Abstract Collagens IX and XI are quantitatively minor components of the collagen fibrils in cartilage. The spectrum of the phenotypes caused by mutations in the COL2A1 gene coding for collagen II, the main cartilage collagen, is relatively well defined, but there is little data on the phenotypes caused by collagen IX and XI mutations. The structure of the human COL11A1 gene coding for the 1 chain of collagen XI was characterized here. It was found to consist of 68 exons and span 160 kb, excluding introns 1 and 4. Over 50 kb of new intronic sequences were defined. The exon-intron organization coding for the major triple helical domain was found to be identical to that of the human COL11A2 gene, which codes for the 2 chain of collagen XI. The sensitivity of conformation sensitive gel electrophoresis (CSGE) for mutation detection was improved and tested with a large number of sequence variations in collagen genes. The sensitivity with the revised conditions was found to be close to 100%. In addition, CSGE was found to be a simple and practical method for analyzing large numbers of samples. Fifteen mutations in the COL11A1 gene and eight in the COL2A1 gene were found by CSGE in patients with Marshall or Stickler syndrome. The genotypic-phenotypic comparison indicated that mutations leading to a premature translation termination codon in the COL2A1 gene resulted in Stickler syndrome and splicing mutations of 54 bp exons in the C terminal half of the COL11A1 gene resulted in Marshall syndrome. The other COL11A1 mutations caused phenotypes overlapping both syndromes. In an analysis of the COL9A2 gene in 157 patients with intervertebral disc disease, six were found to have a tryptophan for glutamine substitution in the central collagenous domain of the collagen IX molecule. None of 174 control individuals had this substitution. The substitution cosegregated with the phenotype in the families studied, and linkage and linkage disequilibrium analyses supported the association of the locus and the disease with a joint lod score of over 11.

Abstract Sciatica is a common musculoskeletal disorder, especially among the working-age population. It causes huge costs to society through work absenteeism and hospital treatments. The common cause of sciatica is the herniated lumbar disc compressing the nerve root. The neurological deficit resulting from this compression can be either sensory or motor-related. Earlier studies have shown both genetic and environmental factors to exist in the aetiology of sciatica. The aim of this study was to investigate how individual, physical and work-related risk factors associate with sciatica, and to determine the prevalence of sciatic pain among Finnish adolescents. The data used in this study were from large, population-based Finnish surveys: the Northern-Finland Birth Cohort 1986, the Mobile Clinic Health Examination Survey, the Mini-Finland Health Survey, Health 2000, the Young Finns Study, and the Helsinki Health Studies. The results of this study showed that sciatic symptoms are already common among adolescents. Young women in particular reported sciatic pain more often than men. Low back pain at the age of 16 predicted sciatic pain at the age of 18. Physically demanding work, smoking and obesity were found to predict an increased risk of hospitalization for sciatica. In the Mobile Clinic Health Examination Survey, leisure-time physical activity protected men from hospitalization for sciatica, whereas among women obesity increased this risk. Occupation also modified the effects of various risk factors. In the Mini-Finland Health Survey, overweight and obese participants who had been exposed to whole body vibration in their work were at a higher risk of hospitalization due to sciatica. In addition, lifting and carrying heavy objects at work, or sedentary work involving the handling of heavy objects predicted an increased risk of hospitalization for sciatica. Heavy or very heavy work protected against hospitalization for sciatica. A meta-analysis of four prospective cohort studies showed that walking and cycling to work reduced the risk of hospitalization for sciatica. This thesis extends our knowledge regarding the risk factors for sciatica. Its results show that these risk factors are complex and can modify each other’s effects. Thus, further research on the interactions of the various risk factors is needed. / Tiivistelmä Iskias on etenkin työikäisten keskuudessa yleinen sairaus, joka aiheuttaa paljon työkyvyttömyyttä ja sairaalahoitoja ja siten kustannuksia yhteiskunnalle. Iskiaksen taustalla on yleensä välilevyn pullistuma, joka painaa hermojuuria. Hermojuuren puristuksesta aiheutuva neurologinen puutosoire voi olla joko sensorinen tai motorinen. Aiemmat tutkimukset ovat osoittaneet iskiaksen taustalla olevan sekä geneettisiä että ympäristötekijöitä. Tämän tutkimuksen tavoitteena oli selvittää yksilöllisten, fyysisten ja työhön liittyvien riskitekijöiden yhteyttä iskiakseen sekä tutkia iskiaskivun yleisyyttä suomalaisilla nuorilla aikuisilla. Aineistoina tutkimuksessa käytettiin laajoja väestöpohjaisia suomalaisia aineistoja: Pohjois-Suomen syntymäkohorttia 1986, Autoklinikka- ja Mini-Suomi-aineistoja sekä Terveys 2000-, Young Finns- ja Helsinki Health Study -tutkimuksia. Tutkimuksessa selvisi, että iskiasoireet ovat yleisiä jo nuorilla aikuisilla ja etenkin naiset raportoivat iskiaskipua useammin miehiin verrattuna. 16-vuotiaana ilmennyt alaselkäkipu oli myös yhteydessä iskiasoireisiin 18 vuoden iässä. Työn fyysisen rasittavuuden, tupakoinnin ja lihavuuden todettiin lisäävän sairaalahoitoon johtaneen iskiaksen riskiä. Autoklinikka-aineistossa vapaa-ajan fyysinen aktiivisuus suojasi miehiä sairaalahoitoon johtaneelta iskiakselta, naisilla taas ylipaino lisäsi iskiaksen riskiä. Lisäksi ammatti näytti muokkaavan riskitekijöiden assosiaatioita. Mini-Suomi-aineistossa ylipainoiset ja lihavat henkilöt, jotka olivat altistuneet työssään koko kehon tärinälle, olivat korkeammassa riskissä sairaalahoitoon johtaneen iskiaksen suhteen. Töissä raskaiden esineiden nostaminen tai kantaminen tai painavien esineiden käsittelyä sisältävä istumatyö lisäsivät myös iskiaksen riskiä. Raskas tai erittäin raskas fyysinen työ taas näytti suojaavan sairaalahoitoon johtaneelta iskiakselta. Neljän prospektiivisen kohorttitutkimuksen meta-analyysissä selvisi, että työmatkapyöräily tai -kävely vähensivät sairaalahoitoon johtaneen iskiaksen riskiä. Tämä väitöstutkimus kasvattaa ymmärtämystä iskiaksen taustalla olevista riskitekijöistä. Tulokset osoittavat, että iskiaksen riskitekijät ovat moniulotteisia ja voivat muokata toistensa vaikutuksia, joten lisätutkimusta eri riskitekijöiden välisistä interaktioista tarvitaan.

ABSTRACT Background: Most cases of lumbar disc herniation are asymptomatic. When symptomatic, LDH may cause a significant physical and mental distress. Initially, most patients are treated conservative but sometimes operations may be required. Aim: The aim of this study was to provide a review of the scientific basis of physiotherapy, including behavioural therapy, as a treatment to lumbar disc herniation regarding pain, function and the size of disc herniation in people suffering from lumbar disc herniation. Method: Four databases were used in the searches of literature. Assessment of the validity of the studies was done with the PEDro-scale and valuation of evidence rate was made according to guidelines made by the Swedish Council on Health Technology Assessment (SBU). Result: Nine RCT-studies were included with a total of 713 participants. The scientific basis is moderate to support a pain reduction and limited regarding improvement of physical function when it comes to physical exercises, including MDT. There is also a limited scientific basis supporting a reduction of pain from manipulation. Laser, on the other hand, showed a limited scientific basis to have no effect on pain. Traction and acupuncture had an insufficient scientific basis. Overall there were an insufficient scientific basis on the size of disc herniation.There was no study found examining the efficacy on behavioural therapy. Conclusion: The scientific basis is moderate to support a pain reduction when it comes to physical exercises, including MDT. There were few studies of high evidential rate and the scientific basis is difficult to determine due to heterogeneous studies. Additional science is required to determine which physiotherapy methods are the most effective for patients with lumbar disc herniation. / SAMMANFATTNING Bakgrund: Många gånger ger ett diskbråck inga besvär men symtomgivande diskbråck kan vara väldigt fysiskt och psykiskt påfrestande för patienten. Initialt behandlas de flesta konservativt. Syfte: Syftet med denna litteraturöversikt är att granska det vetenskapliga underlaget för olika sjukgymnastiska behandlingars effektivitet, inkluderande beteendemedicinska åtgärder, på smärta, funktion och diskbråcksstorlek vid ländryggsdiskbråck. Metod: Fyra databaser användes för litteratursökningar. Bedömning av studiernas validitet gjordes med PEDro-skalan och bevisvärdet bedömdes enligt riktlinjer från SBU. Resultat: Nio RCT-studier inkluderades med totalt 713 deltagare. Det vetenskapliga underlaget (VU) för att träning/ MDT, är effektivt gällande smärtreduktion visade sig vara måttligt, och begränsat gällande funktionsförbättring. Även manipulation hade begränsat VU, då det gäller smärtreduktion. Laser visade sig ha ett begränsat VU för att inte ha någon effekt på smärta. Traktion och akupunktur visade sig ha ett otillräckligt VU. Övergående fanns det ett otillräckligt VU gällande effekten på diskbråcksstorlek. Ingen studie identifierades med beteendemedicinska åtgärder vid ländryggsdiskbråck. Slutsats: Det VU visade sig måttligt för att träning/MDT är effektivt gällande smärtreduktion. Antalet studier av hög kvalitet är begränsat och VU är svårvärderat då studierna är heterogena. Ytterligare forskning behövs för att kunna avgöra vilka behandlingsmetoder som är effektiva vid ländryggsdiskbråck.

Abstract The purpose of the current study was to evaluate the intercorrelations of magnetic resonance imaging (MRI) findings and clinical symptoms and signs in sciatic patients. Furthermore, determinants of spontaneous HNP resorption and the effect of anti-inflammatory treatments (periradicular methylprednisolone injection and intravenous infliximab) on spontaneous HNP resorption were evaluated. MRI follow-up was performed at baseline, after two months, after six months and after one-year for patients with unilateral sciatica to evaluate determinants of spontaneous HNP resorption and the effect of periradicular methylprednisolone injection on spontaneous HNP resorption. At baseline the study population consisted of 160 patients (group A). MRI follow-up for 21 patients with unilateral sciatica was performed at baseline and after two weeks, after three months and after six months to evaluate the effect of infliximab, a monoclonal TNFα antagonist, infusion on spontaneous HNP resorption (group B). Patients in group A were randomized to receive either periradicular saline or methylprednisolone. Volume of HNP, extent and thickness of enhancement (in Gd-DTPA MRI) and degree of disc displacement were measured and the symptoms and signs were followed repeatedly. The extent of rim enhancement correlated significantly with the degree of disc displacement. The duration of sciatic symptoms correlated negatively with enhancement parameters. The clinical symptoms did not correlate significantly with the different enhancement parameters or disc herniation volume. Achilles reflex abnormality correlated significantly with all enhancement parameters for lesions at L5-S1. Significant decrease in HNP volume occurred from baseline to two moths, and even more so during the whole one year follow-up period. Higher baseline scores of rim enhancement thickness, higher degree of HNP displacement in the Komori classification and age category of 41–50 years were associated with a higher resorption rate. Clinical symptoms alleviation occurred concordantly with a faster resorption rate. No significant difference was noted in the decrease of HNP volume in the saline and methylprednisolone injection groups in follow-up imaging during one year. The enhancement parameters (thickness and extent of rim enhancement) did not differ significantly in the different treatment groups. In group B, 11 patients received intravenous infliximab and 10 saline. Baseline demographic data, pain scores, and clinical status, did not differ between the treatment groups. HNP volume decreased significantly in both groups (P < 0.01). There was no significant difference in HNP volume changes between the treatment groups. By two weeks, enhancement thickness increased significantly in the infliximab compared placebo group (p=0.003). Two patients in each group required back surgery prior to the 6-month assessment.

Propósito: Analizar si la adición de un espaciador interespinoso o la fusión intersomática ofrece ventajas en relación con la microdiscetomía aislada en el tratamiento de la hernia discal lumbar. Métodos: Pacientes con hernia de disco lumbar que iban a someterse a cirugía fueron elegidos para participar. En este estudio de cohorte los pacientes se dividieron en 3 grupos; Microdiscectomía sola (MD), microdiscectomía más espaciador interespinoso (IS) y fusión intersomática lumbar posterior (PLIF). La medida de resultado primaria fue la eficacia clínica mediante el índice de discapacidad de Oswestry (ODI). También evaluamos varios otros parámetros de resultado, entre los que se incluyeron: escala analógica visual para el dolor (EVA) de espalda y piernas, duración de la estancia, coste desde el ingreso hasta el alta hospitalaria, tasa de complicaciones de 90 días y tasa de reoperación tras 1 año. Resultados: Se incluyeron un total de 103 pacientes cuya edad media fue de 39,1 (± 8,5) años. En los 3 grupos se detectó una mejora significativa de la puntuación inicial del dolor de espalda y piernas con ODI y EVA. Las puntuaciones del ODI cambiaron de 62.66 a 13.77 en el grupo MD, 62.93 a 13.50 en el grupo IS, y 59.62 a 17.62 en el grupo PLIF (p <0.001). Después de 1 año, no se encontraron diferencias significativas en el ODI, ni en la EVA de espalda y piernas entre los 3 grupos. Hubo un aumento del 169% en el coste hospitalario en el grupo IS y del 287% en el grupo PLIF, en relación con la MD (p <0,001). La duración de la estancia fue un 86% mayor en el grupo IS y un 384% más en el grupo PLIF en comparación con MD (p <0,001). Las tasas de reoperación a 1 año fueron de 5,6%, 10% y 16,2% (p = 0,33) en los grupos MD, IS y PLIF respectivamente. Conclusión: La mejoría clínica parece deberse a la microdiscectomía, sin que el implante (interespinoso o fusión) agregue ningún beneficio. La adición de espaciador interespinoso o fusión no protegió contra la reoperación, y aumentó la duración de la estancia hospitalaria y los gastos quirúrgicos.

The second most common lumbosacral diagnosis in the United States is a herniation or prolapse of the intervertebral disc. Individuals with herniated discs can have a wide variety of clinical presentations, ranging from asymptomatic to severe spinal cord compression and pain. Studies suggest that an individual’s pre-existing perception of a condition is likely to influence their course of recovery. Currently, perceptions the general public holds regarding the consequences of disc herniation is unknown. Therefore, the purpose of this study was to assess current views regarding disc herniations in the general population with their reported prevalence and clinical outcome. This was determined via an electronic Qualtrics survey. This survey included demographic questions, medical history questions, disk herniation perception questions, and coping/resilience questions. Upon conclusion of survey administration, data analysis was performed via JASP. A key finding of this study was that resilience levels play a major role in participant’s views on herniated intervertebral discs (p=0.040). Participants with greater resilience levels had views on disc herniations that were more consistent with the findings in the literature (p=0.018). This may implicate low resilience levels in negative catastrophizing, which can impair the recovery process for patients. Due to this, healthcare providers should further consider a patient’s mental characteristics such as resilience and coping style when administering treatment. By further educating patients on their specific prognosis for a disc herniation, providers may be able to improve their overall perception of herniated discs, leading to a possible improvement in outcome.

Abstract The purpose of this study was to evaluate the role of diminished arterial blood flow in painful disc degeneration. Diffusion in intervertebral discs of 37 asymptomatic adults measured by magnetic resonance imaging (MRI) and their lumbar arterial blood supply measured by magnetic resonance angiography (MRA) correlated significantly. End plate degeneration in intervertebral discs evaluated with MRI was analysed with reference to disc distress evaluated with computed tomography (CT) discography, and a significant correlation between end plate degeneration and disc degeneration was found among 36 low back pain patients. Intradiscal pain caused by discography did not correlate with end plate degeneration. There were significantly more atheromatous plaques in the abdominal aorta among 29 chronic low back pain patients compared to 52 asymptomatic people, especially in the age group under 50 years. Occlusion of lumbar arteries in MRA correlated significantly with disc degeneration in MRI among 113 sciatica patients. Furthermore, the disc degeneration and the occlusion of lumbar arteries were severe among 41 sciatica patients and 41 asymptomatic people. During a three-year follow-up, the occlusion of lumbar arteries in MRA correlated significantly with physical and mental ability measured by a self-efficacy questionnaire at every assessment point (1,2,3 years). Furthermore, the intensity of back pain at 1 year and leg pain at 2 years correlated with the occlusion of lumbar arteries. Re-stenosis of lumbar arteries within 3 years correlated significantly with medical consultations for low back pain, prolonged low back pain and prolonged sciatica during one year before the baseline assessment.

Abstract Low back pain (LBP) is the leading cause of years lived with disabilities worldwide. Intervertebral disc (IVD) degeneration is a strong contributing factor to LBP. Recent studies have shown that genetic determinants contribute markedly to IVD degeneration but knowledge about the actual genes involved as well as their roles is still limited. The aim of this thesis work was to study genetic factors that may predispose to IVD degeneration. Using both family and case-control association study designs, variants in five genes showed association with IVD degeneration on magnetic resonance imaging (MRI) in a population-based sample and among patients with sciatica due to lumbar disc herniation (LDH). We performed a candidate gene association study of the known variants implicated in IVD degeneration in a Finnish cohort of 538 young individuals with a moderate degree of lumbar IVD degeneration on MRI. We were able to confirm the associations of variants in the IL6, SKT, and CILP genes, which provides further evidence for true associations. Based on our earlier linkage study in Finnish sciatica families, we performed a candidate gene analysis and identified IL17F as a potential candidate gene. To the best of our knowledge this is the first study to observe an association between this gene and discogenic sciatica. Both IL-6 and IL-17 are pro-inflammatory cytokines with elevated expression levels in herniated tissues, which suggest a role in IVD degeneration. Study of the role of genes coding for inflammatory mediators is of interest as it may contribute to the understanding of the overall inflammatory response of the disc. In addition, we reported on the involvement of SKT in the etiology of lumbar disc herniation (LDH) both in Japanese and Finnish case-control samples. Experimental studies in mice have shown that Skt homozygous mutants exhibit disc abnormalities resulting in a kinky tale phenotype. We hypothesized that the human homolog SKT could have long-term importance in the onset of IVD degeneration by making the discs more vulnerable. Finally, through linkage studies and in the subsequent association analyses, the role of CHST3 as a novel risk factor for IVD degeneration was identified. CHST3 encodes an enzyme that catalyzes the sulfation of chondroitin, and mutations in this gene are associated with spondylepiphyseal dysplasia and humerospinal dysostosis. In our study, we identified this gene using genome –wide linkage based on data from a Southern Chinese family and speculated that mild CHST3 reduction caused by the reported susceptibility SNP could result in disc degeneration in adults in conjunction with other risk factors. This thesis provides new information about the genetic background of IVD degeneration and new insights into the etiology of the disease. The specific roles of these genes in the IVD function and pathogenesis of sciatica are not clear however, and need to be elucidated. / Tiivistelmä Alaselkäkipu on yksi yleisimmistä sairauksista ja johtava syy työkyvyttömyyteen. Välilevyrappeuma myötävaikuttaa merkittävästi alaselän kipuun. Vaikka aiemmat tutkimukset ovat osoittaneet, että perintötekijöillä on vahva osuus välilevyrappeumaan, altistavat geenit ja niiden rooli tunnetaan huonosti. Tämän tutkimuksen tavoitteena oli arvioida tiettyjen perintötekijöiden osuutta välilevyrappeumassa ja tunnistaa taudille altistava geeni perheaineistossa aiemmin havaitulta kromosomialueelta. Aineistoina tutkimuksessa olivat perheaineistot sekä laajat potilas-kontrolliaineistot suomalaisesta ja aasialaisista väestöistä. Tutkimuksessa osoitimme, että perimän vaihtelut viidessä tutkitussa geenissä altistivat erilaisille välilevyrappeuman taudin muodoille. Tutkimus, jossa analysoimme aiemmin tunnistettuja alttiusgeenejä, vahvisti IL6, SKT ja CILP geenien vaihteluiden osuuden taudin alttiustekijöinä. Tutkimusaineistona oli pohjoissuomalainen syntymäkohortti, jossa välilevyrappeuma oli määritetty magneettikuvauksella (MRI). Suomalaisessa perheaineistossa tehdyn kokogenomin laajuisen kartoituksen pohjalta analysoimme IL17F geenin mahdollisena uutena alttiusgeeninä oireiselle välilevytaudille. Kahdesta geenin variantista koostuva haplotyyppi assosioitui tautiin merkitsevästi. Lisäksi osoitimme, että SKT-geenin tietty muutos altistaa välilevyn pullistumille sekä japanilaisessa että suomalaisessa potilasaineistossa. Hiirikokeissa on havainnoitu, että SKT-geenin homotsygootti mutaatio johtaa välilevy-poikkeamaan, joka edelleen aiheuttaa hiiren poikkeavan häntäilmiasun-. Hypoteesimme oli, että ihmisen SKT -geeni voi myötävaikuttaa välilevypullistuman kehittymiseen altistamalla välilevyt rappeumalle. Edelleen, laajassa usean populaation aineiston käsittävässä tutkimuksessa osoitimme CHST3-geenin muutoksen altistavan välilevyrappeumalle. Peittyvästi periytyvät muutokset tässä geenissä aiheuttavat perinnöllisiä harvinaisia luusairauksia. Tämä väitöstutkimus tarjoaa uutta tietoa välilevyrappeuman geneettisestä taustasta ja auttaa taudin syiden tutkintaa. Geenien rooli välilevyn toiminnassa ja muutosten vaikutus taudin kulkuun vaativat kuitenkin vielä lisätutkimuksia.

The sciatic nerve is the largest nerve in the human body giving both motor and sensory innervations to the lower limb. It can be affected in chronic diseases, such as diabetes, or compressed anatomically by structures such as piriformis and aneurysms leading to sciatica or paralysis of the lower limb. The current study therefore focuses on the arterial supply of the sciatic nerve as well as its course. Embryologically, the sciatic nerve is supplied via the axial artery during the first trimester. As the axial artery regresses, the iliac system develops. A failure of sciatic artery regression leads to several variations of pelvic and femoral arteries, with a risk of iatrogenic injury/trauma for those patients undergoing pelvic, gluteal and thigh surgical procedures. An understanding of the variability of the pelvic arteries in relation to a coexistent sciatic artery will provide an appropriate background for clinicians. The present study proposes a new theory of sciatic artery development and persistence, as well as new theories for the superior and inferior gluteal, internal pudendal and obturator arteries. The thesis is in two parts: first an anatomical study on the dissection of 171 cadavers including the pelvic, gluteal and thigh regions to observe (i) the patterns of the arteries these regions, and (ii) the course of the sciatic nerve. With variable course of sciatic nerve, there is a variability of its blood supply. Moreover, it includes a new classification of sciatic nerve with respect to clinical implications. The thesis clarifies the origins of the sciatic artery and its course. The second part is a literature review of sciatic artery aneurysm cases in 171 patients, which clarifies the risk of aneurysm, together with its incidence with respect to pathologic finding and associated disorders. Radiologists have to be aware of the internal iliac artery classifications to be able to alert general surgeons, orthopaedic surgeons, obstetricians, gynecologists, and urologists so that they can improve patient management.

During recent decades, lumbar spinal stenosis (LSS) has become the most common indication for spine surgery, a change that coincides with a higher worldwide prevalence of overweight and obesity. Thus, surgical treatment of LSS in the overweight and obese population is common and increasing in scope. The overall aim of this thesis was to investigate whether body mass index (BMI) is related to the development of LSS, and whether BMI is linked to outcome after surgery for LSS. We further evaluated whether there are specific experiences of LSS from a patient perspective. Data were obtained for all patients registered in the Swedish Spine Register who had undergone surgery for LSS between January 1, 2006 and June 30, 2008. After adjusting for differences in baseline characteristics, patients with obesity showed both poorer results after surgery and a higher rate of dissatisfaction than patients with normal weight (odds ratio 1.73; 95% confidence interval, CI, 1.36-2.19). Furthermore, patients with obesity in the cohort reported modest weight loss at follow-up (2.0 kg; 95% CI, 1.5-2.4), and only 8% reported a clinical important weight loss 2 years after surgery. Our analysis of 389,132 construction workers, showed that overweight (incidence rate ratio, IRR 1.68; 95% CI, 1.54-1.83) and obesity (IRR 2.18; 95% CI, 1.87-2.53) were associated with an increased future risk in developing LSS when compared with patients with normal weight. To gain insight into the patients' perspective of LSS, we performed interviews with 18 patients who were on a waiting list for LSS surgery. The transcripts, analyzed with content analysis, revealed that living with LSS is a physical, mental and social challenge in which resources to cope with the condition are of major importance. In summary, obesity is associated with poorer results after surgery, and patients with obesity report modest weight loss during follow-up. In addition, obesity is associated with an increased risk to develop LSS. Our findings revealed that being a patient with LSS, naturally involves considerable suffering and pain, but it also implies being a person with his or her own resources who is able to cope with these adverse conditions.