Intravenous Lidocaine and Ketamine Infusions for Headache Disorders: A Retrospective Cohort Study.
The use of lidocaine (lignocaine) and ketamine infusion in the inpatient treatment of patients with headache disorders is supported by small case series. We undertook a retrospective cohort study in order to assess the efficacy, duration and safety of lidocaine and ketamine infusions. Patients admitted between 01/01/2018 and 31/07/2021 were identified by ICD code and electronic prescription. Efficacy of infusion was determined by reduction in visual analog score (VAS), and patient demographics were collected from review of the hospital electronic medical record. Through the study period, 83 infusions (50 lidocaine, 33 ketamine) were initiated for a headache disorder (77 migraine, three NDPH, two SUNCT, one cluster headache). In migraine, lidocaine infusion achieved a ≥50% reduction in pain in 51.1% over a mean 6.2 days (SD 2.4). Ketamine infusion was associated with a ≥50% reduction in pain in 34.4% over a mean 5.1 days (SD 1.5). Side effects were observed in 32 and 42.4% respectively. Infusion for medication overuse headache (MOH) led to successful withdrawal of analgesia in 61.1% of lidocaine, and 41.7% of ketamine infusions. Lidocaine and ketamine infusions are an efficacious inpatient treatment for headache disorders, however associated with prolonged length-of-stay and possible side-effects.


Antimalarial psychosis revisited.
Drug-induced psychosis resulted from the administration of quinacrine hydrochloride at a dosage of 100 mg twice daily for the treatment of discoid lupus. After two weeks of drug treatment, the patient exhibited symptoms similar to those seen in the manic phase of bipolar affective disorder. Although the incidence of antimalarial psychosis is unclear and perhaps small, we recommend close observation of patients for behavioral changes suggesting the development of antimalarial psychosis. Astute observation, leading to the early detection of behavioral changes, may help avert the development of a costly and disabling complication of drug therapy.


Time course of action and recovery of rocuronium bromide in children during halothane anaesthesia--a preliminary report.
In this preliminary study, two groups of 15 patients, aged 1-4 years and 5-10 years respectively, received one of four doses of rocuronium (0.12, 0.17, 0.22 or 0.27 mg kg-1) and when block was maximal a supplementary dose to bring them all to a total of 0.5 mg kg-1. In half the patients, the block was reversed with atropine and neostigmine at a T1 recovery of 25%. The remainder were allowed to recover spontaneously. The total dose produced a block of 95-100% in all patients. The clinical duration of action was shorter under halothane anaesthesia in children (mean 15 min approximately) than has previously been reported in adults under intravenous anesthesia. Mean spontaneous recovery time from T1 25% to a train-of-four ratio of 0.7 was about 11 min. Neostigmine doubled the rate of recovery. There was a moderate increase in heart rate in the younger age range.


Electron Density Difference Analysis on the Oxidative and Reductive Quenching Cycles of Classical Iridium and Ruthenium Photoredox Catalysts.
In this study a detailed scrutiny of the electronic structure changes during the redox events of the oxidative and reductive quenching cycles of the representative homoleptic and heteroleptic octahedral iridium [Ir(bpy)x(ppy)3-x]x+ (x = 0, 1, 2, and 3) and ruthenium [Ru(bpy)x(ppy)3-x]x-1+ (x = 1, 2, and 3) photoredox catalysts is provided through the corresponding electron density difference Δρ(r) distributions. The systematic analysis of the Δρ(r) distributions provides intuitive insights into the details of the metal- and ligand-centered electron transfer processes that take place in the different excited- and ground-state redox steps of classical photoredox catalysis. In addition to the structural metrics, the measured ground-state reduction potentials were also reproduced with great accuracy, typically within 0.15 V, when using the TPSSh functional in combination with the Def2-TZVP basis set coupled to reparameterized implicit solvation model (SMD). We computed the excited-state reduction potentials of these ruthenium and iridium complexes without using TD-DFT, but by directly computing the solution-state Gibbs free energy of the triplet 3MLCT state, giving good agreement with respective experiments. The analyzed Δρ(r) maps reveal the characteristic features of metal- and ligand-centered reductions and oxidations in both ground- and excited states and metal-to-ligand charge transfers (MLCT), sometimes perturbed by additional ligand-to-ligand charge transfer (LLCT) contributions. One of the most interesting features of ligand-centered redox processes is the localization of the accumulated electron density at one redox-active ligand in the case of heteroleptic systems [Ir(bpy)(ppy)2]+ and [Ru(bpy)(ppy)2]0, which is in contrast to the delocalized nature of the ligands-hosted charge in homoleptic photoredox catalysts, such as the classical [Ru(bpy)3]2+ system.


A comparative study of the distribution of ofloxacin and ciprofloxacin in prostatic tissues after simultaneous oral ingestion.
To determine the levels of two quinolones, ofloxacin and ciprofloxacin, potent broad-spectrum antibiotics with very good oral bioavailability and low minimum inhibitory concentrations (MICs) for most pathogens, in the prostates of patients who underwent transurethral resection of the prostate (TURP) after oral ingestion for surgical prophylaxis. Twenty-eight patients with BPH requiring a TURP ingested 250 mg of both drugs 2-4 h before operation. The levels of the drugs in the serum and prostate were measured using high-performance liquid chromatography and the levels of both drugs determined at the 6 and 9 o'clock positions in the prostate to examine any local variations in drug concentration. Ofloxacin concentrations were significantly higher in the serum and prostatic tissues compared with ciprofloxacin for the same dose, but its penetrance into the prostate was lower. This mainly reflected its higher oral bioavailability. Both drugs were present in concentrations 50% higher at the 6 o'clock than at the 9 o'clock position but both exceeded the MICs for most Gram-negative organisms except Pseudomonas. Ofloxacin has the advantage against ciprofloxacin of exceeding the MICs for Staphylococcus and Chlamydia. However, ciprofloxacin has the advantage of having prostate-to-serum ratios of unity, but for the same dose the prostatic concentrations of ofloxacin is significantly higher.


Novel regulatory mechanisms underlying angiogenesis during wound healing revealed by fluorescence-based live-imaging in zebrafish.
Angiogenesis is a dynamic morphogenetic process that refers to the growth of new blood vessels from the pre-existing vessels and is critical for tissue repair during wound healing. In adult normal tissues, quiescent endothelial cells and pericytes maintain vascular integrity, whereas angiogenesis is immediately induced upon tissue injury, thereby forming neovascular networks to maintain homeostasis. However, impaired angiogenesis results in development of chronic and non-healing wounds in various diseases such as diabetes and peripheral artery diseases. Zebrafish are a vertebrate model organism widely used for studying many medical and life science fields. Indeed, the molecular and cellular mechanisms underlying regulation of wound angiogenesis have recently been studied by performing fluorescence-based live-imaging of adult zebrafish. In this review, we describe how endothelial cells and pericytes establish neovascular networks during wound angiogenesis and also introduce a novel role of blood flow-driven intraluminal pressure in regulating angiogenesis during wound healing.


Essential oil from Myrcia ovata: chemical composition, antinociceptive and anti-inflammatory properties in mice.
The leaves of Myrcia ovata, popularly known as "laranjinha do mato", are frequently used as an infusion in folk medicine. The essential oil obtained from these leaves is rich in citral, a mixture of neral and geranial isomers, known for its analgesic effect. Male Swiss mice (20-22 g) were tested in models of acute pain (acetic acid-induced abdominal writhing, tail flick, and formalin tests) and acute inflammation (paw oedema and air pouch tests) as well as in a model for evaluation of spontaneous motor performance (open-field test). The essential oil from M. ovata was administered orally at doses of 50-300 mg/kg. In addition, water, vehicle, morphine (5.01 mg/kg for evaluation of pain and motor performance), acetyl salicylic acid (200 mg/kg in the formalin test), and dexamethasone (2.25 mg/kg for evaluation of oedema formation, leukocyte extravasation, and quantification of cytokines) were administered. The essential oil showed a significant effect at doses of 200 and 300 mg/kg in the acute pain and acute inflammation tests. The effect of the essential oil was reduced by pretreatment with naloxone. The essential oil did not induce motor impairment. The extract was not toxic after oral administration (LD50 > 3000 mg/kg). These data provide initial evidence that the traditional use of M. ovata can be effective in reducing pain and inflammation.


[Seminoma metastasis in the small bowel].
Approximately 95% of testicular cancers are germ-cell tumours and these are divided into non-seminoma and pure seminoma. They rarely metastasize to the gastrointestinal tract (< 5%) and pure seminoma are the least likely to do so with an incidence of < 1%. We describe an unusual case of a 67-year-old man, who presented with gastrointestinal complaints, the first symptoms of testicular seminoma being a small bowel metastasis. The patient had a palpable testicular mass which was not detected until after the tumour in the small bowel had been resected and histology revealed metastasis from a seminoma.


Thromboelastography Detects Possible Coagulation Disturbance in Pediatric Patients with Portal Cavernoma.
Thromboelastography (TEG) allows a dynamic assessment of clot formation and dissolution that might be useful for assessing the relative contribution of the coagulation components to overall clot formation and dissolution, but it has not been fully defined in patients with portal cavernoma (PC). We retrospectively recruited consecutive patients with PC between July 2006 and June 2016 who had no abdominal malignancy or liver cirrhosis. Blood samples were drawn on admission and were subjected to coagulation parameter assessment, including conventional coagulation tests, measurement of the circulating levels of procoagulant and anticoagulant factors, and TEG assessment. Compared with controls, patients with PC showed significant reductions in the serum levels of procoagulant factors and anticoagulants factors, whereas factor VIII was slightly elevated. TEG showed clot formation (α-angle), and the maximal clot strength (MA) was higher in patients with PC than in controls, indicating a hypercoagulable state. Thrombocytopenia decreased both clot formation (α-angle) and the maximal clot strength (MA) but was still significantly higher than the control. Furthermore, patients with PC had a higher level of D-dimer and LY30 than did controls, indicating the in vivo activation of coagulation and fibrinolysis. TEG analysis showed that patients with PC were in a hypercoagulable state that could be partially masked by thrombocytopenia secondary to splenomegaly and hypersplenism in these patients, which indicates that our current prophylaxis and therapy regimen could be improved.


In My Best Interest.
Advance directives (ADs) have traditionally been viewed as clear instructions for implementing patient wishes at times of compromised decision-making capacity (DMC). However, whether individuals prefer ADs to be strictly followed or to serve as general guidelines has not been studied. The Veterans Administration's Advance Directive Durable Power of Attorney for Health Care and Living Will (VA AD) provides patients the opportunity to indicate specific treatment preferences and to indicate how strictly the directive is to be followed. To describe preferences for life-sustaining treatments (LSTs) in various illness conditions as well as instructions for the use of VA ADs. A descriptive study was performed collecting data from all ADs entered into the medical record at 1 VA Medical Center between January and June 2014. Responses to VA AD with emphasis on health care agents (HCAs) and LW responses. Veterans were more likely to reject LST when death was imminent (74.6%), when in a coma (71.1%), if they had brain damage (70.6%), or were ventilator dependent (70.4%). A majority (67.4%) of veterans preferred the document to be followed generally rather than strictly. Veterans were more likely to want VA ADs to serve as a general guide when a spouse was named HCA. Most of the sampled veterans rejected LST except under conditions of permanent disability. A majority intend VA ADs to serve as general guidelines rather than strict, binding instructions. These findings have significant implications for surrogate decision making and the use of ADs more generally.


Scanning tunneling microscopy and surface simulation of zinc-blende GaN(001) intrinsic 4x reconstruction: linear gallium tetramers?
Scanning tunneling microscopy images confirm electron diffraction studies that the zinc-blende GaN(001)-4x reconstruction consists of rows aligned along [110] with a spacing along [110] of 4a. Dual-bias imaging shows a 180 degree shift of the corrugation maximum position between the profiles of empty and occupied states, in agreement with surface simulations based on the 4 x 1 linear tetramer model of Neugebauer et al. [Phys. Rev. Lett. 80, 3097 (1998)]. Electronic structure calculations predict a surface band gap of 1.1 eV, close to the measured value of 1.14 eV and the previously predicted value (1.2 eV). Despite the successes of this model, high-resolution images reveal an unexpected 3x periodicity (not seen in diffraction) along the [110] row direction, indicating the need for a 4 x 3 model, and putting into question the existence of linear Ga tetramers.


Aging and Demographic Transition in Ghana: State of the Elderly and Emerging Issues.
Although the population of Ghana is young and generally youthful, there is evidence of rapid increases in the size of the elderly cohort. Although demographic projections estimate that the proportion of the population younger than 15 years will experience continuous decline overtime due in part to decline in fertility, the rise in the elderly population is expected to also continue due to declining mortality rates resulting in longevity. Unfortunately, the growth in the elderly proportion of the population is occurring at the same time traditional systems of protection and care for the aged are breaking down on account of urbanization, socioeconomic development, and globalization. This has implications for public policy and the overall wellbeing of the elderly. This paper provides a snapshot overview of the demographic dynamics of Ghana focusing on the characteristics of aging, the challenges confronting the elderly, policy interventions, and gaps, as well as some pertinent issues including emerging research that are shaping deliberations about the elderly in the country.


Psychometric evaluation of a self-report measure of depression for individuals with mental retardation.
The psychometric properties of the Self-Report Depression Questionnaire (SRDQ) were evaluated, extending a previous assessment of this instrument. Data from two independent studies (Esbensen, 2004; Seltzer & Krauss, 1989) were pooled to generate a sample of 192 individuals with primarily mild or moderate mental retardation. Reliability estimates of this questionnaire were good to excellent and corroborated prior findings. In addition, the measure was found to have sound validity as evidenced by convergent validity, discriminant validity, and predictive validity and by comparing individuals with and without clinical diagnoses of depression. Thus, the SRDQ appears to be a reliable and valid measure of depressive symptomatology for individuals with mild or moderate mental retardation. Screening procedures are suggested.


Seasat altimeter calibration: initial results.
Preliminary analysis of radar altimeter data indicates that the instrument has met its specifications for measuring spacecraft height above the ocean surface (+/- 10 centimeters) and significant wave height (+/- 0.5 meter). There is ample evidence that the radar altimeter, having undergone development through three earth orbit missions [Skylab, Geodynamics Experimental Ocean Satellite 3 (GEOS-3), and Seasat], has reached a level of precision that now makes possible its use for important quantitative oceanographic investigations and practical applications.


Fluorescein angiographic findings in familial exudative vitreoretinopathy.
We describe the fluorescein angiograms in four cases of familial exudative vitreoretinopathy. The vascular nature of the temporal retinal masses is confirmed. Primary abnormalities within the peripheral retinal circulation are demonstrated. We stress the similarity between familial exudative vitreoretinopathy and retrolental fibroplasia.


Postoperative delirium after pharyngolaryngectomy with esophagectomy: a role for ramelteon and suvorexant.
Postoperative delirium is common after extensive surgery, and is known to be associated with sleeping medications. In this study, we aimed to investigate the relationships between sleeping medications and postoperative delirium after pharyngolaryngectomy with esophagectomy. We performed a retrospective analysis of 65 patients who underwent pharyngolaryngectomy with esophagectomy at Shizuoka Cancer Center Hospital between January 2012 and March 2016. All data were assessed by two psychiatrists, and univariate and multivariate analyses were performed. Postoperative delirium developed in 9 (13.8%) patients, with most cases (77.8%) occurring between postoperative day (POD) 1 and POD 3. Of the 24 patients taking a minor tranquilizer after surgery, 8 (33.3%) became delirious, but, of the remaining 41 patients taking ramelteon with or without suvorexant, only one (2.4%) became delirious after surgery. Moreover, of the 16 patients taking both ramelteon and suvorexant, no postoperative delirium was observed. Ramelteon with or without suvorexant was significantly associated with a decreased rate of postoperative delirium compared with minor tranquilizer use (p = 0.001). Multivariate analysis confirmed that the use of ramelteon with or without suvorexant was the only significant preventive factor of postoperative delirium (odds ratio 0.060, p = 0.013). The use of ramelteon with or without suvorexant was the only significant preventive factor of postoperative delirium after pharyngolaryngectomy with esophagectomy. However, using minor tranquilizers was associated with postoperative delirium. We recommend ramelteon with or without suvorexant for preventing postoperative delirium after pharyngolaryngectomy with esophagectomy.


Suppression of neovascularization and experimental arthritis by D-form of anti-flt-1 peptide conjugated with mini-PEG(™).
Extensive angiogenesis in the synoviums is a characteristic pathology of rheumatoid arthritis (RA). We have demonstrated that anti-flt-1 hexapeptide, GNQWFI, specifically inhibits the interaction of VEGF or PlGF with its receptor flt-1 (Yoo et al. [13]). In this study, we investigate the feasibility of the synthetic D-form of anti-flt-1 hexapeptide conjugated with 8-amino-3,6-dioxaoctanoic acid (mini-PEG™) for treatment of RA. We first modified the structure of anti-flt-1 peptide from the L-form (GNQWFI) to all D-form (gnqwfi; allD) and then conjugated allD with mini-PEG™ to enhance its stability. The result showed that the allD anti-flt-1 peptide showed an increased stability in the sera without major loss of inhibitory activity. The allD and its mini-PEGylated derivative similarly suppressed wounding migration, chemotaxis, and tube formation of endothelial cells in vitro. However, in the Matrigels assay, the in vivo anti-angiogenic activity of mini-PEGylated allD was stronger than that of native allD or L-form. Moreover, oral and subcutaneous administration of mini-PEGylated allD, but not oral feeding of original L-form, successfully suppressed severity of collagen-induced arthritis. After a single subcutaneous injection, the Cy5-labeled mini-PEGylated allD was found to be distributed systemically and accumulated in arthritic joints of mice, particularly in joints with a severe clinical score. In conclusion, our data suggests that mini-PEGylated allD is more beneficial in the treatment of RA than unmodified anti-flt-1 peptides, since it has increased stability and the possibility of oral delivery, and could be applied to treat angiogenesis-dependent human diseases, including RA.


Monitoring of environmental persistent organic pollutants in hair samples collected from wild terrestrial mammals of Primorsky Krai, Russia.
Persistent organic pollutants (POPs) constitute a wide range of chemicals. Their release into the environment has raised great concern due to their potentially harmful impact in humans and wildlife species. The aim of this current study was to detect selected POPs in hair samples of wild terrestrial mammals from Primorsky Krai, Russia, so as to assess potential environmental exposure. The tested wild species were leopard cat, musk deer, wolf, amur hedgehog, and raccoon dog. The targeted organochlorines were hexachlorobenzene (HCB) and DDTs (opDDE, ppDDE, and opDDD), polychlorinated biphenyl (PCB) congeners (28, 52, 101, 118, 138, 153, and 180), and polycyclic aromatic hydrocarbons (PAHs) (acenaphylene (ACEN), fluorene (FLU), anthracene (ANTH) phenathrene (PHEN), and pyrene (PYR)). The detection of POPs was conducted in hair samples by a one-step hair extraction method, by using a headspace solid-phase microextraction technique (HS-SPME) and analyzed then by GC-MS. The majority of the wild animal hair samples were found positive in all tested pollutants. More specifically, the percentage of positive hair samples for HCB was 93.3% and for DDTs, PCBs, and PAHs, 20.0 to 100.0%, 6.7 to 100.0%, and 75.0 to 100.0%, respectively. DDT, PCB, and PAH detection ranged from 1.26 to 52.06 pg mg-1, 0.73 to 31.34 pg mg-1, and 2.59 to 35.00 pg mg-1, respectively. The highest mean concentration levels of all tested pollutants were found for musk deer (PCBs 12.41 pg mg-1, DDTs 21.87 pg mg-1, PAHs 22.12 pg mg-1) compared to the other wild species. To the best of our knowledge, this is the first study that provides results regarding contamination in different terrestrial mammals by POP exposure. The use of hair as a matrix is proven to be an effective tool for nondestructive biological monitoring of POP contamination in terrestrial ecosystems.


Tissue growth and remodeling.
The growth and remodeling of a tissue depends on certain features in the history of its mechanical environment as well as its genetic makeup. The mechanical environment influences the tissue's developing morphology, the process of simply increasing the size of existing morphological structures, and the formation of the proteins of which the tissue is constructed. The relationships between genetic information, various epigenetic mechanisms and tissue development are discussed. The developmental growth and remodeling of most structural tissues are enhanced by the use of those tissues and retarded by their disuse. The mechanical or mathematical modeling of tissue growth and development using cellular automata models and continuum mechanical models is reviewed.


Targeting Human α-Lactalbumin Gene Insertion into the Goat β-Lactoglobulin Locus by TALEN-Mediated Homologous Recombination.
Special value of goat milk in human nutrition and well being is associated with medical problems of food allergies which are caused by milk proteins such as β-lactoglobulin (BLG). Here, we employed transcription activator-like effector nuclease (TALEN)-assisted homologous recombination in goat fibroblasts to introduce human α-lactalbumin (hLA) genes into goat BLG locus. TALEN-mediated targeting enabled isolation of colonies with mono- and bi-allelic transgene integration in up to 10.1% and 1.1%, respectively, after selection. Specifically, BLG mRNA levels were gradually decreasing in both mo- and bi-allelic goat mammary epithelial cells (GMECs) while hLA demonstrated expression in GMECs in vitro. Gene-targeted fibroblast cells were efficiently used in somatic cell nuclear transfer, resulting in production of hLA knock-in goats directing down-regulated BLG expression and abundant hLA secretion in animal milk. Our findings provide valuable background for animal milk optimization and expedited development for agriculture and biomedicine.


Quantum-classical reentrant relaxation crossover in Dy2Ti2O7 spin ice.
We have studied spin relaxation in the spin ice compound Dy2Ti2O7 through measurements of the ac magnetic susceptibility. While the characteristic spin-relaxation time (tau) is thermally activated at high temperatures, it becomes almost temperature independent below T(cross) approximately 13 K. This behavior, combined with nonmonotonic magnetic field dependence of tau, indicates that quantum tunneling dominates the relaxational process below that temperature. As the low-entropy spin ice state develops below T(ice) approximately 4 K, tau increases sharply with decreasing temperature, suggesting the emergence of a collective degree of freedom for which thermal relaxation processes again become important as the spins become strongly correlated.


Gastrointestinal stromal tumor with a PDGFRA mutation masquerading as gastric plexiform fibromyxoma: A comparative clinicopathological study of two cases.
Gastric plexiform fibromyxoma (PF) is a rare mesenchymal tumor with a histologically distinctive multinodular pattern, dissimilar to conventional gastrointestinal stromal tumor (GIST). The current study presents one case of gastric PF, and one case of GIST with a platelet-derived growth factor receptor α (PDGFRA) mutation mimicking PF, and discusses their differential diagnoses. The two patients were a 51-year-old male with PF and a 47-year-old female with GIST, each of whom presented with an occupying lesion in the gastric antrum. Histologically, the two cases shared a rare and approximately unanimous morphological pattern of a prominent multinodular and plexiform figuration in the gastric wall, including mucoid matrix, short spindle cells and small caliber vascular elements, and areas of stromal tumor cells exhibited an epithelioid appearance. Immunohistochemistry revealed that the PF tumor cells were positive for smooth muscle actin (SMA), but negative for mast/stem cell growth factor receptor (KIT), GIST-1 (DOG1), cluster of differentiation (CD) 34, S-100, desmin and cytokeratin AE1/AE3. The case of GIST expressed KIT and DOG1, but was negative for SMA, CD34, S-100, desmin and AE1/AE3. In addition, the GIST case, which was observed to harbor a D842V mutation in exon 18 of PDGFRA, was demonstrated to be genetically distinct from PF. The cases presented in the current study were uncommon in that GIST exhibited a plexiform appearance that mimicked the histology of the rare PF tumor; therefore, GIST must be considered and discounted first when determining a differential diagnosis for a gastrointestinal mesenchymal neoplasm.


[Somatuline(R) Autogel(R), a new formulation of lanreotide for the treatment of acromegalic patients].
Lanreotide Autogel((R)) is a new long-acting aqueous preparation of lanreotide for the treatment of acromegaly, and is administered by deep sc injection from small-volume pre-filled syringes. The aim of this study was to evaluate the efficacy and safety of this new long-acting formulation in a large population of acromegalic patients previously responsive to im lanreotide 30mg (sustained release microparticle formulation). Lanreotide Autogel((R)) was administered by deep sc injection every 28 days to 107 patients (54 males, 53 females; mean age 54+/-1.2 years). All patients had been treated with lanreotide 30mg for at least 3 months before study entry, and had a mean GH level<10 ng/mL after at least four subsequent im injections every 14 days (48%), 10 days (32%) or 7 days (20%). Treatment was switched from lanreotide 30mg injected every 14, 10 or 7 days to lanreotide Autogel((R)) 60, 90 or 120mg, respectively, every 28 days. After three fixed-dose injections of lanreotide Autogel((R)), mean lanreotide levels were similar to those obtained at steady state with lanreotide 30mg. During lanreotide Autogel((R)) treatment, the control of acromegalic symptoms was comparable with that previously achieved during lanreotide 30mg treatment. After three injections of lanreotide Autogel((R)), mean values for GH (2.87+/-0.22ng/mL) and IGF-1 (317+/-15ng/mL) were comparable with those recorded at the end of lanreotide 30mg treatment (GH: 2.82 +/- 0.19ng/mL; IGF-1: 323+/-16ng/mL). GH<2.5ng/mL and age-sex-normalised IGF-1 was achieved in 33% and 39% of patients during lanreotide 30mg and lanreotide Autogel((R)) treatment, respectively. Diarrhoea, abdominal pain and nausea were reported by 38, 22 and 18% of patients during lanreotide 30mg treatment, and by 29, 17 and 9% of patients, respectively, during lanreotide Autogel((R)) treatment. In conclusion, this clinical study shows that lanreotide Autogel((R)) is at least as efficacious and well tolerated as lanreotide 30mg. This new long-acting lanreotide formulation, lanreotide Autogel((R)), which is administered from small-volume pre-filled syringes by deep sc injection, is therefore likely to improve the acceptability of medical treatment for patients requiring long-term somatostatin analogue therapy.


[Up to allergy specialists' consideration: did Pharaoh Menes die of a wasp sting?].
Several allergologists interested in allergies to wasp venom, pass a seemingly probable information that the first Egyptian pharaoh, Menes, was allergic to the venom of stinging insects, and died of an insect sting while on a long journey, somewhere in the area of present-day Great Britain. A relief decorating the pharaoh's sarcophagus and the tomb's walls is to prove the historicity of this event. The whole story is a typical hoax. Insufficient historical sources do not confirm the thesis that Menes visited Europe. The tomb which is considered to be his burial site, contained no sarcophagus, reliefs or paintings. The above-mentioned relief is a contemporary illustration which should raise suspicions even of a layman who looked at it carefully. It is interesting why so many respectable scientists believe the hoax and quote it without previous verification.


Gelatin Zymography to Detect Gelatinase Activity in Melanoma Cells.
Melanoma cells, having highly invasive properties, exhibit the formation of invadopodia-structures formed by tumor cells and responsible for the digestion of the surrounding extracellular matrix (ECM). Several metalloproteases (MMPs) are secreted by cells to hydrolyze ECM proteins. They are mainly secreted through structures known as invadopodia. ECM degradation is crucial for tumor cells while forming metastases as the cells heading towards blood vessels must loosen dense tissue. One group of metalloproteases secreted by melanoma cells comprises the gelatinases, i.e., metalloproteases 2 and 9. Gelatinases cleave gelatin (denatured collagen), a few types of collagen (including type IV), and fibronectin, all structural components of ECM. This paper describes a gelatin zymography assay to analyze the gelatinase activity of melanoma cells. This approach is based on analyzing the extent of digestion of a substrate (gelatin) added to a polyacrylamide gel. Several advantages, such as simplicity, sensitivity, low cost, and semiquantitative analysis by densitometry, as well as the detection of both active and inactive forms of MMPs, make this assay valuable and widely used. This protocol describes how to concentrate medium devoid of intact floating cells, cell debris, and apoptotic bodies. Next, it focuses on preparing polyacrylamide gel with gelatin addition, performing sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), removing SDS, and staining of the gel to detect gelatin-free bands corresponding to the activity of gelatinases secreted by melanoma cells. Finally, the paper describes how to quantitatively analyze data from this assay. This method is a good alternative for estimating the gelatinase activity of melanoma cells to a fluorescent gelatin degradation assay, western blot, or enzyme-linked immunosorbent assays (ELISAs).


Establishment of an Experimental System for Intraperitoneal Chemotherapy in a Rat Model.
To establish an experimental system for comparing different methods of intraperitoneal chemotherapy in a rat model. We used six-week-old Sprague-Dawley rats, and created an early postoperative intraperitoneal chemotherapy (EPIC) system using 18-gauge syringes and evacuators, and a hyperthermic intraperitoneal chemotherapy (HIPEC) system using two peristaltic pumps which controlled the flow rate and temperature. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) was achieved using a nozzle for dispersing aerosols at a flow rate up to 41.5 ml/min. The distribution and intensity of 0.2% trypan blue dye was compared among three methods. The distribution was limited and the intensity was weak after EPIC, and the dye stained moderately in gravity-dependent regions after HIPEC. On the other hand, the distribution was the most comprehensive, and the intensity was the greatest after PIPAC. This experimental system in a rat model may reflect the comparative effect among EPIC, HIPEC and PIPAC in humans.


Ultra high-throughput single molecule spectroscopy with a 1024 pixel SPAD.
Single-molecule spectroscopy is a powerful approach to measuring molecular properties such as size, brightness, conformation, and binding constants. Due to the low concentrations in the single-molecule regime, measurements with good statistical accuracy require long acquisition times. Previously we showed a factor of 8 improvement in acquisition speed using a custom-CMOS 8x1 SPAD array. Here we present preliminary results with a 64X improvement in throughput obtained using a liquid crystal on silicon spatial light modulator (LCOS-SLM) and a novel standard CMOS 1024 pixel SPAD array, opening the way to truly high-throughput single-molecule spectroscopy.


Incentives can spur COVID-19 vaccination uptake.
Recent evidence suggests that vaccination hesitancy is too high in many countries to sustainably contain COVID-19. Using a factorial survey experiment administered to 20,500 online respondents in Germany, we assess the effectiveness of three strategies to increase vaccine uptake, namely, providing freedoms, financial remuneration, and vaccination at local doctors. Our results suggest that all three strategies can increase vaccination uptake on the order of two to three percentage points (PP) overall and five PP among the undecided. The combined effects could be as high as 13 PP for this group. The returns from different strategies vary across age groups, however, with older cohorts more responsive to local access and younger cohorts most responsive to enhanced freedoms for vaccinated citizens.


Olfactory functions scale with circuit restoration in a rapidly reversible Alzheimer's disease model.
Neural circuits maintain a precise organization that is vital for normal brain functions and behaviors, but become disrupted during neurological disease. Understanding the connection between wiring accuracy and function to measure disease progression or recovery has been difficult because of the complexity of behavioral circuits. The olfactory system maintains well-defined neural connections that regenerate throughout life. We previously established a reversible in vivo model of Alzheimer's disease by overexpressing a humanized mutated amyloid precursor protein (hAPP) in olfactory sensory neurons (OSNs). Using this model, we currently show that hAPP is present in the OSN axons of mutant mice, which exhibit strong caspase3 signal and reduced synaptic protein expression by 3 weeks of age. In the olfactory bulb, we show that glomerular structure is distorted and OSN axonal convergence is lost. In vivo functional imaging experiments further demonstrate disruption of the glomerular circuitry, and behavioral assays reveal that olfactory function is significantly impaired. Because OSNs regenerate, we also tested if the system could recover from hAPP-induced disruption. We found that after 1 or 3 weeks of shutting-off hAPP expression, the glomerular circuit was partially restored both anatomically and functionally, with behavioral deficits similarly reversed. Interestingly, the degree of functional recovery tracked directly with circuit restoration. Together, these data demonstrate that hAPP-induced circuit disruption and subsequent recovery can occur rapidly and that behavior can provide a measure of circuit organization. Thus, olfaction may serve as a useful biomarker to both follow disease progression and gauge potential recovery.


Is hexavalent chromium carcinogenic via ingestion? A weight-of-evidence review.
Hexavalent chromium [Cr(VI)] is recognized as a human carcinogen via inhalation, based on elevated rates of lung cancer among occupationally exposed workers in certain industries. Cr(VI) is also genotoxic in bacterial and mammalian cell lines. In contrast, scientific panels in the United States and abroad have reviewed the weight of evidence (WOE) and decided that the available data are insufficient to conclude that Cr(VI) is an oral carcinogen. A criterion of 0.2 ppb was established by a California agency for Cr(VI) in drinking water to prevent cancer, however, this criterion was withdrawn in November, 2001. This criterion was remarkably lower than the promulgated California and federal drinking-water standards for total chromium of 50 ppb and 100 ppb, respectively. Both of the promulgated standards are designed to be protective of humans who ingest Cr(VI). This article describes a WOE analysis to examine the likelihood that Cr(VI) in drinking water poses a cancer hazard at the current U.S. drinking-water standard. The results indicate that: (1) From the historical epidemiological studies, there are a few reports of increased rates of digestive system cancer among Cr(VI)-exposed workers, although most are not statistically significant; (2) the preponderance of evidence from recent epidemiological studies of Cr(VI)-exposed workers does not support an increased risk of cancer outside of the respiratory system; (3) studies of four environmentally exposed populations are negative; (4) there is only one lifetime animal feeding study, and the findings from that study are considered to be flawed and inconclusive; and (5) recent kinetics and in vivo genotoxicity data demonstrate that Cr(VI) is reduced to nontoxic Cr(III) in saliva, in the acidic conditions of the stomach, and in blood. In short, at concentrations at least as high as the current U.S. maximum contaminant level (100 ppb), and probably at least an order of magnitude higher, Cr(VI) is reduced to Cr(III) prior to or upon systemic absorption. The weight of scientific evidence supports that Cr(VI) is not carcinogenic in humans via the oral route of exposure at permissible drinking-water concentrations.


Retrospective Analysis of Cushing's Disease with or without Hyperprolactinemia.
Objective. We compared the characteristics of patients with Cushing's disease alone with those of patients with Cushing's disease and hyperprolactinemia. Methods. Eighty-four patients were enrolled between 2002 and 2011, in a hospital in China. Clinical, endocrinological, and histopathological data, MRI scans, and surgical outcomes were reviewed throughout the follow-up period. Results. Patients with Cushing's disease and hyperprolactinemia had a younger age at diagnosis (30.28 ± 14.23 versus 36.08 ± 10.91 years; P = 0.037) and a larger adenoma maximal diameter (2.44 ± 1.32 versus 1.44 ± 1.05 cm; P < 0.001) than patients with Cushing's disease alone. Menstrual disorders (P = 0.027) and visual field defects (P = 0.021) were more common and progressive obesity (P = 0.009) and hypertension (P < 0.001) were less common in patients with Cushing's disease and hyperprolactinemia. The rate of normalization of hormonal levels was lower (41.7% versus 91.7%; P < 0.001) and the recurrence rate was higher (36.1% versus 8.3%; P < 0.001) in patients with Cushing's disease and hyperprolactinemia. Conclusions. Careful long-term follow-up is needed of patients with Cushing's disease and hyperprolactinemia.


Safety and Tolerability of tDCS across Different Ages, Sexes, Diagnoses, and Amperages: A Randomized Double-Blind Controlled Study.
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique with substantial evidence for its safety and tolerability in adults. However, less than 5% of published tDCS research is in pediatrics. Our primary objective was to investigate tDCS safety, tolerability, and acceptability in a sample of children and adults. We hypothesized that children and adults would be equal with regard to tDCS safety, tolerability, and acceptability. We tested this hypothesis using a Bayesian approach. Sixty participants aged 6-45 (balanced for sex) participated in a randomized double-blind controlled trial. They were randomly assigned to two ten-minute tDCS sessions with varying amperages and electrode locations. The primary outcome measure of this study was the intensity of 13 potential side effects evaluated at six different time points spanning two weeks. Independent sample Bayes factor tests were conducted between children/adults, males/females, clinical/healthy, and low/high amperage groups. As predicted, there was moderate support for the null hypothesis in all between-group analyses. There were no serious adverse events or dropouts, and the number needed to treat for an additional harmful outcome was 23. This study provided evidence supporting the overall short-term safety, tolerability, and acceptability of tDCS including amperages up to 2 mA and different electrode placements.


The immune status of the uremic patient: hemodialysis vs CAPD.
The immune status of the uremic patient is characterised by an affected cellular immunity. The absolute numbers of circulating T-cells are reduced. The relative numbers of OKT8-cells and the suppressor cell activity seem to be increased, the helper cell activity seems to be decreased. Hemodialysis does not restore the impaired immune status. With increasing time of dialysis the alterations become more pronounced. So far a difference in the immune status of CAPD patients compared to HD patients has not been proven. The impairment of immune response might be less than in HD patients. The mechanism of this difference is not established. However, the question of immune response in uremia and its alteration by different forms of dialysis treatment is only in part and insufficiently investigated. Studies in CAPD patients have only a very preliminary character.


The role of nonverbal working memory in morphosyntactic processing by children with specific language impairment and autism spectrum disorders.
Both children with autism spectrum disorders (ASD) and children with specific language impairment (SLI) have been shown to have difficulties with grammatical processing. A comparison of these two populations with neurodevelopmental disorders was undertaken to examine similarities and differences in the mechanisms that may underlie grammatical processing. Research has shown that working memory (WM) is recruited during grammatical processing. The goal of this study was to examine morphosyntactic processing on a grammatical judgment task in children who varied in clinical diagnosis and language abilities and to assess the extent to which performance is predicted by nonverbal working memory (WM). Two theoretical perspectives were evaluated relative to performance on the grammatical judgment task-the "working memory" account and the "wrap-up" account. These accounts make contrasting predictions about the detection of grammatical errors occurring early versus late in the sentence. Participants were 84 school-age children with SLI (n = 21), ASD (n = 27), and typical development (TD, n = 36). Performance was analyzed based on diagnostic group as well as language status (normal language, NL, n = 54, and language impairment, LI, n = 30). A grammatical judgment task was used in which the position of the error in the sentence (early versus late) was manipulated. A visual WM task (N-back) was administered and the ability of WM to predict morphosyntactic processing was assessed. Groups differed significantly in their sensitivity to grammatical errors (TD > SLI and NL > LI) but did not differ in nonverbal WM. Overall, children in all groups were more sensitive and quicker at detecting errors occurring late in the sentence than early in the sentence. Nonverbal WM predicted morphosyntactic processing across groups, but the specific profile of association between WM and early versus late error detection was reversed for children with and without language impairment. Findings primarily support a "wrap up" account whereby the accumulating sentence context for errors positioned late in the sentence (rather than early) appeared to facilitate morphosyntactic processing. Although none of the groups displayed deficits in visual WM, individual differences in these nonverbal WM resources predicted proficiency in morphosyntactic processing.


Immunotherapy Plus Stereotactic Radiosurgery: Building on the Promise of Precision Medicine for CNS Malignancies-PART 2: Existing Experience and Considerations for Future Trials.
The brain has long been considered an immunologically privileged site, and the role of immunotherapy in treating intracranial disease has only recently been revived-with preclinical evidence showing that the systemic immune system responds to immunotherapy for intracranial disease, and with clinical evidence demonstrating improved locoregional control and survival compared with historical outcomes when immune-directed therapies are combined with radiation. Pharmaceutical industry-supported multi-institutional drug efficacy studies routinely exclude patients with brain metastases, so current evidence for treatment of brain metastases using stereotactic radiosurgery combined with immunotherapy comes from single-institution studies. Many studies of combinations of immune checkpoint blockade (with anti-cytotoxic T-lymphocyte-associated antigen 4 and anti-programmed death 1 antibodies) with stereotactic radiosurgery have demonstrated promising improvements in intracranial control and survival. In addition to evaluating the optimal combination of these therapies, future studies will likely search for predictive biomarkers to better select patients whose disease is most appropriately managed with this combined-modality approach.


Nevoid hyperkeratosis of the nipple and the areola.
A 25-year-old woman presented to our dermatology unit with progressive diffuse thickening of the both areolas. A skin biopsy was taken from the right areola showing irregular filiform acanthosis with elongation and anastomosis of rete ridges, irregular orthokeratotic hyperkeratosis, pseudocyst formation, and hyperpigmentation of the basal layer. The cause of nevoid hyperkeratosis of the nipple and areola is unknown. Eighty percent of cases occur in women and are often manifested during puberty or pregnancy. The disease may also occur in men receiving hormonal therapy. There is no uniformly effective treatment. Dermatologists, gynecologists, and general practitioners have an important part to play in recognizing this condition that may be underdiagnosed because of lack of awareness.


Another step through the crux: a new microendemic rock-dwelling Paroedura (Squamata, Gekkonidae) from south-central Madagascar.
Using an integrative taxonomic approach including genetic and morphological data, we formally describe a new microendemic gecko species belonging to the Paroedurabastardi clade, previously referred to as P.bastardi D. We name this taxon currently known from Anja Reserve and Tsaranoro Valley Forest (south-central Madagascar), as P.manongavatosp. nov. The new species differs from other species of the P.bastardi clade by ≥ 12.4% uncorrected p-distance at the mitochondrial 16S rRNA gene and it forms a monophyletic group in the COI mtDNA phylogenetic tree. It lacks haplotype sharing at the nuclear KIAA1239 and CMOS genes with the other species of the same complex, including the syntopic P.rennerae. Given its limited extent of occurrence and high levels of habitat fragmentation linked to forest clearances and fires, we propose the IUCN Red List Category of Critically Endangered, based on the B1ab(iii) criterion. The conservation value of Anja Reserve and Tsaranoro Valley Forest is remarkable. Preserving the remaining deciduous forest habitat is of paramount importance to protect these narrow-range reptile species.


Regulation of mammalian defensin expression by Toll-like receptor-dependent and independent signalling pathways.
The immune system consists of innate and adaptive immune responses. The innate immune system confers non-specific protection against a large number of pathogens, hence, serving as the first line of defence. The innate immune system utilizes Toll-like receptors (TLRs) to recognize and bind pathogen-associated molecular patterns (PAMPs). Binding of PAMPs leads to TLR activation, which, in turn, initiates MAPK- or NF-kappaB-dependent cascades that culminate in a proinflammatory response. This response involves the secretion of cytokines, chemokines and broad-spectrum antibacterial substances, such as defensins. Increased defensin synthesis is also mediated by the activation of receptors other than TLRs, such as NOD2, IL-17R and PAR-2. This review summarizes the recently characterized signalling pathways leading to increased defensin synthesis as well as the pathway by which defensins activate TLRs on immature dendritic and memory T cells. Thus, not only do defensins eliminate pathogens, but they also recruit the adaptive immune system in instances of infection and/or inflammation.


A comprehensive overview of eco-friendly bio-fertilizers extracted from living organisms.
Currently, sustainable agriculture involves ecofriendly techniques, which include biofertilization. Biofertilizers increase plant productivity by improving soil fertility and nutrient content. A wide range of living organisms can be applied as biofertilizers and increase soil fertility without causing pollution due to their biodegradability. The organisms can be microorganisms like bacteria, microalgae, and micro fungi or macro organisms like macroalgae, macro fungi, and higher plants. Biofertilizers extracted from living organisms or their residues will be increasingly used rather than chemical fertilizers, which cause heavy metal accumulation in soil. Biofertilizer use aims for sustainable development in agriculture by maintaining the soil. This will mitigate climate change and related impacts and will also lower many serious diseases resulting from pollution such as cancer, liver and renal failure, and immune diseases. This review is a comprehensive overview of biofertilizers extracted from a range of living organisms from the Kingdoms Monera to Plantae and included bacteria, algae, fungi, and higher plants. Organisms that play a vital role in elevating soil nutrients in a safe, cheap, and ecofriendly manner are included in the review to promote their potential commercial application.


Beyond Fear Emotional Memory Mechanisms in the Human Brain.
Neurobiological accounts of emotional memory have been derived largely from animal models investigating the encoding and retention of memories for events that signal threat. This literature has implicated the amygdala, a structure in the brain's temporal lobe, in the learning and consolidation of fear memories. Its role in fear conditioning has been confirmed, but the human amygdala also interacts with cortical regions to mediate other aspects of emotional memory. These include the encoding and consolidation of pleasant and unpleasant arousing events into long-term memory, the narrowing of focus on central emotional information, the retrieval of prior emotional events and contexts, and the subjective experience of recollection and emotional intensity during retrieval. Along with other mechanisms that do not involve the amygdala, these functions ensure that significant life events leave a lasting impression in memory.


Failure to infect laboratory rodent hosts with human isolates of Rodentolepis (= Hymenolepis) nana.
Confusion exists over the species status and host-specificity of the tapeworm Rodentolepis (= Hymenolepis) nana. It has been described as one species, R. nana, found in both humans and rodents. Others have identified a subspecies; R. nana var. fraterna, describing it as morphologically identical to the human form but only found in rodents. The species present in Australian communities has never been identified with certainty. Fifty one human isolates of Rodentolepis (= Hymenolepis) nana were orally inoculated into Swiss Q, BALB/c, A/J, CBA/ CAH and nude (hypothymic) BALB/c mice, Fischer 344 and Wistar rats and specific pathogen free (SPF) hamsters. Twenty four human isolates of R. nana were cross-tested in flour beetles, Tribolium confusum. No adult worms were obtained from mice, rats or hamsters, even when immunosuppressed with cortisone acetate. Only one of the 24 samples developed to the cysticercoid stage in T. confusum; however, when inoculated into laboratory mice the cysticercoids failed to develop into adult worms. The large sample size used in this study, and the range of techniques employed for extraction and preparation of eggs provide a comprehensive test of the hypothesis that the human strain of R. nana is essentially non-infective to rodents.


[Anaphylactoid reaction to Physiogel SRK 4%--a contribution to the controversy about plasma substitutes].
Allergic reactions caused by colloid plasma substitutes are a well known complication in infusion therapy. The incidence of these adverse effects depends on the type of colloid used. Severe anaphylactic or anaphylactoid reactions are generally rare. Nevertheless, the risk of adverse allergic effects is an important aspect of the crystalloid-versus-colloid controversy. The exact pathophysiologic mechanisms remain as yet unclear; reliable prophylactic measures are not universally available. To draw attention to these problems we report a case of severe anaphylactoid reaction to Physiogel SRK.


[Arthrodesis of the shoulder. A new and soft-tissue-sparing technique with a deep locking plate in the supraspinatus fossa].
Arthrodesis of the glenohumeral joint is a difficult intervention that involves a relatively high probability of complications. A stable internal fixation and secure consolidation is required. The operation needs to achieve several conditions: thorough denudation of the cartilage and partial decortication of the subchondral bone; good congruence of the corresponding surfaces; compression of the gap by tension screws and lasting stability. For increased primary stability a neutralizing plate is generally used as well as a compression screw. Up to now, the plate has usually been applied starting from the scapular spine and extending across the acromial corner to the humeral shaft. A wide exposure is needed for this procedure; the plate is difficult to shape during the operation and often causes some discomfort because it protrudes at the acromial corner. We present an alternative position of the plate in the supraspinatus fossa, where we have sited a 4.5 mm LCP locking plate (Synthes). The implant is inserted under the acromion, does not cause any discomfort at the acromial corner, and is far easier to shape. When it is used in association with a transarticular compressive screw, the technique results in a very stable situation, which allows physiotherapy from the first day after surgery onward.


Mature teratoma presenting as a scalp mass in a newborn.
Neonatal teratomas are rarely located in the scalp. We present a 10-day-old female newborn with mature teratoma of the occipital scalp. The tumor mass, which had no intracranial extension, was excised completely when the patient was 14 days old. The scalp defect was reconstructed with local flaps. No recurrence was detected 3 months after the surgery. Because the patient did not return for routine follow-up 6 months after surgery, we called the parents and learned that the patient had suddenly died. A necropsy to explain the cause of death was not available.


Some remarks on application of macrophages in tumor therapy.
This short review concerns some select aspects of macrophage-activating therapy against tumor. It has been agreed that one of the major host antitumor defense components is the mononuclear phagocyte system. The possibilities of macrophage application in tumor treatment comprise the adoptive transfer of tumoricidal macrophages, the regional administration of macrophage activators, and the systemic administration of such activators given in free form and/or entrapped in liposomes. Special attention is turned to the activation of macrophages by liposome-encapsulated activators.


Laparoscopic resection does not adversely affect early survival curves in patients undergoing surgery for colorectal adenocarcinoma.
To determine the survival curves for laparoscopic resection (LR) of colorectal cancer. Laparoscopic resection for cure of colorectal cancer is controversial, and survival curves have not been determined. A prospective database of 177 consecutive LRs of colorectal cancers performed between November 1991 and 1997 was reviewed. The TNM classification (stage 0, I, II, III, and IV) for colorectal cancers and the Kaplan-Meier method were used to determine survival curves. Of the 177 patients, 5 were excluded for not having adenocarcinomas. Twenty-five patients (14.5%) had conversion to open surgery; most of these patients had rectal cancer or tumor invasion to adjacent organs. Twelve patients were lost to follow-up. All 135 remaining patients had follow-up. Overall, 28 deaths occurred during the follow-up period, 15 of which were cancer-related. The median follow-up was 24 months for patients with stage I, II, and III disease and 9 months for patients with stage IV disease. Observed 2-year survival rates were 100% stage I, 88.7% stage II, 80.6% stage III, and 28.6% stage IV. Survival rates at 4 years were 100% stage I, 79.5% stage II, 53.7% stage III, and 0% stage IV. No trocar site recurrence was observed. Early survival curves for patients with colorectal cancer who underwent LR do not differ negatively from historical controls for conventional surgery. Further validation is needed.


High sensitivity microwave phase noise analyzer based on a phase locked optoelectronic oscillator.
Phase noise is a key parameter to evaluate the short-term stability of a microwave oscillator. This metric is of major concern for many applications. A phase locked loop (PLL) is widely used to extract the phase noise. However, due to the limitation of the phase noise of the reference, it is still a technical challenge to precisely characterize the phase noise of a high frequency carrier. To address this issue, we propose a high sensitivity microwave phase noise analyzer by using a photonic-based reference. By combining an optoelectronic oscillator (OEO) and a direct digital synthesizer, we achieve a 9 GHz to 11 GHz frequency tunable reference with phase noise of -140 dBc/Hz at 10 kHz offset, side-mode suppression ratio of 128 dB, and frequency switching time of 176 ns. Thanks to this low phase noise reference, we attain an X-band phase noise analyzer with an excellent sensitivity of -139 dBc/Hz at 10 kHz offset without cross-correlation. This is the first time to realize a PLL-based phase noise analyzer utilizing an OEO. We thoroughly present a theoretical analysis of our proposed system. Benefiting from the OEO's phase noise independent of frequency, the operation frequency of our proposed system can be extended to the millimeter-wave range while maintaining high sensitivity.


Mouse neuroinvasive phenotype of West Nile virus strains varies depending upon virus genotype.
Despite recent advances in the genetics of West Nile (WN) virus, relatively little is known about the molecular basis of virulence of this virus. In particular, although the genotype of the WN virus strain that was recently introduced into North America has been determined, there have been few experimental studies on the virulence phenotype of the virus. We compared genetic and neurovirulence properties of 19 strains of WN virus, including 2 from North America, and observed significant differences in their neuroinvasive phenotype in mice and hamsters that correlated with virus genotype. Virus isolated in North America was found to be highly neuroinvasive with a lack of age-related resistance to infection in mice normally associated with mosquito-borne flaviviruses.


Simultaneous three-dimensional temperature and velocity field measurements using astigmatic imaging of non-encapsulated thermo-liquid crystal (TLC) particles.
A combination of cutting edge developments is presented to characterize three-dimensional (3D) temperature and velocity fields in microscopic flows. An emulsion of non-encapsulated thermo-liquid crystal (TLC) micro spheres, with a narrow size distribution is used to track the flow's motion and temperature distribution. A state-of-the-art light engine, which combines the spectrum of six light pipes, provides a balanced illumination which allows for strong and detectable color patterns across the TLC's temperature response range. Lastly, the ability of the TLC material to reflect select wavelength bands with an unchanging and independent circular polarization chirality is exploited by a filter that blocks background noise, while exclusively transmitting the color signal of the TLC particles. This approach takes advantage of the peculiar physical properties of TLCs to allow the estimation of individual TLC particle's 3D position, for the first time, using Astigmatism Particle Tracking Velocimetry (APTV).


[Treatment of eyelid burns and results].
Eyelid burns may cause irreversible damage to the eyelids and eye globe. We review 45 patients with eyelid burns, in 8 of whom skin grafting was required due to the deepness of the burn. The results were satisfactory in all except 1, in whom 9 surgical procedures were required to give complete coverage of the cornea. During 1 procedure skin was grafted directly onto the conjunctiva. The other 36 patients were treated conservatively.


Alterations in the testis of hormone sensitive lipase-deficient mice is associated with decreased sperm counts, sperm motility, and fertility.
Hormone-sensitive lipase (HSL, Lipe, E.C.188.8.131.52) functions as a triglyceride and cholesteryl esterase, supplying fatty acids, and cholesterol to cells. Gene-targeted HSL-deficient (HSL(-/-)) mice reveal abnormal spermatids and are infertile at 24 weeks after birth. The purpose of this study was to follow the evolution of spermatid abnormalities as HSL(-/-) mice age, characterize sperm motility in older HSL(-/-) mice, and determine if mice expressing a human testicular HSL transgene (HSL(-/-)ttg) produce normal motile sperm. In situ hybridization indicated that HSL is expressed exclusively in steps 5-16 spermatids, but not in Sertoli cells. In HSL(-/-) mice, abnormalities were evident in step 16 spermatids at 5 weeks after birth, with defects progressively increasing in spermatids with age. The defects included multinucleation of spermatids, abnormal shapes and a reduction of elongating spermatids. In older HSL(-/-) mice, sperm counts appeared reduced by 42%, but this value was lower because samples were compromised by the presence of small degenerating germ cells in addition to sperm, both of which appeared of similar size and density. Sperm motility was dramatically reduced with only 11% classified as motile in HSL(-/-) mice compared to 76-78% of sperm in wild-type and HSL(-/-)ttg mice. Sperm morphology, counts, and motility were normal in HSL(-/-)ttg mice, as was their fertility. Collectively, the data indicate that HSL deficiency results in abnormal spermatid development with defects arising at 5 weeks of age and progressively increasing at later ages. HSL(-/-) mice also show a dramatic reduction in sperm counts and motility and are infertile.


Righting the Misperceptions of Men Having Sex with Men: A Pre-Requisite for Protecting and Understanding Gender Incongruence in Vietnam.
Protecting the rights of the lesbians, gays, bisexuals, transgender, intersex, and queers (LGBTIQ) population requires, first and foremost, a proper understanding of their sexual orientation and gender identity. This study highlights a severe misunderstanding and lack of knowledge among health professionals in Vietnam with regard to the men who have sex with men (MSM) and transgenders. This study uses (i) a survey based on the convenience sampling method among 150 health workers that covered 61 questions and (ii) 12 in-depth interviews in two metropolitan centres in Vietnam, Hanoi and Ho Chi Minh city. Three main topics are explored: (i) the general knowledge of healthcare workers about MSM and transgenders; (ii) their knowledge about the sexual reproductive health and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) risks of MSM and transgenders; and (iii) their attitudes and behaviors towards MSM and transgenders. One of the notable findings is how prevalent the misperceptions are across the board, namely, in staff of both sexes, in both cities, at various kinds of medical facilities, at different work positions and educational levels. Half of the respondents consider transgenders to have a curable mental problem while 45% say MSM only have sex with males. Most remarkably, 12.7% state if they have any choice, they want nothing to do with MSM and transgenders. The study finds there is a considerable percentage of health professionals who lack knowledge about the diversity of sexual orientation, gender identity, and health issues related to the sexual minorities and gender non-conforming population. To improve the clinical process for serving these at-risk groups, the study suggests the continual education for the health workers needs to be added to their formal as well as in-job training.


Oxymorphone Induced Thrombotic Microangiopathy Mimicking Atypical Haemolytic Uremic Syndrome.
Atypical Haemolytic Uremic Syndrome (aHUS) is a rare life threatening entity characterized by thrombocytopenia, haemolytic anaemia and renal dysfunction. It is a thrombotic microangiopathy related to genetic mutations in the alternate complement pathway and has a distinct pathophysiology which makes it harder to distinguish from other microangiopathies. We present a case of a 25-year-old male patient with history of polysubstance abuse who presented with chest pain and dyspnoea. He admitted to using injectable oxymorphone (Opana) two weeks before presentation. Patient's vital signs were stable except for tachycardia and high blood pressure. On physical examination, epigastric tenderness and mild splenomegaly was appreciated. Urine Drug Screen was positive for oxycodone and opiates. Laboratory work up revealed haemolytic anaemia, thrombocytopenia and acute kidney injury. Extensive evaluation resulted in our impression of the disease being atypical haemolytic-uremic syndrome. He was managed with dialysis, intravenous steroids and plasmapheresis with improvement in his hematologic parameters.


A methodology for elemental and organic carbon emission inventory and results for Lombardy region, Italy.
This paper presents a methodology and its application for the compilation of elemental carbon (EC) and organic carbon (OC) emission inventories. The methodology consists of the estimation of EC and OC emissions from available total suspended particulate matter (TSP) emission inventory data using EC and OC abundances in TSP derived from an extensive literature review, by taking into account the local technological context. In particular, the method is applied to the 2008 emissions of Lombardy region, Italy, considering 148 different activities and 30 types of fuels, typical of Western Europe. The abundances estimated in this study may provide a useful basis to assess the emissions also in other emission contexts with similar prevailing sources and technologies. The dominant sources of EC and OC in Lombardy are diesel vehicles for EC and the residential wood combustion (RWC) for OC which together account for about 83% of the total emissions of both pollutants. The EC and OC emissions from industrial processes and other fuel (e.g., gasoline, kerosene and LPG) combustion are significantly lower, while non-combustion sources give an almost negligible contribution. Total EC+OC contribution to regional greenhouse gas emissions is positive for every sector assuming whichever GWP100 value within the range proposed in literature. An uncertainty assessment is performed through a Monte Carlo simulation for RWC, showing a large uncertainty range (280% of the mean value for EC and 70% for OC), whereas for road transport a qualitative analysis identified a narrower range of uncertainty.


[Peculiarities of primary health care organization for patients suffering from chronic obstructive pulmonary disease jointly with coronary heart disease].
Combination of chronic obstructive pulmonary disease (COPD) and coronary heart disease (CHD) leads to some difficulties for diagnostics and for prescription of complex differential treatment as well as increasings risk of complications from the illness and drug's side effects. To develope peculiarities of Primary Health Care (PHC) organisation for patients suffering from COPD jointly with CHD; and to improve the patients surveillance for optimization of early diagnosis of named join pathology and well-timed prescription of appropriate health-promoting treatment. The COPD and CHD morbidity in Chernivtsi region and prevalence of CHD in 955 hospital cases were analyzed. Health survey of 241 patients of age more than 40 years was conducted according to Questionnaire for COPD primary monitoring on an outpatient basis. The decreasing of COPD detection (-15%) and decreasing of CHD morbidity (-7,7%) were observed in 2015. Primary disablement due to pulmonary diseases across the employable population increased on 28,8%. Analyses of smoking prevalence across the man older 40 years show that 97 (40,2%) of persons are smokers. Risk of COPD symptoms appearance in man older 40 was in more than 6 times bigger for smokers in comparison with non-smoking persons. CHD happens reliably more often (72,5%) in patients suffering from COPD of age 49-50 who smoke comparatively to non-smoking patients (48,7). An obligatory COPD primary monitoring in population risk groups and well-timed CHD diagnosis are main peculiarities of PHC organization for patients suffering from COPD jointly with CHD on primary health care level. Improvement of the surveillance for patients suffering from COPD jointly with CHD is also important on all population's health care levels.


[Locally Advanced Ureteral Cancer Seen in an Ectopic Kidney : A Case Report].
An ectopic kidney is a common congenital anomaly of the urogenital system, but malignant tumor in an ectopic kidney has been rarely reported. We report a case of ureteral carcinoma arising from an ectopic kidney in an 83-year-old male. He visited a hospital complaining of gross hematuria. Computed tomography revealed right ectopic kidney, right ureteral tumor and bladder tumor around the right ureteral orifice. Transurethral resection of the bladder tumor was performed and histopathological diagnosis was urothelial carcinoma. He was referred to our clinic for surgery of the right ureteral tumor. We performed open right nephroureterectomy and partial cystectomy. The histopathological diagnosis was a high grade urothelial carcinoma of the right ureter, pT3N0. Four months postoperatively, there was no evidence of recurrence. We discuss the clinical and pathological features of the malignancy in an ectopic kidney.


A comparison of smoking habits among medical and nursing students.
The approach and credibility of future physicians and nurses as treatment providers for smoking- and tobacco-related diseases may be influenced by their smoking habits. We compared smoking habits among medical and nursing students, and examined whether these habits changed during the course of education for each cohort. Over 1,100 medical and nursing students from a university were surveyed in year 2000 using a questionnaire that included the Fagerstrom test for nicotine dependence (FTND). A total of 397 medical students and 126 nursing students completed the survey. Significantly fewer medical students (3.3%) smoked compared to nursing students (13.5%). Also, significantly more nursing students were former smokers (17.8%) than medical students (9.8%). The severity of nicotine dependence, as indicated by the total FTND score as well as scores on five of the six items on the FTND, was significantly lower among medical students compared to nursing students. Smoking or quit rates did not differ across class years in both groups; however, unlike nursing students, time since quitting significantly differed across class years for medical students. Although smoking habits appear to change little during the course of education for both medical and nursing students, many smokers may have quit just prior to entering medical school but not nursing school. The findings confirm the continuing decline in smoking among medical students in the United States; however, increased efforts to promote tobacco education and intervention among nursing students seem necessary. Nevertheless, both groups appear to have the potential to be credible advisors to patients and public regarding smoking cessation.


Bioinformatics analyses of the differences between lung adenocarcinoma and squamous cell carcinoma using The Cancer Genome Atlas expression data.
The present study aimed to explore gene and microRNA (miRNA) expression differences between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified by analyzing mRNA and miRNA expression data in normal and cancerous lung tissues that were obtained from The Cancer Genome Atlas database. A total of 778 DEGs and 7 DEMs were identified. Altered gene functions and signaling pathways were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, which revealed that DEGs were significantly enriched in extracellular matrix organization, cell differentiation, negative regulation of toll signaling pathway, and several other terms and pathways. Transcription factor (TF)‑miRNA‑gene networks in LUAD and LUSC were predicted using the TargetScan, Miranda, and TRANSFAC databases, which revealed the regulatory links among the TFs, DEMs, and DEGs. The central TFs, i.e., the TFs in the middle of the TF‑miRNA‑gene network, of LUAD and LUSC were similar. Although LUAD and LUSC shared similar miRNAs in the predicted networks, miR‑29b‑3p was demonstrated to be upregulated only in LUAD, whereas miR‑1, miR‑105‑5p, and miR‑193b‑5p were altered in LUSC. These findings may improve our understanding of the different molecular mechanisms in non‑small cell lung cancers and may promote new and accurate strategies for prevention, diagnosis, and treatment.


Designer estrogen vs. hormone replacement therapy: the menopausal woman's dilemma.
Although hormone replacement therapy (HRT) has many proven health benefits for postmenopausal women, relatively few women are taking advantage of this option. A major reason for this is lack of understanding by women of the benefits and risks of using HRT. Additionally, many women are uninformed about "designer estrogens," more correctly known as Selective Estrogen Receptor Modulators (SERMs), as an alternative approach to the use of esrogen. One of the major challenges of contemporary nursing is to help women maintain optimum health and enjoy a high quality of life after menopause. One aspect of managing menopausal health is an understanding of the hormonal options available to women. The purpose of this article is to present a synthesis of information comparing HRT and SERMs so that the reader can help his/her clients make informed choices about replacement therapy.


Usefulness of Measuring Thiopurine Metabolites in Children with Inflammatory Bowel Disease and Autoimmunological Hepatitis, Treated with Azathioprine.
Thiopurines, such as azathioprine (AZA) and 6-mercaptopurine (6-MP), are immunomodulatory agents, used for the maintenance of remission in children with inflammatory bowel disease (IBD)-Crohn's disease (CD) and ulcerative colitis (UC), as well as with autoimmunological hepatitis (AIH). Measurements of thiopurine metabolites may allow identifying patients at risk for toxicity and nonadherence. It can also provide an explanation for the ineffectiveness of the treatment, observed in some patients. Patients and Methods. A retrospective analysis was carried out of sixty-eight patients (thirty-six patients with CD, eighteen with UC, and fourteen with AIH), treated with AZA. Thiopurine metabolites, 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP), were assayed by high-performance liquid chromatography (HPLC), and the AZA dose was adjusted when 6-TGN concentration was known. Only twenty-five (41%) children had therapeutic 6-TGN concentrations, ten (16%) subjects had suboptimal 6-TGN concentrations, and twenty-six subjects (43%) had 6-TGN concentrations above the recommended therapeutic range. 6-MMP was not above the therapeutic range in any case. Seven subjects revealed undetectable 6-TGN and 6-MMP levels, indicating nonadherence. The mean AZA dose after the 6-TGN concentration-related adjustment did not differ, in comparison to the initial dose, either in IBD or AIH groups. The mean AZA dose was lower in AIH than in IBD. The subjects with an optimal 6-TGN level presented with a higher ratio of remission (88%) than the under- or overdosed patients (60% and 69%), respectively (Chi - square test = 3.87, p < 0.05). Timely measurements of thiopurine metabolites can be a useful tool to identify nonadherent patients before a decision is taken to switch to another drug. We may also spot the patients who receive either too low or too high doses, compensating dose deviations in an appropriate way. The patients with optimal 6-TGN levels presented a higher percentage of remission than the under- or overdosed patients. In most patients, both initial and adjusted AZA doses, lower than suggested in guidelines, appeared to be sufficient to maintain remission.


Age patterns of fertility in Madhya Pradesh.
"The purpose of this paper is to analyse age-patterns of fertility in Madhya Pradesh [in India] based on district level estimates of aggregate measures of fertility data collected in 1981.... Four clusters of districts have emerged which reveal a clear zonal pattern in age-specific fertility rates in the state. These groups bring out high fertility rates in the north and north-western parts of the state, gradually declining toward the south-eastern zone. The author suggests that separate policies and programmes be evolved for each of the clusters of districts for the purpose of bringing about reduction in fertility and promoting family welfare in the state of Madhya Pradesh."


Association of CFTR gene mutation with bronchial asthma.
Mutation on both the copies of cystic fibrosis transmembrane conductance regulator (CFTR) gene results in cystic fibrosis (CF), which is a recessively transmitted genetic disorder. It is hypothesized that individuals heterozygous for CFTR gene mutation may develop obstructive pulmonary diseases like asthma. There is great heterogeneity in the phenotypic presentation and severity of CF lung disease. This could be due to genetic or environmental factors. Several modifier genes have been identified which may directly or indirectly interact with CFTR pathway and affect the severity of disease. This review article discusses the information related to the association of CFTR gene mutation with asthma. Association between CFTR gene mutation and asthma is still unclear. Report ranges from studies showing positive or protective association to those showing no association. Therefore, studies with sufficiently large sample size and detailed phenotype are required to define the potential contribution of CFTR in the pathogenesis of asthma.


An AGM model for changes in complement during pregnancy: neutralization of influenza virus by serum is diminished in late third trimester.
Pregnant women in the third trimester are at increased risk of severe influenza disease relative to the general population, though mechanisms behind this are not completely understood. The immune response to influenza infection employs both complement (C') and antibody (Ab). The relative contributions of these components to the anti-viral response are difficult to dissect because most humans have pre-existing influenza-specific Abs. We developed the African green monkey (AGM) as a tractable nonhuman primate model to study changes in systemic innate immunity to influenza during pregnancy. Because the AGMs were influenza-naïve, we were able to examine the role of C' in influenza virus neutralization using serum from non-pregnant animals before and after influenza infection. We determined that serum from naïve AGMs neutralized influenza via C', while post-infection neutralization did not require C', suggesting an Ab-mediated mechanism. The latter mimicked neutralization using human serum. Further, we found that ex vivo neutralization of influenza with both naïve and influenza-immune AGM serum occurred by virus particle aggregation and lysis, with immune serum lysing virus at a much higher rate than naïve serum. We hypothesized that the anti-influenza C' response would diminish late in AGM pregnancy, corresponding with the time when pregnant women suffer increased influenza severity. We found that influenza neutralization capacity is significantly diminished in serum collected late in the third trimester. Strikingly, we found that circulating levels of C3, C3a, and C4 are diminished late in gestation relative to nonpregnant animals, and while neutralization capacity and serum C3a return to normal shortly after parturition, C3 and C4 levels do not. This AGM model system will enable further studies of the role of physiologic and hormonal changes in downregulating C'-mediated anti-viral immunity during pregnancy, and it will permit the identification of therapeutic targets to improve outcomes of influenza virus infection in pregnant women.


Genetic analysis of short stature.
Short stature is a major concern for patients and their parents, and represents a diagnostic challenge to the clinician. A correct diagnosis is of particular importance in view of the availability of effective, but costly, therapy in a small subset of cases. Many different genetic etiologies of short stature are known. Therefore, chromosome as well as molecular analysis are requisite diagnostic investigations in children with short stature. Particularly in the group of children with idiopathic short stature, possibilities of molecular analysis are often underestimated. Important options are UPD7 and the FGFR3, SHOX, GH1 and GHR genes. Furthermore, analysis of the IGF and IGF1R genes should be considered. We propose a flow chart for molecular analysis in short stature.


WHO Global Consultation on Public Health Intervention against Early Childhood Caries.
Early Childhood Caries (ECC) is prevalent around the world, but in particular the disease is growing rapidly in low- and middle-income countries in parallel with changing diet and lifestyles. In many countries, ECC is often left untreated, a condition which leads to pain and adversely affects general health, growth and development, and quality of life of children, their families and their communities. Importantly, ECC is also a global public health burden, medically, socially and economically. In many countries, a substantial number of children require general anaesthesia for the treatment of caries in their primary teeth (usually extractions), and this has considerable cost and social implications. A WHO Global Consultation with oral health experts on "Public Health Intervention against Early Childhood Caries" was held on 26-28 January 2016 in Bangkok (Thailand) to identify public health solutions and to highlight their applicability to low- and middle-income countries. After a 3-day consultation, participants agreed on specific recommendations for further action. National health authorities should develop strategies and implement interventions aimed at preventing and controlling ECC. These should align with existing international initiatives such as the Sixtieth World Health Assembly Resolution WHA 60.17 Oral health: action plan for promotion and integrated disease prevention, WHO Guideline on Sugars and WHO breastfeeding recommendation. ECC prevention and control interventions should be integrated into existing primary healthcare systems. WHO public health principles must be considered when tackling the effect of social determinants in ECC. Initiatives aimed at modifying behaviour should focus on families and communities. The involvement of communities in health promotion, and population-directed and individual fluoride administration for the prevention and control of ECC is essential. Surveillance and research, including cost-effectiveness studies, should be conducted to evaluate interventions aimed at preventing ECC in different population groups.


Recent advancement of chitosan-based nanoparticles for oral controlled delivery of insulin and other therapeutic agents.
Nanoparticles composed of naturally occurring biodegradable polymers have emerged as potential carriers of various therapeutic agents for controlled drug delivery through the oral route. Chitosan, a cationic polysaccharide, is one of such biodegradable polymers, which has been extensively exploited for the preparation of nanoparticles for oral controlled delivery of several therapeutic agents. In recent years, the area of focus has shifted from chitosan to chitosan derivatized polymers for the preparation of oral nanoparticles due to its vastly improved properties, such as better drug retention capability, improved permeation, enhanced mucoadhesion and sustained release of therapeutic agents. Chitosan derivatized polymers are primarily the quaternized chitosan derivatives, chitosan cyclodextrin complexes, thiolated chitosan, pegylated chitosan and chitosan combined with other peptides. The current review focuses on the recent advancements in the field of oral controlled release via chitosan nanoparticles and discusses about its in vitro and in vivo implications.


Deletional Alpha-Thalassemia Alleles in Amazon Blood Donors.
Alpha-thalassemia is highly prevalent in the plural society of Brazil and is a public health problem. There is limited knowledge on its accurate frequency and distribution in the Amazon region. Knowing the frequency of thalassemia and the prevalence of responsible mutations is, therefore, an important step in the understanding and control program. Hematological and molecular data, in addition to serum iron and serum ferritin, from 989 unrelated first-time blood donors from Amazonas Hemotherapy and Hematology Foundation (FHEMOAM) were collected. In this study, the subjects were screened for -α 3.7/4.2/20.5, -SEA, -FIL, and -MED deletions. Alpha-thalassemia screening was carried out between 2016 and 2017 among 714 (72.1%) male and 275 (27.9%) female donors. The aims of this analysis were to describe the distribution of various alpha-thalassemia alleles by gender, along with their genotypic interactions, and to illustrate the hematological changes associated with each phenotype. Amongst the patients, 5.35% (n = 53) were diagnosed with deletion -α -3.7 and only one donor with α -4.2 deletion. From the individuals with -α -3.7, 85.8% (n = 46) were heterozygous and 14.20% (n = 7) were homozygous. The frequency of the -α -3.7 deletion was higher in male (5.89%) than in female (4.0%). There is no significant difference in the distribution of -α -3.7 by gender (p = 0.217). The -α 20.5, -SEA, and -MED deletions were not found. All subjects were analyzed for serum iron and serum ferritin, with 1.04% being iron deficient (n = 5) and none with very high levels of stored iron (>220 µg/dL). Alpha-thalassemia-23.7kb deletion was the most common allele detected in Manaus blood donors, which is a consistent result, once it is the most common type of α-thalassemia found throughout the world. As expected, the mean of hematological data was significantly lower in alpha-thalassemia carriers (p < 0.001), mainly homozygous genotype. Leukocytes and platelet count did not differ significantly. Due to the small number of individuals with iron deficiency found among blood donors, the differential diagnosis between the two types of anemia was not possible, even because minor changes were found among hematological parameters with iron deficiency and α-thalassemia. Despite this, the study showed the values of hematological parameters, especially MCV and MCH, are lower in donors with iron deficiency, especially when associated with α-thalassemia, and therefore, it may be useful to discriminate different types of microcytic anaemia. In conclusion, we believed screening for thalassemia trait should be included as part of a standard blood testing before blood donation. It should be noted that this was the first study to perform the screening for alpha deletions in blood donors from the Manaus region, and further studies are required to look at the effects of donated thalassemic blood.


Lamellodiscus aff. euzeti Diamanka, Boudaya, Toguebaye & Pariselle, 2011 (Monogenea: Diplectanidae) from the gills of Cheimerius nufar (Valenciennes) (Pisces: Sparidae) collected in the Arabian Sea, with comments on the distribution, specificity and historical biogeography of Lamellodiscus spp.
Specimens of Lamellodiscus Johnston & Tiegs, 1922 (Monogenea: Diplectanidae) were collected from the gills of Cheimerius nufar (Valenciennes) (Sparidae) in the Arabian Sea. All of these parasites belonged to one and the same species, which is morphologically very close to L. euzeti Diamanka, Boudaya, Toguebaye & Pariselle, 2011. A different host, distant locality and small morphological differences compared with the original description of L. euzeti acted as a stimulus for a detailed redescription. The specimens from the Arabian Sea differ slightly in the details of the male copulatory organ (MCO) from the type-specimens of L. euzeti, which were re-examined, and from the respective drawings in its original description. Such differences include a longer inner process of the large element of the accessory piece associated with the proximal part of the copulatory tube, a longer point on the small element of the accessory piece associated with the distal part of the copulatory tube, and the presence of a smooth or slightly folded inner margin of this element rather than structures resembling spines which occur in the type-specimens of L. euzeti. Therefore, the present specimens infecting C. nufar in the Indo-Pacific may represent a different, but morphologically very similar species to the Atlantic form L. euzeti; consequently, they are recognised here as Lamellodiscus aff. euzeti. This form belongs to the 'ignoratus s. str.' subgroup of the genus. The composition of this subgroup is redefined to comprise 17 species, including L. corallinus Paperna, 1965 but excluding L. acanthopagri Roubal, 1981, and the morphology of the MCO of representatives of this group is clarified. A link between the diversity of Lamellodiscus species and the ancestral origin of present-day sparid species in the Tethys Sea is suggested. It is shown that Lamellodiscus spp. exhibit rather high levels of specificity to their hosts, since half of them parasitise only a single host species and c.90% infect closely related host species. Comparison of the levels of host-specificity of the species of this genus with other narrowly specific genera of the Dactylogyridea revealed that their estimations are comparable. The possibility of intra-host speciation within Lamellodiscus is discussed. It is shown that a co-evolutionary model is more discernible if it includes data on the occurrence of morphologically similar species from different regions and host taxa.


Experiments in the Wild: Introducing the Within-Person Encouragement Design.
The within-person encouragement design introduced here combines methodological approaches from three research traditions: (a) the analysis of within-person couplings using multilevel models, (b) the experimental manipulation of a treatment variable at the within-person level, and (c) the use of random encouragements as instrumental variables to induce exogenous experimental variation when strict treatment adherence is unrealistic. The proposed combination of these approaches opens up new possibilities to study treatment effects of a broad range of behavioral variables in realistic everyday contexts. We introduce this new research design together with a corresponding data analysis framework: instrumental variable estimation with two-level structural equation models. Using simulations, we show that the approach is applicable with feasible design dimensions regarding numbers of measurement occasions and participants and realistic assumptions about adherence to the encouragement conditions. Possible applications and extensions, as well as potential problems and limitations are discussed.


Molecular characterization of illegitimate TCR delta gene rearrangements in acute myeloid leukaemia.
Recently, we and others have shown the occurrence of TCR delta gene rearrangements in acute myeloid leukaemia (AML). In this study we describe the molecular characteristics of these rearrangements by the polymerase chain reaction (PCR) and the direct sequencing of PCR products. 11 rearrangements were characterized in blast cell samples from six patients. We found a heterogenous pattern of TCR delta gene rearrangements with involvement of V delta 1-5 regions. These findings differ from observations in T-ALL and B-cell precursor ALL, where predominantly usage of V delta 1 and V delta 2 regions has been described. Furthermore, extensive diversity of junctional sites was observed, including addition of up to 37 N nucleotides, nucleotide deletions at junction sites of V delta and J delta segments and usage of up to three D delta segments. The D delta 3 fragment was the most frequently used diversity element and was found in 10 rearrangements. Nine of the 11 rearrangements were non-functional, either incomplete or out of the reading frame. Therefore a functional TCR delta cannot be expressed in these myeloid blast cells.


Protective effects of β1/2 adrenergic receptor deletion in a model of oxygen-induced retinopathy.
β-adrenergic receptors (β-ARs) regulate angiogenesis in proliferative retinopathies. We studied the effects of β1/2-AR deletion in a model of oxygen-induced retinopathy (OIR) to confirm the role of β1- and/or β2-ARs in regulating angiogenesis and to get insights into the role of β3-ARs. Mice with β1/2-AR deletion (KO) were used. Levels of norepinephrine (NE), β3-ARs, transcription, and proangiogenic factors were evaluated. Retinas were analyzed for avascular area and neovascular tufts in the superficial plexus. Deep plexus and blood-retinal barrier (BRB) were also analyzed. Neovascularization, proangiogenic factors, protein kinase A (PKA) activity, and nitrite production were assessed after BRL 37344, a β3-AR agonist. Oxygen-induced retinopathy was characterized by NE upregulation with higher levels in wild type (WT) than in KO. Wild type and KO displayed comparable levels of β3-ARs, transcription, and proangiogenic factors, but differed in VEGF receptor (VEGFR) expression with VEGFR-1 in WT lower than in KO and VEGFR-2 in WT higher than in KO. Blood-retinal barrier dysfunction did not differ between WT and KO. Vascular abnormalities in the superficial plexus were abolished by β1/2-AR deletion, which also helped the development of the deep plexus. In both WT and KO, β3-AR agonism, acting through the nitric oxide pathway, caused enhanced neovascular responses with increased levels of VEGF. We confirm that β1- and β2-ARs play a pivotal role in retinal angiogenesis. In their presence, β3-ARs potentiate angiogenic responses, whereas, in their absence, β3-ARs sustain the angiogenic drive. These results suggest β-ARs as promising targets for therapies aimed to counteract proliferative retinopathies.