Synthesis of multi-omic data and community metabolic models reveals insights into the role of hydrogen sulfide in colon cancer.

Multi-omic data and genome-scale microbial metabolic models have allowed us to examine microbial communities, community function, and interactions in ways that were not available to us historically. Now, one of our biggest challenges is determining how to integrate data and maximize data potential. Our study demonstrates one way in which to test a hypothesis by combining multi-omic data and community metabolic models. Specifically, we assess hydrogen sulfide production in colorectal cancer based on stool, mucosa, and tissue samples collected on and off the tumor site within the same individuals. 16S rRNA microbial community and abundance data were used to select and inform the metabolic models. We then used MICOM, an open source platform, to track the metabolic flux of hydrogen sulfide through a defined microbial community that either represented on-tumor or off-tumor sample communities. We also performed targeted and untargeted metabolomics, and used the former to quantitatively evaluate our model predictions. A deeper look at the models identified several unexpected but feasible reactions, microbes, and microbial interactions involved in hydrogen sulfide production for which our 16S and metabolomic data could not account. These results will guide future in vitro, in vivo, and in silico tests to establish why hydrogen sulfide production is increased in tumor tissue.

Updating Normal Organ Weights Using a Large Current Sample Database.

CONTEXT.­: Organ weights are an essential part of autopsy analysis. Deviations from normal organ weights provide important clues to disease processes. The assessment of normal organ weights depends on reliable reference tables, but most widely available reference tables are based on data that are either decades old or derived from relatively small sample sizes. OBJECTIVE.­: To provide an updated reference table of organ weights based on contemporary sources and a large sample size. DESIGN.­: Organ weights from 4197 carefully screened autopsies performed on adults at the Palm Beach County Medical Examiner's Office in West Palm Beach, Florida, and the Mayo Clinic Hospital in Rochester, Minnesota. RESULTS.­: Height and body weight data in this study reflect the well-recognized increases in both variables, but most particularly in body weight, seen during the last decades. The study data show a strong positive association between organ weight and body weight for the heart, liver, and spleen. There is a similar but weaker association between body weight and the weight of the lungs and kidneys. Brain weight is independent of body weight but shows a strong negative association with age. Even when controlling for body weight, men's organs are heavier, except for the weight of the liver, which is comparable in men and women. These associations are in agreement with the findings of previous studies. The current study suggests that, for some of the commonly weighed organs, there has been an increase in median organ weight when compared with existing references. CONCLUSIONS.­: The tables presented here provide an updated reference that should prove useful to autopsy pathologists in the forensic and hospital settings.

Repository Corticotropin Injection as an Alternative Treatment for Refractory Ocular Mucous Membrane Pemphigoid.

PURPOSE: The purpose of this study was to report the clinical course and outcome of patients with refractory ocular mucous membrane pemphigoid (MMP) treated by repository corticotropin injection (RCI). METHODS: Patients with biopsy-proven ocular MMP treated with RCI from 3 tertiary medical centers were evaluated. Medical records between January 2013 and January 2021 were reviewed and deidentified to retrieve relevant disease-related data. Primary outcome measures included conjunctival inflammatory activity, change in Foster clinical conjunctival scarring staging after RCI treatment, and the development of ocular and systemic complications. RESULTS: Included were 15 patients (10 women and 5 men; 36-95 yrs of age) with a mean follow-up of 4.5 years. Most of the patients (80%) had Foster stage 3 at presentation, and all patients had active MMP. Each patient had failed to respond to at least 1 immunomodulatory drug during the follow-up, and 9 (60%) patients had treatment failure of at least 2 other agents before the use of RCI. The mean duration of RCI treatment was 21 months (range, 3-54 mo). Foster stage did not change in any of the 15 patients at the last follow-up. Nine patients continued RCI therapy at the last follow-up, and in all of them, the disease activity of MMP was well controlled. No serious adverse events because of RCI were documented during the follow-up in any treated patient. CONCLUSIONS: RCI may serve as an alternative or an adjunctive treatment in patients with severe and refractory ocular MMP. Treatment with RCI seems to be safe and well-tolerated.

A "shining" example of interstitial keratitis.

We present a case of interstitial keratitis, presumed to be herpetic, with a striking clinical appearance. A 67-year-old woman was initially diagnosed with viral conjunctivitis and ocular hypertension OD with conjunctival injection and elevated intraocular pressure (IOP). She later presented with a 'spot on my right eye' and, after referral, was diagnosed with presumed herpetic keratitis. She was treated with oral valacyclovir and topical prednisolone acetate. The cornea improved, leaving radiating lines in the corneal stroma. This case illustrates an unusual appearance of presumed herpetic stromal keratitis.

Age-related histologic features of the sinoatrial node from normal human hearts during the first 10 decades of life: a study of 200 cases.

Knowledge of the histologic constituency of the sinoatrial (SA) node is based on small studies with unevenly distributed ages and subjective assessments of nodal composition, leading to difficulties in interpreting what constitutes true pathology of the SA node. SA nodes from two-hundred normal hearts (10 male and 10 female from each of the first 10 decades of life) were digitally analyzed to assess their histologic composition. Both nodal area and nodal fat content (≥5%) showed a quadratic relationship with age, peaking in the fifth to eighth decades of life. Increased fat content was also more prevalent with increased BMI (≥25 kg/m2). No differences between sexes were observed. Mean nodal collagen ranged from 7.1% to 50.3%, without a statistically significant differences by age or body mass index (BMI). The data suggests that the designation of pathologic fibrosis should be reserved for SA nodes with >50% collagen content. These findings expand and refine our understanding of the anatomy of the SA node.

Update on Intraocular Lens Formulas and Calculations.

Investigators, scientists, and physicians continue to develop new methods of intraocular lens (IOL) calculation to improve the refractive accuracy after cataract surgery. To gain more accurate prediction of IOL power, vergence lens formulas have incorporated additional biometric variables, such as anterior chamber depth, lens thickness, white-to-white measurement, and even age in some algorithms. Newer formulas diverge from their classic regression and vergence-based predecessors and increasingly utilize techniques such as exact ray-tracing data, more modern regression models, and artificial intelligence. This review provides an update on recent literature comparing the commonly used third- and fourth-generation IOL formulas with newer generation formulas. Refractive outcomes with newer formulas are increasingly more and more accurate, so it is important for ophthalmologists to be aware of the various options for choosing IOL power. Historically, refractive outcomes have been especially unpredictable in patients with unusual biometry, corneal ectasia, a history of refractive surgery, and in pediatric patients. Refractive outcomes in these patient populations are improving. Improved biometry technology is also allowing for improved refractive outcomes and surgery planning convenience with the availability of newer formulas on various biometry platforms. It is crucial for surgeons to understand and utilize the most accurate formulas for their patients to provide the highest quality of care.

Selective deletion of Pten in pancreatic beta cells leads to increased islet mass and resistance to STZ-induced diabetes.

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a lipid phosphatase. PTEN inhibits the action of phosphatidylinositol-3-kinase and reduces the levels of phosphatidylinositol triphosphate, a crucial second messenger for cell proliferation and survival, as well as insulin signaling. In this study, we deleted Pten specifically in the insulin producing beta cells during murine pancreatic development. Pten deletion leads to increased cell proliferation and decreased cell death, without significant alteration of beta-cell differentiation. Consequently, the mutant pancreas generates more and larger islets, with a significant increase in total beta-cell mass. PTEN loss also protects animals from developing streptozotocin-induced diabetes. Our data demonstrate that PTEN loss in beta cells is not tumorigenic but beneficial. This suggests that modulating the PTEN-controlled signaling pathway is a potential approach for beta-cell protection and regeneration therapies.

Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue.

In adipose tissue, insulin controls glucose and lipid metabolism through the intracellular mediators phosphatidylinositol 3-kinase and serine-threonine kinase AKT. Phosphatase and a tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of the phosphatidylinositol 3-kinase/AKT pathway, is hypothesized to inhibit the metabolic effects of insulin. Here we report the generation of mice lacking PTEN in adipose tissue. Loss of Pten results in improved systemic glucose tolerance and insulin sensitivity, associated with decreased fasting insulin levels, increased recruitment of the glucose transporter isoform 4 to the cell surface in adipose tissue, and decreased serum resistin levels. Mutant animals also exhibit increased insulin signaling and AMP kinase activity in the liver. Pten mutant mice are resistant to developing streptozotocin-induced diabetes. Adipose-specific Pten deletion, however, does not alter adiposity or plasma fatty acids. Our results demonstrate that in vivo PTEN is a potent negative regulator of insulin signaling and insulin sensitivity in adipose tissue. Furthermore, PTEN may be a promising target for nutritional and/or pharmacological interventions aimed at reversing insulin resistance.

Endogenous endophthalmitis and osteomyelitis associated with interleukin 17 inhibitor treatment for psoriasis in a patient with diabetes.

A 64-year-old man with type 2 diabetes mellitus and plaque psoriasis presented to the emergency room with 3 days of progressive right eye pain and decreased vision. After extensive workup and multidisciplinary team effort, the patient was diagnosed with and treated for unilateral endogenous methicillin-sensitive Staphylococcus aureus endophthalmitis, bacteraemia and osteomyelitis of the foot. The patient had been started on the interleukin 17 (IL-17) inhibitor secukinumab for his treatment-resistant plaque psoriasis 4 weeks prior to presentation. After treatment, his final vision was light perception and the foot infection resolved without sequelae. To our knowledge, this is the first reported case of both endogenous endophthalmitis and osteomyelitis associated with an IL-17 inhibitor.

Sleep/sedation in children undergoing EEG testing: a comparison of chloral hydrate and music therapy.

This study included a total of 60 pediatric patients ranging from 1 month through 5 years of age. The effects of chloral hydrate and music therapy were evaluated and compared as means of safe and effective ways to achieve sleep/sedation in infants and toddlers undergoing EEG testing. The results of the study indicate that music therapy may be a cost-effective, risk-free alternative to pharmacological sedation.

Sleep/sedation in children undergoing EEG testing: a comparison of chloral hydrate and music therapy.

This study included a total of 60 pediatric patients ranging from 1 month through 5 years of age. The effects of chloral hydrate and music therapy were evaluated and compared as means of safe and effective ways to achieve sleep/sedation in infants and toddlers undergoing EEG testing. The results of the study indicate that music therapy may be a cost-effective, risk-free alternative to pharmacological sedation.