Undiagnosed HIV in Patients on Immunosuppressive Medications Presenting with HIV-Associated Kidney Disease.

Approximately 158,500 adults and adolescents in the United States live with undiagnosed human immunodeficiency virus (HIV). Missed or delayed diagnoses adversely affect disease management and outcomes. This is particularly salient for patients receiving immunosuppressive and immunomodulatory therapy for the management of chronic inflammatory conditions, in which additional immunosuppression may increase the risk and severity of opportunistic infections. Despite this risk, comprehensive HIV testing before the initiation of immunosuppressive therapy is not yet the norm. We describe a case series containing the narratives of three patients recently treated with immunosuppressive agents, who presented with signs concerning for HIV-associated kidney diseases and who were found to have undiagnosed HIV later in the treatment course, which, unfortunately, resulted in poor outcomes. Screening for HIV or related illnesses, such as viral hepatitis or mycobacterial co-infections including tuberculosis, is essential before initiating biologic immunosuppression.

Effects of altering diet carbohydrate profile and physical form on zoo-housed giraffe Giraffa camelopardalis reticulata.

Unlike wild giraffe that primarily consume low starch browse, the preference of zoo-housed giraffe for consuming supplemental feeds over forage could increase the risk of digestive disorders such as ruminal acidosis. Our objective was to evaluate the effects of modifying a supplemental feed's non-fibre carbohydrate profile and physical form on nutritional, behavioural, and blood measures of giraffe in a zoological setting. Six non-lactating, adult, female reticulated giraffes were used in a two-pen modified reversal study using two dietary treatments in seven 21-day periods with data collected on days 15-21. Dietary treatments were a control feed comprised of commercially available products used at the time as the giraffe feed (GF) and an unpelleted experimental feed (EF). On a dry matter basis, GF and EF, respectively, contained 17.0% and 17.4% crude protein, 14.2% and 1.5% starch, 14.9% and 21.3% ethanol-soluble carbohydrates, 22.9% and 26.0% acid detergent fibre (ADF) and 9.50% and 14.9% ND-soluble fibre (NDSF), with modulus of fineness values of 3.62 and 4.82. Supplemental feeds, alfalfa hay, salt, and water were available for ad libitum consumption. Significance was declared at p ≤ 0.05. Intakes of hay, supplemental feeds, and total feed did not differ by diet (p > 0.28), though intakes of starch (0.93 and 0.12 kg; p = 0.05) and ADF (1.83 and 2.23 kg; p = 0.04) differed between GF and EF respectively. Giraffe behaviour values (min/48 h) were greater with EF for total eating (p = 0.04); diets were not detected as different for engagement in oral stereotypes (GF = 433, EF = 318 min/48 h; p = 0.22). Blood glucose was higher on GF than EF (99.0 and 82.3 mg/dL; p = 0.03). The lower EF blood glucose value is more similar to ranges reported for domesticated ruminants. No differences were detected for changes in body weight or body condition score in the 21-day periods (p > 0.32). Modification of supplemental feed carbohydrate profile and physical form can influence behaviour and blood glucose values of zoo-housed giraffe.

Watery Diarrhea Is Not Always Clostridioides difficile: A Case Report of Aeromonas hydrophila Gastroenteritis.

Aeromonas species can cause acute gastroenteritis but are much less commonly observed in the hospital setting than other bacteria. Most cases of Aeromonas hydrophila gastroenteritis reported in the literature have occurred in pediatric, elderly, and/or immunocompromised patients. We present a case of subacute watery diarrhea due to A. hydrophila infection in an otherwise healthy 48-year-old female patient with prior abdominal surgeries and recent hospitalization for a catheter-associated urinary tract infection (CAUTI) for which she received antibiotics. The patient presented with 10 days of increasingly frequent non-bloody, watery, foul-smelling diarrhea as well as decreased oral intake, cramping bilateral upper abdominal pain, chills, and malaise. Initial diagnoses considered included Clostridioides difficile in the setting of CAUTI and antibiotic use, small intestinal bacterial overgrowth, dumping syndrome related to bariatric surgery, and malabsorption. A computed tomography scan of her abdomen/pelvis, admission labs, and flexible sigmoidoscopy showed no relevant findings. Stool cultures eventually returned positive for A. hydrophila. The case is an uncommon presentation of Aeromonas infection that could be easily missed while other diagnoses are pursued. Early treatment of Aeromonas infection can be crucial in preventing advanced forms of disease such as septicemia and necrotizing fasciitis.

An improved pathway for autonomous bioluminescence imaging in eukaryotes.

The discovery of the bioluminescence pathway in the fungus Neonothopanus nambi enabled engineering of eukaryotes with self-sustained luminescence. However, the brightness of luminescence in heterologous hosts was limited by performance of the native fungal enzymes. Here we report optimized versions of the pathway that enhance bioluminescence by one to two orders of magnitude in plant, fungal and mammalian hosts, and enable longitudinal video-rate imaging.

Mapping the scientific literature on obstetrical and perinatal health among sexual and gender minoritised (SGM) childbearing people and their infants: a scoping review protocol.

INTRODUCTION: Sexual and gender minoritised (SGM) populations are disproportionately impacted by multilevel risk factors for obstetrical and perinatal outcomes, including structural (eg, stigma, discrimination, access to care) and individual risk factors (eg, partner violence, poor mental health, substance use). Emerging evidence shows SGM childbearing people have worse obstetrical outcomes and their infants have worse perinatal outcomes, when compared with their cisgender and heterosexual counterparts; this emerging evidence necessitates a comprehensive examination of existing literature on obstetrical and perinatal health among SGM people. The goal of this scoping review is to comprehensively map the extent, range and nature of scientific literature on obstetrical and perinatal physical health outcomes among SGM populations and their infants. We aim to summarise findings from existing literature, potentially informing clinical guidelines on perinatal care, as well as highlighting knowledge gaps and providing directions for future research. METHODS AND ANALYSIS: We will follow the Joanna Briggs Institute (JBI) scoping review framework and report findings according to the PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. We will conduct a broad systematic search in Medline/PubMed, Embase, CINAHL and Web of Science Core Collection. Eligible studies will include peer-reviewed, empirical, English-language publications pertaining to obstetrical and perinatal physical health outcomes of SGM people or their infants. No temporal or geographical limitations will be applied to the search. Studies conducted in all settings will be considered. Records will be managed, screened and extracted by two independent reviewers. Study characteristics, key findings and research gaps will be presented in tables and summarised narratively. ETHICS AND DISSEMINATION: Ethical approval is not required as primary data will not be collected. The findings of this scoping review will be disseminated through a peer-reviewed journal and conference presentations. PROTOCOL REGISTRATION: Open Science Framework https://osf.io/6fg4a/.

Parental Perspectives on Communication from Health Care Providers following a Newborn Diagnosis of Congenital Cytomegalovirus Infection: A Secondary Analysis of a Qualitative Study.

The study objective was to identify communication messages that parents of children diagnosed with congenital cytomegalovirus (cCMV) infection reported as essential and helpful. We performed a secondary analysis of focus groups and interviews conducted with 41 parents of children with cCMV who had enrolled in a long-term follow-up cCMV study at an academic medical center. Three groups of parents who had children with cCMV participated in the study: parents with children symptomatic at birth, parents with children asymptomatic at birth who later developed sensorineural hearing loss, and parents with children asymptomatic at birth who remained asymptomatic into adulthood. Using a health marketing approach, we identified six general themes from the focus group sessions: initial diagnosis, likely health outcome(s), comfort and coping, symptom watch, resources, and prevention. Receiving the initial diagnosis was shocking for many parents, and they wanted to know how their child would or could be affected. They valued access to the information, follow-up visits for early detection of hearing loss and other developmental delays, and support from other parents. Parents wished to obtain this information from their pediatrician but felt that experts offered more up-to-date knowledge about prognosis, monitoring, and treatment. With more U.S. states implementing cCMV screening strategies which would lead to more infant diagnoses, it will be necessary for providers to meet parents' expectations and communication needs.

Comparison of alternative neutral detergent fiber methods to the AOAC definitive method.

Neutral detergent fiber (NDF) is the most commonly reported metric for fiber in dairy cattle nutrition. An empirical method, NDF is defined by the procedure used to measure it. The current definitive method for NDF treated with amylase (aNDF) is AOAC Official Method 2002.04 performed on dried samples ground through the 1-mm screen of a cutting mill with refluxing and then filtration through Gooch crucibles without (AOAC-; reference method) or with (AOAC+) a glass fiber filter filtration aid. Other methods in use include grinding materials through the 1-mm screen of an abrasion mill, using filtration through a Buchner funnel with a glass fiber filter (Buch), and use of the ANKOM system (ANKOM Technology, Macedon, NY) that simultaneously extracts and filters samples through filter bags with larger (F57) or smaller (F58) particle size retentions. Our objective was to compare the AOAC and alternative methods using samples ground through the 1-mm screens of cutting or abrasion mills. Materials analyzed were 2 alfalfa silages, 2 corn silages, dry ground and high-moisture corn grains, mixed grass hay, ryegrass silage, soybean hulls, calf starter, and sugar beet pulp. Samples were run in duplicate in replicate analytical runs performed on different days by experienced technicians. Compared with cutting mill-ground samples, the aNDF% of dry matter results from abrasion mill-ground samples were or tended to be lower for 8 of 11 samples. Method affected aNDF% results for all materials, with method × grind interactions for 6 of 11 samples. For ash-free aNDF% assessed with cutting mill-ground materials, a priori selected contrasts showed that the number of materials for which methods differed or tended to differ from the AOAC methods were 4 (Buch), 8 (F57), and 3 (F58); and 3 for AOAC- versus AOAC+. However, statistically different does not necessarily mean substantially different. For a given feed and grind, a positive value for the absolute difference between the AOAC- mean and an alternative method mean minus 2 times the standard deviation of AOAC- suggests that values for the alternative method fall outside of the range of results likely to be observed for the reference method. The number of observed positive values for materials processed with cutting and abrasion mills, respectively, were 0 and 2 (AOAC+); 2 and 2 (Buch); 8 and 10 (F57); 4 and 7 (F58); and 0 and 4 (AOAC-). With the materials tested, methods in order of agreement with the reference method were Buch, F58, and F57, which often gave lower values. The AOAC+ gave results similar to AOAC-, substantiating it as an allowed modification of AOAC-. Best agreement between the reference method and variant NDF methods was achieved with the 1-mm screen cutting mill grind. The 1-mm abrasion mill grind produced more aNDF% results that were lower than the reference method but with fewer differences when filter particle retention size was smaller. The use of filters that retain finer particles could be explored to improve comparability of variant NDF methods and grinds. Further evaluation with an expanded set of materials is warranted.

Presentations, Diagnosis, and Treatment of Post-COVID Viral Myocarditis in the Inpatient Setting: A Narrative Review.

While coronavirus disease 2019 (COVID-19) infection rates have declined, and mortality outcomes have improved with vaccines, targeted antiviral therapies, and improved care practices over the course of the pandemic, post-acute sequelae of SARS CoV-2 infection (PASC, also referred to as "long COVID") has emerged as a significant concern, even among individuals who appear to have fully recovered from their initial infection. Acute COVID-19 infection is associated with myocarditis and cardiomyopathies, but the prevalence and presentation of post-infectious myocarditis are unclear. We provide a narrative review of post-COVID myocarditis, including symptoms and signs, physical exam findings, diagnosis, and treatment strategies. Post-COVID myocarditis has a wide range of presentations, from very mild symptoms to severe ones that can include sudden cardiac death. Several studies have noted what appears to be a bimodal distribution of affected patients, with individuals under age 16 (particularly males) most affected, followed by those over age 50. The gold standard of diagnosis for myocarditis is endomyocardial biopsy and cardiac magnetic resonance imaging with a confirmed diagnosis of COVID-19. However, if these are not available, other studies such as electrocardiogram, echocardiography, and inflammatory markers can guide clinicians to diagnose post-COVID myocarditis when appropriate. Treatment is largely supportive and may include oxygen therapy, intravenous hydration, diuretics, steroids, and antivirals. Post-COVID myocarditis is rare but important to recognize as more patients present with this condition in the inpatient setting.

Association between RCT methodology and disease indication with mineralocorticoid-related toxicity for patients receiving abiraterone acetate for advanced prostate cancer: A meta-analysis of RCTs.

INTRODUCTION: While abiraterone acetate (AA) has demonstrated survival benefit in advanced prostate cancer (APC), meaningful cardiotoxicity is observed. It is unclear whether the magnitude differs based on disease indication and concurrent steroid administration. METHODS: We performed a systematic review and meta-analysis of phase II/III RCTs of AA in APC published as of August 11, 2020. Primary outcomes examined were all- and high-grade (grade ≥ 3) hypokalemia and fluid retention, and secondary outcomes included hypertension and cardiac events. We performed random effects meta-analysis comparing intervention (AA + steroid) and control (placebo ± steroid), stratified by treatment indication and whether patients received steroids. RESULTS: Among 2,739 abstracts, we included 6 relevant studies encompassing 5901 patients. Hypokalemia and fluid retention were observed more frequently among patients receiving AA (odds ratio [OR] 3.10 [95% CI 1.69-5.67] and 1.41 [95% CI 1.19-1.66]). This was modified by whether patients in the control received steroids: trials where control patients did not demonstrated a larger association between AA and hypokalemia (OR 6.88 [95% CI 1.48-2.36] versus OR 1.86 [95% CI 4.97-9.54], P < .0001) and hypertension (OR 2.53 [95% CI 1.91-3.36] vs. OR 1.55 [95% CI 1.17-2.04], P = .1) than those where steroids were administered. We observed heterogeneity due to indication: there were greater effects on hypokalemia (P < 0001), hypertension (P = .03), and cardiac disorders (P = .01) among patients treated for mHSPC than mCRPC. CONCLUSIONS: The magnitude of cardiotoxicity with AA differs based on trial design and disease indication. These data are valuable in treatment decisions and highlight utilization of appropriate data for counseling.

Maternal immune activation as an epidemiological risk factor for neurodevelopmental disorders: Considerations of timing, severity, individual differences, and sex in human and rodent studies.

Epidemiological evidence suggests that one's risk of being diagnosed with a neurodevelopmental disorder (NDD)-such as autism, ADHD, or schizophrenia-increases significantly if their mother had a viral or bacterial infection during the first or second trimester of pregnancy. Despite this well-known data, little is known about how developing neural systems are perturbed by events such as early-life immune activation. One theory is that the maternal immune response disrupts neural processes important for typical fetal and postnatal development, which can subsequently result in specific and overlapping behavioral phenotypes in offspring, characteristic of NDDs. As such, rodent models of maternal immune activation (MIA) have been useful in elucidating neural mechanisms that may become dysregulated by MIA. This review will start with an up-to-date and in-depth, critical summary of epidemiological data in humans, examining the association between different types of MIA and NDD outcomes in offspring. Thereafter, we will summarize common rodent models of MIA and discuss their relevance to the human epidemiological data. Finally, we will highlight other factors that may interact with or impact MIA and its associated risk for NDDs, and emphasize the importance for researchers to consider these when designing future human and rodent studies. These points to consider include: the sex of the offspring, the developmental timing of the immune challenge, and other factors that may contribute to individual variability in neural and behavioral responses to MIA, such as genetics, parental age, the gut microbiome, prenatal stress, and placental buffering.

Primary Care Considerations for Elderly U.S. Veterans of World War II and the Korean War: A Narrative Review.

Many of the United States' more than 18 million veterans obtain healthcare through the Department of Veterans Affairs' (VA) Veterans Health Administration system; however, recent legislative changes have expanded veterans' access to non-VA care in their communities, particularly for those who do not live near VA medical centers. Veterans are seen by physicians in outpatient practice across the United States and are admitted to non-VA hospitals; this is particularly salient for older veterans, who may require a more frequent and high level of care. We present a review of characteristics of U.S. veterans from two conflicts: World War II (WWII) and the Korean War. While non-VA clinicians are well equipped to provide care for patients of all different ages, veterans of armed conflicts have a unique constellation of exposures and cultural considerations that must be accounted for when providing them care. In this review, we describe characteristics of the generations of American veterans who served in WWII and the Korean War conflicts in a brief historical context. We then note conflict-specific exposures and potential long-term sequelae to watch for during physical examinations and to monitor thereafter, age-specific health and emotional concerns, and best practices for providing care to this cohort of veterans.

Cannabis-Induced Acute Encephalopathy in a 94-Year-Old Woman Due to Family Administration of Cannabidiol (CBD) Products: A Case Report.

In the United States, cannabis use is rising, including among older adults, as is unintentional ingestion. We describe the case of a 94-year-old woman admitted with altered mental status, diarrhea, and hallucinations. She lived with her family, who had noticed recent confusion with weakness, poor oral intake, and loose bowel movements. In the emergency room, her vital signs revealed mild tachycardia and hypotension. She was lethargic, disoriented, confused, and anxious but could answer simple questions. The attending hospitalist administered the Mini-Cog dementia screening and found that the patient was oriented to herself only and was unable to perform word recall tests or complete a clock drawing. The rest of her physical exam was within normal limits for her age. Despite a workup including urine culture, chest X-ray, and computed tomography scan of her head, no organic source for her mental change was found. After five days of admission, a close relative confessed that they had given the patient cannabis oil (marketed as "pure CBD," i.e., cannabidiol, a nonpsychoactive cannabis derivative widely touted as a remedy for pain, anxiety, and anorexia) in the form of edible brownies to help her with her persistent back pain and poor appetite. We performed a urine drug screen for tetrahydrocannabinol (THC), the psychoactive component of cannabis, which verified cannabis use, as well as exposure to THC. The patient recovered to baseline with supportive care. Currently, there is no governing body or framework for the regulation of cannabis products in the United States. Nonprescription CBD products are not regulated by the US Food and Drug Administration, and these products are not tested for safety, efficacy, or quality. Some producers voluntarily conduct such testing, but there is no regulatory oversight, and consumers may be unaware of the need for testing and/or which testing bodies are credible. Given the rapidly increasing proportion of older adults who are cannabis users, physicians should inquire about outpatient use of cannabis in general and CBD in particular during discussions with patients, even the most elderly.

An optimized bioluminescent substrate for non-invasive imaging in the brain.

Bioluminescence imaging (BLI) allows non-invasive visualization of cells and biochemical events in vivo and thus has become an indispensable technique in biomedical research. However, BLI in the central nervous system remains challenging because luciferases show relatively poor performance in the brain with existing substrates. Here, we report the discovery of a NanoLuc substrate with improved brain performance, cephalofurimazine (CFz). CFz paired with Antares luciferase produces greater than 20-fold more signal from the brain than the standard combination of D-luciferin with firefly luciferase. At standard doses, Antares-CFz matches AkaLuc-AkaLumine/TokeOni in brightness, while occasional higher dosing of CFz can be performed to obtain threefold more signal. CFz should allow the growing number of NanoLuc-based indicators to be applied to the brain with high sensitivity. Using CFz, we achieve video-rate non-invasive imaging of Antares in brains of freely moving mice and demonstrate non-invasive calcium imaging of sensory-evoked activity in genetically defined neurons.

Presentations and outcomes among sickle cell disease patients with COVID-19 at a large southern healthcare system.

OBJECTIVES: Compared with the general population, patients with sickle cell disease (SCD) typically have substantially reduced life expectancies. It is unclear whether SCD patients who acquire COVID-19 have higher rates of complications and mortality than the general population. We sought to elucidate COVID-19 presentation and outcomes in patients with SCD. METHODS: Using retrospective chart review, we evaluated demographic characteristics, presenting symptoms, chest imaging findings, blood transfusion requirements, need for mechanical ventilation or pressor support, medication administration (including remdesivir and dexamethasone), and survival among individuals with SCD hospitalized with COVID-19 from March 2020 to December 2021. RESULTS: Among 72 SCD patients, increased pain was the most common presenting symptom followed by cough, fever, and dyspnea. Thirty-seven (44%) received simple transfusion and 14 (17%) underwent exchange transfusion. Lung imaging findings suggestive of COVID-19 were observed in 27 (37%) patients; 21 (29%) patients were treated with remdesivir and 26 (35%) received dexamethasone. Three patients (4%) required mechanical ventilation and pressor support; all three died from COVID complications. CONCLUSIONS: Pain is the most common presenting symptom in SCD patients with COVID-19. We observed a mortality rate higher than that among the general population among patients who required mechanical ventilation and pressor support.

Atypical presentation of cutaneous meningioma.

Cutaneous meningiomas are rare tumors of ectopic meningeal tissue in the dermis or subcutis and are most commonly located on the scalp and around the eyes, ears, nose, and mouth. We present a case of cutaneous meningioma with an unusual presentation on the upper arm, but with positivity for epithelial membrane antigen to support the diagnosis of meningioma. Lack of pancytokeratin AE1/3 and p63 allowed us to rule out a keratinocytic tumor, such as squamous cell carcinoma and basal cell carcinoma. The absence of smooth muscle actin, FXIIIa, CD163, and CD34 allowed us to rule out a leiomyoma, dermatofibroma, and vascular neoplasm respectively. Weak staining of S100 allowed us to rule out a perineuroma. The purpose of this case report is to increase awareness of a rare presentation of cutaneous meningioma not located within the scalp/face region. This may broaden its inclusion within differential diagnoses of neoplasms of uncertain behavior and encourage correct clinical diagnosis, thus improving treatment outcomes.

When It's Not Pancreatitis, Don't Brush It Off: A Case Report of Small Bowel Perforation Caused by a Grill Brush Bristle Masquerading As Pancreatitis.

Injuries caused by grill brush bristle ingestion have been documented in the literature, but most existing literature focuses on consumer safety and increasing public awareness of potential injuries. Small bowel perforation is a serious complication and often difficult to diagnose since symptoms are frequently nonspecific and bristle localization can be challenging. We highlight a case where a diagnosis of acute pancreatitis was initially made by computerized tomography (CT) imaging but was later determined to be small bowel perforation with magnetic resonance imaging (MRI).1 Due to its high resolution and excellent anatomic depiction of different pathologies, including inflammation and tumors, MRI is often used as an imaging modality when the cause of pancreatitis is not clear through initial history, physical exam, or imaging modalities like ultrasound and CT scan. MRI provides an opportunity to detect pathologies that cannot be depicted by CT because of its high contrast resolution (though conversely, CT has a higher spatial resolution, so there are some cases in which it can detect things that MRI cannot). This case highlights the importance of considering MRI to diagnose and evaluate complications in suspected cases of wire bristle ingestion prior to endoscopic or surgical extraction.

Idiopathic Intracranial Hypertension: An Unusual Cause of Headache in a Patient With Sickle Cell Disease.

Idiopathic intracranial hypertension (IIH) is a rare cause of headache and visual disturbance with no known association with sickle cell disease (SCD). We present a patient with SCD with gradual onset of a severe headache and visual changes. Brain magnetic resonance imaging, angiography, and venography were nondiagnostic. Lumbar puncture established a diagnosis of IIH, and the patient had rapid improvement with large-volume lumbar puncture and acetazolamide. To our knowledge, this is the first case of IIH in a nonobese adult with SCD taking hydroxyurea, suggesting an association between SCD or hydroxyurea use and IIH. Furthermore, her clinical course demonstrates the complexities of treating IIH in patients with SCD.

Development of a rapid, simple, and sensitive point-of-care technology platform utilizing ternary NanoLuc.

Point-of-care tests are highly valuable in providing fast results for medical decisions for greater flexibility in patient care. Many diagnostic tests, such as ELISAs, that are commonly used within clinical laboratory settings require trained technicians, laborious workflows, and complex instrumentation hindering their translation into point-of-care applications. Herein, we demonstrate the use of a homogeneous, bioluminescent-based, split reporter platform that enables a simple, sensitive, and rapid method for analyte detection in clinical samples. We developed this point-of-care application using an optimized ternary, split-NanoLuc luciferase reporter system that consists of two small reporter peptides added as appendages to analyte-specific affinity reagents. A bright, stable bioluminescent signal is generated as the affinity reagents bind to the analyte, allowing for proximity-induced complementation between the two reporter peptides and the polypeptide protein, in addition to the furimazine substrate. Through lyophilization of the stabilized reporter system with the formulated substrate, we demonstrate a shelf-stable, all-in-one, add-and-read analyte-detection system for use in complex sample matrices at the point-of-care. We highlight the modularity of this platform using two distinct SARS-CoV-2 model systems: SARS-CoV-2 N-antigen detection for active infections and anti-SARS-CoV-2 antibodies for immunity status detection using chemically conjugated or genetically fused affinity reagents, respectively. This technology provides a simple and standardized method to develop rapid, robust, and sensitive analyte-detection assays with flexible assay formatting making this an ideal platform for research, clinical laboratory, as well as point-of-care applications utilizing a simple handheld luminometer.