Two thumbs up: using popular films in introductory aging courses.

Good teaching requires thoughtful planning and creative thinking, especially when trying to engage students in material that is unfamiliar to them or encumbered by stereotypes, like aging. Classic and contemporary media can provide unique teaching opportunities in gerontology classrooms. Popular films can have a powerful influence over viewers' attitudes and perceptions, and spur in-depth discussions of aging-related topics common to introductory aging courses (e.g., ageism, abuse, inequality, caregiving, healthy aging, and intimate relationships). Additionally, films appeal to multiple learning styles, engaging a variety of learners. This article examines the value of using films in introductory aging courses, offers strategies for incorporating films in the gerontology classroom, suggests sample activities and assignments that pair popular films with aging course topics, identifies challenges of using film in various classrooms settings, and provides a detailed typology of films on each of the following aging topics: ageism and stereotypes, cognitive impairment, death and dying, diversity, family relationships, health and wellness, sexuality and intimacy, and work and retirement.

The Role of Endoscopy in Investigating the Causes of Persistent Anaemia in Post-operative Fractured Neck of Femur Patients.

Introduction Post-operative anaemia in hip fracture patients has been associated with increased risk of blood transfusion, poorer functional outcomes, increased morbidity and mortality. Patients with persisting drop in haemoglobin after fractured neck of femur with no obvious source of blood loss are often referred for endoscopy to find the cause of anaemia. The reported incidence of perioperative acute upper gastrointestinal bleeding varies from 1 to 15%. Objective The aim of our study is to find out the usefulness of endoscopy in finding gastrointestinal causes leading to the occult loss of blood causing irreversible anaemia in post-operative neck of femur fractures. Material and methods The orthogeriatric unit conducted a study using retrospective data on neck of femur fracture patients from January 2015 to December 2020. Out of 1863 cases, 918 (49.3%) developed post-operative anaemia. Forty-five patients (5%) with refractory anaemia underwent endoscopy referral. Patient demographics, fracture patterns, pre-existing anaemia, and co-morbidities (anaemia, heart disease, chronic kidney disease, oral anticoagulant usage) were recorded. The recorded information also included the type of procedure undergone by each patient. Intra-operative tranexamic acid injections were administered to all patients. Results Male patients accounted for 24% (11) and females for 76% (34). The average age was 82.3 years (range: 73-94). In terms of fracture type, 60% (27) were intracapsular and 40% (18) were extracapsular. Iron deficiency anaemia was present in 24% (11), oral anticoagulants in 20% (9), and systemic malignancy in 12% (6) of patients. The mean post-operative hemoglobin level during endoscopy referral was 7.3 g/dL. Endoscopy revealed normal findings in 60% (27), esophagitis/gastritis in 20% (8), and hiatus hernia in 16% (7) of patients. No patients were diagnosed with active gastrointestinal bleeding or malignancy as the cause of post-operative hemoglobin drop. Conclusion The study did not show evidence of any gastrointestinal bleeding in patients with resistant and refractory post-operative anaemia following fractured neck of femur surgery using endoscopy procedure. The value of such difficult, expensive and time-consuming procedure may be reviewed further.

Factors in nephrologists' decision to treat pre-dialysis CKD patients with vitamin D insufficiency and SHPT: A discrete choice experiment.

Little is known about the most important factors that inform a nephrologist's decision to treat (DTT) pre-dialysis chronic kidney disease (CKD) patients with vitamin D insufficiency (VDI) and secondary hyperparathyroidism (SHPT). The objective of this study was to identify such factors and their relative importance in the DTT with a vitamin D therapy. A web-based, adaptive design conjoint analysis discrete-choice survey was developed to study factors that informed the DTT among a sample of 200 nephrologists located throughout the United States. Based on literature review and clinician input, eight attributes were selected that could influence a provider's DTT: age, race, CKD stage, serum 25-hydroxyvitamin D (25D), parathyroid hormone (PTH), serum calcium (Ca), serum phosphorus (P), and history of comorbidities. Respondents were asked to select one patient profile most suitable for treatment from three profiles with varying attribute levels. Each attribute's relative importance score was computed using hierarchical-Bayesian statistics to measure the influence of each factor where higher scores represented greater DTT consideration. The pooled analysis revealed the four most important factors: serum 25D (31.4%), serum Ca (22.7%), plasma PTH (11.5%) levels, and history of comorbidities (8.5%). Age (8.2%), serum P (7.7%), CKD stage (5.7%), and race (4.4%) were relatively less important. Patients' 25D and Ca levels contributed to more than half of nephrologists' DTT, with the consideration of PTH levels being less of a factor. Further understanding of the driving forces behind the factors that inform the DTT may help to standardize the management of CKD patients with SHPT and VDI and improve outcomes.

Thrombotic Thrombocytopenic Purpura Presentation in an Elderly Gentleman Following COVID Vaccine Circumstances.

Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder that results in the formation of thrombi in the small blood vessels throughout the body. The two primary forms of TTP are acquired and familial forms. The acquired form usually presents in late childhood or adulthood. Almost 95% of the cases are due to an autoantibody directed against ADAMTS13, and the remaining 5% are due to drugs like ticlopidine, quinine, cyclosporine, gemcitabine, bevacizumab, and certain recreational drugs like ecstasy and cocaine. The familial forms present in infancy or early childhood, but sometimes they can present later in life. Management for acquired forms includes therapeutic plasma exchange and immunosuppressive agents. While for the hereditary forms, the mainstay of treatment is plasma infusion. We present a case of an 80-year-old male with a known medical history of hypertension, type II diabetes mellitus, hyperlipidemia, gout, iron deficiency anemia, and Pfizer-BioNTech COVID-19 (coronavirus disease-19) vaccine administered two weeks before presentation to the ER for evaluation of generalized weakness and malaise. Laboratory findings showed severe anemia with hemoglobin of 4.8 g/dl, platelet count of 48 x 10^3/mcL, elevated lactate dehydrogenase (LDH), decreased haptoglobin, and peripheral smear showing schistocytes. The serum creatinine, total bilirubin, and troponin were elevated. All these findings were raising concern for presumptive diagnosis of TTP, which was confirmed with ADAMTS13 levels less than 10%. TTP was temporarily resolved in 10 days with plasma exchange therapy and high-dose corticosteroids. It is difficult at this time to differentiate vaccine-induced TTP from coincidental TTP presenting soon after vaccination. Further studies would be needed to understand better if this relationship between vaccination and TTP was coincidental or causal.

Retained catheter fragment from a fractured tunneled catheter--a rare and potentially lethal complication.

Despite efforts to curtail central vein catheter use for dialysis catheters are frequently used in the treatment of end-stage renal disease (ESRD). In 2006, 82% of patients in the USA initiated dialysis via a catheter. The overall of tunnelled cuffed catheter (TCC) use was 35% greater in 2005 compared with 1996. Dialysis catheter tip fracture is a rare and potentially serious complication. Herein, we present the case of an incidental finding of a retained catheter fragment from a fractured TCC in the right atrium. Fragment retrieval (via snare technique) and subsequent placement of a new central venous catheter are outlined.

Hypertension With Brachydactyly Syndrome: A Case Report.

We describe the case of a 23-year-old African American male who presented to the emergency department complaining of unremitting dyspepsia for the last four months. His blood pressure was incidentally found to be 230/157 mm Hg. The initial admitting diagnosis in the intensive care unit was hypertensive "emergency" as he had also displayed acute kidney injury that was deemed to be superimposed on chronic kidney disease. While the diagnostic work-up of his hypertension was inconclusive, physical examination was impressive for the presence of brachydactyly of the bilateral hands, especially the fourth digits. His feet appeared grossly normal. X-rays (XRs) of the bilateral hands revealed absent distal phalanges and fused middle and distal phalanges of the second digits. XRs of the bilateral feet showed similar findings in addition to the absence or hypoplasia of the lateral cuneiform bones. His family medical history was unknown as the patient was adopted and did not have contact with his biological parents. Given these findings in the setting of uncontrolled hypertension in a young adult, he was diagnosed with hypertension with brachydactyly syndrome.

Idiopathic nodular glomerulosclerosis (ING) in an African American (AA) man with hepatitis C.

Idiopathic nodular glomerulosclerosis (ING) in a non-diabetic patient is uncommon. Nodular glomerulosclerosis is hallmark sign of diabetic nephropathy. ING is a very rare clinicopathological disease associated with smoking, obesity and hypertension, chronic obstructive pulmonary disease and metabolic syndrome. A 68-year-old non-obese African American man with hypertension, smoking and history of hepatitis C presented to the clinic with progressive worsening of lower extremity oedema and declining renal function over few months. Renal biopsy demonstrated nodular glomerulosclerosis. In this case, ING is hypothesised to be associated with hepatitis C along with smoking and hypertension (HTN). We present this case to speculate the existence of yet unknown aetiologies of ING.

Isolation, characterization and genetic diversity of NBS-LRR class disease-resistant gene analogs in multiple virus resistant line of chilli (Capsicum annuum L.).

Viruses are serious threat to chilli crop production worldwide. Resistance screening against several viruses resulted in identifying a multiple virus resistant genotype 'IHR 2451'. Degenerate primers based on the conserved regions between P-Loop and GLPL of Resistance genes (R-genes) were used to amplify nucleotide binding sites (NBS)-encoding regions from genotype 'IHR 2451'. Alignment of deduced amino acid sequences and phylogenetic analyses of isolated sequences distinguished into two groups representing toll interleukin-1 receptor (TIR) and non-TIR, and different families within the group confirming the hypotheses that dicots have both the types of NBS-LRR genes. The alignment of deduced amino acid sequences revealed conservation of subdomains P-loop, RNBS-A, kinase2, RNBS-B, and GLPL. The distinctive five RGAs showing specific conserved motifs were subjected to BLASTp and indicated high homology at deduced amino acid level with R genes identified such as Pvr9 gene for potyvirus resistance, putative late blight resistance protein homolog R1B-23 and other disease resistance genes suggesting high correlation with resistance to different pathogens. These pepper RGAs could be regarded as candidate sequences of resistant genes for marker development.

Non-linear heart rate variability and risk stratification in cardiovascular disease.

Traditional time and frequency domain heart rate variability (HRV) have cardiac patients at risk of mortality post-myocardial infarction. More recently, non linear HRV has been applied to risk stratification of cardiac patients. In this review we describe studies of non linear HRV and outcome in cardiac patients. We have included studies that used the three most common non-linear indices: power law slope, the short term fractal scaling exponent and measures based on Poincare plots. We suggest that a combination of traditional and non-linear HRV may be optimal for risk stratification. Considerations in using non linear HRV in a clinical setting are described.

Prevalence of subnormal testosterone concentrations in men with type 2 diabetes and chronic kidney disease.

BACKGROUND: One-third of men with type 2 diabetes have subnormal testosterone concentrations along with inappropriately normal LH and FSH concentrations. It is not known if the presence of renal insufficiency affects free testosterone concentrations in men with type 2 diabetes. HYPOTHESIS: We hypothesized that type 2 diabetic men with chronic renal disease (CKD; estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m(2)) have lower free testosterone concentrations than men with normal renal function (eGFR ≥ 60 ml/min per 1.73 m(2)). STUDY DESIGN AND SETTING: This is a retrospective chart review of patients attending diabetes and nephrology clinics. Men with type 2 diabetes who had the following information available were included in the study: testosterone (total and free) done by LC/MS-MS followed by equilibrium dialysis, sex hormone binding globulin, LH, FSH and prolactin concentrations. PARTICIPANTS: We present data on T and gonadotropin concentrations in 111 men with type 2 diabetes and CKD (stages 3-5) and 182 type 2 diabetic men without CKD. RESULTS: The prevalence of subnormal free testosterone concentrations was higher in men with type 2 diabetes and CKD as compared to those without CKD (66% vs 37%, P < 0.001). Men with CKD had a higher prevalence of hypergonadotropic hypogonadism (26% vs 5%, P < 0.001) but not of hypogonadotropic hypogonadism (HH; 40% vs 32%, P = 0.22). There was an increase in the prevalence of hypergonadotropic hypogonadism with decreasing eGFR. Fifty-two percent of men with renal failure (CKD stage 5) had hypergonadotropic hypogonadism and 25% had HH. In men with CKD, the hemoglobin concentrations were lower in those with subnormal free T concentrations as compared to men with normal free T concentrations (119 ± 19 vs 128 ± 19 g/l, P = 0.04). CONCLUSIONS: Two-thirds of men with type 2 diabetes and CKD have subnormal free T concentrations. The hypogonadism associated with CKD is predominantly hypergonadotropic.

Implant debris particle size affects serum protein adsorption which may contribute to particle size-based bioreactivity differences.

Biologic reactivity to orthopedic implant debris mediates long-term clinical performance of total joint arthroplasty implants. However, the reasons that some facets of implant debris (e.g., particle size, shape, base material, etc.) are more pro-inflammatory remain controversial. This precludes accurate prediction and optimal design of modern total joint replacements. We hypothesized that debris particle size can influence adsorbed protein film composition and affect subsequent bioreactivity. We measured size-dependent proteinfilm adsorption, and adsorbed protein-film-dependent cytokine release using equal surface areas of different sized cobalt-chromium alloy (CoCr-alloy) particles and in vitro challenge of human macrophages (THP-1 and human primary). Smaller (5 µm diameter) versus larger (70 µm diameter) particles preferentially adsorbed more serum protein in general (p<0.03), where higher molecular weight serum proteins consistent with IgG were identified. Additionally, 5-µm CoCr-alloy particles pre-coated with different protein biofilms (IgG vs. albumin) resulted in a difference in cytokine expression in which albumin-coated particles induced more TNF-α release and IgG-coated particles induced more IL-1ß release from human monocytes/macrophages. In these preliminary in vitro studies, we have demonstrated the capability of equal surface areas of different particle sizes to influence adsorbed protein composition and that adsorbed protein differences on identical particles can translate into complex differences in bioreactivity. Together, these findings suggest that adsorbed protein differences on different-sized particles of the same material may be a contributing mechanism by which certain particles induce different reactivities.

BAMBI regulates angiogenesis and endothelial homeostasis through modulation of alternative TGFß signaling.

BACKGROUND: BAMBI is a type I TGFß receptor antagonist, whose in vivo function remains unclear, as BAMBI(-/-) mice lack an obvious phenotype. METHODOLOGY/PRINCIPAL FINDINGS: Identifying BAMBI's functions requires identification of cell-specific expression of BAMBI. By immunohistology we found BAMBI expression restricted to endothelial cells and by electron microscopy BAMBI(-/-) mice showed prominent and swollen endothelial cells in myocardial and glomerular capillaries. In endothelial cells over-expression of BAMBI reduced, whereas knock-down enhanced capillary growth and migration in response to TGFß. In vivo angiogenesis was enhanced in matrigel implants and in glomerular hypertrophy after unilateral nephrectomy in BAMBI(-/-) compared to BAMBI(+/+) mice consistent with an endothelial phenotype for BAMBI(-/-) mice. BAMBI's mechanism of action in endothelial cells was examined by canonical and alternative TGFß signaling in HUVEC with over-expression or knock-down of BAMBI. BAMBI knockdown enhanced basal and TGFß stimulated SMAD1/5 and ERK1/2 phosphorylation, while over-expression prevented both. CONCLUSIONS/SIGNIFICANCE: Thus we provide a first description of a vascular phenotype for BAMBI(-/-) mice, and provide in vitro and in vivo evidence that BAMBI contributes to endothelial and vascular homeostasis. Further, we demonstrate that in endothelial cells BAMBI interferes with alternative TGFß signaling, most likely through the ALK 1 receptor, which may explain the phenotype observed in BAMBI(-/-) mice. This newly described role for BAMBI in regulating endothelial function has potential implications for understanding and treating vascular disease and tumor neo-angiogenesis.

BAMBI is expressed in endothelial cells and is regulated by lysosomal/autolysosomal degradation.

BACKGROUND: BAMBI (BMP and Activin Membrane Bound Inhibitor) is considered to influence TGFß and Wnt signaling, and thereby fibrosis. Surprisingly data on cell type-specific expression of BAMBI are not available. We therefore examined the localization, gene regulation, and protein turnover of BAMBI in kidneys. METHODOLOGY/PRINCIPAL FINDINGS: By immunofluorescence microscopy and by mRNA expression, BAMBI is restricted to endothelial cells of the glomerular and some peritubular capillaries and of arteries and veins in both murine and human kidneys. TGFß upregulated mRNA of BAMBI in murine glomerular endothelial cells (mGEC). LPS did not downregulate mRNA for BAMBI in mGEC or in HUVECs. BAMBI mRNA had a half-life of only 60 minutes and was stabilized by cycloheximide, indicating post-transcriptional regulation due to AU-rich elements, which we identified in the 3' untranslated sequence of both the human and murine BAMBI gene. BAMBI protein turnover was studied in HUVECs with BAMBI overexpression using a lentiviral system. Serum starvation as an inducer of autophagy caused marked BAMBI degradation, which could be totally prevented by inhibition of lysosomal and autolysosomal degradation with bafilomycin, and partially by inhibition of autophagy with 3-methyladenine, but not by proteasomal inhibitors. Rapamycin activates autophagy by inhibiting TOR, and resulted in BAMBI protein degradation. Both serum starvation and rapamycin increased the conversion of the autophagy marker LC3 from LC3-I to LC3-II and also enhanced co-staining for BAMBI and LC3 in autolysosomal vesicles. CONCLUSIONS/SIGNIFICANCE: 1. BAMBI localizes to endothelial cells in the kidney and to HUVECs. 2. BAMBI mRNA is regulated by post-transcriptional mechanisms. 3. BAMBI protein is regulated by lysosomal and autolysosomal degradation. The endothelial localization and the quick turnover of BAMBI may indicate novel, yet to be defined functions of this modulator for TGFß and Wnt protein actions in the renal vascular endothelium in health and disease.

Soluble and particulate Co-Cr-Mo alloy implant metals activate the inflammasome danger signaling pathway in human macrophages: a novel mechanism for implant debris reactivity.

Immune reactivity to soluble and particulate implant debris remains the primary cause of aseptic inflammation and implant loosening. However, the intracellular mechanisms that trigger immune cells to sense and respond to exogenous nonbiological agents such as metal particles or metal ions released from orthopedic implants remain unknown. Recent studies in immunology have outlined the importance of the intracellular inflammasome complex of proteins in sensing danger/stress signals triggered by nonbiological agents in the cytosol of macrophages. We hypothesized that metal implant debris can activate the inflammasome pathway in macrophages that causes caspase-1-induced cleavage of intracellular pro-IL-1beta into its mature form, resulting in IL-1beta secretion and induction of a broader proinflammatory response. We tested this hypothesis by examining whether soluble cobalt, chromium, molybdenum, and nickel ions and Co-Cr-Mo alloy particles induce inflammasome- mediated macrophage reactivity. Our results demonstrate that these agents stimulate IL-1beta secretion in human macrophages that is inflammasome mediated (i.e., NADPH-, caspase-1-, Nalp3-, and ASC-dependent). Thus, metal ion- and particle-induced activation of the inflammasome in human macrophages provides evidence of a novel pathway of implant debris-induced inflammation, where contact with implant debris is sensed and transduced by macrophages into a proinflammatory response.

Analysis of metal ion-induced DNA damage, apoptosis, and necrosis in human (Jurkat) T-cells demonstrates Ni2+ and V3+ are more toxic than other metals: Al3+, Be2+, Co2+, Cr3+, Cu2+, Fe3+, Mo5+, Nb5+, Zr2+.

It remains unclear how metal released from implants affects cells of the immune system and, in particular, cells of the adaptive immune system, that is, T-helper lymphocytes. In this study, we investigated the effects of aluminum, chromium, cobalt, copper, iron, molybdenum, nickel, niobium, vanadium, and zirconium ions at concentrations from 0.05 to 5.0 mM on human CD4+ T lymphocytes. The DNA damage, apoptosis, necrosis, and proliferation responses of a human T-helper lymphocyte (Jurkat) cell line were evaluated to test our hypothesis that some metals will preferentially induce genotoxicity (DNA damage). Our results demonstrated that metal ions did not preferentially induce Jurkat T-lymphocyte DNA damage prior to other forms of toxicity, that is, apoptosis and/or direct necrosis. Nickel and vanadium induced the most DNA damage and were the most apoptotic metals tested, inducing >50% caspase-9 positive T cells at 0.05 mM and 0.1 mM concentrations, respectively. Cobalt and niobium were the most toxic metals, inducing <50% viability at approximately 0.5 mM concentrations. Nickel and vanadium were the only metals to induce DNA damage at nearly the same concentrations that induced >50% apoptosis (i.e., <0.05 mM). All the metals tested induced T-cell apoptosis at a lower dose than that required to affect DNA damage or toxicity, implying that soluble metals released from implants may not be preferentially genotoxic to lymphocytes.