Provider Perceptions of an Electronic Health Record Prostate Cancer Screening Tool.

OBJECTIVES: We conducted a focus group to assess the attitudes of primary care physicians (PCPs) toward prostate-specific antigen (PSA)-screening algorithms, perceptions of using decision support tools, and features that would make such tools feasible to implement. METHODS: A multidisciplinary team (primary care, urology, behavioral sciences, bioinformatics) developed the decision support tool that was presented to a focus group of 10 PCPs who also filled out a survey. Notes and audio-recorded transcripts were analyzed using Thematic Content Analysis. RESULTS: The survey showed that PCPs followed different guidelines. In total, 7/10 PCPs agreed that engaging in shared decision-making about PSA screening was burdensome. The majority (9/10) had never used a decision aid for PSA screening. Although 70% of PCPs felt confident about their ability to discuss PSA screening, 90% still felt a need for a provider-facing platform to assist in these discussions. Three major themes emerged: (1) confirmatory reactions regarding the importance, innovation, and unmet need for a decision support tool embedded in the electronic health record; (2) issues around implementation and application of the tool in clinic workflow and PCPs' own clinical bias; and (3) attitudes/reflections regarding discrepant recommendations from various guideline groups that cause confusion. CONCLUSION: There was overwhelmingly positive support for the need for a provider-facing decision support tool to assist with PSA-screening decisions in the primary care setting. PCPs appreciated that the tool would allow flexibility for clinical judgment and documentation of shared decision-making. Incorporation of suggestions from this focus group into a second version of the tool will be used in subsequent pilot testing.

A Provider-Facing Decision Support Tool for Prostate Cancer Screening in Primary Care: A Pilot Study.

OBJECTIVES: Our objective was to pilot test an electronic health record-embedded decision support tool to facilitate prostate-specific antigen (PSA) screening discussions in the primary care setting. METHODS: We pilot-tested a novel decision support tool that was used by 10 primary care physicians (PCPs) for 6 months, followed by a survey. The tool comprised (1) a risk-stratified algorithm, (2) a tool for facilitating shared decision-making (Simple Schema), (3) three best practice advisories (BPAs: <45, 45-75, and >75 years), and (4) a health maintenance module for scheduling automated reminders about PSA rescreening. RESULTS: All PCPs found the tool feasible, acceptable, and clear to use. Eight out of ten PCPs reported that the tool made PSA screening conversations somewhat or much easier. Before using the tool, 70% of PCPs felt confident in their ability to discuss PSA screening with their patient, and this improved to 100% after the tool was used by PCPs for 6 months. PCPs found the BPAs for eligible (45-75 years) and older men (>75 years) more useful than the BPA for younger men (<45 years). Among the 10 PCPs, 60% found the Simple Schema to be very useful, and 50% found the health maintenance module to be extremely or very useful. Most PCPs reported the components of the tool to be at least somewhat useful, with 10% finding them to be very burdensome. CONCLUSION: We demonstrated the feasibility and acceptability of the tool, which is notable given the marked low acceptance of existing tools. All PCPs reported that they would consider continuing to use the tool in their clinic and were likely or very likely to recommend the tool to a colleague.

Correlation between hip muscle strength and the lower quarter Y-balance test in athletes following anterior cruciate ligament reconstruction.

INTRODUCTION: The lower quarter Y-balance test (YBT-LQ), which measures dynamic postural control, has been reported to be predictive of lower limb injuries in athletes. It requires subjects to control their body while maintaining a single-leg stance, which necessitates sufficient strength of the hip muscles to maintain stability. The purpose of the study was to investigate the correlation between the performance of the YBT-LQ and the hip abductor or extensor muscle strength in athletes following anterior cruciate ligament reconstruction surgery (ACLR). METHODS: Fifteen athletes with post-ACLR participated in this cross-sectional study. The participants completed the YBT-LQ, followed by isokinetic measurement of the hip abductor and extensor muscles of both the legs. The peak and average torque of the hip abductor and extensor muscles were tallied with the composite score of the YBT-LQ for each limb. RESULTS: No correlation was found between the strength of the hip muscles and the YBT-LQ composite score in both injured and non-injured limbs at all velocities except for the eccentric hip abductor and concentric hip extensor torques. The eccentric hip abductor average torque is strongly associated with the YBT-LQ (r = 0.663, p = 0.010) at a speed of 180°/s. The concentric hip extensor peak torque was weakly correlated with balance (r = 0.540, p = 0.046) at a speed of 180°/s. CONCLUSION: Our study demonstrated a positive correlation between the YBT-LQ and eccentric hip abduction and concentric hip extension at higher velocities. This shows the importance of implementing velocity-oriented rehabilitation in an athletic population following ACLR.

Recycling transplanted organs: An exceptional case and literature review.

BACKGROUND: Recycling transplant kidneys, in other words using an allograft which has previously been transplanted in one recipient for transplant in a second recipient, can be a source of opportunity for expanding the pool of available grafts in the United States and beyond. SUMMARY: We describe a case of renal transplantation from a donor who had undergone a kidney transplant 3 years prior and had good graft function at the time of procurement. The recipient underwent transplantation uneventfully and to date has demonstrated excellent graft function. We also include a literature review of reported cases of recycled/retransplanted kidneys. KEY MESSAGES: -Recycling transplanted kidneys is a largely untapped resource which could help decrease the transplant waitlist. -Utilizing such kidneys does need special considerations in terms of procurement technique, backtable, crossmatch, recipient selection and follow-up.

Concomitant Polyoma BK Virus and West Nile Virus in Renal Allografts.

Surveillance of the renal allograft recipient is essential when monitoring renal function to detect the early onset of rejection and alter therapeutic treatments to treat acute rejection or other causes and improve long-term graft function. If renal function begins to deteriorate, a renal biopsy is often indicated to assess the Banff grade of potential rejection or other causes, especially in the setting of polyoma BK viral load elevation. Although BK infection in the allograft is asymptomatic, reactivation of the virus is known to be associated with the acceleration of pathologic change and a poor outcome in the allograft. BK reactivation in a transplant kidney is not uncommon, and determining inflammation related to the virus versus acute rejection is paramount for appropriate immunosuppressive therapy management. We identified a concomitant polyoma BK virus and West Nile Virus (WNV) infection in two renal transplant patients which, to our knowledge, has not previously been reported. However, other concomitant infections have been reported in renal allografts including BK virus and cytomegalovirus (CMV), CMV and hepatitis C (HCV), and HCV and human immunodeficiency virus (HIV). As WNV has become endemic in many regions of the United States, and since the transmission of the virus via transplanted organs is associated with significant morbidity and mortality, it may be prudent to consider serologic screening for WNV in living donors prior to organ procurement. Regardless, the observation we made and report here should underscore the potential for concomitant viral infections that may be masked when a renal allograft has a significant inflammatory response to BK virus.

Novel Model of Oxalate Diet-Induced Chronic Kidney Disease in Dahl-Salt-Sensitive Rats.

Diet-induced models of chronic kidney disease (CKD) offer several advantages, including clinical relevance and animal welfare, compared with surgical models. Oxalate is a plant-based, terminal toxic metabolite that is eliminated by the kidneys through glomerular filtration and tubular secretion. An increased load of dietary oxalate leads to supersaturation, calcium oxalate crystal formation, renal tubular obstruction, and eventually CKD. Dahl-Salt-Sensitive (SS) rats are a common strain used to study hypertensive renal disease; however, the characterization of other diet-induced models on this background would allow for comparative studies of CKD within the same strain. In the present study, we hypothesized that SS rats on a low-salt, oxalate rich diet would have increased renal injury and serve as novel, clinically relevant and reproducible CKD rat models. Ten-week-old male SS rats were fed either 0.2% salt normal chow (SS-NC) or a 0.2% salt diet containing 0.67% sodium oxalate (SS-OX) for five weeks.Real-time PCR demonstrated an increased expression of inflammatory marker interleukin-6 (IL-6) (p < 0.0001) and fibrotic marker Timp-1 metalloproteinase (p < 0.0001) in the renal cortex of SS-OX rat kidneys compared with SS-NC. The immunohistochemistry of kidney tissue demonstrated an increase in CD-68 levels, a marker of macrophage infiltration in SS-OX rats (p < 0.001). In addition, SS-OX rats displayed increased 24 h urinary protein excretion (UPE) (p < 0.01) as well as significant elevations in plasma Cystatin C (p < 0.01). Furthermore, the oxalate diet induced hypertension (p < 0.05). A renin-angiotensin-aldosterone system (RAAS) profiling (via liquid chromatography-mass spectrometry; LC-MS) in the SS-OX plasma showed significant (p < 0.05) increases in multiple RAAS metabolites including angiotensin (1-5), angiotensin (1-7), and aldosterone. The oxalate diet induces significant renal inflammation, fibrosis, and renal dysfunction as well as RAAS activation and hypertension in SS rats compared with a normal chow diet. This study introduces a novel diet-induced model to study hypertension and CKD that is more clinically translatable and reproducible than the currently available models.

Paraoxonases at the Heart of Neurological Disorders.

Paraoxonase enzymes serve as an important physiological redox system that participates in the protection against cellular injury caused by oxidative stress. The PON enzymes family consists of three members (PON-1, PON-2, and PON-3) that share a similar structure and location as a cluster on human chromosome 7. These enzymes exhibit anti-inflammatory and antioxidant properties with well-described roles in preventing cardiovascular disease. Perturbations in PON enzyme levels and their activity have also been linked with the development and progression of many neurological disorders and neurodegenerative diseases. The current review summarizes the available evidence on the role of PONs in these diseases and their ability to modify risk factors for neurological disorders. We present the current findings on the role of PONs in Alzheimer's disease, Parkinson's disease, and other neurodegenerative and neurological diseases.

Immediate and Long-Term Effectiveness of Proprioceptive Neuromuscular Facilitation and Static Stretching on Joint Range of Motion, Flexibility, and Electromyographic Activity of Knee Muscles in Older Adults.

Introduction and Objective: Previously, various stretching techniques were compared to study their effects on the different physiological parameters of hamstring muscles in the elderly population. There is no research that compares the immediate and long-term effects of proprioceptive neuromuscular facilitation-contract-relax (PNF-CR) and static stretching (SS) techniques on knee range of motion (ROM), hamstring flexibility, and knee flexor muscle EMG activity in the elderly. This study intends to compare the same. Methods: A total of 30 males aged 55-75 years were randomly assigned into the PNF-CR group (n = 10), SS group (n = 10), and control group (n = 10). The PNF-CR group received four trials of the contract-relax technique, the SS group received passive stretching of an 80 s duration by the therapist, and the control group received no intervention. A total of 12 sessions were given during the four-week period. Knee range of motion, electromyographic activity of the biceps femoris, and the sit-and-reach test were taken for the dominant side thrice: pre-intervention, immediately after stretching, and after the training period. Results: A statistically significant difference was observed in the maximum voluntary isometric contraction (MVIC) of biceps femoris between the PNF and the control groups (p = 0.01) after four weeks of intervention. The knee ROM and hamstring flexibility for the PNF group showed significant improvement immediately post-test (p = 0.01) and after four weeks of training (p = 0.07 and p = 0.001). SS showed significant results for both ROM and flexibility after four weeks of intervention (p = 0.001), and significant immediate post-test improvements were seen for ROM only (p = 0.007). Conclusions: PNF stretching has an immediate, as well as long-term, effect on knee ROM and hamstring flexibility, whereas it has only a long-term effect on muscle electromyographic activity. SS has an immediate, as well as long-term, effect on knee ROM and only a long-term effect on hamstring flexibility, without any immediate or long-term effects on muscle electromyographic activity.

Does a brief surgeon training in negotiation theory principles decrease rates of contralateral prophylactic mastectomy?

PURPOSE: Despite the lack of any oncologic benefit, contralateral prophylactic mastectomy (CPM) use among women with unilateral breast cancer is increasing. This patient-driven trend is influenced by fear of recurrence and desire for peace of mind. Traditional educational strategies have been ineffective in reducing CPM rates. Here we employ training in negotiation theory strategies for counseling and determine the effect on CPM rates. METHODS: In consecutive patients with unilateral breast cancer treated with mastectomy from 05/2017 to 12/2019, we examined CPM rates before and after a brief surgeon training in negotiation skills. This comprised a systematic framework for patient counseling utilizing early setting of the default option, leveraging social proof, and framing. RESULTS: Among 2144 patients, 925 (43%) were treated pre-training and 744 (35%) post-training. Those treated in the 6-month transition period were excluded (n = 475, 22%). Median patient age was 50 years; most patients had T1-T2 (72%), N0 (73%), and estrogen receptor-positive (80%) tumors of ductal histology (72%). The CPM rate was 47% pre-training versus 48% post-training, with an adjusted difference of -3.7% (95% CI -9.4 to 2.1, p = 0.2). In a standardized self-assessment survey, all 15 surgeons reported a high baseline use of negotiation skills and no significant change in conversational difficulty with the structured approach. CONCLUSION: Brief surgeon training did not affect self-reported use of negotiation skills or reduce CPM rates. The choice of CPM is a highly individual decision influenced by patient values and decision styles. Further research to identify effective strategies to minimize surgical overtreatment with CPM is needed.

Hypertonic Saline Infusion for Hyponatremia: Limitations of the Adrogué-Madias and Other Formulas.

Hypertonic saline infusion is used to correct hyponatremia with severe symptoms. The selection of the volume of infused hypertonic saline ( VInf ) should address prevention of overcorrection or undercorrection. Several formulas computing this VInf have been proposed. The limitations common to these formulas consist of (1) failure to include potential determinants of change in serum sodium concentration ([ Na ]) including exchanges between osmotically active and inactive sodium compartments, changes in hydrogen binding of body water to hydrophilic compounds, and genetic influences and (2) inaccurate estimates of baseline body water entered in any formula and of gains or losses of water, sodium, and potassium during treatment entered in formulas that account for such gains or losses. In addition, computing VInf from the Adrogué-Madias formula by a calculation assuming a linear relation between VInf and increase in [ Na ] is a source of errors because the relation between these two variables was proven to be curvilinear. However, these errors were shown to be negligible by a comparison of estimates of VInf by the Adrogué-Madias formula and by a formula using the same determinants of the change in [ Na ] and the curvilinear relation between this change and VInf . Regardless of the method used to correct hyponatremia, monitoring [ Na ] and changes in external balances of water, sodium, and potassium during treatment remain imperative.

Establishing Responsiveness and Minimal Clinically Important Difference of Quebec Back Pain Disability Scale (Hindi Version) in Chronic Low Back Pain Patients Undergoing Multimodal Physical Therapy.

Increasing emphasis is placed on physical functional measures to examine treatments for chronic low back pain (CLBP). The Quebec Back Pain Disability Scale (Hindi version) (QBPDS-H) has never been evaluated for responsiveness. The objectives of this study were to (1) examine the internal and external responsiveness of the Quebec Back Pain Disability Scale (Hindi version) (QBPDS-H) and (2) find out the minimal clinically important difference (MCID) and minimal detectable change (MDC) in the functional ability of patients with chronic low back pain (CLBP) undergoing multimodal physical therapy treatment. In this prospective cohort study, QBPDS-H responses were recorded at the baseline and after eight weeks from 156 CLBP patients undergoing multimodal physiotherapy treatment. To differentiate between the clinically unimproved (n = 65, age: 44.16 ± 11.8 years) and clinically improved (n = 91, age: 43.28 ± 10.7 years) scores of patients from the initial assessment to the last follow-up, the Hindi version of the Patient's Global Impression of Change (H-PGIC) scale was utilized. Internal responsiveness was large (E.S. (pooled S.D.) (n = 91): 0.98 (95% CI = 1.14-0.85) and Standardized Response Mean (S.R.M.) (n = 91): 2.57 (95% CI = 3.05-2.17)). In addition, the correlation coefficient and receiver operative characteristics (R.O.C.) curve were used to assess the QBPDS-H external responsiveness. MCID and MDC were detected by the R.O.C. curve and standard error of measurements (S.E.M.), respectively. The H-PGIC scale showed moderate responsiveness (ρ = 0.514 and area under the curve (A.U.C.) = 0.658; 95% CI, 0.596-0.874), while the MDC achieved 13.68 points, and the MCID was found have 6 points (A.U.C. = 0.82; 95% CI: 0.74-0.88, sensitivity = 90%, specificity = 61%). This study shows that QBPDS-H has moderate levels of responsiveness in CLBP patients receiving multimodal physical therapy treatment, so it can be used to measure the changes in disability scores. MCID and MDC changes were also reported with QBPDS-H.

Electronic Patient Portal Use After Kidney Transplant: A Single-Center Retrospective Study.

INTRODUCTION: Online patient portals have become a core component of patient-centered care. Limited research exists on such portal use in patients after kidney transplantation. The aim of this study was to examine preoperative, perioperative, and postoperative factors associated with post-transplantation portal use. METHODS: This cross-sectional study included all patients who underwent kidney transplantation from April 2016 to May 2019 at the University of Toledo Medical Center. Exclusion criteria included international travel for transplantation and those without available postoperative lab or follow-up records. Data were collected for 2 y post-transplantation. Univariable and multivariable linear regression was performed to determine associations with portal use. RESULTS: Two hundred and forty-seven kidney transplant recipients were included in the study; 35.6% (n = 88) used the portal versus 64.4% (n = 159) did not. Preoperative factors associated with increased use included income >$40,000 (odds ratio [OR], 2.95; P = 0.006) and cancer history (OR, 2.46; P = 0.007), whereas diabetes history had reduced use (OR, 0.51; P = 0.021). The Black race had the least use. Perioperatively, reduced use was associated with dialysis before transplant (OR, 0.25; P < 0.001) and hospital stay ≥4 d (OR, 0.49; P = 0.009). Postoperatively, associations with increased use included average eGFR >30 (P = 0.04) and hospital readmissions (n = 102), whereas those with ER (n = 138) visits had decreased use. Multivariable analysis revealed increased use with income >$40,000 (OR, 2.51; P = 0.033). CONCLUSIONS: There was no observed difference in clinical outcomes for portal users and nonusers undergoing kidney transplantation, although portal use may decrease the likelihood of ER visits. Socioeconomic status and ethnicity may play a role on who utilizes the patient portals.

Brain-type natriuretic peptide levels and invasive hemodynamic parameters in dialysis dependent patients.

BACKGROUND: Pulmonary hypertension (PH) is associated with increased mortality in patients with end-stage renal disease (ESRD). The prevalence of PH within ESRD as measured by right heart catheterization (RHC) is poorly described, and the correlation of BNP to pulmonary artery pressure (PAP) is unknown. METHODS: The renal transplant database at our center was used to identify adult ESRD patients from July 2013 to July 2015 who had a plasma BNP level measurement and invasive hemodynamic assessment by RHC within a 1-month period. Pulmonary hypertension was defined as a mean pulmonary artery pressure (PAP) ≥ 25 mmHg. Multivariate linear regression analysis was used to identify correlations between BNP and RHC parameters. To estimate the utility of BNP in the screening of PH, a receiver-operating characteristic (ROC) curve was generated. RESULTS: Eighty-eight patients were included in the study of which 43 had PH. Compared to patients without PH, BNP was significantly higher within the PH cohort (1619 ± 2602 pg/ml vs. 352 ± 491 pg/ml). A statistically significant association (r [86] = 0.60, p<0.001) between plasma BNP and mean PAP was identified. ROC curve indicated an acceptable predictive value of BNP in PH with a c-statistic of 0.800 (95% CI 0.708 - 0.892). CONCLUSIONS: In ESRD patients being considered for renal transplantation, PH is highly prevalent and BNP levels are elevated and significantly correlated with higher PAP. BNP may be a useful non-invasive marker of PH in these patients.

Hematopoietic-specific melanocortin 1 receptor signaling protects against nephrotoxic serum nephritis and mediates the beneficial effect of melanocortin therapy.

The melanocortin hormone system has emerged as a novel therapeutic target for treating refractory glomerular diseases. However, the role of hematopoietic melanocortin 1 receptor (MC1R) signaling remains unknown. Upon insult by rabbit nephrotoxic serum, MC1R null-mutant mice developed more severe crescentic glomerulonephritis than wild-type mice, marked by aggravated proteinuria, kidney dysfunction and histologic lesions. Melanocortin therapy, using Repository Corticotropin Injection (Acthar Gel), the pan-melanocortin receptor agonist NDP-MSH, or the MC1R agonist MS05, ameliorated experimental nephritis in wild-type mice but this effect was blunted in null mice. Exacerbated experimental nephritis in null mice was associated with increased glomerular deposition of autologous IgG and C5b-9, in parallel with higher circulating levels of autologous IgG2c and IgG3. Additionally, the Th1 immune response was potentiated in null mice with experimental nephritis, accompanied by diminished kidney FoxP3+ regulatory T cells. Kidney infiltration of macrophages was also augmented by MC1R deficiency with an enhanced M1 polarization. Moreover, adoptive transfer of syngeneic bone marrow-derived cells from wild-type mice mitigated experimental nephritis in null mice and restored the beneficial efficacy of melanocortins. Mechanistically, MC1R was expressed by diverse subsets of kidney leukocytes, including macrophages, T and B lymphocytes, and was inversely associated with the NFκB pathway, a key player in immune responses. MS05 attenuated the production of rabbit IgG-specific IgG2c and IgG3 in cultured wild-type splenocytes, and promoted M2 polarization in M1-primed wild-type macrophages, associated with NFκB inhibition. In contrast, in null splenocytes or macrophages, this effect of MS05 was barely detectable, but was mimicked by an NFκB inhibitor. Thus, hematopoietic MC1R signaling attenuates experimental nephritis and mediates the beneficial effect of melanocortin therapy via, in part, regulating the immune response.

The Time-Based Effects of Kinesio Taping on Acute-Onset Muscle Soreness and Calf Muscle Extensibility among Endurance Athletes: A Randomized Cross-Over Trial.

BACKGROUND: This study aims to determine the effects of kinesio tape (KT) application on acute-onset muscle soreness and the extensibility of the calf muscles in endurance athletes. METHODS: A one-arm repeated-measures randomized cross-over controlled study design investigated 55 endurance athletes, including 10 cyclists, 30 badminton players, and 15 long-distance runners (mean age 16.40 ± 2.69) from different stadia in Delhi NCR, India. KT and sham tapes (ST) were applied randomly to right and left legs (prone position) in a cross-over manner with a gap of 72 h. Ankle dorsiflexion range of motion (ADFROM) and pain due to acute-onset muscle soreness were assessed immediately and 10 min and 30 min after treadmill running, using a universal goniometer and numeric pain rating scale (NPRS), respectively, along with the time to fatigue. RESULTS: A statistically significant difference was observed for the NPRS when the mean scores obtained for the KT and ST groups were compared immediately after cessation of running; however, the difference was not statistically significant in the NPRS score that was recorded ten or thirty minutes after. The range of motion increased significantly after the application of both the KT and the ST. After running on a treadmill, the range of motion decreased significantly with both the KT and ST, and the decrease was similar. CONCLUSION: KT was more effective in reducing the pain intensity immediately after running and increased the time spent running on the treadmill before fatigue set in among endurance athletes. In addition, the two taping methods (KT or ST) were equally effective in enhancing calf muscle extensibility (for both right and left legs) immediately after application. However, both taping methods failed in limiting the decrease in ankle ADFROM after treadmill running.

Microcystin-LR aerosol induces inflammatory responses in healthy human primary airway epithelium.

Harmful algal blooms plague bodies of freshwater globally. These blooms are often composed of outgrowths of cyanobacteria capable of producing the heptapeptide Microcystin-LR (MC-LR) which is a well-known hepatotoxin. Recently, MC-LR has been detected in aerosols generated from lake water. However, the risk for human health effects due to MC-LR inhalation exposure have not been extensively investigated. In this study, we exposed a fully differentiated 3D human airway epithelium derived from 14 healthy donors to MC-LR-containing aerosol once a day for 3 days. Concentrations of MC-LR ranged from 100 pM to 1 µM. Although there were little to no detrimental alterations in measures of the airway epithelial function (i.e. cell survival, tissue integrity, mucociliary clearance, or cilia beating frequency), a distinct shift in the transcriptional activity was found. Genes related to inflammation were found to be upregulated such as C-C motif chemokine 5 (CCL5; log2FC = 0.57, p = 0.03) and C-C chemokine receptor type 7 (CCR7; log2FC = 0.84, p = 0.03). Functionally, conditioned media from MC-LR exposed airway epithelium was also found to have significant chemo-attractive properties for primary human neutrophils. Additionally, increases were found in the concentration of secreted chemokine proteins in the conditioned media such as CCL1 (log2FC = 5.07, p = 0.0001) and CCL5 (log2FC = 1.02, p = 0.046). These results suggest that MC-LR exposure to the human airway epithelium is capable of inducing an inflammatory response that may potentiate acute or chronic disease.

Cardioprotective Role for Paraoxonase-1 in Chronic Kidney Disease.

Paraoxonase-1 (PON-1) is a hydrolytic enzyme associated with HDL, contributing to its anti-inflammatory, antioxidant, and anti-atherogenic properties. Deficiencies in PON-1 activity result in oxidative stress and detrimental clinical outcomes in the context of chronic kidney disease (CKD). However, it is unclear if a decrease in PON-1 activity is mechanistically linked to adverse cardiovascular events in CKD. We investigated the hypothesis that PON-1 is cardioprotective in a Dahl salt-sensitive model of hypertensive renal disease. Experiments were performed on control Dahl salt-sensitive rats (SSMcwi, hereafter designated SS-WT rats) and mutant PON-1 rats (SS-Pon1em1Mcwi, hereafter designated SS-PON-1 KO rats) generated using CRISPR gene editing technology. Age-matched 10-week-old SS and SS-PON-1 KO male rats were maintained on high-salt diets (8% NaCl) for five weeks to induce hypertensive renal disease. Echocardiography showed that SS-PON-1 KO rats but not SS-WT rats developed compensated left ventricular hypertrophy after only 4 weeks on the high-salt diet. RT-PCR analysis demonstrated a significant increase in the expression of genes linked to cardiac hypertrophy, inflammation, and fibrosis, as well as a significant decrease in genes essential to left ventricular function in SS-PON-1 KO rats compared to SS-WT rats. A histological examination also revealed a significant increase in cardiac fibrosis and immune cell infiltration in SS-PON-1 KO rats, consistent with their cardiac hypertrophy phenotype. Our data suggest that a loss of PON-1 in the salt-sensitive hypertensive model of CKD leads to increased cardiac inflammation and fibrosis as well as a molecular and functional cardiac phenotype consistent with compensated left ventricular hypertrophy.

Antioxidant Therapy Significantly Attenuates Hepatotoxicity following Low Dose Exposure to Microcystin-LR in a Murine Model of Diet-Induced Non-Alcoholic Fatty Liver Disease.

We have previously shown in a murine model of Non-alcoholic Fatty Liver Disease (NAFLD) that chronic, low-dose exposure to the Harmful Algal Bloom cyanotoxin microcystin-LR (MC-LR), resulted in significant hepatotoxicity including micro-vesicular lipid accumulation, impaired toxin metabolism as well as dysregulation of the key signaling pathways involved in inflammation, immune response and oxidative stress. On this background we hypothesized that augmentation of hepatic drug metabolism pathways with targeted antioxidant therapies would improve MC-LR metabolism and reduce hepatic injury in NAFLD mice exposed to MC-LR. We chose N-acetylcysteine (NAC, 40 mM), a known antioxidant that augments the glutathione detoxification pathway and a novel peptide (pNaKtide, 25 mg/kg) which is targeted to interrupting a specific Src-kinase mediated pro-oxidant amplification mechanism. Histological analysis showed significant increase in hepatic inflammation in NAFLD mice exposed to MC-LR which was attenuated on treatment with both NAC and pNaKtide (both p ≤ 0.05). Oxidative stress, as measured by 8-OHDG levels in urine and protein carbonylation in liver sections, was also significantly downregulated upon treatment with both antioxidants after MC-LR exposure. Genetic analysis of key drug transporters including Abcb1a, Phase I enzyme-Cyp3a11 and Phase II metabolic enzymes-Pkm (Pyruvate kinase, muscle), Pklr (Pyruvate kinase, liver, and red blood cell) and Gad1 (Glutamic acid decarboxylase) was significantly altered by MC-LR exposure as compared to the non-exposed control group (all p ≤ 0.05). These changes were significantly attenuated with both pNaKtide and NAC treatment. These results suggest that MC-LR metabolism and detoxification is significantly impaired in the setting of NAFLD, and that these pathways can potentially be reversed with targeted antioxidant treatment.

False Positive Pregnancy Test Before Kidney Transplant: Case Report and Review of Literature.

Pregnancy tests are routinely done before any surgery under general anesthesia including kidney transplantation. Positive test usually leads to more investigations to detect a possible pregnancy or malignancy and the surgery gets canceled or postponed. Because a kidney transplant from a deceased donor is not elective, it usually gets canceled in this scenario. Some groups have reported on normally elevated human chorionic gonadotrophin (hCG) levels in perimenopausal women and in patients with chronic kidney disease. This is thought to be from the pituitary. We present a highly sensitized prospective kidney transplant recipient with a positive pregnancy test with low levels of serum human chorionic gonadotrophin. She underwent additional preoperative testing after which we proceeded with the kidney transplant. Herein, we discuss the management of patients who have an unexpected positive pregnancy test before transplant.

Dirty Jobs: Macrophages at the Heart of Cardiovascular Disease.

Cardiovascular disease (CVD) is one of the greatest public health concerns and is the leading cause of morbidity and mortality in the United States and worldwide. CVD is a broad yet complex term referring to numerous heart and vascular conditions, all with varying pathologies. Macrophages are one of the key factors in the development of these conditions. Macrophages play diverse roles in the maintenance of cardiovascular homeostasis, and an imbalance of these mechanisms contributes to the development of CVD. In the current review, we provide an in-depth analysis of the diversity of macrophages, their roles in maintaining tissue homeostasis within the heart and vasculature, and the mechanisms through which imbalances in homeostasis may lead to CVD. Through this review, we aim to highlight the potential importance of macrophages in the identification of preventative, diagnostic, and therapeutic strategies for patients with CVD.