COVID-19 in Patients With a Past History of Chemical War Injury: A Cross-Sectional Study in Southern Iran.

OBJECTIVE: This study aimed to determine whether COVID-19 is associated with a different presenting clinical picture or a more severe course of illness in people with a past history of chemical war injury. METHODS: This is a multicenter retrospective study in Fars Province, Iran, from August 22 to October 4, 2020. People with a past history of chemical war injury and COVID-19 were studied. Two age- and sex-matched control groups, double the size of the patient group each, from the same database of patients with COVID-19 who were hospitalized at the same time (ie, healthy controls and pseudocontrols). RESULTS: A total of 46 people with a past history of chemical war injury, 92 healthy controls, and 92 pseudocontrols were studied. People with COVID-19 and a past history of chemical war injury had a significantly higher rate of chest pain compared with others. There were no other clinical differences between the groups. Mortality rate was 17.39%, 15.21%, and 27.17% in people with a past history of chemical war injury, the control group, and the pseudocontrol group, respectively. CONCLUSIONS: A past history of a chemical war injury does not add to the risk of COVID-19 and does not significantly modify its clinical picture either.

Long-Lasting COVID-Associated Brain Fog: A Follow-Up Study.

INTRODUCTION: We investigated the longevity of COVID-associated brain fog in patients who have survived the COVID-19. METHODS: This was a follow-up study of 2,696 adult patients with COVID-19 from our previous study. We selected every other patient in our database. The follow-up data were collected during a phone call to the participants in January-February 2022 (11 months after the initial study): concentration difficulty and the patient's self-declared status in their ability to concentrate. RESULTS: In total, 1,164 people were included; 35 people (3.0%) had concentration difficulty and 65 individuals (5.6%) had a worsened status in their ability to concentrate and think; 26 people (2.2%) responded yes to both questions and were considered as having long-lasting brain fog. People with long-lasting brain fog were more often admitted to ICUs during the initial hospitalization (23.1% vs. 9.3%; p = 0.032) compared with those without long-lasting brain fog. CONCLUSION: We may conclude that a minority of the hospitalized patients with COVID-19 may suffer from long-lasting post-COVID brain fog, at least for more than 1 year after their initial illness. Long-lasting post-COVID brain fog has a significant association with the severity of the initial illness.

Inequity and disparities mar existing global research evidence on Long COVID.

Since the pandemic began in December 2019, SARS-Cov2 has accentuated the wide gap and disparities in socioeconomic and healthcare access at individual, community, country, and regional levels. More than two years into the current pandemic, up to three-fourths of the patients are reporting continued signs and symptoms beyond the acute phase of COVID-19, and Long COVID portends to be a major challenge in the future ahead. With a comprehensive overview of the literature, we found that most studies concerning long COVID came from high and upper-middle income countries, and people of low-income and lower-and-middle income regions and vulnerable groups with comorbid conditions have been neglected. Apart from the level of income, there is a significant geographical heterogeneity in investigating the Post-Acute Sequelae of COVID-19 (PASC) or what we call now, long COVID. We believe that these recognizing health disparities is crucial from equity perspective and is the first step toward global health promotion.

'Long COVID': Symptom persistence in children hospitalised for COVID-19.

AIM: We aimed to describe the long-term outcome with respect to symptom persistence amongst children hospitalised for COVID-19. METHODS: This was a follow-up study of 58 children and adolescents hospitalised with COVID-19. For all patients, the data were collected in a phone call to the family in December 2021 (9 months after the initial study and more than 13 months after their admission to hospital). We inquired about their current health status and obtained information, if the responding parent consented orally to participate and answer the questions. RESULTS: Fifty-one children and adolescents were studied. Only five patients (10%) had persistent symptoms compatible with long-COVID; the reported symptoms include fatigue in four (8%), weakness in three (6%), exercise intolerance in two (4%) and shortness of breath in two (4%) patients. Four patients (7.8%), who did not have any symptoms of long-COVID in phase 1 of the study, reported new-onset symptoms or complaints that are potentially compatible with the diagnosis of long-COVID (weakness, myalgia, excess sputum, cough, fatigue) in the current phase. CONCLUSIONS: Symptom persistence of long-COVID is infrequent amongst children hospitalised for COVID-19. Most of the symptoms of long-COVID will resolve with the passage of time and the residual symptoms are often mild and tolerable. The scientific community should carefully and clearly define long-COVID and its natural course in order to facilitate and harmonise future studies.

Efficacy of Valproic Acid Against Coronavirus Disease 2019 Infection or Severity: A Pilot Study.

OBJECTIVES: The purpose of the current study was to investigate whether taking valproic acid (VPA) was protective against coronavirus disease 2019 (COVID-19) infection or severity in patients with epilepsy. METHODS: This was a questionnaire study of 150 people who were taking VPA in monotherapy or polytherapy (since the start of the pandemic or longer) and also 150 people who were not taking VPA (since the start of the pandemic), registered in our epilepsy database. The data compared rates of the seropositivity and severity of infection of COVID-19 between the 2 groups. The latter was assessed, by proxy, vis-à-vis rates of hospital admission and intensive care unit admission. RESULTS: Two hundred forty-one patients were studied, including 130 (53.9%) male and 111 (46.1%) female patients. The mean age of the patients was 30.7 ± 11.4 years. The infection rate and severity of COVID-19 did not significantly differ among patients who were taking VPA and those who were not taking VPA (P = 0.587) and (P = 0.648), respectively. CONCLUSIONS: In this pilot study, no support was found for the hypothesis of a protective effect of VPA against the infectivity rate of COVID-19. Neither was there any indication of a disease-modulating effect of VPA in people with active COVID-19 infection. Larger, randomized controlled trials would be warranted to substantiate our conclusion.

Epilepsy management during difficult times

Major disruption in the delivery of healthcare services can occur in exceptional situations such as natural disasters, conflicts, periods of severe economic hardship, and epidemics. These disruptions typically affect to the greatest extent the most vulnerable segments of the population, including people with epilepsy. Inability to access healthcare services can lead to failure to undergo necessary diagnostic investigations, or to receive needed therapeutic interventions, including epilepsy surgery. Stress and other factors associated with the nature or the cause of the disruption can adversely affect seizure control status, or precipitate the occurrence of psychiatric disorders and other comorbid conditions. Failure to access antiseizure medications is a common occurrence in these situations and can result in loss of seizure control, withdrawal seizures, and status epilepticus. In this article, we provide examples of recent disruptions in healthcare and their implications for people with epilepsy. We discuss the consequences of natural disasters, conflicts, economic sanctions, and focus in greater detail on lessons learnt during the COVID-19 pandemic. We also discuss possible mitigation procedures, focusing in particular on the application of telemedicine to epilepsy care. Finally, we underline the need for governments, healthcare authorities, and international organizations to improve their preparedness to deal with exceptional situations that may arise in the future.

New-onset functional seizures during the COVID-19 pandemic.

OBJECTIVE: We investigated whether the COVID-19 pandemic has influenced the characteristics of functional seizures (FS) at the onset of seizures. METHODS: This was a retrospective study of all patients with new-onset FS, who were admitted at the epilepsy monitoring unit at Shiraz University of Medical Sciences, Shiraz, Iran, during two time periods: the onset of FS and also the diagnosis of FS in 2017-2019 (pre-COVID era) and the onset of FS and also the diagnosis of FS in 2020-2021 (COVID era). RESULTS: Forty-five patients were studied (32 patients from the pre-COVID era and 13 patients from the COVID era). Patients who developed FS during the pandemic more likely had comorbid epilepsy compared with the patients who presented with FS before the pandemic [30.1% vs. 9.4%; Odds ratio (OR): 81.2]. Furthermore, those who developed FS during the pandemic more likely were employed compared with the patients who presented with FS before the pandemic (46.2% vs. 12.5%; OR: 16.2). A family history of seizures was associated with the FS timing as a trend (OR: 8.4); those who developed FS during the pandemic more likely had a family history of seizures compared with the patients who presented with FS before the pandemic (53.8% vs. 18.8%). CONCLUSION: This study showed that patients who developed FS during the COVID-19 pandemic had significant underlying differences (i.e., employment status, comorbid epilepsy, and a family history of seizures) compared with those who presented with FS before the pandemic.

COVID-19 vaccine-related frequently asked questions (FAQs) by people with epilepsy and carers in Iran; educational video is included.

OBJECTIVE: The aim of the current study was to inquire the questions and concerns of people with epilepsy (PWE) about COVID-19 vaccines in order to provide a more realistic list of their frequently asked questions (FAQs). METHODS: We surveyed all the consecutive PWE or their care-givers who were referred to our neurology clinics (Shiraz University of Medical Sciences) during January-February 2022. We collected their questions and concerns in relation to COVID vaccines based on a predesigned brief questionnaire. Informed consent to participate in the study was obtained from the participants. RESULTS: In total, 452 people participated in the study; 291 people (64.4%) did not have any questions or concerns with regard to the COVID-19 vaccination. Having any questions or concerns about COVID-19 vaccination was significantly associated with not being vaccinated. Questions and concerns about the adverse effects of COVID-19 vaccines [seizure worsening, general adverse effects, long-term effects (e.g., infertility, cognitive dysfunction)] were by far the most common questions by people with epilepsy and their carers. CONCLUSION: Our findings may be used by policy-makers to prepare appropriate educational materials to provide the best targeted and tailored information to people with epilepsy and their carers to convince them of the necessity and safety of COVID-19 vaccination. Such an educational material must include enough information on the associated adverse effects of COVID-19 vaccines and should also discuss some other important issues such as indications of these vaccines in special populations and drug-vaccine interactions.

Long COVID syndrome-associated brain fog.

We investigated the frequency of brain fog in a large cohort of patients with documented coronavirus disease-2019 (COVID-19) who have survived the illness. We also scrutinized the potential risk factors associated with the development of brain fog. Adult patients (18-55 years of age), who were referred to the healthcare facilities anywhere in Fars province from February 19, 2020 to November 20, 2020 were included. All patients had a confirmed COVID-19 diagnosis. In a phone call, at least 3 months after their discharge from the hospital, we obtained their current information. A questionnaire was specifically designed for data collection. In total, 2696 patients had the inclusion criteria; 1680 (62.3%) people reported long COVID syndrome (LCS). LCS-associated brain fog was reported by 194 (7.2%) patients. Female sex (odds ratio [OR]: 1.4), respiratory problems at the onset (OR: 1.9), and intensive care unit (ICU) admission (OR: 1.7) were significantly associated with reporting chronic post-COVID "brain fog" by the patients. In this large population-based study, we report that chronic post-COVID "brain fog" has significant associations with sex (female), respiratory symptoms at the onset, and the severity of the illness (ICU admission).

An international study of the effects of the COVID-19 pandemic on characteristics of functional seizures.

OBJECTIVE: We investigated whether the COVID-19 pandemic has affected the clinical characteristics of patients with functional seizure (FS) (at the time of diagnosis) in a large multicenter international study. METHODS: This was a retrospective study. We investigated all patients with FS, who were admitted at the epilepsy monitoring units at six centers in the world: 1. Shiraz, Iran; 2. Salzburg, Austria; 3. Nancy, France; 4. Atlanta, USA; 5. Kuwait City, Kuwait; and 6. Cairo, Egypt. Patients were studied during two time periods: admitted in 2018-2019 (pre-COVID era) and 2020-2021 (COVID era). RESULTS: Three hundred and twenty-six patients were studied. Two hundred and twenty-four (68.7%) patients were diagnosed before and 102 (31.3%) persons during the COVID-19 pandemic. Only, a history of family dysfunction was significantly associated with the COVID-19 pandemic era (Odds Ratio: 1.925, 95% Confidence Interval: 1.099-3.371; p = 0.022). A low level of education might also be associated with FS during the COVID-19 pandemic, at least in some cultures (e.g., the Middle-East). CONCLUSION: The COVID-19 pandemic has not affected the clinical characteristics of patients with FS (at the time of diagnosis). However, a history of family dysfunction was significantly more frequently associated with FS during the COVID-19 pandemic. Multiagency integration of law enforcement responses, social services, and social awareness is recommended to address family dysfunction and domestic violence and support the victims during this pandemic.

Neuroscience20 (BRAIN20, SPINE20, and MENTAL20) Health Initiative: A Global Consortium Addressing the Human and Economic Burden of Brain, Spine, and Mental Disorders Through Neurotech Innovations and Policies.

Neurological disorders significantly impact the world's economy due to their often chronic and life-threatening nature afflicting individuals which, in turn, creates a global disease burden. The Group of Twenty (G20) member nations, which represent the largest economies globally, should come together to formulate a plan on how to overcome this burden. The Neuroscience-20 (N20) initiative of the Society for Brain Mapping and Therapeutics (SBMT) is at the vanguard of this global collaboration to comprehensively raise awareness about brain, spine, and mental disorders worldwide. This paper aims to provide a comprehensive review of the various brain initiatives worldwide and highlight the need for cooperation and recommend ways to bring down costs associated with the discovery and treatment of neurological disorders. Our systematic search revealed that the cost of neurological and psychiatric disorders to the world economy by 2030 is roughly $16T. The cost to the economy of the United States is $1.5T annually and growing given the impact of COVID-19. We also discovered there is a shortfall of effective collaboration between nations and a lack of resources in developing countries. Current statistical analyses on the cost of neurological disorders to the world economy strongly suggest that there is a great need for investment in neurotechnology and innovation or fast-tracking therapeutics and diagnostics to curb these costs. During the current COVID-19 pandemic, SBMT, through this paper, intends to showcase the importance of worldwide collaborations to reduce the population's economic and health burden, specifically regarding neurological/brain, spine, and mental disorders.

COVID-19 Vaccine Hesitancy Among Patients With Epilepsy or Other Chronic Conditions.

OBJECTIVES: The aim of this study was to investigate the opinions of different groups of people in Iran on their willingness to receive a coronavirus disease 2019 (COVID-19) vaccine. METHODS: In this cross-sectional study, we surveyed a sample (based on consecutive referrals) of 5 groups of people in late 2020: a group of the general population from Shiraz (without a history of any chronic medical or psychiatric problems), patients with epilepsy, patients with diabetes mellitus (DM), patients with cardiac problems, and patients with psychiatric problems. The survey included 4 general questions and 3 COVID-19-specific questions. RESULTS: A total of 582 people participated. In total, 66 (11.3%) people expressed that they were not willing to receive a COVID-19 vaccine. Psychiatric disorders (odds ratio [OR]: 3.15; 95% confidence interval [CI]: 1.31-7.60; P = 0.006) and male sex (OR: 2.10; 95% CI: 1.23-3.58; P = 0.010) were significantly associated with COVID-19 vaccine hesitancy. CONCLUSION: Vaccine hesitancy is a global issue. Patients with psychiatric disorders had the highest rate of vaccine hesitancy. Previous studies have shown that depression and anxiety are associated with a reduced adherence to the recommended medical advice. Why male sex is associated with vaccine hesitancy is not clear. Researchers should investigate the rates and the factors affecting the vaccine hesitancy in their corresponding communities.

Long COVID in children and adolescents.

BACKGROUND: To identify the prevalence and also the full spectrum of symptoms/complaints of children and adolescents who are suffering from long COVID. Furthermore, we investigated the risk factors of long COVID in children and adolescents. METHODS: All consecutive children and adolescents who were referred to the hospitals anywhere in Fars province, Iran, from 19 February 2020 until 20 November 2020 were included. All patients had a confirmed diagnosis of COVID-19. In a phone call to patients/parents, at least 3 months after their discharge from the hospital, we obtained their current status and information if their parents agreed to participate. RESULTS: In total, 58 children and adolescents fulfilled the inclusion criteria. Twenty-six (44·8%) children/adolescents reported symptoms/complaints of long COVID. These symptoms included fatigue in 12 (21%), shortness of breath in 7 (12%), exercise intolerance in 7 (12%), weakness in 6 (10%), and walking intolerance in 5 (9%) individuals. Older age, muscle pain on admission, and intensive care unit admission were significantly associated with long COVID. CONCLUSIONS: Long COVID is a frequent condition in children and adolescents. The scientific community should investigate and explore the pathophysiology of long COVID to ensure that these patients receive appropriate treatments for their condition.

Long COVID, a comprehensive systematic scoping review.

PURPOSE: To find out what is known from literature about Long COVID until January 30, 2021. METHODS: We undertook a four-step search with no language restriction. A preliminary search was made to identify the keywords. A search strategy of all electronic databases resulted in 66 eligible studies. A forward and backward search of the references and citations resulted in additional 54 publications. Non-English language articles were translated using Google Translate. We conducted our scoping review based on the PRISMA-ScR Checklist. RESULTS: Of 120 papers, we found only one randomized clinical trial. Of the 67 original studies, 22 were cohort, and 28 were cross-sectional studies. Of the total 120 publications, 49.1% focused on signs and symptoms, 23.3% on management, and 10.8% on pathophysiology. Ten publications focused on imaging studies. The results are also presented extensively in a narrative synthesis in separated sections (nomenclature, diagnosis, pathophysiology, risk factors, signs/symptoms, management). CONCLUSIONS: The controversies in its definition have impaired proper recognition and management. The predominant symptoms were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness.

A follow-up study of patients with COVID-19 presenting with seizures.

OBJECTIVE: We performed a follow-up study of patients with COVID-19 presenting with seizures. METHODS: All consecutive patients with seizures, who were referred to Namazee Hospital, Shiraz, Iran, with a diagnosis of COVID-19, from 10 August 2020 until 20 October 2020 were included in this longitudinal study. The clinical data were collected by the admitting physician. In a follow-up phone call to the discharged patients (after eight weeks or more), we inquired their seizure outcome. RESULTS: In total, 32 patients were studied; 28 patients were followed. Twelve patients (37.5%) presented with a single tonic-clonic seizure and nine (28.1%) had convulsive status epilepticus; one patient had functional (psychogenic) seizures. Ten patients (31.3%) had pre-existing epilepsy, eight others (25%) had pre-existing CNS problems (without epilepsy), one person (3.1%) had pre-existing functional seizures, and 13 individuals (40.1%) neither had epilepsy nor had other CNS problems. Eight patients (28.6%) reported experiencing seizure(s) after being discharged from the hospital; six of these had pre-existing epilepsy and one had pre-existing functional seizures. One patient, who had a newly developed ischemic brain infarction, reported experiencing recurrent seizures. CONCLUSION: Seizures in patients with COVID-19 are either acute symptomatic (in about two-thirds) or an exacerbation of a pre-existing epilepsy/functional seizures (in about one-third). A thorough investigation of the underlying etiology of seizures in patients with COVID-19 is necessary. Seizure outcome in patients, who are hospitalized with COVID-19 and seizures, is generally good.

Physicians' opinions on the necessity of COVID-19 vaccination in patients with epilepsy.

The aim of the current study was to investigate the opinions of neurologists and psychiatrists in Iran on the necessity of COVID-19 vaccination in patients with epilepsy (PWE). These data can help policy makers understand the concerns of these healthcare professionals. This was a survey study. On September 1st, 2020 we sent a questionnaire (using Google-forms) to all neurologists and psychiatrists in Iran via WhatsApp. The survey included three general questions (age, sex, and discipline) and six COVID-specific questions. In total, 202 physicians participated in this study (116 neurologists and 86 psychiatrists). Of the participants, 27% believed that PWE are at increased risk of contracting COVID-19. The majority (74%) of the participants would confidently recommend COVID-19 vaccine to their patients. However, only 49% of the physicians would recommend such a vaccine to all patients; others would consider it in special populations only. The overwhelming majority (91%) of the participants would recommend COVID-19 vaccine only when a reliable vaccine becomes available. Many physicians would trust a vaccine that is approved by the World Health Organization (WHO) (46%) or a vaccine that is approved by the Food and Drug Administration (FDA-USA) (34%). Physicians have concerns on the issue of the necessity of (a future) COVID-19 vaccine in PWE. The most important concern is the reliability of a vaccine and in this regard, two health agencies, the WHO and the FDA, are the most trusted organizations to approve a vaccine against COVID-19.

Effects of the COVID-19 pandemic on characteristics of functional (psychogenic) seizures.

OBJECTIVE: We investigated whether the COVID-19 pandemic has affected the clinical characteristics of patients with functional seizure (FS) (at the time of diagnosis). METHODS: In a retrospective study of a prospectively developed and maintained database, all patients diagnosed with FS before and during the COVID-19 pandemic were studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from December 2008 until February 2021. RESULTS: Three hundred and eighty-eight patients were studied. Three hundred and sixty-four patients (94%) were diagnosed before and 24 persons (6%) during the pandemic. Patients diagnosed during the COVID-19 pandemic less frequently had generalized motor seizures [odds ratio (OR): 0.30, 95% confidence interval (CI): 0.12-0.77; p = 0.012] and had higher seizure frequencies (OR: 1.00, 95% CI: 1.00-1.01; p = 0.044). Functional seizures were inversely associated with the education level as a trend during the COVID-19 pandemic (OR: 0.36, 95% CI: 0.13-1.01; p = 0.052). CONCLUSION: The COVID-19 pandemic has affected the characteristics of patients with FS (at the time of diagnosis). Larger and multi-center studies are needed to investigate the links and associations between the COVID-19 pandemic and characteristics of FS.

Mask Wearing Hesitancy During the COVID-19 Pandemic in South Iran.

PURPOSE: The aim of the current study was to investigate the prevalence of face mask wearing among different groups of people in south Iran. We also investigated the associations between mask wearing hesitancy and various factors. METHODS: We surveyed a sample (convenience sampling) of 5 groups of people: general population, people with epilepsy, people with diabetes mellitus (DM), people with cardiac problems, and people with psychiatric problems. The survey included 4 general questions (age, sex, education, and medical/psychiatric problem) and 4 coronavirus disease 2019 (COVID-19)-specific questions (contracting COVID-19, relatives with COVID-19, wearing a face mask while in crowded places, and the frequency of daily hand washings). RESULTS: A total of 582 people (153 people with epilepsy, 127 patients with DM, 98 people with cardiac problems, 96 patients with psychiatric disorders, and 108 healthy individuals) participated. Twenty-eight (4.8%) people expressed that they do not wear a face mask when at crowded places. A lower education and less frequent daily hand washings had associations with mask wearing hesitancy. CONCLUSIONS: Mask wearing hesitancy is a concern during a respiratory viral disease pandemic. Paying attention to personal variables, especially if they are modifiable (eg, education and hygiene), is probably productive and practical in promoting mask wearing culture.

COVID-19 in patients with Down syndrome.

PURPOSE: The aim of the current study was to determine whether COVID-19 is associated with a different presenting clinical picture or a more severe course of illness in people with Down syndrome (DS). METHODS: All consecutive patients who were admitted at healthcare facilities anywhere in Fars province (located in the south of Iran with a population of 4,851,000 people) from 19 February 2020 to 20 November 2020 were included. For every patient with DS, three age- and sex-matched patients with COVID-19 and without any underlying medical conditions were selected as controls. RESULTS: During the study period, 37,968 patients were hospitalized with a diagnosis of COVID-19. Eighteen patients had DS. Patients with DS were significantly more likely to be intubated [7 patients (39%)] compared with those without DS [3 patients (6%)]; p = 0.002. Patients with DS significantly more often died of COVID-19 compared with the controls [8 (44.4%) vs. 1 (1.9%); odds ratio: 24.37; 95% confidence interval 2.39-247.94; p = 0.007]. CONCLUSION: Patients with DS are among the high-risk populations with respect to severe COVID-19 and should receive the vaccine as soon as possible. Furthermore, they should receive more intensive care if they get hospitalized with the illness.

Seizure is a rare presenting manifestation of COVID-19.

OBJECTIVE: The aim of the current study was to investigate whether seizure is among the presenting manifestations of COVID-19. METHODS: All patients referred to emergency rooms anywhere in Iran between 12 and 25 April 2020 and who were sufficiently ill to require hospital admission with COVID-19, confirmed by a positive COVID-19 test, were studied. Data on the presenting manifestations were collected. RESULTS: Of 5872 people, who were admitted to hospitals in Iran with COVID-19 during the study period, 45 came to the emergency room with seizures. This makes seizure as the presenting manifestation of COVID-19 in 0.8 % of all patients with a severe illness. 93 % of the patients were 15 years of age and older. Four of the individuals presenting with seizures (9%) had a past history of epilepsy. Fifteen of these individuals (33 %) had other chronic medical conditions (e.g., cancer, diabetes mellitus, heart disease, etc.). CONCLUSION: This case series provides evidence that seizures are among the presenting manifestations of COVID-19 in 0.8 % of the patients who are admitted to hospital due to a severe illness.