Differential impact of high-salt levels in vitro and in vivo on macrophage core functions.

The consumption of processed food is on the rise leading to huge intake of excess dietary salt, which strongly correlates with development of hypertension, often leading to cardiovascular diseases such as stroke and heart attack, as well as activation of the immune system. The effect of salt on macrophages is especially interesting as they are able to sense high sodium levels in tissues leading to transcriptional changes. In the skin, macrophages were shown to influence lymphatic vessel growth which, in turn, enables the transport of excess salt and thereby prevents the development of high blood pressure. Furthermore, salt storage in the skin has been linked to the onset of pro-inflammatory effector functions of macrophages in pathogen defence. However, there is only little known about the mechanisms which are involved in changing macrophage function to salt exposure. Here, we characterize the response of macrophages to excess salt both in vitro and in vivo. Our results validate and strengthen the notion that macrophages exhibit chemotactic migration in response to salt gradients in vitro. Furthermore, we demonstrate a reduction in phagocytosis and efferocytosis following acute salt challenge in vitro. While acute exposure to a high-salt diet in vivo has a less pronounced impact on macrophage core functions such as phagocytosis, our data indicate that prolonged salt challenge may exert a distinct effect on the function of macrophages. These findings suggest a potential role for excessive salt sensing by macrophages in the manifestation of diseases related to high-salt diets and explicitly highlight the need for in vivo work to decipher the physiologically relevant impact of excess salt on tissue and cell function.

Half-life of serum anti-Müllerian hormone and changes after gonadectomy in adult female and male dogs with normal and abnormal gonads.

Anti-Müllerian hormone (AMH) is a biomarker for the presence of gonadal tissue. Changes in serum AMH after gonadectomy are not well established, and its serum half-life is unknown in dogs. We measured serum AMH with a validated electro-chemiluminescent immunoassay in adult female (n = 12) and male (n = 7) dogs with normal gonads, as well as in dogs with gonadal pathology (ovarian remnant syndrome, ORS n = 3, testicular tumor [Leydig cell, Sertoli cell, seminoma] n = 3, unilateral abdominal cryptorchid n = 4) on the day of gonadectomy (D0), and on D3, D7, D14 (females and males), and D21, D28 (males only). Males had higher AMH concentrations than females independent of gonadal status (P < 0.001). Dogs with ORS had lower initial AMH (0.45 ± 0.43 ng/ml) than bitches with normal gonads (1.16 ± 0.44 ng/ml; P = 0.027). Cryptorchid dogs had higher initial concentrations (80.57 ± 52.81 ng/ml) than males with normal gonads (7.92 ± 2.45 ng/ml; P = 0.004), and those with testicular tumors (18.63 ± 5.04 ng/ml) were intermediate (P ≥ 0.250). AMH decreased over time (P ≤ 0.012) and was 0.01-0.04 ng/ml by D14 in females and 0.02-0.12 ng/ml by D28 in males. Serum half-life in the whole study population was 2.85 ± 0.51 days and did not differ between groups. In conclusion, serum AMH can differentiate between intact and gonadectomized status of adult dogs by 14 days after ovario(hyster)ectomy in females and by 28 days after surgical castration in males.

Effects of different cryopreservation methods on canine isolated preantral follicles.

The aim of the present study was to compare the survival and developmental rate of canine isolated preantral follicles (PAFs) after cryopreservation with different methods (closed vs open vitrification). Follicles were isolated from ovaries randomly divided into three groups: fresh control, OPS (open pulled straw) vitrified and cryotube (CT) vitrified. Post-thaw viability of follicles and oocytes was assessed. Fresh and vitrified/thawed PAFs were cultured in 20 µl drops of FSH-supplemented medium for 10 days. Follicular growth, survival rate, estradiol production and ovulation rate were examined. CT method resulted in lower rate of live cells (58.7%) and oocytes (38.8%) than that of fresh ones (83.6% and 64%, respectively) and OPS (80.3% and 79.3%, respectively). Survival rate was similar to fresh follicles in OPS group (98.5% and 95.4%, respectively), while CT decreased the survival to 81.2%. Fresh follicles showed continuous growth, while CT follicles stopped to increase their size after 2 day. In the OPS vitrified follicles, this halting occurred between Day5 and Day10. Fresh follicles showed the highest estradiol production (range: 26.9 - 266.2 pg/ml). Comparing the two vitrified groups, lower estradiol concentration range was measured in the CT group (7.8-48.7 pg/ml vs. 15.4-89.6 pg/ml). Ovulation rate in each group was lowest in the OPS group (1.7% vs 7% and 8.9% in fesh and CT, respectively). Our data show that OPS vitrification provides superior survival rate, in vitro growth and hormonal production to CT. To our knowledge, these are the first results on comparing different cryopreservation protocols on canine isolated preantral follicles.

Primary Urinary Bladder Tumors in Three Guinea Pigs (Cavia Porcellus).

Urinary bladder tumors are not common in guinea pigs, but case numbers being diagnosed have increased in the past years. The authors present 3 referred cases of primary urinary bladder tumors in pet guinea pigs diagnosed using diagnostic imaging (CT, radiography, and ultrasonography) and exploratory laparotomy. Excision was not possible in the first case as the tumor was located at the neck of the urinary bladder and the owner opted for intraoperative euthanasia. The second and third cases both had tumors originating from the apex of the urinary bladder. The third guinea pig went into cardiac arrest during surgery and resuscitation was unsuccessful. The tumor was removed from the urinary bladder using partial cystectomy in the second case and 1-month postsurgery ultrasonographic examination showed no signs of tumor reoccurrence. Late recognition is the main reason for a negative outcome, as by this time tumors are already large and extensive. Whenever prolonged symptoms of hematuria are present and urolithiasis has been ruled out, ultrasonography should be undertaken to determine if a urinary tumor is the cause. Rechecks should be scheduled on a regular basis for guinea pigs when a definitive diagnosis can not be made at the initial presentation for vague clinical signs, as outcome and survival can reduce significantly when definitive treatment is delayed.

Albuminuria and proteinuria in dogs infected with Dirofilaria repens: A cross-sectional study.

BACKGROUND: It is unknown whether Dirofilaria repens is capable of causing similar glomerular lesions, as does Dirofilaria immitis. OBJECTIVE: To determine whether D. repens infection could cause albuminuria or proteinuria. ANIMALS: Sixty-five clinically healthy laboratory beagle dogs. METHODS: In this cross-sectional study, dogs were tested for D. repens infection (modified Knott test, PCR test, D. immitis antigen test) and were grouped as "D. repens infected" or "control" dogs. Urinary albumin-to-creatinine ratio (UAC) and urinary protein-to-creatinine ratio (UPC) were measured from samples taken by cystocentesis. RESULTS: Forty-three (26 infected, 17 control) dogs were included in the final study group. UAC but not UPC level was significantly higher in the infected group (UAC median 12.5; range, 0-700 mg/g and UPC median 0.15; range, 0.06-1.06) than in the control group (UAC median 6.3; range, 0-28 mg/g and UPC median 0.13; range, 0.05-0.64; P = .02 and P = .65). Overt proteinuria (UPC > 0.5) was present in 6/26 (23%) of the infected dogs and 1/17 (6%) of the control dogs. Albuminuria (UAC > 19 mg/g) was detected in 9/26 (35%) dogs in the infected group, and 2/17 dogs (12%) in the control group. CONCLUSIONS AND CLINICAL IMPORTANCE: D. repens might cause similar glomerular lesions to those caused by D. immitis.

Testicular Expression of Antioxidant Enzymes and Changes in Response to a Slow-Release Deslorelin Implant (Suprelorin® 4.7 mg) in the Dog.

Spermatogenesis takes place in a hypoxic environment, and antioxidant enzymes protect germ and somatic cells from free radical-mediated damage. Expression of the antioxidant enzyme system in the canine testis has not yet been investigated. We hypothesized that the slow-release GnRH superagonist deslorelin 4.7 mg implant, which induces temporary reversible suppression of endocrine and germinative testicular function, would affect the testicular expression of antioxidant enzymes compared to untreated adult and prepubertal dogs. The goal of this study was to investigate and compare gene (by qPCR, in whole-tissue homogenates) and protein expression (by immunohistochemistry) of superoxide dismutase (SOD1, SOD2), catalase (CAT), glutathione peroxidase (GPx1), and glutathione disulfide reductase (GSR) in the testes of untreated adult (CON, n = 7), prepubertal (PRE, n = 8), and deslorelin-treated (DES, n = 5, 16 weeks after implantation) dogs. We found that in DES dogs, the gene expression of SOD1 was significantly (p < 0.05) lower and GPx1 was higher than in CON, and SOD2 was higher than in PRE. Expression of all, except for the SOD2 mRNA, differed between the CON and PRE dogs. Immunohistochemistry showed distinct cell-specific localization and expression patterns for the antioxidant enzymes in each experimental group. Additionally, in the CON animals, cell-specific SOD1, CAT, and GSR expression was dependent on the stage of the seminiferous epithelium cycle. These findings confirm that members of the antioxidant enzyme system are present in normal adult and prepubertal testis as well as in the deslorelin-treated downregulated adult canine testis, and that this local antioxidant system protects developing germ cells and somatic cells from oxidative damage. Different expression patterns of antioxidant enzymes in various germ cell populations and stages of the seminiferous epithelium cycle may indicate differences in their susceptibility to oxidative stress depending on their developmental and maturation stage. The continued presence of the antioxidant enzymes in the testis of DES dogs offers protection to spermatogonia as well as Sertoli and Leydig cells from oxidative stress during temporary infertility, potentially contributing to ensure the reversibility of suppression and the return of normal spermatogenesis and steroidogenesis after the end of deslorelin treatment.

Picomolar detection limits for glyphosate by two-dimensional column-coupled isotachophoresis/capillary zone electrophoresis-mass spectrometry.

Capillary electrophoresis-mass spectrometry often lacks sufficient limits of detection for trace substances in the environment due to its low loadability. To overcome this problem, we conducted a feasibility study for column-coupling isotachophoresis to capillary electrophoresis-mass spectrometry. The first dimension isotachophoresis preconcentrated the analytes. The column-coupling of both dimensions was achieved by a hybrid capillary microfluidic chip setup. Reliable analyte transfer by voltage switching was enabled by an in-chip capacitively coupled contactless conductivity detector placed around the channel of the common section between two T-shaped crossings in the chip connecting both dimensions. This eliminated the need to calculate the moment of analyte transfer. A commercial capillary electrophoresis-mass spectrometry instrument with easily installable adaptations operated the setup. Prior to coupling isotachophoresis with capillary zone electrophoresis-mass spectrometry, both dimensions were optimized individually by simulations and verified experimentally. Both dimensions were able to stack/separate all degradation products of glyphosate, the most important herbicide applied worldwide. The first dimension isotachophoresis also removed phosphate, which is a critical matrix component in many environmental samples. Enrichment and separation of glyphosate and its main degradation product aminomethylphosphonic acid by the two-dimensional setup provided an excellent limit of detection of 150 pM (25 ng/L) for glyphosate.

Stemness Correlates Inversely with MHC Class I Expression in Pediatric Small Round Blue Cell Tumors.

Recently, immunotherapeutic approaches have become a feasible option for a subset of pediatric cancer patients. Low MHC class I expression hampers the use of immunotherapies relying on antigen presentation. A well-established stemness score (mRNAsi) was determined using the bulk transcriptomes of 1134 pediatric small round blue cell tumors. Interestingly, MHC class I gene expression (HLA-A/-B/-C) was correlated negatively with mRNAsi throughout all diagnostic entities: neuroblastomas (NB) (n = 88, r = −0.41, p < 0.001), the Ewing's sarcoma family of tumors (ESFT) (n = 117, r = −0.46, p < 0.001), rhabdomyosarcomas (RMS) (n = 158, r = −0.5, p < 0.001), Wilms tumors (WT) (n = 224, r = −0.39, p < 0.001), and central nervous system-primitive neuroectodermal tumors CNS-PNET (r = −0.49, p < 0.001), with the exception of medulloblastoma (MB) (n = 76, r = −0.24, p = 0.06). The negative correlation of MHC class I and mRNAsi was independent of clinical features in NB, RMS, and WT. In NB and WT, increased MHC class I was correlated negatively with tumor stage. RMS patients with a high expression of MHC class I and abundant CD8 T cells showed a prolonged overall survival (n = 148, p = 0.004). Possibly, low MHC class I expression and stemness in pediatric tumors are remnants of prenatal tumorigenesis from multipotent precursor cells. Further studies are needed to assess the usefulness of stemness and MHC class I as predictive markers.

Establishment of a reference interval for urinary albumin-to-creatinine ratio in dogs.

BACKGROUND: Albuminuria is an important marker of renal damage and can precede proteinuria; thus, it can be a useful analyte in the early diagnosis of kidney diseases. Albuminuria has also been found in dogs with hypertension, inflammatory, infectious, and neoplastic diseases. OBJECTIVES: The aim of this study was to establish a reference interval (RI) for albuminuria in dogs. METHODS: One hundred sixty-four clinically healthy dogs were enrolled in the study. Urinary albumin was determined by the immunoturbidimetric method, and albumin excretion was expressed as the urinary albumin-to-creatinine (UAC) ratio. The RI for UAC was established. RESULTS: After exclusions, 124 dogs from 32 breeds remained. The median UAC of the study population was 3.0 mg/g (range: 0-48). The RI was defined as 0-19 mg/g (with a 90% CI for the upper limit of 13-28 mg/g). No significant difference was found between male and female dogs or between different age and body weight groups. The results of Sighthounds (n = 30) and Beagle dogs (n = 23) did not differ from the other breeds. CONCLUSION: The canine RI of UAC is similar but somewhat narrower than the human RI.

Altered Intestinal Production of Volatile Fatty Acids in Dogs Triggered by Lactulose and Psyllium Treatment.

The intestinal microbiome of dogs can be influenced by a number of factors such as non-starch polysaccharides as well as some non-digestible oligo- and disaccharides. These molecules are only decomposed by intestinal anaerobic microbial fermentation, resulting in the formation of volatile fatty acids (VFAs), which play a central role in maintaining the balance of the intestinal flora and affecting the health status of the host organism. In the present study, the effects of lactulose and psyllium husk (Plantago ovata) were investigated regarding their influence on concentrations of various VFAs produced by the canine intestinal microbiome. Thirty dogs were kept on a standard diet for 15 days, during which time half of the animals received oral lactulose once a day, while the other group was given a psyllium-supplemented diet (in 0.67 and in 0.2 g/kg body weight concentrations, respectively). On days 0, 5, 10 and 15 of the experiment, feces were sampled from the rectum, and the concentration of each VFA was determined by GC-MS (gas chromatography−mass spectrometry). Lactulose administration caused a significant increase in the total VFA concentration of the feces on days 10 and 15 of the experiment (p = 0.035 and p < 0.001, respectively); however, in the case of psyllium supplementation, the concentration of VFAs showed a significant elevation only on day 15 (p = 0.003). Concentrations of acetate and propionate increased significantly on days 5, 10 and 15 after lactulose treatment (p = 0.044, p = 0.048 and p < 0.001, respectively). Following psyllium administration, intestinal acetate, propionate and n-butyrate production were stimulated on day 15, as indicated by the fecal VFA levels (p = 0.002, p = 0.035 and p = 0.02, respectively). It can be concluded that both lactulose and psyllium are suitable for enhancing the synthesis of VFAs in the intestines of dogs. Increased acetate and propionate concentrations were observed following the administration of both supplements; however, elevated n-butyrate production was found only after psyllium treatment, suggesting that the applied prebiotics may exert slightly different effects in the hindgut of dogs. These findings can be also of great importance regarding the treatment and management of patients suffering from intestinal disorders as well as hepatic encephalopathy due to portosystemic shunt.

Capillary electrophoresis applied for the determination of acidity constants and limiting electrophoretic mobilities of ionizable herbicides including glyphosate and its metabolites and for their simultaneous separation.

Thermodynamic acidity constants and limiting ionic mobilities were determined for polyprotic non-chromophore analytes using capillary electrophoresis with capacitively coupled contactless conductivity detection. It was not necessary to work with buffers of identical ionic strength as ionic strength effects on effective electrophoretic mobilities were corrected by modeling during data evaluation (software AnglerFish). The mobility data from capillary electrophoresis coupled to conductivity detection were determined in the pH range from 1.25 to 12.02 with a high resolution (36 pH steps). With this strategy, thermodynamic acidity constants and limiting ionic mobilities for various acidic herbicides were determined, sometimes for the first time. The model analytes included glyphosate, its metabolites, and its acetylated derivates (aminomethyl phosphonic acid, glyoxylic acid, sarcosine, glycine, N-acetyl glyphosate, N-acetyl aminomethyl phosphonic acid, hydroxymethyl phosphonic acid). The obtained data were used in simulations to optimize separations by capillary electrophoresis. Simulations correlated very well to experimental results. With the new method, the separation of glyphosate from interfering components like phosphate in beer samples was possible.

Anti-Müllerian hormone, testosterone, and insulin-like peptide 3 as biomarkers of Sertoli and Leydig cell function during deslorelin-induced testicular downregulation in the dog.

The role of anti-Müllerian hormone (AMH) and insulin-like peptide 3 (INSL3) in male infertility is not fully understood. We used the downregulated testis as a model of gonadotropin-dependent infertility. Serum testosterone and AMH concentrations were studied in five adult male Beagles implanted (day 0) with 4.7 mg deslorelin (Suprelorin®, Virbac) (DES group). Testicular expression of LH receptor (LHR) and androgen receptor (AR), AMH, type 2 AMH receptor (AMHR2), INSL3 and its receptor (RXFP2) was evaluated 112 days (16 weeks) after deslorelin treatment by qPCR and immunohistochemistry, and compared to untreated adult (CON, n = 6) and prepubertal (PRE, n = 8) dogs. Serum testosterone concentration decreased significantly by the onset of aspermia on study day 14 (four dogs) or day 21 (one dog), and was baseline on day 105 (week 15). In contrast, serum AMH started to increase only after the onset of aspermia and reached the maximum detectable concentration of the assay by day 49-105 in individual dogs. Testicular LHR gene expression in DES was lower than in CON and PRE (P < 0.0001), while AR gene expression in DES was similar to CON and significantly higher than PRE (P < 0.0001). Testicular AMH expression in DES was intermediate compared to the lowest mRNA levels found in CON and the highest in PRE (P ≤ 0.006). AMHR2 gene expression was similar between groups. AMH protein was detected in Sertoli cells only, while AMHR2 immunoreactivity was principally detected in Leydig cells which appeared to be increased in DES. INSL3 and RXFP2 gene expression was significantly downregulated in the DES testis along with noticeably weak Leydig cell immunosignals compared to CON. In conclusion, deslorelin treatment caused testicular LH insensitivity without affecting androgen sensitivity, and de-differentiation of Sertoli and Leydig cells. In DES, upregulation of the AMH-AMHR2 feed-back loop and downregulation of the INSL3-RXFP2 feed-forward loop are paracrine-autocrine mechanisms that may additionally regulate testosterone production independent of gonadotropins. Our results support AMH and INSL3 as unique biomarkers and paracrine-autocrine regulators of testis function involved in the intimate interplay between Sertoli and Leydig cells.

Macrophage-Mediated Antibody Dependent Effector Function in Aggressive B-Cell Lymphoma Treatment is Enhanced by Ibrutinib via Inhibition of JAK2.

Targeted inhibition of Bruton's Tyrosine Kinase (BTK) with ibrutinib and other agents has become important treatment options in chronic lymphocytic leukemia, Waldenström's Macroglobulinemia, Mantle cell lymphoma, and non-GCB DLBCL. Clinical trials combining small molecule inhibitors with monoclonal antibodies have been initiated at rapid pace, with the biological understanding between their synergistic interactions lagging behind. Here, we have evaluated the synergy between BTK inhibitors and monoclonal antibody therapy via macrophage mediated antibody dependent cellular phagocytosis (ADCP). Initially, we observed increased ADCP with ibrutinib, whilst second generation BTK inhibitors failed to synergistically interact with monoclonal antibody treatment. Kinase activity profiling under BTK inhibition identified significant loss of Janus Kinase 2 (JAK2) only under ibrutinib treatment. We validated this potential off-target effect via JAK inhibition in vitro as well as with CRISPR/Cas9 JAK2-/- experiments in vivo, showing increased ADCP and prolonged survival, respectively. This data supports inhibition of the JAK-STAT (Signal Transducers and Activators of Transcription) signaling pathway in B-cell malignancies in combination with monoclonal antibody therapy to increase macrophage-mediated immune responses.

Cellular inflammation in pulmonary hypertension: Detailed analysis of lung and right ventricular tissue, circulating immune cells and effects of a dual endothelin receptor antagonist.

Growing evidence suggests that inflammation is crucially involved in the pathogenesis of pulmonary hypertension (PH) and consecutive right heart failure. The present study analyzed the inflammatory response in lung and right ventricle in a rat model of PH and evaluated the effects of the dual endothelin receptor antagonist (ERA) Macitentan. PH was induced by monocrotalin (60 mg/kg body weight s.c.) in Sprague-Dawley rats (PH, n = 10) and compared to healthy controls (CON, n = 10) as well as monocrotalin-induced, macitentan-treated rats (THER, n = 10). Detection of Dendritic cells (DCs), regulatory T cells (Tregs) and others as well as RT-PCR based inflammatory gene expression analysis were performed. Circulating DCs and Tregs were quantified by flow cytometry in the rat model and in PH patients (n = 70) compared to controls (n = 52). Inflammatory cells were increased in lung and right ventricular tissue, whereas DCs and Tregs were decreased in blood. Expression of 17 genes in the lung and 20 genes in the right ventricle were relevantly (>2.0 fold) regulated in the PH group. These effects were, at least in part, attenuated in response to Macitentan treatment. In humans as well as rats, immune cells showed significant correlations to clinical, echocardiographic, and haemodynamic parameters. PH is accompanied by a distinct inflammatory response in lung and right but not left ventricular tissue attenuated by Macitentan. Correlations of circulating DCs as well as tissue resident immune cells with parameters reflecting right ventricular function raise the idea of both, promising biomarkers and novel treatment strategies.

Expression of insulin-like growth factor 1 and its receptor in preovulatory follicles and in the corpus luteum in the bitch.

In the bitch, ovarian follicular and corpus luteum (CL) development and function are regulated by gonadotropins as well as local factors, the role of which is especially important during the early CL phase of relative gonadotrophic independence. We assumed that insulin-like growth factor 1 (IGF1) has a paracrine/autocrine regulatory role in ovarian follicular and luteal function in the dog. To address our hypothesis, we studied gene and protein expression of IGF1 and its receptor (IGF1R) in preovulatory follicles and in the CL of pregnant and non-pregnant dogs, and following antigestagen (aglepristone, progesterone receptor blocker) treatment in mid-gestation. Ovaries in the follicular phase were collected from five bitches. CL were collected on pregnancy Days 8-12 (pre-implantation), 18-25 (post-implantation), 35-40 (mid-gestation), at prepartum luteolysis, and 24 h and 72 h after aglepristone treatment in mid-gestation (n = 3-5 per group). From non-pregnant bitches, CL were collected on Days 5, 15, 25, 35, 45, 65 after ovulation (n = 4-5 per group). Semi-quantitative real-time (TaqMan) PCR and immunohistochemistry were applied. IGF1 immunostaining in preovulatory follicles seemed stronger in theca interna than granulosa cells. IGF1R signals appeared more intense in granulosa cells at the apical part of mural folds. In pregnant dogs, luteal IGF1 mRNA expression decreased significantly from pre-implantation to prepartum luteolysis, while IGF1R expression increased at prepartum luteolysis. Aglepristone treatment in mid-gestation had no effect on IGF1 and IGF1R mRNA levels. In non-pregnant bitches, highest IGF1 mRNA concentrations were found in the early CL and decreased by Days 45 and 65, while IGF1R expression did not change. In the CL of pregnant bitches, signals for IGF1 and IGF1R in luteal cells were strongest at pre- and post-implantation and weakest at prepartum luteolysis. IGF1 and IGF1R immunostaining was also detected in macrophages and in blood vessels. In conclusion, IGF1 may have a paracrine or autocrine role in granulosa and theca interna cells in preovulatory follicles. As IGF1 was highest represented in early luteal stages in pregnant and non-pregnant bitches, this may support a role for IGF1 in steroid synthesis, angiogenesis and cell proliferation as well as in immune function in the early canine CL. The unaffected mRNA levels after aglepristone treatment may support that IGF1 is not directly regulated by local progesterone in an auto- or paracrine manner.

Increased Serum Levels of Fetal Tenascin-C Variants in Patients with Pulmonary Hypertension: Novel Biomarkers Reflecting Vascular Remodeling and Right Ventricular Dysfunction?

Pulmonary vascular remodeling is a pathophysiological feature that common to all classes of pulmonary hypertension (PH) and right ventricular dysfunction, which is the major prognosis-limiting factor. Vascular, as well as cardiac tissue remodeling are associated with a re-expression of fetal variants of cellular adhesion proteins, including tenascin-C (Tn-C). We analyzed circulating levels of the fetal Tn-C splicing variants B⁺ and C⁺ Tn-C in serum of PH patients to evaluate their potential as novel biomarkers reflecting vascular remodeling and right ventricular dysfunction. Serum concentrations of B⁺ and C⁺ Tn-C were determined in 80 PH patients and were compared to 40 healthy controls by enzyme-linked immunosorbent assay. Clinical, laboratory, echocardiographic, and functional data were correlated with Tn-C levels. Serum concentrations of both Tn-C variants were significantly elevated in patients with PH (p < 0.05). Significant correlations could be observed between Tn-C and echocardiographic parameters, including systolic pulmonary artery pressure (B⁺ Tn-C: r = 0.31, p < 0.001, C⁺ Tn-C: r = 0.26, p = 0.006) and right atrial area (B⁺ Tn-C: r = 0.46, p < 0.001, C⁺ Tn-C: r = 0.49, p < 0.001), and laboratory values like BNP (B⁺ Tn-C: r = 0.45, p < 0.001, C⁺ Tn-C: r = 0.42, p < 0.001). An inverse correlation was observed between Tn-C variants and 6-minute walk distance as a functional parameter (B⁺ Tn-C: r = -0.54, p < 0.001, C⁺ Tn-C: r = -0.43, p < 0.001). In a multivariate analysis, B⁺ Tn-C, but not C⁺ Tn-C, was found to be an independent predictor of pulmonary hypertension. Both fetal Tn-C variants may represent novel biomarkers that are capable of estimating both pulmonary vascular remodeling and right ventricular load. The potential beneficial impact of Tn-C variants for risk stratification in patients with PH needs further investigation.

Evaluating Enhancements to a Perioperative Nurse Liaison Program.

The impetus for the perioperative nurse liaison (PNL) program at our cancer center was to reduce anxiety for family members of patients undergoing surgery by improving communication between the family and the perioperative team. The purpose of our quality improvement project was to increase contact with family members during the patient's surgery and to support families and surgeons during the postoperative family consult when findings were unexpected. After implementing process changes, the PNLs evaluated the program using a short survey given to families after the postoperative consult. Families reported a reduction in stress and anxiety when intraoperative updates were received either in person or by telephone. In addition, when the PNL accompanied family members to the postoperative consult, the family felt supported when receiving unexpected findings. Further, family contact with the PNL increased from 77% to 98%, and the number of consults with surgeons that included the PNL rose from an average of 254 to 500 per year.

Thyroxin and progesterone concentrations in pregnant, nonpregnant bitches, and bitches during abortion.

Serum progesterone and thyroxin concentrations were measured weekly until 61 to 62 days after ovulation in 24 pregnant bitches and in the control group of nine nonpregnant bitches in the luteal phase. Fourteen of the 24 dogs had a normal pregnancy and parturition. Ten of the 24 dogs showed mucinous or colored vaginal discharge, decreased appetite, or lethargy. These initial signs of abortion or fetal resorption were noted during the fourth week of pregnancy, and the process occurred over the next 2 weeks. Progesterone and thyroxin concentrations were measured by quantitative ELISAs validated to dog serum. The serum progesterone concentrations of the group going through abortions differed significantly from the third week until the end of the eighth week. The mean serum thyroxin concentrations of healthy pregnant and nonpregnant groups significantly exceeded the reference range (20-45 nmol/L). The serum thyroxin concentrations in the abortion group were between 16.15 ± 3.17 and 40.78 ± 8.97 nmol/L. The values in this group were significantly different from the other two groups at the third week of the luteal phase. Clinical signs of abortion or fetus resorption manifested in midpregnancy. The clinical signs of abortion coincided in each case with a low serum progesterone concentration (<10 ng/mL). This phenomenon indicated, in contrast with other studies, that the decrease of serum progesterone below 10 ng/mL at the fourth week of pregnancy may signal impending abortion. In the second half of pregnancy, the thyroid gland was not able to respond adequately to the elevated requirement in thyroid hormone, although in other periods of the ovarian cycle, there were no clinical signs of hypothyroidism.

Real-World Verbal Communication Performance of Children Provided With Cochlear Implants or Hearing Aids.

OBJECTIVE: To compare the real-world verbal communication performance of children provided with cochlear implants (CIs) with their peers with hearing aids (HAs). STUDY DESIGN: Cross-sectional study in university tertiary referral centers and at hearing aid dispensers. METHODS: Verbal communication performance was assessed by the Functioning after Pediatric Cochlear Implantation (FAPCI) instrument. The FAPCI was administered to 38 parents of children using CIs and 62 parents of children with HAs. According to the WHO classification, children with HAs were categorized into three groups (mild-moderate-severe hearing loss). Analysis of variance (ANOVA) was performed on the FAPCI scores, with study group, hearing age (i.e., device experience), and age at hearing intervention as sources of variation. RESULTS: ANOVA showed that hearing age and study group significantly contribute to the FAPCI outcome. In all study groups except the children with mild hearing loss, FAPCI scores increased alongside growing experience with the devices. Children with mild hearing loss using HAs showed higher scores than those with severe hearing loss or implanted children. There were no significant differences between the children with CIs and the children with moderate or severe hearing loss using HAs. CONCLUSION: Real-world verbal communication abilities of children with CIs are similar to those of children with moderate-to-severe hearing loss using amplification. Because hearing age significantly influences performance, children with moderate-to-severe hearing loss using HAs and implanted children catch up with children with mild hearing loss at a hearing age of approximately 3 years.

Immediate and long-term complications of delayed surgical management in the postpartum period: a retrospective analysis.

OBJECTIVE: To assess the rate of complications of surgical interventions delayed more than 24 h after delivery in women suspected of placental remnants. METHODS: A retrospective review was performed to analyse complications of delayed surgical interventions. Women were identified from the operation database and their medical records were reviewed to determine the rate of immediate and long-term complications, including reproductive outcome. RESULT: A total of 127 women were evaluated. The median interval between delivery and surgery was 42 days. Immediate complications were registered in 22.0% and re-interventions in 16.5%. Placental remnants were histologically confirmed in 63.8%. Intrauterine adhesions (IUAs), only of the severe type, were recorded in 20.5%, although a minority of women was hysteroscopically revised. The difference between women treated by dilatation and curettage (D&C) and hysteroscopy was not statistically significant. Similar reproductive outcomes were encountered in women treated by D&C and hysteroscopy and in women with and without IUAs, although the samples were small. CONCLUSION: Identification of placental remnants remains difficult while delayed interventions are associated with significant immediate and long-term complications. The impact on reproductive performance remains unclear. Further research is necessary to examine treatment options in relation to complications and reproductive outcome.