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The National Aeronautics and Space Administration (NASA) in the United States has been studying a fascinating and unique constellation of neuro-ophthalmic findings collectively known as Spaceflight Associated Neuro-Ocular Syndrome (SANS). SANS is unique to the space environment of microgravity and produces novel physiological and pathological findings that have no direct terrestrial equivalent. The neuro-ophthalmic phenomenon is a major physiologic barrier to future planetary spaceflight. The underlying pathophysiology of SANS remains ill-defined, but since its initial report in 2011, several hypotheses have been proposed including increased intracranial pressure, cerebral venous congestion and glymphatic stasis, compartmentalization of CSF within the orbital nerve sheath sub-arachnoid space (SAS), upward brain shift, inflammation, disrupted axoplasmic transport, and radiation exposure. These aetiologies may not be mutually exclusive and may be interconnected, leading to an integrative, multifactorial aetiology of SANS. This paper critically analyses the various hypotheses of this neuro-ophthalmic phenomenon and the connections between the physiologic and anatomical evidence-based changes observed in spaceflight and terrestrial analogues. Continued prospective, longitudinal study and development of practical countermeasures for SANS will be necessary for future human spaceflight missions including the mission to Mars., Competing Interests: Competing interests: AGL is a consultant for the National Aeronautics and Space Administration (NASA) and serves on the editorial board of Eye., (© 2025. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

A major barrier to cure HIV is the early generation of viral reservoirs in tissues. These viral reservoirs can contain intact or defective proviruses, but both generates low levels of viral proteins contribute to chronic bystander damage even in the ART era. Most viral reservoir detection techniques are limited to blood-based, reactivation, and sequencing assays that lack spatial properties to examine the contribution of the host's microenvironment to latency and cure efforts. Currently, little is known about the contribution of the microenvironment to viral reservoir survival, residual viral expression, and associated inflammation. Only a few spatiotemporal techniques are available, and fewer integrate spatial genomics, transcriptomics, and proteomics into the analysis of the viral reservoir microenvironment-all essential components to cure HIV. During the development of these spatial techniques, many considerations need to be included in the analysis to avoid misinterpretation. This manuscript tries to clarify some critical concepts in viral reservoir detection by spatial techniques and the upcoming opportunities for cure efforts., Competing Interests: Conflict of interest: None., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Background: One anastomosis gastric bypass (OAGB) is an American Society for Metabolic and Bariatric Surgery (ASMBS)-endorsed bariatric surgery. As utilization of OAGB increases, it is important that the safety profile of OAGB be rigorously assessed., Objectives: We studied the 30-day safety of OAGB compared to a similar gastro-jejunal anastomotic procedure, Roux-en-Y gastric bypass (RYGB)., Setting: Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) participating bariatric centers in the United States., Methods: A matched case-control study was conducted of patients who underwent primary gastric bypass surgery 2021-2022, identified in the MBSAQIP database. Each patient who underwent OAGB was matched to 4 controls who underwent RYGB on age (±10), sex, race, body mass index (BMI) (±5 kg/m 2 ), preoperative functional status, American Society of Anesthesiologists (ASA) classification, and 13 comorbidities. Univariate and multivariate regression analyses were performed., Results: A total of 1569 patients who underwent OAGB were matched to 6276 controls. Matched baseline characteristics were similar between groups. Operative time, length of stay (LOS), and overall complication rate were lower in the OAGB cohort (P < .001) with higher 30-day BMI loss percentage (P = .048). Specifically, OAGB was associated with a significantly lower bowel obstruction rate, as compared to RYGB (.1% versus 1.0%, P < .001). On logistic regression adjusting for all variables used in matching, OAGB was associated with a 27% decrease in overall complication rate (odds ratio [OR] .73, 95% confidence interval [CI] .62-.87, P < .001)., Conclusions: Although OAGB is minimally utilized, the 30-day safety profile appears favorable. As compared to RYGB, OAGB was associated with shorter operative time and LOS, and a lower complication rate, partially due to minimization of small bowel obstructions with a loop anatomy. Further evidence in the comparative long-term safety profile is still needed., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background Little is known about health literacy in traumatic brain injury (TBI) survivors. The aims of this study were to compare health literacy in individuals with TBI with that of a control group; to examine the association between health literacy in individuals with TBI and demographic, injury, and cognitive factors; and compare the relationship between health literacy and physical and mental health outcomes. Methods A cross-sectional observational study design was used. Adults (≥18years) were recruited from an outpatient research centre in Victoria, Australia. There were 209 participants with a complicated mild to severe TBI at least 1year previously (up to 30years 6months) and 206 control participants. Results Individuals with TBI did not have poorer health literacy than controls (IRR=1.31, P =0.102, CI95% [0.947, 1.812]). Further analysis could not be completed due to the highly skewed Health Literacy Assessment Using Talking Touchscreen Technology - Short Form (Health LiTT-SF) data. Conclusion Health literacy performance in individuals with TBI was not significantly different to controls. Premorbid education may provide a critical cognitive reserve upon which TBI survivors can draw to aid their health literacy. These findings are specific to the Health LiTT-SF measure only and require replication using more comprehensive health literacy measures in culturally diverse samples.

Background: We hypothesize that creation of a structured curriculum in neuro-ophthalmology principles might improve self-rated learner satisfaction and knowledge base of National Football League (NFL) game officials. Our initial objective is to create the said curriculum in coordination with game official experts and staff at the NFL to increase levels of understanding of neuro-ophthalmology principles. We reviewed the prior published literature on applicable neuro-ophthalmic principles in professional sports. Major neuro-ophthalmic principles reviewed include both the efferent (e.g., saccadic and pursuit eye movements and vestibulo-ocular reflex) and afferent (visual field, dynamic visual acuity during body movement, and selective attention deficits)., Methods: A 6-question survey pertaining to levels of understanding, future applicability, relevance, satisfaction, and interest in additional training was then given to 26 individuals before and after a lecture given by Dr. Andrew Lee in Plano, TX. The primary outcome measure was the creation of the curriculum followed by real-world testing for face and content validity and ending with a self-rated assessment., Results: Twenty-one individuals completed the prelecture and postlecture survey out of 26 individuals who attended. Prelecture means for the level of understanding of oculomotor terms and the likelihood of using said terms were 3.4 and 3.2, respectively. Postlecture means were 8.9 and 8.8, respectively. The lecture was rated 9.2 of 10 for relevance to coaching and teaching officials, and individuals rated their interest in further content as 9.4 of 10., Conclusions: This study found that NFL game officials are interested in learning more about the science behind play-calling in terms of neuro-ophthalmology principles and practices. In addition, from our pilot survey, it is evident that even one lecture can improve participants' level of understanding and likelihood of learning more about neuro-ophthalmic principles., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

Background: Pneumococcal conjugate vaccines (PCVs) significantly reduced pneumococcal disease burden. Nevertheless, alternative approaches for controlling more serotypes are needed. Here, the safety, tolerability, and immunogenicity of a 24-valent (1/2/3/4/5/6A/6B/7F/8/9N/9V/10A/11A/12F/14/15B/17F/18C/19A/19F/20B/22F/23F/33F) pneumococcal vaccine based on Multiple Antigen-Presenting System (MAPS) technology (Pn-MAPS24v) was assessed in toddlers., Methods: In this phase 1, blinded, dose-escalation, active-controlled multicenter study conducted in the United States (September/2020-April/2022), 12-15-month-old toddlers primed with three doses of 13-valent PCV (PCV13) were randomized 3:2 to receive a single dose of one of three Pn-MAPS24v dose levels (1 μg/2 μg/5 μg per polysaccharide) or PCV13 intramuscularly. Reactogenicity (within 7 days), treatment-emergent adverse events (TEAEs, within 180 days), serious/medically attended adverse events (SAEs/MAAEs, within 180 days), and immunogenicity (serotype-specific anti-capsular polysaccharide immunoglobulin G [IgG] and opsonophagocytic activity [OPA] responses at 30 days post-vaccination) were assessed., Results: Of 75 toddlers enrolled, 74 completed the study (Pn-MAPS24v 1 μg/2 μg/5 μg: 15/14/16, PCV13: 29). Frequencies of local (60 %/67 %/31 %) and systemic events (67 %/67 %/75 %) in the Pn-MAPS24v 1 μg/2 μg/5 μg and the PCV13 (55 %, 79 %) groups were in similar ranges. TEAEs were reported by 47 %/40 %/63 % of Pn-MAPS24v 1 μg/2 μg/5 μg recipients and 52 % of PCV13 recipients. No vaccine-related SAE was reported. At 30 days post-vaccination, for each of the 13 common serotypes, ≥93 % of participants in each group had IgG concentrations ≥0.35 μg/mL; >92 % had OPA titers ≥lower limit of quantitation (LLOQ), except for serotype 1 (79 %). For 7/11 unique serotypes (2/8/9N/11A/17F/22F/33F), at all dose levels, ≥78 % of Pn-MAPS24v recipients in each group had IgG concentrations ≥0.35 μg/mL and 80 %-100 % had OPA titers ≥LLOQ., Conclusions: In 12-15-month-old toddlers, a single dose of Pn-MAPS24v showed an acceptable safety profile, regardless of dose level; AEs were reported at similar frequencies by Pn-MAPS24v and PCV13 recipients. Pn-MAPS24v elicited IgG and OPA responses to all common and most unique serotypes. These results support further clinical evaluation in infants., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dorota Borys is an employee of GSK and holds shares from GSK. Gurunadh R Chichili, Laura L Kovanda, Vicki Santos and Ronald Smulders are employees of Astellas Pharma Global Development, Inc. Frank Malinoski, Richard Malley and Shite Sebastian were employees of Affinivax, Inc. at the time the study was designed, initiated, and/or conducted. George Siber and Richard Malley were Affinivax, Inc. board members at the time the study was designed, initiated, and/or conducted. Frank Malinoski holds stock or stock options from Affinivax, Inc. George Siber disclosed that Siber Biotechnologies LLC received consulting fees and stock ownership, as well as support for attending meetings and/or travel, from Affinivax, Inc. Richard Malley declares potential future payments and royalties as equity holder of Affinivax, Inc. and named co-inventor of MAPS technology. Richard Malley is a former employee of GSK and now a consultant of GSK. Richard Malley received consulting fees from GSK as consultant in the area of vaccines and disclosed GSK support for attending meetings and/or travel, and participation to a GSK Advisory board. Richard Malley has issued or pending patents on MAPS technology. Richard Rupp disclosed financial support from Astellas Pharma Global Development, Inc. to the University of Texas Medical Branch for the present study, and financial support from GSK and Affinivax, Inc. for participation to the Data Monitoring Committee (Affinivax, Inc.) and the Data Safety Monitoring Committee (GSK). Shite Sebastian is currently an employee of GSK. Shite Sebastian has issued and pending patents on Multivalent Pneumococcal Vaccine. All authors have no other financial or non-financial interests to declare., (Copyright © 2024 GSK. Published by Elsevier Ltd.. All rights reserved.)

In the past decade, there has been a steady rise in interest in studying novel cellular extensions and their potential roles in facilitating human diseases, including neurologic diseases, viral infectious diseases, cancer, and others. One of the exciting new aspects of this field is improved characterization and understanding of the functions and potential mechanisms of tunneling nanotubes (TNTs), which are actin-based filamentous protrusions that are structurally distinct from filopodia. TNTs form and connect cells at long distance and serve as direct conduits for intercellular communication in a wide range of cell types in vitro and in vivo. More researchers are entering this field and investigating the role of TNTs in mediating cancer cell invasion and drug resistance, cellular transfer of proteins, RNA or organelles, and intercellular spread of infectious agents, such as viruses, bacteria, and prions. Even further, the elucidation of highly functional membrane tubes called "tumor microtubes" (TMs) in incurable gliomas has further paved a new path for understanding how and why the tumor type is highly invasive at the cellular level and also resistant to standard therapies. Due to the wide-ranging and rapidly growing applicability of TNTs and TMs in pathophysiology across the spectrum of biology, it has become vital to bring researchers in the field together to discuss advances and the future of research in this important niche of protrusion biology., (© 2024 Federation of American Societies for Experimental Biology.)

Objective: To characterize health literacy among individuals with traumatic brain injury (TBI) at least a year postinjury and to explore its relationship to sociodemographic variables, injury severity, and cognition., Setting: Community following discharge from inpatient rehabilitation., Participants: In total, 205 individuals with complicated mild to severe TBI who completed follow-up as part of a national longitudinal study of TBI and completed a web-based health literacy measure., Design: Multicenter, cross-sectional, observational study., Main Measures: Health Literacy Assessment Using Talking Touchscreen Technology., Results: Thirty-one percent of the sample demonstrated marginal/inadequate health literacy; 69% demonstrated adequate health literacy. A higher proportion of non-Hispanic White adults had adequate health literacy than non-Hispanic Black and Hispanic adults. Individuals with greater than a high school education were more likely to have adequate health literacy than those with a high school education or less. Better executive functioning performance was related to adequate health literacy. Better episodic memory performance was related to adequate health literacy, but only for those with complicated mild to moderate injury., Conclusions: A substantial proportion of individuals with TBI have marginal/inadequate health literacy, which may impact their understanding, appreciation, and use of health-related information and recommendations. While low health literacy may be preexisting, directly related to TBI, or a combination of both, it should be screened and considered by professionals when communicating with persons with TBI. Healthcare providers should tailor their communication approaches and presentation of health information, particularly for those with low health literacy., Competing Interests: The authors declare no conflicts of interests., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To synthesize evidence for the effectiveness of self-management interventions for chronic health conditions that have symptom overlap with traumatic brain injury (TBI) in order to extract recommendations for self-management intervention in persons with TBI., Design: An umbrella review of existing systematic reviews and/or meta-analyses of randomized controlled trials or nonrandomized studies targeting self-management of chronic conditions and specific outcomes relevant to persons with TBI., Method: A comprehensive literature search of 5 databases was conducted using PRISMA guidelines. Two independent reviewers conducted screening and data extraction using the Covidence web-based review platform. Quality assessment was conducted using criteria adapted from the Assessing the Methodological Quality of Systematic Reviews-2 (AMSTAR-2)., Results: A total of 26 reviews met the inclusion criteria, covering a range of chronic conditions and a range of outcomes. Seven reviews were of moderate or high quality and focused on self-management in persons with stroke, chronic pain, and psychiatric disorders with psychotic features. Self-management interventions were found to have positive effects on quality of life, self-efficacy, hope, reduction of disability, pain, relapse and rehospitalization rates, psychiatric symptoms, and occupational and social functioning., Conclusions: Findings are encouraging with regard to the effectiveness of self-management interventions in patients with symptoms similar to those of TBI. However, reviews did not address adaptation of self-management interventions for those with cognitive deficits or for populations with greater vulnerabilities, such as low education and older adults. Adaptations for TBI and its intersection with these special groups may be needed., Competing Interests: The authors declare no conflicts of interests., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Objective: To examine the associations between health literacy and health outcomes among individuals with traumatic brain injury (TBI) at least a year post-injury., Setting: Community following discharge from inpatient rehabilitation., Participants: A total of 205 individuals with complicated mild to severe TBI who completed a TBI Model Systems National Database follow-up interview and a web-based health literacy measure., Design: A multicenter, cross-sectional, observational study., Main Measures: The Health Literacy Assessment Using Talking Touchscreen Technology (Health LiTT), number of comorbid conditions (Medical and Mental Health Comorbidities Interview [MMHCI]), perceived physical and mental health (PROMIS Global Physical and Mental Health subscales), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7)., Results: After controlling for sociodemographic, injury, cognition, and time post-injury, adequate health literacy was associated with higher odds of greater perceived physical health compared with participants with marginal/inadequate health literacy (odds ratio = 4.10; CI = 1.52-11.70]. Participants with inadequate/marginal health literacy had 3.50 times greater odds of depression (PHQ-9 ≥ 10) compared with those with adequate health literacy. Participants 45 years and older reported a greater number of MMHCI physical health conditions, but fewer MMHCI mental health conditions and GAD-7 anxiety symptoms compared with those who were younger. Non-Hispanic White participants and those with mild/moderate TBI were more likely to report a greater number of MMHCI mental health conditions compared with non-Hispanic Black participants or those with severe TBI. Greater time post-injury was associated with greater number of chronic physical and mental health conditions, and less odds of good-to-excellent perceived global mental health., Conclusions: Inadequate health literacy is associated with worse perceived physical health and greater depressive symptoms among adults with TBI. Greater efforts are needed to explore the mechanisms by which health literacy influences chronic disease management and mental health after TBI to improve postinjury health status and outcomes, particularly among those with limited health literacy skills., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

HIV-associated neurological compromise is observed in more than half of all people with HIV (PWH), even under antiretroviral therapy (ART). The mechanism has been associated with the early transmigration of HIV-infected monocytes across the BBB in a CCL2 and HIV replication-dependent manner. However, the mechanisms of chronic brain damage are unknown. We demonstrate that all PWH under ART have elevated circulating ATP levels that correlate with the onset of cognitive impairment even in the absence of a circulating virus. Serum ATP levels found in PWH with the most severe neurocognitive impairment trigger the transcellular migration of HIV-infected leukocytes across the BBB in a JAM-A and LFA-1-dependent manner. We propose that targeting transcellular leukocyte transmigration could reduce or prevent the devastating consequences of HIV within the brains of PWH under ART., Competing Interests: The authors do not have any conflicts of interest., (© 2024 The Authors.)

Cell-to-cell interactions are essential for proper development, homeostasis, and complex syncytia/organ formation and function. Intercellular communication are mediated by multiple mechanisms including soluble mediators, adhesion molecules and specific mechanisms of cell to cell communication such as Gap junctions (GJ), tunneling nanotubes (TNT), and exosomes. Only recently, has been discovered that TNTs and exosomes enable the exchange of large signaling molecules, RNA, viral products, antigens, and organelles opening new avenues of research and therapeutic approaches. The focus of this review is to summarize these recent findings in physiologic and pathologic conditions., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Correlative light-electron microscopy (CLEM) has evolved in the last decades, especially after significant developments in sample preparation, imaging acquisition, software, spatial resolution, and equipment, including confocal, live-cell, super-resolution, and electron microscopy (scanning, transmission, focused ion beam, and cryo-electron microscopy). However, the recent evolution of different laser-related techniques, such as mass spectrometry imaging (MSI) and laser capture microdissection, could further expand spatial imaging capabilities into high-resolution OMIC approaches such as proteomic, lipidomics, small molecule, and drug discovery. Here, we will describe a protocol to integrate the detection of rare viral reservoirs with imaging mass spectrometry., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Monocyte/macrophages are cells of myeloid origin which play critical roles in innate and adaptive immune responses as well as surveillance and tissue repair. Only recently, the role of monocytes/macrophages in acute and chronic HIV Infection has become accepted. Here, we will focus on monocyte/macrophages on transmigration events and their role as viral reservoirs., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Infectious agents such as human immune deficiency virus-1 (HIV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) use host proteins to infect, replicate, and induce inflammation within the host. A critical component of these diseases is the axis between pannexin-1 channels, extracellular ATP, and purinergic receptors. Here, we describe the potential therapeutic role of Pannexin-1/purinergic approaches to prevent or reduce the devastating consequences of these pathogens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The association of weight loss medications with prostate (PCa), colorectal (CRC) or male breast cancers, including assessment of these cancers combined (HRCs, hormone-associated cancers) remain poorly understood. Testosterone replacement therapy (TTh) is reported to be inversely associated with obesity, PCa and CRC, but it is unclear whether TTh modifies the association of weight loss medications with HRCs., Methods: In 49,038 men (≥ 65 years) of SEER-Medicare, we identified 15,471 men diagnosed with PCa, 4836 with CRC, and 141 with male breast cancers. Pre-diagnostic prescription of weight loss medications and TTh was ascertained for this analysis. Weighted multivariable-adjusted conditional logistic and Cox proportional hazards (mortality) models were conducted., Results: We found an inverse association between use of weight loss medications and incident PCa (OR 0.59, 95% CI 0.57-0.62), CRC (OR 0.86, 95% CI 0.80-0.92), and HRCs (OR 0.65, 95% CI 0.62-0.68). Similar associations were observed for advanced stage at diagnosis of PCa and CRC. Effects of weight loss medications on PCa and HRC remained significant irrespective of the use of TTh but were only suggestive with CRC with positive TTh use. No associations were observed with male breast cancer and HRCs mortality., Conclusion: Pre-diagnostic use of weight loss medications reduced the incidence of PCa, CRC, and HRCs. These associations persisted in the same direction irrespective of the history of TTh use. Future studies are needed to confirm these findings and to identify underlying biological mechanisms of weight loss medications and TTh on the risk of cancer., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

HIV infection has become a chronic and manageable disease due to the effective use of antiretroviral therapies (ART); however, several chronic aging-related comorbidities, including cognitive impairment, remain a major public health issue. However, these mechanisms are unknown. Here, we identified that glial and myeloid viral reservoirs are associated with local myelin damage and the release of several myelin components, including the lipid sulfatide. Soluble sulfatide compromised gap junctional communication and calcium wave coordination, essential for proper cognition. We propose that soluble sulfatide could be a potential biomarker and contributor to white matter compromise observed in HIV-infected individuals even in the current ART era., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Many cancer patients undergoing treatment experience cancer-related fatigue (CRF). Inflammatory markers are correlated with CRF but are not routinely targeted for treatment. We previously demonstrated in an NIH-funded placebo-controlled, double-blind, randomized clinical trial (NCT00878995, closed to follow-up) that seven weekly injections of 100 mg adjunct testosterone preserved lean body mass in cancer patients undergoing standard-of-care treatment in a hospital setting. Because testosterone therapy can reduce circulating proinflammatory cytokines, we conducted an ancillary analysis to determine if this testosterone treatment reduced inflammatory burden and improved CRF symptoms and health-related quality of life. Randomization was computer-generated and managed by the pharmacy, which dispensed testosterone and placebo in opaque syringes to the administering study personnel. A total of 24 patients were randomized (14 placebo, 10 testosterone), and 21 were included in the primary analysis (11 placebo, 10 testosterone). Testosterone therapy did not ameliorate CRF symptoms (placebo to testosterone difference in predicted mean multidimensional fatigue symptom inventory scores: -5.6, 95% CI: -24.6 to 13.3), improve inflammatory markers, or preserve health-related quality of life and functional measures of performance in late-stage cancer patients.

Pulmonary embolism (PE) can present with a wide spectrum of clinical symptoms that can overlap considerably with other cardiovascular diseases. To avoid PE related morbidity and mortality, it is vital to identify this disease accurately and in a timely fashion. Several clinical criteria have been developed to standardize the diagnostic approach for patients with suspected PE. Computed tomographic pulmonary angiogram has significantly improved the detection of pulmonary embolism and is considered the imaging modality of choice to diagnose this disease. However, there are several potential pitfalls associated with this modality which can make diagnosis of PE challenging. In this review, we will discuss various pitfalls routinely encountered in the diagnostic work up of patients with suspected PE, approaches to mitigate these pitfalls and incidental pulmonary embolism., (Copyright © 2022 Elsevier Inc. All rights reserved.)