Touching the dead: Autoethnographical reflections about the researcher's body in the field of death, dying, and bereavement.
This essay presents an account of the influence of the researcher's body within qualitative death research. It suggests that appropriate reflection on the researcher's subjectivity should consider his or her own bodily performances and experiences. At the beginning I offer some introductory thoughts in this regard, referring to Plessner's distinction between 'being a body' (Körper-haben) and 'having a body' (Leib-sein). Here, I highlight the importance of autoethnographic approaches for the understanding of bodily experiences, such as sensations, perceptions and their aesthetics. To demonstrate the importance of considering the researcher's body within the research process, I then draw on my own autoethnographic material, discussing how I experienced in my body frightening and disturbing feelings while dealing with the dead. This material was collected during a six-month internship from April to September 2016 at a small funeral home in Thuringia, Germany. I explain how I was socialised regarding my bodily behaviour towards the dead years ago and how I acquired the knowledge that touching a corpse is often taboo; describe my bodily reactions when I saw a dead body for the first time during my internship and how these reactions influenced my fieldwork; relate how my senses and perceptions when first touching a corpse led to extreme responses that drew most of my attention to the haptic and sensual dimension, making me unable to notice other information in the field; and show how these bodily experiences crossed borders and influenced my life beyond my field research.


TASK Channels Pharmacology: New Challenges in Drug Design.
Rational drug design targeting ion channels is an exciting and always evolving research field. New medicinal chemistry strategies are being implemented to explore the wild chemical space and unravel the molecular basis of the ion channels modulators binding mechanisms. TASK channels belong to the two-pore domain potassium channel family and are modulated by extracellular acidosis. They are extensively distributed along the cardiovascular and central nervous systems, and their expression is up- and downregulated in different cancer types, which makes them an attractive therapeutic target. However, TASK channels remain unexplored, and drugs designed to target these channels are poorly selective. Here, we review TASK channels properties and their known blockers and activators, considering the new challenges in ion channels drug design and focusing on the implementation of computational methodologies in the drug discovery process.


Revision of the Ambrysus pudicus Stål species complex (Heteroptera: Nepomorpha: Naucoridae) with the description of a new species from southern Mexico.
The Ambrysus pudicus Stål species complex is revised, its species diagnosed, and an illustrated key is presented. The complex includes A. abortus La Rivers, A. amargosus La Rivers, A. funebris La Rivers, A. hungerfordi Usinger, A. parviceps Montandon, A. pudicus Stål, and A. relictus Polhemus Polhemus. A new species, A. chinanteco, belonging to this complex is described from southern Mexico. The subspecies A. hungerfordi angularis La Rivers, A. h. spicatus La Rivers, and A. h. triunfo La Rivers are herein elevated to full species level and considered members of this species complex. The subspecies A. pudicus barberi Usinger is synonymized with the nominate subspecies. Based on specific combinations of morphological features, two subcomplexes of species are recognized within the complex. The species A. funebris is transferred from the subgenus Acyttarus La Rivers to the subgenus Ambrysus Stål. In order to fix the identity of three species in the complex, neotypes for A. amargosus and A. spicatus and a lectotype for A. pudicus are designated here. The species in the A. pudicus complex are distributed in North America from the southwestern and southern United States to northern Costa Rica. New country records from Central America are presented for A. parviceps and A. pudicus. New state records from Mexico are presented for A. abortus, A. angularis, A. hungerfordi, A. parviceps, A. pudicus, and A. spicatus.


[Studies on the prediction of intestinal recovery from ischemic injury by fluorescein fluorescence patterns].
Methods for the prediction of intestinal recovery from ischemic injury were evaluated in highly reproducible model of segmental intestinal strangulation in the rat. Systemic variables were minimized and survival was maximized by parenteral administration of antibiotics and nutrient solution, so that necrosis or recovery of the segment itself, not the rat, could be used as an endpoint of experiments. Recovery of ischemic intestine was assessed by two methods: Standard clinical criteria (color, peristalsis, pulsation.) Fluorescence after intravenous fluorescein injection. Findings were compared with ultimate viability assayed by histologic examination of each segment removed 48 hours after release of strangulation. Five distinctive patterns of fluorescein fluorescence were identified, two of which (normal pattern and fine granular pattern) reliably predicted survival of the segment, and two of which (perivascular pattern and no fluorescence) predicted subsequent necrosis. A fifth, coarse granular pattern usually, but not always, predicted non-recovery. Standard clinical criteria were relatively insensitive and could not be relied upon to detect nonviable segments. The fluorescein fluorescence method correctly identified all nonviable segments at the expense of an acceptably low overall false positive rate. This study suggests that the fluorescein methods is the method of choice for the prediction of small intestinal recovery following ischemic injury.


Bilateral clear lens extraction and intraocular lens implantation in a child with microspherophakia and Marfan syndrome.
We report the case of a 4-year-old boy with Marfan syndrome whose parents reported he had had low visual acuity since birth. On examination, there was microspherophakia and a small subluxation of the lens. The objective refraction was -23.75 - 2.75 x 70 in the right eye and -25.50 -3.50 x 90 in the left eye. Since the microspherophakia and the high myopia severely affected the boy's quality of life, clear lens extraction, anterior vitrectomy, posterior surgical capsulotomy via the pars plana, and intraocular lens implantation were performed. Two years postoperatively, the patient had centered intraocular lenses and a corrected visual acuity of 20/30 in both eyes. The child was satisfied with his vision and was able to study and perform daily activities without visual limitations.


Body mass index status and peripheral airway obstruction in school-age children: a population-based cohort study.
Few large prospective studies have investigated the impact of body mass index (BMI) on lung function during childhood. Using data collected between 2002 and 2013, we analysed associations between BMI status and lung function (assessed by spirometry) from 8 to 16 years, as well as cross-sectional associations with small airway function (impulse oscillometry) at 16 years in the BAMSE cohort (n=2889). At 16 years, cross-sectional associations with local and systemic inflammation were investigated by analysing FENO, blood eosinophils and neutrophils. Overweight and obesity at 8 years were associated with higher FVC, but lower FEV1/FVC ratio at 8 and 16 years. In boys, but not girls, obesity at 8 years was associated with a further reduction in FEV1/FVC between 8 and 16 years. In cross-sectional analyses, overweight and obesity were associated with higher frequency dependence of resistance (R5-20) and larger area under the reactance curve (AX0.5) at 16 years. Increased blood neutrophil counts were seen in overweight and obese girls, but not in boys. No association was found between BMI status and FENO. Persistent, but not transient, overweight/obesity between 8 and 16 years was associated with higher R5-20 and AX0.5 and lower FEV1/FVC (-2.8% (95% CI -4.1 to -1.2) in girls and -2.7% (95% CI -4.4 to -1.1) in boys) at 16 years, compared with persistent normal weight. In childhood and adolescence, overweight and obesity, particularly persistent overweight, were associated with evidence of airway obstruction, including the small airways.


Calcium l-Lactate Frameworks as Naturally Degradable Carriers for Pesticides.
Two porous, chiral metal-organic frameworks (MOFs), Ca14(l-lactate)20(acetate)8(C2H5OH)(H2O) (MOF-1201) and Ca6(l-lactate)3(acetate)9(H2O) (MOF-1203), are constructed from Ca2+ ions and l-lactate [CH3CH(OH)COO-], where Ca2+ ions are bridged by the carboxylate and hydroxyl groups of lactate and the carboxylate group of acetate to give a three-dimensional arrangement of Ca(-COO, -OH) polyhedra supporting one-dimensional pores with apertures and internal diameters of 7.8 and 9.6 Å (MOF-1201) and 4.6 and 5.6 Å (MOF-1203), respectively. These MOFs represent the first examples of extended porous structures based on Ca2+ and lactate. They show permanent porosity of 430 and 160 m2 g-1, respectively, and can encapsulate an agriculturally important fumigant, cis-1,3-dichloropropene. MOF-1201 shows a 100 times lower release rate compared with liquid cis-1,3-dichloropropene under the same test conditions (25 °C, air flow rate of 1 cm3 min-1). The hydrolysis of MOF-1201 in water makes it the first example of a degradable porous solid carrier for such fumigants.


Reflecting on choices and responsibility in palliative care in the context of social disadvantage.
There is a need to understand how to improve palliative care provision for people impacted by social inequity. Social inequity, such as that related to socioeconomic circumstances, has profound impacts on experiences of death and dying, posing personal and professional challenges for frontline professionals tasked to ensure that everyone receives the best standard of care at the end of their lives. Recent research has highlighted an urgent need to find ways of supporting healthcare professionals to acknowledge and unpack some of the challenges experienced when trying to deliver equitable palliative care. For example, those involved in patient or person-centred activities within health settings often feel comfortable focusing on individual choice and responsibility. This can become ethically problematic when considering that inequities experienced towards the end of life are produced and constrained by socio-structural forces beyond one individual's control. Ideas and theories originating outside palliative care, including work on structural injustice, cultural safety and capabilities approach, offer an alternative lens through which to consider roles and responsibilities for attending to inequities experienced at the end of life. This paper draws upon these ideas to offer a new way of framing individual responsibility, agency and collective action that may help palliative care professionals to support patients nearing their end of life, and their families, in the context of socioeconomic disadvantage. In this paper, we argue that, ultimately, for action on inequity in palliative care to be effective, it must be coherent with how people understand the production of, and responsibility for, those inequities, something that there is limited understanding of within palliative care.


The successful management of respiratory complications with long-term, low-dose macrolide administration in pediatric heart transplant recipients.
We report three pediatric heart transplant (HTx) patients whose respiratory symptoms were successfully controlled with long-term, low-dose macrolide administration (clarithromycin: CAM; approximately 2.5 mg/kg bid). The first case was an 18-year-old boy who underwent HTx at the age of three for dilated cardiomyopathy (DCM). Beginning at age 5, he had repeated fevers and respiratory symptoms. He was diagnosed with chronic sinusitis at age 11 and sinobronchial syndrome with mild bronchiectasis at age 14. Administration of long-term, low-dose CAM and otolaryngeal topical therapy led to significant improvement of his symptoms. The second case was a 7-year-old boy who underwent HTx for DCM at age one. Starting at age 4, he had repeated fevers and cough due to atelectasis and pneumonia. As antibiotics and respiratory physical therapy proved ineffective, he received long-term, low-dose CAM, resulting in successful control of his atelectasis and recurrent pneumonia. The third case was a 13-year-old boy who underwent HTx at age 6 for DCM. He had chronic sinusitis starting at age 7, and was diagnosed with obstructive sleep apnea syndrome at age 10. Adenotonsillectomy and continuous positive airway pressure support therapy were indicated. At age 13, long-term, lowdose CAM administration was started following mycoplasma infection. In all three cases, the levels of calcineurin inhibitors (cyclosporine and tacrolimus) and everolimus were kept in the optimal range with careful drug monitoring. Longterm, low-dose macrolide administration effectively prevents and treats respiratory complications in pediatric HTx patients as long as attention is paid to potential drug interactions.


Metal-dielectric transition in Sn-intercalated graphene on SiC(0001).
The Sn intercalation into a buffer layer graphene grown on 4H-SiC(0001) substrate has been studied with spectroscopic photoemission and low energy electron microscope. Both SnSix and SnOx interfacial layers are found to form below the buffer layer, converting it into a quasi-free-standing monolayer graphene. Combining the various operation modes of the microscope allows a detailed insight into the formation processes of the interlayers and their thermal stability. In particular, at the interface we observed a reversible transition from silicide to oxide after exposure to ambient pressure and subsequent annealing. This metal-dielectric transition might be useful for interface engineering in graphene-based devices.


[Comparing efficacy of selective penile denervation and circumcision for primary premature ejaculation].
To compare the efficacy and safety of selective penile denervation to that of circumcision for primary premature ejaculation (PPE). A prospective study comprised 138 patients with PPE, divided into two groups. Patients in Group 1 (n=50) underwent selective penile denervation by dissecting about a half of dorsal penile nerve branches. Large nerves (> 2 mm) were subjected to microsurgical neurorrhaphy. In group 2 (n=88) circumcision was carried out using guillotine technique. The evaluation of treatment efficacy was carried out using the Criteria for premature ejaculation questionnaire (CriPE), measuring intravaginal ejaculation latency time (IELT) with a stopwatch and testing penile vibration sensitivity. These examinations were performed at baseline and after 2, 4, 6, 8, 10 and 12 months after operation. By the end of follow-up, 88% and 10.2% of patients of group 1 and group 2 had no signs of PPE, respectively. At 12 months IELT index increased 6-fold in patients of group 1 from 53,6+/-12,7 to 335,6+/-81,5 seconds, while remaining unchanged in group 2 with 51,8+/-10,4 seconds at baseline and 53.9+/-20.1 seconds at the end of follow-up. Group 1 showed statistically significant and sustained reduction in penile vibration sensitivity compared with baseline (p<0,001). In group 2, the baseline and endpoint characteristics of bio-tensiometry did not differ significantly (p>0,05). The resulting effectiveness of selective penile denervation and circumcision for PPE was 88% and 10.2%, respectively, with comparable safety.


Phase II study of irinotecan, 5-fluorouracil, and leucovorin in relapsed or metastatic colorectal cancer as first-line therapy.
The purpose of this study was to assess the efficacy and toxicity of biweekly irinotecan plus 5-fluorouracil (FU) and leucovorin (LV) in patients with relapsed or metastatic colorectal cancer. Between March 2002 and May 2004, 24 patients with histologically confirmed relapsed or metastatic colorectal cancer were enrolled in this study. One chemotherapy cycle consisted of irinotecan 180 mg/m(2) on days 1 and 15; 5-FU 400 mg/m(2) bolus IV with 600 mg/m(2) by a 22 hour intravenous infusion on days 1, 2, 15 and 16; and leucovorin 20 mg/m(2) on days 1, 2, 15 and 16, every 4 weeks. The median age of the 24 was 57.5 years (range, 38 approximately 69). Their metastatic sites included: the liver (62.5%), lung (20.8%), peritoneum (16.7%), lymph node (12.5%), ovary (8.3%) and pelvis/vagina (8.3%). Twenty-two patients were evaluable for a response. Six and 7 patients achieved partial responses and stable diseases, respectively. The overall response rate was 27.3% (95% Confidence interval; 10.3 approximately 44.5%). The median follow-up duration for surviving patients was 14.7 months (range, 1.7 approximately 26.5). Median overall survival (OS) and 1-year OS rates were 19 months and 86.3%, respectively. Median response duration and median progression free survival were 7.47 and 5.57 months, respectively. A total of 83 cycles (median 4 cycles) were administered. The main non-hematologic toxicities were nausea/vomiting (44.5%/18.1%) and diarrhea (8.4%). The most common hematologic toxicity was NCI grade I/II anemia (31.3%) and grade I/II neutropenia was 10.8%. There was no life-threatening toxicity. The results suggested that irinotecan, 5-FU and leucovorin combination chemotherapy in a biweekly schedule is a practical and tolerable treatment option in patients with advanced colorectal cancer.


gamma-Hydroxybutyrate conversion into GABA induces displacement of GABAB binding that is blocked by valproate and ethosuximide.
gamma-Hydroxybutyrate (GHB) has been reported to be a ligand for GABAB receptor(s), although with low or very low affinity (IC50 = 150-796 microM). In addition, several reports argue for a role of GHB via GABAB receptors in both in vivo and in vitro electro-physiological experiments. In the present study, we demonstrate that the inhibition of GHB's conversion into GABA by rat brain membranes blocks the ability of GHB to interfere with GABAB binding. In particular, the inhibition of GHB dehydrogenase by valproate or ethosuximide and the blockade of GABA-T by aminooxyacetic acid induce the disappearance of the GABA-like effect of GHB at GABAB, but also at GABAA, receptors. This finding could explain the misinterpretation of in vitro or in vivo experiments where GHB possesses a GABA-like effect. But in addition, it is postulated that the normal metabolism of GHB in brain induces GABAB mechanisms that could be blocked by the administration of valproate or ethosuximide.


BCS class II drug loaded protein nanoparticles with enhanced oral bioavailability: in vitro evaluation and in vivo pharmacokinetic study in rats.
The aim of the study was to improve the bioavailability of atorvastatin calcium (ATC) by formulating polymeric nanoparticles (NPs) with an easy and cost-effective approach. ATC entrapped gelatin nanoparticles (AEGNPs) were prepared by using a simple one-step desolvation method. The formed NPs were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Morphological study exhibited a homogenous spherical shape of formulated NPs. FTIR studies revealed the chemical compatibility of the drug with gelatin. The improvement in drug delivery kinetics of AEGNPs could be attributed to amorphization along with the reduction in particle size of ATC. The pharmacokinetic study in Sprague-Dawley rats revealed that the Cmax and AUC0-24 of AEGNPs in rats were ∼4-fold and ∼11-fold higher than that of pure ATC suspension. The research presented successfully shows that AEGNPs preparation by one-step desolvation, using minimum excipients is a quick, easy and reproducible method. These results suggest that the ATC encapsulated gelatin NP is a promising approach for the oral delivery of ATC, improving the bioavailability of the drug.


Usage and impact of an online education tool for preventing sudden unexpected death in infancy.
This paper describes the usage, impact and reach of an online education tool for preventing sudden infant death. A 24-slide presentation was formatted for online access. Content was designed for mainstream audiences to align current knowledge, attitudes and actions for a blitz approach to preventing sudden infant death in New Zealand (NZ). The tool was promoted through a network of 'safe sleep' champions across the country and collected basic information on usage, reach and impact. From 3286 completed online sessions between 18 November 2009 and 31 December 2011, there were 2683 (81.7%) with complete data. Average usage was 24.4 completed sessions/week, over a 2-year period, at a cost of NZD1.11 per completed session. Usage reached across regions, ethnic groups and roles. On completion of the course, most rated highly (7-9/9) (68.8%) their 'increased confidence' to discuss infant sleep safety with others. A high increased confidence rating was significantly influenced by spending more time per slide (P < 0.05) and being Maori, Pacific, Asian or 'other' compared with NZ European (P < 0.05). This simple online education tool achieved its aims of high usage, broad participation and cost-effective impact on increasing confidence to discuss infant sleep safety with others. e-Learning modes should be considered where there is a need to align large numbers of people in a short time with understandings and actions for addressing a specific health issue.


Understanding the reactivity of enol ether radical cations: investigation of anodic four-membered carbon ring formation.
The reactivity of enol ether radical cations was investigated in anodic four-membered carbon ring formations, advancing the mechanistic understanding of these reactions. The mono-ring-containing aromatic cations were reduced through inter- or intramolecular electron transfer to give mono- or bis-ring-containing compounds, respectively. Small structural changes in the hydrocarbon linkers tethering two aromatic rings exerted a powerful effect on the efficiency of such electron transfer events.


Solution structure of an intramolecular DNA triplex containing 5-(1-propynyl)-2'-deoxyuridine residues in the third strand.
Incorporation of the modified base 5-(1-propynl)-2'-deoxyuridine (propynylU) in the third strand of a triplex leads to enhanced triplex stabilization. To investigate effects of the propyne nucleotide on triplex structure and the factors underlying the increased stability, we have determined the solution structure of the intramolecular DNA pyrmidine-purine-pyrimdine d(AGAGAGAA-(EG)6-TTCTCTCT-(EG)6-PCPCPCPP) (PDD-EG), which contains 5-(1-propynl)-2'-deoxyuridine (P) in the third strand and hexakis(ethylene glycol) linkers [(EG)6]. The structure was calculated using X-PLOR with distance and dihedral angle restraints obtained from two-dimensional NMR experiments and refined with the direct relaxation matrix method. The structures show that the extended aromatic electron cloud of the propynylU nucleotide stacks well over the 5'-neighboring nucleotides, resulting in increased stabilization. The propynylU nucleotides also affect the overall structure of the triple helix. A comparison of the structure to that of the nonmodified intramolecular DNA triplex of the same sequence, d(AGAGAGAA-(EG)6-TTCTCTCT-(EG)6-TCTCTCTT) (DDD-EG), shows that PDD-EG has a more A-DNA like X displacement and inclination than DDD-EG yet still maintains predominantly S-type sugar puckers as found in DDD-EG and other DNA triplexes.


Cortical bone repair. The relationship of the lacunar-canalicular system and intercellular gap junctions to the repair process.
Repair of cortical bone was studied in 2.4-millimeter-diameter mid-diaphyseal femoral and tibial defects in young New Zealand White rabbits using light microscopy, transmission electron microscopy, and histomorphometry. The initial source of repair tissue is the marrow. Vessels grow into the defect, accompanied by undifferentiated mesenchymal cells. Woven bone is synthesized initially at the periphery of the defect on pre-existing cortex. Differentiating mesenchymal osteoblasts surround themselves with osteoid in a woven conformation. Once a scaffold has formed, surface osteoblasts align themselves in a regular array on the woven matrix surface and synthesize osteoid in a lamellar conformation. The long axes of the repair vessels, lamellae, and osteocyte lacunae are perpendicular to the long axis of the bone. Polarized-light microscopy showed maintenance of this pattern at six, eight, and twelve weeks, even when the defect was filled with lamellar bone. Remodeling is performed slowly by osteoclast cutting cones over a period of several months. The lacunar-canalicular system is clearly demonstrated in plastic-embedded, toluidine blue-stained sections. A canaliculus passes into or away from a lacuna every 1.9 micrometers over the entire osteocyte perimeter. Undifferentiated mesenchymal cells have no processes, as seen by transmission electron microscopy, but soon sprout a florid array of processes as differentiation to early mesenchymal osteoblasts proceeds. Osteoblast and osteocyte cell processes are packed with intermediate filaments that are continuous with those in the cell bodies. Intercellular gap junctions are seen between surface osteoblasts, between osteoblasts and underlying osteocytes, and between osteocyte cell processes in the canaliculi.


Post-viral olfactory loss and parosmia.
The emergence of SARS-CoV-2 has brought olfactory dysfunction to the forefront of public awareness, because up to half of infected individuals could develop olfactory dysfunction. Loss of smell-which can be partial or total-in itself is debilitating, but the distortion of sense of smell (parosmia) that can occur as a consequence of a viral upper respiratory tract infection (either alongside a reduction in sense of smell or as a solo symptom) can be very distressing for patients. Incidence of olfactory loss after SARS-CoV-2 infection has been estimated by meta-analysis to be around 50%, with more than one in three who will subsequently report parosmia. While early loss of sense of smell is thought to be due to infection of the supporting cells of the olfactory epithelium, the underlying mechanisms of persistant loss and parosmia remain less clear. Depletion of olfactory sensory neurones, chronic inflammatory infiltrates, and downregulation of receptor expression are thought to contribute. There are few effective therapeutic options, so support and olfactory training are essential. Further research is required before strong recommendations can be made to support treatment with steroids, supplements, or interventions applied topically or injected into the olfactory epithelium in terms of improving recovery of quantitative olfactory function. It is not yet known whether these treatments will also achieve comparable improvements in parosmia. This article aims to contextualise parosmia in the setting of post-viral olfactory dysfunction, explore some of the putative molecular mechanisms, and review some of the treatment options available.


[Differences in the pattern of iron accumulation in primary and secondary hemochromatosis. Diagnostic importance and clinical consequences].
In secondary haemochromatosis up to fourfold higher amounts of iron are tolerated in the organism than in primary (hereditary) haemochromatosis. This is connected with the marked iron storage of macrophages in secondary iron overloading, which is relatively without any dangers. In primary haemochromatosis, however, a relative insufficiency of storage of extrahepatic macrophages can be observed for iron, a fact which favours a premature parenchymatous iron storage leading to organ lesions. Because of the discrepant behaviour of macrophages characteristic, diagnostically relevant differences will occur in the pattern of iron storage in the bone-marrow, spleen and small intestine between primary and secondary haemochromatosis.


Laparoscopic surgery and polycystic liver disease: Clinicopathological features and new trends in management.
Polycystic liver disease (PLD) has a low frequency overall in the worldwide population. As the patient's symptoms are produced by the expansion of hepatic volume, the different therapeutic alternatives are focused on reducing it. Surgery is still considered the most effective treatment for symptomatic PLD. The aim of this study was to evaluate the long-term outcomes of laparoscopic surgery for PLD. This study included 14 patients who were diagnosed with symptomatic PLD and underwent surgery by a laparoscopic approach between 2004 and 2012. It involved collecting data on the characteristics of those patients and their liver disease, surgical procedures, intra- and postoperative complications, and the long-term follow-up. Twelve laparoscopic multiple-cyst fenestrations and two segmentary liver resections associated with remaining-cyst fenestration were performed. One procedure required conversion to laparotomy and the other was complicated by anhepatic severe bleeding. The rest of the procedures were uneventful. One patient developed persistent self-limited ascites in the immediate postoperative period. Symptoms disappeared after surgical intervention in all patients. During a median follow-up of 62 months (range 14-113 months), there were two clinical recurrences and one asymptomatic radiological recurrence. One patient required further surgery. Laparoscopic cystic fenestration and laparoscopic liver resection are safe and long-term, effective procedures for the treatment of symptomatic PLD. Severity and morphological characteristics of the hepatic disease will determine the surgical indication and the optimal approach for each patient.


Effect of silybin on high-fat-induced fatty liver in rats.
Silybin, a natural antioxidant, has been traditionally used against a variety of liver ailments. To investigate its effect and the underlying mechanisms of action on non-alcoholic fatty liver in rats, we used 60 4-6-week-old male Sprague-Dawley rats to establish fatty liver models by feeding a high-fat diet for 6 weeks. Hepatic enzyme, serum lipid levels, oxidative production, mitochondrial membrane fluidity, homeostasis model assessment-insulin resistance index (HOMA-IR), gene and protein expression of adiponectin, and resistin were evaluated by biochemical, reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Compared with the model group, silybin treatment (26.25 mg·kg(-1)·day(-1), started at the beginning of the protocol) significantly protected against high-fat-induced fatty liver by stabilizing mitochondrial membrane fluidity, reducing serum content of alanine aminotransferase (ALT) from 450 to 304 U/L, decreasing hepatic malondialdehyde (MDA) from 1.24 to 0.93 nmol/mg protein, but increasing superoxide dismutase (SOD) and glutathione (GSH) levels from 8.03 to 9.31 U/mg protein and from 3.65 to 4.52 nmol/mg protein, respectively. Moreover, silybin enhanced the gene and protein expression of adiponectin from 215.95 to 552.40, but inhibited that of resistin from 0.118 to 0.018. Compared to rosiglitazone (0.5 mg·kg(-1)·day(-1), started at the beginning of the protocol), silybin was effective in stabilizing mitochondrial membrane fluidity, reducing SOD as well as ALT, and regulating gene and protein expression of adiponectin (P < 0.05). These results suggest that mitochondrial membrane stabilization, oxidative stress inhibition, as well as improved insulin resistance, may be the essential mechanisms for the hepatoprotective effect of silybin on non-alcoholic fatty liver disease in rats. Silybin was more effective than rosiglitazone in terms of maintaining mitochondrial membrane fluidity and reducing oxidative stress.


Light-Dressing Effect in Laser-Assisted Elastic Electron Scattering by Xe.
The light-dressing effect in Xe atoms was identified in laser-assisted elastic electron scattering (LAES) signals. In the angular distribution of LAES signals with energy shifts of ±ℏω recorded by the scattering of 1 keV electrons by Xe in an intense nonresonant laser field, a peak profile appeared at small scattering angles (<0.5°). This peak was interpreted as evidence of the light dressing of Xe atoms induced by an intense laser field on the basis of a numerical simulation in which the light-dressing effect is included.


Switching from Monthly to Three-Monthly Long-Acting Injectable Paliperidone: A Survey on Subjective Satisfaction and Safety.
Poor adherence to antipsychotic medication is common in the treatment of schizophrenia and other psychotic disorders. Paliperidone palmitate 3-monthly (PP3M) is the first long-acting injectable (LAI) antipsychotic to allow for only four medication administrations per year, and although there is sufficient information available about the clinical effects, there is relatively limited insight into the subjective experience of people with lived experience. This descriptive, cross-sectional survey explored patient's satisfaction and perspectives on the advantages and disadvantages of switching from monthly to 3-monthly paliperidone while also reporting on perceived levels of safety with regard to the reducing dose regimen during the Covid-19 pandemic. Information on discontinuation and hospitalisation rates at one year was also collected from the electronic records. Of the 46 patients included in the study, the vast majority reported feeling satisfied (89.2%) and safer (93.5%) after switching to the three-monthly formulation. Participants highlighted several advantages of changing to PP3M, most notably convenience (93.5%), improved quality of life (58.7%), decreased stigma (39.1%) and better adherence (28.3%). Furthermore, 93.5% of respondents experienced no disadvantages, while 6.5% described worsening side effects or symptoms. In fact, only one patient discontinued PP3M at one year with the overall number of hospitalisations also reducing in the same period compared to the year before switching. Our findings add to the small, but growing, body of evidence supporting patient satisfaction and acceptance with the use of PP3M and may reinforce the use of less frequent LAIs in clinical practice to enhance individual experience and treatment persistence and decrease levels of stigmatisation.


Modulating host gene expression via gut microbiome-microRNA interplay to treat human diseases.
The human gastrointestinal (GI) tract hosts trillions of microbial inhabitants involved in maintaining intestinal homeostasis, dysbiosis of which provokes a motley of pathogenic and autoimmune disorders. While the mechanisms by which the microbiota modulates human health are manifold, their liberated metabolites from ingested dietary supplements play a crucial role by bidirectionally regulating the expression of micro-ribonucleic acids (miRNAs). miRNAs are small endogenous non-coding RNAs (ncRNAs) that have been confirmed to be involved in an interplay with microbiota to regulate host gene expression. This comprehensive review focuses on key principles of miRNAs, their regulation, and crosstalk with gut microbiota to influence host gene expression in various human disorders, by bringing together important recent findings centric around miRNA-microbiota interactions in diseases along various axis of the gut with other organs. We also attempt to lay emphasis on exploiting the avenues of gut-directed miRNA therapeutics using rudimentary dietary supplements to regulate abnormal host gene expression in diseases, opening doors to an accessible and economical therapeutic strategy.


[A case of remnant gastric cancer with afferent loop syndrome treated by left upper exenteration].
A 64-year-old man with sudden upper abdominal pain and emesis was admitted to our hospital. Forty years ago, he had undergone distal gastrectomy and reconstruction by Billroth II anastomosis for gastric cancer. Abdominal computed tomography revealed a dilated afferent loop and anastomotic tumor. Gastrofiberscopy showed crookedness and edematization of the afferent loop anastomosis. A biopsy revealed a poorly differentiated adenocarcinoma. He was operated on under the diagnosis of remnant gastric cancer. Left upper exenteration was performed because the transverse colon, lateral segment of the liver, pancreas, and left renal hilus were involved. Liver metastasis and abdominal dissemination were not observed. Histopathological findings revealed severe invasion of poorly differentiated adenocarcinoma to other organs, and intraoperative peritoneal lavage cytology was positive. He was discharged from our hospital; however, adjuvant chemotherapy was impossible because of his poor condition. Four months after the operation, he died from peritoneal carcinomatosis. Remnant gastric cancer with afferent loop syndrome has a poor prognosis. Therefore, it is necessary to select surgical resection or palliative care after immediate chemotherapy, considering each patient's condition and cancer stage.


Homocysteine Increases Tau Phosphorylation, Truncation and Oligomerization.
Increased plasma homocysteinemia is considered a risk factor of dementia, including Alzheimer's disease (AD) and vascular dementia. However, the reason elevated plasma homocysteinemia increases the risk of dementia remains unknown. A pathological hallmark of AD is neurofibrillary tangles (NFTs) that consist of pathologically phosphorylated tau proteins. The effect of homocysteine (Hcy) on tau aggregation was explored using human neuroblastoma M1C cells that constitutively express human wild-type tau (4R0N) under the control of a tetracycline off system, primary mouse cultured neurons, and by inducing hyperhomocysteinemia in a mouse model of tauopathy (HHCy mice). A wide range of Hcy concentrations (10-1000 µM) increased total tau and phosphorylated tau protein levels. Hcy activated glycogen synthase kinase 3, and cyclin dependent kinase 5, major tau phosphokinases, and inactivated protein phosphatase 2A, a main tau phosphatase. Hcy exhibited cytotoxic effects associated with enhanced activation of caspase. Truncation of tau in the C-terminus, the cleavage site of caspase 3 (i.e., D421, detected by the TauC3 antibody) was also increased. Total tau, phosphorylated tau, as well as C-terminal cleaved tau were increased in the sarkosyl insoluble tau fraction. Hcy also increased the level of tau oligomers, as indicated by the tau oligomer complex 1 (TOC1) antibody that specifically identifies oligomeric tau species, in the tris insoluble, sarkosyl soluble fraction. The levels of TOC1-positive oligomeric tau were increased in brain lysates from HHCy mice, and treating HHCy mice with S-adenosylmethionine, an intermediate of Hcy, reduced the levels of oligomeric tau to control levels. These observations suggest that Hcy increases the levels of phosphorylated tau as well as truncated tau species via caspase 3 activation, and enhanced tau oligomerization and aggregation.


Downregulation of SWI5 and CTC1 genes: hepatitis B virus DNA polymerase transactivated protein 1-mediated inhibition of DNA repair.
Hepatitis B virus (HBV) DNA polymerase transactivated protein 1 (HBVDNAPTP1) is a novel protein upregulated by HBV DNA polymerase, which has been screened by suppression subtractive hybridization technique (SSH) (GenBank Acc. No. AY450389). A vector pcDNA3.1 (-)/myc-His A-HBVDNAPTP1 was constructed and used to transfect acute monocytic leukemia cell line THP-1. HBVDNAPTP1 expression was detected by Western blot analysis in the cells. A cDNA library of genes downregulated by HBVDNAPTP1 in THP-1 cells was made in pGEM-T Easy using SSH. The cDNAs were sequenced and analyzed with BLAST search against the sequences in GenBank. Some sequences, such as DNA repair protein SWI5 homolog (SWI5) and CTS telomere maintenance complex component 1 (CTC1), might be involved in DNA repair. Protein expression of SWI5 and CTC1 was identified by Western blot in THP-1 cells. HBVDNAPTP1 could downregulate the expression of SWI5 and CTC1 at translation level.


[Secondary posterior chamber lenses. Implantation in intact, partially intact and missing posterior lens capsule].
Between January 1988 and December 1991, 63 patients (75 eyes) underwent secondary posterior chamber intraocular lens (IOL) implantation. The mean period since primary cataract extraction was 85 months, and the mean age of these patients was 58 years. In 47 eyes with extracapsular aphakia the IOL was ciliary sulcus-fixated following polishing of the posterior capsule and synecholysis. In 8 eyes with remnants of the posterior capsule an anterior vitrectomy was performed. In 17 virtually intracapsular aphakic eyes additional transscleral suturing of the IOL was required. Mean visual acuity (VA) improved from 20/60 to 20/30. The following complications were observed during the mean postoperative follow-up of 15 (range 3-45) months. There were 6 limited anterior chamber and 1 vitreous hemorrhage that resolved spontaneously. Two IOLs required surgical repositioning--both with scleral suturing--because of postoperative IOL subluxation. A delayed but reversible fibrin reaction was seen in 1 eye, while 1 eye developed a cystoid macular edema with reduction of VA from 20/30 to 20/60. With careful attention to the status of the posterior capsule, which determines the individual surgical approach, secondary posterior chamber IOL implantation has become a relatively safe procedure that can be recommended for many patients.


[Monoclonal antibodies].
Since the first successful application of somatic cell fusion by Kohler and Milstein to generate hybridomas secreting monoclonal antibodies (Mabs), this hybridoma technique has been widely applied for production of Mabs against a wide variety of antigens. In the lecture, general procedures for establishment of hybridomas and characteristic properties of Mabs were briefly explained and followed by presentation of our clinical studies using Mabs produced in our laboratory to hCG, sperm and tumor cells. 1. Monoclonal antibodies to hCG. Three hybridomas (5D4, 6E4, 2F8) were established by fusing mouse myeloma cells (P3U1) with spleen cells from BALB/c mice immunized with partially purified hCG. Mabs were obtained either from hybridoma culture media or from ascites of mice inoculated the hybridoma cells intraperitoneally. Three Mabs obtained were all IgG1 and each had a unique binding specificity to hCG, hCG-beta, hCG-alpha and LH. They were applied for development of specific, sensitive and easy to perform hCG assays. A reverse passive hemagglutination assay of urinary hCG with a sensitivity of 12.5 IU/l and a sandwich-enzyme immunoassay of serum hCG with a sensitivity of 0.1 mIU/ml were presented. 2. Monoclonal antibodies to human spermatozoa. For elucidation of mechanisms for induction of auto- or iso-sperm immunization and infertility by antisperm antibodies, antigen analysis of seminal components was essential. For this purpose, several Mabs with strong sperm immobilizing (SI) and agglutinating (SA) activities were generated in mice, rats and humans and the corresponding antigens were analysed.(ABSTRACT TRUNCATED AT 250 WORDS)


Evolutionary roots of arginase expression and regulation.
classical (M1), producing nitric oxide, NO, and M2, in which arginase activity is primarily expressed. Ornithine, the product of arginase, is a substrate for synthesis of polyamines and collagen, important for growth and ontogeny of animals. M2 macrophages, expressing high level of mitochondrial arginase, have been implicated in promoting cell division and deposition of collagen during ontogeny and wound repair. Arginase expression is the default mode of tissue macrophages, but can also be amplified by signals, such as IL-4/13 or transforming growth factor-β (TGF-β) that accelerates wound healing and tissue repair. In worms, the induction of collagen gene is coupled with induction of immune response genes, both depending on the same TGF-β-like pathway. This suggests that the main function of M2 "heal" type macrophages is originally connected with the TGF-β superfamily of proteins, which are involved in regulation of tissue and organ differentiation in embryogenesis. Excretory-secretory products of metazoan parasites are able to induce M2-type of macrophage responses promoting wound healing without participation of Th2 cytokines IL-4/IL-13. The expression of arginase in lower animals can be induced by the presence of parasite antigens and TGF-β signals leading to collagen synthesis. This also means that the main proteins, which, in primitive metazoans, are involved in regulation of tissue and organ differentiation in embryogenesis are produced by innate immunity. The signaling function of NO is known already from the sponge stage of animal evolution. The cytotoxic role of NO molecule appeared later, as documented in immunity of marine mollusks and some insects. This implies that the M2-wound healing promoting function predates the defensive role of NO, a characteristic of M1 macrophages. Understanding when and how the M1 and M2 activities came to be in animals is useful for understanding how macrophage immunity, and immune responses operate.


What more can community nurses do to manage adult malnutrition.
This article gives an outline of the key groups at risk of malnutrition in the community and the effects and clinical consequences of not identifying and managing these groups. It outlines the potential health and social costs of not identifying and treating malnutrition in the community and advises how malnutrition arises in these 'at-risk' groups. As 93% of those affected by malnutrition are living in our communities, advice is given on how community nurses can play a pivotal role in identifying malnutrition by initiating conversations about dietary intake with patients and integrating screening and nutritional care into pathways of care.


Reduced expression of the atl autolysin gene and susceptibility to autolysis in clinical heterogeneous glycopeptide-intermediate Staphylococcus aureus (hGISA) and GISA strains.
To assess a link between resistance to Triton X-100 induced autolysis (TIA) and lowered atl expression in a collection of clinical glycopeptide-intermediate Staphylococcus aureus (GISA) and heterogeneous GISA (hGISA). Nine clinical GISA, 11 hGISA and 11 glycopeptide-susceptible S. aureus (GSSA), including three pairs of related isolates, were analysed using TIA assays. Lysostaphin MICs were determined by a broth microdilution technique and reverse transcriptase PCR was used to compare atl expression levels in all isolates. Eight of nine clinical GISA and six of 11 hGISA exhibited lower susceptibility to TIA and higher MICs of lysostaphin than GSSA. Eight of nine GISA and all hGISA strains had lowered atl expression levels compared with GSSA. The majority of GISA and hGISA isolates exhibited lowered susceptibility to TIA and lysostaphin and reduced atl expression when compared with GSSA isolates. These factors could contribute to, or predispose to the development of, a thickened cell wall and glycopeptide-intermediate resistance.


Simultaneous bilateral hip fractures in a level I trauma center.
Hip fractures are a common occurrence among the population today, especially in the elderly. However, the incidence of simultaneous bilateral hip fractures is very rare, and there is a paucity of data in the current literature documenting patients with these hip fractures. A retrospective case review was performed on all patients treated for hip fractures during the past ten years at our Level I trauma center. From 1993 to 2002 there were eight patients who sustained simultaneous bilateral hip fractures. The mean age of the patients was 63 years (range, 34-88 years). The overall survival rate was 63%. In the patients of age group younger than 65, the survival rate was three out of four (75%). In the patients of age group 65 and older, the survival rate was two of four (50%). The length of hospital stay was shorter on average for the younger population, 19 days (range, 17-27 days). The average hospital duration for the older population was 29 days (range, 28-30). Bilateral hip fractures are usually the result of a high-energy trauma and are associated with other injuries. The morbidity and mortality of this injury are quite high. Patient age, associated injuries, and comorbid conditions should be examined closely because they may influence the patient's recovery.


Age, sex, and hospital factors are associated with the duration of cardiopulmonary resuscitation in hospitalized patients who do not experience sustained return of spontaneous circulation.
Variability in the duration of attempted in‐hospital cardiopulmonary resuscitation (CPR) is high, but the factors influencing termination of CPR efforts are unknown. We examined the association between patient and hospital characteristics and CPR duration in 45 500 victims of in‐hospital cardiac arrest who did not experience return of spontaneous circulation (ROSC) and who were enrolled in the Get With the Guidelines registry between 2001 and 2010. In a secondary analysis, we performed analyses in 46 168 victims of in‐hospital cardiac arrest who experienced ROSC. We used ordered logistic regression to identify factors associated with CPR duration. Analyses were conducted by tertile of CPR duration (tertiles: ROSC group: 2 to 7, 8 to 17, and 18 to 120 minutes; no‐ROSC group: 2 to 16, 17 to 26, 27 to 120 minutes). In those without ROSC, younger age (aged 18 to 40 versus >65 years; odds ratio [OR] 1.81; 95% CI 1.69 to 1.95; P<0.001), female sex (OR 1.05; 95% CI 1.02 to 1.09; P=0.005), ventricular tachycardia or fibrillation (OR 1.50; 95% CI 1.42 to 1.58; P<0.001), and the need to place an invasive airway (OR 2.59; 95% CI 2.46 to 2.72; P<0.001) were associated with longer CPR duration. In those with ROSC, ventricular tachycardia or fibrillation (OR 0.89; 95% CI 0.85 to 0.93; P<0.001) and witnessed events (OR 0.87; 95% CI 0.82 to 0.91; P<0.001) were associated with shorter duration. Age and sex were associated with attempted CPR duration in patients who do not experience ROSC after in‐hospital cardiac arrest but not in those who experience ROSC. Understanding the mechanism of these interactions may help explain variability in outcomes for in‐hospital cardiac arrest.


ARLTS1, MDM2 and RAD51 gene variations are associated with familial breast cancer.
Genetic factors that contribute to the risk of breast cancer are largely not known and association studies have revealed several genes with low penetrance risk alleles for breast cancer. Analysis of these genes may provide important information on the risk factors affecting carcinogenesis. Variations in the ARLTS1, RAD51 and MDM2 genes have been associated with increased risk of different cancer types but for breast cancer the results are not consistent. In this study we investigated the role of the allelic variants in candidate genes acting in the tumor suppressor, DNA repair and p53 pathways as risk factors for familial breast cancer in 147 patients displaying characteristics of familial disease. Presence of the polymorphic variants were investigated by amplification of the corresponding regions and restriction fragment length polymorphism analysis. Genotype and allele frequencies in the patients were significantly different for all three variants. Our results indicate that the polymorphic variants might affect individual susceptibility towards breast cancer.


Review of Studies on Phlomis and Eremostachys Species (Lamiaceae) with Emphasis on Iridoids, Phenylethanoid Glycosides, and Essential Oils.
As the sixth-largest Angiosperm family, Lamiaceae contains more than 245 genera and 7886 species that are distributed worldwide. It is also the third-largest family based on the number of taxa in Turkey where it is represented by 46 genera and 782 taxa with a high endemism ratio (44%). Besides, Lamiaceae are rich in plants with economic and medicinal value containing volatile and nonvolatile compounds. Many aromatic plants of Lamiaceae such as Salvia, Sideritis, Stachys, Phlomis, and Teucrium species are used in traditional herbal medicine throughout Turkey as well as in other Mediterranean countries. Salvia (Sage tea "Adaçayı"), Sideritis (Mountain tea "Dağçayı"), Stachys (Hairy Tea "Tüylü Çay"), and Phlomis (Turkish sage "Çalba or Şalba") are the largest genera that are used as herbal teas. This review focuses on the volatile and nonvolatile compounds of Lamiaceae from the genera Phlomis and Eremostachys of the subfamily Lamioideae with emphasis on iridoids, phenylethanoid glycosides, and essential oils.


Heart Block as a Rare Complication of Tricuspid Valve Endocarditis: Awareness is the Key.
Infective endocarditis (IE) occurs when bacterial or fungal pathogens enter the blood and attach to the endocardium. Right-sided endocarditis is usually associated with intravenous drug use (IVDU), intracardiac devices, and central venous catheters. There is more data published about left-side endocarditis when compared to right-sided endocarditis. Tricuspid valve infective endocarditis (TVIE) accounts for 5%-10% of IE, and of those cases, roughly 10% are complicated by conduction deficits due to inflammatory edema, myocarditis, and abscess formation. Tricuspid valve (TV) surgical repair carries its own risks, one of which includes the development of conduction abnormalities. Here, we review the current data of TVIE complicated by heart block after tricuspid valve replacement. Also, we present a case of a 21-year-old IVDU female who presented with tricuspid valve endocarditis, subsequently underwent tricuspid valve replacement, and developed a heart block.


[Congenital bilateral amastia in a mother and a daughter (author's transl)].
A 23 year-old primigravida with bilateral congenital amastia was delivered at 38 weeks gestation following early rupture of the membranes. The mature newborn female also showed congenital bilateral amastia. In addition mother and daughter showed a mild hook finger of both 5th fingers. The mother only had 19 permanent teeth. About the permanent in the infant no data were obtained. This type of manifestation of a congenital anhydrotic ectodermal dysplasia is probably due to a sex-linked recessive gene. Newer investigations in experimental embryology show that the complete inhibition of the growth of the ectodermal milkridge occurs in the 6-12 th week of intra-uterine life and may also occur as an embryopathy due to dehydroepiandrosterone.


Longitudinal Course of Sex Steroids From Pregnancy to Postpartum.
Sex steroids (SS) typically rise during pregnancy and decline after birth, but no consistent reference values exist for these hormonal courses. We aimed to establish an overview of SS secretion patterns during the peripartum and to better understand how SS contribute to maternal and fetal pathologies. A systematic literature search was conducted in accordance with the PRISMA guidelines using PubMed, Cochrane Library, and PsycINFO. Additionally, we conducted a supplementary manual search of references. Observational studies published in English and assessing estradiol, progesterone, and testosterone over the course of the peripartum in physically healthy female subjects were included, without restrictions on year of publication. Extracted data were analyzed descriptively and visually. SS increase progressively during pregnancy, with an extremely wide range of reported concentrations, especially in the third trimester. In fact, reported concentrations varied up to 5000-fold at comparable measurement time points. A comprehensive understanding of the influence of SS levels on associated maternal and fetal pathologies is currently hindered by 2 main factors. First, reported SS levels vary widely during the peripartum period. Second, the current state of knowledge on how SS are associated with pathologies in mothers and babies is largely based on correlational studies, and causality thus remains unclear. Consequently, we recommend the development of a systematic reference framework that follows the suggestions presented in this review. This would enable the establishment of SS reference values for a healthy population, resulting in the possibility to draw conclusions about deviations and related pathologies.


Pharmacophore features of potential drugs.
Drug discovery efforts rely increasingly on the identification of quality lead compounds through high-throughput synthesis and screening. However, large-scale random libraries have yielded only a low number of quality lead molecules. To address this shortcoming researchers have paid more attention to the concept of "drug-likeness" of molecules in combinatorial and screening libraries. Database profiling and analysis methods have been employed to identify the structural features of known drug molecules. Neural networks and machine learning methods help to distinguish between drugs and nondrugs. More recently, database-independent pharmacophore filters have been introduced that provide simple intuitive rules to classify potential drugs.


The human sodium-dependent ascorbic acid transporters SLC23A1 and SLC23A2 do not mediate ascorbic acid release in the proximal renal epithelial cell.
Sodium-dependent ascorbic acid membrane transporters SLC23A1 and SLC23A2 mediate ascorbic acid (vitamin C) transport into cells. However, it is unknown how ascorbic acid undergoes cellular release, or efflux. We hypothesized that SLC23A1 and SLC23A2 could serve a dual role, mediating ascorbic acid cellular efflux as well as uptake. Renal reabsorption is required for maintaining systemic vitamin C concentrations. Because efflux from nephron cells is necessary for reabsorption, we studied whether SLC23A1 and SLC23A2 mediate efflux of ascorbic acid in the human renal nephron. We found high gene expression of SLC23A1 but no expression of SLC23A2 in the proximal convoluted and straight tubules of humans. These data rule out SLC23A2 as the ascorbic acid release protein in the renal proximal tubular epithelia cell. We utilized a novel dual transporter-based Xenopus laevis oocyte system to investigate the function of the SLC23A1 protein, and found that no ascorbate release was mediated by SLC23A1. These findings were confirmed in mammalian cells overexpressing SLC23A1. Taken together, the data for SLC23A1 show that it too does not have a role in cellular release of ascorbic acid across the basolateral membrane of the proximal tubular epithelial cell, and that SLC23A1 alone is responsible for ascorbic acid uptake across the apical membrane. These findings reiterate the physiological importance of proper functioning of SLC23A1 in maintaining vitamin C levels for health and disease prevention. The ascorbate efflux mechanism in the proximal tubule of the kidney remains to be characterized.


Transport of biologically active material in laser cutting.
The transport of biologically active material during laser cutting with CO2 and Er lasers is demonstrated. This transport mechanism removes particles from the surface of gelatin, agar, and liver samples into the depth of the laser-formed craters. The transport phenomenon is explained by a contraction and condensation of enclosed hot water vapor. We show by cultivating transported bacteria in agar that biological particles can survive the shock of the transport. Determination of the numbers of active cells evidences a more pronounced activity of the cultivated bacteria after impact with an Er laser than with a CO2 laser.


Simultaneous determination of piperaquine and its N-oxidated metabolite in rat plasma using LC-MS/MS.
A sensitive and efficient liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of piperaquine (PQ) and its N-oxidated metabolite (PQ-M) in plasma. A simple protein precipitation procedure was used for sample preparation. Adequate chromatographic retention was achieved on a C18 column under gradient elution with acetonitrile and 2 mm aqueous ammonium acetate containing 0.15% formic acid and 0.05% trifluoroacetic acid. A triple-quadrupole mass spectrometer equipped with an electrospray source was set up in the positive ion mode and multiple reaction monitoring mode. The method was linear in the range of 2.0-400.0 ng/mL for PQ and 1.0-50.0 ng/mL for PQ-M with suitable accuracy, precision and extraction recovery. The lower limits of detection (LLOD) were established at 0.4 and 0.2 ng/mL for PQ and PQ-M, respectively, using 40 μL of plasma sample. The matrix effect was negligible under the current conditions. No effect was found for co-administrated artemisinin drugs or hemolysis on the quantification of PQ and PQ-M. Stability testing showed that two analytes remained stable under all relevant analytical conditions. The validated method was successfully applied to a pharmacokinetic study performed in rats after a single oral administration of PQ (60 mg/kg).


Caring for Patients Treated With Therapeutic Hypothermia.
Numerous studies have indicated that therapeutic hypothermia can improve neurological outcomes after cardiac arrest. This treatment has redefined care after resuscitation and offers an aggressive intervention that may mitigate postresuscitation syndrome. Caregivers at Lehigh Valley Health Network, Allentown, Pennsylvania, an academic, community Magnet hospital, treated more than 200 patients with therapeutic hypothermia during an 8-year period. An interprofessional team within the hospital developed, implemented, and refined a clinical practice guideline for therapeutic hypothermia. In their experience, beyond a protocol, 5 critical elements of success (interprofessional stakeholders, coordination of care delivery, education, interprofessional case analysis, and participation in a global database) enhanced translation into clinical practice.


Combination Effect of Bowman-Birk Inhibitor and α-Tocopheryl Succinate on Prostate Cancer Stem-Like Cells.
The reoccurrence of androgen-dependent prostate cancer after anti-androgen therapy mainly depends on prostate cancer stem-like cells. To reduce the risk, it is important to delete the cancer stem-like cells. Furthermore, to induce differentiation of cancer stem-like cells is critical to abrogate stemness of the cells. Therefore, we tried to investigate a possibility on the establishment of a new effective therapy to eradicate the cancer stem-like cells via the induction of differentiation in this study. Prostate cancer stem-like cells from an androgen-dependent prostate cancer cell line (LNCaP cell) had severe resistance against an anti-androgen therapeutic agent. We selected Bowman-Birk inhibitor (BBI) from soybeans reported as a chemopreventive agent in prostate cancer to differentiate the caner stem-like cells and α-tocopheryl succinate (TOS) known as a mitocan to induce effectively cytotoxic effect against the cancer stem-like cells. In fact, only TOS treatment had cytotoxic effect against the cancer stem-like cells, but the addition of BBI treatment to the cells treated with TOS reinforced TOS-mediated cytotoxicity in the cancer stem-like cells. This reinforcement coincided with the combination-enhanced apoptosis in the stem-like cells. Also, we confirmed caspase9-caspase3 cascade mainly contributed to the enhancement of the cytotoxicity in the stem-like cells caused by the combination, indicating that the reinforcement of BBI on TOS-mediated apoptosis via mitochondria related to the enhancing cytotoxic effect of the combination on the prostate cancer stem-like cells. Overall, it seems that the combination is an effective new approach to reduce the reoccurrence of prostate cancer targeting prostate cancer stem cells.


The Slr0924 protein of Synechocystis sp. strain PCC 6803 resembles a subunit of the chloroplast protein import complex and is mainly localized in the thylakoid lumen.
An isolated 25 kDa protein of Synechocystis sp. PCC 6803 was N-terminally sequenced and assigned to a protein encoded by the ORF slr0924. This ORF shows a certain degree of sequence similarity to a subunit from the protein Translocon at the Inner envelope of pea Chloroplasts (Tic22). The deduced amino acid sequence of Slr0924 has a N-terminal extension, that contains two possible translational start points and two possible cleavage sites for leader peptidases. Immunostaining with an antibody raised to the over-produced protein revealed two cross-reacting forms, which probably correspond to a larger intermediate and the mature protein. Immunogold labelling of thin sections showed that the protein is located mainly in the thylakoid region. This result was verified by thylakoid membrane fractionation indicating that Slr0924 is a lumenal protein. The slr0924 gene product is essential for the viability of Synechocystis sp. PCC 6803 as shown by interposon mutagenesis. The merodiploid strain showed reduced photosynthetic activity compared to the wild-type. Furthermore, growth of the merodiploid strain was found to be completely inhibited after cultivation with glucose. Accordingly, the amount of the slr0924 gene product was regulated by glucose and light intensities in wild-type cells. The potential function of the protein in Synechocystis sp. PCC 6803 will be discussed.


Cancer stem cells of the digestive system.
Stem cells of the digestive system are ideal in many ways for research, given they are abundant, highly proliferative and have a uniform structural arrangement. This in turn has enormously aided the research of cancer stem cells of the digestive system, which is now shaping our understanding of cancer stem cells. In this review, the recent advances in the understanding of cancer stem cells of the digestive system have been summarized, including aspects such as their identification, origin, cell-cycle dormancy, relationship with epithelial-mesenchymal transition, cellular metabolism and the underlying molecular mechanisms. Newly acquired knowledge concerning cancer stem cells have led to the development of novel cancer therapeutics with provisional yet encouraging results.


Did abortion legalization reduce the number of unwanted children? Evidence from adoptions.
The legalization of abortion in the United States led to well-known changes in reproductive behavior, but its effect on adoptions has not been investigated. Variation across states in the timing and extent of abortion legalization is used to identify the effects of changes in the legal status of abortion on adoption rates from 1961 to 1975. These effects are estimated in regression analyses that control for states' economic, demographic and political characteristics, as well as for health care availability within states. The rate of adoptions of children born to white women declined by 34-37% in states that repealed restrictive abortion laws before Roe v. Wade. The effect was concentrated among adoptions by petitioners not related to the child. Legal reforms resulting in small increases in access, such as in cases of rape and incest, were associated with a 15-18% decline in adoptions of children born to nonwhite women; however, this decline may have been due to other changes in the policy environment for such adoptions. Rates of adoption of children born to white women appear to have declined after Roe v. Wade, but this association is not statistically significant. The estimated effect of abortion legalization on adoption rates is sizable and can account for much of the decline in adoptions, particularly of children born to white women, during the early 1970s. These findings support previous studies' conclusions that abortion legalization led to a reduction in the number of "unwanted" children; such a reduction may have improved average infant health and children's living conditions.


Reactions of radicals with hydrolyzed Bi(III) ions: a pulse radiolysis study.
Radiolytic reduction of BiOClO4 in aqueous solutions leads to the formation of bismuth clusters and larger nanoparticles. The mechanisms of redox reactions of the polycationic Bi(III) species that exist in the solution were investigated with pulse radiolysis. The kinetic and spectral properties of the transients formed by the reaction of these species with the primary radicals from water radiolysis are reported. The single-electron reduction product, Bi9(OH)224+, absorbs at lambdamax = 273 nm, while the OH adduct, Bi9(OH)235+, has a broad absorption spectrum with a maximum at 280 nm and a shoulder at 420 nm. Several rate constants were measured: k (e-aq + Bi9(OH)225+) = 1.2 x 1010 M-1 s-1 and k (OH + Bi9(OH)225+) = 1.5 x 109 M-1 s-1. The reduced species, Bi9(OH)224+ further reacts with (CH3)2COH radicals, but not with CH2C(CH3)2OH radicals from t-butanol, to produce a doubly reduced polynuclear species. A few reactions of the reduction of the Bi salt in the presence of poly(acrylic acid) are also described. In the presence of the polymer, a metal-polymer complex is formed prior to the irradiation, and the reduction reactions are significantly slowed down.


A staff nurse's perspective of infection control problems.
Earlier this month astonishing figures causing major concern were released from the Department of Health (DoH) showing the number of cases of Clostridium difficile in the over 65s in hospitals in England. This article focuses upon what is already known about infection control and concludes that a greater collaborative approach to infection control is needed, with a prudent use of broad spectrum antibiotics and a greater use of precautionary isolation measures based on patient symptoms, if infection rates are to fall.


Indications for Open Reduction Internal Fixation of Anterior Pelvic Ring Disruptions.
In acute trauma, pelvic ring instability can lead to hemorrhage and hemodynamic instability. Pelvic ring instability and displacement that is not stabilized may lead to chronic pain, sitting imbalance, and limb length inequality. Methods and timing of securing anterior pelvic ring injuries operatively is controversial and debatable. Many orthopaedic trauma surgeons would agree that acceptable methods to treat a disrupted anterior pelvic ring fracture include nonoperative care, external fixation, internal spanning fixators, intramedullary superior ramus screws, and open reduction internal fixation. We will review the indications for open reduction internal fixation fractures and disruptions of the anterior pelvic ring.


Clinical outcomes associated with anti-obesity medications in real-world practice: A systematic literature review.
Anti-obesity medications (AOMs) are efficacious and well tolerated in randomized controlled trials, but findings may not be generalizable to routine clinical practice. This systematic literature review aimed to identify real-world (RW) evidence for AOMs to treat adults ( ≥ 18 years) with obesity or overweight (BMI ≥ 27 kg/m2 ). Searches conducted in MEDLINE, Embase, Health Technology Assessment (HTA) Database, National Health Service (NHS) Economic Evaluation Database, and Cochrane Central Register of Controlled Trials for studies of relevant FDA-approved AOMs yielded 41 publications. Weight loss (WL) was consistently observed, with 14% to 58.6% of patients achieving ≥ 5% WL on orlistat, phentermine/topiramate, naltrexone/bupropion, phentermine, or liraglutide in studies of 3-6 months' duration where this was measured. When cardiometabolic risk factors were assessed, AOMs reduced or had no impact on blood pressure, lipids, or glycemia. RW data on the impact of AOMs on existing obesity-related comorbidities and mortality were generally lacking. AOMs were associated with various adverse events, but these were of mild to moderate severity and no unexpected safety signals were reported. A pattern of poor adherence and persistence with AOMs was observed across studies. Overall, the review confirmed the effectiveness of AOMs in RW settings but demonstrated large gaps in the evidence base.


Mycotoxic porcine nephropathy and spontaneous occurrence of ochratoxin A residues in kidneys and blood of Polish swine.
Kidneys showing renal changes characteristic for mycotoxic porcine nephropathy were collected during the period 1 April 1982 to 31 March 1983 from 225,000 swine processed in a large slaughterhouse in the district of Poznań, Poland. Of 113 kidneys suspected of mycotoxic porcine nephropathy, 27 exhibited ochratoxin A levels from traces to 23 ng/g. In 17 kidneys the level of the toxin was lower than 2 ng/g. Increased frequency of ochratoxin A presence and its level in kidneys were observed during the spring. Of 195 porcine blood samples collected at random, 36 exhibited toxin levels from 3 to 270 ng/ml.


[Culture and purification of olfactory ensheathing cells from human fetal using different attachment rates combined with the technique of using NT3 intermittently].
To explore a simple and pragmatic method to obtain sufficient olfactory ensheathing cells from human fetal by using different attachment rates in harvested cells with the combinating of the technique of using NT3 intermittently. DMEM/F12 culture solution including 100 mL/L of fetal bovine serum or including NT3 was used to culture olfactory ensheathing cells intermittently every 48 h. The conditions and growth degree of OECs were observed, and P75 immunocytochemistry was used to estimate the purity of the cells. Human fetal OECs were positive after P75 immunocytochemistry. They appeared to be dipolar or tripolar cells and their processes formed a network in vitro. The purity of OECs in good conditions reached about 95% on 9 d and 83% on 12 d. The method of using different attachment rates combined with the technique of using NT3 intermittently can culture and purify OECs simply and effectively.


Physiologically based pharmacokinetic model for digoxin disposition in dogs and its preliminary application to humans.
A physiologically based pharmacokinetic model for digoxin disposition developed in the rat was modified to account for the interspecies differences in tissue-to-plasma digoxin concentration ratios and applied to the dog. The model provided a quantitative assessment of the time course of digoxin concentrations in dog plasma, various tissues, and urine. It also predicted the effect of renal failure on digoxin pharmacokinetics in the dog. An attempt to scale the dog model to humans by simply considering differences in organ volumes, organ flow rates, and digoxin clearances was partially successful. Good predictions of plasma digoxin concentration and urinary digoxin excretion after a single dose and of steady-state plasma, heart, and skeletal muscle digoxin concentrations were obtained. However, the model predicted considerably higher kidney digoxin concentrations than are actually found. Although the model adequately characterized the time course of digoxin concentrations in patients with moderate renal impairment, it provided a relatively poor fit to that observed in anuric patients.


The Flip Side of NIFTP: an Increase in Rates of Unfavorable Histologic Parameters in the Remainder of Papillary Thyroid Carcinomas.
The term noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was recently proposed to replace noninvasive follicular variant of papillary thyroid carcinoma (FVPTC) both to promote more conservative management of these tumors and spare patients the psychological burden of a cancer diagnosis. This reclassification will lower the incidence of papillary thyroid carcinoma (PTC). In addition, it could result in an increase in the rates of unfavorable histologic prognosticators for PTC overall because NIFTPs had previously accounted for many of the PTCs without these features. Our aim was to evaluate the potential impact of the reclassification of NIFTP on the rates of extrathyroidal extension, lymphovascular invasion, and lymph node metastases in PTC. We identified all PTCs clinically over 1 cm diagnosed on surgical resection between August 2010 and August 2012. The histopathologic characteristics, including PTC subtype, tumor size, presence of extrathyroidal extension and lymphovascular invasion, and surgical margin and lymph node status were all recorded. Based on these parameters, cases were classified according to the American Thyroid Association (ATA) risk stratification system for structural disease recurrence. Tumor slides for cases initially diagnosed as FVPTC were reviewed to identify tumors that would now be classified as NIFTPs. Our cohort included 348 cases of PTC, of which 94 (27%) would now be classified as NIFTPs. After excluding NIFTPs from the PTC category, there were increased rates of extrathyroidal extension (26% up from 19%, p = 0.046), lymphovascular invasion (37% up from 27%, p = 0.0099), and lymph node metastases (26% up from 19%, p = 0.045) among the remaining PTCs. Based on these changes in histologic features, 10% fewer cases were defined as ATA low risk (62% down from 72%, p = 0.0081). Our results indicate that the downgrading of some carcinomas to NIFTP will increase the rates of higher risk histologic parameters in the remaining PTCs by statistically significant margins. Although the overall survival for PTC is very high and would likely not be changed significantly by the introduction of NIFTP, additional studies evaluating the impact of the NIFTP shift are warranted.


Behaviour of lymphocytes from cancer patients and normal individuals cultured with phytohaemagglutinin.
Blood lymphocytes from cancer patients with solid tumours without any previous immunosuppressive treatment and from normal individuals, were cultured in vitro with a wide range of phytohaemagglutinin (PHA). Sixty two per cent of all the cancer patients studied show a minimal of no response to PHA in comparison with the normal population. The rest (38%), show a quantitative identical response than normals. However, the maximal response in these patients occur in the high PHA doses, while the normal individuals show their maximal activity with low PHA doses. The low or no PHA response showed by the 62% of patients, may indicate they have impaired cellular immunity. The high response showed by the other 38%, may indicate that the patients of this group have high cellular immunity capacity. This immunity, however, higher PHA doses are required to reach the maximal response compared with the seems to be different from that of normal individuals, since higher PHA doses are required in cancer patients to reach maximal response. These results also suggest that a large range of PHA doses may be important to detect the degree of cellular immunity in cancer patients compared with the normal population. One or two random PHA doses, may not show a distinction.


Mannan oligosaccharide supplementation in diets of sow and (or) their offspring improved immunity and regulated intestinal bacteria in piglet1.
The objectives of the current study were to explore the effects of mannan oligosaccharide (MOS) supplementation in the diets of sow and (or) their offspring on intestinal bacteria, intestinal and systemic inflammation in the piglet. A total of 60 multiparous sows (4 ± 1 parity; Landrace × Yorkshire) were fed either control diet (sCON, n = 30) or a diet containing 400 mg kg-1 MOS (sMOS, n = 30) from day 86 of gestation until weaning (day 20 of postpartum). On day 7 of age, offspring (Duroc × Landrace Yorkshire) were assigned within sow treatments and fed control diet (pCON) or diet containing 800 mg kg-1 MOS (pMOS) for 28 d (end at 35 d of age), resulting in four piglet diet groups (n = 15 litters per diet group): sCON-pCON, sCON-pMOS, sMOS-pCON, and sMOS-pMOS. Results found that piglet diet MOS increased or tend to increase Lactobacillus amount in the ileum digesta (P < 0.01) and jejunum digesta (P = 0.07), respectively; while tend to decrease Escherichia coli amount in jejunum digesta (P =0.06) and cecum digesta (P = 0.08). Both sow and piglet diets add MOS (sMOS-pMOS) increased Lactobacillus amount but decreased E. coli amount in jejunum digesta (P < 0.05) compared with the sCON-pCON diet group. In addition, sow diet MOS (rather than piglet diet MOS) increased sIgA content in piglet jejunum mucosa compared with control (P = 0.04). Sow diet MOS decreased toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), and interleukin 8 (IL-8) mRNA levels (P < 0.05) and tended to decrease nuclear factor-κB p65 (NF-κB p65) mRNA level (P = 0.07) in piglet intestinal lymphatic. The interaction effects between sow and piglet diets were found on the mRNA levels of NF- κB p65 (P = 0.03) and IL-8 (P = 0.02) in piglet jejunum. Finally, the sow diet MOS decreased proinflammatory cytokines IL-2 (P < 0.01) and IL-4 (P < 0.01) concentrations in piglet serum. Piglets diet MOS decreased the contents of IL-2 (P = 0.03), IL-4 (P = 0.01) and interferon (IFN)-γ (P < 0.01) while increased anti-inflammatory cytokine IL-10 (P < 0.01) content in serum. The interaction effects between sows and piglet diets on IL-4 (P = 0.02), IL-10 (P < 0.01), and IFN-γ (P = 0.08) were observed. In conclusion, sow and/or piglet diet MOS could improve intestinal microbiota, enhance intestinal mucosal immune competence, and suppress intestinal and systemic inflammation in the piglet.


A real-time PCR screening assay for the universal detection of lumpy skin disease virus DNA.
The resurgence of lumpy skin disease virus isolates of different genotypic natures abolishes the accuracy of assays that target either vaccine or field strain genome. The aim of the present study was to develop a universal real-time PCR assay using TaqMan chemistry to cover field, vaccine, and recombinant strains of lumpy skin disease virus isolates. The PCR assay was designed based on a LSDV044 target region that offers a unique identification locus to facilitate the sensitive and specific detection of all isolates known to date. The efficiency of amplification, determined over five orders of magnitude, was 93%, with the standard deviation remaining in the range of 0.11-0.23. Evaluation of the assay repeatability on three different days revealed that the inter-run variability ranged from 0.83 to 1.22 over five repetitions across three runs. This new screening assay is proposed as a fast, efficient, and sensitive tool that can be employed in the basic or applied surveillance studies regardless of the genotype. Moreover, the assay can be used for the routine laboratory testing of animal samples during eradication programs for lumpy skin disease.


Transition metal complexes meet the rylenes.
This Perspective highlights an emerging area of metal-organic chromophore science related to the photochemistry and photophysics of coordination compounds and organometallic structures covalently tethered to rylene (naphthalene-cored) imide and diimide scaffolds. This combination of molecules renders highly colourful structures producing an array of excited state behaviour and in some instances strongly aggregated self-assembled metal-organic architectures.


Differentiating feline T and B lymphocytes by rosette formation.
The number of bone marrow-derived and thymus-dependent lymphocytes in the peripheral blood of felines was assessed. Feline bone marrow-derived lymphocytes were determined by erythrocyte antibody complement (EAC)-rosette formation and membrane immunofluorescence. A good correlation was observed between the cells forming EAC-rosettes (mean of 40.2 +/- 9.7%) and those possessing membrane immunoglobulins (mean of 45.3 +/- 4.1%). Feline thymus-dependent lymphocytes form non-immune (E)-rosettes with rodent erythrocytes (mouse, rat, guinea pig) but not with erythrocytes from humans, monkeys, dogs, mongooses, chickens, rabbits, sheep, and hamsters. An average of 32.3 +/- 992% of the peripheral blood lymphobytes of cats formed rosettes with guinea pig erythrocytes. Antibody blocking, cytotoxicity, and mix-rosette studies demonstrated that guinea pig red blood cells bind specifically to T lymphocytes. Of feline peripheral blood lymphocytes, 41.0 +/- 7.5% showed fluorescent staining with fluorescein-labeled rabbit anti-cat thymus antiserum.


Infant Trauma Management in the Emergency Department: An Emergency Medicine Simulation Exercise.
In a trauma situation, it is essential that emergency room physicians are able to think clearly, make decisions quickly and manage patients in a way consistent with their injuries. In order for emergency medicine residents to adequately develop the skills to deal with trauma situations, it is imperative that they have the opportunity to experience such scenarios in a controlled environment with aptly timed feedback. In the case of infant trauma, sensitivities have to be taken that are specific to pediatric medicine. The following describes a simulation session in which trainees were tasked with managing an infantile patient who had experienced a major trauma as a result of a single vehicle accident. The described simulation session utilized human patient simulators and was tailored to junior (year 1 and 2) emergency medicine residents.


Paradox in melanoma: more patients fewer publications.
The incidence of melanoma has increased more dramatically than any other malignancy in the last years. In this study, we compared the numbers of publications between melanoma and other cancers over the last 20 years, and we aimed to understand the relationship between publications on melanoma and other cancers using publication rates and frequencies. We conducted a systematic search through PubMed using search terms 'melanoma' and 'cancer' to identify the numbers of publications on melanoma and other cancers. The numbers and life-time risk rates of both melanoma and other cancer patients over the years were obtained from 'Cancer Statistics' articles published annually by American Cancer Society. Both melanoma and other cancer related publications increased in number steadily at the same rate (3.01 times) and the ratio of melanoma-related publications to all cancer publications has not changed over the years: around 3.4% on average. The rates of melanoma increased more rapidly than those of other cancers; 2.02 and 1.44 times, respectively. Similarly, the incidence of melanoma among all malignancies has increased from 3.91 to 5.47%. The lifetime risk of developing cancer has stayed stable at around 40%, whereas the lifetime risk of developing melanoma has increased by 2.12 times over the years, from 1.47 to 3.1%. In conclusion, the increase in the melanoma-related publication numbers has failed short to meet the dramatic increment of melanoma patient numbers. We believe that more publications are required according to the rising incidence of the disease.


[Brief analytical review of additional possible mechanisms in the pathogenesis of AIDS].
It is generally agreed that HIV itself has the primary role in the initiation and propagation of the pathogenic process of the infection. Nonetheless, a number of important issues concerning the pathogenesis of HIV infection remain unresolved. For example, it remains unclear how CD4+ T cells are lost after HIV infection. The low frequency of infected cells seen even in advanced infection implies that a direct cythopathic effect of HIV on infected CD4+ T cells cannot explain their disappearance. Multiple and diverse mechanisms have been proposed as supplements to the HIV in the destruction of CD4+ cells and the pathogenesis of AIDS. However, it is not yet possible to state confidently which additional mechanism(s) is important. Identification of the nature of this supplemental process has become essential for successful, non-harmful intervention. We propose here a short analytical review of the possible supplemental mechanisms of immunological destruction in AIDS in order to emphasize the complexity of the pathogenesis of the disease.


Chemokine receptor CCR1 regulates inflammatory cell infiltration after renal ischemia-reperfusion injury.
Neutrophils and macrophages rapidly infiltrate the kidney after renal ischemia-reperfusion injury, however specific molecular recruitment mechanisms have not been fully delineated for these cell types. Here we provide genetic and pharmacologic evidence supporting a positive role for the chemokine receptor CCR1 in macrophage and neutrophil infiltration in a 7 day mouse model of renal ischemia-reperfusion injury. By day 7, injured kidneys from mice lacking CCR1 contained 35% fewer neutrophils and 45% fewer macrophages than injured kidneys from wild-type control mice. Pretreatment of wild-type mice with the specific CCR1 antagonist BX471 also suppressed neutrophil and macrophage infiltration in the model. Injured kidneys from mice lacking CCR1 also had reduced content of the CCR1 ligands CCL3 (MIP-1alpha) and CCL5 (RANTES) compared with injured kidneys from wild-type controls, suggesting a leukocyte source for these inflammatory chemokines and existence of a CCR1-dependent positive feedback loop for leukocyte infiltration in the model. Local leukocyte proliferation and apoptosis were detected after injury, but were not dependent on CCR1. Also, the extent of necrotic and fibrotic damage and decline in renal function in injured kidneys was similar in wild-type and CCR1-deficient mice. Thus, CCR1 appears to regulate trafficking of macrophages and neutrophils to kidney in a mouse model of renal ischemia-reperfusion injury, however this activity does not appear to affect tissue injury.


[The physician executive and laboratory tests].
Sera Central Hospital was founded in 1953 as Sera District Medical Center under the auspices of the neighboring five towns. At that time, the hospital had 3 doctors, 10 nurses, and 20 beds. But now in 1992, we have 12 doctors, 53 nurses and 110 beds. The present medical specialists are physician (4), surgeon (2), orthopedist (3), pediatrician (1), clinical laboratory physician (1), and dentist (1). Although the yearly income and expenditures were well balanced until 1989, thereafter the income began to decrease insidiously and expenditures began to increase year by year. In this symposium titled "Suggestions for Clinical Laboratory Medicine by Experienced Hospital Directors," I must refer to the issue of "Clinical Laboratory Medicine Administrator's Standpoint". Recently, the unaccustomed phrase "Physician Executive" is occasionally heard as the details of medical care become more numerous and more intricate and economic efficiency is strictly persued. From this perspective, the clinical laboratory physician is responsible for managing the laboratory department with well disciplined knowledge and technique. Therefore, training as "Physician Executive" has developed naturally within the field of Clinical Laboratory Medicine. So, I cannot help coming to the conclusion that the management of a hospital, as a matter of course, will be entrusted to a doctor including clinical laboratory physician who can do his best for the citizens, for the patients, and ultimately for ourselves.


PBP bridged [3]ferrocenophane: a bisphosphanylborane with a redox trigger.
Stereospecific access to the unprecedented P-B-P bridged [3]ferrocenophane Fe(C5H4PtBu)2BMes is presented. In contrast to acyclic ferrocenylphosphanes, we find evidence for a shift of spin-density from Fe to P upon pyramidal inversion of the P centers in the mono-cation; the latter has a lifetime of τ = 0.31(4) s.


Cognitive processess and cognitive reserve in multiple sclerosis.
Multiple Sclerosis (MS) is characterized by motor, cognitive, and neuropsychiatric symptoms, which can occur independently. While MS is traditionally considered an inflammatory disease of the white matter, degeneration of gray matter is increasingly recognized as an important contributor to the progressive cognitive decline. A protective factor against the progression of cognitive dysfunction in MS could be the cognitive reserve, defined as resistance to brain dysfunction. Aim of the present study is to evaluate the role of cognitive reserve for different aspects of cognitive dysfunction of patients with MS. We found that patients with MS and lower cognitive reserve have poorer neuropsychological performance and slower information speed processing. These findings support the notion that intellectual reserve may protect some aspects of cognitive function in patients with MS.


[Operative treatment of anterior cranial base meningiomas].
The aim of the study is to assess outcome of surgical treatment of anterior cranial base meningiomas with special emphasis on the evaluation of visual skills after surgery. A series of 52 consecutive patients operated on for anterior cranial base meningioma in the last ten years is reported. 18 patients had decreased visual acuity on admission, 6 experienced blindness in one eye, and 4 were totally blind; defects of visual fields were found in 17 patients. Primary optic atrophy and secondary optic atrophy were noted in fundcoscopy in 20 and 2 patients, respectively. Papilloedema was found in 3 patients. Meningiomas were resected radically (Simpson I surgery) in 13 patients and in 34 patients Simpson II surgery with coagulation of the dural attachment was made; meningiomas were partially removed in 5 patients (Simpson IV surgery). In one patient dense hemiparesis occurred after the surgery, and 3 others presented adynamic syndrome, one of whom made a good recovery in follow-up examination. Two patients died: the first one due to a large brain oedema and the second one due to myocardial infarction after uncomplicated postoperative course. The postoperative course in the other 46 patients was uneventful with good outcome. Visual acuity improved in 15 cases and did not change in 10 patients; visual acuity further decreased in 3 patients. Visual recovery is significantly related to preoperative visual acuity values of no less than 0.3 D and to the presence of normal optic discs on fundoscopic examination additionally tumour size less than 3.5 cm favourably affects visual prognosis in meningiomas of tuberculum sellae.


[The evolution of mortality in the first year of life in Spain (1975-1988)].
In recent years, the rate of decline in infant mortality and the proportional mortality by some causes of death in the first year of life have had important changes. The objectives of this study are to describe such changes, and to suggest hypotheses about their meaning. Infant, early neonatal, late neonatal and postneonatal mortality rates from 1975 to 1988 were calculated with information from the death register. Also, several indicators of the trends of those rates and proportional mortality by "certain conditions originating in the perinatal period" have been calculated. The reduction in infant mortality was due, mainly, to early neonatal mortality, which had an annual average decline of 4.6% during the study period. The proportional mortality and the mortality rate by perinatal conditions in the postneonatal period increased between 1975 and 1988. The first increased from 1.3% to 5.2%, and the second from 0.07 to 0.15 per 1000 live births. Hypotheses about the meaning of these results are suggested, and some actions are proposed in order to monitor and conduct research on mortality during the first year of life.


Angiographic and intravascular ultrasonographic findings after endovascular stent implantation.
The study was an attempt to evaluate the benefit of intravascular ultrasound imaging (IVUS) as a supplement to follow-up angiography after endovascular stent implantation. A consecutive series of 15 patients underwent stent implantation in the peripheral or coronary arteries. Ten Palmaz stents, 3 Palmaz-Schatz stents and 2 Wallstents were used. After a period from 1 to 6 months (mean 3.2 months) follow-up angiography was performed. In 12 cases the angiography was combined with IVUS of the stent and the adjacent vessel segments. In one case IVUS failed due to the tortuous course of the vessel, in another case the stent was occluded, and in one case IVUS was considered too hazardous. In stents of diameter > or = 5 mm, ultrasound (US) did not reveal more information concerning vessel and stent diameter, stent stenosis and intraluminal surface contact than angiography alone. Smaller stents were insufficiently visualized by conventional radiologic methods. In small stents only IVUS permitted an exact stent identification and differentiation between stent stenosis and stenosis of the native vessel. At US imaging artifacts, caused by the highly reflectant metallic stent struts, interfered with the native vessel wall and partly obscured its structural details.


Recombinant ovine atadenovirus induces a strong and sustained T cell response against the hepatitis C virus NS3 antigen in mice.
Ovine atadenovirus (OAdV) is a novel gene transfer vector with excellent in vivo gene transfer characteristics. In the present study, we have investigated the ability of an OAdV vector to mediate a T cell response to an antigen of the hepatitis C virus (HCV) in mice. Specifically, an expression cassette coding for non-structural protein 3 (NS3) of hepatitis C virus was inserted into the OAdV genome and the resulting recombinant virus (OAdV-ns3) was shown to propagate stably and to express the ns3 gene at a high level in vitro. A single injection of this non-replicating vector into BALB/c mice resulted in a strong induction of NS3-specific, IFN-gamma secreting T-lymphocytes as measured by direct ex vivo ELISpot assay. The number of IFN-gamma secreting lymphocytes remained nearly unaltered for a period of at least 10 weeks. The immune response was shown to depend on virus dose but a single intramuscular injection of less than 10(8) infectious particles of OAdV-ns3 was sufficient to induce a significant NS3-specific T cell response. Moreover, this response was not affected by prior immunisation of animals with human adenovirus type 5 (HAdV-5). The results of our study provide proof for the concept that OAdV vectors may be valuable tools for vaccination and immunotherapy even in the face of natural immunity to human adenoviruses.