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Introduction: The Intertrochanteric fracture is a common hip trauma encountered in elderly patients. There is a lack of general agreement regarding its surgical management and choice of implant. Purpose of this study to conclude the final decision matrix regarding surgical management of intertrochanteric fractures based on parameters assessed on plain radiographs and CT scan. Materials and methods: We have retrospectively evaluated 55 patients with intertrochanteric fractures presented to our institute after informed consent with radiographs and CT scans between July 2017 to July 2018. Assessment of various parameters regarding fracture geometry and classification as well as measurement was done. Results: Mean lateral wall thickness in present study was 20.76mm. Incidence of coronal fragments was 90.9% and absence of coronal fragment in 5 patients. We noted the cases with anterior comminution had also a posterior comminution rendered the fracture unstable in almost 20 % cases. Conclusion: Better understanding of fracture geometry by combined used of radiograph and CT scan enhanced preoperative planning, choice of suitable implant, helps in reduction manoeuvre and improving quality of osteosynthesis.

Background: Beta-lactams are the most common antibiotic class reported to cause allergic drug reactions. Previous literature suggests an increased prevalence of penicillin drug allergy in female patients in both inpatient and outpatient settings. However, the effects of sex and gender have not been well characterized regarding the entire class of beta-lactam antibiotics., Objective: This systematic review and meta-analysis aimed to identify sex and gender-based differences in the prevalence of immediate beta-lactam allergy., Methods: We performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library between 2013-2023. Patients with a documented beta-lactam allergy who underwent allergy testing with skin testing, oral drug challenge, or serum-specific IgE were included. We quantitatively assessed sex- and gender-based differences in beta-lactam allergy with meta-analysis., Results: We included 69 primary studies, assessing 53,989 participants from outpatient and inpatient cohorts. 7,558 patients had a confirmed beta-lactam allergy. There was no difference in the prevalence of positive beta-lactam allergy test between males and females. Sub-group analysis of studies that performed oral challenges did show a higher risk of beta-lactam allergy in females than males (RR 1.40, 95% CI 1.18-1.66, p < 0.001, I 2 =77.8%). Finally, there was a higher proportion of females (64.8%) than males enrolled in beta-lactam allergy studies., Conclusions: Our findings suggest both sex-based and gender-based differences in the prevalence of immediate beta-lactam allergy. Both biological factors, such as sex hormones, and gender-based behaviors, including increased healthcare utilization, may contribute to higher rates of beta-lactam allergy diagnosis in females., (Copyright © 2024. Published by Elsevier Inc.)

Background: Perianal draining tunnels in hidradenitis suppurativa (HS) and perianal fistulizing inflammatory bowel disease (IBD) present diagnostic and management dilemmas., Methods: We conducted a retrospective chart review of patients with perianal disease evaluated at Mayo Clinic from January 1, 1998, through July 31, 2021. Patients' demographic and clinical data were extracted, and 28 clinical features were collected. After experimenting with several machine learning techniques, random forests were used to select the 15 most important clinical features to construct the diagnostic prediction model to distinguish perianal HS from fistulizing perianal IBD., Results: A total of 263 patients were included (98 with HS, 100 with IBD, and 65 with both IBD and HS). Patients with HS had a higher mean body mass index, a higher smoking rate, and more commonly showed cutaneous manifestations of tunnels and comedones, while fistulas, abscesses, induration, anal tags, ulcers, and anal fissures were more common in patients with IBD. In addition to having lesions in the perianal area, patients with IBD often had lesions in the buttocks and perineum, while those with HS had additional lesions in the axillae and groin. Among the statistically significant features, the 15 most important were identified by random forest: fistula, tunnel, digestive symptom, knife-cut ulcer, perineum, body mass index, age, axilla, abscess, tags, smoking, groin, genital cutaneous edema, erythema, and bilateral/unilateral., Conclusions: The results of this study may help differentiate perianal lesions, especially perineal HS and fistulizing perineal IBD, and provide promise for a better therapeutic outcome., (© 2024 the International Society of Dermatology.)

Dengue infection can take on many different forms, ranging from no symptoms to a mild fever, all the way to a severe condition known as dengue shock syndrome. Although the typical symptoms of dengue are well known, the virus can also cause rare neurological complications. Dengue encephalitis is a severe form of neuroinvasive dengue that can be fatal as the virus directly affects the central nervous system. This case series provides a comprehensive overview of dengue, its clinical spectrum, and the potential for severe neurological complications such as dengue encephalitis. It highlights the importance of considering dengue as a possible diagnosis in patients with encephalitis, particularly during a dengue epidemic., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Purpose: The purpose of this study was to determine the effects of axial elongation on optic nerve head morphology and macula inner retinal thickness in young rhesus monkeys., Methods: Both eyes of 26 anisometropic, 1-year-old rhesus monkeys were imaged using optical coherence tomography (OCT). Before imaging, the animals were sedated, their eyes were dilated, and axial length was measured using an optical biometer. OCT imaging included a 20 degrees, 24-line radial scan centered on the optic nerve head (ONH) and two 20 degrees × 20 degrees raster scans, one centered on the ONH and the other on the macula. Radial scans were analyzed using programs written in MATLAB to quantify the Bruch's membrane opening (BMO) area and position, minimum rim width (MRW), anterior lamina cribrosa surface (ALCS) position, size of any scleral crescent, circumpapillary retinal nerve fiber layer (RNFL), and choroid thickness (pCh). Macula total retinal thickness (mTRT) and ganglion cell inner plexiform layer (GCIPL) thicknesses were quantified from macula scans. Linear least square regression was determined for OCT measures and axial length of the right eye, and for inter-eye differences., Results: Animals were 341 ± 18 days old at the time of imaging. BMO area (R2 = 0.38), ALCS position (R2 = 0.45), scleral crescent area (R2 = 0.35), pCh thickness (R2 = 0.21), mTRT (R2 = 0.24), and GCIPL thickness (R2 = 0.16) were correlated with the axial length (all P < 0.05). For each of these parameters, the right-eye regression slope did not differ from the slope of the interocular difference (P > 0.57)., Conclusions: There are posterior segment morphological differences in anisometropic rhesus monkeys related to axial length. Whether these differences increase the risk of pathology remains to be investigated.

Purpose: To characterize inner retinal microvasculature of rhesus monkeys with a range of refractive errors using optical coherence tomography angiography., Method: Refractive error was induced in right eyes of 18 rhesus monkeys. At 327 to 347 days of age, axial length and spherical equivalent refraction (SER) were measured, and optical coherence tomography and optical coherence tomography angiography scans (Spectralis, Heidelberg) were collected. Magnification-corrected metrics included foveal avascular zone area and perfusion density, fractal dimension, and lacunarity of the superficial vascular complex (SVC) and deep vascular complex (DVC) in the central 1-mm diameter and 1.0- to 1.5-mm, 1.5- to 2.0-mm, and 2.0- to 2.5-mm annuli. Pearson correlations were used to explore relationships., Results: The mean SER and axial length were 0.78 ± 4.02 D (-7.12 to +7.13 D) and 17.96 ± 1.08 mm (16.41 to 19.93 mm), respectively. The foveal avascular zone area and SVC perfusion density were correlated with retinal thickness for the central 1 mm (P < 0.05). SVC perfusion density of 2.0- to 2.5-mm annulus decreased with increasing axial length (P < 0.001). SVC and DVC fractal dimensions of 2.0- to 2.5-mm were correlated with axial length and SER, and DVC lacunarity of 1.5- to 2.0-mm annulus was correlated with axial length (P < 0.05)., Conclusions: Several inner retinal microvasculature parameters were associated with increasing axial length and SER in juvenile rhesus monkeys. These findings suggest that changes in retinal microvasculature could be indicators of refractive error development., Translational Relevance: In juvenile rhesus monkeys, increasing myopic refraction and axial length are associated with alterations in the inner retinal microvasculature, which may have implications in myopia-related changes in humans.

Immunization programs against SARS-CoV-2 with commercial intramuscular vaccines prevent disease but are less efficient in preventing infections. Mucosal vaccines can provide improved protection against transmission, ideally for different variants of concern (VOCs) and related sarbecoviruses. Here, we report a multi-antigen, intranasal vaccine, NanoSTING-SN (NanoSTING-Spike-Nucleocapsid), eliminates virus replication in both the lungs and the nostrils upon challenge with the pathogenic SARS-CoV-2 Delta VOC. We further demonstrate that NanoSTING-SN prevents transmission of the SARS-CoV-2 Omicron VOC (BA.5) to vaccine-naïve hamsters. To evaluate protection against other sarbecoviruses, we immunized mice with NanoSTING-SN. We showed that immunization affords protection against SARS-CoV, leading to protection from weight loss and 100% survival in mice. In non-human primates, animals immunized with NanoSTING-SN show durable serum IgG responses (6 months) and nasal wash IgA responses cross-reactive to SARS-CoV-2 (XBB1.5), SARS-CoV and MERS-CoV antigens. These observations have two implications: (1) mucosal multi-antigen vaccines present a pathway to reducing transmission of respiratory viruses, and (2) eliciting immunity against multiple antigens can be advantageous in engineering pan-sarbecovirus vaccines., (© 2024. The Author(s).)

Purpose: To determine the relationship between visual sensitivities from white-on-white Goldmann size I to V stimuli and the underlying retinal ganglion cell (RGC) content in the non-human primate (NHP) experimental glaucoma model., Methods: Normative data were collected from 13 NHPs. Unilateral experimental glaucoma was induced in seven animals with the least variable fields who were monitored using optical coherence tomography and 30-2 full-threshold standard automated perimetry (SAP). At varying endpoints, animals were euthanized followed by perfusion fixation, and 1-mm retinal punches were obtained from 34 corresponding SAP locations. RGCs were immunolabeled with an antibody against an RNA-binding protein (RBPMS) marker and imaged using confocal microscopy. RGC counts from each location were then related to visual sensitivities for each stimulus size, after accounting for ocular magnification., Results: At the endpoint, the circumpapillary retinal nerve fiber layer thickness for experimental glaucoma eyes ranged from 47 to 113 µm. RGC density in control eyes was greatest for the 4.24° sample (18,024 ± 6869 cells/mm2) and decreased with eccentricity. Visual sensitivity at each tested location followed that predicted by spatial summation, with the critical area increasing with eccentricity (slope = 0.0036, R2 = 0.44). The relationship between RGC counts and visual sensitivity was described using a two-line fit, where the intercept of the first segment and hinge points were dependent on eccentricity., Conclusions: In NHPs, SAP visual thresholds are related to the underlying RGCs. The resulting spatial summation based structure-function model can be used to estimate RGC content from any standard white-on-white stimulus size.

Background: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process., Objective: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form., Methods: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed., Results: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form., Conclusion: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Compound 1 is formed by a microwave-assisted multicomponent reaction of 1-methylpiperidin-4-one, 2-amino-4-methoxy-6-methyl-1,3,5-triazine, and thiosemicarbazide, followed by the synthesis of Schiff base 2a-l with a variety of aldehydes. A comparison was made between the conventional and microwave methods, and the microwave approach was shown to be considerably superior to the classical method since it takes less time and produces higher yields. Several spectral investigations, including 1 H NMR, 13 C NMR, Mass, and IR spectroscopy, are used to characterize the complete series. In vitro antibacterial testing suggests that compounds 2c, 2f, and 2g are promising antibacterial agents, although compounds 2d, 2e, and 2l are effective antimycobacterial agents when compared to the conventional medicine Rifampicin. The docking score from docking studies is considerable, which validates the results of the biological examination. Molecular docking was performed on Escherichia coli DNA gyrase. According to the in silico ADME analysis, each drug molecule is ideal for use in terms of drug solubility, hydrogen bonding, and cell permeability., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: This study aims to examine the short-term peripheral choroidal thickness (PChT) response to signed defocus blur, both with and without native peripheral aberrations. This examination will provide insights into the role of peripheral aberration in detecting signs of defocus., Methods: The peripheral retina (temporal 15°) of the right eye was exposed to a localized video stimulus in 11 young adults. An adaptive optics system induced 2D myopic or hyperopic defocus onto the stimulus, with or without correcting native peripheral ocular aberrations (adaptive optics [AO] or NoAO defocus conditions). Choroidal scans were captured using Heidelberg Spectralis OCT at baseline, exposure (10, 20, and 30 minutes), and recovery phases (4, 8, and 15 minutes). Neural network-based automated MATLAB segmentation program measured PChT changes from OCT scans, and statistical analysis evaluated the effects of different optical conditions over time., Results: During the exposure phase, NoAO myopic and hyperopic defocus conditions exhibited distinct bidirectional PChT alterations, showing average thickening (10.0 ± 5.3 µm) and thinning (-9.1 ± 5.5 µm), respectively. In contrast, induced AO defocus conditions did not demonstrate a significant change from baseline. PChT recovery to baseline occurred for all conditions. The unexposed fovea did not show any significant ChT change, indicating a localized ChT response to retinal blur., Conclusions: We discovered that the PChT response serves as a marker for detecting peripheral retinal myopic and hyperopic defocus blur, especially in the presence of peripheral aberrations. These findings highlight the significant role of peripheral oriented blur in cueing peripheral defocus sign detection.

Purpose: Studies report conflicting findings regarding choroidal thickness changes in response to myopic defocus in humans. This study aimed to investigate the choroidal response to myopic defocus in children and adults using automated analysis., Methods: Participants (N = 46) were distance-corrected in both eyes and viewed a movie on a screen for 10 minutes. Two optical coherence tomography (OCT) radial scans were collected for each eye, then +3 diopters was added to one eye. Participants continued to watch the movie, OCT scans were repeated every 10 minutes for 50 minutes, and then recovery was assessed at 60 and 70 minutes. Defocus was interrupted for approximately two out of each 10 minutes for OCT imaging. OCT images were analyzed using an automated algorithm and trained neural network implemented in MATLAB to determine choroidal thickness at each time point. Repeated-measures ANOVA was used to assess changes with time in three age groups (6-17, 18-30, and 31-45 years) and by refractive error group (myopic and nonmyopic)., Results: Choroidal thickness was significantly associated with spherical equivalent refraction, with the myopic group having a thinner choroid than the nonmyopic group (P < 0.001). With imposed myopic defocus, there were no significant changes in choroidal thickness at any time point for any age group and for either refractive error group (P > 0.05 for all)., Conclusions: Findings demonstrate that, using the described protocol, the choroidal thickness of children and adults does not significantly change in response to short-term, full-field myopic defocus, in contrast to several previously published studies.

Background: Depression, a relevant comorbidity with asthma, has been reported to be associated with asthma morbidity. Asthma self-management is essential to asthma control and may be negatively impacted by depression. We examined these associations in rural adolescents, a group with relatively high asthma morbidity and depressive symptoms, a population often ignored in asthma research., Methods: We used baseline data from a randomized trial of an asthma intervention for adolescents in rural South Carolina ( n  = 197). Adolescents completed the Center for Epidemiological Studies-Depression (CES-D), three indices of asthma self-management (the Asthma Prevention Index, the Asthma Management Index and the Asthma Self-Efficacy Index), and the Asthma Control Test (ACT). Poisson and linear regression tested associations between depression, self-management, and asthma control. The models controlled for demographic variables and included school as a fixed effect., Results: Most participants (mean age = 16.3 ± 1.2 years) self-identified as female (68.5%) and Black (62.43%). The mean CES-D score was 19.7 ± 10.3, with 61.4% of participants at risk for depression. The depressive symptoms were significantly related to asthma control [ β  = -0.085, 95% confidence interval (CI) = -0.14 to -0.03] but not to prevention [relative risk (RR) = 1.00, 95% CI = 0.99-1.01], management (RR = 1.00, 95% CI = 0.99-1.01), or self-efficacy ( β  = -0.002, 95% CI = -0.01 to 0.01)., Conclusions: In this sample of rural adolescents, as depressive symptoms increased, asthma control declined. Depressive symptoms were not associated with asthma self-management, suggesting that the aspects of self-management we assessed are not an avenue by which depression impacts asthma control. Additional research is needed to further understand the relationship between depressive symptoms, asthma self-management, and control., 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., (© 2024 Patel, Céspedes, Liu and Bruzzese.)

Isonicotinohydrazide is the first-line medication in the prevention and treatment of tuberculosis. Antitubercular, antibacterial, antifungal, antiviral, anti-inflammatory, antimalarial activity, anticancer, antineoplastic activity, and anti-HIV activity are all demonstrated by drugs with a pyrimidine ring. The current study focuses on the synthesis of N-(4-(substituted-phenyl)-6-(substituted-aryl) pyrimidin-2-yl)-2-(2-isonicotinoylhydrazinyl) acetamide from isonicotinohydrazide. Newly synthesized compounds were characterized by spectral studies (IR, 1 H-NMR, 13 C-NMR, and mass spectroscopy). They were screened for their antituberculosis, antimalarial, and antiprotozoal activities and compared with standard drugs. Molecular docking of isonicotinohydrazide-bearing pyrimidine motifs was also done for some of the active compounds., (© 2024 Wiley Periodicals LLC.)

Purpose: Intracranial pressure increases in head-down tilt (HDT) body posture. This study evaluated the effect of HDT on the optic nerve sheath diameter (ONSD) in normal subjects., Methods: Twenty six healthy adults (age 28 [4.7] years) participated in seated and 6° HDT visits. For each visit, subjects presented at 11:00 h for baseline seated scans and then maintained a seated or 6° HDT posture from 12:00 to 15:00 h. Three horizontal axial and three vertical axial scans were obtained at 11:00, 12:00 and 15:00 h with a 10 MHz ultrasonography probe on the same eye, randomly chosen per subject. At each time point, horizontal and vertical ONSD (mm) were quantified by averaging three measures taken 3 mm behind the globe., Results: In the seated visit, ONSDs were similar across time (p > 0.05), with an overall mean (standard deviation) of 4.71 (0.48) horizontally and 5.08 (0.44) vertically. ONSD was larger vertically than horizontally at each time point (p < 0.001). In the HDT visit, ONSD was significantly enlarged from baseline at 12:00 and 15:00 h (p < 0.001 horizontal and p < 0.05 vertical). Mean (standard error) horizontal ONSD change from baseline was 0.37 (0.07) HDT versus 0.10 (0.05) seated at 12:00 h (p = 0.002) and 0.41 (0.09) HDT versus 0.12 (0.06) seated at 15:00 h (p = 0.002); mean vertical ONSD change was 0.14 (0.07) HDT versus -0.07 (0.04) seated at 12:00 h (p = 0.02) and 0.19 (0.06) HDT versus -0.03 (0.04) seated at 15:00 h (p = 0.01). ONSD change in HDT was similar between 12:00 and 15:00 h (p ≥ 0.30). Changes at 12:00 h correlated with those at 15:00 h for horizontal (r = 0.78, p < 0.001) and vertical ONSD (r = 0.73, p < 0.001)., Conclusion: The ONSD increased when body posture transitioned from seated to HDT position without any further change at the end of the 3 h in HDT., (© 2023 College of Optometrists.)

Amblyopia is a common visual impairment that develops during the early years of postnatal life. It emerges as a sequela to eye misalignment, an imbalanced refractive state, or obstruction to form vision. All of these conditions prevent normal vision and derail the typical development of neural connections within the visual system. Among the subtypes of amblyopia, the most debilitating and recalcitrant to treatment is deprivation amblyopia. Nevertheless, human studies focused on advancing the standard of care for amblyopia have largely avoided recruitment of patients with this rare but severe impairment subtype. In this review, we delineate characteristics of deprivation amblyopia and underscore the critical need for new and more effective therapy. Animal models offer a unique opportunity to address this unmet need by enabling the development of unconventional and potent amblyopia therapies that cannot be pioneered in humans. Insights derived from studies using animal models are discussed as potential therapeutic innovations for the remediation of deprivation amblyopia. Retinal inactivation is highlighted as an emerging therapy that exhibits efficacy against the effects of monocular deprivation at ages when conventional therapy is ineffective, and recovery occurs without apparent detriment to the treated eye., 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 Duffy, Bear, Patel, Das and Tychsen.)

The blood-brain barrier (BBB) is a unique set of properties of the brain vasculature which severely restrict its permeability to proteins and small molecules. Classic chick-quail chimera studies have shown that these properties are not intrinsic to the brain vasculature but rather are induced by surrounding neural tissue. Here, we identify Spock1 as a candidate neuronal signal for regulating BBB permeability in zebrafish and mice. Mosaic genetic analysis shows that neuronally expressed Spock1 is cell non-autonomously required for a functional BBB. Leakage in spock1 mutants is associated with altered extracellular matrix (ECM), increased endothelial transcytosis, and altered pericyte-endothelial interactions. Furthermore, a single dose of recombinant SPOCK1 partially restores BBB function in spock1 mutants by quenching gelatinase activity and restoring vascular expression of BBB genes including mcamb. These analyses support a model in which neuronally secreted Spock1 initiates BBB properties by altering the ECM, thereby regulating pericyte-endothelial interactions and downstream vascular gene expression., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Fatal anaphylaxis to food is thankfully rare, but every death is a potentially avoidable tragedy. Usually, there will be a coronial inquest to establish the 'how and why' for each death. Reviewing these food allergy-related deaths identifies a number of common themes and risk factors. While some are non-modifiable (such as age, gender and ethnicity), others are and include delayed epinephrine administration and communication difficulties in allergen avoidance. This review highlights the key messages in food allergy-related fatality prevention for healthcare professionals and patients alike, and where available, we explain the evidence behind such recommendations. We describe the data behind the good practice points to facilitate their adoption in routine practice without generating additional anxiety for what is a comparatively rare event. We also propose an information leaflet for patients and carers, developed with patients and endorsed by two major allergy charities, to facilitate dissemination of the recommendations in this review., Competing Interests: Competing interests: PT reports grants from the UK Medical Research Council, NIHR/Imperial BRC and J.M. Charitable Foundation and personal fees from UK Food Standards Agency, Aimmune Therapeutics, Allergenis and Aquestive Therapeutics, outside the submitted work. GCR has received consultant fees from ALK-Abello, Viatris, DBV and AstraZeneca. ATF is a member of the Indedendent Drug Safety Monitoring committee for 2 ALK-Abello commercial trials and has received consultancy fees from Aimmune, GS1 and LG., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Evidence suggests that upregulation of tumor necrosis factor-alpha (TNF-α) plays a role in immune dysregulation in both preeclampsia and inflammatory bowel disease (IBD)., Aims: We aimed to investigate whether anti-TNF therapy during pregnancy decreases the risk of preeclampsia in women with IBD., Methods: The study population included women with IBD and pregnancies who were followed at a tertiary care center from 2007 to 2021. Cases of preeclampsia were compared with controls with a normotensive pregnancy. Data on patient demographics, disease type and activity, pregnancy complications, and additional risk factors for preeclampsia were collected. The association between anti-TNF therapy and preeclampsia was analyzed using univariate analysis and multivariate logistic regression., Results: Women with preeclampsia were more likely to have a preterm delivery (44% vs. 12%, p < 0.001). More women without preeclampsia were exposed to anti-TNF therapy during pregnancy than women with preeclampsia (55% vs. 30%, p = 0.029). The majority of women (32/44) on anti-TNF therapy, either adalimumab or infliximab, continued to have some degree of exposure during the third trimester. Though not significant, multivariate analysis showed a trend towards a protective effect of anti-TNF therapy against developing preeclampsia if exposed during the third trimester (OR 0.39; 95% CI 0.14-1.12, p = 0.08)., Conclusions: In this study, anti-TNF therapy exposure was higher in IBD patients who did not develop preeclampsia than in those who did. While not significant, there was a trend towards a protective effect of anti-TNF therapy against preeclampsia if exposed during the third trimester., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Patella alta is an anatomic risk factor for patellar instability in adolescents that is also linked to the risk factor of trochlear dysplasia. This study aims to determine the age of onset and age-related incidence of patella alta in a pediatric population of patients with patellar instability. We hypothesized that patellar height ratios would not increase with age, suggesting a congenital rather than the developmental origin of patella alta., Methods: A retrospective cross-sectional cohort of patients was collected with the following inclusion criteria: patients aged 5 to 18 who had a knee magnetic resonance imaging performed from 2000 to 2022 and the International Classification of Diseases code for patellar dislocation. Demographic information and details of the patellar instability episode(s) were collected with a chart review. Sagittal magnetic resonance imaging was used to measure Caton-Deschamps Index (CDI) and the Insall-Salvati Ratio (ISR) by 2 observers. Data were analyzed to assess for associations between patellar height ratios and age of the first dislocation and to assess if the proportion of patients categorized as having patella alta changed with age., Results: The 140 knees included in the cohort had an average age of 13.9 years (SD=2.40; range: 8-18) and were 55% female. Patella alta was present in 78 knees (55.7%) using CDI>=1.2 and in 59 knees (42.1%) using ISR>=1.3. The earliest age patella alta was observed was at age 8 using CDI>=1.2 and age 10 using ISR>=1.3. There were no statistically significant associations between CDI and age without adjustment ( P =0.14) nor after adjustment for sex and body mass index ( P =0.17). The proportion of knees above the CDI threshold for patella alta to the knees below the cutoff did not show a significant change with age ( P =0.09)., Conclusions: Patella alta, as defined by CDI, is seen in patients as young as 8 years old. Patellar height ratios do not change with age in patients with patellar dislocation, suggesting that patella alta is established at a young age rather than developing during the adolescent years., Level of Evidence: Level III-diagnostic, cross-sectional., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Marine macroalgae, such as Padina boergesenii , are gaining recognition in the cosmetics industry as valuable sources of natural bioactive compounds. This study aimed to investigate the biochemical profile of P. boergesenii and evaluate its potential as a cosmetic ingredient. Fourier-transform infrared (FTIR), gas chromatography-mass spectrometry (GCMS), and high-resolution liquid chromatography-mass spectrometry quadrupole time-of-flight (HRLCMS QTOF) analyses were employed to assess the functional groups, phycocompounds, and beneficial compounds present in P. boergesenii . Pigment estimation, total phenol and protein content determination, DPPH antioxidant analysis, and tyrosinase inhibition assay were conducted to evaluate the extracts' ability to counteract oxidative stress and address hyperpigmentation concerns. Elemental composition and amino acid quantification were determined using inductively coupled plasma atomic emission spectrometry (ICP-AES) and HRLCMS, respectively. FTIR spectroscopy confirmed diverse functional groups, including halo compounds, alcohols, esters, amines, and acids. GCMS analysis identified moisturizing, conditioning, and anti-aging compounds such as long-chain fatty alcohols, fatty esters, fatty acids, and hydrocarbon derivatives. HRLCMS QTOF analysis revealed phenolic compounds, fatty acid derivatives, peptides, terpenoids, and amino acids with antioxidant, anti-inflammatory, and skin-nourishing properties. Elemental analysis indicated varying concentrations of elements, with silicon (Si) being the most abundant and copper (Cu) being the least abundant. The total phenol content was 86.50 µg/mL, suggesting the presence of antioxidants. The total protein content was 113.72 µg/mL, indicating nourishing and rejuvenating effects. The ethanolic extract exhibited an IC 50 value of 36.75 μg/mL in the DPPH assay, indicating significant antioxidant activity. The methanolic extract showed an IC 50 value of 42.784 μg/mL. Furthermore, P. boergesenii extracts demonstrated 62.14% inhibition of tyrosinase activity. This comprehensive analysis underscores the potential of P. boergesenii as an effective cosmetic ingredient for enhancing skin health. Given the increasing use of seaweed-based bioactive components in cosmetics, further exploration of P. boergesenii 's potential in the cosmetics industry is warranted to leverage its valuable properties.

Background: Baseline diaphragmatic dysfunction (DD) at the initiation of non-invasive ventilation (NIV) correlates positively with subsequent intubation. We investigated the utility of DD detected 2 hours after NIV initiation in estimating NIV failure in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients., Methods: In a prospective-cohort design, we enrolled 60 consecutive patients with AECOPD initiated on NIV at intensive care unit admission, and NIV failure events were noted. The DD was assessed at baseline (T1 timepoint) and 2 hours after initiating NIV (T2 timepoint). We defined DD as ultrasound-assessed change in diaphragmatic thickness (ΔTDI) <20% (predefined criteria [PC]) or its cut-off that predicts NIV failure (calculated criteria [CC]) at both timepoints. A predictive-regression analysis was reported., Results: In total, 32 patients developed NIV failure, nine within 2 hours of NIV and remaining in next 6 days. The ∆TDI cut-off that predicted NIV failure (DD-CC) at T1 was ≤19.04% (area under the curve [AUC], 0.73; sensitivity, 50%; specificity, 85.71%; accuracy; 66.67%), while that at T2 was ≤35.3% (AUC, 0.75; sensitivity, 95.65%; specificity, 57.14%; accuracy, 74.51%; hazard ratio, 19.55). The NIV failure rate was 35.1% in those with normal diaphragmatic function by PC (T2) versus 5.9% by CC (T2). The odds ratio for NIV failure with DD criteria ≤35.3 and <20 at T2 was 29.33 and 4.61, while that for ≤19.04 and <20 at T1 was 6, respectively., Conclusions: The DD criterion of ≤35.3 (T2) had a better diagnostic profile compared to baseline and PC in prediction of NIV failure.

Purpose: To determine if the optic nerve head (ONH) response to transient elevated intraocular pressure (IOP) can predict the extent of neural loss in the nonhuman primate experimental glaucoma model., Methods: The anterior chamber pressure of 21 healthy animals (5.4 ± 1.2 years, 8 female) was adjusted to 25 mm Hg for two hours followed by 10 mm Hg for an additional two hours. For the duration of IOP challenge the ONH was imaged using radial optical coherence tomography (OCT) scans at five-minute intervals. Afterward, a randomized sample of 14 of these subjects had unilateral experimental glaucoma induced and were monitored with OCT imaging, tonometry, and ocular biometry at two-week intervals., Results: With pressure challenge, the maximum decrease in ONH minimum rim width (MRW) was 40 ± 10.5 µm at 25 mm Hg and was correlated with the precannulation MRW, Bruch's membrane opening (BMO) position, and the anterior lamina cribrosa surface position (P = 0.01). The maximum return of MRW at 10 mm Hg was 16.1 ± 5.0 µm and was not associated with any precannulation ONH feature (P = 0.24). However, healthy eyes with greater thickness return at 10 mm Hg had greater loss of MRW and retinal nerve fiber layer (RNFL) at a cumulative IOP of 1000 mm Hg · days after induction of experimental glaucoma. In addition, MRW and RNFL thinning was correlated with an increase in axial length (P < 0.01)., Conclusion: This study's findings suggest that the ONH's response to transient changes in IOP are associated with features of the ONH and surrounding tissues. The neural rim properties at baseline and the extent of axial elongation are associated with the severity of glaucomatous loss in the nonhuman primate model.

Introduction: Over the last decade, the field of systems vaccinology has emerged, in which high throughput transcriptomics and other omics assays are used to probe changes of the innate and adaptive immune system in response to vaccination. The goal of this study was to benchmark key technical and analytical parameters of RNA sequencing (RNA-seq) in the context of a multi-site, double-blind randomized vaccine clinical trial., Methods: We collected longitudinal peripheral blood mononuclear cell (PBMC) samples from 10 subjects before and after vaccination with a live attenuated Francisella tularensis vaccine and performed RNA-Seq at two different sites using aliquots from the same sample to generate two replicate datasets (5 time points for 50 samples each). We evaluated the impact of (i) filtering lowly-expressed genes, (ii) using external RNA controls, (iii) fold change and false discovery rate (FDR) filtering, (iv) read length, and (v) sequencing depth on differential expressed genes (DEGs) concordance between replicate datasets. Using synthetic mRNA spike-ins, we developed a method for empirically establishing minimal read-count thresholds for maintaining fold change accuracy on a per-experiment basis. We defined a reference PBMC transcriptome by pooling sequence data and established the impact of sequencing depth and gene filtering on transcriptome representation. Lastly, we modeled statistical power to detect DEGs for a range of sample sizes, effect sizes, and sequencing depths., Results and Discussion: Our results showed that (i) filtering lowly-expressed genes is recommended to improve fold-change accuracy and inter-site agreement, if possible guided by mRNA spike-ins (ii) read length did not have a major impact on DEG detection, (iii) applying fold-change cutoffs for DEG detection reduced inter-set agreement and should be used with caution, if at all, (iv) reduction in sequencing depth had a minimal impact on statistical power but reduced the identifiable fraction of the PBMC transcriptome, (v) after sample size, effect size (i.e. the magnitude of fold change) was the most important driver of statistical power to detect DEG. The results from this study provide RNA sequencing benchmarks and guidelines for planning future similar vaccine studies., Competing Interests: JG, TLJ, TG, CEG, KJS were employed by The Emmes Company. EA has consulted for Pfizer, Sanofi Pasteur, GSK, Janssen, Moderna, and Medscape, and his institution receives funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Sanofi-Pasteur, Janssen, and Micron. He also serves on a safety monitoring board for Kentucky BioProcessing, Inc. and Sanofi Pasteur. He serves on a data adjudication board for WCG and ACI Clinical. His institution has also received funding from NIH to conduct clinical trials of COVID-19 vaccines. MM reported potential competing interests: laboratory and clinical trial contract funding for vaccines or MAB vs SARS-CoV-2 with Lilly, Pfizer, and Sanofi; personal fees for Scientific Advisory Board service from Merck, Meissa Vaccines, Inc., and Pfizer. The remaining 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. The reviewer MG declared a shared affiliation with the author RH to the handling editor at the time of review., (Copyright © 2023 Goll, Bosinger, Jensen, Walum, Grimes, Tharp, Natrajan, Blazevic, Head, Gelber, Steenbergen, Patel, Sanz, Rouphael, Anderson, Mulligan and Hoft.)

Competing Interests: Competing interests: None declared.

Importance: Approximately 70% of crew members who complete long-duration missions to the International Space Station develop signs of optic disc edema, a hallmark finding of spaceflight-associated neuro-ocular syndrome. The onset and magnitude of edema differ across individuals, and the reason for this variability remains unknown. Identifying risk factors for spaceflight-induced disc edema is important because this condition may become more severe during extended-duration missions to the moon and Mars and could be associated with irreversible vision loss., Objective: To assess whether preflight indicators of crowded optic nerve head morphology, other ocular measures (such as choroid thickness and axial length), body weight, body mass index, sex, age, and previous flight experience are associated with optic disc edema development., Design, Setting, and Participants: This cohort study analyzed ocular, body weight, and demographic data collected from 31 US and international crew members before, during, and after spaceflight at the NASA Johnson Space Center and International Space Station. Ocular factors assessed included preflight and in-flight peripapillary total retinal thickness, minimum rim width, optic cup volume, mean cup depth, mean cup width, cup-disc ratio, Bruch membrane opening area, retinal nerve fiber layer thickness, choroid thickness, axial length, and refractive error. In addition, body weight, body mass index, sex, age, and previous spaceflight experience were assessed for associations with optic disc edema development. The data were analyzed from August 2021 to June 2022., Exposure: Approximately 6 to 12 months of spaceflight., Main Outcomes and Measures: In-flight increases in peripapillary total retinal thickness. Linear mixed models were used to assess for associations between a wide range of risk factors and in-flight increases in peripapillary total retinal thickness, which is a sensitive objective measure for detecting optic disc edema., Results: This study included 31 International Space Station crew members with a mean (SD) age of 46.9 (6.0) years (25 men [80.6%]). During spaceflight, mean (SE) peripapillary total retinal thickness increased from 392.0 (5.8) μm to 430.2 (9.6) μm (P < .001), and greater individual changes were associated with smaller preflight cup volume (slope [SE], -62.8 [18.9]; P = .002), shallower preflight cup depth (slope [SE], -0.11 [0.03]; P < .001), and narrower preflight cup width (slope [SE], -0.03 [0.01]; P = .03). No associations were observed between changes in peripapillary total retinal thickness and any other variable evaluated., Conclusions and Relevance: Findings of this cohort study suggest that smaller optic cup morphology may be associated with optic disc edema development during spaceflight. Crew members with this cup profile may benefit from enhanced ophthalmic monitoring during spaceflight and use of countermeasures against spaceflight-associated neuro-ocular syndrome.

Background: Previous research shows that children from ethnic minority groups spend less time outdoors. Using data collected in 3 regions of Canada, we investigated the correlates of outdoor time among schoolchildren who spoke a nonofficial language at home., Methods: A total of 1699 children were recruited from 37 schools stratified by area-level socioeconomic status and type of urbanization. Among these, 478 spoke a nonofficial language at home. Children's outdoor time and data on potential correlates were collected via questionnaires. Gender-stratified linear multiple regression models examined the correlates of outdoor time while controlling for age and sampling variables., Results: In boys, higher independent mobility, higher outdoor air temperature, mobile phone ownership, having older parents, and parents who biked to work were associated with more outdoor time. Boys living in suburban (vs urban) areas spent less time outdoors. The association between independent mobility and outdoor time became weaker with increasing age for boys. In girls, lower parental education and greater parental concerns about neighborhood safety and social cohesion were associated with less outdoor time., Conclusions: Correlates of outdoor time differ by gender and span the social ecological model underscoring the need for gender-sensitized interventions targeted at individual, family, social, and physical environmental correlates to increase outdoor time.