bluuebunny/crossref_metadata_2025 huggingface dataset:
An Experimental and Computational Investigation of Ranque–Hilsch Vortex Tube Heat Transfer Characteristics
Authors: Fuqua Matthew N. , Rutledge James L.
Published: October 2023

Ranque–Hilsch vortex tubes have the extraordinary ability to split an incoming stream of fluid into two streams—one with a lower absolute total temperature than the incoming flow and the other with greater total temperature. The physical mechanism involves inducing an intense swirl of the flow down the length of the tube. The warmer flow exits around the periphery at the end of the tube, while the cooler central flow changes direction within the core and exits the opposite end. While much research has focused on the physical mechanisms of the energy separation, relatively little attention has been paid to the heat transfer behavior should a heat flux be applied to the walls. In the present work, experiments were performed using a vortex tube with air and varying levels of heat addition, up to approximately 15 kW/m2. Companion computational experiments were performed that allowed the determination of axially resolved Nusselt number distributions, the first of their kind for vortex tube flows. A notable finding is that the vast majority of heat added to the vortex tube flow remains within the hot stream; i.e., the cold stream experiences relatively little temperature rise due to the heat addition. For example, even when only 30% of the flow exits the hot side of the tube, it retains more than 80% of the heat added to the flow. Additionally, a modified swirl number was also defined that was found to scale the Nusselt number augmentation across the two different total flowrates examined presently.
Neurological disorders after severe pneumonia are associated with translocation of endogenous bacteria from the lung to the brain
Authors: Ma Qingle , Yao Chenlu , Wu Yi , Wang Heng , Fan Qin , Yang Qianyu , Xu Jialu , Dai Huaxing , Zhang Yue , Xu Fang , Lu Ting , Dowling Jennifer K. , Wang Chao
Published: October 2023

Neurological disorders are a common feature in patients who recover from severe acute pneumonia. However, the underlying mechanisms remain poorly understood. Here, we show that the neurological syndromes after severe acute pneumonia are partly attributed to the translocation of endogenous bacteria from the lung to the brain during pneumonia. Using principal components analysis, similarities were found between the brain’s flora species and those of the lungs, indicating that the bacteria detected in the brain may originate from the lungs. We also observed impairment of both the lung-blood and brain-blood barriers, allowing endogenous lung bacteria to invade the brain during pneumonia. An elevated microglia and astrocyte activation signature via bacterial infection–related pathways was observed, indicating a bacterial-induced disruption of brain homeostasis. Collectively, we identify endogenous lung bacteria that play a role in altering brain homeostasis, which provides insight into the mechanism of neurological syndromes after severe pneumonia.
Multivalent, asymmetric IL-2–Fc fusions show enhanced selectivity for regulatory T cells
Authors: Orcutt-Jahns Brian T. , Emmel Peter C. , Snyder Eli M. , Taylor Scott D. , Meyer Aaron S.
Published: October 2023

The cytokine interleukin-2 (IL-2) has the potential to treat autoimmune disease but is limited by its modest specificity toward immunosuppressive regulatory T (T
reg
) cells. IL-2 receptors consist of combinations of α, β, and γ chains of variable affinity and cell specificity. Engineering IL-2 to treat autoimmunity has primarily focused on retaining binding to the relatively T
reg
-selective, high-affinity receptor while reducing binding to the less selective, low-affinity receptor. However, we found that refining the designs to focus on targeting the high-affinity receptor through avidity effects is key to optimizing T
reg
selectivity. We profiled the dynamics and dose dependency of signaling responses in primary human immune cells induced by engineered fusions composed of either wild-type IL-2 or mutant forms with altered affinity, valency, and fusion to the antibody Fc region for stability. T
reg
selectivity and signaling response variations were explained by a model of multivalent binding and dimer-enhanced avidity—a combined measure of the strength, number, and conformation of interaction sites—from which we designed tetravalent IL-2–Fc fusions that had greater T
reg
selectivity in culture than do current designs. Biasing avidity toward IL2Rα with an asymmetrical multivalent design consisting of one α/β chain–binding and one α chain–binding mutant further enhanced T
reg
selectivity. Comparative analysis revealed that IL2Rα was the optimal cell surface target for T
reg
selectivity, indicating that avidity for IL2Rα may be the optimal route to producing IL-2 variants that selectively target T
regs
.
Organ agar serves as physiologically relevant alternative for
in vivo
bacterial colonization
Authors: Pearson Melanie M. , Shea Allyson E. , Pahil Sapna , Smith Sara N. , Forsyth Valerie S. , Mobley Harry L. T.
Published: October 2023

Animal models for host-microbial interactions have proven valuable, yielding physiologically relevant data that may be otherwise difficult to obtain. Unfortunately, such models are lacking or nonexistent for many microbes. Here, we introduce organ agar, a straightforward method to enable the screening of large mutant libraries while avoiding physiological bottlenecks. We demonstrate that growth defects on organ agar were translatable to bacterial colonization deficiencies in a murine model. Specifically, we present a urinary tract infection agar model to interrogate an ordered library of
Proteus mirabilis
transposon mutants, with accurate prediction of bacterial genes critical for host colonization. Thus, we demonstrate the ability of
ex vivo
organ agar to reproduce
in vivo
deficiencies. Organ agar was also useful for identifying previously unknown links between biosynthetic genes and swarming motility. This work provides a readily adoptable technique that is economical and uses substantially fewer animals. We anticipate this method will be useful for a wide variety of microorganisms, both pathogenic and commensal, in a diverse range of model host species.
Draft genome sequences of nine non-O157 Shiga toxin-producing
Escherichia coli
in ready-to-eat food from supermarkets in Argentina
Authors: Alotaibi Khulud , Hikal Ahmed F. , Sung Kidon , Zhang Guodong , Khan Ashraf A.
Published: October 2023

Non-O157 Shiga toxin-producing
Escherichia coli
(STEC) are recognized as an important group of bacterial enteropathogens. Here, we report the draft genome sequence of nine strains of non-O157 STEC isolated from ready-to-eat foods in Argentina. The whole-genome sequence data provide a better understanding of these isolates and will aid epidemiological investigation during outbreaks.
Ocular blood flow biomarkers may predict long-term glaucoma progression
Authors: Verticchio Vercellin Alice Chandra , Harris Alon , Oddone Francesco , Siesky Brent , Eckert George , Belamkar Aditya , Antman Gal , Segev Fani
Published: October 2023

Background/aim

To examine the relationship between baseline blood flow biomarkers and long-term open-angle glaucoma (OAG) progression.

Methods

112 patients with early to moderate OAG (mean age 64.9±11.0 years; 68 female) were evaluated at baseline and every 6 months from 2008 to 2013. Biomarkers of retinal capillary blood flow were assessed by Heidelberg retinal flowmetry. Functional disease progression was monitored via Humphrey visual field examinations, defined as two consecutive visits with a mean deviation decrease ≥2 decibels and/or Advanced Glaucoma Intervention Study score increase ≥2 compared with baseline. Structural progression was monitored with optical coherence tomography and Heidelberg retinal tomograph, defined as two consecutive visits with retinal nerve fibre layer thickness decrease ≥8% and/or horizontal or vertical cup/disk ratio increase ≥0.2 compared with baseline. Mixed-model analysis of covariance was used to test for significant change from baseline to 5-year follow-up. Times to functional and structural progression were analysed using Cox proportional hazards models.

Results

Lower HRF retinal capillary blood flow in the superior retina was significantly associated with structural progression (p=0.0009).

Conclusion

In our OAG sample, baseline lower retinal capillary perfusion in the superior retina was predictive of structural progression after 5 years.

Trial registration number

NCT01145911
.
Estimated health benefits, costs and cost-effectiveness of eliminating dietary industrial trans fatty acids in Kenya: cost-effectiveness analysis
Authors: Marklund Matti , Aminde Leopold N , Wanjau Mary Njeri , Huang Liping , Awuor Celine , Steele Lindsay , Cobb Laura K , Veerman J Lennert , Wu Jason HY
Published: October 2023

Objectives

To model the potential health gains and cost-effectiveness of a mandatory limit of industrial trans fatty acids (iTFA) in Kenyan foods.

Design

Multiple cohort proportional multistate life table model, incorporating existing data from the Global Burden of Disease study, pooled analyses of observational studies and peer-reviewed evidence of healthcare and policy implementation costs.

Setting

Kenya.

Participants

Adults aged ≥20 years at baseline (n=50 million).

Intervention

A mandatory iTFA limit (≤2% of all fats) in the Kenyan food supply compared with a base case scenario of maintaining current trans fat intake.

Main outcome measures

Averted ischaemic heart disease (IHD) events and deaths, health-adjusted life years; healthcare costs; policy implementation costs; net costs; and incremental cost-effectiveness ratio.

Results

Over the first 10 years, the intervention was estimated to prevent ~1900 (95% uncertainty interval (UI): 1714; 2148) IHD deaths and ~17 000 (95% UI: 15 475; 19 551) IHD events, and to save ~US$50 million (95% UI: 44; 56). The corresponding estimates over the lifespan of the model population were ~49 000 (95% UI: 43 775; 55 326) IHD deaths prevented, ~113 000 (95% UI: 100 104; 127 969) IHD events prevented and some ~US$300 million (256; 331) saved. Policy implementation costs were estimated as ~US$9 million over the first 10 years and ~US$20 million over the population lifetime. The intervention was estimated to be cost saving regardless of the time horizon. Findings were robust across multiple sensitivity analyses.

Conclusions

Findings support policy action for a mandatory iTFA limit as a cost-saving strategy to avert IHD events and deaths in Kenya.
Spatial multilevel analysis of age at death of under-5 children and associated determinants: EDHS 2000–2016
Authors: Agidew Bezawit Tarekegn , Belay Denekew Bitew , Tesfaw Lijalem Melie
Published: October 2023

Objective

This study examines trends, spatial distribution and determinants of age at death of under-5 children in Ethiopia.

Design

This study used secondary data from the 2000, 2005, 2011 and 2016 Ethiopian Demographic and Health Surveys. A multilevel partial ordinal logistic regression model was used to assess the effects of variables on the age at death of children under 5 years.

Setting

Ethiopia.

Participants

The final analysis included a sample of 3997 deaths of newborns, infants and toddlers.

Results

A total of 1508, 1054, 830 and 605 deaths of under-5 children were recorded in the 2000, 2005, 2011 and 2016 survey years, respectively. The death of newborns, infants and toddlers showed a significant decrease from 2000 to 2016, with reductions of 33.3% to 17.4%, 42.4% to 12.6% and 45.2% to 11.6%, respectively. The analysis using Global Moran’s Index revealed significant spatial autocorrelation in mortality for each survey year (p<0.05). The intraclass correlation of age at death of under-5 children within regions was substantial. Furthermore, the odds of newborn deaths among under-5 children (OR: 0.638, 95% CI: 0.535, 0.759) were lower for those delivered in health institutions compared with those delivered at home.

Conclusions

Throughout the survey years from 2000 to 2016, newborn children had higher mortality rates compared with infants and toddlers, and significant spatial variations were observed across different zones in Ethiopia. Factors such as child’s sex, age of mother, religion, birth size, sex of household head, place of delivery, birth type, antenatal care, wealth index, spatial autocovariate, Demographic and Health Survey year, place of residence and region were found to be significant in influencing the death of under-5 children in Ethiopia. Overall, there has been a decreasing trend in the proportion of under-5 child mortality over the four survey years in Ethiopia.
Work characteristics and emotional exhaustion among young workers: a latent class analysis
Authors: van Veen Malte , Schelvis Roosmarijn MC , Hoekstra Trynke , Bongers Paulien M , Boot Cécile RL , Oude Hengel Karen M
Published: October 2023

Objectives

This study aims to assess the heterogeneity of psychosocial working conditions of young workers by identifying subgroups of work characteristic configurations within young workers and to assess these subgroups’ associations with emotional exhaustion.

Design

Latent class analysis. Groups were formed based on 12 work characteristics (8 job demands and 4 job resources), educational level and sex. Differences in emotional exhaustion between subgroups were analysed using analysis of variance and post hoc comparisons.

Setting

Data from the 2019 wave of the Netherlands Working Conditions Survey.

Participants

7301 individuals between the age of 18 and 30 years, who worked more than 16 hours per week.

Main outcome measure

Emotional exhaustion.

Results

Five subgroups of work characteristics could be identified and were labelled as: (1) ‘low-complexity work’ (24.4%), (2) ‘office work’ (32.3%), (3) ‘manual and non-interpersonal work’ (12.4%), (4) ‘non-manual and interpersonal work’ (21.0%), and (5) ‘manual and interpersonal work’ (9.9%). Mean scores for emotional exhaustion in the two interpersonal work groups (M=3.11, SD=1.4; M=3.45, SD=1.6) were significantly higher than in the first three groups (M=2.05, SD=1.1; M=1.98, SD=1.0; M=2.05, SD=1.1) (all 95% CIs excluding 0). Further, mean scores for emotional exhaustion were significantly higher in the ‘manual and interpersonal work’ group than in the ‘non-manual and interpersonal work’ group (95% CI 0.24, 0.45). All results could be replicated in the 2017 and 2021 waves of the Netherlands Working Conditions Survey.

Conclusions

Young workers reported heterogeneous work characteristic configurations with substantial differences in degrees of emotional exhaustion between the identified subgroups. Preventing emotional exhaustion should focus on the two interpersonal work subgroups, which showed a high degree of emotional exhaustion. In prevention efforts, these groups’ configurations of work characteristics should be taken into account.
Water-in-Salt Electrolytes for Reversible Zinc Electrodeposition for Dynamic Windows
Authors: Madu Desmond C. , Thompson Andrew A. , Leahy Madeline J. , Lilo Micah V. , Barile Christopher J.
Published: October 2023

Reversible metal electrodeposition (RME) is an emerging and promising method for designing dynamic windows with electrically controllable transmission, excellent color neutrality, and wide dynamic range. Despite its very negative deposition voltage, Zn is a viable option for metal-based dynamic windows due to its fast switching kinetics and reversibility. In this manuscript, we describe the construction of Zn RME dynamic windows using water-in-salt electrolytes (WISe). By systematically comparing different electrolytes, we study the effects of different WISe components on Zn RME spectroelectrochemistry. This insight allows us to design practical two-electrode 25 cm2 Zn dynamic windows, the first examples of RME devices with WISe. We also establish a link between the morphology of the Zn electrodeposits and the optical contrast of the transparent electrodes during switching. Taken together, these studies highlight a potential design strategy for the construction of RME dynamic windows.
Loss of prolyl hydroxylase 1 and 2 in SM22α-expressing cells prevents Hypoxia-Induced pulmonary hypertension
Authors: Barnes Elizabeth A. , Ito Reiji , Che Xibing , Alvira Cristina M. , Cornfield David N.
Published: October 2023

In a mouse model wherein hypoxia-inducible factor 1 alpha (HIF-1α) is stabilized in vascular smooth muscle cells, we found that HIF-1α regulates vasoconstriction by limiting phosphorylation of myosin light chain and regulates vascular remodeling through p27 induction. These findings highlight a cell-specific role for HIF-1α in the inhibition of pulmonary vasoconstriction and vascular remodeling.
Work Engagement among Acute Care Nurses: A Qualitative Study
Authors: Al Mamari Hind , Groves Patricia S.
Published: October 2023

Aims. To understand how Omani nurses conceptualize work engagement, explore factors influencing engagement, and identify strategies to improve work engagement. Design. A qualitative study design. Methods. Semistructured interviews were conducted with twenty-one Omani nurses from four acute-care hospitals. Interview transcripts were examined using directed content analysis. Results. Participants defined work engagement as a positive state where nurses are engaged physically, emotionally, and mentally with work. Mentally engaged nurses’ minds are occupied with patients even when they are off duty. Organizational factors affecting work engagement were leadership, teamwork, autonomy, pay, and job demand. Individual factors affecting engagement included considering nursing a rewarding profession. A social factor was family commitments. Strategies suggested to improve engagement included improved pay and monetary incentives, working system flexibility, open-door policy, performance feedback, recognition, and resources. Conclusion. Mentally engaged nurses are attached to work even when they are off duty. Nurses’ gait and facial expressions can indicate high or low work engagement. Nurses with family obligations felt drained of energy, affecting their vigor and enthusiasm at work. Implications. Management skills and practices impact work engagement. Nurse’s feedback can be used to improve practice and design interventions that promote nurses’ engagement.
Prevalence and Distribution of Oral Mucosal Lesions and Normal Variants among Nepalese Population
Authors: Gupta Abhishek , Shrestha Parikshya , Poudyal Sijan , Kumar Sandeep , Lamichhane Ram Sudan , Acharya Surendra Kumar , Shivhare Peeyush
Published: October 2023

Background. Oral mucosa is encountered by various lesions and normal variants. Some are not to be worried about, whereas others may be of significance. Knowing the prevalence of oral mucosal lesions in a particular region helps better evaluate, diagnose, and, thus, manage these lesions. Objectives. To assess the prevalence and distribution of oral mucosal lesions and normal variants among various age groups, genders, and sites of the orofacial region. Methods. This cross‐sectional study was conducted in the Department of Oral Medicine and Radiology, KIST Medical College and Teaching Hospital from January 2021 to March 2021. Three different proformas were designed according to age, gender, and location of lesions for entry as per the WHO’s guide. The obtained data were entered into a Microsoft Excel sheet for frequency analysis by SPSS, and the results were tabulated. Results. Among the records of 16572 (9703 (58.55%) males and 6869 (41.44%) females) OPD patients, 3495 (21.08%) (1934 (55.33%) males and 1561 (44.66%) females) had OMLs and 2314 (13.96%) (1626 (70.26%) males and 688 (29.73%) females) had normal mucosal variants. The most commonly seen OML categories were tobacco‐associated lesions, i.e., 2056 (34.07%), tongue lesions, i.e., 1598 (26.48%), oral potentially malignant disorders, i.e., 815 (13.50%), ulcers i.e., 728 (12.06%), and infectious lesions, i.e., 256 (4.24%). Conclusion. The Nepalese population has a wide range of oral mucosal lesions and normal variants, and this study has attempted to have baseline data for the same. The most common OML was smoker’s melanosis.
Persistent Vulvar Itch Unresponsive to Treatment: A Case of Vulvar Schistosomiasis Caused by Schistosoma mansoni and a Brief Review of Literature
Authors: Gyening-Yeboah Anthony , Quayson Solomon E.
Published: October 2023

Background. Vulvar schistosomiasis is a female genital schistosomiasis (FGS), which occurs because of the damage caused by the presence of schistosome ova within the vulva. FGS is mostly misdiagnosed as a sexually transmitted infection. There is no reported case of vulvar schistosomiasis from Schistosoma mansoni in an immunocompetent or immunocompromised person in Ghanaian medical literature; however, there is a reported case of S. haematobium in an immunocompromised person. This is the first case of vulvar schistosomiasis from S. mansoni infection in an immunocompromised person. This case report discusses the need to consider vulvar schistosomiasis in patients with itchiness of the vulva. Case Presentation. A sixty-nine-year-old married woman presents with a persistent vulvar itch that is unresponsive to treatment. A clinical diagnosis of vulvar lichen planus unresponsive to medical therapy was made. A histopathological diagnosis of vulvar schistosomiasis was, however, made. Ziehl–Neelsen stain revealed the ova of Schistosoma mansoni. Symptoms resolved on administration of oral praziquantel. Conclusion. Vulvar schistosomiasis must be considered in clinical history-taking and investigation of signs and symptoms related to itchiness of the vulva. Ziehl–Neelsen staining is a helpful histopathology armamentarium to determine the species of schistosome ova.
Comparing Surgical and Oncological Outcomes between Indocyanine Green (ICG) Sentinel Lymph Node Mapping with Routine Lymphadenectomy in the Surgical Staging of Early-Stage Endometrioid Endometrial Cancer
Authors: Koh Krystal Miao Lin , Ng Zheng Yuan , Chin Felicia Hui Xian , Wong Wai Loong , Wang Junjie , Lim Yong Kuei
Published: October 2023

Introduction and Aim. Sentinel lymph node (SLN) mapping has been developed as an alternative to complete lymphadenectomy for the surgical staging of early-stage, uterine-confined endometrial cancer to reduce the morbidity of lymphadenectomy and has been demonstrated as a safe and feasible alternative. We compare the surgical and oncological outcomes between SLN mapping with routine lymphadenectomy in the surgical staging of early-stage endometrial cancer in our centre. Methods. A retrospective single-centre cohort study of patients with early-stage endometrioid endometrial cancer undergoing staging surgery (total hysterectomy, bilateral salpingo-oophorectomy with/without pelvic lymph node, and/or para-aortic lymph node dissection (PLND)) with either SLN mapping or routine lymphadenectomy between July 2017 and December 2018. Results. 203 cases with clinical and radiological International Federation of Gynaecology and Obstetrics (FIGO) stage I endometrioid endometrial cancer were included, out of which 109 cases underwent SLN mapping and 94 cases complete lymphadenectomy. Compared to the PLND group, the SLN group had shorter operative time (129 vs. 162 minutes), less blood loss (100 vs. 300 ml), and decreased length of postoperative hospital stay (3 vs. 4 days) (

p
<
0.001

). The lymph node metastases detection rate was 4.6% and 7.4% for the SLN and PLND groups, respectively (

p
=
0.389

). With a median follow-up of 14 months for the SLN and 15 months for the PLND group, the disease-free (DFS) and overall survival (OS) were comparable for both at 13 months (

p
=
0.538

and

p
=
0.333

, respectively). Conclusion. SLN mapping has been shown to be an acceptable alternative to routine lymphadenectomy in the surgical staging of early-stage endometrial cancer in our centre, with a comparable lymph node metastases detection rate, DFS and OS, and reduction in operative morbidity. Our results with SLN mapping reproduce comparable outcomes to those reported in the literature.
Supplementary Table 3 from Impact of Eliminating Cost-Sharing by Medicare Beneficiaries for Follow-Up Colonoscopy After a Positive Stool-based Colorectal Cancer Screening Test
Authors: Fendrick A. Mark , Lieberman David , Chen Jing Voon , Vahdat Vahab , Ozbay A. Burak , Limburg Paul J.
Published: October 2023

Table S3. Model utility inputs and references.
Data from Impact of Eliminating Cost-Sharing by Medicare Beneficiaries for Follow-Up Colonoscopy After a Positive Stool-based Colorectal Cancer Screening Test
Authors: Fendrick A. Mark , Lieberman David , Chen Jing Voon , Vahdat Vahab , Ozbay A. Burak , Limburg Paul J.
Published: October 2023

Abstract
Medicare coverage of a follow-up colonoscopy after a positive stool-based colorectal cancer screening test with no patient cost-sharing started January 2, 2023, which may favorably affect screening behavior. This analysis estimated the clinical and economic effects of increased colorectal cancer screening participation potentially resulting from this policy change in Medicare beneficiaries. The validated Colorectal Cancer and Adenoma Incidence & Mortality (CRC-AIM) model simulated three guideline-endorsed colorectal cancer screening strategies for average-risk individuals (colonoscopy every 10 years, annual fecal immunochemical test, triennial multitarget stool DNA) from ages 65–75 years. The base-case scenario assumed 0% coinsurance for initial screening and follow-up colonoscopy, real-world screening test use (colonoscopy = 45.3%, stool-based test = 24.4%, unscreened = 30.3%), and real-world follow-up colonoscopy rates. Comparative scenarios assumed an increase in the overall screening rate from 0% to 15% (5% increments) and an increase in the follow-up colonoscopy rate from 0% to 15% (5% increments). The base-case scenario resulted in 128 life-years gained (LYG)/1,000 individuals versus no screening and total screening and treatment costs of $7,938/person. The changes resulted in an increase of up to 26 LYG/1,000 individuals and a decrease in total screening and treatment costs by as much as $128/person. Follow-up colonoscopy at $0 coinsurance became cost-saving with any increase in either overall screening or follow-up colonoscopy. Policies that remove cost barriers to completing colorectal cancer screening may increase rates of screening participation, potentially improving economic and clinical outcomes.
Significance:
A follow-up colonoscopy after a positive stool-based colorectal cancer screening test is necessary to complete the full screening process. Policies that remove cost barriers to completing colorectal cancer screening may lead to increases in overall participation rates and use of follow-up colonoscopy, improving clinical and economic outcomes.
A Rare Pathogenic Variant in the SERPINF1 Gene in Association with Early-Onset Severe Presentation of Autosomal Recessive Type of Osteogenesis Imperfecta VI: A Case Report
Authors: Anand Siddharth , Pawal-Aute Pratibha , Gunale Shashikant , Agarwal Meenal
Published: October 2023

Osteogenesis imperfecta (OI) refers to a group of genetic disorders with the typical clinical presentation of increased bone fragility. More than 90% of OI cases have an underlying genetic mutation in the collagen genes COL1A1 or COL1A2. However, there are now 22 different recognized OI subtypes based on the underlying gene implicated. OI type VI is caused by pathogenic variants in the serine proteinase inhibitor clade F (SERPINF1) gene. In this case study, the patient was a 4-year-old female, born in a consanguineous family, with a history of delayed gross motor milestones and recurrent fractures after trivial trauma since the age of 8 months. The results of skeletal surveys and bone scans indicated that the patient suffered from OI. To confirm the diagnosis, we performed a next-generation sequencing (NGS) analysis of genes implicated in OI using the TruSight One NGS Panel. Bioinformatics analysis showed the presence of a rare pathogenic variant in exon 7 of the SERPINF1 gene in a homozygous state (NM_002615.5:c.907C>T; NP_002606.3:p.Arg303Ter; ClinVar submission ID: SUB10491966). The variant results in the termination of the polypeptide chain at position 303. Targeted capillary sequencing confirmed the presence of this variant in a homozygous state in the patient and in heterozygous state for both parents. Additionally, the patient’s younger sibling, aged 10 months, harbored the variant in a homozygous state. The sibling started bisphosphonate therapy and did not suffer any fractures in over 2 years after initiating the therapy. The etiological genetic diagnosis helped provide genetic counseling to the family. This highlights the utility of NGS for the confirmation of a clinical analysis in cases where alterations in multiple genes can result in similar clinical presentation.
Management of Chronic Anal Fissure with a Novel Topical Hemp-Herbal-Based Ointment: A Pilot Study
Authors: Ram Edward , Zager Yaniv , Meyer Raanan , Carter Dan , Joubran Samia , Horesh Nir
Published: October 2023

Introduction: Anal fissure (AF) is a common anorectal disease. Although several pharmacological treatments are available, many patients still require surgical interventions. In this study, we aimed to evaluate the efficacy of an ointment based on a multifunctional blend of herbal ingredients including hemp (ProctoFiz) for chronic AF. Methods: A single-arm, questionnaire-based prospective study was conducted in a large tertiary center to evaluate the outcomes of patients suffering from chronic AF treated with topical ProctoFiz. Results: Ninety-two patients were included in the study, 54 (58.7%) were females with a median age of 39 (range 17–78). 32 patients (34.7%) suffered from recurrent AF before enrolling in the study, and 5 patients (5.4%) underwent previous surgical interventions for AF. Three patients (3.2%) were lost to follow-up, leaving 89 patients for analysis. Eighty patients (89.9%) reported significant improvement of symptoms after 1 week using ProctoFiz, and 79 patients reported continued improvement after 1 month of treatment. The mean pain Visual Analog Score (VAS) declined by 6.6 points (8.9 vs. 2.3; 95% CI: 7.20 to −5.99, p < 0.0001) following 1 week of treatment, with continuous improvement to a mean of 0.64 after 1 month. Negative impact on quality of life significantly decreased from a mean of 8.8 to 0.38 following a month of treatment (p < 0.0001), with significant reduction in the number of patients suffering from bleeding following bowel movements (64.1–2.5%; p = 0.0001). Conclusion: Hemp-based topical treatment of AF is feasible and significantly improves AF-correlated symptoms.
A Rare ND5 Mutation Causing Leber’s Hereditary Optic Neuropathy
Authors: Pandya Bhadra U , Vosoughi Amir R. , Jhaveri Aaditeya , Micieli Jonathan A.
Published: October 2023

Mutations to the ND5 gene are uncommonly associated with Leber’s hereditary optic neuropathy (LHON). Herein, we describe a 57-year-old man with the m. 13528A>G, p. (Thr398Ala) mutation at the ND5 gene who presented with progressive bilateral vision loss over the course of 3 months. He had a significant history of smoking and alcohol consumption. Visual field testing demonstrated bilateral central scotomas. At 2-year follow-up, his visual acuity improved relative to baseline and temporal optic disc pallor was observed in both eyes. There are scarce reports of this mutation in the literature, and this case report further expands the clinical presentation of the m. 13528A>G mutation at the ND5 gene in patients with LHON phenotype.
Unusual Presentations of Low-Tension Glaucoma
Authors: He Jody Z. , Chopra Vikas
Published: October 2023

Low-tension glaucoma can sometimes be difficult to diagnose, particularly if patients do not have a classic presentation. This case series shows the value of Humphrey visual field (HVF) 10-2 tests to identify deficits in central vision. Case 1 describes a female in her mid-60s who presented complaining of a “blind spot” in her right eye. While a HVF 24-2 suggested her test was “within normal limits,” an HVF 10-2 showed an unusually shaped scotoma in her right eye that matched her visual complaint. Case 2 describes a male in his mid-60s who was referred to the glaucoma service by a retina specialist. He complained of a “blind spot” in his left eye and was revealed to have a focal central scotoma on his HVF 10-2 test. Both patients presented with normal intraocular pressures, and both had been cleared by retina specialists and neuro-ophthalmologists. Both patients were then diagnosed with low-tension glaucoma, and treatment to date has been successful in slowing vision loss.
The Effects of Long-Term Self-Dosing of Cannabidiol on Drowsiness, Testosterone Levels, and Liver Function
Authors: Kaufmann Robert , Harris Bozer Amber , Jotte Amanda Rose Kube , Aqua Keith
Published: October 2023

Introduction: Previous research indicated that cannabidiol (CBD) may result in low levels of male total testosterone (TT), elevations in liver tests (LTs), and daytime drowsiness (DD). We investigated the prevalences of TT and LT in a large adult sample self-administering CBD and determined the effect self-dosing of CBD has on the severity of DD. Methods: Adult participants (18–75 years of age) who self-dose CBD orally for a minimum of 30 days were recruited for this decentralized observational study from companies that offer CBD products. Participants were sent their usual CBD regimen. A clinical study platform was used on a phone app to obtain consent and collect study data. Data included demographic information, reasons for self-dosing, dosage, current medications and dosage, medical history, adverse effects, effects on DD, and efficacy. After 30 days, LT and TT were obtained and follow-up LT was offered to participants who demonstrated elevated values of alanine transaminase (ALT). Results: A total of 28,121 individuals were contacted, 1,475 met the criteria and were enrolled, and 1,061 (female: 65.2%, male: 34.8%) completed the study. Most of the participants used full-spectrum CBD oil or CBD isolate with the mean ± SD daily dose of CBD for all users of 55.4 ± 37.8 mg. CBD use was associated with a significant decrease in DD and a decrease in the prevalence of low TT in males >40 years of age. The prevalences of elevations in ALT and aspartate aminotransferase were not significantly different from those of the general adult population, and the prevalences of elevated levels of alkaline phosphatase and bilirubin were less than those of a healthy adult population. There was no relationship between LT and CBD dose. Conclusions: In this large-sample study, self-dosing CBD was not associated with an increased prevalence of elevation of LT or low levels of TT in men. Furthermore, CBD administration decreased DD and was associated with a lower prevalence of low testosterone levels in older men as compared to age-adjusted population norms.
Long-Term Follow-Up of a Family with Retinal Dystrophy Caused by RPE65 Mutation
Authors: Jánossy Ágnes , Vizvári Eszter , Lőrincz Máté , Pál Szilvia , Nagy Dóra , Benedek György , Tóth-Molnár Edit , Janáky Márta
Published: October 2023

We present here the case histories of two siblings, a boy and a girl, with Leber’s congenital amaurosis (LCA). The diagnosis was based on non-recordable full-field electroretinogram (ffERG). The long-term ophthalmologic follow-up included kinetic perimetry (Goldmann), visual evoked potentials with flash stimulation, optical coherence tomography (OCT: B-scan images at the area of fovea), and multifocal ERG. The boy (sibling 1, born in 1986) was sent for electrophysiological examination at the age of four because he had nystagmus from birth. The diagnosis would be LCA based on non-recordable ffERG. Four years later, his visual acuity decreased rapidly due to vitreous opacification, caused by the autoimmune reaction of the retinal pigment epithelial cells. This was treated successfully with steroid injections, administered parabulbarly. Retinal autoimmune panel was not performed. Genetic testing became available only in 2019, and it revealed a RPE65 gene mutation: (NM_000329.2) c.{442G>A};{442G>A} (p.{Glu148Lys}; {Glu148Lys}). His sister (sibling 2, born in 1993) showed similar symptoms, caused by the same genetic mutation. Even though their parents were free of symptoms, it appeared that they were heterozygous carriers of the same mutation. Research of the family tree revealed a consanguineous marriage four generations before. Both siblings received successful gene therapy relatively late in their age: sibling 1 was 35 and sibling 2 was 28 years old, meaning that they were at an advanced stage of the disease. Nevertheless, follow-up examinations showed measurable improvements in their retinal function. The study shows that electrophysiological examinations, including flash-evoked responses, are useful in the objective evaluation of the progression in the central photoreceptor loss during the follow-up of LCA. The results also show that gene therapy can have beneficial effects even at an advanced stage of the disease.
Practical Utilization of Prediction Equations in Chronic Kidney Disease
Authors: Tangri Navdeep , Ferguson Thomas W.
Published: October 2023

Chronic kidney disease (CKD) is common and can lead to kidney failure, cardiovascular complications, and early mortality. While nephrologists can provide valuable insights for patients at all stages of CKD, these scarce resources should be targeted at patients with the highest risk of progression and adverse outcomes. Prediction models are tools that can help providers risk stratify patients if they are effectively implemented into the clinical workflow. We believe these equations should demonstrate (1) clinical utility: where they can provide useful information to the physician and patients; and (2) clinical usability: where they are able to be easily integrated into clinical workflow and do not result in unnecessary costs or visits. CKD often remains unrecognized until later stages when a large window of opportunity to delay progression has already passed. Models to determine progression of CKD using thresholds such as a 40% decline in eGFR can provide clinical utility in risk stratifying patients at all stages of CKD, an endpoint that has been recommended by the FDA for the evaluation of drug approvals for disease-modifying therapies. For patients at more advanced stages of CKD with a greater risk of kidney failure, tools such as the kidney failure risk equation can be implemented to help guide most costly decisions, such as referral to multidisciplinary care, commencing dialysis modality education, or planning for vascular access placement surgery. In addition, models focused on determining outcomes following dialysis initiation can help inform shared decision-making between patient and provider to better inform decisions around conservative care. To ensure widespread adoption of these tools, it is important to ensure that they are broadly generalizable to many health settings and easily implemented into existing clinic workflows with minimum disruption.
Documented Adverse Drug Reactions and Discontinuation of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Chronic Kidney Disease
Authors: Gregg L. Parker , Richardson Peter A. , Herrera Michael A. , Akeroyd Julia M. , Jafry Shehrezade A. , Gobbel Glenn T. , Wydermyer Sheena , Arney Jennifer , Hung Adriana , Matheny Michael E. , Virani Salim S. , Navaneethan Sankar D.
Published: October 2023

Introduction: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are frequently discontinued in patients with chronic kidney disease (CKD). Documented adverse drug reactions (ADRs) in medical records may provide insight into the reasons for treatment discontinuation. Methods: In this retrospective cohort of US veterans from 2005 to 2019, we identified individuals with CKD and a current prescription for an ACEi or ARB (current user group) or a discontinued prescription within the preceding 5 years (discontinued group). Documented ADRs in structured datasets associated with an ACEi or ARB were categorized into 17 pre-specified groups. Logistic regression assessed associations of documented ADRs with treatment discontinuation. Results: There were 882,441 (73.0%) individuals in the current user group and 326,794 (27.0%) in the discontinued group. There were 26,434 documented ADRs, with at least one documented ADR in 7,520 (0.9%) current users and 9,569 (2.9%) of the discontinued group. ADR presence was associated with treatment discontinuation, aOR 4.16 (95% CI: 4.03, 4.29). The most common documented ADRs were cough (37.3%), angioedema (14.2%), and allergic reaction (10.4%). ADRs related to angioedema (aOR 3.81, 95% CI: 3.47, 4.17), hyperkalemia (aOR 2.03, 95% CI: 1.84, 2.24), peripheral edema (aOR 1.53, 95% CI: 1.33, 1.77), or acute kidney injury (aOR 1.32, 95% CI: 1.15, 1.51) were associated with treatment discontinuation. Conclusion: ADRs leading to drug discontinuation were infrequently documented. ADR types were differentially associated with treatment discontinuation. An understanding of which ADRs lead to treatment discontinuation provides an opportunity to address them at a healthcare system level.
Optic Neuritis following Second Administration of COVID-19 Vaccine: A Case Report
Authors: Saxton Edward , Panchasara Binita , Sarangapani Susan
Published: October 2023

A 28-year-old woman presented to eye casualty with signs and symptoms suggestive of optic neuritis following a recent COVID-19 vaccination (the Moderna mRNA-1273 vaccine). The best corrected visual acuity was 6/15 in the right eye and 6/6 in the left eye with a relative afferent pupillary defect in the right eye. Following examination and investigation, she was found to fit the McDonald criteria for multiple sclerosis and was commenced on disease-modifying therapy. Demyelinating events have been identified to occur following COVID-19 vaccinations. In this case, we have found that the Moderna mRNA-1273 vaccine could have contributed to the development of optic neuritis following a second dose of the vaccine.
Massive Uveal Relapse of Retinoblastoma Presumed to Be Choroidal Tumorous Involvement: Case Series
Authors: Ghassemi Fariba , Rahimi Masoud , Riazi-Esfahani Hamid , Khodabandeh Alireza , Masoomian Babak , Taghizadeh Sara , Sharifkashani Shervin
Published: October 2023

We report the choroidal and ciliary body invasion by retinoblastoma (RB) in a salvaged eye after complete and successful primary treatment. Case 1: A 25-month-old boy was referred due to group B RB lesions based on the International Classification of RB (ICRB; groups A–E) in the right eye (OD). His left eye (OS) was enucleated because of advanced group E RB. After 47 months of uneventful follow-up (F/U), a new lesion recurred and was treated with transpupillary thermotherapy. Four months later, a fast-growing pigmented subretinal mass was detected that was treated by brachytherapy with the apical dose of 80 Gy. Three weeks later, the lesion regressed completely, and no recurrence happened after 6 years of F/U. Case 2: A 4-month-old girl with a deletion in chromosome 13 was referred for bilateral RB. OD was enucleated because of unresponsive RB and anterior segment involvement. In OS, group B lesions had multiple recurrences after systemic chemotherapy. After a while, a single mass appeared in the nasal periphery which was controlled well with brachytherapy. Four months later, AC involvement was controlled with IAC, intravitreal, and intracameral chemotherapy, but posterior synechia and cataract appeared later. One year after the last treatment, UBM showed a ring-shaped ciliary body mass. Her parents refused enucleation again, and she received intravenous chemotherapy. Two years later, magnetic resonance imaging showed orbital and optic canal involvement with a deformed globe. In conclusion, RB recurrence can appear as local choroidal and ciliary body involvement even after a time of complete remission. The role of B-scan and UBM in early diagnosis and successful treatment is valuable.
A Rare Case of Direct Spontaneous Carotid-Cavernous Fistula in a 6-Month-Old Infant and Review of the Literature
Authors: Pal Sandeep , Sen Pradhnya A. , Patidar Narendra , Gabba Harshdeep Singh , Bhadra Sangeeta
Published: October 2023

Direct or type A CCFs are the direct connection between the cavernous segment of the internal carotid artery and the cavernous sinus. While most direct CCFs are caused by trauma, spontaneous direct CCFs are extremely rare in infants. In this report, we describe a 6-month-old child with bulges in the right eye that had been present since 20 days after birth. On examination, there was a right eye abduction limitation with no deviation associated with proptosis. Bruit was present during auscultation. CEMRI showed an enlarged right cavernous sinus with dilatation of the superior ophthalmic vein, suggesting a carotid-cavernous fistula. The patient was referred to an advanced center where he was advised patch therapy to prevent amblyopia. He was kept under observation by a neurosurgeon until 3 years, after which he was scheduled to undergo transarterial coiling.
Atypical Central Retinal Artery Occlusion following COVID-19 Infection: A Case Report
Authors: Heidarzadeh Hamid Reza , Abrishami Mojtaba , Motamed Shariati Mehrdad , Ghavami Shahri Seyed Hossein , Ansari Astaneh Mohammad Reza
Published: October 2023

Herein, we report a patient with atypical central retinal artery occlusion (CRAO) following COVID-19 recovery. A 44-year-old male was referred to the emergency room with a history of diplopia and sudden-onset painless visual loss in his left eye. He had a history of 1-week hospitalization for severe COVID-19 infection with pneumonia 3 weeks before, with positive real-time reverse transcription polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a nasopharyngeal sample. His visual acuity in the left eye was light perception which became no light perception later. Relative afferent pupillary defect was positive in the left eye. He had anterior chamber and anterior vitreous cells due to spillover and white cotton-wool-like patches in the left eye. He was diagnosed with atypical CRAO with uveitis-like features. After 3 weeks, he developed neovascular glaucoma and was treated with panretinal photocoagulation. In conclusion, SARS-CoV-2-induced vasculopathy and hypercoagulopathy conditions may be involved in the progression of CRAO in our patient. COVID-19 could be a considerable predisposing factor for CRAO.