Determinants of family functioning in caregivers of persons with obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is known to cause significant burden to patients and their caregivers. However, there is limited data on its impact on family functioning, especially from families with an adult member having OCD. METHODS: Four hundred subjects, which included treatment-seeking adult OCD patients (n = 200) and their caregivers (n = 200) were recruited. Patients were evaluated using the Mini International Neuropsychiatric Interview (MINI) and the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Caregivers were evaluated using the MINI, the Caregiver Strain Index (CSI), the Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), the Socio-Occupational Functioning Assessment Scale (SOFAS), the Family Accommodation Scale (FAS) and the Connor-David Resilience scale (CD-RISC) in a cross-sectional interview. Family functioning was measured using the OCD Family Functioning (OFF) Scale. Structural equation modeling (SEM) was carried out to evaluate the relationships between the patient and caregiver variables to predict family functioning. RESULTS: From the best-fitting path model, we ascertained that OCD symptoms did not have a direct relationship with family dysfunction. Their effects were in turn was mediated by family accommodation, anxiety, caregiver stress/burden and depression. "Contamination & washing" was the only significant symptom dimension within the model. Caregiver resilience was found to predict only their individual functioning, and not family functioning. LIMITATIONS: Study sample included patients from a tertiary care OCD service, only one caregiver from each patient's family was interviewed. CONCLUSIONS: Evaluating family functioning, addressing it as part of interventional modules for patients and caregivers may help improving treatment outcomes.

Zinc Biofortified Rice Varieties: Challenges, Possibilities, and Progress in India.

Zinc malnutrition is a major issue in developing countries where polished rice is a staple food. With the existing significant genetic variability for high zinc in polished rice, the development of biofortified rice varieties was targeted in India with support from HarvestPlus, Department of Biotechnology, and Indian Council of Agricultural Research of Government of India. Indian Institute of Rice Research (IIRR) facilitates rice varietal release through All India Coordinated Rice Improvement Project (AICRIP) and also supports rice biofortification program in India. Various germplasm sets of several national institutions were characterized at IIRR for their zinc content in brown rice using energy-dispersive X-ray fluorescence spectroscopy indicating the range of zinc to be 7.3 to 52.7 mg/kg. Evaluation of different mapping populations involving wild germplasm, landraces, and varieties for their zinc content showed the feasibility of favorable recombination of high zinc content and yield. Ninety-nine genotypes from germplasm and 344 lines from mapping populations showed zinc content of ≥28 mg/kg in polished rice meeting the target zinc content set by HarvestPlus. Through AICRIP biofortification trial constituted since 2013, 170 test entries were nominated by various national institutions until 2017, and four biofortified rice varieties were released. Only the test entry with target zinc content, yield, and quality parameters is promoted to the next year; thus, each test entry is evaluated for 3 years across 17 to 27 locations for their performance. Multilocation studies of two mapping populations and AICRIP biofortification trials indicated the zinc content to be highly influenced by environment. The bioavailability of a released biofortified rice variety, viz., DRR Dhan 45 was found to twice that of control IR64. The technology efficacy of the four released varieties developed through conventional breeding ranged from 48 to 75% with zinc intake of 38 to be 47% and 46 to 57% of the RDA for male and female, respectively. The observations from the characterization of germplasm and mapping populations for zinc content and development of national evaluation system for the release of biofortified rice varieties have been discussed in the context of the five criteria set by biofortification program.

The power of peers: an effectiveness evaluation of a cluster-controlled trial of group antenatal care in rural Nepal.

BACKGROUND: Reducing the maternal mortality ratio to less than 70 per 100,000 live births globally is one of the Sustainable Development Goals. Approximately 830 women die from pregnancy- or childbirth-related complications every day. Almost 99% of these deaths occur in developing countries. Increasing antenatal care quality and completion, and institutional delivery are key strategies to reduce maternal mortality, however there are many implementation challenges in rural and resource-limited settings. In Nepal, 43% of deliveries do not take place in an institution and 31% of women have insufficient antenatal care. Context-specific and evidence-based strategies are needed to improve antenatal care completion and institutional birth. We present an assessment of effectiveness outcomes for an adaptation of a group antenatal care model delivered by community health workers and midwives in close collaboration with government staff in rural Nepal. METHODS: The study was conducted in Achham, Nepal, via a public private partnership between the Nepali non-profit, Nyaya Health Nepal, and the Ministry of Health and Population, with financial and technical assistance from the American non-profit, Possible. We implemented group antenatal care as a prospective non-randomized, cluster-controlled, type I hybrid effectiveness-implementation study in six village clusters. The implementation approach allowed for iterative improvement in design by making changes to improve the quality of the intervention. We evaluated effectiveness through a difference in difference analysis of institutional birth rates between groups prior to implementation of the intervention and 1 year after implementation. Additionally, we assessed the change in knowledge of key danger signs and the acceptability of the group model compared with individual visits in a nested cohort of women receiving home visit care and home visit care plus group antenatal care. Using a directed content and thematic approach, we analyzed qualitative interviews to identify major themes related to implementation. RESULTS: At baseline, there were 457 recently-delivered women in the six village clusters receiving home visit care and 214 in the seven village clusters receiving home visit care plus group antenatal care. At endline, there were 336 and 201, respectively. The difference in difference analysis did not show a significant change in institutional birth rates nor antenatal care visit completion rates between the groups. There was, however, a significant increase in both institutional birth and antenatal care completion in each group from baseline to endline. We enrolled a nested cohort of 52 participants receiving home visit care and 62 participants receiving home visit care plus group antenatal care. There was high acceptability of the group antenatal care intervention and home visit care, with no significant differences between groups. A significantly higher percentage of women who participated in group antenatal care found their visits to be 'very enjoyable' (83.9% vs 59.6%, p = 0.0056). In the nested cohort, knowledge of key danger signs during pregnancy significantly improved from baseline to endline in the intervention clusters only (2 to 31%, p < 0.001), while knowledge of key danger signs related to labor and childbirth, the postpartum period, and the newborn did not in either intervention or control groups. Qualitative analysis revealed that women found that the groups provided an opportunity for learning and discussion, and the groups were a source of social support and empowerment. They also reported an improvement in services available at their village clinic. Providers noted the importance of the community health workers in identifying pregnant women in the community and linking them to the village clinics. Challenges in birth planning were brought up by both participants and providers. CONCLUSION: While there was no significant change in institutional birth and antenatal care completion at the population level between groups, there was an increase of these outcomes in both groups. This may be secondary to the primary importance of community health worker involvement in both of these groups. Knowledge of key pregnancy danger signs was significantly improved in the home visit plus group antenatal care cohort compared with the home visit care only group. This initial study of Nyaya Health Nepal's adapted group care model demonstrates the potential for impacting women's antenatal care experience and should be studied over a longer period as an intervention embedded within a community health worker program. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02330887 , registered 01/05/2015, retroactively registered.

Needs of Persons with Neurological Disorders.

BACKGROUND: In India, many persons with neurological disorder (PwND) get discharged from several hospitals with significant unmet needs. AIM: To assess the needs of persons with neurological disorders in a tertiary care hospital, Bangalore, India. METHOD AND MATERIALS: It was a cross-sectional descriptive study where thirty PwND availing the in-patient services at NIMHANS, Bangalore were selected through purposive sampling. Camberwell Assessment of Need - Research version was used. RESULTS: Large majority (90%) of the respondents have unmet needs in daytime activities, psychological distress, information about illness and sex. Majority (70%) have unmet needs in job, self-care, medicines, mobility, child care. Half (50%) of the respondents have unmet need in accommodation, intimate and social relationships, finance. Three-fourth revealed that their need for food, safety and social welfare needs have been met. CONCLUSION: Patients from lower economic, educational status and urban domicile have more service needs. Present study attempts a systematic need assessment which has implication in addressing the unmet needs of PwND to improve their quality of life.

The Question is the Answer: concerns and queries raised by patients and caregivers referred to rehabilitation services.

BACKGROUND: The philosophy of recovery emphasises consumer participation and engagement in developing effective rehabilitation services. Assessment of consumer perspectives and concerns lies at the heart of responsive and relevant rehabilitation frameworks. AIM: The study aimed to document and examine patient and caregiver queries, at their first contact with Rehabilitation Services. METHODS: The sample consisted of 124 consecutive inpatients and their accompanying caregiver/s, referred to Psychiatric Rehabilitation Services, within a tertiary care psychiatric hospital in India. The data were collected using the semi-structured Inpatient Intake proforma during the intake session. The spontaneous queries raised by patients and/or caregivers were documented and content analysis identified themes, separately for patients and caregivers. RESULTS: The results indicated both similarities and differences in the frequency of themes that emerged from questions asked by patients and their caregivers. Two prominent themes centered on specific queries about rehabilitation services and the treatment and prognosis of the psychiatric illness. CONCLUSIONS: The findings have implications for training, practice and research in the field of psychosocial rehabilitation. Recommendations are made for training and practice frameworks to facilitate consumer-service provider communication towards the development of responsive recovery-oriented services.

Innovative dual impression technique for patients with atrophia idiopathica mucosa oris.

Atrophia idiopathica mucosa oris is an oral fibrosing disease resulting in marked rigidity and an eventual inability to open the mouth or had limited mouth opening. Patients with limited mouth opening are a common occurrence in prosthodontic practice. The majority of these patients can be treated with exercise and stretching movements before impressions are made. Some will not respond to these procedures because of facial scarring and surgical manipulation of the facial muscles. This article presents an impression procedure for overcoming difficulties encountered in such reduced mouth opening patients that can be assembled intraorally, disassembled intraorally, and reassembled extraorally.

Medication Adherence, Work Performance and Self-Esteem among Psychiatric Patients Attending Psychosocial Rehabilitation Services at Bangalore, India.

CONTEXT: Work benefits mental health in innumerable ways. Vocational rehabilitation can enhance self-esteem. Medication adherence can improve work performance and thereby the individuals' self-esteem. AIM: To test the hypothesis that there would be a significant correlation between medication adherence, work performance and self-esteem. SETTING AND DESIGN: A quantitative, descriptive correlational research design was adopted to invite patients attending psychiatric rehabilitation services to participate in the research. MATERIAL AND METHODS: Data was collected from a convenience sample of 60 subjects using the 'Medication Adherence Rating scale', 'Griffiths work behaviour scale' and the 'Rosenberg's Self-esteem scale'. STATISTICAL ANALYSIS USED: Analysis was done using spss18 with descriptive statistics, Pearsons correlation coefficient and multiple regression analysis. RESULTS: There were 36 males and 24 females who participated in this study. The subjects had good mean medication adherence of 8.4 ± 1.5 with median of 9.00, high mean self-esteem of 17.65 ± 2.97 with median of 18.0 and good mean work performance of 88.62 ± 22.56 with median of 93.0. Although weak and not significant, there was a positive correlation (r = 0.22, P = 0.103) between medication adherence and work performance; positive correlation between (r = 0.25, P = 0.067) medication adherence and self-esteem; positive correlation between (r = 0.136, P = 0.299) work performance and self-esteem. Multiple regression analysis showed no significant predictors for medication adherence, work performance and self-esteem among patients with psychiatric illness. CONCLUSIONS: Medication monitoring and strengthening of work habit can improve self-esteem thereby, strengthening hope of recovery from illness.

N-Benzoyl-2-nitro-benzene-sulfonamide.

In the title compound, C(13)H(10)N(2)O(5)S, the N-C bond in the C-SO(2)-NH-C segment has gauche torsion angles with respect to the S=O bonds. The conformation between the N-H bond and the ortho-nitro group in the sulfonyl benzene ring is syn. The mol-ecule is twisted at the S-N bond with a torsion angle of -63.4 (2)°. The sulfonyl benzene ring is tilted by 77.1 (1)° relative to the -SO(2)-NH-C-O segment. The dihedral angle between the sulfonyl and the benzoyl benzene rings is 88.6 (1)°. In the crystal, pairs of N-H⋯O(S) hydrogen bonds link the mol-ecules into inversion dimers, which are linked by weak C-H⋯O and C-H⋯π inter-actions along the b axis.

Barriers to discharge of patients from a government-run day-care psychiatric rehabilitation center in India.

OBJECTIVE: Many psychiatric patients undergoing vocational training do not achieve successful transition to regular work. In this study, we evaluated the barriers for discharge from day care center to actual work place. MATERIALS AND METHODS: In a cross-sectional study at a government-run day-care center at National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, we studied 76 patients who were undergoing vocational training for more than 1 year. We did a semi-structured interview with patients, their family members, and instructors of various occupational sections. We used a questionnaire of 17 different barriers to assess the obstacles in their discharge from day-care center to actual work place. RESULTS: The majority of them had a diagnosis of mental retardation (n=47) followed by schizophrenia (n=29), and bipolar disorder (n=9). The mean (SD) age and duration of illness was 33.6 (9.7) years and 12.5 (9.3) years, respectively. Patients had more than one diagnosis. The median duration of stay in day-care center was 5.9 years. Doubts regarding performance at a new work place (n=60), fear of performance at new work place (n=65), and the fear of transition to regular work (n=64) were the most common barriers reported by patients, their family members and instructors of various occupational sections, respectively. DISCUSSION: Educating patients and their family members, gradual exposure to new working environment, and increased community level vocational opportunities may potentially overcome above barriers. Getting them to the actual job early in their course of treatment will improve their adjustment to a new work place and overall outcome.

Blood pressure measurement: one arm or both arm?

Guidelines for measuring blood pressure includes measurement of blood pressure on both arms but it is often ignored. Our case report aims at highlighting the need follow the guidelines. A 60 year old 59 kg weighing male asymptomatic patient without any comobidities was posted for bilateral inguinal hernia repair. The interarm blood pressure difference was discovered incidentally during his preanaesthetic evalution. On further evaluation patient was found to be having subclavian stenosis on left side which was asymptomatic. Intraoperative and post operative period was uneventful. Blood pressure measurement should be done in accordance with the stipulated guidelines. Inter arm blood pressure difference should be noted in all patients as not only for diagnosis and treatment of hypertension but also as a tool to diagnose asymptomatic peripheral vascular disesase.

Expressed emotion and caregiver burden in patients with schizophrenia.

BACKGROUND: Family's expressed emotion has been shown to be predictive of outcome in mental and physical illnesses in a variety of cultural settings. The relationship between caregiver burden and high level of expressed emotions has demonstrated a high level of relapse among the psychiatric patients in the West. AIM: The current study explores the relationship between caregivers' burden and level of expressed emotions by the patients with schizophrenia in Indian setting. MATERIALS AND METHODS: The sample for the study consisted of totally 70 subjects comprising 35 schizophrenic patients and 35 caregivers. The schizophrenic patients who were attending the Day Care Center run by Department of Psychiatric and Neuro Rehabilitation Unit at National Institute of Mental Health and Neuro Sciences (NIMHANS) in Bangalore, India (a tertiary care center) and their primary caregivers were included. Family emotional involvement and criticism scale and The burden assessment schedule were administered to assess the expressed emotions and caregivers' burden. Carl Pearson Correlation test used to study the relationship between the variables. RESULTS AND CONCLUSION: The study highlighted the need for addressing expressed emotion in comprehensive psychosocial intervention plan. More attention should be paid to the needs of the caregivers in order to alleviate their burden in managing mentally ill patients.

Work-Life Balance among Married Women Employees.

UNLABELLED: Family-work conflict (FWC) and work-family conflict (WFC) are more likely to exert negative influences in the family domain, resulting in lower life satisfaction and greater internal conflict within the family. Studies have identified several variables that influence the level of WFC and FWC. Variables such as the size of family, the age of children, the work hours and the level of social support impact the experience of WFC and FWC. However, these variables have been conceptualized as antecedents of WFC and FWC; it is also important to consider the consequences these variables have on psychological distress and wellbeing of the working women. AIM: to study various factors which could lead to WFC and FWC among married women employees. MATERIALS AND METHODS: The sample consisted of a total of 90 married working women of age between 20 and 50 years. WFC and FWC Scale was administered to measure WFC and FWC of working women. The obtained data were analyzed using descriptive and inferential statistics. Carl Pearson's Correlation was used to find the relationship between the different variables. FINDINGS AND CONCLUSION: The findings of the study emphasized the need to formulate guidelines for the management of WFCs at organizational level as it is related to job satisfaction and performance of the employees.

Detection of intercellular adhesion genes and biofilm production in Staphylococcus aureus isolated from bovine subclinical mastitis.

Biofilm production by Staphylococcus aureus, an important virulence factor was investigated employing phenotypic and genotypic methods. A total of 102 S. aureus isolates from bovine subclinical mastitis cases were included in the study. Maximum number of biofilm producing strains were detected by Congo red agar (CRA) method (48.03%) followed by tube method (36.27%). Tissue culture plate method (TCP) without and with destaining identified 19.60 and 29.41% of S. aureus as biofilm producers, respectively. A polymerase chain reaction for detection of intercellular adhesion genes, icaA and icaD, responsible for biofilm formation was standardized. Of the 102 S. aureus isolates investigated, 36 (35.29%) strains revealed presence of both the genes. Considering polymerase chain reaction as a standard test, CRA and TCP without destaining were the most sensitive and specific, respectively. PCR technique standardized for detection of the icaA and icaD genes is reliable for identifying biofilm producing potential of S. aureus which may help in rapid detection of biofilm-producer Staphylococci. This would allow the early application of control measures.

Production of monoclonal antibodies against recombinant human zona pellucida glycoproteins: utility in immunolocalization of respective zona proteins in ovarian follicles.

The zona pellucida (ZP) glycoproteins play an important role in oocyte development and gamete biology. To analyze their expression in follicles during various developmental stages, murine monoclonal antibodies (MAbs) were generated against the baculovirus-expressed recombinant human ZP2, ZP3 and ZP4. A panel of MAbs specific for the respective zona protein in ELISA and Western blot, and devoid of cross-reaction with other zona proteins was selected. Immunohistochemistry has shown that ZP2 MAb, MA-1620, did not react with oocytes in resting primordial follicles but showed reactivity with degenerating oocytes in primordial follicles undergoing atresia, and with oocytes in growing and antral follicles. Three MAbs against ZP3 did not react with oocytes in primordial follicles, but reacted only with oocytes in growing and antral follicles. Out of four MAbs against ZP4, three MAbs reacted with oocytes in primordial, growing and antral follicles. No reactivity of these MAbs with other ovarian cell types and other tissues studied (endometrium, uterine cervix, fallopian tubes and kidney) was detected except for a strong reactivity of ZP2 MA-1620 with epithelial cells of the uterine ectocervix or endometrium in some samples investigated. Altogether, these studies document generation of MAbs exhibiting high specificity for human zona proteins, which will be useful reagents to study their immunobiology.

Study origin of germ cells and formation of new primary follicles in adult human and rat ovaries.

The central thesis regarding the human ovaries is that, although primordial germ cells in embryonal ovaries are of extraovarian origin, those generated during the fetal period and in postnatal life are derived from the ovarian surface epithelium (OSE) bipotent cells. With the assistance of immune system-related cells, secondary germ cells and primitive granulosa cells originate from OSE stem cells in the fetal and adult human gonads. Fetal primary follicles are formed during the second trimester of intrauterine life, prior to the end of immune adaptation, possibly to be recognized as self-structures and renewed later. With the onset of menarche, a periodical oocyte and follicular renewal emerges to replace aging primary follicles and ensure that fresh eggs for healthy babies are always available during the prime reproductive period. The periodical follicular renewal ceases between 35 and 40 yr of age, and the remaining primary follicles are utilized during the premenopausal period until exhausted. However, the persisting oocytes accumulate genetic alterations and may become unsuitable for ovulation and fertilization. The human OSE stem cells preserve the character of embryonic stem cells, and they may produce distinct cell types, including new eggs in vitro, particularly when derived from patients with premature ovarian failure or aging and postmenopausal ovaries. Our observations also indicate that there are substantial differences in follicular renewal between adult human and rat ovaries. As part of this chapter, we present in detail protocols utilized to analyze oogenesis in humans and to study interspecies differences when compared to the ovaries of rat females.

Origin of germ cells and formation of new primary follicles in adult human ovaries.

Recent reports indicate that functional mouse oocytes and sperm can be derived in vitro from somatic cell lines. We hypothesize that in adult human ovaries, mesenchymal cells in the tunica albuginea (TA) are bipotent progenitors with a commitment for both primitive granulosa and germ cells. We investigated ovaries of twelve adult women (mean age 32.8 +/- 4.1 SD, range 27-38 years) by single, double, and triple color immunohistochemistry. We show that cytokeratin (CK)+ mesenchymal cells in ovarian TA differentiate into surface epithelium (SE) cells by a mesenchymal-epithelial transition. Segments of SE directly associated with ovarian cortex are overgrown by TA, forming solid epithelial cords, which fragment into small (20 micron) epithelial nests descending into the lower ovarian cortex, before assembling with zona pellucida (ZP)+ oocytes. Germ cells can originate from SE cells which cover the TA. Small (10 micron) germ-like cells showing PS1 meiotically expressed oocyte carbohydrate protein are derived from SE cells via asymmetric division. They show nuclear MAPK immunoexpression, subsequently divide symmetrically, and enter adjacent cortical vessels. During vascular transport, the putative germ cells increase to oocyte size, and are picked-up by epithelial nests associated with the vessels. During follicle formation, extensions of granulosa cells enter the oocyte cytoplasm, forming a single paranuclear CK+ Balbiani body supplying all the mitochondria of the oocyte. In the ovarian medulla, occasional vessels show an accumulation of ZP+ oocytes (25-30 microns) or their remnants, suggesting that some oocytes degenerate. In contrast to males, adult human female gonads do not preserve germline type stem cells. This study expands our previous observations on the formation of germ cells in adult human ovaries. Differentiation of primitive granulosa and germ cells from the bipotent mesenchymal cell precursors of TA in adult human ovaries represents a most sophisticated adaptive mechanism created during the evolution of female reproduction. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. An essential mission of such follicular turnover might be elimination of spontaneous or environmentally induced genetic alterations of oocytes in resting primary follicles.

Multiple luteinizing hormone receptor (LHR) protein variants, interspecies reactivity of anti-LHR mAb clone 3B5, subcellular localization of LHR in human placenta, pelvic floor and brain, and possible role for LHR in the development of abnormal pregnancy, pelvic floor disorders and Alzheimer's disease.

Distinct luteinizing hormone receptor (LHR) protein variants exist due to the posttranslational modifications. Besides ovaries, LHR immunoreactivity (LHRI) was also found in other tissues, such as the brain, fallopian tube, endometrium, trophoblast and resident tissue macrophages. The 3B5 mouse monoclonal antibody was raised against purified rat LHR. In rat, porcine and human ovaries, the 3B5 identified six distinct LHR bands migrating at approximately 92, 80, 68, 59, 52 and 48 kDa. Characteristic LHRI was detected in rat, human and porcine corpora lutea. During cellular differentiation, subcellular LHR distribution changed from none to granular cytoplasmic, perinuclear, surface, nuclear and no staining. There were also differences in vascular LHR expression--lack of LHRI in ovarian vessels and strong staining of vessels in other tissues investigated. In normal human term placentae, villous LHRI was associated with blood sinusoids and cytotrophoblast cells, and rarely detected in trophoblastic syncytium. In all abnormal placentae, the LHRI of sinusoids was absent, and syncytium showed either enhanced (immature placental phenotypes) or no LHRI (aged placental phenotype). LHRI in human brain was identified in microglial cells (CD68+ resident macrophages). Protein extracts from human vaginal wall and levator ani muscle and fascia showed strong approximately 92 and 68 kDa species, and LHRI was detected in smooth muscle cells, fibroblasts, resident macrophages and nuclei of skeletal muscle fibers. Our observations indicate that, in contrast to the theory on the role of vascular hormone receptors in preferential pick up of circulating hormones, there is no need to enhance selective pick up rather only prevent LH/CG transport to inappropriate sites. Abnormal placental LHR expression may play a role in the development of abnormal pregnancy. Expression of LHR in the pelvic floor compartments suggests that high LH levels in postmenopausal women may contribute to the pelvic floor relaxation and increased incidence of pelvic floor disorders. Since chorionic gonadotropin increases secretion of a variety of cytokines by monocytes, and induces their inflammatory reaction and phagocytic activity, high LH levels in aging individuals may also activate microglia (mononuclear phagocyte system in the central nervous system) and contribute to the development of Alzheimer's disease and other inflammation-mediated neurodegenerative diseases.