Identification of infection by Leishmania spp. in wild and domestic animals in Brazil: a systematic review with meta-analysis (2001-2021).
Leishmaniasis is a zoonosis caused by protozoan species of the genus Leishmania. It generates different clinical manifestations in humans and animals, and it infects multiple hosts. Leishmania parasites are transmitted by sandfly vectors. The main objective of this systematic review was to identify the host, or reservoir animal species, of Leishmania spp., with the exception of domestic dogs, that were recorded in Brazil. This review included identification of diagnostic methods, and the species of protozoan circulating in the country. For this purpose, a literature search was conducted across index journals. This study covered the period from 2001 to 2021, and 124 studies were selected. Eleven orders possible hosts were identified, including 229 mammalian species. Perissodactyla had the highest number of infected individuals (30.69%, 925/3014), with the highest occurrence in horses. In Brazil, the most commonly infected species were found to be: horses, domestic cats, rodents, and marsupials. Bats, that were infected by one or more protozoan species, were identified as potential reservoirs of Leishmania spp. Molecular tests were the most commonly used diagnostic methods (94 studies). Many studies have detected Leishmania spp. (n = 1422): Leishmania (Leishmania) infantum (n = 705), Leishmania (Viannia) braziliensis (n = 319), and Leishmania (Leishmania) amazonensis (n = 141). Recognizing the species of animals involved in the epidemiology and biological cycle of the protozoan is important, as this allows for the identification of environmental biomarkers, knowledge of Leishmania species can improve the control zoonotic leishmaniasis.


Decreased serum level of HMGB1 and MyD88 during human aging progress in healthy individuals.
Previous studies have suggested that high mobility group box-1 protein (HMGB1) binds to the toll-like receptor 4 (TLR4) signaling mediates the progression of various inflammatory diseases. But the roles of HMGB1 and TLR4 in aging remain poorly unknown. In this study, we aimed to investigate the serum levels of HMGB1 and myeloid differentiation factor 88 (MyD88), which is one of TLR4's intracellular adaptor proteins during human aging process and their relevance with cathepsin B (CTSB). This research was conducted using the blood samples provided by healthy people (n = 90, 63 men and 27 women). Subjects were subdivided into groups with respect to age: young (about 25 years old, n = 30), middle age (about 40 years old, n = 30), and aged (above 65 years old, n = 30). Altered serum levels of HMGB1, MyD88 and CTSB were measured using an enzyme-linked immunosorbent assay. The serum levels of HMGB1 and MyD88 were significantly decreased in the aged group compared with those in the young group. Linear regression analysis showed that HMGB1 and MyD88 positively correlated with CTSB among the whole healthy people. A negative correlation was determined between MyD88 and age. The serum levels of HMGB1 and MyD88 significantly decreased with age. MyD88, but not HMGB1, was negatively correlated with age.


Exploring the UDP pocket of LpxC through amino acid analogs.
Lipopolysaccharide (LPS) biosynthesis is an attractive antibacterial target as it is both conserved and essential for the survival of key pathogenic bacteria. Lipid A is the hydrophobic anchor for LPS and a key structural component of the outer membrane of Gram-negative bacteria. Lipid A biosynthesis is performed in part by a unique zinc dependent metalloamidase, LpxC (UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase), which catalyzes the first non-reversible step in lipid A biosynthesis. The UDP portion of the LpxC substrate-binding pocket has been relatively unexplored. We have designed and evaluated a series of hydroxamate based inhibitors which explore the SAR of substitutions directed into the UDP pocket with a range of substituted α-amino acid based linkers. We also provide the first wild type structure of Pseudomonas aeruginosa LpxC which was utilized in the design of many of these analogs.


Antagonism by taurine of morphine induced growth hormone secretion.
The intraperitoneal (IP) or intraventricular (IVT) administration of small amounts of taurine did not modify pentobarbital-induced sleep or pituitary hormone release. However, the drastic increment in plasma GH values induced by morphine administration was completely blocked by the IVT injection of the amino acid. Whether taurine plays a physiological role in the control of GH secretion is highly speculative.


Descending influences on the responses of spinocervical tract neurones to chemical stimulation of fine muscle afferents.
1. In cats, extracellular micro-electrode recordings were made from axons of the spinocervical tract (s.c.t.) in both the decerebrate state and during cold block of the spinal cord (reversible spinal state) to examine the effects of intra-arterial injection of algesic agents (bradykinin, potassium, 5-hydroxytryptamine) into the gastrocnemius-soleus (g.s.) muscle on the discharge behaviour of s.c.t. neurones.2. In the decerebrate state without cooling the spinal cord 13% of the cells (eleven out of eighty-three) responded to intra-arterial injection of bradykinin, 33% (twenty-two out of sixty-nine) to 5-hydroxytryptamine, and 38% (thirty-five out of ninety-one) to potassium injection.3. The general time course and the latency of the responses of s.c.t. cells induced by injection of pain-producing substances into the g.s. muscle reflect in many respects the activations of g.s. group III and group IV primary afferent units studied previously.4. For twenty-seven s.c.t. neurones the period of recording was long enough to record the responses of the same cell to injections of algesic agents in both the decerebrate and the reversible spinal state. In the reversible spinal state 83% (nineteen out of twenty-three) of the s.c.t. neurones tested with all the three substances responded to at least one of the algesic agents. In the decerebrate state the percentage was lower (39%).5. Reversible spinalization led not only to a significant increase in the number of s.c.t. neurones responding to the algesic agents used but also to an increase in the magnitude of the chemically induced responses.6. The mean latency of the responses of neurones that were activated in both preparations were shorter in the reversible spinal state than in the decerebrate state.7. Control experiments showed that the responses to bradykinin and potassium were entirely due to the nervous outflow from the g.s. muscle. In contrast, intra-arterially applied 5-hydroxytryptamine influenced the s.c.t. cells via unknown additional sites of action.8. The results indicate that muscular group III and/or group IV units excitable by algesic substances do project on to neurones of the spinocervical tract. Furthermore it is concluded that the responses of s.c.t. neurones to activation of fine muscle afferents by algesic agents are subject to a descending control similar to the well known descending modulation of their responsiveness to cutaneous input. Therefore, in addition to serving as a cutaneous pathway the spinocervical tract may take part in muscular nociception.


Paroxysmal symptoms in neuromyelitis optica spectrum disorder: Results from an online patient survey.
Paroxysmal symptoms (PS), defined as short-lasting, recurrent, and stereotyped neurological symptoms, are frequently reported by patients with Neuromyelitis Optica Spectrum Disorder (NMOSD). Their prevalence and spectrum of presentations in NMOSD have not been fully characterized. Patients with NMOSD, who were members of a closed international Facebook Group, were recruited to complete an anonymous survey on REDCap. Participants were queried regarding demographic and NMOSD-related characteristics and PS history. The sample consisted of 219 responders with self-reported NMOSD, of whom 134 (63.8%) reported testing positive for AQP4 Antibody. 156 responders (71.9%) reported ≥1 type of PS during the disease course. The most common PS were intermittent tingling/numbness sensation (N=106, 67.9%), followed by involuntary muscle contractions/abnormal posture (N=95, 60.9%), hot/cold/burning sensations (N=87, 55.8%), and shock-like sensations along the spine or limbs (N=77, 49.4%). 150 responders (96% of those with PS) reported that PS were painful; in 82 responders (54.6%), the pain intensity reached ≥ 8/10 and in 40 responders (26.0%) - 10/10 level. PS were most commonly aggravated by fatigue (105 responders, 70.0%), physical activity (N=86, 57.3%), and neck flexion (N=39 responders, 26.0%). 82 patients (52.5% of those with PS) reported having been prescribed one or more medications for PS. Less than 50% reported them to be 'very helpful.' This survey highlights that PS occurs commonly in NMOSD patients. The symptomatology of PS is diverse. PS are often painful and not adequately treated. Our study represents a novel method to learn more about a rare disease from the patient's perspective. Given the fact that the study was conducted using an anonymous questionnaire and the diagnosis of NMOSD was self-reported by the survey participants, its' results should be regarded as a first step towards the understanding of PS in NMOSD, which should be further validated in a larger, controlled study.


South Africa: airline found guilty of employment discrimination.
On 28 September 2000, the Constitutional Court of South Africa ruled that South African Airways (SAA) violated the constitutional rights of Jacques Hoffmann in September 1996 by refusing to employ him as a cabin attendant on the ground that he is HIV-positive.


Sacrococcygeal teratoma: prenatal diagnosis with elevated alphafetoprotein and acetylcholinesterase in amniotic fluid.
A sacrococcygeal teratoma was suspected by ultrasound examination at 24 weeks gestation. The amniotic fluid alphafetoprotein was markedly elevated, as was maternal serum AFP. Gel electrophoresis of amniotic fluid showed an acetylcholinesterase band. Labour began at 25 weeks gestation and the chromosomally normal male fetus was found to have a sacrococcygeal teratoma equal to three-quarters of the weight of the fetus.


Desmoplastic fibroma of the jaw bones: A series of twenty-two cases.
Desmoplastic fibroma (DF) is an intraosseous counterpart of desmoid-type soft tissue fibromatosis. It is most frequently seen in the jawbones. The clinical and radiological features of the present cases were nonspecific. The accumulation of beta-catenin in the nuclei of neoplastic cells which is a diagnostic feature of desmoid-type soft tissue fibromatosis could not be detectED in the present DF series. The aim of this study is to report a series of 22 cases of DF involving either mandible or maxilla. A retrospective evaluation of desmoplastic fibroma and beta-catenin, smooth muscle actin, nestin, cyclin D1 immunostaining's patterns. Most of the DF cases expressed only cytoplasmic beta-catenin immunostainings. We suggest that nuclear beta-catenin staining may not be used as a corroborating the diagnosis of DF. Immunohistochemical staining difference of jaw bone desmoplastic fibromas from other soft tissue and bone lesions may be related to the origination of jaw bone from The neural crest. Strong nestin and cyclin D1 positivity in our series supported this. A combined clinical, radiological, and histopathological analysis of the DF cases is essential in the diagnosis and management.


Cathelicidin modulates synthesis of Toll-like Receptors (TLRs) 4 and 9 in colonic epithelium.
Cathelicidin are innate antimicrobial peptides with broad immunomodulatory functions; however, their role in regulating intestinal defenses is not well characterized. This study aimed to investigate the role of cathelicidin modulating expression of Toll-like receptors (TLRs) 4 and 9 in colonic epithelium in response to bacterial patterns. We demonstrated herein that intestinal epithelial cells, when primed by bacterial lipopolysaccharide (LPS), responded to cathelicidin by increased transcription and protein synthesis of TLR4. This cathelicidin-induced response required the interaction of LPS-TLR4 and activation of MAPK signalling pathways. However, cathelicidin blocked TLR9 responses induced by TLR9 ligand CpG oligodeoxynucleotide (CpG ODN) in these colonic epithelial cells. Modulations of TLRs triggered by cathelicidin in intestinal epithelium occurred mainly in the apical compartment of intestinal cells. Activation of TLR4 by ligands in combination with cathelicidin promoted CXCL8 chemokine secretion and epithelial antimicrobial defenses against Escherichia coli. We concluded that cathelicidin selectively modulated synthesis of TLR4 and 9 in intestinal epithelium, but only when cells were exposed to virulence factors, mostly from apical surfaces. Enhanced TLR4 expression promoted by cathelicidin in intestinal epithelium may be crucial for controlling enteric infectious diseases.


Should the clinic matter to nonphysician scientists?
Translational medicine has been nurtured by the creation of M.D.-Ph.D. programs, a system that now needs to reinvent itself. Now, clinically oriented training programs targeting nonphysician scientists have opened new avenues to improve transdisciplinary approaches in health sciences.


Increased Prevalence of Generalized Joint Hypermobility Observed in Patients With Recurrent Temporomandibular Joint Dislocation.
Generalized joint hypermobility (GJH), determined by the Beighton score, is a fundamental part of diagnosing benign joint hypermobility syndrome (BJHS), which may also present extra-articular manifestations, and is determined by the Brighton criteria. This study was designed to investigate whether there is an association between recurrent temporomandibular joint (TMJ) dislocation and these disorders. A retrospective cross-sectional study was conducted. Hospital-based patients with a history of recurrent TMJ dislocation were compared to population-based patients that did not experience TMJ dislocations or any other TMJ disorders. Age and sex matching were performed between the study groups. All subjects reached the age of skeletal maturity. A history of recurrent TMJ dislocations. Measurements of Beighton score (range from 0 to 9 with a score of ≥ 4 indicating GJH) and correspondence to the Brighton criteria (with at least two "major" criteria or one "major" criterion plus two "minor" criteria or four "minor" criteria indicating BJHS). Included age and sex. Mann-Whitney U-test for continuous variables and the χ2 test or Fisher's exact test for categorical variables. Statistical significance was set at P < .05. A total of 68 participants were included, of whom 34 patients presented with recurrent TMJ dislocations compared with a control population of 34. The Mean participants were 31.35 ± 8.06 years, and 29.4% (n = 20) were males. Of the dislocation group, 16 (47.0%) patients had a Beighton score of 4 or higher. The Beighton sum score was significantly higher, with a TMJ dislocation group mean score of 3.06 ± 2.8, compared with a control score of 0.82 ± 1.1 (P = .001). A total of 58.8% (n = 20) of the TMJ dislocation group participants met the Brighton criteria versus none (0.0%) of the control group (P = .001). We found an association between recurrent TMJ dislocation and GJH. An association with BJHS was also found, based mainly on articular manifestations. Early detection of these disorders in patients suffering from recurrent TMJ dislocation may help identify individuals at increased risk for joint instabilities and allow the implementation of appropriate preventive management strategies.


General practitioners' use of computers for prescribing and electronic health records: results from a national survey.
To describe how general practitioners use computers for clinical purposes. Mail survey of a cross-sectional national stratified random sample of 3000 GPs in primary care settings between 10 October and 31 December 2005. Use of computers, and use of computerised clinical functions such as prescribing, medication checking, generating health summaries, running recall systems, and writing progress notes. Of 1186 GPs responding (39.5% response rate), 90% used a clinical software package. GPs used clinical packages for prescribing (98%), checking for drug-drug interactions (88%), recording a reason for prescribing (65%), to order laboratory tests (85%), run recall systems (78%), and record progress notes (64%). Less frequently used functions included generating lists of patients needing vaccines (43%) and taking the same medication (39%). Less than 20% of GPs who used a clinical package accessed computerised information during the consultation. Australian general practice has achieved near-universal clinical computerisation. Electronic prescribing alone has probably improved efficiency and quality of care, and reduced medication errors. Increasing the use of other functions, such as accessing online decision support and maintaining registries of patients, is likely to lead to further health gains, especially in managing chronic conditions.


Headspace Characterization and Quantification of Aromatic Organosulfur Compounds in Garlic Extracts Using Surface-Enhanced Raman Scattering with a Mirror-in-a-Cap Substrate.
Surface-enhanced Raman scattering (SERS) has been deployed in the analysis of food at solid and aqueous states. However, its capability has not been fully explored in headspace profiling. To develop an innovative SERS method for analyzing headspace volatile compounds in foods. A volatile-capture device was developed by depositing a film of silver nanoparticles in a vial cap to capture the volatiles released from a model flavor compound (garlic). SERS peaks at 1632, 1400, 1291, 1191, 731, and 577 cm-1 were identified in the headspace of the garlic sample, which was representative of an organosulfur compound (diallyl disulfide), and its concentration was determined at 135 ppm, which was comparable to the value determined using GC. Preparation and analysis could be carried out in <10 min for the SERS method. The sensitivity of the SERS method (10 ppm), however, was slightly less than that of the GC method (5 pm). The SERS method was able to quantify the concentration of diallyl disulfide in the headspace of a raw garlic ethanolic extract. Compared to GC, the SERS method had a much shorter analysis time and simpler sample preparation procedure than GC when analyzing large numbers of samples. The innovative "mirror-in-a-cap" substrate was simpler and faster than other reported SERS substrates used for this purpose. Additionally, SERS has much better portability and the potential for real-time monitoring of changes in the garlic headspace concentration during manufacturing and processing.


Plasma metabolic disturbances and reperfusion injury following partial limb ischaemia in man.
Despite efficient revascularisation procedures for vascular disease, the limb can occasionally be lost following reperfusion. One contributing factor might be the formation of oxygen free radicals. This study attempts to describe the conditions necessary for oxy-radical formation from adenine nucleotide breakdown products and the role of plasma creatine content as a marker of cellular injury. Twelve patients undergoing aortic reconstructive surgery were studied. Only partial ischaemia of the lower limbs was induced by the aortic clamping, since varying degrees of collateral circulation existed. Radial arterial and external iliac venous blood was obtained simultaneously before, during and after cross-clamping of the aorta, and plasma levels of ATP, ADP, hypoxanthine, phosphocreatine, creatine, creatinine and lactate measured using luminescence and spectrophotometry. Venous creatine content increased during ischaemia and was doubled 30 min after recirculation. This increase was possibly due to leakage following cellular injury agreeing with a previously observed decrease in muscle tissue creatine content. The iliac arterio-venous difference of hypoxanthine and lactate markedly increased immediately post-ischaemia, while the phosphocreatine difference decreased. Plasma hypoxanthine was abundant in the leg on reoxygenation. The existence of a xanthine oxidase system in skeletal muscle could produce favourable conditions for oxy-radical formation through hypoxanthine degradation, which may contribute to the known muscle tissue injury.


Recovery of sensation in the skin of non-innervated radial flaps after subfascial and suprafascial dissection.
We compared the extent of recovery of sensation in 40 non-innervated radial free flaps, 20 of which had been raised subfascially and 20 suprafascially. We found no significant difference in sensory recovery between the two groups. The mean extent of sensory recovery was light touch (68%); sharp touch (84%); warm (29%) and cold (40%) temperature; and static (25%) and moving (31%) two-point discrimination. Nearly all the flaps responded to at least one stimulus (excluding two-point discrimination) and half of them to three or more. Sharp touch sensation in the flap was similar to that in the surrounding tissues and light touch was less sensitive. There was no dysaesthesia. Recovery was not related to sex, age, alcohol consumption, or site of reconstruction. Smoking and radiotherapy had a slight effect.


[Emphysema after cochlear implantation - risk factors and therapeutic options].
In case of cochlear implantation seroma, hematoma, local wound infections or vertigo are rare but typical complications. In contrast, emphysema is seldom reported. They can occur after cochlear implantation both in the postoperative healing phase and years later. A therapeutic algorithm does not yet exist. We report on 3 patients with subcutaneous emphysema in the area of the receiver-stimulator. An unsystematic review of the literature of cases with emphysema after cochlear implantation highlights possible risk factors and the therapeutic options. The 3 cases developed subcutaneous emphysema 2-11 month after cochlear implantation due to nose blowing or CPAP therapy in obstructive sleep apnea. The current literature reports another 35 cases of emphysema after cochlear implantation. Air insufflation via the Eustachian tube is the most frequently described cause. Diseases of the nose and sinuses, tube dysfunction and obstructive sleep apnea are potential risk factors. Pressure bandage, puncture, tympanic tubes, and surgical revision are common treatments. Most emphysema can be controlled by conservative methods such as pressure bandaging and behavioral instruction. Punctures should be avoided due to the risk of upcoming infections. The prophylactic use of antibiotics seems dispensable. Surgical revision should be considered especially in cases of pneumocephalus with suspected leakage in the dura. The coverage of the mastoidectomy by a bony cap can be precautious and beneficial in cases with risk factors.


Impact of Intraocular Pressure Control on Rates of Retinal Nerve Fiber Layer Loss in a Large Clinical Population.
To investigate the impact of intraocular pressure (IOP) control on rates of change of spectral-domain OCT (SD-OCT) retinal nerve fiber layer (RNFL) thickness in a large clinical population. Retrospective cohort study. A total of 85 835 IOP measurements and 60 223 SD-OCT tests from 14 790 eyes of 7844 patients. Data were extracted from the Duke Glaucoma Registry, a large database of electronic medical records of patients with glaucoma and suspected disease followed over time at the Duke Eye Center and satellite clinics. All records from patients with a minimum of 6 months of follow-up and at least 2 good-quality SD-OCT scans and 2 clinical visits with Goldmann applanation tonometry were included. Eyes were categorized according to the frequency of visits with IOP below cutoffs of 21 mmHg, 18 mmHg, and 15 mmHg over time. Rates of change for global RNFL thickness were obtained using linear mixed models and classified as slow if change was slower than -1.0 μm/year; moderate if between -1.0 and -2.0 μm/year; and fast if faster than -2.0 μm/year. Multivariable models were adjusted for age, gender, race, diagnosis, central corneal thickness, follow-up time, and baseline disease severity. Rates of change in SD-OCT RNFL thickness according to levels of IOP control. Eyes had a mean follow-up of 3.5±1.9 years. Average rate of change in RNFL thickness was -0.68±0.59 μm/year. Each 1 mmHg higher mean IOP was associated with 0.05 μm/year faster RNFL loss (P < 0.001) after adjustment for potentially confounding variables. For eyes that had fast progression, 41% of them had IOP <21 mmHg in all visits during follow-up, whereas 20% of them had all visits with IOP <18 mmHg, but only 9% of them had all visits with IOP <15 mmHg. Intraocular pressure was significantly associated with rates of progressive RNFL loss in a large clinical population. Eyes with stricter IOP control over follow-up visits had a smaller chance of exhibiting fast deterioration. Our findings may assist clinicians in establishing target pressures in clinical practice.


Chemoimmunotherapy for hairy cell leukemia.
Success in the treatment of patients with hairy cell leukemia (HCL) over the last several decades is largely due to the high efficacy of the nucleoside analogs, cladribine and pentostatin. However, the relapse-free survival curves have not shown a plateau and many patients treated with these agents will eventually relapse. Although better understanding of the pathogenic mechanisms in HCL have led to effective and novel options for the treatment of relapse, long term durability of the responses obtained with these agents still remains unclear. Combination of nucleoside analogs with monoclonal antibodies such as rituximab has been shown to be safe and effective and has the potential to supersede the nucleoside analogs as the frontline strategy. Such chemo-immunotherapy approaches are under further investigation and will have to be assessed with socioeconomic considerations in mind. Other novel monoclonal antibodies, approved for the treatment of other lymphoid neoplasms, may also be considered for future studies of chemo-immunotherapy.


Feasibility and Acceptability of Remote Physical Exercise Programs to Prevent Mobility Loss in Pre-Disabled Older Adults during Isolation Periods Such as the COVID-19 Pandemic.
This study aimed to assess the feasibility and acceptability of remote physical exercise (PE) to prevent mobility loss among pre-disabled older adults during the COVID-19 lockdowns. Participants followed a 12-week PE remote program in Zoom© supervised groups (Web-Ex group, n=11) or phone-supervised individual booklet-based home-program (Booklet group, n=33). The total rate of adherence was 82.5% in the Web-Ex group and 85.8% in the Booklet group. The level of satisfaction was « a lot » for 60% of the participants in the Web-ex group and for 37.9% of those included in the Booklet group. Respectively 10% and 31% of the participants rated the difficulty as « low » in the web-ex and Booklet groups. Remote physical exercise using a web technology or booklets at home with regular and personalized follow-up during the lockdown was feasible and acceptable among pre-disabled seniors.


Placental transfer of cefazolin and piperacillin in pregnancies remote from term complicated by Rh isoimmunization.
Although the administration of prophylactic antibodies for intrauterine transfusion is controversial, little information is available regarding placental transfer of antibiotics administered to the mother, or whether the presence of hydrops affects this placental transfer. Sixteen intravascular intrauterine transfusions were performed in 10 patients. Seven (10 procedures) patients were given 2 gm of cefazolin before the procedure and samples were obtained by fetal vascular access. Three patients (six procedures) were given 4 gm of piperacillin and samples were similarly obtained. Specimens were obtained for fetal serum, maternal serum, and amniotic fluid antibiotic concentration. The mean serum cefazolin concentration in hydropic fetuses was 18.04 +/- 3.37 micrograms/ml, and in nonhydropic fetuses the concentration was 21.02 +/- 17.8 micrograms/ml (p = 0.72). The mean fetal serum concentration of piperacillin was 22 +/- 12 micrograms/ml. The placental transfer of both drugs was similar. We conclude that the transplacental passage of these antibiotics is prompt and that the presence of hydrops does not significantly impair the passage of cefazolin.


Prospects for HIV-1 therapeutic immunisation and vaccination: the potential contribution of peptide immunogens.
Human immunodeficiency virus (HIV)-1 infection continues to challenge the development of antigen-specific immune-based strategies for the management (therapeutic immunisation) and prevention (vaccination) of HIV-1 infection. This review aims to assess current prospects for HIV-1 therapeutic immunisation with particular emphasis on the contribution of peptide-based immunogens. The potential for therapeutic immunisation to provide immunological support that can allow for prolonged safe ART-free periods is discussed in light of the Strategies for Management of Antiretroviral Therapy (SMART) study. Different approaches to peptide design are considered including the quality of T-cell responses desired. Synthetic peptide immunogens are amenable to modification to improve immunogenicity and reactivity to multiple virus subtypes. Ideally peptide immunogens should incorporate combinations that target restricted, relevant polyfunctional epitopes to regions of HIV-1 associated with control of infection. Peptides showing a beneficial effect following therapeutic immunisation may provide the basis for a future preventative vaccine.


Antiphospholipid syndrome and the idiotypic network.
To study whether monoclonal anticardiolipin antibodies (aCL), derived from patients with antiphospholipid syndrome (APS), have similar pathogenic potential, we have employed an experimental model of antiphospholipid syndrome. Monoclonal aCL were produced by the combined method of EBV transformation and somatic cell hybridization of lymphocytes, derived from patients with APS. The monoclonal aCL were used to immunize mice at the footpads and the mice were followed for serological and clinical manifestations of APS. The monoclonal antibody EY2C9, was found to bind weakly to cardiolipin and other phospholipids (i.e. phosphatidyl-serine, phosphatidyl-ethanolamine and phosphatidyl-inositol). The antibody TM1B9, although derived from a patient with SLE and with secondary APS, did not react with phospholipids. Immunization of naive BALB/c mice with EY2C9 was followed by production of sustained high titers of antiphospholipid antibodies associated with prolonged activated partial thromboplastin time (APTT) (46.8 +/- 5.0 s vs. 22.4 +/- 1.7 s, in the non-immunized mice). Mice immunized with TM1B9 had a more moderate titer of antiphospholipid antibodies and did not show prolonged APTT. The pregnant mice, that were immunized with EY2C9, had increased fetal resorption rate (the equivalent of fetal loss in the human) of 36.8 +/- 10% (vs. 2 +/- 4% in mice immunized with TM1B9). Our results confirm that monoclonal aCL, derived from a patient with APS, can have a pathogenic potential, dysregulating the idiotypic network and leading to the development of characteristic signs of APS.(ABSTRACT TRUNCATED AT 250 WORDS)


A new ruthenium-catalyzed cleavage of a carbon-carbon triple bond: efficient transformation of ethynyl alcohol into alkene and carbon monoxide.
We report a new and efficient ruthenium-catalyzed reaction that transforms ethynyl alcohol into alkene and carbon monoxide. The most efficient catalysts are TpRu(PPh3)(CH3CN)2PF6 (10 mol %) and lithium triflate (20 mol %). The mechanism of this reaction was elucidated using an isotope-labeling experiment.


Perceived impact of resident work hour limitations on medical student clerkships: a survey study.
To assess medical students' perceptions of the impact of recent Accreditation Council for Graduate Medical Education policies limiting resident work hours on students' clerkship experiences, resident teaching, and quality of patient care. In May/June 2003 and May/June 2004, an original questionnaire was administered to 252 medical students completing required clinical rotations at two teaching hospitals to assess students' perceptions of endpoints that might be affected by resident work hours limits. Response data were analyzed to determine statistical significance of differences between the two years studied. Questionnaires were completed by 129 students in 2003 (98%) and 112 students in 2004 (93%), for an overall response rate of 96%. A higher proportion of students perceived limits on work hours in 2004 [46 (41%)] than 2003 [36 (28%), p = .03]. Ratings of resident availability and primary resident's interest in teaching improved in 2004. Otherwise, ratings of the interest, skill, and availability of resident teachers and attending physicians remained stable between 2003 and 2004. Students reported spending similar amounts of time in formal teaching sessions and rated feedback similarly between 2003 and 2004. In 2004, fewer students [28 (25%)] reported considering leaving medicine due to long hours in training than in 2003 [49 (38%), p = .04]. No significant differences in the proportion of students reporting suboptimal care were found [44 (34%) in 2003, 34 (35%) in 2004, p = .57]. This small, early study suggests that reductions in resident work hours might be implemented without a significant negative impact upon medical students' self-assessed learning experiences, and that limiting resident work hours may even have a positive impact on medical students.


The impulse pattern formulation (IPF) as a model of musical instruments-Investigation of stability and limits.
The Impulse Pattern Formulation (IPF) is an analytical modeling approach for synergetic systems in general, motivated by research on musical instruments. Based on the assumption that the coupling of system components can be described by the interaction between individually propagating and exponentially damped impulse trains, the IPF describes tone generation in musical instruments as self-organized systems. In contrast to other nonlinear recursive functions such as the Logistic Map, system predictions cannot be derived easily from knowledge on other theories, neither can the system be completely examined analytically. Therefore, several numerical simulations are performed to explore stable regions and limits of the IPF.


Turkish validity and reliability of the COVERS pain scale.
The objective of this study is to determine the Turkish validity and reliability of COVERS. This study was conducted on 41 newborns as methodological design. The scales, such as newborn information form, COVERS, preterm infant pain profile (PIPP), and neonatal infant pain scale (NIPS), were used in the study. Validity (e.g., language, content concurrent, and construct) and internal consistency and inter-rater reliability of the scale were conducted. It was found that COVERS showed a high correlation with PIPP and NIPS, and the item-total correlation of COVERS was above 0.30 during and after heel lance procedure. The Cronbach's α values were 0.77 and 0.83 during and after heel lance procedure, respectively. The kappa values of the items of COVERS were between 0.38 and 0.78 during heel lance procedure. It was concluded in this study that there was a moderate correlation in intraclass correlation coefficients for scores of COVERS during both diaper change and heel lance procedures. It has been concluded that the scale is valid and reliable in 27-week-old and older newborns.


A novel non-ATP competitive FGFR1 inhibitor with therapeutic potential on gastric cancer through inhibition of cell proliferation, survival and migration.
Fibroblast growth factor receptor 1 (FGFR1), belonging to receptor tyrosine kinases (RTKs), possesses various biological functions. Over-expression of FGFR1 has been observed in multiple human malignancies. Hence, targeting FGFR1 is an attractive prospect for the advancement of cancer treatment options. Here, we present a novel small molecular FGFR1 inhibitor L16H50, which can inhibit FGFR1 kinase in an ATP-independent manner. It potently inhibits FGFR1-mediated signaling in a gastric cancer cell line, resulting in inhibition of cell growth, survival and migration. It also displays an outstanding anti-tumor activity in a gastric cancer xenograft tumor model by targeting FGFR1 signaling. These results show that L16H50 is a potent non-ATP-competitive FGFR1 inhibitor and may provide strong rationale for its evaluation in gastric cancer patients.


The N-pentenoyl protecting group for aminoacyl-tRNAs.
The elaboration of misacylated transfer RNAs by T4 RNA ligase-mediated condensation of an aminoacylated pdCpA derivative and a tRNA (transcript) missing the two 3'-terminal nucleotides requires that the aminoacyl moiety of the dinucleotide be stabilized during the ligation reaction. This can be done conveniently by the use of a simple 4-pentenoyl group attached to N(alpha) of the amino acid. The pentenoyl amide can be deblocked readily with aqueous iodine, presumably via an iodolactone intermediate. This protecting group can be used in conjunction with side chain protecting group for amino acids having side chain functionality, thus permitting the elaboration of proteins bearing side chain protecting groups that can be removed in a subsequent step (e.g., caged proteins). In addition, an aminated analogue of the pentenoyl protecting group, the unnatural amino acid allylglycine, can be employed as part of the peptide backbone to afford a protein cleavable by iodine.


The lncRNA LETS1 promotes TGF-β-induced EMT and cancer cell migration by transcriptionally activating a TβR1-stabilizing mechanism.
Transforming growth factor-β (TGF-β) signaling is a critical driver of epithelial-to-mesenchymal transition (EMT) and cancer progression. In SMAD-dependent TGF-β signaling, activation of the TGF-β receptor complex stimulates the phosphorylation of the intracellular receptor-associated SMADs (SMAD2 and SMAD3), which translocate to the nucleus to promote target gene expression. SMAD7 inhibits signaling through the pathway by promoting the polyubiquitination of the TGF-β type I receptor (TβRI). We identified an unannotated nuclear long noncoding RNA (lncRNA) that we designated LETS1 (lncRNA enforcing TGF-β signaling 1) that was not only increased but also perpetuated by TGF-β signaling. Loss of LETS1 attenuated TGF-β-induced EMT and migration in breast and lung cancer cells in vitro and extravasation of the cells in a zebrafish xenograft model. LETS1 potentiated TGF-β-SMAD signaling by stabilizing cell surface TβRI, thereby forming a positive feedback loop. Specifically, LETS1 inhibited TβRI polyubiquitination by binding to nuclear factor of activated T cells (NFAT5) and inducing the expression of the gene encoding the orphan nuclear receptor 4A1 (NR4A1), a component of a destruction complex for SMAD7. Overall, our findings characterize LETS1 as an EMT-promoting lncRNA that potentiates signaling through TGF-β receptor complexes.


Evidence of bias during liver transplant evaluation of non-alcoholic steatohepatitis cirrhosis patients.
Cardiovascular disease (CVD) is the leading cause of death among non-alcoholic steatohepatitis (NASH) patients and a major source of post-transplant mortality. We sought to examine the effect of comorbidities on listing for orthotopic liver transplant (OLT) in NASH patients. In this retrospective cohort study, we included all patients (n = 955) referred to Beth Israel Deaconess Medical Center for OLT between January 2002 and September 2011 and followed their outcomes through March 2018. Compared with non-NASH patients (n = 881), NASH patients (n = 74) were older, more likely female, more overweight, with higher rates of diabetes, hypertension and CVD. NASH patients were less likely to be listed for OLT (55% vs 68.9%, P = 0.01) and were more often declined for 'medical comorbidities' (36.1% vs 15.7%, P < 0.001). However, on multivariate analysis, the only significant predictors of listing were model for end-stage liver disease (MELD) score (OR 1.04, P = 0.01), HCC (OR 2.16, P = 0.01), and diagnosis of non-NASH cirrhosis (OR 2.56, P = 0.003) while controlling for comorbidities. NASH patients declined for OLT died primarily from their liver disease and were not more likely to die from CVD than non-NASH patients. There was no difference in outcomes of NASH vs non-NASH patients on the waitlist and post-transplant. This study demonstrates potential bias against NASH patients referred for OLT arising from heightened concern for comorbidities. Despite being declined for comorbidities, NASH patients are likely to die of their liver disease.


Probing the interaction between encapsulated ethoxyquin and its β-cyclodextrin inclusion complex with bovine serum albumin.
Ethoxyquin (EQ) is a synthetic antioxidant that is derived from quinolines and found in many meat products. EQ is strictly regulated in feed due to its potential health implications. An investigation of the interaction mechanism between EQ and transporter protein before and after β-cyclodextrin (β-CD) encapsulation was conducted with the use of multi-spectroscopy, cyclic voltammetry, and molecular docking. EQ formed complexes with bovine serum albumin (BSA), and affected secondary structure and microenvironment polarity of BSA. However, at 298 K, EQ's fluorescence quenching constants decreased from (9.81 ± 0.05) × 103 L mol-1 to (4.94 ± 0.09) × 103 L mol-1, binding constants decreased from (10.28 ± 0.02) × 103 L mol-1 to (2.08 ± 0.07) × 103 L mol-1, after encapsulation in β-CD as well as the binding distance increased. β-CD contains part of EQ in its hydrophobic cavity, inhibiting its binding to BSA. β-CD inclusion complex prevented adverse effects of EQ on BSA conformation. However, β-CD encapsulation had no effect on EQ's antioxidant activity.


Antiplatelet efficacy of prasugrel in patients with high on-clopidogrel treatment platelet reactivity and a history of coronary stenting.
Little is known about the antiplatelet action of the 3 rd generation thienopyridine prasugrel in patients showing high platelet reactivity (PR) levels on clopidogrel. Thus, we aimed to determine the antiplatelet efficacy of prasugrel loading (LD) and maintenance dose (MD) treatment in a registry of patients with high PR levels on clopidogrel and a consecutive switch over to prasugrel in a setting of routine platelet function testing. In our registry of patients treated by percutaneous coronary intervention (n=73) with high levels of PR on clopidogrel, the ADP-induced platelet aggregation (PA, in AU x min) was assessed on a Multiplate analyser 1) after clopidogrel LD, 2) after prasugrel LD and 3) on prasugrel MD (5 vs. 10 mg/day). In patients with high PR levels on clopidogrel, prasugrel LD resulted in significantly lower PA values (574 [462-698] vs. 156 [89-234] AU x min; p<0.0001). Only 2.7% of patients showed high PR (HPR, ≥468 AU x min) following prasugrel LD. On prasugrel MD, PA was significantly higher as compared to prasugrel LD (248 [145-406] vs. 156 [89-234] AU x min; p<0.0001) with more patients showing HPR on MD vs. LD (16.4% vs. 2.7%; p=0.009). For prasugrel MD, HPR rates were higher in 5 vs. 10 mg/day treated patients (46.2% vs. 10.0%; p=0.006). In conclusion, for patients with high PR levels on clopidogrel, prasugrel LD abolished this status in the majority of patients. However, prasugrel response variability was detected, being more pronounced on prasugrel MD vs. LD treatment. The clinical impact of these findings warrants further investigation.


Differential influence of a selective melanocortin MC4 receptor antagonist (HS014) on melanocortin-induced behavioral effects in rats.
We injected i.c.v. the natural agonist alpha-MSH (melanocyte-stimulating hormone) and the first selective melanocortin MC4 receptor antagonist HS014 (cyclic [AcCys11, D-Nal14, Cys18, Asp-NH(2)22]-beta-MSH(11-22) in rats and scored a number of behavioral effects which have been related to the melanocortic peptides. The results showed that HS014 (5 microg/rat) completely blocked alpha-MSH (3 and 5 microg/rat)-induced grooming, yawning and stretching. Penile erections induced by alpha-MSH were, however, only partially blocked by HS014. Injections of alpha-MSH decreased food intake in food-deprived rats, whereas HS014 increased food intake. When the peptides were given together, the food intake was similar to that of saline treated controls. Locomotion/exploration and resting were not influenced by either peptide. Our data show that exogenous beta-MSH decreases food intake, and that an endogenous central melanocortinergic inhibitory tone on feeding prevails which can be blocked with HS014, leading to an increase in food intake. Our data also provide evidence that grooming, stretching and yawning in rats may be mediated by the melanocortin MC4 receptor, whereas penile erections might perhaps be mediated by some other melanocortin receptor.


The effect of tunicamycin on Leishmania brasiliensis. Glycosylation and the cell surface components.
Culture conditions of Leishmania cells were developed to allow the study of the effect of tunicamycin (TM) on glycosylation and on the cell surface components. Leishmania incorporate [14C]-mannose and [35S]-methionine in vitro. The incorporation of [14C]-mannose is linear for 150 min and is inhibited by TM (2 micrograms/ml) in a time dependent effect which reaches a plateau of 45% inhibition at 36 h. Under the same experimental conditions [35S]-methionine incorporation into protein is slightly affected. This is reflected by an almost identical polypeptide pattern for TM treated and non-treated cells when analyzed on SDS-PAGE. On the contrary, strong differences were detected on the labeled compounds analyzed on SDS-PAGE followed by autoradiography when the precursor used was [14C]-mannose. A shift in the electrophoretic mobility of most of the glycopeptides synthesized in the presence of TM was observed, which is also reflected in the structure of the main Leishmania cell surface components. The findings are discussed in the light of biological implications.


Sequence comparison of the major capsid protein gene from 18 diverse iridoviruses.
Insect iridoviruses (IV) have been found on all continents of the world and in a broad range of insect hosts. The host range for a single strain can cross several insect orders. This along with a paucity of molecular information on all but a few members has led to confusion in the taxonomy and classification of these viruses and in the identification of potentially novel isolates. To address this problem consensus PCR primers were designed to amplify and sequence a 500 bp region of the major capsid protein (MCP) gene. PCR products were amplified from eighteen IVs belonging to the genus Iridovirus. No product was observed for the chloriridovirus IV3. Phylogenetic analysis of the partial MCP gene sequence showed that the iridovirus genus can be divided into three groups. These results support previous studies where a range of molecular techniques were used. Group I contained PjIV and IV31, group II contained IV6 (CIV), IV21, and IV28, and group III contained IV1 (TIV), IV2 (SIV), IV9 (WIV), IV10, IV16, (CzIV), IV18, IV22, IV23 (BbIV), IV24, IV29, IV30, AgIV and an undescribed weevil IV. There was no correlation of relatedness with host of isolation but there was some correlation with geographic region of isolation. Sequence analysis also raised issues concerning the purity of some virus stocks and supported the view that some isolates should be considered as variants of one virus species.


Bovine steroid hormone and SHBG concentrations postpartum and during the oestrous cycle.
Changes in consecutive estimates of milk progesterone concentrations and serum steroid hormone and sex hormone-binding globulin (SHBG) concentrations in the postpartum period were examined in Finnish Ayrshire and Friesian dairy cows which were divided according to feeding into a hay group and a silage group. Milk progesterone concentrations rose above 10 nmol/l, indicating the start of ovarian luteal activity, slightly earlier in the silage group (28.4 +/- 8.7 (S.D.) days, n = 19) than in the hay group (33.4 +/- 10.3, n = 28) after calving. Likewise, the first normal oestrous cycles began slightly earlier in cows fed with silage. On the other hand, no differences in the beginning of ovarian luteal activity were observed between the breeds. Serum oestradiol-17 beta, oestrone, testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), pregnenolone and progesterone concentrations were fairly unchanged during postpartum anoestrus after uterine involution and before ovarian cyclic activity. After first ovulation, considerable increases in milk and serum progesterone concentrations were observed. The increase was accompanied by elevations in serum pregnenolone and 5 alpha-DHT concentrations. In the late luteal phase, progesterone, 5 alpha-DHT and pregnenolone concentrations rapidly declined, leading to low hormone levels in pro-oestrus. Thereafter, serum pregnenolone and 5 alpha-DHT concentrations slightly increased during the follicular phase. On the other hand, oestradiol-17 beta concentrations were elevated in pro-oestrus and decreased after that, being lowest at met-oestrous. Serum testosterone concentrations appeared to be unchanged during postpartum anoestrus and over the oestrous cycle. Serum SHBG concentrations were unchanged during postpartum anoestrus and over the oestrous cycle, as well as in pregnant animals. The serum SHBG concentrations were about double those found in women with normal menstrual cycles, whereas oestradiol concentrations were much lower. At present, it cannot be explained how the biological effects of oestradiol become evident under such conditions.


Effects of functional group loss on biochar activated persulfate in-situ remediation of phenol pollution in groundwater and its countermeasures.
Biochar is considered a good activator for use in advanced oxidation technology. However, dissolved solids (DS) released from biochar cause unstable activation efficiency. Biochar prepared from saccharification residue of barley straw (BC-SR) had less DS than that prepared directly from barley straw (BC-O). Moreover, BC-SR had a higher C content, degree of aromatization, and electrical conductivity than BC-O. Although the effects of BC-O and BC-SR on activation of Persulfate (PS) to remove phenol were similar, the activation effect of DS from BC-O was 73% higher than that of DS from BC-SR. Moreover, the activation effect of DS was shown to originate from its functional groups. Importantly, BC-SR had higher activation stability than BC-O owing to the stable graphitized carbon structure of BC-SR. Identification of reactive oxygen species showed that SO4•-, •OH, and 1O2 were all effective in degradation by BC-SR/PS and BC-O/PS systems, but their relative contributions differed. Furthermore, BC-SR as an activator showed high anti-interference ability in the complex groundwater matrix, indicating it has practical application value. Overall, this study provides novel insight that can facilitate the design and optimization of a green, economical, stable, and efficient biochar-activated PS for groundwater organic pollution remediation.


Characterization and mapping of four novel human expressed polymorphic trinucleotide microsatellites.
Recently, several important human genetic diseases have been shown to be due to pathological expansion of expressed trinucleotide microsatellites. Discovery of other such 'expansion diseases' will depend on characterization of more expressed loci containing trinucleotide repeats. We searched the expressed sequence tag database (dbEST) for repetitive trinucleotides and selected four loci for further studies (EST00586 EST05486, EST13299 and HHEA48B). For each locus, we have identified size polymorphism by PCR amplification and achieved chromosomal mapping using a somatic hybrid cell panel and the Stanford G3 radiation hybrid panel. Further searches of GenBank, dbEST and UniGene unraveled EST clusters for three of the loci, allowing construction of contigs and, in one instance, identification of a partial open reading frame. Three of the loci were linked to autosomal dominant human genetic diseases whose primary gene defect has not yet been established. Although it is a priori improbable that there is an etiological connection between the loci studied and the diseases, our results demonstrate that dbEST constitutes a useful starting point in the search for candidate loci for new expansion diseases.


Muscle spike artifact minimization in EEGs by time-domain filtering.
An electronic circuit is described for minimizing or eliminating muscle artifact in EEGs. The principle of operation of the circuit is that of a relatively high frequency (250 Hz) sample-and-hold procedure which is interrupted for the duration of a muscle potential. Detection of the presence of the latter is based on a steepness criterion, with a manually adjusted threshold. The circuit is primarily effective for repetitive single muscle spikes. It is not effective if there is a continuous muscle interference pattern, but it can still be useful if the muscle interference pattern is not truly continuous. Very sharp EEG spikes may also be eliminated or at least altered, but less sharp EEG spikes can be passed with little or no change in their wave form.


Electron microprobe analysis of intracellular electrolytes in resting and isoproterenol-stimulated exocrine glands of frog skin.
In the intact, in vitro frog skin, isoproterenol (ISO) stimulates an amiloride-insensitive increase in short-circuit current (SCC) that can be localized to the exocrine glands and is associated with secretion of chloride. To determine which cells in the glands respond to stimulation we measured the intracellular electrolyte concentrations of the various cell types of the mucous and seromucous glands of the skin using freeze-dried cryosections and electron microprobe analysis. In the resting state, the various cell types of the glands have intracellular electrolyte concentrations similar to the epithelial cells of the skin. Exposure to amiloride (10(-4) M) has little effect on the concentration of Na and Cl in the cells of the glands. The effect of isoproterenol has two distinct phases. Analysis of glands in tissues frozen at the peak of the SCC response (13 min after addition of isoproterenol) shows that the only significant change is an increase in Na and Ca in a group of cells at the ductal pole of the acini of both gland types. These are termed "gland" cells. The duct cells and cells that secrete macromolecules did not show any significant changes at this timepoint. In the gland cells, after a one-hour exposure to isoproterenol the Na concentration is at prestimulation levels while Cl drops. There is also a smaller drop in Cl in the duct and skin epithelial cells. Ouabain, which can completely block the isoproterenol SCC response, has little short-term effect on Na and Cl in the control gland but accentuates the gain of Na and drop in Cl in the isoproterenol-treated condition. Bumetanide and, to a lesser extent, furosemide, also blocks the isoproterenol SCC response and causes a further drop in Cl. The results provide indirect evidence that a major portion of the ionic component of the gland secretion is produced by a distinct group of cells separate from those producing the macromolecular component and that the mechanism of secretion involves a Na: Cl coupled transport system linked to the activity of the basolateral Na pump.


Altitudinal variation in metabolic parameters of a small Afrotropical bird.
Of the numerous factors affecting avian metabolic rate, altitude is one of the least studied. We used mass-flow respirometry to measure resting metabolic rate (RMR), evaporative water loss (EWL) and respiratory exchange ratio (RER) in two populations of a small (10-12g) Afrotropical bird, the Cape White-eye (Zosterops virens), in summer and in winter. In total, 51 freshly wild-caught adult Cape White-eyes were measured overnight. Altitude was included as a source of variation in the best approximating models for body mass, whole-animal RMR, RER, whole-animal standard EWL and whole-animal basal EWL. RER was significantly lower in winter, suggesting a greater proportion of lipid oxidation at lower ambient temperatures (Ta). Cape White-eyes were 0.8g heavier at the higher altitude site and 0.5g heavier in winter, suggesting they may have increased their metabolic machinery to cope with cooler temperatures. EWL was generally significantly lower in winter than in summer, suggesting that birds may increase EWL with increasing Ta, as the need for evaporative cooling increases. Our results support the argument that the subtle and complex effects of altitude (and ambient temperature) should be taken into account in studies on avian metabolic rate. Of the numerous studies known to affect avian metabolic rate, altitude is one of the least studied. Although trends are not always clear, generally, at higher altitudes, avian metabolic rate increases. There were statistically significant seasonal and altitudinal differences in various physiological parameters of Cape White-eyes. These results highlight the importance of accounting for altitude in studies of avian metabolic rate.


Developing and evaluating training for pharmacists to offer a pharmacy-led public health service in primary care.
Currently in Greece, no formal organisation offers post-academic education to pharmacists. To improve the clinical practice of pharmacists, there is a need for training that will educate them on how to approach and consult their patients. The study aimed to evaluate the training required by pharmacists to offer a pharmacy-led weight management service in Greece. The study consisted of 3 phases. During the first phase educational needs of the participating pharmacists were identified. A pre-training quiz was given consisting of 14 questions to investigate the participating pharmacists' knowledge on guidance, causes and facts of obesity. The second phase comprised the training design and delivery. The final phase dealt with training evaluation (27 questions in total), which included the perceived rating of knowledge and confidence levels pre- and post-training, and a post-training quiz (the same as the pre-training quiz). The post-evaluation questionnaire and the quiz (pre- and post-training) results were entered into SPSS Version 23 for statistical analysis. The mean total quiz score was 6.38 (SD = 2.56) pre-training compared to 11.92 (SD = 1.20) post-training (P < 0.001). Nearly all community pharmacists, 96.2% (n = 25) stated that they had an excellent/good experience and 88.5% (n = 23) strongly agreed/agreed that their expectations were met. Training delivered was well received and it enhanced participants' knowledge on the topic. Limitations include the small number of participating pharmacists and investigation of short-term training effects only. Due to the positive outcomes of the training, however, it has the potential to become a model for Greek pharmacists to offer different pharmacy-led public health services.


Engineered Living Materials: Taxonomies and Emerging Trends.
At the intersection of synthetic biology and materials science, the field of engineered living materials (ELMs) has evolved into a new, standalone discipline. The fusion of bioengineering's design-build-test-learn approaches with classical materials science has yielded breakthrough innovations in the synthesis of complex, biologically active materials for functional applications in therapeutics, electronics, construction, and beyond. However, the transdisciplinary nature of the ELM field - and its rapid growth - has made holistic comprehension of achievements related to the tools, techniques, and applications of ELMs difficult across disciplines. To this end, this review proposes an emergent taxonomy of ELM research and uses the categorization to discuss current trends and state-of-the-art advancements, significant opportunities, and imminent challenges for scientists and engineers in the field.


[Evaluation of the vitamin D activity of yeasts with altered sterol metabolism].
The sterol content of Saccharomyces strains with altered ergosterol metabolism was studied by UV-spectrophotometry, thin-layer chromatography and chromatographic mass-spectroscopy. A technique for estimation of D-vitamin activity of the yeast strains is proposed. The irradiated biomass of the strains accumulated ergosta-5,7-dien-3 beta-ol and also cholesta-5,7,24-trien-3 beta-ol and cholesta-5,7,22,24-tetraen-3 beta-ol is characterized by high antirachitic activity.


Effects of preoperative combined aerobic and resistance exercise training in cancer patients undergoing tumour resection surgery: A systematic review of randomised trials.
Surgical management remains the cornerstone of treatment for many cancers, but is associated with a high rate of postoperative complications, which are linked to poor preoperative functional capacity. Prehabilitation may have beneficial effects on functional capacity and postoperative outcomes. We evaluated the effects of prehabilitation combining endurance and resistance training (CT) on physical fitness, quality of life (QoL) and postoperative outcomes in cancer patients undergoing tumour resection surgery. We performed a literature search in PubMed, PEDro, EMBASE (via Scopus) and the Cochrane library for clinical trials until September 2017. Randomised controlled trials investigating the effects of CT in adult cancer patients undergoing surgery were included when at least one of the following outcomes was reported: physical capacity, muscle strength, QoL, length of stay (LOS), postoperative complications and mortality. Ten studies (360 patients) were retrieved and included patients with lung, colorectal, bladder and oesophageal cancer. No adverse effects of CT were reported. Compared with the control group, CT improved physical capacity (3 of 5 studies), muscle strength (2 of 3 studies) and some domains of QoL (2 of 4 studies), shortened LOS (1 of 6 studies) and reduced postoperative pulmonary complications (2 of 6 studies). The benefits of CT in cancer population are demonstrated. CT may improve physical fitness and QoL and decrease LOS and postoperative pulmonary complications. However, our conclusions are limited by the heterogeneity of the preoperative CT programs, patient characteristics and measurement tools. Future research is required to determine the optimal composition of CT.


Thallium tomography in the detection of myocardial perfusion defects.
Tomographic 201-Tl scintigrams (SPECT) were compared with conventional planar images (PLAN) in 100 consecutive patients with ischaemic heart disease (IHD). Agreement was obtained in 78/100 and disagreement in 7/100. In 15 patients the results were equivocal. The sensitivity of PLAN and SPECT was studied in 35 patients with IHD and angina pectoris who were also examined with coronary angiography. SPECT had a sensitivity of 88 per cent compared with 84 per cent for PLAN. SPECT was better in matching perfusion defects to coronary stenoses in this small patient group.


Male-induced early puberty correlates with the maturation of arcuate nucleus kisspeptin neurons in does.
In goats, early exposure of spring-born females to sexually active bucks induces an early puberty onset assessed by the first ovulation. This effect is found when females are continuously exposed well before the male breeding season starting in September. The first aim of this study was to evaluate whether a shortened exposure of females to males could also lead to early puberty. We assessed the onset of puberty in Alpine does isolated from bucks (ISOL), exposed to wethers (CAS), exposed to intact bucks from the end of June (INT1), or mid-August (INT2). Intact bucks became sexually active in mid-September. At the beginning of October, 100% of INT1 and 90% of INT2 exposed does ovulated, in contrast to the ISOL (0%) and CAS (20%) groups. This demonstrated that contact with males that become sexually active is the main factor prompting precocious puberty in females. Furthermore, a reduced male exposure during a short window before the breeding season is sufficient to induce this phenomenon. The second aim was to investigate the neuroendocrine changes induced by male exposure. We found a significant increase in kisspeptin immunoreactivity (fiber density and number of cell bodies) in the caudal part of the arcuate nucleus of INT1 and INT2 exposed females. Thus, our results suggest that sensory stimuli from sexually active bucks (e.g., chemosignals) may trigger an early maturation of the ARC kisspeptin neuronal network leading to gonadotropin-releasing hormone secretion and first ovulation.


The effects of treatment with aspirin and an antithrombotic agent SH1117 upon platelet thrombus formation in living blood vessels.
The work reported here describes an in vivo study, over several days in each animal, of the formation and behaviour of platelet thrombi in injured living blood vessels in response to topically applied adenosine diphosphate in rabbits which have been treated with oral doses of SH1117 alone or together with acetyl-salicylic (ASA) before and after i.v. injection of alloxan. These two substances SH1117 and ASA when given together display a synergism which is similar to that described for dipyridamole and ASA, but the antithrombotic action of SH1117 and ASA seems to be more profound. It may be of significance that oral SH1117 given alone appears to confer a degree of insensitivity of the injured vessel in its response to ADP, as such an effect is not displayed by dipyridamole.


Amphiphilic diblock copolymers with adhesive properties: I. Structure and swelling with water.
We study asymmetric block copolymers with the simple diblock AB architecture, in the case where the longer block A is both hydrophobic and "soft", whereas the shorter block B is hydrophilic and "hard". Materials with such a particular combination of physico-chemical and mechanical properties have distinctive advantages, in particular for designing water-compatible adhesive materials. The phase diagram is established, combining NMR and SAXS characterisations of the materials. The swelling with water is monitored through gravimetry and "time-resolved" SAXS. Indications of maintained adhesive properties in a wet environment are given.


Inflight head stabilization associated with wingbeat cycle and sonar emissions in the lingual echolocating Egyptian fruit bat, Rousettus aegyptiacus.
Sensory processing of environmental stimuli is challenged by head movements that perturb sensorimotor coordinate frames directing behaviors. In the case of visually guided behaviors, visual gaze stabilization results from the integrated activity of the vestibuloocular reflex and motor efference copy originating within circuits driving locomotor behavior. In the present investigation, it was hypothesized that head stabilization is broadly implemented in echolocating bats during sustained flight, and is temporally associated with emitted sonar signals which would optimize acoustic gaze. Predictions from these hypotheses were evaluated by measuring head and body kinematics with motion sensors attached to the head and body of free-flying Egyptian fruit bats. These devices were integrated with ultrasonic microphones to record sonar emissions and elucidate the temporal association with periods of head stabilization. Head accelerations in the Earth-vertical axis were asymmetric with respect to wing downstroke and upstroke relative to body accelerations. This indicated that inflight head and body accelerations were uncoupled, outcomes consistent with the mechanisms that limit vertical head acceleration during wing downstroke. Furthermore, sonar emissions during stable flight occurred most often during wing downstroke and head stabilization, supporting the conclusion that head stabilization behavior optimized sonar gaze and environmental interrogation via echolocation.


Transcription of a Drosophila tRNAArg gene in yeast extract: 5'-flanking sequence dependence for transcription in a heterologous system.
The Drosophila tRNA gene encoded on pArg is efficiently transcribed in extracts of Saccharomyces cerevisiae, but the efficiency is 5'-flanking sequence dependent: deletion to between positions -21 and -17 (relative to position +1 of the mature coding sequence) reduces transcription to a very low level. This demonstrates that requirement for wild-type 5'-flanking sequence exists in the case of a heterologous combination of a tRNA gene and transcription extract. Expression of pArg in vivo in S. cerevisiae is also dependent on the wild-type 5'-flanking sequence, but only with deletion to between -17 and -11 is the steady-state level of pArg transcripts reduced to near zero. The 5'-flanking sequence requirement in S. cerevisiae extract is similar to that found in Drosophila Kc cell extract. However, transcription kinetics distinguish S. cerevisiae extract from that of Drosophila Kc cells. tRNA genes added to S. cerevisiae extract exhibit a lag phase before initiation of active transcription, but this lag is much shorter and much less temperature dependent than is the lag phase in Drosophila Kc cell extract.


Response biases in preschool children's ratings of pain in hypothetical situations.
Response biases are systematic biases in responding to test items that are unrelated to the content of the items. Examples often reported in young children include choosing only the lowest or highest anchors of a scale, or choosing a left-to-right sequence of responses. We investigated the presence of response biases in young children's ratings of pain in hypothetical situations, as a way of gauging their developing understanding of a pain scale over the preschool years. Children aged 3-5 years (N=185) rated items from the Charleston Pediatric Pain Pictures (CPPP) using the Faces Pain Scale-Revised (FPS-R). Response biases were identified objectively by computer pattern identification. Anchor biases (choosing the lowest and highest pain faces) occurred in 16% of children. Left-right or right-left sequences occurred in 35%. Monte Carlo simulation established that such patterns occur infrequently by chance (<3% for anchor biases; <6% for sequence biases). Response biases were identified more often in younger than older children. These results reveal that response biases are common in children under 5 years. Clinicians should consider self-report pain ratings from preschoolers with caution, seek complementary observational assessment, and investigate discrepancies between self-report and observational estimates of pain. Simplified forms, instructions, and methods of administration for self-report scales should be developed and validated for use with 3- and 4-year-olds.


Pain in women with HIV/AIDS.
Poor women and women of color are disproportionately affected by HIV and this is particularly evident in sub-Saharan Africa. Even with increased access to antiretroviral therapy that makes HIV/AIDS a chronic manageable condition, little progress has been made to address the issues of pain caused by HIV disease in women. Women experience pain differently from men due to biological, psychological, and social factors. Despite a high prevalence of pain associated with HIV disease, pain is usually under-diagnosed and poorly treated. HIV-related pain is usually divided into two categories: nociceptive or neuropathic. Lack of knowledge of health care providers and reluctance to prescribe potent medication or antidepressants concomitantly to relieve pain contribute to the inadequate management of pain. In poor settings, the weak public health infrastructure with its limited human resources and inadequate drug supplies make high-quality palliative and end-of-life care virtually impossible. As the existing hospital infrastructure is unable to manage the large number of AIDS-related deaths, community-based palliative and end-of-life care models are urgently required. Health care providers in the developing world require training on basic pharmacology and effective analgesic care. An improved ability to assess pain and a greater understanding of HIV-specific pain syndromes and their mechanisms will enable health care providers to better alleviate pain in women. Unless the conditions under which women live are addressed, and attempts made to empower them in their daily lives, their limited ability to access treatment, care and pain relief will continue to be unacceptable.


Highly stable glycosylated serine protease from the medicinal plant Euphorbia milii.
A serine protease, named as "Milin" was purified to homogeneity from the latex of Euphorbia milii, a medicinal plant of Euphorbiaceae family. The molecular mass (SDS-PAGE), optimum pH and temperature of the enzyme were 51kDa, pH 8.0 and 60 degrees C, respectively. Milin retains full proteolytic activity over a wide range of pH (5.5-12) and temperature (up to 65 degrees C) with casein and azoalbumin as substrates. The activity of milin is inhibited by serine proteases inhibitors like PMSF, APMSF and DFP, but not by any other protease inhibitors such as E-64 and PCMB. Like the other serine proteases from the genus Euphorbia, the activity of milin was not inhibited by the proteinaceous inhibitor soyabean trypsin inhibitor (SBTI) even at very high concentrations that is naturally present in plants. The specific extinction coefficient (epsilon(280 nm)(1%)), molar extinction coefficient (a(m)) and isoelectric point of the enzyme were found to be 29, 152,500 M(-1) cm(-1) and pH 7.2, respectively. The enzyme is a glycoprotein with detectable carbohydrate moiety (7-8%) in its constitution, which is essential for the activity. The numbers of tryptophan, tyrosine and cysteine residues in the sequence of milin were estimated chemically and are 23, 14 and 14, respectively. Of the 14-cysteine residues, 12 constituted 6-disulfide linkages while two are free cysteines. The N-terminal sequence (first 12 amino acid residues) was determined and does not match with any sequence of known plant serine proteases. Perturbation studies by temperature, pH and chaotropes of the enzyme also reveal its high stability as seen by CD, fluorescence and proteolytic activity. Thus, this serine protease may have potential applications in food industry.


Isolation and characterization of wild type yellow fever virus in cases temporally associated with 17DD vaccination during an outbreak of yellow fever in Brazil.
A mass vaccination was carried out in the state of Minas Gerais, Southeast region of Brazil, to control an outbreak of sylvatic yellow fever in 2001. During the outbreak the surveillance system identified two fatal cases temporally associated with YF vaccination. Virus recovered from blood and postmortem samples of both cases was identified as yellow fever virus. Partial nucleotide sequence of parts of prM/E and the non-structural (NS) 5 genes and 3' non-coding region (3' NCR) was employed to characterize the origin of yellow fever virus (YFV) involved in both cases. Wild-type YFV was identified as the etiologic agent responsible for the disease.


C-reactive protein in urologic cancers.
C-reactive protein is an acute-phase reactant that is elevated in the setting of systemic infections, trauma, and malignancies. Urologic cancers have been shown to promote changes in c-reactive protein levels. Pre-treatment serum levels can predict disease characteristics, extent of disease, and prognosticate survival after intervention in renal cell carcinoma, prostate cancer, bladder cancer, upper tract urothelial carcinoma, and penile cancer. Changes in post-treatment serum levels have also shown promise in determining survival. As a result, c-reactive protein has been incorporated into various survival nomograms to improve predictive accuracy. While the association between c-reactive protein and survival in testicular cancer has not been studied, elevated serum levels may correlate with treatment side effects, such as cardiovascular disease and chronic cancer-related fatigue. Understanding the relationship between c-reactive protein and urologic cancers can help physicians determine the appropriate course of treatment and improve patient care.


Update on incretin hormones.
The incretin hormones glucagon-like-peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the intestine following oral ingestion of nutrients. Incretins promote insulin secretion, while GLP-1 also inhibits glucagon release and gastric emptying, minimizing postprandial glucose excursions. The incretins share similar effects on the pancreatic β cell; however, there are a number of differences in extrapancreatic actions. Type 2 diabetes (T2DM) is associated with abnormal incretin physiology, and although treatment with GIP is ineffective, GLP-1 effects are preserved. The current incretin-based approaches to T2DM include the GLP-1 agonists that are resistant to the serine protease dipeptidylpeptidase-4 (DPP4), which normally rapidly degrades the incretins, and DPP4 inhibitors (DPP4i). Incretin-based treatments have provoked much interest due to use-associated weight loss (GLP-1 agonists), minimal hypoglycemia, and potential for positive effects on pancreatic β cell biology and the cardiovascular system. However, the long-term safety of these agents has yet to be established. This review outlines the current understanding of incretin biology, available data pertaining to incretin-based treatment in T2DM, and differences between GLP-1 and DPP4i therapy.


[Increased expression of plasminogen activator inhibitor-1 in hypoxic renal injury and its pathological significance in progression of advanced renal disease].
Chronic hypoxia has been newly proposed as a common mechanism of progressive renal fibrosis where PAI-1 plays important roles in the accumulation of extracellular matrix (ECM) through inhibition of plasmin-dependent ECM degradation. Hypoxia is also presumably associated with macrophage recruitment and angiogenesis that form fibrotic lesions. In the present study, we examined the effects of hypoxia and TNF-alpha on PAI-1, MCP-1 and VEGF expression in cultured human proximal renal tubular cells (HPTECs). We also investigated the presence of PAI-1 in renal tubular cells by immunostaining renal biopsy samples and measuring urinary PAI-1 levels in different kidney diseases. cDNA array analysis identified PAI-1 as a major gene highly induced by hypoxia in HPTECs. Hypoxia, TNF-alpha and their combination induced a 2.8-fold, a 1.8-fold, and a 4.6-fold increase in PAI-1 protein secretion, and produced a 3.6-fold, a 3.3-fold, and a 12.1-fold increase at the PAI-1 mRNA level, respectively. Similar results were confirmed by luciferase assay. Immunoblot analysis and immunocytochemistry revealed that hypoxia-inducible factor-1alpha (HIF-1alpha) was markedly accumulated in nuclei after 16-hours of hypoxia. Hypoxia reduced basal and TNF-alpha-stimulated MCP-1 expression, while it induced VEGF expression in HPTECs. In crescentic glomerulonephritis (CrGN) or diabetic nephropathy (DN) with severe proteinuria, clusters of proximal tubules and a part of the fibrotic interstitium were specifically stained for PAI-1, while no stainings were found in minor glomerular abnormality or minimal change nephrotic syndrome. Urinary PAI-1 levels were significantly higher in CrGN and DN than in healthy controls. In DN, urinary TNF-alpha levels were significantly correlated with urinary PAI-1 levels. PAI-1 induced by hypoxia and inflammation may contribute to further progression of advanced kidney disease, CrGN or DN. Hypoxia together with inflammation may also be involved in promotion of renal fibrosis in part by modulating MCP-1 and VEGF expression.


Human hypoxanthine-guanine phosphoribosyltransferase. Development of a spectrophotometric assay and its use in detection and characterization of mutant forms.
A simple and rapid spectrophotometric assay for the estimation of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity in human tissues is described. It is based on the increase in absorbance at 257.5 nm which occurs when the substrate guanine is converted to its 5'-mononucleotide, GMP. The assay has been developed to measure HGPRT activity in erythrocyte and lymphocyte lysates and in brain homogenates, and has been used in the screening of patients with hyperuricaemia and/or hyperuricosuria for HGPRT deficiency. It has also been used to determine the steady-state kinetic constants of a mutant form of the enzyme. The spectrophotometric assay is compared with the radioactive assay currently used to measure HGPRT activity.


Cells isolated from fetal rat calvaria by isopycnic separation express different collagen phenotypes.
Calvaria from 20-21 day old fetuses were obtained under sterile conditions and the endo- and exoperiosteum stripped off. Cells were dispersed by sequential collagenase-DNase treatment and suspended in 0.5% low Tm agarose in the presence of DMEM supplement with 10% FCS. After 4-5 days of incubation some 30% of these cells showed active synthesis of metachromatic extracellular matrix. Cells from skin, muscle and periosteum failed to show metachromatic matrix positive colonies to a comparable extent. The phenotypic expression of these cells was determined by analysis of collagen types. Eleven day old cultures were incubated in the presence of [3H]-proline plus beta-aminopropionitrile and ascorbic acid and the collagen extracted analyzed by polyacrylamide electrophoresis of their intact chains or CNBr-derived peptides. The results show that anchorage independence is a requirement for calvaria cells to express type II collagen. Type I collagen was preferentially expressed in monolayer culture or when pre-attached to a substrate before being cultured in agarose. Type II collagen was the predominant collagen when cells were cultured in agarose. Further characterization of cell populations was achieved by isopycnic centrifugation in a percoll gradient. Cell fractions were tested for their collagen phenotype when cultured in agarose. Cells recovered from densities 1.04 g/ml or higher synthesized type II collagen, while cells with densities lower than 1.04 g/ml synthesized mainly type I collagen. Isopycnic centrifugation appears to be a novel method for separation of phenotypically different cells from a heterogeneous population in fetal calvaria. The high density cell fractions may represent a mixture of pre-chondrocytes as well as pluripotential cells.


Derivation in culture of primordial germ cells from cells of the mouse epiblast: phenotypic induction and growth control by Bmp4 signalling.
Primordial germ cells (PGCs) are the embryonic precursors of the gametes of the adult. PGCs derive from cells of the most proximal part of the cup-shaped epiblast corresponding to the presumptive region of the extraembryonic mesoderm. At 7.2 days post coitum (dpc) a small group of PGCs located at the base of the allantois can be recognised due to a strong alkaline phosphatase activity. Thus far, scant information was available on the mechanism(s) controlling the lineage of PGCs in the mouse embryo. However, results obtained in mice defective for bone morphogenetic protein-4 (Bmp4) secreted molecule revealed that this growth factor has important functions for the derivation of PGCs from extraembryonic mesoderm cells. In this paper, we have studied the effects in culture of Bmp4 on epiblast cells obtained from egg-cylinder stage mouse embryos (5.5-6.0 dpc) and PGCs from 11.5 dpc embryos. We found that Bmp4 treatment enables recruitment of pluripotent cells to a PGC phenotype by a multi-step process involving an initial pre-commitment of epiblast cells and a following stage of PGC phenotypic determination. We further provide evidences that Bmp4 may promote the growth of gonadal PGCs through a Smad1/4 signalling.


Endocrinology: advances through omics and related technologies.
The rapid development of new omics technologies to measure changes at genetic, transcriptomic, proteomic, and metabolomics levels together with the evolution of methods to analyze and integrate the data at a systems level are revolutionizing the study of biological processes. Here we discuss how new approaches using omics technologies have expanded our knowledge especially in nontraditional models. Our increasing knowledge of these interactions and evolutionary pathway conservation facilitates the use of nontraditional species, both invertebrate and vertebrate, as new model species for biological and endocrinology research. The increasing availability of technology to create organisms overexpressing key genes in endocrine function allows manipulation of complex regulatory networks such as growth hormone (GH) in transgenic fish where disregulation of GH production to produce larger fish has also permitted exploration of the role that GH plays in testis development, suggesting that it does so through interactions with insulin-like growth factors. The availability of omics tools to monitor changes at nearly any level in any organism, manipulate gene expression and behavior, and integrate data across biological levels, provides novel opportunities to explore endocrine function across many species and understand the complex roles that key genes play in different aspects of the endocrine function.


Hematological, biochemical and antioxidant indices variations in regular blood donors among Mediterranean regions.
One of the most important problems in Mediterranean regions is finding blood donors to overcome the high need of its population. Understanding the health benefits of blood donation frequency will activate more volunteers to donate. The aim of this study variations of hematological and biochemical indices in regular male and female donors from Greece and Italy METHODS: A cross-sectional study consisted of 350 voluntary blood donors (VDs)was conducted in two mediterranean Blood Banks, Greece and Italy. The first one from the General Hospital of Naousa, Greece on samples of 90 regular and 60 first-time blood donors. The second one from AOU Sassari, Sardinia, Italy on convenient samples of 100 first-time samples and 100 regular blood donors. Donors' particulars were obtained from blood bank records. The hematological and biochemical parameters were determined for all donors and Total Antioxidant Status (TAS) only for greek VDs. High frequency blood donation of Greek VDs could be associated with evidence of reduction of body iron stores, reduced oxidative stress and improvement of liver function biomarkers in regular groups. Interestingly, Sardinian regular male VDs presented increased iron stores in compare with the first time VDs. In both Mediterranean populations (Greeks and Italians) the lipid profile of the female regular blood donors has been improved in compare with the first timers. Regular blood donation increases antioxidant capacity and affects positively the hematological parameters and biochemical biomarkers in donors. Gender plays an important role in relation to all hematological and biochemical parameters. Further studies in larger population should evaluate the beneficial-effect of blood donation and promote people to donate more frequent.


Henoch-Schönlein Purpura in children: not only kidney but also lung.
Henoch-Schönlein Purpura (HSP) is the most common vasculitis of childhood and affects the small blood vessels. Pulmonary involvement is a rare complication of HSP and diffuse alveolar hemorrhage (DAH) is the most frequent clinical presentation. Little is known about the real incidence of lung involvement during HSP in the pediatric age and about its diagnosis, management and outcome. In order to discuss the main clinical findings and the diagnosis and management of lung involvement in children with HSP, we performed a review of the literature of the last 40 years. We identified 23 pediatric cases of HSP with lung involvement. DAH was the most frequent clinical presentation of the disease. Although it can be identified by chest x-ray (CXR), bronchoalveolar lavage (BAL) is the gold standard for diagnosis. Pulse methylprednisolone is the first-line of therapy in children with DAH. An immunosuppressive regimen consisting of cyclophosphamide or azathioprine plus corticosteroids is required when respiratory failure occurs. Four of the twenty-three patients died, while 18 children had a resolution of the pulmonary involvement. DAH is a life-threatening complication of HSP. Prompt diagnosis and adequate treatment are essential in order to achieve the best outcome.


Intra-urban variation of antibiotic utilization in children: influence of socio-economic factors.
The aim of this study was to investigate the intra-urban variation of antibiotic utilization in children in Malmö and to evaluate the influence of socio-economic factors on this variation. In an ecological analysis, the variations in antibiotic utilization in children, expressed as defined daily dose (DDD) or as the number of prescriptions per 1000 inhabitants per day, were compared with variations in socio-economic and demographic factors in the 17 administrative districts of the Swedish city of Malmö (235000 inhabitants). There were large between-area differences in antibiotic utilization, especially in children aged 0-6 years. Socio-economic factors reflecting a privileged situation correlated positively with antibiotic utilization. Thus, in districts with a high median family income and a high employment rate, the utilization of antibiotics was higher than in other districts. Conversely, in districts with a high proportion of blue-collar workers, people with foreign backgrounds and recipients of social benefit, antibiotic utilization was comparatively low. In contrast, the utilization of penicillin V relative to other antibiotics showed an opposite pattern, including positive correlations with the proportion of social benefit, immigrants and blue-collar workers and a negative correlation with employment rate. Conversely, the utilization of macrolides in relation to other antibiotics in children aged 0-6 years was highest in districts inhabited by those who were socio-economically privileged. The findings suggest that utilization of antibiotics in children may vary considerably within a city, that it may increase with the degree of parental affluence, and that such affluence may reduce the utilization of penicillin V relative to other antibiotics.


Is elevated serum ceruloplasmin level associated with increased risk of coronary artery disease?
An imbalance between the lipid peroxidation process and antioxidative protection is associated with the pathophysiology of coronary artery disease (CAD). The authors aimed to determine the relationship between the contributors of antioxidant protection, such as paraoxonase-1 (PON1) activity, albumin, vitamin C and ceruloplasmin (CP) levels, and lipid peroxidation indicators. In the present study, the activity of PON1 was measured, together with serum concentrations of a variety of lipid constituents, albumin, vitamin C and CP levels, and lipid peroxidation indicators (conjugated dienes [CDs] and thiobarbituric acid-reactive substances [TBARS]). Data were gathered from 26 nondiabetic, angiographically proven, Turkish CAD patients and 26 healthy controls living in the Antalya region (Turkey). CAD patients had significantly lower PON1 activity, high-density lipoprotein cholesterol, vitamin C and albumin concentrations, and higher CP, CD and TBARS concentrations than the controls. In the entire study population (n=52), serum CP levels were positively correlated with TBARS and CD levels, and negatively correlated with albumin and vitamin C levels, as well as with PON1 activity. On multiple logistic regression analysis, risk factors associated with CAD included high CP and low albumin levels. CAD patients and controls were matched for age and sex, and high CP and low albumin levels were found to be independent risk factors for CAD. The present data gathered from the study group living in the Antalya region verifies that in CAD patients, CP impairs the oxidant-antioxidant balance in favour of the oxidants.


Phenylalanine and aspartame fail to alter feeding behavior, mood and arousal in men.
Two experiments were designed to investigate the neurobehavioral effects of phenylalanine (PHE; 0.84, 2.52, 5.04, and 10.08 g) and aspartame (APM; 5.04 and 10.08 g) on energy and macronutrient selection and on subjective feelings of hunger, mood and arousal in normal weight adult males. Neither phenylalanine nor aspartame altered mean energy intakes or macronutrient selection at a lunch begun 60 to 105 min after the amino acids were consumed. During this time, increased (p less than 0.05) visual analog scale (VAS) scores for emptiness, rumbling, weakness, degree of hunger and urge to eat were found in both experiments, but no treatment effects or interactions were seen for any variable in either experiment. Plasma PHE levels and ratios to other large neutral amino acids (NAA) rose significantly (p less than 0.05) after all treatments except 0.84 g PHE; plasma tyrosine (TYR) levels increased (p less than 0.05) only when greater than or equal to 2.52 g PHE was given. TYR/NAA ratios were higher (p less than 0.05) after 2.52 and 5.04 g PHE, and 10.08 g APM. No relationships were found between food intake and plasma amino acid levels. We conclude that, in normal weight men, PHE and APM, in doses up to 10 g, do not affect short-term energy and macronutrient intakes, or subjective feelings of hunger, mood and arousal.


Further studies on the acute dependence produced by morphine in opiate naive rats.
Morphine appears to be capable of initiating the opiate dependence process with the first exposure. This can be demonstrated within 3 hrs by the administration of a low dose of naloxone which results in a significant elevation in plasma corticosterone. The response was still evident if the interval between morphine-priming and naloxone was extended to 6, 12, or 24 hours. The magnitude of the hormone elevation varied with the priming dose of morphine or with the dose of naloxone used to precipitate the response. Results are presented suggesting that the stress/withdrawal hormone response may be evident as early as 30 min after morphine-priming. Rats pretreated for eight days with either diazepam, phenobarbital, or amphetamine showed similarities in hormone responses after morphine-priming and naloxone administration when compared to saline-pretreated controls. The exception being the phenobarbital-pretreated group, where the response was attenuated and not observed at the 24 hr interval. These results emphasize the parallels between acute dependence and chronic dependence, suggesting that the same mechanism is involved.


Cardiac dysfunction in StrepTSS: group A streptococcus disrupts the directional cardiomyocyte-to-macrophage crosstalk that maintains macrophage quiescence.
Myocardial dysfunction in group A streptococcal (GAS) toxic shock syndrome (StrepTSS) is characterized by severe biventricular dilatation and a striking reduction in ventricular performance; however, the mechanisms have not been fully elucidated. We have previously shown that pro-inflammatory cytokines are upregulated in the hearts of experimental animals with GAS bacteremia and that cardiomyocytes themselves as well as macrophages are the principal cytokine sources. Although macrophage-derived cytokines can clearly affect cardiac contractility, we questioned whether soluble cardiomyocyte-derived mediators might in turn affect macrophage function. Thus, we sought evidence of cardiomyocyte-to-macrophage directional cross-talk under resting versus GAS-stimulated conditions, using production of matrix metalloproteinase-9 (MMP-9) as an indicator of such signaling. Our results demonstrate that unstimulated cardiomyocytes produce a soluble inhibitor/s that maintains macrophage functional quiescence. Further, viable GAS induced production of cardiomyocyte-derived stimulator/s that overcomes quiescence and boosts macrophages production of MMP-9 and expression of pro-inflammatory cytokines (IL-1β, IL-6) and cardiodepressant factors (iNOS). Understanding the role of these cardiomyocyte-derived effectors of macrophage function (herein termed "cardiokines") in sepsis-associated cardiomyopathy may suggest new targets for therapeutic intervention.


Involvement of cyclic AMP and protein synthesis in the desensitization of the prepubertal rat ovary.
Luteinizing hormone (LH) stimulates cyclic AMP (cAMP) production in ovarian cells. After the initial stimulation there is a development of refractoriness (desensitization) to a subsequent LH stimulation. The present investigation was designed to study the role of cAMP in this desensitization process and the influence of protein-synthesis inhibitors. Ovaries from 23-day-old rats were preincubated in buffer, dibutyryl-cAMP, 8-bromo-cAMP or LH. After a washing period in buffer, the ovaries were incubated in the presence of LH. Those ovaries preexposed to the cAMP analogues showed a reduced cAMP-production to LH. This reduction was found to be both dose- and time-dependent, but was never as marked as after preincubation with LH. Desensitization developed more slowly after preincubation with cAMP than with LH. Inhibitors of protein synthesis (puromycin, cycloheximide) completely abolished the cAMP-induced desensitization but only partially prevented the LH-induced desensitization. These results show that processes, dependent and independent of cAMP, are involved in the desensitization after LH stimulation of the prepubertal rat ovary.


[A new treatment of Huntington's chorea. Report of three cases (author's transl)].
The authors report their experience in three cases of Huntington's chorea treated with tiapride (Tiapridal). A real efficacy and an interesting effect of the drug were observed on choreic hyperkinesias. No regression of the other symptoms were noted and the course of the disease not changed.