International application of the "Multidimensional Intervention for Social Anxiety" (MISA) program: II. Treatment effectiveness for social anxiety-related problems

This study is part of the I+D+i project with reference RTI2018-093916-B-I00, funded by MCIN/AEI/10.13039/501100011033/and FEDER "A way of doing Europe". Support from the Foundation for the Advancement of Clinical Behavioral Psychology (FUNVECA) is also acknowledged.In a previous work (Caballo et al., 2021) we tested the effectiveness of the Multidimensional Intervention for Social Anxiety (MISA) program in reducing social anxiety symptoms. In this quasi-experimental study, with pre/post-treatment and follow-up measures, we examined the impact of the MISA program on other problems related to social anxiety. 57 people diagnosed with social anxiety disorder (SAD), according to DSM-5, were assessed with a diagnostic interview and questionnaires measuring social skills, depression, avoidant personality disorder symptoms, alcoholism, self-esteem, personal sensitivity, worries, and quality of life. Different therapists carried out the treatment in Ecuador, Spain, and Paraguay. The results showed significant improvements at post-treatment in virtually all measures assessing the above variables, improvements that were maintained at six months. Effect sizes on treatment effectiveness ranged from medium to large. The MISA program was also compared with individual cognitive behavioral therapy and pharmacological treatment, with favorable results for the MISA program. In conclusion, this new program for the treatment of social anxiety has a significant impact on other problems usually related to SAD.In a previous work (Caballo et al., 2021) we tested the effectiveness of the Multidimensional Intervention for Social Anxiety (MISA) program in reducing social anxiety symptoms. In this quasi-experimental study, with pre/post-treatment and follow-up measures, we examined the impact of the MISA program on other problems related to social anxiety. 57 people diagnosed with social anxiety disorder (SAD), according to DSM-5, were assessed with a diagnostic interview and questionnaires measuring social skills, depression, avoidant personality disorder symptoms, alcoholism, self-esteem, personal sensitivity, worries, and quality of life. Different therapists carried out the treatment in Ecuador, Spain, and Paraguay. The results showed significant improvements at post-treatment in virtually all measures assessing the above variables, improvements that were maintained at six months. Effect sizes on treatment effectiveness ranged from medium to large. The MISA program was also compared with individual cognitive behavioral therapy and pharmacological treatment, with favorable results for the MISA program. In conclusion, this new program for the treatment of social anxiety has a significant impact on other problems usually related to SAD.I+D+i project RTI2018-093916-B-I00Foundation for the Advancement of Clinical Behavioral Psychology (FUNVECA)FEDER "A way of doing Europe" MCIN/AEI/10.13039/501100011033

Recent Developments in Chiral Unitary Dynamics of Resonances

In this talk I summarize recent findings made on the description of axial vector mesons as dynamically generated states from the interaction of peseudoscalar mesons and vector mesons, dedicating some attention to the two $K_1(1270)$ states. Then I review the generation of open and hidden charm scalar and axial states. Finally, I present recent results showing that the low lying $1/2^+$ baryon resonances for S=-1 can be obtained as bound states or resonances of two mesons and one baryon in coupled channels dynamics.Comment: Talk at the International Conference on Hadron Physics, Troia07, Canakkale, Turkey, Sep. 2007 and at the Chiral Symmetry in Hadron and Nuclear Physics Workshop, Chiral07, Osaka, November 200

Renal ammonia in autosomal dominant polycystic kidney disease

Renal ammonia in autosomal dominant polycystic kidney disease. Recent studies have suggested that defective medullary trapping of ammonia underlies the acidosis associated with renal failure and sets in motion maladaptive compensatory mechanisms that contribute to the progression of renal disease. Since a renal concentrating defect is an early functional abnormality in autosomal dominant polycystic kidney disease (ADPKD), defective medullary trapping and urinary excretion of ammonia may also occur early and have important pathophysiological consequences. The urinary pH and excretions of ammonia, titratable acid, and bicarbonate, were measured during a 24-hour baseline period and following the administration of ammonium chloride (100 mg/kg body wt) in ADPKD patients with normal glomerular filtration rate and in age- and gender-matched healthy control subjects. The distal nephron hydrogen ion secretory capacity was assessed during a bicarbonate infusion. Ammonia, sodium, pH, C3dg, and C5b-9 were measured in cyst fluid samples. The excretion rates of ammonia during the 24-hour baseline period and following the administration of ammonium chloride were significantly lower, and the relationship of ammonia excretion to urinary pH was significantly shifted downward in ADPKD. No difference in the increment of urinary pCO2 (Δ pCO2) or the peripheral blood-urine pCO2 gradient (U-B pCO2) between ADPKD patients and control subjects was detected during a sodium bicarbonate infusion. Calculated concentrations of free-base ammonia in cyst fluid samples exceeded those calculated from reported concentrations of ammonia in renal venous blood of normal subjects. C3dg and C5b-9 were detected in some cyst fluids. The urinary excretion of ammonia is reduced in ADPKD patients with normal glomerular filtration rate. This reduction is not explained by a lower production of ammonia in the renal cortex or by a defect of proton secretion in the collecting ducts. It is likely due to an impaired renal concentrating mechanism and reduced trapping of ammonia in the renal medulla. It may contribute to the pathogenesis of nephrolithiasis and, more importantly, to the progression of the interstitial inflammation and cystic changes seen in ADPKD

Epidermal growth factor receptor tyrosine kinase inhibition is not protective in PCK rats

Epidermal growth factor receptor tyrosine kinase inhibition is not protective in PCK rats.BackgroundAdvances in the understanding of cystogenesis, identification of the PKHD1 gene and availability of a rat model (the PCK rat) caused by a Pkhd1 mutation facilitate testing of therapies for autosomal-recessive polycystic kidney disease (ARPKD). Considerable support exists for the importance of the epidermal growth factor (EGF)/transforming growth factor-alpha (TGF-α)/EGF receptor (EGFR) axis and of the adenylyl cyclase-adenosine 3′,5′-cyclic monophosphate (cAMP) pathway in the pathogenesis of cyst formation and progressive enlargement.MethodsTo determine whether EGFR tyrosine kinase inhibition is protective in the PCK rat, male and female animals were treated with EKI-785 or EKB-569 or with vehicle alone between 3 and 10 weeks of age. Biochemical and histomorphometric analysis, immunohistochemistry, immunoblotting, enzyme immunoassay, and quantitative reverse transcription-polymerase chain reaction (RT-PCR) were used to ascertain the effects of treatment.ResultsContrary to other murine models of ARPKD, overexpression and apical mislocalization of EGFR were not detected in the PCK rats. Consistent with these expression results, EKI-785 or EKB-569 administration had no effect or worsened PKD, and had no effect on the development of fibrocystic liver disease. Increased renal cAMP and vasopressin V2 receptor expression were observed in the EKI-785–treated animals.ConclusionEGFR tyrosine kinase inhibition did not protect PCK rats from the development of PKD. This may be due to effects on collecting duct cAMP that counteract possible beneficial effects on the extracellular-regulated protein kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway, particularly in the absence of EGFR overexpression or mislocalization. The relevance of these observations to the treatment of human cystic kidney diseases deserves further study

Pioglitazone, an Insulin Sensitizing Drug, Attenuates the Development of Kidney and Liver Disease in the PCK Rodent Model of Polycystic Kidney Disease

poster abstractPolycystic kidney disease is a genetic disorder characterized by growth of fluid-filled cysts predominately in kidney and liver. The only treatment currently available is the removal/aspiration of the largest cysts or organ transplantation. Promising pharmaceutical agents in clinical trials interfere with the action of hormones that increase cAMP thereby inhibiting secretion of Cl-, and compensatory fluid flux, into the cysts. Other treatments proposed include chemotherapeutic and immunosuppressive drugs that interfere with cellular proliferation as well as with signaling pathways for Cl- secretion. Long-term use of these agents will have multiple side effects. Based on a recent observation that peroxisome proliferator activated receptor γ agonists such as Actos (pioglitazone) and Avandia (rosiglitazone) decrease mRNA levels of a Cl- transport protein and the Cl- secretory response to vasopressin stimulation in cultured renal cells, it is hypothesized that PPARγ agonists will inhibit cyst growth. The current studies show that a 7 or 14 week feeding regimen of 20 mg/Kg BW pioglitazone inhibits renal and hepatic bile duct cyst growth in a rodent model orthologous to human PKD. In addition, the degree of renal cortical fibrosis was diminished in the pioglitazone-treated animals after 14 weeks. These results suggest that PPARγ agonists may be effective in controlling both renal and hepatic cyst growth and renal fibrotic development in polycystic kidney disease

Polycystic Kidney Disease and the Vasopressin Pathway

Vasopressin, also known as arginine vasopressin or antidiuretic hormone, plays a pivotal role in maintaining body homeostasis. Increased vasopressin concentrations, measured by its surrogate copeptin, have been associated with disease severity as well as disease progression in polycystic kidney disease (PKD), and in experimental studies vasopressin has been shown to directly regulate cyst growth. Blocking vasopressin effects on the kidney via the vasopressin V2-receptor and lower circulating vasopressin concentration are potential treatment opportunities that have been the subject of study in PKD in recent years. Treatment with vasopressin V2-receptor antagonist tolvaptan has been shown to inhibit disease progression in experimental studies, as well as in a large randomized controlled trial involving 1,445 patients with autosomal dominant PKD, lowering total kidney volume growth from 5.5 to 2.8%, and the slope of the reciprocal of the serum creatinine level from -3.81 to -2.61 mg per mL(-1)/year. Alternatively, lowering circulating vasopressin could delay disease progression. Vasopressin is secreted in response to an increased plasma osmolality, which in turn is caused by a low fluid or high osmolar intake. Other lifestyle factors, like smoking, increase vasopressin concentration. Here, we provide a comprehensive review of the physiology as well as pathophysiology of vasopressin in PKD, the promising effects of tolvaptan treatment, and potential synergistic or additive treatments in combination with tolvaptan. In this study, we also review current evidence regarding the effect of influencing disease progression in PKD by lifestyle changes, especially by fluid intake. (C) 2017 The Author(s) Published by S. Karger AG, Base

Organic matter accumulation during the Holocene in the Guadalquivir marshlands (SW Spain)

The distribution of biomarker compounds and magnetic susceptibility observed in the sediment from a 20 m core drilled in the marshlands of the estuarine region of the Guadalquivir River (southwest coast of Spain) has allowed us to reconstruct the palaeoenvironmental evolution of this area during the Holocene. Several organic compounds (n-alkanes, ra-ketones, n-alkanols, n-alkanoic acids and organic sulphur), as well as different biomarker ratios, have been used to show changing environmental conditions through time. These geochemical proxies suggest good preservation of the organic matter, although some diagenesis has occurred to particular organic compounds, especially the n-alkanoic acids. Our data indicate a major allochthonous supply of terrestrial plants, with less influence from aquatic plants or algae through the core. There are markedly different palaeoenvironmental conditions between the uppermost 5 m (last 6ka cal. B.P.) and the rest of the core. From 5 m (ca 6ka cal. B.P.) to 19 m (ca 8ka cal. B.P.) depth the palaeoenvironmental conditions were almost constant. Based on organic sulphur content and n-alkane content logs, anoxic conditions prevailed from 8 to 6ka cal. B.P., while oxic conditions with enhanced convection of water (prevalence of fluvial input), and consequently a greater organic matter supply, predominated in the upper 5 m of the core. Similarly, little variation in the magnetic susceptibility profile below 5 m indicates stable environmental conditions, while in the upper 5 m conditions shifted to one with elevated water input and clastic sediment supply. This is linked to palaeofloral alterations in the Guadiamar/Guadalquivir drainage basins and/or anthropogenic effects. We propose that from ca 8 to 6 ka cal. B.P. a stable landscape physiognomy in the surroundings of the estuarine area of the Guadalquivir River, with a predominance of pines and grassland. However, over the last 6ka cal. B.P. a variation in the terrestrial plant biomarker compounds suggests an alternation of relatively dry and humid phases and/or the impact of human populations on altering the vegetation community have occurred

Pioglitazone Attenuates Cystic Burden in the PCK Rodent Model of Polycystic Kidney Disease

Polycystic kidney disease (PKD) is a genetic disorder characterized by growth of fluid-filled cysts predominately in kidney tubules and liver bile ducts. Currently, the clinical management of PKD is limited to cyst aspiration, surgical resection or organ transplantation. Based on an observation that PPARγ agonists such as pioglitazone and rosiglitazone decrease mRNA levels of a Cl− transport protein, CFTR (cystic fibrosis transmembrane conductance regulator), and the Cl− secretory response to vasopressin in cultured renal cells, it is hypothesized that PPARγ agonists will inhibit cyst growth. The current studies show that a 7- or 14-week pioglitazone feeding regimen inhibits renal and hepatic bile duct cyst growth in the PCK rat, a rodent model orthologous to human PKD. These studies provide proof of concept for the mechanism of action of the PPARγ agonists and suggest that this class of drugs may be effective in controlling both renal and hepatic cyst growth and fibrosis in PKD

Baryon Resonances

In this talk I show recent results on how many excited baryon resonances appear as systems of one meson and one baryon, or two mesons and one baryon, with the mesons being either pseudoscalar or vectors. Connection with experiment is made including a discussion on old predictions and recent results for the photoproduction of the $\Lambda(1405)$ resonance, as well as the prediction of one $1/2^+$ baryon state around 1920 MeV which might have been seen in the $\gamma p \to K^+ \Lambda$ reaction.Comment: Talk given at the 10th International Conference on Hypernuclear and Strange Particle Physics, Tokai, Japan, Sptember 200

Functional megalin is expressed in renal cysts in a mouse model of adult polycystic kidney disease

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive growth of cysts and a decline of renal function. The clinical feasibility of the number of potential disease-modifying drugs is limited by systemic adverse effects. We hypothesize that megalin, a multiligand endocytic receptor expressed in the proximal tubule, may be used to facilitate drug uptake into cysts, thereby allowing for greater efficacy and fewer side effects. METHODS: The cyst expression of various tubular markers, including megalin and aquaporin 2 (AQP2), was analysed by immunohistochemistry (IHC) of kidney sections from the ADPKD mouse model (PKD1(RC/RC)) at different post-natal ages. The endocytic function of megalin in cysts was examined by IHC of kidney tissue from mice injected with the megalin ligand aprotinin. RESULTS: Cyst lining epithelial cells expressing megalin were observed at all ages; however, the proportion decreased with age. Concomitantly, an increasing proportion of cysts revealed expression of AQP2, partial expression of megalin and/or AQP2 or no expression of the examined markers. Endocytic uptake of aprotinin was evident in megalin-positive cysts, but only in those that remained connected to the renal tubular system. CONCLUSIONS: Megalin-expressing cysts were observed at all ages, but the proportion decreased with age, possibly due to a switch in tubular origin, a merging of cysts of different tubular origin and/or a change in the expression pattern of cyst lining cells. Megalin expressed in cysts was functional, suggesting that megalin-mediated endocytosis is a potential mechanism for drug targeting in ADPKD if initiated early in the disease