Treatment of Acute Bronchitis and its Impact on Return Emergency Department Visits.

BACKGROUND: Antibiotics are not recommended in healthy, uncomplicated adults for the treatment of acute bronchitis, yet are still often prescribed. No randomized studies have examined whether prescribing antibiotics in the emergency department (ED) impacts hospital return rates. OBJECTIVE: Our aim was to compare hospital return rates between those who were prescribed an antibiotic vs. those who were not prescribed an antibiotic for the treatment of acute bronchitis. METHODS: A retrospective cohort study was completed evaluating patients aged 18-64 years who presented to a community teaching hospital ED with acute bronchitis between January 2017 and December 2019. The primary outcomes were 30-day ED return and hospital admissions from initial ED visit. The rates of ED return or readmitted were compared for patients prescribed an antibiotic for treatment of acute bronchitis vs. those patients who were not prescribed an antibiotic. RESULTS: Of the 752 patients included, 311 (41%) were prescribed antibiotics. Baseline demographics were similar between both groups. Of those prescribed an antibiotic, 26 of 311 (8.4%) returned to the hospital within 30 days compared with 33 of 441 patients (7.5%) who were not prescribed an antibiotic (odds ratio 1.13; 95% confidence interval 0.66-1.92). CONCLUSIONS: There was no association found between antibiotic therapy for treatment of acute bronchitis and return to the hospital.

The second branchial cleft fistula.

OBJECTIVE: To review the surgical anatomy and histopathology of second branchial cleft fistulae. STUDY DESIGN: Retrospective study of patients treated for second branchial cleft fistulae at a tertiary care pediatric hospital. The senior author noted anatomic and histologic features of second branchial cleft fistulae, not previously described. SETTING: Tertiary care children's hospital. PATIENTS AND METHODS: Retrospective examination of 28 patients was conducted who were operated upon for second branchial cleft fistula. Data collected included age at surgery, initial presentation, imaging characteristics prior to surgery, laterality of the fistula tract, pathology results and follow-up data. RESULTS: Twenty-eight patients met the criteria for inclusion. Three patients (11%) had bilateral fistulae. 11 (39%) were male and 17 (61%) were female. 23 (74.2%) tracts were lined with ciliated columnar epithelium, 3 (9.7%) had cuboidal epithelium, and 5 (16.7%) had squamous epithelium. Nineteen (61.3%) tracts contained salivary tissue. Of the unilateral fistula tracts, 25 (100%) were on the right side. Of the 3 patients with bilateral lesions, 2 (66%) had associated branchio-oto-renal syndrome (BORS). CONCLUSIONS: Second branchial cleft fistulae are rare. They are usually right-sided. If bilateral fistulae are present, one should consider an underlying genetic disorder. The histology of the fistulae mostly demonstrates ciliated columnar epithelium with the majority of specimens showing salivary tissue. There is a clear association with the internal jugular vein (IJV). Dissection should continue until superior to the hyoid bone, ensuring near complete surgical dissection and less risk of recurrence.

Wideband energy harvesting for piezoelectric devices with linear resonant behavior.

In this paper, an active energy harvesting technique for a spring-mass-damper mechanical resonator with piezoelectric electromechanical coupling is investigated. This technique applies a square-wave voltage to the terminals of the device at the same frequency as the mechanical excitation. By controlling the magnitude and phase angle of this voltage, an effective impedance matching can be achieved which maximizes the amount of power extracted from the device. Theoretically, the harvested power can be the maximum possible value, even at off-resonance frequencies. However, in actual implementation, the efficiency of the power electronic circuit limits the amount of power harvested. A power electronic full-bridge converter is built to implement the technique. Experimental results show that the active technique can increase the effective bandwidth by a factor of more than 2, and harvests significantly higher power than rectifier-based circuits at off-resonance frequencies.

Sex- and age-specific incidence of fractures in mental illness: a historical, population-based cohort study.

OBJECTIVE: To estimate risks of fracture at any site, and at sites linked with osteoporosis, in mentally ill adults compared with the general population. METHOD: We created a community-based cohort by using the U.K. General Practice Research Database, with follow-up from January 1987 through April 2005. We investigated age- and sex-specific fracture risks in psychotic illness(N = 4283), nonpsychotic affective disorder (N = 95,228), and any other psychiatric condition (N = 49,439). Comparison cases were subjects with no psychiatric code (N = 182,851); age-stratified (18-44 years, 45-74 years, > or = 75 years) relative risks (RRs) were estimated by Poisson regression. Outcomes were incident cases of fracture at any site, at the hip, and at the distal radius. RESULTS: Among all mentally ill women, highest RRs of fracture at any site were in the youngest age group, whereas the strongest effects in men were with older age. The highest raised risk of any fracture occurred in premenopausal women with psychotic disorders (RR = 2.5, 95% CI = 1.5 to 4.3). Hip fracture rates were raised in elderly women and men with psychiatric illness and were especially high in women (RR = 5.1, 95% CI = 2.7 to 9.6) and men (RR = 6.4, 95% CI = 2.6 to 16.1) with psychotic disorders at ages 45 to 74 years. Data were too sparse to estimate RR of distal radius fracture, although risk was modestly (but significantly) higher among women with any mental illness in each age group than the reference population, i.e., women with no history of psychiatric disorder. CONCLUSION: Raised risks of fracture in mental illness are likely to be explained by a range of mechanisms. Further research is needed to elucidate these mechanisms and to inform the development of targeted interventions.

A review of research on violence in same-gender couples: a resource for clinicians.

This paper reviews current research that has primarily focused on domestic violence among same-gender couples. Several key issues pertaining to the identification, assessment, and treatment of domestic violence among same-gender couples are examined and outlined to assist clinicians in effectively working with gay and lesbian clients who may be experiencing domestic violence. Resource information is included to help mental health clinicians recognize specific stressors of marginalized individuals as well as assessment and treatment recommendations are made.

Single crystal PMN-PT/epoxy 1-3 composite for energy-harvesting application.

One key parameter in using electroactive materials to harvest electric energy from mechanical sources is the energy conversion efficiency. Recently, it was shown that, in the relaxor ferroelectric PMN-PT single crystals, a very high longitudinal electromechanical coupling factor (>90%) can be obtained. This paper investigates energy harvesting using 1-3 composites of PMN-PT single crystals in a soft epoxy matrix. It is shown that 1-3 composites enable the single crystals operating in the longitudinal mode to achieve high efficiency for energy harvesting, and the soft-polymer, matrix-supported single-crystal rods maintain high mechanical integrity under different external loads. For comparison, 1-3 composites with piezoceramic PZT also are investigated in energy-harvesting applications, and the results show that the high coupling factor of single crystal PMN-PT 1-3 composites leads to much higher electric energy output for similar mechanical energy input. The harvested energy density of 1-3 composite with single crystal (22.1 mW/cm3 under a stress of 40.4 MPa) is about twice of that harvested with PZT ceramic 1-3 composite (12 mW/cm3 under a stress of 39 MPa). At a higher stress level, the harvested-energy density of 1-3 PMN-PT single crystal composite can reach 96 mW/cm3.

Investigation of electrostrictive polymers for energy harvesting.

The recent development of electrostrictive polymers has generated new opportunities for high-strain actuators. At the current time, the investigation of using electrostrictive polymer for energy harvesting, or mechanical to electrical energy conversion, is beginning to show its potential for this application. In this paper we discuss the mechanical and electrical boundary conditions for maximizing the energy harvesting density and mechanical-to-electrical coupling of electrostrictive materials. Mathematical models for different energy harvesting approaches were developed under quasistatic assumptions. Energy harvesting densities then are determined for representative electrostrictive material properties using these models. Comparison with a magnetic-based energy harvesting system suggests that electrostrictive energy harvesting systems are preferable for "small" energy harvesting applications with low-frequency excitation.

Functional characterization of two low density lipoprotein receptor gene mutations by fluorescence flow cytometric assessment of receptor activity in stimulated human T-lymphocytes.

We report a functional characterization of the W23X and W66G low density lipoprotein (LDL) receptor gene mutations. The authors used two-color fluorescence flow cytometry to measure LDL receptor activity in stimulated T-lymphocytes, prepared from patients heterozygous for the W23X or W66G mutation, and compared the results with measurements of LDL receptor activity in stimulated T-lymphocytes prepared from unrelated healthy control subjects. It was found that the W23X mutation significantly reduced LDL receptor expression and LDL binding and internalization, and that the W66G mutation significantly reduced LDL receptor expression and LDL binding. LDL internalization in patients heterozygous for the W66G mutation was not significantly reduced. The data support the concepts that the W23X mutation prevents production of LDL receptors (class I) and that the W66G mutation produces LDL receptors unable to recycle normally in cells (class V).

Flow cytometric assessment of LDL ligand function for detection of heterozygous familial defective apolipoprotein B-100.

BACKGROUND: Familial defective apolipoprotein (apo) B-100 (FDB) is caused by a mutation in the apoB gene and characterized by decreased binding of LDL to LDL receptors because of reduced function of the apoB-100 ligand. FDB may be associated with severe hypercholesterolemia and cannot always be distinguished from familial hypercholesterolemia phenotypically. METHODS: We used a fluorescence flow cytometry assay with Epstein-Barr virus-transformed lymphocytes to detect reduced LDL ligand function by competitive binding with fluorescently conjugated LDL (DiI-LDL). The assay was tested and validated using LDL from patients heterozygous for the Arg(3500)-Gln mutation and their first-degree relatives. Knowing the actual apoB genotype of patients and relatives allowed us to assess the ability of the assay to predict the results of DNA analysis. The results were compared to measurements of LDL ligand function in unrelated healthy control subjects to characterize functionally the Arg(3500)-Gln mutation. RESULTS: Fluorescence was significantly increased in cells incubated with DiI-LDL in competition with unlabeled LDL from FDB(R3500Q) heterozygotes compared with cells incubated with DiI-LDL in competition with unlabeled LDL from relatives or unrelated healthy control subjects. Thus, patients heterozygous for the Arg(3500)-Gln mutation had significantly reduced LDL ligand function. The binding affinity of LDL from FDB(R3500Q) heterozygotes was 32% of that in non-FDB relatives and healthy controls. The assay had a diagnostic sensitivity of 0.95 and diagnostic specificity of 0.89. CONCLUSIONS: The diagnostic accuracy of the assay was too low to allow reliable diagnosis of individual cases of heterozygous FDB(R3500Q). However, fluorescence flow cytometry may supplement genetic identification of FDB and functionally characterize gene mutations associated with major reductions in LDL ligand function.

Flow cytometric assessment of LDL receptor activity in peripheral blood mononuclear cells compared to gene mutation detection in diagnosis of heterozygous familial hypercholesterolemia.

BACKGROUND: Studies indicate that human peripheral blood mononuclear cells mirror low-density lipoprotein (LDL) receptor activity of other cells in the body. To measure LDL receptor activity in patients with heterozygous familial hypercholesterolemia (FH), we prepared peripheral blood mononuclear cells from individuals with molecularly verified LDL receptor defective (Trp66-Gly mutation, n = 18) or receptor negative (Trp23-stop mutation, n = 17) heterozygous FH and from healthy individuals (n = 24). METHODS: The cells were stimulated to express maximum LDL receptor by preincubation in lipoprotein-free medium. They were then incubated at 4 degrees or 37 degrees C with fluorescently conjugated LDL (DiI-LDL). T-lymphocytes and monocytes were identified by fluorescently conjugated monoclonal antibodies. DiI-LDL bound (at 4 degrees C) or internalized (at 37 degrees C) by the cells was measured using flow cytometry. Knowing the LDL receptor gene mutation of the FH patients allowed us to compare the diagnostic capability of our functional assay with the DNA diagnosis. RESULTS: The diagnostic accuracy did not allow our assay to be used for diagnosis of individual cases of heterozygous FH. CONCLUSIONS: We suggest that our two-color fluorescence flow cytometry assay can be used to characterize functionally gene mutations causing LDL receptor dysfunction in patients with heterozygous FH.

Flow cytometry with a monoclonal antibody to the low density lipoprotein receptor compared with gene mutation detection in diagnosis of heterozygous familial hypercholesterolemia.

We used a fluorescence flow cytometry assay with a monoclonal low density lipoprotein (LDL) receptor-specific antibody to detect LDL receptor expression on blood T lymphocytes and monocytes. We prepared peripheral blood mononuclear cells from patients with genetically verified LDL receptor-defective (Trp66-Gly mutation, n = 17) or receptor-negative (Trp23-stop mutation, n = 17) heterozygous familial hypercholesterolemia (FH) and from healthy individuals (n = 24). The cells were stimulated to express the maximum amount of LDL receptor by preincubation in lipoprotein-deficient medium. A dual-labeling technique allowed flow cytometric analysis of LDL receptor expression on cells identified by fluorescently conjugated surface marker antibodies. Knowing the LDL receptor gene mutation of the FH patients allowed us to compare the diagnostic capability of this functional assay with the DNA diagnosis and to validate the assay with molecular genetics instead of clinical indices of heterozygous FH. T lymphocytes expressed more LDL receptors and gave better diagnostic results than monocytes, and cells from patients with either the Trp66-Gly or the Trp23-stop mutation had variable but significantly reduced LDL receptor expression. The data indicate that this fluorescence flow cytometry assay is unsuitable for diagnosis of individual cases of heterozygous FH but that it may be useful for functionally characterizing mutations in the LDL receptor gene.

Physical examination as a screening test for pelvic fractures in blunt trauma patients.

This article describes our study of 82 awake, alert blunt trauma victims over the age of 18 with Glasgow Coma Scores of 14 or 15. The purpose was to assess whether the examining physicians were able to determine without benefit of X-ray whether the patients had pelvic fractures. Physicians were asked to complete a questionnaire regarding pain on examination of the pelvis, and were then asked if they believed a fracture was clinically present. Seventy-one patients were tested for alcohol; 15 were positive, and 11 had levels greater than 100 mg%. Fifty-five were tested for mind-altering drugs; 20 were positive. Nine had pelvic fractures; seven required no treatment. Eighteen had pain on examination in at least one plane. Seven of these had fractures; six were suspected clinically. Sixty-four patients had no pain; two had fractures that were not suspected clinically and required no specific treatment. We conclude that selective use of pelvic x-rays in awake, alert blunt trauma patients does not result in any clinically significant missed fractures.

A common W556S mutation in the LDL receptor gene of Danish patients with familial hypercholesterolemia encodes a transport-defective protein.

In a group of unrelated Danish patients with familial hypercholesterolemia (FH) we recently reported two common low-density lipoprotein (LDL) receptor mutations, W23X and W66G, accounting for 30% of the cases. In this study, we describe another common LDL receptor mutation, a G to C transition at cDNA position 1730 in exon 12, causing a tryptophan to serine substitution in amino acid position 556 (W556S). In the Danish patients, the W556S mutation was present in 12% of 65 possible mutant alleles. The pathogenicity of the W556S mutation, which is located in one of the five conserved motifs Tyr-Trp-Thr-Asp in the epidermal growth factor homology region, was studied in transfected COS-7 cells expressing normal and mutant LDL receptor cDNAs. Results obtained by immunofluorescence flow cytometry and confocal microscopy, as well as by immunoprecipitation, were compatible with complete retention of the mutant protein in the endoplasmic reticulum. The transport-defective W556S mutation and the W23X and W66G mutations seem to account for about 40% of the LDL receptor defects in Danish families with FH.

Two mutations in the same low-density lipoprotein receptor allele act in synergy to reduce receptor function in heterozygous familial hypercholesterolemia.

Mutations in genes are not necessarily pathogenic. Expression of mutant genes in cells can therefore be required to demonstrate that mutations in fact disturb protein function. This applies especially to missense mutations, which cause an amino acid to be replaced by another amino acid. In the present study of two families with familial hypercholesterolemia in the heterozygous form, we found two mutations in the same allele of the low-density lipoprotein (LDL) receptor gene: a missense Asn543. His mutation (N543H) in exon 11, and an in-frame 9-bp deletion (2393del9) in exon 17. The two mutations were identified in heterozygous FH index patients in whom no other pathogenic mutations were detected by SSCP analysis of the remaining 16 exons and the promoter region. Both mutations cosegregated with hypercholesterolemia within the families. Each of these mutations had little or no effect on receptor function in transfected COS cells, but when both mutations were present simultaneously, receptor function, as assessed by flow cytometric measurement of fluorescent LDL uptake in cells, was reduced by 75%. Immunostainable receptors on the cell surface were decreased by 80% as measured by flow cytometry. The two mutations therefore acted in synergy to affect receptor function, possibly during intracellular receptor transport, since Northern blot analysis suggested that mRNA levels were unaffected. Without screening of the entire coding regions of the gene, the synergistic action of these two LDL receptor mutations would not have been detected.

Phenotypic characterization of a patient homozygous for the D558N LDL receptor gene mutation.

We describe the clinical, biochemical, and genetic features of a patient with true homozygous familial hypercholesterolemia due to the D558N low-density lipoprotein receptor gene mutation, previously designated FH Cincinnati-4. Functional flow-cytometric analysis of the LDL receptorR protein on upregulated EBV-transformed lymphocytes indicated reduction of the number of receptors on the cell surface by 87% and reduction of receptor activity by 89% compared to control cells. With drugs and a portacaval shunt operation, performed when the patient was 15 years old, serum cholesterol was reduced from about 28 to about 15 mmol/l. He died at the age of 32 of a myocardial infarction. The autopsy showed generalized atherosclerosis, especially in the coronary arteries, which were severely stenosed proximally. A rare finding was a large intracranial xanthoma that apparently had been asymptomatic.

Rapid characterization of disease-causing mutations in the low density lipoprotein receptor (LDL-R) gene by overexpression in COS cells.

To characterize disease-causing mutations in the low density lipoprotein receptor (LDL-R) gene, COS cells are transfected with the mutant gene in an EBV-based expression vector and characterized by flow cytometry. Using antibodies against the LDL-receptor the amount of receptor protein on the cell surface is quantitated. The receptor activity is measured by incubating the cells with fluorescence labeled LDL (Dil-labelled LDL) at 37 degrees C and 4 degrees C. The transfected cells stained with anti-LDL-R antibodies can also be analysed by immunofluorescence microscopy allowing the study of the intracellular location of variants of the receptor. To evaluate these methods, we are analyzing four previously well-characterized LDL-R mutations, belonging to each of the classes 2 to 5. Preliminary data show that mutant genes belonging to class 3 and 4A give rise to receptor protein on the cell surface, but impaired LDL uptake, while mutant receptors belonging to class 2A and 5 can only be detected intracellularly. Expression of the class 2A mutation results in an ER staining pattern, whereas the class 5 mutation gives rise to an intracellular staining compatible with localization in the endosomal/lysosomal compartments. We conclude that this system is useful for a rapid functional analysis of newly discovered mutations in the LDL-R gene.

A flow cytometric competition technique for measuring interaction of LDL with cellular LDL-receptors applied to patients with mutant (Arg3500-->Gln) apolipoprotein B.

We report our experience with a method to evaluate binding and uptake in cells of low density lipoprotein (LDL) from heterozygous patients with familial defective apolipoprotein B-100 (FDB-LDL) and LDL from normolipidemic subjects (nonFDB-LDL). The method is based on competition for binding/uptake in Epstein-Barr Virus (EBV)-transformed lymphocytes or COS cells overexpressing an LDL-receptor transgene between fluorescently labeled LDL and the unlabeled LDL of interest, and measurements are by flow cytometry. With EBV-lymphoblasts, the ability of FDB-LDL to displace fluorescent LDL ("Dil"-LDL) from cells at 4 degrees C (binding) was reduced to approximately 1/3 of normal. Displacement of "Dil"-LDL by FDB-LDL from cells at 20 degrees C (binding/uptake) was reduced to less than 1/2 of normal. Similar results were obtained with COS cells. Freezing of serum to -80 degrees C for 24 hours did not affect results, and we could discriminate between binding/uptake of FDB-LDL and nonFDB-LDL prepared from serum that had been stored at -80 degrees C for three months.