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Minali Prasad,1,&ast; Deniz Goodman,1,&ast; Jia Xu,2 Sanhit Gutta,2 Daniella Zubieta,2 Sreevardhan Alluri,2 Nicole H Siegel,1,2 Crandall E Peeler,1,2 Hyunjoo J Lee,1,2 Howard J Cabral,3 Manju L Subramanian1,2 1Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA; 2Department of Ophthalmology, Boston Medical Center, Boston, MA, USA; 3Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA&ast;These authors contributed equally to this workCorrespondence: Manju L Subramanian, Department of Ophthalmology, Boston Medical Center, 85 East Concord Street, &num;8813, Boston, MA, 02118, USA, Tel +1 (617) 638 – 4555, Fax +1 (617) 414 – 2929, Email Manju.Subramanian@bmc.orgPurpose: Long-term patient satisfaction may influence patients’ perspectives of the quality of care and their relationship with their providers. This is a follow up to a comparative effectiveness study investigating oral to intravenous sedation (OIV study). The OIV study found that oral sedation was noninferior in patient satisfaction to standard intravenous (IV) sedation for anterior segment and vitreoretinal surgeries. This study aims to determine if patient satisfaction with oral sedation remained noninferior long term.Patients and Methods: Patients were re-interviewed using the same satisfaction survey given during the OIV study. Statistical analysis involved t-tests for noninferiority of the long-term mean satisfaction score of oral and IV sedation. We also compared the original mean satisfaction score and the follow-up mean satisfaction score for each type of sedation and for both groups combined.Results: Participants were interviewed at a median of 1225.5 days (range 754– 1675 days) from their surgery. The original mean satisfaction score was 5.26 ± 0.79 for the oral treatment group (n = 52) and 5.27 ± 0.64 for the intravenous treatment group (n = 46), demonstrating noninferiority with a difference in mean satisfaction score of 0.015 (p < 0.0001). The follow-up mean satisfaction score was 5.23 ± 0.90 for oral sedation and 5.60 ± 0.61 for IV sedation, with a difference in the mean satisfaction score of 0.371 (p = 0.2071). Satisfaction scores did not differ between the original mean satisfaction score and the follow-up mean satisfaction score for the oral treatment group alone (p = 0.8367), but scores in the intravenous treatment group increased longitudinally (p = 0.0004).Conclusion: In this study, long-term patient satisfaction with oral sedation was not noninferior to satisfaction with IV sedation, unlike our findings with short-term patient satisfaction in our original study. Patient satisfaction also remained unchanged over time for the oral treatment group, but patients in the intravenous treatment group reported higher long-term satisfaction with their anesthesia experience compared to the immediate post-operative period.Keywords: longitudinal, ocular surgery, anesthesia, oral triazolam, intravenous midazolam, noninferiority

Steven L Maskin, Sreevardhan AlluriDry Eye and Cornea Treatment Center, Tampa, FL, USAAbstract: Obstructive meibomian gland dysfunction is the most common cause of dry eye. Its conventional treatment has focused on using heat and pressure with anti-inflammatory and antimicrobial therapies but has often been a frequent, frustrating experience for patient and physician. New evidence from Meibomian gland intraductal probing suggests fixed intraductal strictures and obstruction correlating to periductal fibrosis first described in 1997. The use of intraductal probing has been reported, by this author and in at least ten independent peer-reviewed academic papers from around the world, to consistently lead to statistically significant improvement in signs and symptoms of gland dysfunction including cases refractory to other extensive treatments. This review will focus on the background of meibomian gland intraductal probing as well as patient selection, procedure, and perspectives.Keywords: meibomian gland dysfunction, meibomian gland probing, maskin probing, lipiflow,R IPL, dry eye

Background and Aims: Efficacy and safety of EUS-guided placement of lumen-apposing metal stents (LAMS) has been reported yet advantage of using 15-mm LAMS over 10-mm LAMS yet to be explored., Methods: International, retrospective, case-matched study of patients with intra-abdominal abscess who underwent EUS-guided drainage with 15-mm (case) and 10-mm (control) LAMS between 03/2019 and 09/2022., Results: 51 patients underwent EUS-guided drainage using LAMS [15-mm 29 (57%), 10-mm 22 (43%)]. The most common location of the abscess was peri-pancreatic 43%. Technical success rate was achieved in 97% of cases and 100 % of controls (p=0.412), while clinical success was achieved in 98% and 96%, respectively, (OR 1.3; p=0.089). AE occurred in 7.8% of the cases. Patients with 15-mm LAMS underwent fewer total endoscopic procedures (mean 2.5 vs.3.6; P < 0.023)., Conclusion: Both sizes showed comparable clinical success and safety profiles, with a significant trend of the need for fewer endoscopic procedures with the 15-mm LAMS., (Copyright © 2025 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Overactivation of the Transforming Growth Factor Beta (TGF-β) pathway is implicated in the pathogenesis of cytopenias in Myelodysplastic syndromes (MDS) and Acute Myeloid Leukemia (AML). IOA-359 and IOA-360 are potent small molecule inhibitors of the TGF-beta Receptor type I kinase (TGF-βRI, also referred to as ALK5, activin receptor-like kinase 5) that abrogate SMAD phosphorylation in hematopoietic cell lines. Both inhibitors were able to inhibit TGF-β mediated gene transcription at specific doses. ALK5 inhibitors abrogated the growth inhibitory effects of TGF-β on healthy hematopoietic stem cells and stimulated hematopoietic differentiation in cell lines and MDS/AML specimens. These data demonstrate preclinical efficacy of two novel ALK5 inhibitors, IOA-359 and IOA-360, in stimulating erythroid differentiation in MDS and AML.

Background: Interoperable clinical decision support system (CDSS) rules provide a pathway to interoperability, a well-recognized challenge in health information technology. Building an ontology facilitates creating interoperable CDSS rules, which can be achieved by identifying the keyphrases (KP) from the existing literature. Ontology construction is traditionally a manual effort by human domain experts, and the newly advanced natural language processing techniques, such as KP identification, can be a critical complementary automatic part of building ontology. However, KP identification requires human expertise, consensus, and contextual understanding for data labeling., Methods: This paper presents a semi-supervised KP identification framework (long short-term memory-based encoders and the conditional random fields -based decoder models, BiLSTM-CRF) using minimal human labeled data based on hierarchical attention (i.e., at word, sentence, and abstract levels) over the documents and domain adaptation. We created synthetic labels for initial training and human-labeled data for fine-tuning. We also tested different options during NLP preprocessing and ML training to optimize the ML pipeline., Results: Our method outperforms the prior neural architectures by learning through synthetic labels for initial training, document-level contextual learning, language modeling, and fine-tuning with limited gold standard label data. After comparison, we found that the BIO encoding schema performed slightly better than Blue, and domain adaptation techniques can improve the quality of synthetic labels. In addition, document-level context, pre-trained LM, and pre-trained WE all contributed to better model performance in our tasks. Add 2 to 4 human-labeled documents for every 100 synthetic labeled documents improves the model performance without exhausting human-labeled documents too quickly., Conclusions: To the best of our knowledge, this is the first functional framework for the CDSS sub-domain to identify KPs, which is trained on limited human labeled data. It contributes to the general natural language processing (NLP) architectures in areas such as clinical NLP, where manual data labeling is challenging, and light-weighted deep learning models play an important role in real-time KP identification as a complementary approach to human experts' effort., Competing Interests: Competing interests None to disclose.

Background: Protein biomarkers have been broadly investigated in cerebrospinal fluid and blood for the detection of neurodegenerative diseases, yet a clinically useful diagnostic test to detect early, pre-symptomatic Alzheimer's disease (AD) remains elusive. We conducted this study to quantify Aβ40, Aβ42, total Tau (t-Tau), hyperphosphorylated Tau (ptau181), glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) in eye fluids relative to blood., Methods: In this cross-sectional study we collected vitreous humor, aqueous humor, tear fluid and plasma in patients undergoing surgery for eye disease. All six biomarkers were quantitatively measured by digital immunoassay. Spearman and Bland-Altman correlation analyses were performed to assess the agreement of levels between ocular fluids and plasma., Results: Seventy-nine adults underwent pars-plana vitrectomy in at least one eye. Of the 79, there were 77 vitreous, 67 blood, 56 tear fluid, and 51 aqueous samples. All six biomarkers were quantified in each bio-sample, except GFAP and NfL in tear fluid due to low sample volume. All six biomarkers were elevated in vitreous humor compared to plasma samples. T-Tau, ptau181, GFAP and NfL were higher in aqueous than in plasma, and t-Tau and ptau181 concentrations were higher in tear fluid than in plasma. Significant correlations were found between Aβ40 in plasma and tears (r = 0.5; p = 0.019), t-Tau in plasma and vitreous (r = 0.4; p = 0.004), NfL in plasma and vitreous (r = 0.3; p = 0.006) and plasma and aqueous (r = 0.5; p = 0.004). No significant associations were found for Aβ42, ptau181 and GFAP among ocular fluids relative to plasma. Bland-Altman analysis showed aqueous humor had the closest agreement to plasma across all biomarkers. Biomarker levels in ocular fluids revealed statistically significant associations between vitreous and aqueous for t-Tau (r = 0.5; p = 0.001), GFAP (r = 0.6; p < 0.001) and NfL (r = 0.7; p < 0.001)., Conclusion: AD biomarkers are detectable in greater quantities in eye fluids than in plasma and show correlations with levels in plasma. Future studies are needed to assess the utility of ocular fluid biomarkers as diagnostic and prognostic markers for AD, especially in those at risk with eye disease., (© 2024. The Author(s).)

Ontology is essential for achieving health information and information technology application interoperability in the biomedical fields and beyond. Traditionally, ontology construction is carried out manually by human domain experts (HDE). Here, we explore an active learning approach to automatically identify candidate terms from publications, with manual verification later as a part of a deep learning model training and learning process. We introduce the overall architecture of the active learning pipeline and present some preliminary results. This work is a critical and complementary component in addition to manually building the ontology, especially during the long-term maintenance stage.

Background: Firearm violence is an American public health crisis that negatively impacts children and disproportionately affects Black youth. Few firearm injury prevention programs have been described in pre-adolescent children. The Future Healers Program is a novel collaboration constructed via partnership between the medical school, trauma center, academic surgery department, and local non-profit community organization. Our study sought to evaluate if (1) partnering with community organizations facilitated recruitment of children with prior exposure to firearm violence and (2) the health care community was a potential trusted partner appropriate for program delivery., Methods: Children aged 4-13 were recruited to join the program via news outlets and social media and in partnership with a local non-profit organization. Of the children and parents participating in the program, 48% (44/92) and 59% (38/64), respectively, completed an IRB-approved survey study. Pearson's chi-square, percentages, and 95% confidence intervals evaluated differences between children and caregivers on sociodemographic characteristics, firearm exposure (FE), firearm violence exposure (FVE), and perception of health care. Participant's residence was geocoded in relationship to incidents of firearm injury (2008-2021) in the same region., Results: Caregivers (95%) and children (84%) reported substantial exposure to firearm violence and resided in areas with frequent firearm injury incidents. Notably, 82% of caregivers and 66% of children reported having a family member injured by gunfire. A high percentage of caregivers (79%) and children (91%) self-reported trust in the health care system., Conclusion: Partnerships between community organizations and health care systems can develop prevention programs that effectively recruit and engage pre-adolescent children impacted by firearm violence., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Repetitive transcranial magnetic stimulation (rTMS) is a rapidly developing therapeutic modality for the safe and effective treatment of neuropsychiatric disorders. However, clinical rTMS driving systems and head coils are large, heavy, and expensive, so miniaturized, affordable rTMS devices may facilitate treatment access for patients at home, in underserved areas, in field and mobile hospitals, on ships and submarines, and in space. The central component of a portable rTMS system is a miniaturized, lightweight coil. Such a coil, when mated to lightweight driving circuits, must be able to induce B and E fields of sufficient intensity for medical use. This paper newly identifies and validates salient theoretical considerations specific to the dimensional scaling and miniaturization of coil geometries, particularly figure-8 coils, and delineates novel, key design criteria. In this context, the essential requirement of matching coil inductance with the characteristic resistance of the driver switches is highlighted. Computer simulations predicted E- and B-fields which were validated via benchtop experiments. Using a miniaturized coil with dimensions of 76 mm × 38 mm and weighing only 12.6 g, the peak E-field was 87 V/m at a distance of 1.5 cm. Practical considerations limited the maximum voltage and current to 350 V and 3.1 kA, respectively; nonetheless, this peak E-field value was well within the intensity range, 60-120 V/m, generally held to be therapeutically relevant. The presented parameters and results delineate coil and circuit guidelines for a future miniaturized, power-scalable rTMS system able to generate pulsed E-fields of sufficient amplitude for potential clinical use.

This retrospective study aims to evaluate the safety of everolimus when used as part of the immunosuppression regimen in patients who underwent liver transplant from 2009 to 2019 at a tertiary liver transplant center. Patients were divided into two groups: those who received everolimus as part of the post-transplant regimen and those who did not. The primary safety outcome measured was the development of new pulmonary complications that had been associated with everolimus use in prior studies. Lung function was determined by pulmonary function tests if available or CT scans of the chest. Secondary outcomes measured included everolimus discontinuation rates and survival rates. During the study period, 450 patients underwent liver transplant; 35% of patients received everolimus (n=156) and 65% of patients did not receive everolimus (n=292). Primary safety outcome of pulmonary complications was seen in 3.9% of patients who received everolimus (n=6) and 6.3% of the control group patients who did not receive everolimus (n=19). The association between everolimus use and new pulmonary complications was not significant with a chi-square statistic of 1.33 (p=0.249). Overall, 51.3% of patients who received everolimus during their post-transplant course discontinued the medication (n=80). Everolimus is safe from a pulmonary toxicity standpoint in liver transplant immunosuppression regimens as there was no significant difference found in pulmonary complications between patients who received the medication and those who did not., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Obri et al.)

Background: Hepatocellular Carcinoma (HCC) is a malignancy with increasing incidence and morbidity. For patients with a poor prognosis, engagement with advanced care planning and end-of life (EOL) services (I.e., palliative care, hospice) can address physical, financial, and social complications of a terminal diagnosis. Minimal data exist on the demographics of the patients being referred to and enrolling in EOL services for HCC., Aims: We aim to report the relationship between demographics and EOL service referral., Methods: Retrospective review of a prospectively maintained high-volume liver center registry of patients diagnosed with HCC from 2004 to 2022. EOL services eligible patients were defined as BCLC stage C or D, evidence of metastases, and/or transplant ineligible., Results: Black patients were more likely to be referred than white patients (OR 1.47 (1.03, 2.11)). Once referred, patients were significantly more likely to be enrolled if they had insurance coverage, though no other factors in models were significant. There were no significant differences in survival among those referred who did or did not enroll, after controlling for other factors., Conclusion: Black patients were more likely to be referred compared to white patients and patients who were insured were more likely to be enrolled. Whether this is indicative of black patients being appropriately referred at a higher rate, being offered EOL care instead of aggressive treatment, or other unknown factors warrants further study., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

As one of the nine subtypes of adrenergic receptors (ARs) in the brain, α2C-ARs play essential roles in emotion and memory, and are implicated in neuropsychiatric disorders, including depression, Alzheimer's disease, substance use disorder, and schizophrenia. A recently developed α2C-AR specific positron emission tomography (PET) radiotracer, [ 11 C]ORM-13070, showed promise for imaging α2C-ARs in the brain. Herein, we prepared highly potent C-11 labeled benzo-1,4-dioxane derivatives and compared them with [ 11 C]ORM-13070, aiming to improve the specific binding signal, as evaluated by in vivo rodent brain PET imaging.© 2022 Elsevier Inc. All rights reserved., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Masson SAS.)

Introduction: NCCN and ASCO guidelines recommend breast cancer (BC) follow-up to include clinical breast examination (CBE) every 6 months and annual mammography (AM) for 5 years. Given limited data to support CBE, we evaluated the modes of detection (MOD) of BC-events in a contemporary practice., Methods: We conducted a retrospective review of registry patients with early stage BC (DCIS, Stage I or II) diagnosed between 2010 and 2015 with at least 5 years of follow-up. Second events were defined as malignant (contralateral primary, ipsilateral breast tumor recurrence (IBTR), chest wall recurrence, regional node recurrence or distant relapse) or benign. MOD was categorized as patient complaint, clinical examination or breast imaging., Results: Sixty-three of 351 BC patients experienced second events. 15 had BC malignant events, including 4 distant disease, 5 contralateral primary, and 3 IBTR. 7/8 of IBTR and contralateral primary BC were AM detected. Patient complaints identified 4/4 distant relapses. Clinical exam identified 2/2 chest wall recurrences in post-mastectomy patients., Conclusions: Only 2.8% (10/351) of early stage BC patients experienced recurrence during 5 years of follow-up. AM was the predominate MOD of both IBTR and new contralateral primary following breast conserving therapy. Patient complaints prompted evaluation for distant disease. Provider CBE was MOD in only 2/351, 0.6% 95% CI (2.1%-0.1%) of patients as chest wall recurrences postmastectomy. Given modern enhancements to imaging and lower recurrence rates, this data encourages the reassessment of guidelines for every 6-month CBE and provides basis to study telehealth in survivorship care., (Copyright © 2022. Published by Elsevier Inc.)

Primary spinal epidural lymphoma (PSEL) comprises a group of tumors present only in the spinal epidural space with a histopathological picture of lymphoma and negative diagnostic workup for lymphoma at other sites. We present the case of an older male adult with primary spinal diffuse large B-cell lymphoma (DLBCL) presenting with spinal cord compression who was treated with surgery followed by high dose methotrexate in combination with RCHOP (rituximab, cyclophosphamide, prednisone, vincristine, and doxorubicin). This case report and review of literature on DLBCL limited to the spine provide a novel chemotherapy regimen and a comprehensive perspective on the optimal management of these patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Bhardwaj et al.)

Background: Though reports of neurological manifestations of COVID-19 have emerged from various parts of the world, the cohorts reported are from the West and mostly derived from electronic databases. Much remains unknown regarding neuro-COVID in developing countries. India is the second-worst affected country, and this study reports the neurological manifestations of COVID-19 in a comprehensively evaluated cohort., Objective: The aim of this study was to describe the range of neurological manifestations of COVID-19 in India with an emphasis on the risk factors, laboratory and imaging findings and short-term outcome., Methods: Retrospective review of hospital records of all confirmed COVID-19 patients with neurological manifestations, receiving inpatient care in two neurology referral hospitals were done. All demographic, clinical details, investigations, and treatment were analysed., Results: A total of 120 confirmed COVID-19 cases presenting with neurological symptoms were included. The mean age of illness and duration of illness was 48.03 ± 17.3 years and 10.9 ± 17.3 days respectively. New onset of neurological symptoms occurred in 100 cases while 20 patients had worsening of pre-existing neurological illness. Stroke was the commonest neurological disorder (43%), followed by encephalopathy (23%) and Guillain-Barre syndrome (10%). Other unusual neurological manifestations included new-onset headache (7%), seizures including denovo status epilepticus (5%) and meningo-encephalitis (5%). Nearly half of the patients had preceding COVID-19 symptoms. Poor outcome at discharge was seen in 40% and mortality occurred in 15%., Conclusion: Stroke and encephalopathy constitute the most common neurological manifestations. The absence of preceding COVID-19 symptoms in nearly half the cases is striking. Poor outcome was seen in nearly 50% despite early recognition and management., Competing Interests: There are no conflicts of interest., (Copyright: © 2006 - 2022 Annals of Indian Academy of Neurology.)

The concept of a portable, wearable system for repetitive transcranial stimulation (rTMS) has attracted widespread attention, but significant power and field intensity requirements remain a key challenge. Here, a circuit topology is described that significantly increases induced electric field intensity over that attainable with similar current levels and coils in conventional rTMS systems. The resultant electric field is essentially monophasic, and has a controllable, shortened duration. The system is demonstrated in a compact circuit implementation for which an electric field of 94 V/m at a depth of 2 cm is measured (147 V/m at 1 cm depth) with a power supply voltage of 80 V, a maximum current of 500 A, and an effective pulse duration (half amplitude width) of 7 µsec. The peak electric field is on the same order as that of commercially available systems at full power and comparable depths. An electric field boost of 5x is demonstrated in comparison with our system operated conventionally, employing a 70 µsec rise time. It is shown that the power requirements for rTMS systems depend on the square of the product of electric field Ep and pulse duration tp, and that the proposed circuit technique enables continuous variation and optimization of the tradeoff between Ep and tp. It is shown that the electric field induced in a medium such as the human brain cortex at a specific depth is proportional to the voltage generated in a given loop of the generating coil, which allows insights into techniques for its optimization. This rTMS electric field enhancement strategy, termed 'boost rTMS (rbTMS)' is expected to increase the effectiveness of neural stimulation, and allow greater flexibility in the design of portable rTMS power systems.Clinical Relevance- This study aims to facilitate a compact, battery-powered rTMS prototype with enhanced electric field which will permit broader and more convenient rTMS treatment at home, in a small clinic, vessel, or field hospital, and potentially, on an ambulatory basis.

Acoustofluidics has promised to enable lab-on-a-chip and point-of-care devices in ways difficult to achieve using other methods. Piezoelectric ultrasonic transducers-as small as the chips they actuate-provide rapid fluid and suspended object transport. Acoustofluidic lab-on-chip devices offer a vast range of benefits in early disease identification and noninvasive drug delivery. However, their potential has long been undermined by the need for benchtop or rack-mount electronics. The piezoelectric ultrasonic transducers within require these equipment and thus acoustofluidic device implementation in a bedside setting has been limited. Here we detail a general process to enable the reader to produce battery or mains-powered microcircuits ideal for driving 1-300 MHz acoustic devices. We include the general design strategy for the circuit, the blocks that collectively define it, and suitable, specific choices for components to produce these blocks. We furthermore illustrate how to incorporate automated resonance finding and tracking, sensing and feedback, and built-in adjustability to accommodate devices' vastly different operating frequencies and powers in a single driver, including examples of fluid and particle manipulation typical of the needs in our discipline. With this in hand, the many groups active in lab-on-a-chip acoustofluidics can now finally deliver on the promise of handheld, point-of-care technologies.

Trichomoniasis in humans, caused by the protozoal parasite Trichomonas vaginalis, is the most common non-viral sexually transmitted disease, while Tritrichomonas foetus causes trichomonosis, an infection of the gastrointestinal tract and diarrhea in farm animals and domesticated cats. As part of an effort to determine the inhibitory effects of plant-based extracts and pure compounds, seven commercially available cherry tomato varieties were hand-peeled, freeze-dried, and pounded into powders. The anti-trichomonad inhibitory activities of these peel powders at 0.02% concentration determined using an in vitro cell assay varied widely from 0.0% to 66.7% against T. vaginalis G3 (human); from 0.9% to 66.8% for T. foetus C1 (feline); and from 0.0% to 81.3% for T. foetus D1 (bovine). The organic Solanum lycopersicum var. cerasiforme (D) peels were the most active against all three trichomonads, inhibiting 52.2% (G3), 66.8% (C1), and 81.3% (D1). Additional assays showed that none of the powders inhibited the growth of foodborne pathogenic bacteria, pathogenic fungi, or non-pathogenic lactobacilli. Tomato peel and pomace powders with high content of described biologically active compounds could serve as functional food and feed additives that might help overcome adverse effects of wide-ranging diseases and complement the treatment of parasites with the anti-trichomonad drug metronidazole.

Purpose: To evaluate use of infrared meibography video to visualise meibomian gland probing and correlate probe findings of intraductal space with meibography images., Methods: Videos were reviewed and probe findings recorded of 996 probed gland orifices from 38 lower lids., Results: 996/997 (99.9%) of gland orifices were successfully probed with 91.8% revealing probe location. There were no false passages. 14% (140/997) of all gland orifices showed whole gland atrophy (WGA) with 99.3% (139/140) probed to 1 mm. Cumulative probe findings for all WGA (not differ significantly from non-WGA) showed 106 (76%), 21 (15%) and 12 (9%) glands with fixed, non-fixed and no resistance (NR), respectively. Lids without WGA showed increased NR/total glands probed while lids with WGAs (≥5) showed increased NR/WGA compared with lids with only 1-4 WGAs (p=0.011, p=0.005, respectively, Mann-Whitney U test) suggesting bimodal NR profile. Visualisation of microtube placement was successfully obtained for therapeutic injections and retrieval of meibum specimens., Conclusion: Video confirmed intraductal location and safety of devices. For 73% of non-WGA and 76% of WGAs as well as proximal ducts of glands with proximal atrophy, probing released fixed resistance restoring ductal integrity. A bimodal profile of NR suggests it is found with less diseased gland ducts as well as more advanced atrophic gland disease. Gland and ducts appeared flexible but not distendable while periglandular tissue appeared spongy. Visualisation of devices enables whole or localised gland therapy and meibum specimen retrieval, elegantly raising future research, therapeutic and regenerative opportunities., Competing Interests: Competing interests: SM is the owner of MGD Innovations, Inc which holds patents on instrumentation and methods for intraductal diagnosis and treatment of meibomian gland disease (MGD), plus related pending patents including visualisation of real-time intraductal diagnostics, probing and other therapies. SM also has patents on the use of jojoba-based treatment options for MGD., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Prior work has indicated that thymosin beta 4 (Tβ4) administered with ciprofloxacin markedly improves disease outcome for Pseudomonas aeruginosa (PA)-induced keratitis. As a result, the goal of the current study was to elucidate mechanisms by which Tβ4 mitigates the corneal response; specifically, regarding its bactericidal influence and potential synergy with ciprofloxacin. An in vitro approach was carried out using minimum inhibitory concentration (MIC) assays to assess bactericidal activity against PA. In addition, antimicrobial peptide (AMP) production was evaluated at the mRNA levels using human corneal epithelial cells in response to lipopolysaccharide (LPS) challenge. The results of the MIC assays did not show direct bactericidal activity with Tβ4 alone, although ciprofloxacin exhibited significant killing at concentrations far lower than clinically dosed. Tβ4, however, displayed an indirect effect on bacterial killing, as shown by an upregulation of AMPs and related molecules. The cumulative data from this study indicate an indirect bactericidal role of Tβ4, as well as a synergistic relationship with ciprofloxacin. Furthermore, ciprofloxacin alone was found to influence cellular functions that otherwise have yet to be reported. These results highlight a mechanism of intracellular communication for Tβ4 and further strengthen its development as an adjunct therapy with antibiotics for corneal infections.

Background: Incisional hernia is one of the most common complications of abdominal surgery, and repairs are associated with significant recurrence rates. Mesh repairs are associated with the best outcomes, but failures are not uncommon. Doxycycline has been demonstrated to enhance mesh hernia repair outcomes with associated increases in collagen deposition and improved tensiometric strength. This study compares the outcomes of incisional hernia repair with doxycycline administration and the antioxidant tempol., Materials and Methods: Twenty-eight male Sprague Dawley rats underwent a midline hernia creation and an intraabdominal polypropylene mesh repair. The animals were administered saline, doxycycline, tempol, or both, daily for 8 wk. The abdominal wall was harvested at 8 wk and tensiometric strength and biochemical analysis was performed., Results: The tensiometric strength of the repair was increased in all experimental groups. Collagen type 1 deposition was increased, and collagen type 3 deposition was decreased in each of the experimental groups relative to control. There was no difference in MMP-2 and MMP-9 levels between control and experimental groups., Conclusions: The hernia repair strength is equally enhanced with the administration of doxycycline or tempol. Dual therapy provided no benefit over treatment with either single agent. All treatment groups had an increase in collagen type 1:3 ratios, but the mechanism is not well understood. The benefits of antioxidant treatment following hernia repair are similar to treatment with doxycycline. Given the high frequency of incisional hernia repair failures, this study has implications for improving outcomes following ventral hernia repair through the use of either doxycycline or antioxidant therapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has emerged as a serious global threat causing a large number of fatalities and putting enormous strain on the health care resources across the world. This has resulted in preferentially triaging the coronavirus infected patients and placing others, especially cardiovascular patients at increased risk for adverse complications. The effective management of cardiac patients in the hospital environment during this COVID-19 pandemic has emerged as a real challenge. We try to address this issue and also highlight the interplay between COVID-19 and cardiovascular diseases. We hereby review the available literature and emerging guidelines about cardiovascular implications related to COVID-19 which will have a bearing on the patient care, health care professionals and cardiac centres., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To assess the capacity of different techniques to reduce non-operative times during parathyroid surgery. The impact of monitored anesthesia care (MAC) instead of general anesthesia, and the pre-operative placement of a second peripheral intravenous catheter (PIV) were analyzed., Methods: A retrospective case series at an academic medical center was performed to study patients undergoing parathyroidectomy by a single surgeon between November 2013 and October 2016. Three operating room (OR) time measurements were compared: pre-incision time, post-closure time, and total OR time., Results: Surgeries performed under MAC (n = 21) had statistically shorter pre-incision (33.2 min vs. 39.7 min, p < .001), post-closure (10.1 min vs. 16.2 min, p = .002), and total operative times (113.0 min vs. 151.5 min, p < .001) compared to those in which general anesthesia (n = 169) was used. Of the 169 patients who underwent general anesthesia, 25 had a second PIV placed preoperatively and 144 had only a single PIV. All 3 time periods were statistically shorter in patients who had a second PIV versus those who had only a single PIV (pre-incision 32.2 min vs. 41.0 min, p < .001; post-closure 12.2 min vs. 16.9 min, p < .001; total 117.9 min vs. 157.4 min, p < .001)., Conclusions: In patients undergoing parathyroid surgery in which ioPTH levels will be used, the placement of a second PIV in the pre-operative holding area and performance of surgery under MAC can significantly shorten non-operative and total OR time., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To describe and quantify findings of intraductal obstruction during probing expressible and nonexpressible meibomian glands (MGs) in patients with obstructive meibomian gland dysfunction using a 1-mm intraductal MG probe., Methods: A retrospective study of probe findings from 108 consecutive patients. Nonparametric tests using SPSS software 25.0 to explore relationships between expressibility and probe findings., Results: Of 11,776 probed glands of 404 lids, 84% showed mechanical resistance (MR) and 16% showed no resistance (NR). Fixed, firm, focal unyielding resistance (FFFUR) occurred in 79.5% of obstructed glands, and nonfixed, nonfocal easily yielding soft resistance (SFT) in 20.4%. FFFUR was characterized by an audible and tactile "firm pop" (FP) or "firm gritty" (FG) sensation. No significant difference in MR and FFFUR for lids between 0% and >90% gland expressibility was observed. FP correlated with increased expressibility (P = 0.011), lid tenderness (P = 0.045), and complete proximal obstruction (P = 0.037), whereas SFT correlated with reduced expressibility (P = 0.016). Upper lids showed greater incidence of MR (P < 0.001), FFFUR (P < 0.001), and FG (P < 0.001), whereas lower lids showed greater expressibility (P < 0.001) and NR (P < 0.001)., Conclusions: FFFUR was the most common probe finding in a large series of consecutively probed MGs, with an incidence of 67% of glands and 80% of obstructed glands. FFFUR was independent of gland expressibility, demonstrating expressible glands harbor FFFUR deep to at least one acinus. FP was associated with expressible gland occult obstruction and lid tenderness. SFT correlated with reduced expressibility, perhaps related to altered duct/duct contents. Upper lids correlated with increased MR, FFFUR, and FG and lower lids with increased expressibility and NR, possibly reflecting contrasting anatomy and blink-related microtrauma.

Purpose: This is a review of the literature on nonsurgical treatment of non-healing medication related osteonecrosis of the jaw (MRONJ) utilizing a phosphate buffer-stabilized 0.1% chlorine dioxide mouthrinse., Methods: A literature search in PubMed revealed only six case reports. MRONJ lesion site description, patient's medication history, the healing time, and the MRONJ treatment protocol followed by those authors were recorded. Additional literature review of the scientific mechanism, risks and benefits, safety and efficacy of the phosphate buffer-stabilized 0.1% chlorine dioxide mouthrinse was also performed and discussed., Results: Many of the authors of the published case reports utilized 0.12% chlorhexidine as the initial mouthrinse, but the lesions did not decrease in size. After switching to a phosphate buffer-stabilized 0.1% chlorine dioxide mouthrinse for a duration ranging from 1-12 months, there was complete healing of the MRONJ lesions in all of the cases. The phosphate buffer-stabilized 0.1% chlorine dioxide mouthrinse can be helpful in the management of active MRONJ lesions as well as the prevention of recurrent MRONJ lesions in the susceptible patient population., Clinical Significance: This literature review supports the use of phosphate buffer-stabilized 0.1% chlorine dioxide mouthrinse in the management of MRONJ lesions either as a first line of therapy or after 0.12% chlorhexidine had not been effective., Competing Interests: The authors declared no conflict of interest. The project was funded by Rowpar Pharmaceuticals Inc, Scottsdale, AZ, USA

Calcitriol-mediated hypercalcemia has been reported in malignant lymphomas and granulomatous diseases but not in lung carcinoma. We describe a patient with squamous cell lung carcinoma with hypercalcemia and elevated calcitriol levels. A 60-year-old Caucasian male patient with stage IIIB squamous cell lung cancer developed hypercalcemia at 14.8 mg/dL two years after receiving chemotherapy and radiotherapy where labs showed a serum intact PTH: 7 pg/mL, PTHrP: 30 pmol/L, 1,25-hydroxyvitamin D (calcitriol): 76 pg/mL, and 25-hydroxyvitamin D levels: <4 ng/mL. Calcitriol levels were elevated despite undetectable 25-hydroxyvitamin D levels. There are no reported lung cancer cases with elevated calcitriol as an etiology of hypercalcemia. We believe that the elevated calcitriol levels in this case were due to a PTHrP-independent mechanism, possibly from either ectopic production of calcitriol in tumor cells or from increased activity of 1-alpha hydroxylase in the same cells. The patient died before the effects of prednisone therapy could be assessed. Studies are needed to investigate the cellular source of calcitriol and its role in hypercalcemia in patients with lung cancer.

Introduction: Avascular necrosis of hip typically presents in young patients. Core decompression in precollapse stage provides pain relief and preservation of femoral head. The results of core decompression vary considerably despite early diagnosis. The role of MRI in monitoring patients post surgically has not been clearly defined., Aim: To study pre and post core decompression MRI changes in avascular necrosis of hip., Materials and Methods: This is a contiguous observational cohort of 40 hips treated by core decompression for precollapse avascular necrosis of femoral head, who had a baseline MRI performed before surgery. Core decompression of the femoral head was performed within 4 weeks. Follow up radiograph and MRI scans were done at six months. Harris hip score preoperatively, 1 month and 6 months after the surgery was noted. Success in this study was defined as postoperative increase in Harris hip score (HHS) by 20 points and no additional femoral collapse. End point of clinical adverse outcome as defined by fall in Harris hip score was conversion or intention to convert to total hip replacement (THR). MRI parameters in the follow up scan were compared to the preoperative MRI. Effect of core decompression on bone marrow oedema and femoral head collapse was noted. Results were analysed using SPSS software version., Results: Harris hip score improved from 57 to 80 in all patients initially. Six hips had a fall in Harris hip score to mean value of 34.1 during follow up (9 to 12 months) and underwent total hip replacement. MRI predictors of positive outcome are lesions with grade A extent, Grade A & B location. Bone marrow oedema with lesions less than 50% involvement, medial and central location., Conclusion: Careful selection of patients by MR criteria for core decompression provides satisfactory outcome in precollapse stage of avascular necrosis of hip.

Human apolipoprotein A-I (apo A-I) possesses multiple tandem repeating 22-mer amphipathic alpha-helixes. Computer analysis and studies of model synthetic peptides and recombinant protein-lipid complexes of phospholipids have suggested that apo A-I interacts with HDL surface lipids through cooperation among its individual amphipathic helical domains. To delineate the overall lipid-associating properties of apo A-I, the first step is to understand the lipid-associating properties of individual amphipathic helical domains. To this end, we synthesized and studied each of the eight tandem repeating 22-mer domains of apo A-I: residues 44-65, 66-87, 99-120, 121-142, 143-164, 165-186, 187-208, and 220-241. Among the 22-mers, only the N- and C-terminal peptides (44-65 and 220-241) were effective in clarifying multilamellar vesicles (MLVs) of dimyristoylphosphatidylcholine (DMPC). These two peptides also exhibited the highest partition coefficient into 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine liposomes, the highest exclusion pressure for penetration into an egg yolk phosphatidylcholine monolayer, and the greatest reduction in the enthalpy of the gel-to-liquid crystalline phase transition of DMPC MLVs. These results suggest that the strong, lipid-associating properties of apo A-I are localized to the N- and C-terminal amphipathic domains. Although each of the eight peptides studied has an amphipathic structure, models based on changes in residual effective amino acid hydrophobicity resulting from differing depths of helix penetration into the lipid are best able to explain the high lipid affinity possessed by the two terminal domains. Differential scanning calorimetry (DSC) studies showed that on a molar basis, apo A-I is about 10 times more effective than the most effective peptide analyzed in reducing the enthalpy of the gel-to-liquid crystalline phase transition of DMPC MLVs. Because previous proteolysis experiments coupled with the present DSC results suggest that the lipid-associating domains of apo A-I are distributed throughout the length of the 243 amino acid residues, we propose that the terminal amphipathic helical domains are involved in the initial binding of apo A-I to the lipid surface to form HDL particles, followed by cooperative binding of the middle six amphipathic helical domains, perhaps aided by salt-bridge formation between adjacent helixes arranged in an antiparallel orientation.