Li-Fraumeni Syndrome: Adopting a Diagnosis with an Unknown Family History

Introduction: Li-Fraumeni Syndrome (LFS) is a rare, autosomal dominant disease that is typically screenedfor and identified in patients with a known history of cancer and family history ofcancer.Presentation of Case: Ms. DA is an adopted 39-year-old South American female with a past medical history of iron deficiency anemia, celiac disease, and polio. She presented with ductal carcinoma in-situ with spindle cell atypia at age 35 and leiomyosarcoma of the ankle at age 36. Genetic counseling was offered due to her age and cancer types, with subsequent genetic testing revealing a TP53-R337H mutation, which was diagnostic of LFS. Given her high risk status, extensive cancer screenings at common LFS body sites were recommended, but she was lost to follow-up. Four years later, she returned after discovering a new right breast mass on self-examination. She was referred to a new breast surgeon, who was able to establish consistent and close follow-up while providing counseling and education regarding lifetime risk and cancer trajectory of classical LFS compared to the Brazilian LFS-subtype.Conclusion: The importance of having a high level of suspicion for patients with anunknown family history is crucial as seen in this case. Without a biological familyhistory, clinicians rely on their judgement to decide when further work-up is warranted.Advancements in medicine and genetic testing have increased the ability to accuratelydiagnose genetic diseases to help patients make life-saving decisions about theirhealth

Postpartum psychosis in a non-native language-speaking patient: A perspective on language barriers and cultural competency.

Postpartum psychosis is a condition characterised by rapid onset of psychotic symptoms several weeks after childbirth. Outside of its timing and descriptions of psychotic features, minimal research exists due to its relative rarity (1 to 2 per 1000 births in the USA), with greater emphasis on postpartum sadness and depression. With the existing literature, cultural differences and language barriers previously have not been taken into consideration as there are no documented cases of postpartum psychosis in a non-English-speaking patient. Correctly differentiating postpartum psychosis from other postpartum psychiatric disorders requires adeptly evaluating for the presence of psychotic symptoms with in-depth history taking. Here, we present a case of postpartum psychosis in a Japanese-speaking only patient, with an associated clinical course and culturally appropriate approach to treatment. A review of postpartum psychosis and language/cultural considerations are also discussed, with attention on the Japanese concept of \u27Satogaeri bunben\u27

Open-Source Conceptual Sizing Models for the Hyperloop Passenger Pod

Hyperloop is a new mode of transportation proposed as an alternative to California's high speed rail project, with the intended benefits of higher performance at lower overall costs. It consists of a passenger pod traveling through a tube under a light vacuum and suspended on air bearings. The pod travels up to transonic speeds resulting in a 35 minute travel time between the intended route from Los Angeles and San Francisco. Of the two variants outlined, the smaller system includes a 1.1 meter tall passenger capsule traveling through a 2.2 meter tube at 700 miles per hour. The passenger pod features water-based heat exchangers as well as an on-board compression system that reduces the aerodynamic drag as it moves through the tube. Although the original proposal looks very promising, it assumes that tube and pod dimensions are independently sizable without fully acknowledging the constraints of the compressor system on the pod geometry. This work focuses on the aerodynamic and thermodynamic interactions between the two largest systems; the tube and the pod. Using open-source toolsets, a new sizing method is developed based on one-dimensional thermodynamic relationships that accounts for the strong interactions between these sub-systems. These additional considerations require a tube nearly twice the size originally considered and limit the maximum pod travel speed to about 620 miles per hour. Although the results indicate that Hyperloop will need to be larger and slightly slower than originally intended, the estimated travel time only increases by approximately five minutes, so the overall performance is not dramatically affected. In addition, the proposed on-board heat exchanger is not an ideal solution to achieve reasonable equilibrium air temperatures within the tube. Removal of this subsystem represents a potential reduction in weight, energy requirements and complexity of the pod. In light of these finding, the core concept still remains a compelling possibility, although additional engineering and economic analyses are markedly necessary before a more complete design can be developed

Antimicrobial activity of spherical silver nanoparticles prepared using a biocompatible macromolecular capping agent: evidence for induction of a greatly prolonged bacterial lag phase

<p>Abstract</p> <p>Background</p> <p>We have evaluated the antimicrobial properties of Ag-based nanoparticles (<it>Np</it>s) using two solid phase bioassays and found that 10-20 μL of 0.3-3 μM keratin-stabilized <it>Np</it>s (depending on the starting bacterial concentration = <it>C</it>_I) completely inhibited the growth of an equivalent volume of <it>ca</it>. 10³to 10⁴colony forming units per mL (CFU mL^-1) <it>Staphylococcus aureus</it>, <it>Salmonella </it>Typhimurium, or <it>Escherichia coli </it>O157:H7 on solid surfaces. Even after one week at 37°C on solid media, no growth was observed. At lower <it>Np </it>concentrations (= [<it>Np</it>]s), visible colonies were observed but they eventually ceased growing.</p> <p>Results</p> <p>To further study the physiology of this growth inhibition, we repeated these experiments in liquid phase by observing microbial growth via optical density at 590 nm (OD) at 37°C in the presence of a [<it>Np</it>] = 0 to 10^-6M. To extract various growth parameters we fit all OD[t] data to a common sigmoidal function which provides measures of the beginning and final OD values, a first-order rate constant (<it>k</it>), as well as the time to calculated 1/2-maximal OD (<it>t</it>_m) which is a function of <it>C</it>_I, <it>k</it>, as well as the microbiological lag time (<it>T</it>).</p> <p>Performing such experiments using a 96-well microtitre plate reader, we found that growth <it>always </it>occurred in solution but <it>t</it>_mvaried between 7 (controls; <it>C</it>_I= 8 × 10³CFU mL^-1) and > 20 hrs using either the citrate-([<it>Np</it>] ~ 3 × 10^-7M) or keratin-based ([<it>Np</it>] ~ 10^-6M) <it>Np</it>s and observed that {∂<it>t</it>_m/∂ [<it>Np</it>]}_citrate~ 5 × 10⁷and {∂<it>t</it>_m/∂ [<it>Np</it>]}_keratin~ 10⁷hr·L mol^-1. We also found that there was little effect of <it>Np</it>s on <it>S. aureus </it>growth rates which varied only between <it>k </it>= 1.0 and 1.2 hr^-1(1.1 ± 0.075 hr^-1). To test the idea that the <it>Np</it>s were changing the initial concentration (<it>C</it>_I) of bacteria (<it>i.e</it>., cell death), we performed probabilistic calculations assuming that the perturbations in <it>t</it>_mwere due to <it>C</it>_Ialone. We found that such large perturbations in <it>t</it>_mcould only come about at a <it>C</it>_Iwhere the probability of any growth at all was small. This result indicates that much of the <it>Np</it>-induced change in <it>t</it>_mwas due to a greatly increased <it>T </it>(<it>e.g</it>., from <it>ca</it>. 1 to 15-20 hrs). For the solid phase assays we hypothesize that the bacteria eventually became non-culturable since they were inhibited from undergoing further cell division (<it>T </it>> many days).</p> <p>Conclusion</p> <p>We propose that the difference between the solid and liquid system relates to the obvious difference in the exposure, or residence, time of the <it>Np</it>s with respect to the bacterial cell membrane inasmuch as when small, <it>Np</it>-inhibited colonies were selected and streaked on fresh (<it>i.e</it>., no <it>Np</it>s present) media, growth proceeded normally: <it>e.g</it>., a small, growth-inhibited colony resulted in a plateful of typical <it>S. aureus </it>colonies when streaked on fresh, solid media.</p

Free-hand thoracic pedicle screws placed by neurosurgery residents: a CT analysis

Free-hand thoracic pedicle screw placement is becoming more prevalent within neurosurgery residency training programs. This technique implements anatomic landmarks and tactile palpation without fluoroscopy or navigation to place thoracic pedicle screws. Because this technique is performed by surgeons in training, we wished to analyze the rate at which these screws were properly placed by residents by retrospectively reviewing the accuracy of resident-placed free-hand thoracic pedicle screws using computed tomography imaging. A total of 268 resident-placed thoracic pedicle screws was analyzed using axial computed tomography by an independent attending neuroradiologist. Eighty-five percent of the screws were completely within the pedicle and that 15% of the screws violated the pedicle cortex. The majority of the breaches were lateral breaches between 2 and 4 mm (46%). There was no clinical evidence of neurovascular injury or injury to the esophagus. There were no re-operations for screw replacement. We concluded that under appropriate supervision, neurosurgery residents can safely place free-hand thoracic pedicle screws with an acceptable breach rate

Chemical-Equilibrium Analysis with Adjoint Derivatives for Propulsion Cycle Analysis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143118/1/1.B36215.pd

Perceptions of the osteopathic profession in New York City\u27s Chinese Communities

Objective: The purpose of this study was to assess knowledge of and barriers to osteopathic medicine in Chinese immigrant communities in New York City (NYC). Design: A cross-sectional study was designed in which a culturally appropriate survey in Chinese and English versions was administered anonymously to measure immigrant perceptions and knowledge of osteopathic medicine. Setting: Data collection occurred in the municipal delineations for the Chinatown neighbourhood within the New York, New York borough of Manhattan. Participants: Community members were selected using convenience sampling from high-density areas to participate. Information gathered from the survey included demographics, education level, healthcare habits and knowledge of the osteopathic profession. Results: 120 surveys were conducted with 68 males and 52 females, with an average age=40. Respondents in the age range of 18-29 years, those with fluent English-language proficiency, and participants with graduate-level education status demonstrated a higher proportion of knowledge of osteopathic manipulative medicine and osteopathic physicians (doctors of osteopathic medicine) among the study variables. Conclusion: Compared with research on the general US population, a general lack of knowledge of osteopathic medicine exists within NYC\u27s Chinese immigrant community. Although this difference may be ascribed to linguistics and ethnosociological factors, greater outreach and education is needed in urban minority communities to make immigrants aware of all healthcare resources available during the current shortage of US primary care physicians

Utility of serum biomarker indices for staging of hepatic fibrosis before and after venesection in patients with hemochromatosis caused by variants in HFE

Background & Aims Hemochromatosis that is associated with variants in the homeostatic iron regulator gene (HFE) is characterized by intestinal absorption of iron and excessive body and hepatic iron stores; it can lead to hepatic fibrosis and cirrhosis. Fibrosis has been staged by analysis of liver biopsies, but non-invasive staging methods are available. We evaluated the ability of aspartate aminotransferase:platelet ratio index (APRI), the fibrosis-4 (FIB-4) index, and gamma-glutamyl transferase:platelet ratio (GPR) to assess hepatic fibrosis staging in subjects with HFE-associated hemochromatosis, using liver biopsy-staged fibrosis as the reference standard. Methods We performed a retrospective, cross-sectional analysis of 181 subjects with HFE-associated hemochromatosis and hepatic fibrosis staged by biopsy analysis and available serum samples. We calculated APRI, FIB-4, and GPR at diagnosis for all 181 subjects and following venesection therapy in 64 of these subjects (7 subjects had follow-up biopsy analysis). We used area under the receiver operating characteristic curve (AUROC) analysis to assess the relationships between APRI score, FIB-4 score, and GPR and advanced (F3–F4) fibrosis and to select cut-off values. Results Hepatic fibrosis stage correlated with APRI score (r = 0.54; P \u3c .0001), FIB-4 score (r = 0.35; P \u3c .0001), and GPR (r = 0.36, P \u3c .0001). An APRI score above 0.44 identified patients with advanced fibrosis with an AUROC of 0.88, 79.4% sensitivity, 79.4% specificity, and 81% accuracy. A FIB-4 score above 1.1 identified patients with advanced fibrosis with an AUROC of 0.86, 80% sensitivity, 80.3% specificity, and 81% accuracy. A GPR above 0.27 identified patients with advanced fibrosis with an AUROC of 0.76, 67.7% sensitivity, 70.3% specificity, and 69% accuracy. APRI score was significantly more accurate than GPR (P = .05) in detecting advanced fibrosis; there was no difference between APRI and FIB-4. Venesection treatment was associated with significant reductions in APRI (P \u3c .0001) and GPR (P\u3c .001), paralleling fibrosis regression observed in available liver biopsies. Post-venesection APRI identified 87% of subjects with advanced fibrosis that decreased to levels that indicate stage F1–F2 fibrosis. Conclusions In a retrospective study of 181 subjects with HFE-associated hemochromatosis, we found that APRI and FIB-4 scores identified patients with advanced hepatic fibrosis with 81% accuracy. APRI scores might also be used to monitor fibrosis regression following venesection

Utility of hepatic or total body iron burden in the assessment of advanced hepatic fibrosis in HFE hemochromatosis

Development of advanced hepatic fibrosis in HFE Hemochromatosis (HH) is influenced by hepatic iron concentration (HIC) and age. In patients with HH, it is important to assess the likelihood of cirrhosis and thus the need for confirmatory liver biopsy. Therapeutic phlebotomy also provides an estimate of mobilisable iron stores. We determined whether mobilisable iron stores may predict the presence of advanced fibrosis. Retrospective analysis of 137 male and 65 female HH subjects was undertaken. Biochemical, histological and phlebotomy data were available on all subjects. The mean values of HIC, HIC × [age], mobilisable iron, mobilisable iron × [age] and serum ferritin in the cohort were higher in the group with advanced fibrosis. HIC had an optimum sensitivity and specificity of 73% for the diagnosis of advanced liver fibrosis, with a cut-off HIC level of 200 µmol/g (AUROC 0.83, p \u3c 0.0001). AUROC for HIC was greater in females (0.93) than males (0.79). Mobilisable iron had an optimum sensitivity and specificity both of 83% at a cut-off of 9.6 g for the prediction of advanced fibrosis in all subjects (AUROC 0.92, p \u3c 0.0001). Mobilisable iron stores provide a simple, clinically useful indication of the risk of advanced fibrosis and should routinely be considered

Thermodynamics of Gas Turbine Cycles with Analytic Derivatives in OpenMDAO

A new equilibrium thermodynamics analysis tool was built based on the CEA method using the OpenMDAO framework. The new tool provides forward and adjoint analytic derivatives for use with gradient based optimization algorithms. The new tool was validated against the original CEA code to ensure an accurate analysis and the analytic derivatives were validated against finite-difference approximations. Performance comparisons between analytic and finite difference methods showed a significant speed advantage for the analytic methods. To further test the new analysis tool, a sample optimization was performed to find the optimal air-fuel equivalence ratio, , maximizing combustion temperature for a range of different pressures. Collectively, the results demonstrate the viability of the new tool to serve as the thermodynamic backbone for future work on a full propulsion modeling tool