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Medically unexplained physical symptoms (MUPS) are somatic symptoms for which it is not possible to trace the origin and nature to a psychopathological explanation. These ailments are very difficult to treat, they tend to become chronic and disabling, and they require continuous medical consultations resulting in enormous health-care costs. Various levels of psychological intervention are common practice in the management of patients afflicted by MUPS. The article, through the systematic survey of the literature on the subject and by taking into account the most recent reviews, aims to detect the therapeutic efficacy of psychotherapy treatments for MUPS, and for somatic symptom disorders in general. We also intended to track down the therapeutic aspects which, if improved, can increase the effectiveness of standard protocols. Particular attention has been paid to the data concerning the cognitive-behavioral therapy (CBT). This research demonstrates that psychotherapy is a therapeutic option that may be proposed to MUPS patients. CBT is the first-line and evidence-based treatment. Personalizing the psychotherapy taking into accounts the psychopathological variables of patients, the intensification of treatments (> 6 months, 1-2 sessions per week), and the optimization of third wave therapies use, represent a possible improvement in terms of effectiveness. [ABSTRACT FROM AUTHOR]

Expression and pharmacological properties of endothelin receptors (ETRs) were investigated in H9c2 cardiomyoblasts. The mechanism of receptor-mediated modulation of intracellular Ca2+ concentration ([Ca2+]i) was examined by measuring fluorescence increase of Fluo-3-loaded cells with flow cytometry. Binding assays showed that [125I]endothelin-1 (ET-1) bound to a single class of high affinity binding sites in cardiomyoblast membranes. Endothelin-3 (ET-3) displaced bound [125I]ET-1 in a biphasic manner, in contrast to an ETB-selective agonist, IRL-1620, that was ineffective. The ETB-selective antagonist, BQ-788, inhibited [125I]ET-1 binding in a monophasic manner and with low potency. An ETA-selective antagonist, BQ-123, competed [125I]ET-1 binding in a monophasic manner. This antagonist was found to be 13-fold more potent than BQ-788. Immunoblotting analysis using anti-ETA and -ETB antibodies confirmed a predominant expression of the ETA receptor. ET-1 induced a concentration-dependent increase of Fluo-3 fluorescence in cardiomyoblasts resuspended in buffer containing 1 mM CaCl2. Treatment of cells with antagonists, PD-145065 and BQ-123, or a phospholipase C-β inhibitor, U-73122, abolished ET-1-mediated increases in fluorescence. The close structural analogue of U-73122, U-73343, caused a minimal effect on the concentration–response curve of ET-1. ET-3 produced no major increase of Fluo-3 fluorescence. Removal of extracellular Ca2+ resulted in a shift to the right of the ET-1 concentration–response curve. Both the L-type voltage-operated Ca2+ channel blocker, nifedipine, and the ryanodine receptor inhibitor, dantrolene, reduced the efficacy of ET-1. Two protein kinase C inhibitors reduced both potency and efficacy of ET-1. Our results demonstrate that ETA receptors are expressed and functionally coupled to rise of [Ca2+]i in H9c2 cardiomyoblasts. ET-1-induced [Ca2+]i increase is triggered by Ca2+ release from intracellular inositol 1,4,5-trisphosphate-gated stores; plasma membrane Ca2+ channels and ryanodine receptors participate in sustaining the Ca2+ response. Regulation of channel opening by protein kinase C is also involved in the process of [Ca2+]i increase. [Copyright &y& Elsevier]

Purpose. Autoregulation and control of blood flow within the retina is dependent on vascular endothelial release of vasoconstrictors and dilators. The effector cells are the pericytes and vascular smooth muscle cells of the retinal microvascular bed. Many studies show that the responses of these effector cells are affected by diabetes or artificially elevated glucose. In particular, the contractile response of pericytes to endothelin-1 (ET-1) is markedly reduced. ET-1 and related isopeptides exert their effects by binding and activating specific cell surface receptors (ETRs). Pericytes express two subtypes of ETRs, ET[sub A] and ET[sub B]B. The purpose of this study was to assess the dynamics of [[sup 125]I]ET-1 binding to ETA and ET[sub B] receptors when cultured in normal and high glucose concentrations. Methods. Bovine retinal pericytes (BRP) were exposed to normal (5 mM) or high glucose (25 mM) concentrations for up to 14 days. Displacement of binding and competitive inhibition of binding was carried out in perictye membranes. mRNA expression for ETR subtypes was examined using northern blotting. The expression of G protein α subunits (Gα[sub s] and Gα[sub q]) was detected by western blotting. Results. Highly specific binding of [[sup 125]I]ET-1 was seen with BRP membranes. In competition assays, ET-3 was found to displace [[sup 125]I]ET-1 binding to BRP membranes in a biphasic manner, indicating the presence of two classes of binding sites. The presence of both ETR subtypes was supported by competition experiments with selective ligands. The expression of Gα[sub s] and Gα[sub q] subunits decreased in pericytes incubated with 25 mM glucose. Conclusions. No significant differences in binding parameters were evident after culture in high glucose concentrations. However northern blot analysis which confirmed the presence of ET[sub B] receptor mRNA did identify an increase in the expression of this receptor. [ABSTRACT FROM AUTHOR]

In rat striatum A2A adenosine receptors activate adenylyl cyclase through coupling to Gs-like proteins, mainly Golf that is expressed at high levels in this brain region. In this study we report that the sulfhydryl alkylating reagent, N-ethylmaleimide (NEM), causes a concentration- and time-dependent inhibition of [3H] 2-p-(2-carboxyethyl)phenylethylamino)-5′-N-ethylcarboxamido adenosine ([3H]CGS21680) binding to rat striatal membranes. Membrane treatment with [14C]N-ethylmaleimide ([14C]NEM) labels numerous proteins while addition of 5′-guanylylimidodiphosphate (Gpp(NH)p) reduces labeling of only three protein bands that migrate in SDS-polyacrylamide gel electrophoresis with apparent molecular masses of ∼52, 45 and 39 kDa, respectively. The 52- and 45-kDa labeled bands show electrophoretic motilities as Gαs-long and Gαs-short/Gαolf subunits. An anti-Gαs/olf antiserum immunoprecipitates two 14C labeled bands of 44 and 39 kDa. The band density decreases by 21–26% when membranes are treated with NEM in the presence of Gpp(NH)p. An anti-A2A receptor antibody also immunoprecipitates two 14C labeled bands of 40 and 38 kDa, respectively. However, such protein bands do not show any decrease of their density upon membrane treatment with NEM plus Gpp(NH)p. These results indicate that in rat striatal membranes NEM alkylates sulfhydryl groups of both Gαs/olf subunits and A2A adenosine receptors. In addition, cysteine residues of Gαs/olf are easily accessible to modification when the subunit is in the GDP-bound form. The 39- and 38-kDa labeled proteins may represent proteolytic fragments of Gαs/olf and A2A adenosine receptor, respectively. [Copyright &y& Elsevier]

Purpose: The aim of this study was to delineate the personality traits of patients affected by keratoconus (KC) compared with a group of nonkeratoconic controls matched in age and sex., Methods: In this prospective interventional case-control study, 60 consecutive subjects (30 KC cases and 30 healthy controls), aged 18 to 30, were enrolled at the time of their first encounter at the ophthalmology unit of the Fondazione Policlinico "Tor Vergata", Roma. After completing the ophthalmic evaluation, participants were asked to respond to the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). A complete psychiatric assessment was performed, including the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (SCID-5); the Symptom Check List-90-Revised (SCL-90); the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Modified (TEMPS-M); and the NEO Five-Factor Inventory (NEO-FFI)., Results: Cases had lower quality of life than controls, as demonstrated by lower scores in all NEI VFQ-25 subdomains. Nine patients with KC (30.0%) were diagnosed by the SCID-5 with at least 1 cluster C personality disorder, resulting in a 9-fold increased risk compared with controls. Moreover, keratoconic patients showed a more pronounced psychosomatic symptomatology (SCL-90) and a characteristic neurotic temperament (TEMPS-M and NEO-FFI)., Conclusions: Our results support the hypothesis that subjects with KC feature dysfunctional coping mechanisms and personality traits, which might already be present at the first clinical encounter. Ophthalmologists should question the mental and emotional status of patients with KC and be especially careful in managing these patients., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: . The fact that only a small percentage of cord blood units (CBU) stored are actually used for transplantation contributes to raising the already high costs of their processing and cryopreservation. The identification of predictors allowing the early identification of suitable CBU would allow a reduction of costs for the collection, storage and characterisation of CBU with insufficient volume or cell numbers. In our bank we have adopted a cut-off value for using CBU of 8 x 10(8) nucleated cells and a volume >or= 60 mL., Materials and Methods: In 365 banked CBU, we evaluated the correlation between neonatal/gestational parameters and laboratory data used to assess their quality., Results: Biparietal diameter (BPD) and abdominal circumference were significantly and positively correlated with CBU volume (r(2)=0.12, p=0.0011 and r(2)=0.092, p=0.0063, respectively). Receiver operating characteristic (ROC) analysis showed that both parameters can be used to identify CBU with insufficient volume (BPD: area under the curve 0.69, 95% CI=0.57-0.82, p=0.004; abdominal circumference: area under the curve 0.67, 95% CI=0.54-0.79, p<0.01). BPD and head circumference, but not abdominal circumference or femoral length, were positively correlated with white blood cell (WBC) count (r(2)=0.215, p=0.031, and r(2)=0.299, p=0.015, respectively). Abdominal circumference, but not BPD, head circumference or femoral length, was statistically significantly correlated with the number of CD34(+) cells in the CBU. Weight at birth and placental weight were positively correlated with WBC count, blood volume, CD34(+) cell count, total colony-forming units and burst-forming units., Conclusion: . Pre-birth assessment of BPD might allow the selection of donors who would yield CBU of sufficient volume and WBC count and avoid the costs of collecting, transferring, storing and analysing CBU with a high probability of resulting unsuitable for transplantation.

The diagnostic differentiation of breast lesions is very important because of the frequency with which they occur. Though fibroadenoma is easy to diagnose, some cases prove really hard to distinguish. Therefore, various methods have been suggested both for diagnosis and therapy, but no common approach has been achieved to date. We report our experience with 1350 cases diagnosed over a twenty-year period. The diagnosis was made on the basis of a diagnostic protocol drawn up over the years where cytology is of primary importance. With regard to therapy, we decide to operate when the cytological findings prompt the need for a histological examination of the lesion. Moreover, we operate on those cases where either an increase in size or a morphological change of the lesion has taken place. Histological examinations were carried out in 420 cases out of 1350 and only one of these cases turned out to be a carcinoma. As a result, the 0.24% error in the diagnosis can be considered irrelevant. In spite of the different therapies suggested (cryoablation, laser hyperthermia, i.a.), we believe that surgical treatment with local anaesthetic is the most suitable solution in those cases requiring treatment. Obviously, the diagnosis has to be accurate and made by surgeons with appropriate expertise. When the diagnosis is certain and the conditions of the lesion are stable, the best policy seems to be periodic follow-up.

Financing health-care expenditure has become increasingly more difficult. Considering the high frequency of breast cancer, which affects one million women in the world each year, the reductions of medical expenditure for the treatment of this disease is highly desirable within the limits of medical efficiency and safety. One hundred and fifty patients with carcinoma of the breast underwent surgery in our department with one-day hospitalization. Patients were discharged with the drainage tube still in place and later treated in the out-patient setting, for dressing and checking the wound, and removing the stitches and drainage tube. Four cases of seroma were registered, all resolved by aspiration of the fluid in a single visit, 1 case of haematoma and 1 case of infection. Patients who underwent this short-stay treatment were amply satisfied. Our experience demonstrates that this type of treatment is both safe and effective. Moreover, it provides considerable benefits in terms of national health-care costs as well as being psychologically better for the patients.