Risk of infertility in patients with Hodgkin's disease treated with ABVD vs MOPP vs ABVD/MOPP.
The gonadal function of 38 patients with Hodgkin's disease (HD) treated with MOPP chemotherapy (12 patients), ABVD (9 patients) and alternating MOPP/ABVD (17 patients) has been retrospectively investigated with semen analysis. Median age of patients was 25 years (range 16-41 years). Azoospermia was found in all patients from the MOPP group (100%), in 3 of the ABVD group (33%) and in 13 of the MOPP/ABVD group (76%). After temporary oligospermia full recovery of spermatogenesis was observed in 67% of patients treated with ABVD, versus 25% of MOPP-treated patients following a prolonged period of azoospermia and oligospermia. Patients receiving MOPP/ABVD scheme had complete recovery of testicular function after oligospermia in 24% of cases. These results confirm the higher gonadal toxicity of the MOPP regimen as compared to others such as ABVD without alkylating agents.


Expression of full-length and truncated Rep genes from Mungbean yellow mosaic virus-Vigna inhibits viral replication in transgenic tobacco.
Mungbean yellow mosaic virus-Vigna (MYMV-Vig) is a bipartite geminivirus that causes a severe yellow mosaic disease in blackgram. An assay was developed to study MYMV-Vig replication by agroinoculation of tobacco leaf discs with partial dimers of the virus. This assay, in a non-host model plant, was used to evaluate pathogen-derived resistance contributed by MYMV-Vig genes in transgenic plants. Viral DNA accumulation was optimum in tobacco leaf discs cultured for 10 days after infection with Agrobacterium tumefaciens strain Ach5 containing partial dimers of both DNA A and DNA B of MYMV-Vig. Transgenic tobacco plants with MYMV-Vig genes for coat protein (CP), replication-associated protein (Rep)-sense, Rep-antisense, truncated Rep (T-Rep), nuclear shuttle protein (NSP) and movement protein (MP) were generated. Leaf discs from transgenic tobacco plants, harbouring MYMV-Vig genes, were agroinoculated with partial dimers of MYMV-Vig and analyzed for viral DNA accumulation. The leaf discs from transgenic tobacco plants harbouring CP and MP genes supported the accumulation of higher levels of MYMV-Vig DNA. However, MYMV-Vig accumulation was inhibited in one transgenic plant harbouring the Rep-sense gene and in two plants harbouring the T-Rep gene. Northern analysis of these plants revealed a good correlation between expression of Rep or T-Rep genes and inhibition of MYMV-Vig accumulation.


Sorption and interaction of the flavonoid naringenin on tomato fruit cuticles.
The flavonoid naringenin accumulates in tomato fruit epidermis during ripening. The sorption of this flavonoid to enzymatically isolated cuticles of Solanum lycopersicum was studied as a function of the temperature and naringenin concentration at two stages of fruit growth. The selected stages were mature green, without flavonoids in the cuticle, and ripe tomato, with significant amounts of flavonoids in the cuticle. Sorption isotherms showed different behaviors that could be explained in terms of different affinities of the sorbed flavonoid for the cuticular matrix. The partition coefficient of naringenin in the system cuticle/water solution was a function of temperature and concentration. Changes in the free energy, enthalpy, and entropy for the phase transfer of naringenin to cuticle were also calculated, indicating the existence of naringenin-naringenin interactions replacing naringenin-cuticular matrix interactions at high concentrations with the final result of solid precipitations in the form of clusters within the cutin matrix.


Hemoptysis in children.
Pulmonary hemorrhage and hemoptysis are uncommon in childhood, and the frequency with which they are encountered by the pediatrician depends largely on the special interests of the center to which the child is referred. Diagnosis and management of hemoptysis in this age group requires knowledge and skill in the causes and management of this infrequently occurring potentially life-threatening condition. We reviewed the causes and treatment options for hemoptysis in the pediatric patient using Medline and Pubmed. A focused physical examination can lead to the diagnosis of hemoptysis in most of the cases. In children, lower respiratory tract infection and foreign body aspiration are common causes. Chest radiographs often aid in diagnosis and assist in using two complementary diagnostic procedures, fiberoptic bronchoscopy and high-resolution computed tomography. The goals of management are threefold: bleeding cessation, aspiration prevention, and treatment of the underlying cause. Mild hemoptysis often is caused by an infection that can be managed on an outpatient basis with close monitoring. Massive hemoptysis may require additional therapeutic options such as therapeutic bronchoscopy, angiography with embolization, and surgical intervention such as resection or revascularization. Hemoptysis in the pediatric patient requires prompt and thorough evaluation and treatment. An efficient systematic evaluation is imperative in identifying the underlying etiology and aggressive management is important because of the potential severity of the problem. This clinical review highlights the various etiological factors, the diagnostic and treatment strategies of hemoptysis in children.


HLA-B27 up-regulation causes accumulation of misfolded heavy chains and correlates with the magnitude of the unfolded protein response in transgenic rats: Implications for the pathogenesis of spondylarthritis-like disease.
HLA-B27 is implicated in the pathogenesis of spondylarthritis (SpA), yet the molecular mechanisms are incompletely defined. HLA-B27 misfolding has been associated with endoplasmic reticulum stress and activation of the unfolded protein response (UPR) in macrophages from HLA-B27/human beta(2)-microglobulin-transgenic (B27-transgenic) rats. This study was performed to assess the mechanisms that drive activation of the HLA-B27-induced UPR and to determine whether splenocytes respond in a similar manner. Splenocytes were isolated and bone marrow macrophages were derived from B27-transgenic and wild-type rats. Cells were treated for up to 24 hours with cytokines that induce class I major histocompatibility complex expression. HLA-B27 expression and misfolding were assessed by real-time reverse transcription-polymerase chain reaction, flow cytometry, and immunoblotting. Activation of the UPR was measured by quantifying UPR target gene expression and X-box binding protein 1 messenger RNA (mRNA) splicing. HLA-B27 mRNA up-regulation was accompanied by a dramatic increase in the accumulation of misfolded heavy chains and preceded robust activation of the UPR in macrophages. When macrophages were treated with various cytokines, the magnitude of the UPR correlated strongly with the degree of HLA-B27 up-regulation. In contrast, B27-transgenic splenocytes exhibited only low-level differences in the expression of UPR target genes after exposure to interferon-gamma or concanavalin A, which resulted in minimal HLA-B27 up-regulation. These results suggest that HLA-B27-associated activation of the UPR in macrophages is attributable to the accumulation of misfolded heavy chains, and that certain cell types may be more susceptible to the effects of HLA-B27 misfolding. Strategies that eliminate HLA-B27 up-regulation and/or the accumulation of misfolded heavy chains may be useful in evaluating the role of these events in the pathogenesis of SpA.


A finite mixture model of growth trajectories of adolescent alcohol use: predictors and consequences.
The current study sought to identify classes of growth trajectories of adolescent alcohol use and to examine the predictors and outcomes associated with the classes. Alcohol use was assessed from Grades 7 to 12 in a school-based sample. Latent growth mixture modeling was used, and results indicated 5 discrete longitudinal drinking patterns. The 2 most common drinking patterns included occasional very light drinking from Grades 7 to 12 and moderate escalation in both quantity and frequency of alcohol use. One group drank infrequently but at high levels throughout the study period. Another group exhibited rapid escalation in both quantity and frequency. The final group started at high levels of frequency and quantity in Grade 7 and showed rapid de-escalation in frequency. Emotional distress and risk taking distinguished the classes, and all classes, particularly rapid escalators, showed elevated levels of alcohol-related problems relative to occasional very light drinkers.


Comparison of peptide analysis results for horse, bovine and dog cytochrome c using capillary electrophoresis/mass spectrometry with untreated capillary column and basic buffer condition.
Peptide analysis of cytochrome c using capillary electrophoresis/mass spectrometry was demonstrated to be a rapid, sensitive and useful technique for providing information concerning the location of variation. We analyzed tryptic digests of horse, bovine and dog cytochrome c, and compared the peptide analysis results for information concerning amino acid sequences in proteins. The differences in amino acid sequence were confirmed by taking into consideration that all the other fragments are identical in each map. The use of an untreated capillary column with basic buffer condition (water+acetonitrile+(20 g/L) ammonium carbonate (70/20/10), pH 9.2) had a reproducibility of migration times to within about 2%.


The reliability and variation of measurements of the os calcis angles in children.
The databases of the Picture Archiving and Communication Systems of two hospitals were searched and all children who had a lateral radiograph of the ankle during their attendance at the emergency department were identified. In 227 radiographs, Bohler's and Gissane's angles were measured on two separate occasions and by two separate authors to allow calculation of inter- and intra-observer variation. Intraclass correlation coefficients were used to assess the reliability of the measurements. For Bohler's angle the overall inter-observer reliability, the intraclass correlation coefficient was 0.90 and the intra-observer reliability 0.95, giving excellent agreement. This reliability was maintained across the age groups. For Gissane's angle, inter- and intra-observer reliability was only fair or poor across most age groups. Further analysis of the Bohler's angle showed a significant variation in the mean angle with age. Contrary to published opinion, the angle is not uniformly lower than that of adults but varies with age, peaking towards the end of the first decade before attaining adult values. The age-related radiologic changes presented here may help in the interpretation of injuries to the hindfoot in children.


Damage assessment in composite laminates via broadband Lamb wave.
Time of flight (ToF) based method for damage detection using Lamb waves is widely used. However, due to the energy dissipation of Lamb waves and the non-ignorable size of damage in composite structure, the performance of damage detection is restricted. The objective of this research is to establish an improved method to locate and assess damages in composite structure. To choose appropriate excitation parameters, the propagation characters of Lamb waves in quasi-isotropic composite laminates are firstly studied and the broadband excitation is designed. Subsequently, the pulse compression technique is adopted for energy concentration and high-accuracy distance estimation. On this basis, the gravity center of intersections of path loci is employed for damage localization and the convex envelop of identified damage edge points is taken for damage contour estimation. As a result, both damage location and size can be evaluated, thereby providing the information for quantitative damage detection. The experiment consisting of five different sizes of damage is carried for method verification and the identified results show the efficiency of the proposed method.


Arthroscopic and computer-assisted high tibial osteotomy using standard total knee arthroplasty navigation software.
Opening-wedge high tibial osteotomy is an increasingly performed procedure for treatment of varus gonarthrosis and correction of malalignment during meniscal transplantation or cartilage restoration. Precise preoperative planning and meticulous surgical technique are required to achieve an appropriate mechanical axis correction. We describe our technique of arthroscopic and computer-assisted high tibial osteotomy using commonly available total knee arthroplasty navigation software as an intraoperative goniometer. We believe that our technique, by providing intraoperative real-time guidance of the degree of correction that is accurate and reliable, represents a useful tool for the surgeon who uncommonly performs high tibial osteotomy.


Acetate assimilation by Nitrobacter agilis in relation to its "obligate autotrophy".
Acetate (1 to 10 mm) had no effect on the rate of nitrite oxidation or exponential growth by Nitrobacter agilis. However, acetate-1-(14)C and -2-(14)C were both assimilated by growing cultures, and acetate carbon contributed 33 to 39% of newly synthesized cell carbon. Carbon from acetate was incorporated into all of the major cell constituents, including most of the amino acids of cell protein and poly-beta-hydroxybutyrate (PHB). Cultures grown in the presence of acetate showed a significant increase in turbidity, attributable in part to protein synthesis and the accumulation of PHB in the "post-exponential phase," when the supply of nitrite was completely exhausted. Cell suspensons of N. agilis assimilated acetate in the absence of bicarbonate and even in the absence of nitrite. However, the addition of nitrite increased the rate of acetate assimilation by cell suspensions. The distribution of (14)C-acetate incorporated by cell suspensions was qualitatively similar to that found with growing cultures. Cell suspensions of N. agilis slowly oxidized acetate to CO(2). Addition of nitrite suppressed CO(2) production from acetate but increased the assimilation of acetate carbon into cell material. N. agilis contained all the enzymes of the tricarboxylic acid cycle. Growth of N. agilis in the presence of acetate did not significantly affect the levels of the enzymes of the tricarboxylic acid cycle, but did result in a 100-fold increase in the specific activity of isocitratase. In contrast, carboxydismutase was partially repressed. N. agilis was grown heterotrophically through seven transfers on a medium containing acetate and casein hydrolysate. The addition of nitrite increased the rate of heterotrophic growth. Heterotrophically grown organisms still retained their ability to grow autotrophically with nitrite. However, these organisms oxidized nitrite at a slower rate. Organisms from autotrophic and heterotrophic cultures were analyzed to determine the mean guanine plus cytosine content of their deoxyribonucleic acid; in both cases this mean was 61.2 +/- 1%. We concluded that N. agilis is not an obligate autotroph; it appears to be a facultative autotroph which resembles the novel facultative autotroph, Thiobacillus intermedius, very closely.


Arterial vascularization of the extraocular muscles on its importance for orbital approaches.
The anatomic description of the arterial supply of the muscles of the eyeball was studied because medial and lateral approaches to the orbit to treat various disorders might severely damage the main trunk of the ophthalmic artery. The different arterial pedicles for each muscle, as well as their origins and points of penetration into the muscle, were studied in 19 male human orbits. In all cases, the muscular branches originated from the ophthalmic artery, and generally from the inferior face of this artery, just after crossing the optic nerve. The inferomedial muscular trunk arose from the distal of the ophthalmic artery (63.16%). The inferolateral muscular trunk, the superior oblique, levator palpebrae superioris, superior rectus, lateral rectus, and medial rectus arose from the lacrimal artery (43.36%), the bend of the ophthalmic artery (36.84%), the supraorbital artery (36.84%), the distal end of the ophthalmic artery (52.6%), the lacrimal artery (89.47%), and the inferomedial muscular trunk (84.51%), respectively. Complications resulting from damaging the artery can cause inadequacy in eye position, mobility, superior oblique function, or binocular vision, which are expected to be corrected postoperatively.


Comparison of the cardiac electrophysiological effects of flecainide and hydroquinidine in anesthetized dog: concentration-response relationship.
The concentration-dependent effects of flecainide and hydroquinidine were studied in closed-chest anesthetized dogs. The electrophysiological effects of three doses (i.v. infusions followed by an appropriate perfusion to plateau the plasma levels) of flecainide (1, 2, and 3.9 mg/kg) and hydroquinidine (2, 4, 7.5 mg/kg) were tested. Sinus cycle length, QRS duration, His-Purkinje and AV nodal conduction times, Wenckebach period, atrial, nodal, and ventricular refractory periods, and corrected QT interval were measured before and 30 min after the beginning of each bolus infusion. Both hydroquinidine and flecainide increased the sinus cycle length, and slowed cardiac conduction to different degrees. Hydroquinidine and flecainide prolonged ventricular conduction; flecainide had a greater effect at the His-Purkinje level. Hydroquinidine exhibited only a weak and nonsignificant effect at the AV node, whereas flecainide dramatically prolonged conduction and refractoriness. The two drugs increased AERP equally. The QT interval and ventricular refractoriness were similarly prolonged to the same extent by both drugs (32 and 35% after the third doses of hydroquinidine and flecainide, respectively). The high plasma flecainide levels reached in our study (1.47 and 2.9 micrograms/ml after the second and third doses, respectively) may explain these effects, which are unexpected for a class Ic agent. These results suggest that flecainide could increase the QT interval, like a class Ia drug when its plasma level exceeds the therapeutic range.


The BeUpstanding Program™: Scaling up the Stand Up Australia Workplace Intervention for Translation into Practice.
Too much sitting is now recognised as a common risk factor for several health outcomes, with the workplace identified as a key setting in which to address prolonged sitting time. The Stand Up Australia intervention was designed to reduce prolonged sitting in the workplace by addressing influences at multiple-levels, including the organisation, the environment, and the individual. Intervention success has been achieved within the context of randomised controlled trials, where research staff deliver several of the key intervention components. This study describes the initial step in the multi-phase process of scaling up the Stand Up Australia intervention for workplace translation. A research-government partnership was critical in funding and informing the prototype for the scaled up BeUpstanding program™. Evidence, protocols and materials from Stand Up Australia were adapted in collaboration with funding partner Workplace Health and Safety Queensland to ensure consistency and compatibility with existing government frameworks and resources. In recognition of the key role of workplace champions in facilitating workplace health promotion programs, the BeUpstanding program™ is designed to be delivered through a stand-alone, free, website-based toolkit using a 'train the champion' approach. The BeUpstanding program™ was influenced by the increasing recognition of prolonged sitting as an emerging health issue as well as industry demand. The research-government partnership was critical in informing and resourcing the development of the scaled-up program.


Rectal inflammatory fibroid polyp resected with endoscopic submucosal dissection.
Inflammatory fibroid polyp (IFP) is a rare benign tumor originating from the submucosa of the gastrointestinal tract. Most are found in the stomach, with only one previous case reported in the rectum. IFPs are typically larger than 1 cm in diameter and present symptoms. Colonoscopic examination of an asymptomatic 66-year-old man revealed a small submucosal tumor, 3 mm in diameter, in the rectum. The lesion was completely resected by endoscopic submucosal dissection (ESD) and was histopathologically diagnosed as IFP. We report herein a very rare rectal IFP that could be treated and diagnosed with ESD.


[Immunoreactivity and immunogenicity analysis of the recombinant cathepsin L-like protease of Fasciola hepatica in SD rats].
To analyze the immunoreactivity of recombinant cathepsin L-like proteases (CatL) protein of Fasciola hepatica and its immunogenicity in SD rats. The E. coli BL21(DE3) cells harbouring recombinant plasmid pET30a-FhCatL were inoculated in LB medium, and the protein expression was induced with IPTG. The recombinant protein FhCatL was analyzed by SDS-PAGE and the immunoreactivity was identified by Western blotting with sera from Fasciola hepatica-infected goat as the primary antibody. Twenty SD rats were randomly divided into immunized group and adjuvant control group. SD rats in immunized group were injected subcutaneously with 200 microg of purified FhCatL protein. All the rats received three immunizations at 3-week intervals. The adjuvant control group with 10 SD rats received only adjuvants emulsified with the same amount of PBS. Serum samples were collected at the day before the second and final immunization, 3, 6, and 9 weeks after the final immunization. The IgG antibody of rats' sera was examined by indirect ELISA and spleen lymphocyte proliferation (SLP) was tested by methyl thiazolyl tetrazolium (MTT). The molecular weight of purified FhCatL was about Mr 42,000. The recombinant FhCatL was recognized by pool sera of goats naturally infected with F. hepatica. The titer of specific antibody IgG in SD rats induced by the recombinant protein against CatL protein was significantly higher than that of the control, and the antibody titer reached the peak at three weeks after the final immunization (1 : 102,400). The stimulation index of splenocytes in immunized group was 2.176 +/- 0.047, which was significantly higher than that of the control (1.171 +/- 0.032) (P<0.05). The recombinant FhCatL protein bears stronger immnoreactivity and immunogenicity.


Functional characterization of class Ia- and non-class Ia-restricted Chlamydia-reactive CD8+ T cell responses in humans.
CD8(+) T cells are a key immune component for the eradication of many intracellular pathogens. This study aims to characterize the human CD8(+) T cell response to naturally processed chlamydial Ags in individuals exposed to the intracellular pathogen Chlamydia trachomatis. By using C. trachomatis-infected autologous dendritic cells (DCs) as stimulators, Chlamydia-reactive CD8(+) T cell responses were detected in all 10 individuals tested. The majority of the Chlamydia-reactive CD8(+) T cells were non-MHC class Ia restricted in all three of the individuals tested. From one donor, three non-class Ia-restricted and two class Ia-restricted Chlamydia-specific CD8(+) T cells were cloned and characterized further. All five T cell clones secreted IFN-gamma in response to autologous DCs infected with viable Chlamydia, but not with DCs pulsed with inactivated chlamydial elementary bodies. MHC class Ia-restricted and non-class Ia-restricted responses were inhibited by DC treatment with a proteasomal inhibitor and an endoplasmic reticulum-Golgi transport inhibitor, suggesting that these T cells recognize a peptide Ag translocated to the host cell cytosol during infection that is processed via the classical class Ia Ag-processing pathway. Even though both restricted and nonrestricted CD8(+) T cells produced IFN-gamma in response to Chlamydia-infected fibroblasts, only the non-class Ia-restricted cells were lytic for these targets. The class Ia-restricted CTLs, however, were capable of cytolysis as measured by redirected killing. Collectively, these data demonstrate that both class Ia-restricted and non-classically restricted CD8(+) T cells are elicited in C. trachomatis-exposed individuals. Their role in host immunity remains to be elucidated.


Medically resistant pediatric insular-opercular/perisylvian epilepsy. Part 2: outcome following resective surgery.
OBJECTIVE Seizure onset in the insular cortex as a cause of refractory epilepsy is underrepresented in the pediatric population, possibly due to difficulties localizing seizure onset in deep anatomical structures and limited surgical access to the insula, a complex anatomical structure with a rich overlying vascular network. Insular seizure semiology may mimic frontal, temporal, or parietal lobe semiology, resulting in false localization, incomplete resection, and poor outcome. METHODS The authors retrospectively reviewed the records of all pediatric patients who underwent insular cortical resections for intractable epilepsy at Miami Children's Hospital from 2009 to 2015. Presurgical evaluation included video electroencephalography monitoring and anatomical/functional neuroimaging. All patients underwent excisional procedures utilizing intraoperative electrocorticography or extraoperative subdural/depth electrode recording. RESULTS Thirteen children (age range 6 months-16 years) with intractable focal epilepsy underwent insular-opercular resection. Seven children described symptoms that were suggestive of insular seizure origin. Discharges on scalp EEG revealed wide fields. Four patients were MRI negative (i.e., there were no insular or brain abnormalities on MRI), 4 demonstrated insular signal abnormalities, and 5 had extrainsular abnormalities. Ten patients had insular involvement on PET/SPECT. All patients underwent invasive investigation with insular sampling; in 2 patients resection was based on intraoperative electrocorticography, whereas 11 underwent surgery after invasive EEG monitoring with extraoperative monitoring. Four patients required an extended insular resection after a failed initial surgery. Postoperatively, 2 patients had transient hemiplegia. No patients had new permanent neurological deficits. At the most recent follow-up (mean 43.8 months), 9 (69%) children were seizure free and 1 had greater than 90% seizure reduction. CONCLUSIONS Primary insular seizure origin should be considered in children with treatment-resistant focal seizures that are believed to arise within the perisylvian region based on semiology, widespread electrical field on scalp EEG, or insular abnormality on anatomical/functional neuroimaging. There is a reasonable chance of seizure freedom in this group of patients, and the surgical risks are low.


Differential effects of 4 types of environmental enrichment on aggressive pecking, feather pecking, feather loss, food wastage and productivity in Japanese quail.
1. We examined the effects of 4 types of environmental enrichment (foraging opportunities, structural complexity, sensory stimulation/novelty, and social companionship) on aggressive and feather pecking, feather condition, food wastage, body weight, feed conversion, and egg production in adult Japanese quail. Sex differences were examined where possible. 2. GLM analysis was used to evaluate the effects of enrichment and housing, while test-retest reliability and the stability of measures over 18 d were assessed using partial correlation. 3. Foraging enrichment reduced food wastage. 4. Body weight, feed conversion, and egg production were not affected by enrichment. Rates of aggressive and feather pecking were also not significantly affected, but these behaviours were observed very infrequently in this study. 5. Socially-housed birds had poorer feather condition, lower body weight and less efficient feed conversion than singly-housed birds. Social housing did not affect food wastage. 6. There were not sex differences in feather pecking, feather condition, food wastage, or feed conversion. 7. All measures except feather pecking were reliable over 24 h, but only feather condition and body weight were stable over 18 d. The instability f the behavioural measures over time suggest that enrichment effects may vary with age.


SAW Characteristics of AlN/SiO2/3C-SiC Layered Structure With Embedded Electrodes.
A layered structure of aluminum nitride (AlN)/silicon dioxide (SiO2)/cubic silicon carbide with embedded electrodes, which enables the growth of high-quality AlN thin films, is proposed and studied. The phase velocity, coupling factor, and temperature coefficient of frequency (TCF) of surface acoustic waves in the proposed structure have been investigated using the finite-element method. The simulation results show that a high velocity of 5485 m/s and a large effective coupling factor ( K2<sup/>) of 1.45% can be simultaneously obtained for the first mode. The dramatic enhanced K2 of 10.5% is also obtainable on the proposed structure employing Sc0.4Al0.6N thin film. Besides, the excellent zero TCF is also achieved without deteriorating the coupling factor by adding an amorphous SiO2 overlay.


Modeling of bispecific antibody elution in mixed-mode cation-exchange chromatography.
The increasing demand for cost-efficient manufacturing of biopharmaceuticals has been the main driving force for the development of novel chromatography resins, which resulted in the development of multimodal or mixed-mode chromatographic resins. Most of them combine electrostatic and hydrophobic functionalities and are designed to deliver unique selectivity and increased binding capacities also at increased ionic strength. However, the mechanism of the protein-resin interaction in mixed-mode chromatography is still not fully understood. The performance of protein separations in mixed-mode chromatography is consequently difficult to predict. In this work, we present a model combining both salt and pH dependence to characterize and to predict protein retention in mixed-mode chromatography. The model parameters are determined based on simple linear pH gradient elution experiments at different ionic strengths and they are directly transferable for the prediction of salt-induced elution at fixed pH. Validity of the model is demonstrated for a bispecific antibody and its product-related impurities.


Inpatient and outpatient psychiatric services: substitutes or complements?
Patients at risk for psychiatric hospitalization make only limited use of outpatient services, although clinical research has demonstrated that outpatient treatments and home care can be as effective as inpatient psychiatric treatment in treating certain mental health problems. The substitution of ambulatory services for inpatient care has in part been limited because insurers have restricted outpatient mental health benefits to control utilization. The authors critically review evidence from the economic and clinical literatures to determine the extent to which outpatient psychiatric treatment substitutes or complements inpatient treatment. To encourage clinically effective substitution of outpatient for inpatient services, further research is needed to identify the patient populations for whom substitution is possible and the treatment and environmental conditions in which it is most likely to be successful.


Endoparasites of three species of house geckoes in Lampung, Indonesia.
Thirty-four house geckoes (21 Cosymbotus platyurus, four Gehyra mutilata and nine Hemidactylus frenatus) in December, 1997 (rainy season) and 26 geckos (16 C. platyurus, six G. mutilata and four H. frenatus) in July, 2000 (dry season) were captured in Lampung, Indonesia. Some species of geckoes have been inadvertently introduced to many tropical regions from their native region, but the three species of geckoes in this study are native to Indonesia. Six species of endoparasites were recovered: Oochoristica javanensis (Cestoda) from the small intestine, Paradistomum geckonum (Digenea) from the small intestine and gallbladder, Postorchigenes ovatus (Digenea) from the small intestine, Spauligodon hemidactylus (Nematoda) from the large intestine, and Raillietiella gehyra and R. frenatus (Pentastomida) from the lungs. The prevalence and mean intensity of infection in each species of geckoes are also presented. The prevalence of S. hemidactylus from C. platyurus and H. frenatus in the rainy season was significantly higher than in the dry season. The low prevalence of S. hemidactylus in G. mutilata in the present study corresponded to a previous report from a non-native area. According to the original description, the male of S. hemidactylus lacked a spicule, but in the present study, one male was found with a spicule. The present study suggests male dimorphism occurs in Spauligodon. The number of endoparasite species and snout vent length of geckoes were positively correlated. Geckoes with high worm burdens may be more easily captured by predators.


[Lack of evidence that inducible nitric oxide synthase participates in the development of ischemic brain damage].
We have already reported that the concentration of nitric oxide (NO) increases during and after cerebral ischemia and a selective inhibitor of neuronal NO synthase (nNOS) suppresses this increase and subsequently mitigates brain damage in rats. Although the selective inhibition of nNOS is a promising pharmacological strategy for the treatment of stroke, the role of inducible NOS (iNOS) remains to be clarified. Toward this end, we investigated temporal alterations in iNOS mRNA by the RT-PCR method in a rat model of middle cerebral artery (MCA) occlusion. We found that iNOS mRNA in the ischemic hemisphere began to increase at 3 hr and reached the maximum level at 24 hr of reperfusion following 3 hr of MCA occlusion. However, quantitative analysis revealed that no significant difference existed between 6 hr or 24 hr reperfusion group and their respective time-matched sham operation group. In addition, neither Western blotting nor immunocytochemical study disclosed an apparent induction of iNOS at any time points examined. Similar results were obtained at 24 hr of permanent MCA occlusion. Taken together, these data indicate that iNOS induction during and after MCA occlusion may be not a critical event for the development of infarction caused by ischemia itself.


COVID-19 in kidney transplant recipients.
There is minimal information on coronavirus disease 2019 (COVID-19) in immunocompromised individuals. We have studied 10 patients treated at 12 adult care hospitals. Ten kidney transplant recipients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction, and 9 were admitted. The median age was 57 (interquartile range [IQR] 47-67), 60% were male, 40% Caucasian, and 30% Black/African American. Median time from transplant to COVID-19 testing was 2822 days (IQR 1272-4592). The most common symptom was fever, followed by cough, myalgia, chills, and fatigue. The most common chest X-ray and computed tomography abnormality was multifocal patchy opacities. Three patients had no abnormal findings. Leukopenia was seen in 20% of patients, and allograft function was stable in 50% of patients. Nine patients were on tacrolimus and a mycophenolic antimetabolite, and 70% were on prednisone. Hospitalized patients had their antimetabolite agent stopped. All hospitalized patients received hydroxychloroquine and azithromycin. Three patients died (30%), and 5 (50%) developed acute kidney injury. Kidney transplant recipients infected with COVID-19 should be monitored closely in the setting of lowered immunosuppression. Most individuals required hospitalization and presenting symptoms were similar to those of nontransplant individuals.


Database of calculated values of retention and excretion for members of the public following acute intake of radionuclides.
Intakes of radionuclides can be estimated from measurements of radioactivity in the whole body or in specific organs or in excreta by comparing them with predicted retention or excretion data calculated using standard biokinetic models. For occupational exposure monitoring, data are presented by ICRP for 29 radionuclides in Publication 78 (1997) and by the authors for 42 radionuclides as electronic look-up tables in Microsoft Excel. In the present work, values of retention and excretion were computed for selected radionuclides inhaled or ingested by members of the public. Graphs were constructed from the computed results showing the predicted monitoring data as functions of time following acute intakes of radionuclides. A graphical database was assembled on the Web site http//www.nirs.go.jp/RPD/ to provide a tool for the interpretation of bioassay measurements.


Distribution of haloacetic acids in the water columns of the Laurentian Great Lakes and Lake Malawi.
Haloacetic acids (HAAs) are persistent and mildly phytotoxic compounds that have been detected in many aquatic environments, including the waters of the Great Lakes. Sources of HAAs, especially of trifluoroacetic acid (TFA), are not well understood. In this study we assessed the influence of urbanization on the concentrations and profiles of HAAs in the Laurentian Great Lakes and in Lake Malawi, an African Great Lake. Vertical depth profiles for these compounds were taken for each of the Great Lakes with additional profiles taken 2 years later for Lakes Erie and Ontario. The results showed that while TFA was relatively constant throughout the water column, the chloroacetic acids (CAAs) varied with depth. There was a trend of increasing TFA proceeding from Lake Superior to Lake Ontario (18-150 ng/L). Total CAA concentrations were relatively constant throughout the lakes (approximately 500 ng/L) with dichloroacetic acid being the most abundant. No bromoacetic acids were detected. In the Detroit River, a connecting channel between Lakes Huron and Erie, the TFA values were similar to those in Lake Huron, but the CAAs levels were higher than in the upstream lakes and dependent on location, indicating inputs from urban areas along the river. These results were compared to those from Lake Malawi, which has a high population density within the watershed but no heavy industry. CAAs were nondetectable, and TFA concentrations were just at the detection limit (1 ng/L). Total HAA in the water column of Lakes Superior and Huron was compared to annual precipitation inputs at a site situated near both lakes. For Lake Huron, precipitation was a minor contributor to the total HAA inventory of the lake, but for Lake Superior precipitation could be the major contributor to the mass of HAA in this lake. Generally, high HAA levels paralleled the degree of industrial activity in the adjacent waters.


Determinants of Vitamin B6 Status in Community-Dwelling Older Adults: A Longitudinal Study Over a Period of 18 Years.
Cross-sectional studies indicate an age-related decline in vitamin B6 status. Because longitudinal studies are lacking, the present study investigates the long-term association between age and vitamin B6 status in older adults by considering potential confounding factors. The study population consists of 249 women and 111 men aged ≥ 60 years, who had at least three follow-ups between 1996 and 2014 with complete data records on relevant parameters. Vitamin B6 status was assessed by serum pyridoxal 5'-phosphate (PLP) concentrations measured by high-performance liquid chromatography. Linear mixed models were used to analyze the influence of age, sex, body composition, supplements, diet, lifestyle, and serum creatinine on PLP concentrations. At baseline, 37% of the subjects showed PLP concentrations < 30 nmol/L and more than half failed to meet the recommended dietary intake. Longitudinal analyses revealed that age, use of supplements and protein intake were positive determinants of PLP concentrations, whereas body fat showed a negative impact. No influence of sex, dietary vitamin B6 intake, lifestyle factors or serum creatinine on PLP concentrations was found. The present study provides no evidence that in the course of aging PLP concentrations decline between 60 and 90 years. However, age-related changes in body composition, such as an increased ratio of fat mass to fat-free mass may negatively affect vitamin B6 status.


Swallowed ocular prostheses: report of three cases in children with retinoblastoma.
To report 3 instances of 2 children who swallowed their ocular prostheses. A 30-month-old boy whose eye had been enucleated for retinoblastoma swallowed his ocular prosthesis on 2 different occasions, and a 32-month-old boy whose eye had also been enucleated for retinoblastoma swallowed his ocular prosthesis once. In the second child, an abdominal radiograph was obtained, but the swallowed prosthesis was not apparent, and radiographic imaging of the recovered prosthesis failed to demonstrate an identifiable object. In each case, the prosthesis was recovered in the child's stool without incident several weeks later. Neither child had physical complications as a result of the swallowing events. We report 3 instances in which a child fitted for an ocular prosthesis after enucleation swallowed his prosthesis and had no untoward effects. The failure of imaging to detect the prostheses in the second child is attributed to the radiolucent nature of materials used in the manufacture of the prosthesis. Each of the children was having life stresses in addition to his medical treatment that may have accounted for his behavior.


[Risk Factors for Postoperative Delirium after Cardiac Surgery].
Background Delirium is a common psychiatric disorder after cardiac surgery and predisposes patients to increased mortality and morbidity. Its prevention requires knowledge of the risk factors involved. Objective What are preoperative risk factors for postoperative delirium after cardiac surgery? Methods Prospective longitudinal study of 241 elective cardiac surgical patients with preoperative assessment of potential risk factors and delirium assessment twice daily over five postoperative days. Results 13 % of the patients experienced delirium. Reduced cognitive performance (OR: 3.80; 95 % CI: 1.66 - 8.66), higher comorbidity (OR: 1.36; 95 % CI: 1.07 - 1.7) and higher age (OR: 1.08; 95 % CI: 1.02 - 1.13) increased the risk of delirium. Conclusion Delirium after cardiac surgery is common. It occurs in particular in patients with low cognitive performance, higher comorbidity and higher age.


Detection of herpes simplex virus infection using glucose oxidase-antiglucose oxidase immunoenzymatic stain.
Herpes simplex virus (HSV) infected cells have been detected in tissue culture and human cell specimens by an immunoenzymatic staining method using the fungal enzyme glucose oxidase. Infected cells from culture or human specimens appear as dark blue, brown, or red, depending on the tetrazolium salt used in the disclosing reaction, with virtually no staining of uninfected cells. The specificity and sensitivity of this method and of the more commonly used immunoperoxidase method are comparable, but the immunoglucose oxidase method avoids the problems of nonspecific staining by the endogenous peroxidase present in mucosecretions and inflammatory cells. Staining time can be reduced up to 40% of that necessary for the unlabeled immunoperoxidase procedure without compromising the quality of staining results.


Porphyromonas gingivalis Infection Promoted the Proliferation of Oral Squamous Cell Carcinoma Cells through the miR-21/PDCD4/AP-1 Negative Signaling Pathway.
Recent epidemiological studies have revealed that Porphyromonas gingivalis, a major pathogen in periodontal disease, is associated with the development of oral squamous cell carcinoma (OSCC). However, the underlying mechanisms induced by P. gingivalis have not been well-defined. We aimed to determine the role of P. gingivalis in OSCC proliferation and the relevant molecular mechanisms. A cellular proliferation model of OSCC Tca8113 cells infected by P. gingivalis at a multiplicity of infection (MOI) of 50 was established. Cell proliferation was drastically increased in the infected cells compared with the control cells, while the proportion of cells in S phase was increased and the proportion of cells in G1 phase was decreased in the infected cells compared with the control cells. Additionally, the levels of activator protein 1 (AP-1; c-Jun and c-Fos) and its target gene cyclin D1 were increased in P. gingivalis-infected Tca8113 cells compared with control cells. miR-21 expression was elevated when programmed cell death 4 (PDCD4) expression was downregulated. Cyclin D1 expression was regulated by miR-21, PDCD4, and AP-1. The disruption of the pathway by silencing c-Jun, blocking miR-21 expression, or overexpressing PDCD4 led to decreased cyclin D1 expression and inhibited cell proliferation. P. gingivalis DNA levels were positively correlated with miR-21 and c-Jun expression and negatively correlated with PDCD4 expression in clinical OSCC samples. Our findings indicated that P. gingivalis might promote OSCC proliferation by regulating cyclin D1 expression via the miR-21/PDCD4/AP-1 negative feedback signaling pathway.


Evaluation of the Mycobacterium leprae particle agglutination (MLPA) test as a tool in the epidemiology of leprosy in high prevalence village in South Sulawesi, Indonesia.
This study reports on the usefulness of an IgM phenolic glycolipid-1 (PGL-1) Mycobacterium leprae particle agglutination (MLPA) test for serodiagnosis of leprosy in a prospective longitudinal community survey in a high prevalence village in South Sulawesi, Indonesia, IgM PGL-1 MLPA has simple and limited value as a screening method for detection of transmission of leprosy in the community. Many normal persons in the community in a high prevalence area had increased IgM anti PGL-1 antibodies, presumably as a consequence of early subclinical infection. In conclusion, this study demonstrated that the MLPA test can only reliably detect anti-PGL-1 antibodies in the community and may be useful for follow-up study of subclinical infection of leprosy among individuals living the an endemic area.


Psychiatric disorders in Ehlers-Danlos syndrome are frequent, diverse and strongly associated with pain.
Ehlers-Danlos syndromes (EDS) are a heterogeneous group of hereditary connective tissue disorders characterized by joint hypermobility, widespread musculoskeletal pain and tissue fragility. Psychiatric disorders and psychosocial impairment are common, yet poorly characterized, findings in EDS patients. We investigated the frequency and types of psychiatric disorders and their relationship to systemic manifestations in a cohort of 106 classic and hypermobility type EDS patients. In this retrospective study, extensive medical chart review was performed for patients referred at two genetics clinics who were diagnosed with EDS. Statistical analysis was undertaken to determine the frequency of psychiatric disorders and association with systemic findings. Psychiatric disorders were found in 42.5% of the EDS cohort, with 22.7% of patients affected with 2 or more psychiatric diagnoses. Anxiety and depression were most commonly reported, with frequencies of 23.6 and 25.5%, respectively. A variety of other psychiatric diagnoses were also identified. Abdominal pain [odds ratio (OR) 7.38], neuropathic pain (OR 4.07), migraines (OR 5.21), joint pain (OR 2.85) and fatigue (OR 5.55) were significantly associated with the presence of a psychiatric disorder. The presence of any pain symptom was significantly associated with having a psychiatric disorder (OR 9.68). Muscle pain (OR 2.79), abdominal pain (OR 5.78), neuropathic pain (OR 3.91), migraines (OR 2.63) and fatigue (OR 3.78) were significantly associated with having an anxiety or mood disorder. Joint hypermobility and the classic dermatological features of EDS showed no significant association with having a psychiatric disorder. Our findings demonstrate a high frequency of psychiatric disorders and an association with pain symptoms in EDS.


Sub-optimal control of fuzzy linear dynamical systems under granular differentiability concept.
This paper deals with sub-optimal control of a fuzzy linear dynamical system. The aim is to keep the state variables of the fuzzy linear dynamical system close to zero in an optimal manner. In the fuzzy dynamical system, the fuzzy derivative is considered as the granular derivative; and all the coefficients and initial conditions can be uncertain. The criterion for assessing the optimality is regarded as a granular integral whose integrand is a quadratic function of the state variables and control inputs. Using the relative-distance-measure (RDM) fuzzy interval arithmetic and calculus of variations, the optimal control law is presented as the fuzzy state variables feedback. Since the optimal feedback gains are obtained as fuzzy functions, they need to be defuzzified. This will result in the sub-optimal control law. This paper also sheds light on the restrictions imposed by the approaches which are based on fuzzy standard interval arithmetic (FSIA), and use strongly generalized Hukuhara and generalized Hukuhara differentiability concepts for obtaining the optimal control law. The granular eigenvalues notion is also defined. Using an RLC circuit mathematical model, it is shown that, due to their unnatural behavior in the modeling phenomenon, the FSIA-based approaches may obtain some eigenvalues sets that might be different from the inherent eigenvalues set of the fuzzy dynamical system. This is, however, not the case with the approach proposed in this study. The notions of granular controllability and granular stabilizability of the fuzzy linear dynamical system are also presented in this paper. Moreover, a sub-optimal control for regulating a Boeing 747 in longitudinal direction with uncertain initial conditions and parameters is gained. In addition, an uncertain suspension system of one of the four wheels of a bus is regulated using the sub-optimal control introduced in this paper.


Brain mesenchymal stem cells: physiology and pathological implications.
Mesenchymal stem cells (MSCs) are defined as progenitor cells that give rise to a number of unique, differentiated mesenchymal cell types. This concept has progressively evolved towards an all-encompassing concept including multipotent perivascular cells of almost any tissue. In central nervous system, pericytes are involved in blood-brain barrier, and angiogenesis and vascular tone regulation. They form the neurovascular unit (NVU) together with endothelial cells, astrocytes and neurons. This functional structure provides an optimal microenvironment for neural proliferation in the adult brain. Neurovascular niche include both diffusible signals and direct contact with endothelial and pericytes, which are a source of diffusible neurotrophic signals that affect neural precursors. Therefore, MSCs/pericyte properties such as differentiation capability, as well as immunoregulatory and paracrine effects make them a potential resource in regenerative medicine.


The effects of direction and movement of attractors on users' behavior in virtual environments.
Despite fast technological developments in virtual reality (VR), methodologies and guidelines for evaluating the design of virtual environments (VEs) are lacking. The theory of perceptual opportunities (POs) has previously been proposed as a basis of such a design methodology. This paper presents an empirical study investigating the effect of representation of POs on users' behavior in VEs. The effects of both direction and movement of attractor on choice of objects in a simple VE were studied. Results showed that vertical static attractors were chosen least frequently. Furthermore, there was an effect of direction for static attractors in favor of the take-off direction. Implications for VE design in the framework of POs are discussed.


Comparison of the Panther Fusion and a laboratory-developed test targeting the envelope gene for detection of SARS-CoV-2.
Numerous nucleic acid amplification assays have recently received emergency use authorization (EUA) for the diagnosis of SARS-CoV-2 infection, and there is a need to assess their test performance relative to one another. The aim of this study was to compare the test performance of the Hologic Panther Fusion SARS-CoV-2 assay targeting two regions of open reading frame 1ab (ORF1ab) to a high complexity molecular-based, laboratory-developed EUA from Stanford Health Care (SHC) targeting the SARS-CoV-2 envelope (E) gene. We performed a diagnostic comparison study by testing nasopharyngeal samples on the two assays. Assay agreement was assessed by overall percent agreement and Cohen's kappa coefficient. A total of 184 nasopharyngeal samples were tested using the two assays, of which 180 showed valid results and were included for the comparative analysis. Overall percent agreement between the assays was 98.3 % (95 % confidence interval (CI) 95.2-99.7) and kappa coefficient was 0.97 (95 % CI 0.93-1.0). One sample was detected on the SHC laboratory developed test (LDT) and not on the Panther Fusion, and had a Ct of 35.9. Conversely, 2 samples were detected on the Panther Fusion and not on the LDT, and had Ct values of 37.2 and 36.6. The Panther Fusion SARS-CoV-2 assay and the SHC LDT perform similarly on clinical nasopharyngeal swab specimens. Other considerations, including reagent availability, turnaround time, labor requirements, cost and instrument throughput should guide the decision of which assay to perform.


Prophylaxis of deep venous thrombosis after acute abdominal operation.
Two hundred and forty-five patients who underwent acute extensive abdominal operations were randomized into three regimens to achieve optimal prophylaxis of postoperative thromboembolic complications. All of the patients were screened by the 125I-fibrinogen uptake test for seven days and if the phlebographic findings were positive. Of 81 patients receiving low dose heparin, 12 had thromboembolism. Of 79 receiving a combination of low dose heparin and graded compression stockings, two had thromboembolism, and of 85 receiving a combination of dextran and graded compression stockings, 13 had this complication. This difference is significant in favor of the second treatment (p = 0.013). It is concluded that the combination of low dose heparin and graded compression stockings is an effective way to prevent thromboembolism after acute abdominal operations.


[Establishment of detection test for hepatitis C virus antigen].
To establish the enzyme linking immunosorbent assay (ELISA) test with the specific monoclonal antibody (McAb) for detecting the hepatitis C virus (HCV) antigen so as to study the possibility of HCV antigen detection from plasma and serum samples. Among the McAbs against HCV core and NS3 region, several kinds of combination models were analyzed to choose the optimal one. 348 samples from volunteer donors were tested by this test to calculate the cutoff value. 371 samples, among which 146 samples were positive to anti-HCV and 225 ones were negative to anti-HCV, were screened. The antigen positive samples were confirmed by HCV nested PCR. The model of detection test was constructed with the C39,C7-6 as capture McAb and C39,C7-57 as HRP Conjugated McAb. This test could detect the C7 antigen to 5 ng/ml, and its cutoff value was determined as the average value of negative control by adding 0.25. Eleven of 146 samples positive to anti-HCV and 16 of 225 ones negative to anti-HCV were positive to HCV antigen. Among these 27 antigen positive samples, there were 23 positive to HCV RNA by PCR detection. With this HCV antigen detection test, some of samples positive to HCV antigen can be found from plasma positive to and negative to anti-HCV and be confirmed by PCR. It is shown that it is possible to detect HCV antigen directly from plasma samples and it is important for HCV basic research and for control of transmission of HCV.


[Research progress of in vivo bioreactor as vascularization strategies in bone tissue engineering].
To review the application and research progress of in vivo bioreactor as vascularization strategies in bone tissue engineering. The original articles about in vivo bioreactor that can enhance vascularization of tissue engineered bone were extensively reviewed and analyzed. The in vivo bioreactor can be created by periosteum, muscle, muscularis membrane, and fascia flap as well as biomaterials. Using in vivo bioreactor can effectively promote the establishment of a microcirculation in the tissue engineered bones, especially for large bone defects. However, main correlative researches, currently, are focused on animal experiments, more clinical trials will be carried out in the future. With the rapid development of related technologies of bone tissue engineering, the use of in vivo bioreactor will to a large extent solve the bottleneck limitations and has the potential values for clinical application.


Factors influencing the outcome of sequential renal transplants.
Of 181 kidney transplantations performed on 151 patients in our center during the years 1971-82, 34 were retransplantations performed on 26 patients with follow-up periods ranging from 1 month to 10 years. One-year actuarial patient survival was 77.2% (82 of 122) for first cadaveric-graft recipients, 95.8% (21 of 26) for second- and 100% (6 of 6) for third-graft recipients. One-year actuarial graft survival was 44.5% (52 of 122) for first cadaveric grafts, 40.8% (10 of 26) for second grafts and 67% (4 of 6) for third grafts. Age, sex and blood group of the recipients did not seem to influence second-graft survival, nor did cumulative duration of hemodialysis and cold ischemic time. A beneficial influence, although not statistically significant, was noted by a longer first-graft survival time, better HLA matching and shorter total warm ischemic time. Retransplantation within 2 months after loss of the first graft and/or the absence of cytotoxic antibodies was found to have a statistically significant beneficial influence.


State of the science: does the theory of maternal role attainment apply to African American motherhood?
This article reviews the current state of knowledge of the theory of maternal role attainment (MRA) and its relevance in describing African American motherhood. EBSCOhost Research Databases that included PubMed, CINAHL plus, MEDLINE, PsycINFO, SCOPUS, and Web of Science were searched for journal articles that examined maternal identity and MRA. Keyword searches included maternal identity, maternal role attainment, becoming a mother, prenatal attachment, maternal-fetal attachment, and maternal-infant attachment. Inclusion criteria for this review were published journal articles of studies conducted in the United States, with a clear delineation of the theoretical framework of MRA. Journal articles that measured MRA among women with depression or medically fragile infants were excluded. Two hundred and twelve studies were reviewed; 25 studies, published between 1975 and 2007, met the inclusion criteria. Nine articles described the theory of MRA, 11 articles measured variables thought to influence MRA, and 6 articles described maternal-fetal attachment, a construct of MRA. Studies were reviewed, categorized, and analyzed to determine current knowledge of how the theory of MRA describes African American motherhood. Categories included studies describing the theoretical framework of maternal identity and MRA, studies measuring key variables thought to impact MRA, and studies measuring maternal-fetal attachment and maternal-infant attachment. The studies were limited by homogenous samples of upper-middle-class white women and low-income, single, African American adolescents. Study results of MRA cannot be generalized to African American women. Further research is essential to identify attributes influencing MRA, specifically among larger samples of African American women with demographics similar to that of the white populations that have been included in studies thus far.


Evolution of elongation factor-like (EFL) protein in Rhizaria is revised by radiolarian EFL gene sequences.
Elongation factor 1α (EF-1α) and elongation factor-like (EFL) proteins are considered to carry out equivalent functions in translation in eukaryotic cells. Elongation factor 1α and EFL genes are patchily distributed in the global eukaryotic tree, suggesting that the evolution of these elongation factors cannot be reconciled without multiple lateral gene transfer and/or ancestral co-occurrence followed by differential loss of either of the two factors. Our current understanding of the EF-1α/EFL evolution in the eukaryotic group Rhizaria, composed of Foraminifera, Radiolaria, Filosa, and Endomyxa, remains insufficient, as no information on EF-1α/EFL gene is available for any members of Radiolaria. In this study, EFL genes were experimentally isolated from four polycystine radiolarians (i.e. Dictyocoryne, Eucyrtidium, Collozoum, and Sphaerozoum), as well as retrieved from publicly accessible expressed sequence tag data of two acantharean radiolarians (i.e. Astrolonche and Phyllostaurus) and the endomyxan Gromia. The EFL homologs from radiolarians, foraminiferans, and Gromia formed a robust clade in both maximum-likelihood and Bayesian phylogenetic analyses, suggesting that EFL genes were vertically inherited from their common ancestor. We propose an updated model for EF-1α/EFL evolution in Rhizaria by incorporating new EFL data obtained in this study.


[Psychological status and sleep quality of nursing interns during the outbreak of COVID-19].
To investigate the psychological status and sleep quality of nursing interns in collective isolation during the outbreak of coronavirus disease 2019 (COVID-19) and provide evidence for adequate interventions. We surveyed a total of 95 nursing interns who were isolated collectively in a general teaching hospital in Guangzhou using a self-designed questionnaire, which consisted of a basic information form, self-rating anxiety scale (SAS), self-rating depression scale (SDS) and Pittsburgh Sleep Quality Index (PSQI). Descriptive analysis, single factor analysis and correlation analysis were used to analyze the current status of the interns' psychology and sleep quality, the potential factors affecting their psychology and sleep quality, and the correlation between their psychological status and sleep quality. The surveyed interns had SAS, SDS and PSQI score of 37.79±6.59, 43.98±9.74 and 5.20±3.14, respectively, which were significant higher than the national norms in China (P < 0.05). Correlation analysis indicated that both anxiety and depression were positively correlated with the sleep quality score (r=0.508 and 0.546, respectively). Univariate analysis showed that the major factors affecting the psychological status and sleep quality of the interns during collective isolation included recent contact with persons from the affected area before isolation and the onset of fever during the isolation. These interns showed relatively high levels of anxiety and depression during the collective isolation to affect their sleep quality, and interventions should be timely administered to improve their mental health and sleep quality.


New vistas in psychosomatic medicine.
Further understanding in the field of psychosomatic medicine has come to light recently as the result of new approaches and methods of research. Such diseases as hypertension, ulcerative colitis, rheumatoid arthritis, peptic ulcer, diabetes and cardiovascular dysfunction may represent the body's method of adapting to chronic stress, according to Selye's concept of the general adaptation syndrome, with the phases of alarm, resistance and exhaustion. It has been postulated that unconscious dynamics of which patients are unaware are crucial in the understanding and interpretation of physiological research and therapy of patients with psychosomatic disorders. The concept of partial regression was applicable to patients with psychosomatic illness who were highly successful in social, economic and professional spheres. The illness was viewed as a protection against psychological regression by limited somatic regression. Pilot studies suggested that patients seriously ill with such disorders as ulcerative colitis and asthma responded favorably to enforced psychological regression and exploitation of dependency by excessive coddling, babying and mothering by an "all-giving" physician in a hospital setting. Good physician-patient relationship remains the keystone in therapy and is the common denominator to many so-called successful modes of treatment.


Treatment of acute cellular rejection in renal transplantation patients on ciclosporin with antithymocyte globulin.
Our treatment of acute renal cellular rejection in patients on ciclosporin (cyclosporin A) involves the almost complete elimination of T cells (according to individual T cell monitoring in peripheral blood) through antithymocyte globulin (ATG) therapy. We present here the results of treatment of 44 histologically or cytologically proven acute rejection episodes in 33 of 62 consecutive renal transplantation patients. ATG therapy resulted in a 95.5% success rate when duration and dosage were individually adjusted according to T cell elimination in peripheral blood. Only two grafts were lost, both because of vascular occlusions. In neither case could it be clarified whether the loss was due to primary vascular lesions or the result of severe rejection or side effects of ATG. Our data show that the elimination of primed T cells with ATG permits the use of ciclosporin even in the presence of an established immune response.


c-Fos-deficient mice are susceptible to Salmonella enterica serovar Typhimurium infection.
c-Fos is a component of transcription factor AP-1. We show that macrophages lacking c-Fos exhibit enhanced production of proinflammatory cytokines, potentiated NF-kappaB phosphorylation, and increased cell death following Salmonella enterica serovar Typhimurium infection. Furthermore, mice lacking c-Fos are highly susceptible to infection, suggesting that c-Fos confers resistance to Salmonella infection in mice.


Expression from leukocyte integrin promoters in retroviral vectors.
Human gene therapy for diseases involving leukocytes would be facilitated by the identification of specific promoter/enhancer sequences capable of directing high levels of tissue and stage-specific expression of the requisite cDNA when used in a retroviral vector. We tested the promoter sequences from the leukocyte integrin CD11a (LFA-1), CD11b (Mac-1), and CD18 subunits in retroviral vectors to express a reporter gene, adenosine deaminase, in the human leukocyte cell lines K562 and HL-60. The leukocyte integrins are expressed in leukocytes, and they are inducible in HL-60 cells, a model system for myeloid differentiation. Although the leukocyte integrin promoter/enhancer sequences direct the expression of reporter genes in myeloid lineage cell lines in transient transfection assays, in these studies, the leukocyte integrin promoters direct low levels of reporter gene expression following retroviral-mediated transduction in K562 and HL-60 cells and selection of stable integrants. Treatment of HL-60 cells transduced with retroviral vectors containing the leukocyte integrin promoters with retinoic acid or phorbol myristate acetate results in less than a two-fold increase in reporter gene expression. These studies indicate that: (i) expression from the leukocyte integrin promoters from stable integrants in retroviral vectors does not parallel the results observed in transient transfection assays, and (ii) additional promoter/enhancer sequences will likely be required for these promoters to direct high levels of tissue and stage-specific expression in retroviral vectors.


Inhibition of B56-containing protein phosphatase 2As by the early response gene IEX-1 leads to control of Akt activity.
The importance of PP2A in the regulation of Akt/PKB activity has long been recognized but the nature of the holoenzyme involved and the mechanisms controlling dephosphorylation are not yet known. We identified IEX-1, an early gene product with proliferative and survival activities, as a specific inhibitor of B56 regulatory subunit-containing PP2A. IEX-1 inhibits B56-PP2A activity by allowing the phosphorylation of B56 by ERK. This leads to sustained ERK activation. IEX-1 has no effect on PP2A containing other B family subunits. Thus, studying IEX-1 contribution to signaling should help the discovery of new pathways controlled by B56-PP2A. By using overexpression and RNA interference, we show here that IEX-1 increases Akt/PKB activity in response to various growth factors by preventing Akt dephosphorylation on both Thr(308) and Ser(473) residues. PP2A-B56beta and gamma subunits have the opposite effect and reverse IEX-1-mediated Akt activation. The effect of IEX-1 on Akt is ERK-dependent. Indeed: (i) a IEX-1 mutant deficient in ERK binding had no effect on Akt; (ii) ERK dominant-negative mutants reduced IEX-1-mediated increase in pAkt; (iii) a B56beta mutant that cannot be phosphorylated in the ERK.IEX-1 complex showed an enhanced ability to compete with IEX-1. These results identify B56-containing PP2A holoenzymes as Akt phosphatases. They suggest that IEX-1 behaves as a general inhibitor of B56 activity, enabling the control of both ERK and Akt signaling downstream of ERK.


Incorporating a Mindfulness Program in a Graduate Family Nurse Practitioner Program.
Mindfulness-based stress reduction (MBSR) activities have been shown to have psychological benefits. Studies have identified increased perceived levels of stress in graduate students; however, this is not specific to graduate nursing students. There is very little data on the use of MBSR as a nonpharmacologic tool to decrease stress levels in graduate nurse practitioner students. Therefore, the purpose of this study was to determine if the implementation of MBSR improves the overall perceived stress of graduate nursing students. The pilot MBSR program covered topics such as different forms of mindfulness meditation practice, mindful awareness during yoga postures, and mindfulness during stressful situations. Perceived stress scores mean for the sample (n = 25) was elevated at 26 (+4) indicating moderate stress prior to the MBSR training and significantly decreased post 14-week MBSR training (+6) (p < .05). This finding suggests that the MBSR activities have contributed to the overall reduction in stress in these students. The graduate family nurse practitioner students are now familiar with the benefits of MBSR and can share this practice with their patients. Having this skill as a part of their clinical tool kit and practice will allow them to apply this to patient care and subsequently provide holistic care.


Kinetic isotope effect in hydrogen transfer arising from the effects of rotational excitation and occurrence of hydrogen tunneling in molecular systems.
Hydrogen kinetic isotope effect with values of alpha identical with ln(kH/kT)/ln(kD/kT)>3.3 which are generally ascribed to quantum tunneling of hydrogen are shown to arise in O+HCl(DCl,TCl) reactions due to the effects of rotational excitation on the distribution of encounters with the critical dividing surface. At higher rotational excitations these distributions are shifted towards the regions of the critical dividing surface with low barrier energies which can lead to a large enhancement of the barrier crossing. This effect depends strongly on the hydrogen isotope involved in the reaction and, at some temperatures, gives rise to alpha much larger than 3.3. It can be readily seen that the effect should arise also in condensed molecular systems, due to internal rotations or other vibrations "perpendicular" to the reaction coordinate.


Absolute CD4 vs. CD4 percentage for predicting the risk of opportunistic illness in HIV infection.
Current guidelines recommend consideration of CD4 cell percentage as well as CD4 cell count in therapeutic decisions. The relative value of CD4 cell count compared with CD4 cell percentage in predicting risk of AIDS-defining illnesses (ADIs) in the post-HAART (highly active antiretroviral therapy) era is unknown. Data from an observational clinical cohort of adult HIV-infected patients were used to assess the risk of developing an ADI associated with specific absolute CD4 counts (CD4) and CD4%'s (CD4%) using all CD4-CD4% pairs obtained after January 1996. The incidence of developing an ADI was assessed over a maximum of 6 months after the CD4-CD4% pair was obtained. Using multivariable negative binomial regression, the incidence rate ratio (IRR) for developing an ADI by CD4 and CD4% categories was computed. A total of 15,736 CD4-CD4% pairs from 2185 patients who developed 608 ADIs was analyzed. The IRR for developing an ADI by absolute CD4 was 17.9 (95% CI: 13.2, 24.4) events/100 person-years for <50 cells/mm, 6.2 (95% CI: 4.4, 7.9) for 50-100 cells/mm, and 2.7 (95% CI: 1.9, 4.0) for 100-200 cells/mm, compared with the referent stratum of 200-350 cells/mm. Without adjustment for absolute CD4, the IRR was 14.4 (95% CI: 9.3,22.6) for CD4% <7%, 3.7 (95% CI: 2.4,5.9) for 7-14%, 1.9 (95% CI: 1.1, 3.1) for 15-21%, compared with the referent stratum of >21%. However, in a multivariable analysis adjusting for absolute CD4, CD4%, and other clinical and demographic variables, the absolute CD4 but not the CD4% was associated strongly with developing an ADI. The results suggest that CD4% adds little further predictive information after accounting for the absolute CD4 count for the short-term risk of developing an ADI. The absolute CD4 count is the more important measure of immune status and is preferred over the CD4% for making treatment decisions in HIV-infected adults.


Synthesis and Structure of a Functionalized [9]Cycloparaphenylene Bearing Three Indeno[2,1-a]fluorene-11,12-dione-2,9-diyl Units.
A synthetic pathway to a functionalized [9]cycloparaphenylene bearing three indeno[2,1-a]fluorene-11,12-dione-2,9-diyl units in the macrocyclic ring structure ([3]CIFO) has been developed. The 1H and 13C NMR spectra show that only the anti rotamer (anti-[3]CIFO) is produced. DFT calculations indicate that the anti rotamer is thermodynamically more stable than the syn rotamer by 4.3 kcal/mol, and the rotational barrier from the anti to syn rotamer is estimated to be 23.3 kcal/mol. The UV-vis and fluorescence spectra and cyclic voltammogram of anti-[3]CIFO were investigated.


Chemical profiling, cytotoxicity and phytotoxicity of foliar volatiles of Hyptis suaveolens.
In the present study, the essential oil (EO) of Hyptis suaveolens has been explored for the first time for its phytotoxic and cytotoxic activities. The phytotoxic activity was assessed against rice (Oryza sativa) and its major troublesome weed, Echinochloa crus-galli, under laboratory and screenhouse conditions. GC-MS analysis revealed EO to be monoterpenoid (~ 79% monoterpenes) in nature with α-phellandrene (22.8%), α-pinene (10.1%) and limonene (8.5%) as the major chemical constituents. The laboratory bioassay showed a complete growth inhibitory effect of EO (≥ 2 mg mL-1) towards the germination and seedling growth of E. crus-galli. However, the inhibitory effect on rice was much less (~40% inhibition). EO caused visible injury, reduction in chlorophyll content, cell viability and ultimately led to complete wilting of E. crus-galli plants. In addition, EO altered the cell division in the meristematic cells of Allium cepa as depicted by ~63% decrease in mitotic index. EO exposure induced several aberrations at chromosomal (c-mitosis, anaphase bridges, chromosomal breakage, vagrant chromosomes, and sticky chromosomes) and cytological level (cytoplasm destruction, peripheral nuclei, and bi-nucleate cells). The present study concludes that H. suaveolens EO possesses phytotoxic activity due to its mito-depressive activity, and could serve as a natural herbicide under sustainable agricultural practices.


New directions in nursing home ethics.
We believe that a new agenda for the ethics of long-term nursing home care could be set by seeing nursing homes as communities of caring and interdependency. The goal should be not simply to eliminate or minimize dependency whenever possible, but to make a genuinely creative and nurturing use of the dependency that is an inevitable reality for most nursing home residents. Nursing homes are rarely places of curing, but they can and should be places of healing -- of making whole -- of enabling frail or chronically ill persons to use their dependency to grow as human beings... In general, nursing home regulation is a matter of striking a delicate balance between that degree of control necesary to ensure a basic standard of decent and humane care, and that degree of professional discretion needed to allow nursing homes to respond to their own particular problems of care as they make creative use of the dependency that is an essential fact of nursing home life.


Particle number fractionalization of an atomic Fermi-Dirac gas in an optical lattice.
We show that a dilute two-species gas of Fermi-Dirac alkali-metal atoms in a periodic optical lattice may exhibit fractionalization of the particle number when the two components are coupled via a coherent electromagnetic field with a topologically nontrivial phase profile. This results in fractional eigenvalues of the spin operator with vanishing fluctuations. The fractional part can be accurately controlled by modifying the effective detuning of the electromagnetic field.


Osteoclastic Response on Titanium Surfaces in Modified Simulated Body Fluid.
It was hypothesized that calcium phosphate (CaP) deposition onto Ti surfaces using biomimetic deposition contributed to not only improving osteogenesis but also suppressing osteoclastogenesis in terms of high surface hydrophilicity. Ti discs with two different surfaces were prepared: machined and anodic oxidized surfaces. The specimens of two different surfaces were soaked in modified simulated body fluid solution for 14 days at physiologic condition. Murine RAW 264.7 cells were utilized as osteoclast precursor cells. To evaluate osteoclast differentiation activity on Ti surfaces, tartrate-resistant acid phosphatase activity assay was conducted, and cells on Ti discs were investigated with a field emission-scanning electron microscope (FE-SEM). The expression of nuclear factor of activated T cells 1 (NFATc1) and c-Fos, two critical transcriptional factors involved in osteoclastogenesis, were also assessed in terms of mRNA and protein levels by real-time reverse transcriptase-polymerase chain reaction and western blot, respectively. Tartrate-resistant acid phosphatase activities on both machined and anodic oxidized Ti surfaces soaked in modified simulated body fluid were significantly lower compared with nonimmersed ones. FE-SEM observation showed that the number of differentiated osteoclasts was lower on anodic oxidized surfaces immersed in modified simulated body fluid compared with nonimmersed Ti surfaces. Protein and mRNA expression of NFATc1 and c-Fos were significantly decreased on anodic oxidized Ti surfaces immersed in modified simulated body fluid compared with those on nonimmersed ones. The effects of immersion of Ti discs in modified simulated body fluid on osteoclastogenesis were higher on anodic oxidized surfaces than on machined surfaces. It can be concluded that osteoclastogenesis was inhibited by biomimetic deposition using modified simulated body fluid, especially on anodic oxidized Ti surfaces.


MoSe2 Embedded CNT-Reduced Graphene Oxide Composite Microsphere with Superior Sodium Ion Storage and Electrocatalytic Hydrogen Evolution Performances.
Highly porous MoSe2-reduced graphene oxide-carbon nanotube (MoSe2-rGO-CNT) powders were prepared by a spray pyrolysis process. The synergistic effect of CNTs and rGO resulted in powders containing ultrafine MoSe2 nanocrystals with a minimal degree of stacking. The initial discharge capacities of MoSe2-rGO-CNT, MoSe2-CNT, MoSe2-rGO, and bare MoSe2 powders for sodium ion storage were 501.6, 459.7, 460.2, and 364.0 mA h g-1, respectively, at 1.0 A g-1. The MoSe2-rGO-CNT composite powders had superior cycling and rate performances compared with the MoSe2-CNT, MoSe2-rGO composite, and bare MoSe2 powders. The electrocatalytic activity of MoSe2-rGO-CNT in the hydrogen evolution reaction (HER) was also compared with that of MoSe2-CNT, MoSe2-rGO, and bare MoSe2. MoSe2-rGO-CNT composite powders exhibited an overpotential of 0.24 V at a current density of 10 mA cm-2, which was less than that of MoSe2-CNT (0.26 V at 10 mA cm-2), MoSe2-rGO (0.32 V at 10 mA cm-2), and bare MoSe2 (0.33 V at 10 mA cm-2). Tafel slopes for the MoSe2-rGO-CNT, MoSe2-CNT, MoSe2-rGO, and bare MoSe2 powders were 53, 76, 86, and 115 mV dec-1, respectively. Because a large electrochemical surface area and ultrafine MoSe2 nanocrystals, the MoSe2-rGO-CNT composite possesses more active sites than the MoSe2-CNT, MoSe2-rGO composite, and bare MoSe2 powders with extensive stacking and large crystalline size, which provide greater catalytic HER activity.


Synthesis of 3-Alkylideneisoindolin-1-ones via Sonogashira Cyclocarbonylative Reactions of 2-Ethynylbenzamides.
Cyclocarbonylative Sonogashira reactions of ortho-ethynylbenzamides have been investigated. The process is carried out under CO pressure, in the presence of a very small amount of PdCl2(PPh3)2 (0.4 mol %) as a catalytic precursor and without the need for a Cu salt as the co-catalyst. 2-Ethynylbenzamide reacted successfully with iodoarenes bearing electron-withdrawing and electron-donating groups, giving rise to different classes of compounds depending on the solvent used. On the contrary, N-(4-chlorophenyl)-2-ethynylbenzamide afforded exclusively polyfunctionalized isoindolinones with high stereoselectivity toward (E) isomers.


Aberration in de novo ether lipid biosynthesis in peroxisomal disorders.
The Zellweger syndrome is a rare inborn error of metabolism characterized by the absence of morphologically distinguishable peroxisomes. As a consequence tissues and cells from Zellweger patients contain severely reduced levels of ether phospholipids. These are replaced by diacylphospholipids while keeping the polar headgroup composition of the cellular phospholipids constant. Both peroxisomal enzymes involved in glycero-ether lipid bond formation appear to be deficient. The experiments clearly establish that peroxisomes are indispensible for ether lipid biosynthesis. The peroxisomal deficiency in de novo ether lipid biosynthesis in fibroblasts and amniotic fluid cells can be applied in diagnostic assays. The mutation can be by-passed by feeding the cells with alkylglycerol. Similar characteristics as found for plasmalogen biosynthesis in Zellweger syndrome were assessed in other diseases with a general impairment of peroxisomal functions such as infantile Refsum disease and neonatal adrenoleukodystrophy as well as in rhizomelic chondrodysplasia punctata, a disease characterized by the absence of some, but not all, peroxisomal functions. Complementation analysis after somatic cell fusion has revealed that at least three genes must be involved in the biogenesis of fully functional peroxisomes.


Oxalate content of foods and its effect on humans.
Oxalic acid and its salts occur as end products of metabolism in a number of plant tissues. When these plants are eaten they may have an adverse effect because oxalates bind calcium and other minerals. While oxalic acid is a normal end product of mammalian metabolism, the consumption of additional oxalic acid may cause stone formation in the urinary tract when the acid is excreted in the urine. Soaking and cooking of foodstuffs high in oxalate will reduce the oxalate content by leaching. The mean daily intake of oxalate in English diets has been calculated to be 70-150 mg, with tea appearing to contribute the greatest proportion of oxalate in these diets; rhubarb, spinach and beet are other common high oxalate-content foods. Vegetarians who consume greater amounts of vegetables will have a higher intake of oxalates, which may reduce calcium availability. This may be an increased risk factor for women, who require greater amounts of calcium in the diet. In humans, diets low in calcium and high in oxalates are not recommended but the occasional consumption of high oxalate foods as part of a nuritious diet does not pose any particular problem.


Effectiveness of virtual reality on activities of daily living in children with cerebral palsy: a systematic review and meta-analysis.
No meta-analysis has been conducted on the effect of specific virtual reality (VR) treatment modes on activities of daily living (ADL) in children with cerebral palsy (CP). Therefore, this study aimed to confirm whether VR therapy is effective in improving ADL in children with CP according to subgroups. Literature published in the Cumulated Index to Nursing and Allied Health Literature (CINAHL), Embase, the Physiotherapy Evidence Database (PEDro), and PubMed was reviewed, and Risk of Bias 2.0 (RoB 2) was used to evaluate the quality of the literature. A funnel plot was visually observed to confirm publication bias, supplemented with Egger's regression test. Data analysis was performed using R version 4.2.1. Subgroup analysis was performed according to the Gross Motor Function Classification System (GMFCS), the Manual Ability Classification System (MACS), treatment minutes per week, treatment period, age, and RoB. Eleven of 2,978 studies were included, and the overall effect size was 0.37 (95% confidence interval = 0.17-0.57). Regarding GMFCS, effect sizes of 0.41 and 0.33 was observed for the low- and high-function groups, respectively. For MACS, 0.27 and 0.43 were observed for the low and high-function groups. Regarding treatment minutes per week, the values were 0.22, 0.44, and 0.27 in the 1-100, 101-200, and 201-300 min groups, respectively. In the classification according to age, 0.29 was observed for school-age children and 0.98 for preschool children. Lastly, in the classification according to the RoB, 0.52, -0.01, and 0.23 indicated studies with low risk, some concern, and high risk, respectively. The highest effect was observed when VR was applied within 6 weeks of 101-200 per week. Therefore, it is suggested that if the results of this review are applied to children with cerebral palsy in the community, it will be an effective intervention method. PROPEROS (registration number CRD42023409801).


Characterizing changes in soil microbiome abundance and diversity due to different cover crop techniques.
Soil-based microorganisms assume a direct and crucial role in the promotion of soil health, quality and fertility, all factors known to contribute heavily to the quality and yield of agricultural products. Cover cropping, used in both traditional and organic farming, is a particularly efficient and environmentally favorable tool for manipulating microbiome composition in agricultural soils and has had clear benefits for soil quality and crop output. Several long-term investigations have evaluated the influence of multi-mix (multiple species) cover crop treatments on soil health and microbial diversity. The present study investigated the short-term effects of a seven species multi-mix cover crop treatment on soil nutrient content and microbial diversity, compared to a single-mix cover crop treatment and control. Analysis of 16S sequencing data of isolated soil DNA revealed that the single-mix cover crop treatment decreased overall microbial abundance and diversity, whereas the control and multi-mix treatments altered the overall microbial composition in similar fluctuating trends. Furthermore, we observed significant changes in specific bacteria belonging to the phyla Acidobacteria, Actinobacteria, Planctomycetes, Proteobacteria and Verrucombicrobia for all treatments, but only the single-mix significantly decreased in abundance of the selected bacteria over time. Our findings indicate that the control and multi-mix treatments are better at maintaining overall microbial composition and diversity compared to the single-mix. Further study is required to elucidate the specific difference between the treatment effect of the multi-mix treatment and the control, given that their microbial composition changes over time were similar but they diverge into two populations of unique bacterial types by the end of this short-term study.


Reduction in total plasma ghrelin levels following catecholamine depletion: relation to bulimic and depressive symptoms.
There is increasing preclinical and clinical evidence of the important role played by the gastric peptide hormone ghrelin in the pathogenesis of symptoms of depression and eating disorders. To investigate the role of ghrelin and its considered counterpart, peptide tyrosine tyrosine (PYY), in the development of bulimic and depressive symptoms induced by catecholamine depletion, we administered the tyrosine hydroxylase inhibitor alpha-methyl-paratyrosine (AMPT) in a randomized, double-blind, placebo-controlled crossover, single-site experimental trial to 29 healthy controls and 20 subjects with fully recovered bulimia nervosa (rBN). We found a decrease between preprandial and postprandial plasma ghrelin levels (p<0.0001) and a postprandial rise in plasma PYY levels (p<0.0001) in both conditions in the entire study population. Plasma ghrelin levels decreased in the entire study population after treatment with AMPT compared to placebo (p<0.006). AMPT-induced changes in plasma ghrelin levels were negatively correlated with AMPT-induced depressive symptoms (p<0.004). Plasma ghrelin and plasma PYY levels were also negatively correlated (p<0.05). We did not observe a difference in ghrelin or PYY response to catecholamine depletion between rBN subjects and healthy controls, and there was no correlation between plasma ghrelin and PYY levels and bulimic symptoms induced by catecholamine depletion. These findings suggest a relationship between catecholamines and ghrelin with depressive symptoms.


Lentivector prime and vaccinia virus vector boost generate high-quality CD8 memory T cells and prevent autochthonous mouse melanoma.
Most cancer vaccines, to date, fail to control established tumors. However, their application in preventing tumors is another question that is understudied. In the current study, we investigated the CD8 memory T cell responses of lentivector (lv) immunization and its potential to prevent melanoma using both transplantable B16 tumor and autochthonous melanoma models. We found that lv-expressing xenogenic human gp100 could induce potent CD8 responses that cross-react with mouse gp100. Importantly, the lv-primed CD8 response consisted of a high number of memory precursors and could be further increased by recombinant vaccinia virus vector (vv) boost, resulting in enhanced CD8 memory response. These long-lasting CD8 memory T cells played a critical role in immune surveillance and could rapidly respond and expand after sensing B16 tumor cells to prevent tumor establishment. Although CD8 response plays a dominant role after lv immunization, both CD4 and CD8 T cells are responsible for the immune prevention. In addition, we surprisingly found that CD4 help was not only critical for generating primary CD8 responses, but also important for secondary CD8 responses of vv boost. CD4 depletion prior to lv prime or prior to vv boost substantially reduced the magnitude of secondary CD8 effector and memory responses, and severely compromised the effect of cancer immune prevention. More importantly, the CD8 memory response from lv-vv prime-boost immunization could effectively prevent autochthonous melanoma in tumor-prone transgenic mice, providing a strong evidence that lv-vv prime-boost strategy is an effective approach for cancer immune prevention.


Toxicity of monazite particulates and its attenuation with a complex of bio-protectors.
Workers employed on mining, processing and storage of monazite are at risk of exposure to dust with expected adverse health effects. To study the adverse health effects of monazite particles in experiments on rats and to test the possibility of attenuating these effects. Outbred white rats were injected intratracheally with a suspension of ground monazite concentrate (MC) in order to investigate the cellular response of the lower airways 24 hours later and the organism's status 6 months after the injection. The bio-protective complex (BPC) tested in these experiments consisted of glutamate, an iodine preparation, methionine, a polyvitamin-polymineral composition, and/or "Eicosavitol" (fish oil preparation rich in PUFA, predominantly of the omega 3-group). Bio-protectors were administered together with the rat food and drink daily for one month before the MC injection in the short-term experiment, or over 6 months after such injection in the long-term experiment. MC induced manifestations of its cytotoxicity, fibrogenicity and systemic toxicity as well as genotoxicity. The tested BPC attenuated virtually all these effects. Although a similar protective potential of "Eicosavitol" against almost all of them was lower compared with that of BPC, combining BPC with "Eicosavitol" provided, as a rule, the greatest protective effect. It may be assumed that the many-sided adverse effects of MC on the organism is due, at least partially, to the presence in its composition of not only rare earth elements but also of natural radioisotopes of the thorium and uranium families. The combination of the bio-protectors tested was highly effective and may be recommended for administering in periodic preventive programmes to exposed workers.


31P NMR studies of enzyme-bound substrate complexes of yeast 3-phosphoglycerate kinase. 1. Effects of sulfate and pH. Mg(II) affinity at the two ATP sites.
31P NMR measurements were made (at 121.5 MHz and 5 degrees C) on enzyme-bound substrate complexes of 3-phosphoglycerate kinase in order to address three questions pertaining to (i) the integrity of the enzyme-substrate complexes with Mg(II) in the presence of sulfate concentrations typical of those used for crystallization in X-ray studies, (ii) the relative affinities of Mg(II) to ATP bound at the two sites on the enzyme, and (iii) the pH behavior of the different phosphate groups in the enzyme complexes. 31P chemical shift and spin-spin coupling constant changes showed that at concentrations of 0.5 M and higher, sulfate ion interferes with Mg(II) chelation to ATP and ADP free in solution as well as in their enzyme-bound complexes. The effect on enzyme complexes is stronger for the E.MgATP complex than for the E.MgADP complex. Sulfate ion (50 mM) also causes a approximately 0.5 ppm upfield chemical shift of the 31P resonance of enzyme-bound 3-P-glycerate even in the absence of ATP or Mg(II). A quantitative estimate of the dispartate affinities of Mg(II) to ATP bound at the two sites on the enzyme was made on the basis of computer simulation of changes in the line shape of beta-P (ATP) resonance and of changes in 31P chemical shift of the corresponding gamma-P (ATP) in the E.ATP complex with increasing [Mg(II)]. The concentrations of the relevant species that contribute to these 31P NMR signals were computed by assuming independent binding at the two sites.(ABSTRACT TRUNCATED AT 250 WORDS)


A mathematical perspective on CD4(+) T cell quorum-sensing.
We analyse a mathematical model of the peripheral CD4(+) T cell population, based on a quorum-sensing mechanism, by which an optimum number of regulatory T cells can be established and maintained. We divide the population of a single T cell receptor specificity into four pools: naive, IL-2 producing, IL-2 non-producing, and regulatory CD4(+) T cells. Proliferation, death and differentiation of cells are introduced as transition probabilities of a stochastic Markov model, with the assumption that the amount of IL-2 available to CD4(+) T cells is proportional to the size of the population of IL-2 producing CD4(+) T cells. We explore the population dynamics both in the absence and in the presence of specific antigen. We study the establishment of the peripheral CD4(+) T cell pool from thymic output in the absence of antigen, and its return to homeostasis after an immune challenge, by steady state analysis of the deterministic approximation. The number of regulatory T cells at steady state is greater in the presence of antigen than in its absence. We also consider the stochastic dynamics of the model after an immune challenge, in particular the behaviour leading to ultimate extinction of the IL-2 producing and regulatory T cell populations.


Quantitative measurement of BN50727 in human plasma and urine by combined liquid chromatography/negative ion chemical ionization mass spectrometry using a particle beam interface.
A new sensitive assay has been developed for the quantitative measurement of BN50727 at the picomole level in human plasma and urine. The drug and the internal standard (BN50788) were measured by combined liquid chromatography/negative ion chemical ionization mass spectrometry with methane as the reagent gas. A simple solid-liquid extraction procedure was used to isolate BN50727 from the complex biological matrices. The mass spectrometer was tuned to monitor the intense and stable ion at m/z 333 which was generated in the ion source by a dissociative capture process. This assay was performed with 1 ml of plasma or 0.1 ml of urine and the quantification limit of the method was statistically calculated as 1 ng ml-1. The very low relative standard deviations and mean percentages of error calculated during the different within-day or between-day repeatability assays have clearly demonstrated the ruggedness of the technique for the routine determination of BN50727 in biological fluids. Some preliminary results on the pharmacokinetics of the drug are presented to illustrate the applicability of this powerful liquid chromatographic/mass spectrometric method.