Targeted therapy of cognitive deficits in fragile X syndrome.

Breaking an impasse in finding mechanism-based therapies of neuropsychiatric disorders requires a strategic shift towards alleviating individual symptoms. Here we present a symptom and circuit-specific approach to rescue deficits of reward learning in Fmr1 knockout mice, a model of Fragile X syndrome (FXS), the most common monogenetic cause of inherited mental disability and autism. We use high-throughput, ecologically-relevant automated tests of cognition and social behavior to assess effectiveness of the circuit-targeted injections of designer nanoparticles, loaded with TIMP metalloproteinase inhibitor 1 protein (TIMP-1). Further, to investigate the impact of our therapeutic strategy on neuronal plasticity we perform long-term potentiation recordings and high-resolution electron microscopy. We show that central amygdala-targeted delivery of TIMP-1 designer nanoparticles reverses impaired cognition in Fmr1 knockouts, while having no impact on deficits of social behavior, hence corroborating symptom-specificity of the proposed approach. Moreover, we elucidate the neural correlates of the highly specific behavioral rescue by showing that the applied therapeutic intervention restores functional synaptic plasticity and ultrastructure of neurons in the central amygdala. Thus, we present a targeted, symptom-specific and mechanism-based strategy to remedy cognitive deficits in Fragile X syndrome.

Superconductivity in CaBi2.

Superconductivity is observed with critical temperature Tc = 2.0 K in self-flux-grown single crystals of CaBi2. This material adopts the ZrSi2 structure type with lattice parameters a = 4.696(1) Å, b = 17.081(2) Å and c = 4.611(1) Å. The crystals of CaBi2 were studied by means of magnetic susceptibility, specific heat and electrical resistivity measurements. The heat capacity jump at Tc is ΔC/γTc = 1.41, confirming bulk superconductivity; the Sommerfeld coefficient γ = 4.1 mJ mol(-1) K(-2) and the Debye temperature ΘD = 157 K. The electron-phonon coupling strength is λel-ph = 0.59, and the thermodynamic critical field Hc is low, between 111 and 124 Oe CaBi2 is a moderate coupling type-I superconductor. Results of electronic structure calculations are reported and charge densities, electronic bands, densities of states and Fermi surfaces are discussed, focusing on the effects of spin-orbit coupling and electronic property anisotropy. We find a mixed quasi-2D + 3D character in the electronic structure, which reflects the layered crystal structure of the material.

A massive binary black-hole system in OJ 287 and a test of general relativity.

Tests of Einstein's general theory of relativity have mostly been carried out in weak gravitational fields where the space-time curvature effects are first-order deviations from Newton's theory. Binary pulsars provide a means of probing the strong gravitational field around a neutron star, but strong-field effects may be best tested in systems containing black holes. Here we report such a test in a close binary system of two candidate black holes in the quasar OJ 287. This quasar shows quasi-periodic optical outbursts at 12-year intervals, with two outburst peaks per interval. The latest outburst occurred in September 2007, within a day of the time predicted by the binary black-hole model and general relativity. The observations confirm the binary nature of the system and also provide evidence for the loss of orbital energy in agreement (within 10 per cent) with the emission of gravitational waves from the system. In the absence of gravitational wave emission the outburst would have happened 20 days later.

Ability to share emotions of others as a foundation of social learning.

The natural habitats of most species are far from static, forcing animals to adapt to continuously changing conditions. Perhaps the most efficient strategy addressing this challenge consists of obtaining and acting upon pertinent information from others through social learning. We discuss how animals transfer information via social channels and what are the benefits of such exchanges, playing out on different levels, from theperception of socially delivered information to emotional sharing, manifesting themselves across different taxa of increasing biological complexity. We also discuss how social learning is influenced by different factors including pertinence of information for survival, the complexity of the environment, sex, genetic relatedness, and most notably, the relationship between interacting partners. The results appear to form a consistent picture once we shift our focus from emotional contagion as a prerequisite for empathy onto the role of shared emotions in providing vital information about the environment. From this point of view, we can propose approaches that are the most promising for further investigation of complex social phenomena, including learning from others.

Synthesis, structure and physical properties of new intermetallic spin glass-like compounds RE 2PdGe3 (RE = Tb and Dy).

New intermetallic compounds Tb2Pd1.25Ge2.75 and Dy2Pd1.25Ge2.75 have been synthesized using the arc-melting method. The crystallographic structure and magnetic, electronic transport, and thermal properties are reported. The crystal structure obtained from powder x-ray diffraction analysis suggests that these compounds crystallize in the AlB2-type structure (space group P6/mmm, no. 191) with lattice parameters a = 4.228 53(5)/4.230 54 (2) Å and c = 3.942 25(9)/3.945 52(5) Å for the compounds with Tb and Dy respectively. The ac and dc magnetic susceptibility studies reveal spin-glass like behavior, with freezing temperature T f = 10.5 K for Tb2Pd1.25Ge2.75 and 4.5 K for Dy2Pd1.25Ge2.75. These data are in good agreement with the heat capacity measurements.

Person perception as a function of drinking behavior, gender and sex role stereotypes.

Gender and the level of drinking of the protagonist in a vignette were systematically varied to examine the effects of these variables on the inferences 400 undergraduates drew about the personal attributes and future of the character. Results showed that gender of the target did not significantly affect judgments about the protagonist, but perceptions of the character were strongly influenced by the alcohol-related behaviors attributed to him or her in the vignette. Evaluations of the protagonist generally became less favorable as drinking level increased. Abstainers were also viewed more positively than at least some comparison groups of drinkers on most measures. Although heavier drinkers were often stigmatized, they were also seen as having more fun. Subject gender, sex role attributes and attitudes toward women failed to influence judgments about the protagonists, but raters' own drinking habits did have an impact. Heavier drinkers showed a tendency to rate heavier drinking protagonists more favorably than did lighter drinkers. Implications of these results for prevailing theories about norms and evaluations affecting drinkers are discussed.

[The effect of surgical trauma on the level of plasma iron]. / Wplyw urazu operacyjnego na poziom zelaza w osoczu.

UNLABELLED: The serum iron level drops in many diseases and after bone fractures or elective surgical operations. The aim of this study was to determine if the degree of stress hypoferremia depends on severity of the operation. Serum iron concentration and TIBC was measured during two weeks in 37 patients. The first group consisted of 29 patients operated for ingunal hernia or cholelithiasis. It was laparoscopic cholecystectomy or classical or laparoscopic hernia repair. These types of operations were considered as mild surgical stress. The second group consisted of 8 patients with colon cancer, who had segmental colon resection. This operation was considered as severe surgical stress. The patients with colon cancer had significantly lower preoperative serum iron level. After operations, profound but temporal drop in serum iron concentration was observed in both groups of patients. TIBC drops but not so significantly. The diagrams illustrating changes of iron concentration after operations looked similar in both groups. CONCLUSION: The changes of iron concentration after abdominal operations are independent of the severity of surgical stress.

[Primary peritoneal mesothelioma--report of two cases]. / Pierwotny miedzybloniak otrzewnej--opis dwóch przypadków.

We report two cases of primary peritoneal mesothelioma. In both of them contact with asbestos was negative. In the first case the patient was hospitalized in another hospital five years earlier. The performed USG and CT of the abdomen revealed the tumor near the spleen. But then the patient was not operated. In the second case the symptoms lasted for several months. In both cases the tumors were nonoperative because of the advanced malignant process.

[The cause of upper gastrointestinal bleeding and the value of emergency endoscopic hemostasis]. / Przyczyny krwawien z górnego odcinka przewodu pokarmowego i wartosc doraznej sklerotyzacji endoskopowej.

Introduction of endoscopy and endoscopic hemostasis had substantial impact on the treatment of diseases of stomach and duodenum complicated by bleeding. We compared two 4-years' periods analysing etiology of bleeding and influence of endoscopic haemostasis on outcome of patients with upper gastrointestinal haemorrhage. Number of patients in both groups were comparable. Ratio of bleeding related to gastric and duodenal ulcer didn't change substantially. Number of patients with haemorrhagic gastritis decreased somehow while those with bleeding oesophageal varies increased. Number of patients submitted to emergency operation for bleeding ulcer decreased significantly. Mortality was lower in the second period of time only in patients with haemorrhage requiring transfusion of 4-7 units of blood.

Magnetic phase transitions and superconductivity in strained FeTe.

The influence of hydrostatic pressure and ab-plane strain on the magnetic structure of FeTe is investigated from first principles. The results of calculations reveal a phase transition from antiferromagnetic double-stripe ordering at ambient pressure to ferromagnetic ordering at 2 GPa, or under compressive strain reducing the lattice parameter a by about 3%. In turn, a tensile strain of less than 2% induces the phase transition to antiferromagnetic single-stripe ordering. It corresponds to the superconducting FeTe thin films, thereby confirming that the superconducting state is positively linked to single-stripe antiferromagnetic fluctuations. Both types of transition indicate that the position of Te atoms in the crystal is crucial for the magnetic and superconducting properties of iron chalcogenides.

Short hospital stays after laparoscopic gastric surgery under an Enhanced Recovery After Surgery (ERAS) pathway: experience at a single center.

INTRODUCTION: Recently, first reports on benefits from Enhanced Recovery After Surgery (ERAS) pathway in patients undergoing gastric surgery have appeared. It seems that maximal reduction of unfavorable surgery-induced trauma in patients with gastric malignancy via ERAS protocol combined with minimally invasive techniques can improve outcomes. OBJECTIVE: The aim of this study was to determine the influence of laparoscopic surgery and ERAS protocol in oncological gastric surgery on early outcomes. MATERIALS AND METHODS: Prospective analysis involved 28 patients (18 female and 10 male) with gastric malignancy who underwent laparoscopic gastric resection between 2009 and 2013. Gastric tumors (gastrointestinal stromal tumors or adenocarcinoma) were the indication for the surgery. A total of 17 patients underwent laparoscopic local excision, and 11 patients with adenocarcinoma or multiple neuroendocrine tumors underwent laparoscopic D2 total gastrectomy. Perioperative care was based on ERAS principles. Length of hospital stay, postoperative course, perioperative complications, and readmission rates were analyzed. RESULTS: There was one conversion in the gastrectomy group. All patients were mobilized on the day of surgery. Oral fluids were introduced on day 0 and were well tolerated. Full hospital diet was started on day 2 in all patients, but was well tolerated in only 18 of them. One postoperative complication requiring reoperation was noted. The length of stay after gastrectomy and gastric wedge resection was 4.6 (2-6) and 3.3 (2-6) days, respectively. No readmissions were noted in the entire group. CONCLUSIONS: The implementation of ERAS protocol to clinical practice in combination with laparoscopy in patients with gastric tumors can result in improved postoperative care quality, shortening of hospital stay, and quicker return to normal activity.

IL-6 and IL-8 responses of colorectal cancer in vivo and in vitro cancer cells subjected to simvastatin.

Recent investigations suggest that proinflammatory cytokines such as IL-6 and IL-8 are involved in the development of colorectal cancer (CRC), whereas statins, primarily used to decrease high levels of blood cholesterol, exhibit pleiotropic effects on carcinogenesis. In the present study we compared the expression of IL-8 and IL-6 in tissue samples of tumor and adjacent normal colon mucosa obtained from patients with advanced colorectal cancer (CRC). The analysis of mRNAs expression for these proinflammatory cytokines determined by RT-PCR showed a higher level of IL-8-mRNA in tumor tissue than in normal mucosa, while IL-6 was similarly expressed in tumor and normal tissue. The mean values of serum levels of both IL-6 and IL-8 were significantly higher in CRC patients than in healthy volunteers. Surgical removal of the tumor resulted in a prompt decrease of serum level of IL-8 already on the third day, whereas IL-6 level was transiently increased to become lower only after 7-10 days. Treatment of CRC with simvastatin (80 mg/day for 14 days) led to a significant decrease of serum IL-6, while the IL-8 level was less affected. The in vitro experiments on colorectal cancer-derived cell lines (HT-29 and Caco-2) demonstrated that application of simvastatin decreased generation of both IL-6 and IL-8. The differences in response of serum levels of IL-6 and IL-8 after tumor removal and treatment with simvastatin are novel observations suggesting distinct pathological roles of the two cytokines in CRC development. We conclude that 1) colorectal carcinogenesis is accompanied by increased synthesis and release of proinflammatory cytokines such as IL-6 and IL-8; 2) simvastatin therapy results in a decrease in serum level of proinflammatory cytokines, especially IL-6 in CRC and 3) simvastatin inhibits release of IL-8 and IL-6 from colorectal cell lines.

Acute biliary pancreatitis in the era of minimally invasive surgery.

PURPOSE: Opinions about early endoscopic sphincterotomy and time of laparoscopic cholecystectomy in acute biliary pancreatitis are still controversial. Some authors reserved this procedure only for cases in which the stones were visualized during ERCP or patients had clinical symptoms of acute cholangitis. The aim was the assessment of the dynamic of changes of proinflammatory cytokines and white blood cells in time in patients with acute biliary pancreatitis after performed endoscopic sphincterotomy and laparoscopic cholecystectomy. MATERIAL AND METHODS: We enrolled 43 consecutive patients with clinically diagnosed mild forms of acute biliary pancreatitis. All were treated by early endoscopic sphincterotomy and laparoscopic cholecystectomy performed during the first 48 hours after admission. The course of the disease was monitored by measurement of the level of proinflammatory cytokines. RESULTS: Marked decrease of the level of proinflammatory interleukins within 24 hours after endoscopic sphincterotomy was observed. Mean values of IL-6 and IL-8 were statistically lower immidiately after this procedure (p < 0.001). Subsequent decrease was achieved after laparoscopic cholecystectomy. The mean values of TNF-alpha and IL-12p40 were relatively constant throughout the study period. CONCLUSION: All patients suffering from mild acute biliary pancreatitis should be treated by using minimally invasive procedures. However, such a only treatment should be reserved for experienced centers.

Outcomes of an inner-city HIV mental health programme integrated with primary care and emphasizing cultural responsiveness.

Effectiveness of HIV-related mental health practice in inner cities has not been adequately documented despite an urgent need for interventions for populations disproportionately affected by the epidemic. Practices must take into account and respond to cultural issues of people of colour and the needs of those infected through injection drug use or heterosexual sex with IDUs. We report the effectiveness of an HIV mental health programme integrated with primary care and emphasizing cultural responsiveness. A sample of 47 of 188 patients who received psychiatric and psychotherapy services was compared with other subjects. The 47 had an average of 8.34 encounters over an average of 36.23 weeks. Consumers of project services used mental health care at a higher rate than did comparison subjects. Regression analyses indicated that utilization was related to reduction in reported mental health problems, HIV-related physical symptoms, and use of alcohol and powdered cocaine, as well as to improvement in social functioning. Our clients, individuals often viewed as not likely to avail themselves of or benefit from mental health care, were highly motivated for self-improvement and, given access to competent, convenient and culturally respectful services, improved their well-being in significant domains.