Structure and dynamics of aqueous norspermidine solutions: anin situultrasonic relaxation spectroscopic study.

Anin situultrasonic relaxation spectroscopic study is presented in an effort to determine the structural changes and the dynamics involved when norspermidine (NSpd) is dissolved in water. Our aim is to elucidate the mechanism responsible for the observed relaxation mechanism in acoustic spectra and estimate the corresponding thermodynamic parameters and the associated volume change. The experimental spectra of aqueous NSpd solutions revealed a single Debye-type relaxation mechanism attributed to proton-transfer reaction. The concentration and temperature dependence of the acoustic parameters supports this assignment. The activation enthalpy and entropy were estimated equal to ΔH*= 1.79 ± 0.20 kcal mol-1and ΔS*= -18.31 ± 0.73 cal mol-1 K-1, respectively. The concentration and temperature dependence of the sound velocity and absorption in the solutions exhibit characteristic features that are related to alterations in the network rigidity due to variations in hydrogen-bonding interactions at molecular level. The volume change associated to proton-transfer reaction for NSpd has been estimated and compared with the volume change observed for an analogous guanidine, the 1,1,3,3 tetramethyl guanidine. The obtained results are discussed in the framework of an existing theoretical structural model highlighting the strong molecular association in these liquid mixtures leading to complementary information on the structure and dynamics of guanidine amines. A comprehensive model of the whole relaxation processes is presented and discussed in detail.

Prevalence, pathophysiology and management of itch in epidermolysis bullosa.

Epidermolysis bullosa (EB) is a highly diverse group of inherited skin disorders, resulting from mutations in genes encoding proteins of the dermoepidermal junction. Itch (pruritus) is one of the most common symptoms across all EB subtypes. It occurs in blistered or wounded sites, or manifests as a generalized phenomenon, thereby affecting both intact skin and healing wounds. The mechanism of pruritus in EB is unclear. It is likely that skin inflammation secondary to barrier disruption, wound healing cascades and dysregulated activation of epidermal sensory nerve endings are all involved in its pathophysiology on the molecular and cellular level. Understanding these mechanisms in depth is crucial in developing optimized treatments for people with EB and improving quality of life. This review summarizes current evidence on the prevalence, mechanisms and management of itch in EB.

Long-term outcomes of imiquimod-treated lentigo maligna.

BACKGROUND: Lentigo maligna (LM) may be disfiguring and can progress to LM melanoma. Surgical excision remains the mainstay of treatment, but may result in disfigurement when used for large facial lesions. Topical imiquimod is a nonsurgical alternative although data on its long-term efficacy remain limited. AIM: To assess long-term outcomes of LM treated with imiquimod cream. METHODS: We collected data retrospectively for 33 patients treated with imiquimod cream for biopsy-proven LM from 2001 to 2016. Patients initially applied imiquimod once daily, 5 days/week for 6 weeks, aiming to produce a brisk local inflammatory response. If there was no response, the dose was increased to twice daily 7 days/week for 6 weeks and if again there was no response, to twice daily for 10 weeks. RESULTS: An inflammatory response developed in 29 (88%) of the 33 patients, and of these, 4 patients stopped treatment earlier than planned because they could not tolerate the inflammatory reaction, while 3 patients reported systemic side effects. There was lesion clearance in 21 (72%) of the 29 patients, and they remained clear after a mean follow-up of 4.1 years. Eight failed to clear; in five the lesion was excised, while the remaining three were managed expectantly. CONCLUSIONS: Our results support the use of imiquimod as an alternative to surgery for the treatment of LM in selected cases. With adequate patient preparation, imiquimod is generally tolerated and can achieve excellent cosmetic results. A clinical response is more likely if there is a brisk inflammatory response, and LM will not resolve if there is no inflammatory response.

Store-operated calcium entry is essential for glial calcium signalling in CNS white matter.

'Calcium signalling' is the ubiquitous response of glial cells to multiple extracellular stimuli. The primary mechanism of glial calcium signalling is by release of calcium from intracellular stores of the endoplasmic reticulum (ER). Replenishment of ER Ca2+ stores relies on store-operated calcium entry (SOCE). However, despite the importance of calcium signalling in glial cells, little is known about their mechanisms of SOCE. Here, we investigated SOCE in glia of the mouse optic nerve, a typical CNS white matter tract that comprises bundles of myelinated axons and the oligodendrocytes and astrocytes that support them. Using quantitative RT-PCR, we identified Orai1 channels, both Stim1 and Stim2, and the transient receptor potential M3 channel (TRPM3) as the primary channels for SOCE in the optic nerve, and their expression in both astrocytes and oligodendrocytes was demonstrated by immunolabelling of optic nerve sections and cultures. The functional importance of SOCE was demonstrated by fluo-4 calcium imaging on isolated intact optic nerves and optic nerve cultures. Removal of extracellular calcium ([Ca2+]o) resulted in a marked depletion of glial cytosolic calcium ([Ca2+]i), which recovered rapidly on restoration of [Ca2+]o via SOCE. 2-aminoethoxydiphenylborane (2APB) significantly decreased SOCE and severely attenuated ATP-mediated calcium signalling. The results provide evidence that Orai/Stim and TRPM3 are important components of the 'calcium toolkit' that underpins SOCE and the sustainability of calcium signalling in white matter glia.

Effect of external classroom noise on schoolchildren's reading and mathematics performance: correlation of noise levels and gender.

The present study investigated the effect of low, medium, and high traffic road noise as well as irrelevant background speech noise on primary school children's reading and mathematical performance. A total of 676 participants (324 boys, 47.9% and 352 girls, 52.1%) of the 4th and 5th elementary classes participated in the project. The participants were enrolled in public primary schools from urban areas and had ages ranging from 9 to 10 years and from. Schools were selected on the basis of increasing levels of exposure to road traffic noise and then classified into three categories (Low noise: 55-66 dB, Medium noise: 67-77 dB, and High noise: 72-80 dB). We measured reading comprehension and mathematical skills in accordance with the national guidelines for elementary education, using a test designed specifically for the purpose of this study. On the one hand, children in low-level noise schools showed statistically significant differences from children in medium- and high-level noise schools in reading performance (p<0.001). On the other hand, children in low-level noise schools differed significantly from children in high-level noise schools but only in mathematics performance (p=0.001). Girls in general did better in reading score than boys, especially in schools with medium- and high-level noise. Finally the levels of noise and gender were found to be two independent factors.

Body composition changes in protease inhibitor-naive HIV-infected patients treated with two nucleoside reverse transcriptase inhibitors.

OBJECTIVES: In the era of highly active antiretroviral treatment (HAART), there are insufficient data regarding lipodystrophy syndromes in HIV-1-infected patients treated with regimens that do not include protease inhibitors (PIs). We studied changes in body composition in HIV-1-infected patients before and 2 years after starting a non-PI-containing antiretroviral treatment regimen. METHODS: We studied retrospectively the whole body dual energy X-ray absorptiometry (DEXA) scans of 23 PI-naive HIV-1-infected patients (17 males, six females), aged 37.4 +/- 9.3 years with mean CD4 count 401 +/- 130 cells/microL. Thirteen patients were on zidovudine (ZDV) + lamivudine (3TC) and 10 on ZDV + didanosine (ddI). Subjects were evaluated before the beginning of antiretroviral treatment and approximately 24 months later. For each patient body weight, CD4 T-cell counts, bone mineral content (BMC), bone mineral density (BMD) and whole body as well as regional fat and lean body mass were evaluated. RESULTS: A significant decrease in BMC was observed, although the T scores remained within the normal limits. Our patients also exhibited a significant decrease in body weight due almost exclusively to fat loss, while lean mass was minimally affected. Fat loss was statistically significant in the arms and legs, but not in the trunk. The above changes were most prominent in the ZDV + 3TC treatment group; in this group of patients, fat loss was also evident in the trunk. Patients on ZDV + ddI, on the other hand, only showed a significant increase in their legs' lean mass; they preserved their total fat mass and exhibited no other significant changes between the two assessments. CONCLUSIONS: Dual NRTI therapy contributes to fat loss and reduction of bone mineral content in otherwise healthy, clinically stable, PI-naive HIV-infected adults. Compared with patients on ZDV + ddI, patients on ZDV + 3TC had a more prominent fat loss in all body regions.

Bacterial sepsis-induced rhabdomyolysis.

OBJECTIVE: To describe the syndrome of rhabdomyolysis during bacterial sepsis with regard to incidence, blood bacteriology and complications and to examine the association between hyperosmolal state and rhabdomyolysis, evaluating the relationship between plasma osmolality (Posm) and serum creatine phosphokinase (CPK) levels. DESIGN: Prospective study including all patients admitted to the intensive care unit (ICU) for sepsis with positive blood culture and rhabdomyolysis over a 3-year period. SETTING: Seven-bed medical/surgical ICU of a teaching hospital. PATIENTS: 35 patients (group 1) with bacterial sepsis-induced rhabdomyolysis (15 males, 20 females; mean age 71+/-13 years) and 122 (group 2) bacteraemic septic patients without rhabdomyolysis (49 males, 73 females; mean age 68+/-15) were studied. Patients with rhabdomyolysis were divided into gram(+) and gram(-) subgroups according to the blood culture growth. RESULTS: From 491 patients recorded, 35 fulfilled the inclusion criteria for bacterial sepsis-induced rhabdomyolysis (7.1%). Gram-positive bacteria predominated in group 1 (69%), while gram-negative predominated (60%) in group 2. There was a correlation between CPK and Posm levels in the rhabdomyolysis Group (r = 0.52, R2 = 0.27, p = 0.003). There was a stronger correlation between these two variables (r = 0.67, R2 = 0.45, p = 0.001) in the gram(+).subgroup. Acute renal failure (68.5%) and electrolyte disorders such as hyperkalaemia (34%) and hypocalcaemia (48.5%) were the major complications in the rhabdomyolysis group. Sixteen (45.7%) patients in group 1 and 49 (40%) in group 2 died during their stay in the ICU from sepsis and multiple organ failure. Rhabdomyolysis was not considered a contributing factor to their death, as none of our patients died during or immediately after the syndrome. CONCLUSION: Bacterial sepsis-induced rhabdomyolysis results from certain types of microorganisms, mainly gram-positive and to a lesser extent gram-negative. Hyperosmolality is a predisposing mechanism for rhabdomyolysis during bacteraemic sepsis from any type of bacterial microorganism.

Psychological factors influencing the surgical patients' consent to regional anaesthesia.

To investigate the preoperative attitude of surgical patients to regional anaesthesia, 162 subjects scheduled for elective surgery were studied. On the day before operation, patients were interviewed by an anaesthesiologist, using a semi-structured schedule. Topics investigated were sociodemographic variables and clinical correlates, such as past anaesthetic experience, information about anaesthesia and surgery, as well as questions and fears related to anaesthesia. Subjects were assessed for personality characteristics and emotional symptoms by Eysenck's Personality Questionnaire (EPQ), Zung's Self-rating Anxiety and Depression Rating Scales, Schalling-Sifneos' Personality Scale and the 43-item Life Events Inventory of Holmes and Rahe. Seventy-one patients (44%) consented to regional anaesthesia. Consent to regional anaesthesia was associated with advanced age, low neuroticism and high extroversion score in the EPQ, as well as longer duration of illness. The deniers of consent asked more questions and expressed more fears about anaesthesia. It is suggested that the patients' characteristics influence their preference, acceptance or refusal of regional anaesthesia.

Influence of psychological and clinical factors on postoperative pain and narcotic consumption.

Demographic, psychological and clinical factors influencing postoperative pain and narcotic analgesic requirements in 162 patients undergoing elective operations under general anesthesia were studied. Eysencks Personality Questionnaire, Foulds Hostility Questionnaire, Zung's Anxiety-Depression (self-rating) Scales and the 43 Item Life Events Inventory by Holmes and Rahe were used. Clinical correlates such as surgical department, outcome of the operation, patient's knowledge of the diagnosis, were studied. Using multiple regression analysis the following results were obtained: postoperative pain levels increase with higher score of extroverted hostility (p = 0.038), abdominal surgery (p = 0.004), longer stay at hospital postoperatively (p = 0.15) and higher educational status (p = 0.13). Postoperative narcotic requirements increase with increased postoperative pain levels (p = 0.039) and preoccupation with pain postoperatively (p = 0.025), preoperative analgesic drug use (p = 0.017), abdominal surgery (p = 0.009) and longer stay at hospital preoperatively (p = 0.016). Also the department in which the patients were hospitalized influenced narcotic consumption.