Latin American formal consensus on the indications for the surgical treatment of massive and irreparable rotator cuff tears.

OBJECTIVES: To implement the Formal Consensus Method among a group of experts in shoulder surgery in Latin America, in order to establish appropriate indications for the surgical treatment of massive and irreparable rotator cuff injuries. METHODS: The Formal Consensus Method was used to develop surgical treatment recommendations for massive and irreparable rotator cuff tears (MIRCT). Three independent groups of experts in shoulder surgery were confirmed. The steering group conducted a systematic literature review and constructed a voting matrix consisting of 348 clinical scenarios. The rating group, composed of 15 members, rated each scenario on two occasions: first anonymously and then during an in-person discussion meeting. The median and voting ranges were used to classify each scenario as inappropriate, uncertain, or appropriate for each surgical technique. Finally, the reading group, consisting of 10 surgeons, reviewed, evaluated and rated the recommendations derived from the detailed analysis of the voting grids. RESULTS: The main finding of the study reveals a high percentage (70%) of clinical scenarios in which consensus was achieved regarding the appropriateness or inappropriateness of different surgical alternatives for the treatment of massive and irreparable rotator cuff injuries. Through a detailed analysis of the voting grids, a total of 20 recommendations were elaborated concerning the appropriateness of various surgical techniques in addressing irreparable rotator cuff tears. CONCLUSIONS: The indications for the operative treatment of MIRCT were determined based on expert consensus and the best available evidence, they seek to provide guidance on the appropriateness of various surgical techniques for different clinical scenarios. LEVEL OF EVIDENCE: V.

Impulsivity and sexual addiction: factor structure and criterion-related validity of the sexual addiction screening test in Mexican adults.

Sexual addiction is associated with serious health problems. Due to that fact, it is quite important to perform a comprehensive assessment. The Sex Addiction Screening Test (SAST-R) is a self-administered questionnaire with good psychometric properties used in several countries. Our study conducts a cross-cultural adaptation of the SAST-R on the Mexican population. The original version of the SAST-R was translated into Mexican Spanish, and we performed a pilot with 23 participants to be sure that the participants understood the meaning of the items. The final version was administered to 370 adults who completed the SAST-R, and measures of impulsivity (the Kirby questionnaire), reward/punishment responsivity (BIS-BAS scale), personality (BIG-Five), and psychological distress (SCL-90). The confirmatory factor analysis (CFA) with a five-factor model with one second-order factor model had the best fit. Reliability analysis suggests acceptable internal consistency (α = 0.80). The SAST-R scores exhibited significant correlations with several variables. Specifically, they showed a positive correlation with the neuroticism scale (r = 0.11, p < 0.05), a negative correlation with the conscientiousness scale (r = -0.21, p < 0.01), a negative correlation with the BIS scale (r = -0.11, p < 0.05), and a positive correlation with psychological distress (r = 0.34, p < 0.01). Notably, there were no significant correlations observed with variables that we initially expected to have a substantial association, such as impulsivity (r = -0.004, p > 0.05) and the three BAS subscales (p > 0.05). We found with an algorithm that psychological distress, impulsivity, neuroticism, and agreeableness were the good predictors to identify high scores of hypersexuality. Our results confirmed that the Mexican Spanish version of the SAST-R has good psychometric properties to be used in future research.

Individual and Combined Effect of MAO-A/MAO-B Gene Variants and Adverse Childhood Experiences on the Severity of Major Depressive Disorder.

BACKGROUND: Major depressive disorder (MDD) is a mood disorder with a high prevalence worldwide that causes disability and, in some cases, suicide. Although environmental factors play a crucial role in this disease, other biological factors may predispose individuals to MDD. Genetic and environmental factors influence mental disorders; therefore, a potential combined effect of MAO-A/MAO-B gene variants may be a target for the study of susceptibility to MDD. This study aimed to evaluate the effects of MAO-A and -B gene variants when combined with adverse childhood experiences (ACEs) on the susceptibility and severity of symptoms in MDD. METHODS: A case-control study was performed, including 345 individuals, 175 MDD cases and 170 controls. Genotyping was performed using real-time PCR with hydrolysis probes. The analysis of the rs1465107 and rs1799836 gene variants of MAO-A and -B, respectively, was performed either alone or in combination with ACEs on the severity of depression, as determined through specific questionnaires, including DSM-IV diagnostic criteria for MDD. RESULTS: According to individual effects, the presence of ACEs, as well as the allele G of the rs1465107 of MAO-A, is associated with a higher severity of depression, more significantly in females. Furthermore, the allele rs1799836 G of MAO-B was associated with the severity of depression, even after being adjusted by gene variants and ACEs (IRR = 1.67, p = 0.01). In males, the allele rs1799836 G of MAO-B was shown to interact with SNP with ACEs (IRR = 1.70, p < 0.001). According to combined effect analyses, the severity of depression was associated with ACEs when combined with either allele rs1465107 of MAO-A or allele rs17993836 of MAO-B, whereas SNP risk association was influenced by gender. CONCLUSIONS: The severity of depression is related to either individual or combined effects of temperamental traits and genetic susceptibility of specific genes such as MAO-A and MAO-B.

Endothelial Progenitor Cells May Be Related to Major Amputation after Angioplasty in Patients with Critical Limb Ischemia.

BACKGROUND: Critical limb ischemia represents an advanced stage of peripheral arterial disease. Angioplasty improves blood flow to the limb; however, some patients progress irreversibly to lower limb amputation. Few studies have explored the predictive potential of biomarkers during postangioplasty outcomes. AIM: To evaluate the behavior of endothelial progenitor cells in patients with critical limb ischemia, in relation to their postangioplasty outcome. METHODS: Twenty patients with critical limb ischemia, candidates for angioplasty, were enrolled. Flow-mediated dilation, as well as endothelial progenitor cells (subpopulations CD45+/CD34+/CD133+/CD184+ and CD45+/CD/34+/KDR[VEGFR-2]+ estimated by flow cytometry) from blood flow close to vascular damage, were evaluated before and after angioplasty. Association with lower limb amputation during a 30-day follow-up was analyzed. RESULTS: Endothelial progenitor cells were related with flow-mediated dilation. A higher number of baseline EPCs CD45+CD34+KDR+, as well as an impaired reactivity of endothelial progenitor cells CD45+CD34+CD133+CD184+ after angioplasty, were observed in cases further undergoing major limb amputation, with a significant discrimination ability and risk (0.75, specificity 0.83 and RR 4.5 p < 0.05). CONCLUSIONS: Endothelial progenitor cells were related with endothelial dysfunction, whereas a higher baseline number of the subpopulation CD45+CD34+KDR+, as well as an impaired reactivity of subpopulation CD45+CD34+CD133+CD184+ after angioplasty, showed a predictive ability for major limb amputation in patients with critical limb ischemia.

Family Functioning and Suicide Attempts in Mexican Adolescents.

Suicide is considered a public health problem that affects families worldwide. Family functioning is the capability of the family system to fulfill needs during the stages of its development. In this study, we focused on evaluating family cohesion and adaptability in a group of adolescents who had attempted suicide and were hospitalized at a hospital for mental health disorders, compared to a control group. Methods: based on Olson's circumplex model, we used the FACES III scale to gain insights into the family functioning of both suicidal and control groups. Results: The case group presented lower scores in cohesion and adaptability compared to the control group, with moderate effect-size for cohesion (Cohen's d/r test = 1.217/0.52) and low effect-size for adaptability (Cohen's d/r test = 0.746/0.35) (p < 0.001 for both variables), and also presented predominantly disengaged families (72.5% in the case group vs. 27.5% in the control group) and structured families (45% in the case group vs. 23.8% in the control group). The type of family described by the adolescents with a history of suicide attempts may explain the presence of low self-esteem and little emotional support usually present in this type of patient.

Neurological Involvement in Pediatric Patients with Acute Leukemia: A Retrospective Cohort.

Acute leukemia (AL) is an important cause of morbidity and mortality in children, and neurological manifestations (NM) are frequent. The objective of this study was to analyze neurological manifestations in children with acute leukemia from cases attended in the last five years at the Centro Médico Nacional "20 de Noviembre". METHODS: Conducting a retrospective and analytical study from 1 January 2015 to 31 December 2020 in children with AL classified according to sex, age range and AL type. Participants were grouped according the presence of NM. RESULTS: We analyzed 607 patients: 54.85% boys and 44.14% girls, with a mean age of 7.27 ± 4.54 years. When comparing groups, the NM group was significantly older (p = 0.01), and the highest prevalence was between 6 and 12 years old. ALL was predominant over the other lineages (p ≤ 0.01). The most frequent NM was CNS infiltration, seizures, headache and neuropathy. Death outcomes occurred in 18.7% of children with AML, 11.8% with ALL and 50% with MPAL (p ≤ 0.002). The NM group was associated with higher mortality during a follow-up time of 77.9 ± 49 months (44.4% vs. 8.9% deaths, NM vs. non-NM, respectively; OR = 3.3; 95% CI 2.4 to 4.6; p ≤ 0.0001). CONCLUSIONS: ALL was the most prevalent leukemia type. CNS infiltration, seizures, headache, neuropathy and PRES were the most frequent symptoms in the NM group. NM was associated with a higher mortality rate.

Diagnostic Performance of AST Scale in Mexican Male Population for Alcohol Withdrawal Syndrome.

Alcohol withdrawal syndrome (AWS) represents an adverse consequence of chronic alcohol use that may lead to serious complications. Therefore, AWS requires timely attention based on its early recognition, where easy-to-apply diagnostic tools are desirable. Our aim was to characterize the performance of a short-scale AST (Anxiety, Sweats, Tremors) in patients from public general hospitals. We conducted a cross-sectional study of patients attended at the Emergency Department diagnosed with AWS. Three scales were applied: CIWA-Ar (Clinical Institute Retirement Assessment Scale-Revised), GMAWS (Glasgow Modified Alcohol Withdrawal Syndrome) and AST. Cronbach's alpha and Cohen's kappa tests were used for reliability and concordance. Factorial analysis and diagnostic performance including ROC curve were carried out. Sixty-eight males with a mean age of 41.2 years old, with high school education and robust alcohol consumption, were included. Mean scores for CIWA-Ar, GMWAS and AST were 17.4 ± 11.2, 3.9 ± 2.3 and 3.8 ± 2.6, respectively, without significant differences. The AST scale showed an acceptable reliability and concordance (0.852 and 0.439; p < 0.0001) compared with CIWA-Ar and GMAWS. AST component analysis evidenced tremor (77.5% variance), sweat (12.1% variance) and anxiety (10.4% variance). Diagnostic performance of the AST scale was similar to the GMAWS scale, evidencing a sensitivity of 84%, specificity of 83.3% and Area Under the Curve (AUC) of 0.837 to discriminate severe AWS, according to CIWA-Ar. The performance of the AST scale to evaluate AWS is comparable with the commonly used CIWA-Ar and GMAWS scales. AST further represents an easy-to-apply instrument.

Neurological Manifestations in Pediatric Patients Hospitalized for COVID-19: Experiences of the National Medical Center "20 de Noviembre" in Mexico City.

COVID-19 has affected millions of children and, while it was previously considered as a respiratory disease, neurologic involvement has also been documented. The objective of this study was to identify the neurological manifestations (NMs) and the outcomes of children with COVID-19 who attended the National Medical Center "20 de Noviembre". METHODS: A retrospective cohort study of children hospitalized for COVID-19 from April 2020 to March 2021 was conducted. Clinical-demographic data were registered. Neurologic manifestations were defined as any clinical neurological expression of the central and/or peripheral nervous system that occurred during admission or hospitalization. RESULTS: In total, 46 children with a confirmed COVID-19 result, 26 (56.5%) boys and 20 (43.5%) girls with a median age of 8.9 ± 4.6 years, constituted the study population. Half of the children showed some NMs, and this group of patients concomitantly showed acute lymphoblastic leukemia (ALL, 56%), obesity (17.3%), or acute myeloblastic leukemia (AML, 4.3%). The most frequently described NMs were headache (13, 56%), encephalopathy (10, 43.47%), and epilepsy (4, 17.39%). The mortality rate in children with NMs was 21.7% and they had a higher mortality rate when compared to those without NM p ≤ 0.025. CONCLUSIONS: NMs occurred predominantly in male children aged 6 to 12 years; ALL was the most frequent comorbidity. Headache prevailed and hypoxemia, hypocalcemia, elevated ferritin, and C-reactive protein were associated with NM. Finally, NMs were a risk factor for mortality.

Pectoralis major and pectoralis minor transfer for irreparable subscapularis tendon tears.

OBJECTIVE: Irreparable rotator cuff injuries in young patients with moderate to high levels of physical activity remain a challenging pathology for shoulder surgeons. Irreparable anterior rotator cuff injuries require treatment that seeks to restore the dynamic anterior forces of the glenohumeral joint. Among surgical treatment options, transfer of the pectoralis major and minor muscle, have shown good functional outcomes. This technique attempts to reproduce the vector of the subscapular muscle in cases with irreparable tear. Restoration of the dynamic external and internal couple forces to maintain the humeral head in the center of rotation. INDICATIONS: Pectoralis major transfer (PMa): Irreparable subscapularis tendon (SSC) tear in active patients without osteoarthritis. Pectoralis minor transfer (PMi): Irreparable superior SSC tear with concomitant irreparable supraspinatus tendon (SSP) tear in active patients with no osteoarthritis. CONTRAINDICATIONS: Primary osteoarthritis Samilson grade C, cuff tear arthropathy Hamada III-V, infection, axillary nerve palsy, older patients with low physical demand, combination with irreparable SSP/infraspinatus tendon (ISP) tear for PMa or combination with irreparable ISP tear for PMi. SURGICAL TECHNIQUE: General anesthesia and beach-chair position with the arm freely mobile in an arm holder. Deltopectoral approach. Exposure of the humeral head and confirmation of the irreparability of the subscapularis tendon. PMa: Detachment of the tendon to be transferred from the humeral insertion, blunt anatomic dissection medially. Exposure of the conjoined tendon and coracoid process. PMi: Detachment of the tendon with an osteotomy at the coracoid process. Passing the PMa or PMi tendon under the conjoined tendon. The PMa tendon is fixed in a 2-row configuration, the PMi in a single row with suture anchors to the lesser tuberosity. POSTOPERATIVE MANAGEMENT: Shoulder abduction sling (30°) for 6 weeks. Assisted range-of-motion (ROM) exercises with abduction/adduction 60-0-0°, internal/external rotation free-0-0° for 6 weeks. Free active ROM exercises after 6 weeks, muscle strengthening after 12 weeks. RESULTS: The pectoralis major and minor transfer shows an improvement in strength and range of motion in young active patients and an improved Constant score (CS) in long-term follow-up examinations.

Neurological Manifestations and Outcomes in a Retrospective Cohort of Mexican Inpatients with SARS-CoV-2 Pneumonia: Design of a Risk Profile.

We analyzed the neurological manifestations in Mexican patients hospitalized with pneumonia due to COVID-19 and investigated the association between demographic, clinical, and biochemical variables and outcomes, including death. A retrospective, analytical study was conducted using the electronic records of patients hospitalized between 1 April 2020 and 30 September 2020. Records of 1040 patients were analyzed: 31.25% died and 79.42% had neurological symptoms, including headache (80.62%), anosmia (32.20%), ageusia (31.96%), myopathy (28.08%), disorientation (14.89%), encephalopathy (12.22%), neuropathy (5.4%), stroke (1.3%), seizures (1.3%), cerebral hemorrhage (1.08%), encephalitis (0.84%), central venous thrombosis (0.36%), and subarachnoid hemorrhage (0.24%). Patients also had comorbidities, such as hypertension (42.30%), diabetes mellitus (38.74%), obesity (61.34%), chronic obstructive pulmonary disease (3.17%), and asthma (2.01%). Factors associated with neurological symptoms were dyspnea, chronic obstructive pulmonary disease, advanced respiratory support, prolonged hospitalization, and worsening fibrinogen levels. Factors associated with death were older age, advanced respiratory support, amine management, chronic obstructive pulmonary disease, intensive care unit management, dyspnea, disorientation, encephalopathy, hypertension, neuropathy, diabetes, male sex, three or more neurological symptoms, and obesity grade 3. In this study we designed a profile to help predict patients at higher risk of developing neurological complications and death following COVID-19 infection.

Analysis of Impulse Control Disorders (ICDs) and Factors Associated with Their Development in a Parkinson's Disease Population.

Parkinson's Disease (PD) is a neurodegenerative disease in which non-motor symptoms may appear before motor phenomena, which include Impulse Control Disorders (ICDs). The objective of this study is to identify factors associated with the development of ICDs in PD. An analytical, cross-sectional study was conducted using clinical records from patients diagnosed with PD, both genders, from 40 to 80 years old. Clinical and demographic data were collected: 181 patients were recruited; 80 of them showed PD and ICDs, and they constituted the study group, whereas 101 patients with PD without ICDs constituted the control reference group. The duration of PD was longer in the group with ICDs (p < 0.008), and all patients showed at least one ICD: binge eating (61.29%), compulsive shopping (48.75%), hypersexuality (23.75%), gambling behavior (8.75%), and punding (3.75%). After logistic regression analysis, only the use of dopamine agonists remained associated with ICDs (p < 0.001), and the tremorgenic form was suggested to be a protective factor (p < 0.001). Positive associations were observed between the rigid-akinetic form and compulsive shopping (p < 0.007), between male and hypersexuality (p < 0.018), and between dopamine agonists and compulsive shopping (p < 0.004), and negative associations were observed between motor fluctuations and compulsive shopping (p < 0.031), between Deep Brain Stimulation and binge eating (p < 0.046), and between levodopa consumption and binge eating (p < 0.045). Binge eating, compulsive shopping, and hypersexuality were the most frequent ICDs. Complex forms and motor complications of PD were associated with the development of ICDs.

Quality and Safety in Healthcare for Medical Students: Challenges and the Road Ahead.

Background: The development of skills, behaviors and attitudes regarding patient safety is of utmost importance for promoting safety culture for the next generation of health professionals. This study describes our experience of implementing a course on patient safety and quality improvement for fourth year medical students in Mexico during the COVID-19 outbreak. The course comprised essential knowledge based on the patient safety curriculum provided by the WHO. We also explored perceptions and attitudes of students regarding patient safety. Methods: Fourth year medical students completed a questionnaire regarding knowledge, skills, and attitudes on patient safety and quality improvement in medical care. The questionnaire was voluntarily answered online prior to and after the course. Results: In total, 213 students completed the questionnaires. Most students were able to understand medical error, recognize failure and the nature of causation, perform root-cause analysis, and appreciate the role of patient safety interventions. Conversely, a disapproving perspective prevailed among students concerning the preventability of medical errors, utility of reporting systems, just culture and infrastructure (p < 0.05). Conclusion: We found students had a positive perspective concerning learning quality in healthcare and patient safety during our course; nevertheless, their perception of the usefulness of reporting systems to prevent future adverse events and prevent medical errors is uncomplimentary. Medical education should promote error reporting and just culture to change the current perception of medical students.

Automatic Classification of Sarcopenia Level in Older Adults: A Case Study at Tijuana General Hospital.

This paper presents a study based on data analysis of the sarcopenia level in older adults. Sarcopenia is a prevalent pathology in adults of around 50 years of age, whereby the muscle mass decreases by 1 to 2% a year, and muscle strength experiences an annual decrease of 1.5% between 50 and 60 years of age, subsequently increasing by 3% each year. The World Health Organisation estimates that 5-13% of individuals of between 60 and 70 years of age and 11-50% of persons of 80 years of age or over have sarcopenia. This study was conducted with 166 patients and 99 variables. Demographic data was compiled including age, gender, place of residence, schooling, marital status, level of education, income, profession, and financial support from the State of Baja California, and biochemical parameters such as glycemia, cholesterolemia, and triglyceridemia were determined. A total of 166 patients took part in the study, with an average age of 77.24 years. The purpose of the study was to provide an automatic classifier of sarcopenia level in older adults using artificial intelligence in addition to identifying the weight of each variable used in the study. We used machine learning techniques in this work, in which 10 classifiers were employed to assess the variables and determine which would provide the best results, namely, Nearest Neighbors (3), Linear SVM (Support Vector Machines) (C = 0.025), RBF (Radial Basis Function) SVM (gamma = 2, C = 1), Gaussian Process (RBF (1.0)), Decision Tree (max_depth = 3), Random Forest (max_depth=3, n_estimators = 10), MPL (Multilayer Perceptron) (alpha = 1), AdaBoost, Gaussian Naive Bayes, and QDA (Quadratic Discriminant Analysis). Feature selection determined by the mean for the variable ranking suggests that Age, Systolic Arterial Hypertension (HAS), Mini Nutritional Assessment (MNA), Number of chronic diseases (ECNumber), and Sodium are the five most important variables in determining the sarcopenia level, and are thus of great importance prior to establishing any treatment or preventive measure. Analysis of the relationships existing between the presence of the variables and classifiers used in moderate and severe sarcopenia revealed that the sarcopenia level using the RBF SVM classifier with Age, HAS, MNA, ECNumber, and Sodium variables has 82'5 accuracy, a 90'2 F1, and 82'8 precision.

Analysis of the rs13306560 functional variant in the promoter region of the MTHFR gene in sporadic Parkinson´s disease.

OBJECTIVE: Among susceptibility genes for Sporadic Parkinson´s Disease (SPD), the MTHFR gene has been suggested as candidate. The A allele of the functional variant rs13306560 in its promoter region has been liked to decreased transactivation capacity. Therefore, we sought to determine a possible association of the rs13306560 and SPD. METHODS: In total, 237 individuals were genotyped, 113 patients with SPD diagnosed according to the Queen Square Brain Bank criteria and 124 neurologically healthy controls. Genotyping was performed using TaqMan probes for the rs13306560 and real-time PCR. RESULTS: The A allelle was associated to protection in SPD, under the dominant model, (OR=0.22, C.I.=[0.048-1.080], p=0.04), nevertheless, after logistic regression analysis with adjustment for gender, resulted only in a trend (Exp (ß)=0.211, [I.C. 95.0%, 0.042-1.057], p=0.058). CONCLUSION: Although further studies are needed, our data suggest an important role of the MTHFR gene variants in the fine-tuning regulation of one-carbon metabolism in the brain.

Barriers to Clinical Research in Latin America.

Enhancing health research capacity in developing countries is a global health priority. Understanding the orthopedic burden of disease in Latin America will require close partnership between more-developed and less-developed countries. To this end, the Osteosynthesis and Trauma Care Foundation assembled a research consortium of Latin-American orthopedic leaders. Prior to the meeting, we surveyed attendees on perceived barriers to conducting research at their institutions. During the event, working groups discussed these barriers, developed strategies for addressing them, and planned future steps for collaboration. The participants established the need for global relationships that allow colleagues from Latin America to access to training and established investigational infrastructure of North American centers to address research questions relevant to their communities. As a result of the discussion, the International Orthopaedic Multicenter Study (INORMUS) in Fracture Care was initiated. Since then, an expanded international working group, Associación de Cirujanos Traumatológicos en las Americas (ACTUAR), has been created with the purpose of promoting increased global partnership for research capacity development.

Polysomnography-based diagnosis in Mexican adult patients with Obstructive Sleep Apnea Syndrome (OSAS) clinical suspicion.

INTRODUCTION: Obstructive sleep apnea syndrome (OSA) occurs in 2-4% of adults, increasing by 2.5 times the risk of sudden death. OBJECTIVE: Establish the concordance of the clinical diagnostic and electrical diagnosis in an adult series that underwent polysomnography. MATERIALS AND METHODS: Patients with sleep disorders that underwent consecutively polysomnography recording. RESULTS: In this study, 51 subjects from 24 to 77 years old (54.1±12.12) were included in the study; 23 males and 28 females; 78.43% were overweight or obese; 35.29% were smokers; 31.37% alcohol consumers; 47.05% hypertensive; 21% diabetics; 35.29% with airway alterations; 29.41% with depression; 13.72% dyslipidaemic and 7.84% with ischemic heart disease. Only 22 of the subjects qualified for OSA and the concordance between the clinical diagnostic and polysomnographic recording was 54% (Ko=0.60, Ke 0.50, Ka=0.20) with a 0.55 sensibility, 0.66 specificity, PPV 0.54, NPV 0.65, PLR 1.2, RVN 0.69 and PPP 0.47. The neck circumference in OSA was 40.68±5 vs. 37.7±3.5 cm. (p<0.02) and BMI was 36.48±13.16 vs 29.37±6.58 (p<0.008); male/female proportion was 1.8:1 (p<0.01), BMI was higher in OSA (p<0.002). The Epworth Sleepiness Scale did not discriminate between OSA and other sleep alteration (p<0.29). DISCUSSION AND CONCLUSIONS: We observed a poor agreement between clinical diagnosis and polysomnography. The Epworth Sleepiness Scale did not discern between OSA and other sleep disorders and finally there was no association with a systemic process.