Bilateral Pleural Effusion: A Rare Case Report.

A 24-year-old female presented with complaints of distension of abdomen, lower limb swelling and shortness of breath. On examination, she had bilateral pedal oedema, tender mild hepatomegaly, bilateral pleural effusion and ascites. She had received treatment on lines of chronic liver disease, congestive heart failure but did not manifest any improvement. Laboratory investigations including haemogram, echocardiography and liver function testing were inconclusive. Ultrasonography and computed tomography of abdomen revealed obstruction at the junction of inferior vena cava and hepatic vein with pre-stenotic dilatation confirming the diagnosis of Budd-Chiari syndrome. She was treated with balloon dilatation from right femoral vein and the patient showed marked recovery with decrease in ascites and bilateral pleural effusion and improvement in dyspnoea and leg swelling.

Pulmonary Agenesis.

Unilateral opaque lung with ipsilateral mediastinal shift is an uncommon cause of respiratory distress in newborn which can be found on simple radiograph of the chest. Pulmonary agenesis is a rare cause of unilateral opaque lung in the newborn. Nearly 50% cases of pulmonary agenesis are associated with other congenital defects including cardiovascular, skeletal, gastrointestinal or genitourinary systems. We report an infant with agenesis of the right lung associated with other congenital anomalies.

NCCP-ICS joint consensus-based clinical practice guidelines on medical thoracoscopy.

ABSTRACT: Medical Thoracoscopy (MT) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. The aim of the study was to provide evidence-based information regarding all aspects of MT, both as a diagnostic tool and therapeutic aid for pulmonologists across India. The consensus-based guidelines were formulated based on a multistep process using a set of 31 questions. A systematic search of published randomized controlled clinical trials, open labelled studies, case reports and guidelines from electronic databases, like PubMed, EmBase and Cochrane, was performed. The modified grade system was used (1, 2, 3 or usual practice point) to classify the quality of available evidence. Then, a multitude of factors were taken into account, such as volume of evidence, applicability and practicality for implementation to the target population and then strength of recommendation was finalized. MT helps to improve diagnosis and patient management, with reduced risk of post procedure complications. Trainees should perform at least 20 medical thoracoscopy procedures. The diagnostic yield of both rigid and semirigid techniques is comparable. Sterile-graded talc is the ideal agent for chemical pleurodesis. The consensus statement will help pulmonologists to adopt best evidence-based practices during MT for diagnostic and therapeutic purposes.

Pleural effusion guidelines from ICS and NCCP Section 1: Basic principles, laboratory tests and pleural procedures.

Pleural effusion is a common problem in our country, and most of these patients need invasive tests as they can't be evaluated by blood tests alone. The simplest of them is diagnostic pleural aspiration, and diagnostic techniques such as medical thoracoscopy are being performed more frequently than ever before. However, most physicians in India treat pleural effusion empirically, leading to delays in diagnosis, misdiagnosis and complications from wrong treatments. This situation must change, and the adoption of evidence-based protocols is urgently needed. Furthermore, the spectrum of pleural disease in India is different from that in the West, and yet Western guidelines and algorithms are used by Indian physicians. Therefore, India-specific consensus guidelines are needed. To fulfil this need, the Indian Chest Society and the National College of Chest Physicians; the premier societies for pulmonary physicians came together to create this National guideline. This document aims to provide evidence based recommendations on basic principles, initial assessment, diagnostic modalities and management of pleural effusions.

Doxycycline for the prevention of progression of COVID-19 to severe disease requiring intensive care unit (ICU) admission: A randomized, controlled, open-label, parallel group trial (DOXPREVENT.ICU).

BACKGROUND: After admission to hospital, COVID-19 progresses in a substantial proportion of patients to critical disease that requires intensive care unit (ICU) admission. METHODS: In a pragmatic, non-blinded trial, 387 patients aged 40-90 years were randomised to receive treatment with SoC plus doxycycline (n = 192) or SoC only (n = 195). The primary outcome was the need for ICU admission as judged by the attending physicians. Three types of analyses were carried out for the primary outcome: "Intention to treat" (ITT) based on randomisation; "Per protocol" (PP), excluding patients not treated according to randomisation; and "As treated" (AT), based on actual treatment received. The trial was undertaken in six hospitals in India with high-quality ICU facilities. An online application serving as the electronic case report form was developed to enable screening, randomisation and collection of outcomes data. RESULTS: Adherence to treatment per protocol was 95.1%. Among all 387 participants, 77 (19.9%) developed critical disease needing ICU admission. In all three primary outcome analyses, doxycycline was associated with a relative risk reduction (RRR) and absolute risk reduction (ARR): ITT 31.6% RRR, 7.4% ARR (P = 0.063); PP 40.7% RRR, 9.6% ARR (P = 0.017); AT 43.2% RRR, 10.8% ARR (P = 0.007), with numbers needed to treat (NTT) of 13.4 (ITT), 10.4 (PP), and 9.3 (AT), respectively. Doxycycline was well tolerated with not a single patient stopping treatment due to adverse events. CONCLUSIONS: In hospitalized COVID-19 patients, doxycycline, a safe, inexpensive, and widely available antibiotic with anti-inflammatory properties, reduces the need for ICU admission when added to SoC.

Guidelines for endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA): Joint Indian Chest Society (ICS)/Indian Association for Bronchology (IAB) recommendations.

Over the past decade, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become an indispensable tool in the diagnostic armamentarium of the pulmonologist. As the expertise with EBUS-TBNA has evolved and several innovations have occurred, the indications for its use have expanded. However, several aspects of EBUS-TBNA are still not standardized. Hence, evidence-based guidelines are needed to optimize the diagnostic yield and safety of EBUS-TBNA. For this purpose, a working group of experts from India was constituted. A detailed and systematic search was performed to extract relevant literature pertaining to various aspects of EBUS-TBNA. The modified GRADE system was used for evaluating the level of evidence and assigning the strength of recommendations. The final recommendations were framed with the consensus of the working group after several rounds of online discussions and a two-day in-person meeting. These guidelines provide evidence-based recommendations encompassing indications of EBUS-TBNA, pre-procedure evaluation, sedation and anesthesia, technical and procedural aspects, sample processing, EBUS-TBNA in special situations, and training for EBUS-TBNA.

An Overview of Phytotherapy Used in the Management of Type II Diabetes.

Diabetes mellitus is related to unconstrained high blood sugar and linked with long-term impairment, dysfunction and failure of several organs. Since 1980, the global frequency of diabetes has almost doubled in the adult population. In very rare cases due to poor prevention and management programs, diabetes causes worsening of health and reduced lifespan of the world population, thus impacting on the world's economy. Supplements, however, help in the improvement of nutritional deficiencies. Phytotherapeutics has the advantage of being economical and easy to access with marginal side effects. So, it is a preferred candidate for the management of diabetes. Currently, a multitude of pharmaceuticals are used which are obtained from natural sources having medicinal properties. The mechanistic approaches are based on the regulation of insulin signaling pathways, translocation of GLUT-4 receptors and/or activation of PPAR γ. These natural compounds include numerous flavonoids which help in preventing glucose absorption by preventing the absorption of α-amylase and α-glucosidase. But to validate the efficacy and safety profile of these compounds, detailed validatory clinical studies are required. This review majorly focuses on the mechanistic approaches of various naturally derived compounds relevant for the condition of Diabetes Mellitus.

From stress to stigma - Mental health considerations of health care workers involved in COVID19 management.

BACKGROUND: Healthcare workers (HCWs) involved in administration and patient management during COVID-19 pandemic are at high risk of developing psychological problems related to fear and stress of contacting COVID infection. This is augmented by the stigma faced at home and society, owing to the nature of their job. AIM: To assess the mental health issues and stigma amongst health care workers involved in COVID care. METHODOLOGY: We conducted a hospital based cross sectional study where 150 health care workers involved in the care of COVID-19 patients, directly and indirectly, were selected using systematic random sampling. They were assessed using Depression, Anxiety and Stress Scale (DASS-21) Hindi Version, The Impact of Event Scale - Revised scale and a Modified Stigma scale. RESULTS: Significant psychological stress, anxiety, depression and high risk for developing post-traumatic stress disorder was found in more than half of the healthcare workers, albeit more in those having direct contact with COVID patients (p < 0.05). Stigma was significantly reported in most HCWs, especially with concerns regarding public attitude and disclosure of their work profile. CONCLUSION: Healthcare Workers are at a higher risk for developing psychological disorders and post-traumatic stress disorder because of the immensely stressful work-related conditions and stigma related to working with COVID patients. This may lead to long lasting psychosocial consequences which may affect more severely than the infection itself. Early identification of psychological issues of HCWs and timely intervention is the key.

Diaphragmatic rupture in case of COVID-19 pneumonia- A rare presentation.

We describe the case of a male patient admitted to our emergency department during the COVID-19 pandemic with complaints of fever, severe breathlessness and dry cough associated with symptoms of gastric reflux for 5 days. Chest HRCT showed subtle multiple areas of diffuse patchy opacities with ground-glass haze with associated left subdiaphragmatic hernia and atelectasis of the left pulmonary lobe. Barium meal revealed subdiaphragmatic hernia. A nasopharyngeal swab for 2019-nCoV was positive. A diagnosis of diaphragmatic hernia in COVID-19 pneumonia was made. To our knowledge, spontaneous herniation of the diaphragm is a rare entity. Treatment for COVID-19 and empiric antibiotic therapy were promptly started and a decision of elective surgery was made.

Sjogren's syndrome-An interesting case.

OBJECTIVE: To present a case of Sjogren syndrome with pulmonary manifestations in an adult female and discuss its assessment and management. DESIGN: Case Report. SETTING: Tertiary care hospital. PATIENT: One. RESULTS: A 50 yrs female admitted with complaints of dryness of eyes with decreased salivation causing difficulty in swallowing since last 3 years, with persistent dry cough since 10-15 days and progressive dyspnea since 4-5 days. Anti-nuclear antibody (ANA) profile revealed Anti- Ro/SS-A and Anti- La/SS-B Positive. Also, sub-lingual excisional biopsy was done which was consistent with findings of Sjogren's syndrome. Patient showed significant improvement after starting oral glucocorticoids, systemic anti inflammatory agents (Tab. HCQS), artificial tear drops, oral iron supplements and other supportive treatment. CONCLUSION: Sjögren syndrome (SS) is a chronic inflammatory disorder characterized by diminished lacrimal and salivary gland function and associated with lymphocytic infiltration of exocrine glands, and can affect extraglandular organ systems including the skin, lung, heart, kidney, neural, and hematopoietic systems. We present a case of Sjogren syndrome in an adult female presenting with xerostomia and dyspnea and was diagnosed upon detection of anti-Ro and anti-La antibodies and confirmed by histopathological examination of lip biopsy. Patient was started on oral steroids and other supportive treatment, General condition improved significantly and is doing very well on regular follow-up.

Mycobacterium W. - An unusual side effect.

OBJECTIVE: To present an interesting case of unusual side effect of Mycobacterium W. in an adult COVID 19 positive male and discuss its assessment and management. METHODS: - DESIGN: Case Report. SETTING: Tertiary care hospital. PATIENT: One. RESULTS: 70 years male was admitted with complaints of fever, persistent dry cough since 10-12 days and progressive breathlessness since 3-4 days. Patient was found COVID-19 RTPCR positive and is known case of Type-II Diabetes with CAD (Post PTCA). Patient was managed conservatively with Oxygen support, I/V antibiotics, I/V Steroids, oral Favipiravir and other supportive treatment. Patient was also given injection Mycobacterium W. in dose of 0.3 ml per day intradermally at 3 different sites (both deltoids) consecutively for three days. 7-8 days after administration, patient developed bright red pustules which later got converted into small punched out ulcerations on all nine local sites of administration, which were managed conservatively with oral analgesics and local steroids for 8-10 days which healed without any scar formation. CONCLUSION: Injection Mycobacterium W. is used in COVID 19 patients as an immunomodulator agent and has been proved to be safe in most of the cases but we encountered this unusual side effect of bright red pustules formation at all nine local sites of injection in our case most likely because of being administered subcutaneously instead of intradermally, making this an interesting case which is being reported to scientific fraternity.

Beware of spurious tracheo-bronchial stents.

OBJECTIVE: To present a case of accidental sheath removal of tracheo-bronchial self-expandable metallic airway stent in a patient with endotracheal tumour. METHODS: Design: Case Report; Setting: Tertiary care hospital; Patient: One. RESULTS: A 65 years male, follow up case of endotracheal tumor with tracheo-bronchial self-expandable metallic stenting done presented with dry cough and difficulty in breathing since 8-10 days and suddenly coughed out thin whitish paper-like material 2 days back (which later proved as sheath of metallic stent). Direct laryngoscopy with flexible videobronchoscopy was done which showed tracheal stent well placed and intact, coughed out sheath couldn't be replaced back. Procedure was uneventful and patient was discharged in satisfactory condition and is doing well on regular follow up. CONCLUSION: Self-expandable metallic airway stents (SEMAS) represents a standard method of airways stenting especially when employed for the management of malignant central airway obstruction. Despite the obvious stenting advantages, it may be complicated with stent migration and accidental removal or coughing out of stent especially in high tracheal stenosis. In our case, as a peculiar complication there was accidental removal of the tracheal stent sheath which couldn't be replaced back whereas stent was well in place and intact. We need to be beware of such spurious tracheo-bronchial stents.

Impact of training on use of inhalational techniques of different inhaler devices: A single institutional cross sectional observation study.

OBJECTIVE: To assess the impact of training on use of inhalational techniques of different inhaler devices in spirometry proved cases of COPD and Bronchial Asthma in a tertiary care centre. METHODS: A total of 128 spirometry proved cases of Asthma and COPD were enrolled. They were equally distributed in four groups comprising of 32 patients each according to their inhalation devices namely pMDI, Rotahaler, Accuhaler and Turbohaler. Patients were asked to demonstrate their inhalation technique and errors were noted according to their inhaler specific checklist. Patients were also interviewed regarding their knowledge about inhalation devices. Training about proper inhalation techniques was given to every participant. Rechecking of inhalation technique was again done at the second visit after 2 wks in the similar manner. Correct and incorrect steps of inhalation technique again evaluated by filling the checklist of the individual device to see post training improvement. RESULT: In our study, out of total cases more than one third of the patients were >60 yrs of age (41.4%) and most of the patients were males (62.5%). During the interview at first visit, almost 92% patients claimed to know how to use the inhalation device correctly but in reality most of the patients (around 96.1%) had committed at least one mistakes in their inhalation technique among all the inhalation steps. Errors were noted in different steps of inhalation including the essential steps among all the four devices. Statistically significant improvement in inhalation techniques including the essential steps were found among all the four devices after educational intervention and demonstration of sequential steps involved in particular inhaler. CONCLUSION: Our study confirmed a significant increase in the percentage of improvement in inhalation technique after proper demonstration and training about the inhalation devices. Inhalation technique including essential steps of inhalation significantly improved in all the four devices used.

Impact of COVID-19 on (Non-COVID) chronic respiratory disease outcome survey in India (CCROS study).

BACKGROUND: India has high prevalence of chronic respiratory diseases, especially bronchial asthma and chronic obstructive pulmonary disease (COPD). Both of these are also recognized as risk factors for severity and poor outcome of COVID-19 disease. It is assumed that COVID-19 outbreak as well as an effective lockdown might have affected the incidence and outcome of some of these. METHODS: To substantiate above hypothesis, an online survey was mailed to 547 pulmonologists across the country; 314 (54.7%) responses were recorded in the given period. The survey included observations on incidence and outcome of common chronic respiratory diseases such as asthma, COPD and interstitial lung diseases (ILD) in predefined pre-COVID and during COVID period in a total of 24 questions. RESULTS: It was observed that the reduction in incidence of outpatient department cases, acute exacerbations and hospitalization for asthma, COPD and ILD was statistically significant. The outcome of acute exacerbations of these chronic respiratory diseases was analyzed in terms of discharges from hospitals after satisfactory recovery and/ or mortalities. For COPD and ILD, it was not significantly affected during the COVID period. At the same time, a relatively higher proportion of acute asthma mortality was reported. A wide variation in nebulization practices was reported during this period. The doses of inhaled corticosteroids in asthma management were not affected. A wide variety of factors including effective lockdown, better quality of air and regular use of masks were probably responsible for reduced incidence of exacerbations of these chronic respiratory diseases. CONCLUSION: We conclude that while outpatient department visits, acute exacerbations and hospitalizations were significantly reduced during COVID-19 period, outcome of asthmatics was relatively unfavorable as compared to that of COPD and ILDs.

Exploring status of emergency drugs and vaccine development in Covid-19 pandemic: an update.

COVID-19 outburst initiated from the city of Wuhan in China in December 2019 and has been declared as a public health emergency of international concern. This pandemic portrays a spectrum of clinical complications, primarily affecting the respiratory system reported to be caused by a pathogen SARS-CoV-2 belonging to the family of beta coronavirus. Currently, the main objective of the government authorities of all affected countries and research organizations is to find a potential solution in the form of a pharmacological intervention or a vaccination to eradicate the disease and to have a long-term solution to deal with the pandemic. A multitude of anti-viral regimens is proposed based on the repurposing of currently available drugs for other issues or the compassionate use of drugs to immediately control and optimize the healthcare facilities. Meanwhile, a number of agencies are proposing new drug candidates to recreate the possibility of treating the disease. Similarly, a lot of research work is going on worldwide for the development of vaccination. Currently, a good number of candidates has finally reached the borders of Clinical Trials and are expected to be launched as soon as possible. However, the regulatory framework and authorization of these candidates is the most significant aspect of the whole scenario, which needs a specific set of time for validation purposes. The present work is widely focused on the general aspects of COVID-19 and the regulatory landscape for the emergency authorization of repurposed drug candidates, compassionate use of drugs, investigational entities, and vaccine development worldwide. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13337-021-00684-5.

Radiology quiz- dancing ball.

We are presenting an interesting case of Pneumonia, who after good initial response deteriorated with recurrent hemoptysis. On culture of bronchial aspirate, patient had coexisting fungal infection and on repeat bronchoscopy showed a unique and rare picture. There was a dancing ball in RUL which was moving. Patient was initially managed conservatively but finally had to undergo lobectomy to achieve permanent cure.

Predictors of success and failure of non-invasive ventilation use in type-2 respiratory failure.

BACKGROUND: Non-invasive ventilation is widely used now a days in patients with hypercapnic respiratory failure. Non-invasive ventilation can be used in Intensive Care Unit setting and wards provided trained staff is there to monitor. METHODS: This was a prospective observational study of 100 adult patients who were admitted with hypercapnic respiratory failure. Demographic information such as Age, Sex were recorded. Clinical parameters like Respiratory Rate, Heart Rate, Oxygen saturation and Arterial Blood Gas variables like pH, PaCO2, HCO3 were measured at the time of admission and at 1st hour, 4 hours and 24 hours after start of non-invasive ventilation. Outcome was recorded as success and failure with Non invasive ventilation. RESULTS: Out of 100 patients, 76 (76%) managed successfully with non-invasive ventilation and 24 patients (24%) needed intubation and invasive mechanical ventilation in this study. Majority of patients (76%) were with clinical diagnosis of Chronic Obstructive Pulmonary Disease. Respiratory Rate and Heart Rate were significantly lower and showed significant improvement at 1st hour, 4 hours and 24 hours in patients who successfully improved with Non invasive ventilation. Oxygen saturation was found to be significantly higher among patients successfully managed with Non invasive ventilation (84.35 ± 8.55 vs 76.87 ± 7.33) as compared to patients who required intubation. pH was found to be significantly higher (7.28 ± 0.06 vs 7.23 ± 0.05) in patients showing good response to Non invasive ventilation and improvement in pH at 1st hour, 4 hours and 24 hours was observed in patients successfully managed with Non invasive ventilation. PaCO2 level was found to be significantly lower and significant improvement in PaCO2 at 1st hour, 4 hours and 24 hours was seen in patients with Non invasive ventilation success. CONCLUSION: Improvement in clinical parameters like respiratory rate, heart rate, Oxygen saturation and improvement in ABG variables like pH, PaCO2 after 1st and 4 hours of start of Non invasive ventilation and maintaining the improvement at 24 hours are predictors of success of non-invasive ventilation in hypercapnic patients.

Opaque hemithorax - An interesting case.

OBJECTIVE: To present an interesting case of left opaque hemithorax in an adult female and discuss its assessment and management. METHODS: Design: Case Report. SETTING: Tertiary care hospital. PATIENT: One. RESULTS: 44yrs retropositive female admitted with complaints of acute onset dry cough since 15-20 days, sudden breathlesness since 5 days which was progressive in nature, left sided heaviness in chest since 5 days. CECT Thorax showed complete collapse of left lung with cut off of left main bronchus while video bronchoscopy showed left main bronchus completely blocked with very thick necrotic mass and was difficult to dislodge. Debulking with cryo probe was done and left main bronchus was completely cleared off. Allergen panel showed very high serum IgE, high S.IgE against aspergillus and high specific S.IgG against aspergillus. Patient and her Chest X-ray showed significant improvement post cryo debulking and was discharged satisfactorily on oral voriconazole therapy. CONCLUSION: Endobronchial aspergillosis is characterized by massive intrabronchial overgrowth of the aspergillus species, mainly aspergillus fumigatus. Most patients with chronic pulmonary aspergillosis, including those with simple aspergillomas and Aspergillus nodules, have positive Aspergillus IgG antibodies in the blood. We hereby present a case of 44 yrs female presenting with complaints of dry cough and dyspnea and was diagnosed with endobronchial aspergillosis with complete obliteration of left main bronchus by fungal debris in which cryo debulking was done which relieved the symptoms significantly and was discharged in satisfactory condition on oral voriconazole therapy.

DISPOSABLE COVID BOX - A new invention.

OBJECTIVE: To introduce a new method to do safe bronchoscopy, a highly aerosol generating procedure through disposable COVID box in this difficult COVID time. METHODS: We have introduced an unbelievably cheap and effective method "DISPOSABLE COVID BOX". We took an acrylic board 70 × 20 cm and attached 3 bars 32 cm long and slide it under the side of the patient. A similar contraption is used on the other side. Then, it is covered by a polypropylene sheet 2' × 2'. It makes a completely disposable airtight chamber with the polypropylene sheet. We make a 1 cm nick in the sheet and introduce the video-bronchoscope, which is further navigated into the patient without any discomfort either to the patient or Bronchoscopist. When the procedure is finished, scope is withdrawn from the patient and the polypropylene sheet is squeezed out. The polypropylene sheet is removed and disposed off with all precautions, and the acrylic boards and the bars are cleaned with 1% Sodium hypochlorite solution. This way, the cost is only of polypropylene sheet which is negligible. RESULTS: Videobronchoscopies in indicated patients were done using this novel disposable covid box. This new invention called Disposable COVID box has been practiced for the first time, it's an innovative technique about which we want the world to be known. CONCLUSION: To conclude, there are no aerosols released in atmosphere after the procedure, making it absolutely safe for bronchoscopist and at same time patient also remains safe. We are ready again in no time with fresh polypropylene sheet to do the next bronchoscopy.

Transbronchial lung cryobiopsy by twin bronchoscopes (kissing technique).

OBJECTIVE: To introduce a new & novel method of obtaining big lung tissue samples by transbronchial lung cryobiopsy by twin bronchoscopes (kissing technique) in an advanced interventional pulmonology suite. METHODS: In patients of diffuse parenchymal lung diseases, transbronchial lung cryobiopsy were taken using this novel approach using simultaneously two bronchoscopes under C- arm guidance under conscious sedation. First, a standard fibreoptic bronchoscope was inserted intranasally and fixed just above the area to be biopsied, then fogarty's catheter was introduced through FOB's suction channel and protruded it at the biopsy site. Second, another video bronchoscope was introduced orally by the side of FOB and cryobiopsy were taken using cryobiopsy forceps. Immediately, Fogarty's catheter was inflated and sealed the opening from where biopsy was taken to stop the bleeding. Third Video bronchoscope was also used which went up to larynx to take photograph of two bronchoscopes kissing each other and entering the vocal cords only, after which it was withdrawn. RESULTS: Transbronchial lung cryobiopsy in patients of diffuse parenchymal lung diseases were taken using this novel approach. This new technique called twin bronchoscopy (Kissing technique) has been practiced for the first time, it's a technique about which we want the world to be known. CONCLUSION: This new and novel two scope kissing bronchoscopy technique for TBLC under conscious sedation can be an alternative and fruitful method, especially the use of Fogarty's catheter to contain intra-bronchial bleeding. There is no deleterious effect on the patient and the patient can be discharged on the same day.