ABSTRACT
BACKGROUND: Information about pain and injury from equipment on a particular deployment is not disaggregated in the literature; thus, the nature of the issue is unclear. AIMS: To determine the prevalence of pain or injury during a particular deployment that military personnel attributed to equipment they used on this deployment; and to document the types of equipment they identified, the type of pain or injury and how they thought the pain or injury occurred. METHODS: This paper analyses data from a deployment and health survey of Australian Defence Force personnel. The participants are 8932 personnel who deployed to Iraq and 6534 who deployed to Afghanistan. Participants indicated whether they experienced pain or injury from equipment they used on deployment and detailed their experiences in response to an open-ended question (n = 563). RESULTS: Sixteen per cent of Iraq-deployed and 21% of Afghanistan-deployed participants reported pain or injury from equipment they used on deployment. Body armour was the most common equipment identified; however, a wide range of equipment was related to pain or injury. A new finding is that pain or injury related to armour was attributed to its wear in vehicles and during vehicle ingress or egress. CONCLUSIONS: Knowledge of the nature of pain or injury related to equipment used on deployment may help inform improved designs and practices to reduce or prevent avoidable harm to serving personnel.
Subject(s)
Military Deployment , Military Personnel , Afghan Campaign 2001- , Australia/epidemiology , Humans , Iraq War, 2003-2011 , Pain , Self ReportABSTRACT
BACKGROUND: Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Active cigarette smoking may have a significant impact on treatment responses to anti-tuberculosis treatment. OBJECTIVE: To ascertain the effect of smoking on Mycobacterium tuberculosis sputum culture conversion rates following treatment initiation in patients with susceptible, multidrug-resistant and extensively drug-resistant TB (M/XDR-TB). METHOD: Sputum cultures of smoking and non-smoking patients with pulmonary TB (PTB) treated at a referral centre in Germany were evaluated. RESULTS: Between January 2012 and March 2017, 247 patients with PTB treated at the Medical Clinic of Research Center Borstel, Borstel, Germany, were included in the study. Of 247 patients, 65 (26.3%) were infected with multidrug-resistant strains of M. tuberculosis (MDR-TB). Sputum culture examinations were performed on a weekly basis. Active smoking (n = 111; time to culture conversion [TCC] 50.7 days, interquartile range [IQR] 26.5-73.0) and former smoking (n = 72; TCC 43.1 days, IQR 19.8-56.0) significantly delayed culture conversion rates (P < 0.001) when compared with never smoking (n = 64; TCC 33.2 days, IQR 8.0-50.3). Delay in TCC among smoking, non-MDR-TB patients (n = 138; TCC 47.3 days, IQR 19.0-89.0) was comparable with non-smoking, MDR-TB patients (n = 20; TCC 53.0 days, IQR 18.0-71.0). The shortest TCC was observed in non-smoking, non-MDR-TB patients (n = 44; TCC 33.0 days, IQR 10.0-48.5), whereas the longest was seen in smoking, MDR-TB patients (n = 45; TCC 60.7 days, IQR 33.3-89.0); P < 0.001). CONCLUSION: Active cigarette smoking and, to a lesser extent, former cigarette smoking, substantially delayed culture conversion in PTB.
Subject(s)
Antitubercular Agents/pharmacology , Cigarette Smoking/adverse effects , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology , Adult , Antitubercular Agents/therapeutic use , Extensively Drug-Resistant Tuberculosis/drug therapy , Extensively Drug-Resistant Tuberculosis/microbiology , Female , Germany , Humans , Logistic Models , Male , Middle Aged , Mycobacterium tuberculosis/isolation & purification , Retrospective Studies , Sputum/microbiology , Time Factors , Treatment Outcome , Young AdultABSTRACT
Tissues of the central nervous system (CNS), including the optic nerve (ON), are considered a-lymphatic. However, lymphatic structures have been described in the dura mater of human ON sheaths. Since it is known that lymphatic markers are also expressed by single non-lymphatic cells, these results need confirmation according to the consensus statement for the use of lymphatic markers in ophthalmologic research. The aim of this study was to screen for the presence of lymphatic structures in the adult human ON using a combination of four lymphatic markers. Cross and longitudinal cryo-sections of human optic nerve tissue (n = 12, male and female, postmortem time = 15.8 ± 5.5 h, age = 66.5 ± 13.8 years), were obtained from cornea donors of the Salzburg eye bank, and analyzed using immunofluorescence with the following markers: FOXC2, CCL21, LYVE-1 and podoplanin (PDPN; lymphatic markers), Iba1 (microglia), CD68 (macrophages), CD31 (endothelial cell, EC), NF200 (neurofilament), as well as GFAP (astrocytes). Human skin sections served as positive controls and confocal microscopy in single optical section mode was used for documentation. In human skin, lymphatic structures were detected, showing a co-localization of LYVE-1/PDPN/FOXC2 and CCL21/LYVE-1. In the human ON however, single LYVE-1+ cells were detected, but were not co-localized with any other lymphatic marker tested. Instead, LYVE-1+ cells displayed immunopositivity for Iba1 and CD68, being more pronounced in the periphery of the ON than in the central region. However, Iba1+/LYVE-1- cells outnumbered Iba1+/LYVE-1+ cells. PDPN, revealed faint labeling in human ON tissue despite strong immunoreactivity in rat ON controls, showing co-localization with GFAP in the periphery. In addition, pronounced autofluorescent dots were detected in the ON, showing inter-individual differences in numbers. In the adult human ON no lymphatic structures were detected, although distinct lymphatic structures were identified in human skin tissue by co-localization of four lymphatic markers. However, single LYVE-1+ cells, also positive for Iba1 and CD68 were present, indicating LYVE-1+ macrophages. Inter-individual differences in the number of LYVE-1+ as well as Iba1+ cells were obvious within the ONs, most likely resulting from diverse medical histories of the donors.
Subject(s)
Biomarkers/metabolism , Chemokine CCL21/metabolism , Forkhead Transcription Factors/metabolism , Lymphatic Vessels/metabolism , Membrane Glycoproteins/metabolism , Optic Nerve/metabolism , Vesicular Transport Proteins/metabolism , Aged , Aged, 80 and over , Female , Fluorescent Antibody Technique, Indirect , Humans , Macrophages/metabolism , Male , Microscopy, Fluorescence , Middle Aged , Skin/metabolism , Young AdultABSTRACT
INTRODUCTION: An obturator nerve block (ONB) and a femoral triangle block (FTB) provide effective analgesia after total knee arthroplasty (TKA) without impeding the ambulation, although the ONB produces motor blockade of the hip adductor muscles. The popliteal plexus (PP) in the popliteal fossa is formed by contribution from the tibial nerve and the posterior obturator nerve, innervating intraarticular genicular structures and the posterior capsule of the knee. We hypothesised that a popliteal plexus block (PPB) as a supplement to an FTB would reduce pain after TKA without anaesthetising motor branches from the sciatic nerve in the popliteal fossa. AIM: To assess the analgesic effect of adding a PPB to an FTB in 10 subjects with significant pain after TKA. METHODS: All subjects underwent unilateral TKA with spinal anaesthesia and received an FTB. The cutaneous sensation and the postoperative pain were assessed. The primary outcome was the proportion of subjects with pain above numeric rating scale (NRS) 3 followed by a reduction to NRS 3 or below after conducting a PPB. RESULTS: Ten subjects with a median pain of NRS 5.5 (interquartile range [IQR] 4-8) after unilateral TKA received a PPB. All 10 subjects experienced a reduction in pain to NRS 3 or below (NRS 1.5 [IQR 0-3]) within a mean time of 8.5 (95% CI 6.8-10.2) minutes. Three subjects were completely pain free after the PPB. The ankle muscle strength was not affected. CONCLUSIONS: The PPB provided effective pain relief without affecting the ankle muscle strength in all 10 subjects with significant pain after TKA and an FTB.
ABSTRACT
Only few tissues lack lymphatic supply, such as the CNS or the inner eye. However, if the scleral border is compromised due to trauma or tumor, lymphatics are detected in the eye. Since the situation in the optic nerve (ON), part of the CNS, is not clear, the aim of this study is to screen for the presence of lymphatic markers in the healthy and lesioned ON. Brown Norway rats received an unilateral optic nerve crush (ONC) with defined force, leaving the dura intact. Lesioned ONs and unlesioned contralateral controls were analyzed 7 days (n = 5) and 14 days (n = 5) after ONC, with the following markers: PDGFRb (pericyte), Iba1 (microglia), CD68 (macrophages), RECA (endothelial cell), GFAP (astrocyte) as well as LYVE-1 and podoplanin (PDPN; lymphatic markers). Rat skin sections served as positive controls and confocal microscopy in single optical section mode was used for documentation. In healthy ONs, PDGFRb is detected in vessel-like structures, which are associated to RECA positive structures. Some of these PDGFRb+/RECA+ structures are closely associated with LYVE-1+ cells. Homogenous PDPN-immunoreactivity (IR) was detected in healthy ON without vascular appearance, showing no co-localization with LYVE-1 or PDGFRb but co-localization with GFAP. However, in rat skin controls PDPN-IR was co-localized with LYVE-1 and further with RECA in vessel-like structures. In lesioned ONs, numerous PDGFRb+ cells were detected with network-like appearance in the lesion core. The majority of these PDGFRb+ cells were not associated with RECA-IR, but were immunopositive for Iba1 and CD68. Further, single LYVE-1+ cells were detected here. These LYVE-1+ cells were Iba1-positive but PDPN-negative. PDPN-IR was also clearly absent within the lesion site, while LYVE-1+ and PDPN+ structures were both unaltered outside the lesion. In the lesioned area, PDGFRb+/Iba1+/CD68+ network-like cells without vascular association might represent a subtype of microglia/macrophages, potentially involved in repair and phagocytosis. PDPN was detected in non-lymphatic structures in the healthy ON, co-localizing with GFAP but lacking LYVE-1, therefore most likely representing astrocytes. Both, PDPN and GFAP positive structures are absent in the lesion core. At both time points investigated, no lymphatic structures can be identified in the lesioned ON. However, single markers used to identify lymphatics, detected non-lymphatic structures, highlighting the importance of using a panel of markers to properly identify lymphatic structures.
Subject(s)
Blood Vessels/pathology , Lymphatic Vessels/pathology , Membrane Glycoproteins/biosynthesis , Optic Nerve Injuries/diagnosis , Optic Nerve/blood supply , Receptors, Cell Surface/biosynthesis , Animals , Biomarkers/metabolism , Cell Count , Disease Models, Animal , Female , Immunohistochemistry , Male , Microscopy, Confocal , Microscopy, Immunoelectron , Optic Nerve Injuries/metabolism , RatsABSTRACT
The Queensland branch of the Royal Australasian College of Physicians (RACP) commissioned this study to update their workforce profile and examine rural practice. The present investigation aimed to describe characteristics of Queensland physicians and determine the influence of childhood and training locations on current rural practice. A cross-sectional online survey, conducted 4 July-4 November 2013, was administered to Fellows of The RACP, Queensland. Descriptive statistics report characteristics and logistic regression analyses identify associations and interactions. The outcome measure was current practice location using the Australian Standard Geographic Classification - Remoteness Area. Data were obtained for 633 physicians. Their average age was 49.5 years, a third was female and a quarter was in rural practice. Rural practice was associated with a rural childhood (odds ratio (OR) (95% confidence interval, CI) 1.89 (1.10, 3.27) P = 0.02) and any time spent as an intern (OR 4.07 (2.12, 7.82) P < 0.001) or registrar (OR 4.00 (2.21, 7.26) P < 0.001) in a rural location. Physicians with a rural childhood and rural training were most likely to be in rural practice. However, those who had a metropolitan childhood and a rural internship were approximately five times more likely to be working in rural practice than physicians with no rural exposure (OR 5.33 (1.61, 17.60) P < 0.01). The findings demonstrate the positive effect of rural vocational training on rural practice. A prospective study would determine if recent changes to the Basic Physician Training Pathway and the Basic Paediatric Training Network (more rural training than previous pathways) increases the rate of rural practice.
Subject(s)
Career Choice , Internship and Residency , Physicians/statistics & numerical data , Rural Health Services , Adult , Cross-Sectional Studies , Female , Humans , Logistic Models , Male , Middle Aged , Queensland , WorkforceABSTRACT
Glaucoma is a group of neurodegenerative diseases characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons, and is the second leading cause of blindness worldwide. Elevated intraocular pressure is a well known risk factor for the development of glaucomatous optic neuropathy and pharmacological or surgical lowering of intraocular pressure represents a standard procedure in glaucoma treatment. However, the treatment options are limited and although lowering of intraocular pressure impedes disease progression, glaucoma cannot be cured by the currently available therapy concepts. In an acute short-term ocular hypertension model in rat, we characterize RGC loss, but also microglial cell activation and vascular alterations of the retina at certain time points. The combination of these three parameters might facilitate a better evaluation of the disease progression, and could further serve as a new model to test novel treatment strategies at certain time points. Acute ocular hypertension (OHT) was induced by the injection of magnetic microbeads into the rat anterior chamber angle (n = 22) with magnetic position control, leading to constant elevation of IOP. At certain time points post injection (4d, 7d, 10d, 14d and 21d), RGC loss, microglial activation, and microvascular pericyte (PC) coverage was analyzed using immunohistochemistry with corresponding specific markers (Brn3a, Iba1, NG2). Additionally, the tightness of the retinal vasculature was determined via injections of Texas Red labeled dextran (10 kDa) and subsequently analyzed for vascular leakage. For documentation, confocal laser-scanning microscopy was used, followed by cell counts, capillary length measurements and morphological and statistical analysis. The injection of magnetic microbeads led to a progressive loss of RGCs at the five time points investigated (20.07%, 29.52%, 41.80%, 61.40% and 76.57%). Microglial cells increased in number and displayed an activated morphology, as revealed by Iba1-positive cell number (150.23%, 175%, 429.25%,486.72% and 544.78%) and particle size analysis (205.49%, 203.37%, 412.84%, 333.37% and 299.77%) compared to contralateral control eyes. Pericyte coverage (NG2-positive PC/mm) displayed a significant reduction after 7d of OHT in central, and after 7d and 10d in peripheral retina. Despite these alterations, the tightness of the retinal vasculature remained unaltered at 14 and 21 days after OHT induction. While vascular tightness was unchanged in the course of OHT, a progressive loss of RGCs and activation of microglial cells was detected. Since a significant loss in RGCs was observed already at day 4 of experimental glaucoma, and since activated microglia peaked at day 10, we determined a time frame of 7-14 days after MB injection as potential optimum to study glaucoma mechanisms in this model.
Subject(s)
Blood-Retinal Barrier/pathology , Disease Models, Animal , Microglia/pathology , Ocular Hypertension/pathology , Retinal Ganglion Cells/pathology , Acute Disease , Animals , Antigens/metabolism , Biomarkers/metabolism , Blood-Retinal Barrier/metabolism , Calcium-Binding Proteins/metabolism , Female , Fluorescent Antibody Technique, Indirect , Intraocular Pressure , Male , Microfilament Proteins/metabolism , Microglia/metabolism , Microscopy, Confocal , Ocular Hypertension/etiology , Ocular Hypertension/metabolism , Proteoglycans/metabolism , Rats , Rats, Inbred BN , Real-Time Polymerase Chain Reaction , Retinal Ganglion Cells/metabolism , Time Factors , Transcription Factor Brn-3A/metabolismABSTRACT
Doublecortin (DCX) is predominantly expressed in neuronal precursor cells and young immature neurons of the developing and adult brain, where it is involved in neuronal differentiation, migration and plasticity. Moreover, its expression pattern reflects neurogenesis, and transgenic DCX promoter-driven reporter models have been previously used to investigate adult neurogenesis. In this study, we characterize dsRed2 reporter protein-expressing cells in the adult retina of the transgenic DCX promoter-dsRed2 rat model, with the aim to identify cells with putative neurogenic activity. Additionally, we confirmed the expression of the dsRed2 protein in DCX-expressing cells in the adult hippocampal dentate gyrus. Adult DCX-dsRed2 rat retinas were analyzed by immunohistochemistry for expression of DCX, NF200, Brn3a, Sox2, NeuN, calbindin, calretinin, PKC-a, Otx2, ChAT, PSA-NCAM and the glial markers GFAP and CRALBP, followed by confocal laser-scanning microscopy. In addition, brain sections of transgenic rats were analyzed for dsRed2 expression and co-localization with DCX, NeuN, GFAP and Sox2 in the cortex and dentate gyrus. Endogenous DCX expression in the adult retina was confined to horizontal cells, and these cells co-expressed the DCX promoter-driven dsRed2 reporter protein. In addition, we encountered dsRed2 expression in various other cell types in the retina: retinal ganglion cells (RGCs), a subpopulation of amacrine cells, a minority of bipolar cells and in perivascular cells. Since also RGCs expressed dsRed2, the DCX-dsRed2 rat model might offer a useful tool to study RGCs in vivo under various conditions. Müller glial cells, which have previously been identified as cells with stem cell features and with neurogenic potential, did express neither endogenous DCX nor the dsRed2 reporter. However, and surprisingly, we identified a perivascular glial cell type expressing the dsRed2 reporter, enmeshed with the glia/stem cell marker GFAP and colocalizing with the neural stem cell marker Sox2. These findings suggest the so far undiscovered existence of perivascular associated cell with neural stem cell-like properties in the adult retina.
Subject(s)
Luminescent Proteins/genetics , Microtubule-Associated Proteins/genetics , Neuropeptides/genetics , Retina/cytology , Animals , Doublecortin Domain Proteins , Doublecortin Protein , Female , Immunohistochemistry , Luminescent Proteins/metabolism , Male , Microtubule-Associated Proteins/metabolism , Neuropeptides/metabolism , Rats , Rats, Transgenic , Red Fluorescent ProteinABSTRACT
Impaired ocular blood flow is involved in the pathogenesis of numerous ocular diseases like glaucoma or AMD. The purpose of the present study was to introduce and validate a novel, microscope based, non-invasive Laser Doppler Flowmeter (NI-LDF) for measurement of blood flow in the choroid. The custom made NI-LDF was compared with a commercial fiber optic based laser Doppler flowmeter (Perimed PF4000). Linearity and stability of the NI-LDF were assessed in a silastic tubing model (i.d. 0.3 mm) at different flow rates (range 0.4-3 ml/h). In a rabbit model continuous choroidal blood flow measurements were performed with both instruments simultaneously. During blood flow measurements ocular perfusion pressure was changed by manipulations of intraocular pressure via intravitreal saline infusions. The NI-LDF measurement correlated linearly to intraluminal flow rates in the perfused tubing model (r = 0.99, p < 0.05) and remained stable during a 1 h measurement at a constant flow rate. Rabbit choroidal blood flow measured by the PF4000 and the NI-LDF linearly correlated with each other over the entire measurement range (r = 0.99, y = x∗1.01-12.35 P.U., p < 0.001). In conclusion, the NI-LDF provides valid, semi quantitative measurements of capillary blood flow in comparison to an established LDF instrument and is suitable for measurements at the posterior pole of the eye.
Subject(s)
Choroid/blood supply , Laser-Doppler Flowmetry/instrumentation , Microscopy/instrumentation , Regional Blood Flow/physiology , Animals , Blood Flow Velocity/physiology , Female , Intraocular Pressure/physiology , Male , RabbitsABSTRACT
A thorough understanding of intraocular pressure homeostasis is the biological foundation for the development of new strategies to treat patients with elevated intraocular pressure or glaucoma. However, investigations on the physiology of intraocular pressure homeostasis are also important to gain more comprehensive insights into the pathogenesis of glaucoma and other diseases with associated alterations of intraocular pressure. The present review intends to give alternative insights into the biological and physical aspects of intraocular pressure regulation. The pressure-volume as well as the hydraulic model of intraocular pressure and also the relationship between ciliary blood flow and aqueous humor production, which has moved into the centre of interest because of its possible clinical relevance for glaucoma patients, will be explained. The authors Have attempted to interrelate the different aspects of intraocular pressure genesis and regulation in a comprehensive but understandable way.
Subject(s)
Aqueous Humor , Glaucoma/physiopathology , Intraocular Pressure , Models, Biological , HumansABSTRACT
BACKGROUND: The TEMPO study has shown that the combination of etanercept and methotrexat (MTX) in the treatment of rheumatoid arthritis (RA) is superior to monotherapy. It further suggested that remission of RA is a realistic treatment objective. A health-economic assessment of the combination needs to demonstrate the suitability of the combination for daily clinical practice taking economic aspects into consideration. PATIENTS AND METHODS: For the 686 patients in the TEMPO study, a re-analysis was carried out in the form of a Monte-Carlo-Markov-Chain simulation. Study types were cost-effectiveness analysis and cost-utility analysis. Comparators were combined etanercept and MTX vs. MTX alone; the perspective was that of society as a whole. RESULTS: The incremental cost-effectiveness ratio of the combination is
Subject(s)
Antirheumatic Agents/economics , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/economics , Drug Costs/statistics & numerical data , Immunoglobulin G/economics , Immunoglobulin G/therapeutic use , Methotrexate/economics , Methotrexate/therapeutic use , National Health Programs/economics , Receptors, Tumor Necrosis Factor/therapeutic use , Adult , Aged , Cost-Benefit Analysis/statistics & numerical data , Drug Therapy, Combination , Etanercept , Germany , Humans , Middle Aged , Monte Carlo Method , Outcome Assessment, Health Care , Quality-Adjusted Life Years , Randomized Controlled Trials as TopicSubject(s)
Bioelectric Energy Sources/trends , Conservation of Energy Resources/methods , Ecology/trends , Zea mays , Bioelectric Energy Sources/economics , Conservation of Energy Resources/economics , Crops, Agricultural/economics , Crops, Agricultural/metabolism , Ethanol/economics , Ethanol/metabolism , Fertilizers/adverse effects , Zea mays/economics , Zea mays/metabolismABSTRACT
The private and social costs of obesity have many causes, and their consequences can be grimly predicted with only rough accuracy. Among the most devastating is the increased incidence of diabetes, of which 60% can be directly attributed to weight gain. There are now about one billion people worldwide who are overweight or obese, compared with 850 million who are chronically underweight. It is estimated that the number of people worldwide with diabetes will increase from 175 million in 2000 to 353 million in 2030, with India and China together accounting for 24% of the total in 2050. Obesity and its economic costs are borne on three levels. At an individual level, obesity imposes costs by limiting personal opportunity in many ways, only some of which can be quantified. In the workplace (assuming the obese are employed, which they may not be, due in part to their condition), costs are borne by employers due to lost productivity, absences, underperformance, and higher insurance premia, which in the aggregate are quite large. Finally, obesity affects expenditures by local, state, and national governments, where programs compensate for or cover some of the private and workforce costs of illness and unemployment.
Subject(s)
Cost of Illness , Obesity/economics , Diabetes Mellitus/epidemiology , Global Health , Humans , Incidence , Medicaid , Medicare , Overweight , United States/epidemiologyABSTRACT
BACKGROUND: Satisfaction with care and quality of life (QoL) are indicative of the quality of care of cancer patients. The purpose of this study was to lay a cornerstone for patient-centred quality management by assessing the current status of satisfaction with care and QoL among oncological outpatients in Germany, and by identifying the key factors that determine a patient's willingness to recommend a medical facility. PATIENTS AND METHODS: A self-constructed and validated patient satisfaction questionnaire plus the SF-36 were distributed to a random sample of 3384 cancer patients who presented at 24 investigators' offices nationwide within a defined recruiting period and who met the inclusion criteria. The return rate was 81.9% (n=2772). A total of 2659 (78.6%) questionnaires were evaluable. The most common cancer types were breast (22.9%) and intestine (19.8%). RESULTS: Overall satisfaction was high, but specific reporting questions revealed many areas for improvement such as shared decision making, doctor-patient communication and organization of care. QoL was significantly impaired in many domains. Patient-provider relationship, facility setting and information on diagnosis and treatment options are major determinants of a patient's willingness to recommend a facility to a friend or relative if needed. CONCLUSIONS: This multicentre study focusing on patient perspectives highlights that, although the overall degree of satisfaction was quite high, there are numerous areas for improvement.
Subject(s)
Neoplasms/physiopathology , Neoplasms/psychology , Outpatients , Patient Satisfaction , Quality of Life , Adult , Aged , Aged, 80 and over , Female , Germany , Humans , Male , Middle Aged , Patient-Centered Care , Surveys and QuestionnairesABSTRACT
With costs of approximately 5.8 billion EUR annually, bipolar disorders represent a substantial burden on German society. The costs are mainly due to high indirect costs caused by morbidity-related unemployment, suicide-related losses of productivity, time off from work, and early retirement. Inpatient care, with a considerable average length of stay for patients with bipolar disorders, accounts for two-thirds of direct costs. This paper refers to statistics on use of healthcare services based primarily on the International Statistical Classification of Diseases, Tenth Revision. Representing a relatively narrow definition of bipolar disorders in comparison with the clinically relevant spectrum, this classification leads to a conservative estimate of the total costs. The significant lag between first acute episode and a correct diagnosis causes a delayed onset of maintenance treatment that leads to increased costs. Increasing public awareness, destigmatizing the disease, and educating physicians are necessary steps to limit the substantial economic burden for society.
Subject(s)
Bipolar Disorder/economics , Cost of Illness , Health Expenditures/statistics & numerical data , National Health Programs/economics , Social Security/economics , Absenteeism , Adult , Aged , Cost Control/trends , Drug Costs/statistics & numerical data , Fees, Medical/statistics & numerical data , Female , Forecasting , Germany , Humans , Male , Middle Aged , Patient Care Team/economics , Pensions/statistics & numerical data , Sensitivity and Specificity , Suicide/economics , Suicide/statistics & numerical data , Unemployment/statistics & numerical dataSubject(s)
Bone Substitutes/chemistry , Culture Techniques/methods , Durapatite/chemistry , Manufactured Materials , Materials Testing , Organophosphorus Compounds/chemistry , Polymers/chemistry , Tissue Engineering/methods , 3T3 Cells/physiology , 3T3 Cells/ultrastructure , Absorbable Implants , Animals , Biocompatible Materials/adverse effects , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Bone Substitutes/adverse effects , Bone Substitutes/chemical synthesis , Cell Adhesion/physiology , Cell Division/physiology , Cells, Cultured , Durapatite/chemical synthesis , Elasticity , Extracellular Matrix/physiology , Extracellular Matrix/ultrastructure , Mice , Organophosphorus Compounds/chemical synthesis , Polymers/chemical synthesis , Surface PropertiesABSTRACT
We report that mutation of COL11A2 causes deafness previously mapped to the DFNA13 locus on chromosome 6p. We found two families (one American and one Dutch) with autosomal dominant, non-syndromic hearing loss to have mutations in COL11A2 that are predicted to affect the triple-helix domain of the collagen protein. In both families, deafness is non-progressive and predominantly affects middle frequencies. Mice with a targeted disruption of Col11a2 also were shown to have hearing loss. Electron microscopy of the tectorial membrane of these mice revealed loss of organization of the collagen fibrils. Our findings revealed a unique ultrastructural malformation of inner-ear architecture associated with non-syndromic hearing loss, and suggest that tectorial membrane abnormalities may be one aetiology of sensorineural hearing loss primarily affecting the mid-frequencies.
Subject(s)
Collagen/genetics , Hearing Loss, Sensorineural/genetics , Mutation, Missense , Amino Acid Sequence , Animals , Base Sequence , Chromosomes, Human, Pair 6/genetics , DNA/genetics , Disease Models, Animal , Female , Genes, Dominant , Hearing Loss, Sensorineural/pathology , Hearing Loss, Sensorineural/physiopathology , Humans , In Situ Hybridization , Male , Mice , Mice, Knockout , Molecular Sequence Data , Pedigree , Polymorphism, Single-Stranded ConformationalABSTRACT
Previous studies have identified two discrete strategies for the control of posture in the sagittal plane based on EMG activations, body kinematics, and ground reaction forces. The ankle strategy was characterized by body sway resembling a single-segment-inverted pendulum and was elicited on flat support surfaces. In contrast, the hip strategy was characterized by body sway resembling a double-segment inverted pendulum divided at the hip and was elicited on short or compliant support surfaces. However, biomechanical optimization models have suggested that hip strategy should be observed in response to fast translations on a flat surface also, provided the feet are constrained to remain in contact with the floor and the knee is constrained to remain straight. The purpose of this study was to examine the experimental evidence for hip strategy in postural responses to backward translations of a flat support surface and to determine whether analyses of joint torques would provide evidence for two separate postural strategies. Normal subjects standing on a flat support surface were translated backward with a range of velocities from fast (55 cm/s) to slow (5 cm/s). EMG activations and joint kinematics showed pattern changes consistent with previous experimental descriptions of mixed hip and ankle strategy with increasing platform velocity. Joint torque analyses revealed the addition of a hip flexor torque to the ankle plantarflexor torque during fast translations. This finding indicates the addition of hip strategy to ankle strategy to produce a continuum of postural responses. Hip torque without accompanying ankle torque (pure hip strategy) was not observed. Although postural control strategies have previously been defined by how the body moves, we conclude that joint torques, which indicate how body movements are produced, are useful in defining postural control strategies. These results also illustrate how the biomechanics of the body can transform discrete control patterns into a continuum of postural corrections.
Subject(s)
Ankle Joint/physiology , Hip Joint/physiology , Knee Joint/physiology , Muscle, Skeletal/physiology , Posture/physiology , Adult , Biomechanical Phenomena , Electromyography , Female , Humans , MaleABSTRACT
Patients with bilateral vestibular loss have difficulty maintaining balance without stepping when standing in tandem, on compliant surfaces, across narrow beams, or on one foot, especially with eyes closed. Normal individuals (with no sensory impairment) maintain balance in these tasks by employing quick, active hip rotation (a "hip strategy"). The absence of a hip strategy in vestibular patients responding to translations of a short support surface has previously been taken as evidence that the use of hip strategy requires an intact vestibular system. However, many tasks requiring hip strategy alter one or a combination of important system characteristics, such as initial state of the body (tandem stance), dynamics (compliant surfaces), or biomechanical limits of stability (narrow beams). Therefore, the balance deficit in these tasks may result from a failure to account for these support surface alterations when planning and executing sensorimotor responses. In this study, we tested the hypothesis that vestibular information is critical to trigger a hip strategy even on an unaltered support surface, which imposes no changes on the system characteristics. We recorded the postural responses of vestibular patients and control subjects with eyes closed to rearward support surface translations of varying velocity, in erect stance on a firm, flat surface. Subjects were instructed to maintain balance without stepping, if possible. Faster translation velocities (25 cm/s or more) produced a consistent pattern of early hip torque (first 400 ms) in control subjects (i.e., a hip strategy). Most of the patients with bilateral vestibular loss responded to the same translation velocities with similar torques. Contrary to our hypothesis, we conclude that vestibular function is not necessary to trigger a hip strategy. We postulate, therefore, that the balance deficit previously observed in vestibular patients during postural tasks that elicit a hip strategy may have been due to the sensorimotor consequences of the system alterations imposed by the postural tasks used in those studies. Preliminary results from two younger patients who lost vestibular function as infants indicate that age, duration of vestibular loss, and/or the timing of the loss may also be factors that can influence the use of hip strategy as a rapid postural response.