Survival analysis and predictors of long-term outcomes following radical nephrectomy with inferior vena cava (IVC) thrombectomy in renal cell carcinoma

Background: Renal cell carcinoma (RCC) presents with inferior vena cava (IVC) thrombus in 10%�% cases and surgical management forms the mainstay of the treatment. The objective of this study is to assess the outcomes of the patients undergoing radical nephrectomy with IVC thrombectomy. Methods: A retrospective analysis of patients undergoing open radical nephrectomy with IVC thrombectomy between 2006 till 2018 was done. Results: A total of 56 patients were included. The mean (眘tandard deviation) age was 57.1 (�.2) years. The number of patients with levels I, II, III, and IV thrombus were 4, 29,10, and 13, respectively. The mean blood loss was 1851.8 mL, and the mean operative time was 303.3 minutes. Overall, the complication rate was 51.7%, while the perioperative mortality rate was 8.9%. The mean duration of hospital stay was 10.6 � 6.4 days. The majority of the patients had clear cell carcinoma (87.5%). There was a significant association between grade and stage of thrombus (P = 0.011). Using Kaplan朚eier survival analysis, the median overall survival (OS) was 75 (95% confidence interval [CI] = 43.5�6.5) months, and the median recurrence-free survival (RFS) was 48 (95% CI = 33.1�.3) months. Age (P = 0.03), presence of systemic symptoms (P = 0.01), radiological size (P = 0.04), histopathological grade (P = 0.01), level of thrombus (P = 0.04), and invasion of thrombus into IVC wall (P = 0.01) were found to be significant predictors of OS. Conclusion: The management of RCC with IVC thrombus poses a major surgical challenge. Experience of a center along with high-volume and multidisciplinary facility particularly cardiothoracic facility provides better perioperative outcome. Though surgically challenging, it offers good overall-survival and recurrence-free survival

Retinitis pigmentosa in Laurence-Moon-Bardet-Biedl syndrome in India: Electronic medical records driven big data analytics: Report II

Purpose: To describe the clinical presentation and demographic distribution of retinitis pigmentosa (RP) in Laurence–Moon–Bardet–Biedl (LMBB) syndrome patients. Methods: This is a cross?sectional observational hospital?based study wherein 244 patients with RP in LMBB syndrome presenting to our hospital network between March 2012 and October 2020 were included. An electronic medical record database was used for data retrieval. Results: There were 244 patients in total, with a hospital?based prevalence rate of 0.010% or 1000/100,000 population. The mean and median age of patients was 15.22 ± 7.56 and 14 (IQR: 10–18.5) years, respectively, with the majority being in the age group of 11–20 years (133/244 patients; 54.50%). Males were more commonly affected (164 patients; 67.21%), and the majority (182 patients; 74.59%) were students. All 244 patients (100%) complained of defective central vision at presentation. More than one?fourth of the patients had severe visual impairment to blindness at presentation. Prominent retinal feature at presentation was diffuse or widespread retinal pigment epithelial degeneration in all patients. Conclusion: Patients with RP in LMBB syndrome present mainly in the first to second decade of life with severe visual acuity impairment to blindness early in life. It is important to rule out LMBB syndrome in early?onset RP with central visual acuity impairment. On the contrary, all patients diagnosed or suspected with LMBB syndrome systemic features at physician clinic should also be referred for ophthalmic evaluation, low vision assessment, rehabilitation, and vice versa

Labial fusion: A rare cause of obstructive lower urinary tract symptoms in old age females

Lower urinary tract symptoms in females can be due to various factors. Most of the time it is due to simple urinary tract infection and lower urinary tract pathology such as urethral stricture, meatal stenosis, bladder stones, underactive detrusor, and primary bladder neck obstruction. Commonly found neurologic causes among females are detrusor–external sphincter dyssynergia, associated with various brain and spine diseases and diabetic neuropathy. Labial fusion is a rare cause of female voiding difficulty. We herein present two elderly postmenopausal diabetic female patients who had nearly total urethral occlusion due to labial fusion. After thorough history taking and local genitourinary examination, the patients were operated. Treatment included surgical correction followed by the local application of 1% estrogen ointment. Both patients were symptom-free after the procedure. Thus, with a correct diagnosis followed by simple operative procedure, we can treat such patients successfully.

Antimicrobial, Antioxidant and Antibiofilm Potential of Peppermint (Mentha piperita) Essential Oil for Application in Meat Products

The current study was carried out to examine in-vitro antimicrobial, antioxidant and antibiofilm efficacy of Peppermint essential oil (PEO) for its potential application in meat products. Antimicrobial activity was measured by using zone inhibition assay (ZOI) and Minimum Inhibitory Concentration (MIC) against ten food borne pathogens including four Gram-positive viz. Listeria monocytogenes, Enterococcus faecalis, Bacillus cereus and Staphylococcus aureus and six Gram-negative viz. Proteus mirabilis, Salmonella enterica serovar Typhi, Klebsiella pneumonia, Shigella flexneri, Escherichia coli and Pseudomonas aeruginosa whereas antioxidant assay was measured using 1,1 diphenyl-2 picrylhydrazyl (DPPH) and 2-2- azinobis-3 ethylbenthiazoline-6-sulphonic acid (ABTS) radical scavenging activity. Maximum zone size was observed for Proteus mirabilis whereas, MIC values ranged from 5000-20000 ppm for all tested organisms. The oil was found to be more effective against Pseudomonas aeruginosa and Salmonella enterica serovar Typhi. Antibiofilm activity (%) was also performed against pure cultures of two pathogens i.e. Listeria monocytogenes and Proteus mirabilis as positive control. The results exhibited that with application of PEO, biofilm formation of both Listeria monocytogenes and Proteus mirabilis was inhibited by 45.80% and 73.01%, respectively in contrast to their respective controls. ABTS and DPPH radical scavenging activity of PEO was measured at five different concentrations and values were ranging from 17.24-49.07% for ABTS whereas 35.16 – 60.70% for DPPH under investigation. It can be concluded that peppermint essential oil possesses potent antimicrobial, antioxidant and antibiofilm activity and can be further used as a natural alternative for preservation in meat industry

Role of miRNA-182 and miRNA-187 as potential biomarkers in prostate cancer and its correlation with the staging of prostate cancer

ABSTRACT Purpose The microRNAs expression has emerged as a potential biomarker for the diagnosis and prognosis of prostate cancer. This study investigated the expression of miRNA-182 and miRNA-187 in prostate cancer patients and established a correlation between miRNA expression and staging of prostate cancer. Materials and Methods This prospective observational study involved patients undergoing transrectal ultrasound-guided biopsy for suspicion of prostate cancer. Pre-biopsy urine samples and prostatic core tissue samples of the patients were preserved and the miRNA-182 and miRNA-187 were studied. Results Sixty-three patients were included in this study, thirty-three patients were diagnosed with prostate cancer and thirty patients having benign histopathology were considered as controls. The expression of miRNA-182 was significantly increased (p=0.002) and miRNA-187 significantly decreased (p <0.001) in prostate cancer tissue specimens. However, the expression of these miRNAs did not significantly differ in the urine of prostate cancer patients as compared to controls. Serum Prostatic Specific Antigen (PSA) inversely correlated with the median expression of miR-187 in prostatic tissue (p=0.002). Further, the expression of miRNA-187 in prostate cancer tissue was significantly decreased in metastatic prostate cancer (p=0.037). Using ROC analysis, miRNA-187 expression was able to distinguish the presence or absence of bone metastasis [area under ROC (AUROC) (±SD) was 0.873±0.061, p <0.001]. Conclusion The miRNA-182 and miRNA-187 appear to be promising biomarkers in prostate cancer and miRNA-187 can serve as an important diagnostic marker of metastatic prostate cancer.

Comparison of Basement Membrane in Normotensive and Pregnancy Induced Hypertensive Placentae

Introduction: Placenta is related to mother and foetus viaindirect interaction with maternal blood that spurts out ofuteroplacental vessels. By study of placental bed newinformation has come to light, especially for pre – eclampsiaand intra uterine fetal growth retardation.Aim: To study changes in basement membrane in pregnancyinduced hypertensive and normotensive placentae.Materials and Methods: The present study was conducted inthe Department of Anatomy, MMMCH, Kumarhatti, Solan tostudy the histological changes in placenta in pregnancyinduced hypertensive parturients as compared to normotensivesubjects. It was based on 100 cases, 25 from normotensivesubjects (control group) and 75 from clinically proven cases ofpregnancy induced hypertension (study group).An attempt was made to see any changes in histologicalfeatures of placentae of pregnancy induced hypertensive casesand compare it with normotensive placentae.Results and Conclusion: The microscopic study showedsignificant thickening of basement membrane in PIH placentae.As compared to normotensive placentae (control) and are dueto occlusion or narrowing of utero placental vasculaturesuggesting thereby compromised foeto – placental circulation.

The Spectrum of Clinical and Urodynamic Findings in Patients with Spinal Tuberculosis Exhibiting Lower Urinary Tract Symptoms, before and after Spinal Surgical Intervention with Antitubercular Treatment: A Prospective Study

STUDY DESIGN: Observational study. PURPOSE: This study aims to assess the clinical and urodynamic parameters in patients with spinal tuberculosis (TB) exhibiting lower urinary tract symptoms (LUTS) at the time of presentation and after spinal surgical intervention. OVERVIEW OF LITERATURE: Variable urodynamic findings in patients with spinal TB. METHODS: We prospectively evaluated 10 patients with spinal TB exhibiting LUTS. Urinary symptoms were assessed by the American Urological Association (AUA) symptom score. We performed a urodynamic study (UDS), including electromyography, in all patients before and 3 months after spinal surgery. RESULTS: The mean age of patients was 29.7 years (range, 15–52 years), and the mean AUA symptom score was 12.5 and 11.8 before and after spinal surgery, respectively. Overall, five patients exhibited improvement in the AUA symptom score, and three showed no change, while two patients’ condition worsened. We observed detrusor overactivity (DO) in two patients, and detrusor sphincter dyssynergia (DSD) in four patients. In addition, high-pressure voiding (HPV) was noted in two patients. On follow-up after spinal surgery, DO and DSD exhibited no improvement. Although HPV resolved, two patients developed new-onset poor compliance with worsening DO and DSD. Furthermore, two patients had bilateral hydronephrosis before surgery, which resolved on follow-up. CONCLUSIONS: Patients with spinal TB exhibiting LUTS can display a spectrum of clinical presentations and variable UDS findings. As two patients exhibited new onset poor compliance with bilateral hydronephrosis in one of them, this study concludes that a close follow-up for upper tracts in these patients is required despite successful spinal surgery.

A Study Of Sacral Index In Eastern Rajasthan Population In Comparison To Other North-west Populations Of India

Background: Human skeleton is an excellent source for genetic, anthropological and forensic investigations.Pelvic bones are very important for sex determination, followed by skull & the long bones. Various parametersand indices are available based on which the sex can be determined using sacrum. These parameters and indicesvary region wise also. The sacrum has always attracted the attention of the medico-legal experts for establishingits gender, because of its contribution to pelvic girdle and associated functional gender differences. In presentstudy the sacral index in Eastern Rajasthan population is calculated and compared with the study done earlierin Western Rajasthan & North Indian Population.Objective: To study the Sacral Index in the population of Eastern Rajasthan, so that it can be compared with otherstudies on populations of Western Rajasthan & other regions of North India.Materials and Methods: Study was carried out in Department of Anatomy, Jaipur National University IMSRC,Jaipur, Rajasthan. Adult, dry sacra were collected randomly from Anatomy department of different Medicalcolleges of Eastern Rajasthan, with the kind permission of the concerned department. 87 sacra were classifiedinto 48 male and 39 female bones by observing the parameters like – Maximum length of sacrum, Maximumwidth of sacrum and Sacral index.Results: In this present study Mean of sacral index in Males was 104.39 and that for Females was 121.02. Meanvalue of Sacral Index in females was significantly higher than in males. Difference between male and femalemean was statistically highly significant.Conclusion: It was found after comparison that sacral index is more in females than males in different populations.The comparative analysis with other races showed a clear racial difference for the sacral index. Hence it is areliable and significant criteria for sex determination of sacrum

Feasibility of ultra low-dose coronary computed tomography angiography

There is an urgent need to develop new protocols to reduce radiation dose of coronary computed tomography angiography (CTA). The aim of this pilot study was to demonstrate the feasibility of an ultra-low dose CTA scanning.

Bone Marrow Aspiration Findings in HIV Positive Patients and Correlation with CD4 Count

Background: Bone marrow abnormalities are common in HIV infected individuals and patients with AIDS. Most of the bone marrow abnormalities associated with HIV infection appear to be related directly to the infection or its complications and not to therapeutic intervention. Bone marrow study is an important investigation in HIV infected patients with peripheral hematological abnormalities. The primary objective was to study bone marrow aspiration findings in HIV positive patients and their correlation with CD4 count. Methods: The interventional, crossectional and prospective study was conducted in Department of Pathology, Government Medical College and Rajindra Hospital Patiala on 100 HIV positive patients, during a period of 2 years. Hematological investigations including complete hemogram, peripheral blood film and bone marrow aspiration was done. Absolute CD4 counts were done. Correlation of various bone marrow abnormalities was done with CD4 count. Results: Bone marrow revealed normocellular marrow in majority of cases, followed by hypocellular. Overall prevalence of myelodysplasia was 78%. Dyserythropoiesis was most common dysplastic change (62%) followed by dysmegakaryopoies (36%), dysgranulopoiesis (25%). Reactive plasmacytosis was seen in 44% cases in the range from 6-20%. Increased lymphocytes seen in 9% cases. There was seen significant correlation between myelodysplasia and CD4 count. Conclusion: Bone marrow abnormalities are common in HIV infected individuals and patients with AIDS.So HIV infection should be considered in the differential diagnosis of patients with secondary myelodysplasia or unexplained bone marrow changes.

Histopathological and Endoscopic Correlation of Gastric Lesions in Endoscopic Gastric Biopsies

ackground: There are a number of lesions that could affect the stomach varying from dyspepsia to highly lethal cancers; that can be chronic and incapacitating or merely an occasional discomfort or asymptomatic. Objective: The study was done to establish a correlation between endoscopic findings and histopathological characteristics of the various pathological gastric lesions. Methods: The study was a prospective study and done on 150 affected patients in 2 years. The endoscopic biopsy was taken from number of points of suspicious lesion for histopathologic diagnosis of the type of gastric lesions. The biopsies were fixed in formalin and adequately processed. The sections were stained with routine Haematoxylin and Eosin stain. Giemsa staining for H.pylori was also done. Results: In this study the most common clinical indications for endoscopic biopsy were pain epigastrium (82.0%) and dyspepsia (67.3%) with mean age of 54.25 and male predominance (1.9:1). The various gastric lesions were chronic gastritis (66.0%), adenocarcinoma (8.0%), no specific diagnosis (8.0%), dysplasia (4.7%), hyperplastic polyp (4.7%), acute on chronic gastritis (3.3%), eosinophilic gastritis (2.0%), acute gastritis (1.3%), intestinal metaplasia (1.3%) and chronic atrophic gastritis (0.7%). Conclusion: H. pylori is most commonly associated with acute on chronic gastritis.

A comparative study of the effects of medical versus surgical androgen deprivation therapy on health-related quality of life in patients with metastatic carcinoma prostate

INTRODUCTION: Androgen deprivation therapy (ADT) is known to adversely affect the quality of life (QoL). One may choose between surgical and medical forms depending on his economic status, education status, and taboos. The aim of this study was to assess the impact of medical versus surgical ADT on health-related quality of life (HRQoL) in patients with metastatic cancer prostate in Indian population. MATERIALS AND METHODS: From July 2012 to December 2014, 50 patients (10 medical castration and 40 surgical castration) of hormone-naïve metastatic prostate cancer who were started on combined ADT were included in this study. Before starting therapy, baseline data and QoL score (short form [SF-36] scale) were noted and all patients were followed up at 3 months, 6 months, and 1 year. Baseline data and HRQoL at all time intervals between surgical and medical castration groups were compared. RESULTS: All patients, except two, completed the 1-year follow-up period. Patients who opted for medical castration were more educated and belonged to higher socioeconomic status. For all the domains of SF-36 QoL questionnaire, a similar improvement in the score was noted at first 3-month follow-up which deteriorated in the next follow-up at 6 months and then further at 1 year. There was no difference in HRQoL after medical or surgical castration. CONCLUSIONS: In patients with metastatic cancer, prostate initiation of ADT, irrespective of method, causes an initial improvement in HRQoL followed later by a more gradual decline below the baseline

Study of Carpal Bone Ossification by Using Radiological Method for Age Estimation of Infant and Paediatric Group in North Indian Population

Background: Ossification of carpal bones forms the most significant aspect of development in clinical sciences and in medical jurisprudence. Important factors influencing the process of ossification include age, sex, heredity, the state of nourishment and particular geographical region may not be exactly similar to that in another area. The main purpose of this study is to evaluate the average age of appearance of the ossification centre of Indian population in comparison with western data. Materials & Methods: Present work was performed in 200 healthy individual of both sexes of which  date of birth proof was present .  X-ray of carpal bones were taken for presence or absence of centre of ossification of the individual carpal bones. Results: In the present study 102(51%)males  and 98 (49%) females  were taken who had accurate birth certificate indicating their age from  < 6 month to 12 year. Variation in the appearance of centre of ossification in carpal bones shows influence of race, climate, nutritional, and geographical factors. Conclusion: Ossification of carpal bones  in the population of North India occur 1-2 year later then  Europeans and  appearance of the ossification centre is earlier in females  than males .

Aggressive Angiomyxoma of Vagina: A Rare Case Report

Aggressive angiomyxoma is a rare, locally invasive mesenchymal tumor predominantly presenting in women of reproductive age and also having a moderate-to-high risk for local relapse. Hence, it needs to be differentiated from other mesenchymal tumors occurring in this region. We present here a case of a 47 Year old female, with chief complaints of prolapsed uterus since 6 months. During clinical examination, posterior vaginal wall swelling was also identified. Total Abdominal Hysterectomy with Bilateral Salpingoophrectomy was done along with removal of posterior vaginal wall swelling. On histopathology, diagnosis of aggressive angiomyxoma was made. We report this case because of its rarity.

Infiltrating Intramuscular Lipoma: A Rare Case Report

ipomas are the common benign tumors of adipose tissue, but sometimes clinically and grossly they simulate malignancy. Lipomas can also occur in deep soft tissues. One of its rare subtype is Intramuscular lipoma which arise within the skeletal muscle fibers. Most common site is trunk, but can also occur in thigh and head and neck. 20 % recur due to incomplete excision. Histopathology is must for confirmation of the diagnosis. Prognosis of intramuscular lipoma is very good and marginal excision is the treatment of choice. We report a case of a 23 Year old female, who presented in surgery OPD with chief complaint of swelling at upper right side of back since 1 year. She got operated for the same 8 months back but presented with similar complaint at same site after 4 months. Excision of the swelling was done and sent for histopathology. On gross examination skin covered soft tissue piece, grayish brown in color was received. Histopathology revealed Infiltrating intramuscular lipoma. The case was reported because of its rarity.

Adenomatoid Tumor of Epididymis: A Rare Case Report

Adenomatoid tumors are rare benign neoplasms of the paratesticular region, most commonly occurring at the tail of the epididymis. We present a case of adenomatoid tumor in a 65 year old male, known case of prostatic adenocarcinoma, who presented in Urology OPD with painless swelling in testis. Bilateral orchidectomy was done with clinical suspicion of testicular carcinoma. On histopathology, diagnosis of adenomatoid tumor of epididymis was made. Due to its rarity, it is important for the physician and pathologist to be aware of this interesting entity in order to make a correct diagnosis.

Child Survival Status in India.

The National Health Mission (NHM, previously called National Rural Health Mission) was launched by Government of India in 2005 to make architectural correction of the Health system. One of the primary Goals of the Mission was to reduce Under five Mortality rate (U5MR) vis a vis Global commitment made under Millennium development Goals especially Goal numbering 4. Although, India still contributes to about one fifth of U5MR and Maternal Mortality rate but unfortunately it contributes to one third of Global Neonatal Mortality Rate. In sheer numbers alone, these rates are alarming. However, India has achieved a faster pace of reduction in U5MR by 46.5% in comparison to 41% for the entire world. In this article, data from Sample Registration System of the Registrar General of India which is available for most of the States/UTs has been analyzed for child health indicators in the country. In the next NHM phase, focused efforts need to be made with state specific Goals so as that the desired targets could be achieved.

Caracterización de hábitos relacionados con enfermedades crónicas en población universitaria de Honduras / Characterization of habits related to chronic diseases in the university population of Honduras

Objetivo: caracterizar por primera vez los principales hábitos relacionados con las enfermedades crónicas no transmisibles en estudiantes universitarios. Método: estudio descriptivo transversal en una muestra estimada de 248 estudiantes entre indígenas y mestizos que ingresaron en 2012 en la Universidad Nacional de Agricultura, Honduras. Se contó con la aprobación del Comité de Ética del Instituto de Nutrición de Centroamérica y Panamá y con el consentimiento de los participantes. Se aplicó el cuestionario STEPS para recolectar información sociodemográfica, consumo de frutas, verduras, tabaquismo, alcoholismo y actividad física. Se realizó examen físico que incluyó toma de presión arterial, medida de la cintura, talla, peso y glucometría. Resultados: en la muestra, 139 (56,28 por ciento) eran hombres. La edad promedio fue de 21,5 años. El 22,22 por ciento tenía sobrepeso; 4,12 por ciento bajo peso y 3,29 por ciento obesidad; 12,75 por ciento declararon fumar y 53,5 por ciento consumir alcohol. En promedio, hombres y mujeres, consumían 1,6 y 1,1 porciones de frutas y verduras al día respectivamente. El 94,74 por ciento utilizaba bicicleta o caminaba al menos 10 minutos; 58,1 por ciento practicaba deportes. El 98 pior ciento tenía presión arterial normal y el 5,74 por ciento prediabetes (101-125 mg/dL en ayunas). Conclusiones: la población estudiantil lenca y otras etnias no se diferencian en su estado nutricional de los mestizos. La población posee factores protectores para las enfermedades crónicas no transmisibles como actividad física y bajo consumo de tabaco, pero ingieren apenas frutas y verduras. Las mujeres participan menos en deportes(AU)

Objective: to characterize for the first time the main habits related to non-communicable chronic diseases in university students. Methods: a cross-sectional and descriptive study was conducted in an estimated sample of 248 students from native and mixed groups, who joined the National University of Agriculture in 2012 in Honduras. The study was approved by the Ethics Committee of the Institute of Nutrition of Central America and Panama. The participants gave their informed consent. The questionnaire STEPS was used for collecting socio-demographic information, data on consumption of fruits, vegetables, smoking, alcohol and physical activity. A physical examination including measurement of height, weight, waist, blood pressure and blood glucose levels was performed in all of them. Results: of the surveyed 248 students, 139 (56.28 percent) were men. The average age was 21.5 years and 63.71 percent of the participants had a monthly family income of less than US$255. In the group, 22.22 percent ere overweighed, 3.29 percent obese and 4.12 percent low weighed. Alcohol was taken by 53.5 percent and 12.75 percent were current smokers. An average of 1.6 and 1.1 portions of fruits and vegetables per day were consumed, respectively. In this sample, 94.74 percent rode a bicycle or walked at least 10 minutes a day; 58.1 percent played sports. Most of them (98 percent ad normal blood pressure and 5.74 percent howed pre-diabetic glucose levels (101-125 mg/dL on fasting). Conclusions: the lencas and other native groups were not important different in nutritional status from students of mixed race. The population has protective factors that prevent it from developing non communicable diseases like physical activity and low smoking indexes; however, they barely consume fruits and vegetables. Women were especially less involved in sports(AU)

Functional and structural abnormalities associated with empathy in patients with schizophrenia: An fMRI and VBM study.

Empathy deficit is a core feature of schizophrenia which may lead to social dysfunction. The present study was carried out to investigate functional and structural abnormalities associated with empathy in patients with schizophrenia using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). A sample of 14 schizophrenia patients and 14 healthy control subjects matched for age, sex and education were examined with structural highresolution T1-weighted MRI; fMRI images were obtained during empathy task in the same session. The analysis was carried out using SPM8 software. On behavioural assessment, schizophrenic patients (83.00±29.04) showed less scores for sadness compared to healthy controls (128.70±22.26) (p<0.001). fMRI results also showed reduced clusters of activation in the bilateral fusiform gyrus, left lingual gyrus, left middle and inferior occipital gyrus in schizophrenic subjects as compared to controls during empathy task. In the same brain areas, VBM results also showed reduced grey and white matter volumes. The present study provides an evidence for an association between structural alterations and disturbed functional brain activation during empathy task in persons affected with schizophrenia. These findings suggest a biological basis for social cognition deficits in schizophrenics.