Pedicle screw placement in the thoracic spine: a comparison study of computer-assisted navigation and conventional techniques.
The technique of computer-assisted pedicle screw installation and its clinical benefit as compared with conventional pedicle screw installation was evaluated. Twenty-two patients had thoracic screw insertion under 3-dimentional computer-assisted navigation (92 screws) and 20 patients under conventional fluoroscopic control (84 screws). The 2 groups were compared for accuracy of screw placement, screw insertion time by postoperative thin-cut computed tomography scans, and statistical analysis. The cortical perforations were graded by 2-mm increments. In the computer group, 88 (95.65%) were grade I (good), 4 (4.35%) were grade II (<2 mm), and 0 were grade III (>2 mm) violations. There were 4 cortical violations (3.57%). In the conventional group, there were 14 cortical violations (16.67%), 70 (83.33%) were grade I (good), 11 (13.1%) were grade II (<2 mm), and 3 (3.57%) were grade III (>2 mm) violations (P<.001). The number (19.57%) of upper thoracic pedicle screws (T1-T4) inserted under 3-dimensional computer-assisted navigation was significantly higher than that (3.57%) by conventional fluoroscopic control (P<.001). Average screw insertion time in the conventional group was more than in the computer group (P<.001). Three-dimensional computer-assisted navigation pedicle screw placement can increase accuracy, reduce surgical time, and be performed safely and effectively at all levels of the thoracic spine, particularly the upper thoracic spine.


Renal artery stenosis in association with congenital anomalies of the kidney and urinary tract.
To describe 8 cases of renal artery stenosis (RAS) in children with congenital anomalies of the renal tract. We conducted a retrospective chart review of 78 children with RAS who were followed up at Great Ormond Street Hospital, London, United Kingdom between 2003 and 2012. We used an interventional radiology database to identify all patients who had RAS confirmed by digital subtraction angiography and examined all cases of congenital anomaly of the renal tract that had been diagnosed during childhood. We documented the following renal anomalies: multicystic dysplastic kidney (n=2), renal hypoplasia (n=1), congenital solitary kidney with hydronephrosis (n=1), and unilateral vesicoureteric reflux with poorly functioning kidneys (n=2). The anomaly was unknown in 2 cases. Seven children had unilateral nephrectomy at a median age of 2.5 years (range, 0.4-10 years) for various urological abnormalities. All children were confirmed to have RAS after presentation with hypertension at a median age of 10 (3.5-16.2) years. Angioplasty was performed in 7 children, of which 6 achieved control of their blood pressure on reduced medications. We highlight the association between RAS and other renal anomalies, which indicates that they could share a common genetic background.


Expenditures for ambulatory episodes of care: the Michigan Medicaid experience.
It is widely accepted that ambulatory care furnished in hospital outpatient department (OPD) settings is more costly than similar care furnished in office settings, but few researchers have explored whether practice patterns differ between the two settings. Differences in practice patterns may account for differences in the overall cost of care associated with these settings. Diagnosis-specific episodes of care were used to compare the costs of treating disease episodes in OPDs and offices. The findings suggest that OPD care is more costly not only because of price, but also because continuity of care is less common and the likelihood of hospital admission is substantially greater.


The fate of the Arctic seaweed Fucus distichus under climate change: an ecological niche modeling approach.
Rising temperatures are predicted to melt all perennial ice cover in the Arctic by the end of this century, thus opening up suitable habitat for temperate and subarctic species. Canopy-forming seaweeds provide an ideal system to predict the potential impact of climate-change on rocky-shore ecosystems, given their direct dependence on temperature and their key role in the ecological system. Our primary objective was to predict the climate-change induced range-shift of Fucus distichus, the dominant canopy-forming macroalga in the Arctic and subarctic rocky intertidal. More specifically, we asked: which Arctic/subarctic and cold-temperate shores of the northern hemisphere will display the greatest distributional change of F. distichus and how will this affect niche overlap with seaweeds from temperate regions? We used the program MAXENT to develop correlative ecological niche models with dominant range-limiting factors and 169 occurrence records. Using three climate-change scenarios, we projected habitat suitability of F. distichus - and its niche overlap with three dominant temperate macroalgae - until year 2200. Maximum sea surface temperature was identified as the most important factor in limiting the fundamental niche of F. distichus. Rising temperatures were predicted to have low impact on the species' southern distribution limits, but to shift its northern distribution limits poleward into the high Arctic. In cold-temperate to subarctic regions, new areas of niche overlap were predicted between F. distichus and intertidal macroalgae immigrating from the south. While climate-change threatens intertidal seaweeds in warm-temperate regions, seaweed meadows will likely flourish in the Arctic intertidal. Although this enriches biodiversity and opens up new seaweed-harvesting grounds, it will also trigger unpredictable changes in the structure and functioning of the Arctic intertidal ecosystem.


Oestradiol negative feedback inhibition on LH secretion during lactation is prolonged in adolescent primiparous rhesus monkeys.
Lactational infertility in rhesus monkeys is significantly prolonged in adolescent primiparous compared with adult multiparous mothers. In order to determine if this longer period of infertility for young mothers is the result of a greater sensitivity to nursing-induced inhibition of LH release either by enhanced oestradiol negative feedback or a direct non-gonadally mediated suppression, the effects of periodic administration of oestradiol on serum LH concentrations in nursing ovariectomized adolescent primiparous (Prp; n = 5) and adult multiparous (Mlt; n = 7) mothers was assessed. Females were treated every 5-6 weeks with a 21-day time-release capsule of oestradiol which produced serum concentrations of approximately 250, 90 and 45 pmol/l by +6, +13 and +20 days after treatment. Thus, the design permitted assessment of LH and prolactin concentrations under a regime of 21 days of decreasing oestradiol levels followed by 2-3 weeks of no oestradiol treatment. Females were studied from week 3 to week 42 post partum and oestradiol treatment occurred during weeks 5, 11, 21, 26, 31, 36 and 41. Behavioural observations indicated that the amount of time mothers nursed their offspring decreased in a similar fashion throughout the lactational period for both Prp and Mlt females. LH concentrations under the 'no oestradiol' conditions progressively increased throughout lactation reaching maximum levels by week 36 post partum in a similar manner for both Prp and Mlt mothers. These data suggest that differences in fertility between adolescent and adult nursing mothers observed previously cannot be attributed to a difference in a direct non-gonadally-mediated affect on LH. With respect to oestradiol negative feedback inhibition of LH, oestradiol treatment effectively suppressed serum LH concentrations at all points during lactation up to week 31, at which time LH concentrations were maximally suppressed in both Prp and Mlt mothers at +6 days after treatment but by day +13 LH values were significantly higher in Mlt females. After oestradiol treatment during week 36, LH values were again maximally suppressed on day +6 in Prp females but not in Mlt females. However, the response of serum LH after oestradiol treatment during week 41 was similar between Prp and Mlt females at all sampling points.(ABSTRACT TRUNCATED AT 400 WORDS)


Videothoracoscopic treatment of a rare complication of nasojejunal tube insertion.
Intubation of the tracheobronchial tree is the most common type of malposition during the placement of narrow-bore enternal tubes. In addition to other treatment components in a 65-year-old female, nasojejunal feeding was started to treat her for severe acute pancreatitis. After the placement of the narrow-bore feeding tube, she developed dyspnea and huskiness. On auscultation and X-ray investigation, the right pneumothorax was detected and the tube was found in the chest cavity. The diagnosis was confirmed by bronchoscopy. Videothoracoscopic resection and closure of the lacerated lung, using a tube thoracostomy, were performed. The patient recovered after postoperative conservative treatment for her pancreatitis. Pneumothorax and laceration of the lung-caused by the malposition of narrow-bore enternal tube-can be successfully treated by applying videothoracoscopy.


Acupuncture modulates the frequency-specific functional connectivity density in primary dysmenorrhea.
The study aimed to investigate how acupuncture modulates brain activities across multiple frequency bands to achieve therapeutic effects in PDM. A total of 47 patients with PDM were randomly assigned to the verum acupuncture group and sham acupuncture group with three menstrual cycles of the acupuncture course. The fMRI scans, visual analog scale (VAS) scores, and other clinical evaluations were assessed at baseline and after three menstrual-cycles treatments. The global functional connectivity density (gFCD) analyses were performed between the pre-and post-acupuncture course of two groups at full-low frequency band, Slow-3 band, Slow-4 band, and Slow-5 band. After the acupuncture treatments, the patients with PDM in the verum acupuncture group showed significantly decreased VAS scores (p < 0.05). The frequency-dependent gFCD alternations were found in the verum acupuncture group, altered regions including DLPFC, somatosensory cortex, anterior cingulate cortex (ACC), middle cingulate cortex (MCC), precuneus, hippocampus, and insula. The sham acupuncture modulated regions including angular gyrus, inferior frontal gyrus, and hippocampus. The gFCD alternation in DLPFC at the Slow-5 band was negatively in the patients with PDM following verum acupuncture, and S2 at the Slow-4 band was positively correlated with VAS scores. These findings supported that verum acupuncture could effectively modulate frequency-dependent gFCD in PDM by influencing abnormal DLPFC at Slow-5 band and hippocampus at the Slow-3 band. The outcome of this study may shed light on enhancing the potency of acupuncture in clinical practice.


Perinatal Outcome of Pregnant Women with RhD Sensitization: A Five-Year Cross-Sectional Study at a Tertiary Care Hospital in Ethiopia.
Isoimmunization is a process of immunizing an antigen-negative pregnant individual with a paternally derived fetal antigen. Although the Rh systems contain many antigen subtypes (D, C, c, E, e), the RhD antigen is highly immunogenic. This research aimed to investigate the perinatal Outcome of pregnant women with RhD sensitization at St. Paul's Hospital Millennium Medical College (SPHMMC), Ethiopia. A facility-based retrospective cross-sectional study was conducted on 98 pregnant women with RhD alloimmunization at SPHMMC from September 11, 2016, to September 10, 2021. SPSS 26 was used for data analysis. Descriptive statistics were utilized to assess the perinatal outcome of pregnant women with RhD alloimmunization. Fisher's exact test was used to determine which association, and a P value <0.05 was considered statistically significant. From the 98 pregnancies (06 - hydropic, 92 - non-hydropic) at high risk for fetal anemia, 45.9% of cases had MCA-PSV above 1.5MoM. Among these, 21.42% of all fetuses received an intrauterine transfusion. Forty-three IUTs were performed in 21 fetuses. The median number of transfusions per fetus was two. About 52.4% of the transfused fetuses had severe anemia, and 28.6% had moderate anemia. Prediction of MCA PSV ≥1.5MOM in diagnosing moderate-severe anemia in pregnant women with RhD sensitization 81%. General neonatal survival of alloimmunizations was 93.8%, 90.5% with IUT, 50% with hydrops fetalis, and 96.7% without hydrops. This research provides evidence that MCA PSV ≥1.5MoM is modest predictor of moderate-severe anemia in untransfused fetuses. This study was a step toward the development of more extensive and multicenter studies on the Perinatal Outcome of pregnant women with RhD sensitization in Ethiopia. Extra studies are needed to evaluate strategies for estimates of fetal anemia after blood transfusion as a result of the absence of information on the IUT database.


Complete remission of a diffuse pontine glioma.
A patient is described in whom a large diffuse glioma of the pons extending into the midbrain was diagnosed at the age of 2 years. Biopsy showed a fibrillary astrocytoma. After shunting of a hydrocephalus, the clinical symptoms abated without conventional therapy. Repeated MRI studies showed a continuous decrease of the tumour which was no longer visible when the patient was 6.6 years old. In reviews on spontaneous remissions of oncologic disorders we were unable to find a case of a biologically benign brain stem tumour. There is one isolated report on a similar case, though without histologic documentation.


Pretransplant Thyroid Findings in Patients With End-Stage Renal Disease.
Patients with end-stage renal diseases can display abnormal thyroid gland function due to altered hormone excretion and transport. In this study, we aimed to evaluate the incidence of thyroid diseases by fine-needle aspiration cytology in kidney transplant candidates and to estimate the outcomes of these patients. We reevaluated thyroid fineneedle aspiration biopsies, which were performed between January 2000 and December 2015, of 181 candidates for kidney transplant. Patient demographics and thyroid ultrasonography and biopsy findings were recorded. The fine-needle aspiration biopsy findings of 181 patients were as follows: 162 were benign 5 were thyroiditis, 9 were atypia of undetermined significance/follicular lesion of undetermined significance, and 5 were malignant. Only 13 patients (7.1%) underwent thyroid operation after fine-needle aspiration, with 5 of these patients receiving a benign diagnosis, 3 receiving diagnosis of atypia of undetermined significance/follicular lesion of undetermined significance, and 5 patients showing malignancy. In the 5 patients with benign cytology, histopathologic findings were also benign. In the 3 patients with atypia of undetermined significance/follicular lesion of undetermined significance, the final diagnosis was adenomatous hyperplasia. Finally, in the 5 patients (2.8%) showing malignancy, results after fine-needle aspiration showed papillary thyroid carcinoma. In the 5 patients with papillary thyroid carcinoma, 4 underwent renal transplant. Survival of these 4 patients was 92 ± 42 months without tumor recurrence. Fine-needle aspiration is a useful diagnostic modality in evaluation of thyroid nodules in kidney transplant candidates. Early detection and treatment of thyroid nodules are essential to decrease the morbidity and mortality of these patients.


An in-the-groove view of DNA structures in complexes with proteins.
DNA structures bound to transcription factors are studied by using the crystal coordinates of complexes. Structural characteristics which are found at the sites where a protein secondary structure, an alpha-helix or a beta-sheet binds, can be understood in terms of fitting of the concave surface of the DNA major groove and the convex surface of the protein secondary structure; the former changes, becoming narrower or wider so that it fits the latter. An alpha-helix, independent of which groove it binds to, tends to produce a narrow major groove and a wide minor groove. When the major groove becomes narrower, the DNA helix axis bends around the major groove. Bending of DNA, which is overall structural change, is achieved by changes in local parameters (in particular, the roll parameter) so that an intermediate feature, the groove, fits the protein surface.


Acute and sub-acute oral toxicity of ethanol extract of Cassia fistula fruit in male rats.
The plant Cassia fistula L. (Caesalpiniaceae) is traditionally used to treat heart diseases, abdominal pain and fever. The present study was aimed to investigate the toxic effects acute and sub-acute administration of ethanol extract of C. fistula fruit (CFE) in male Wistar rats. In acute toxicity, the effects of a single oral dose (1000, 3000 and 5000 mg/kg) of CFE have been determined. Animal behaviour and mortality were determined for up to 14 days. In sub-acute study, the effects of CFE in daily single oral administration at the doses of 250, 500 and 1000 mg/kg during 28 days were determined. The blood haematological and biochemical parameters, as well as the histopathological examination of the liver, heart and kidneys were studied. In acute study, a single administration of the CFE up to a dose of 5000 mg/kg did not induce mortality. Thus, the LD50 of the CFE has been estimated higher than 5000 mg/kg. In sub-acute toxicity study, administration of CFE at the doses of 250, 500 and 1000 mg/kg to rats did not induce mortality. No significant differences were found in relative organ weight, and haematological and biochemical analyses in treated groups compared to control group. No noticeable histological changes were observed in organs of CFE-treated rats compared to controls. These results have shown that oral administration of C. fistula fruit did not produce any significant toxic effect in male rats. Hence, C. fistula fruit could be regarded as a safe natural product for therapeutic use.


Seroprevalence of Hepatitis E Virus in Moose (Alces alces), Reindeer (Rangifer tarandus), Red Deer (Cervus elaphus), Roe Deer (Capreolus capreolus), and Muskoxen (Ovibos moschatus) from Norway.
Hepatitis E virus (HEV), a major cause of viral hepatitis worldwide, is considered an emerging foodborne zoonosis in Europe. Pigs (Sus scrofa domestica) and wild boars (S. scrofa) are recognized as important HEV reservoirs. Additionally, HEV infection and exposure have been described in cervids. In Norway, HEV has been identified in pigs and humans; however, little is known regarding its presence in wild ungulates in the country. We used a species-independent double-antigen sandwich ELISA to detect antibodies against HEV in the sera of 715 wild ungulates from Norway, including 164 moose (Alces alces), 186 wild Eurasian tundra reindeer (Rangifer tarandus tarandus), 177 red deer (Cervus elaphus), 86 European roe deer (Capreolus capreolus), and 102 muskoxen (Ovibos moschatus). The overall seroprevalence was 12.3% (88/715). Wild reindeer had the highest seropositivity (23.1%, 43/186), followed by moose (19.5%, 32/164), muskoxen (5.9%, 6/102), and red deer (4%, 7/177). All roe deer were negative. According to our results, HEV is circulating in wild ungulates in Norway. The high seroprevalence observed in wild reindeer and moose indicates that these species may be potential reservoirs of HEV. To the authors' knowledge, this is the first report of HEV exposure in reindeer from Europe and in muskoxen worldwide.


The Development and Preliminary Psychometric Evaluation of the Theory of Mind Inventory: Self Report-Adult (ToMI:SR-Adult).
This study describes the development and psychometric evaluation of a new self-report measure of social cognition: the Theory of Mind Inventory:Self-report-Adult (ToMI:SR-Adult). Adults with autism (or a suspicion of autism; n = 111) and typically developing adults (n = 109) completed a demographic questionnaire and the ToMI:SR-Adult online. Both quantitative and qualitative self-reports of one's own theory of mind functioning were collected. The ToMI:SR-Adult performed well under all examinations of reliability and validity (internal consistency, accuracy of classification, contrasting-groups). The qualitative data confirmed impressions of validity and revealed that the adults in our sample had high levels of self-insight regarding their own theory of mind. The ToMI:SR-Adult is offered as a promising research and clinical tool for the assessment of social cognition in adults.


Lower airway clinical outcome measures for use in primary ciliary dyskinesia research: a scoping review.
Disease-specific, well-defined and validated clinical outcome measures are essential in designing research studies. Poorly defined outcome measures hamper pooling of data and comparisons between studies. We aimed to identify and describe pulmonary outcome measures that could be used for follow-up of patients with primary ciliary dyskinesia (PCD). We conducted a scoping review by systematically searching MEDLINE, Embase and the Cochrane Database of Systematic Reviews online databases for studies published from 1996 to 2020 that included ≥10 PCD adult and/or paediatric patients. We included 102 studies (7289 patients). 83 studies reported on spirometry, 11 on body plethysmography, 15 on multiple-breath washout, 36 on high-resolution computed tomography (HRCT), 57 on microbiology and 17 on health-related quality of life. Measurement and reporting of outcomes varied considerably between studies (e.g. different scoring systems for chest HRCT scans). Additionally, definitions of outcome measures varied (e.g. definition of chronic colonisation by respiratory pathogen), impeding direct comparisons of results. This review highlights the need for standardisation of measurements and reporting of outcome measures to enable comparisons between studies. Defining a core set of clinical outcome measures is necessary to ensure reproducibility of results and for use in future trials and prospective cohorts.


Parental history of hypertension, sodium loading, and cardiovascular response to stress.
Parental history of hypertension, dietary sodium, and psychological stress have all been implicated in the development of essential hypertension and may interact in elevating disease risk. The mechanism by which this might occur is unclear, but it may be related to changes in the peripheral vasculature. The present study examined the effects of parental history and sodium on cardiovascular responses to an extended stressor. Eighteen normotensive offspring of hypertensives and 18 offspring of normotensives were exposed to a 1-hour shock-avoidance video-game procedure after 14 days of sodium loading (10 1-g tablets/day) and again after 14 days of placebo tablets. Order of sessions was counterbalanced between subjects in a double-blind design. In offspring of hypertensives, sodium loading elevated total peripheral resistance and norepinephrine responses to stress relative to placebo conditions and compared with offspring of normotensives. These increases were accompanied by decreases in stroke volume and cardiac output, which may explain the absence of familial differences in blood pressure responses to stress and sodium. Sodium loading had no effect on offspring of normotensives. The elevated resistance in offspring of hypertensives may suggest the initiation of pathological processes. The absence of sodium effects on resting values indicates the importance of research under conditions of stress.


Searching for health equity: validation of a search filter for ethnic and socioeconomic inequalities in transport.
Efforts to improve health equity should be informed by the best available evidence. However, equity-related research is inconsistently indexed, and uses a variety of terms to describe key concepts, making it difficult to reliably identify all relevant studies. We report the development and validation of a search strategy for studies investigating whether the effects of interventions differ by ethnicity or socio-economic status, using the field of transport and health as an example. Adapting previously described methods, we followed four steps: generation of a test set of eligible studies, search strategy development, search strategy validation, and documentation. Drawing from 12 systematic reviews, supplemented by additional studies identified by experts and colleagues, we identified a test set of 11 studies that met our eligibility criteria. We assigned five studies to a development set, which we used to develop and refine our search strategy. We assigned the remaining six studies to a validation set, against which we tested our final search strategy. The final search strategy identified all studies in both validation and development sets. The validated search strategy derived in this study facilitates the conduct of systematic reviews and other literature searches investigating whether the effects of interventions differ by ethnicity or socio-economic status and may be further developed in future for other equity-focused searches and reviews.


Sternoclavicular joint infection: a case report.
Infection of the sternoclavicular joint (SJI) is a rare problem accounting for approximately 1 % of cases of septic arthritis. Patients typically present with symptoms of localized pain lasting a period of several weeks with or without systemic signs of fever and chills. Confirmation is made by aspirating the joint, and broad spectrum antibiotics should be tailored to treat the identified organisms. SJI can be treated conservatively with intravenous antibiotics and repeat imaging, but surgical intervention is required if patients present with an abscess, osteomyelitis or mediastinitis.


Hypopyon following laser iridotomy.
Two patients who had laser iridotomy performed for pupillary block glaucoma developed hypopyon following surgery. One case had iris bombé with rubeosis iridis, and the other had chronic angle closure glaucoma. Factors contributing to inflammation and possible hypopyon following laser iridotomy are discussed.


Is positive mental health and the absence of mental illness the same? Factors associated with flourishing and the absence of depressive symptoms in postpartum women.
Exploring a wide range of factors associated with flourishing and with the absence of depressive symptoms among postpartum women. A sample of 661 postpartum women completed a set of questionnaires assessing sociodemographic and infant-related data, flourishing, psychological flexibility, self-compassion, resilience, and maternal confidence. Younger infant age, higher levels of maternal confidence, and resilience increased the likelihood of flourishing. In turn, higher income, fewer problems with an infant's sleep, perceiving an infant's temperament as easy, and higher psychological flexibility increased the likelihood of not having depressive symptoms. Appraising the support received by others as good and having higher self-compassion increased the likelihood of both outcomes. Our results support positive mental health and mental illness being related but distinct dimensions. Promoting positive mental health in the postpartum period should be an additional goal in public health care as it may efficiently complement the prevention of psychopathology.


Low measuring temperature induced artifactual increase in chlorophyll a fluorescence.
Measurement of in vivo chlorophyll a fluorescence at temperatures lower than 20 degrees C can cause an artifactual, nonphotochemically related overestimation of variable fluorescence leading to the calculation of negative values for the nonphotochemical quenching parameter and an underestimation of the photochemical quenching parameter. This artifact is observed only upon exposure of the leaf sample to actinic light. We suggest that a temperature differential between the fiber-optic probe and the leaf sample results in the deposition of water vapor on the probe that distorts the light path such that an increased modulated fluorescence signal is observed. This artifact is eradicated by ensuring that the end of the fiber-optic probe is kept free of condensation.


Role of endoscopic ultrasound guided fine needle aspiration/biopsy in the evaluation of intra-abdominal lymphadenopathy due to tuberculosis.
Intra-abdominal lymphadenopathy due to tuberculosis (TB) poses a diagnostic challenge due to difficulty in tissue acquisition. Although endoscopic ultrasound guided fine needle aspiration/biopsy (EUS-FNA/B) has shown promise in the evaluation of mediastinal lymph nodes, its role in the evaluation of intra-abdominal lymphadenopathy is not clear. To assess the role of EUS-FNA/B in the evaluation of intra-abdominal lymphadenopathy due to TB. This was a retrospective study where patients with intra-abdominal lymphadenopathy who underwent evaluation with EUS-FNA/B were included. TB was diagnosed if the patient had any one of the following: (1) Positive acid fast bacilli (AFB) stain/TB GeneXpert/TB-polymerase chain reaction/AFB culture of tissue sample; and (2) Positive Mantoux test and response to anti-tubercular therapy. EUS-FNA reports, clinical reports and imaging characteristics of patients were recorded for a detailed analysis of patients with TB. A total of 149 patients underwent an EUS-FNA/B from lymph nodes (mean age 51 ± 17 years, M:F = 1.2). Benign inflammatory reactive changes were seen in 45 patients (30.2%), while 54 patients (36.2%) showed granulomatous inflammation with/without caseation. Among these, 51 patients (94.4%) were confirmed to have TB as per pre-defined criteria. Patients with TB were more likely to have hypoechoic and matted nodes [40 patients (67.7%)]. EUS-FNA/B was found to have a sensitivity and specificity of 86% and 93% respectively, with a diagnostic accuracy of 88% in the evaluation of intra-abdominal lymphadenopathy due to TB. EUS-FNA/B has a high diagnostic yield with a good sensitivity and specificity in the evaluation of intra-abdominal lymphadenopathy due to TB. However, the validity of these findings in populations with low prevalence of TB needs further evaluation.


Effect of interface conditions between ultrahigh molecular weight polyethylene and polymethyl methacrylate bone cement on the mechanical behaviour of total shoulder arthroplasty.
The aim of this study was to investigate the effect of the interface condition between polymethyl methacrylate (PMMA) bone cement and the ultrahigh molecular weight (UHMWPE) glenoid component on cement stresses and glenoid component tilting in a finite element (FE) model. The background of this research is that most FE models assume bonding between the PMMA bone cement and the UHMWPE component, although it is very doubtful that this bonding is present. An FE model of a cemented glenoid component was developed and a joint compression force and subluxation force of 725 and 350 N respectively were applied. The maximal principal stresses in the cement layer ranged between 21.30 and 32.18 MPa. Glenoid component tilting ranged between 0.943 degrees and 0.513 degrees. It was found that the interface condition has a large effect on the maximal principal stresses and glenoid component tilting. Whether adhesion between the UHMWPE component and PMMA bone cement occurs is unknown beforehand and, as a result, design validation using the FE technique should be carried out both by using contact elements in combination with a coefficient of friction as well as by a full bonding at this interface.


A low-temperature-responsive gene from barley encodes a protein with single-stranded nucleic acid-binding activity which is phosphorylated in vitro.
A low-temperature-responsive gene, blt 801, isolated from a winter barley (Hordeum vulgare L.) cDNA library prepared from leaf meristematic tissue, was sequenced. The deduced amino acid sequence predicts a glycine-rich RNA-binding protein (GR-RNP) which was homology to stress-responsive GR-RNPs from several other plant species. BLT 801 is a two-domain protein, the amino-terminal domain comprises a consensus RNA-binding domain similar to that found in many eukaryotic genes and the carboxy-terminal domain is extremely glycine-rich (68.5% glycine). Blt 801 mRNA also accumulates in response to the phytohormone abscisic acid. The protein encoded by blt 801 has been produced as a recombinant fusion protein using a bacterial expression vector. The fusion protein, a chimaera of glutathione S-transferase and BLT 801, has been used in studies to determine nucleic acid binding and other characteristics. Binding studies with single-stranded nucleic acids show that BLT 801 has affinity for homoribopolymers G, A and U but not C, it also binds to single-stranded DNA and selects RNA molecules containing open loop structures enriched in adenine but low in cytosine. Blt 801 has a consensus motif for phosphorylation by cAMP protein kinase (PKA) at the junction between the two domains which can be phosphorylated by PKA in vitro and which, by analogy to animal studies, may have significance for controlling enzyme function.


Autosomal recessive woolly hair with hypotrichosis caused by a novel homozygous mutation in the P2RY5 gene.
During the last decade, several causative genes for hereditary hair diseases have been identified, which have disclosed the molecular mechanisms involved in hair follicle morphogenesis and cycling. We and others recently reported that mutations in the P2RY5 gene, encoding an orphan G protein-coupled receptor, underlie autosomal recessive woolly hair (WH)/hypotrichosis. Although these findings clearly reveal the involvement of P2RY5 mutations in hereditary hair diseases, the clinical manifestations of P2RY5 mutations have not completely been elucidated because of limited information to date. In this study, we ascertained a consanguineous family of Iranian origin with an affected girl showing sparse and hypopigmented scalp hair. She exhibited the WH phenotype with normal hair density at birth, but progressed with age to develop hypotrichosis. Direct sequencing analysis resulted in the identification of a novel homozygous mutation in the P2RY5 gene of the patient, which results in a non-conservative amino acid change, G146R, at the protein level. Our findings extend the mutation spectrum of P2RY5 mutations, and further support a crucial role of P2Y5 in hair growth in humans.


Matrix-bound sixth Ig-like domain of cell adhesion molecule L1 acts as an angiogenic factor by ligating alphavbeta3-integrin and activating VEGF-R2.
Angiogenic signals can be matrix attached or freely diffusible. Here, the sixth Ig-like domain of L1 (L1Ig6), a ligand for alphavbeta3-integrin, was investigated. This domain was expressed as a fusion protein having a substrate sequence for factor XIII to enable covalent binding into three-dimensional fibrin matrices. Matrix-bound L1Ig6 induced endothelial cell (EC) process extension in vitro, which was associated with ligation and phosphorylation of alphavbeta3-integrin. VEGF-R2 and alphavbeta3 were observed to co-associate after stimulation with either L1Ig6 or VEGF-A165, whereas no co-association with bFGF-R was observed. Furthermore, VEGF-R2 was tyrosine phosphorylated after stimulation with L1Ig6, even in the absence of exogenous VEGF-A165, indicating close cooperation between VEGF-R2 and alphavbeta3. Angiogenesis was investigated in vivo by stimulating chicken chorioallantoic membranes (CAMs) with L1Ig6-modified matrices with or without co-incorporation of VEGF-A165 or bFGF. Matrix-immobilized L1Ig6 induced angiogenesis to a similar degree as VEGF-A165; co-stimulation with bFGF increased vascular branching, whereas VEGF-A165 did not. Matrix-immobilized L1Ig6 induced up-regulation of alphav in CAMs by a similar degree as stimulation with VEGF-A165, and this up-regulation was increased further by co-stimulation with matrix-bound L1Ig6 and VEGF-A165. alpha5 and beta1 levels were not increased. The similarity of action of matrix-bound L1Ig6 and soluble VEGF-A165 indicate a close link between specific ligation of alphavbeta3-integrin and VEGF-R2 and suggest the possible use of matrix-bound L1Ig6 in local therapeutic angiogenesis.


Cell-mediated targeting drugs delivery systems.
Drug delivery systems have shown tremendous promise to improve the diagnostic and therapeutic effects of drugs due to their special property. Targeting tissue damage, tumors, or drugs with limited toxicity at the site of infection is the goal of successful pharmaceuticals. Targeted drug delivery has become significantly important in enhancing the pharmaceutical effects of drugs and reducing their side effects of therapeutics in the treatment of various disease conditions. Unfortunately, clinical translation of these targeted drug delivery system mechanisms faces many challenges. At present, only a few targeted drug delivery systems can achieve high targeting efficiency after intravenous injection, even though numerous surface markers and targeting approaches have been developed. Thus, cell-mediated drug-delivery targeting systems have received considerable attention for their enhanced therapeutic specificity and efficacy in the treatment of the disease. This review highlights the recent advances in the design of the different types of cells that have been explored for cell-mediated drug delivery and targeting mechanisms. A better understanding of cell biology orientation and a new generation of delivery strategies that utilize these endogenous approaches are expected to provide better solutions for specific site delivery and further facilitate clinical translation.


Violent self-harm in schizophrenia.
Patients with schizophrenia have a substantial lifetime suicide risk, especially by violent means. Little published work exists on self-harm (SH) in this population. The goal of this study was to examine whether patients with schizophrenia were also more likely to self-harm in a violent manner. A retrospective analysis performed on method, motive, and suicidal intent in patients with schizophrenia (n = 50) and adjustment reaction (n = 138) who presented with SH over a 3-year period found that there was no significant difference between the two groups in terms of violence of method or suicidal intent. Presence of positive symptoms of schizophrenia was not significantly associated with use of a violent method. This study suggests that the expected pattern of violent SH in schizophrenia is inaccurate and for the majority the acts are of a similar nature to those seen in adjustment reactions.


A survey of the risk of zoonoses for veterinarians.
The objectives of this study were to identify factors associated with zoonotic infections in veterinarians, the incidence of physician consultation and treatment and the incidence of diagnostic and treatment errors. Veterinarians in any area of practice were solicited to participate in an online survey through an invitation letter sent to the Oregon Veterinary Medical Association. Proportions of respondents to various factors were analyzed for differences among gender, age, time since graduation and type of practice in which they worked. In all, 216 complete responses were received. In all, 13.9% of respondents had never been vaccinated against rabies, and 20.8% had been exposed to suspect rabid animals, mostly (64.4%) a single time. Other zoonoses were reported by 47.2% of respondents: mostly diseases transmitted via contact (57.4%) especially ringworm, followed by those with oral transmission (21.7%). Most zoonotic infections were reportedly acquired by young veterinarians working in primary care veterinary practice. Cats were the species most commonly reported as the animal source of a zoonotic infection. Veterinarians likely self-diagnosed zoonotic diseases, especially those transmitted by contact. Medical care providers were consulted for diagnosis of more serious diseases. Diagnosis and treatment errors were uncommon. Results of this study emphasize the need to educate future veterinarians during their early years in veterinary school about the risks associated with their future jobs.


Inhibition of interferon regulatory factor-1 expression results in predominance of cell growth stimulatory effects of interferon-gamma due to phosphorylation of Stat1 and Stat3.
Interferon-gamma (IFN-gamma) is a potent inhibitor of hematopoiesis in vitro and has been implicated in the pathophysiology of human bone marrow failure syndromes. IFN-gamma both inhibits cell cycling and induces expression of the Fas-receptor, resulting in subsequent apoptosis of hematopoietic progenitor cells. IFN regulatory factor-1 (IRF-1) mediates some of these suppressive effects by activation of downstream inducible genes, such as double-stranded RNA-activatable protein kinase and inducible nitric oxide synthase. However, under certain experimental conditions, IFN-gamma appears to stimulate proliferation of hematopoietic cells. Based on the hypothesis that IFN-gamma-receptor triggering may activate diverse signaling cascades, we designed experiments to determine which intracellular mechanisms (in addition to the IRF-1 transduction pathway) influence the biologic effects of IFN-gamma. Using antisense technique, we inhibited the IRF-1-mediated pathway in KG1a cells stimulated with IFN-gamma. In contrast to the suppressive effects of IFN-gamma observed in control cells, untreated and IFN-gamma-treated KG-1a cells that were transduced with retroviral vectors expressing IRF-1 antisense mRNA showed enhanced proliferation. The increased growth rate was associated with decreased levels of IRF-1 mRNA and protein but unchanged levels of IRF-2. We inferred that IFN-gamma could also activate a stimulatory transduction pathway that, under specific conditions, may control the cellular response to this cytokine. The family of Stat proteins is involved in signal transduction of hematopoietic growth factors. We showed that, in KG-1a cells, IFN-gamma also induced phosphorylation of Stat1 and Stat3, whereas p42 MAP kinase was phosphorylated regardless of the presence of IFN-gamma. Using electrophoresis mobility shift assays, IFN-gamma enhanced Stat1-Stat1 homodimer and Stat1-Stat3 heterodimer formation, suggesting that, in addition to inhibitory signals mediated by IRF-1, IFN-gamma may activate proliferative signals by phosphorylation of Stat1 and Stat3 proteins. The observations made in experiments with KG-1a cells were confirmed in primary hematopoietic cells. After inhibition of the IRF-1 pathway by transduction of an antisense IRF-1 retrovirus into human CD34+ cells, IFN-gamma produced an aberrant stimulatory effect on hematopoietic colony formation. Conversely, in control vector-transduced CD34+ cells, the typical inhibitory response to IFN-gamma was seen. Our results indicate that inhibitory cytokines such as IFN-gamma may exhibit diverse biologic effects depending on the intracellular balance of transcriptional regulators, in turn influenced by the activation and differentiation status of the target cells.


Radiomics Analysis Based on Magnetic Resonance Imaging for Preoperative Overall Survival Prediction in Isocitrate Dehydrogenase Wild-Type Glioblastoma.
This study aimed to develop a radiomics signature for the preoperative prognosis prediction of isocitrate dehydrogenase (IDH)-wild-type glioblastoma (GBM) patients and to provide personalized assistance in the clinical decision-making for different patients. A total of 142 IDH-wild-type GBM patients classified using the new classification criteria of WHO 2021 from two centers were included in the study and randomly divided into a training set and a test set. Firstly, their clinical characteristics were screened using univariate Cox regression. Then, the radiomics features were extracted from the tumor and peritumoral edema areas on their contrast-enhanced T1-weighted image (CE-T1WI), T2-weighted image (T2WI), and T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) magnetic resonance imaging (MRI) images. Subsequently, inter- and intra-class correlation coefficient (ICC) analysis, Spearman's correlation analysis, univariate Cox, and the least absolute shrinkage and selection operator (LASSO) Cox regression were used step by step for feature selection and the construction of a radiomics signature. The combined model was established by integrating the selected clinical factors. Kaplan-Meier analysis was performed for the validation of the discrimination ability of the model, and the C-index was used to evaluate consistency in the prediction. Finally, a Radiomics + Clinical nomogram was generated for personalized prognosis analysis and then validated using the calibration curve. Analysis of the clinical characteristics resulted in the screening of four risk factors. The combination of ICC, Spearman's correlation, and univariate and LASSO Cox resulted in the selection of eight radiomics features, which made up the radiomics signature. Both the radiomics and combined models can significantly stratify high- and low-risk patients (p < 0.001 and p < 0.05 for the training and test sets, respectively) and obtained good prediction consistency (C-index = 0.74-0.86). The calibration plots exhibited good agreement in both 1- and 2-year survival between the prediction of the model and the actual observation. Radiomics is an independent preoperative non-invasive prognostic tool for patients who were newly classified as having IDH-wild-type GBM. The constructed nomogram, which combined radiomics features with clinical factors, can predict the overall survival (OS) of IDH-wild-type GBM patients and could be a new supplement to treatment guidelines.


Microencapsulated cells genetically modified to overexpress human transforming growth factor-beta1: viability and functionality in allogeneic and xenogeneic implant models.
This study explores the suitability of using encapsulated genetically modified fibroblasts for orthopedic tissue engineering by examining cell survival and persistence of human transforming growth factor-beta (hTGF-beta) overexpression in xenogeneic and allogeneic implant models. Human wild-type fibroblasts, modified to produce a latent form of hTGF-beta, and murine mutant-type fibroblasts, engineered to release a constitutively active form of hTGF-beta, were encapsulated separately in Ca2+ -alginate microcapsules. Following a percentage viability assessment by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) test, microcapsules were implanted into either the subcutaneous or intraperitoneal cavities of mice. Explanted encapsulated cells were characterized for percentage viability and subjected to a release study and a viability test 1 week and 3 weeks following implantation, a time frame consistent with the requirement for orthopedic tissue engineering application of this growth factor. On average, percentage viabilities of encapsulated cells were 64%at implantation, 52% at explantation, and 56%after 1 week following either 1- or 3-week explantation. hTGF-beta release declined following in vivo implantation, more so for xenogeneic than allogeneic models, but remained in the clinically attractive range of 2 to 30 ng/(10(6) implanted cells 24 h). This technical platform for hTGF-beta is very encouraging for cartilage regeneration using orthopedic tissue engineering, and further evaluation is warranted.


Low-grade cervical squamous intraepithelial lesion during pregnancy: conservative antepartum management.
The purpose of this retrospective study was to determine the regression rate and management of low-grade squamous intraepithelial lesions (LSIL) in pregnancy. Seventy-four women with cytological findings of LSIL were analysed during the pregnant-puerperal period (until 12 months postpartum). Age, parity, cytological and colposcopic findings, route of delivery, and postpartum follow-up were studied. The age and parity of patients ranged (average) from 12 to 32 years (21.2 +/- 4.9), 0-5 (0.89 +/- 1.14), and 9-32 years (16.1 +/- 3.5), respectively. Thirty-nine of 55 (70.9%) and 12 of 19 (63.1%) pregnant women had normal cytology after vaginal delivery and caesarean section, respectively (p > 0.05). In postpartum, eight patients (10.8%) persisted with LSIL and ten (13.5%) presented high-grade squamous intraepithelial lesions. No case of unsatisfactory colposcopy and invasive carcinoma were found. LSIL during pregnancy has a high rate of regression, regardless of the route of delivery. Conservative management with colposcopic evaluation is proposed during gestation.


A case of hand mirror cell variant of acute lymphoblastic leukemia.
A 30 year old female patient diagnosed as acute lymphoblastic leukemia (ALL) with hand mirror like configuration of lymphoblastic-lymphocytic cells is reported. Although the leukemia was resistant to conventional chemotherapeutic regimens, the patient always looked well and survived for more than 20 months. Surface marker analysis showed that the cell was non-T, non-B, and not reactive to antiserum against common ALL antigen. A cytogenetic study of all the analyzable metaphases of the direct bone marrow preparation had a normal female karyotype. The clinical and hematological course is described. The immunological significance and the influence of hand mirror cell on chemosensitivity and prognosis are discussed.


Emotional Control in Psychotherapy Discourse.
Emotional control may be observed to be (1) too excessive as in avoidant behaviors during psychotherapy, (2) suitable to a frank expression of feelings, or (3) lacking in regulation causing too intense affective experiences. This article offers a theory that may help clinicians make observations about this range of possible states, formulate the patient's defensive processes, and choose if, how, and when to act. The observations and formulations presented focus on specific and present moment situations rather than habitual defense mechanisms.


Can the response to iron therapy be predicted in anemic nondialysis patients with chronic kidney disease?
Anemia is iron responsive in 30 to 50% of nondialysis patients with chronic kidney disease (CKD), but the utility of bone marrow iron stores and peripheral iron indices to predict the erythropoietic response is not settled. We investigated the accuracy of peripheral and central iron indices to predict the response to intravenous iron in nondialysis patients with CKD and anemia. A diagnostic study was conducted on 100 nondialysis patients who had CKD and anemia and were erythropoiesis-stimulating agent and iron naive. Bone marrow iron stores were evaluated by aspiration. Hemoglobin, transferrin saturation index (TSAT), and ferritin were measured at baseline and 1 month after 1000 mg of intravenous iron sucrose. Posttest predictive values for the erythropoietic response (> or =1-g/dl increase in hemoglobin) of peripheral and central iron indices were calculated. The erythropoietic response was noted in a higher proportion in bone marrow iron-deplete than in iron-replete patients (63 versus 30%). Peripheral iron indices had a moderate accuracy in predicting response. The positive (PPV) and negative predictive values (NPV) were 76 and 72% for a TSAT of 15% and 74 and 70% for a ferritin of 75 ng/ml, respectively. In the final logistic regression model, including TSAT and ferritin, the chances of a positive response increased by 7% for each 1% decrease in TSAT. Because an erythropoietic response is seen in half of patients and even one third of those with iron-replete stores responded whereas peripheral indices had only a moderate utility in predicting response, the therapeutic trial to intravenous iron seems to be a useful tool in the management of anemia in nondialysis patients with CKD.


Proliferation of anti-DNA-producing NZB B cells in a non-autoimmune environment.
This study demonstrates that purified NZB B cells, but not other NZB spleen cell populations, are capable of transferring anti-DNA antibody production into unirradiated H-2-compatible xid recipients. The number of autoantibody-producing B cells and the concentration of anti-DNA antibody found in the recipients correlated directly with the number of NZB B cells transferred. In addition, the number of anti-DNA-secreting lymphocytes found in the xid hosts increased exponentially with time post cell transfer. Several lines of evidence suggest that this phenomenon reflected the rapid proliferation of donor NZB B cells in the xid environment. Significantly, such proliferation was characteristic of donor cells that produced autoantibodies, but not of splenic B cells as a whole. These results suggest that stimulated NZB B cells can both induce and perpetuate autoantibody production in a normally non-autoimmune environment and in the absence of autoimmune helper cells.


Ab initio based tight-binding molecular dynamics simulation of the sticking and scattering of O2Pt(111).
The sticking and scattering of O(2)Pt(111) has been studied by tight-binding molecular dynamics simulations based on an ab initio potential energy surface. We focus, in particular, on the sticking probability as a function of the angle of incidence and the energy and angular distributions in scattering. Our simulations provide an explanation for the seemingly paradox experimental findings that adsorption experiments suggest that the O(2)Pt(111) interaction potential should be strongly corrugated while scattering experiments indicate a rather small corrugation. The potential energy surface is indeed strongly corrugated which leads to a pronounced dependence of the sticking probability on the angle of incidence. The scattered O(2) molecules, however, experience a rather flat surface due to the fact that they are predominantly scattered at the repulsive tail of the potential.


Copper selenide nanosnakes: bovine serum albumin-assisted room temperature controllable synthesis and characterization.
Herein we firstly reported a simple, environment-friendly, controllable synthetic method of CuSe nanosnakes at room temperature using copper salts and sodium selenosulfate as the reactants, and bovine serum albumin (BSA) as foaming agent. As the amounts of selenide ions (Se2-) released from Na2SeSO3 in the solution increased, the cubic and snake-like CuSe nanostructures were formed gradually, the cubic nanostructures were captured by the CuSe nanosnakes, the CuSe nanosnakes grew wider and longer as the reaction time increased. Finally, the cubic CuSe nanostructures were completely replaced by BSA-CuSe nanosnakes. The prepared BSA-CuSe nanosnakes exhibited enhanced biocompatibility than the CuSe nanocrystals, which highly suggest that as-prepared BSA-CuSe nanosnakes have great potentials in applications such as biomedical engineering.


[Clinical study on acupuncture and moxibustion for frozen shoulder: an evidence map].
The clinical evidences on acupuncture and moxibustion for the treatment of frozen shoulder were sorted and summarized systematically. The relevant articles of frozen shoulder treated with acupuncture and moxibustion were searched from PubMed, EMbase, Cochrane database of systematic review (CDSR), Cochrane database of controlled trials register (CENTRAL), China national knowledge infrastructure (CNKI), Wanfang, VIP, and Chinese biomedical literature databases (SinoMed), from database inception to May 31, 2021. Using AMSTAR-2, the methodological quality of the included systematic reviews was evaluated. With evidence map, the current status of clinical evidence was summarized on acupuncture and moxibustion in treatment of frozen shoulder. A total of 266 original studies and 6 systematic reviews were included finally. At present, many randomized controlled trials are designed with small sample size and the simple acupuncture and moxibustion therapy is dominant as the intervention, e.g. warm acupuncture, acupuncture with filiform needle, acupotomy and electroacupuncture. The outcomes considered in the current trials focus on clinical effective rate, the score of shoulder pain, the score of shoulder function and the score of quality of life. Most of the studies have shown that acupuncture and moxibustion is advantageous as an adjunctive therapy for frozen shoulder, but its clinical evidence is few in terms of the recurrence rate and safety. Moreover, it needs to improve the evidence quality of the relevant studies on acupuncture and moxibustion for frozen shoulder.


A tobacco-specific lung carcinogen in the urine of men exposed to cigarette smoke.
Environmental tobacco smoke has been classified by the Environmental Protection Agency as a carcinogen causally associated with lung cancer in adults, but there have been no reports of lung carcinogens or their metabolites in the body fluids or tissues of nonsmokers exposed to environmental tobacco smoke. Five male nonsmokers were exposed to sidestream cigarette smoke generated by machine smoking of reference cigarettes for 180 minutes on each of two days, six months apart. Sidestream smoke is the smoke that originates from the smoldering end of a cigarette between puffs. Twenty-four-hour urine samples were collected before and after exposure. The urine samples were analyzed for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide, which are metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a powerful lung carcinogen in rodents. NNAL is also a lung carcinogen in rodents. The urinary excretion of the metabolites increased after exposure to sidestream smoke in all the men. The mean (+/- SD) amount of NNAL and NNAL glucuronide was significantly higher after exposure than at base line (33.9 +/- 20.0 vs. 8.4 +/- 11.2 ng per 24 hours [127 +/- 74 vs. 31 +/- 41 pmol per day], P < 0.001) and was correlated with urinary cotinine excretion (r = 0.89, P < 0.001). The nicotine concentrations in the air to which the men were exposed were comparable to those in a heavily smoke-polluted bar. Nonsmokers exposed to sidestream cigarette smoke take up and metabolize a lung carcinogen, which provides experimental support for the proposal that environmental tobacco smoke can cause lung cancer.


Gene expression of macrophage colony-stimulating factor and its receptor in human placenta and decidua.
Macrophage colony-stimulating factor (M-CSF) induces proliferation of monocyte/macrophage progenitor cells and can also activate some functions of mature cells including fetally derived placental cells. To study the role of M-CSF in the pregnant female reproductive tract, the expression of M-CSF mRNA and its receptor, c-fms proto-oncogene, in human placenta and decidua was identified. M-CSF and c-fms mRNAs, 4.7Kb and 3.9Kb respectively, were detected by Northern blotting in the early stage placenta and subsequently increased during pregnancy. These mRNAs were not detected in the nonpregnant endometrium but were strongly induced in maternal decidua with the same mRNA size as in the placenta. Northern blot hybridization on the endometrium of a pseudopregnant uterus revealed that the expression of endometrial M-CSF and c-fms mRNAs is regulated by synergistic action of female sex steroid hormones. These findings indicate that, in an autocrine and/or paracrine manner, M-CSF is deeply involved in the local proliferation and differentiation of cells at the materno-fetal interface, and support the placental immunotrophism hypothesis.


Multidrug resistance in B-cell chronic lymphocytic leukemia.
Multidrug resistance (MDR) was investigated in peripheral blood cells isolated from 40 patients with B cell chronic lymphocytic leukemia (B-CLL) and from 7 healthy volunteers, using a flow cytometric assay that detects cellular efflux of the fluorescent dye rhodamine 123 (Rh 123), which has been demonstrated to be transported from the cell by the P-glycoprotein pump. The proportion of B leukemic cells effluxing Rh 123 and thus displaying MDR was low (14 +/- 17%) in B-CLL and in only 4 cases did the contingent of B leukemic cells showing MDR represent more than 30% of the total leukemic cells. In contrast, a higher proportion of cells effluxing Rh 123 (44 +/- 13%) was demonstrated in normal B lymphocytes. No statistical correlation was found between the number of leukemic B cells displaying MDR and clinical parameters or previous treatment. These results clearly suggest that MDR activity is usually low in B-CLL.


Transketolase (TKT) activity and nuclear localization promote hepatocellular carcinoma in a metabolic and a non-metabolic manner.
Metabolic reprogramming is one of the hallmarks of cancer cells. The pentose phosphate pathway (PPP), a branch of glycolysis, is an important metabolic pathway for the survival and biosynthesis of cancer cells. Transketolase (TKT) is a key enzyme in the non-oxidative phase of PPP. The mechanistic details of TKT in hepatocellular carcinoma (HCC) development remain unclear. TKT level and subcellular location were examined in HCC cell lines and tissue samples. We established the TKT overexpression and knocking-down stable cells in HCC cell lines. Proliferation, migration, viability and enzyme activity assays in vitro, tumor growth and metastasis assays in vivo were employed to test the effects of TKT on HCC development. GFP-tagged TKT truncations and mutants were used to locate the nuclear localization sequence (NLSs) of TKT. Cross-linking co-IP/MS was applied to identify the interaction proteins of nuclear TKT. We showed that TKT increased the proliferation and migration of HCC cells, as well as the viability under oxidative stress in vitro and accelerated the growth and metastasis of HCC cells in vivo. We found as a key enzyme of PPP, TKT could promote the proliferation, cell cycle, migration and viability by regulating the metabolic flux. Moreover, it was firstly reported that unlike other key enzymes in PPP, TKT showed a strong nuclear localization in HCC cells. We found not only high TKT expression, but also its nuclear localization was a prediction for poor prognosis of HCC patients. We further identified the nuclear localization sequences (NLS) for TKT and demonstrated the NLS mutations decreased the pro-tumor function of TKT independent of the enzyme activity. Cross-linking Co-IP/MS showed that nuclear TKT interacted with kinases and transcriptional coregulators such as EGFR and MAPK3, which are associated with cell activation or stress response processes. EGF treatment significantly increased the viability and proliferation of HCC cells in the enzyme-inactivating mutation TKT-D155A overexpression cells but not in the NLS-D155A double mutant group, which could be blocked by EGFR inhibitor erlotinib treatment. Our research suggests that in addition to the metabolic manner, TKT can promote the development of HCC in a non-metabolic manner via its nuclear localization and EGFR pathway.


A Novel Approach for Sampling in Approximate Dynamic Programming Based on $F$ -Discrepancy.
Approximate dynamic programming (ADP) is the standard tool to solve Markovian decision problems under general hypotheses on the system and the cost equations. It is known that one of the key issues of the procedure is how to generate an efficient sampling of the state space, needed for the approximation of the value function, in order to cope with the well-known phenomenon of the curse of dimensionality. The most common approaches in the literature are either aimed at a uniform covering of the state space or driven by the actual evolution of the system trajectories. Concerning the latter approach, F -discrepancy, a quantity closely related to the Kolmogorov-Smirnov statistic, that measures how strictly a set of random points represents a probability distribution, has been recently proposed for an efficient ADP framework in the finite-horizon case. In this paper, we extend this framework to infinite-horizon discounted problems, providing a constructive algorithm to generate efficient sampling points driven by the system behavior. Then, the algorithm is refined with the aim of acquiring a more balanced covering of the state space, thus addressing possible drawbacks of a pure system-driven sampling approach to obtain, in fact, an efficient hybrid between the latter and the pure uniform design. A theoretical analysis is provided through the introduction of an original notion of the F -discrepancy and the proof of its properties. Simulation tests are provided to showcase the behavior of the proposed sampling method.


Echocardiographic ultrasonic tissue characterization in a case of Fabry's disease following renal transplantation.
We report a case of Fabry's disease where stabilization of progressive cardiac involvement was recorded in a 29-yr-old Caucasian man, to our knowledge, for the first time by ultrasonic tissue characterization echocardiography after 1 yr of successful renal transplantation. Three echocardiographic evaluations have been made: the first 3 months before, the second 6 months after, and the third 1 yr after kidney transplantation. The myocardial structural damage - evaluated by integrated backscatter index - shows a persistence of the impairment of intrinsic myocardial contractility at septum level, probably due to coexistent hypertensive status, which is able to induce per se alterations of myocardial textural parameters. On the other hand, the cyclic variation index at posterior free wall, which is less dependent on strictly hemodynamic factors than the septum, appears quite normal at the third observation. These data could reflect the improvement of the ultrastuctural myocardial findings in relation to renal transplantation, which could correct not only renal failure but also the enzymatic deficiency by replacement of alpha-galactosidase A through the transplanted kidney.


Identification and characterization of the novel FAD-binding lobe G75S mutation in cytochrome b(5) reductase: an aid to determine recessive congenital methemoglobinemia status in an infant.
NADH-cytochrome b(5) reductase deficiency results clinically in either type I or type II recessive congenital methemoglobinemia. The more severe type II form is associated with a global deficiency of cytochrome b(5) reductase and is characterized by cyanosis with neurological dysfunction. In contrast, the only symptom for type I is cyanosis. We have identified a novel G to A mutation at position 15,635 in the DIAI gene of a 4-month-old baby that results in a glycine to serine substitution at codon 75 in the cytochrome b(5) reductase protein. The G75S mutation, located in the FAD-binding lobe of cytochrome b(5) reductase, was found in association with the previously described V252M variant. The V252M mutation is present in the NADH-binding domain and associated with both types I and II recessive congenital methemoglobinemia. Since the G75S and V252M mutations represent radical changes in differing regions of cytochrome b(5) reductase, generating and characterizing these variants singly and in combination using a rat heterologous expression system would provide insight into the differences between types I and II disease at the molecular level. Although all three variants were found to retain stoichiometric levels of FAD with spectroscopic and thermodynamic properties comparable to those of native cytochrome b(5) reductase, all exhibited decreased catalytic efficiency and reduced protein stability reflecting the position of the mutations in the primary structure. The G75S variant retained only 11% of the catalytic efficiency of the wild-type enzyme. Thus, cytochrome b(5) reductase deficient patients who are heterozygous for either FAD- or NADH-binding lobe mutations can exhibit the clinically less severe type I phenotype.


Obesogenic Environment in Childhood: Implications of High Socioeconomic Level in a Developing Country.
Today, obesity in childhood is considered as an important health problem, especially in developed countries. This study aims to determine the prevalence of obesity in children and to reveal the relationship between television watching habit, computer use and socioeconomic status in children. A cross-sectional study was performed in 11 public schools selected with random sampling in Istanbul. A total of 1479 children (767 males (51.9%)) were included in the study. Their ages ranged from 10-15, and the mean age was 11.95±1.36 years for girls and 12.06±1.39 years for boys. Demographic characteristics and factors affecting obesity were inquired with the structured questionnaire form.The height, and body weights of the students were measured, and their body mass ındexes were calculated. Those with a BMI above the 95th percentile were considered obese, and those between the 85th and 95th percentiles were considered as overweight. In the study group, the obesity rate was calculated as 5.3%, and the mild obesity rate as 14.9 percent. The total prevalence of overweight and obese children was 20.2%. The frequency of obesity in the high socioeconomic level group was significantly higher than low one (p<0.01). The average daily screen time was 3.74±1.58 hours. The obesity risk was found to increase three times when this period exceeded five hours. In the logistic regression analysis, while high socioeconomic level was found as the main determinant among the risk factors for obesity, the effects of daily screen time were found to be marginally significant (p<0.045). The lifestyle of the families with high socioeconomic status is the main determinant of obesity in adolescents. Nutrition with higher calorie foods, more frequent media use and a more sedentary life brought about is an obesogenic environment created by a high socioeconomic status. Environmental risk factors for obesity should be assessed.


Interaction of cyanine dyes with nucleic acids. XXI. Arguments for half-intercalation model of interaction.
The spectral luminescent properties of two groups of monomethine cyanine dyes were studied in the presence of DNA. The first group included five dyes with 5,6-methylenedioxy-[d]-benzo-1,3-thiazole heterocycle and their unsubstituted analogs. Five monomethine pyrylium cyanines and their N-methyl-pyridine analogs were included in the second group. In each pair the pyrylium and pyridine dyes had similar geometry but differed in charge density distribution. The results presented some evidence in favor of the half-intercalation interaction mode between the studied dyes and DNA. When the benzothiazole residue had the lowest electron donor ability between the two heterocycles in the dye molecule, its substitution with the bulky methylenedioxy group led to a significant decrease in fluorescence enhancement of the dye-DNA complex. On the contrary, when the substituents that create steric hindrance (e.g., methylenedioxy and methyl groups) were introduced into the heterocycle with the higher electron donor ability, the fluorescence enhancement value of the dye-DNA complex was virtually unchanged. The changes in the Stock's shift values upon the formation of the dye-DNA complexes were in agreement with the proposed half-intercalation model. Interestingly, in the dye-DNA complexes the pyrylium dyes probably resided in a place similar to the pyridine ones. It is possible that the benzothiazole (or benzooxazole) ring intercalated between the DNA bases and the pyrylium (or pyridine) residue was located in the DNA groove closer to the phosphate backbone.


Fear, avoidance and physiological symptoms during cognitive-behavioral therapy for social anxiety disorder.
We examined fear, avoidance and physiological symptoms during cognitive-behavioral therapy (CBT) for social anxiety disorder (SAD). Participants were 177 individuals with generalized SAD who underwent a 14-week group CBT as part of a randomized controlled treatment trial. Participants filled out self-report measures of SAD symptoms at pre-treatment, week 4 of treatment, week 8 of treatment, and week 14 of treatment (post-treatment). Cross-lagged Structural Equation Modeling indicated that during the first 8 weeks of treatment avoidance predicted subsequent fear above and beyond previous fear, but fear did not predict subsequent avoidance beyond previous avoidance. However, during the last 6 weeks of treatment both fear and avoidance predicted changes in each other. In addition, changes in physiological symptoms occurred independently of changes in fear and avoidance. Our findings suggest that changes in avoidance spark the cycle of change in treatment of SAD, but the cycle may continue to maintain itself through reciprocal relationships between avoidance and fear. In addition, physiological symptoms may change through distinct processes that are independent from those involved in changes of fear and avoidance.


Prothymosin alpha in human blood.
The major cross-reacting peptide in human plasma detected with a radioimmunoassay (RIA) for thymosin alpha 1 was identified as prothymosin alpha, based on its elution properties in gel-filtration chromatography and its amino acid composition after purification by HPLC. A small quantity (less than 10%) of the total cross-reacting material was recovered in fractions corresponding to lower molecular weight thymosin alpha 1-like peptides. The total quantity of cross-reacting material detected in human blood, expressed as thymosin alpha 1 equivalents, was 11-14 pmol/ml (approximately 90% was recovered in the leukocyte fraction, approximately 10% was in the plasma fraction, and 1-2% was in the erythrocyte fraction). The peptide present in leukocytes was also identified as prothymosin alpha. After correction for the 5-times lower molar reactivity of prothymosin alpha in the thymosin alpha 1 RIA employed in these experiments, we estimate that the content of prothymosin alpha in human blood is 55-70 pmol/ml (0.6-0.8 microgram/ml). The relatively small quantities recovered in the erythrocyte and plasma fractions may be attributed to contamination of the former by leukocytes or to leakage from leukocytes into the plasma.


Species identification of Candida isolates obtained from oral lesions of HIV infected patients.
A total of 60 patients suspected to have AIDS with oral lesions suggestive of oral candidiasis were studied. Candida species were isolated from 50 patients. Candida albicans was the commonest isolate (70 %) followed Candida parapsilosis(15%), Candida glabrata (7.5%) and Candida tropicalis (5%) respectively. Candida dubliniensis was isolated from a single case only. Though the reports from developed countries show more prevalence of the novel species Candida dubliniensis, in our study it was isolated in a single case. All the patients were treated successfully with oral fluconazole for 7 days except for the patients from which Candida glabrata was isolated, who were treated with Amphotericin B.


In search of adrenocortical stem and progenitor cells.
Scientists have long hypothesized the existence of tissue-specific (somatic) stem cells and have searched for their location in different organs. The theory that adrenocortical organ homeostasis is maintained by undifferentiated stem or progenitor cells can be traced back nearly a century. Similar to other organ systems, it is widely believed that these rare cells of the adrenal cortex remain relatively undifferentiated and quiescent until needed to replenish the organ, at which time they undergo proliferation and terminal differentiation. Historical studies examining cell cycle activation by label retention assays and regenerative potential by organ transplantation experiments suggested that the adrenocortical progenitors reside in the outer periphery of the adrenal gland. Over the past decade, the Hammer laboratory, building on this hypothesis and these observations, has endeavored to understand the mechanisms of adrenocortical development and organ maintenance. In this review, we summarize the current knowledge of adrenal organogenesis. We present evidence for the existence and location of adrenocortical stem/progenitor cells and their potential contribution to adrenocortical carcinomas. Data described herein come primarily from studies conducted in the Hammer laboratory with incorporation of important related studies from other investigators. Together, the work provides a framework for the emerging somatic stem cell field as it relates to the adrenal gland.


Coordinating care for the dual-eligible population.
Many patients who are eligible for Medicare also are eligible for Medicaid. IDSs that deliver care to these patients, called "dual eligibles," face a challenge of conflicting rules and incentives under existing Federal and state laws governing coverage of these patients. Differences in the Medicare and Medicaid payment rules give IDSs a financial incentive to transfer patients from long-term and postacute to acute care settings in situations in which the patients might receive more appropriate care remaining where they are. Many states are implementing pilot programs to allow IDSs to better coordinate care for dual eligibles. Before states begin implementing pilot or statewide programs, IDSs should be involved in the design of the pilot programs, thereby ensuring that the coordinated funding effectively meets an IDS's requirements for optimum care delivery with adequate payment.


Htr2a Gene and 5-HT(2A) Receptor Expression in the Cerebral Cortex Studied Using Genetically Modified Mice.
Serotonin receptors of the 5-HT(2A) subtype are robustly expressed in the cerebral cortex where they have been implicated in the pathophysiology and therapeutics of mental disorders and the actions of hallucinogens. Much less is known, however, about the specific cell types expressing 5-HT(2A) receptors in cortex. In the current study we use immunohistochemical and electrophysiological approaches in genetically modified mice to address the expression of the Htr2a gene and 5-HT(2A) receptors in cortex. We first use an EGFP-expressing BAC transgenic mice and identify three main Htr2A gene expressing neuronal populations in cortex. The largest of these cell populations corresponds to layer V pyramidal cells of the anterior cortex, followed by GABAergic interneurons of the middle layers, and non-pyramidal cells of the subplate/Layer VIb. We then use 5-HT(2A) receptor knockout mice to identify an antibody capable of localizing 5-HT(2A) receptors in brain and use it to map these receptors. We find strong laminar expression of 5-HT(2A) receptors in cortex, especially along a diffuse band overlaying layer Va. This band exhibits a strong anteroposterior gradient that closely matches the localization of Htr2A expressing pyramidal cells of layer V. Finally we use electrophysiological and immunohistochemical approaches to show that most, but not all, GABAergic interneurons of the middle layers are parvalbumin expressing Fast-spiking interneurons and that these cells are depolarized and excited by serotonin, most likely through the activation of 5-HT(2A) receptors. These results clarify and extend our understanding of the cellular distribution of 5-HT(2A) receptors in the cerebral cortex.


Monolayer culture of adult rat pancreatic islets on extracellular matrix: modulation of B-cell function by chronic exposure to high glucose.
Studies in vivo indicate that chronic hyperglycemia is deleterious for insulin secretion. We have used an improved islet monolayer culture system to study chronic modulations of B-cell function. Adult rat islets maintained over several weeks on extracellular matrix in the presence of 11.1 mM glucose responded to an acute stimulation with 16.7 mM glucose by a 5- to 8-fold increase in insulin secretion. When cultured in the presence of higher glucose concentrations, the response to an acute glucose stimulus diminished time and dose dependently. In islets desensitized by exposure to 33.3 mM glucose for 1 week, reduction of the glucose level to 11.1 mM reversed the desensitization within 2 weeks. This desensitization was not limited to the glucose stimulus; responses to other nutrient secretagogues, such as glyceraldehyde and alpha-ketoisocaproic acid, were also reduced. In contrast, responses of insulin secretion to nonnutrient stimulators (tolbutamide and quinine) and amplifiers (isobutylmethylxanthine and carbachol) showed no desensitization in islets exposed to 33.3 mM glucose. Desensitization similar to that caused by 33.3 mM glucose could be induced by 11.1 mM glucose together with 0.1 mM isobutylmethylxanthine. High glucose also caused a time-dependent loss in compact monolayer organization with disruption of cell contacts. Our studies suggest that 1) generation of the reduced insulin response may be related to the prolonged high insulin secretion rate; 2) expression of the functional change is specific to the nutrient stimulus-secretion coupling; and 3) modifications in intercellular contacts may be involved in B-cell desensitization.


Abnormal static and dynamic functional connectivity of resting-state fMRI in multiple system atrophy.
In order to explore the topological alterations in functional brain networks between multiple system atrophy (MSA) patients and healthy controls (HC), a new joint analysis method of static and dynamic functional connectivity (FC) is proposed in this paper. Twenty-four MSA patients and twenty HCs were enrolled in this study. We constructed static and dynamic brain networks from resting-state fMRI data and calculated four graph theory attributes. Statistical comparisons and correlation analysis were carried out for static and dynamic FC separately before combining both cases. We found decreased local efficiency (LE) and weighted degree (WD) in cerebellum from both static and dynamic graph attributes. For static FC alone, we identified increased betweenness centrality (BC) at left dorsolateral prefrontal cortex, left Cerebellum_Crus9 and decreased WD at Vermis_6. For dynamic FC alone, decreased BC, clustering coefficients and LE at several cortical regions and cerebellum were identified. All the features had significant correlation with total UMSARS scores. Receiver operating characteristic analysis showed that dynamic features had the highest area under the curve value. Our work not only added new evidence for the underlying neurobiology and disrupted dynamic disconnection syndrome of MSA, but also proved the possibility of disease diagnosis and progression tracking using rs-fMRI.


Autophagy Is Involved in the Sevoflurane Anesthesia-Induced Cognitive Dysfunction of Aged Rats.
Autophagy is associated with regulation of both the survival and death of neurons, and has been linked to many neurodegenerative diseases. Postoperative cognitive dysfunction is commonly observed in elderly patients following anesthesia, but the pathophysiological mechanisms are largely unexplored. Similar effects have been found in aged rats under sevoflurane anesthesia; however, the role of autophagy in sevoflurane anesthesia-induced hippocampal neuron apoptosis of older rats remains elusive. The present study was designed to investigate the effects of autophagy on the sevoflurane-induced cognitive dysfunction in aged rats, and to identify the role of autophagy in sevoflurane-induced neuron apoptosis. We used 20-month-old rats under sevoflurane anesthesia to study memory performance, neuron apoptosis, and autophagy. The results demonstrated that sevoflurane anesthesia significantly impaired memory performance and induced hippocampal neuron apoptosis. Interestingly, treatment of rapamycin, an autophagy inducer, improved the cognitive deficit observed in the aged rats under sevoflurane anesthesia by improving autophagic flux. Rapamycin treatment led to the rapid accumulation of autophagic bodies and autophagy lysosomes, decreased p62 protein levels, and increased the ratio of microtubule-associated protein light chain 3 II (LC3-II) to LC3-I in hippocampal neurons through the mTOR signaling pathway. However, administration of an autophagy inhibitor (chloroquine) attenuated the autophagic flux and increased the severity of sevoflurane anesthesia-induced neuronal apoptosis and memory impairment. These findings suggest that impaired autophagy in the hippocampal neurons of aged rats after sevoflurane anesthesia may contribute to cognitive impairment. Therefore, our findings represent a potential novel target for pro-autophagy treatments in patients with sevoflurane anesthesia-induced neurodegeneration.


The Genetics of Urinary Tract Infections and the Innate Defense of the Kidney and Urinary tract.
The urinary tract is a sterile organ system. Urinary tract infections (UTIs) are common and often serious infections. Research has focused on uropathogen, environment, and host factors leading to UTI pathogenesis. A growing body of evidence exists implicating genetic factors that can contribute to UTI risks. In this review, we highlight genetic variations in aspects of the innate immune system critical to the host response to uropathogens. This overview includes genetic variations in pattern recognition receptor molecules, chemokines/cytokines, and neutrophil activation. We also comprehensively cover murine knockout models of UTI, genetic variations involved in renal scarring as a result of ascending UTIs, and asymptomatic bacteriuria.


Stage I-II low-grade lymphomas: a prospective trial of combination chemotherapy and radiotherapy.
Between 1984-1989, 44 patients with stage I-II low grade lymphoma were treated prospectively with sequential chemotherapy and involved-field radiotherapy. The chemotherapy was cyclophosphamide, vincristine, prednisone, and bleomycin (COP-Bleo); doxorubicin was included (CHOP-Bleo) for patients with adverse prognostic features (high LDH; extranodal sites; bulky nodes). Of the 44 patients, 37 had measurable disease and all have responded. With a median follow-up of 32 months, the 5-year survival and failure-free survival were 89% and 74%, respectively. Compared to past experience with involved-field radiotherapy alone, the failure-free survival is significantly better with COP-Bleo plus radiotherapy. The potentially cured fraction has risen from 40% to 74%.


Modification of polymer networks with bone sialoprotein promotes cell attachment and spreading.
Biomaterials used for tissue engineering scaffolds act as temporary substrates, on which cells deposit newly synthesized extracellular matrix. In cartilage tissue engineering, polycaprolactone/poly(2-hydroxyethyl methacrylate) (PCL/pHEMA) polymer blends have been used as scaffold materials, but their use in osseous tissue engineering has been more limited. The objective of this study was to evaluate modification of PCL/pHEMA surfaces with bone sialoprotein (BSP), an extracellular matrix protein important in regulating osseous tissue formation. Modification of surfaces with BSP significantly enhanced osteoblastic cell attachment and spreading, without compromising proliferation. Thus, BSP-immobilization may be a useful strategy for optimizing scaffolds for skeletal tissue engineering.


[Small cell carcinoma of the prostate: a case report].
Pure small cells carcinoma of the prostate is a rare tumour with a pejorative forecast. We report a case of neuroendocrine small cells carcinoma developed at a 68 years old patient. This tumour expressed a positive marking immunohistochimic with chromogranin A, the rate of PSA was on the other hand normal (2.9 ng/ml). The patient was treated by chemotherapy associating etoposide and cisplatinium and external radiotherapy. He is deceased 4 months afterwards.


Transient neurological symptoms after spinal anaesthesia with 4% mepivacaine and 0.5% bupivacaine.
Several studies have reported transient neurological symptoms after spinal anaesthesia with 5% lignocaine. In order to evaluate the role of concentrated solutions of local anaesthetic in the development of transient neurological symptoms, 200 ASA I or II patients undergoing minor orthopaedic or rectal surgery under spinal anaesthesia were allocated randomly to receive 4% mepivacaine 80 mg or hyperbaric 0.5% bupivacaine 10 mg. All patients were interviewed by an anaesthetist approximately 24 h after spinal anaesthesia, and after 1 week patients were asked to return a written questionnaire. The incidence of transient neurological symptoms consisting of pain in the buttocks or pain radiating symmetrically to the lower extremities differed (P < 0.001) between patients receiving mepivacaine (30%) and those receiving bupivacaine (3%). Hyperbaric 0.5% bupivacaine can be recommended for minor operations on the lower abdomen or lower extremities.


Involvement of nuclear receptor coactivator SRC-1 in estrogen-dependent cell growth of MCF-7 cells.
Steroid hormones regulate cell growth and function through the transcriptional control of target genes by their cognate nuclear receptors. These receptors bind to ligands and associate with transcriptional cofactors to stimulate transcription. SRC-1, one of the nuclear receptor coactivators, is known to interact with nuclear receptors and enhance transactivation function in a ligand-dependent manner. In this study, to assess the function of SRC-1 in cell growth regulated by nuclear receptor ligands, we established a stable transformant cell line overexpressing human SRC-1 and studied the action of 17beta-estradiol (E(2)) on cell growth as well as the expression of E(2)-responsive genes in MCF-7 cells. We found that SRC-1 overexpression potentiates cell growth stimulated by E(2) in accordance with enhancement of transcriptional activation of exogenous and endogenous E(2)-responsive genes. These findings clearly indicate the importance of nuclear receptor coactivators for the activities of steroid/lipophilic vitamins in cell growth and gene expression.


Angiomyolipoma of the bladder.
Angiomyolipoma of the bladder is an extremely rare neoplasm. We report a case of a 55-year-old woman with an angiomyolipoma of the bladder visualized on pelvic sonogram as a 5 mm polyp in the floor of the bladder. The lesional tissue consisted of spindle cells, epithelioid cells, and adipocytes, with occasional thick-walled blood vessels. Immunohistochemical studies showed the spindle and epithelioid cells to be focally positive for HMB-45 and diffusely positive for actin and muscle cell antigen (HHF-35), which confirmed the diagnosis of angiomyolipoma. A review of the recent literature on the pathogenesis of angiomyolipoma follows.


Histone methylation defines epigenetic asymmetry in the mouse zygote.
The oocyte cytoplasm regulates and enhances the epigenetic asymmetry between parental genomes and, consequently, functional differences observed between them during development in mammals. Here we demonstrate a preferential interaction of HP1beta with the maternal genome immediately after fertilisation in the mouse zygote, which also shows a high level of lysine 9-methylated histone H3. In contrast, the paternal genome has neither HP1beta binding nor methylated histone H3 at these early stages. Paternal binding of HP1beta is only detected at the pronuclear stage, prior to the appearance of lysine 9-methylated histone H3. The early recruitment of heterochromatic factors specifically to the maternal genome could explain the preferential DNA demethylation of the paternal genome in the zygote.


Rostral mandibulectomy for treatment of an ameloblastic fibro-odontoma in a cow.
A 1-year-old polled Hereford heifer was admitted with a mass of the rostral mandibular area that had been observed 17 days earlier. Cytologic examination of fluid aspirated from the mass revealed normal blood. Radiography revealed an expansile, osteolytic mass involving the rostral portion of the mandible. Mineralization of the soft-tissue component was evident. Rostral mandibulectomy was performed to remove the mass in its entirety. The histologic diagnosis was ameloblastic fibro-odontoma. One year after surgery, cosmetic appearance of the mandible was acceptable, and there was no evidence of tumor regrowth. Radiation therapy, cryotherapy, and thermocautery have been recommended in conjunction with surgical excision to prevent tumor regrowth in the oral cavity. Tumor regrowth was not a factor in long-term prognosis in this cow.


Monoclonal Antibodies against Nucleocapsid Protein of SARS-CoV-2 Variants for Detection of COVID-19.
Mitigation strategies of the coronavirus disease 2019 (COVID-19) pandemic have been greatly hindered by the continuous emergence of SARS-CoV-2 variants. New sensitive, rapid diagnostic tests for the wide-spectrum detection of viral variants are needed. We generated a panel of 41 monoclonal antibodies against the SARS-CoV-2 nucleocapsid protein (NP) by using mice hybridoma techniques. Of these mAbs, nine exhibited high binding activities and were applied in latex-based lateral flow immunoassays (LFIAs). The LFIAs utilizing NP-mAb-7 and -40 had the best sensitivity and lowest limit of detection: 8 pg for purified NP and 625 TCID50/mL for the authentic virus (hCoV-19/Taiwan/4/2020). The specificity tests showed that the NP-mAb-40/7 LFIA strips did not cross-react with five human coronavirus strains or 20 other common respiratory pathogens. Importantly, we found that 10 NP mutants, including alpha (B.1.1.7), beta (B.1.351), gamma (P.1), and delta (B.1.617.2) variants, could be detected by NP-mAb-40/7 LFIA strips. A clinical study (n = 60) of the NP-mAb-40/7 LFIA strips demonstrated a specificity of 100% and sensitivity of 90% in infected individuals with cycle threshold (Ct) values < 29.5. These anti-NP mAbs have strong potential for use in the clinical detection of SARS-CoV-2 infection, whether the virus is wild-type or a variant of concern.


Typing of Candida glabrata in clinical isolates by comparative sequence analysis of the cytochrome c oxidase subunit 2 gene distinguishes two clusters of strains associated with geographical sequence polymorphisms.
We tested whether comparative sequence analysis of the mitochondrion-encoded cytochrome c oxidase subunit 2 gene (COX2) could be used to distinguish intraspecific variants of Candida glabrata. Mitochondrial genes are suitable for investigation of close phylogenetic relationships because they evolve much faster than nuclear genes, which in general exhibit very limited intraspecific variation. For this survey we used 11 clinical isolates of C. glabrata from three different geographical locations in Brazil, 10 isolates from one location in the United States, 1 American Type Culture Collection strain as an internal control, and the published sequence of strain CBS 138. The complete coding region of COX2 was amplified from total cellular DNA, and both strands were sequenced twice for each strain. These sequences were aligned with published sequences from other fungi, and the numbers of substitutions and phylogenetic relationships were determined. Typing of these strains was done by using 17 substitutions, with 8 being nonsynonymous and 9 being synonymous. Also, cDNAs made from purified mitochondrial polyadenylated RNA were sequenced to confirm that our sequences correspond to the expressed copies and not nuclear pseudogenes and that a frameshift mutation exists in the 3' end of the coding region (position 673) relative to the Saccharomyces cerevisiae sequence and the previously published C. glabrata sequence. We estimated the average evolutionary rate of COX2 to be 11.4% sequence divergence/10(8) years and that phylogenetic relationships of yeasts based on these sequences are consistent with rRNA sequence data. Our analysis of COX2 sequences enables typing of C. glabrata strains based on 13 haplotypes and suggests that positions 51 and 519 indicate a geographical polymorphism that discriminates strains isolated in the United States and strains isolated in Brazil. This provides for the first time a means of typing of Candida strains that cause infections by use of direct sequence comparisons and the associated divergence estimates.


Detection of Treponema pallidum DNA During Early Syphilis Stages in Peripheral Blood, Oropharynx, Ano-Rectum and Urine as a Proxy for Transmissibility.
Syphilis diagnosis may be challenging, especially in the asymptomatic and early clinical stages. We evaluated the presence of Treponema pallidum DNA (TP-DNA) in various sample types to elucidate transmissibility during various syphilis stages. The study was conducted at the Amsterdam Centre for Sexual Health. We included adult men who have sex with men (MSM), who were suspected of having syphilis. The 2020 European guidelines definitions were followed for the diagnosis and staging of syphilis. Using a polymerase chain reaction (PCR) targeting the polA gene of Treponema pallidum (TP-PCR), we tested the following study samples on TP-DNA: peripheral blood, oropharyngeal swab, ano-rectal swab, and urine. From November 2018 to December 2019 we included 293 MSM. Seventy clients had primary syphilis, 73 secondary syphilis, 86 early latent syphilis, 14 late latent syphilis, 23 treated syphilis, and 27 had no syphilis. TP-DNA was detected in at least 1 study sample in 35/70 clients with primary syphilis (2/70 peripheral blood, 7/70 oropharynx, 13/70 ano-rectum, and 24/70 urine); in 62/73 clients with secondary syphilis (15/73 peripheral blood, 47/73 oropharynx, 37/73 ano-rectum, and 26/73 urine); and in 29/86 clients with early latent syphilis (5/86 peripheral blood, 21/86 oropharynx, 11/86 ano-rectum, and 6/86 urine). TP-DNA was not detected in clients with late latent syphilis or treated syphilis, nor in clients without syphilis. TP-DNA was frequently detected in various sample types in the absence of lesions. This is in line with the high transmission rate of syphilis and opens diagnostic opportunities for early presymptomatic syphilis stages.


Prediction and prognostic potential of NR3C1 gene expression level in DLBCL patients.
Objective: Diffuse Large B-Cell Lymphoma (DLBCL) is a common and frequently occurring subtype of Non-Hodgkin Lymphoma (NHL). The effective treatment and prognosis of DLBCL are still urgently needed to be explored. This article aims to shed light on the connection between DLBCL survival and NR3C1 expression levels. Methods: First, we divided the 952 DLBCL patients into an NR3C1 high-expression group and an NR3C1 low-expression group and compared the baseline characteristics of the two groups. Second, we used multivariate analysis to predict the dependent variable for age, pathology, ECOG score, lactate dehydrogenase (LDH) ratio, and NR3C1 expression level. Finally, we analyzed the progression-free survival (PFS) and overall survival rate (OS) of DLBCL patients with high or low NR3C1 expression. Results: DLBCL patients with high NR3C1 expression had a better prognosis than those with low NR3C1 expression (OS, P < 0.0001). In DLBCL patients of CHOP therapy, high NR3C1 expression was associated with a good survival prognosis in OS (OS, P = 0.028). Conclusion: In multivariate analysis, NR3C1 high expression was an independent prognostic factor that predicted a longer OS of DLBCL (OS, P = 0.0003). NR3C1 is considered an independent predictor of DLBCL patients and can be used as a biomarker for the prognosis of DLBCL.