Nocturia as an Unrecognized Symptom of Uncontrolled Hypertension in Black Men Aged 35 to 49 Years.

Background Hypertension is assumed to be asymptomatic. Yet, clinically significant nocturia (≥2 nightly voids) constitutes a putative symptom of uncontrolled hypertension. Black men with hypertension may be prone to nocturia because of blunted nocturnal blood pressure ( BP ) dipping, diuretic drug use for hypertension, and comorbidity that predisposes to nocturia. Here, we test the hypothesis that nocturia is a common and potentially reversible symptom of uncontrolled hypertension in black men. Methods and Results We determined the strength of association between nocturia (≥2 nightly voids) and high BP (≥135/85 mm Hg) by conducting in-person health interviews and measuring BP with an automated monitor in a large community-based sample of black men in their barbershops. Because nocturia is prevalent and steeply age-dependent after age 50 years, we studied men aged 35 to 49 years. Among 1673 black men (mean age, 43±4 years [ SD ]), those with hypertension were 56% more likely than men with normotension to have nocturia after adjustment for diabetes mellitus and sleep apnea (adjusted odds ratio, 1.56; 95% CI , 1.25-1.94 [ P<0.0001]). Nocturia prevalence varied by hypertension status, ranging from 24% in men with normotension to 49% in men whose hypertension was medically treated but uncontrolled. Men with untreated hypertension were 39% more likely than men with normotension to report nocturia ( P=0.02), whereas men whose hypertension was treated and controlled were no more likely than men with normotension to report nocturia ( P=0.69). Conclusions Uncontrolled hypertension was an independent determinant of clinically important nocturia in a large cross-sectional community-based study of non-Hispanic black men aged 35 to 49 years. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unqiue identifier: NCT 02321618

Elevated Pressure Improves the Extraction and Identification of Proteins Recovered from Formalin-Fixed, Paraffin-Embedded Tissue Surrogates

Proteomic studies of formalin-fixed paraffin-embedded (FFPE) tissues are frustrated by the inability to extract proteins from archival tissue in a form suitable for analysis by 2-D gel electrophoresis or mass spectrometry. This inability arises from the difficulty of reversing formaldehyde-induced protein adducts and cross-links within FFPE tissues. We previously reported the use of elevated hydrostatic pressure as a method for efficient protein recovery from a hen egg-white lysozyme tissue surrogate, a model system developed to study formalin fixation and histochemical processing.In this study, we demonstrate the utility of elevated hydrostatic pressure as a method for efficient protein recovery from FFPE mouse liver tissue and a complex multi-protein FFPE tissue surrogate comprised of hen egg-white lysozyme, bovine carbonic anhydrase, bovine ribonuclease A, bovine serum albumin, and equine myoglobin (55∶15∶15∶10∶5 wt%). Mass spectrometry of the FFPE tissue surrogates retrieved under elevated pressure showed that both the low and high-abundance proteins were identified with sequence coverage comparable to that of the surrogate mixture prior to formaldehyde treatment. In contrast, non-pressure-extracted tissue surrogate samples yielded few positive and many false peptide identifications. Studies with soluble formalin-treated bovine ribonuclease A demonstrated that pressure modestly inhibited the rate of reversal (hydrolysis) of formaldehyde-induced protein cross-links. Dynamic light scattering studies suggest that elevated hydrostatic pressure and heat facilitate the recovery of proteins free of formaldehyde adducts and cross-links by promoting protein unfolding and hydration with a concomitant reduction in the average size of the protein aggregates.These studies demonstrate that elevated hydrostatic pressure treatment is a promising approach for improving the recovery of proteins from FFPE tissues in a form suitable for proteomic analysis

Cranial Cruciate Ligament Desmotomies in Sheep Resulting in Peroneus Tertius Injury

Surgical destabilization of the stifle joint via cranial cruciate ligament desmotomy (CCLD) is a routine procedure for the study of osteoarthritis (OA). Traditionally performed in rats, rabbits, cats, and dogs, CCLD in sheep provides an opportunity to study the pathology and treatment of joint instability in a species whose stifle better represents the equivalent human femorotibial joint. The surgical approaches for CCLD in sheep are variable and can result in inconsistent outcomes. Eight sheep underwent CCLD for use in a gene therapy study. We report this case in which six of the eight sheep were clinically diagnosed by pathognomonic signs and later confirmed by postmortem dissection, with injury of the peroneus tertius (PT) muscle. The PT plays a crucial role in the normal gait of large animals, including sheep. Injury to the PT results in failure of the reciprocal apparatus of the hind limb in which the hock can be extended during stifle flexion creating a varied gait and an indiscriminate increase in instability of the stifle and hock joints. Restricted movement postoperatively may provide decreased variability in surgical outcomes. Alternatively, increased stifle instability via CCLD coupled with PT transection or PT transection alone could potentially provide a superior model of stifle instability and OA development in sheep

Pressure-Assisted Protein Extraction: A Novel Method for Recovering Proteins from Archival Tissue for Proteomic Analysis

Formaldehyde-fixed, paraffin-embedded (FFPE) tissue repositories represent a valuable resource for the retrospective study of disease progression and response to therapy. However, the proteomic analysis of FFPE tissues has been hampered by formaldehyde-induced protein modifications, which reduce protein extraction efficiency and may lead to protein misidentification. Here, we demonstrate the use of heat augmented with high hydrostatic pressure (40,000 psi) as a novel method for the recovery of intact proteins from FFPE mouse liver. When FFPE mouse liver was extracted using heat and elevated pressure, there was a 4-fold increase in protein extraction efficiency, a 3-fold increase in the extraction of intact proteins, and up to a 30-fold increase in the number of nonredundant proteins identified by mass spectrometry, compared to matched tissue extracted with heat alone. More importantly, the number of nonredundant proteins identified in the FFPE tissue was nearly identical to that of matched fresh-frozen tissue

Performance of van der Waals Corrected Functionals for Guest Adsorption in the M-2(dobdc) Metal-Organic Frameworks

Small-molecule binding in metal–organic frameworks (MOFs) can be accurately studied both experimentally and computationally, provided the proper tools are employed. Herein, we compare and contrast properties associated with guest binding by means of density functional theory (DFT) calculations using nine different functionals for the M2(dobdc) (dobdc4– = 2,5-dioxido,1,4-benzenedicarboxylate) series, where M = Mg, Mn, Fe, Co, Ni, Cu, and Zn. Additionally, we perform Quantum Monte Carlo (QMC) calculations for one system to determine if this method can be used to assess the performance of DFT. We also make comparisons with previously published experimental results for carbon dioxide and water and present new methane neutron powder diffraction (NPD) data for further comparison. All of the functionals are able to predict the experimental variation in the binding energy from one metal to the next; however, the interpretation of the performance of the functionals depends on which value is taken as the reference. On the one hand, if we compare against experimental values, we would conclude that the optB86b-vdW and optB88-vdW functionals systematically overestimate the binding strength, while the second generation of van der Waals (vdW) nonlocal functionals (vdw-DF2 and rev-vdW-DF2) correct for this providing a good description of binding energies. On the other hand, if the QMC calculation is taken as the reference then all of the nonlocal functionals yield results that fall just outside the error of the higher-level calculation. The empirically corrected vdW functionals are in reasonable agreement with experimental heat of adsorptions but under bind when compared with QMC, while Perdew–Burke–Ernzerhof fails by more than 20 kJ/mol regardless of which reference is employed. All of the functionals, with the exception of vdW-DF2, predict reasonable framework and guest binding geometries when compared with NPD measurements. The newest of the functionals considered, rev-vdW-DF2, should be used in place of vdW-DF2, as it yields improved bond distances with similar quality binding energies

Pretransplant gastroesophageal reflux compromises early outcomes after lung transplantation

ObjectivesGastroesophageal reflux disease (GERD) is implicated as a risk factor for bronchiolitis obliterans syndrome after lung transplantation, but its effects on acute rejection, early allograft function, and survival are unclear. Therefore, we sought to systematically understand the time-related impact of pretransplant GERD on graft function (spirometry), mortality, and acute rejection early after lung transplantation.MethodsFrom January 2005 to July 2008, 215 patients underwent lung transplantation; 114 had preoperative pH testing, and 32 (28%) had objective evidence of GERD. Lung function was assessed by forced 1-second expiratory volume (FEV1; percent of predicted) in 97 patients, mortality by follow-up (median, 2.2 years), and acute rejection by transbronchial biopsy.ResultsPretransplant GERD was associated with decreased FEV1 early after lung transplantation (P = .01) such that by 18 months, FEV1 was 70% of predicted in double lung transplant patients with GERD versus 83% among non-GERD patients (P = .05). A similar decrease was observed in single lung transplantation (50% vs 60%, respectively; P = .09). GERD patients had lower survival early after transplant ( P = .02)—75% versus 90%. Presence of GERD did not affect acute rejection (P = .6).ConclusionsFor lung transplant recipients, pretransplant GERD is associated with worse early allograft function and survival, but not increased acute rejection. The compromise in lung function is substantial, such that FEV1 after double lung transplant in GERD patients approaches that of single lung transplant in non-GERD patients. We advocate thorough testing for GERD before lung transplantation; if identified, aggressive therapy early after transplant, including fundoplication, may prove efficacious