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Oxyuriasis, caused by the nematode Enterobius vermicularis, is one of the cosmopolitan intestinal infections of humans. Aspiculuris tetraptera commonly infects mice and it is morphologically similar to E. vermicularis. Parasitic resistance reduces the efficiency of synthetic drugs and poses economic impacts on the dairy sector, thus necessitating novel anthelmintic agents. Olea europaea L. (Olive) is a bioactive plant with potent pharmacological activities. However, its effects on oxyurids are poorly known, and no studies are currently exploring olives’ anthelmintic potential. In this study, we investigated the pharmacokinetic behaviors of O. europaea leaves extract (OLE) and its phenolic compound oleuropein in mice infected with A. tetraptera, in comparison with Albendazole (ABZ), a standard drug used to treat parasitic worms. Fecal flotation method was used to identify the infestation with A. tetraptera eggs by examining the stool samples from mice. Infected animals were divided into 7 groups. 250 mg/kg, 500 mg/kg, and 1000 mg/kg doses of OLE, 5 mg/kg and 20 mg/kg doses of oleuropein, 10 mg/kg of ABZ and tap water were orally administered by gavage for 7 days during treatments. Drug efficacies and statistical differences between the treatments and controls were evaluated. Our results revealed 92.43 % efficacy of ABZ, similar to 92.19 % efficacy of 1000 mg/kg of OLE. At the same time, 250 mg/kg and 500 mg/kg concentrations of OLE remained 70.03 % and 63.18 % effective in reducing worm counts. Efficacy percentages of 5 mg/kg and 20 mg/kg of oleuropein were 9.27 % and 70.56 %, respectively. Statistical analysis of ABZ was significant compared to 1000 mg/kg of OLE, which was almost equal but insignificant. In general, our results confirm the anthelmintic potential of OLE and oleuropein against mice pinworms and open the way for targeted extraction of bioactive compounds from plants to optimize its use in human and veterinary medicine.

Keratoconus (KC) is a corneal thinning dystrophy that leads to visual impairment. While the cause of KC remains poorly understood, changes in sex hormone levels have been correlated with KC development. This study investigated circulating gonadotropin-releasing hormone (GnRH) in control and KC subjects to determine if this master hormone regulator is linked to the KC pathology. Plasma and saliva were collected from KC subjects (n = 227 and n = 274, respectively) and non-KC controls (n = 58 and n = 101, respectively), in concert with patient demographics and clinical features. GnRH levels in both plasma and saliva were significantly lower in KC subjects compared to controls. This finding was retained in plasma when subjects were stratified based on age, sex, and KC severity. Control and KC corneal fibroblasts (HKCs) stimulated with recombinant GnRH protein in vitro revealed significantly increased luteinizing hormone receptor by HKCs and reduced expression of α-smooth muscle actin with treatment suggesting that GnRH may modulate hormonal and fibrotic responses in the KC corneal stroma. Further studies are needed to reveal the role of the hypothalamic–pituitary–gonadal axis in the onset and progression of KC and to explore this pathway as a novel therapeutic target.

Purpose: To present the clinical outcome of mitomycin intravascular chemoembolization (MICE) as a prophylactic treatment in a patient with HSV-induced corneal neovascularization (NV) before penetrating keratoplasty (PKP). Observations: A 53-year-old male patient presented with a medical history of recurrent herpes simplex virus (HSV) corneal infection. The patient reported worsening visual acuity despite maintenance treatment with systemic antivirals and topical corticosteroids. After the appearance of corneal NV, subconjunctival triamcinolone and bevacizumab injections were given with limited and temporary improvement. Due to worsening corneal NV, MICE was subsequently performed, resulting in the elimination of corneal NV from the visual axis, which allowed for successful PKP 4 months later. Cataract surgery was performed 6 months after PKP. Conclusions and importance: This report describes the potential efficacy of MICE as a prophylactic treatment for corneal NV prior to PKP.

Abstract Purpose To evaluate whether the volume of wash out rinse after povidone iodine (PI) application for intravitreal injections (IVI) affects patients’ ocular surface irritation. Methods This was a prospective, single-masked, randomized-controlled trial consisting of 142 subjects. A total of 51, 45, and 46 patients received 3-mL, 10-mL, and 15-mL of ocular rinse respectively. Reductions in the Ocular Surface Disease Index (OSDI) and the Standardized Patient Evaluation of Eye Dryness II (SPEED II) surveys, conducted before and at 24–72 h post-injection, were analyzed. Results There was no statistical difference in objective dry eye findings of Schirmer test (p-value = 0.788), tear break-up time (p-value = 0.403), Oxford fluorescein grade (p-value = 0.424) between the study groups prior to injections. Dry eye symptoms as measured by reductions in the OSDI and SPEEDII scores were not different between the study groups (p-value = 0.0690 and 0.6227, respectively). Conclusion There is no difference in patients’ ocular surface irritation between 3-mL, 10-mL, and 15-mL post injection rinse. Given the large number of IVIs performed, modification of practice patterns based on these findings could lead to significant reduction in global cost burden for IVIs.

BackgroundIncreasing numbers of residency applications create challenges for applicants and residency programs to assess if they are a good fit during the residency application and match process. Applicants face limited or conflicting information as they assess programs, leading to overapplying. A holistic review of residency applications is considered a gold standard for programs, but the current volumes and associated time constraints leave programs relying on numerical filters, which do not predict success in residency. Applicants could benefit from increased transparency in the residency application process. ObjectiveThis study aims to determine the information applicants find most beneficial from residency programs when deciding where to apply, by type of medical school education background. MethodsMatch 2023 applicants voluntarily completed an anonymous survey through the Twitter and Instagram social media platforms. We asked the respondents to select 3 top factors from a multiple-choice list of what information they would like from residency programs to help determine if the characteristics of their application align with program values. We examined differences in helpful factors selected by medical school backgrounds using ANOVA. ResultsThere were 4649 survey respondents. When responses were analyzed by United States-allopathic (US-MD), doctor of osteopathic medicine (DO), and international medical graduate (IMG) educational backgrounds, respondents chose different factors as most helpful: minimum United States Medical Licensing Examination (USMLE) or Comprehensive Osteopathic Medical Licensing Examination (COMLEX) Step 2 scores (565/3042, 18.57% US-MD; 485/3042, 15.9% DO; and 1992/3042, 65.48% IMG; P

Syeda Samar Mustafa,1 Rida Batool,1 Muhammad Kamran,2 Hasnain Javed,3 Nazia Jamil1 1Institute of Microbiology and Molecular Genetics, Quaid e Azam Campus, University of the Punjab 54590, Lahore, Pakistan; 2Queensland Alliance for Agriculture and Food Innovation Centre for Animal Science, University of Queensland, Brisbane, Queensland, 4072, Australia; 3Provincial Public Health Reference Lab, Punjab AIDS Control Program, Lahore, PakistanCorrespondence: Syeda Samar Mustafa, Email samarmustafa14@gmail.comIntroduction: Wastewaters carrying thousands of human specimens from the community and representing the diversity of antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs) directly from the community mirror the extent of AR spread in the community and environment. This study aimed to investigate the occurrence and distribution of antibiotic-resistant ESKAPEE bacteria in the community versus clinical settings through monitoring nonclinical and clinical wastewaters.Methodology: Seven wastewater samples were collected from different environmental sources. Isolates were obtained on general and selective media, biochemically characterized and antimicrobial-susceptibility tests performed by disk diffusion against 13 antibiotics according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines using MastDisc disk cartridges, and 16S rRNA metagenomic analysis was performed for two water samples.Results: Of 43 isolates, all representatives of the ESKAPEE group were recovered from clinical wastewaters, but Gram-positive cocci were not obtained from nonclinical wastewaters. The most predominant isolate was Pseudomonas aeruginosa (n=15; 33%), followed by Escherichia coli (n=9; 20%). Complete (100%) resistance to eleven of the tested antibiotics was observed, with only a few isolates being susceptible to clarithromycin, amikacin, and gentamicin. The lowest (79%) resistance rate was observed for linezolid. The multiple antibiotic resistance (MAR) index was calculated, and the resistance phenotype was independent of the wastewater source, indicated by x2 (P=0.766). Metagenomic analysis replicated the results, as Pseudomonas spp., Acinetobacter spp., and Escherichia spp. were found to be predominant. The integrase gene (IntI1) was also amplified in Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa.Conclusion: Wastewaters are significant carriers of drug-resistant ESKAPEE bacteria and play an important role in their dissemination. This study endorses the periodic surveillance of water systems to evaluate the presence and burden of antibiotic-resistant pathogens.Graphical Abstract: Keywords: resistance profiling, ESKAPEE, wastewater, metagenome, IntI1

Mirvetuximab soravtansine (MIRV) is a first-in-class antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα) and is indicated for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received 1 to 3 prior systemic treatment regimens. MIRV has demonstrated single-agent anticancer activity in clinical trials, with a differentiated safety profile comprising primarily low-grade, resolvable gastrointestinal and ocular adverse events (AEs). Pooled safety analysis of 464 MIRV-treated patients across 3 trials, including the phase 2 SORAYA study, found that 50% of patients had ≥1 ocular AEs of interest (AEIs) of blurred vision or keratopathy, the majority being grade ≤2. Grade 3 ocular AEIs occurred in 5% of patients, and 1 patient (0.2%) had a grade 4 event of keratopathy. All grade ≥2 AEIs of blurred vision and keratopathy resolved to grade 1 or 0 in patients with complete follow-up data. MIRV-associated ocular AEs were primarily characterized by resolvable changes to the corneal epithelium, with no cases of corneal ulcers or perforations. This reflects the distinctive, milder ocular safety profile for MIRV compared with that of other ADCs with ocular toxicities in clinical use. To maintain a generally low incidence of severe ocular AEs, patients should follow recommendations for maintaining ocular surface health, including daily use of lubricating eye drops and periodic use of corticosteroid eye drops, and should undergo an eye examination at baseline, at every other cycle for the first 8 cycles of treatment, and as clinically indicated. Dose modification guidelines should be followed to maximize patients’ ability to remain on therapy. Close collaboration between all care team members, including oncologists and eye care professionals, will help patients benefit from this novel and promising anticancer agent. This review focuses on the etiology, rates, prevention, and management of MIRV-associated ocular events.

Abstract Acute myeloid leukemia (AML) arises from clonal expansion of malignant hematopoietic precursor cells in the bone marrow. In rare instances, AML can recur with prominent extramedullary manifestations (i.e., leukemia cutis or myeloid sarcoma), either simultaneously or preceding marrow involvement, or as a sole site of primary disease relapse.

Rashid Menhas,1 Jianhui Dai,2 Muhammad Azeem Ashraf,3 Sohail M Noman,4 Sumaira Khurshid,5 Sajid Mahmood,6 Yu Weng,2 Rizwan Ahmad Laar,7 Xuehui Sang,2 Muhammad Kamran,8 Babar Shahzad,9 Waseem Iqbal9 1Research Center of Sports Social Sciences, School of Physical Education and Sports, Soochow University, Suzhou, 215006, Jiangsu Province, People’s Republic of China; 2School of Physical Education and Sports, Soochow University, Suzhou, 215006, Jiangsu Province, People’s Republic of China; 3Research Institute of Educational Science, Hunan University, Changsha, 410082, People’s Republic of China; 4Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China; 5School of Education and Science, Neijiang Normal University, Neijiang, Sichuan Province, People’s Republic of China, 641112; 6Department of Zoology, Hazara University, Mansehra, 21120, Pakistan; 7School of Sports Science and Physical Education, Nanjing Normal University, Nanjing, 210023, People’s Republic of China; 8NRSP Microfinance Bank Shorkot City Branch, Shorkot, 35050, Punjab, Pakistan; 9School of Energy, Soochow University, Suzhou, 215006, Jiangsu Province, People’s Republic of ChinaCorrespondence: Muhammad Azeem AshrafResearch Institute of Educational Science, Hunan University, Changsha, 410082, People’s Republic of ChinaEmail azeem20037@gmail.comBackground: China has the world’s largest population, going under health transition due to industrialization, urbanization, and a sedentary lifestyle. About 82% of China’s disease burden is due to the prevalence of non-communicable diseases (NCDs). Physical activity (active travel) is the best preventive measure against NCDs. The Chinese government has introduced several steps to improve national fitness and overcome NCDs among the aging population. Exercise and sports play a vital role in promoting physical activity and helpful in accomplishing the national fitness level for Healthy China under the national fitness plan (NFP).Objective: The current study aimed to explore the role of national fitness plan (NFP) in promoting physical activity and health well-being preventing NCDs under built environment intervention.Methods: The study was exploratory, and the mixed-method approach was used to analyze the primary and secondary data. Quantitative content analysis was used to analyze the collected data. A purposive sampling technique was used to collect the primary data from those individuals rich in knowledge about the National Fitness Plan (NFP) of China and its role in promoting physical activity for physical fitness.Results: The majority of the participants (32.0%) said that the national fitness plan helps promote sports environment and health. About 28.0% reported that NFP helps promote cycling and walk environments for physical activity and health promotion and preventing non-communicable diseases (NCDs).Conclusion: Participation in physical exercise and sports is the preferred approach to prevent different diseases. In the context of rising active living among the Chinese people, the facilities such as built environment and green parks under the national fitness plan (NFP) for sports play a crucial role in the mitigation of NCDs.Keywords: non-communicable diseases, physical activity, built environment, sports, national fitness

The mTOR pathway is an essential regulator of cell growth and metabolism. Midbrain dopamine neurons are particularly sensitive to mTOR signaling status as activation or inhibition of mTOR alters their morphology and physiology. mTOR exists in two distinct multiprotein complexes termed mTORC1 and mTORC2. How each of these complexes affect dopamine neuron properties, and whether they have similar or distinct functions is unknown. Here, we investigated this in mice with dopamine neuron-specific deletion of Rptor or Rictor, which encode obligatory components of mTORC1 or mTORC2, respectively. We find that inhibition of mTORC1 strongly and broadly impacts dopamine neuron structure and function causing somatodendritic and axonal hypotrophy, increased intrinsic excitability, decreased dopamine production, and impaired dopamine release. In contrast, inhibition of mTORC2 has more subtle effects, with selective alterations to the output of ventral tegmental area dopamine neurons. Disruption of both mTOR complexes leads to pronounced deficits in dopamine release demonstrating the importance of balanced mTORC1 and mTORC2 signaling for dopaminergic function.

Collagen crosslinking (CXL) is a widely used treatment to halt the progression of keratoconus (KC). Unfortunately, a significant number of patients with progressive KC will not qualify for CXL, including those with corneas thinner than 400 µm. The present study aimed to investigate the molecular effects of CXL using in vitro models, mirroring the normal, as well as thinner corneal stroma seen in KCs. Primary human corneal stromal cells were isolated from healthy (HCFs) and keratoconus (HKCs) donors. Cells were cultured and stimulated with stable Vitamin C resulting in 3D self-assembled extracellular matrix (ECM), cell-embedded, constructs. CXL was performed on (a) thin ECM with CXL performed at week 2 and (b) normal ECM with CXL performed at week 4. Constructs without CXL served as controls. All constructs were processed for protein analysis. The results showed modulation of Wnt signaling, following CXL treatment, as measured by the protein levels of Wnt7b and Wnt10a, correlated to the expression of α-smooth muscle actin (SMA). Further, the expression of a recently identified KC biomarker candidate, prolactin-induced protein (PIP), was positively impacted by CXL in HKCs. CXL-driven upregulation of PGC-1 and the downregulation of SRC and Cyclin D1 in HKCs were also noted. Although the cellular/molecular impacts of CXL are largely understudied, our studies provide an approximation to the complex mechanisms of KC and CXL. Further studies are warranted to determine factors influencing CXL outcomes.

Context: Overwhelmed by COVID-19 patients requiring urgent medical attention and intensive care beds, majority of our medical resources are allocated for the management of the current pandemic. Other urgent cases requiring surgical attention also need to be optimally addressed. Aims: The aim of this article is to report the early results and organizational protocol in the management of traumatic spinal fractures at a level-1 trauma center during the current pandemic. Settings and Design: This is a retrospective study of patients with vertebral fractures operated by a single surgeon between April and October 2020. All patients were tested for the SARS-CoV-2 virus, and the tests were repeated every 72 h. We modified our institutional protocol to aid the early management of emergency traumatic spine cases during this pandemic. Descriptive analysis of data collected from hospital records was carried out using Statistical Package for Social Sciences, Virginia, USA, Version 20. Results: A total of 44 patients were operated. Burst fracture was the most common fracture with a fall from height being the most common mechanism of injury. Two patients tested positive for the novel corona virus. There were no complications and none of the healthcare staff involved in the patient care or patients reported symptoms of COVID-19 during a 30-day follow‐up period. Conclusion: Surgical treatment of patients with vertebral fractures, with strict adherence to personal protective measures and local guidelines, did not increase the risk of contracting SARS‐CoV2 to either healthcare workers or patients during the lockdown period.

Vaccines for COVID-19 are now a crucial public health need, but the degree of protection provided by conventional vaccinations for individuals with compromised immune systems is unclear. The use of viral vectors to express neutralizing monoclonal antibodies (mAbs) in the lung is an alternative approach that does not wholly depend on individuals having intact immune systems and responses. Here, we identified an anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody, NC0321, which can efficiently neutralize a range of SARS-CoV-2 variants, including alpha, beta, delta, and eta. Both prophylactic and therapeutic NC0321 treatments effectively protected mice from SARS-CoV-2 infection. Notably, we adopted viral vector-mediated delivery of NC0321 IgG1 as an attractive approach to prevent SARS-CoV-2 infection. The NC0321 IgG1 expression in the proximal airway, expressed by a single direct in-vivo intranasal (I.N.) administration of a self-inactivating and recombinant lentiviral vector (rSIV.F/HN-NC0321), can protect young, elderly, and immunocompromised mice against mouse-adapted SARS-CoV-2 surrogate challenge. Long-term monitoring indicated that rSIV.F/HN-NC0321 mediated robust IgG expression throughout the airway of young and SCID mice, importantly, no statistical difference in the NC0321 expression between young and SCID mice was observed. A single I.N. dose of rSIV.F/HN-NC0321 30 or 180 days prior to SARS-CoV-2 challenge significantly reduced lung SARS-CoV-2 titers in an Ad5-hACE2-transduced mouse model, reconfirming that this vectored immunoprophylaxis strategy could be useful, especially for those individuals who cannot gain effective immunity from existing vaccines, and could potentially prevent clinical sequelae.

Abstract Background To examine the effect of pharmacologic dilation on biometric parameters measured by the Lenstar LS 900, and whether these changes affect the power of the calculated intraocular lens (IOL) using multivariable formulas in an undilated versus pharmacologically dilated state. Methods Prospective study of 98 phakic eyes from 53 patients. Axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), and keratometry (K) readings were measured. The first set of measurements was taken prior to dilation. After dilation (pupil diameter ≥ 6.0 mm), a second set of measurements was taken. The Barrett, Olsen, Hill-RBF, Haigis, SRK/T, and Holladay I formulas were used to calculate IOL power before and after dilation. Two calculation methods were used: method A used a commonly available IOL targeted to achieve the lowest myopic spheroequivalent residual refraction; method B calculated ideal IOL power for emmetropia. Results Statistically significant increases were seen in CCT (p

Purpose. To describe a case of acute anterior uveitis (AAU) with HLA-B27 positivity following epithelium-off corneal cross-linking (CXL) in a patient with a previous intrastromal corneal ring segment. Observations. A 28-year-old male with keratoconus (KCN) developed ophthalmalgia, perilimbal injection, hypopyon, and decline in corrected distance visual acuity (CDVA) 3 days after CXL. A working diagnosis of inflammatory versus infectious AAU was made, and the patient was treated with topical tobramycin, polymyxin B/trimethoprim, prednisolone, and oral valacyclovir. Clinical appearance and CDVA improved, ultimately returning to baseline by two weeks postoperatively. Diagnostic laboratory workup revealed HLA-B27 positivity. Conclusions and Importance. A comprehensive laboratory workup is helpful to identify potential causative and associated systemic conditions when encountering AAU after CXL. Given the overlap in patient demographics for KCN and HLA-B27 positivity, clinicians should consider this entity in the differential diagnosis and treatment of such cases.

Tuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder caused by mutations in the TSC1 or TSC2 genes, which negatively regulate mTORC1 signalling. Here the authors selectively delete Tsc1 from dopamine neurons in mice and find impairments in striatal dopamine release that are sufficient to reduce cognitive flexibility.

Abstract Aplastic anemia is a disorder of bone marrow failure characterized by a hypocellular bone marrow. We report two cases with an initial hypercellular bone marrow at the time of presentation, suggesting a new phase in the pathogenesis of the disease.

The frequent maintenance required on asphalt concrete (AC) pavement sections has made reconstruction with portland cement concrete pavement (PCCP) a feasible alternative. However, many constructability issues need to be addressed in order to realize the full potential of this alternative. Accelerated paving encompasses three classes of activities: methods to accelerate the rate of strength gain, methods to minimize the construction time, and traffic control strategies to minimize user delay. In this paper a case study will be presented in which an AC intersection was reconstructed with portland cement concrete pavement. The entire reconstruction of the intersection, including demolition of the AC pavement and its replacement with PCCP, took place over a period of three days, starting on Thursday evening and opening the intersection to the traffic on Sunday afternoon. This paper documents this effort in order to provide practitioners additional options for rapid reconstruction of urban intersections and includes documentation of the construction process, traffic management strategies, and an analysis of the costs. The results of this investigation can be used to educate pavement construction professionals and the academic community on the use of PCCP for accelerated reconstruction of major urban intersections with minimal user and traffic disruption, using innovative construction techniques and traffic management optimization principles. This investigation produced valuable information to demonstrate that concrete pavements can be constructed efficiently and quickly.

The COVID-19 pandemic put most in-person pathology electives on-hold as departments adapted to changes in education and patient care. To address the subsequent void in pathology education, we created a free, virtual, modular, and high-quality pathology elective website. Website traffic from June 1, 2020, to October 1, 2020, was monitored using the built-in analyses on Squarespace. Twitter engagement was analyzed using Twitter analytics and the Symplur Social Graph Score. A voluntary satisfaction survey was sent to all PathElective users and results were analyzed. During this time, the site saw 25 467 unique visitors, over 34 988 visits, 181 302 page views, and 4449 subscriptions from 99 countries. Countries with the highest traffic are the United States (14 682), India (5210), and the Philippines (2195). PathElective’s Twitter social graph score increased from 63.59 to 89.3 with the addition of 1637 followers. Data from surveyed users (n = 177) show most to be pathology residents (41%). Most subscribers (89%) are committed to a career in pathology. The majority heard of the website via Twitter (55%). Almost half of those surveyed engaged with the PathTwitter community on Twitter and of those who participated, 99% found that interaction useful. In all survey questions surrounding satisfaction and usefulness, a large majority of the users were either satisfied or very satisfied. PathElective is a novel pathology elective that offers a unique opportunity to educate medical students and residents from around the globe and demonstrates high effectiveness and satisfaction among users.

Salivary exosomes have demonstrated vast therapeutic and diagnostic potential in numerous diseases. This study pioneers previously unexplored roles of SE in the context of corneal wound healing by utilizing primary corneal stromal cells from healthy (HCFs), type I diabetes mellitus (T1DMs), type II DM (T2DMs), and keratoconus (HKCs) subjects. Purified, healthy human SEs carrying tetraspanins CD9+, CD63+, and CD81+ were utilized. Scratch and cell migration assays were performed after 0, 6, 12, 24, and 48 h following SE stimulation (5 and 25 µg/mL). Significantly slower wound closure was observed at 6 and 12 h in HCFs with 5 μg/mL SE and T1DMs with 5 and 25 μg/mL SE. All wounds were closed by 24-hour, post-wounding. HKCs, T1DMs, and T2DMs with 25µg/mL SE exhibited a significant upregulation of cleaved vimentin compared to controls. Thrombospondin 1 was significantly upregulated in HCFs, HKCs, and T2DMs with 25 µg/mL SE. Lastly, HKCs, T1DMs, and T2DMs exhibited a significant downregulation of fibronectin with 25 μg/mL SE. Whether SEs can be utilized to clinical settings in restoring corneal defects is unknown. This is the first-ever study exploring the role of SEs in corneal wound healing. While the sample size was small, results are highly novel and provide a strong foundation for future studies.

The use of social media at academic conferences is expanding, and platforms such as Twitter are used to share meeting content with the world. Pathology conferences are no exception, and recently, pathology organizations have promoted social media as a way to enhance meeting exposure. A social media committee was formed ad hoc to implement strategies to enhance social media involvement and coverage at the 2018 and 2019 annual meetings of the Association of Pathology Chairs. This organized approach resulted in an 11-fold increase in social media engagement compared to the year prior to committee formation (2017). In this article, the social media committee reviews the strategies that were employed and the resultant outcome data. In addition, we categorize tweets by topic to identify the topics of greatest interest to meeting participants, and we discuss the differences between Twitter and other social media platforms. Lastly, we review the existing literature on this topic from 23 medical specialties and health care fields.

Keratoconus (KC) is a progressive corneal thinning disease that manifests in puberty and worsens during pregnancy. KC onset and progression are attributed to diverse factors that include: environmental, genetics, and hormonal imbalances; however, the pathobiology remains elusive. This study aims to determine the role of corneal stroma sex hormone receptors in KC and their interplay with estrone (E1) and estriol (E3) using our established 3D in vitro model. Healthy cornea stromal cells (HCFs) and KC cornea stromal cells (HKCs), both male and female, were stimulated with various concentrations of E1 and E3. Significant changes were observed between cell types, as well as between males and females in the sex hormone receptors tested; androgen receptor (AR), progesterone receptor (PR), estrogen receptor alpha (ERα), and estrogen receptor beta (ERβ) using Western blot analysis. E1 and E3 stimulations in HCF females showed AR, PR, and ERβ were significantly upregulated compared to HCF males. In contrast, ERα and ERβ had significantly higher expression in HKC’s females than HKC’s males. Our data suggest that the human cornea is a sex-dependent, hormone-responsive tissue that is significantly influenced by E1 and E3. Therefore, it is plausible that E1, E3, and sex hormone receptors are involved in the KC pathobiology, warranting further investigation.

Initiatives like “American Medical Association (AMA)-Reimagining Residency” and “Accreditation Council for Graduate Medical Education (ACGME)-Next Accreditation System” are examples of a paradigm shift toward learner-centered pedagogy in resident education. Such interventions require an understanding of the basics of the learning process itself. This study aimed to identify preferred learning styles in pathology with the intent to use specialty-specific pattern data, if any, to improve pathology training modalities. Kolb’s learning tool questionnaire was sent to pathology-inclined medical students, pathology residents, fellows, and faculty in 5 academic programs. Data from 84 respondents (6 students, 37 residents, 12 fellows, 29 attendings) were analyzed. There was remarkable similarity in learning styles of fellows and faculty, revealing a dominance of observational learning styles (“assimilating” and “diverging”) that was consistent with pathology being a visual field. In contrast, residents showed dominance of “learn by doing” styles (“converging” and “accommodating”). Residents’ stratification by training year showed a scattered distribution with an upward trend toward “learn by doing” behavior. While the difference in styles between residents and faculty/fellows may be due to a generational gap, transition from medical school, or acquisition of technical skills required for grossing specimens, this is an opportunity for adopting blended learning models and active learning processes to cater to residents’ different styles and to allow for flexibility to use all styles as and when needed. Based on these findings, we hypothesize that partnering juniors and seniors with similar styles has a potential for successful mentorship and exploration of other psychometrics is recommended for further understanding and improvement of pathology training.

* Context.--PathElective.com was created in response to the pandemic's restrictions on interactions with trainees, and since has been incorporated into many training programs worldwide, serving as a unique means of delivering high-quality pathology and laboratory medical education at multiple levels of training. Objective.--To analyze student usage, performance, and satisfaction to provide insight into the effectiveness of virtual education to guide curricular evolution. Design.--Squarespace (Squarespace, Inc) was used for website development and to collect website analytics. Students were assessed before and after course participation using a dual-form crossover quiz design. Quiz data were anonymous and analyzed with a paired t test to account for varying student backgrounds. A novel analysis was performed aimed at examining the attrition rate of students across multiple modules. Results.--During the study period (May 1, 2020 to October 31, 2021), PathElective.com received 577 483 page views, 126180 visits, 59 928 unique visitors, and 10 278 registered users who earned 15 305 certificates. A total of 7338 premodule and postmodule quiz pairs were analyzed. The overall average increase in score was 13.83% (P = .02). All but 5 of the 56 courses experienced a statistically significant increase in score. All courses received median scores of Very Satisfied/ Satisfied in all 6 assessment domains. Aggregate attrition data revealed a unique, negative polynomial relationship ([R.sup.2] = 0.656). Conclusions.--PathElective.com is a free, effective means of enhancing anatomic/clinical pathology training in medical education. These analyses offer a unique perspective on the online user experience and could guide the development of future online medical education resources., As a result of the COVID-19 pandemic, medical education delivery transformed overnight. In-person experiences were converted to virtual experiences, with varying success. (1) Formal medical student exposure to pathology is [...]

Abstract Purpose This article evaluates whether a targeted, stepwise curriculum for microbypass stent placement leads to successful insertion of the iStent (Glaukos, Laguna Hills, CA) by resident surgeons. Participants Senior (postgraduate year 4) ophthalmology residents (9 residents) from three classes during the 2015 to 2016, 2016 to 2017, and 2017 to 2018 academic years. Design Residents participated in a three-stage surgical curriculum. First, a wet laboratory was held for residents to gain familiarity with the device and develop bimanual surgical proficiency. The wet laboratory involved several stations, with each station requiring increased dexterity for successful completion. Next, residents practiced bimanual intraoperative gonioscopy after routine phacoemulsification procedures. Finally, residents performed combined phacoemulsification and iStent insertion under the supervision of an experienced attending surgeon. Primary success was determined by correct anatomical placement of the device confirmed via subsequent intraoperative gonioscopy by the supervising surgeon. Secondary success was measured by change in intraocular pressure (IOP) and number of topical hypotensive medications used after surgery. Residents provided feedback about the effectiveness of the curriculum via an online survey. Results There were a total of 43 cases. There were no significant intraoperative complications, including hyphema. The iStent location was confirmed during both intraoperative and postoperative gonioscopy and was noted to be in appropriate position for the duration of the follow-up period (6–12 months) for all patients. Average preoperative IOP in our subjects was 17.5 ± 4.0 mm Hg and mean number of preoperative medications was 1.4 ± 1.0. At 6 months' postoperative, average IOP was 14.5 ± 2.2 mm Hg (13% reduction from baseline [±15%]). At 12 months' postoperative, average IOP was 14.4 ± 3.5 mm Hg, with a reduction of 14% (±18%). The mean number of medications at follow-up was 1.2 ± 1.1. Mean postoperative IOP at 6 and 12 months was significantly lower compared with baseline (p = 0.0002, p = 0.0001). Residents agreed that the curriculum prepared them to perform iStent insertion during residency and most residents felt prepared after residency. Conclusion This stepwise surgical curriculum for trabecular microbypass stent placement leads to successful performance of the procedure by residents and is a useful model for other residency programs.

Purpose. Obesity is being considered a “global epidemic.” Surgical procedures are rendered more difficult in obese patients. We aimed to see whether any benefits were evident with use of computer navigation during total knee replacement in these cases. Methods. A retrospective analysis of 287 TKR performed by a single surgeon was undertaken, including 133 TKR undertaken with computer navigation and 154 using standard instrumentation. Each group was further divided into subgroups depending on whether the patients were obese or nonobese. Results. We found that TKR in obese patients took longer with standard instruments, but not with computer navigation. A chronological analysis revealed that the surgeon progressively got quicker using computer navigation to the point that there was no difference in time with either of the operative techniques in obese patients. The mid-term clinical outcomes at five years were similar. Computer navigated TKR were more consistently accurately aligned. Conclusions. In obese patients, a dual advantage is provided by computer navigation: better alignment and no time penalty.

Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting.We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005-2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization.Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.

The mTOR pathway is an essential regulator of cell growth and metabolism. Midbrain dopamine neurons are particularly sensitive to mTOR signaling status as activation or inhibition of mTOR alters their morphology and physiology. mTOR exists in two distinct multiprotein complexes termed mTORC1 and mTORC2. How each of these complexes affect dopamine neuron properties, and whether they have similar or distinct functions is unknown. Here, we investigated this in mice with dopamine neuron-specific deletion of Rptor or Rictor, which encode obligatory components of mTORC1 or mTORC2, respectively. We find that inhibition of mTORC1 strongly and broadly impacts dopamine neuron structure and function causing somatodendritic and axonal hypotrophy, increased intrinsic excitability, decreased dopamine production, and impaired dopamine release. In contrast, inhibition of mTORC2 has more subtle effects, with selective alterations to the output of ventral tegmental area dopamine neurons. Disruption of both mTOR complexes leads to pronounced deficits in dopamine release demonstrating the importance of balanced mTORC1 and mTORC2 signaling for dopaminergic function.

Context.--Myriad forces are changing teaching and learning strategies throughout all stages and types of pathology education. Pathology educators and learners face the challenge of adapting to and adopting new methods and tools. The digital pathology transformation and the associated educational ecosystem are major factors in this setting of change. Objective.--To identify and collect resources, tools, and examples of educational innovations involving digital pathology that are valuable to pathology learners and teachers at each phase of professional development. Data Sources.--Sources were a literature review and the personal experience of authors and educators. Conclusions.--High-quality digital pathology tools and resources have permeated all the major niches within anatomic pathology and are increasingly well applied to clinical pathology for learners at all levels. Coupled with other virtual tools, the training landscape in pathology is highly enriched and much more accessible than in the past. Digital pathology is well suited to the demands of peer-to-peer education, such as in the introduction of new testing, grading, or other standardized practices. We found that digital pathology was well adapted to apply our current understanding of optimal teaching strategies and was effective at the undergraduate, graduate, postgraduate, and peer-to-peer levels. We curated and tabulated many existing resources within some segments of pathology. We identified several best practices for each training or educational stage based on current materials and proposed high-priority areas for potential future development. doi: 10.5858/arpa.2021-0473-RA, We could just as well be writing this paper with a manually powered typewriter, or with ink drawn from a well by a quill pen, had not a series of [...]