Preoperative staging of colorectal cancer using virtual colonoscopy: correlation with surgical results

The aim of this study was to evaluate the clinical usefulness of computed tomography colonography (CTC) in the preoperative staging in patients with abdominal pain for occlusive colorectal cancer (CRC) and to compare the results of CTC with the surgical ones

Detection of GAD65 Autoreactive T-Cells by HLA Class I Tetramers in Type 1 Diabetic Patients

Type 1 diabetes (T1D) is an autoimmune disease, in which pancreatic β cells are destroyed in genetically predisposed individuals. While the direct contribution of autoantibodies to the disease pathogenesis is controversial, it is generally recognised that the mechanism of β cell destruction is mediated by autoreactive T cells that had escaped the thymic selection. We aimed to design a method to detect circulating CD8+ T cells autoreactive against an epitope of the glutamic acid decarboxylase autoantigen, isoform 65 (GAD65) ex vivo in T1D patients by using HLA class I tetramers. Low frequencies of GAD65 peptide-specific CD8+ cytotoxic T lymphocytes were detected in peripheral blood lymphocytes (PBMC) of normal controls after GAD65 peptide-specific stimulation. Conversely, their frequencies were significantly higher than in controls in PBMC of T1D patients after GAD65 peptide stimulation. These preliminary data are encouraging in order to develop a reliable assay to be employed in large-scale screening studies

Sexual offenders al femminile

Women who sexually abuse minors: It is not often seen, and case histories are scarce. Less is known about abusive mothers who enjoy a lack of negative prejudice. It is difficult to discover an abusive mother as they often disguise their practices during normal acts of care giving. It is very difficult for cases of maternal abuse to be uncovered, and when it does happen, the abusers enjoy a different standard of evaluation based on the belief that a mother possesses the innate task of protecting her child. This further prolongs her protective role in a non-culpable manner. This contributes to the fact that the sexual mother-child relationship does not usually involve violent acts, but rather, their “forms of abuse” are accompanied by normal acts of care, love, and cleanliness, which serve to further confuse matters. Gabbard (1995) maintains, for example, that women, who suffered sexual violence as children may utilize an exasperated model of feminine sexuality to vindicate themselves from the abuse perpetrated by men and to reassure their own sexuality. From a “passive” role, which she plays as submissive victim, the woman attempts to find redemption, as well as her own affirmation in an “active” role via her relationship with the child who she can control. It is well known how inner psychology has demonstrated that one of the most important consequences of an unresolved trauma (abandonment, loss, experience of abuse) is the compulsion to repeat it. By abusing children, these women are able to reproduce the original traumatic situation, putting themselves in a position of control rather than that of victim. It may be defined as “a control principle and the mastery over the trauma”. In the literature, female perpetrators of sexual crimes are often described as people who have not completely resolved the processes of identification and differentiation with the mother figure (M.Tardif et al 2005), and who have suffered long term sexual abuse as children.They are people who have not been able to develop a good and healthy maternal identity.Their conflict between the desire to become a good mother and their tendency toward repeating those behaviours of the female parent, or other abuser consumes them.Donne che abusano sessualmente di minori. Non capita spesso di vederne e povere sono in generale le casistiche. Si sa meno, dunque, delle madri abusanti, che godono anche di una mancanza di pregiudizio negativo. La madre abusante viene scoperta con più difficoltà, più spesso utilizza pratiche camuffate in normali gesti di accudimento. E’ più difficile che i casi di abuso materno escano allo scoperto e quando questo accade godono di un diverso metodo di valutazione basata sulla credenza che una madre, che ha l’innato compito di proteggere, stia semplicemente prolungando, in maniera non colpevole, il suo ruolo protettivo. Contribuisce a crearlo il fatto che la relazione sessuata madre-figlio non si accompagna solitamente ad atti violenti, che le sue “forme di abuso” si accompagnino, confondendosi, con normali gesti di cura, amore e pulizia. Gabbard (1995) sostiene ad esempio che donne che da bambine hanno subito violenze sessuali potranno utilizzare un modello di sessualità femminile esasperato per vendicarsi degli uomini e per rassicurarsi sulla propria femminilità. Dal ruolo “passivo” che l’ha vista vittima e sottomessa, la donna tenta, attraverso il rapporto con un minore che può controllare, il riscatto e la propria affermazione in un ruolo “attivo”. E’ noto come la psicologia del profondo abbia dimostrato che una delle conseguenze più importanti di un trauma non risolto (abbandono, perdita, esperienza di abuso) sia la coazione a ripeterlo.Abusando di minori queste donne possono riprodurre la situazione traumatica originaria, mettendo se stesse nella posizione di controllo anziché di vittima. Potremmo definirlo “principio del controllo e del padroneggiamento del trauma”, In letteratura le autrici di reati sessuali vengono spesso descritte come persone che non hanno risolto completamente i processi di identificazione e differenziazione con la figura materna (M.Tardif et al 2005), che hanno subito abusi da bambine per lungo tempo (CF. Lewis CR Stanley 2000). Persone che non sono riuscite a sviluppare una sana e buona identità materna. Il loro conflitto si consuma tra il desiderio di diventare una madre buona ed i loro comportamenti che tenderanno a ripetere quelli della genitrice o di altro abusante

Uremic Toxin Lanthionine Interferes with the Transsulfuration Pathway, Angiogenetic Signaling and Increases Intracellular Calcium

(1) The beneficial effects of hydrogen sulfide (H2S) on the cardiovascular and nervous system have recently been re-evaluated. It has been shown that lanthionine, a side product of H2S biosynthesis, previously used as a marker for H2S production, is dramatically increased in circulation in uremia, while H2S release is impaired. Thus, lanthionine could be classified as a novel uremic toxin. Our research was aimed at defining the mechanism(s) for lanthionine toxicity. (2) The effect of lanthionine on H2S release was tested by a novel lead acetate strip test (LAST) in EA.hy926 cell cultures. Effects of glutathione, as a redox agent, were assayed. Levels of sulfane sulfur were evaluated using the SSP4 probe and flow cytometry. Protein content and glutathionylation were analyzed by Western Blotting and immunoprecipitation, respectively. Gene expression and miRNA levels were assessed by qPCR. (3) We demonstrated that, in endothelial cells, lanthionine hampers H2S release; reduces protein content and glutathionylation of transsulfuration enzyme cystathionine--synthase; modifies the expression of miR-200c and miR-423; lowers expression of vascular endothelial growth factor VEGF; increases Ca2+ levels. (4) Lanthionine-induced alterations in cell cultures, which involve both sulfur amino acid metabolism and calcium homeostasis, are consistent with uremic dysfunctional characteristics and further support the uremic toxin role of this amino acid

Lamin A/C Missense Mutation R216C Pinpoints Overlapping Features Between Brugada Syndrome and Laminopathies

A 31-year-old man experienced at-rest cardiac arrest. After successful resuscitation, the baseline ECG demonstrated sinus rhythm with concave ST segment elevation in right precordial leads (V1–V3) followed by a negative and symmetrical T-wave. Neither coronary artery disease nor electrolytes’ imbalances were detected. In the following days, ECG showed a spontaneous type 1 Brugada ECG pattern (Figure [A1]), more evident with right precordial leads in II and III intercostal spaces. Transthoracic echocardiography (Figure [A2]) failed to show any cardiomyopathy. Cardiac MRI showed normal chambers dimension, wall thickness, volume, and function (left ventricular end diastolic volume, 67.7 mL/m2; IVS, 1 cm; left ventricular end fraction, 59.7%). Late gadolinium enhancement sequences were negative; adipose and fibrous tissue infiltration were excluded. The patient was implanted with a transvenous single chamber cardioverter defibrillator (Medtronic). Several appropriate ICD interventions on VT and ventricular fibrillation were recorded in the following years. Family history (Figure [B]) was positive for sudden cardiac death: the maternal grandfather died at age 45 years, aII degree maternal cousin died during sleep at age 40 years. The proband’s mother showed a first degree atrioventricular block (PR interval=280 ms) and right bundle branch block (Figure [A3]). A neurological examination in the index case and his mother was negative and creatine phosphokinase levels were normal in both. Informed written consent was obtained from all family members. Study was approved by the Local Ethics Committee (152/2013/O/Oss, June 1, 2013). Molecular genetic analysis was performed by next generation sequencing using PED MASTR Plus assay comprising 52 cardiac electrical disorders related genes, SCN5A included (www.agilent.com)

Oxidoreductases and metal cofactors in the functioning of the earth

: Life sustains itself using energy generated by thermodynamic disequilibria, commonly existing as redox disequilibria. Metals are significant players in controlling redox reactions, as they are essential components of the engine that life uses to tap into the thermodynamic disequilibria necessary for metabolism. The number of proteins that evolved to catalyze redox reactions is extraordinary, as is the diversification level of metal cofactors and catalytic domain structures involved. Notwithstanding the importance of the topic, the relationship between metals and the redox reactions they are involved in has been poorly explored. This work reviews the structure and function of different prokaryotic organometallic-protein complexes, highlighting their pivotal role in controlling biogeochemistry. We focus on a specific subset of metal-containing oxidoreductases (EC1 or EC7.1), which are directly involved in biogeochemical cycles, i.e., at least one substrate or product is a small inorganic molecule that is or can be exchanged with the environment. Based on these inclusion criteria, we select and report 59 metalloenzymes, describing the organometallic structure of their active sites, the redox reactions in which they are involved, and their biogeochemical roles

ATP Sensitive Potassium Channels in the Skeletal Muscle Function: Involvement of the KCNJ11(Kir6.2) Gene in the Determination of Mechanical Warner Bratzer Shear Force

The ATP-sensitive K-channels (KATP) are distributed in the tissues coupling metabolism with K ions efflux. KATP subunits are encoded by KCNJ8 (Kir6.1), KCNJ11 (Kir6.2), ABCC8 (SUR1), and ABCC9 (SUR2) genes, alternative RNA splicing give rise to SUR variants that confer distinct physiological properties on the channel. An high expression/activity of the sarco-KATP channel is observed in various rat fast-twitch muscles, characterized by elevated muscle strength, while a low expression/activity is observed in the slow twitch muscles characterized by reduced strength and frailty. Down-regulation of the KATP subunits of fast-twitch fibers is found in conditions characterized by weakness and frailty. KCNJ11 gene knockout mice have reduced glycogen, lean phenotype, lower body fat, and weakness. KATP channel is also a sensor of muscle atrophy. The KCNJ11 gene is located on BTA15, close to a QTL for meat tenderness, it has also a role in glycogen storage, a key mechanism of the postmortem transformation of muscle into meat. The role of KCNJ11 gene in muscle function may underlie an effect of KCNJ11 genotypes on meat tenderness, as recently reported. The fiber phenotype and genotype are important in livestock production science. Quantitative traits including meat production and quality are influenced both by environment and genes. Molecular markers can play an important role in the genetic improvement of animals through breeding strategies. Many factors influence the muscle Warner-Bratzler shear force including breed, age, feeding, the biochemical, and functional parameters. The role of KCNJ11gene and related genes on muscle tenderness will be discussed in the present review

Pre- and postsynaptic N-methyl-D-aspartate receptors are required for sequential printing of fear memory engrams

The organization of fear memory involves the participation of multiple brain regions. However, it is largely unknown how fear memory is formed, which circuit pathways are used for "printing" memory engrams across brain regions, and the role of identified brain circuits in memory retrieval. With advanced genetic methods, we combinatorially blocked presynaptic output and manipulated N-methyl-D-aspartate receptor (NMDAR) in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) before and after cued fear conditioning. Further, we tagged fear-activated neurons during associative learning for optogenetic memory recall. We found that presynaptic mPFC and postsynaptic BLA NMDARs are required for fear memory formation, but not expression. Our results provide strong evidence that NMDAR-dependent synaptic plasticity drives multi-trace systems consolidation for the sequential printing of fear memory engrams from BLA to mPFC and, subsequently, to the other regions, for flexible memory retrieval

Analysis of Italian requests for compensation in cases of responsibility for healthcare-related infections: A retrospective study

IntroductionThe aim of this study was to examine the type of compensation claims for alleged medical malpractice in the field of healthcare-related infections in Italy.MethodsIt was analyzed which was the most frequent clinical context, the characteristics of the disputes established, which were the alleged damages most often complained of, which were the possibly censurable behaviors of the health professionals, and which were the reasons for acceptance or rejection of the request for compensation.ResultsIn 90.2%, the issue questioned regarded surgical site infections. The most common pathogens involved were coagulase-negative Staphylococci (34.1%) and Staphylococcus aureus (24.4%). The lack or non-adherence to protocols of prophylaxis and/or prevention of healthcare-related infections was the most reported cause of acceptance of the request of compensation.DiscussionAccording to our data, a stronger effort should be made in terms of risk management perspective in order to ensure the develop and application of protocols for prevention of Gram-positive healthcare-related infections and strengthen infection control and antimicrobial stewardship programs