Social determinants of health for moderate and severe periodontal disease in rural and urban populations.

OBJECTIVE: We assessed the prevalence of moderate and severe periodontitis and its association with social determinants of health in rural and urban population from the State of Chiapas, in Southern Mexico. MATERIAL AND METHODS: A cross-sectional population-based study was conducted in 2013 comprising people 20 years and older. The determinants were categorized as proximal (age, sex, indigenous origin, diabetes, smoking, diet), intermediate (level of schooling, occupation, medical and dental care), and structural (type of institution of health care provision, residence area). Periodontal status was assessed using the Periodontal Screening and Recording (PSR) Index. RESULTS: In total, 467 persons (72.4% women; mean age 43.0 years [s.d 14.7]) participated. Of them, 76.5% lived in rural areas and 56.7% were of indigenous origin. Participants with moderate and severe periodontitis had a significantly lower toothbrushing frequency (44.1% and 44.8%, respectively), and poorer oral hygiene (90% and 90.3%, respectively) compared with people without periodontitis (29.4% for toothbrushing frequency and 74.5% for oral hygiene). Moderate periodontitis was associated with poor oral hygiene (OR=2.63) and no schooling (OR=1.86). Severe periodontitis was associated with age (OR=1.05), poor oral hygiene (OR=3.99), no schooling (OR=2.08), and the interaction term of rural area and indigenous origin (RM=5.23). CONCLUSIONS: Social determinants of health play an important role in the development of periodontitis. Preventive oral health programs should thus focus on the specific social, economic, and geographical context of the population.

Lipoatrophia semicircularis: Clinical study and follow-up of 76 cases in Madrid, Spain. Classification proposal. / Lipoatrofia semicircular: estudio y seguimiento clínico de 76 casos en Madrid, España. Propuesta de clasificación.

INTRODUCTION: The clinical presentations of Lipoatrophia semicircularis (LS) vary, and diagnostic criteria are unclear. Several etiopathogenic factors, including occupational environmental ones, have been suggested. We aimed to describe a cluster of cases of suspected LS that started to appear in May 2008 among employees of the city council of Madrid, Spain. We report the actions taken by the council's Occupational Health Service and propose clinical categories with prognostic implications. MATERIAL AND METHOD: Retrospective observational case series study including prospectively collected data from patients evaluated between 2008 and 2021 at the Madrid City Council STI/Dermatology Department. Information on measures taken by the Occupational Health Service is detailed. The recording of clinical variables for statistical analysis and the proposal of defined clinical patterns were carried out. RESULTS: We studied the cases of 75 women and one man, most of whom attended follow-up visits for a median of 37 months. Local symptoms were observed in just 14.5% of patients. The cases were classified into 4 groups: typical LS, unilateral LS, band-like lipoatrophy in the lower limbs, and nonspecific LS. Clinical outcomes were more often favorable in the first 2 groups, in which 76% of patients achieved total or partial improvement of lesions (vs. 25.8% in the last 2 groups). LS was negatively associated with the presence of hypertrophic subcutaneous adipose tissue (P<.001). DISCUSSION: Typical LS, which can often be unilateral, generally has a satisfactory outcome. The clinical characteristics of this form distinguish it from other types of lipoatrophy. Measures taken by the Occupational Health Service contributed to favorable outcomes. In this series, LS was not associated with marked subcutaneous adipose tissue hypertrophy in the thighs. Our proposed categories may help distinguish between cases of LS with a favorable prognosis and other cases presenting with skin surface depressions, which are often persistent.

Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental.

BACKGROUND: Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. METHOD: Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. RESULTS: The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. CONCLUSION: The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.

Clinical guidelines for the management of depression with specific comorbid psychiatric conditions French recommendations from experts (the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental).

BACKGROUND: Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. METHOD: The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. RESULTS: The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. CONCLUSION: These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.

[French Society for Biological Psychiatry and Neuropsychopharmacology and Fondation FondaMental task force: Formal Consensus for the management of treatment-resistant depression]. / Prise en charge des troubles dépressifs résistants : recommandations françaises formalisées par des experts de l'AFPBN et de la fondation FondaMental.

Major depression represents among the most frequent psychiatric disorders in the general population with an estimated lifetime prevalence of 16-17%. It is characterized by high levels of comorbidities with other psychiatric conditions or somatic diseases as well as a recurrent or chronic course in 50 to 80% of the cases leading to negative repercussions on the daily functioning, with an impaired quality of life, and to severe direct/indirect costs. Large cohort studies have supported that failure of a first-line antidepressant treatment is observed in more than 60% of patients. In this case, several treatment strategies have been proposed by classical evidence-based guidelines from internationally recognized scientific societies, referring primarily on: I) the switch to another antidepressant of the same or different class; II) the combination with another antidepressant of complementary pharmacological profile; III) the addition of a wide range of pharmacological agents intending to potentiate the therapeutic effects of the ongoing antidepressant medication; IV) the association with appropriate psychological therapies; and, V) the use of non-invasive brain stimulation techniques. However, although based on the most recently available data and rigorous methodology, standard guidelines have the significant disadvantage of not covering a large variety of clinical conditions, while currently observed in everyday clinical practice. From these considerations, formalized recommendations by a large panel of French experts in the management of depressed patients have been developed under the shared sponsorship of the French Association of Biological Psychiatry and Neuropsychopharmacology (AFPBN) and the Fondation FondaMental. These French recommendations are presented in this special issue in order to provide relevant information about the treatment choices to make, depending particularly on the clinical response to previous treatment lines or the complexity of clinical situations (clinical features, specific populations, psychiatric comorbidities, etc.). Thus, the present approach will be especially helpful for the clinicians enabling to substantially facilitate and guide their clinical decision when confronted to difficult-to-treat forms of major depression in the daily clinical practice. This will be expected to significantly improve the poor prognosis of the treatment-resistant depression thereby lowering the clinical, functional and costly impact owing directly to the disease.

Are hip hemiarthroplasty and total hip arthroplasty infections different entities? The importance of hip fractures.

Hip hemiarthroplasty (HHA) and total hip arthroplasty (THA) infections are usually considered as one entity; however, they may show important differences. We analyze these differences, as well as predictors of treatment failure (TF) and poor functional status among patients with prosthetic hip infections (PHIs). A multicenter cohort study of consecutive patients with PHIs was performed. The main outcome variable was TF after the first surgical treatment performed to treat the infection. Multivariate analysis was used to identify predictors of TF. A total of 127 patients with PHI were included (43 HHA, 84 THA). Patients with HHA infections were more frequently women (88% vs. 54%; p < 0.001), had comorbidities (86% vs. 67%, p = 0.02), and were older (median age 79 vs. 65 years, p < 0.001), and the reason for arthroplasty was more frequently a fracture (100% vs. 18%, p < 0.001). Failure of initial treatment and crude mortality were more frequent among HHA patients (44% vs. 23%, p = 0.01 and 28% vs. 7%, p = 0.001, respectively). However, HHA was not associated with TF in the multivariate analysis when hip fracture was considered; thus, variables independently associated with TF were hip fracture, inadequate surgical management, prosthesis retention, and higher C-reactive protein level. Failure of the first surgical treatment was associated with poorer functional status. HHA and THA infections showed significant differences in epidemiology, clinical features, and outcome. Although patients with HHA infections had a higher risk of TF, this was related to the reason for hip implant: a hip fracture. Success of the initial management of infection is a predictor of better clinical and functional outcome.

Social value framing of physical activity in European Member State policies: a content analysis.

Background: Engagement in physical activity (PA) benefits physical and mental health as well as many other areas of society. In Europe however, 1/3 adults do not meet minimum PA recommendations. Social value, and its quantification through social return on investment (SROI) evidence, may be a useful framing to enhance PA promotion. This study aimed to assess the current use of social value framing of PA in European Union (EU) policies. Methods: Content analysis of 45 EU member state policies which contain reference to PA was conducted to evaluate the presence of five social value domains and SROI evidence. Data was analysed using manual inductive coding, supported by DeepL translation and NVivo tools. Results: Social value framing was present to a certain extent in existing policies, with improved health being the most commonly referenced benefit of PA, followed by reference to social and community and then environmental benefits. Acknowledgement of the positive impacts of PA on wellbeing and education was the least present. Reference to SROI evidence was also limited. Generally, policies lacked holistic recognition of the social value of PA. Policies from the health sector were particularly limited in recognising the wider benefits of PA, whilst those from the environmental sector acknowledged the widest range of co-benefits. Conclusion: Adopting social value framing could be a useful approach for enhancing PA promotion. Whilst it is present to a certain extent in existing policy, this could be increased in terms of comprehensiveness to increase issue salience and multisectoral policy action.

Consensus on a social return on investment model of physical activity and sport: a Delphi study protocol.

Background: Physical activity and sport (PAS) have been related to many health outcomes and social benefits. The main aim of this research is to build a Social Return on Investment (SROI) model of PAS based on experts' opinion to clarify the domains of impact and how to measure and value them. Methods and analysis: A Delphi method will be employed with a systematic review on the SROI framework applied to PAS and initial interviews with experts informing the design of the Delphi survey statements. Three iterative rounds of communication with the expert panel will be carried out. Participants will indicate their level of agreement with each statement on a five-point Likert scale. During the second and third iterative rounds, experts will reappraise the statements and will be provided with a summary of the group responses from the panel. A statement will have reached consensus if ≥70% of the panel agree/strongly agree or disagree/strongly disagree after round 3. Finally, group meetings (3-4 experts) will be conducted to ask about the measurement and valuation methods for each domain. Discussion: The final goal of this project will result in the design of a toolkit for organizations, professionals, and policymakers on how to measure the social benefits of PAS.

[Translated article] Pericapsular nerves block (PENG) is an effective and safe alternative for postoperative pain management after primary total hip arthroplasty: A randomised clinical trial.

BACKGROUND: Postoperative pain after total hip arthroplasty can affect postoperative rehabilitation and delay hospital discharge. The objective of this study is to compare pericapsular nerves group (PENG) block with pericapsular infiltration (PAI) and plexus nerve block (PNB) for postoperative pain management, response to physical therapy, opioid consumption, and length of hospital stay after a primary total hip arthroplasty. METHODS: Randomised clinical trial of parallel and blinded groups was performed. Sixty patients who underwent elective THA between December 2018 and July 2020 were randomised into the different groups (PENG, PAI and PNB). The visual analogue scale was used to assess pain; and motor function was measured with the Bromage scale. We also record opioid usage, length of hospital stay, and related medical complications. RESULTS: Pain level at discharge was similar in all groups. Hospital stay was 1 day shorter in the PENG group (p<0.001) and they also had lower opioid consumption (p=0.044). Optimal motor recovery was similar in the groups (p=0.678). Pain control when performing physical therapy was better in the PENG group (p<0.0001). CONCLUSIONS: PENG block is an effective and safe alternative for patients undergoing THA as it reduces opioid consumption and hospital stay compared to other analgesic methods.

Pericapsular nerves block (PENG) is an effective and safe alternative for postoperative pain management after primary total hip arthroplasty: A randomized clinical trial. / El bloqueo de nervios pericapsulares (PENG) es una alternativa efectiva y segura para el manejo del dolor postoperatorio después de una artroplastia total de cadera primaria: ensayo clínico aleatorizado.

BACKGROUND: Postoperative pain after total hip arthroplasty can affect postoperative rehabilitation and delay hospital discharge. The objective of this study is to compare pericapsular nerves group (PENG) block with pericapsular infiltration (PAI) and plexus nerve block (PNB) for postoperative pain management, response to physical therapy, opioid consumption, and length of hospital stay after a primary total hip arthroplasty. METHODS: Randomized clinical trial of parallel and blinded groups was performed. Sixty patients who underwent elective THA between December 2018 and July 2020 were randomized into the different groups (PENG, PAI and PNB). The visual analog scale was used to assess pain; and motor function was measured with the Bromage scale. We also record opioid usage, length of hospital stay, and related medical complications. RESULTS: Pain level at discharge was similar in all groups. Hospital stay was 1 day shorter in the PENG group (p<0.001) and they also had lower opioid consumption (p=0.044). Optimal motor recovery was similar in the groups (p=0.678). Pain control when performing physical therapy was better in the PENG group (p<0.0001). CONCLUSIONS: PENG block is an effective and safe alternative for patients undergoing THA as it reduces opioid consumption and hospital stay compared to other analgesic methods.

Age-related functional and structural retinal modifications in the Igf1-/- null mouse.

BACKGROUND: Mutations in the gene encoding human insulin-like growth factor-I (IGF-I) cause syndromic neurosensorial deafness. To understand the precise role of IGF-I in retinal physiology, we have studied the morphology and electrophysiology of the retina of the Igf1(-/-) mice in comparison with that of the Igf1(+/-) and Igf1(+/+) animals during aging. METHODS: Serological concentrations of IGF-I, glycemia and body weight were determined in Igf1(+/+), Igf1(+/-) and Igf1(-/-) mice at different times up to 360days of age. We have analyzed hearing by recording the auditory brainstem responses (ABR), the retinal function by electroretinographic (ERG) responses and the retinal morphology by immunohistochemical labeling on retinal preparations at different ages. RESULTS: IGF-I levels are gradually reduced with aging in the mouse. Deaf Igf1(-/-) mice had an almost flat scotopic ERG response and a photopic ERG response of very small amplitude at postnatal age 360days (P360). At the same age, Igf1(+/-) mice still showed both scotopic and photopic ERG responses, but a significant decrease in the ERG wave amplitudes was observed when compared with those of Igf1(+/+) mice. Immunohistochemical analysis showed that P360 Igf1(-/-) mice suffered important structural modifications in the first synapse of the retinal pathway, that affected mainly the postsynaptic processes from horizontal and bipolar cells. A decrease in bassoon and synaptophysin staining in both rod and cone synaptic terminals suggested a reduced photoreceptor output to the inner retina. Retinal morphology of the P360 Igf1(+/-) mice showed only small alterations in the horizontal and bipolar cell processes, when compared with Igf1(+/+) mice of matched age. CONCLUSIONS: In the mouse, IGF-I deficit causes an age-related visual loss, besides a congenital deafness. The present results support the use of the Igf1(-/-) mouse as a new model for the study of human syndromic deaf-blindness.

[Prevalence and risk factors for suicide ideation, plans and attempts in the French general population: results from the ESEMeD study]. / Idéation et conduites suicidaires en France : prévalence sur la vie et facteurs de risque dans l'étude ESEMeD.

BACKGROUND AND OBJECTIVE: Suicide is a public health problem worldwide. The objective of this study is to analyse the prevalence and risk factors of suicide related outcomes (ideation, plan and attempt) using data from the ESEMeD-France project. SUBJECTS AND METHOD: This is a face-to-face household survey carried out in a probability representative sample of the adult general population of France. A total of 6796 subjects were interviewed using the Composite International Diagnostic Interview (CIDI) developed framework of the World Mental Health Survey Initiative. Based on evidence that reports of such potentially embarrassing behaviour are higher in self-administered than interviewer-administered surveys, these questions were printed in a self-administered booklet and referred to by letter. RESULTS: Lifetime prevalence of suicide ideation, plan and attempts were 12.4, 4.4 and 3.4% respectively. Risk of suicide-related outcomes was significantly higher among women and younger cohorts. Having a mental disorder was associated with an increased risk, especially in the case of psychiatric comorbidity. Mental disorders that are associated with an increase in suicidal attempts are anxiety disorders (except social phobia), major depressive episodes, oppositional defiant disorders, and attention deficit hyperactivity disorders. The suicidal risk notably increases in conjunction with multiple mental disorders. In this study, employment and marital status do not appear to be a risk factor for suicidal behaviour. CONCLUSIONS: The prevalence of suicide-related outcomes is high when compared with other countries. Results identified groups with higher risk (women, young, subjects with a mental disorder and having a plan) in which suicide prevention could to be targeted. The results of this study suggest that to improve suicide prevention strategies it is necessary to perform an in-depth clinical evaluation of suicidal ideas and projects, and identify precisely psychiatric comorbidity to allow a more efficient treatment.

[ACNES syndrome, exploring the abdominal wall as source of abdominal pain]. / Síndrome de ACNES, explorando la pared abdominal como noxa del dolor abdominal.

Abdominal wall pain, specifically ACNES syndrome (Anterior Cutaneous Nerve Entrapment Syn drome), is part of the differential diagnosis of chronic abdominal pain. This syndrome is frequently overlooked and therefore underdiagnosed. OBJECTIVES: To describe the clinical and evolutionary cha racteristics of patients diagnosed with ACNES and to draw attention to this pathology. PATIENTS AND METHOD: A retrospective descriptive study was carried out in a reference center, between October 2016 and July 2021, in patients under 17 years of age, diagnosed with ACNES, who met at least two of four of the following findings: Carnett's sign, Pinch test, dysesthesia at the point of maximum pain, improvement after infiltration of local anesthetic, having ruled out visceral or functional abdo minal pathology. Epidemiological variables, symptoms, physical examination, complementary tests, treatment, and evolution data were collected. Descriptive statistics were used. RESULTS: 20 patients diagnosed with ACNES, 75% women, median age 12.85 years. The abdominal examination revea led Carnett's sign in 95%, Pinch test sign in 65%, and dysesthesia in 90% of patients. 65% reported pseudovisceral symptoms. 7 patients were overweight or obese. The most frequent location (50%) was the right iliac fossa, at T10-T11 level. One patient reported spontaneous improvement; 7 impro ved with oral analgesia; 9 patients were referred to the pain unit, of which 5 attended, and improved with anesthetic infiltration with bupivacaine-triamcinolone. The remaining 4 were lost to follow-up. CONCLUSION: ACNES should be considered in patients with chronic pain. A combination of typical findings in medical history and physical examination allows its diagnosis, therefore, avoiding unne cessary complementary tests. A step-up treatment strategy should be applied, beginning with oral analgesia, followed by anesthetic infiltration, and, finally, anterior neurectomy.

Assessment of calving progress and reference times for obstetric intervention during dystocia in Holstein dairy cows.

The objectives of this observational study were (1) to assess the time from the appearance of the amniotic sac (AS) or feet outside the vulva to birth in Holstein cows (primiparous and multiparous) with (dystocia) or without assistance (eutocia) at calving, and (2) to estimate reference times to be used as guidelines for obstetric intervention in Holstein cows that need assistance during difficult births. Cows (n=92) from 1 commercial dairy operation were used in this study. Periparturient dairy cows (primiparous, n=58; multiparous, n=34) were placed in a maternity pen and constantly monitored until birth. The calving ease of cows, time from AS or feet appearance to birth, calving progress from a subset of 15 cows (frequency and duration of abdominal contractions during labor), calf birth weight, calf sex, and stillbirths (born dead or died within 24h after birth) were recorded. The reference times for obstetric intervention during dystocia were estimated based on values from unassisted births (normal). The normal range of times from the appearance of AS or feet outside the vulva to birth was estimated based on the mean+2 standard deviations (SD) of unassisted births. According to farm protocol, assistance was provided to cows without calving progress 80 min after AS appearance or earlier (e.g., to correct malpositions). Cows with dystocic births had a longer time from AS appearance to birth and increased incidence of stillbirth compared with cows with eutocic calvings. After the appearance of the AS, calving progress was evident every 15 min for eutocic births. The estimated reference times (mean+2 SD) from AS appearance to birth were 69.7 min and from feet appearance to birth were 64.6 min for eutocic births. Findings from this study suggested that calving personnel should start assisting cows 70 min after AS appearance (or 65 min after feet appearance) outside the vulva. The time spent in labor (straining) combined with the time from the appearance of the AS or feet to birth, and the assessment of calving progress (as described for eutocic births) should be used as guidelines for obstetric intervention during difficult births under field conditions. These reference times should be interpreted in combination with adequate obstetrical knowledge and examination.

Adherence to treatment guidelines in clinical practice for using electroconvulsive therapy in major depressive episode.

BACKGROUND: ECT is the most effective treatment of major depressive episode (MDE) but remains a neglected treatment. The French Society for Biological Psychiatry and Neuropsychopharmacology aimed to determine whether prescribing practice of ECT followed guidelines recommendations. METHODS: This multicenter, retrospective study included adult patients with major depressive disorder (MDD) or bipolar disorder (BD), who have been treated with ECT for MDE. Duration of MDE and number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. RESULTS: Seven hundred and forty-five individuals were included. The mean duration of MDE before ECT was 10.1 months and the mean number of lines of treatment before ECT was 3.4. It was significantly longer for MDD single episode than recurrent MDD and BD. The presence of first-line indications for using ECT was significantly associated to shorter duration of MDE (9.1 vs 13.1 months, p<0.001) and lower number of lines of treatment before ECT (3.3 vs 4.1, p<0.001). LIMITATIONS: This is a retrospective study and not all facilities practicing ECT participated that could limit the extrapolation of the results. CONCLUSION: Compared to guidelines, ECT was not used as first-line strategy in clinical practice. The presence of first-line indications seemed to reduce the delay before ECT initiation. The improvements of knowledge and access of ECT are needed to decrease the gap between guidelines and clinical practice.

Hypotensive activity of fibroblast growth factor.

Acidic and basic fibroblast growth factors (FGFs) are members of a family of proteins that are broad-spectrum mitogens, have diverse hormone-like activities, and function in tumorigenesis. FGF's ability to raise the concentration of intracellular calcium ion suggests that FGF could induce the synthesis of endothelium-derived relaxing factor (EDRF) and consequently vasodilation. Systemic administration of FGF decreased arterial blood pressure. This effect was mediated by EDRF and by adenosine triphosphate-sensitive potassium ion channels. The hypotensive effect of FGF was segregated from its mitogenic activity by protein engineering. These results extend the range of FGF autocrine activities and potential therapeutic applications, emphasize the role of endothelium as an arterial blood pressure--regulating organ, and provide insight on the structural basis of FGF functions.

Dialysis outcomes in Colombia (DOC) study: a comparison of patient survival on peritoneal dialysis vs hemodialysis in Colombia.

The goal of the Dialysis Outcomes in Colombia (DOC) study was to compare the survival of patients on hemodialysis (HD) vs peritoneal dialysis (PD) in a network of renal units in Colombia. The DOC study examined a historical cohort of incident patients starting dialysis therapy between 1 January 2001 and 1 December 2003 and followed until 1 December 2005, measuring demographic, socioeconomic, and clinical variables. Only patients older than 18 years were included. As-treated and intention-to-treat statistical analyses were performed using the Kaplan-Meier method and Cox proportional hazard model. There were 1094 eligible patients in total and 923 were actually enrolled: 47.3% started HD therapy and 52.7% started PD therapy. Of the patients studied, 751 (81.3%) remained in their initial therapy until the end of the follow-up period, death, or censorship. Age, sex, weight, height, body mass index, creatinine, calcium, and Subjective Global Assessment (SGA) variables did not show statistically significant differences between the two treatment groups. Diabetes, socioeconomic level, educational level, phosphorus, Charlson Co-morbidity Index, and cardiovascular history did show a difference, and were less favorable for patients on PD. Residual renal function was greater for PD patients. Also, there were differences in the median survival time between groups: 27.2 months for PD vs 23.1 months for HD (P=0.001) by the intention-to-treat approach; and 24.5 months for PD vs 16.7 months for HD (P<0.001) by the as-treated approach. When performing univariate Cox analyses using the intention-to-treat approach, associations were with age > or =65 years (hazard ratio (HR)=2.21; confidence interval (CI) 95% (1.77-2.755); P<0.001); history of cardiovascular disease (HR=1.96; CI 95% (1.58-2.90); P<0.001); diabetes (HR=2.34; CI 95% (1.88-2.90); P<0.001); and SGA (mild or moderate-severe malnutrition) (HR=1.47; CI 95% (1.17-1.79); P=0.001); but no association was found with gender (HR=1.03, CI 95% 0.83-1.27; P=0.786). Similar results were found with the as-treated approach, with additional associations found with Charlson Index (0-2) (HR=0.29; Cl 95% (0.22-0.38); P<0.001); Charlson Index (3-4) (HR=0.61; Cl 95% (0.48-0.79); P<0.001); and SGA (mild-severe malnutrition) (HR=1.43; Cl 95% (1.15-1.77); P<0.001). Similarly, the multivariate Cox model was run with the variables that had shown association in previous analyses, and it was found that the variables explaining the survival of patients with end-stage renal disease in our study were age, SGA, Charlson Comorbidity Index 5 and above, diabetes, healthcare regimes I and II, and socioeconomic level 2. The results of Cox proportional risk model in both the as-treated and intention-to-treat analyses showed that there were no statistically significant differences in survival of PD and HD patients: intention-to-treat HD/PD (HR 1.127; CI 95%: 0.855-1.484) and as-treated HD/PD (HR 1.231; CI 95%: 0.976-1.553). In this historical cohort of incident patients, there was a trend, although not statistically significant, for a higher (12.7%) adjusted mortality risk associated with HD when compared to PD, even though the PD patients were poorer, were more likely to be diabetic, and had higher co-morbidity scores than the HD patients. The variables that most influenced survival were age, diabetes, comorbidity, healthcare regime, socioeconomic level, nutrition, and education.

[Neurotrophic action of insulin-like growth factor-I in the inner ear]. / Acciones neurotróficas del factor de crecimiento similar a la insulina de tipo I en el oído interno.

INTRODUCTION: Loss of hearing constitutes one of the most frequent disabling sensory impairments in the developed world. Different therapeutic approaches are currently being studied, including treatment with stem cells, genetic manipulation and pharmacological protection. AIM: To evaluate the role played by insulin-like growth factor-I (IGF-I) in the development, maintenance and repair of auditory functioning. DEVELOPMENT: Proper development of the inner ear is dependent on a suitable coordination of the cell processes of proliferation, differentiation, neurogenesis and programmed cell death, which are regulated by different factors, one of which is IGF-I. During the embryogenesis of the inner ear, this factor is expressed in abundance and is essential for cell survival and maintaining neuronal precursors. Studies conducted in Igf-1-/- null mice have highlighted its importance in the development and continued functioning of the inner ear. Mice with a deficit in this gene display morphological disorders that correspond to severe functional deficiencies, which are confirmed by analysing brainstem auditory evoked potentials. A deficit of IGF-I in humans is also accompanied by profound sensory hypoacusis. CONCLUSIONS: In a scenario like this, IGF-I appears as a key factor in the development of auditory functioning and a candidate for regenerative therapy of the inner ear.

IGF-1 deficiency causes atrophic changes associated with upregulation of VGluT1 and downregulation of MEF2 transcription factors in the mouse cochlear nuclei.

Insulin-like growth factor 1 (IGF-1) is a neurotrophic protein that plays a crucial role in modulating neuronal function and synaptic plasticity in the adult brain. Mice lacking the Igf1 gene exhibit profound deafness and multiple anomalies in the inner ear and spiral ganglion. An issue that remains unknown is whether, in addition to these peripheral abnormalities, IGF-1 deficiency also results in structural changes along the central auditory pathway that may contribute to an imbalance between excitation and inhibition, which might be reflected in abnormal auditory brainstem responses (ABR). To assess such a possibility, we evaluated the morphological and physiological alterations in the cochlear nucleus complex of the adult mouse. The expression and distribution of the vesicular glutamate transporter 1 (VGluT1) and the vesicular inhibitory transporter (VGAT), which were used as specific markers for labeling excitatory and inhibitory terminals, and the involvement of the activity-dependent myocyte enhancer factor 2 (MEF2) transcription factors in regulating excitatory synapses were assessed in a 4-month-old mouse model of IGF-1 deficiency and neurosensorial deafness (Igf1 (-/-) homozygous null mice). The results demonstrate decreases in the cochlear nucleus area and cell size along with cell loss in the cochlear nuclei of the deficient mouse. Additionally, our results demonstrate that there is upregulation of VGluT1, but not VGAT, immunostaining and downregulation of MEF2 transcription factors together with increased wave II amplitude in the ABR recording. Our observations provide evidence of an abnormal neuronal cytoarchitecture in the cochlear nuclei of Igf1 (-/-) null mice and suggest that the increased efficacy of glutamatergic synapses might be mediated by MEF2 transcription factors.

Strict regulation of c-Raf kinase levels is required for early organogenesis of the vertebrate inner ear.

Regulation of organogenesis involves a dynamic balance of the mechanisms regulating cell division, differentiation and death. Here we have investigated the pattern of expression of c-Raf kinase in the inner ear during early developmental stages and the consequences of manipulating c-Raf levels by misexpression of c-raf viral vectors in organotypic cultures of otic vesicle explants. We found that otic vesicles expressed c-Raf and its level remained constant during embryonic days 2 and 3 (E2-E3). c-Raf activity was increased in response to insulin like growth factor-I (IGF-I) and the activation by IGF-I of the c-Raf kinase pathway was a requirement to turn on cell proliferation in the otic vesicle. Overexpression of c-raf in E2.5 explants increased the proliferative response to low serum and IGF-I and blocked differentiation induced by retinoic acid. The increase in c-Raf levels also prevented nerve growth factor (NGF)-dependent induction of programmed cell death. Consistent with these results, the expression of a dominant negative c-Raf mutant potentiated retinoic acid action and decreased the rate of cell proliferation. We conclude that a strict control of c-Raf levels is essential for the co-ordination of the biological processes that operate simultaneously during early inner ear development.