Transcriptomic Modulation Reveals the Specific Cellular Response in Chinese Sea Bass (Lateolabrax maculatus) Gills under Salinity Change and Alkalinity Stress.

Salinity and alkalinity are among the important factors affecting the distribution, survival, growth and physiology of aquatic animals. Chinese sea bass (Lateolabrax maculatus) is an important aquaculture fish species in China that can widely adapt to diverse salinities from freshwater (FW) to seawater (SW) but moderately adapt to highly alkaline water (AW). In this study, juvenile L. maculatus were exposed to salinity change (SW to FW) and alkalinity stress (FW to AW). Coordinated transcriptomic responses in L. maculatus gills were investigated and based on the weighted gene co-expression network analysis (WGCNA), 8 and 11 stress-responsive modules (SRMs) were identified for salinity change and alkalinity stress, respectively, which revealed a cascade of cellular responses to oxidative and osmotic stress in L. maculatus gills. Specifically, four upregulated SRMs were enriched with induced differentially expressed genes (DEGs) for alkalinity stress, mainly corresponding to the functions of "extracellular matrix" and "anatomical structure", indicating a strong cellular response to alkaline water. Both "antioxidative activity" and "immune response" functions were enriched in the downregulated alkaline SRMs, which comprised inhibited alkaline specific DEGs, revealing the severely disrupted immune and antioxidative functions under alkalinity stress. These alkaline-specific responses were not revealed in the salinity change groups with only moderately inhibited osmoregulation and induced antioxidative response in L. maculatus gills. Therefore, the results revealed the diverse and correlated regulation of the cellular process and stress response in saline-alkaline water, which may have arisen through the functional divergence and adaptive recruitment of the co-expression genes and will provide vital insights for the development of L. maculatus cultivation in alkaline water.

Steroidogenic Effects of Salinity Change on the Hypothalamus-Pituitary-Gonad (HPG) Axis of Male Chinese Sea Bass (Lateolabrax maculatus).

As lower vertebrates, teleost species could be affected by dynamic aquatic environments and may respond to environmental changes through the hypothalamus-pituitary-gonad (HPG) axis to ensure their normal growth and sexual development. Chinese sea bass (Lateolabrax maculatus), euryhaline marine teleosts, have an extraordinary ability to deal with a wide range of salinity changes, whereas the salinity decrease during their sex-maturation season may interfere with the HPG axis and affect their steroid hormone metabolism, resulting in abnormal reproductive functioning. To this end, in this study, 40 HPG axis genes in the L. maculatus genome were systematically characterized and their copy numbers, phylogenies, gene structures, and expression patterns were investigated, revealing the conservation of the HPG axis among teleost lineages. In addition, freshwater acclimation was carried out with maturing male L. maculatus, and their serum cortisol and 11-ketotestosterone (11-KT) levels were both increased significantly after the salinity change, while their testes were found to be partially degraded. After salinity reduction, the expression of genes involved in cortisol and 11-KT synthesis (cyp17a, hsd3b1, cyp21a, cyp11c, hsd11b2, and hsd17b3) showed generally upregulated expression in the head kidneys and testes, respectively. Moreover, cyp11c and hsd11b2 were involved in the synthesis and metabolism of both cortisol and 11-KT, and after salinity change their putative interaction may contribute to steroid hormone homeostasis. Our results proved the effects of salinity change on the HPG axis and steroidogenic pathway in L. maculatus and revealed the gene interactions involved in the regulation of steroid hormone levels. The coordinated interaction of steroidogenic genes provides comprehensive insights into steroidogenic pathway regulation, as well as sexual development, in teleost species.

Polyacrylic acid grafted silica fume as an excellent adsorbent for dysprosium(III) removal from industrial wastewater.

In the development of industrial life, an enormous amount of silica fume (SF) has been accumulated and cannot be reused properly, and a large quantity of rare-earth elements in industrial wastewater has been inappropriately discharged, both of which pose a threat to human health and the environment. By using UV photocatalytic grafting technology, a polymer brush grafted from modified SF, which can be used as a high efficiency adsorbent, can solve both problems at the same time. Specifically, SF was firstly silanol-functionalized by γ-methacryloxypropyltrimethoxysilane (KH570), then grafted with polyacrylic acid brushes by UV photocatalytic grafting to finally obtain the adsorbent. Under optimal conditions, adsorption capacity of the adsorbent for dysprosium(III) (Dy3+) could reach 278.49 mg/g. It took 1 min for the adsorbent to reach adsorbing equilibrium at a relatively low concentration of Dy3+ (40 mg/L), and only 3 min at a medium and high concentration (130 mg/L and 200 mg/L). After six adsorption-desorption cycles, the adsorbent still possessed high adsorption capacity for Dy3+ (251.20 mg/g). The adsorption behavior of the adsorbent fit the Langmuir isotherm model (R2 > 0.97) and pseudo-second-order kinetic model (R2 > 0.98) well. The functional group of carboxylate anion, -COO-, played a central role during the adsorption process, which was verified by Fourier transform infrared and X-ray photoelectron spectroscopy analyses.

The ROKS nomogram for predicting a second symptomatic stone episode.

Most patients with first-time kidney stones undergo limited evaluations, and few receive preventive therapy. A prediction tool for the risk of a second kidney stone episode is needed to optimize treatment strategies. We identified adult first-time symptomatic stone formers residing in Olmsted County, Minnesota, from 1984 to 2003 and manually reviewed their linked comprehensive medical records through the Rochester Epidemiology Project. Clinical characteristics in the medical record before or up to 90 days after the first stone episode were evaluated as predictors for symptomatic recurrence. A nomogram was developed from a multivariable model based on these characteristics. There were 2239 first-time adult kidney stone formers with evidence of a passed, obstructing, or infected stone causing pain or gross hematuria. Symptomatic recurrence occurred in 707 of these stone formers through 2012 (recurrence rates at 2, 5, 10, and 15 years were 11%, 20%, 31%, and 39%, respectively). A parsimonious model had the following risk factors for recurrence: younger age, male sex, white race, family history of stones, prior asymptomatic stone on imaging, prior suspected stone episode, gross hematuria, nonobstructing (asymptomatic) stone on imaging, symptomatic renal pelvic or lower-pole stone on imaging, no ureterovesicular junction stone on imaging, and uric acid stone composition. Ten-year recurrence rates varied from 12% to 56% between the first and fifth quintiles of nomogram score. The Recurrence of Kidney Stone nomogram identifies kidney stone formers at greatest risk for a second symptomatic episode. Such individuals may benefit from medical intervention and be good candidates for prevention trials.

Adjuvant immunotherapy of experimental autoimmune encephalomyelitis: immature myeloid cells expressing CXCL10 and CXCL16 attract CXCR3+CXCR6+ and myelin-specific T cells to the draining lymph nodes rather than the central nervous system.

CFA is a strong adjuvant capable of stimulating cellular immune responses. Paradoxically, adjuvant immunotherapy by prior exposure to CFA or live mycobacteria suppresses the severity of experimental autoimmune encephalomyelitis (EAE) and spontaneous diabetes in rodents. In this study, we investigated immune responses during adjuvant immunotherapy of EAE. Induction of EAE in CFA-pretreated mice resulted in a rapid influx into the draining lymph nodes (dLNs) of large numbers of CD11b(+)Gr-1(+) myeloid cells, consisting of immature cells with ring-shaped nuclei, macrophages, and neutrophils. Concurrently, a population of mycobacteria-specific IFN-γ-producing T cells appeared in the dLNs. Immature myeloid cells in dLNs expressed the chemokines CXCL10 and CXCL16 in an IFN-γ-dependent manner. Subsequently, CD4(+) T cells coexpressing the cognate chemokine receptors CXCR3 and CXCR6 and myelin oligodendrocyte glycoprotein (MOG)-specific CD4(+) T cells accumulated within the chemokine-expressing dLNs, rather than within the CNS. Migration of CD4(+) T cells toward dLN cells was abolished by depleting the CD11b(+) cells and was also mediated by the CD11b(+) cells alone. In addition to altering the distribution of MOG-specific T cells, adjuvant treatment suppressed development of MOG-specific IL-17. Thus, adjuvant immunotherapy of EAE requires IFN-γ, which suppresses development of the Th17 response, and diverts autoreactive T cells away from the CNS toward immature myeloid cells expressing CXCL10 and CXCL16 in the lymph nodes.

Phenotypic characterization of kidney stone formers by endoscopic and histological quantification of intrarenal calcification.

Interstitial Randall's plaques and collecting duct plugs are distinct forms of renal calcification thought to provide sites for stone retention within the kidney. Here we assessed kidney stone precursor lesions in a random cohort of stone formers undergoing percutaneous nephrolithotomy. Each accessible papilla was endoscopically mapped following stone removal. The percent papillary surface area covered by plaque and plug were digitally measured using image analysis software. Stone composition was determined by micro-computed tomography and infrared analysis. A representative papillary tip was biopsied. The 24-h urine collections were used to measure supersaturation and crystal growth inhibition. The vast majority (99%) of stone formers had Randall's plaque on at least 1 papilla, while significant tubular plugging (over 1% of surface area) was present in about one-fifth of patients. Among calcium oxalate stone formers the amount of Randall's plaque correlated with higher urinary citrate levels. Tubular plugging correlated positively with pH and brushite supersaturation but negatively with citrate excretion. Lower urinary crystal growth inhibition predicted the presence of tubular plugging but not plaque. Thus, tubular plugging may be more common than previously recognized among patients with all types of stones, including some with idiopathic calcium oxalate stones.

Effect of age on the clinical presentation of incident symptomatic urolithiasis in the general population.

PURPOSE: We characterized variation in the clinical presentation between older and younger first time symptomatic stone formers in the general population. MATERIALS AND METHODS: We studied a random sample of Olmsted County, Minnesota residents with their first diagnostic code for urolithiasis between 1984 and 2003. Chart validated symptomatic stone formers had a confirmed stone by imaging or stone passage. Clinical presentation characteristics were compared between age groups. RESULTS: Among the 3,473 charts reviewed there were 1,590 validated incident symptomatic stone formers (mean age 43 years, range 18 to 96). Older individuals were more likely to present with atypical or no pain, fever, diarrhea, pyuria, urinary tract infections and bacteremia (p <0.001). Stone size and location did not differ by patient age. Calcium phosphate stone disease was associated with younger age, while uric acid stone and atypical stone composition was associated with older age (p <0.001). Older individuals were less likely to pass the stone spontaneously and were more likely to require surgical intervention (p <0.001). Surgical intervention was required in 516 (32.5%) individuals. Younger individuals were more likely to undergo ureteroscopy while older individuals were more likely to undergo shock wave lithotripsy, temporizing stent placement and percutaneous nephrolithotomy. CONCLUSIONS: The detection of stone disease in older individuals can be challenging due to atypical pain or absence of pain, as well as the presence of other comorbid conditions such as urinary tract infections and diarrhea. A higher index of suspicion for urolithiasis may be needed in the elderly for a more timely diagnosis and intervention to prevent morbidity.

Characteristics of children with asthma who achieved remission of asthma.

OBJECTIVE: To characterize two groups of asthmatics who had achieved remission and those who had not achieved remission of asthma. METHODS: The study was a retrospective cohort study based on 117 asthmatic children who participated in a previous study. We categorized the children into two groups: asthmatics with remission versus asthmatics without remission. We defined remission of asthma as lack of symptoms/signs of asthma or asthma-related medications or health care services for at least three consecutive years. Long-term remission was defined by no relapse of asthma after achieving remission. We characterized these groups. RESULTS: Of the 117 subjects, 70 (60%) were male, 91 (78%) were Caucasians, and the mean age at index date of asthma was 8.1 years. A total of 59 asthmatic children (50%) achieved remission and 28 asthmatics (24%) achieved long-term remission. Asthmatics with remission were more likely to be Caucasian (87%) compared to those without (69%) (p = .039) There were no differences in the frequency of visits for viral (0.3 vs. 0.4 per person-years, p = .29) or bacterial infections (0.7 vs. 0.5 per person-years, p = .49) between asthmatics with and without remission. Gender, socioeconomic status, smoking exposure, family history of asthma or atopy, breastfeeding history, peak flow meter availability, asthma action plan, and influenza vaccinations were not associated with remission. CONCLUSIONS: Only half of asthmatic children accomplished remission of asthma ever and 24% of asthmatic children had long-term remission. Ethnicity may affect remission of asthma but microbial infections may not influence the likelihood of remission of asthma and vice versa.

Wool keratin/zeolitic imidazolate framework-8 composite shape memory sponge with synergistic hemostatic performance for rapid hemorrhage control.

Uncontrollable hemorrhage and subsequent wound infection pose severe threats to life, especially in the case of deep, non-compressible, massive bleeding. Here, a wool keratin/zeolitic imidazolate framework-8 (WK/ZIF-8) composite shape memory sponge is prepared by incorporating ZIF-8 nanoparticles into wool keratin. The combination of keratin and ZIF-8 particles not only reduces the effect of ZIF-8 particles on cell viability but also bolsters the mechanical properties of the keratin sponge and endows it with antibacterial efficacy. Due to the synergistic effect of the excellent hemostatic performance of keratin and Zn2+ release from ZIF-8 nanoparticles, the porous structure suitable for blood cell adhesion and the shape recovery ability of sponges, the WK/ZIF-8 composite sponge exhibits superior hemostatic performance to commercial medical sponges in SD rat and rabbit hemorrhage models. In addition, in vitro and in vivo antibacterial experiments demonstrate the anti-infection activity of the composite sponge. Overall, the WK/ZIF-8 composite sponge provides a promising approach to rapidly control bleeding and promote wound healing.

Polydopamine functionalized polyurethane shape memory sponge with controllable expansion performance triggered by near-infrared light for incompressible hemorrhage control.

Uncontrolled expansion of shape memory sponges face a significant challenge in the treatment of lethal incompressible hemorrhage, which can lead to blood overflow or damage to the surrounding tissue. Herein, we developed a polydopamine functionalized polyurethane shape memory sponge (PDA-TPI-PU) with a controllable degree of expansion by near-infrared (NIR) light-triggered stimulation for the treatment of incompressible hemorrhage. The sponge has excellent liquid absorption performance and robust mechanical strength as well as good photothermal conversion ability. Under NIR light of 0.32 W/cm2, the maximum recovery rate of the fixed-shape compression sponge was 91% within 25 s in air and 80% within 25 s in blood. In the SD rat liver penetrating injury model, compared with commercial medical gelatin sponge and PVA sponge, the PDA-TPI-PU sponge could effectively control the bleeding under the NIR light irradiation and did not cause excessive compression of the wound. The sponge with these characteristics shows potential application prospects as a hemostatic material.

Gelatin Methacryloyl-Based Sponge with Designed Conical Microchannels for Rapidly Controlling Hemorrhage and Theoretical Verification.

It remains a challenge to develop effective hemostatic products in battlefield rescue for noncompressible massive hemorrhage. Some previous research had concentrated on the modification of different materials to improve the hemostasis ability of sponges. Herein, to investigate the relationship between the taper of microchannels and hemostatic performance of porous sponges, gelatin methacryloyl-based sponges with designed conical microchannels and a disordered porous structure were prepared using the 3D printing method and freeze-drying technology. Experiments and theoretical model analysis demonstrated that the taper and distribution of microchannels in the sponge affected the water and blood absorption properties, as well as the expansion ability. In treatment of SD rat liver defect and SD rat liver perforation wound, GS-1 sponge with the taper (1/15) microchannels exhibited an excellent hemostatic effect with blood loss of 0.866 ± 0.093 g and a hemostasis time of 280 ± 10 s. Results showed that the hemostatic capacities of GelMA sponges were increased with the bottom diameter (taper) of conical microchannels. This is a potential strategy to develop designed taper sponges with designed taper microchannels for rapidly controlling hemorrhage.

Regulation of antigen-expressing dendritic cells by double negative regulatory T cells.

TCRαß(+) CD3(+) CD4(-) CD8(-) NK1.1(-) double negative (DN) Tregs comprise 1-3% of peripheral T lymphocytes in mice and humans. It has been demonstrated that DN Tregs can suppress allo-, xeno- and auto-immune responses in an Ag-specific fashion. However, the mechanisms by which DN Tregs regulate immune responses remain elusive. Whether DN Tregs can regulate DCs has not been investigated previously. In this study, we demonstrate that DN Tregs express a high level of CTLA4 and are able to down-regulate costimulatory molecules CD80 and CD86 expressed on Ag-expressing mature DCs (mDCs). DN Tregs from CTLA4 KO mice were not able to downregulate CD80 and CD86 expression, indicating that CTLA4 is critical for DN Treg-mediated downregulation of costimulatory molecule expression on Ag-expressing mature DCs. Furthermore, DN Tregs could kill both immature and mature allogeneic DCs, as well as Ag-loaded syngeneic DCs, in an Ag-specific manner in vitro and in vivo, mainly through the Fas-FasL pathway. These data demonstrate, for the first time, that DN Tregs are potent regulators of DCs and may have the potential to be developed as a novel immune suppression treatment.

Somatostatin analog therapy for severe polycystic liver disease: results after 2 years.

BACKGROUND: We showed in a randomized double-blinded placebo-controlled clinical trial that octreotide long-acting repeatable depot.® (OctLAR(®)) for 12 months reduces kidney and liver growth in autosomal dominant polycystic kidney patients with severe polycystic liver disease (PLD) and liver growth in patients with severe isolated PLD. We have now completed an open-label extension for one additional year to assess safety and clinical benefits of continued use of OctLAR for 2 years (O → O) and examined drug effect in the placebo group who crossed over to OctLAR in Year 2 (P → O). METHODS: The primary end point was change in total liver volume (TLV) measured by magnetic resonance imaging (MRI); secondary end points were changes in total kidney volume (TKV) measured by MRI, glomerular filtration rate (GFR), quality of life (QOL), safety, vital signs and laboratory parameters. RESULTS: Forty-one of 42 patients received OctLAR (n = 28) or placebo (n = 14) in Year 1 and received OctLAR in Year 2 (maximum dose 40 mg). Patients originally randomized to placebo (P → O) showed substantial reduction in TLV after treatment with OctLAR in Year 2 (Δ% -7.66 ± 9.69%, P = 0.011). The initial reduction of TLV in the OctLAR group (O → O) was maintained for 2 years (Δ% -5.96 ± 8.90%), although did not change significantly during Year 2 (Δ% -0.77 ± 6.82%). OctLAR inhibited renal enlargement during Year 1 (Δ% +0.42 ± 7.61%) in the (O → O) group and during Year 2 (Δ% -0.41 ± 9.45%) in the (P → O) group, but not throughout Year 2 (Δ% +6.49 ± 7.08%) in the (O → O) group. Using pooled analyses of all individuals who received OctLAR for 12 months, i.e. in Year 1 for O → O patients and Year 2 for P → O patients, average reduction in TLV was -6.08 ± 7.58% (P = 0.001) compared to net growth of 0.9 ± 8.35% in the original placebo group. OctLAR-treated individuals continued to experience improvements in QOL in Year 2, although overall physical and mental improvements were not significant during Year 2 compared to Year 1. Changes in GFR were similar in both groups. CONCLUSION: Over 2 years, OctLAR significantly reduced the rate of increase in TLV and possibly the rate of increase in TKV.

Impact of delay in asthma diagnosis on chest X-ray and antibiotic utilization by clinicians.

OBJECTIVE: To evaluate the effect of the timeliness of asthma diagnosis on chest X-ray (CXR) and antibiotic utilization in children. PATIENTS AND METHODS: This was a retrospective cohort study of 276 asthmatic children aged 5-12 years from Rochester, Minnesota. From the time when children met our predetermined asthma criteria, the frequency of CXR and antibiotic utilizations for respiratory illnesses were collected from medical records until age 18 years. Using a Poisson regression model, the frequency of CXR and antibiotic utilizations were compared in children with timely, delayed, or no clinician diagnosis of asthma. RESULTS: Of the 276 asthmatic patients, 97 (35%) had a timely diagnosis, 122 (44%) had a delayed diagnosis, while 57 patients (21%) had no clinician diagnosis of asthma. There was no significant difference in CXR or antibiotic utilization for respiratory illness between these groups. In addition, this was true for the comparison between the timely diagnosed group and the delayed diagnosed group combining both the group with a delay in asthma diagnosis and the group who never had asthma diagnosis. CONCLUSIONS: A delay in the diagnosis of asthma in children is common and overall it may not influence antibiotic and CXR utilization for respiratory symptoms by clinicians. However, its impact on access to asthma-related therapies and other healthcare utilizations could be possible and was not assessed in this study. Given the limitations of our study, a larger prospective study needs to be considered.

Assessment of the association between atopic conditions and tympanostomy tube placement in children.

This study assesses the relationship between otitis media and atopic conditions in children by comparing the incidence of tympanostomy tube placement between children with and without atopic conditions: asthma, allergic rhinitis, and atopic dermatitis. Study subjects were a cohort of 323 healthy children who participated in a study of vaccine response. All episodes of tympanostomy tube placement and physician diagnoses of allergic rhinitis and atopic dermatitis were collected through comprehensive medical record review. Asthma status was ascertained through application of established criteria. We compared incidence rates of tympanostomy tube placement between children with and without atopic conditions. We fitted data to a Poisson regression model to calculate relative risk ratios (RRs) and their corresponding 95% confidence intervals (95% CI). Three subjects were excluded who did not have parental authorization for using records for research. Of the remaining 320 subjects, 170 (53%) were male subjects, 268 (94%) were white, 124 (39%) were asthmatic patients, and 20 (6%) had tympanostomy tube placement. Children with asthma before the index date of tympanostomy tube placement were more likely to have tympanostomy tube placement compared with those without asthma (RR, 19.33; 95% CI, 11.41; 32.75; p < 0.001). We found a similar association between asthma ever (before or after index date) and the incidence of tympanostomy tube placement (RR, 1.53; 95% CI, 0.93-2.53; p = 0.095). This was true for children with allergic rhinitis compared with those without allergic rhinitis (RR, 1.70; 95% CI, 1.01-2.86; p = 0.007). Atopic dermatitis was not associated with the incidence of tympanostomy tube placement. Asthma or allergic rhinitis may be unrecognized risk factors for recurrent or persistent otitis media. However, given the small sample size of the study, a cohort study with a larger sample size is necessary.

Streptococcus pyogenes upper respiratory infection and atopic conditions other than asthma: a retrospective cohort study.

BACKGROUND: Patients with asthma have an increased risk of Streptococcus pyogenes infection compared with those without asthma. It is unknown whether this is true for children with other atopic conditions such as atopic dermatitis or allergic rhinitis. AIMS: To determine the risk of developing S. pyogenes infections of the upper respiratory tract in children and adolescents with atopic dermatitis and/or allergic rhinitis. METHODS: We conducted a retrospective cohort study that followed a convenience sample of 340 healthy children. Atopic dermatitis or eczema and allergic rhinitis or hay fever were determined based on a physician diagnosis documented in medical records. All laboratory test results of cultures, rapid antigen detection, and polymerase chain reaction tests for S. pyogenes infections during the first 18 years of life were collected to compare the incidence of S. pyogenes infections between children with and without a physician diagnosis of atopic conditions. A Poisson regression was fit to determine the association between asthma and S. pyogenes infections, controlling for other covariates including asthma. RESULTS: Of the 340 subjects, 327 were eligible for the study. Of these 327 subjects, 143 (44%) had atopic conditions other than asthma. The incidence of S. pyogenes infections in children with atopic conditions other than asthma and those without atopic conditions was 0.24 per person-year and 0.18 per person-year, respectively. The adjusted risk ratios for allergic rhinitis and atopic dermatitis were 1.36 (95% CI 1.07 to 1.66, p=0.011) and 1.30 (95% CI 0.98 to 1.71, p=0.06), respectively, controlling for asthma and other covariates. CONCLUSIONS: In addition to asthma, allergic rhinitis but not atopic dermatitis is associated with an increased risk of S. pyogenes upper respiratory tract infections.

Genomic and Transcriptomic Landscape and Evolutionary Dynamics of Heat Shock Proteins in Spotted Sea Bass (Lateolabrax maculatus) under Salinity Change and Alkalinity Stress.

The heat shock protein (Hsp) superfamily has received accumulated attention because it is ubiquitous and conserved in almost all living organisms and is involved in a wide spectrum of cellular responses against diverse environmental stresses. However, our knowledge about the Hsp co-chaperon network is still limited in non-model organisms. In this study, we provided the systematic analysis of 95 Hsp genes (LmHsps) in the genome of spotted sea bass (Lateolabrax maculatus), an important aquaculture species in China that can widely adapt to diverse salinities from fresh to sea water, and moderately adapt to high alkaline water. Through in silico analysis using transcriptome and genome database, we determined the expression profiles of LmHsps in response to salinity change and alkalinity stress in L. maculatus gills. The results revealed that LmHsps were sensitive in response to alkalinity stress, and the LmHsp40-70-90 members were more actively regulated than other LmHsps and may also be coordinately interacted as co-chaperons. This was in accordance with the fact that members of LmHsp40, LmHsp70, and LmHsp90 evolved more rapidly in L. maculatus than other teleost lineages with positively selected sites detected in their functional domains. Our results revealed the diverse and cooperated regulation of LmHsps under alkaline stress, which may have arisen through the functional divergence and adaptive recruitment of the Hsp40-70-90 co-chaperons and will provide vital insights for the development of L. maculatus cultivation in alkaline water.

Shock wave lithotripsy is not predictive of hypertension among community stone formers at long-term followup.

PURPOSE: Concern exists over the subsequent development of hypertension after shock wave lithotripsy for the treatment of symptomatic urolithiasis. Referral bias and lack of long-term followup have been limitations of prior studies. MATERIALS AND METHODS: We identified all Olmsted County, Minnesota residents with a diagnosis of urolithiasis from 1985 to 2008. The charts were electronically queried for hypertension and obesity by diagnostic codes, and use of shock wave lithotripsy by surgical codes. All patients first diagnosed with hypertension before or up to 90 days after the first documented kidney stone were considered to have prevalent hypertension and were excluded from analysis. Cox proportional hazards models were used to assess the association of shock wave lithotripsy with a subsequent diagnosis of hypertension. RESULTS: We identified 6,077 patients with incident urolithiasis with more than 90 days of followup. We excluded 1,295 (21.3%) members of the population for prevalent hypertension leaving 4,782 patients with incident urolithiasis for analysis. During an average followup of 8.7 years new onset hypertension was diagnosed in 983 (20.6%) members of the cohort at a mean of 6.0 years from the index stone date. Only 400 (8.4%) patients in the cohort were treated with shock wave lithotripsy. There was no significant association between shock wave lithotripsy and the development of hypertension in univariate (p = 0.33) and multivariate modeling controlling for age, gender and obesity (HR 1.03; 95% CI 0.84, 1.27; p = 0.77). CONCLUSIONS: In a large population based cohort of kidney stone formers we failed to identify an association between shock wave lithotripsy and the subsequent long-term risk of hypertension.

Incidence and timing of venous thromboembolism after surgery for gynecological cancer.

OBJECTIVE: This study aims to determine the incidence, timing, and risk factors of clinical venous thromboembolism. METHODS: A cohort of patients who had major gynecologic cancer surgery between 1998 and 2008 was identified. Secondarily, a nested case-control design wherein patients who had clinical VTE within 90 days after surgery were considered cases. Controls were matched on age, race, surgery date, and cancer site. Risk factors were evaluated for VTE within 90 days, and late VTE between 8 and 90 days. RESULTS: We identified 4158 women, 18 years or older, without a history of recent thrombosis. We observed 126 cases of clinical VTE within 90 days of surgery (incidence 4%) of which 96 (76%) occurred after post-operative day 7. In a multivariable model including age, ASA, BMI, race, and site of cancer, only ovarian cancer was a significant predictor for VTE within 90 days (HR 2.8; 95% CI 1.6, 5.0). In the nested case-control study, we identified hospital stay ≥ 5 days (OR 2.8; 95% CI 1.5, 5.1) and prior VTE (OR 2.6; 95% CI 1.1, 6.1) as significant risk factors for VTE within 90 days. Only hospital stay ≥ 5 days (OR 2.5; 95% CI 1.3, 4.7) was significantly associated with late VTE between 8 and 90 days. CONCLUSION: In gynecologic cancer patients, over 75% of VTE are detected more than 7 days after surgery. Patients with ovarian cancer, prolonged hospitalization, or a history of VTE are at highest risk of developing clinical VTE. Such patients would be optimal candidates for clinical trials evaluating extended VTE prophylaxis.