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An introduction to the rhinoceros, with a focus on its endangerment.

Dysfunctional cGMP signaling is implicated in multiple neurodegenerative diseases of the central nervous system (CNS), including glaucoma, an optic neuropathy and leading cause of irreversible blindness. Female mice lacking the alpha catalytic subunit of soluble guanylate cyclase ( sGCα1 −/− ), the active site that binds nitric oxide (NO) to produce cGMP, exhibit progressive retinal ganglion cell (RGC) degeneration with age. Yet, the role of sGC in age- and sex-dependent RGC function remains uncharacterized. We investigated how preventing NO binding to sGC influences RGC function in the context of aging and sex by combining bulk and single-cell RNA sequencing, Western blotting, mitochondrial ultrastructural analysis, visual acuity measurements, and in vivo measurements of retinal oxidative metabolism. We found that global sGCα1 deletion impairs visual function and RGC health in aging female mice, while male mice remained unaffected. Glucose uptake was significantly disrupted in female sGCα1 −/− retinas with age, and accompanied by reduced retinal expression of the glucose transporter, GLUT1. Aged sGCα1 −/− females also exhibited dysregulated retinal mitochondrial gene and protein expression and increased nitrosative stress localized to the RGC layer. RGC mitochondria in male mice increased in size with age, while female mitochondria did not. Furthermore, retinal metabolic analysis showed decreased oxygen consumption rate in aged female but not male sGCα1 −/− retinas, suggesting impaired oxidative metabolism. These findings reveal a potential sex-specific role for cGMP signaling in maintaining retinal metabolic integrity and RGC function with age. Our results point to a possible mechanistic link between impaired cGMP signaling and age-related retinal neurodegeneration in females, highlighting the sGC-cGMP signaling pathway as a promising therapeutic target for glaucoma and other CNS neurodegenerative diseases.

Objective Both diabetes and obesity can affect the brain, yet their impact is not well characterized in children with type 2 (T2) diabetes and obesity. This pilot study aims to explore differences in brain function and cognition in adolescents with T2 diabetes and obesity and nondiabetic controls with obesity and lean controls. Research design and methods Participants were 12‐17 years old (5 T2 diabetes with obesity [mean HgbA1C 10.9%], 6 nondiabetic controls with obesity and 10 lean controls). Functional MRI (FMRI) during hyperglycemic/euglycemic clamps was performed in the T2 diabetes group. Results When children with obesity, with and without diabetes, were grouped (mean BMI 98.8%), cognitive scores were lower than lean controls (BMI 58.4%) on verbal, full scale, and performance IQ, visual‐spatial and executive function tests. Lower scores correlated with adiposity and insulin resistance but not HgbA1C. No significant brain activation differences during task based and resting state FMRI were noted between children with obesity (with or without diabetes) and lean controls, but a notable effect size for the visual‐spatial working memory task and resting state was observed. Conclusions In conclusion, our pilot study suggests that obesity, insulin resistance, and dysglycemia may contribute to relatively poorer cognitive function in adolescents with T2 diabetes and obesity. Further studies with larger sample size are needed to assess if cognitive decline in children with obesity, with and without T2 diabetes, can be prevented or reversed.

Deficiency of the short stature homeobox-containing (SHOX) gene is a frequent cause of short stature in children (2–15%). Here, we report 7 siblings with SHOX deficiency due to a point mutation in the SHOX gene. Index case was a 3-year-old male who presented for evaluation of short stature. His past medical history and birth history were unremarkable. Family history was notable for multiple individuals with short stature. Physical exam revealed short stature, with height standard deviation score (SDS) of −2.98, as well as arm span 3 cm less than his height. His laboratory workup was noncontributory for common etiologies of short stature. Due to significant familial short stature and shortened arm span, SHOX gene analysis was performed and revealed patient is heterozygous for a novel SHOX gene mutation at nucleotide position c.582. This mutation is predicted to cause termination of the SHOX protein at codon 194, effectively causing haploinsufficiency. Six out of nine other siblings were later found to also be heterozygous for the same mutation. Growth hormone was initiated in all seven siblings upon diagnosis and they have demonstrated improved height SDS.

Public health emergencies create challenges for the accommodation of visitors to hospitals and other care facilities. To mitigate the spread of COVID-19 early in the pandemic, health care institutions implemented severe visitor restrictions, many remaining in place more than 2 years, producing serious unintended harms. Visitor restrictions have been associated with social isolation and loneliness, worse physical and mental health outcomes, impaired or delayed decision-making, and dying alone. Patients with disabilities, communication challenges, and cognitive or psychiatric impairments are particularly vulnerable without caregiver presence. This paper critically examines the justifications for, and harms imposed by, visitor restrictions during the COVID-19 pandemic and offers ethical guidance on family caregiving, support, and visitation during public health emergencies. Visitation policies must be guided by ethical principles; incorporate the best available scientific evidence; recognize the invaluable roles of caregivers and loved ones; and involve relevant stakeholders, including physicians, who have an ethical duty to advocate for patients and families during public health crises. Visitor policies should be promptly revised as new evidence emerges regarding benefits and risks in order to prevent avoidable harms.

Abstract Immunoglobulin G4-related disease (IgG4-RD), which affects many organ systems, has been recognized as a distinct clinical entity in human medicine for just over a decade but has not been previously identified in dogs. In humans, IgG4-RD is characterized by diffuse IgG4-positive lymphoplasmacytic infiltrates that commonly lead to increased serum concentrations of IgG4 and IgE, peripheral eosinophilia, tumorous swellings that often include the parotid salivary glands, obliterative phlebitis, and extensive fibrosis. Herein we describe the diagnosis, clinical progression, and successful treatment of IgG4-RD in an 8-year-old female spayed Husky mixed breed dog. Immunoglobulin G4-related disease should be considered as a differential diagnosis for dogs with vague clinical signs, lymphoplasmacytic swellings, restricted polyclonal gammopathy, eosinophilia or some combination of these findings.

Changes in cancer cell identity can alter malignant potential and therapeutic response. Loss of the pulmonary lineage specifier NKX2-1 augments the growth of KRAS-driven lung adenocarcinoma and causes pulmonary to gastric transdifferentiation. Here, we show that the transcription factors FoxA1 and FoxA2 are required for initiation of mucinous NKX2-1-negative lung adenocarcinomas in the mouse and for activation of their gastric differentiation program. Foxa1/2 deletion severely impairs tumor initiation and causes a proximal shift in cellular identity, yielding tumors expressing markers of the squamocolumnar junction of the gastrointestinal tract. In contrast, we observe downregulation of FoxA1/2 expression in the squamous component of both murine and human lung adenosquamous carcinoma. Using sequential in vivo recombination, we find that FoxA1/2 loss in established KRAS-driven neoplasia originating from SPC-positive alveolar cells induces keratinizing squamous cell carcinomas. Thus, NKX2-1, FoxA1 and FoxA2 coordinately regulate the growth and identity of lung cancer in a context-specific manner. Among all cancers, lung cancers cause the most deaths worldwide. There are many different types of lung cancer, each of which contain lung cancer cells that look different. As a general rule, lung cancer cells that look the most like healthy lung cells are the least aggressive. Cancer cells that take on the appearance of other tissues in the body are more aggressive and often respond poorly to treatment. In one uncommon type of lung cancer called invasive mucinous adenocarcinoma (IMA, for short), the cancer cells start to resemble the cells that line the inside of the stomach. For example, these lung cancer cells activate genes more typically active in stomach cells, and they start to make a lot of mucus. Previous studies with mice showed that losing a single protein called NKX2-1 can cause this switch from lung to stomach cell identity. However, it is not clear exactly how this switch happens and which other proteins are involved. Camolotto et al. have now addressed these issues by studying two DNA-binding proteins called FoxA1 and FoxA2. There were two main reasons for choosing these specific proteins. First, they can physically interact with the NKX2-1 protein, so losing NKX2-1 affects how FoxA1 and FoxA2 interact with DNA. Second, the two proteins switch on many of the stomach-related genes that are also activated in IMA. Camolotto et al. activated a gene that commonly drives lung cancer and deleted the gene for NKX2-1 in the lungs of mice, mimicking IMA. As expected, these mice developed lung tumors that resembled stomach tissue. When the genes for FoxA1 and FoxA2 were deleted at the same time, the tumors stopped producing the mucus-related proteins. Further experiments showed that these cancer cells adopt a different cell identity also found in the digestive tract. Mice with tumors lacking both FoxA1 and FoxA2 survived for longer than those still containing these proteins. Lastly, when the genes for NKX2-1, FoxA1 and FoxA2 were deleted later, in lung tumors that had already formed, the outcome was a more aggressive type of lung cancer that also occurs in human patients. These experiments demonstrate that losing FoxA1 and FoxA2 at different times affects what kind of lung tumor can grow. Future studies will need to examine how these different lung cancer types respond to therapy and whether lung cancer cells switch identities to evade therapy. This knowledge may eventually lead to new treatments for lung cancer patients.

Carbon black is a common powder for latent print development on nonporous surfaces. Black powders in general have been extensively and frequently researched. However, these powders cannot always be used depending on the contrast, texture, and composition of the surface that needs to be pro d for latent prints. In these situations, a good alternative is to use a white or lighter-colored powder. One of these powders is lanconide, an inorganic mixture of zinc sulfide (ZnS). zinc oxide (ZnO), barium sulfate (BaSO4), titanium oxide (TiO2), bismuth oxychloride (BiOCI), and calcium carbonate (CaCO3). This study removed one of these six compounds per trial to create seven different lanconide compositions to preliminarily assess performance with sebum-charged latent prints deposited by one donor. Overall, the literature lanconide powder was effective for print development, but the highest quality prints resulted when TiO2 was removed. As such, this compound could be obstructing print development, possibly due to its nonhygroscopic nature. TiO2 has also been identified as a possible carcinogen when inhaled, so removing titanium oxide from lanconide recipes creates a safer composition while still effectively enhancing latent fingerprint development.

Public health emergencies create challenges for the accommodation of visitors to hospitals and other care facilities. To mitigate the spread of COVID-19 early in the pandemic, health care institutions implemented severe visitor restrictions, many remaining in place more than 2 years, producing serious unintended harms. Visitor restrictions have been associated with social isolation and loneliness, worse physical and mental health outcomes, impaired or delayed decision-making, and dying alone. Patients with disabilities, communication challenges, and cognitive or psychiatric impairments are particularly vulnerable without caregiver presence. This paper critically examines the justifications for, and harms imposed by, visitor restrictions during the COVID-19 pandemic and offers ethical guidance on family caregiving, support, and visitation during public health emergencies. Visitation policies must be guided by ethical principles; incorporate the best available scientific evidence; recognize the invaluable roles of caregivers and loved ones; and involve relevant stakeholders, including physicians, who have an ethical duty to advocate for patients and families during public health crises. Visitor policies should be promptly revised as new evidence emerges regarding benefits and risks in order to prevent avoidable harms.