The impact of intraocular pressure on optical coherence tomography angiography: A review of current evidence.

A scoping review of 45 peer-reviewed manuscripts involving intraocular pressure (IOP) change and concurrent optical coherence tomography angiography (OCTA) assessments was performed to aggregate knowledge, summarize major findings, and identify gaps in literature and methodology relating to the effect of IOP change on OCTA. Articles were identified through PubMed/Medline, Google Scholar, Cochrane, Web of Science, and article reference lists. A total of 838 results were identified, and 45 articles met the inclusion and exclusion criteria for detailed analysis. OCTA metrics including vessel density (VD), perfusion density, and flow density of the superficial capillary plexus and the radial peripapillary capillaries were analyzed in relation to relative temporal IOP changes. Overall, IOP changes were found to affect superficial vascular plexus (VD) measurements on OCTA, especially when IOP elevated above the physiologic normal range (10-21 mmHg). No significant association was found between diurnal IOP variation and OCTA metrics. Cataract surgery improved the whole-image signal strength and VD regardless of changes in IOP. Beta-blockers were associated with paradoxically reduced vessel density in normal tension glaucoma patients in two studies. Although glaucoma surgical intervention studies were inconsistent and limited by scan quality and low sample sizes, patients requiring glaucoma surgery exhibited attenuated postoperative superficial VD recovery despite significant IOP reductions with surgical intervention. In addition to ensuring near-perfect signal strength with minimal media opacities and controlling for high myopia, central corneal thickness, and the presence of retinopathy, clinicians should consider the statistically significant impact of IOP on OCTA metrics when interpreting results.

IFN-λ uniquely promotes CD8 T cell immunity against SARS-CoV-2 relative to type I IFN.

Optimization of protective immune responses against SARS-CoV-2 remains an urgent worldwide priority. In this regard, type III IFN (IFN-λ) restricts SARS-CoV-2 infection in vitro, and treatment with IFN-λ limits infection, inflammation, and pathogenesis in murine models. Furthermore, IFN-λ has been developed for clinical use to limit COVID-19 severity. However, whether endogenous IFN-λ signaling has an effect on SARS-CoV-2 antiviral immunity and long-term immune protection in vivo is unknown. In this study, we identified a requirement for IFN-λ signaling in promoting viral clearance and protective immune programming in SARS-CoV-2 infection of mice. Expression of both IFN and IFN-stimulated gene (ISG) in the lungs were minimally affected by the absence of IFN-λ signaling and correlated with transient increases in viral titers. We found that IFN-λ supported the generation of protective CD8 T cell responses against SARS-CoV-2 by facilitating accumulation of CD103+ DC in lung draining lymph nodes (dLN). IFN-λ signaling specifically in DCs promoted the upregulation of costimulatory molecules and the proliferation of CD8 T cells. Intriguingly, antigen-specific CD8 T cell immunity to SARS-CoV-2 was independent of type I IFN signaling, revealing a nonredundant function of IFN-λ. Overall, these studies demonstrate a critical role for IFN-λ in protective innate and adaptive immunity upon infection with SARS-CoV-2 and suggest that IFN-λ serves as an immune adjuvant to support CD8 T cell immunity.

Beta Burst-Driven Adaptive Deep Brain Stimulation Improves Gait Impairment and Freezing of Gait in Parkinson's Disease.

Background: Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) that is often refractory to medication. Pathological prolonged beta bursts within the subthalamic nucleus (STN) are associated with both worse impairment and freezing behavior in PD, which are improved with deep brain stimulation (DBS). The goal of the current study was to investigate the feasibility, safety, and tolerability of beta burst-driven adaptive DBS (aDBS) for FOG in PD. Methods: Seven individuals with PD were implanted with the investigational Summit™ RC+S DBS system (Medtronic, PLC) with leads placed bilaterally in the STN. A PC-in-the-loop architecture was used to adjust stimulation amplitude in real-time based on the observed beta burst durations in the STN. Participants performed either a harnessed stepping-in-place task or a free walking turning and barrier course, as well as clinical motor assessments and instrumented measures of bradykinesia, OFF stimulation, on aDBS, continuous DBS (cDBS), or random intermittent DBS (iDBS). Results: Beta burst driven aDBS was successfully implemented and deemed safe and tolerable in all seven participants. Gait metrics such as overall percent time freezing and mean peak shank angular velocity improved from OFF to aDBS and showed similar efficacy as cDBS. Similar improvements were also seen for overall clinical motor impairment, including tremor, as well as quantitative metrics of bradykinesia. Conclusion: Beta burst driven adaptive DBS was feasible, safe, and tolerable in individuals with PD with gait impairment and FOG.

The effects of supplemental instruction derived from peer leaders on student outcomes in undergraduate human anatomy.

Supplemental instruction (SI) confers student success, as represented by grades, knowledge retention, and student engagement. However, studies often report professional, not undergraduate, program findings. To measure these effects, students studying human anatomy at a university in Ontario, Canada, attended structured (peer-assisted) or unstructured (nonpeer-assisted) SI sessions and completed a pre-/post-survey. Fifty-eight learners (39 systems (SYS) and 19 musculoskeletal (MSK) anatomy) completed both surveys and had responses analyzed. Both cohorts, maintained initial perceptions across pre-/post-analyses (MSK p = 0.1376 and SYS p = 0.3521). Resource usage was similar across both cohorts with discrepancies in skeletal model and textbook use. No MSK learner ranked any lab resources as "not at all useful." MSK learners felt more prepared to write a graded assessment (p = 0.0269), whereas SYS learners did not (p = 0.0680). Stratification of learners in MSK and SYS revealed learners spending between 30 and 60 min in SI sessions during the study period had the highest grades compared to students who spent less than 30 (p = 0.0286) or more than 60 (p = 0.0286) min attending SI sessions, respectively. Most learners in MSK (89.4%) and SYS (66%) concluded that they preferred structured over unstructured SI. Sentiment/thematic analysis using a generative AI-driven large language model revealed learners held positive perceptions of SI, emphasizing structured learning, resources, personalized learning, and support offered as the most prevalent themes surrounding SI. Ultimately, this study provides evidence that supports SI for improving student outcomes related to perceived preparedness for completing assessments and preferred teaching/learning styles in undergraduate human anatomy.

Novel Z-DNA binding domains in giant viruses.

Z-nucleic acid structures play vital roles in cellular processes and have implications in innate immunity due to their recognition by Zα domains containing proteins (Z-DNA/Z-RNA binding proteins, ZBPs). Although Zα domains have been identified in six proteins, including viral E3L, ORF112, and I73R, as well as, cellular ADAR1, ZBP1, and PKZ, their prevalence across living organisms remains largely unexplored. In this study, we introduce a computational approach to predict Zα domains, leading to the revelation of previously unidentified Zα domain-containing proteins in eukaryotic organisms, including non-metazoan species. Our findings encompass the discovery of new ZBPs in previously unexplored giant viruses, members of the Nucleocytoviricota phylum. Through experimental validation, we confirm the Zα functionality of select proteins, establishing their capability to induce the B-to-Z conversion. Additionally, we identify Zα-like domains within bacterial proteins. While these domains share certain features with Zα domains, they lack the ability to bind to Z-nucleic acids or facilitate the B-to-Z DNA conversion. Our findings significantly expand the ZBP family across a wide spectrum of organisms and raise intriguing questions about the evolutionary origins of Zα-containing proteins. Moreover, our study offers fresh perspectives on the functional significance of Zα domains in virus sensing and innate immunity and opens avenues for exploring hitherto undiscovered functions of ZBPs.

Expectations and outcomes of varying treatment strategies for CML presenting during pregnancy.

Diagnosing chronic myeloid leukaemia (CML) during pregnancy is rare. Tyrosine kinase inhibitors (TKIs) have traditionally been contraindicated owing to their teratogenicity. Management decisions should consider the risks to mother and foetus of uncontrolled disease and teratogenic medications. Further cases are required to build upon the paucity of current literature. We report 22 cases of CML diagnosed during pregnancy from 2002 to date. Twenty-one pregnancies resulted in healthy babies and one patient miscarried. Some patients remained untreated throughout pregnancy but the majority received one or both of interferon-α and leucapheresis. One patient was started on imatinib at Week 26, and one on hydroxycarbamide in the third trimester. We report haematological parameters during pregnancy to provide clinicians with realistic expectations of management. There were no fetal abnormalities related to treatment during pregnancy. Seventeen patients achieved at least major molecular response on first-line TKI. A diagnosis of CML during pregnancy can be managed without significant consequences for mother or child. Leucapheresis and interferon-α are generally safe throughout pregnancy. Despite having been avoided previously, there is growing evidence that certain TKIs may be used in particular circumstances during the later stages of pregnancy. Future work should aim to further elucidate this safety profile.

Sustaining attention in affective contexts during adolescence: age-related differences and association with elevated symptoms of depression and anxiety.

Sustained attention, a key cognitive skill that improves during childhood and adolescence, tends to be worse in some emotional and behavioural disorders. Sustained attention is typically studied in non-affective task contexts; here, we used a novel task to index performance in affective versus neutral contexts across adolescence (N = 465; ages 11-18). We asked whether: (i) performance would be worse in negative versus neutral task contexts; (ii) performance would improve with age; (iii) affective interference would be greater in younger adolescents; (iv) adolescents at risk for depression and higher in anxiety would show overall worse performance; and (v) would show differential performance in negative contexts. Results indicated that participants performed more poorly in negative contexts and showed age-related performance improvements. Those at risk of depression performed more poorly than those at lower risk. However, there was no difference between groups as a result of affective context. For anxiety there was no difference in performance as a function of severity. However, those with higher anxiety showed less variance in their reaction times to negative stimuli than those with lower anxiety. One interpretation is that moderate levels of emotional arousal associated with anxiety make individuals less susceptible to the distracting effects of negative stimuli.

Anomalous origin of the circumflex artery from the right pulmonary artery.

Anomalous origin of the circumflex artery from the pulmonary artery (ACxAPA) is a rare but clinically significant condition in which the circumflex artery arises from either the main pulmonary artery or one of its main branches. Untreated patients with ACxAPA may develop severe heart failure or sudden cardiac death. Diagnosis is established with either catheter or CT angiography. We present a case of an adult male with no prior known cardiac history who was found to have ACxAPA after presenting to our institution in acute decompensated heart failure.

Thermal damage to the skin from 8.2 and 95 GHz microwave exposures in swine.

A study of burn thresholds from superficially penetrating radio-frequency (RF) energy at 8.2 and 95 GHz for swine skin was conducted. The study determined the thresholds for superficial, partial-thickness, and full-thickness burn severities after 5 seconds of exposure at power densities of 4-30 W/cm2and 2-15 W/cm2at 8.2 and 95 GHz, respectively. There were significant differences in he burn thresholds at the different severities between the two frequencies due to the large difference in energy penetration depths. Biopsies were collected from each burn site at 1, 24, 72, and 168 hr post exposure. Each sample was assessed by a burn pathologist against 20 histological factors to characterize the damage resulting from these RF overexposures. A one-dimensional, layered digital phantom that utilized realistic values for dielectric and thermal properties was used to explain some observed thresholds. The results of the heating and cooling response of the animal model and histology scores of each exposure are provided to enhance future efforts at simulation of RF overexposures and to establish damage thresholds.

Psychobiotics and the Microbiota-Gut-Brain Axis: Where Do We Go from Here?

The bidirectional relationship between the gut microbiota and the nervous system is known as the microbiota-gut-brain axis (MGBA). The MGBA controls the complex interactions between the brain, the enteric nervous system, the gut-associated immune system, and the enteric neuroendocrine systems, regulating key physiological functions such as the immune response, sleep, emotions and mood, food intake, and intestinal functions. Psychobiotics are considered tools with the potential to modulate the MGBA through preventive, adjunctive, or curative approaches, but their specific mechanisms of action on many aspects of health are yet to be characterized. This narrative review and perspectives article highlights the key paradigms needing attention as the scope of potential probiotics applications in human health increases, with a growing body of evidence supporting their systemic beneficial effects. However, there are many limitations to overcome before establishing the extent to which we can incorporate probiotics in the management of neuropsychiatric disorders. Although this article uses the term probiotics in a general manner, it remains important to study probiotics at the strain level in most cases.

A histological and diceCT-derived 3D reconstruction of the avian visual thalamofugal pathway.

Amniotes feature two principal visual processing systems: the tectofugal and thalamofugal pathways. In most mammals, the thalamofugal pathway predominates, routing retinal afferents through the dorsolateral geniculate complex to the visual cortex. In most birds, the thalamofugal pathway often plays the lesser role with retinal afferents projecting to the principal optic thalami, a complex of several nuclei that resides in the dorsal thalamus. This thalamic complex sends projections to a forebrain structure called the Wulst, the terminus of the thalamofugal visual system. The thalamofugal pathway in birds serves many functions such as pattern discrimination, spatial memory, and navigation/migration. A comprehensive analysis of avian species has unveiled diverse subdivisions within the thalamic and forebrain structures, contingent on species, age, and techniques utilized. In this study, we documented the thalamofugal system in three dimensions by integrating histological and contrast-enhanced computed tomography imaging of the avian brain. Sections of two-week-old chick brains were cut in either coronal, sagittal, or horizontal planes and stained with Nissl and either Gallyas silver or Luxol Fast Blue. The thalamic principal optic complex and pallial Wulst were subdivided on the basis of cell and fiber density. Additionally, we utilized the technique of diffusible iodine-based contrast-enhanced computed tomography (diceCT) on a 5-week-old chick brain, and right eyeball. By merging diceCT data, stained histological sections, and information from the existing literature, a comprehensive three-dimensional model of the avian thalamofugal pathway was constructed. The use of a 3D model provides a clearer understanding of the structural and spatial organization of the thalamofugal system. The ability to integrate histochemical sections with diceCT 3D modeling is critical to better understanding the anatomical and physiologic organization of complex pathways such as the thalamofugal visual system.

Laser Measurement of Anomalous Electron Diffusion in a Crossed-Field Plasma.

The anomalous diffusion of particles and energy in magnetized plasma systems is a widespread phenomenon that can adversely impact their operation and preclude predictive models. In this Letter, this diffusion is characterized noninvasively in a low-temperature, Hall-type plasma. Laser-induced fluorescence and incoherent Thomson scattering measurements are combined with a 1D generalized Ohm's law to infer the time-averaged inverse Hall parameter, a transport coefficient that governs cross-field diffusion. While the measured diffusion profile agrees with model-based estimates in magnitude, the measurements do not exhibit the steep "transport barrier" typically imposed in models. Instead, these results show that the electric field is primarily driven by a diamagnetic contribution due to the large peak electron temperature exceeding 75 eV. This finding motivates a reconsideration of nonclassical energy transport across field lines in low-temperature plasmas.

Prognostic value of HER2DX in early-stage HER2-positive breast cancer: a comprehensive analysis of 757 patients in the Sweden Cancerome Analysis Network-Breast dataset (SCAN-B).

BACKGROUND: The HER2DX risk-score has undergone rigorous validation in prior investigations involving patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer. In this study, we present the outcomes of the HER2DX risk-score within the most recent release of the Sweden Cancerome Analysis Network-Breast (SCAN-B) HER2+ cohort. This updated examination benefits from a larger patient sample, an extended follow-up duration, and detailed treatment information. MATERIALS AND METHODS: Clinical and RNAseq data from the SCAN-B dataset were retrieved from Gene Expression Omnibus (GSE81538). Among the 6600 patients, 819 had HER2+ breast cancer, with 757 individuals with research-based HER2DX risk-scores and corresponding survival outcomes. The HER2DX risk-score was evaluated (i) as a continuous variable and (ii) using predefined cut-offs. The primary endpoint for this study was overall survival (OS). The Kaplan-Meier method and Cox models were used to estimate OS and a multistate model with four states was fitted to better characterize patients' follow-up. RESULTS: The median follow-up time was 7.5 years (n = 757). The most common systemic therapy was chemotherapy with trastuzumab (82.0%) and most tumors were classified as T1-T2 (97.1%). The HER2DX risk-score as a continuous variable was significantly associated with OS after adjustment for clinical variables and treatment regimen [hazard ratios (HR) per 10-unit increment = 1.31, 95% confidence interval (CI) 1.13-1.51, P < 0.001] as well as within predefined risk groups (high versus low; HR = 2.57, 95% CI 1.36-4.85, P < 0.001). Patients classified as HER2DX high-risk also had higher risk of (i) breast cancer recurrence and (ii) death without previous recurrence. Within the subgroup of HER2+ T1N0 tumors (n = 297), those classified as high-risk demonstrated inferior OS compared to low-risk tumors (7-year OS 77.8% versus 96.8%, P < 0.001). The HER2DX mRNA ERBB2 score was associated with clinical HER2 status (area under the receiver operating characteristic curve = 0.91). CONCLUSIONS: In patients with early-stage HER2+ breast cancer, HER2DX risk-score provides prognostic information beyond clinicopathological variables, including treatment regimen with or without trastuzumab.

Analytical validation of HER2DX genomic test for early-stage HER2-positive breast cancer.

BACKGROUND: HER2DX, a multianalyte genomic test, has been clinically validated to predict breast cancer recurrence risk (relapse risk score), the probability of achieving pathological complete response post-neoadjuvant therapy (pCR likelihood score), and individual ERBB2 messenger RNA (mRNA) expression levels in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study delves into the comprehensive analysis of HER2DX's analytical performance. MATERIALS AND METHODS: Precision and reproducibility of HER2DX risk, pCR, and ERBB2 mRNA scores were assessed within and between laboratories using formalin-fixed paraffin-embedded (FFPE) tumor tissues and purified RNA. Robustness was appraised by analyzing the impact of tumor cell content and protocol variations including different instruments, reagent lots, and different RNA extraction kits. Variability was evaluated across intratumor biopsies and genomic platforms [RNA sequencing (RNAseq) versus nCounter], and according to protocol variations. RESULTS: Precision analysis of 10 FFPE tumor samples yielded a maximal standard error of 0.94 across HER2DX scores (1-99 scale). High reproducibility of HER2DX scores across 29 FFPE tumors and 20 RNAs between laboratories was evident (correlation coefficients >0.98). The probability of identifying score differences >5 units was ≤5.2%. No significant variability emerged based on platform instruments, reagent lots, RNA extraction kits, or TagSet thaw/freeze cycles. Moreover, HER2DX displayed robustness at low tumor cell content (10%). Intratumor variability across 212 biopsies (106 tumors) was <4.0%. Concordance between HER2DX scores from 30 RNAs on RNAseq and nCounter platforms exceeded 90.0% (Cohen's κ coefficients >0.80). CONCLUSIONS: The HER2DX assay is highly reproducible and robust for the quantification of recurrence risk, pCR likelihood, and ERBB2 mRNA expression in early-stage HER2-positive breast cancer.

Structural and chemical properties of anion exchanged CsPb(Br(1-x)Clx)3heterostructured perovskite nanowires imaged by nanofocused x-rays.

Over the last years metal halide perovskites have demonstrated remarkable potential for integration in light emitting devices. Heterostructures allow for tunable bandgap depending on the local anion composition, crucial for optoelectronic devices, but local structural effects of anion exchange in single crystals is not fully understood. Here, we investigate how the anion exchange of CsPbBr3nanowires fully and locally exposed to HCl vapor affects the local crystal structure, using nanofocused x-rays. We study the nanoscale composition and crystal structure as function of HCl exposure time and demonstrate the correlation of anion exchange with changes in the lattice parameter. The local composition was measured by x-ray fluorescence and x-ray diffraction, with general agreement of both methods but with much less variation using latter. The heterostructured nanowires exhibit unintentional gradients in composition, both axially and radially. Ferroelastic domains are observed for all HCl exposure times, and the magnitude of the lattice tilt at the domain walls scales with the Cl concentration.

Rahnella Aquatilis Endophthalmitis after Intravitreal Injection in an Immunocompetent Patient.

PURPOSE: To present a novel case of exogenous Rahnella aquatilis endophthalmitis following an intravitreal injection. METHODS: Case report. RESULTS: A 74-year-old male presented with acute progressive vision loss and pain in the left eye, 5 days after an intravitreal injection for diabetic macular edema. The patient was diagnosed with exogenous endophthalmitis and empirically treated with intravitreal injections of vancomycin and ceftazidime as well as topical and oral ciprofloxacin. In follow up two days later, the patient was treated with preoperative povidone-iodine followed by prompt vitrectomy with additional vancomycin and ceftazidime due to pharmacy sterile hood issues that delayed antibiotic availability. Microbiological cultures and two mass spectrometry identification tests confirmed the diagnosis of exogenous Rahnella aquatilis endophthalmitis. Despite the presence of scattered retinal hemorrhagic infarcts involving the macula and subsequent full-thickness atrophic macular holes seen in follow up, the patient achieved a favorable anatomical and functional outcome of BCVA 20/80 at 1 year of follow-up. CONCLUSION: This case highlights the occurrence of exogenous Rahnella aquatilis endophthalmitis following an intravitreal injection for diabetic macular edema. Prompt diagnosis and treatment produced a favorable outcome relative to other typical Gram-negative Enterobacteriaceae organisms.

Zα Domain of ADAR1 Binds to an A-Form-like Nucleic Acid Duplex with Low Micromolar Affinity.

The left-handed Z-conformation of nucleic acids can be adopted by both DNA and RNA when bound by Zα domains found within a variety of viral and innate immune response proteins. While Z-form adoption is preferred by certain sequences, such as the commonly studied (CpG)n repeats, Zα has been reported to bind to a wide range of sequence contexts. Studying how Zα interacts with B-/A-form helices prior to their conversion to the Z-conformation is challenging as binding coincides with Z-form adoption. Here, we studied the binding of Zα fromHomo sapiens ADAR1 to a locked "A-type" version of the (CpG)3 construct (LNA (CpG)3) where the sugar pucker is locked into the C3'-endo/C2'-exo conformation, which prevents the duplex from adopting the alternating C2'/C3'-endo sugar puckers found in the Z-conformation. Using NMR and other biophysical techniques, we find that ZαADAR1 binds to the LNA (CpG)3 using a similar interface as for Z-form binding, with a dissociation constant (KD) of ∼4 µM. In contrast to Z-DNA/Z-RNA, where two ZαADAR1 bind to every 6 bp stretch, our data suggests that ZαADAR1 binds to multiple LNA molecules, indicating a completely different binding mode. Because ZαADAR1 binds relatively tightly to a non-Z-form model, its binding to B/A-form helices may need to be considered when experiments are carried out which attempt to identify the Z-form targets of Zα domains. The use of LNA constructs may be beneficial in experiments where negative controls for Z-form adoption are needed.

Gasdermin D promotes influenza virus-induced mortality through neutrophil amplification of inflammation.

Influenza virus activates cellular inflammasome pathways, which can be both beneficial and detrimental to infection outcomes. Here, we investigate the function of the inflammasome-activated, pore-forming protein gasdermin D (GSDMD) during infection. Ablation of GSDMD in knockout (KO) mice (Gsdmd-/-) significantly attenuates influenza virus-induced weight loss, lung dysfunction, lung histopathology, and mortality compared with wild type (WT) mice, despite similar viral loads. Infected Gsdmd-/- mice exhibit decreased inflammatory gene signatures shown by lung transcriptomics. Among these, diminished neutrophil gene activation signatures are corroborated by decreased detection of neutrophil elastase and myeloperoxidase in KO mouse lungs. Indeed, directly infected neutrophils are observed in vivo and infection of neutrophils in vitro induces release of DNA and tissue-damaging enzymes that is largely dependent on GSDMD. Neutrophil depletion in infected WT mice recapitulates the reductions in mortality, lung inflammation, and lung dysfunction observed in Gsdmd-/- animals, while depletion does not have additive protective effects in Gsdmd-/- mice. These findings implicate a function for GSDMD in promoting lung neutrophil responses that amplify influenza virus-induced inflammation and pathogenesis. Targeting the GSDMD/neutrophil axis may provide a therapeutic avenue for treating severe influenza.

A 48-Year-Old Man With a Hip Fracture and Skin Rash: A Case Report.

Background/Objective: Patients with systemic mastocytosis are at high risk of developing osteoporosis and fractures. Herein, we report a case of hip fragility fracture in a patient with indolent systemic mastocytosis and normal bone density. Case Report: A 48-year-old man experienced a left femoral neck fracture after a fall. After a dose of oxycodone/hydromorphone postoperatively, he developed an anaphylactic reaction. Previously, he experienced a few other episodes of flushing, dizziness, and syncope precipitated by stress and alcohol. His examination was notable for pink and brown macules on his chest, back, arms, and legs. His laboratory test revealed a markedly elevated tryptase level of 171 ng/mL (<11 ng/mL). Treatment including cetirizine, montelukast, and ranitidine controlled his symptoms. His bone density test result was normal. Ten months after hip surgery, his c-terminal telopeptide of collagen type 1 and bone-specific alkaline phosphatase levels significantly increased. The bone scan demonstrated diffusely increased radiotracer uptake throughout the osseous structures. Given high bone turnover and the prior hip fracture, he received zoledronic acid yearly for 3 years, and no further fractures have occurred. Discussion: The case is unusual as the fracture occurred despite normal bone density and significant osteosclerosis, which was previously considered protective against fractures. Additionally, rather than the spine, the fracture occurred in the hip, which is an uncommon site for mastocytosis-induced fractures. Conclusion: Mastocytosis is a rare cause of osteoporosis, and it is important to keep this condition in the differential diagnosis of osteoporosis, particularly when the fracture presentation is atypical.

Free mebrofenin clearance.

OBJECTIVES: To determine if three new simplified equations for measurement of free mebrofenin clearance give similar results to the equations defined by Ekman et. al ., and to evaluate the properties of all four methods. Regional mebrofenin clearance has been used to predict future remnant liver function and liver failure after regional liver therapy, such as partial hepatic resection. METHODS: The means, standard deviations, and correlations of the free mebrofenin clearance measured by the Ekman method and the three simplified methods were compared in a consecutive series of 26 studies in 20 patients. The fractional change in the blood and free mebrofenin activities were compared, and integrals of normalized blood and free mebrofenin ("effective times") were compared. RESULTS: The average percent free mebrofenin clearance for the Ekman and the first, second and third simplified methods were 13.62 ± 2.88%/min, 12.98 ± 2.97%/min, 12.52 ± 2.81%/min and 15.03 ± 2.27%/min, respectively. The correlations of the new methods with Ekman were 0.97, 0.93 and 0.93. The fractional changes during the measurement interval for the blood and free mebrofenin activities were 0.381 ± 0.065 and 0.329 ± 0.062, difference 0.052, P < 0.5. The integrals of normalized blood and free mebrofenin activities were 2.566 ± 0.160 min and 2.661 ± 0.158 min, difference of 0.094 min and P < 0.05. CONCLUSIONS: The results of the three new methods were similar to the Ekman method. The first simplified method was identified as the lead method for clinical validation in a larger population.