High Dosages of Equine Chorionic Gonadotropin Exert Adverse Effects on the Developmental Competence of IVF-Derived Mouse Embryos and Cause Oxidative Stress-Induced Aneuploidy.
Gonadotropins play vital roles in the regulation of female reproductive ability and fertility. Our study aimed to determine the effects of superovulation induced by increasing doses of equine chorionic gonadotropin [eCG; also referred to as pregnant mare serum gonadotropin (PMSG)] on the developmental competence of mouse embryos and on aneuploidy formation during in vitro fertilization (IVF). eCG dose-dependently enhanced the oocyte yield from each mouse. Administration of 15 IU eCG significantly reduced the fertilization rate and the formation of four-cell embryos and blastocysts and increased the risk of chromosome aneuploidy. The IVF-derived blastocysts in the 15 IU eCG treatment group had the fewest total cells, inner cell mass (ICM) cells and trophectoderm (TE) cells. Moreover, more blastocysts and fewer apoptotic cells were observed in the 0, 5, and 10 IU eCG treatment groups than in the 15 IU eCG treatment group. We also investigated reactive oxygen species (ROS) levels and variations in several variables: mitochondrial membrane potential (MMP); active mitochondria; mitochondrial superoxide production; adenosine triphosphate (ATP) content; spindle structures; chromosome karyotypes; microfilament distribution; and the expression of Aurora B [an important component of the chromosomal passenger complex (CPC)], the spindle assembly checkpoint (SAC) protein mitotic arrest deficient 2 like 1 (MAD2L1), and the DNA damage response (DDR) protein γH2AX. Injection of 15 IU eCG increased ROS levels, rapidly reduced MMP, increased active mitochondria numbers and mitochondrial superoxide production, reduced ATP content, increased abnormal spindle formation rates, and induced abnormalities in chromosome number and microfilament distribution, suggesting that a high dose of eCG might alter developmental competence and exert negative effects on IVF-obtained mouse embryos. Additionally, the appearance of γH2AX and the significantly increased expression of Aurora B and MAD2L1 suggested that administration of relatively high doses of eCG caused Aurora B-mediated SAC activation triggered by ROS-induced DNA damage in early mouse IVF-derived embryos for self-correction of aneuploidy formation. These findings improve our understanding of the application of gonadotropins and provide a theoretical basis for gonadotropin treatment.


Current status of leprosy: epidemiology, basic science and clinical perspectives.
Leprosy has affected humans for millennia and remains an important health problem worldwide, as evidenced by nearly 250 000 new cases detected every year. It is a chronic infectious disorder, caused by Mycobacterium leprae, that primarily affects the skin and peripheral nerves. Recent advances in basic science have improved our knowledge of the disease. Variation in the cellular immune response is the basis of a range of clinical manifestations. The introduction of multidrug therapy has significantly contributed to a decrease in the prevalence of the disease. However, leprosy control activities, including monitoring and prevention programs, must be maintained.


The cell adhesion molecule nectin-1 is critical for normal enamel formation in mice.
Nectin-1 is a member of a sub-family of immunoglobulin-like adhesion molecules and a component of adherens junctions. In the current study, we have shown that mice lacking nectin-1 exhibit defective enamel formation in their incisor teeth. Although the incisors of nectin-1-null mice were hypomineralized, the protein composition of the enamel matrix was unaltered. While strong immunostaining for nectin-1 was observed at the interface between the maturation-stage ameloblasts and the underlying cells of the stratum intermedium (SI), its absence in nectin-1-null mice correlated with separation of the cell layers at this interface. Numerous, large desmosomes were present at this interface in wild-type mice; however, where adhesion persisted in the mutant mice, the desmosomes were smaller and less numerous. Nectins have been shown to regulate tight junction formation; however, this is the first report showing that they may also participate in the regulation of desmosome assembly. Importantly, our results show that integrity of the SI-ameloblast interface is essential for normal enamel mineralization.


Diet-induced increase of colonic bile acids stimulates lytic activity of fecal water and proliferation of colonic cells.
The proposed intermediate steps in the relationship between a diet-dependent increase in colonic bile acids and proliferation of colonic cells were studied in rats. Male Wistar rats were fed diets supplemented with increasing amounts of steroids to increase the bile acid concentration of the colon. After 2 weeks, in vivo colonic proliferation was measured using tritiated thymidine incorporation into DNA. Luminal lytic activity was measured as lysis of erythrocytes by fecal water. To quantify hemolysis in the presence of fecal water, a method was developed which measures Fe-release using atomic absorption spectrophotometry. This method proved to be superior to the cell-counter method published earlier. Our results showed that steroid supplementation increased, in a dose-dependent manner, the total fecal and the soluble bile acid concentration as well as lytic activity of fecal water and colonic proliferation. A highly significant correlation between lytic activity of fecal water and colonic proliferation (r = 0.85, n = 24, P less than 0.001) was observed. These results indicate that the increase in colonic proliferation is mediated by diet-dependent increases in soluble colonic bile acid concentration and luminal lytic activity. This sequence of effects illustrates how diet could influence the risk for colon cancer.


Diversity of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from inpatients of 30 hospitals in Orange County, California.
There is a need for a regional assessment of the frequency and diversity of MRSA to determine major circulating clones and the extent to which community and healthcare MRSA reservoirs have mixed. We conducted a prospective cohort study of inpatients in Orange County, California, systematically collecting clinical MRSA isolates from 30 hospitals, to assess MRSA diversity and distribution. All isolates were characterized by spa typing, with selective PFGE and MLST to relate spa types with major MRSA clones. We collected 2,246 MRSA isolates from hospital inpatients. This translated to 91/10,000 inpatients with MRSA and an Orange County population estimate of MRSA inpatient clinical cultures of 86/100,000 people. spa type genetic diversity was heterogeneous between hospitals, and relatively high overall (72%). USA300 (t008/ST8), USA100 (t002/ST5) and a previously reported USA100 variant (t242/ST5) were the dominant clones across all Orange County hospitals, representing 83% of isolates. Fifteen hospitals isolated more t008 (USA300) isolates than t002/242 (USA100) isolates, and 12 hospitals isolated more t242 isolates than t002 isolates. The majority of isolates were imported into hospitals. Community-based infection control strategies may still be helpful in stemming the influx of traditionally community-associated strains, particularly USA300, into the healthcare setting.


Viability of hypokinetic segments: influence of tethering from adjacent segments: influence of tethering from adjacent segments.
Hypokinetic myocardium is presumed to be reversibly dysfunctional. However, hypokinetic segments do not necessarily improve after revascularization since their outcome can be influenced by tethering effects of adjacent myocardium. To assess whether hypokinetic segments improve following revascularization, 24 patients underwent resting and dobutamine stress echocardiography (DSE), with a total of 420 (20 per patient) myocardial segments studied pre- and postrevascularization. One hundred fifty-five hypokinetic segments were identified prerevascularization. Postrevascularization, only 57% of these segments improved in wall motion, while 43% showed no improvement or worsening of wall motion. Low dose (5-10 microg/kg/min) DSE identified correctly 57 (65%) of 88 segments that improved, and falsely predicted improvement in 26 (39%) of 67 segments that ultimately did not improve postrevascularization. Of the hypokinetic segments that did not improve, 90% were adjacent to at least one severely hypokinetic or akinetic segment as compared with 73% of the segments that improved following revascularization (P = 0.009). Sixty-five percent of all true positive DSE responses were adjacent to at least one akinetic or severely hypokinetic segment, while 87% of all false negative DSE responses were adjacent to at least one akinetic or severely hypokinetic segment (P = 0.03). In conclusion, myocardial segments found to be hypokinetic do not necessarily improve after revascularization. This may be related to tethering influences of adjacent segments, which have a contrasting level of function.


Increased ion traffic through non-specific cation pathways in the ageing human lens. Evidence from radiotracer fluxes studies.
86Rb efflux studies were carried out on normal human lenses in vitro. The data confirmed previous studies showing that 86Rb efflux increases with age. Removal of Ca2+ from the lens perifusate increased 86Rb efflux at all ages. The fractional increase above baseline was highest in the younger lenses, while the net increase of the 86Rb efflux induced by a Ca(2+)-free medium increased with age. This study supports the idea that Ca(2+)-sensitive, non-specific cation channels are present in the human lens and that their contribution to membrane permeability increases as the lens ages.


[Need for creating Polish registry of multiple sclerosis patients].
Multiple sclerosis (MS) is the most common cause of neurological disability of young people. It is estimated that 40 000-60 000 people in the country suffer from MS, and approximately 2000 new cases are diagnosed annually. These are, however, estimated data and require verification by nation-wide research. Results published so far concern only certain regions of Poland. It is also vital to precisely describe the needs of patients in terms of immunomodulating treatment and to perform detailed pharmacoeconomical analysis. In order to estimate basic epidemiological parameters there is a need of creating, in imitation of many other countries, a national register of MS patients which would concentrate all assets concerning MS around this project. The article presented the most important of American and European databases and explained the basis of the Polish register of MS patients, which is already functioning in one of the regions.


Infidelity in the structure of ectopic transcripts: a novel exon in lymphocyte dystrophin transcripts.
Ectopic (or "illegitimate") transcripts have recently become popular as a means of facilitating the study of transcripts normally considered to have a pattern of expression restricted to one or a few tissues. It has been generally assumed that the structure of an ectopic transcript faithfully represents that of its tissue-specific counterpart. We describe here the inclusion of a novel exon in 50% of ectopic dystrophin transcripts from human peripheral blood lymphocytes. The novel sequence resembles a conserved region in the 3' untranslated region of members of the carcinoembryonic antigen gene family and lies within the first intron of the human dystrophin gene. This constitutes a significant departure from the expected in vivo splicing behaviour in an ectopic transcript and suggests that there may be exceptions to the assumption that ectopic transcripts are processed in a similar way to their tissue-specific counterparts.


[Equipment for blood detoxication in critical care of patients].
The paper deals with the development of a new more improved blood detoxicating system in critical patients. Based on the design of a [symbol: see text]-0.5 plasmapheresis device, the authors have designed a new [symbol: see text] 2-0.5 system, by including into the extracorporeal circuit the second rotor which cultures biologically active agents (hepatocytes, fragments of splenic and placental tissue) enhancing a patient's detoxification. The paper also outlines the operating principles of the [symbol: see text] K 2-0.5 device, its operational preparation and procedure.


PAH biomarkers in common eelpout (Zoarces viviparus) from Danish waters.
Eelpouts (Zoarces viviparus) sampled at surveillance stations during the fall of 2007 and spring 2008 in different Danish coastal areas, were studied for biomarkers of polycyclic aromatic hydrocarbons (PAHs) exposure and effects. Two analytical techniques, synchronous fluorescence spectrometry (SFS) and high-performance liquid chromatography with fluorescence detection (HPLC/F), were applied for detecting PAH metabolites in bile and urine. CYP1A activity, in this study regarded as potential biomarker of effect, was measured as 7-ethoxyresorufin-O-deethylase (EROD) activity in liver of eelpouts from different stations. Biliary PAH metabolite measurements were used for monitoring the environmental PAH load at the surveillance stations. There was found significant difference in biliary PAH metabolite content between sexes with male fish containing higher concentrations of PAH metabolites than females. The urinary PAH metabolite content did not show the same spatial trends as biliary PAH metabolites. However, fish from Aarhus Bight and Vejle Fjord had significantly higher levels of PAH metabolites in both urine and bile compared to the reference station Agersø. Normalisation methods applied for bile and urine matrices did not have any effect or only slightly reduced the coefficients of variation in data sets. The CYP1A activity in eelpout liver did not show the same spatial distribution trends between sampling sites as did biliary or urinary PAH metabolite contents. Male eelpouts showed significantly higher CYP1A activity than females in fall sampling period but there were no differences found in the spring period. General comparison between both seasons showed that eelpouts sampled in the fall had significantly higher CYP1A activity than fish sampled during spring season. Overall, the results of this study describe selected biomarker responses in eelpouts to environmental PAH load at the different areas along Danish coasts.


2D-Material-integrated hydrogels as multifunctional protective skins for soft robots.
Soft robots provide compliant object-machine interactions, but they exhibit insufficient material stability, which restricts them from working in harsh environments. Herein, we developed a class of soft robotic skins based on two-dimensional materials (2DMs) and gelatin hydrogels, featuring skin-like multifunctionality (stretchability, thermoregulation, threat protection, and strain sensing). The 2DM-integrated hydrogel (2DM/H) skins enabled soft robots to execute designated missions in the presence of high levels of heat and various environmental threats while maintaining mild machine temperatures. Via adopting different 2DMs (graphene oxide (GO), montmorillonite (MMT), and titanium carbide (MXene)), the 2DM/H-protected robots were able to perform soft grasping in organic liquids (GO/H) and open fire (MMT/H), and in the presence of electromagnetic radiation and biocontamination (MXene/H). Through blending MXene nanosheets into gelatin, the MXene-blended hydrogel (M-H) skin became strain sensitive, and a GO/M-H gripper exhibited the high-level integration of skin-mimicking capabilities. Finally, we incorporated 2DM/H skins onto an origami-inspired walker robot and a soft batoid-like robot to execute vision-guided searching in fire and underwater locomotion/navigation in chemical spills.


V.D. and the pill.
Since the mid-1960s oral contraceptives have been frequently criticized on the ground that they are either a direct or indirect but significant cause of the increasing numbers of cases of venereal disease - especially gonorrhea. These criticisms have often been confused and unsupported by facts. The Family Planning Information Service in London concludes that "there is no evidence that conclusively supports the argument for a relationship between increased use of the pill and venereal disease." For women with gonorrhea, oral contraceptive use may protect them from developing pelvic inflammatory disease. However, there is sometimes the danger of pill-users mistakenly believing that the pill will prevent venereal disease.


Transitioning Community Health Clinical Experiences to an Online Format During COVID-19.
This article describes how nursing students in a community health course transitioned to an online clinical experience when coronavirus disease 2019 limited in-person gatherings. A weekly video series was created to provide content to help educate 18 at-risk women using the Plan-Do-Study-Act cycle. Objectives for the nursing students were met. Successful implementation occurred, and objectives for the community health class were met; however, engagement was more difficult to achieve. Transitioning to online video conferencing allowed the nursing students to still engage with the study participants. Using the PDSA cycle allowed for structured changes to be made. [J Nurs Educ. 2022;61(3):159-161.].


Scintigraphic findings in progressive diaphyseal dysplasia.
A 14-yr-old white male with a severe form of progressive diaphyseal dysplasia (Engelmann-Camurati disease) was referred to our institution for evaluation of splenomegaly, which is not usually associated with the disease. Our studies included bone-marrow, and liver-spleen scans. These scintigraphic findings, along with the probable cause for splenomegaly, are discussed.


Novel insights into gene expression regulation during meiosis revealed by translation elongation dynamics.
The ability to dynamically control mRNA translation has a great impact on many intracellular processes. Whereas it is believed that translational control in eukaryotes occurs mainly at initiation, the condition-specific changes at the elongation level and their potential regulatory role remain unclear. Using computational approaches applied to ribosome profiling data, we show that elongation rate is dynamic and can change considerably during the yeast meiosis to facilitate the selective translation of stage-specific transcripts. We observed unique elongation changes during meiosis II, including a global inhibition of translation elongation at the onset of anaphase II accompanied by a sharp shift toward increased elongation for genes required at this meiotic stage. We also show that ribosomal proteins counteract the global decreased elongation by maintaining high initiation rates. Our findings provide new insights into gene expression regulation during meiosis and demonstrate that codon usage evolved, among others, to optimize timely translation.


Low CD4+ T cell nadir is an independent predictor of lower HIV-specific immune responses in chronically HIV-1-infected subjects receiving highly active antiretroviral therapy.
The influence of CD4(+) T cell nadirs on human immunodeficiency virus (HIV)-specific immune responses in subjects with apparently normal CD4(+) T cell counts is not known. We evaluated the frequency of HIV-1-specific immune responses in a cohort of patients with complete viral suppression (HIV-1 RNA load, <50 copies/mL) who were receiving highly active antiretroviral therapy and had a wide range of CD4(+) T cell nadirs. We found positive associations between CD4(+) T cell nadirs and the magnitude of HIV-specific CD8(+) T cell responses (P=.02) and of T cell helper responses (P=.04). These data show the CD4(+) T cell nadir to be an independent predictor of HIV-specific CD4(+) and CD8(+) T cell responses in HIV-1-infected subjects with optimal suppression of viremia.


Nitric Oxide Fumigation for Control of Ham Mite, Tyrophagus putrescentiae (Sarcoptiformes: Acaridae).
The ham mite, Tyrophagus putrescentiae (Schrank) (Sarcoptiformes: Acaridae), is a common pest infesting several stored products, particularly the aged hams. In this study, we reported the efficacy of nitric oxide (NO) fumigation, a recently discovered fumigation treatment under the ultra-low oxygen environment, at various concentrations and time under the laboratory conditions at 25°C against different mite stages on both dietary media and ham meat. Our results showed that NO fumigation was effective against all mite stages and 100% control was achieved. Generally, the egg was the most tolerant stage and required 48-, 24-, 16-, and 8-h treatments to achieve 100% mortality at 0.5, 1, 1.5, and 2% NO concentration on dietary media, respectively. Tyrophagus putrescentiae mobile immatures and adult stages were less tolerant, and 100% mortality was achieved after 16-, 8-, 8-, and 4-h treatment at 0.5, 1, 1.5, and 2% NO, respectively. The median lethal concentration (LC50) of NO on egg was 0.86, 0.68, and 0.32% for 8-, 16-, and 24-h treatments. In addition, a confirmatory test was conducted on ham meat at 0.5 and 1.0% of NO and similar efficacy was found. Complete control of egg was achieved after 48- and 24-h treatment at 0.5 and 1.0% of NO, respectively, and larvae and adult mites were 100% controlled after 16 and 8 h at 0.5 and 1.0% of NO, respectively. Our results demonstrated that NO fumigation was effective against T. putrescentiae and can be a potential alternative treatment to methyl bromide for cured-ham pest control.


Occupational dermatitis in health care workers evaluated for suspected allergic contact dermatitis.
Contact dermatitides occur commonly among health care workers (HCWs). To contrast the atopic status and incidence, location, and final diagnosis of skin diseases afflicting HCWs versus non-HCWs (NHCWs) evaluated for suspicion of allergic contact dermatitis (ACD); and among the population diagnosed with ACD, to compare the incidence and occupational relatedness of allergens found in HCWs with the rates observed in NHCWs. Between July 1, 1994, and May 30, 2014, 2611 patients underwent patch testing by the senior author. Of these, 165 were classified as HCWs based on their primary occupation. Statistical analysis was done using a χ test. Health care workers were more likely than NHCWs to be women and to have hand dermatitis. Women, but not men, HCWs suffered more irritant contact dermatitis. Health care workers had significantly more work-related ACD, especially to formaldehyde, quaternium-15, 2-bromo-2-nitropropane-1,3-diol, cocamide diethanolamine (DEA), thiuram mix, carba mix, thimerosal, benzalkonium chloride, glutaraldehyde, and bacitracin. Only patients suspected of having ACD were tested. Our population was geographically limited to metropolitan Kansas City, MO and metropolitan New York, NY. Health care workers suffer more from occupational ACD, especially of the hands, than do NHCWs, including to allergens not present on available standard allergen series.


The role of psychotherapy in the treatment of substance-use disorders.
Psychotherapies for substance-use disorders are reviewed, with particular attention to modifications of standard treatments necessary to make them effective for patients with disorders. Treatments reviewed include cognitive-behavioral therapies (Relapse Prevention, Cognitive Therapy, Contingency Contracting, Behavioral Treatment, Cue Exposure, Network Therapy, and Aversion Therapy) and psychodynamic/interpersonal methods (Supportive-Expressive Therapy, Interpersonal Therapy, Motivational Interviewing, and Modified Psychoanalytic Therapy). The psychotherapies selected are individual, verbally based treatments for substance-use disorders; except for modified psychoanalytic therapy, all have been presented in treatment manuals and empirically studied. Research shows that these forms of psychotherapy can be effective, with some treatments providing more benefit than others for specific subpopulations, but no one treatment is consistently more effective than any other. General guidelines consistent across psychotherapies for substance-use disorders are discussed, with emphasis on phases of treatment, the importance of a compassionate stance by the therapist, the difficulty of engaging substance abusers in treatment, the need for urine and breath-alcohol testing, assessment of comorbid disorders, countertransference problems, the need for multiple treatment modalities, evaluation of the therapist's effectiveness, adjusting the amount of treatment, and appropriate termination. Directions for future research are also discussed.


Thallium-201 single photon emission tomography after injecting an antimuscarinic agent compared with computed tomography for the diagnosis of recurrent colorectal cancer. Report of three cases.
Thallium-201 chloride ((201)TlCl) is frequently used for imaging of a variety of malignant tumors viz., thyroid, lung, brain, bone and breast, however in patients with colorectal cancer, its role is not well established. In this case report we present three patients with colorectal cancer recurrence, with inconclusive computed tomography (CT) findings while (201)TlCl single photon emission tomography (SPET) after injecting an anti-muscarinic agent, showed findings corroborating with the final diagnosis. Correlating CT with (201)TlCl-SPET findings, recurrence of the colorectal cancer was diagnosed in two cases; surgical treatment accordingly planned, confirmed the diagnosis. In the third case, CT was falsely positive while (201)TlCl-SPET was negative, compatible with the final diagnosis.


Cutaneous malignancies mimicking herpes zoster.
Cutaneous metastases occur in 2.5% to 5% of patients with malignant disease. The relative frequency of the primary site roughly parallels the frequency of the various malignancies in each sex. We present two cases of cutaneous malignancy occurring in a dermatomal distribution and masquerading as herpes zoster. The differential diagnosis of zosteriform eruptions is reviewed and the possible pathogenesis of metastatic disease in this cutaneous distribution is discussed. Skin biopsy is recommended in these cases to determine the etiology of the eruption.


The Common but Complicated Tool: Review of Embolic Materials for the Interventional Radiologist.
Embolization is an important and widely utilized technique in interventional radiology. There are a variety of different categories and individual products which can be utilized to perform embolization. Understanding the different classes of embolic agents, the important features of each of these classes including strengths and limitations, and the variation in individual products within the classes is critical for interventional radiologist to practice safely and effectively. This article reviews the different kinds of embolics and relays some of the pertinent physical and chemical properties of individual products which should be considered when determining which embolic to select for a given purpose.


The effect of preparation for lumbar puncture on children undergoing chemotherapy.
At the University Hospital in Lund, Sweden, a preparation program was developed for children undergoing lumbar punctures (LPs) during chemotherapy for leukemia or lymphoma. Subsequently, a study was initiated to determine whether a preparation program for children prior to treatment would reduce their anxiety and improve their cooperation. This study also was undertaken to examine whether reinforcing the preparation information prior to each LP would be beneficial. The 30 children who participated in the study were divided into three groups: a control group whose members did not receive preparation and two other groups whose members were exposed to different numbers of preparation programs. The parents and the nurse in charge evaluated the children's reactions during treatment using two 6-point rating scales: an anxiety scale and a noncooperation behavior scale. Two unbiased, trained observers later viewed video recordings of the children's reactions and evaluated them using the same tools. In addition, each child rated his or her experience of pain on a 10 cm visual analogue scale. Based on these ratings, the groups were analyzed to determine if within-group differences existed from one treatment to the next and to determine if between-group differences existed at the various times of treatment. Few statistically significant differences were found, but the results indicate that the children in the most informed group exhibited sustained reductions in their perceptions of pain. This may signify that reinforcing the preparation information before each of the LPs enabled these children to cope with the pain more effectively.


Relationship between ATP Level and Activity of Fusicoccin-stimulated H/K-Exchange System in Plant Tissues.
The treatment with fusicoccin causes a slight but significant decrease (about 15%) in the ATP level in pea-internode and maize-coleoptile segments. This decrease is detectable within 15 minutes and is accompanied by a parallel increase in O(2) uptake. Sodium azide inhibits O(2) uptake and completely blocks the stimulation of O(2) uptake by fusicoccin in both pea and coleoptile segments. Benzohydroxamic acid does not affect either basal or fusicoccin-induced O(2) uptake in maize-coleoptile sections. The drop of ATP level induced by various treatments (sodium arsenate, 2-deoxyglucose, limiting O(2), and anaerobiosis) is accompanied by a parallel inhibition of K(+) uptake in maize coleoptiles treated with or without fusicoccin. These results are consistent with the hypothesis that ATP is the energy source for the fusicoccin-activated H(+)/K(+)-exchange system.


Charge-tunnelling and self-trapping: common origins for blinking, grey-state emission and photoluminescence enhancement in semiconductor quantum dots.
Understanding instabilities in the photoluminescence (PL) from light emitting materials is crucial to optimizing their performance for different applications. Semiconductor quantum dots (QDs) offer bright, size tunable emission, properties that are now being exploited in a broad range of developing technologies from displays and solar cells to biomaging and optical storage. However, instabilities such as photoluminescence intermittency, enhancement and bleaching of emission in these materials can be detrimental to their utility. Here, we report dielectric dependent blinking, intensity-"spikes" and low-level, "grey"-state emission, as well as PL enhancement in ZnS capped CdSe QDs; observations that we found consistent with a charge-tunnelling and self-trapping (CTST) description of exciton-dynamics on the QD-host system. In particular, modulation of PL in grey-states and PL enhancement are found to have a common origin in the equilibrium between exciton charge carrier core and surface-states within the CTST framework. Parameterized in terms of size and electrostatic properties of the QD and its nanoenvironment, the CTST offers predictive insight into exciton-dynamics in these nanomaterials.


Preventive Suboccipital Decompressive Craniectomy for Cerebellar Infarction: A Retrospective-Matched Case-Control Study.
No evidence is available on the benefits of preventive suboccipital decompressive craniectomy (SDC) for patients with cerebellar infarction. The purpose of this matched case-control study was to investigate whether preventive SDC was associated with good clinical outcomes in patients with cerebellar infarction and to evaluate its predisposing factors. Between March 2007 and September 2015, 28 patients underwent preventive SDC. We performed propensity score matching to establish a proper control group among 721 patients with cerebellar infarction during the same period. Group A (n=28) consists of those who underwent preventive SDC, and group B (n=56) consists of those who did not undergo preventive SDC. We analyzed and compared clinical outcomes between groups. Clinical outcomes were better in group A than in group B at discharge (P=0.048) and 12-month follow-up (P=0.030). Group B had more deaths within 12 months than group A (log-rank, P<0.05). Logistic regression analysis showed that preventive SDC (odds ratio, 4.815; P=0.009) and the absence of brain stem infarction (odds ratio, 2.862; P=0.033) were independently associated with favorable outcomes (modified Rankin Scale score of 0-2) at 12-month follow-up. Favorable clinical outcomes including overall survival can be expected after preventive SDC in patients with a volume ratio between 0.25 and 0.33 and the absence of brain stem infarction. Among these patients, preventive SDC might be better than the best medical treatment alone.


Multiple forms of long-term plasticity at unitary neocortical layer 5 synapses.
Long-term potentiation and depression (LTP and LTD) are cellular plasticity phenomena expressed at a variety of central synapses, and are thought to contribute to learning and developmental changes in circuitry. Recurrent neocortical layer-5 synapses are thought to express a presynaptic form of LTP that influences the short-term plasticity of the synapse. Here we show that changes in synaptic strength elicited by pairing high frequency pre- and postsynaptic firing at this synapse result from a mixture of presynaptic and postsynaptic forms of plasticity, as assessed by the analysis of changes in coefficient of variation, short-term plasticity, and NMDA:AMPA current ratios. Pharmacological dissection of this plasticity revealed that block of presynaptic LTD with an endocannabinoid inhibitor enhanced LTP, while the apparently presynaptic component of LTP could be prevented by induction in the presence of blockers of nitric oxide. These data suggest that correlated high-frequency firing at layer-5 synapses simultaneously induces a mixture of presynaptic LTD, presynaptic LTP, and postsynaptic LTP.


[Injection of anaesthetic-corticosteroid to relieve sacroiliac joint pain after lumbar stabilisation].
Both the range of motion and load transfer of the sacroiliac (SI) joint improve considerably after lumbar spine surgery. When, following surgery, SI joint pain develops in spite of appropriate physical therapy, injection of an anaesthetic with added corticosteroid into the SI joint is a first choice treatment. The aim of this presentation is to provide information on our experience with this therapy. Thirty-four patients after lumbar spine fusion reported lumbalgia different form pain before surgery. In 14 (41%) of them, pain in one of the SI joints was diagnosed as the cause. This group included 12 women and two men at an average age of 56 (range, 47 to 68) years. Ten patients underwent lumbosacral fixation and four had segmental ("floating") lumbar spine fusion. All patients experienced lumbalgia at more than 3 months following surgery, at 8 months on the average (range, 4 to 12 months). None of them had SI joint pain before surgery. The diagnosis was based on specific manoeuvres on physical examination of the joint. Each patient was given an injection of 20 mg (0.5 ml) Methylprednisolone (Depo-Medrol®, Pfizer, Puurs, Belgium) and 4.5 ml 1% Mesocain (Zentiva, Praha, CR).They were inquired as to pain relief 24 h later and then at 1, 3 and 6 months after injection. Subjective feelings were assessed by a visual analogue scale (VAS). The results were analysed using descriptive statistics. All patients reported pain relief within 24 h of injection, but not its complete resolution. The average VAS score before and after the blockage of the SI joint was 9.1 points (8-10) and 4.8 points (2-7), respectively; this implies improvement by an average of 4.3 points (1-6), i.e., approximately by 47.3% (12.5-62.5). The duration of effects varied greatly from patient to patient. The average interval between injection and pain recurrence lasted for 5 weeks (1-28). Most frequently, relief was experienced for 2 weeks, or for 6.8 weeks with the standard deviation included. DISCUSSION Sacroiliac joint dysfunction is a very frequent cause of lumbalgia, particularly after lumbar spine surgery. Physical therapy may not always be effective. SI joint arthrodesis is indicated only in rare cases. One of the few possibilities of pain relief involves intra-articular injection of an anaesthetic with corticosteroid for booster effect. The treatment of SI joint blockage after spinal fusion has recently been dealt with in three reports in the international literature; their conclusions are in accordance with the results of this study. Lumbar spine stabilisation surgery may result in overloading the SI joints as the "adjacent segments". An intra-articular injection of anaesthetic can be considered a reliable method for ascertaining the SI joint as the source of a patient's problems. However, even with corticosteroid added, pain relief is not usually long-lasting.


Periprostatic fat thickness measured on MRI correlates with lower urinary tract symptoms, erectile function, and benign prostatic hyperplasia progression.
This study investigated the correlation between periprostatic fat thickness (PPFT) measured on magnetic resonance imaging and lower urinary tract symptoms, erectile function, and benign prostatic hyperplasia (BPH) progression. A total of 286 treatment-naive men diagnosed with BPH in our department between March 2017 and February 2019 were included. Patients were divided into two groups according to the median value of PPFT: high (PPFT >4.35 mm) PPFT group and low (PPFT <4.35 mm) PPFT group. After the initial evaluation, all patients received a combination drug treatment of tamsulosin and finasteride for 12 months. Of the 286 enrolled patients, 244 completed the drug treatment course. Patients with high PPFT had larger prostate volume (PV; P = 0.013), higher International Prostate Symptom Score (IPSS; P = 0.008), and lower five-item version of the International Index of Erectile Function (IIEF-5) score (P = 0.002) than those with low PPFT. Both high and low PPFT groups showed significant improvements in PV, maximum flow rate, IPSS, and quality of life score and a decrease of IIEF-5 score after the combination drug treatment. The decrease of IIEF-5 score was more obvious in the high PPFT group than that in the low PPFT group. In addition, more patients in the high PPFT group underwent prostate surgery than those in the low PPFT group. Moreover, Pearson's correlation coefficient analysis indicated that PPFT was positively correlated with age, PV, and IPSS and negatively correlated with IIEF-5 score; however, body mass index was only negatively correlated with IIEF-5 score.


High-sugar diet intake, physical activity, and gut microbiota crosstalk: Implications for obesity in rats.
This study aims to evaluate the effect of long-term high-sugar diet (HSD) intake and regular physical activity on gut microbiota as well as its health impact. Weaned male Wistar rats were fed with standard chow diet (SSD) or HSD ad libitum and subjected or not to regular swimming training with a workload (2% of body weight) for 15 weeks. Feces samples were used on microbiome analysis using 16S rRNA amplicon sequencing. HSD increased body mass, adipose cushions, and the serum levels of triglycerides and VLDL, also changed the bacteria taxons associated with metabolic disorders (increase taxons belonging to Proteobacteria phylum and decrease Pediococcus genus); the swim training reverted these changes. SSD intake increased the abundance of bacteria associated with metabolization of dietary fiber. Training in association with SSD consumption beneficially modulated the microbiota, increasing the Bacteroidetes, Bacteroidaceae, Porphyromonadaceae, Parabacteroides, and Lactobacillaceae, and decreasing the Firmicute/Bacteroidetes ratio; training was not able to maintain this profile in animals SHD-fed. Physical training modulates the gut microbiota reversing the obesogenic response caused by SHD. However, training itself is not efficient for up-regulating the probiotic bacteria in comparison to its association with a balanced diet.


F-box protein Skp2: a novel transcriptional target of E2F.
The F-box-containing protein Skp2 plays a critical role in coordinating the G1/S transition and progression through the S phase of the mammalian cell cycle. Skp2 is overexpressed in a broad spectrum of human cancers and the expression level correlates with tumor malignancy. However, the Skp2 gene is neither amplified nor rearranged in most human cancers and the underlying mechanism of Skp2 overexpression remains poorly understood. We show here that the Skp2 gene contains a functional E2F response element (hSRE2). Ectopic expression of E2F1 induces expression of the endogenous Skp2 gene in human fibroblast cells, whereas antisense-mediated knockdown of E2F1 in human tumor cell lines reduces expression of endogenous Skp2 gene. The hSRE2 element not only participates in activation of Skp2 promoter function during normal cell cycle progression into S phase, it is also required for the high-level Skp2 gene expression in many human tumor cell lines. These results reveal Skp2 as a novel target for E2F regulation that is disrupted in several human tumor cell lines.


Novel platelet antiaggregating substances.
We describe herein a novel action of four stable analogs of the hepoxilins. These analogs inhibit to different degrees, the aggregation of washed human platelets evoked by collagen. One of the analogs, PBT-3, is particularly effective with an IC(50) = 8 x 10(-7) M. The other analogs are about 5-fold less active, but all analogs are about 500-fold more active than the native hepoxilins. The PBT analogs inhibit the collagen-enhanced formation of thromboxane A(2) and HHT but do not affect the formation of 12-HETE or the release of arachidonic acid except at doses higher than those needed to block platelet aggregation. These results demonstrate that these novel compounds may have potential for development into drugs in the treatment of thromboxane-mediated cardiovascular disease.


The incidence of total hip arthroplasty after hip arthroscopy in osteoarthritic patients.
To assess the incidence of total hip arthroplasty (THA) in osteoarthritic patients who were treated by arthroscopic debridement and to evaluate factors that might influence the time interval from the first hip arthroscopy to THA. Retrospective clinical series Follow-up data and surgical reports were retrieved from 564 records of osteoarthritic patients that have had hip arthroscopy between the years 2002 to 2009 with a mean follow-up time of 3.2 years (range, 1-6.4 years). The time interval between the first hip arthroscopy to THA was modelled as a function of patient age; level of cartilage damage; procedures performed and repeated arthroscopies with the use of multivariate regression analysis. Ninety (16%) of all participants eventually required THA. The awaiting time from the first arthroscopy to a hip replacement was found to be longer in patients younger than 55 years and in a milder osteoarthritic stage. Patients that experienced repeated hip scopes had a longer time to THA than those with only a single procedure. Procedures performed concomitant with debridement and lavage did not affect the time interval to THA. In our series of arthroscopic treatment of hip osteoarthritis, 16% required THA over a period of 7 years. Factors that influence the time to arthroplasty were age, degree of osteoarthritis and recurrent procedures.


Multi-channel absolute distance measurement system with sub ppm-accuracy and 20 m range using frequency scanning interferometry and gas absorption cells.
We present an implementation of an absolute distance measurement system which uses frequency scanning interferometry (FSI). The technique, referred to as dynamic FSI, uses two frequency scanning lasers, a gas absorption cell and a reference interferometer to determine the unknown optical path length difference (OPD) of one or many measurement interferometers. The gas absorption cell is the length reference for the measurement system and is traceable to international standards through knowledge of the frequencies of its absorption features. The OPD of the measurement interferometers can vary during the measurement and the variation is measured at the sampling rate of the system (2.77 MHz in the system described here). The system is shown to measure distances from 0.2 m to 20 m with a combined relative uncertainty of 0.41 × 10⁻⁶ at the two sigma level (k = 2). It will be shown that within a scan the change in OPD of the measurement interferometer can be determined to a resolution of 40 nm.


Conscientiousness, Activity Engagement, and Momentary Affect in Oldest-Old Adulthood.
Remaining engaged with life is a hallmark of aging well and pursuing personally meaningful activities is presumably important for late-life affect. We examined how moment-to-moment variability in meaning and degree of challenge ascribed to daily activities relate to positive and negative affect in very old adults. Possible moderating effects of between-person differences in conscientiousness on meaning-affect associations were also examined. Participants were 73 adults aged 89 years on average from the Australian Daily Life Time-Sampling module of the Australian Longitudinal Study of Aging. Participants provided self-report data on activity engagement (meaning and challenge associated with activities) and affect, on 5 occasions per day for a period of 7 consecutive days. Within-person associations of activity meaning with affect varied as a function of within-person challenge ratings. Specifically, gains in positive affect associated with meaningful activity were more strongly evident when activities were regarded as more challenging. In contrast, meaningful activity was associated with higher negative affect when activities were regarded as more challenging and lower negative affect when activities were regarded as less challenging. Conscientiousness did not moderate associations of activity meaning with affect. Our findings shed light on the intricate interplay between maintaining meaningful engagement and daily emotional experiences in very old age. We discuss theoretical and practical implications and consider the role of late-life conscientiousness for self- and emotion regulation.


Satb2 is required for dendritic arborization and soma spacing in mouse cerebral cortex.
Self-avoidance is a mechanism by which dendrites from the same neuron repel one another in order to establish uniform coverage of the dendritic field. The importance of self-avoidance for the development of complex arborization patterns has been highlighted by studies of Drosophila sensory and mouse retinal neurons. However, it is unclear whether branch patterning in the mammalian central nervous system is also governed by this strategy. We reduced Satb2 expression in a population of layer II/III pyramidal neurons in vivo by RNA interference and found that the somas of Satb2-deficient neurons clumped together, and their dendrites failed to expand laterally but instead formed fascicles. Furthermore, experiments showed that reducing Satb2 caused the adhesion of not only neighboring Satb2-deficient neurons but also neighboring wild-type neurons. Our results indicate a cell autonomous and non-cell autonomous role for Satb2 in regulating the adhesive and/or repulsive properties of cerebral pyramidal neurons.


Computer Based Body Exposure in Adolescents With Anorexia Nervosa: A Study Protocol.
Body dissatisfaction is a core feature of eating disorders (EDs) and plays an essential role in the development and maintenance of anorexia nervosa (AN). In the current study, a computer based body exposure intervention is conducted and evaluated regarding short-term effects on body dissatisfaction, psychopathology, viewing patterns, and stress reactivity. Within a randomized controlled trial (RCT) female adolescents and young women with AN are either receiving the intervention or treatment as usual (TAU). Furthermore, in a transdiagnostic approach, a highly body-dissatisfied group of clinical control participants obtaining the intervention will be surveyed to identify AN-specific processes. The standardized four-session body exposure intervention using photographs of the own body is adapted from a manualized body image treatment program for computer use. Psychopathology (body dissatisfaction, body image avoidance, body checking, depression, anxiety) is assessed via standardized questionnaires before and after the intervention. During each session, attentional biases regarding one's own body are measured via eye tracking, stress levels are measured via subjective ratings, heart rate variability, as well as salivary cortisol and alpha amylase. Between- and within-subject effects will be assessed. The pilot study aims to identify short-term effects of the intervention on body dissatisfaction and attentional bias, as well as to investigate the potential underlying mechanism of physiological habituation.


Oral health behaviors of children in low and high socioeconomic status families.
This prospective longitudinal study compared the patterns of oral health behaviors between low and high socioeconomic status (SES) families participating in the Iowa Fluoride Study for a period of 9 years. Information on oral health behaviors, including consumption of juices/juice drinks, soda pop, and powder-based drinks, dental visits, and tooth-brushing frequency, was collected longitudinally at periodic intervals from 6 to 108 months of age. Dental exams were conducted at 5 and 9 years of age. Classification of low socioeconomic status (SES; n=70) and high-SES (n= 128) children was based on baseline family income and mothers' education levels, with middle SES excluded. Low SES children consistently had significantly greater consumption of soda pop and powder-based beverages. There were, however, virtually no differences at any time point between groups in: (1) tooth-brushing frequency; (2) use of dentifrice; or (3) fluoride concentration in drinking water. Furthermore, the mean number of decayed and filled surfaces was significantly higher in the low-SES group. Results suggest that beverage consumption patterns are a key difference between high- and low-socioeconomic status families and could in part explain differences in caries experience between subjects of different SES. Modification of the pattern of soda pop and powder-based beverage consumption in the low-SES groups might reduce their caries experience.


Ultrasensitive Label-Free Detection of Unamplified Multidrug-Resistance Bacteria Genes with a Bimodal Waveguide Interferometric Biosensor.
Infections by multidrug-resistant bacteria are becoming a major healthcare emergence with millions of reported cases every year and an increasing incidence of deaths. An advanced diagnostic platform able to directly detect and identify antimicrobial resistance in a faster way than conventional techniques could help in the adoption of early and accurate therapeutic interventions, limiting the actual negative impact on patient outcomes. With this objective, we have developed a new biosensor methodology using an ultrasensitive nanophotonic bimodal waveguide interferometer (BiMW), which allows a rapid and direct detection, without amplification, of two prevalent and clinically relevant Gram-negative antimicrobial resistance encoding sequences: the extended-spectrum betalactamase-encoding gene blaCTX-M-15 and the carbapenemase-encoding gene blaNDM-5 We demonstrate the extreme sensitivity and specificity of our biosensor methodology for the detection of both gene sequences. Our results show that the BiMW biosensor can be employed as an ultrasensitive (attomolar level) and specific diagnostic tool for rapidly (less than 30 min) identifying drug resistance. The BiMW nanobiosensor holds great promise as a powerful tool for the control and management of healthcare-associated infections by multidrug-resistant bacteria.


Clinical screening and intervention in cases of partner violence.
Partner violence is a long-term health risk factor that can potentially have far-reaching, negative consequences on both those abused and their loved ones. The term "partner" is used to define opposite and same sex couples who are in relationships on a continuum ranging from casually dating to marriage. Partner violence includes physical, sexual, psychological, and economic abuse, as well as stalking behaviors. Even though the American Medical Association recommends screening for partner violence at multiple levels, there are many shortcomings of the current screening and intervention practice. Several factors facilitating the ineffectiveness of current practice include a lack of information related to the prevalence, duration, and severity of partner violence; physician s misguided beliefs regarding a victim s desire to disclose; and barriers that the victim faces when deciding whether to disclose partner violence. This article addresses these shortcomings and identifies nurses as an invaluable resource that has been under-utilized for screening and responding to partner violence. Also highlighted is one technique know by the acronym "RADAR" that is designed to address issues of both screening and intervention. Finally, resources for both health care practitioners and victims of abuse are provided.


Resveratrol protects the brain of obese mice from oxidative damage.
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic phytoalexin that exerts cardioprotective, neuroprotective, and antioxidant effects. Recently it has been shown that obesity is associated with an increase in cerebral oxidative stress levels, which may enhance neurodegeneration. The present study evaluates the neuroprotective action of resveratrol in brain of obese (ob/ob) mice. Resveratrol was administered orally at the dose of 25 mg kg(-1) body weight daily for three weeks to lean and obese mice. Resveratrol had no effect on body weight or blood glucose levels in obese mice. Lipid peroxides were significantly increased in brain of obese mice. The enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and nonenzymatic antioxidants tocopherol, ascorbic acid, and glutathione were decreased in obese mice brain. Administration of resveratrol decreased lipid peroxide levels and upregulated the antioxidant activities in obese mice brain. Our findings indicate a neuroprotective effect of resveratrol by preventing oxidative damage in brain tissue of obese mice.


The Role and Regulation of Autophagy and the Proteasome During Aging and Senescence in Plants.
Aging and senescence in plants has a major impact on agriculture, such as in crop yield, the value of ornamental crops, and the shelf life of vegetables and fruits. Senescence represents the final developmental phase of the leaf and inevitably results in the death of the organ. Still, the process is completely under the control of the plant. Plants use their protein degradation systems to maintain proteostasis and transport or salvage nutrients from senescing organs to develop reproductive parts. Herein, we present an overview of current knowledge about the main protein degradation pathways in plants during senescence: The proteasome and autophagy. Although both pathways degrade proteins, autophagy appears to prevent aging, while the proteasome functions as a positive regulator of senescence.


Identification of a new murine tumor necrosis factor receptor locus that contains two novel murine receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
Tumor necrosis factor (TNF) ligand and receptor superfamily members play critical roles in diverse developmental and pathological settings. In search for novel TNF superfamily members, we identified a murine chromosomal locus that contains three new TNF receptor-related genes. Sequence alignments suggest that the ligand binding regions of these murine TNF receptor homologues, mTNFRH1, -2 and -3, are most homologous to those of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors. By using a number of in vitro ligand-receptor binding assays, we demonstrate that mTNFRH1 and -2, but not mTNFRH3, bind murine TRAIL, suggesting that they are indeed TRAIL receptors. This notion is further supported by our demonstration that both mTNFRH1:Fc and mTNFRH2:Fc fusion proteins inhibited mTRAIL-induced apoptosis of Jurkat cells. Unlike the only other known murine TRAIL receptor mTRAILR2, however, neither mTNFRH2 nor mTNFRH3 has a cytoplasmic region containing the well characterized death domain motif. Coupled with our observation that overexpression of mTNFRH1 and -2 in 293T cells neither induces apoptosis nor triggers NFkappaB activation, we propose that the mTnfrh1 and mTnfrh2 genes encode the first described murine decoy receptors for TRAIL, and we renamed them mDcTrailr1 and -r2, respectively. Interestingly, the overall sequence structures of mDcTRAILR1 and -R2 are quite distinct from those of the known human decoy TRAIL receptors, suggesting that the presence of TRAIL decoy receptors represents a more recent evolutionary event.


Leaf Conductance during the Final Season of a Senescing Aspen Branch.
Leaf conductance, transpiration, and environmental conditions were measured on two aspen (Populus tremuloides Michx.) branches in a natural stand, using an automatic cuvette system. Fortuitously, leaves on one branch senesced about 10 days early, allowing comparison between a senescing branch and a normal branch. Terminal bud development was retarded on the senescent branch, and a portion of the branch eventually abscised about 20 centimeters from the end. Roughly 1% to 2% of the other branches on the study tree and adjacent trees of that clone also senesced and were dead the following spring.Although no visual symptoms of senescence were observed until September, stomatal behavior was atypical shortly after leaves were fully expanded. During July and August, leaf conductances under full sunlight were higher on the branch which senesced than on the branch which was normal, reaching values greater than 1.0 centimeters per second, and conductance was highly variable.


Temporomandibular disorders. Part 3. Surgical treatment.
Surgery of the temporomandibular joint has a small but nonetheless important role in the overall management of temporomandibular disorders. Appropriate case selection is the mandatory requirement for successful surgical intervention in order to achieve the desired outcome of treatment, such as relief of symptoms and improved function. In this, the third article in the series, a general overview of the current surgical treatment modalities for temporomandibular disorders will be presented.


Research methods in international business: The challenge of complexity.
International business (IB) research is designed to explore and explain the inherent complexity of international business, which arises from the multiplicity of entities, multiplexity of interactions, and dynamism of the global economic system. To analyze this complexity, IB scholars have developed four research lenses: difference, distance, diversity, and disparity. These four lenses on complexity have created not only unique research opportunities for IB scholarship but also unique research methodological challenges. We therefore view complexity as the underlying cause of the unique methodological challenges facing international business research. We offer several recommendations to help IB scholars embrace this complexity and conduct reliable, interesting, and practically relevant research.


Accuracy of national mortality codes in identifying adjudicated cardiovascular deaths.
This study investigated the sensitivity and specificity of the national mortality codes in identifying cardiovascular disease (CVD) deaths and documents methods of verification. A 12-year retrospective case ascertainment of all ICD-coded CVD deaths was performed for deaths between 1990 and 2002 in the Melbourne Collaborative Cohort Study, comprising 41,528 subjects. Categories of non-CVD codes were also examined. Stratified samples of 750 deaths were adjudicated from a total of 2,230 deaths. Expert panels of cardiologists and neurologists adjudicated deaths. Of the 750 deaths adjudicated, 582 were verified as CVD [392 coronary heart disease (CHD) and 92 stroke] and 168 non-CVD. Estimated sensitivity and specificity of national mortality codes for identifying specific causes of death were: CHD 74.2% (95% CI: 69.8-78.5%) and 97.6% (96.0-99.2%), respectively; myocardial infarction 59.9% (50.9-69.0%) and 94.2% (92.4-96.0%), respectively; haemorrhagic stroke 58.9% (46.0-71.7%) and 99.8% (99.4-100.0%), respectively and; ischaemic stroke 38.7% (20.5-56.9%) and 99.9% (99.6-100.0%), respectively. Misclassification was most common for deaths with primary ICD codes for endocrine-metabolic and genito-urinary diseases. National mortality coding under-estimated the true proportion of CHD and stroke deaths in the cohort by 13.6% and 50.8%, respectively. Misclassification of cause of death may have implications for conclusions drawn from epidemiological research.


Rapid amplification of genetically modified organisms using a circular ferrofluid-driven PCR microchip.
The use of genetically modified organisms (GMOs) as food and in food products is becoming more and more widespread. Polymerase chain reaction (PCR) technology is extensively used for the detection of GMOs in food products in order to verify compliance with labeling requirements. In this paper, we present a novel close-loop ferrofluid-driven PCR microchip for rapid amplification of GMOs. The microchip was fabricated in polymethyl methacrylate by CO2 laser ablation and was integrated with three temperature zones. PCR solution was contained in a circular closed microchannel and was driven by magnetic force generated by an external magnet through a small oil-based ferrofluid plug. Successful amplification of genetically modified soya and maize were achieved in less than 13 min. This PCR microchip combines advantages of cycling flexibility and quick temperature transitions associated with two existing microchip PCR techniques, and it provides a cost saving and less time-consuming way to conduct preliminary screening of GMOs.


Metastatic castration-resistant prostate cancer: two case reports of dramatic response with abiraterone acetate in patients heavily pretreated with chemotherapy.
Metastatic castration-resistant prostate cancer (mCRPC) with visceral involvement requires new, effective and safe treatments after chemotherapy failure. The CYP17A1 inhibitor abiraterone acetate has been approved as a treatment for mCRPC, both after docetaxel chemotherapy and more recently for patients who are not responding to chemotherapy. In published studies, most patients previously treated with docetaxel had received a limited number of lines of chemotherapy and a small proportion of these patients presented with visceral metastases. We report two mCRPC patients with extensive visceral disease, who were heavily pretreated with chemotherapy. They experienced major responses to treatment with abiraterone acetate. For both patients, responses to abiraterone were noticeable within 1 month, encompassing a marked regression of visceral metastases and a decrease in prostate-specific antigen. The clinical benefit of abiraterone was maintained for at least 6 months and the treatment was well tolerated.


Accurate flexible refinement for atomic-level protein structure using cryo-EM density maps and deep learning.
With the rapid progress of deep learning in cryo-electron microscopy and protein structure prediction, improving the accuracy of the protein structure model by using a density map and predicted contact/distance map through deep learning has become an urgent need for robust methods. Thus, designing an effective protein structure optimization strategy based on the density map and predicted contact/distance map is critical to improving the accuracy of structure refinement. In this article, a protein structure optimization method based on the density map and predicted contact/distance map by deep-learning technology was proposed in accordance with the result of matching between the density map and the initial model. Physics- and knowledge-based energy functions, integrated with Cryo-EM density map data and deep-learning data, were used to optimize the protein structure in the simulation. The dynamic confidence score was introduced to the iterative process for choosing whether it is a density map or a contact/distance map to dominate the movement in the simulation to improve the accuracy of refinement. The protocol was tested on a large set of 224 non-homologous membrane proteins and generated 214 structural models with correct folds, where 4.5% of structural models were generated from structural models with incorrect folds. Compared with other state-of-the-art methods, the major advantage of the proposed methods lies in the skills for using density map and contact/distance map in the simulation, as well as the new energy function in the re-assembly simulations. Overall, the results demonstrated that this strategy is a valuable approach and ready to use for atomic-level structure refinement using cryo-EM density map and predicted contact/distance map.


Disparity minimisation, cyclovergence, and the validity of nonius lines as a technique for measuring torsional alignment.
Frisby et al (1993 Perception 22 Supplement, 115) proposed that the visual system might make cyclovergent eye movements in order to minimise the overall pattern of both vertical and horizontal disparities when an observer views an inclined stereoscopic surface. Their measurements of cyclovergence, which used vertically oriented nonius lines, were found to be consistent with that proposal. In our experiment 1, we measured torsional eye movements objectively, using scleral coils, and found no evidence of a cyclovergent response to either a real inclined surface or to a simulated inclined surface in which the two stereoscopic images were related by a horizontal shear transformation. These results are inconsistent with the disparity minimisation hypothesis. In order to account for the discrepant findings of the two studies, we propose that vertically oriented nonius lines may not be a valid method for assessing cyclovergence because the lines can be seen as lying 'within' the inclined surface. In experiment 2, we tested the predictions of the cyclovergence hypothesis of Frisby et al against our own 'within surface' explanation, using both horizontally and vertically oriented nonius lines and dichoptic images related by either a horizontal or a vertical shear. If cyclovergence were the cause of the misalignment, both horizontal and vertical nonius lines should appear misaligned to the same extent. This was not found to be the case. We conclude that vertical nonius lines may not be a valid technique for measuring cyclovergence when the lines are seen against a background of an inclined surface.


Improving paediatric residents' knowledge and perspectives regarding the insulin pump using a novel educational workshop.
As a pilot study, we aimed to investigate the knowledge and perceptions of categorical paediatric residents (RES) at our institution regarding insulin pumps (IPs) and the impact following a targeted workshop. All RES at our institution in attendance at a routine noon conference participated in a workshop, completing an anonymous survey before and right after the intervention to evaluate knowledge, attitudes and self-reported comfort regarding IPs. The workshop consisted of a didactic lecture followed by an insulin pump (IP) device demonstration of three commonly available brands. Knowledge score (KS) was calculated for each RES based on the total correct responses. Attitudes were assessed via 5-point Likert scale. Frequencies, t-test and McNemar tests were used to analyse data. Thirty four completed surveys were analysed out of 49 RES (69.3%) who attended the workshop. Among them, there were 19 first-year, 8 second-year and 7 third-year residents. Following the intervention, KS increased significantly (p<0.001) with progression in residents' attitudes. Overall, more RES reported being comfortable with handling the IP, including looking up and changing the settings (p<0.001). There is scope for improvement in the knowledge and perceptions of RES regarding IPs. Educational interventions like ours are needed to familiarise our future physicians with IPs to allow hospitals to provide their systematic and safe inpatient use.


[Difference in osteoporosis in men and women].
Burden of osteoporosis in men on our society is increasing with aging in population. Prevalence of osteoporosis and incidence of osteoporotic fracture are less frequent in men than in women since bone mineral density is higher, bone size is greater, and hence the bone is stronger in men than in women. In spite of these facts, the number of male patients with osteoporosis was projected to be 3 million in 2005 and is increasing thereafter. Hip fracture was estimated to occur in 33,100 men in 2007 and is increasing as well. Once a man suffers from hip fracture, prognosis is worse in men than in women. However, screening methods for osteoporosis in men are not established, and this causes delay in diagnosis and treatment. Further studies are necessary to answer whether the current young adult value of bone density necessary for diagnosis is appropriate, whether therapeutic regimens are effective in men, whether the cost for diagnosis and treatment is comparable to benefit, whether a valid screening method for osteoporosis in men exists, and whether the screening method is cost-effective.


Stacking interactions of hydrogen-bridged rings – stronger than the stacking of benzene molecules.
Analysis of crystal structures from the Cambridge Structural Database showed that 27% of all planar five-membered hydrogen-bridged rings, possessing only single bonds within the ring, form intermolecular stacking interactions. Interaction energy calculations show that interactions can be as strong as -4.9 kcal mol(-1), but dependent on ring structure.


Effects of a Novel Rotator Cuff Rehabilitation Device on Shoulder Strength and Function.
Savitzky, JA, Abrams, LR, Galluzzo, NA, Ostrow, SP, Protosow, TJ, Liu, SA, Handrakis, JP, and Friel, K. Effects of a novel rotator cuff rehabilitation device on shoulder strength and function. J Strength Cond Res 35(12): 3355-3363, 2021-The glenohumeral joint, a multiaxial ball and socket joint, has inherent instability counterbalanced by the muscular stability of the rotator cuff (RC) and connective tissue. Exercise has been shown to alleviate pain and disability arising from degenerative changes of the RC due to overuse, trauma, or poor posture. This study compared the training effects of ShoulderSphere (SS), an innovative device that uses resistance to centrifugal force, to TheraBand (TB), a traditional device that uses resistance to elasticity. Thirty-five healthy male and female adults (24.2 ± 2.4 years) were randomized into 3 groups: SS, TB, and control. Five outcomes were assessed before and after the twice-weekly, 6-week intervention phase: strength (shoulder flexion [Fx], extension [Ext], external rotation [ER], and internal rotation [IR]), proprioception (6 positions), posterior shoulder endurance (ShEnd), stability (Upper Quarter Y-Balance Test [YBal] (superolateral [YBalSup], medial [YBalMed], and inferolateral [YBalInf]), and power (seated shot put [ShtPt]). Data were analyzed using a 3 (group: SS, TB, and control) × 2 (time: pre and post) generalized estimating equation. Analyses demonstrated a main effect of time for all strength motions (p < 0.01): YBalInf (p < 0.0001), ShtPt (p < 0.05), and ShEnd (p < 0.0001) but no interaction effects of group × time. There were no main or interaction effects for proprioception. Both SS and TB groups had significant within-group increases in Ext, IR, YBalInf, and ShEnd. Only the SS group had significant increases in ER, Fx, and ShtPt. ShoulderSphere demonstrated comparable conditioning effects with TB and may afford additional strength gains in Fx and ER, and power. ShoulderSphere should be considered a viable alternative in RC conditioning.


Metal Substitution in Keggin-Type Tridecameric Aluminum-Oxo-Hydroxy Clusters.
The species resulting from a typical preparation for metal-substituted hybrids of the Keggin tridecamer, Al13 or [AlO4Al12(OH)24(OH2)12]7+, were examined by performing 27Al NMR on the solutions during aging and by studying the precipitated sulfate salts via solid state 27Al NMR and powder X-ray diffraction (XRD). Aqueous mixtures (0.25 mol L-1) of AlCl3 and another metal ion (M), in a 12:1 mole ratio (Al:M), where M = Fe3+, Zn2+, Ga3+, In3+, Sn2+, La3+, and Bi3+, were subjected to forced hydrolysis by addition of NaOH (1.0 mol L-1) until OH/(Al + M) = 2.25, and the kinetics of Al13 formation and disappearance with aging at 80 °C was monitored by 27Al NMR spectroscopy. Al13 units polymerize on aging with an apparent rate constant (k) of 4.8(8) × 10-2 h-1 to form a species referred to as AlP2. Only the solutions containing Ga3+ and Sn2+ exhibited faster Al13 conversion rates. GaAl12 forms quickly at 80 °C (k = 0.54 h-1) and is more stable than AlP2. Sn2+ apparently promotes AlP2 formation (k = 0.38 h-1). XRD and solid state NMR reveal that only the Ga hybrid can be prepared by this method. No hybrid formation was evidenced using M = Mg2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, In3+, La3+, or Ce3+ at 25 °C or M = Co2+ or La3+ under reflux conditions. Isostructural (cubic symmetry) single crystals were obtained for the sulfate salts of Al13 and GaAl12. Single-crystal XRD analysis of these two polyoxocations provides the first rigorous comparison between them and shows they have very similar structures. The main crystallographic data for Al13 and GaAl12 are as follows: Na[AlO4Al12(OH)24(H2O)12](SO4)4·10H2O, cubic, F4̄3m, a = 17.856(2) Å, Z = 4; Na[GaO4Al12(OH)24(H2O)12](SO4)4·10H2O, cubic, F4̄3m, a = 17.869(3) Å, Z = 4. Thus, the greater thermal stability of GaAl12 cannot be rationalized in terms of the overall geometric considerations, as suggested by others. Solid state NMR also shows the coordination symmetries of the outer 12 Al nuclei in both clusters to be similar.


Un-thought out metaphysics in analytical psychology: a critique of Jung's epistemological basis for psychic reality.
The author investigates the relation of Kant, Schopenhauer and Heidegger to Jung's attempts to formulate theory regarding the epistemological conundrum of what can and what cannot be known and what must remain uncertain. Jung's ambivalent use and misuse of Kant's division of the world into phenomenal and noumenal realms is highlighted in discussion of concepts such as the psychoid archetype which he called 'esse in anima' and his use of Schopenhauer's concept of 'will' to justify a transcendence of the psyche/soma divide in a postulation of a 'psychoid' realm. Finally, the author describes Jung's reaction to Heidegger's theories via his assertion that Heidegger's 'pre-given world design' was an alternate formulation of his concept of the archetypes. An underlying theme of the paper is a critique of Jung's foundationalism which perpetuates the myth of an isolated mind. This model of understanding subjectivity is briefly contrasted with Heidegger's 'fundamental ontology' which focuses on a non-Cartesian 'understanding' of the 'presencing of being' in everyday social and historical contexts.


Plant-Derived Lactobacillus paracasei IJH-SONE68 Improves Chronic Allergy Status: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
We have recently demonstrated that the exopolysaccharides (EPSs) produced by a plant-derived lactic acid bacterium, Lactobacillus paracasei IJH-SONE68, prevent and ameliorate allergic reaction on contact in dermatitis model mice. In the present study, we conducted a clinical trial using a capsule containing spray-dried powder from pineapple juice broth fermented with the LAB strain as an experimental diet. The clinical trial was conducted as a double-blind and placebo-controlled randomized comparative study from May 2019 to July 2021. Males and females between the ages of 21 and 70 who experience chronic allergies participated in the study. Sixty subjects were instructed to orally take a capsule containing the IJH-SONE68 powder or placebo, every day for 12 weeks. After the clinical trial was over, the scores based on subjects' self-assessment of allergic status were significantly improved in the intervention group, as compared with the placebo group. Some serum biochemicals associated with inflammation response were also significantly improved by intake of the experimental diet. In conclusion, the IJH-SONE68-derived EPS improves chronic allergy status in humans and is expected to decrease their inconvenience.


The effects of a primary care low-carbohydrate, high-fat dietary educational intervention on laboratory and anthropometric data of patients with chronic disease: a retrospective cohort chart review.
Low-carbohydrate and high-fat (LCHF) diets are shown to have health benefits such as weight loss and improved cardiovascular health. Few studies, however, on LCHF diets have been completed in a real-world primary care setting over an extended period of time. To examine the efficacy of a low-carbohydrate, high-fat dietary educational intervention delivered in a family practice setting on weight, body mass index (BMI), blood pressure, glycated haemoglobin (HbA1c), fasting insulin, estimated glomerular filtration rate (eGFR), and albumin to creatinine ratio (ACR). A secondary objective was to determine whether compliance to the program had an effect on outcomes. In this retrospective chart review, we collected laboratory and anthropometric data from an electronic medical record system for patients (n = 122) at least 19 years of age, who attended at least 2 LCHF educational sessions between January 2018 and May 2020. Pre-post mean differences of outcome were analysed using paired sample t-tests. Independent sample t-tests examined the effect of compliance on the outcomes. Statistically significant reductions in weight (3.96 kg [P < 0.001]) and BMI (1.46 kg/m2 [P = 0.001]) were observed. Compared with patients who participated in ≤5 educational visits, patients who participated in >5 visits showed trends towards more clinically significant changes in weight, BMI, systolic blood pressure, diastolic blood pressure, HbA1c, eGFR, and ACR. Improvements in weight and BMI indicate the utility of providing LCHF health promotion interventions in primary care settings. Greater compliance to LCHF interventions results in greater improvement in laboratory and anthropometric outcomes, including HbA1c.


Spatial and Functional Distribution of MYBPC3 Pathogenic Variants and Clinical Outcomes in Patients With Hypertrophic Cardiomyopathy.
Pathogenic variants in MYBPC3, encoding cardiac MyBP-C (myosin binding protein C), are the most common cause of familial hypertrophic cardiomyopathy. A large number of unique MYBPC3 variants and relatively small genotyped hypertrophic cardiomyopathy cohorts have precluded detailed genotype-phenotype correlations. Patients with hypertrophic cardiomyopathy and MYBPC3 variants were identified from the Sarcomeric Human Cardiomyopathy Registry. Variant types and locations were analyzed, morphological severity was assessed, and time-event analysis was performed (composite clinical outcome of sudden death, class III/IV heart failure, left ventricular assist device/transplant, atrial fibrillation). For selected missense variants falling in enriched domains, myofilament localization and degradation rates were measured in vitro. Among 4756 genotyped patients with hypertrophic cardiomyopathy in Sarcomeric Human Cardiomyopathy Registry, 1316 patients were identified with adjudicated pathogenic truncating (N=234 unique variants, 1047 patients) or nontruncating (N=22 unique variants, 191 patients) variants in MYBPC3. Truncating variants were evenly dispersed throughout the gene, and hypertrophy severity and outcomes were not associated with variant location (grouped by 5'-3' quartiles or by founder variant subgroup). Nontruncating pathogenic variants clustered in the C3, C6, and C10 domains (18 of 22, 82%, P<0.001 versus Genome Aggregation Database common variants) and were associated with similar hypertrophy severity and adverse event rates as observed with truncating variants. MyBP-C with variants in the C3, C6, and C10 domains was expressed in rat ventricular myocytes. C10 mutant MyBP-C failed to incorporate into myofilaments and degradation rates were accelerated by ≈90%, while C3 and C6 mutant MyBP-C incorporated normally with degradation rate similar to wild-type. Truncating variants account for 91% of MYBPC3 pathogenic variants and cause similar clinical severity and outcomes regardless of location, consistent with locus-independent loss-of-function. Nontruncating MYBPC3 pathogenic variants are regionally clustered, and a subset also cause loss of function through failure of myofilament incorporation and rapid degradation. Cardiac morphology and clinical outcomes are similar in patients with truncating versus nontruncating variants.


A point cloud-based deep learning strategy for protein-ligand binding affinity prediction.
There is great interest to develop artificial intelligence-based protein-ligand binding affinity models due to their immense applications in drug discovery. In this paper, PointNet and PointTransformer, two pointwise multi-layer perceptrons have been applied for protein-ligand binding affinity prediction for the first time. Three-dimensional point clouds could be rapidly generated from PDBbind-2016 with 3772 and 11 327 individual point clouds derived from the refined or/and general sets, respectively. These point clouds (the refined or the extended set) were used to train PointNet or PointTransformer, resulting in protein-ligand binding affinity prediction models with Pearson correlation coefficients R = 0.795 or 0.833 from the extended data set, respectively, based on the CASF-2016 benchmark test. The analysis of parameters suggests that the two deep learning models were capable to learn many interactions between proteins and their ligands, and some key atoms for the interactions could be visualized. The protein-ligand interaction features learned by PointTransformer could be further adapted for the XGBoost-based machine learning algorithm, resulting in prediction models with an average Rp of 0.827, which is on par with state-of-the-art machine learning models. These results suggest that the point clouds derived from PDBbind data sets are useful to evaluate the performance of 3D point clouds-centered deep learning algorithms, which could learn atomic features of protein-ligand interactions from natural evolution or medicinal chemistry and thus have wide applications in chemistry and biology.


Further Chemical and Morphological Characterization of Chloroplast Membranes from a Chlorophyll b-less Mutant of Hordeum vulgare.
A comparative study of peptide composition and freeze-fracture morphology of chloroplast membranes from a chlorophyll b-less mutant and a normal barley plant (Hordeum vulgare L.) is reported in this work. Using a high resolution, discontinuous sodium dodecyl sulfate-acrylamide gel electrophoretic system, we show that the mutant chloroplast membranes not only completely lack the 25-kilodalton peak, which accounts for about 18% of the chloroplast membrane protein in the normal plant, but also exhibit gross reduction in other components at 27.5- and 20-kilodalton regions. Despite such extensive deletions in the peptide composition of the mutant chloroplast lamellae, no alteration could be detected in either density or size of the intramembranous particles, visualized by freeze-fracturing.


Low dose reconstruction algorithm for differential phase contrast imaging.
Differential phase contrast imaging computed tomography (DPCI-CT) is a novel x-ray inspection method to reconstruct the distribution of refraction index rather than the attenuation coefficient in weakly absorbing samples. In this paper, we propose an iterative reconstruction algorithm for DPCI-CT which benefits from the new compressed sensing theory. We first realize a differential algebraic reconstruction technique (DART) by discretizing the projection process of the differential phase contrast imaging into a linear partial derivative matrix. In this way the compressed sensing reconstruction problem of DPCI reconstruction can be transformed to a resolved problem in the transmission imaging CT. Our algorithm has the potential to reconstruct the refraction index distribution of the sample from highly undersampled projection data. Thus it can significantly reduce the dose and inspection time. The proposed algorithm has been validated by numerical simulations and actual experiments.


Regulating Oxygen Configuration in Hierarchically Porous Carbon Nanosheets for High-Rate and Durable Na+ Storage.
Surface oxygen functionalities (particularly C-O configuration) in carbon materials have negative influence on their electrical conductivity and Na+ storage performance. Herein, we propose a concept from surface chemistry to regulate the oxygen configuration in hierarchically porous carbon nanosheets (HPCNS). It is demonstrated that the C-O/C=O ratio in HPCNS reduces from 1.49 to 0.43 and its graphitization degree increases by increasing the carbonization temperature under a reduction atmosphere. Remarkably, such high graphitization degree and low C-O content of the HPCNS-800 are favorable for promoting its electron/ion transfer kinetics, thus endowing it with high-rate (323.6 mAh g-1 at 0.05 A g-1 and 138.5 mAh g-1 at 20.0 A g-1 ) and durable (96 % capacity retention over 5700 cycles at 10.0 A g-1 ) Na+ storage performance. This work permits the optimization of heteroatom configurations in carbon for superior Na+ storage.


Selectivity over coverage in de novo sequencing of IgGs.
Although incredibly diverse in specificity, millions of unique Immunoglobulin G (IgG) molecules in the human antibody repertoire share most of their amino acid sequence. These constant parts of IgG do not yield any useful information in attempts to sequence antibodies de novo. Therefore, methods focusing solely on the variable regions and providing unambiguous sequence reads are strongly advantageous. We report a mass spectrometry-based method that uses electron capture dissociation (ECD) to provide straightforward-to-read sequence ladders for the variable parts of both the light and heavy chains, with a preference for the functionally important CDR3. We optimized this method on the therapeutic antibody Trastuzumab and demonstrate its applicability on two monoclonal quartets of the four IgG subclasses, IgG1, IgG2, IgG3 and IgG4. The method is based on proteolytically separating the variable F(ab')2 part from the conserved Fc part, whereafter the F(ab')2 portions are mass-analyzed and fragmented by ECD. Pure ECD, without additional collisional activation, leads to straightforward-to-read sequence tags covering the CDR3 of both the light and heavy chains. Using molecular modelling and structural analysis, we discuss and explain this selective fragmentation behavior and describe how structural features of the different IgG subclasses lead to distinct fragmentation patterns. Overall, we foresee that pure ECD on F(ab')2 or Fab molecules can become a valuable tool for the de novo sequencing of serum antibodies.


Adaptive Synaptogenesis Constructs Neural Codes That Benefit Discrimination.
Intelligent organisms face a variety of tasks requiring the acquisition of expertise within a specific domain, including the ability to discriminate between a large number of similar patterns. From an energy-efficiency perspective, effective discrimination requires a prudent allocation of neural resources with more frequent patterns and their variants being represented with greater precision. In this work, we demonstrate a biologically plausible means of constructing a single-layer neural network that adaptively (i.e., without supervision) meets this criterion. Specifically, the adaptive algorithm includes synaptogenesis, synaptic shedding, and bi-directional synaptic weight modification to produce a network with outputs (i.e. neural codes) that represent input patterns proportional to the frequency of related patterns. In addition to pattern frequency, the correlational structure of the input environment also affects allocation of neural resources. The combined synaptic modification mechanisms provide an explanation of neuron allocation in the case of self-taught experts.


[Treatment of Hodgkin's malignant lymphoma in children and adolescents by immunomodulation with a dialysate of human leukocytes].
The authors assessed in a group of children with malignant lymphoma the effect of dialysate of human leucocytes on some immunological indicators. Assessment of T lymphocytes by the E rosette test before and after administration of a dialysate of human leucocytes did not reveal any significant changes in the number of T lymphocytes. Similarly the assessed number of NK cells in the peripheral blood stream was not markedly affected. The immunostimulating action was manifested by an increased activation of lymphocytes assessed by the nuclear test and the blastic transformation test. In lymphocytic sub-populations examined by means of monoclonal antibodies a rise of CD4+ and T lymphocytes was recorded.


Drug hypersensitivity in human immunodeficiency virus-infected patient: challenging diagnosis and management.
Human immunodeficiency virus (HIV)-infected patients present complex immunological alterations. Multiple drugs that usually prescribed for prevention or treatment of opportunistic infections and antiretroviral pose these patients a higher risk of developing drug hypersensitivity. All antiretroviral agents and drugs to treat opportunistic infections have been reported to cause drug hypersensitivity reactions. Allergic reactions with antiretroviral are not restricted to older agents, although newer drugs usually more tolerated. Cutaneous adverse drug reactions are the most common manifestation of drug hypersensitivity in HIV, typically manifesting as maculopapular rash with or without systemic symptoms in the presence or absence of internal organ involvement. The onset of an allergic reaction is usually delayed. Severe drug hypersensitity reactions as erythema multiforme, Stevens Johnson syndrome and toxic epidermal necrolysis develop more often in HIV-infected patients compared to other populations. Mild to moderate rash without systemic symptom or organ involvement usually do not need drug discontinuation. Appropriate diagnosis and management of drug hypersensitivity reactions are essential, especially in patients with very low CD4+ T-cell count and multiple opportunistic infections. Clinicians should aware of different half-life of each drug when decided to stop the drug. Knowledge of the metabolism, recognition of the risk factors, and the ability to suggest the probability of particular drug as causative are also important points. A step wise rechallenge test or desensitization with the offending drug might be a preferable action and more commonly used in managing drug hypersensitivity in HIV-infected patients. Desensitization protocols have been successfully done for several antiretroviral and opportunistic infection drugs.


Transient expression of luciferase reporter gene after lipofection in oyster (Crassostrea gigas) primary cell cultures.
Transient expression of the luciferase gene, under transcriptional control of several heterologous promoters, was obtained in heart primary cell cultures of the Pacific oyster, Crassostrea gigas. Drosophila heat shock protein 70 promoter (hsp70), cytomegalovirus, and simian virus early promoters, controlling the luciferase gene, were transfected into the cell cultures using liposomes. Two culture media were used to establish primary cell cultures and tested as transfection media. Parameters such as the quantity of DNA and the ratio of DNA to liposome were analyzed to define the best transfection conditions. In oysters, the Drosophila inducible hsp70 promoter behaved in a way similar to that observed in other animal species. Moreover, for this study, hsp70 was more efficient than the cytomegalovirus and simian virus promoters.


Temperature control design for a high-resolution gamma-ray tomography detector.
In this paper, a thermal control design for a high-resolution gamma-ray computed tomography detector is presented. It accounts for the generation of heat produced by active electronic components as well as heat transfer from external heat sources. The development and implementation of this feature were motivated by stringent requirements for measurement accuracy at thermal hydraulic test facilities, where ambient thermal conditions are constantly changing. As a first step, the thermal behavior of the existing tomography detector was analyzed, critical components were identified, and different approaches for heat removal were tested. Eventually, an improved thermal detector design was elaborated and a controlled active cooling system was implemented. Performance tests proved its effectiveness and accuracy improvement.


Histochemical localization of N-acetyl-galactosamine in the midgut Lutzomyia longipalpis (Diptera: Psychodidae).
The binding of lectins to the midgut of the female sand fly Lutzomyia longipalpis (Lutz & Neiva) was investigated using lectin-gold conjugates. Midguts from laboratory-reared flies provided fructose solution and/or blood fed on hamster were dissected at 6, 24, and 48 h and at 5 and 7 d after feeding. Before examination by transmission electron microscopy, each midgut was sectioned, incubated with lectins from four sources (Canavalia ensiformis [ConA], Helix pomata agglutinin [HPA], peanut agglutinin [PNA], and wheat germ agglutinin [WGA] ), then conjugated with colloidal gold. Only HPA, which is specific for N-acetyl-galactosamine (GalNAc), bound to the midgut. Binding sites were cytoplasmic secretory granules and microvilli throughout the length of the midgut epithelium. Binding occurred in sand flies fed fructose as well as in flies receiving a blood meal. The presence of GalNAc on the midgut microvilli of sand flies before, during, and after blood feeding indicates this amino-sugar is not altered by digestion. As a structural component, GalNAc may represent a terminal on a receptor molecule. The failure of the sand fly peritrophic matrix to bind WGA by N-acetylglucosamine may be caused by the complex composition of the membrane, which renders N-glycan inaccessible to the lectin-gold conjugate.


Decellularized Avian Cartilage, a Promising Alternative for Human Cartilage Tissue Regeneration.
Articular cartilage defects, and subsequent degeneration, are prevalent and account for the poor quality of life of most elderly persons; they are also one of the main predisposing factors to osteoarthritis. Articular cartilage is an avascular tissue and, thus, has limited capacity for healing and self-repair. Damage to the articular cartilage by trauma or pathological causes is irreversible. Many approaches to repair cartilage have been attempted with some potential; however, there is no consensus on any ideal therapy. Tissue engineering holds promise as an approach to regenerate damaged cartilage. Since cell adhesion is a critical step in tissue engineering, providing a 3D microenvironment that recapitulates the cartilage tissue is vital to inducing cartilage regeneration. Decellularized materials have emerged as promising scaffolds for tissue engineering, since this procedure produces scaffolds from native tissues that possess structural and chemical natures that are mimetic of the extracellular matrix (ECM) of the native tissue. In this work, we present, for the first time, a study of decellularized scaffolds, produced from avian articular cartilage (extracted from Gallus Gallus domesticus), reseeded with human chondrocytes, and we demonstrate for the first time that human chondrocytes survived, proliferated and interacted with the scaffolds. Morphological studies of the decellularized scaffolds revealed an interconnected, porous architecture, ideal for cell growth. Mechanical characterization showed that the decellularized scaffolds registered stiffness comparable to the native cartilage tissues. Cell growth inhibition and immunocytochemical analyses showed that the decellularized scaffolds are suitable for cartilage regeneration.


Whole-body vibration training induces hypertrophy of the human patellar tendon.
Animal studies suggest that regular exposure to whole-body vibration (WBV) induces an anabolic response in bone and tendon. However, the effects of this type of intervention on human tendon properties and its influence on the muscle-tendon unit function have never been investigated. The aim of this study was to investigate the effect of WBV training on the patellar tendon mechanical, material and morphological properties, the quadriceps muscle architecture and the knee extension torque-angle relationship. Fifty-five subjects were randomized into either a vibration, an active control, or an inactive control group. The active control subjects performed isometric squats on a vibration platform without vibration. Muscle and tendon properties were measured using ultrasonography and dynamometry. Vibration training induced an increase in proximal (6.3%) and mean (3.8%) tendon cross-sectional area, without any appreciable change in tendon stiffness and modulus or in muscle architectural parameters. Isometric torque at a knee angle of 90° increased in active controls (6.7%) only and the torque-angle relation remained globally unchanged in all groups. The present protocol did not appreciably alter knee extension torque production or the musculo-tendinous parameters underpinning this function. Nonetheless, this study shows for the first time that WBV elicits tendon hypertrophy in humans.