Validation of the wild-type influenza A human challenge model H1N1pdMIST: an A(H1N1)pdm09 dose-finding investigational new drug study.
Healthy volunteer wild-type influenza challenge models offer a unique opportunity to evaluate multiple aspects of this important virus. Such studies have not been performed in the United States in more than a decade, limiting our capability to investigate this virus and develop countermeasures. We have completed the first ever wild-type influenza A challenge study under an Investigational New Drug application (IND). This dose-finding study will lead to further development of this model both for A(H1N1)pdm09 and other strains of influenza. Volunteers were admitted to an isolation unit at the National Institutes of Health Clinical Center for a minimum of 9 days. A reverse genetics, cell-based, Good Manufacturing Practice (GMP)-produced, wild-type A(H1N1)pdm09 virus was administered intranasally. Escalating doses were given until a dose was reached that produced disease in a minimum of 60% of volunteers. An optimal dose of 10(7) tissue culture infectious dose 50 was reached that caused mild to moderate influenza disease in 69% of individuals with mean viral shedding for 4-5 days and significant rises in convalescent influenza antibody titers. Viral shedding preceded symptoms by 12-24 hours and terminated 2-3 days prior to symptom resolution, indicating that individuals may be infectious before symptom development. As expected, nasal congestion and rhinorrhea were most common, but interestingly, fever was observed in only 10% of individuals. This study represents the first healthy volunteer influenza challenge model using a GMP-produced wild-type virus under an IND. This unique clinical research program will facilitate future studies of influenza pathogenesis, animal model validation, and the rapid, efficient, and cost-effective evaluation of efficacy of novel vaccines and therapeutics. Clinical Trials Registration.NCT01646138.


Syntheses, Structures, and Electrochemistry of the Defective ccp [Pt33(CO)38](2-) and the bcc [Pt40(CO)40](6-) Molecular Nanoclusters.
The molecular [Pt33(CO)38](2-) nanocluster was obtained from the thermal decomposition of Na2[Pt15(CO)30] in methanol. The reaction of [Pt19(CO)22](4-) with acids (1-2 equiv) affords the unstable [Pt19(CO)22](3-) trianion, which evolves with time leading eventually to the [Pt40(CO)40](6-) hexa-anion. The total structures of both nanoclusters were determined via single-crystal X-ray diffraction. [Pt33(CO)38](2-) displays a defective ccp Pt33 core and shows that localized deformations occur in correspondence of atomic defects to "repair" them. In contrast, [Pt40(CO)40](6-) shows a bcc Pt40 core and represents the largest Pt cluster with a body-centered structure. The rich electrochemistry of the two high-nuclearity platinum carbonyl clusters was studied by cyclic voltammetry and electrochemical in situ Fourier transform infrared spectroscopy. The redox changes of [Pt33(CO)38](2-) show features of chemical reversibility and electrochemical quasi-reversibility, and the vibrational spectra in the CO stretching region of the nine redox forms of the cluster [Pt33(CO)38](n) (n = 0 to -4, -6 to -9) are reported. Almost all the redox processes exhibited by [Pt40(CO)40](6-) are chemically and electrochemically reversible, and the eight oxidation states of [Pt40(CO)40] from -4 to -11 were spectroscopically characterized. The effect of the more regular bcc Pt-carbonyl cluster structure of [Pt40(CO)40](6-) with respect to that of the defective ccp Pt33 core on the redox behavior is discussed.


Application of Multinuclear MAS NMR for the in situ Monitoring of Hydrothermal Synthesis of Zeolites.
In situ MAS NMR studies on the monitoring of hydrothermal synthesis of zeolites are reviewed. The first part of the review contains information on the experimental techniques used for the in situ NMR studies in static and MAS conditions. In the second part, the main capabilities of the in situ 1 H, 11 B, 13 C, 14 N, 19 F, 23 Na, 27 Al, 29 Si and 31 P MAS NMR for the elucidation of the mechanism of hydrothermal synthesis of zeolites are examined and the data on NMR lines identification are summarized. In the last part the main application areas of the techniques are considered and illustrated with examples taken from the mechanistic studies of zeolites A, X, MFI and BEA synthesis. A cross-reference index between the materials studied, the experimental approaches used, the mechanistic information obtained, and the corresponding literature sources is established.


Highly Electron-Deficient Pyridinium-Nitrones for Rapid and Tunable Inverse-Electron-Demand Strain-Promoted Alkyne-Nitrone Cycloaddition.
Highly accelerated inverse-electron-demand strain-promoted alkyne-nitrone cycloaddition (IED SPANC) between a stable cyclooctyne (bicyclo[6.1.0]nonyne (BCN)) and nitrones delocalized into a Cα-pyridinium functionality is reported, with the most electron-deficient "pyridinium-nitrone" displaying among the most rapid cycloadditions to BCN that is currently reported. Density functional theory (DFT) and X-ray crystallography are explored to rationalize the effects of N- and Cα-substituent modifications at the nitrone on IED SPANC reaction kinetics and the overall rapid reactivity of pyridinium-delocalized nitrones.


Effect of dorsal and ventral limb ectoderm on the development of the limb of the embryonic chick.
Limb ectoderm plus a small amount of subjacent mesoderm obtained from the dorsal or the ventral surface of each of the four limbs of the chick embryo were grafted to the dorsal surface of the right wing in either reversed or normal orientation. The host wings developed in abnormal humerus in all cases except when the graft was obtained from the dorsal surface of the right wing and was in normal orientation. However, the nature of the abnormalities varied with the source of the graft and with the orientation of the graft. It is unlikely that the abnormalities were related solely to the small amount of mesoderm grafted since previous experiments have demonstrated that the mesoderm would regulate. Flank ectoderm plus a small amount of flank mesoderm did not cause limb abnormalities when grafted in the same manner.


[Increased level of Th17 cells in peripheral blood correlates with the development of hepatocellular carcinoma].
To investigate the potential correlation between the level of Th17 cells in peripheral blood and the development of human hepatocellular carcinoma (HCC). Th17 cells in the blood samples from 61 HCC patients and 38 healthy controls were assessed by flow cytometry (FCM). The mRNA expression levels of IL-17, IL-23p19 and RORc in peripheral blood mononuclear cells (PBMC) were detected by quantitative real-time PCR. The potential correlation of increased Th17 cells in blood with the clinical characteristics of the 61 patients, including gender, age, preoperative AFP concentration, tumor diameter, portal vein tumor thrombus (PVTT), metastasis and TNM stages was analyzed. Statistical analysis was performed using the software GraphPad Prizm 5.0. The number of Th17 cells in 61 HCC patients was significantly higher than that in the normal controls (4.67% ± 0.79% vs 3.25% ± 0.68%, P < 0.0001). The same tendency was also found in the mRNA levels of IL-17, IL-23p19 and RORc in PBMC (P < 0.05). The increased level of Th17 cells in HCC patients showed a positive correlation with the tumor size, PVTT, metastasis and TNM stages (P < 0.05 for each group). The level of Th17 cells in HCC patients was increased along with the increasing TNM stages I to stage IV: 4.05% ± 0.82%, 4.32% ± 0.67%, 4.94% ± 0.70%, and 5.22% ± 0.87%, respectively, where the level of Th17 cells in patients with advanced stage of HCC (III-IV) was significantly higher than that in early stage (I-II, P = 0.0008). The increased of level of Th17 cells in peripheral blood of HCC is significantly correlated with the tumor size, PVTT, metastasis and TNM stage, indicating that the Th17 cells might participate in promoting invasion and progression of HCC directly or indirectly by secreting characteristic cytokines.


X-ray radiation shielding and microscopic studies of flexible and moldable bandage by in situ synthesized cerium oxide nanoparticles/MWCNTS nanocomposite for healthcare applications.
This research reports a robust method for developing advanced flexible and moldable X-ray shielding bandages by harnessing an in situ synthesized polygonal cerium oxide nanoparticles/MWCNTs nanocomposite. The developed advanced hybrid nanocomposite was thoroughly blended with silicone rubber, namely polydimethylsiloxane (PDMS) to form an advanced hybrid gel which was then coated on a conventional cotton bandage to develop an advanced flexible, moldable X-ray shielding bandage. The combined effects were analyzed to determine their unique X-ray reduction properties and were very effective. The linear attenuation value of the developed bandage (untreated cotton bandage coated with CeO2/MWCNT/PDMS), varied from 1.274 m-1 to 0.549 m-1 and the mass attenuation values from 0.823 m2 kg-1 to 0.354 m2 kg-1 for kVp 40 to 100 respectively. The improved features of high density and efficiency of protection are because of the binary protective effect of CeO2 nanoparticles and MWCNT. The morphological features of the developed material were characterized using various techniques such as TEM, SEM, XRD, and EDXA. The developed bandage is an entirely lead-free product, thin and light, has high shielding performance, flexibility, durability, good mechanical strength, doesn't crack easily (no crack), and can be washed in water. It may therefore be useful in various fields, including diagnostic radiology, cardiology, urology, and neurology treatments, attenuating emergency radiation leakages in CT scanner rooms or via medical equipment, and safeguarding complex shielding machinery in public areas.


Combating insulin resistance with the paleo diet.
Lifestyle changes that include adopting a healthy diet, such as the paleo diet, can help prevent prediabetes and T2DM. This article explores the potential benefits of replacing low-calorie diets with the paleo diet. As primary care providers, NPs are positioned to help inform patients, particularly those with prediabetes and T2DM, about healthy lifestyle choices and provide them with resources to achieve weight loss success.


Plasma IGFBP-2 levels reveal heterogeneity in hepatic fat content in adults with excess visceral adiposity.
Obesity is frequently accompanied by a fatty liver. However, some individuals with high abdominal fat levels nevertheless have low levels of liver fat. Reasons for such discordant phenotypes are unclear. In this paper, we report that among asymptomatic individuals with high levels of visceral fat, low concentrations of IGFBP-2 in the circulation were associated with significantly higher hepatic fat content compared to those with high IGFBP-2 levels. We conclude that quantification of plasma IGFBP-2 concentrations may be useful to identify the early risk for liver fat accumulation in apparently healthy individuals without cardiovascular symptoms. Although excess visceral adiposity (VAT) is generally associated with increased liver fat (LF), recent evidence has revealed heterogeneity in LF content among adults with visceral obesity, potentially contributing to specific differences in cardiometabolic outcomes. Reasons for such discordant VAT-LF phenotypes are largely unknown. The present study aimed at assessing whether circulating levels of insulin growth-factor binding protein-2 (IGFBP-2) could be a useful biomarker in the identification of heterogenous and discordant VAT-LF phenotypes. A sample of 308 middle-aged Caucasian apparently healthy men and women without cardiovascular symptoms were studied for the present cross-sectional analyses. Fasting plasma glucose and lipid levels were assessed and an oral glucose tolerance test was performed. Hepatic fat fraction (HFF) was measured using magnetic resonance spectroscopy whereas VAT was assessed by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants were then classified on the basis of median VAT (81 mL) and IGFBP-2 levels (233 ng/mL). Individuals with high levels of VAT were characterized by higher waist circumference, lower insulin sensitivity, as well as by higher plasma triglyceride and lower HDL-cholesterol levels. Plasma IGFBP-2 levels were inversely correlated with HFF (r = -0.39, p < 0.0001). Among men and women with high levels of VAT, those with low levels of IGFBP-2 had significantly higher HFF (7.5 ± 0.7%), compared to participants with high IGFBP-2 concentrations (3.2 ± 0.5%, p < 0.0001). In the presence of excess VAT, high IGFBP-2 concentrations are associated with low levels of LF. Although additional studies will be necessary to establish causality and further clarify the clinical implications of these observations, these findings are concordant with a novel function of IGFBP-2 in modulating susceptibility to non-alcoholic fatty liver disease (NAFLD) in the presence of visceral obesity.


Targeting macrophage and microglia activation with colony stimulating factor 1 receptor inhibitor is an effective strategy to treat injury-triggered neuropathic pain.
Introduction Neuropathic pain is a debilitating condition. The importance of neuroimmune interactions in neuropathic pain has been evidenced by the involvement of different immune cells in peripheral and central sensitization of pathological pain. Macrophages and microglia are the most abundant immune cells activated in injured nerves and spinal cord, respectively. Several lines of evidence showed that macrophage/microglia survival, activation, proliferation, and differentiation require the involvement of macrophage-colony stimulating factor. In this study, we investigated whether blocking macrophage-colony stimulating factor/colony stimulating factor 1 receptor signaling can be effective in relieving neuropathic pain. Materials and methods Partial sciatic nerve ligation was performed in mice to induce neuropathic pain behavior. Mice were orally treated with a selective colony stimulating factor 1 receptor inhibitor, PLX5622, daily in both preventive (two days prior to surgery until D14 post-partial sciatic nerve ligation) and reversal paradigms (D28-D33 post-partial sciatic nerve ligation). Animal neuropathic pain behavior was monitored using von Frey hairs and acetone application. Phenotype of macrophages in injured nerves was analyzed at D3 and D33 post-injury using flow cytometry analysis. The effect of PLX5622 on microglia activation in lumbar spinal cord was further examined by immunohistochemistry using Iba-1 antibody. Results Significant alleviation of both mechanical and cold allodynia was observed in PLX5622-treated animals, both in preventive and reversal paradigms. PLX5622 treatment reduced the total number of macrophages in injured nerves, it appears colony stimulating factor 1 receptor inhibition affected more specifically CD86+ (M1 like) macrophages. Consequently, the expression of various pro-inflammatory cytokines (TNF-α, IL-1β) was reduced. Microglia activation in dorsal horn of lumbar spinal cord following partial sciatic nerve ligation was significantly inhibited with PLX5622 treatment in both preventive and reversal paradigms. Conclusion Macrophages in peripheral nerve and microglia in the spinal cord are required in the generation and maintenance of injury-associated neuropathic pain. Blocking macrophage-colony stimulating factor/colony stimulating factor 1 receptor signaling on these myeloid cells along the pain transmission pathway is an effective strategy to alleviate neuropathic pain.


Multiple epithelioid hemangioedothelioma of the skull in a child: A case report.
Epithelioid hemangioedothelioma (EHE) is a rare vascular tumor characterized by neoplastic proliferation of epithelioid or histiocytoid epithelial cells. EHE of bone constitutes <1% of primary malignant bone tumor. EHE in the skull is an extremely rare case. Here, we report a case of multiple neoplasm of the skull in a 15-month-old boy who presented with gradual facial swelling for 2 months. On computed tomography (CT) scan, multiple irregular osteolytic lesions were seen on the right maxillary, sphenoid, left zygoma, and roof of the left orbit. Excisional surgery of the lesion was planned. Histopathological and immunohistochemical examination of excised specimen suggest it to be epithelioid hemangioedothelioma. Follow-up for 6 months showed no recurrence. Epithelioid hemangioedothelioma is a locally aggressive tumor with metastatic potential. CT imaging could help in assessment of lesion, but final diagnosis is possible only with histopathology. Complete surgical resection at the early stage of the disease is the most effective treatment with better prognosis.


Acute complicated sphenoiditis in childhood. Case report and literature review.
In ENT practice, acute uncomplicated sphenoiditis is rarely diagnosed: very often diagnosis is involved for multiform and unspecific symptomatology, such as to sham nervous, visual and upper respiratory tract diseases. Only a careful differential diagnostics and an instrumental investigation consents to realise quickly a specific treatment, avoiding some complications, still frequent. This case-report, underlines that the polyspecialists' co-operation is necessary to make a correct diagnosis, and to avert important and dangerous complications into shapes of sphenoiditis.


Controlled self-assembly of collagen fibrils by an automated dialysis system.
In vitro self-assembled collagen fibrils form a variety of different structures during dialysis. The self-assembly is dependent on several parameters, such as concentrations of collagen and alpha1-acid glycoprotein, temperature, dialysis time, and the acid concentration. For a detailed understanding of the assembly pathway and structural features like banding pattern or mechanical properties it is necessary to study single collagen fibrils. In this work we present a fully automated system to control the permeation of molecules through a membrane like a dialysis tubing. This allows us to ramp arbitrary diffusion rate profiles during the self-assembly process of macromolecules, such as collagen. The system combines a molecular sieving method with a computer assisted control system for measuring process variables. With the regulation of the diffusion rate it is possible to control and manipulate the collagen self-assembly process during the whole process time. Its performance is demonstrated by the preparation of various collagen type I fibrils and native collagen type II fibrils. The combination with the atomic force microscope (AFM) allows a high resolution characterization of the self-assembled fibrils. In principle, the represented system can be also applied for the production of other biomolecules, where a dialysis enhanced self-assembly process is used.


Extracellular vesicles in type 2 diabetes mellitus: key roles in pathogenesis, complications, and therapy.
Type 2 diabetes mellitus (T2DM), a chronic disease, is widely prevalent all over the world. In recent years, the roles of some extracellular vesicles (EVs) in T2DM have attracted much attention. EVs are bilayer membrane vesicles secreted from most cells and can participate in regulating various physiological and pathological processes in vivo by being transported between cells. Recently, it was discovered that some abnormal EVs can contribute to the occurrence of T2DM by inducing insulin resistance and can also participate in the complications of T2DM. In addition, some stem/progenitor cells-derived EVs have a potential application in the therapy of T2DM. This review introduces basic concepts of EVs and summarizes the roles of EVs in the pathogenesis, complications, and therapy of T2DM.


Evidence that the newly cloned low-density-lipoprotein receptor related protein (LRP) is the alpha 2-macroglobulin receptor.
The human placental receptor (alpha 2MR) for alpha 2-macroglobulin-proteinase complexes contains 3 polypeptides of approx. 500 kDa, 85 kDa, and 40 kDa. N-terminal sequence analysis of the 500 kDa and 85 kDa polypeptides, analysis of a random selection of peptides convering 536 residues from these polypeptides, and analysis of a 1772 bp cDNA encoding part of the 500 kDa polypeptide provide evidence that the 500 kDa and 85 kDa chains are the alpha- and beta-subunits, respectively, of a recently cloned hepatic membrane protein, termed the low density lipoprotein receptor related protein (LRP) (Herz, J., Hamann, U., Rogne, S., Myklebost, O., Gausepohl, H. and Stanley, K.K. (1988) EMBO J. 7, 4119-4127; Herz, J., Kowal, R.C., Goldstein, J.L. and Brown, M.S. (1990) EMBO J. 9, 1769-1776). N-terminal sequence analysis of the 40 kDa polypeptide shows that it is of distinct genetic origin. It is suggested that LRP is the functional receptor for alpha 2-macroglobulin-proteinase complexes (alpha 2MR) and in addition may have as yet unsettled functions in lipoprotein metabolism.


Poly-p-hydroquinone Ethers: Isoenergetic Molecular Wires with Length-Invariant Oxidation Potentials and Cation Radical Excitation Energies.
Typical poly-p-phenylene wires are characterized by strong interchromophoric electronic coupling with redox and optical properties being highly length-dependent. Herein we show that an incorporation of a pair of para-methoxy groups at each p-phenylene unit in poly-p-phenylene wires (i.e., PHEn) changes the nodal structure of HOMO that leads to length-invariant oxidation potentials and cation radical excitation energies. As such, PHEn represents a unique class of isoenergetic wires where hole delocalization mainly occurs via dynamic hopping and thus may serve as an efficient medium for long-range charge transfer. Availability of these wires will allow demonstration of long-range electron transfer via incoherent hopping using donor-bridge-acceptor systems with isoenergetic PHEn-based wires as bridges.


[Acute form of primary bilharziasis].
Acute schistosomiasis is observed in subjects with primary infestation, Schistosoma mansoni and S. japonicum being the responsible parasites in the vast majority of cases. The disease occurs between 2 weeks and 6 months from the first infesting bath and presents as fever with cutaneous, pulmonary and gastrointestinal manifestations. Eosinophilia is frequent. The diagnosis is made by serological tests. Myelopathies are rare and may leave severe sequelae. Treatment rests on praziquantel combined with a short course of corticosteroid therapy.


Safety assessment of gamma-glutamylcysteine sodium salt.
γ-Glutamylcysteine (GGC) is a relatively unexplored option for the treatment of chronic glutathione depletion related disorders that involve down regulation of GGC synthetase. High purity GGC (sodium salt) has only recently become available and, given its reactive capacity, required an investigation of its safety profile. In this report, GGC sodium salt was demonstrated to be safe according to Organisation for Economic Cooperation and Development (OECD) toxicology protocols for acute and repeated doses. No mortalities or adverse effects were observed in Wistar rats following the acute oral (gavage) administration of 2000mg sodium GGC /kg body weight. No animal deaths occurred with daily administration (1000mg/kg sodium GGC) over 90days, with a post trial 28day observation period. GGC had no significant effect on feed consumption, body weights, physical appearance, neurological behaviour and urine chemistry. No consistent significant differences between treatment groups were observed in haematological and clinical chemistry parameters. Similarly, no post-mortem necroscopically identified abnormalities could be attributed to GGC. Based on these observations, sodium GGC can be classed as not acutely toxic at 2000mg/kg, with a no-observed-adverse-effect level (NOAEL) of at least 1000mg/kg/day for systemic toxicology from repeated dose oral gavage administration.


Lead toxicity in humans from contaminated flour in Albania.
In April 1997, a severe lead poisoning in humans was reported in rural Albania and a 30-y-old male and a 17-y-old female died. Twenty-three persons exhibiting signs of lead intoxication recovered following intensive EDTA-Ca chelation therapy. The poisoning resulted from lead contaminated flour originating from repair of a mill's cracked grindstone with metallic lead. Lead levels in flour samples averaged 325 +/- 18 ppm and in bran were 370 +/- 22 ppm. Blood lead levels in intoxicated individuals averaged 0.42 +/- 0.05 ppm and were compatible with their symptomatic status. Contaminated bran from the same mill was fed to lactating cows as well. Lead levels in blood and milk of exposed cows averaged 0.27 +/- 0.06 and 0.61 +/- 0.04 ppm, respectively.


Comprehensive health care for women in Georgia.
In summary, comprehensive health care for women begins first with a paradigm shift that acknowledges women's health is more than reproductive health. Second, it requires viewing women's health issues from an across the lifespan perspective. This perspective includes addressing women's health beginning with the formative years, through reproductive health and sexuality to the frail elderly. The OWH has launched a statewide effort, with input from the leadership of Georgia, including an eleven-member advisory council attached to the office to develop a comprehensive women's health plan. The OWH will partner with public and private organizations, academic institutions and other government agencies to devise a course of action that addresses the health needs of all women, of all ages, including racial and ethnic backgrounds, and socioeconomic and education levels. This plan will serve as a guide for those organizations whose interest is meeting Healthy People 2010 broad objective of increasing the quality and years of healthy life for women.


Expectancies related to thinness, dietary restriction, eating, and alcohol consumption in women with bulimia nervosa.
To investigate behavior-outcome expectancies relating to thinness, dietary restriction, eating, and alcohol consumption in women with bulimia nervosa (BN). Women with BN (N = 29), women with BN and a co-morbid lifetime alcohol use disorder (AUD; N = 18), and control women (N = 24), completed interviews and questionnaires assessing eating- and alcohol-related symptoms, as well as questionnaires measuring expectancies relating to thinness, dietary restriction, eating, and alcohol consumption. Compared with the control group, both bulimic groups reported greater positive expectancies relating to thinness, dietary restriction and eating; expectancy endorsements were also predictive of the severity of eating-related symptoms. Compared with the other groups, the bulimic group with comorbid lifetime AUD had elevated positive alcohol-related expectancies, and alcohol expectancy endorsements predicted severity of alcohol-related symptoms. Women with BN endorsed more positive expectancies relating to thinness, dietary restriction, and eating, whereas women with BN and a lifetime comorbid AUD endorsed more positive alcohol expectancies. The results are consistent with expectancy theory in that positive expectancy endorsements were associated with symptom severity in a syndrome-specific manner. Expectancies related to thinness, dietary restriction, eating, and alcohol consumption in women with BN.


Current treatment landscape for relapsed and/or refractory multiple myeloma.
Recent developments in the treatment of multiple myeloma have led to improvements in response rates and to increased survival; however, relapse is inevitable in almost all patients. Recurrence of myeloma is typically more aggressive with each relapse, leading to the development of treatment-refractory disease, which is associated with a shorter survival. Several phase II and III trials have demonstrated the efficacy of recently approved agents in the setting of relapsed and/or refractory multiple myeloma, including immunomodulatory agents, such as lenalidomide and pomalidomide, and proteasome inhibitors, such as bortezomib and carfilzomib. Currently, however, there is no standard treatment for patients with relapsed and/or refractory disease. This Review discusses the current treatment landscape for patients with relapsed and/or refractory multiple myeloma and highlights disease-related and patient-related factors--such as pre-existing comorbidities or toxicities--that are important considerations for clinicians when selecting an appropriate treatment regimen.


Flare of the silent pandemic in the era of the COVID-19 pandemic: Obstacles and opportunities.
A noteworthy public health problem, antimicrobial resistance (AMR) has been impeded in many ways by the coronavirus disease 2019 (COVID-19) pandemic. This narrative review discusses the two-sided impact of COVID-19 on the magnitude of AMR. The pandemic has put tremendous strain on healthcare systems, diverting resources, personnel, and attention away from AMR diagnosis and management toward COVID-19 diagnosis and contact tracking and tracing. AMR research has been severely hampered, and surveillance and antimicrobial stewardship (AMS) programs have been de-emphasized, delayed, or halted. Antibiotics, particularly broad-spectrum, were prescribed more frequently without diagnostic confirmation of bacterial infection than before the pandemic. Nonetheless, the COVID-19 pandemic has highlighted the vulnerability of healthcare systems in controlling infectious disease threats and raised awareness of the importance of infection prevention and control. Yet, the pandemic has created opportunities to capitalize on positive effects on AMR management. The review concludes that it is now more important than ever to focus on AMR and strengthen AMS programs to ensure appropriate antibiotic use and other AMR prevention measures in healthcare. We must ensure that one of the COVID-19 legacies is increased support for AMR research, diagnostic implementation, appropriate diagnostic stewardship, and the strengthening of our health systems. The COVID-19 pandemic has demonstrated that prevention is better than cure. Countries will need to step up their efforts to combat AMR as a multidisciplinary community. We must prepare our public health systems to combat multiple threats at the same time.


Free fatty acid receptor 3 activation suppresses neurogenic motility in rat proximal colon.
Short-chain fatty acids (SCFA) are microbial fermentation products absorbed by the colon. We recently reported that activation of the SCFA receptor termed free fatty acid receptor 3 (FFA3), expressed on cholinergic nerves, suppresses nicotinic acetylcholine receptor (nAChR)-mediated transepithelial anion secretion. This study aimed to clarify how activation of neurally expressed FFA3 affects colonic motor function. FFA3-expressing myenteric neurons were identified by immunostaining; contractions of isolated circular muscle strips obtained from rat proximal colon were measured by isometric transducers. The effect of FFA3 agonists on defecation in vivo was examined in an exogenous serotonin-induced defecation model. FFA3 immunoreactivity was located in nitrergic and cholinergic neurons in the myenteric plexus. In isolated circular muscle strips without mucosa and submucosa, the addition of nicotine (10 μM) or serotonin transiently relaxed the muscle through nitrergic neurons, whereas high concentrations of nicotine (100 μM) induced large-amplitude contractions that were mediated by cholinergic neurons. Pretreatment with FFA3 agonists inhibited nicotine- or serotonin-induced motility changes but had no effect on bethanechol-induced direct muscle contractions. The Gi/o inhibitor pertussis toxin reversed the inhibitory effect of an FFA3 agonist AR420626 on nicotine-evoked contractions, suggesting that FFA3 activation suppresses nAChR-mediated neural activity in myenteric neurons, consistent with an FFA3-mediated antisecretory effect. In conscious rats, exogenous serotonin increased the volume of fecal output, compared with the vehicle- or AR420626-treated groups. Pretreatment with AR420626 significantly suppressed serotonin-induced fecal output. FFA3 is a promising target for the treatment of neurogenic diarrheal disorders by suppressing nAChR-mediated neural pathways.


Conformer specific nonadiabatic reaction dynamics in the photodissociation of partially deuterated thioanisoles (C6H5S-CH2D and C6H5S-CHD2).
In this work, we have investigated nonadiabatic dynamics in the vicinity of conical intersections for predissociation reactions of partially deuterated thioanisole molecules: C6H5S-CH2D and C6H5S-CHD2. Each isotopomer has two distinct rotational conformers according to the geometrical position of D or H of the methyl moiety with respect to the molecular plane for C6H5S-CH2D or C6H5S-CHD2, respectively, as spectroscopically characterized in our earlier report [J. Lee, S.-Y. Kim and S. K. Kim, J. Phys. Chem. A, 2014, 118, 1850]. Since identification and separation of two different rotational conformers of each isotopomer have been unambiguously done, we could interrogate nonadiabatic dynamics of thioanisole in terms of both H/D substitutional and conformational structural effects. Nonadiabatic transition probability, estimated by the experimentally measured branching ratio of the nonadiabatically produced ground-state channel giving C6H5S·(X[combining tilde]) versus the adiabatic excited-state channel leading to the C6H5S·(Ã) radical, shows resonance-like increases at symmetric (νs) or asymmetric (7a) S-CH2D (or S-CHD2) stretching mode excitation in S1 for all conformational isomers of two isotopomers. However, absolute probabilistic value of the nonadiabatic transition is found to vary quite drastically depending on different conformers and isotopomers. The experimental finding that nonadiabatic transition dynamics are very sensitive to subtle changes in the nuclear configuration within the Franck-Condon region induced by the H/D substitution indicates that the S1/S2 conical intersection seam is quite narrowly defined in the multi-dimensional nuclear configurational space as far as the S-methyl predissociation reaction is concerned. In order to understand the relation between molecular structure and nonadiabaticity of reaction, potential energy surfaces near S1/S2 conical intersections have been theoretically calculated along νs and 7a normal mode coordinates for all conformational isomers. Slow-electron velocity map imaging (SEVI) spectroscopy is employed to unravel the extent of intramolecular vibrational redistribution (IVR) for particular mode excitations of S1, providing insights into the dynamic interplay between IVR and nonadiabatic transition probability near the conical intersection seam.


Lactosylated PLGA nanoparticles containing ϵ-polylysine for the sustained release and liver-targeted delivery of the negatively charged proteins.
The acidic internal pH environment, initial burst release and lack of targeting property are main limitations of poly(lactide-co-glycolide) (PLGA) nanoparticles for carrying proteins. In this study, ϵ-polylysine (ϵ-PL) was used as an anti-acidic agent and a protein protectant to prepare PLGA nanoparticles for the protein delivery. To obtain the liver-targeting capability, lactosylated PLGA (Lac-PLGA) was synthesized by conjugation of lactose acid to PLGA at both ends, and then used to prepare nanoparticles containing ϵ-PL by the nanoprecipitation method. Bovine serumal bumin (BSA), a negatively charged protein, was efficiently loaded into Lac-PLGA/ϵ-PL nanoparticles and exhibited significant decreased burst release in vitro, sustained release in the blood and increased liver distribution in mice after intravenous injections. The enhanced stability of BSA was due to its electrical interaction with ϵ-PL and the neutralized internal environment of nanoparticles. In conclusion, Lac-PLGA/ϵ-PL nanoparticle system can be used as a promising carrier for the negatively charged proteins.


Recent evolution of extreme cestode growth suppression by a vertebrate host.
Parasites can be a major cause of natural selection on hosts, which consequently evolve a variety of strategies to avoid, eliminate, or tolerate infection. When ecologically similar host populations present disparate infection loads, this natural variation can reveal immunological strategies underlying adaptation to infection and population divergence. For instance, the tapeworm Schistocephalus solidus persistently infects 0-80% of threespine stickleback (Gasterosteus aculeatus) in lakes on Vancouver Island. To test whether these heterogeneous infection rates result from evolved differences in immunity, we experimentally exposed laboratory-reared fish from ecologically similar high-infection and no-infection populations to controlled doses of Schistocephalus We observed heritable between-population differences in several immune traits: Fish from the naturally uninfected population initiated a stronger granulocyte response to Schistocephalus infection, and their granulocytes constitutively generate threefold more reactive oxygen species in cell culture. Despite these immunological differences, Schistocephalus was equally successful at establishing initial infections in both host populations. However, the no-infection fish dramatically suppressed tapeworm growth relative to high-infection fish, and parasite size was intermediate in F1 hybrid hosts. Our results show that stickleback recently evolved heritable variation in their capacity to suppress helminth growth by two orders of magnitude. Data from many natural populations indicate that growth suppression is widespread but not universal and, when present, is associated with reduced infection prevalence. Host suppression of helminth somatic growth may be an important immune strategy that aids in parasite clearance or in mitigating the fitness costs of persistent infection.


Croatian aquatic dance flies (Diptera: Empididae: Clinocerinae and Hemerodromiinae): species diversity, distribution and relationship to surrounding countries.
A checklist of aquatic Empididae (dance flies) from Croatia (36 species in subfamily Clinocerinae and 14 species in subfamily Hemerodromiinae) is presented, including information related to the Ecoregions in which species were found and specific species traits. Clinocerinae are represented by five genera, with Wiedemannia Zetterstedt being most species rich (20 species) and Clinocerella Engel least numerous with only one species. In Hemerodromiinae there are 8 species of Chelifera Macquart and 6 species and Hemerodromia Meigen. In addition, a discussion related to the species included and excluded from the list is provided. Most species are univoltine with adults emerging in Spring and Summer, although Kowarzia barbatula Mik and Wiedemannia (Eucelidia) zetterstedti (Fallén) are present throughout the year and Wiedemannia (Chamaedipsia) aequilobata Mandaron occurrs in Winter. The Croatian species assemblage is similar to the well-studied fauna of neighboring Slovenia (63 spp.). It is recommended that some rare species and the streams they inhabit should be considered for greater protection.


Re-introducing bacteria in mosquitoes--a method for determination of mosquito feeding preferences based on coloured sugar solutions.
In this study, sugar-feeding was investigated as a possible means of re-introducing bacteria into mosquito midguts with the aim of identifying bacteria that are suitable for creating paratransgenic mosquitoes. In a paratransgenic approach, bacteria are utilised to deliver effector molecules capable of inhibiting pathogen development in the midgut of the vector. To determine if mosquitoes discriminate between sterile sugar solutions and sugar solutions with bacteria, a method for screening mosquito feeding preferences was developed. This method was tested for Aedes aegypti, Anopheles arabiensis and An. gambiae s.s. mosquitoes and is based on a dual-choice test of solutions labelled with food dyes. Three different tests (dye/colour detection, sugar detection and sugar-concentration detection) were performed to evaluate the method, after which bacteria previously isolated from mosquitoes were used in the experiments. It was shown that mosquitoes do not discriminate between sugar solutions with or without these bacteria indicating that sugar-feeding is a possible means to introduce bacteria into mosquitoes. Furthermore, two different setups of the method were used, enabling us to differentiate between tactile/taste and olfactory responses. The method described in this paper is easy to use, cost-effective and allows broad screening of mosquito sugar-feeding preferences.


Intermolecular interactions in cyanodimethylarsine and cyanodimethylstibine.
Cyanodimethylarsine, [As(CH(3))(2)(CN)], and cyanodimethylstibine, [Sb(CH(3))(2)(CN)], have closely related, but not isomorphous, crystal structures containing XCN.XCN. chains. The N. As distance of 3.185 (3) A is slightly shorter than the expected van der Waals distance of 3.5 A, while the N.Sb distance of 2.862 (9) A, compared with the expected value of 3.7 A, is much shorter. This is consistent with Sb being a stronger Lewis acid than As.


PrrC from Rhodobacter sphaeroides, a homologue of eukaryotic Sco proteins, is a copper-binding protein and may have a thiol-disulfide oxidoreductase activity.
PrrC from Rhodobacter sphaeroides provides the signal input to a two-component signal transduction system that senses changes in oxygen tension and regulates expression of genes involved in photosynthesis (Eraso, J.M. and Kaplan, S. (2000) Biochemistry 39, 2052-2062; Oh, J.-I. and Kaplan, S. (2000) EMBO J. 19, 4237-4247). It is also a homologue of eukaryotic Sco proteins and each has a C-x-x-x-C-P sequence. In mitochondrial Sco proteins these cysteines appear to be essential for the biogenesis of the CuA centre of respiratory cytochrome oxidase. Overexpression and purification of a water-soluble and monomeric form of PrrC has provided sufficient material for a chemical and spectroscopic study of the properties of the four cysteine residues of PrrC, and its ability to bind divalent cations, including copper. PrrC expressed in the cytoplasm of Escherichia coli binds Ni2+ tightly and the data are consistent with a mononuclear metal site. Following removal of Ni2+ and formation of renatured metal-free rPrrC (apo-PrrC), Cu2+ could be loaded into the reduced form of PrrC to generate a protein with a distinctive UV-visible spectrum, having absorbance with a lambda(max) of 360 nm. The copper:PrrC ratio is consistent with the presence of a mononuclear metal centre. The cysteines of metal-free PrrC oxidise in the presence of air to form two intramolecular disulfide bonds, with one pair being extremely reactive. The cysteine thiols with extreme O2 sensitivity are involved in copper binding in reduced PrrC since the same copper-loaded protein could not be generated using oxidised PrrC. Thus, it appears that PrrC, and probably Sco proteins in general, could have both a thiol-disulfide oxidoreductase function and a copper-binding role.


Health savings accounts: should you consider these plans for your own staff?
Two of the latest buzzwords to take center stage in healthcare are health savings accounts (HSAs) and consumer-driven healthcare, but who knows what they mean? This article defines these two concepts and relates how they will work together to save money for consumers and drive down the cost of healthcare. Should physicians be concerned about the impact these initiatives will have on their practices? Physicians should always be concerned about what is going in the marketplace and do everything they can to prepare for the way new plans will affect patient behavior. As an employer, HSAs are worth considering for coverage for your practice staff Employers of all sizes are looking into ways these plans will save money yet provide the adequate coverage that employees hold dear. This article considers the characteristics of HSAs and explores the administrative and operational challenges HSAs will present.


Age-related changes in brain catecholamine responses to a single footshock.
The responses of forebrain and brainstem catecholamine levels to a single footshock were studied in 70-day, one-year, and two-year-old Fischer-344 rats. Brain catecholamine concentrations were assessed 10 minutes after a single 2 second footshock (0, 0.3, or 2.0 mA). In samples taken from non-footshocked rats, only forebrain dopamine concentrations showed a significant age-related decline. However, because the net weights of both the forebrain and the brainstem samples increased significantly with age, the content of forebrain dopamine did not exhibit a significant decline. Both norepinephrine and dopamine levels showed age-related changes in responsiveness to footshock. Norepinephrine concentrations were reduced in both the forebrain and brainstem samples obtained 10 minutes after the high footshock in both the 70-day and one-year-old animals. In two-year-old rats, however, neither forebrain nor brainstem norepinephrine concentrations were altered in response to footshock. Seventy-day-old rats demonstrated significant footshock-induced increases in brainstem dopamine levels, one-year olds showed no appreciable change, and two-year olds demonstrated a non-significant footshock-induced decrease. Thus, both noradrenergic and dopaminergic systems demonstrated age-related changes in their responsiveness to a single brief footshock. These alterations may contribute to the declining ability of the senescent animals to adapt to stressful situations.


[Current trends in treatment and follow-up of patients with differentiated thyroid carcinoma - experience with the use of recombinant human thyrotropin].
Differentiated thyroid carcinoma is the most common endocrine malignancy with an excellent prognosis in the case of its early detection. Radioiodine 131I and thyroid hormones continue to be the pivotal drugs in treatment and follow-up for more than 50 years. The therapeutical and diagnostic options were recently expanded by the use of recombinant human thyrotropin (rhTSH). Our experience with the diagnostic administration of rhTSH confirms the outcomes of official trials and also indicates that the effect of rational therapy with 131I after rhTSH is similar to the outcome after standard regime using long-term thyroid hormone withdrawal.


Hepatic arterial infusion chemotherapy combined with hyperthermia for metastatic liver tumors of colorectal cancer.
The efficacy of combined hepatic arterial infusion chemotherapy and hyperthermia for unresectable hepatic tumors of colorectal cancer was retrospectively compared with hepatic arterial infusion chemotherapy alone. Nine cases were treated with combination therapy and eight cases were treated with hepatic arterial infusion alone. The response rate in the combined hepatic arterial infusion/hyperthermia group was higher (44% v 25%) and the survival period longer (2-year survival, 35% v 12%) than in the group treated with hepatic arterial infusion alone. The toxicity was not severe, with the exception of gastrointestinal symptoms, suggesting that this combination of modalities is useful in the treatment of metastatic liver tumors.


Bacterial Surface Traits Influence Digestion by Tetrahymena pyriformis and Alter Opportunity to Escape from Food Vacuoles.
Endosymbiotic interactions are frequently found in nature, especially in the group of protists. Even though many endosymbioses have been studied in detail, little is known about the mechanistic origins and physiological prerequisites of endosymbiont establishment. A logical step towards the development of endocytobiotic associations is evading digestion and escaping from the host's food vacuoles. Surface properties of bacteria are probably involved in these processes. Therefore, we chemically modified the surface of a transformant strain of Escherichia coli prior to feeding to Tetrahymena pyriformis. N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide allows any substance carrying amino- or carboxyl groups to be bound covalently to the bacterial surface by forming a peptide bond, thus, altering its properties biochemically and biophysically in a predictable manner. The effect of different traits on digestion of T. pyriformis was examined by fluorescence and transmission electron microscopy. The efficiency of digestion differs considerably depending on the coupled substances. Alkaline substances inhibit digestion partially, resulting in incomplete digestion and slightly enhanced escape rates. Increasing hydrophobicity leads to much higher escape frequencies. Both results point to possible mechanisms employed by pathogenic bacteria or potential endosymbionts in evading digestion and transmission to the host's cytoplasm.


Progress in Thyroid Cancer Genomics: A 40-Year Journey.
Background: Very little was known about the molecular pathogenesis of thyroid cancer until the late 1980s. As part of the Centennial celebration of the American Thyroid Association, we review the historical discoveries that contributed to our current understanding of the genetic underpinnings of thyroid cancer. Summary: The pace of discovery was heavily dependent on scientific breakthroughs in nucleic acid sequencing technology, cancer biology, thyroid development, thyroid cell signaling, and growth regulation. Accordingly, we attempt to link the primary observations on thyroid cancer molecular genetics with the methodological and scientific advances that made them possible. Conclusions: The major genetic drivers of the common forms of thyroid cancer are now quite well established and contribute to a significant extent to how we diagnose and treat the disease. However, many challenges remain. Future work will need to unravel the complexity of thyroid cancer ecosystems, which is likely to be a major determinant of their biological behavior and on how they respond to therapy.


Dendrimer encapsulated and conjugated delivery of berberine: A novel approach mitigating toxicity and improving in vivo pharmacokinetics.
Berberine (BBR) is a nitrogenous cyclic natural alkaloid with potential anticancer activity. However it has been less explored due to its poor pharmacokinetic profile. Dendrimers (e.g. PAMAM) have promising potential to deliver anticancer drugs/bio-actives because of their well-defined architecture, monodispersity and tailor-made surface functionality. In the present study it was attempted to deliver berberine through G4 PAMAM dendrimers by conjugation (BPC) as well as encapsulation (BPE) approach. The developed encapsulated and conjugated berberine formulations were found to have size in the approximate range of 100-200nm while zeta potential was almost same as PAMAM G4 dendrimer. The entrapment efficiency in BPE was found to be 29.9%, whereas, the percentage conjugation in BPC was found to be 37.49% indicating high drug payload in conjugation. The developed nano-formulations were characterized through 1H NMR, FT-IR as well as electron microscopy (SEM and TEM). The in vitro release study in different media (water and PBS 7.4) showed sustained release pattern of BBR. Almost 72% and 98% drug was released within 24h respectively; whereas in PBS almost 80% and 98% release was observed within 24h, respectively. The formulations followed Higuchi release and first order release as best fit release kinetic model. MTT assay results showed significantly higher anticancer activity for the PAMAM-BBR (BPC) (p<0.01) against MCF-7 and MDA-MB-468 breast cancer cells. The time dependent ex vivo hemolytic toxicity of the BPC and BPE was significantly less (<5%) even after 24h, which indicated that the formulations can be regarded as significantly safe and biocompatible. Similarly, the in vivo hematological parameters were analyzed through auto-analyzer and the formulations were found to be safer and biocompatible with very least but insignificant (p>0.05) effects. The in vivo pharmacokinetic parameters were found to be impressively improved in albino rat model. The pharmacokinetic parameters such as half-life (t1/2) and AUC of berberine were impressively improved in the plasma level time in vivo studies in albino rat model. The obtained t1/2 was 14.33h for BPC compared to 6.7h for BBR alone. The overall conclusion says that among both the developed formulations the conjugated formulation (BPC) was found to be more prominent than the encapsulated one (BPE). Therefore conclusively conjugation can be a better option for the delivery of natural bio-actives through dendrimers.


Role of phosphatidylinositol(4,5)bisphosphate organization in membrane transport by the Unc104 kinesin motor.
Unc104 (KIF1A) kinesin transports membrane vesicles along microtubules in lower and higher eukaryotes. Using an in vitro motility assay, we show that Unc104 uses a lipid binding pleckstrin homology (PH) domain to dock onto membrane cargo. Through its PH domain, Unc104 can transport phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P2)-containing liposomes with similar properties to native vesicles. Interestingly, liposome movement by monomeric Unc104 motors shows a very steep dependence on PtdIns(4,5)P2 concentration (Hill coefficient of approximately 20), even though liposome binding is noncooperative. This switch-like transition for movement can be shifted to lower PtdIns(4,5)P2 concentrations by the addition of cholesterol/sphingomyelin or GM1 ganglioside/cholera toxin, conditions that produce raft-like behavior of Unc104 bound to lipid bilayers. These studies suggest that clustering of Unc104 in PtdIns(4,5)P2-containing rafts provides a trigger for membrane transport.


Effects of ginsenoside Rg1-loaded alginate-chitosan microspheres on human bone marrow stromal cells.
The ginsenoside Rg1 is the most abundant compound in ginseng. Recent studies showed that Rg1 had neuroprotective effects on neuronal cells. The present study was to prepare Rg1-loaded alginate-chitosan microspheres and research the effects of microspheres on human bone marrow (BM) stromal cells (hBMSC). The alginate-chitosan microspheres were prepared by mechanical emulsification technique in combination with ion (Ca2+) and chitosan solidification. Subsequently, the microspheres were employed to load Rg1 ginseng extracts. The microspheres had a smooth surface and were spherical in shape. The average diameter of the microspheres was 3.95 µm. The loading efficiency was approximately 2.12%. The purity of isolated hBMSC was over 98.8%. Rg1-loaded microspheres could promote hBMSC proliferation and differentiation. Meanwhile, Rg1-loaded microspheres could also suppress hBMSC apoptosis induced by hypoxia-reoxygenation. In conclusion, these loaded microspheres may be used in the research of neuroprotective effects of Rg1.


Production of minimally disturbed synchronous cultures of hematopoietic cells.
A method is describedforproducing sizable quantities of synchronously dividing, minimally disturbed mammalian cells. Cultures were grown immobilized on surfaces such that cell division within the population resulted in the continuous release of synchronous newborn cells. As judged by the quality and duration of synchronous growth, cell size distributions, and DNA compositions, newborn mouse L1210 cells grew with a very high level of synchrony without overt evidence of growth disturbances. The technology should be applicable to a variety of hematopoietic cells, as evidenced by similar results with human MOLT-4 and U937 cell lines.


Thyroid disease and gestational diabetes mellitus (GDM): is there a connection?
The primary objective of this study is to assess for differences in incidence of gestational diabetes mellitus (GDM) for patients with thyroid hypofunction versus patients with thyroid hyperfunction. A retrospective chart review of all women with clinical thyroid disease delivering at Johns Hopkins Hospital from January 2005 to December 2008 was performed. Clinical parameters were abstracted and appropriate statistical tests were performed. GDM occurred in 12.3% of women in the study cohort. Of the women with hypothyroidism, 14.3% developed GDM compared to 5.8% of hyperthyroid women. Cesarean delivery was significantly higher in women with hypothyroidism versus women with hyperthyroidism (p = 0.002). There were no differences between groups with respect to preterm delivery, postpartum hemorrhage or hypertensive disorders of pregnancy. If larger studies confirm the trends observed in our study, consideration should be given to including women with known thyroid disease in the subset of women who should be offered screening for diabetes early in pregnancy and appropriate clinical surveillance.


CCR2 antagonism leads to marked reduction in proteinuria and glomerular injury in murine models of focal segmental glomerulosclerosis (FSGS).
Focal segmental glomerulosclerosis (FSGS) comprises a group of uncommon disorders that present with marked proteinuria, nephrotic syndrome, progressive renal failure and characteristic glomerular lesions on histopathology. The current standard of care for patients with FSGS include immunosuppressive drugs such as glucocorticoids followed by calcineurin inhibitors, if needed for intolerance or inadequate response to glucocorticoids. Renin-angiotensin-aldosterone (RAAS) blockers are also used to control proteinuria, an important signature of FSGS. Existing treatments, however, achieved only limited success. Despite best care, treatment failure is common and FSGS is causal in a significant proportion of end stage renal disease. Thus, an unmet need exists for novel disease modifying treatments for FSGS. We employed two widely-used murine models of FSGS to test the hypothesis that systemic inhibition of chemokine receptor CCR2 would have therapeutic benefit. Here we report that administration CCX872, a potent and selective small molecule antagonist of CCR2, achieved rapid and sustained attenuation of renal damage as determined by urine albumin excretion and improved histopathological outcome. Therapeutic benefit was present when CCX872 was used as a single therapy, and moreover, the combination of CCX872 and RAAS blockade was statistically more effective than RAAS blockade alone. In addition, the combination of CCR2 and RAAS blockade was equally as effective as endothelin receptor inhibition. We conclude that specific inhibition of CCR2 is effective in the Adriamycin-induced and 5/6 nephrectomy murine models of FSGS, and thus holds promise as a mechanistically distinct therapeutic addition to the treatment of human FSGS.


[Enzymatic catalysis in non-aqueous solvents].
It is well known that non-aqueous enzymatic catalysis has emerged as an important area of enzyme engineering with the advantages of higher substrate solubility, increased stereoselectivity, modified substrate specificity and suppression of unwanted water-dependent side reactions. As a result, non-aqueous enzymatic catalysis has been applied in the biocatalytic synthesis of important pharmaceuticals and nutriceuticals. With the advancement of non-aqueous enzymatic catalysis in recent years, the efforts have been centered on the discovery and modification of solvent-tolerant biocatalysts for non-aqueous environments. Additionally, with the inevitable trends of green chemistry and sustainable development, green solvents have been utilized for increased number of enzymatic reactions to replace conventional organic solvents. In this review, modification, immobilization and mutagenesis of various enzymes for non-aqueous catalysis are discussed. Recent progress of non-aqueous enzymatic catalysis in solvent-free environments, reverse micelles, supercritical liquid and ionic liquid are also presented. In particular, while direct evolution, high-throughput screening and site-directed mutagenesis are combined as powerful tools for protein engineering, vapor/solid/ice water mixture, sticky solid-state liquid crystal and high density salt suspension are the future directions for solvent engineering in order to broaden the utility and elevate the efficiency of non-aqueous enzymatic catalysis.


[Regulatory effects of acupuncture on exercise tolerance in patients with chronic obstructive pulmonary disease at stable phase: a randomized controlled trial].
To verify the regulatory effects of acupuncture on exercise tolerance in patients with chronic obstructive pulmonary disease (COPD) at stable phase. Thirty cases of COPD were randomly divided into a treatment group (16 cases) and a placebo group (14 cases). Based on specified aerobic exercise, acupuncture was applied in the treatment group and placebo acupuncture was used in the placebo group. The acupoints included Danzhong (CV 17), Rugen (ST 18), Guanyuan (CV 4), Zhongwan (CV 12), Tianshu (ST 25) and so on. The needle did not penetrate into the skin for the placebo group. The treatment was required for 2 to 3 times per week for totally 5 weeks. The indices of exercise tolerance, including 6-min walking distance (6-MWD), exercise time, maximum oxygen uptake (VO2max) forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC), maximum ventilatory volume (MVV), St. George respiratory questionnaire (SGRQ) were observed in two groups before and after treatment. (1) Exercise tolerance: the differences of 6-MWD and exercise time were statistically significant between groups, which were more superior in the treatment group (both P<0.01); the VO2max was significantly increased after treatment in the treatment group (P<0.05), but there was no difference between two groups (P>0.05). (2) Pulmonary ventilation function: the differences of FEV1%, FEV1/FVC and MVV% were statistically significant between groups, which were more superior in the treatment group (P<0.05, P<0.01); (3) SGRQ: the SGRQ was significantly improved after treatment in the treatment group (P<0.05), but there was no difference between two groups (P>0.05). The acupuncture could improve the exercise tolerance in patients with chronic obstructive pulmonary disease at stable phase, and shorten the onset time of aerobic exercise. Besides, acupuncture combined with aerobic exercise could effectively improve the pulmonary function.


Cardiac neoplasms at the Canadian Reference Centre for Cancer Pathology.
To review the Canadian Reference Centre for Cancer Pathology's experience with cardiac neoplasms by reviewing all cases with tumours involving the heart referred to the Centre from 1949 to 1995. Referred patient records, panel and consensus statement submissions and glass slides were reviewed in all cases. In selected cases additional immunohistochemical stains were obtained from paraffin block tissues. National referral centre for difficult or interesting cancer pathology-related cases. All cases were derived from referral of autopsy material and/or surgically resected neoplasms. Material was referred from 35 patients during 1949 to 1995. The group consisted of 17 males, 17 females and one infant patient in whom the sex was not specified. The patient age ranged from infancy to 85 years. The neoplasms referred consisted of 12 myxomas, 10 sarcomas, five lymphomas, two carcinomas, two papillary fibroelastomas and one each of rhabdomyoma, mesothelioma of the atrioventricular node, lipomatous hypertrophy of the intra-atrial septum and fibroma. The sarcomas were difficult to classify even with the use of additional immunohistochemical stains. All the lymphomas were of non-Hodgkin's type and were not of primary cardiac origin. The series of neoplasms referred to the Canadian Reference Centre for Cancer Pathology reflects changes in cardiac surgery, cardiac imaging and cardiac pathology as disciplines. Even with modern pathological techniques some cases, especially sarcomas, are still difficult to diagnose. The clinical presentation often reflects the chamber of origin of the neoplasm rather than being indicative of a specific tumour type.


Standards for comprehensive sexual health services for young people under 25 years.
This document is a first response to the need to develop sexual health services for young people on a single site whilst awaiting research from pilot studies of 'one stop shops' suggested in the Sexual Health and HIV strategy. It is a document which is intended to be a tool to use for those wishing to set up a service providing testing for sexually transmitted infections and provision of contraceptive services for those under 25 years. It is not intended that such a service would replace existing specialist or general practice care but complement it, allowing clients to choose the service most appropriate and acceptable to them, with close links and clear pathways of care for referral between services. This paper should be used as a template when initiating and monitoring a clinic but some of the standards may not be achievable without significant financial input. However, economic limitations should not detract from striving to achieve the best possible care for those most at risk from sexually transmitted infections and unwanted pregnancies. For example, not all clinics will be able to provide the recommended tests for the diagnosis for gonorrhoea and chlamydia immediately, but should work towards achieving them. Although the upper age limit in this document is defined as 25 years, some providers may wish to limit clinics to those under 20 depending on local needs. Detailed information on specific issues such as consent and confidentiality, provision of contraception, investigation of non-sexually transmitted vaginal infections and sexually transmitted infection management and diagnosis are referenced and we recommend these are accessed by the users of this document. Many of the references themselves are live documents available on the worldwide web, and are constantly updated. The Sexual Health and HIV Strategy has now been published and these standards are aimed at those who wish to provide a level 2 sexual health service for young people wherever the setting e.g. genitourinary outreach clinic, contraceptive services, general practice. This document is a starting point to be reviewed and updated as new research becomes available, as the Sexual Health Strategy is implemented and with further input from providers of care (family planning, general practice, genitourinary medicine, gynaecology and paediatrics) and service users. All service providers must maintain a high quality of care and have networks both with those who provide more specialized services (Level 3) and Level 1 services. This document is an initial attempt to ensure that there is equity of clinical provision wherever a Level 2 sexual health service is provided and should be a useful tool for those setting up or monitoring services.


Fluorescent Amino Acid Initiated de novo Cyclic Peptides for the Label-Free Assessment of Cell Permeability*.
The major obstacle in applying peptides to intracellular targets is their low inherent cell permeability. Standard approaches to attach a fluorophore (e. g. FITC, TAMRA) can change the physicochemical properties of the parent peptide and influence their ability to penetrate and localize in cells. We report a label-free strategy for evaluating the cell permeability of cyclic peptide leads. Fluorescent tryptophan analogues 4-cyanotryptophan (4CNW) and β-(1-azulenyl)-L-alanine (AzAla) were incorporated into in vitro translated macrocyclic peptides by initiator reprogramming. We then demonstrate these efficient blue fluorescent emitters are good tools for monitoring peptide penetration into cells.


Metagenomic analysis of rhizosphere microflora of oil-contaminated soil planted with barley and alfalfa.
The role of rhizosphere microbial communities in the degradation of hydrocarbons remains poorly understood and is a field of active study. We used high throughput sequencing to explore the rhizosphere microbial diversity in the alfalfa and barley planted oil contaminated soil samples. The analysis of 16s rRNA sequences showed Proteobacteria to be the most enriched (45.9%) followed by Bacteriodetes (21.4%) and Actinobacteria (10.4%) phyla. The results also indicated differences in the microbial diversity among the oil contaminated planted soil samples. The oil contaminated planted soil samples showed a higher richness in the microbial flora when compared to that of untreated samples, as indicated by the Chao1 indices. However, the trend was different for the diversity measure, where oil contaminated barley planted soil samples showed slightly lower diversity indices. While the clustering of soil samples grouped the oil contaminated samples within and across the plant types, the clean sandy soil samples formed a separate group. The oil contaminated rhizosphere soil showed an enrichment of known oil-degrading genera, such as Alcanivorax and Aequorivita, later being specifically enriched in the contaminated soil samples planted with barley. Overall, we found a few well known oil-degrading bacterial groups to be enriched in the oil contaminated planted soil samples compared to the untreated samples. Further, phyla such as Thermi and Gemmatimonadetes showed an enrichment in the oil contaminated soil samples, indicating their potential role in hydrocarbon degradation. The findings of the current study will be useful in understanding the rhizosphere microflora responsible for oil degradation and thus can help in designing appropriate phytoremediation strategies for oil contaminated lands.


mRNA deep sequencing reveals 75 new genes and a complex transcriptional landscape in Mimivirus.
Mimivirus, a virus infecting Acanthamoeba, is the prototype of the Mimiviridae, the latest addition to the nucleocytoplasmic large DNA viruses. The Mimivirus genome encodes close to 1000 proteins, many of them never before encountered in a virus, such as four amino-acyl tRNA synthetases. To explore the physiology of this exceptional virus and identify the genes involved in the building of its characteristic intracytoplasmic "virion factory," we coupled electron microscopy observations with the massively parallel pyrosequencing of the polyadenylated RNA fractions of Acanthamoeba castellanii cells at various time post-infection. We generated 633,346 reads, of which 322,904 correspond to Mimivirus transcripts. This first application of deep mRNA sequencing (454 Life Sciences [Roche] FLX) to a large DNA virus allowed the precise delineation of the 5' and 3' extremities of Mimivirus mRNAs and revealed 75 new transcripts including several noncoding RNAs. Mimivirus genes are expressed across a wide dynamic range, in a finely regulated manner broadly described by three main temporal classes: early, intermediate, and late. This RNA-seq study confirmed the AAAATTGA sequence as an early promoter element, as well as the presence of palindromes at most of the polyadenylation sites. It also revealed a new promoter element correlating with late gene expression, which is also prominent in Sputnik, the recently described Mimivirus "virophage." These results-validated genome-wide by the hybridization of total RNA extracted from infected Acanthamoeba cells on a tiling array (Agilent)--will constitute the foundation on which to build subsequent functional studies of the Mimivirus/Acanthamoeba system.


[On the actual nomenclature of myocardial infarcts].
Certain criteria are examined for infarctions currents defined as inferior or inferolateral. To do this, certain considerations on the anatomical aspects of isolated and in situ heart are laid out. The topographical relationship of the in situ heart with other adjacent thoracic organs is described. The heart is schematically represented as a pyramid with a triangular base and its walls and borders are related to walls of the thorax. The spatial orientation of the main resulting vectors from ventricular depolarization and repolarization are summarized also. Usefulness of registering the unipolar thoracic leads V7, V8, V9 or a complete electrocardiographic thoracic circle, is underlined. This method allows to detect for of the existence of an acute myocardial infarction in the inferior and inferolateral segments in as third basal and mid cardiac regions previously denominated posterolateral. On the base of previous electroanatomical comparisons, it is concluded that the thoracic posterior leads V7 - V9, as well as the magnetic resonance images, explore the same heart regions. Therefore, these two methods: electrocardiography which is an essentially functional method and magnetic resonance that especially focus on structural changes are not contradictory but rather complementary tests."


Filtration mapping as complete Bell state analyzer for bosonic particles.
In this paper, we present the approach to complete Bell state analysis based on filtering mapping. The key distinctive feature of this appoach is that it avoids complications related to using either hyperentanglement or representation of the Bell states as concatenated Greenber-Horne-Zeilinger (C-GHZ) state to perform discrimination procedure. We describe two techniques developed within the suggested approach and based on two-step algorithms with two different types of filtration mapping which can be called the non-demolition and semi-demolition filtrations. In the method involving non-demolition filtration measurement the filtration process employs cross-Kerr nonlinearity and the probe mode to distinguish between the two pairs of the Bell states. In the case of semi-demolition measurement, the two states are unambiguously discriminated and hence destroyed, whereas filtraton keeps the other two states intact. We show that the measurement that destroys the single photon subspace in every mode and preserves the superposition of zero and two photons can be realized with discrete photodetection based on microresonator with atoms.


Psychosocial functioning and depressive symptoms among HIV-positive persons receiving care and treatment in Kenya, Namibia, and Tanzania.
In sub-Saharan Africa, the prevalence of depressive symptoms among people living with HIV (PLHIV) is considerably greater than that among members of the general population. It is particularly important to treat depressive symptoms among PLHIV because they have been associated with poorer HIV care-related outcomes. This study describes overall psychosocial functioning and factors associated with depressive symptoms among PLHIV attending HIV care and treatment clinics in Kenya, Namibia, and Tanzania. Eighteen HIV care and treatment clinics (six per country) enrolled approximately 200 HIV-positive patients (for a total of 3,538 participants) and collected data on patients' physical and mental well-being, medical/health status, and psychosocial functioning. Although the majority of participants did not report clinically significant depressive symptoms (72 %), 28 % reported mild to severe depressive symptoms, with 12 % reporting severe depressive symptoms. Regression models indicated that greater levels of depressive symptoms were associated with: (1) being female, (2) younger age, (3) not being completely adherent to HIV medications, (4) likely dependence on alcohol, (5) disclosure to three or more people (versus one person), (6) experiences of recent violence, (7) less social support, and (8) poorer physical functioning. Participants from Kenya and Namibia reported greater depressive symptoms than those from Tanzania. Approximately 28 % of PLHIV reported clinically significant depressive symptoms. The scale-up of care and treatment services in sub-Saharan Africa provides an opportunity to address psychosocial and mental health needs for PLHIV as part of comprehensive care.


The influence of reduced insulin sensitivity via short-term reductions in physical activity on cardiac baroreflex sensitivity during acute hyperglycemia.
Reduced insulin sensitivity and impaired glycemic control are among the consequences of physical inactivity and have been associated with reduced cardiac baroreflex sensitivity (BRS). However, the effect of reduced insulin sensitivity and acute hyperglycemia following glucose consumption on cardiac BRS in young, healthy subjects has not been well characterized. We hypothesized that a reduction in insulin sensitivity via reductions in physical activity would reduce cardiac BRS at rest and following an oral glucose tolerance test (OGTT). Nine recreationally active men (23 ± 1 yr; >10,000 steps/day) underwent 5 days of reduced daily physical activity (RA5) by refraining from planned exercise and reducing daily steps (<5,000 steps/day). Spontaneous cardiac BRS (sequence technique) was compared at rest and for 120 min following an OGTT at baseline and after RA5. A substudy (n = 8) was also performed to independently investigate the influence of elevated insulin alone on cardiac BRS using a 120-min hyperinsulinemic-euglycemic clamp. Insulin sensitivity (Matsuda index) was significantly reduced following RA5 (BL 9.2 ± 1.3 vs. RA5 6.4 ± 1.1, P < 0.001). Resting cardiac BRS was unaffected by RA5 and significantly reduced during the OGTT similarly at baseline and RA5 (baseline 0 min, 28 ± 4 vs. 120 min, 18 ± 4; RA5 0 min, 28 ± 4 vs. 120 min, 21 ± 3 ms/mmHg). Spontaneous cardiac BRS was also reduced during the hyperinsulinemic-euglycemic clamp (P < 0.05). Collectively, these data demonstrate that acute elevations in plasma glucose and insulin can impair spontaneous cardiac BRS in young, healthy subjects, and that reductions in cardiac BRS following acute hyperglycemia are unaffected by reduced insulin sensitivity via short-term reductions in physical activity.


Impact of COVID-19 on Indian optometrists: A student, educator, and practitioner's perspective.
The optometry profession has experienced massive changes amid lockdown in COVID 19 pandemic. This study gauges the impact of COVID-19 on optometry education and practices in India. The impact of COVID-19 among key stakeholders of Indian optometry that included educators, students, and practitioners was surveyed. The content validity of the survey tool was achieved through a focused group discussion with experts. Of the 1408 responses, 118 were educators, 845 were students and 445 were practitioners. Post COVID-19 lock-down, a high percentage of students (96%) and educators (94%) were now using online mode of education to learn and teach. The blended learning methods were reported to be used by 81% of educators. Practical skills were the most difficult to teach by educators and to learn by students. Almost a third of the students were concerned about their internships and job opportunities amid the pandemic. Practitioners felt confident in performing routine eye examinations with personal protective equipment (PPE). Telemedicine was found to be adopted by 55% of the private practitioners and 49% of the eye hospitals. The COVID-19 pandemic has provided an opportunity to reform Indian optometry education through blended learning methods. Optometry practices changed and adapted instantly to the new hygiene norms that have raised the standard of care provided to patients. Telemedicine emerged as a mode of providing care by optometrists. Overall, all key stakeholders of optometry in India were found to have adapted well to the sudden changes due to COVID 19 pandemic.


Alterations in adipocyte glucose transporter GLUT4 and circulating adiponectin and visfatin in rat adjuvant induced arthritis.
Rheumatoid arthritis in humans brings about impaired insulin sensitivity and glucose tolerance. Since adipose tissue plays a role in glucose homeostasis, we evaluated the size of adipocytes, the amount of glucose transporter type 4 (GLUT4) in adipocyte plasma membranes, and circulating insulin, glucose, and adipokines affecting glucose metabolism, resistin, adiponectin and visfatin during experimental adjuvant arthritis (AA) in male Lewis rats. AA was induced by a single injection of complete Freund's adjuvans. Adipocyte diameter was assessed microscopically, GLUT4 was measured by Western blotting. Plasma insulin, adiponectin, visfatin were quantitated by RIA, and resistin by ELISA. Arthritic rats showed cachexia, reduced adipocyte size, and downregulated membrane GLUT4 (4065 +/- 962 vs. 9911 +/- 680 arb. units of optic density, p < 0.01), reduced plasma adiponectin (1.956 +/- 0.10 vs. 3.16 +/- 0.22 microg/ml, p < 0.001), and enhanced visfatin (1.84 +/- 1.05 vs. 1.24 +/- 0.1 ng/ml, p < 0.01). Plasma glucose and insulin were unaltered, as were the resistin levels. AA induced cachexia results in reduction of adipocyte size, and paradoxically also in downregulation of GLUT4 in adipocyte membranes. This is supposed to be functionally related to the reduced adiponectin levels. The upregulated visfatin in rat arthritis is a novel finding, and it confirms its role in autoimmunity across the species.


Reducing Degrees of Freedom in Surgical Suturing: Implications for Minimally Invasive Device Development-A Prospective Experimental Study.
Open surgery allows the use of all 6 degrees of freedom (DOF; x-y-z and roll-pitch-yaw), whereas laparoscopy requires working under limitation to 4 axes. We present a prospective experimental study evaluating translational and rotational DOF restriction in surgical suturing tasks. An experimental platform included a kinematic structure that limited the maneuverability of the surgical instruments. The subjects (n=20) worked in a randomized order using (1) 6DOF, (2) 4DOF with 3 translational and 1 rotational DOF (4TRANS), and (3) 4DOF with 1 translational and 3 rotational DOF (4ROT). The time required to perform each task was recorded. Suturing and knot tying were significantly faster under 6DOF compared with 4ROT (both P<0.001) and 4TRANS (both P<0.001). Assessment of subjective difficulty and impairment showed most favorable results for 6DOF. The advantage of rotational compared with translational DOF should be considered in the development of future surgical devices.


Spinal anesthesia for cesarean section in a patient with systemic sclerosis associated interstitial lung disease: a case report.
Systemic sclerosis or scleroderma is a rare autoimmune disorder characterized by excessive fibrosis and, vasculopathy, with multiorgan involvement. Anesthetic considerations in patients with systemic sclerosis must take into account the degree of organ dysfunction as well as airway management. Regional anesthesia is a preferable alternative to general anesthesia despite the reports of prolonged sensory block. Spinal anesthesia in patients with systemic sclerosis has been reported for only one patients undergoing cesarean section. Concurrent systemic sclerosis and pregnancy raise many obstetric and anesthetic considerations. We describe the case of a pregnant patient with systemic sclerosis who had a history of dyspnea and interstitial lung disease. The cesarean section was performed uneventfully under spinal anesthesia.


An Evaluation of GuttaFlow2 in Filling Artificial Internal Resorption Cavities: An in vitro Study.
Obturation of root canal with internal resorption represents a major challenge in Endodontics. In spite of that, usual obturation techniques are often employed without considering the best technique to solve this problem. The goal of this study was to investigate the ability of GuttaFlow2 in filling artificial internal resorption cavities. The study sample included 36 human upper central incisors that were prepared using Protaper system (F4). Internal resorption cavities were prepared by cutting each tooth at 7 mm from the apex and preparing hemispherical cavities on both the sides and then re-attaching them. The sample was randomly separated into three groups (n = 12 in each group). In the first group, thermal injection technique (Obtura II) was employed and served as the control group. In the second group, injection of cold free-flow obturation technique with a master cone (GF2-C) was employed, whereas in the third group injection of cold free-flow obturation without a master cone (GF2) was followed. The teeth were re-cut at the same level as before and examined under a stereomicroscope. Subsequently, the captured images were transferred to AutoCAD program to measure the percentage of total filling "TF," gutta-percha "G," sealer "S," and voids "V" out of the total surface of the cross sections. All materials showed high filling properties in terms of "total filling," ranging from 99.17% (for Obtura II) to 99.72% (for GF2-C). Regarding gutta-percha percentages of filling, they ranged from 83.15 to 83.93%, whereas those for the sealer ranged from 5.71 to 15.24%. GuttaFlow2 group with a master cone appeared to give the best results despite the insignificant differences among the three groups. The GuttaFlow2 with a master cone technique seemed to be a promising filling material and gave results similar to those observed with Obtura II. It is recommended for use to obturate internal resorption cavities in clinical practice due to its good adaptability to root canal walls, ease of handling, and application. Internal resorption defects can be successfully filled with GuttaFlow2 material when supplemented with a master cone, and the results are comparable with those obtained with the Obtura II technique.


Intralysosomal generation of ammonia from urea by endocytosed urease results in secretion of free lysosomal arylsulfatase-A and increased activity of membrane-bound beta-glucosidase in cultured brain cells.
Hyperammonemia interferes with normal brain function. The effect of ammonia on free and membrane-bound lysosomal enzymes and on mucopolysaccharide metabolism was studied in cultured rat brain cells (ROC-1, hybridoma between C6-astrocytoma and oligodendrocytes). Intralysosomal ammoniagenesis was achieved from urea by endocytosed Jackbean urease followed by incubation of the cultures with urea. The intralysosomal location of urease was evidenced by the protective effects of leupeptin and urea on the stability of intracellular urease. Ammonia formed from urea resulted in an increased secretion of lysosomal arylsulfatase-A (AS-A), but not of the membrane-bound lysosomal beta-glucosidase into the culture medium, thus intralysosomal AS-A activity decreased. Lysosomal, membrane-bound beta-glucosidase activity increased, presumably due to intralysosomal proteolytic protection following an increased lysosomal pH. Intralysosomal ammoniagenesis temporarily impaired 35SO4-glycosaminoglycan degradation of prelabeled cells. The results support the hypothesis that hyperammonemic states may interfere with lysosomal functions in vivo as well in cultured cells.


A ghost covered in lice: a case of severe blood loss with long-standing heavy pediculosis capitis infestation.
An 11-year-old child presented with poor school attendance, and signs and symptoms of severe anaemia. He was heavily covered in lice. He was investigated for other causes of anaemia. Following treatment for head lice and also iron supplementation, he was back in full-time education. This case highlights the link between head lice (pediculosis capitis) infestation and iron-deficiency anaemia.


Rolling Shutter Camera Absolute Pose.
We present minimal, non-iterative solutions to the absolute pose problem for images from rolling shutter cameras. The absolute pose problem is a key problem in computer vision and rolling shutter is present in a vast majority of today's digital cameras. We discuss several camera motion models and propose two feasible rolling shutter camera models for a polynomial solver. In previous work a linearized camera model was used that required an initial estimate of the camera orientation. We show how to simplify the system of equations and make this solver faster. Furthermore, we present a first solution of the non-linearized camera orientation model using the Cayley parameterization. The new solver does not require any initial camera orientation estimate and therefore serves as a standalone solution to the rolling shutter camera pose problem from six 2D-to-3D correspondences. We show that our algorithms outperform P3P followed by a non-linear refinement using a rolling shutter model.


Nursing research with refugee clients: a call for more qualitative approaches.
Nursing research with refugee populations, who lack an understanding of the importance of research, presents unique challenges. These challenges include bureaucratic requirements for gaining permission for research, navigating through camps, identifying potential participants, gaining acceptance, building rapport and trust, maintaining privacy, and respecting participants' status in the camp. Few studies exist regarding Palestinian refugees, with no reported studies that address nursing or healthcare, especially in Jordan. Quantitative research, which often requires participants who read and write, may be ineffective with long-term refugee populations. Additionally, many research tools are not culturally valid. Consequently, refugees, many of whom are illiterate, are largely unstudied. Qualitative approaches, such as interviewing and observation, allow participants to describe their healthcare concerns, and their management of them. Rapport and trust can then enable the researcher to provide interventions and education.


Interleukin-10 is a mesangial cell growth factor in vitro and in vivo.
Macrophages are involved in the pathogenesis of mesangioproliferative glomerulonephritis. As macrophages are known to produce interleukin-10 (IL-10), we investigated the effect of recombinant murine IL-10 (rIL-10) on mesangial cell growth. In vitro studies were performed using the rat 1097 mesangial cell line. These cells exhibited a dose-dependent proliferative response to rIL-10 (23% to 70% increases at 80 ng/mL; p < 0.01), as assessed by both 3H-thymidine uptake and cell count. This effect was inhibited by preincubation of rIL-10 with a neutralizing anti-IL-10 antibody. When added to cultures of growth-arrested 1097 cells, IL-10 induced dose-dependent proliferation that paralleled the effects of platelet-derived growth factor. Incubation with a neutralizing anti-IL-10 Ab for 48 hours reduced 3H-thymidine uptake (median, 27% decreases; range, 2% to 56% decreases) versus a control Ab; p < 0.05). Rat mesangial cells were also shown to express IL-10 mRNA and protein, as determined by Northern blotting and immunostaining, thereby suggesting a role for IL-10 in autocrine mesangial cell growth. To examine the effects of IL-10 in vivo, inbred male Sprague-Dawley rats were given subcutaneous rIL-10 (0.5 mg/kg) for 3 (n = 6), 7 (n = 3), or 14 days (n = 4), or vehicle control, then killed. IL-10 administration induced a transient reduction in creatinine clearance of 35% at Day 3 (p < 0.01). Following IL-10 administration, an increase in glomerular cellularity was seen, which was maximal at Day 3 (82.7 +/- 5.9 nuclei/glomerular cross section versus control 64.6 +/- 4.6, 28% increases; p < 0.001) and maintained at Day 14 (23% increases; p < 0.01). Immuno-histochemical staining for proliferating cell nuclear antigen demonstrated an increased number of proliferating cells per glomerular cross section at day 3 (48% increases versus controls; p < 0.05). Staining for alpha-smooth-muscle actin showed significant labeling only in the glomeruli of IL-10-treated animals; double-labeling with an anti-proliferating cell nuclear antigen Ab demonstrated that some of these mesangial cells were proliferating. Collectively, these results suggest that IL-10 is a growth factor for rat mesangial cells both in vitro and in vivo.


[Vegetarian nutrition: preventive potential and possible risks. Part 2: animal foods and recommendations].
As shown in the first part of this article, consuming high amounts of fruits, vegetables, whole grains and nuts can lower the risk for several chronic diseases. However, the relevance of animal foods consumed within a vegetarian diet is less well-known. We followed a nutritive and a metabolic-epidemiological approach to obtain dietary recommendations. A MEDLINE-research was performed for all animal food groups relevant with a vegetarian diet (key words: "eggs", "milk", "dietary pattern" "vegetarian diet", "cancer", "cardiovascular disease", "diabetes mellitus", "osteoporosis", "vitamin D", "vitamin B(12)", "iron", "iodine"). All relevant food groups were characterized regarding their nutrient content and rated with respect to the available metabolic-epidemiological evidence. Based on the evidence criteria of the WHO/FAO, colorectal cancer risk reduction by a high intake of milk and milk products is assessed as probable, while a higher risk of prostate and ovarial carcinomas is also probable. The evidence of a risk-increasing effect of eggs relating to cardiovascular disease, colorectal cancer and breast cancer is assessed as probable. As the data of prospective cohort studies suggest, a prudent diet pattern characterized high in fruits, vegetables, whole grains and nuts is associated with a lower risk of coronary heart disease and diabetes mellitus type 2. In contrast, there is no overall association between prudent diet pattern and risk of breast cancer or colorectal cancer. The critical key nutrients for vegetarians are vitamin D and B12, iodine and iron. For the first time evidence based dietary recommendations were provided for persons on a vegetarian diet in the D-A-CH-region.


The development of spicules in Heligmosomoides bakeri (Nematoda, Heligmosomidae).
The spicules of male parasitic nematodes are key morphological features, which vary between species in shape and length and are used often for species identification. However, little is known about spicules and particularly if/how their length varies during growth. We first assessed the degree of variation in spicule length of male Heligmosomoides bakeri 21 days post infection (PI), and then in two follow-up experiments measured spicule lengths at half daily/daily intervals between days 6 and 14 PI. Mean spicule length in 21-day worms was 0.518 mm with a range of 94 μm, and variation between the two spicules of individual worms from 2 to 32 μm. Spicules were first detectable on day 6-6.5, after which their lengths increased until day 7 PI (mean = 0.61 and 0.59). This was followed by significant contraction, initially relatively quickly over the following 48 h and then more slowly over a longer period, stabilizing by days 10-14, with only minor further reduction in length. We conclude that the length of spicules varies significantly over the first few days after they have formed, and, consequently, the age of worms is an important factor for consideration when spicule lengths are measured for experimental/diagnostic or taxonomical purposes.


[Prevention of bacterial infections after bone marrow graft by broad-spectrum oral antibiotics, absorbable (pefloxacin, penicillin) and non absorbable (cephalosporin, gentamycin, bacitracin)].
In a consecutive series of 65 patients treated by allogeneic bone marrow transplantation, we have compared the efficacy on prevention of bacterial infection of total gut decontamination with oral non absorbable antibiotics or with oral absorbable broad spectrum antibiotics. On day-8, all patients were randomly allocated to one group: Group I received orally pefloxacin 400 mg/day and penicillin 3 M UI/day. Group II received capsules containing cephalothin 250 mg, gentamicin 20 mg and bacitracin 150 UI. Each patient received 9 to 12 capsules per day according to body weight. Patients less than 5 years old or with severe hepatic abnormalities were excluded from the study. All patients were treated in LAF room with usual precautions of asepsis. They received sterile food. In addition, they were on ketoconazole for prophylaxis of fungal infections and acyclovir for prevention of herpes infections. Antibiotics were started on day-8 before bone marrow transplantation and stopped 15 days after discharge from the hospital. 32 patients were allocated to Group I and 33 in Group II. There was no difference between both groups according to age, sex, diagnosis. After transplant, the one year survival and the complications were similar in both groups. The median time of decontamination was 65 days, the mean number of days of agranulocytosis was 20 days, the mean number of days of fever was 7 days in both groups. The compliance was better in Group I but the treatment had to be modified in 9 patients of Group I because of liver abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)


What is happening to industrial relations?
Individual contracts in the form of Australian and Queensland Workplace Agreements remove the social justice foundation provided by arbitration and seek to return us to the 'higgling of the market' as the determinant of wages and working conditions. However wages and working conditions are more than just a cost to an employer--the level of wages and working conditions also has a social impact, and it was recognition of this that lead to the setting of a 'living wage' in Australia. As a union we have opposed the purely bean-counter approach to health care, consistently arguing that 'care' cannot be costed. This is also our approach to wages and working conditions--the setting of which has an impact on society as a whole and not just the bottom line of an individual company!


The heterozygous R155C VCP mutation: Toxic in humans! Harmless in mice?
Heterozygous missense mutations in the human VCP gene cause inclusion body myopathy associated with Paget disease of bone and fronto-temporal dementia (IBMPFD) and amyotrophic lateral sclerosis (ALS). The exact molecular mechanisms by which VCP mutations cause disease manifestation in different tissues are incompletely understood. In the present study, we report the comprehensive analysis of a newly generated R155C VCP knock-in mouse model, which expresses the ortholog of the second most frequently occurring human pathogenic VCP mutation. Heterozygous R155C VCP knock-in mice showed decreased plasma lactate, serum albumin and total protein concentrations, platelet numbers, and liver to body weight ratios, and increased oxygen consumption and CD8+/Ly6C + T-cell fractions, but none of the typical human IBMPFD or ALS pathologies. Breeding of heterozygous mice did not yield in the generation of homozygous R155C VCP knock-in animals. Immunoblotting showed identical total VCP protein levels in human IBMPFD and murine R155C VCP knock-in tissues as compared to wild-type controls. However, while in human IBMPFD skeletal muscle tissue 70% of the total VCP mRNA was derived from the mutant allele, in R155C VCP knock-in mice only 5% and 7% mutant mRNA were detected in skeletal muscle and brain tissue, respectively. The lack of any obvious IBMPFD or ALS pathology could thus be a consequence of the very low expression of mutant VCP. We conclude that the increased and decreased fractions of the R155C mutant VCP mRNA in man and mice, respectively, are due to missense mutation-induced, divergent alterations in the biological half-life of the human and murine mutant mRNAs. Furthermore, our work suggests that therapy approaches lowering the expression of the mutant VCP mRNA below a critical threshold may ameliorate the intrinsic disease pathology.