Acciones metodológicas para implementar la estrategia curricular de Inglés con fines profesionales en Medicina / Methodological actions to implement the English language curricular strategy in English for specific purposes in medicine

Fundamento: la finalidad de la estrategia curricular Dominio del Idioma Inglés, propuesta por la subcomisión de estrategias curriculares de la Universidad de Ciencias Médicas de la Habana desde el 2009, es la competitividad idiomática de los profesionales de la salud. Objetivo: diseñar acciones metodológicas para la implementación de la estrategia curricular Dominio del Idioma Inglés en la carrera de Medicina de la Filial Universitaria Municipal de Santo Domingo. Métodos: se realizó una investigación de desarrollo con enfoque mixto entre enero de 2011 y diciembre de 2013; se utilizaron métodos teóricos: análisis-síntesis e inducción-deducción y empíricos: análisis documental de la Resolución 210/2007, planes de trabajo metodológico y actas en los diferentes niveles organizativos, modelo del profesional y planes de clase; y la encuesta en forma de entrevista a directivos, y de cuestionario a docentes para identificar las principales insuficiencias en la preparación idiomática y metodológica. Resultados: se constató que las principales insuficiencias están relacionadas con la dirección y ejecución del trabajo metodológico interdisciplinar y con el pobre desarrollo de habilidades para la gestión de la información médica en idioma inglés, por lo que se diseñaron acciones metodológicas para lograr una mayor objetividad en la implementación interdisciplinar de esta estrategia que tribute al actual modelo del profesional de la salud. Conclusiones: las acciones fueron valoradas como pertinentes por criterios de especialistas, porque contribuyeron a transformar progresivamente la realización del trabajo metodológico para desarrollar una competencia idiomática interdisciplinar y profesional como garantía de un desempeño competente en contextos de habla inglesa.

Background: the purpose of the curricular strategy of the English Language command, proposed by the subcommittee of curricular strategies of Havana University of Medical Sciences since 2009 is the idiomatic competence of health professionals. Objective: to design methodological actions for the implementation of the curricular strategy of the English Language command in the Medicine career of Santo Domingo's Municipality Health University Site. Methods: it was carried out a development investigation with a combined approach from January 2011 to December 2013; theoretical methods were used: analysis-synthesis and induction-deduction and empiric ones: documental analysis of the 210/2007 Regulation from the Ministry of Higher Education , methodological plans and meeting records at different organizational levels, model of the professional and lesson plans; and the survey in interview form was applied to administrative leaders and a questionnaire was applied to the professors to identify the main inadequacies in the idiomatic and methodological preparation. Results: it was verified that the main inadequacies are related with the management and execution of the interdisciplinary methodological work and with the poor development of abilities for the medical information management in the English language, that's why methodological actions were designed to achieve a bigger objectivity in the interdisciplinary implementation of this strategy that contributes with the current model of health professionals. Conclusions: the actions were valued as pertinent by the specialists' criteria, because they contributed to transform the work with the methodological activity progressively to develop an interdisciplinary and professional idiomatic competence as guarantee of a competent performance in English-speaking contexts.

Fitoplancton del río Tehuantepec, Oaxaca, México y algunas relaciones biogeográficas / Phytoplankton from Tehuantepec River, Oaxaca, Mexico and some biogeographical relationships

Phytoplankton species collected from the limnetic to euryhaline sections of Tehuantepec River were identified, classified and compared with regional information from Mexico and South America. We collected 15 samples every three months from July 1997 through August 1998 with a 20 microm net and a Van Dorn bottle. Indicator values and a code checklist are included. A total of 58 families, 121 genera, 273 species, one subspecies, 75 varieties, 13 forms and one morphotype were identified in the taxa Bacillariophyta (42.0 %), Chlorophyta (29.0 %), Cyanoprocaryota (18.0 %), Euglenophyta (5.0 %), Dinophyta (3.0 %), Cryptophyta (2.0 %) and Chrysophyta (1.0 %). The predominant families were Scenedesmaceae (24 species), Oocystaceae (22), Bacillariophyceae (21), Chaetocerotaceae (15) and Euglenaceae (14). Five families, eight genera, 72 species, 45 varieties and eight forms are first records for Mexico. The species Chroococcus turgidus, Microcystis flosaquae and Pseudanabaena limnetica (which produce massive blooms or red tides) are important in this river of moderate water quality.

El fitoplancton recolectado en el río Tehuantepec con características limnéticas a eurihalinas se determinó, clasificó y comparó con información regional de México y Suramérica. Se incluyen valores indicadores y un código del listado florístico para facilitar el manejo de estas algas. Se determinó un total de 58 familias, 121 géneros, 273 especies, una subespecie, 75 variedades, 13 formas y un morfotipo, pertenecientes a las divisiones Bacillariophyta (42.0 %), Chlorophyta (29.0 %), Cyanoprocaryota (18.0 %), Euglenophyta (5.0 %), Dinophyta (3.0 %), Cryptophyta (2.0 %) y Chrysophyta (1.0 %). Las familias mejor representadas fueron Scenedesmaceae (24 especies), Oocystaceae (22), Bacillariophyceae (21), Chaetocerotaceae (15) y Euglenaceae (14). Se establecen nuevos registros para México: cinco familias, ocho géneros, 72 especies, 45 variedades y ocho formas. En este río, que presenta una moderada calidad del agua, sobresalieron las especies Chroococcus turgidus, Microcystis flosaquae y Pseudanabaena limnetica (como productoras de mareas rojas).

Endoscopic Injection Treatment for Gastric Dieulafoy Lesion in Two Newborn Infants / 대한소화기학회지

Dieulafoy lesion is an abnormally large calibered submucosal artery associated with a minute mucosal defect in the gastrointestinal mucosa. It is a rare cause of profuse, but intermittent gastrointestinal bleeding. The lesion is usually located in the stomach, although it may occur anywhere in the gastrointestinal tract. Dieulafoy lesion is extremely rare in the neonates. We report two newborn infants with a gastric Dieulafoy lesion which was treated by endoscopic epinephrine injection therapy without complication and recurrence.

A Case of Metastasis-induced Acute Pancreatitis Improved by Chemotherap / 대한소화기학회지

Pancreatic metastases are found in up to 40% of patients with small cell lung cancer, but metastasis-induced acute pancreatitis is rare. Treatment of metastasis-induced acute pancreatitis is initially supportive, but failure of conservative management are common. There are few reports on aggressive treatment with chemotherapy which lead to rapid clinical improvement and prolongation of survival in patients with metastasis-induced acute pancreatitis. We experienced a case of metastasis-induced acute pancreatitis in a patient with small cell lung cancer. Despite conservative treatment with dietary restriction and intravenous fluid supply, serum amylase levels increased persistently with severe abdominal pain. After chemotherapy with irinotecan and carboplatin, abdominal pain and serum amylase levels resolved dramatically.

A Case of Primary Angiosarcoma of Small Intestine Presenting as Recurrent Gastrointestinal Bleeding / 대한소화기학회지

Angiosarcoma is a rare malignant tumor which occurs frequently in the skin and soft subcutis. Moreover, primary gastrointestinal angiosarcomas are very rare. This tumor manifests as non-specific symptoms such as gastrointestinal bleeding, abdominal pain and nausea. The diagnosis is often made at an advanced stage. Surgery, chemotherapy and radiotherapy are the mainstay of treatment. However, the prognosis is very poor. We report a case of primary angiosarcoma of the small intestine presenting as recurrent gastrointestinal bleeding. A 54-year-old man was admitted with recurrent gastrointestinal bleeding. An abdominal CT scan revealed an ileo-ileal intussusception. Segmental resection was performed with ileo-ileal anastomosis. The ileal mass was diagnosed as angiosarcoma on immunohistochemical stain. He received 3 cycles of chemotherapy, but died 5 months after the diagnosis.

Disintegration of Pancreatic Duct Stones with Extracorporeal Shockwave Lithotripsy / 대한소화기학회지

BACKGROUND/AIMS: Treatment of pancreatic duct stones by extracorporeal shockwave lithotripsy (ESWL) serves as a nonsurgical treatment modality in patients with stones that are located in upstream of the strictures or in patients with impacted stones. We present the results of ESWL in endoscopically unretrievable pancreatic duct stones in the past 2 years. METHODS: Between January 2002 and December 2003, 58 patients with chronic pancreatitis were treated by ESWL for pancreatic duct stones. ESWL was performed with an electrohydraulic lithotripter ultrasound focusing system. RESULTS: The mean number of shockwave treatments was 2.5, and the patients received 4,578 (1,527-10,155) shockwave discharges with a mean energy of 15.8 kV. Fragmentations of the stones were achieved in 54 patients (93.2%), and complete clearance of the stones were noticed in 27 patients (46.6%). Fragmentation of stones equal or less than 3 mm in diameter was associated with successful removal of stones (p<0.05). Complete relief of pain occurred in 32 patients (55.2%). The procedures were well tolerated and no patient had significant complications such as acute pancreatitis. CONCLUSIONS: ESWL is an effective and a safe procedure for endoscopically unretrievable main pancreatic duct stones. ESWL combined with endoscopic therapy can increase the success rate of nonsurgical removal of pancreatic duct stones in patients with chronic pancreatitis.

Effects of Tamoxifen on the Voltage-dependent Ionic Currents in Mouse Colonic Smooth Muscle Cells / 대한소화기학회지

BACKGROUND/AIMS: Tamoxifen is a widely used anticancer drug for breast cancer with frequent gastrointestinal side effects. Changes in gastrointestinal motility is associated with altered activities of membrane ion channels. Ion channels have important role in regulating membrane potential and cell excitability. This study was performed to investigate the effects of tamoxifen on the membrane ionic currents in colonic smooth muscle cells. METHODS: Murine colonic smooth muscle cells were isolated from the proximal colon using collagenase, and the membrane currents were recorded using a whole-cell patch clamp technique. RESULTS: Two types of voltage-dependent K+ currents were recorded (A-type and delayed rectifier K+ currents). Tamoxifen inhibited both types of voltage-dependent K+ currents in a dose-dependent manner. However, tamoxifen did not change the half-inactivation potential and the recovery time of voltage-dependent K+ currents. Chelerythrine, a protein kinase C inhibitor or phorbol 12, 13-dibutyrate, a protein kinase C activator did not affect the voltage-dependent K+ currents. Guanosine 5'-O-(2-thio-diphosphate) did not affect the tamoxifen-induced inhibition of voltage-dependent K+ currents. Tamoxifen inhibited voltage-dependent Ca2+ currents completely in whole-test ranges. CONCLUSIONS: These results suggest that tamoxifen can alter various membrane ionic currents in smooth muscle cells and cause some adverse effects on the gastrointestinal motility.

Colonoscopic Surveillance after Curative Resection for Colorectal Cancer with Synchronous Adenoma / 대한소화기학회지

BACKGROUND/AIMS: Guidelines for current postoperative colonoscopic surveillance are not specified in colorectal cancer (CRC) patients with synchronous adenoma (SA). We performed this retrospective study to determine the postoperative colonoscopic surveillance interval for the CRC patients with SA. METHODS: One hundred and twenty-four CRC patients with SA (SA-group) and the same number of patients without SA (NSA-group) were selected from our database. Two groups were matched by the stage of CRC. Median colonoscopic surveillance period was 55 (12-99) months. The colonoscopic surveillance frequency and interval were similar between the two groups. RESULTS: Mean age was higher and male was more frequent in SA-group than NSA-group (p= 0.0001). The incidence of missed adenoma, advanced missed adenoma and metachronous adenoma (MA) were higher in SA-group (30.8% vs. 5.8% at 1st yr., p=0.0001; 4.4% vs. 0%, p=0.0001; 31.1% vs. 9.1% at 2nd yr., p=0.016) during the first consecutive two years of surveillance. The MA- and advanced-MA-free survival rate were lower in SA-group (24.6% vs. 6.6%, p=0.0001; 4.1% vs. 0%, p=0.02) during three years after surgery. Dysplasia of the SA (p=0.04; OR, 110.3; 95% CI, 1.13-10742.6) and presence of missed adenoma (p=0.036; OR, 43.6; 95% CI, 1.28-1490.1) were risk factors for the advanced MA on a multivariate analysis in SA-group. CONCLUSIONS: Postoperative colonoscopic surveillance at first year after surgery is warranted in CRC patients with SA.

The Influence of Non-steroidal Anti-inflammatory Drugs on Clinical Outcome in Patients with Bleeding Peptic Ulcers / 대한소화기학회지

BACKGROUND/AIMS: We conducted this study to find the clinical characteristics of ulcer bleeding that occurred in patients who had been taking non-steroidal anti-inflammatory drugs (NSAIDs) and to evaluate the influences of NSAIDs on clinical outcomes. METHODS: Between January 2000 and December 2002, a total of 310 patients with ulcer bleeding were analyzed. Study group composed of 49 patients who had taken NSAIDs regularly for at least 4 weeks before the admission. Other 261 patients who had not taken NSAIDs were classified as control group. Relevant informations were obtained from the medical records. RESULTS: Of the NSAIDs group, aspirin was the most common medication. The mean age and the proportion of females in the NSAIDs group were significantly higher than those of the control group. Prevalence of co-morbid illness was significantly higher in the NSAIDs group than in the control group (85.7% vs 30.7%, p<0.001). The severity of bleeding which was assessed by hemoglobin level at presentation, amount of transfusion, and duration of admission, was not different between two groups. There were no significant differences in frequency of re-bleeding, urgent surgery, and mortality. CONCLUSIONS: Ulcer bleeding among patients taking NSAIDs occurred more frequently in older females with co- morbid illness. However, NSAIDs is not associated with higher morbidity and mortality.

Effectiveness of Triple Therapy and Quadruple Therapy for Helicobacter pylori Eradication / 대한소화기학회지

BACKGROUND/AIMS: Quadruple therapy can be considered as a first-line therapy in areas where the resistance rate to clarithromycin is high. Comparison study of triple therapy and quadruple therapy for Helicobacter pylori (H. pylori) eradication is still lacking in Korea despite the increasing prevalence of antibiotic resistance. This study was conducted to compare the efficacy of triple and quadruple therapy as a first-line treatment in H. pylori infected patients with peptic ulcer. METHODS: Consecutive 149 cases of peptic ulcer disease associated with H. pylori infection were randomized either to proton pump inhibitor (PPI, bid), amoxicillin (1,000 mg, bid), and clarithromycin (500 mg, bid) (PAC group) or to PPI (bid), bismuth subcitrate (300 mg, qid), metronidazole (500 mg, tid), and tetracycline (500 mg, qid) (PBMT group) eradication treatments for 7 days. Outcome of eradication therapy was assessed by 13C-urea breath test performed 4-6 weeks after eradication. RESULTS: Eradication rates in PAC and PBMT group were 78.7% (59/75) and 71.6% (53/74) by intention to treat analysis, respectively (p=0.424). By per protocol analysis, eradication rates of PAC and PBMT group were 85.5% (59/69) and 85.5% (53/62), respectively (p=1.012). Adverse reactions occurred in 5 (6.6%) and 7 (9.5%) patients in PAC and PBMT group, respectively (p=0.346). CONCLUSIONS: One week-quadruple therapy as a first-line treatment for H. pylori infection does not offer any advantage over PPI-based triple therapy in Korean patients.

Hereditary Pancreatitis / 대한소화기학회지

The first family of hereditary pancreatitis was described in 1952. The mode of inheritance is autosomal dominant trait with an 80% of penetrance rate. Although hereditary pancreatitis is rare, this disorder has provided valuable insights in understanding the pathophysiology of pancreatitis and pancreatic cancer. The causative gene of hereditary pancreatitis was identified in 1996 through mutational analysis of genes within chromosome 7q35. Most forms of hereditary pancreatitis are caused by one of two common mutations, R122H in the third exon or N29I in the second exon of the cationic trypsinogen gene (protease serine 1, PRSS1). R122H mutation is the most common PRSS1 mutation. Additional mutations of the cationic trypsinogen gene have been described. In Korea, first family of hereditary pancreatitis with cationic trypsinogen gene mutation revealed an arginine to histidine amino acid substitution at the residue 122. Patients with hereditary pancreatitis present with symptoms at an early age and have significant risk for the development of chronic pancreatitis and pancreatic cancer. The risk of pancreatic cancer is estimated to be 53-fold higher after the age of 50 years than the general population. The risk of pancreatic cancer is not related to the type of mutation. Since hereditary pancreatitis is a strong risk factor for pancreatic cancer, it is important to establish a diagnostic criteria for diagnosis and surveillance. However, there are potential benefits, risks and limitations in genetic testing for hereditary pancreatitis. It is difficult to provide the proper treatment, but recent developments in therapeutic approaches may be helpful in caring hereditary pancreatitis. This article includes the current status, pathogenesis, clinical features, and management of hereditary pancreatitis including the aspects of pancreatic cancer.

Surgical Treatment of Pancreatitis / 대한소화기학회지

The management of pancreatitis remained controversial over the past decades, varying from conservative medical treatment to surgical treatment. However, in recent years, treatment of severe acute pancreatitis is shifting from an early surgical debridement and necrosectomy to an aggressive intensive medical care. While the treatment is conservative in the earlier phase of the disease, surgery might be considered in the later phase. In chronic pancreatitis and in pancreatic pseudocyst, various surgical approaches are available these days. Apart from the conventional open surgery, laparoscopic procedure became popular since it is minimally invasive and effective. In addition, with the great improvements in interventional radiology and endoscopic techniques, multidisciplinary approaches including medical, interventional, and surgical management become much more important in the proper treatment of pancreatitis. In this review, pancreatitis is classified into three categories (acute pancreatitis, chronic pancreatitis, and pancreatic pseudocyst) for convenience, and the surgical treatment is described in each category.

Natural Course and Medical Treatment of Chronic Pancreatitis / 대한소화기학회지

Chronic pancreatitis is a progressive disease without curative treatment. Abdominal pain is the most predominant symptom of chronic pancreatitis that initially brings most of the patients to the physician's attention. Some studies have correlated the course of pain in chronic pancreatitis in comparison with the duration of the disease, progressing exocrine and endocrine pancreatic insufficiency, and morphological changes such as pancreatic calcification and duct abnormalities. Furthermore, the course of pain has been studied after alcohol abstinence or surgery in some groups. However, there are only few well-performed and valid studies, and some of them even have produced diversing results, in part. Further controlled studies harvoring a large number of patients in a multicenter setting should be considered. Therapeutic efforts on chronic pancreatitis have focused on palliative treatment of pain which is present in about 80% of cases. Endoscopic treatment of pain in chronic pancreatitis is useful and feasible in many patients. Selecting candidate for endotherapy is mandatory. Main indication of pancreatic stent insertion in chronic pancreatitis is the presence of an obvious ductal stricture. Complications of chronic pancreatitis are also indications of endoscopic intervention. Exocrine and endocrine insufficiencies should be meticulously managed to prevent complications and to maintain good quality of life.

Medical Management of Acute Pancreatitis and Complications / 대한소화기학회지

Medical management of acute pancreatitis relies on supportive care such as fluid resuscitation and pain control. Prophylactic antibiotics can reduce the opportunity of infection in severe pancreatitis. The effect of somatostatin or protease inhibitors still needs to be evaluated through further study. Early endoscopic retrograde cholangiopancreatography (ERCP) can ameliorate the course of severe biliary pancreatitis. Although sterile pancreatic necrosis, acute fluid collection, and pseudocyst usually resolve spontaneously, endoscopic or percutaneous drainages are needed when these complications are infected.

Diagnosis and Predicting Severity in Acute Pancreatitis / 대한소화기학회지

Acute pancreatitis is an inflammatory disease of pancreas which come from various etiologies. The pathologic spectrum of acute pancreatitis varies from mild edematous pancreatitis to severe necrotizing pancreatitis. To diagnose and to predict severity in acute pancreatitis, various biochemical marker, imaging modalities and clinical scoring sytstem are needed. Ideal parameters should be accurate, be performed easily and enable earlier assess. Unfortunately, no ideal parameter is available up to date. Serum amylase and lipase are still useful for the diagnosis but meaningless in predicting severity. C-reactive protein and inflammatory cytokines are promising single parameters to predict the severity. CT finding is also an useful determinant of severity, but is expensive and is delayed in assessment.

Pancreatitis - Etiology and Pathogenesis - / 대한소화기학회지

Pancreatic inflammatory disease can be classified as acute pancreatitis (AP) and chronic pancreatitis (CP) primarily by clinical criteria, with an obvious difference by restoration of normal function in the former or by permanent residual damage in the latter. Gallstones and alcohol are the most common causes of AP. Recent investigations have established that AP from all cause may disrupt normal stimulus-secretion coupling function within the acinar cell. This disruption within the acinar cell leads to an event termed 'co-localization' in which the digestive and lysosomal enzymes merge resulting in a premature activation of proteases. The mechanisms of inflammatory cells which adhere to endothelial cell are determined by a variety of mediators of cytokines released at the site of tissue damage. Cytokines hold the key for both local and systemic inflammatory response in AP. Besides, CP is a debilitating disease characterized by progressive and irreversible destruction of pancreatic tissue leading to exocrine and endocrine insufficiencies. Alcohol intake is the most common cause of CP. Mutations in the cationic trypsinogen gene were identified as causative gene for hereditary pancreatitis. The recognition of frequent cystic fibrosis transmembrane conductance regulator (CFTR) mutations and serine protease inhibitor, Kazal type 1 (SPINK1) mutations in idiopathic CP has hightened the awareness of importance of genetic mutations in CP. Pancreatic stellate cells represent the main cellular source of extracellular matrix in CP and play a key role in pancreatic fibrosis.

Two Cases of Histopathologically Advanced (Stage IV)Early Gastric Cancer / 대한소화기학회지

Various minimally invasive surgical techniques in some cases of early gastric cancer are becoming common practice. However, there are rare cases of advanced cancer with distant metastasis although the invasion of the gastric wall is limited to the mucosa and/or submucosa (defined as early gastric cancer according to UICC-TNM classification). We report two cases of early gastric cancer with distant metastasis (stage IV). Both tumors were defined as early cancer because they were confined to the submucosa. One was a type IIa early cancer, histologically classifiable as a signet ring cell carcinoma (according to the Japanese Classification of Gastric Carcinoma and UICC-TNM classification); the other was a surface spreading type IIb IIc, classifiable as a signet ring cell carcinoma, too. Stage IV factors were ovarian metastasis (Krukenberg tumor) in the former and N3 in the latter case.

A Case of Intestinal Tuberculosis Presenting Massive Hematochezia Controlled by Endoscopic Coagulation Therapy / 대한소화기학회지

The clinical manifestations of intestinal tuberculosis are non-specific. But, abdominal pain, low grade fever, weight loss, anorexia, and diarrhea are major symptoms of intestinal tuberculosis. Massive bleeding has been reported as a rare manifestation of intestinal tuberculosis. Massive hematochezia from intestinal tuberculosis has rarely been reported in the medical literature. Also, most of them were treated with anti-tuberculosis medication only or with surgery. We treated a case of intestinal tuberculosis presenting massive hematochezia with colonoscopic coagulation therapy and anti-tuberculosis medication. Here, we report a Korean man who presented with massive hematochezia from ileal tuberculosis and treated by endoscopic coagulation therapy.

Expression of Epidermal Growth Factor Receptor, ErbB2 and Matrix Metalloproteinase-9 in Hepatolithiasis and Cholangiocarcinoma / 대한소화기학회지

BACKGROUND/AIMS: Hepatolithiasis is a common disease in East Asia and presents as a histological feature of proliferative glands containing mucin. 5-10% of hepatolithiasis is known to be associated with cholangiocarcinoma. Recent studies reported that epidermal growth factor receptor (EGFR) could be activated through heparin binding- EGF cleavage by metalloproteinases. Matrix metalloproteinases (MMPs) which digest the extracellular matrix are required for cancer cell invasion and the expression of MMP-9 is known to be increased in cholangiocarcinoma. However, there has been few studies on the expressions and roles of EGFR and MMP in hepatolithiasis. This study was performed to clarify and compare the expressions of EGFR, erbB2 and MMP-9 in hepatolithiasis and cholangiocarcinoma. METHODS: Surgically resected liver tissues with hepatolithiasis (n=14), cholangiocarcinoma (n=20) and trauma (n=2 as controls) were included. The expressions of EGFR, erbB2 and MMP-9 in tissue samples were examined by immunohistochemistry using respective monoclonal antibodies. RESULTS: In traumatic livers, the expressions of EGFR, erbB2 and MMP-9 were all negative. The expression of EGFR was increased in hepatolithiasis group (79%, 11/14) compared with cholangiocarcinoma group (25%, 5/20) (p0.05). CONCLUSIONS: EGFR expression appears to be the dominant component in periductular hyperplasia of hepatolithiasis and MMP-9 is upregulated not only in cholangiocarcinoma but also in hepatolithiasis. This study suggests that EGFR and MMP-9 are associated with cholangiocarcinoma and hepatolithiasis.