to 6-acetyl-7,7-dimethyl-5,6,7,8-tetrahydropterin 4 is required for activity. Compound 4 was prepared by reduction of the corresponding 7,8-dihydropterin with sodium cyanoborohydride and has been shown to be a competent cofactor for nitric oxide production by nNOS. Together, the results show that the 7,7-dimethyl-7,8-dihydropterin is a novel structural framework for effective tetrahydrobiopterin analogues.