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Abstract Introduction Multiple sclerosis (MS) patients of African descent have increased risk for disease progression and may be less responsive to disease-modifying therapy. Methods Patients in the CARE-MS studies received alemtuzumab 12 mg/day [initial alemtuzumab treatment (IAT); baseline: 5 days; 12 months later: 3 days] or subcutaneous interferon beta-1a (SC IFNB-1a) 3 ×/week. Core study outcomes were compared between treatment groups. In the extension study CAMMS03409, SC IFNB-1a-treated patients switched to alemtuzumab [delayed alemtuzumab treatment (DAT)]. Data from IAT and DAT arms were pooled to assess outcomes through 6 years post alemtuzumab initiation; IAT patients had an additional 2 years of follow-up in TOPAZ. Results Of 1200 CARE-MS patients, 43 (4%) were of African descent (35 IAT; 8 DAT) and received alemtuzumab in the 2-year core and/or 6-year extension; 29 (67%) remained on study at the time of analysis (24 IAT patients completed year 8 post alemtuzumab; 5 DAT patients completed year 6 post alemtuzumab). In year 2, annualized relapse rate (ARR; 0.09 versus 0.42), percentage of patients with improved Expanded Disability Status Scale (EDSS; 18% versus 11%), 6-month confirmed disability improvement (CDI; 28% versus 13%), no evidence of disease activity (55% versus 13%), and cumulative brain volume loss (BVL; − 0.55% versus − 1.32%) favored alemtuzumab versus SC IFNB-1a. Alemtuzumab remained efficacious at year 6 (pooled IAT/DAT) and at year 8 (IAT only) post alemtuzumab (ARR: 0.15 and 0.30; improved EDSS: 17% and 25%; CDI: 47% and 55%; BVL: − 1.14% and − 0.70%, respectively). No safety signals were unique to this population. Conclusions Alemtuzumab was efficacious in a small cohort of relapsing-remitting MS patients of African descent over 8 years. Safety was consistent with the overall CARE-MS population, although the small sample size may have prevented the detection of known low-frequency adverse events. ClinicalTrials.gov Registration Numbers CARE-MS I, II, extension, TOPAZ: NCT00530348, NCT00548405, NCT00930553, NCT02255656. Funding Sanofi (Cambridge, MA, USA) and Bayer HealthCare Pharmaceuticals (Leverkusen, Germany).

Background In the I CARE study, colon cancer patients were randomly assigned to receive follow-up care from either a general practitioner (GP) or a surgeon. Here, we address a secondary outcome, namely, detection of recurrences and effect on time to detection of transferring care from surgeon to GP. Methods Pattern, stage, and treatment of recurrences were described after 3 years. Time to event was defined as date of surgery, until date of recurrence or last follow-up, with death as competing event. Effects on time to recurrence and death were estimated as hazard ratios (HRs) using Cox regression. Restricted mean survival times were estimated. Results Of 303 patients, 141 were randomly assigned to the GP and 162 to the surgeon. Patients were male (67%) with a mean age of 68.0 (8.4) years. During follow-up, 46 recurrences were detected; 18 (13%) in the GP vs 28 (17%) in the surgeon group. Most recurrences were detected via abnormal follow-up tests (74%) and treated with curative intent (59%). Hazard ratio for recurrence was 0.75 (95% confidence interval [CI] = 0.41 to 1.36) in GP vs surgeon group. Patients in the GP group remained in the disease-free state slightly longer (2.76 vs 2.71 years). Of the patients, 38 died during follow-up; 15 (11%) in the GP vs 23 (14%) in the surgeon group. Of these, 21 (55%) deaths were related to colon cancer. There were no differences in overall deaths between the groups (HR = 0.76, 95% CI = 0.39 to 1.46). Conclusion Follow-up provided by GPs vs surgeons leads to similar detection of recurrences. Also, no differences in mortality were found. [ABSTRACT FROM AUTHOR]

Background and Aims There are concerns regarding the potential impact of the COVID-19 outbreak on patients with inflammatory bowel disease [IBD]. We report on the impact of the COVID-19 outbreak in a European prospective cohort study of patients with IBD Patients and Methods We prospectively collected data from 5457 patients with IBD nested in the ongoing I-CARE project and still followed up in April 2020, with monthly online monitoring of clinical activity, treatment, imaging and endoscopy. Investigators were also contacted to report incidental cases. Results In total, 233 [4.3%] reported COVID-19 and 12 [0.2%] severe COVID-19, with no COVID-19 deaths. The risk of COVID-19 in patients with IBD was not increased compared to the general population (standardized incidence ratio [SIR]: 1.18, 95% confidence interval [CI] [1.03–1.34], p  = 0.009), as well as the risk of severe COVID-19 (SIR: 0.69, 95% CI [0.35–1.20], p  = 0.93). We did not observe any negative impact of the different IBD-related medication on the risk of either COVID-19 or severe COVID-19. In 2020, the COVID-19 outbreak resulted in a drastic decrease in endoscopic and imaging procedures from March to May 2020 compared to 2018 and 2019. No impacts on clinical IBD disease activity as well as ongoing treatment were noted. Conclusion No increases in either COVID-19 or severe COVID-19 incidences were observed in patients with IBD. There was no impact of COVID-19 on IBD-related medication and clinical activity. Access to endoscopy and imaging was restricted during the first months of the first COVID-19 outbreak. [ABSTRACT FROM AUTHOR]

Background: Alemtuzumab efficacy versus subcutaneous interferon-β-1a (SC IFNB-1a) was demonstrated over 2 years in patients with relapsing-remitting multiple sclerosis, with continued efficacy over 7 additional years. Alemtuzumab is included as a recommended treatment for patients with highly active disease (HAD) by the American Academy of Neurology Practice Guidelines, and the label indication in Europe was recently restricted to the treatment of HAD patients. There is currently no consensus definition for HAD, and alemtuzumab efficacy across various HAD definitions has not been explored previously.Objectives: In this post hoc analysis, we assess the efficacy and safety of alemtuzumab in Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) trial patients who met criteria for at least one of four separate definitions of HAD (one primary and three alternatives). Over 2 years, alemtuzumab-treated HAD patients were compared with SC IFNB-1a-treated HAD patients, with additional 7-year follow-up in patients from the alemtuzumab arm.Methods: Patients in the CARE-MS studies received either alemtuzumab (baseline: 5 days; 12 months later: 3 days) or SC IFNB-1a (3 times weekly). Alemtuzumab-treated patients who enrolled in the extensions could receive additional courses ≥ 12 months apart. Four definitions of HAD were applied to assess alemtuzumab efficacy: the pre-specified primary definition (two or more relapses in the year prior to baseline and at least one gadolinium [Gd]-enhancing lesion at baseline) and three alternative definitions that focused on relapse, magnetic resonance imaging (MRI), or prior treatment response criteria. Efficacy outcomes were annualized relapse rate, change in Expanded Disability Status Scale score, 6-month confirmed disability worsening, 6-month confirmed disability improvement, MRI disease activity, and brain volume change. Adverse events were summarized for HAD patients meeting the primary definition.Results: In the pooled CARE-MS population, 208 alemtuzumab-treated patients met the primary HAD definition. Annualized relapse rate was 0.27 in years 0-2 and 0.16 in years 3-9. Over 9 years, 62% of patients were free of 6-month confirmed disability worsening, 50% had 6-month confirmed disability improvement, and median cumulative change in brain volume was - 2.15%. During year 9, 62% had no evidence of disease activity, and 69% were free of MRI disease activity. Similar efficacy outcomes were observed using an alternative relapse-driven HAD definition. For patients meeting alternative HAD definitions focused on either higher MRI lesion counts or disease activity while on prior therapy, reduced efficacy for some endpoints was seen. Safety was consistent with the overall CARE-MS population through year 9.Conclusions: Over 9 years, alemtuzumab efficacy was maintained in CARE-MS HAD patients based on four HAD definitions. These results support intervention with alemtuzumab in patients with early indicators of HAD, including frequent relapse without high MRI activity. No safety signals were observed over 9 years that were unique to the HAD populations. CLINICALTRIALS.Gov Identifiers: NCT00530348; NCT00548405; NCT00930553; NCT02255656. [ABSTRACT FROM AUTHOR]

Introduction Charles-Bonnet syndrome was described in 1760 by the Swiss philosopher Charles-Bonnet, who reported that his grandfather’s visual hallucinations were due to eye disease rather than mental illness. It is characterized by the presence of visual hallucinations, which are usually complex and structured, in elderly patients with preserved cognitive status, significant deterioration in visual acuity and no evidence of associated psychiatric or neurological disease. Objectives The objective of this poster is to contribute a case to the existing series, and thus get closer to the knowledge of this clinical entity. Methods To review the case, a search was made in Pubmed with the terms hallucinations and Charles Bonnet’s Syndrome. Results This is a 76-year-old man, in follow-up by the ophthalmology service in the context of bilateral cataract, which causes severe visual disturbance. He went to our hospital, accompanied by his wife, reporting that for some months he has had complex visual hallucinations of various animals, colors in space, as well as children playing around him. All this generates a lot of anxiety, although the patient makes adequate criticism of them. The neurological examination performed was normal. The CT scan and laboratory tests were also within normal limits. Cognitive impairment was explored using the MMSE scale, which did not show any alteration. In addition, after a psychiatric evaluation, the patient does not meet the criteria for any disorder included in the DSM V. After reviewing the literature and taking into account the clinical picture described, the case is framed within a Charles-Bonnet syndrome. Regarding the therapeutic plan carried out, it was decided to start treatment with Gabapentin up to a maximum dose of 900 mg/day, with a considerable improvement in the hallucinatory symptoms. In addition, given the repercussion at the affective level, especially with a predominance of anxious symptoms, it was decided to start sertraline at a dose of 50 mg/day, with an adequate therapeutic response. Conclusions Charles-Bonnet syndrome refers to hallucinosis, generally of a visual nature, that appear in patients with a sensory deficit associated with the type of sensory-perceptive alteration. It is important to take it into account in the differential diagnosis of the elderly patient with hallucinosis. There is no established treatment, although neuroleptics, benzodiazepines, antidepressants and antiepileptics are used. Disclosure of Interest None Declared

Introduction Obsessive-compulsive disorder (OCD) is a mental disorder in which patients who suffer from it have repetitive and undesirable thoughts, feelings, ideas, sensations (obsessions) and behaviors that drive them to do something over and over again (compulsions). Often the person tries to get rid of the obsessive thoughts through compulsions, but this only provides short-term relief. Not carrying out the obsessive rituals can cause enormous anxiety and suffering. Objectives To describe a 23-year-old male patient, who suffers from anxiety and mood symptoms, reacts to ego-dystonic obsessive ideas and sexual content, of months of evolution, and who manages to calm down through compulsive masturbation or watching sexual videos on the internet. All this clinic negatively interferes with their quality of life, asking the patient for medical help to calm these ideas. Methods We carried out a review in Pubmed with the terms Antiandrogens and TOC, in order to make a better description of the clinical case. Results After several treatment attempts (Sertraline, Paroxetine, Clomipramine, Clomipramine + SSRI), reaching maximum doses according to clinical guidelines, and with poor therapeutic response, it was decided to discuss the case with the endocrinology department of our hospital, deciding to start treatment with antiandrogens, in order to alleviate the persistent intrusive ideas of a sexual nature. The administration of antiandrogens in men can cause a decrease or increase in the development or involution of secondary sexual characteristics in men, reducing the activity or function of accessory sexual organs, and hyposexuality, with decreased sexual desire or libido. After several weeks, there was improvement in the obsessive symptoms with a decrease in compulsive rituals. However, after the 3rd mo, some symptoms reappeared, but not with the same severity and intensity as before treatment. In addition, we cannot ignore the adverse effects that have occurred, such as involution of secondary sexual characteristics. However, and taking into account the negative repercussion that this clinic had on the patient’s quality of life, the benefit obtained exceeded the risk, having noted clear improvement with this therapy, and maintaining evolutionary controls by both psychiatry and endocrinology. Conclusions Patients suffering from obsessive-compulsive disorder can be effectively treated with anti-androgenic pharmacological agents with various modes of action. The most effective group of such agents is the long-acting analogues of the gonadotropin-releasing hormone. The objective of this review is to elucidate the possibility of using such powerful anti-androgenic agents in the treatment of obsessive-compulsive disorder. Disclosure of Interest None Declared

Background: Colon cancer is associated with an increased risk of physical and psychosocial morbidity, even after treatment. General practitioner (GP) care could be beneficial to help to reduce this morbidity. We aimed to assess quality of life (QOL) in patients who received GP-led survivorship care after treatment for colon cancer compared with those who received surgeon-led care. Furthermore, the effect of an eHealth app (Oncokompas) on QOL was assessed in both patient groups.Methods: We did a pragmatic two-by-two factorial, open-label, randomised, controlled trial at eight hospitals in the Netherlands. Eligible patients were receiving primary surgical treatment for stage I-III colon cancer or rectosigmoid carcinoma and qualified for routine follow-up according to Dutch national guidelines. Patients were randomly assigned (1:1:1:1)-via computer-generated variable block randomisation stratified by age and tumour stage-to survivorship care overseen by a surgeon, survivorship care overseen by a surgeon with access to Oncokompas, survivorship care overseen by a GP, or survivorship care overseen by a GP with access to Oncokompas. Blinding of the trial was not possible. The primary endpoint of the trial was QOL at 5 years, as measured by the change from baseline in the European Organistion for Research and Treatment of Cancer QLQ-C30 summary score. Here, we report an unplanned interim analysis of QOL at the 12-month follow-up. Grouped comparisons were done (ie, both GP-led care groups were compared with both surgeon-led groups, and both Oncokompas groups were compared with both no Oncokompas groups). Differences in change of QOL between trial groups were estimated with linear mixed-effects models. A change of ten units was considered clinically meaningful. Analysis was by intention to treat. This trial is registered with the Netherlands Trial Register, NTR4860.Findings: Between March 26, 2015, and Nov 21, 2018, 353 patients were enrolled and randomly assigned. There were 50 early withdrawals (27 patient decisions and 23 GP withdrawals). Of the remaining 303 participants, 79 were assigned to surgeon-led care, 83 to surgeon-led care with Oncokompas, 73 to GP-led care, and 68 to GP-led care with Oncokompas. Median follow-up was 12·2 months (IQR 12·0-13·0) in all groups. At baseline, QOL was high in all trial groups. At 12 months, there was no clinically meaningful difference in change from baseline in QOL between the GP-led care groups and the surgeon-led care groups (difference in summary score -2·3 [95% CI -5·0 to 0·4]) or between the Oncokompas and no Oncokompas groups (-0·1 [-2·8 to 2·6]).Interpretation: In terms of QOL, GP-led survivorship care can be considered as an alternative to surgeon-led care within the first year after colon cancer treatment. Other outcomes, including patient and physician preferences, will be important for decisions about the type of survivorship care.Funding: Dutch Cancer Society (KWF). [ABSTRACT FROM AUTHOR]

Tuberculosis is one of the leading causes of death due to a single infectious agent. Upon infection, Mycobacterium tuberculosis ( M.tb ) is deposited in the alveoli and encounters the lung mucosa or alveolar lining fluid (ALF). We previously showed that, as we age, ALF presents a higher degree of oxidation and inflammatory mediators, which favors M.tb replication in human macrophages and alveolar epithelial cells (ATs). Here, we define the transcriptional profile of M.tb when exposed to healthy ALF from adult (A-ALF) or elderly (E-ALF) humans before and during infection of ATs. Prior to infection, M.tb exposure to E-ALF upregulated genes essential for bacterial host adaptation directly involved in M.tb pathogenesis. During infection of ATs, E-ALF exposed M.tb further upregulated genes involved in its ability to escape into the AT cytosol bypassing critical host defense mechanisms, as well as genes associated with defense against oxidative stress. These findings demonstrate how alterations in human ALF during the aging process can impact the metabolic status of M.tb , potentially enabling a greater adaptation and survival within host cells. Importantly, we present the first transcriptomic analysis on the impact of the elderly lung mucosa on M.tb pathogenesis during intracellular replication in ATs.IMPORTANCETuberculosis is one of the leading causes of death due to a single infectious agent. Upon infection, Mycobacterium tuberculosis ( M.tb ) is deposited in the alveoli and comes in contact with the alveolar lining fluid (ALF). We previously showed that elderly ALF favors M.tb replication in human macrophages and alveolar epithelial cells (ATs). Here we define the transcriptional profile of when exposed to healthy ALF from adult (A-ALF) or elderly (E-ALF) humans before and during infection of ATs. Prior to infection, exposure to E-ALF upregulates genes essential for bacterial host adaptation and pathogenesis. During infection of ATs, E-ALF further upregulates M.tb genes involved in its ability to escape into the AT cytosol, as well as genes for defense against oxidative stress. These findings demonstrate how alterations in human ALF during the aging process can impact the metabolic status of M.tb , potentially enabling a greater adaptation and survival within host cells.

Importance: Information on long-term benefits and harms of screening with digital breast tomosynthesis (DBT) with or without supplemental breast magnetic resonance imaging (MRI) is needed for clinical and policy discussions, particularly for patients with dense breasts., Objective: To project long-term population-based outcomes for breast cancer mammography screening strategies (DBT or digital mammography) with or without supplemental MRI by breast density., Design, Setting, and Participants: Collaborative modeling using 3 Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer simulation models informed by US Breast Cancer Surveillance Consortium data. Simulated women born in 1980 with average breast cancer risk were included. Modeling analyses were conducted from January 2020 to December 2023., Intervention: Annual or biennial mammography screening with or without supplemental MRI by breast density starting at ages 40, 45, or 50 years through age 74 years., Main Outcomes and Measures: Lifetime breast cancer deaths averted, false-positive recall and false-positive biopsy recommendations per 1000 simulated women followed-up from age 40 years to death summarized as means and ranges across models., Results: Biennial DBT screening for all simulated women started at age 50 vs 40 years averted 7.4 vs 8.5 breast cancer deaths, respectively, and led to 884 vs 1392 false-positive recalls and 151 vs 221 false-positive biopsy recommendations, respectively. Biennial digital mammography had similar deaths averted and slightly more false-positive test results than DBT screening. Adding MRI for women with extremely dense breasts to biennial DBT screening for women aged 50 to 74 years increased deaths averted (7.6 vs 7.4), false-positive recalls (919 vs 884), and false-positive biopsy recommendations (180 vs 151). Extending supplemental MRI to women with heterogeneously or extremely dense breasts further increased deaths averted (8.0 vs 7.4), false-positive recalls (1088 vs 884), and false-positive biopsy recommendations (343 vs 151). The same strategy for women aged 40 to 74 years averted 9.5 deaths but led to 1850 false-positive recalls and 628 false-positive biopsy recommendations. Annual screening modestly increased estimated deaths averted but markedly increased estimated false-positive results., Conclusions and Relevance: In this model-based comparative effectiveness analysis, supplemental MRI for women with dense breasts added to DBT screening led to greater benefits and increased harms. The balance of this trade-off for supplemental MRI use was more favorable when MRI was targeted to women with extremely dense breasts who comprise approximately 10% of the population.

Background: For decades, dengue has posed a significant threat as a viral infectious disease, affecting numerous human lives globally, particularly in tropical regions, yet no cure has been discovered. The genetic trait of vector competence in Aedes mosquitoes, which facilitates dengue transmission, is difficult to measure and highly sensitive to environmental changes., Methods: In this study we attempt, for the first time in a non-laboratory setting, to quantify the vector competence of Aedes mosquitoes assuming its homogeneity across both species; aegypti and albopictus and across the four Dengue serotypes. Estimating vector competence in relation to varying rainfall patterns was focused in this study to showcase the changes in this vector trait with respect to environmental variables. We quantify it using an existing mathematical model originally developed for malaria in a Bayesian inferencing setup. We conducted this study in the Colombo district of Sri Lanka where the highest number of human populations are threatened with dengue. Colombo district experiences continuous favorable temperature and humidity levels throughout the year creating ideal conditions for Aedes mosquitoes to thrive and transmit the Dengue disease. Therefore we only used the highly variable and seasonal rainfall as the primary environmental variable as it significantly influences the number of breeding sites and thereby impacting the population dynamics of Aedes., Results: Our research successfully deduced vector competence values for the four identified seasons based on Monsoon rainfalls experienced in Colombo within a year. We used dengue data from 2009 - 2022 to infer the estimates. These estimated values have been corroborated through experimental studies documented in the literature, thereby validating the malaria model to estimate vector competence for dengue disease., Conclusion: Our research findings conclude that environmental conditions can amplify vector competence within specific seasons, categorized by their environmental attributes. Additionally, the deduced vector competence offers compelling evidence that it impacts disease transmission, irrespective of geographical location, climate, or environmental factors., (© 2024. The Author(s).)

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is a major global health concern, particularly affecting those with weakened immune systems, including the elderly. CD4 + T cell response is crucial for immunity against M.tb, but chronic infections and aging can lead to T cell exhaustion and senescence, worsening TB disease. Mitochondrial dysfunction, prevalent in aging and chronic diseases, disrupts cellular metabolism, increases oxidative stress, and impairs T-cell functions. This study investigates the effect of mitochondrial transplantation (mito-transfer) on CD4 + T cell differentiation and function in aged mouse models and human CD4 + T cells from elderly individuals. Mito-transfer in naïve CD4 + T cells is found to promote protective effector and memory T cell generation during M.tb infection in mice. Additionally, it improves elderly human T cell function by increasing mitochondrial mass and altering cytokine production, thereby reducing markers of exhaustion and senescence. These findings suggest mito-transfer as a novel approach to enhance aged CD4 + T cell functionality, potentially benefiting immune responses in the elderly and chronic TB patients. This has broader implications for diseases where mitochondrial dysfunction contributes to T-cell exhaustion and senescence., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

With devastating health and socioeconomic impact worldwide, much work is left to understand the Coronavirus Disease 2019 (COVID-19), with emphasis in the severely affected elderly population. Here, we present a proteomics study of lung tissue obtained from aged vs. young rhesus macaques (Macaca mulatta) and olive baboons (Papio Anubis) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using age as a variable, we identified common proteomic profiles in the lungs of aged infected non-human primates (NHPs), including key regulators of immune function, as well as cell and tissue remodeling, and discuss the potential clinical relevance of such parameters. Further, we identified key differences in proteomic profiles between both NHP species, and compared those to what is known about SARS-CoV-2 in humans. Finally, we explored the translatability of these animal models in the context of aging and the human presentation of the COVID-19., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Context: Concerns about brolucizumab's (Pagenax®) association with intraocular inflammation (IOI) limit its use despite its cost-effectiveness and efficacy. This multicentric study analyzes IOI incidence across 21 tertiary eyecare centers in India since its introduction in October 2020., Purpose: To determine the real-world incidence rate of IOI in Indian patients secondary to intravitreal brolucizumab across 21 tertiary eye care centers in India., Settings and Design: Retrospective multicentric, survey-based study., Methods: Data including number of patients treated, clinical indications, side effects encountered, and IOI case details was collected via Google Forms in 21 Indian tertiary eye care centers since October 2020. Mean, median, frequency, and standard deviation were calculated for statistical analysis., Results: All centers used pro re nata protocol for brolucizumab injections with a minimum injection interval of 8 weeks. The incidence of IOI was 0.79% (21 events out of 2655 eyes). Treatment indications included idiopathic polypoidal choroidal vasculopathy, neovascular age-related macular degeneration, diabetic macular edema, and off-label uses. IOI was experienced after the first injection (57%) in majority of cases with a median onset of 14 days (range: 1-65 days). IOI was mild in 28.5%, moderate in 33%, and severe in 38% of cases. Eighteen out of 21 IOI eyes recovered preinjection best corrected visual acuity or better., Conclusions: Our study found a lower IOI incidence (0.79%) with brolucizumab (Pagenax) in Indian patients compared to previously reported literature. IOI events were mostly mild to moderate, and post-treatment, most patients improved or maintained BCVA. Larger prospective multicentric studies with PRN dosing protocol are needed to confirm these findings., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Tuberculosis is the leading cause of death for people living with HIV (PLWH). We hypothesized that altered functions of innate immune components in the human alveolar lining fluid of PLWH (HIV-ALF) drive susceptibility to Mycobacterium tuberculosis (M.tb) infection. Our results indicate a significant increase in oxidation of innate proteins and chemokine levels and significantly lower levels and function of complement components and Th1/Th2/Th17 cytokines in HIV-ALF versus control-ALF (non-HIV-infected people). We further found a deficiency of surfactant protein D (SP-D) and reduced binding of SP-D to M.tb that had been exposed to HIV-ALF. Primary human macrophages infected with M.tb exposed to HIV-ALF were significantly less capable of controlling the infection, which was reversed by SP-D replenishment in HIV-ALF. Thus, based on the limited number of participants in this study, our data suggest that PLWH without antiretroviral therapy (ART) have declining host innate defense function in their lung mucosa, thereby favoring M.tb and potentially other pulmonary infections., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still an ongoing global health crisis. Clinical data indicate that the case fatality rate (CFR) is age dependent, with a higher CFR percentage in the elderly population. We compared the pathogenesis of SARS-CoV-2 in young and aged K18-hACE2 transgenic mice. We evaluated morbidity, mortality, viral titers, immune responses, and histopathology in SARS-CoV-2-infected young and old K18-hACE2 transgenic mice. Within the limitation of having a low number of mice per group, our results indicate that SARS-CoV-2 infection resulted in slightly higher morbidity, mortality, and viral replication in the lungs of old mice, which was associated with an impaired IgM response and altered cytokine and chemokine profiles. Results of this study increase our understanding of SARS-CoV-2 infectivity and immuno-pathogenesis in the elderly population., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

The elderly population is highly susceptible to developing respiratory diseases, including tuberculosis, a devastating disease caused by the airborne pathogen Mycobacterium tuberculosis (M.tb) that kills one person every 18 seconds. Once M.tb reaches the alveolar space, it contacts alveolar lining fluid (ALF), which dictates host-cell interactions. We previously determined that age-associated dysfunction of soluble innate components in human ALF leads to accelerated M.tb growth within human alveolar macrophages. Here we determined the impact of human ALF on M.tb infection of alveolar epithelial type cells (ATs), another critical lung cellular determinant of infection. We observed that elderly ALF (E-ALF)-exposed M.tb had significantly increased intracellular growth with rapid replication in ATs compared to adult ALF (A-ALF)-exposed bacteria, as well as a dampened inflammatory response. A potential mechanism underlying this accelerated growth in ATs was our observation of increased bacterial translocation into the cytosol, a compartment that favors bacterial replication. These findings in the context of our previous studies highlight how the oxidative and dysfunctional status of the elderly lung mucosa determines susceptibility to M.tb infection, including dampening immune responses and favoring bacterial replication within alveolar resident cell populations, including ATs, the most abundant resident cell type within the alveoli., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The presence of lipoarabinomannan (LAM) in the Mycobacterium tuberculosis ( Mtb ) cell envelope was first reported close to 100 years ago. Since then, numerous studies have been dedicated to the isolation, purification, structural definition, and elucidation of the biological properties of Mtb LAM. In this review, we present a brief historical perspective on the discovery of Mtb LAM and the herculean efforts devoted to structurally characterizing the molecule because of its unique structural and biological features. The significance of LAM remains high to this date, mainly due to its distinct immunological properties in conjunction with its role as a biomarker for diagnostic tests due to its identification in urine, and thus can serve as a point-of-care diagnostic test for tuberculosis (TB). In recent decades, LAM has been thoroughly studied and massive amounts of information on this intriguing molecule are now available. In this review, we give the readers a historical perspective and an update on the current knowledge of LAM with information on the inherent carbohydrate composition, which is unique due to the often puzzling sugar residues that are specifically found on LAM. We then guide the readers through the complex and myriad immunological outcomes, which are strictly dependent on LAM's chemical structure. Furthermore, we present issues that remain unresolved and represent the immediate future of LAM research. Addressing the chemistry, functions, and roles of LAM will lead to innovative ways to manipulate the processes that involve this controversial and fascinating biomolecule.

Mycobacterium tuberculosis ( M.tb ) and SARS-CoV-2 are both infections that can lead to severe disease in the lower lung. However, these two infections are caused by very different pathogens ( Mycobacterium vs. virus), they have different mechanisms of pathogenesis and immune response, and differ in how long the infection lasts. Despite the differences, SARS-CoV-2 and M.tb share a common feature, which is also frequently observed in other respiratory infections: the burden of disease in the elderly is greater. Here, we discuss possible reasons for the higher burden in older adults, including the effect of co-morbidities, deterioration of the lung environment, auto-immunity, and a reduced antibody response. While the answer is likely to be multifactorial, understanding the main drivers across different infections may allow us to design broader interventions that increase the health-span of older people., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Allué-Guardia, Torrelles and Sigal.)

Background: Fathers are key influencers of complementary feeding practices, but few studies in low- and middle-income countries have measured the effects of complementary feeding social and behavior change communication (SBCC) targeted at both fathers and mothers., Objectives: The aims of this study were to measure the effects of an SBCC intervention on children's dietary diversity (primary outcome) and other complementary feeding indicators, fathers' and mothers' complementary feeding knowledge, and fathers' support for complementary feeding (secondary outcomes)., Methods: The 12-mo intervention in Kaduna State, Nigeria, engaged parents through community meetings, religious services, home visits from community health extension workers (CHEWs), mobile phone messages (fathers only), and mass media. Cross-sectional population-based surveys of cohabiting fathers and mothers with a child aged 6-23 mo were conducted, and regression models were used to compare results at baseline ( n  = 497) and endline ( n  = 495)., Results: Children's minimum dietary diversity did not change from baseline to endline (62% to 65%, P  = 0.441). Children's consumption of fish (36% to 44%, P  = 0.012) and eggs (8% to 20%, P  = 0.004) and minimum meal frequency (58% to 73%, P  < 0.001) increased. Fathers' and mothers' knowledge of the timing of introduction of different foods and meal frequency improved. Fathers' support for child feeding by providing money for food increased (79% to 90%, P  < 0.001). Fathers' and mothers' reported intervention exposure was low (11-26% across types of SBCC). Child feeding outcomes were not associated with fathers' exposure. Children's odds of both fish and egg consumption increased significantly with mothers' exposure to community meetings, religious services, home visits, and television spots, and children's odds of minimum meal frequency increased significantly with mothers' exposure to home visits., Conclusions: A multipronged SBCC intervention improved complementary feeding practices, fathers' and mothers' knowledge of complementary feeding, and fathers' support for complementary feeding, despite low levels of reported exposure, which may have been influenced by coronavirus disease 2019 (COVID-19) disruptions. This trial was registered at ClinicalTrials.gov as NCT04835662., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Artificial intelligence (AI) has shown promising results in digestive endoscopy, especially in capsule endoscopy (CE). However, some physicians still have some difficulties and fear the advent of this technology. We aimed to evaluate the perceptions and current sentiments toward the use of AI in CE. An online survey questionnaire was sent to an audience of gastroenterologists. In addition, several European national leaders of the International CApsule endoscopy REsearch (I CARE) Group were asked to disseminate an online survey among their national communities of CE readers (CER). The survey included 32 questions regarding general information, perceptions of AI, and its use in daily life, medicine, endoscopy, and CE. Among 380 European gastroenterologists who answered this survey, 333 (88%) were CERs. The mean average time length of experience in CE reading was 9.9 years (0.5-22). A majority of CERs agreed that AI would positively impact CE, shorten CE reading time, and help standardize reporting in CE and characterize lesions seen in CE. Nevertheless, in the foreseeable future, a majority of CERs disagreed with the complete replacement all CE reading by AI. Most CERs believed in the high potential of AI for becoming a valuable tool for automated diagnosis and for shortening the reading time. Currently, the perception is that AI will not replace CE reading.

One of the most important features of the proper operation of technical objects is monitoring the vibrations of their mechanical components. The currently significant proportion of the research methods in this regard includes a group of research methods based on the conversion of vibrations using sensors providing data from individual locations. In parallel with the continuous improvement of these tools, new methods for acquiring information on the condition of the object have emerged due to the rapid development of visual systems. Their actual effectiveness determined the switch from research laboratories to actual industrial installations. In many cases, the application of the visualization methods can supplement the conventional methods applied and, under particular conditions, can effectively replace them. The decisive factor is their non-contact nature and the possibility for simultaneous observation of multiple points of the selected area. Visual motion magnification (MM) is an image processing method that involves the conscious and deliberate deformation of input images to the form that enables the visual observation of vibration processes which are not visible in their natural form. The first part of the article refers to the basic terms in the field of expressing motion in an image (based on the Lagrangian and Eulerian approaches), the formulation of the term of optical flow (OF), and the interpretation of an image in time and space. The following part of the article reviews the main processing algorithms in the aspect of computational complexity and visual quality and their modification for applications under specific conditions. The comparison of the MM methods presented in the paper and recommendations for their applications across a wide variety of fields were supported with examples originating from recent publications. The effectiveness of visual methods based on motion magnification in machine diagnosis and the identification of malfunctions are illustrated with selected examples of the implementation derived from authors' workshop practice under industrial conditions.

Purpose: To assess the corneal endothelial cells morphology and count in keratoconus patients and their correlation with different stages of keratoconus., Methods: Prospective non randomized multi-centric clinical study included 150 eyes of 150 keratoconus patients. Four centers in Egypt participated in this study included: Departments of Ophthalmology in Alexandria University, Tanta University and Port Said University and Alex I-Care hospital. Pentacam (Wavelight Oculyzer II) and specular microscopy (Tomey EM-3000) were done to all eyes. Keratoconic eyes were classified according to Amsler classification into stage 1, 2 and 3. Stage 1 included 99 eyes, stage 2 included 32 eyes & stage 3 included 19 eyes., Results: The mean age of keratoconus patients was 24.07 ± 6.154 years. Forty five cases were males (30%) and 105 cases were females (70%). There was statistically significant difference in endothelial cell density (p < 0.001) and coefficient of variation (p = 0.012) between different stages of keratoconus eyes. Regarding cell surface area, there was statistically significant difference in cell surface area between different stages of keratoconus eyes (p < 0.001). In addition, for cell morphology, there was statistically significant difference between different stages of keratoconus eyes (p < 0.001)., Conclusions: Qualitative and quantitative structural changes were seen in endothelial cells of keratoconus eyes by using specular microscopy. For stages 1 and 2, keratoconus may not affect the corneal endothelim significantly. The endothelium in stage 3 shows significant changes regarding polymegathism and pleomorphism.

Competing Interests: The authors declare that they have no competing interests.

Purpose: To assess ophthalmic manifestations in patients with stroke and emphasize the importance of a formal screening for visual problems in stroke patients in hospital and rehabilitation settings., Methods: This was a cross-sectional study of 50 newly diagnosed patients with stroke with Glasgow Coma Scale (GCS) > 8 examined within 3 days of onset. A detailed ophthalmic examination was performed for each patient including visual acuity, fields, ocular motility, slit lamp and fundus examination, line bisection tests and cranial nerve assessment. Radiological investigations were reviewed and anatomically correlated., Results: A total of 50 patients (41 male and nine female) were included in the study. Mean age of the stroke cohort was 51.36 years. Twenty-nine patients (58%) had a subcortical stroke, while 42% (n = 21) patients had a cortical stroke. Nineteen patients (38%) demonstrated visual field defects. Twenty-one patients (42%) had a gaze palsy. Vertical gaze palsy (n = 8) was more common in cortical stroke, while internuclear ophthalmoplegia (n = 2), horizontal gaze palsies (n = 4) and Parinaud's syndrome (n = 1) were seen more commonly in those with subcortical stroke. Twenty-four percent (n = 12) patients had nystagmus. Twelve percent (n = 6) patients had diplopia. Thirty-eight percent (n = 19) patients had convergence insufficiency. Sixteen patients (32%) complained of visual impairment. Retinal abnormalities were seen in 58% (n = 29) of patients., Conclusions: Ophthalmic manifestations were seen in 90% of stroke survivors. Their presence in majority of the patients in our cohort suggests that earliest routine ophthalmic examination should be mandatory in all patients with acute stroke.

Purpose: To describe a new surgical technique "crescentic tuck in lamellar keratoplasty" for the management of advanced pellucid marginal corneal degeneration (PMCD)., Methods: A 45-year-old man with advanced PMCD and maximal thinning in the inferior juxtalimbal periphery underwent a crescentic lamellar keratoplasty in the right eye. Best-corrected visual acuity was 6/60 with no further improvement because of severe irregular astigmatism. Thinnest pachymetry in the peripheral cornea was 280 μm. Peripheral crescent-shaped lamellar corneal dissection of 3.5-mm width was performed, and an intrastromal pocket was fashioned from 4 to 8 O'clock, extending beyond limbus. A crescent-shaped donor corneal button of 3.5-mm width was denuded of its endothelium and beveled in inferior periphery to create a flange. The flange was tucked into the peripheral scleral pocket. The donor graft was secured to the host bed using 10-0 nylon interrupted sutures., Results: Donor cornea integrated with the host bed over time and best spectacle-corrected visual acuity at 1 year improved to 6/9 with -1.25/-3.5 D × 90°. The simK (simulated keratometry) changed from 41.6/56.3 diopters (D) to 45.1/50.6 D. The astigmatism reduced from 14.6 D to 5.5 D., Conclusion: Crescentic tuck in lamellar keratoplasty provides good apposition of the donor lenticule and tectonic support to the peripheral thin cornea while preserving the peripheral limbal stem cells. Additionally, there is a significant reduction in the astigmatism, resulting in visual improvement.

In an effort to prevent medication errors, barcode medication administration technology has been implemented in many health care organizations. An integrative review was conducted to understand the effect of barcode medication administration technology on medication errors, and characteristics of use demonstrated by nurses contribute to medication safety. Addressing poor system use may support improved patient safety through the reduction of medication administration errors.